1

Table of Contents
Preface CARDIOVASCULAR Congestive Heart Failure Pediatric Hypertension Kawasaki Disease Acute Rheumatic Fever GENERAL PEDIATRICS AND PHARMOCOLOGY Bite Wounds Inborn Errors of Metabolism and Metabolic Diseases Pediatric Nutrition Dysmetabolic Syndrome General Approach to Poisonings/Ingestions Pediatric Antibiotics Radiologic Studies and Basic Indications Henoch-Schonlein Purpura GASTROINTESTINAL Gastrointestinal Hemorrhage Gastroesophageal Reflux Disease Neonatal Hyperbilirubinemia RESPIRATORY AND ALLERGY Acute Airway Obstruction/Stridor Parapneumonic Effusion and Empyema Anaphylaxis Asthma Cystic Fibrosis NEUROLOGY Seizure Disorders Stroke in Childhood Ataxia 83 86 88 65 69 72 73 76 53 56 58 23 26 31 35 38 44 46 48 7 10 13 17 3

2 ENDOCRINE Diabetes Mellitus Adrenal Crisis Hypoglycemia Puberty FLUIDS AND RENAL Acute Renal Failure Fluids and Electrolytes Rickets Renal Tubular Acidosis Hematuria Nephrology Cocktails Proteinuria Hydronephrosis INFECTIOUS DISEASE Meningitis Shunt Infections Infant with fever of uncertain source Urinary Tract Infections Catheter Related Sepsis MRSA Infections in Children HEMATOLOGY/ONCOLOGY Emergency Treatment of Bleeding Disorders Fever in Immunocompromised Children Thrombotic Disorders Sickle Cell Disease Oncologic Emergencies Transfusions APPENDICES Quick Calculations IVIG Administration Protocol Phone Directory 179 180 181 153 158 160 165 173 175 135 139 140 143 147 149 107 111 115 118 122 125 126 130 93 97 99 101

Preface
This handbook is designed to assist housestaff with common pediatric problems. This edition represents the fourth major revision. Changes to this edition include new chapters on Henoch-Schnlein Purpura, Neonatal Hyperbilirubinemia, Ataxia, Delayed/Precocious Puberty, Rickets, Renal Tubular Acidosis, Hydronephrosis, and MRSA infections. In addition, some chapters have been condensed, revised, or expanded to provide a more accurate resource. Finally, every attempt has been made to provide an up-to-date reference, yet medicine is rapidly changing and what is standard of care today, may be archaic in a few years. Thus, if in doubt, always consult other sources or your attending. We would like to thank the following people, in addition to those who have previously contributed to this handbook, for their assistance with this edition: Kathryn Stephenson, M.D. Michael Gonzalez, M.D. Carla Roberts, M.D. Matt Wienecke, M.D. Ozzie Shuler, M.D. Kelly Lewis, R.D. Rathna Amarnath, M.D. David Schwartz, M.D. Trey Brown, M.D. David Amrol, M.D. Kevin McRedmond, M.D. Tim Livingston, M.D. Rob Holleman, M.D. Laura Pirich, M.D. Ron Neuberg, M.D. Mark McDonald, M.D. Erika Clark, PharmD Malaka Jackson, M.D. Jennifer Bair, PharmD Matthew Garber, M.D.

Editors Caughman Taylor, M.D. James Stallworth, M.D. Sara Lindsey, M.D. Jason Hawn, M.D. Joseph Delaney, M.D.

(NINTH EDITION)

Cardiovascular

Congestive Heart Failure

ETIOLOGY CHF may result from congenital or acquired heart diseases with volume and/or pressure overload or from myocardial dysfunction. Congenital Heart Disease: most common cause in pediatric age group. Acquired Heart Disease: Rheumatic Fever, Collage Vascular Disorders, Vitamin deficiencies, Kawasaki Disease Myocardial Dysfunction: Myocarditis, Endocardial fibroelastosis, Metabolic abnormalities, Cardiomyopathy Arrhythmia: Tachyarrhythmias (SVT), Bradyarrhythmias (AV Block) Miscellaneous: Acute Hypertension, Severe anemia, Volume overload, Sepsis CLINICAL MANIFESTATIONS Diagnosis is based on clinical judgement, relying on history, physical examination, chest x-ray, ECG, and echocardiogram. Decompensated CHF (inadequate cardiac output) can present with end organ dysfunction/failure. History Tachypnea and grunting Poor feeding (sweating, increased RR, tiring with feeds) Poor weight gain Physical Exam Tachycardia and tachypnea Gallop rhythm Heart murmur Cyanosis (most often cyanosis in the face of CHF will be peripheral although occasionally it can be central) Weak and thready pulses Cardiomegaly, Hepatomegaly Peripheral edema rarely seen in infants with CHF Left-sided Failure Tachypnea Orthopnea Wheezing and pulmonary crackles Pulmonary edema, Pleural effusion Right-sided Failure Hepatosplenomegaly Pleural effusion, Ascites Edema: eyelid, sacral, less frequently lower extremity (in pediatric population) Jugular venous distention (rarely seen in infants)

7 Chest X-ray Cardiomegaly and increased vascular markings ECG Signs of LVH and RVH may be present, as well as signs of strain with ST and Twave changes Echocardiography May be diagnostic for a congenital or acquired heart defect Can be used to evaluate systolic and diastolic cardiac function MANAGEMENT Elevate head of bed Oxygen Salt restriction in older children to less than 0.5gm/day Fluid restriction to 2/3 maintenance (NPO initially) Correct anemia (slowly if severe), reduce fever, and treat underlying infection Treat underlying causes (hypertension, arrhythmias) and correct electrolyte imbalances DRUG THERAPY Management involves preload as well as afterload reduction and inotropic agents. For acute management of decompensated CHF consider a combination of dopamine, dobutamine, milrinone, and/or Lasix. If CHF is due to duct dependant lesions or severe coarctation consider PGE1. Less commonly, epinephrine is required. Management of Chronic CHF includes one or more of the following: Diuretics Acts through preload reduction Use may preclude need for digoxin Lasix 1-4 mg/kg/day, po in 1 to 4 divided doses (typically dose does not exceed 2mg/kg/dose) Spironolactone 1-3.3mg/kg/day po in 2-4 divided doses, may be used in conjunction with Lasix for its potassium-sparing effect (most often used if lasix dose exceeds 2mg/kg/day) Side effects of diuretics, which predispose to digoxin toxicity, include hypokalemia, hypochloremia, alkalosis, and dehydration Digitalis Should not be used in children with IHSS, complete heart block, WPW, or cardiac tamponade Digoxin/Lanoxin is preferred and po route should be used. Digitalizing dose typically is not used for treatment of CHF. Maintenance dose is variable depending on the age of the patient. See Harriet Lane Handbook for dosing.

8 Common ECG effects are shortening of QTc (earliest sign), sagging ST segment, diminished amplitude of T-wave, and slowing of heart rate Digitalis Toxicity Non-cardiac symptoms include nausea, vomiting, diarrhea, restlessness, drowsiness, fatigue, and visual disturbances in older children ECG signs are probably more reliable and appear earlier. These include prolonged PR interval, profound bradycardia or SA block, and arrhythmias. Factors that exacerbate toxicity include hypokalemia, hypomagnesemia, low T4, and hypercalcemia For management of digitalis toxicity see Poisondex or Harriet Lane Handbook Oral Angiotensin-Converting Enzyme Inhibitors (ACE inhibition) Afterload reduction Captopril and Enalpril are the most commonly used ACE inhibitors May cause neutropenia, angioedema, cough (more common with captopril), azotemia, hyperkalemia (use with caution in combination with potassium sparing diuretics), rash AVOID use with dialysis with high-flux membranes because anaphylactoid reactions have been reported NOTES

Pediatric Hypertension
DEFINITION Hypertension is defined as average systolic and/or diastolic blood pressure that is 95th percentile for gender, age, and height on 3 or more separate occasions. Essential hypertension is now the most common form in pediatrics when all ages are included. Secondary hypertension is more common in younger children with renal parenchymal disease being the most common cause. Normal BP: <90th percentile for age, sex, and height Pre-HTN: 90th percentile, <95th percentile, (>120/80 in teens) HTN(stage I): 95th percentile 99th HTN(stage II): >99th percentile + 5 mmHg Malignant HTN: Findings of target organ disease SIGNS OF HYPERTENSIVE CRISIS Headache, lethargy, vomiting, visual disturbances, altered mental status May progress to seizures Congestive heart failure may be present depending upon duration and severity. This is more common in infants. COMMON CAUSES OF HYPERTENSIVE CRISIS IN CHILDHOOD Acute post-streptococcal or post-infectious glomerulonephritis Other forms of nephritis: HUS, Lupus, HSP Chronic pyelonephritis Renal vascular disease (renal artery stenosis (RAS)) Pheochromocytoma Chronic renal failure Steroids and miscellaneous drugs Essential hypertension Coarctation CNS- increased ICP, mass, tumor DIAGNOSIS AND WORK-UP Initial evaluation for all children includes BMP, U/A and urine culture, renal ultrasound, and echo. Consider fasting lipid panel and insulin if pt is obese. Other studies as indicated by history, age of patient, or severity of hypertension: MRI or CT Head Plasma renin and aldosterone Urine for VMA and metanephrines ASO, complement levels, ANA ANCA

10 Thyroid levels VCUG Renal biopsy TREATMENT OF HYPERTENSION IN CHILDREN Therapeutic lifestyle changes are recommended for all children with hypertension and pre-hypertension. Weight reduction is the primary therapy for obesity related hypertension. Recommended diet changes, in addition to calorie limits, include avoidance of caffeine and reduction of sodium intake by limiting consumption of high salt processed foods and increasing fresh vegetables and fruits. Stage II hypertension generally requires referral to pediatric nephrology and management with medication. BLOOD PRESSURE MEDICATION FOR CHILDREN ACE Inhibitors Good first choice if suspect renovascular HTN, proteinuria, DM, Chronic Kidney Disease Contraindications - pregnancy, bilateral RAS, or solitary kidney with RAS Adverse affects: cough, angioedema, bone marrow suppression, K+, GFR Drugs: Enalapril, Lisinopril (start 0.08 mg/kg dose qam-bid, max 40 mg/day), Captopril (0.1-0.5 mg/kg/dose q8hrs, mostly for infants) Calcium Channel Blockers Good first choice, very well tolerated and safe Adverse effects: flushing, HA, edema, gingival hypertrophy Drugs: Acute: Isradipine (0.1mg/kg/dose q6 hrs prn, suspension can be made), Nifedipine (0.25 mg/kg/dose q 4hr prn, comes in 10mg cap) Chronic: Nifedipine XL (for teens, start 30mg qam, may need BID), Amlodipine (0.1-0.3mg/kg/dose qam-BID) Angiotensin Receptor Blockers Used primarily when cannot tolerate ACE-I or for added anti-proteinuric effect Drugs: Losartan (start 0.8mg/kg/day qam, max 50mg BID) Diuretics Most commonly used as second or third agents (except patients with Na sensitive primary hypertension) Drugs: HCTZ (1-2mg/kg/day qAM-BID), K-sparing- Spironolactone (13mg/kg/day qam-BID) Beta Blockers Less well tolerated, so recommended mainly for difficult to treat patients Contraindications- RAD, Heart Block, Bradyarrhythmia, DM Drugs: Atenolol (0.5-1.0 mg/kg/day qam-BID), Labetalol (4mg/kg/day divided BID, max start 100mg BID)

11 CHOICE OF DRUG FOR SPECIFIC CIRCUMSTANCES Renovascular HTN, proteinuria, DM, mircroalbuminuria - ACE-I Acute GN with HTN from volume overload - Lasix Autosomal dominant pattern of HTN with hypokalemia (Liddles syndrome) Amiloride ADHD and HTN with compliance issues - Clonidine patch Work up in progress but need to start med on young child - Calcium channel blocker NOTES

12

Kawasaki Disease
Kawasaki Disease (KD) is an acute febrile, systemic vasculitis of unknown etiology. It can result in coronary artery abnormalities in up to 20% of untreated children. The diagnosis of KD is based on clinical criteria as established by the CDC. DIFFERENTIAL DIAGNOSIS Scarlet Fever Toxic Shock Syndrome Staphylococcal Scalded Skin Stevens-Johnson Syndrome/Drug Reactions Collagen Vascular Disease Rheumatic Fever/SBE Serum Sickness Leptospirosis RMSF/Other Rickettsial Disease Viral Syndromes: EBV, Hepatitis B, Adenovirus, Influenza, Measles DIAGNOSIS No diagnostic test exists for KD. Diagnosis is based on exclusion of other etiologies and the fulfillment of clinical criteria. Specifically, diagnosis requires fever lasting over 5 days and at least four of five other criteria. Diagnostic Criteria Criteria Comments Bilateral Non-Exudative Conjunctivitis Usually more prominent in the bulbar than palpebral conjunctiva with sparing of the limbus Associated eye features include anterior uveitis and acute iridocyclitis in >80% Polymorphous Exanthem Usually generalized and erythematous Can be morbilliform, maculopapular, scarletiniform, or erythema multiforme Generally not bullous or vesicular Typically worse in the GU area Cervical Lymphadenopathy Nodes should be > 1.5 cm Usually single and unilateral adenopathy Generalized lymphadenopathy is not seen

13 Changes in the Hands or Feet Edema of the hands and feet Palm or sole erythema Periungal desquamation in convalescent phase Fissured, red lips Strawberry tongue Diffuse erythema oropharyngeal mucosa

Changes of the Oropharynx

Associated Features Clinical Findings Anterior uveitis, iridocyclitis in 80% Arthritis or arthralgia in 35% Hydrops of gallbladder in 10% Pericardial effusion or arrhythmia in 20% Aseptic meningitis or carditis in 5% Irritability Laboratory Findings Leukocytosis Anemia Increased CRP and ESR Increased AST, ALT, and bilirubin Thrombocytosis after 10-14 days (subacute phase) Sterile pyuria in 70%

INCOMPLETE KAWASKAI DISEASE Some patients do not fulfill the above criteria and are subsequently diagnosed with incomplete or atypical Kawasaki Disease Incomplete KD is more common in young infants. Accurate diagnosis is especially important in this age group as they are at higher risk of developing coronary artery abnormalities. Infants 6 months old or on day 7 of fever without other explanation should undergo laboratory testing and, if evidence of systemic inflammation is found, an echo, even if the infants have no clinical criteria Supplemental lab criteria include albumin 3.0g/dL, anemia for age, elevations of ALT, platelets after 7days 450,000/mm, wbc 15,000/mm, and urine 10 wbc/hpf See algorithm for workup of children with suspected incomplete KD

14

Evaluation of Suspected Incomplete Kawasaki Disease (KD)

Fewer 5 days and 2 or 3 clinical criteria

Assess Patient Characteristics

Persistent Fever Consistent with KD Inconsistent with KD

Assess Laboratory Tests

KD unlikely

CRP <3.0 mg/DL and ESR <40 mm/hr

CRP 3.0 mg/DL and/or ESR 40 mm/hr

Follow Daily

<3 Supplemental Laboratory Criteria

3 Supplemental Laboratory Criteria

Fever Continues for 2 days

Fever Resolves

Echo

Treat and Echo

No Peeling

Typical Peeling

Echo + Echo Fever Abates Fever Persists

No f/u

Echo Treat Repeat Echo Consult KD Expert

KD Unlikely

15 CARDIAC INVOLVEMENT Cardiac pathology represents the major cause of morbidity and mortality in patients with KD. Cardiac involvement ranges from carditis to coronary aneurysms. Echocardiogram may also reveal pericardial effusion, mitral regurgitation, or left ventricular dysfunction. Aneurysms can occur anytime during the acute and subacute phase of illness. Treatment in the acute phase is aimed at reducing inflammation in the coronary artery wall and preventing thrombosis. The use of IVIG within the first 10days of illness has been shown to decrease the incidence of transient coronary artery dilation to 5% and that of giant aneurysms to 1%. Long term therapy is aimed at preventing MI or ischemia. MANAGEMENT AND THERAPY Echocardiogram should be performed at time of diagnosis and repeated 6-8 weeks later Intravenous immunoglobulin initiated within 10 days of the onset of fever in conjunction with ASA reduces the incidence of coronary artery aneurysm and causes fever resolution See Appendices for IVIG Administration Protocol Aspirin therapy is given in the acute and subacute phase. Initial dose is 80-100 mg/kg/days divided QID until fever resolves, then 3-5 mg/kg/day (maximum 4080mg/day) given as a single dose until the platelet count and sedimentation rate are normal. Patients with documented coronary artery disease need prolonged low-dose aspirin therapy If the patient does not respond within 48 hours of IVIG administration, the dose can be repeated. Patients with a pre-IVIG treatment CRP over 10 mg/DL, LDH over 590U/L, and /or HgB less than 10gm/dL are at increased risk for IVIG failure. Steroids can be tried if the patient fails to respond to 2 doses of IVIG. Steroids are dosed at 30mg/kg/day for 3 days. Live virus vaccines should be delayed 11 months after receiving IVIG to avoid suppression of immunologic response to the vaccine NOTES

16

Acute Rheumatic Fever

Acute Rheumatic Fever (ARF) is one of the primary causes of acquired heart disease worldwide. It is a delayed (usually 2-4weeks) nonsuppurative sequela of pharyngeal infection (not skin) with group A streptococcus (GAS). It is a clinical diagnosis based on the Jones Criteria. Diagnosis of ARF requires two major criteria or one major plus two minor criteria to be present as well as evidence of a GAS infection. The first episode typically occurs between 5 and 15 years of age (rarely seen before the age of 3 and after 15 years of age). JONES CRITERIA FOR ARF Major Criteria Polyarthritis Occurs in 60-85% and is often the earliest manifestation Involves the large joints, usually extremities Extremely painful but responsive to NSAIDs Migratory involvement: two or more joints involved Carditis Occurs in 40-50% Signs of carditis include: tachycardia, new heart murmur, pericarditis, cardiomegaly, or signs of CHF Erythema Marginatum Occurs in 5-10% Rash is evanescent, nonpruritic, and erythematous in a serpiginous or annular pattern Occurs on trunk and proximal extremities (never on the face) Rarely seen in other diseases Subcutaneous Nodules Occurs in less than 10% Hard, painless, nonpruritic, freely mobile, up to 2.0cm in diameter; persist for weeks Symmetric distribution on extensor surfaces of joints, scalp, and spine Sydenham Chorea (St. Vitus Dance) Occurs in up to 15% Due to late onset (often 3 month or longer latency), other criteria may be absent and ASO and ESR may be normal; therefore, chorea may stand alone as a diagnostic criteria for ARF. Manifests as emotional lability that progresses to motor incoordination (may initially see handwriting deterioration) then to spontaneous purposeless movements Minor Criteria Fever Fever is usually low grade and present early in the course of ARF

17 Arthralgia Cannot be counted towards diagnosis if arthritis present Elevated Acute Phase Reactants CRP and ESR (ESR may be spuriously low in the face of CHF; CRP is unaffected by CHF) May be normal in patients with only chorea or when steroids, ASA, or NSAIDs have been administered Prolonged PR interval Cannot be counted towards diagnosis if carditis is present Previous Rheumatic Fever PRECEDING GAS INFECTION Evidence of GAS infection is required for the diagnosis of ARF. A recent history of scarlet fever without laboratory confirmation of GAS is inadequate evidence. Only 25% of patients with ARF will have a positive throat culture or rapid antigen test. The most frequently used tests are the anti-streptolysin O (ASO) and anti-DNase B. ASO is considered significantly elevated if the acute titer is 2 or more times greater than the convalescent titer. This can be drawn at presentation and then in 3 weeks. Likewise, a single ASO titer greater than the 85th percentile of the normal population is strong evidence for recent infection. Anti-DNase B is the next best test. Other antibody tests, such as streptozyme, anti-streptokinase and anti-hyaluronidase, can also be used. Overall 95% of patients with ARF will have at least one antibody test indicating preceding GAS infection. TREATMENT Treatment of ARF is designed to reduce inflammation, eradicate the streptococcal infection, treat CHF if present, and prevent recurrence Patients should limit their activity if actively symptomatic with arthritis, carditis, or chorea ALL patients should receive appropriate antibiotic therapy Each patients anti-inflammatory treatment should be individually tailored depending on the severity of arthritis. Begin aspirin at doses 50-100mg/kg/day divided in 4 doses. Other NSAIDs can also be used at anti-inflammatory doses as alternatives to aspirin. Joint pain should disappear within 24-36 hours and if not the diagnosis should be questioned. Carditis may require treatment with steroids if high dose NSAIDs are not effective. Dose prednisone 2mg/kg/day divided BID for 2 weeks, then taper. Add ASA when taper begins and continue until CRP is normal and the ESR is falling. Chorea is usually self-limited but may last several months. If severe, Thorazine, Haldol, Valium, or sodium valproate may be used. There is evidence that steroids may shorten the course of chorea.

18 Length of secondary prophylaxis is variable. See AAP Red Book for prophylactic regimens. NOTES

19 NOTES

20

General Pediatrics and Pharmacology

21

22

Bite Wounds
The most common bites seen are those of dogs (~80% of animal bites), cats, and humans. The most common complication associated with these injuries is infection. Most can be treated on an outpatient basis. Incidence of infection in dog bites is between 5 and 10 % (higher risk with bites to hands or feet). Incidence of infection in cats is higher approaching 30 to 50%. MANAGEMENT Initial history should include information surrounding bite (provoked or unprovoked) as well as type of animal and immunization history of the animal. Patient specific past medical history should also be gathered including any underlying medical disease process. DHEC should be alerted and attempts should be made to collect the animal for observation if possible Initial wound management should include washing with soap and water and irrigation with sterile saline under moderate pressure as well as debridement of devitalized tissue Local anesthesia can be used to facilitate wound cleansing if needed Examine for vascular, joint, muscle, tendon, or nerve damage. Obtain an x-ray if foreign body is suspected or if there is apparent bone or joint disruption. Suturing: Large wounds or wounds that are on the face (cosmesis-low incidence of infection) may be sutured. Do not suture puncture wounds or wounds on the hand or feetthese wounds have the highest incidence of infectious complications. Suturing of wounds that are more than 8 hours old should be avoided. Follow up frequently to monitor for infection. Immobilize and elevate affected limb(s) when possible. Indications for admission/inpatient treatment include: failure of outpatient oral antibiotics, concerns for infection and delay in seeking medical care, systemic illness, and an immunocompromised patient ANTIBIOTIC THERAPY Antibiotic therapy is indicated in all of the following circumstances: Moderate to severe injuries Significant crush injuries (such as those seen with some dog bites) Deep puncture wounds Facial wounds Wounds on the hands or feet Wounds on the genitals Immunocompromised patient Bites >8 hours old at first evaluation Any signs of infection

23 Most cat bites Human bites Prophylactic antibiotic treatment is not indicated for most dog bite wounds with the exception of wounds to the hand. There is evidence to support prophylactic antibiotic treatment of cat bite wounds. (Usual prophylactic course of treatment is 5 days.) Possible choices of antibiotics include: 1)amoxicillin-clavulanic acid (40 mg/kg/day) for dog or cat bites as well as 2)dicloxacillin or 3)cephalexin for dog bites (erythromycin or TMP-SMX for penicillin allergic patient) 4)cefuroxime or 5)dicloxacillin + penicillin for cat bites (levofloxacin or moxifloxacin, azithromycin, TMP-SMX for penicillin allergic patient) *Note that single drug therapy may not be adequate in penicillin-allergic patients. Consider wound culture if the injury is more than 8 hours old or if there are signs of infection

Species Dogs and Cats2

Humans3,4

Organisms of Infection1 Common Pathogens Staph aureus -hemolytic Strep (most common in dogs) Pasteurella multicoda (most common in cats) Capnocytophaga canimorsus (severe sepsis in asplenic or alcoholic patients) Other Staph and Strep species Klebsiella Bacillus subtilis Pseudomonas Enterobacteriaceae Anaerobes (Bacteroides, Fusobacterium, Peptostreptococcus, and Actinomyces) Staph aureus Eikenella corrodens Haemophilus influenza Strep species Anaerobes

1No single organism is responsible for > 30% of infections. 2Also consider cat scratch disease and tularemia in cat bites. 3More prone to infection than cat or dog bites. 4Must also consider Hepatitis B and HIV in any human bite.

24 TETANUS PROPHYLAXIS Bite wounds are considered dirty, and tetanus prophylaxis must be addressed if needed based on the following guidelines. Clean/Minor Wounds TIG Td1 Other Wounds

TIG Previous number of adsorbed tetanus toxoid Td1 doses Yes No Yes Yes Status unknown or number received <3 No No 3 previous doses No2 No3 1For children <7 yo, give DTaP unless otherwise contraindicated. For persons 7 yo, give Td. 2Yes, if it has been >10 years since the last dose. 3Yes, if it has been >5 years since the last dose. RABIES PROPHYLAXIS Prophylaxis for rabies consists of Rabies Immune Globulin (RIG) which is given on the first day of treatment. The dose is 20 IU/kg, with half being infiltrated into the wound and the other half given IM. The patient should also be given the primary rabies vaccine (2 types: HDCVhuman diploid cell vaccine or RVA-rabies vaccine adsorbed). This is an IM vaccine given on days 3, 7, 14, and 28.

When to Give Rabies Prophylaxis Clinical Scenario Approach Dog, Cat, or Ferret Bite Rabies prophylaxis if the animal develops Animal is healthy and available for symptoms of rabies observation. Dog, Cat, or Ferret Bite Administer immunization and RIG1 Animal is rabid or rabies is suspected. Dog, Cat, or Ferret Bite Consult DHEC Unknown status of animal Skunk, Raccoon, Bat, Fox, Woodchuck, or Consider the animal rabid unless proven other Carnivore Bite otherwise or in an area free of rabies. Administer immunization and RIG1. Livestock, Rodent, or Rabbit Bite Generally not considered rabid. Consult DHEC. 1RIG is not recommended in previously vaccinated individuals NOTES

25

Inborn Errors of Metabolism and Metabolic Diseases

Inborn errors of metabolism are a diverse collection of disorders including organic acidemias, urea cycle defects, fatty acid metabolism defects, and storage disorders. Most are caused by a single enzyme deficiency or cofactor that disrupts one step of the metabolic pathway. Majority are autosomal recessive. Early detection is vital to prognosis. COMMON SIGNS AND SYMPTOMS Symptoms of lethargy, poor feeding, vomiting, apnea, tachypnea Acute encephalopathy or seizures Unexplained jaundice, liver failure, metabolic acidosis, or hypoglycemia Dysmorphic features or unusual odors Myopathy Failure to thrive IEM PRESENTATIONS AND ASSOCIATED DISORDERS Class of Disorders Organic Acidemias (includes Methylmalonic acidemia, Proprionic acidemia, Isovaleric acidemia) Characteristic Lab Findings Metabolic acidosis with increased anion gap; Elevated plasma and urine ketones; Variably elevated plasma ammonia and lactate; Abnormal urine organic acids; Neutropenia and thrombocytopenia can be present. Urea Cycle Defects (includes Ornithine Markedly elevated plasma ammonia; No transcarbamylase deficiency, Citrullinemia) metabolic acidosis; No ketonuria; Variable respiratory alkalosis; Elevated orotic acid in OTCD; Abnormal plasma amino acids Fatty Acid Oxidation (includes Medium Illness or stress increase metabolic chain acyl-CoA dehydrogenase deficiency) demands leading to hypoglycemia, metabolic acidosis, hyperammonemia; Nonketotic; Elevated acylcarnitine; Often presents when meals are more spread out, i.e., the infant is sleeping more. Amino acidopathies (includes PKU, Metabolic acidosis with increased anion Maple Syrup disease, Homocystinuria) gap; Elevated plasma amino acids Fasting hypoglycemia and ketosis; +/Glycogen Storage Diseases hepatomegaly; Symptoms worse with fasting Mitochondrial Disorders (includes Elevated lactate and pyruvate MELAS, Pyruvate dehydrogenase deficiency, Pyruvate carboxylase deficiency)

26 Nonketotic Hyperglycinemia Acute encephalopathy; No metabolic acidosis; No hyperammonemia; Abnormal plasma amino acids

LABORATORY EVALUATION FOR IEM If possible, laboratory evaluation should be obtained while the patient is symptomatic, because metabolites of certain disorders are not detectable when the patient is asymptomatic. FIRST TIER EVALUATION ABG CMP- calculate anion gap CBC Ammonia Urinalysis Urine and plasma amino acids Urine organic acids Urine reducing substances Plasma lactate and pyruvate SECOND TIER EVALUATION Plasma total carnitine and acetylcarnitine CSF lactate and pyruvate Urine orotic acid Plasma citrulline Chromosome analysis Plasma long chain fatty acids Muscle biopsy MITOCHONDRIAL DEFECTS When complex neurological or multisystem involvement is present, consider mitochondrial defects; virtually any organ system or presentation is possible. All disorders of mitochondrial DNA are maternally derived. MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke Like Episodes) can appear at any age but usually present as stroke of the young. Look for myopathy, ataxia, cardiomyopathy, and diabetes mellitus presenting before the stroke. PRESENTATIONS OF MITOCHONDRIAL DEFECTS Organ System Possible Involvement Central Nervous System Encephalopathy, mental retardation, ataxia, strokes, deafness, seizures

27 Cardiovascular Gastrointestinal Endocrine Musculoskeletal Renal Heme Cardiomyopathy, heart block Liver disease, pancreatic insufficiency, villous atrophy Diabetes mellitus, diabetes insipidus, hypoglycemia Myopathy Renal tubular acidosis Pancytopenia, neutropenia, or anemia
NEONATAL HYPERAMMONEMIA

Symptoms in first 24 hours of life

Symptoms after 24 hours of life

Premature

Full-Term

Acidosis

No acidosis

THAN

INBORN ERRORS OF METABOLISM (i.e. organic academia or PC deficiency)

ORGANIC ACIDEMIAS

UREA CYCLE DEFECT

PLASMA AMINO ACIDS

Absent citrulline Citrulline moderately elevated; ASA present Urine orotic acid Citrullinemia Argininosuccinic aciduria Low CPS deficiency Elevated OTC deficiency Citrulline markedly elevated; no ASA

THAN-Transient Hyperammonemia of Newborn

28

METABOLIC ACIDOSIS WITH INCREASED ANION GAP

Elevated lactate Normal lactate

Abnormal organic acidsccidsac ids ORGANIC ACIDEMIA Abnormal organic acids Hypoglyemic METHYLMALONIC ACIDEMIA; PROPIONIC ACIDEMIA; MULTIPLE CARBOXLYASE DEFICIENCY; OTHERS

Normal organic acids

Elevated pyruvate; normal L-P ratio

Normal or low pyruvate elevated L-P ratio

No hypoglycemia

Dicarboxylic aciduria

FATTY ACID OXIDATION DEFECTS

GSD TYPE 1; FRUCTOSE 1, 6-DP DEFICIENCY; PEP CARBOXYKINASE DEFICIENCY

RESPIRATORY CHAIN DEFECTS; PYRUVATE CARBOXYLASE DEFICIENCY

PYRUVATE DEHYDROGENASE DEFICIENCY; PYRUVATE CARBOXYLASE DEFICENCY

EMERGENT THERAPY FOR POSSIBLE IEM Appropriate and aggressive treatment before the confirmation of a diagnosis may be lifesaving and may avert or reduce the neurologic sequelae of some of these disorders. The first goal is the removal of accumulating metabolites such as organic acid intermediates or ammonia. If a there is a suspicion of a disorder with protein intolerance, protein intake should be discontinued immediately. Critically ill infants with hyperammonemia may need hemodialysis. In patients suspected of having a urea cycle defect, an infusion of arginine can be given. An IV arginine preparation is available commercially and a protocol is described below. If an organic acidemia is suspected vitamin B12 and Biotin can be given to improve enzymatic activity. The second goal of therapy is to prevent catabolism. IV glucose should be administered to provide as many calories as possible. IV lipids can be given to infants with urea cycle defects and other disorders in which dietary fat plays no role.

29 SAMPLE PROTOCOL FOR TREATMENT OF HYPERAMMONEMIA If ammonia level is significantly elevated, admit to hospital for IV therapy: If lethargic or stuporous, admit to PICU. If not lethargic, admit to general pediatrics floor. Bolus Medication To infuse over 90 120 minutes. Ammonul (sodium phenylacetate and sodium benzoate) 55 ml / m2 Mixed with Arginine 10% 6 ml / kg and Dextrose 10% to a total volume of 25 ml / kg. Maintenance medication To infuse over 24 hours at 1.5 x maintenance fluid rate. Ammonul (sodium phenylacetate and sodium benzoate) 55 ml / m2 Mixed with Arginine 10% 6 ml / kg and Dextrose 10% to a total volume of 1.5 x maintenance fluids. Example: Current: weight 28kg and BSA 0.95m2

Bolus dose: Ammonul 52 ml mixed with Arginine 10% 168 ml. QS to 700 ml total volume of Dextrose 10%. To run over 2 hours. Maintenance dose: Ammonul 52 ml mixed with Arginine 10% 168ml. QS to 2450 ml total volume of Dextrose 10%. To run at 102 ml / hour (1.5 x maintenance fluids) for 24 hours. NOTES

30

Pediatric Nutrition
Infant Formulas Protein Carbs (gm/100cc) (gm/100cc) Milk Protein Based 1.1 7.2 1.4 7.3 1.4 1.5 7.3 7.5

Formula

Calories (cal/oz) 20 20 20 20

Fat (gm/100cc) 3.9 3.6 3.5 3.4

Uses

Breastmilk Similac Advance Enfamil Lipil Goodstart DHA/ARA Supreme Similac Sensitive Enfamil Lactofree Prosobee

Preferred Basic Formula Basic Formula 100% whey protein, partially hydrolyzed Lactose free Lactose free

20 20

1.4 1.4

7.2 7.3

3.6 3.5

20

Soy Protein Based 1.7 7.1

3.5

Isomil

20

1.7

7.0

3.7

Goodstart DHA/ARA Supreme Soy Nutramigen

20

1.7

7.5

3.4

Lactose/milk protein intolerance Lactose/milk protein intolerance Lactose/milk protein intolerance Milk/Soy protein sensitivity No MCT Sucrose/Lactose Free Malabsorption Neonatal Biliary Stasis 33% MCT Malabsorption Biliary Stasis 55% MCT Sucrose/Lactose Free Free amino acids

20

Casein Hydrolysates 1.9 6.9

3.5

Alimentum

20

1.9

6.9

3.7

Pregestimil

20

1.9

6.8

3.7

Neocate

20

Elemental Based 2.0 7.8

3.0

31 Elecare 20 2.0 7.2 3.2 Free amino acids Unflavored <1 year of age 33% MCT Increased protein/vitamins/ minerals Catch up growth Can be used to 1year of age Can be used into toddler years

Neosure Enfacare

22 22

Preterm Infants 2.1 7.6 2.1 7.7

4 3.9

Sim 60/40

20

Renal Formulas 1.5 6.9

3.8

Enfamil Gentlease also available. 25% less lactose. For infants with reflux, consider use of Enfamil AR (added rice starch) or Similac Sensitive RS (rice starch). Similac Sensitive is also lactose free. Goodstart Natural Cultures contains Bifidus BL cultures. Formulas for Children over 1 year Calories Protein Osmolality Uses (cal/oz) (gm/100cc) 30 3.0 430 30 3.4 345 30 3.0 350 50%casein/50% whey Gtube/Oral formula 30 2.5 610 Free amino acids 30 45 3.0 4.2 260 390 Elemental

Formula Pediasure Kindercal Nutren Jr Neocate One Plus Peptamen Jr Resource Just for Kids 1.5 Portagen

30

Fat Modified 3.5

87% MCT oil, risk of essential fatty acid deficiency Cow milk based

Formula Nutren 1.0

Formulas for Children over 6years Calories Protein Osmolality (cal/oz) (gm/100cc) 30 4.0 300

Uses Basic Substitute for Ensure Fluid restriction CF Substitute for Deliver 2.0

Nutren 1.5 Nutren 2.0

45 60

6.0 8.0

430 745

32

Propass Description Protein Supplement

Modular Additives MCT oil Microlipid Fat Source used for Calorie Supplement Medium Chain Triglycerides Liquid 7.7/cc 0.93 50% fat emulsion for oral/TF Safflower Oil

Polycose Powder CHO Calorie Supplement Glucose Polymers

Duocal Fat and CHO Source Hydrolyzed corn starch MCT oil Powder 42/tbsp 1.9/tbsp 6.2/tbsp 1.7 0.42 0.42 0.42 1.7

Source

Form Liquid Powder Calories 4.5/cc 23/tbsp Protein (g) Fat (g) 0.51 CHO (g) 5.6 Sodium 7.8 (mg) Potassium 0.6 (mg) Calcium 40/scoop 1.8 (mg) Phosphorus 0.9 (mg) Chloride 13.3 (mg) Better to use microlipid in formula because MCT oil separates out.

Whey protein concentrate Powder 30/scoop 6/scoop 0.5/scoop 1/scoop

OTHER INFORMATION Increase total daily fluid by 25% if a child is on a fiber formula Use fiber containing formulas if diarrhea present (not constipation) One salt packet (1/8 tsp) gives 12.8 mEq of sodium MCT (medium chain triglycerides) oil is easier to absorb compared to other fats. Used often with Cystic Fibrosis and Biliary disease. Goats milk is not indicated in children secondary to folic acid deficiency Typically, infants should double their birth weight by 6months and triple it by 1 year Rule of thumb: Infants should be taking about 2 oz of formula per pound up to a maximum of 32-40 oz All exclusively breastfeed infants (taking less than 16oz of formula/day) should be started on 200 IU of Vitamin D by 2months of life

33 FORMULA RECIPES Similac Advance 22cal 1tsp powder to 120 cc ready to feed (hospital) OR 3 scoops powder to 5 oz of water Goodstart DHA/ARA Supreme 22cal 2 scoops powder to 4.5oz of water Goodstart DHA/ARA Supreme 24 cal 1tsp powder to 75cc ready to feed (hospital) OR 3 scoops powder to 142 cc water Breastmilk 22cal 1 tsp Similac powder to 120cc Breastmilk OR 1 tsp Enfamil powder to 150cc Breastmilk Breastmilk 22cal (preterm infant) 1 tsp Neosure with 120cc Breastmilk OR tsp Enfacare with 90cc Breastmilk Breastmilk 24cal 1 tsp Similac powder to 60cc Breastmilk OR 1 tsp Enfamil powder to 75cc Breastmilk Neosure/Enfacare 24cal 3 scoops powder to 5 ounces of water (home) NOTES

34

Dysmetabolic Syndrome
Obesity is currently the single most prevalent chronic disease in childhood. Obese children with any two of the following abnormal findings (hypertension, dyslipidemia, hyperinsulinemia, acanthosis nigricans, glucose intolerance) have the metabolic syndrome. Defining the obese Youth (2-20 years old): BMI percentile for age Underweight: < 5th percentile Healthy weight: 5-84th percentile Overweight: 85-94th percentile Obesityt: 95th percentile 95% BMI estimate after 9 years of age Boys: Age in years + 13 Girls: Age in years + 14 HISTORY AND PHYSICAL ESSENTIALS Children who meet the diagnostic guidelines for Dysmetabolic Syndrome should be assessed for the following comorbidities of obesity: Headaches, chest pain, blurry vision, papilledema- Hypertension and Pseudotumor cerebri Snoring, daytime somnolence- Obstructive sleep apnea Abdominal pain, nausea/vomiting- Nonalcoholic fatty liver, gallstones Hip or knee pain- SCFE Menstrual irregularities- PCOD, Hypothyroidism Weight gain, cold intolerance, dry skin- Hypothyroidism Polyuria, polyphagia, wt loss- Type II DM SOB, DOE- Asthma Psychosocial-Depression, eating disorders Acanthosis nigricans-hyperinsulinemia Hirsutism-PCOS Violaceous striae- Cushing Syndrome Abdominal tenderness-Gallbladder disease Stature- most children with exogenous obesity are 75% for age, consider bone age for short obese children where genetic abnormalities may need investigating RECOMMENDED LABS BMI 85-94th percentile without risk factors Fasting lipid panel BMI 85-94th percentile with risk factors Fasting lipid panel Fasting glucose ALT and AST

35 BMI 95th percentile Fasting lipid panel Fasting glucose ALT and AST Other tests as indicated by Health Risks such as sleep study, echo, bone age, thyroid studies, testosterone level, etc. FURTHER LABS TO CONSIDER Fasting insulin HOMA- homeostasis model assessment of insulin resistance (Fasting insulin)(Fasting plasma glucose) 22.5 CMP, U/A, Urine microalbumin/creatinine ratio (if hypertensive), HbA1c LABORATORY PARAMETERS Prehypertension Systolic or diastolic BP > 90th percentile for age or 120/80, whichever is less Stage I hypertension Systolic or diastolic BP >95th percentile Stage II hypertension Systolic or diastolic BP >99th percentile Glucose(fasting) 126 mg/dl Glucose tolerance test 140 mg/dl Insulin 20 microIU/ml Urine microalbumin/cr ratio >30 mg/g LIPID PARAMETERS High 200mg/dl 110mg/dl 130mg/dl <40mg/dl Borderline 170-199mg/dl 100-130mg/dl Desirable < 170mg/dl <110mg/dl < 100mg/dl

Cholesterol Triglycerides LDL HDL

EVIDENCE BASED TREATMENT STRATEGIES Limit sugar sweetened beverages Consume recommended fruits and vegetables Eat daily breakfast Limit fast foods Use appropriate portion sizes Eat meals together as a family Limit TV time and video games to <2 hours per day. Keep TV out of the childrens bedrooms. Encourage moderately vigorous physical activity of 60 minutes a day or more

36 Motivational interviewing patient centered communication MEDICATIONS Weight loss used in conjunction with behavior modification Sibutramine 10mg approved for children 16 years Orlistat approved for children 12 years COMORBID TREATMENT Hypertriglyceridemia/Hyperlipidemia Lifestyle changes and dietary changes Weight management and increased physical activity Fiber dose of age (years) + 5 gm/d up to 25 gm/d Lipitor has been approved for children > 12 years of age with an abnormal lipid panel who have not responded to an adequate trial of diet and lifestyle modification consider multivitamin for all children on Lipitor Insulin resistance Exercise/nutritional changes to cause weight loss Glucophage (metformin): <12 year old- start with 500 mg qhs, increase every week up to 15001800 mg/day divided BID 12 years old-start with 500-850 mg qhs, increase every week up to 1600-2000 mg/day Check LFT before and after starting therapy NOTES

37

General Approach to Poisonings/Ingestions

Poisoning should be suspected when a patient shows signs of altered consciousness, seizure activity or unusual behavior. The major toxic signs of poisonings, in general, include cardiac arrhythmia, metabolic acidosis, coma, gastrointestinal symptoms, and CNS symptoms. See Harriet Lane Handbook for antidotes to specific toxins. The hospital computers have Poisondex which can be found by accessing Micromedex. STEPS IN EMERGENCY MANAGEMENT Management of ABCs, including securing compromised airways, insuring adequate ventilation/oxygenation, treating hypotension, shock, or cardiac arrhythmias and any other stabilizing measures Decontamination measures to remove further hazards, such as chemicals on the patients clothing and/or skin as well as flushing eyes as appropriate Obtaining as much history and details of the encounter as possible to aid in identification of substance ingested, time of ingestion, amount of ingestion, and treatments attempted at home as well as any pertinent past medical history Take steps toward further decontamination with administration of activated charcoal, gastric lavage, and/or whole bowel irrigation. Remember that if the airway is compromised it must be secured (i.e. intubation) before attempting GI decontamination. Most pertinent physical exam findings include mental status, papillary response, and vital signs Initial lab data include BMP, osmolality, ECG, and urine drug screen on all patients. Consider aspirin and Tylenol levels in teenagers, CT of head or LP(altered MS), CMP (for a baseline), quantitative specific drug levels. ACTIVATED CHARCOAL Substances that charcoal does not bind or binds poorlyiron, lithium, mineral acids/bases, alcohols, cyanides, solvents, all heavy metals Absorbs toxins and prevents systemic absorption Dose is 1 g/kg with adult dose being 50 to 100g per dose given in a slurry. Can add coca-cola, chocolate or fruit syrup to make more palatable. Do not need to give a cathartic to any pediatric patient for the initial dose of charcoal. Can consider cathartic (Charcoal with sorbitol) for multiple dose charcoal. Only one dose typically used. Can use multiple doses with the initial dose repeated every 2-4 hours important for substances with enterohepatic circulation. Drop NG tube if decreased mental status. Give charcoal and remove tube. Contraindications include signs/symptoms concerning for possible aspiration with absent gag reflex, etc.; ileus or intestinal obstruction; ingestion of hydrocarbon or caustic agent, boric acid

38 WHOLE BOWEL IRRIGATION Helpful with substances that are poorly absorbed by activated charcoal and with ingestions of substances that have delayed or sustained release formulations Generally, use polyethylene glycol solution as continuous infusion through an NG tube For pediatric patients: 25 to 40 mL/hour, increase until results, for 4-6 hours; in adolescents or adults; 1 to 2 L/hour for 4-6 hours Contraindications include intestinal obstruction, hemorrhage, ileus or in situations where the airway is compromised. GASTRIC LAVAGE No longer recommended in most ingestion cases since you recover only ~30% of stomach contents and force the rest across pylorus for absorption May be considered in patients who have ingested a large quantity of potentially lethal pills if lavage can be performed within 1 hour Typically, use 15 mL/kg of normal saline per cycle to max of 200 mL/cycle Contraindications include caustic ingestions or ingestions of hydrocarbons and in patients who are seizing Need to intubate patients with depressed level of consciousness or absent gag reflex to protect against aspiration HEMODIALYSIS Indicated for low-molecular weight substances with low volume of distribution and low capacity to bind to plasma proteins Use in ingestions of aspirin, lithium, phenobarbital, theophylline, and alcohols URINE ALKALINIZATION Use for elimination of weak acids like salicylates, barbiturates, methotrexate Use sodium bicarbonate by bolus (1 to 2 mEq/kg) or continuous infusion (D5W with 150 mEq/L NaHCO3 at 1.5 to 2 times maintenance rate) Goal urine pH of 7 to 8 Must monitor serum electrolytes to watch for disturbances IPECAC No longer recommended by AAP for home use due to risk of prolonged emesis limiting other interventions (charcoal) and has limited use in ED or hospital setting.

39 ACETAMINOPHEN INGESTION The most common pediatric ingestion Toxic ingestions normally are more than 150 mg/kg in a child or 7.5 g in an adult patient Acetaminophen is metabolized by the liver to toxic metabolite N-acetyl-pbenzoquinone imine (NAPQI). NAPQI removed by conjugation with glutathione; glutathione stores are exhausted in overdose. Evidence of liver damage develops 24 to 48 hours after ingestion with peak damage after 72 to 96 hours Initial workup should include a thorough history to help clearly define amount of ingestion, time of ingestion, and any signs of toxicity Lab workup should include a plasma acetaminophen level as soon as possible but at least 4 hours after the ingestion. Repeat level at 8 hours with extended release formulations. Plot level on Rumack-Matthew nomogram in Harriet Lane to help identify potential toxicity. Treat possible and probable hepatotoxicity. Chronic Tylenol ingestion may also cause toxicity. If considering, check level and hepatic panel. No intervention is required if ingestion is less than 140-150 mg/kg and 4 hour level is less than 150 Activated charcoal should be given immediately up to 4 hours after ingestion and should be considered after 4 hours with an extended release formulation Treatment with N-acetylcysteine (NAC) should be initiated with plasma levels that indicate potential hepatic toxicity. May give activated charcoal followed by NAC on initial dose Oral NAC dose is 140 mg/kg then 70 mg/kg every 4 hours for a total of 17 doses. Acetadote is the IV formulation that is now available in the U.S.the dose is 150 mg/kg IV x 1 (over 1 hour), then 50 mg/kg IV x 1 (over 4 hours), then 100 mg/kg IV x 1 (over 16 hours) Do NOT wait to initiate treatment with NAC if the patient ingested staggered overdoses, if presentation is more than 6-8 hours after ingestion or if hepatotoxicity is suggested on baseline laboratory values (still obtain a level) It is more cost effective to treat with the IV formulation SALICYLATE INGESTION Salicylates include aspirin, bismuth subsalicylate (Pepto-Bismol), and methyl salicylate (oil of wintergreen) Minimal potentially toxic dose is 150 mg/kg Causes uncoupling of oxidative phosphorylation leading to increased heat production, excessive sweating, and dehydration; also interferes with glucose metabolism. Primary respiratory alkalosis and primary metabolic acidosis

40 Leads to hyperventilation and respiratory alkalosis from stimulation of respiratory center. Symptoms: nausea/vomiting; ototoxicity leading to tinnitus; altered mental status, tachypnea, pulmonary edema, coma Evaluation should include thorough history and physical as well as serum salicylate level initially and 6 hours after ingestion Use of Done nomogram is currently not recommended Repeat serum levels every 2 to 4 hours until patient is showing clinical improvement and has non-toxic level (<30 mg/dL) Activated charcoal or whole bowel irrigation should be used for gastric decontamination Urinary alkalinization also is used to reduce absorption in distal tubules (See above) Hemodialysis also an option in severe cases CLONIDINE INGESTION Overdose leads to symptoms from alpha-2 receptor stimulation: decreased level of consciousness, miosis, respiratory depression, bradycardia, hypotension (may have hypertension from alpha-1 cross stimulation), hypotonia Initial toxic effects within 30 to 90 minutes and may persist for up to 3 days Treatment is supportivemay need to support blood pressure Needs PICU or PIICU monitoring TRICYCLIC ANTIDEPRESSANTS Exert effects on the reuptake of norepinephrine, Ach and serotonin Also influences histamine (H1), dopamine (D2), muscarinic (M1), and sympathetic 1 receptors Signs and symptoms include: Anticholinergic signs: dilated pupils, dry mucous membranes, urinary retention, decreased bowel activity, tachycardia Dysrhythmias: most common sinus tachycardia, conduction delays, heart block, ventricular dysrhythmias, widened QRS, prolonged QTc (Blockade of sodium channels hallmark of TCA toxicity). Late: V-tach and/or V-fib. Hypotension Seizures Altered mental status Coma Initial altered mental status indicates a significant ingestion has occurred Treatment involves gastric decontamination with activated charcoal or gastric lavage. Should perform gastric decontamination as far out as 12 hours from ingestion. Supportive care for anti-cholinergic symptoms (Ativan) Benzodiazepines or barbiturates for seizures

41 Volume and norepinephrine or phenylephrine for hypotension Sodium bicarbonate for signs of cardiac toxicity (prolonged QRS)1 to 2 mEq/kg. (To help overcome sodium channel blockade and to alkalinize the serum and bind TCA to albumin). Alkalinize serum not urine to Ph ~7.50. If V.tach or fib, bicarb, bicarb, bicarb. Do not give lidocaine (sodium channel blocker) Special note: class IA and IC antidysrhythmics are contraindicated due to effects on sodium channels AND phenytoin should be avoided for any related seizure activity because it may potentiate ventricular dysrhythmias OPIOID INGESTION CNS depression, respiratory depression, miosis Also can lead to seizures, stupor, coma, vomiting, hypothermia, hyporeflexia, hypotension, apnea, cyanosis, pulmonary edema, dry mucous membranes, facial flushing, decreased GI motility, bronchospasm, bradycardia Mostly treatment is supportive: intubate and monitor Naloxone (competitive antagonist) may be considered. But you may induce seizures and death if patient dependent on opioids. Initial dose is 0.1 mg/kg IV however 1/10 of the dose should be effective. Has short half-life so may need repeat dosing or a naloxone drip. TOXIC ALCOHOLS Include ethanol, isopropanol, methanol, ethylene glycol Variety of common substances (antifreeze, brake fluid, de-icing solutions, solvents, wiper fluid, coolants, sterno, paints, varnishes, contaminated homebrewed beveragesi.e. moonshine, rubbing alcohol) Can lead to CNS depression of variable degrees Must obtain serum osmolality. Osmolar gap evident. Methanol and Ethylene glycol toxicity present with coma, metabolic acidosis and renal failure Methanol: metabolized into formaldehyde and then to formic acid leading to metabolic acidosis. Coma, visual disturbances Ethylene glycol: Metabolized to oxalic acid, see oxalate crystals with woods lamp to urine Isopropanol: 2-3x intoxicating effects of ethanol; CNS depression, respiratory depression, hypotension, coma, gastritis. No metabolic acidosis. Management: correction of acidosis, use Ethanol drip or fomepizole to inhibit alcohol dehydrogenase, hemodialysis with methanol/ethylene glycol, isopropanol NOTES

42 NOTES

43

Pediatric Antibiotics
AMINOGLYCOSIDES The concept of once daily aminoglycosides is based on the theories of enhanced concentration-dependent bactericidal activity, decreased development of adaptive resistance, and decreased toxicity due to aminoglycoside free interval with protection against bacterial regrowth due to a post-antibiotic effect. It is not indicated for infants <6months, meningitis, burn patients, or endocarditis. Caution when using neuromuscular blockades or calcium channel blockers. Monitoring Levels for Toxicity Once Daily Dosing Obtain a single random serum level 6-14 hours after the 1st dose. Plot on nomogram (See next page) If the level falls in the area designated q24, q36, or q48, then the dosing interval should be every 24, 36, 48 hours respectively. If it is on the line, choose the longer interval. If the level is above the nomogram, the scheduled doses should be held and serial levels followed to determine timing of the next dose If the level is less than 2mcg/ml, the dosing interval should be every 24 hours If length of therapy is greater than 5days, obtain a random level weekly In patients with altered body habitus (i.e., obese), patients with altered volume of distribution (i.e., edema), or patients who are not responding to antibiotic therapy monitoring a peak will help determine the dose needed for maximal response The peak should be drawn at the end of the one hour infusion. A clinical response of 90% is achieved when the serum peak concentration is 8-10 times the MIC of the organism. Traditional Dosing Peaks and troughs should be monitored with traditional dosing The trough is drawn 30min prior to the next dose and the peak is drawn 30 min after a 30 min infusion Gentamicin/Tobramycin peaks should be 5-10 mcg/ml and troughs < 2mcg/ml Amikacin peaks should be 20-30mcg/ml and troughs < 10mcg/ml VANCOMYCIN This is a time dependent bactericidal antibiotic The trough should be 5-15 mcg/ml and the peak between 25-40mcg/ml A peak level should be drawn 60mins after A 60min infusion. A peak is recommended if treating osteomyelitis, endocarditis, or meningitis. The trough is drawn immediately prior to the next dose. A trough is recommended if the patient is on dialysis, has rapidly changing renal function, receiving Vancomycin and other nephrotoxic drugs, clinical deterioration in status

44 after 5 or more days of therapy, or treating an identified culture with susceptibilities. In dialysis patients, a trough should be measured prior to dialysis. If within the normal range, administer Vancomycin following dialysis. ONCE DAILY AMINOGLYCOSIDES DOSING NOMOGRAM

*Antimicrobial Agents and Chemotherapy 1995; 39(3): 650-655. 14

12

10
Concentration (mcg/ml)

q48h 8 q36h

6 q24h 4

0 6 7 8 9 10 11 12 Time Between Start of Infusion and Sample Draw (hrs.) 13 14

NOTES

45

Radiologic Studies and Basic Indications

UPPER GI In an infant or young child the first test ordered should always be the Upper GI. This assures visualization of the duodenal C loop, which is necessary to assess for possible malrotation. Order an Upper GI if primary concern is beyond the esophagus (esophagus will still be visualized). An Upper GI with SBFT is ordered to evaluate for obstruction, inflammatory bowel disease, small bowel masses, etc. The duodenum and proximal jejunum are always included with the upper GI, so no need for SBFT if one is only interested in the duodenum If truly interested in only in the esophagus, order an esophagram and patient does not need to be NPO. BARIUM ENEMA, SOLID COLUMN Solid column enema is used to evaluate strictures, constipation, Hirschsprung disease Magnesium Citrate is often given as a laxative to prep the bowel Do not order colon prep when evaluating for Hirschsprung disease. The colon needs to be evaluated in the normal, non-stimulated state. Laxatives can distort the configuration of the rectum. BARIUM ENEMA, AIR CONTRAST This examination is performed to evaluate for inflammatory bowel disease or polyps. AIR ENEMA This study is used to diagnose and reduce an intussusception. The patient needs to be evaluated for peritoneal signs. If none are present, then proceed with study. There is no prep necessary Prior to the study, the patient needs IV access and a surgical consult, in case of complications during the study. ULTRASOUND For gallbladder evaluation the prep is the same for upper GI Ultrasound is the test of choice for pyloric stenosis For a pelvic ultrasound the bladder should be full

46 COMPUTED TOMOGRAPHY SCANS Non-contrast CT requires no prep unless sedation is to be used If sedation is to be used, the patient should be NPO at 4-6 hrs prior to sedation For a CT scan with contrast and without sedation, the infants and toddlers should be NPO for 4 hours prior to the study and children older than 6 years should be NPO after midnight VOIDING CYSTOURETHROGRAM No prep or sedation is necessary However, mild sedation can be ordered if patient is older than 2 years old. Patient should be NPO as above if patient is to be sedated. NPO GUIDELINE FOR PEDIATRIC PATIENTS SCHEDULED FOR RADIOLOGY EXAM CT: NPO for at lease 2 hours prior to any contrast given Nuclear Medicine: HIDA scans, Gastric emptying and Reflux (milk) scans NPO 4-6 hours prior MRI: MR cholangiogram/gallbladder- NPO 6 hours prior Other MRI: NPO status based on sedation criteria only Diagnostic Barium Enema: NPO after MN. For constipation or Hirschsprung disease there is no prep. Upper GI and Small Bowel Series: 0-6 months- NPO 3 hours prior 6mo-3 years- NPO 4 hours prior 3yrs and older- NPO after MN Ultrasound Less than 1 yr- NPO 2hours prior Over 1 yr- NPO 4 hours prior NOTES

47

Henoch-Schnlein Purpura
GENERAL INFORMATION Most common systemic vasculitis affecting children IgA deposition found in small vessels Unknown etiology but often preceded by respiratory illness Male predominance with presentation more common in the winter Typical age is less than 10 with younger children having milder disease Course usually lasts 4-6weeks with 1/3rd having recurrences CLINICAL MANIFESTATIONS Skin: Present in 100% of cases and is the most common presenting symptom. Nonthrombocytopenic purpura often begin as urticarial lesions with progression to petechiae/purpura. Symmetric distribution in gravity dependent areas such as the legs and buttocks. Infants may have lesions on the trunk/face. Subcutaneous edema prominent especially in ages less than 3. Arthritis: 2nd most common manifestation and can often precede the skin findings. Usually periarticular disease involving the ankles and knees. Not associated with joint effusion, erythema, warmth. No permanent deformity. Gastrointestinal: 3rd most common manifestation. Usually colicky abdominal pain but can range from mild symptoms to GI hemorrhage, ischemia, and perforation. 50% with heme positive stools. Intussusception is a rare complication. Its ileoileal location is better diagnosed with ultrasound. Nephritis: Important cause of morbidity/mortality. Most commonly microscopic hematuria but can have associated proteinuria. Rarely progresses to acute nephropathy and renal insufficiency. Can present up to 3months post diagnosis. Scrotal Pain/Swelling: rule out testicular torsion EVALUATION Clinical diagnosis: Palpable purpura required with one of the following four features: Abdominal Pain, Biopsy with predominant IgA deposition, Arthritis/Arthralgia, Renal Involvement Blood pressure Laboratory tests: CBC with diff, PT/PTT, CMP, stool for heme, Urinalysis Follow urinalysis at diagnosis and with all recurrences. Repeat weekly-bimonthly up to 3months depending on degree of abnormality.

48 MANAGEMENT Supportive care Steroids are used for joint involvement and abdominal pain only. Does not prevent recurrences or shorten duration of acute illness. Dose 1-2mg/kg/day x 714 days. Nephrology consult needed for persistent proteinuria, nephrotic range proteinuria, hypertension, renal insufficiency NOTES

49 NOTES

50

Gastrointestinal

51

52

Gastrointestinal Hemorrhage
Differential diagnosis of hematemesis and rectal bleeding varies with age. Confirming the presence of blood is important. A number of substances may simulate hematemesis (red food dyes or coloring), hematochezia (food coloring, Kool Aid, beets, Omnicef), or melena (iron preparations, bismuth or spinach). Hemoccult can have false-positive results with ingestion of red meat, iron, peroxidase-containing vegetables. LOCALIZATION OF BLEED Distinction must be made between upper and lower tract bleeding. Localization can be frequently made by history and clinical findings. Gastric aspiration should be done in all patients with a GI bleed. A negative aspirate suggests a lower tract bleed. The following characteristics help establish the most likely source: Hematemesis: Vomiting of bright, red blood (BRB) or coffee grounds is associated with a lesion proximal to ligament of Treitz in the distal duodenum Melena: Passage of black, tarry stools. Indicative of bleeding proximal to the ileocecal valve as well as significant blood loss (over 50-100ml/24hours) Hematochezia: BRB or dark, red blood in stools is consistent with lesions in the ileum or colon Blood streaks on the outside of stool suggests origin as anal canal or rectum History of recent epistaxis, coughing, etc., may help localize bleeding to systems other than the GI tract In a newborn or breastfeeding infant, consider a maternal source (Apt test) ETIOLOGIES OF UPPER GI BLEEDS Differential Diagnosis Duodenal/Gastric Ulcer/Gastritis Causative Factors H. pylori infection, immunocompromised state, ICU patients, severe burns, Head Trauma, NSAID use Erosive/Herpetic esophagitis, Hiatal Hernia, GERD End Stage Liver Disease, Portal Vein Thrombosis Acute Vomiting and retching Congenital, acquired (post surgical, etc.) Liver disease, drugs, malnutrition, Vitamin K deficiency, DIC, consumptive coagulopathy

Esophagitis Esophageal varices Mallory-Weiss Tears AV Malformations Coagulopathy

Milk Protein Allergy

53 Trauma Ingestion, sharp foreign bodies, Accidental injuries

ETIOLOGIES OF LOWER GI BLEEDS Differential Diagnosis Colitis Causative Factors Infants: Milk Protein Allergy (MPI), Hirschsprung Disease, Infectious Colitis, NEC Toddlers: MPI, Infectious colitis Constipation Malnutrition, Vitamin K deficiency, Liver diseases, MPI E. coli O157, Shigella, Campylobacter, Salmonella, CMV, C. difficile Viral Illness Post-viral illness Acute or Chronic Liver failure <5years: Retention polyps (benign, non-recurring) >5 years: Juvenile Polyposis (adenoma, Hamartoma,etc.) acute presentation usually ulcerative

Anal Fissure Prematurity/Low Birth Weight Infectious Colitis

Henoch-Schonlein Purpura Meckels diverticulum Intussusception Coagulopathy Hypersplenism, DIC Polyps

Malrotation/Volvulus Inflammatory Bowel Disease

DIAGNOSTIC PROCEDURES Upper GI Bleeds Endoscopy is the procedure of choice. Most accurate when done within 2448hours of the active bleed. Abdominal Ultrasound with doppler flow is helpful when considering portal hypertension or hepatobiliary lesions UGI may reveal lesions beyond the reach of the endoscope. Contrast may hinder further studies so this must be considered carefully. Lower GI Bleeds Colonoscopy/Sigmoidoscopy: may be difficult in the case of active bleeding. Good for biopsy and diagnosis/treatment of polyps. Air Contrast Enema: study of choice when intussusception is suspected. May be diagnostic and therapeutic. Scintigraphy Scan: useful for occult, active bleeding, can detect bleeding at rates as low as 0.1ml/min

54 Meckels Scan: technetium pertechnetate concentrates in areas of gastric mucosa and bladder epithelium. Needs to be performed prior to any barium study. Angiography: rarely used in pediatric patients Barium Enema: NO role in lower GI bleeds MANAGEMENT Assess hemodynamic stability. If tachycardia, orthostatic changes, hypotension, or thready pulses are present, volume expansion should be initiated until PRBCs NOTES

55

Gastroesophageal Reflux Disease

Gastroesophageal reflux (GER): physiologic in most infants. It is brief, asymptomatic and self-limited. Gastroesophageal reflux disease (GERD): reflux associated with symptoms or complications Warning signs (suggestive of non-GER diagnosis): bilious/forceful emesis, hematemesis, hematochezia, diarrhea, abdominal distention /tenderness, onset >6months of age, fever, hepatosplenomegaly, macrocephaly, microcephaly, seizures COMPLICATIONS Systemic: Failure to thrive, ALTE, apnea, anemia, irritability Esophageal: Esophagitis, hematemesis, dysphagia, vomiting, heartburn, stricture Respiratory: Stridor, wheezing, chronic cough, hoarseness, recurrent pneumonia EVALUATION UGI: most useful when anatomical abnormality suspected (visualizes through the duodenal C-loop). Due to short period of time involved with study, results can be misleading. Also, does not discriminate between physiologic and nonphysiologic GER episodes. pH probe: A probe is placed at the distal esophagus and the pH is recorded for 24hours. Usually a second line test because it requires hospitalization and is invasive in nature. It detects acid reflux, evaluates esophageal clearance, determines association with symptoms, and assesses adequacy of therapy in unresponsive patients. Multichannel impedance pH probes can detect brief acidic reflux episodes as well as non-acidic GER episodes and can be done when the patient is on medications. Nuclear Medicine Milk Scan: useful in diagnosing non-acid reflux and aspiration Endoscopy: Can be useful for diagnosing complications of GERD such as esophagitis or strictures through visualization. It can also be diagnostic when pH probe and UGI are normal. TREATMENT Reflux precautions: Upright posture with feedings, frequent burping, small feeds Thickened feeds: Addition of cereal to bottles (1/2-1 tsp/oz) will decrease spitting. Watch for added calories. Enfamil AR (added rice starch) works only in acid medium (pH less than 5). Do not use with PPI or H2 blockers. Formula: small percentage of infants with milk protein allergy. Consider 2week trial of hypoallergenic formula. Acid reduction therapy: Antacids, Histamine-2 receptor antagonists (Zantac), Proton pump inhibitors (Prevacid)

56 Prokinetic agents: i.e. Reglan, Bethanechol, Erythromycin. No RTCs supporting their use. Surface agents: Carafate (not as effective in an alkaline environment) Consider GI referral if symptoms still present after 18months of age or any of the warning signs exist. NOTES

57

Neonatal Hyperbilirubinemia
DIFFERENTIAL DIAGNOSIS Indirect Increased Production or Bilirubin Load Hemolytic Disease Immune-mediated Rh alloimmunization, ABO and other blood group incompatibilities Heritable Red cell membrane defects: Hereditary spherocytosis, elliptocytosis, pyropoikilocytosis, stomatocytosis Red cell enzyme deficiencies: G6PD, pyruvate kinase deficiency Hemoglobinopathies: alpha or beta thalassemia Unstable hemoglobins: Congenital Heinz body hemolytic anemia Other causes of increased production Sepsis Disseminated intravascular coagulation, consumptive coagulopathy, large hemangiomas Extravasation of blood: Hematomas; pulmonary, abdominal, cerebral, or other occult hemorrhage Polycythemia Macrosomia in infants of diabetic mothers Increased Enterohepatic Circulation Breast milk jaundice Pyloric stenosis Small or large bowel obstruction or ileus Decreased Clearance Prematurity Glucose-6-phosphate dehydrogenase deficiency Inborn Errors of Metabolism (may also have direct component) Crigler-Najjar Syndrome Gilbert Syndrome Galactosemia, Glycogen Storage Disorders Tyrosinemia Hypermethioninemia Metabolic Hypothyroidism Hypopituitarism

58 Direct Obstructive Extrahepatic biliary atresia Choledochal cyst, annular pancreas, diaphragmatic hernia (right sided) Spontaneous perforation of the bile duct Mass: stone, tumor Hepatocellular Idiopathic neonatal hepatitis, prematurity Disorders of the intrahepatic bile ducts Alagille syndrome (paucity of the intrahepatic bile ducts) Nonsyndromic paucity of the intrahepatic bile ducts Caroli disease: congenital hepatic fibrosis with bile duct cysts Metabolic disorders Amino acid metabolism: Tyrosinemia Lipid metabolism: Gaucher disease, Niemann-Pick disease, Cholesterol ester storage disease (Wolman disease) Carbohydrate Metabolism: Galactosemia, Hereditary fructose intolerance, Glycogen storage disease Bile acid metabolism and transport excretion Zellweger syndrome and other peroxisomal metabolism Bilirubin transport: Dubin-Johnson syndrome, Rotor syndrome Mitochondrial disorders, Acyl-carnitine deficiency Alpha-1-antitrypsin deficiency Cystic fibrosis Neonatal iron storage disease Endocrine Hypothyroid Hypopituitarism and septo-optic dysplasia Infectious Sepsis TORCH infections Hepatitis B HIV Drugs and Toxins TPN Medications Fetal Alcohol syndrome Vascular anomalies Budd-chiari syndrome Hepatoendothelioma/hemangioma Cardiac insufficiency and hypoperfusion Chromosomal abnormalities Trisomy 21 and 18

59 EVALUATION Fractionated bilirubin: Direct component > 2mg/dL or more than 20% of total is abnormal. Maternal ABO and Rh blood types: If mom is group O or Rh-negative, infants blood type should be obtained along with a Direct antibody test (DAT). In infants receiving phototherapy, a fractionated bilirubin, Blood type and DAT, CBC with smear, and reticulocyte count should be drawn Measure glucose-6-phosphate dehydrogenase level in all infants approaching exchange levels or if FH/ethnic origin suggests likelihood. Level may be falsely elevated during hemolysis. Repeat level in 3months if high suspicion. Elevated direct component: Obtain urinalysis and urine culture. Evaluate infant for sepsis. Rule out cholestasis with CMP and GGT. Consider an abdominal ultrasound and a HIDA scan. Infants should be on Phenobarb or Actigall for 48hours prior to HIDA scan. Liver biopsy may ultimately be needed. Infants with jaundice at or beyond 3weeks should have a repeat fractionated bilirubin Check neonatal screens Additional workup is guided by the historical facts and physical exam, i.e. alpha1-antitrypsin level, chromosomes, TORCH titers, Hepatitis panel, etc. MANAGEMENT AND PREVENTION The goal is to prevent severe neonatal hyperbilirubinemia and subsequently kernicterus (chronic bilirubin encephalopathy). All newborns discharged at less than 72hours of age should be seen within 2days or sooner if major risk factors. Serum bilirubin levels generally peak at day 3-5. Major risk factors for development of severe hyperbilirubinemia: bilirubin in the high-risk zone, early jaundice, Blood group incompatibility with positive DAT, gestational age 35-36weeks, previous sibling requiring phototherapy, significant bruising/cephalohematoma, exclusive breastfeeding, East Asian race Promote and support successful breastfeeding. Advise frequent feedings (at least 8-12 times/day). Breastfeeding jaundice occurs within the first 2-4 postnatal days and is from relative dehydration. Breastmilk jaundice can cause prolonged jaundice (beyond 2-3weeks) in 20% of infants. Recognize visual estimation often leads to errors Interpret bilirubin levels according to the infants age in hours. Jaundice within the first 24hours of life is always abnormal. Establish the risk zone: See Figure 1 Phototherapy remains the mainstay of treatment for indirect hyperbilirubinemia. See Figure 2 for guidelines for the initiation of phototherapy. Phototherapy with elevated direct component may lead to the bronze baby syndrome or severe blistering Discontinue phototherapy when bilirubin <14mg/dL. Significant rebound is rare.

60 If total bilirubin level is >25mg/dL or lower if <72hours of age, obtain a type and cross and request blood for possible exchange transfusion. Immediate exchange needed for infants manifesting signs of acute bilirubin encephalopathy. In isoimmune hemolytic disease, administer IVIG (0.5-1g/kg over 2hours) if the total bilirubin level continues to rise despite intensive phototherapy or if it is approaching exchange level. The dose can be repeated in 12 hours.

FIGURE 1: ESTABLISHING RISK ZONE

25

20
High Risk Zone 95th %tile

Serum Bilirubin (mg/dL)

75th
High Intermediate Zone

15

40th %tile

Low Intermediate Zone

10

5
Low Risk Zone

0 0 12 24 36 48 60 72 84 96 Postnatal Age (hours) 108 120 132 144

61

FIGURE 2
Guidelines for Phototherapy in Hospitalized Infants >35 Weeks
25

Total Serum Bilirubin (mg/dL)

20 15 10 5 0 Birth 24hrs 48hrs 72hrs 96hrs Age Infants @ lower risk (>38 wk and well) Infants @ medium risk (.38 wk + risk factors or 35-37 6/7 wk. and well) Infants @ higher risk (35-37 6/7 wk. + risk factors)

5 days

6 days

7 days

NOTES

62

Respiratory and Allergy

63

64

Acute Airway Obstruction/Stridor

CLINICAL ASSESSMENT History Duration of symptoms, acute vs. chronic course Recurrent episodes or present since birth Presence of drooling Ask about choking episodes, possible FB aspiration, appropriate weight gain History of prematurity, previous intubations, cardiac surgery or PDA ligation Fever or URI symptoms Pattern of stridor: inspiratory vs. expiratory, worse with position, related to feeds, presence during sleep Physical Exam ABCs/Vital signs Pattern of stridor: Inspiratory stridor suggests extrathoraic origin while expiratory suggests intrathoraic origin. Biphasic stridor suggests fixed lesion. Wheezing can be present with lower airway disease. Quality of cry (i.e. hoarse) Tonsillar size, position, asymmetry, or fluctuance Position of comfort: neck hyperextension, tripoding Hemangiomas Cardiac murmur Macroglossia, micrognathia DIAGNOSTIC PROCEDURES Evaluation will depend on clinical situation but workup may include: AP and lateral inspiratory neck films (usually not helpful with chronic stridor) CXR (inspiratory and expiratory): assess lung volume and r/o mass ABG, CBC, and blood culture if toxic Esophagram (i.e. UGI): evaluate anatomy and for evidence of compression Airway fluoroscopy: assess airway dynamics (normal study does not rule out pathology) Echo: cardiac and vascular anatomy CT or MRI of chest/neck/skull: for choanal stenosis or piriform aperture stenosis Bronchoscopy/Laryngoscopy: direct visualization SPECIFIC ILLNESS AND MANAGEMENT Croup Usually viral etiology: Parainfluenza, Influenza, Adenovirus, RSV

65 Spasmodic croup: Acute onset, often no prodrome, recurrent Generally occurs between age 6months to 3years Child will have a hoarse voice, barking cough, and audible inspiratory stridor May have low grade fever and viral prodrome Inspiratory lateral and AP neck film reveals steeple sign Decadron 0.6mg/kg IM/IV x1dose (half life 36hours). Maximum dosage 10mg. May repeat in 18-24hours. Racemic epinephrine (2.25% soln) 0.05ml/kg/dose diluted to 3ml with NS. Maximum dose is 0.5ml. Watch for rebound in 3-4hours. Heliox (available 70:30) to improve laminar flow Epiglottitis Generally occurs 7months to 10years Decreased incidence with introduction of H flu immunization Onset is abrupt and the child is toxic Symptoms include dysphagia, odynophagia, and drooling Older children complain of severe sore throat but have normal exam May appear anxious and prefer to sit with hyperextended neck (tripod) Lateral neck films reveal the thumb sign. Omega epiglottis is a normal variant Visualize epiglottis in OR and place endotracheal tube Labwork and procedures should be performed after airway stabilized Begin antibiotics to cover typical pathogens (Group A Strep, H.flu, Strep pneumoniae, S. aureus); i.e. 3rd generation cephalosporin. Consider the addition of clindamycin or vancomycin if concerned for MRSA. Tracheitis Can occur at any age during childhood Often superinfectious complication of croup Sudden onset of fever and deteriorates clinically Radiographs reveal irregular tracheal air column with some degree of subglottic narrowing Direct laryngoscopy reveals copious purulent secretions Secure airway and obtain tracheal and blood cultures Start antibiotics to cover S. aureus, GABHS, and H. flu Foreign Body Most common under age 3 Onset can be sudden or have an indolent course ALWAYS consider FB. Presentation depends on location. If the FB is laryngeal, there are voice changes, pain, and stridor Tracheal FB will have brassy cough and wheezing If located distally, there will be wheezing, rales, and recurrent pneumonia

66 Inspiratory/expiratory chest films as well as decubitus films aid diagnosis Laryngoscopy and/or rigid bronchoscopy is diagnostic and therapeutic Peritonsillar Abscess Typically in adolescence History of sore throat and fever The patient may have pain, hot potato voice, trismus, and possibly otalgia Physical exam: Medially displaced tonsil with fluctuance, deviated uvula If no toxicity or fluctuance treat with antibiotics, such as Augmentin or Clindamycin, to cover Group A Strep, S. aureus, and anaerobes If toxicity, fluctuance, neck swelling, or symptoms fail to resolve in 48hours, hospitalize and begin IV antibiotics. Obtain ENT consult for I&D. Consider Decadron with severe airway obstruction or pain Retropharyngeal Abscess Usually in children under age 4years Patient typically has a history of preceding sore throat and fever The patient may have difficulty breathing or swallowing, a stiff neck, drooling Lateral inspiratory neck film shows increased retropharyngeal soft tissue which may be defined as an AP diameter >5-7mm at 2nd cervical vertebrae, >14mm at the 6th vertebrae, or the diameter greater than vertebral body diameter CT scan may be a better tool for diagnosis. Consider presence of cellulitis (usually GABHS) if no abscess ENT consult for I&D Start antibiotics for Staph aureus, Strep sp, and anaerobes (e.g. Clindamycin with 3rd generation cephalosporin). Usually polymicrobial infection. Other causes Angioedema Laryngomalacia: inspiratory stridor, improves with prone position Tracheomalacia: expiratory stridor, central/low-pitched wheeze GERD Vocal cord paralysis/dysfunction (Bilateral VCP should have CNS imaging to evaluate for tumors/lesions or structural abnormalities) Tumor/Papillomas/Hemangiomas Laryngeal webs or cysts Vascular rings Hypocalcemia Subglottic stenosis

67

CHRONIC STRIDOR Upper airway causes of chronic stridor: Piriform aperture stenosis, choanal atresia/stenosis, vallecular cysts, thryoglossal cysts, macroglossia, micrognathia, laryngomalacia, laryngeal web, laryngeal papilloma, vocal cord paralysis, vocal cord dysfunction Lower airway causes of chronic stridor: Subglottic stenosis, subglottic cyst/nodule, airway hemangioma, extrinsic airway compression, tracheomalacia, tracheal stenosis, tracheal rings Who needs a bronch for chronic stridor: SPECSR and HIVE Severity: Parents subjective impression of severity Progression of the obstruction over time Eating or feeding difficulties, aspiration, and failure to thrive Cyanotic episodes, ALTEs Sleep: obstruction causing retractions even during sleep Radiology: specific abnormalities detected by radiographs OR H: I: V: E: Hemangioma Intubation Voice Expiratory or Biphasic NOTES

68

Parapneumonic Effusion and Empyema

Parapneumonic effusions (pleural fluids associated with pneumonia) may be uncomplicated, free-flowing effusions that resolve spontaneously with antibiotic therapy, or complicated effusions that require pleural space drainage. The natural course of a complicated parapneumonic effusion is to develop into single or multiple loculations and to progress to an empyema cavity. Pleural empyema is a serious complication and rarely resolves without appropriate medical therapy and drainage procedures. If a child remains febrile or unwell 48 hours after admission for pneumonia, parapneumonic effusion/empyema must be excluded. All children with parapneumonic effusion or empyema should be admitted to the hospital and blood cultures obtained. COMMON CAUSES OF PLEURAL EFFUSIONS Pneumonia Trauma Malignancy Collagen Vascular Disease Congenital Heart Disease Renal disease Immunodeficiency disorders Adjacent infection involving the oropharynx, esophagus, mediastinum (abdominal infections can also cause a reactive effusion) COMMON ORGANISMS Streptococcus pneumoniae Staphylococcus aureus Streptococcus pyogenes Haemophilus influenzae Anaerobes DIAGNOSTIC WORKUP AND MICROBIOLOGY Postero-anterior radiographs should be taken. Lateral decubitus films may also be obtained. Ultrasound should be used to confirm the presence of a pleural fluid collection and is helpful in determining if loculations are present Patients with pleural effusions which have not been treated with antibiotics should be considered for a thoracentesis to obtain fluid for culture Ultrasound should be used to guide thoracentesis or drain placement if the effusion is not large or multiloculated

69 If ultrasound suggests a large loculated or multiloculated effusion then a CT scan of the chest to rule out intraparenchymal lung abscess or other anatomical lesions is usually required by pediatric surgery prior to proceeding with VATS. Blood cultures should be performed in all patients with parapneumonic effusion All cases should be treated with intravenous antibiotics. Where possible, antibiotic choice should be guided by microbiology results. There is no indication for diagnostic bronchoscopy SURGICAL PROCEDURES VATS (video assisted thoracoscopic surgery) - Achieves debridement of fibrinous pyogenic material, break down of loculations, and drainage of pus from the pleural cavity under direct vision. Decortication- Involves an open thoracotomy and excision of the thick fibrous pleural rind with evacuation of pyogenic material. It is a longer and more complicated procedure. MANAGEMENT PROTOCOL FOR PEDIATRIC EFFUSION
Treatment Failure @ 48

New Presentation

Suspicion of Parapneumonic Effusion Chest Ultrasound

Small, free effusion no loculations

Consider thoracentesis

Small to moderate loculated effusion Insert chest tube

Large loculated or multiloulated Chest CT

Institute antibiotics and/or consider AB change for resistant pathogen

Consider intrapleural fibrinolytics

VATS or Thoracotomy

1. The algorithm is for presumed infectious effusion; immediate thoracentesis should be done if malignancy, etc. is a consideration. 2. No indication for bronchoscopy. 3. Consult Pediatric Surgery for chest tube placement.

70 NOTES

71

Anaphylaxis
Anaphylaxis is an immediate IGE-mediated hypersensitivity reaction. These reactions usually occur within seconds to minutes in individuals with preexisting antibodies. Common causes include insect venoms, foods (such as peanuts, eggs, milk, seafood), drugs, contrast, and latex. Additional manifestations of immediate hypersensitivity include angioedema and urticaria. If the diagnosis is in question, obtain a serum tryptase level within 90 minutes. It should be elevated with acute anaphylaxis. CLINICAL FEATURES Sense of impending doom may proceed or accompany symptoms Cutaneous symptoms: feeling of warmth, itching, flushing, urticaria, and angioedema. 15% of patients have no urticaria or angioedema. Respiratory: stridor, bronchospasm, hoarseness, or dysphagia Gastrointestinal: nausea, vomiting, and diarrhea Cardiovascular: tachycardia, hypotension, shock, and death MANAGEMENT ABCs. Maintain airway. Trendelenburg position if hypotensive. Administer epinephrine (1:1000) 0.01ml/kg/dose (max single dose 0.5ml) IM every 10-15minutes. Can be repeated up to 3 doses. If anaphylaxis results from a sting or injection, the epinephrine should be administered at the same site to minimize further absorption. Tourniquets are no longer advised. Treat hypotension with NS bolus 20cc/kg. If hypotension persists, repeat bolus and consider adding pressor support. H1-blocker (Benadryl) 1-2mg/kg/dose po/IV/IM up to 75mg/dose q4-6hours Consider, H2-blocker (Zantac) 1.5mg/kg/dose (max 50mg) IV q8hours Methylprednisolone (Solumedrol) 2mg/kg/day IV divided q6hours. A loading dose of 2mg/kg/dose may be given as the initial dose. For patients with bronchospasm, administer nebulized beta-agonists Anaphylaxis is often biphasic. Delayed worsening can occur several hours later. Once acute attack subsides, H-1 blocker should be continued for 48-72hours. Wean steroids according to severity of attack. Discharge patient with an Epi-Pen. Children <30kg should get the Epi-Pen Jr. They have limited shelf life (27months) and will lose their effectiveness. Individuals with anaphylaxis warrant an allergy referral. NOTES

72

Asthma
Asthma is a chronic disease of recurrent, reversible airway obstruction. It is characterized by the triad of smooth muscle spasm, mucosal inflammation, and mucus hypersecretion. HISTORY Previous history of asthma, wheezing, hospitalizations, and medications Previous PICU admissions or intubations are risk factors for death from asthma Ask about frequency of steroid or Beta-agonist use as well as ED visits Asthma triggers: weather changes, allergens, colds, exercise, smoke Comorbid conditions: GERD, chronic sinusitis, allergic rhinitis, ABPA Night cough or chronic cough Exercise-induced symptoms Rule of Twos: Symptoms more than two times per week or more than two nights a month should be considered persistent asthma. PRESENTING SYMPTOMS It is important to understand that all wheezes are not asthma and all asthma does not present with wheezing. The presentation can be subtle and varied. Wheezing Dyspnea with little provocation Cough Exercise intolerance Chest tightness/pain Night awakenings Recurrent croup, pneumonia, or bronchitis DIFFERENTIAL DIAGNOSIS OF WHEEZING Infectious: Bronchiolitis, pneumonia, viral croup Respiratory: Asthma, reactive airway disease, congenital airway anomalies, foreign body, alpha-1-antitrypsin deficiency, primary ciliary dyskinesia, intrabronchial lesions (i.e. tumor/granulation tissue), bronchiectasis, interstitial lung disease, cystic fibrosis, hypersensitivity pneumonitis, ABPA, Wegener Cardiovascular: Vascular rings, mitral valve prolapse, pulmonary edema, congestive heart failure Gastrointestinal: Gastroesophageal reflux PHYSICAL EXAM General appearance: accessory muscle use (esp. SCM), retractions, nasal flaring, grunting, difficulty with completing full sentences, anxiety, agitation, cyanosis

73 Vital signs: Tachycardia (from distress or Beta agonist use), Pulsus paradoxus (reduction of systolic BP more than >10mmHg during inspiration) HEENT: nasal polyps, allergic shiners, Morgan Dennie lines, conjunctival cobblestoning Respiratory: Inspiratory/expiratory wheezing. Rales/rhonchi may be present. Wheezing may not be heard with poor air exchange. Prolonged expiratory phase. Quality of wheeze (i.e. monophonic vs. polyphonic, high vs. low pitch, diffuse vs. focal). Musculoskeletal: Clubbing LABORATORY EVALUATION Blood gas: Evaluate PaCO2 as indication of patients ability to ventilate. Interpret in light of respiratory rate. Normal PaCO2 may be an ominous sign in a tachypneic child. Chest X-Ray: Hyperinflation. 20% will have infiltrates, atelectasis, or a combination of the two. Look for pneumomediastinum or pneumothorax. Potassium: Beta-agonists drive potassium into the cells, leading to low serum levels. Pulmonary Function Testing (PFTs) have no place in an acute attack. However, peak flows can be used as an objective measure. PFTs should be obtained yearly in stable, chronic asthma or more often depending on symptoms. TREATMENT Oxygen as needed Inhaled beta2-agonists (albuterol) are the mainstay of acute treatment. MDI and spacer are equally effective if not superior to nebulization. An inhaled anticholinergic agent (Atrovent) works synergistically with Albuterol. It should be used acutely in the outpatient or ED setting but not for routine hospital use. PO/IV steroids (i.e. Orapred, Solumedrol) depending on severity. Usually given 2mg/kg/day divided BID as 5day course. Steroids do not need to be tapered if given less than 10days. PO and IV steroids are equally efficacious. Severe exacerbations may require continuous albuterol nebulization, SQ or IV drip of Terbutaline, or Magnesium. Consider PICU admission if these therapies are required. NOTES

74 NOTES

75

Cystic Fibrosis
Cystic Fibrosis (CF) has an incidence of 1 in 3200 newborns in the United States. It is an autosomal recessive disorder with the genetic defect located on chromosome 7q31.2. This gene codes for a chloride channel named the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The most common mutation is the F508, which accounts for over 70% of CF cases. DIAGNOSIS OF CF SC currently screens all infants for CF with blood immunoreactive trypsinogen (IRT). If elevated (105ng/ml), repeat screen indicated. If continued elevation (70ng/ml), the following is needed for diagnosis: Requires one of the following Presence of one or more characteristic clinical features Family history of CF Positive neonatal screening test AND evidence of CFTR abnormality Sweat chloride 60mmol/L (mEq/L) on 2 occasions: quantitative pilocarpine iontophoresis collected by Gibson-Cooke procedure. Requires collection of at least 100mg sweat in 30minutes. False positives and negatives can occur. Children with sweat values between 40 and 60 should be considered for genotyping if there is an elevated suspicion for CF. Mutation analysis with 2 characteristic alleles Increased nasal transmembrane potential differences CLINICAL PRESENTATION CFPANCREAS Mnemonic: exacerbations/presentation C Cough worsening/chronic cough F Fever/FTT P Pulmonary Function Tests decreased/Pancreatic Insufficiency A Appetite decreased/Alkalosis N Nutritional failure/Neonatal meconium ileus or nasal polyps C CBC abnormality/Clubbing R Radiographic changes/Rectal prolapse E Exam (increased rales, wheezes, tachypnea, retractions)/Electrolyte abnormalities A Activity decrease/Absent vas deferens S Sputum changes/Sputum with Staph or Pseudomonas Pulmonary Pulmonary disease is the major cause of morbidity and mortality Superimposed on chronic disease are episodes of acute exacerbations

76 Causative organisms include S. aureus, H. flu, Pseudomonas, B cepacia, Alcaligines, Stenotrophomonas, NTM Pneumothorax occurs in 3-5%. There is a high incidence of recurrence. RAD/asthma occurs in 25-50% Allergic Bronchopulmonary Aspergillosis occurs in 5-10% and typically presents as wheezing, rusty sputum, pulmonary infiltrates, or eosinophilia Other problems encountered include nasal polyps, pansinusitis, and hemoptysis Clubbing is found in almost 100% of patients and correlates with severity of lung disease Cor pulmonale, due to chronic hypoxemia, is a common finding with end stage disease Gastrointestinal Pancreas Pancreatic insufficiency affects 85% of patients and leads to malabsorption. Those who are pancreatic sufficient generally have less severe disease. Malabsorption may present as steatorrhea or FTT Pancreatic insufficiency can lead to fat-soluble vitamin deficiencies, hypoproteinemia with/without edema, and anemia Pancreatitis is rare. It is more common in pancreatic sufficient patients. Abnormal glucose tolerance and diabetes can occur Vitamin Deficiencies Vitamin A: Vitamin D: Vitamin E: Vitamin K: Xerophthalmia, night blindness, dry skin Osteopenia, rickets Hemolytic anemia, neuropathies/spinocerebellar syndrome Impaired coagulation Gastrointestinal Rectal prolapse GERD Several intestinal obstructive lesions can occur at different ages. Each of these will present with signs and symptoms of bowel obstruction, such as abdominal pain and emesis. Meconium Ileus is a small intestine obstruction. It is pathognomonic for CF. Meconium Plug Syndrome is much less common and affects the large intestine. This is also associated with Hirschsprung Disease. Distal Intestinal Obstruction Syndrome (DIOS) is equivalent to meconium ileus in the older child. Typically, there is partial or complete obstruction of the terminal ileum.

77 Hepatobiliary Clinically significant cholestasis is found in 5% of patients Fatty infiltrate of the liver is a common finding (steatohepatitis) Focal biliary cirrhosis, portal HTN, and liver failure can develop Other Clinical Findings Impaired fertility in males (absent vas deferens) and females Electrolyte abnormalities including hyponatremia, hypochloremia, hypokalemia, metabolic alkalosis Hypertrophic pulmonary osteoarthropathy occurs in about 15% of patients. It includes clubbing and may involve the distal ends of tubular bones. Hypercalciuria, nephrocalcinosis, and microscopic hematuria MANAGEMENT Pulmonary The major goal is to delay and possibly prevent development of chronic lung disease. Airway clearance can be improved with chest physiotherapy (CPT). Many devices such as the Vest or procedures are available. CPT should be done minimum of BID as an outpatient, and more often with exacerbations Pulmonary secretions can be thinned with Pulmozyme (one vial, 2.5mg, nebulized qday-BID). Side effects include anaphylaxis, hemoptysis, and hoarseness. Hypertonic saline may be used in both the acute and chronic settings to normalize airway surface liquid and to enhance mucous clearance. Strengths range from 310% and should be administered BID following Albuterol to prevent bronchoconstriction. Recommend pre and post testing prior to its initiation due to risk of bronchoconstriction. Bronchodilator therapy has been controversial, but up to 50% of patients have an RAD component. 2-agonists are generally used BID-QID. PFTs are the most accurate and objective measure of pulmonary status. They should be performed on admission and every 5-7days during the exacerbation. Response to therapy is indicated by improvement of FEV1 and FVC. Overnight pulse oximetry should be used during hospitalizations to evaluate for hypoxemia. If hemoptysis develops, check PT/PTT. Give vitamin K if needed. Stop pulmozyme and CPT. Emergent Pulmonology involvement if severe.

78 Infectious Disease Antibiotics are the mainstay for treating pulmonary exacerbations. Typically antibiotics are administered IV and dosages are high in comparison to those used in other children. Once daily aminoglycosides are frequently utilized. Treatment for exacerbation generally includes 14-21 days of IV therapy, but duration is based on PFTs and clinical course. Combination therapy is used to slow the emergence of resistant organisms. Antibiotic choice is based on prior sputum cultures until a new sample can be obtained and cultured If a culture reveals a multidrug resistant organism, the sample should be sent for synergy studies if not performed within the past year Inhaled antibiotics are recommended for maintenance prophylactic therapy, but are typically not used in acute exacerbations. TOBI (300mg tobramycin/5cc ampule) is dosed 1 ampule BID for 4weeks, then off for 4weeks. Azithromycin is given for kids >6years who have chronic Pseudomonas and no history of NTM infection. Dose is 500mg M,W,F for >40kg and 250mg for <40kg. Contact precautions for children with MRSA, B. cepacia, and multi-drug resistant Pseudomonas (defined as resistance to all antibiotics within 2 out of the following 3 drug classes: beta lactams, aminoglycosides, fluoroquinolones) Administer influenza vaccine annually Gastrointestinal and Nutrition Optimal growth and nutrition is associated with improved long term outcome Caloric goals should be 130-150% of normal caloric intake for age Formulas with MCT oil may be easier to absorb (i.e. Portagen, Alimentum) Dietary supplements such as shakes or glucose polymers should be considered. Some patients require enteral feeding to ensure adequate calories. Prealbumin and daily weights should be followed in the hospital Oral enzyme replacement therapy with all meals and snacks is crucial. Doses in excess of 10,000 units of lipase/kg/day should be avoided as they have been associated with fibrosing colonopathy. Acid suppression may be needed to enhance enzyme activity. To evaluate, obtain 72hour fecal fat. Fat-soluble vitamins should be supplemented Vitamin A, D, and E as well as PT/PTT (Vit K) should be performed annually Patients on aminoglycosides should be on twice weekly po Vit K regardless of PT. Those with prolonged PT should have daily Vit K until PT normalizes. In adolescents consider yearly fasting glucose to evaluate for diabetes. HbA1C is not the most accurate test in CF but should be done yearly. Diagnosis is made through oral glucose tolerance testing. This also should not be done during acute exacerbations as many CF patients will have impaired glucose tolerance during illness. These patients may need insulin during exacerbations. Periodic evaluation of CMP and GGT should be performed

79 For hepatomegaly or abnormal LFTs, consider abdominal ultrasound and Actigall Guidelines for Initiation of Pancreatic Enzymes Infants: 2,000-4,000 units lipase/120cc of formula or breastmilk Children <4years: 1,000 units of lipase/kg/meal, 500 units lipase/kg/snack Children >4years: 500 units of lipase/kg/meal, 250 units lipase/kg/snack NOTES

80

Neurology

81

82

Seizure Disorders
TYPES OF SEIZURES Status Epilepticus A prolonged or repetitive seizure lasting greater than 10minutes which is considered a medical emergency. Convulsive (generalized or focal, clonic, tonic, tonic-clonic, myoclonic) Non-convulsive (absence or partial) Treat sequentially until controlled (every 10-20 minutes with lorazepam then fosphenytoin, then Phenobarbital, then midazolam infusion or pentobarbital drip if needed under the guidance of the ED or PICU) Generalized Seizures Loss of consciousness is usually the first manifestation. Seizures involve both sides of the body from the onset of seizure. Different types include: Tonic/clonic Absence seizures have a brief impairment of consciousness. Classically, involves staring (infrequently with automatisms) in a 4-12 year old. EEG demonstrates generalized 3 Hz/sec spikes. These are often provoked by hyperventilation. Atonic seizures, often referred to drop attacks, typically occur in children 2-5 years old. There is a generalized loss of muscle tone causing collapse. Myoclonic seizures are sudden, brief shock-like contractions of the childs entire body, face, or trunk. Partial Seizures Focal seizure activity is often seen clinically on one side of the body. Partial seizures may generalize, so it is important to obtain history regarding the seizures first manifestation. Partial seizures are divided into simple or complex. Simple partial seizures may be motor, sensory, or autonomic. There is no change in the patients mental status. Complex partial seizures involve impairment of consciousness. The patient may have automatisms, aura, dj vu, or semi-purposeful movements. Febrile Seizures Age of onset between 6 months and 6 years Temperature greater than 101F No previous episodes of non-febrile seizures Simple FS: generalized, less than 15 minutes, no more than 1 per 24 hours Complex FS: partial/focal, longer than 15 minutes or more than 1 per 24 hours Excellent long term prognosis (97-98% resolve by 5-6 years of age)

83 Neonatal Seizures Seizures in the neonate can present with repetitive contractions, sustained posturing, bicycling, tongue thrusting, or eye deviation. Due to the neonates immature neurologic system, generalized seizures are rare. Infantile Spasms Typically occurs 3months 1 year of age Typically presents as clusters of spasms on awakening. These movements are characterized by repetitive flexor/extensor spasms. EEG demonstrates hypsarrhythmia INITIAL SEIZURE WORKUP A detailed history should be obtained of the duration, nature at onset (focal vs. generalized), and surrounding circumstances of the seizure. Past medical history should focus on previous seizures, trauma, developmental, and birth history. Imitators of seizures include syncope, breath-holding spells, night terrors, GER, cardiac arrhythmia, pseudoseizure, tremor, and paroxysmal vertigo. Consider non-accidental trauma and ingestion. A thorough physical exam should be completed with attention to vital signs, head circumference, fundoscopic, neurologic, and cutaneous exams. Laboratory tests are of little value in evaluation of the first, unprovoked seizure in children over 2 without prolonged post-ictal confusion. Laboratory evaluation (performed in historical context) to consider include CBC, CMP, Magnesium, Urinalysis, drug screen, lead level, amino acid screen , ANA, and serum ammonia. Give particular attention to the laboratory evaluation of the neonate. A full sepsis workup should be performed with consideration of HSV. Screen for inborn errors of metabolism. In children with febrile seizures, a lumbar puncture should be performed in children less than 1 year of age. It should be strongly considered in children 12 18 months. In a child older than 18 months, clinical skills should be used to determine the need for an LP. Neuroimaging has a low yield in evaluating children with a first, unprovoked nonfocal seizure as well as with a first simple febrile seizure. It is indicated in cases of trauma, focal or prolonged seizure, abnormal neurologic exam, developmental delay, or delayed return to baseline. Also consider imaging in neonates and patients older than 16 years at onset of seizures. MRI is the best imaging modality, but CT is often easier to obtain. EEG is recommended as part of the neuro-diagnostic evaluation except for a healthy child presenting with a first typical febrile seizure. Exceptions can be made if the treating physician feels otherwise. Up to 50% of patients with new onset seizures may have a normal EEG initially. The yield is repeated with subsequent routine studies or prolonged monitoring. However, over-reliance on EEG should not be used to delay treatment and/or other testing in patients with a history clinically consistent with seizures.

84

NOTES

85

Stroke in Childhood
Stroke in childhood usually presents with acute focal neurologic disturbance. The most common clinical manifestation is acute hemiparesis. Infrequently strokes may present with subacute symptoms/signs, and/or multifocal/generalized neurologic dysfunction. Pathophysiologically, stroke arises from ischemia, hemorrhage, and/or thrombosis. LOCALIZATION Anterior circulation (carotid, anterior cerebral or middle cerebral distribution) Language difficulty and right hemiparesis suggest left carotid or left MCA Left hemiparesis suggests right carotid or right MCA Posterior circulation (vertebral and/or basilar distribution) Vertigo, cranial nerve signs/symptoms DIFFERENTIAL DIAGNOSIS Migraine Seizure +/- Todds paralysis Hypertensive Encephalopathy Hypoglycemia ADEM/MS Brain Tumor Infection: abscess, encephalitis Subdural/Epidural hemorrhage Alternating hemiplegia of childhood ETIOLOGY Cardiac Disease (accounts for 50% of ischemic stroke) Infection: Varicella (postinfectious), Meningitis, HIV Metabolic: Homocystinuria, Mitochondrial disorders, Fabry disease Arterial Dissection: Marfan, Ehlers-Danlos Vasculitis: SLE, PAN, Kawasaki disease, Takayasu arteritis Hemoglobinopathies: Sickle Cell Hematologic: Polycythemia, Malignancy, Thrombocytosis Coagulopathy/Thrombocytopenia Vascular Dysplasias: Moyamoya disease, Fibromuscular Dysplasia, AVMs, Intracranial aneurysm Head Trauma Vasospasm: Migraine, Cocaine use Diminished systemic perfusion: anaphylaxis, sepsis, hypoxia/asphyxia Drugs: OCPs, chemotherapeutic agents Idiopathic (up to 1/3 with unidentified cause)

86 EVALUATION MRI/MRA investigation of choice, include imaging of cervical and proximal intracranial arterial vasculature CT if MRI not readily available Echocardiogram CBC, PT, PTT ESR, ANA, Antiphospholipid profile Lipid profile Urinalysis and drug screen Blood Pressure Prothrombotic workup: see Thrombotic Disorders Metabolic workup: as directed by the Neurologist Varicella titers HIV ACUTE MANAGEMENT ABCs Maintain normal temperatures and glucose homeostasis Do not treat hypertension acutely unless formally agreed upon by neurology, neurosurgery, hematology, and/or PICU (potentially can worsen ischemia) Early neurosurgical/neurology consult Aspirin 5mg/kg/day should be administered initially for arterial ischemic stroke, do not use in a hemorrhagic stroke or in those with sickle cell disease Consider the use of Aggrenox or Plavix in the older child (long term prevention) Consider anticoagulation for extracranial arterial dissection associated with arterial ischemic stroke, cerebral venous sinus thrombosis, and for those with a cardiac source of embolism If sickle cell disease: See Sickle Cell Disease CVAs NOTES

87

Ataxia
Ataxia is defined as impaired balance and incoordination of intentional movement. The most common presenting symptom is an abnormal gait or tremor. HISTORY Onset and duration Fever, headache, vomiting, photophobia, vertigo, AMS, diplopia, paraesthesias, weakness, tremor Developmental screen Recent infection, seizure, head injury, or environmental exposures FH of migraine, ataxia, or neurologic disease LOCALIZATION Cerebellar Ataxia Wide based gait Truncal ataxia (with sitting and standing) Titubation (head bobbing) Dysmetria Nystagmus Sensory Ataxia (involving position and vibration sense) High stepping gait Sensory changes (joint position sense/proprioception) Diminished reflexes Romberg sign Abnormalities of fine finger movement DIFFERENTIAL DIAGNOSIS Consider age appropriate developmental skills before diagnosing ataxia. Myelopathy (spinal cord), myopathy and neuropathy can also present with gait disturbances. Acute Cerebellar Ataxia Brain Tumor: Medulloblastomas, Astrocytomas, brainstem Gliomas Congenital malformation: Chiari malformation, Dandy Walker, hydrocephalus, etc. Ingestion: anticonvulsants, antihistamines, alcohol, heavy metals, etc Infection: meningitis, encephalitis, cerebellar abscess Multiple Sclerosis (MS): recurrent demyelinating disease, often monosymptomatic, MRI with periventricular lesions Acute Disseminated Encephalomyelitis (ADEM): monophasic demyelinating disease, systemic symptoms present with widespread CNS disturbance

88 Miller Fisher Syndrome: variant of Guillain-Barre; Triad of ataxia, ophthalmoplegia, and areflexia; CSF with elevated protein Opsoclonus myoclonus ataxia: paraneoplastic syndrome associated with Neuroblastoma Acute Cerebellar Ataxia (ACA): diagnosis of exclusion, postinfectious etiology with abrupt onset, age 2-6years most commonly, no systemic symptoms Vascular Disorders: stroke, vasculitis Trauma/Postconcussion Syndrome Recurrent Cerebellar Ataxia Migraine variants Basilar migraine Benign Paroxysmal Vertigo Dominant recurrent ataxias: episodic ataxias caused by ion channel defects, often a positive family history Metabolic disorders Maple syrup urine disease Hartnup disease Pyruvate dehydrogenase deficiency Acute Sensory Ataxia Guillain-Barre Syndrome (GBS): acute, post-infectious demyelinating disease; characterized by symmetrical ascending weakness, areflexia, and sensory complaints WORKUP This is guided by historical facts and physical exam supporting localization and suspected diagnosis Neuroimaging: CT scan is essential for emergent imaging but MRI is more efficacious in visualizing the posterior fossa. Complex or unclear exam and localization may need MRI of the spinal cord. Urine drug screen, specific medication levels, CMP. With complex or unclear exam/localization should consider CPK to rule out myopathy. If concern for infection, obtain pan cultures with lumbar puncture Lumbar puncture: Elevated protein is found in Miller Fisher syndrome/GBS, ADEM, MS, and ACA. Oligoclonal bands are also present with MS. Caution if patient has mass effect, increased ICP, or spinal cord tumor. Urine HVA/VMA and chest/abdomen images for neuroblastoma Metabolic workup to include serum/urine amino acids, urine organic acids, urine ketones, ammonia, plasma/CSF lactate and pyruvate NOTES

89 NOTES

90

Endocrine

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92

Diabetes Mellitus
DEFINITION Fasting glucose >126 mg/dL Random glucose >200 mg/dL PLUS symptoms DKA defined as Glucose >250 mg/dL and pH <7.25 or HCO3 <15 mmol/L and presence of urinary or serum ketones EVALUATION History Physical

Polyuria, polydipsia, nocturia, weight loss Polyphagia (often not present in children and new onset Type I diabetes with ketosis) Vomiting, headache, abdominal pain If known diabetic, ask insulin dose and regime (units/kg/day) and time of last insulin. If they have an insulin pump, ask about last site change and if any problems occurring. Assess for symptoms or FH of autoimmune disease (e.g. DM, thyroid dx, Vitiligo, Rheumatoid Arthritis, SLE, Celiac disease, Multiple Sclerosis,etc.) ABCs With DKA, look for hypotension or Cushings triad Assess hydration status Looks for signs of infection and evaluate neurologic status Plot on growth chart/BMI: Obesity see Dysmetabolic section. If short stature, think celiac dx, thyroid dx, or adrenal dx. Thyroid exam Skin: Acanthosis nigricans, striae, vitiligo Pubertal status

Laboratory Fingerstick blood glucose Stat BMP and urinalysis (dipstick okay). +/- Blood gas. New onset diabetic: HbA1C, GAD 65 Ab, ICA 512 (IA-2) Ab, Insulin Autoantibodies Thyroid functions (when out of DKA): TSH, Total T4, anti-peroxidase and anti-thyroglobulin antibody Test for celiac disease only if symptomatic (tissue transglutaminase IgA with concurrent total IgA for validation) If obese consider insulin level or C-peptide level. Lipids and urine for microalbumin should be checked as outpatient when sugars better controlled. Blood glucose checked qac, qhs, and 0200 (0200 may be omitted in established diabetics). Will vary with insulin plan.

93 Urinary ketones should be checked for all sugars >240. If positive, check urine for ketones with next blood sugar. Consult Endocrinologist on call. THERAPY Sliding Scale with Regular Insulin: Can use for mild-moderate DKA treated on the floor or if initiation of insulin is not immediately conducive wt(kg)/8 = #units for BS 150-200, then add 1-2 for every 50 above 200. This is for Regular insulin. Usually start insulin at 1unit/kg/day, less than age 5 start 0.6-0.8 units/kg/day. Insulin regime: Split-fixed (3 shot method): This method requires less injections but involves a fixed diet. 2/3rd total dose before breakfast 2/3rd as intermediate acting insulin (i.e. NPH) 1/3rd as short or rapid acting insulin (i.e. Regular or Humalog/NovoLog/Apidra) 1/3rd total dose in PM 1/3rd as short or rapid acting insulin before dinner 2/3rd as intermediate acting insulin at Bedtime Basal-Bolus (Multiple Daily Injection, MDI): This method is diet flexible but requires more injections. Long acting insulin (e.g. Lantus, Levemir): 40-60% of total daily dose given at bedtime Rapid acting based on carb counting with meals. The insulin:carb ratio is determined by dividing 500 by the total daily dose of insulin. Example: In a 50 kg child receiving 1unit/kg/day, they would receive 1 unit of rapid acting insulin per every 10 grams of carbs. Give a correction formula: Blood sugar target glucose divided by sensitivity factor. *The target glucose is usually 120. *Sensitivity factor: If insulin sensitive divide 1800 by total daily dose of insulin. If insulin insensitive divide 1500 by total daily dose of insulin. You can give meal bolus and correction insulin concurrently Alternate insulin regimes may be used at the discretion of Endocrinology INSULIN PREPARATIONS Rapid: 5-15minute onset. Peak 1-2hours. E.g. lispro (Humalog), Aspart (NovoLog), Glulisine (Apidra). Often used with insulin pumps and other basalbolus plans. Short: 30 minute onset. Peak 2-4hours. Regular (Humulin R/Novolin R) Intermediate: 2 hour onset. Peak 6-10 hours. Duration 10-18hours. NPH (Humulin N/Novolin N)

94 Long: 1-2 hour onset with 24hour duration (peakless). E.g. Glargine (Lantus), Detemir (Levemir). Often used with basal-bolus regimen. HYPOGLYCEMIA IN THE DIABETIC If awake and alert, give 15 grams of carbs and reassess in 15 minutes. If not, give Glucagon kit IM/SQ (available on the floor). Watch for emesis. DKA MANAGEMENT Initial Management Place 2 large bore IVs Bolus 10-20cc/kg NS over 1hour, reassess after first bolus Do NOT give insulin bolus. Anticipate starting insulin after fluid bolus. Sodium Bicarbonate should be avoided unless hemodynamic instability. PICU admission required for altered level of consciousness, need for insulin drip, etc. Nursing Orders Cumulative I&Os Vital signs with neuro checks q1hour Ranitidine 1.5mg/kg/dose IV q8hours (max 50mg/dose) Consider an arterial line (1unit heparin per cc NS @3cc/hour) if repeat blood draws needed. Fluid Management Calculate fluids by adding maintenance fluids, fluid deficit, and ongoing losses. Subtract the rate of the insulin drip and arterial line fluids. This is usually 1 MIVFs. Fluid requirement should be replaced over 36 to 48 hours. (Hypernatremic dehydration over 48hours). Do not give more than 4L/m2/day. Mindful to try to limit Chloride infusion. Insulin Infusion Began insulin infusion at 0.1units/kg/hour. Use Regular insulin. The goal is for the glucose to decrease at a rate of 75-100mg/dl/hour. Adjust as rate as needed. Monitoring Q1hour: Bedside glucose, VS, neuro checks, and cumulative I&Os Q2hour: BMP, Phosph, serum osmolality. +/- Blood gas Q6-12hours: urine glucose and ketones Consider following urine ketones until clear. Transition to Maintenance Therapy The time to transition, and the type of insulin to switch to, hinges on clinical presentation, patients home insulin regimen (if available) and time of day.

95 If transition occurs at usual meal time, you can use the past (or projected) home regimen. If transitioning at other times, you may wish to first use a temporary sliding scale of Regular insulin. Consult Endocrinology if not already done. Start po fluids (sugar-free) when HCO3 >15-18. If using a spit fixed insulin regime, give Regular SubQ insulin 30minutes before 1st meal and then feed. Turn off insulin infusion and dextrose fluids 30min after SubQ Regular insulin given. If using a basal bolus insulin regime, turn off the insulin infusion and dextrose fluids at the same time the Rapid acting insulin is given. Depending on the time of day, the basal insulin (i.e. Lantus) may be given. If Lantus is not given immediately, give the correction insulin (see formula above) until it is time for the basal insulin. When doing this it is important to follow glucoses q2hours so corrections can be given. Reassess patients need for persistent IVFs. NOTES

96

Adrenal Crisis
Adrenal crisis: hypotension (may be postural), mental status changes, or shock Non-acute: weakness, fever, abdominal pain, vomiting, dehydration Metabolic disturbance: hyponatremia, hyperkalemia, hypoglycemia, and acidosis Physical exam: hyperpigmentation (fingernails, gums, elbows, knees, palms) DIAGNOSIS BMP, glucose, ACTH, cortisol If electrolyte abnormalities, check aldosterone and renin. In infants (esp. with ambiguous genitalia), check 17-hydroxyprogesterone Interpret random cortisol levels in the context in which they were drawn. Cosyntropin stimulation testing can aid in diagnosis. ACTH and cortisol should be drawn at baseline. Dexamethasone does not interfere with testing. To diagnose a primary adrenal source, 250mcg is given and cortisol is checked in 1hour. A level 18mcg/dl or lower is abnormal. To diagnose a central source, 1mcg Cosyntropin is given and cortisol is checked at 10 minutes and repeated at 30 minutes. TREATMENT AND MANAGEMENT ABCs If patient is hypotensive, bolus NS 20cc/kg, repeat if necessary If patient is hypoglycemic, 2cc/kg of D25 (centrally) or 5cc/kg D10 Fluids should be given at 1.5-2 times maintenance Correct life-threatening electrolyte abnormalities (hyperkalemia) Other electrolyte abnormalities may correct with the institution of therapy Identify precipitating condition (i.e. infection) and treat appropriately Need to give stress dose of glucocorticoid (hydrocortisone) in cases of acute adrenal crisis. This is 2-3 times the normal physiologic replacement dose Physiologic dosing: Hydrocortisone NaSuccinate (Solu-Cortef) 7-15mg/m2 BSA/day po Stress Dosing: Solu-Cortef load 25-50mg/m2 BSA IV bolus then 100mg/m2 BSA/day IV continuous infusion or divided q6hours See Quick calculations for BSA calculation When stable, the dose should be tapered back to maintenance and changed to po Stress mineralocorticoid replacement is generally not necessary if giving hydrocortisone Mild hyponatremia may exist as cortisol is required to excrete free water If patient is a salt loser use Florinef 0.05-0.2mg/day (only available po) for mineralocorticoid replacement

97 BIOEQUIVALENCY OF GLUCOCORTICOIDS 1mg of prednisone equivalent to 4mg hydrocortisone 1mg of prednisolone equivalent to 5mg hydrocortisone 1mg dexamethasone equivalent to 50-100 mg hydrocortisone Dexamethasone and Methylprednisolone have no mineralcorticoid effect Prednisone and prednisolone have less mineralcorticoid effect than hydrocortisone NOTES

98

Hypoglycemia
The definition of pathologic hypoglycemia is defined as serum glucose (not fingerstick) less than 40mg/dl. Symptoms may include altered mental status, nausea, tremor, pallor, or seizure. ETIOLOGY Ketotic Hypoglycemia: most common etiology. Seen in thin children age 18mo5years. Male predominance. Symptoms with prolonged fasting or illness. Unknown etiology. Prevention with frequent complex carbs and protein. May need to teach families to monitor for ketones during illness. Hyperinsulinism: Insulin overdose, Infants of diabetic mothers, congenital hyperinsulinism (focal vs. diffuse), insulinomas (rare) Adrenal (cortisol) or Growth Hormone Deficiency, Hypopituitarism Drugs: Alcohol, oral hypoglycemics, recent steroid use (iatrogenic adrenal insufficiency), Aspirin, Iron, unripe Ackee fruit Inborn errors of metabolism (IEM): Fatty Acid Oxidation Disorders (e.g. MCAD deficiency), Carbohydrate Metabolic Disorders (e.g. Galactosemia, Hereditary Fructose Intolerance), Glycogen Storage Disorders (eg.von Gierke Disease), Amino Acidopathy (e.g. Organic acidurias, Maple Syrup Urine Disease) Sepsis or other hypermetabolic states Dumping syndrome (children with Gtube/Nissen) EVALUATION Historical Facts: diet, new foods, medications, developmental delay, FH, social history (exposure to alcohol) Plot on growth curve: Short stature concerning for endocrine/IEM etiology Physical Exam: Organomegaly (IEM), hyperpigmentation (primary adrenal), and look for midline defects (i.e. microphallus, small optic nerves, cleft lip/palate, central incisor (i.e. hypopituitarism)). It is important to collect critical sample while the patient is hypoglycemic.

99 CRITICAL SAMPLE Serum Glucose ( confirmation of fingerstick) Red Top (3-5cc, iced) for Cortisol, Growth Hormone, Insulin and/or C-peptide Red Top (3-5cc) refrigerate for possible later use Urinalysis (ketones/reducing substances) Other lab tests: CMP, Ammonia need not be done at time of hypoglycemia If symptoms recurrent or suggestive of IEM, workup should include: serum amino acids, urine organic acids, plasma acylglycines, free/total carnitine profile (to Greenwood Genetics), ideally during acute episode but can be done later. If suspect insulin overdose, workup should include: insulin, pro-insulin, and Cpeptide. Ketones are not seen with hyperinsulinism, fatty acid oxidation defects, or Glycogen Storage Diseases Nonglucose reducing substances are seen with Galactosemia and Hereditary Fructose Intolerance Acidosis and elevated ammonia suggest IEM Insulin level over 2-3 micro-IU/ml or insulin to glucose ratio > 0.25 suggests hyperinsulin state Low C-peptide with elevated insulin suggests exogenous administration TREATMENT Bolus with 5cc/kg of D10 peripherally or 2cc/kg of D25 centrally Begin continuous infusion of D10 at a rate to provide 6-8mg of glucose/kg/min (3.6-4.8cc/kg/hr). Formula for Glucose Infusion Rate (see Quick Calculations). If >10-15mg glucose/kg/min required, consider hyperinsulinemic state. Consult Endocrine and consider starting oral diazoxide (3-8mg/kg/day given TID, 15mg/kg/day given TID for infants), somatostatin, or glucagon. Further treatment is guided by suspected underlying pathology. NOTES

100

Puberty
Normal ages of onset: Males 9-14 and Females 8-13. There is controversial data suggesting that Caucasian girls in North America may have normal pubertal onset after age 7 and African-American girls after the age of 6; however, earlier onset does not negate the need for some evaluation. Pulsatile secretion of LH and FSH (gonadotropins) heralds the onset of puberty leading to gonadal maturation and production of the sex steroids. Random LH and FSH may not be helpful in evaluation of precocious puberty. They are helpful when evaluating delayed or late puberty. Clinically, maturation of the hypothalamic-pituitary-adrenal (HPA) axis parallels the activation of the hypothalamic-pituitary-gonadal (HPG) axis leading to adrenarche (pubic/axillary hair, acne). Biochemically, adrenal DHEA-sulfate (DHEA-S) may be measurable before gonadal steroids. In Girls, thelarche is typically the first sign of true puberty. Peak linear growth rate in height occurs at Tanner II-III. Menarche occurs at Tanner IV (2 years after thelarche). Signs of virilization: clitoromegaly, hirsuitism, male patterned (temporal) baldness, recalcitrant acne, deepening of the voice Signs of estrogen: breast tissue, thickened, pink vaginal mucosa, menses, and increased height velocity In Boys, testicular enlargement is the first sign of true puberty. They have a higher peak growth velocity and longer duration of growth (occurs at Tanner IV). It is important to follow the rate of growth. Early rapid growth is abnormal. Obtaining a bone age is essential for the workup of abnormal puberty. This is a film of the left hand/wrist. Under age 2, a left hemi-skeleton should be requested. It is considered abnormal if a difference of 2 standard deviations exists (typically >2years). PRECOCIOUS PUBERTY Defined as Girls < 8 and Boys < 9 True Puberty (gonadotropin dependent) Normal cascade of events with activation of HPG axis. +/- adrenarche Etiologies include: idiopathic, CNS lesions, non-progressive CNS disorders (CP) In girls, this is most likely idiopathic while in boys it is most likely pathologic Rapid progression through stages is abnormal Complete neurologic exam needed (including visual fields) Workup includes: Gender-specific sex steroid (sensitive estradiol in girls and total testosterone in boys), total T4, TSH, and consider LH, FSH, and DHEA-S 2nd tier includes MRI of brain with contrast and hypothalamic-pituitary cuts (1st tier if concerning history or physical findings) False Puberty (gonadotropin independent, peripheral precocious puberty) Does not proceed through normal order of pubertal events.

101 Etiology secondary to abnormal sex steroids from gonads/adrenal gland or exogenous (ingested, topical) source. McCune-Albright syndrome or severe hypothyroidism can do this as can, rarely, HCG secreting tumors (in boys). Premature Pubarche (only pubic hair) and/or Adrenarche (pubic and axillary hair): Etiologies include benign premature adrenarche, simple virilizing/nonclassic congenital adrenal hyperplasia, and virlizing drugs/tumors (includes anabolic steroids, creams/lotions). Initial w/u includes 17-hydroxyprogesterone, total testosterone, DHEA-S, and a bone age. Premature Adrenarche: Most common cause of early pubarche. Benign elevation of adrenal androgens (DHEA-S). No growth acceleration, advanced bone age, rapid progression, or virilization. Premature Thelarche: Appearance of breasts prior to age 8. No evidence of growth acceleration, rapid progression, or other signs of estrogen exposure. If present consider bone age, sensitive estradiol, total T4, and TSH. If labs abnormal proceed with pelvic ultrasound. 10% evolve to true precocious puberty. Actually not an uncommon finding in girls ages 18-24 months. Premature menarche: Rare presentation of precocity. If no other evidence of sexual maturation exists, ovarian disease (dominant cyst or malignancy) must be excluded. Rule out foreign body, infection, abuse/trauma, or local neoplasm. Evaluation includes sensitive estradiol, T4, TSH, pelvic ultrasound and bone age. DELAYED PUBERTY Defined as Girls > 13 and Boys >14 Absence of menarche by 16 Arrested puberty when menarche occurs 5years after normal thelarche Confusing nomenclature: late puberty is normal puberty but along the latter end of the normal timing of adolescence. Delayed puberty is when the signs of puberty occur after the above noted ages. Historical facts: chronic illness, anosmia/hyposmia, colored-blindness, signs of hypothyroid, Family history Physical Exam: Measurement of growth, assess pubertal status (Tanner staging), stigmata of Turner Syndrome or other genetic disorders, complete neurologic exam (includes visual fields; may need to assess olfactory sense or color perception (can be done in the Endocrinology Office)) Initial evaluation includes LH, FSH, thyroid functions, and bone age Hypergonadotropic Hypogonadism (increased LH/FSH): Turner syndrome, Klinefelter syndrome, Bilateral gonadal failure (traumatic, postinfectious (mumps), galactosemia (poorly controlled esp. in girls), autoimmune, iatrogenic (post-surgical), vanishing testes syndrome) Turner Syndrome: Most common cause of ovarian failure in females. All significantly short females, and especially those with pubertal delay warrant a karyotype to rule this out. Request 50-100 cells to exclude mosaic Turner. May have minimal breast development; menses rare. Adrenarche typically normal.

102 Normal to low Gonadotropins: Constitutional Delay, Hypothalamic dysfunction, Chronic Illness, Hypopituitarism, Hypothyroid, Hyperprolactinemia, Kallman syndrome (isolated Gonadotropin deficiency) Constitutional Delay: Pubertal increase in gonadotropins is slow to develop. More common in boys. Usually + family history. Evaluation normal except delayed bone age consistent with pubertal stage and height age. Amenorrhea with normal pubertal development: Rule out pregnancy and Rokitansky syndrome. Consider thyroid functions, prolactin, pelvic ultrasound. Gyn referral to assess anatomy. Polycystic Ovarian Syndrome/Hirsutism: Associated with obesity, glucose intolerance, and anovulatory cycles. Differential diagnosis includes late-onset CAH. Work up includes free testosterone, 17-hydroxyprogesterone, and fasting insulin with glucose, T4 (free T4 may be superior here). Treatment may include Metformin and/or OCPs. NOTES

103 NOTES

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FLUIDS AND RENAL

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Acute Renal Failure

When the diagnosis of ARF is entertained, one must rule out severe dehydration. Oliguria/anuria and azotemia are often seen in the setting of ARF. Oliguria is defined as urine output less than 0.5 ml/kg/hr in infants or less than 500cc/m2 per day in older children. Anuria is defined as total cessation of urinary output. ARF occasionally presents with high urine output (high output failure). There are several laboratory parameters that will help in identifying the location of pathology (prerenal vs. renal vs. postrenal). One such parameter is the fractional excretion of sodium (Una/Pna)(Pcr/Ucr) x 100. The FENa is typically less than 1% in prerenal failure and over 2% in renal failure. Urinary Indices to Classify ARF Urine OSM Urine NA FENa% >500 <20 <1% >350 <2.5%(Newborn) (newborn) <350 >40 >2.5% >350 >60 ETIOLOGY Pre-Renal Disease Hypoperfusion of the kidneys is secondary to a decreased effective circulating blood volume. It can occur in these clinical settings: Hypovolemia Hyper/normovolemia Dehydration Congestive heart failure Hemorrhage Hepatorenal syndrome DI Cardiac tamponade Insensible losses (burns) 3rd space losses (sepsis, cap leak, NS) Lab findings in Pre-Renal Disease BUN>>Cr Uosm > 400-500 Una < 10-20 FENa < 1% Intrinsic Renal Disease Acute Tubular Necrosis (ATN) Ischemic/hypoxic injury

Classification Prerenal

Renal Postrenal

107 Evolution of pre-renal failure as vasoconstriction leads to tubular injury and necrosis Labs: BUN, Uosm < 350, Una > 30-40, FENa> 2 U/A: protein, WBCs, granular casts Nephrotoxic ARF Drugs: aminoglycosides, amphotericin B, acyclovir, NSAIDS, IV contrast, Chemotherapy Labs: same as ATN Exogenous toxins Ethylene glycol, methanol, heavy metals Labs: large anion gap metabolic acidosis, hypocalcemia, U/A: hematuria, Ca oxalate crystals Endogenous toxins Hemoglobinuria Myoglobinuria Labs: metabolic acidosis, CPK, hyperkalemia, heme + urine Nephropathy of malignancy ALL B-cell lymphoma Labs: hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia Acute Interstitial nephritis Drugs: penicillins, NSAIDS, sulfonamides, rifampin, lasix, cimetidine Post-infectious Idiopathic Labs: U/A: eosinophils, WBC casts Eosinophilia Acute glomerulonephritis Post infectious, IgA Nephropathy, SLE, HSP, MPGN, Wegeners granulomatosis, Goodpastures disease Labs: gross hematuria, proteinuria, RBC and/or WBC casts, Low C3, C4, +ANA, ANCA, anti-GBM Ab Vascular Disease HUS Thrombosis- renal artery, renal vein Cortical necrosis Labs: hemolytic anemia, thrombocytopenia, hematuria/proteinuria Post-Renal (Obstruction) Bladder outlet obstruction (PUV) Ureteropelvic junction obstruction (UPJ) Ureterovesicular junction obstruction (UVJ) Labs: hydronephrosis, Type IV RTA

108 EVALUATION Urinalysis and culture Urine osmolality, creatinine, and sodium CBC CMP Magnesium and phosphorous Renal ultrasound or other imaging study Renal biopsy in certain cases Other tests as indicated: CPK, urine myoglobin, C3, C4, ASO, ANA MANAGEMENT Remove any offending agent Fluid balance: Hypovolemia vs. Euvolemia vs. Hypervolemia Therapy for prerenal failure involves volume replacement and treatment of the underlying condition that resulted in prerenal failure. Initial fluid administration of isotonic saline (10-20 cc/kg/dose) should be used to restore intravascular volume. Monitor strict Is and Os, weights (BID or more often if needed), vital signs, capillary refill, skin turgor. For the oliguric euvolemic patient, start fluids to replace insensible loss ( 1/3 maintenance) + urinary losses cc for cc. Watch for polyuric recovery phase Initiate therapy for complications such as hyponatremia, hyperkalemia, metabolic acidosis, hypocalcemia, hyperphosphatemia, and hypertension should they arise RENAL REPLACEMENT THERAPY Indications Childs age, Cause of ARF, Rapidity of onset Electrolyte abnormalities Nutritional issues Fluid overload Modalities Hemodialysis: aggressive solute and water removal over limited period of time by passing blood through artificial filter with countercurrent dialysate flow. Advantages include rapid correction of metabolic disturbances. Treatment of choice for toxin removal. Disadvantages include large venous access required, difficult if hemodynamically unstable. Peritoneal Dialysis: solute and water exchange from peritoneal capillaries into dialysate instilled into the peritoneal cavity. Ultrafiltration is driven by osmotic pressure gradient generated by dextrose. Advantages include relatively easy to

109 perform, vascular access not required, does not require hemodynamic stability. Disadvantages include slower correction of metabolic disturbances, risk of peritonitis, less control. CRRT: continuous more gentle removal of solute and water by passing blood through artificial filter +/- countercurrent dialysate flow. Advantages include tighter control, safe for hemodynamically unstable patients. Disadvantage requires sedated patient and vascular access. NOTES

110

Fluids and Electrolytes

GENERAL PRINCIPLES Total body water as a % of body water decreases with age. TBW is comprised of the intracellular (2/3) and extracellular (1/3) compartments. TBW equals Birth: wt(kg) x 80% 6 mo: wt(kg) x 75% 1-15 yr: wt(kg) x 65% Adult: wt(kg) x 50-60% MAINTENANCE REQUIREMENTS Surface Area Water: 1500-1800 ml/m/day NA+: 30-60 mEq/m/day K+: 20-40 mEq/m/day Weight Water: 0-10 kg = 100 ml/kg/day 11-20 kg = 1000ml + 50 ml/kg over 10 kg >20 kg = 1500 ml + 20 ml/kg over 20 kg Na+: 3-4 mEq/kg/day K+: 1-2 mEq/kg/day ASSESSMENT OF DEHYDRATION The degree of dehydration can be determined clinically from history and exam. Serum sodium is necessary in order to determine the type of dehydration (hypotonic, isotonic, or hypertonic). Sign and Symptoms 5% Decreased fluid intake Postural pulse change No change Postural DBP change No change Fontanel/skin turgor Mucous membranes Tears Urine output Urine SG BUN Urine Na/FENa Hct/Albumin Normal Normal Present Normal/slight decrease Normal Normal Normal Normal 10% 10 beats/min 10 mmHg Dry Reduced Oliguria 15% or frank hypotension Very dry Severe oliguria or anuria

111 HYPOTONIC AND ISOTONIC DEHYDRATION For hypotonic (sodium less than 130) or isotonic (sodium 130-150) dehydration, rehydrate over 24 hours by giving 50% over the first 8 hours, then the remainder over 16 hours. Calculate fluid and electrolyte replacement as follows: Water Replacement Maintenance + Deficit = Total water needed. Wt1 = present wt in Kg, Wt2 = calculated rehydrated weight Deficit: Pts Wt2 = Wt2/(100 - % dehydration) Rehydrated weight (Wt2) present weight (Wt1) = deficit water (1gm=1ml) Sodium Replacement Maintenance Sodium + Deficit Sodium + Corrected Sodium (hypotonic only) = total sodium needed in mEq for the next 24 hours. Maintenance Sodium: 3-4 mEq/kg/day or 30-60mEq/m2/day Deficit Sodium: Assume water loss is isotonic. Therefore, 140 mEq/L x water loss in liters equals deficit sodium in mEq. Corrected Sodium: (135-actual Na) x 0.6 x Wt (kg) Convert total sodium over total water to amount/liter to write fluid orders.

Potassium Replacement If not acidotic (HCO3 > 18): K < 3.5 give 40 mEq/L K 3.5-5.0 give 20 mEq/L K > 5.0 give none initially If patient is acidotic K < 4.0 give 40 mEq/L K 4.0-5.0 give 30 mEq/L K 5.0-6.0 give 20 mEq/L K > 6.0 give none initially Example: 8 kg child who at 0.4 m is clinically 8% dehydrated, admission sodium is 125. Maintenance water: (1500)(0.4) = 600cc Rehydrated weight: 8/100-8% = 8.7 kg Water deficit: 8.7 kg - 8.0 kg = 0.7 or 700cc Total water needed = 600cc + 700cc= 1300cc Maintenance sodium = (40mEq)(0.4m) = 16 mEq Corrected sodium = (135-125)(0.6)(8kg) = 48 mEq Deficit sodium = (140 mEq) (0.7) = 98 mEq Total sodium = 16 + 48 + 98 = 162 mEq Fluid concentration = 162mEq = 124 meEq = approximately 0.75 NS 1300cc 1000cc

112 Order written as follows: D5 0.75 NS at 81 cc/hr x 8 hours, then 40 cc/hr x 16 hours HYPERTONIC DEHYDRATION Hypertonic dehydration is corrected slowly over 48 hours with D5 0.2 to D5 0.45 NS. If re-hydrated too quickly, there is a risk of cerebral edema. Monitor serum sodium closely. METABOLIC ACIDOSIS If initial HCO3 < 12 then replace as follows: (12 serum bicarb) x 0.6 x Wt(kg) = mEq of NaHCO3 needed. Administer over 8 hours. Remember that for every mEq HCO3, a mEq of NA is given and this should be considered when calculating sodium needs. SYMPTOMATIC HYPONATREMIA Severe hyponatremia can lead to mental status changes and seizures. Symptomatic hyponatremia should be corrected with 3% saline. (120 serum NA) x (weight in kg) x (0.6) = number of mEq of sodium needed 3 % saline contains 0.513 mEq Na/mL. Administer the volume necessary in ccs to correct the sodium over 10-15 minutes In an emergent situation, 12cc of 3% saline per kg should raise the patients serum sodium by 10 HYPOMAGNESEMIA For serum magnesium level less than 1 mg/dl (<0.4mmol/l), treat with magnesium sulfate(50% solution) Typical dose is 50 mg/kg up to max of 2 grams per dose Should be given IV slowly INTERPRETING AND CORRECTING POTASSIUM LEVELS Serum potassium levels should be interpreted in the context of the patients clinical status, acid/base status, ECG findings, and urine output. Samples obtained by heel stick often are hemolyzed which will falsely elevate the potassium level. Thrombocytosis will also falsely elevate the potassium level. If it is felt that the potassium level is falsely elevated, a repeat level should be obtained by venous stick. Hypokalemia Treat with 1 mEq/kg/dose of KCL given at rate of 0.5 mEq/kg/hour for symptomatic hypokalemia. The patient should have continuous ECG monitoring during replacement. If pt is asymptomatic, replacing potassium by the PO route is preferred.

113 Hyperkalemia The emergent treatment of hyperkalemia is designed to stabilize the cardiac membrane and drive potassium into the cells. Depending on the degree of ECG changes present the treatment varies. 1-2 mEq/kg NaHCO3 over 20 minutes for T wave changes For widened QRS complex or rhythm changes, give 10% calcium chloride 10-20 mg/kg over 5 minutes. May be repeated twice. If necessary, may give glucose 1-2 grams/kg and regular insulin 0.3 units/gram of glucose. Infuse over 2 hours. Then if necessary, Kayexalate 1gm/kg PO in 70% sorbitol or PR in 30% sorbitol. Beta agonists, such as albuterol aerosols, also drive the potassium intracellularly HYPOCALCEMIA Hypocalcemia is defined as a total serum calcium of < 7.0 mg/dl or an ionized calcium < 3.5 mg/dl (0.87 mmol/l). In an asymptomatic patient, hypocalcemia should be corrected with oral supplements. If the patient is symptomatic or hemodynamically compromised, the calcium should be corrected IV preferably through a central line. Use IV calcium cautiously due to possibility of extravasation and subsequent necrosis of surrounding tissue. Calcium Chloride (10%) 20mg/kg to max of 1 gram per dose. The patient should have cardio-respiratory monitoring during administration. Give slowly. Calcium Gluconate (10%) 50 mg/kg to max of 2 grams per dose Exclude hypomagnesemia NOTES

114

Rickets
Vitamin deficiency rickets remains a significant cause of nutritional disease in infants. Vitamin D deficiency is more common among breastfed than formula fed infants. In addition, African American infants are at increased risk because of decreased production of vitamin D in the skin. Decreased sunlight exposure during the winter months also increases the risk for developing rickets. PATHOGENESIS There are 2 sources of Vitamin D- cholecalciferol and ergocalciferol Ergocalciferol- vitamin D2, obtained exogenously from the diet Cholecalciferol- vitamin D3, produced endogenously in the skin following exposure to ultraviolet radiation Vitamin D is hydroxylated in the liver to 25-hydroxyvitamin D and subsequently in the kidney to 1,25-dihydroxyvitamin D As 25-hydroxyvitamin D levels decrease, PTH increases the activity of 1-alpha hydroxylase enzyme in the kidney to increase 1,25-dihydroxyvitamin D levels. The end result is increased mobilization of calcium from the bone matrix leading to the development of rickets. PREVENTION OF RICKETS AND VITAMIN D DEFICIENCY It is recommended that all infants, including those who are exclusively breastfed, have a minimum intake of 200 IU of vitamin D per day beginning during the first two months of life. All infant formulas are supplemented with Vitamin D to provide 400 IU/L. Thus, if an infant is ingesting at least 500cc (approximately 16 oz) per day of formula, he or she will receive the recommended vitamin D intake. PRIMARY PRESENTATION Incidental finding on radiograph or physical exam- craniotabes, enlargement at the wrist and ankles or costochondral junctions, coxa vara, scoliosis Failure to thrive/short stature Nonspecific musculoskeletal complaints Delayed development Seizures Tetany Weakness RADIOGRAPHIC FINDINGS IN VITAMIN D DEFICIENCRY RICKETS Widening of metaphysis Cup shaped metaphysis Osteopenia

115 Rib flaring- rachitic rosary Multiple fractures in various stages of healing LABORATORY EVALUATION CMP Mg and Phos PTH 25-hydroxyvitamin D 1,25-hydroxyvitamin D Long bone radiographs CAUSES OF HYPOCALCEMIA AND THEIR BIOCHEMICAL PROFILE CLUES
Serum Causes of Hypocalcemia Vitamin D-deficient Rickets Vitamin D-dependent Rickets: type 1 Vitamin D-dependent rickets type II Ca P PTH Alk Phos 250HD3 1, 25(OH)2 * Mg Urine Ca

Vitamin D Resistant rickets (hypophosphatemic rickets) Hypoparathyroidsim

Pseudohypoparathyroidism Rickets of prematurity Renal osteodystrophy Calcium-sensing receptor defect Mg deficiency

** **

Ca= calcium, P=phosphorus, PTH= parathyroid hormone, alk phos= alkaline phosphatase, Mg= magnesium, = normal, = decrease, = increase, ?= difficult to interpret owing to different degree of renal immaturity in preterm infants, *= decrease or normal or increase, **= decrease or normal or slight increase (relatively low for degree of hypocalcemia).

116

TREATMENT AND MANAGEMENT Vitamin D supplementation may be initiated once laboratory and radiologic tests confirm the diagnosis. Most experts recommend administration of oral vitamin D (ergocalciferol- 2000-5000 IU/day). Continue supplements until serum alkaline phosphatase levels and skeletal deformities return to normal. NOTES

117

Renal Tubular Acidosis

Renal Tubular Acidosis is a clinical syndrome characterized by impaired renal acidification due to either impaired reabsorption of bicarbonate or impaired excretion of hydrogen ions. This results in a hyperchloremic metabolic acidosis with a normal anion gap. METABOLIC ACIDOSIS Normal anion gap (AG = Na (Cl+CO2), normal 12 mEq/l +/- 2) RTA GI loss of bicarbonate from diarrhea, fistula, or s/p GI surgery Increased anion gap MUDPILES CLINICAL MANIFESTATIONS FTT Polyuria Constipation Vomiting Nephrocalcinosis/nephrolithiasis Rickets TYPE I DISTAL RTA Distal tubule is impaired and cannot excrete acid due to defect in H+ secretion. Common features and associated findings include: Nonanion gap hyperchloremic metabolic acidosis Urine pH inappropriately high ( > 5.5) Variable potassium abnormalities- Hypokalemia- diminished Na+ reabsorption causes volume contraction and secondary hyperaldosteronism Hypercalciuria Hypocitriuria Nephrocalcinosis/nephrolithiasis Bone dissolution Sensorineural deafness MAJOR CAUSES OF TYPE I DISTAL RTA Primary Idiopathic/sporadic Familial

118 Autosomal dominant Autosomal recessive Secondary Genetic diseases- Ehlers-Danlos, Wilsons, Fabrys, Marfan, Sickle cell Autoimmune-SLE, Sjogrens, Thyroiditis, Rheumatoid arthritis Nephrocalcinosis- Idiopathic hypercalciuria, Hyperparathyroid, Vit D intoxication Obstructive uropathy, chronic pyelonephritis, transplant rejection Drugs- Amphotericin B, Lithium, Ifosfamide TYPE II PROXIMAL RTA Characterized by impaired capacity of the proximal tubule to reabsorb bicarbonate. Associated with decreased renal bicarbonate threshold. Features include: Hypokalemia- due to secondary hyperaldosterism- more common and severe than in Distal RTA Loss of glucose, amino acids, phosphate, bicarbonate, and uric acid in the urine secondary to Fanconis syndrome Rickets Urine pH may be either high or low depending on serum bicarbonate level MAJOR CAUSES OF TYPE II PROXIMAL RTA WITH/WITHOUT FANCONI SYNDROME Primary Idiopathic/sporadic Familial Cystinosis Tyrosinemia Galactosemia Hereditary fructose intolerance Glycogen storage disease Wilsons disease Lowes syndrome Acquired Malignancy Multiple myeloma Renal transplant Heavy metals-lead, mercury, copper Carbonic anhydrase inhibitors TYPE IV RTA Due to either aldosterone deficiency or aldosterone resistance (obstructive uropathy). Type IV is the most common form of RTA. Features include: Hyperkalemia

119 Urine pH usually < 5.5

Conditions associated with Type IV RTA Hypoaldosteronism DM, Addisons, interstitial nephritis, SLE, NSAIDs, Nephrosclerosis, Amyloidosis Aldosterone-resistance states Obstructive uropathy Tubulointerstitial diseases LABORATORY EVALUATION Tier I Tier II

Urine electrolytes (Urine Na + K- Cl). Determine urinary anion gap BMP (venous) Phosphorous U/A, Urine culture Urine Ca/Cr ratio Renal ultrasound Serum uric acid Urine AA Tubular reabsorption of phosphate Fractional excretion of bicarbonate Bone films Aldosterone/renin levels (if suspect Type IV) TREATMENT OF RTA

Type I- Replacement bicarbonate (average dose 3.5 mEq/kg/day), K Citrate supplementation as needed. Type II- replacement bicarbonate usually requires more alkali therapy than Type I- dose can be as high as 14 mEq/kg/day. K+ supplementation. Phosphate supplements if rickets present. Type IV- bicarbonate replacement- 1.5-2 mEq/kg/day. K+ restriction. Surgical repair of obstruction if present.

120

OVERVIEW OF RTA Type I Impaired distal acidification Type II Impaired proximal bicarb reabsorption Fanconi- waste bicarb,glu/phos/aa/uric acid Usually 12-20 mEq Variable Low/normal Negative Rickets Fanconi Type IV Decreased aldosterone secretion or resistance

Defect

Serum Bicarbonate Urine pH Plasma K+ Urine anion gap Comments

Variable, <10 mEq Greater than 5.5 Low or high Positive Nephrocalcinosis Hypercalciuria

Mildly acidotic Usually < 5.5 High Positive Obstructive uropathy

NOTES

121

Hematuria
DEFINITION Hematuria is defined as 5 or more red blood cells per high power field on a spun urine sample on at least 2 weekly urines (Dipstick only helpful if negative). PREVALANCE 4-6% of asymptomatic school age children on a single specimen. CLASSIFICATION Functional- strenuous exercise, fever, dehydration Isolated/Asymptomatic- microscopic, gross, or intermittent gross with persistent micro Non-Isolated/Symptomatic- microscopic, gross, intermittent gross with persistent micro

Isolated Hematuria- lack of associated history, symptoms, physical exam findings (nl growth and BP), or other urine abnormalities. May be microscopic or gross. Most likely a benign process when microscopic hematuria only. Factitious Hematuria: A positive dipstick without the presence of RBCs on microscopic exam may suggest hemoglobinuria secondary to hemolysis or myoglobinuria secondary to rhabdomyolysis. Check urine myoglobin. There is also a high false positive rate with the urine dipstick for heme so keep that in mind with the well asymptomatic child. PERTINENT HISTORICAL FACTS Birth history: asphyxia, umbilical vessel catherization Preceding infection- URI, Strep, Impetigo, Diarrhea Urinary symptoms- dysuria, frequency, presence of gross hematuria, blood clots Abdominal pain or Flank pain, abdominal mass Presence of arthralgias, rash, edema, easy bruising History of HSP Trauma Chronic illnesses, medications FAMILY HISTORY Hematuria Hearing loss

122 Renal failure Stones Cystic kidney disease Recurrent UTI Hypertension Lupus Sickle cell disease Bleeding disorders PHYSCIAL EXAM Growth parameters (short stature or failure to thrive) Blood pressure Fundoscopic exam Signs of fluid overload- edema, ascites, rales, pleural rub, gallop Presence of abdominal bruits Abdominal exam- masses, HSM, pain Skin- rashes, petechiae, purpura ETIOLOGIES OF HEMATURIA Glomerular Benign familial Exercise induced Post-infectious GN IgA nephropathy HSP Alport syndrome SLE Membranoproliferative GN,FSGS,MCNS Nonglomerular renal Hypercalciuria Pyelonephritis Sickle cell disease Polycystic kidney Reflux nephropathy Renal tumor Renal Vein thrombosis Renovascular HTN Nonrenal Stones Cystitis/prostatitis Foreign body Bladder tumors AV malformation Hydronephrosis HUS UPJ

LABORATORY EVALUATION Phase I Complete H&P, Family hx U/A with micro, Urine culture (if symptomatic) Spot urine Ca:Cr ratio UA of first degree relatives Sickle screen if indicated Hearing screen If ALL above is normal, follow BP and U/A yearly. If HTN, proteinuria, or decreased renal function, then proceed to phase II workup. Phase II (Add to phase 1 if gross hematuria present)

123 CBC, BMP, ASO or streptozyme, C3, C4, ANA, Hep B & C Renal ultrasound VCUG if indicated by RUS Phase III Further imaging as indicated Further serology: ANCA, dsDNA Renal biopsy Indications for phase II workup include non-isolated hematuria, gross hematuria, proteinuria, hypertension, significant family history, duration for > 6 -12 months. Indications for renal biopsy include persistent renal insufficiency, persistently low complement levels, coexistent gross hematuria, and as suggested by phase II workup. IDIOPATHIC HYPERCALCIURIA Ca to Cr ratio: >0.2 ( 7 yrs and older) >0.4 (19 mos to 6 yrs) 0.6 (7 to 18 mos) 0.8 (under 7 mos) PROGNOSIS Isolated/asymptomatic microscopic hematuria- excellent prognosis with very low incidence of pathology Asymptomatic gross hematuria- very good prognosis but identifiable causes more likely Non-isolated hematuria- variable and often guarded prognosis NOTES

124

Nephrology Cocktails
CALCIUM AND VITAMIN D Product Calcitriol Calcium Acetate Dose 0.25-2 mcg/day PO or IV 1-2 tablets PO with meals Comments Vitamin D analog. Used to treat renal osteodystrophy Goal phosphorous level < 6. Give with meals to bind dietary phosphorous. Goal phosphorous level < 6. Give with meals to bind dietary phosphorous.

Calcium Carbonate

1-2 tablets PO with meals

OTHERS Renagel Phos level Dose 6-7.5 mg/dl 2 caps TID 7.5-9 mg/dl 3 caps TID >9 mg/dl 4 caps TID 50-100 units/kg three times a week <10 kg = 25 mg 10-20 kg = 50 mg >20 kg = 100 mg Lasix up to 1mg/kg/hr. Albumin (5%) - 0.5-1 gram/kg/dose. Max dose 6 grams/kg/day. NOTES Dosing varies with phosphorous level, but usually is 1-2 capsules TID with meals. When hematocrit 36% then decrease epogen dose by 25% A test dose of of total dose should be given prior to starting therapy. Used for treating fluid overload and occasionally nephrotic syndrome.

Erythropoietin

Iron dextran

Albumin/Lasix

125

Proteinuria
DEFINITION Proteinuria is a fairly common finding in the pediatric patient and may be benign. The first step in evaluation is determining whether the proteinuria is significant or a laboratory phenomenon. False positives can be obtained on the urine dipstick by concentrated or alkaline urine or with certain antiseptics. False negatives can be obtained if the urine is very dilute. MEASUREMENT OF PROTEINURIA Dipstick Random urine protein:creatinine ratio 24 hour urine collection Fractionated 24 hour urine collection (recumbent/upright) Serum albumin DIPSTICKS Trace (10-20mg/dl) +1 (30 mg/dl) +2 (100 mg/dl) +3 (300 mg/dl) +4 (1000 mg/dl) DETERMINING IF PROTEINURIA IS SIGNIFICANT Dipstick Pro/Cr 24 hr urine 1+ if urine SG 1.015 or 2+ if urine SG > 1.015 > 0.5 for age 6 mos to 2yrs > 0.25 for age > 2yrs > 100 mg/m2/day

CLASSIFICATION AND CAUSES OF PROTEINURIA Functional Proteinuria Fever Pregnancy Seizures CHF Emotional stress Exercise Isolated Proteinuria- lack of associated signs or symptoms such as casts hematuria, HTN, renal insufficiency, or growth failure. Negative history.

126 Transient asymptomatic-no long term sequelae. Persistent asymptomatic- proteinuria in 80% of specimens, guarded prognosis. Orthostatic- 60% of children with proteinuria, transient vs. fixed, benign clinical course, should be < 1 gm/24hr. Pathologic Proteinuria Glomerular- FSGS, MCNS, Postinfectious, HSP, SLE, Membranoproliferative, Membranous, IgA nephropathy, Sickle Cell Tubulointerstitial obstructive uropathy, reflux nephropathy, cystic disease, pyelo, toxic or ischemic injury, interstitial nephritis, Fanconi syndrome LABORATORY EVALUATION Phase I Complete history and physical First AM U/A with micro, Urine culture 24 hour split urine collection (recumbent/upright)- label 2 jugs- one AM and one PM. On day 1 of collection, the first morning void is flushed and then all other subsequent voids during the day are collected in the AM jug. During the night, all voids are collected in the PM jug including the first morning void of Day 2. AM and PM random Pro/Cr ratio (if not potty trained) BMP If above consistent with orthostatic proteinuria, follow with yearly first AM urine for U/A and Pro/Cr ratio Phase II CMP CBC Lipid profile C3,C4, ANA, ASO or streptozyme, Hepatitis B and C RUS, +/- VCUG if indicated by the RUS or prior UTI Phase III Further serology- ANCA, ds-DNA, etc. Renal biopsy ORTHOSTATIC PROTEINURIA Benign condition in which the patient spills protein when in the erect position, but not when recumbent 50-60% of otherwise healthy kids with proteinuria (primarily adolescents) Usually < 1000 mg total protein in 24 hrs Transient vs. fixed- both have benign clinical course Follow yearly with first AM urine for U/A and protein:Creatinine ratio

127 NEPHROTIC SYNDROME Nephrotic syndrome is defined by massive proteinuria, hypoalbuminemia, and edema and is often associated with hypercholesterolemia and hypertriglyceridemia. Nephrosis is a constellation of findings, and not a diagnosis. The underlying disease causing the nephrosis should be determined. If nephrotic syndrome is associated with hypertension, hematuria, or red cell casts, consider nephritis as the underlying kidney pathology. MINIMAL CHANGE DISEASE The most common cause of nephrotic syndrome in pediatrics is minimal change disease. This is a clinical diagnosis and does not require a renal biopsy prior to initiation of treatment. After initial work up, these patients are treated with steroids and tend to improve quickly. There are certain incidences, however, when renal biopsy should be considered in patients with nephrotic syndrome: Children less than 1 year of age Atypical presentation- nephritis, HTN, renal insufficiency Non-responsive to steroids after 8 week course Frequently relapsing or steroid dependent If you are considering cytoxan or cyclosporine treatment CLINICAL COURSE OF MINIMAL CHANGE NS Steroid responsive- Prednisone works(on avg 2-3 weeks, allow up to 8 weeks) Frequent relapser- 2 or more relapses in 6 months Steroid dependent- at least 2 consecutive relapses on therapy or within 14 days of treatment Steroid resistant- lack of response after 8 weeks Treatment includes: Prednisone 1mg/kg/dose (max 40mg) BID- Initial course 12 weeks (6 weeks daily and 6 weeks QOD with taper) Low sodium (2000-2500mg/day); Do not restrict fluids Cytoxan for frequent relapser or steroid dependent- need Biopsy first COMPLICATIONS Infection- leading cause of mortality; loss of immunoglobulins and opsonins. Antibiotics are given if patient is febrile or there is suspicion for infectionpatients at risk for serious pneumococcal infections such as peritonitis. Thrombosis- increased fibrinogen, decreased antithrombin III, and hyperaggregable platelets Edema- 25% salt poor albumin (0.5-1 gm/kg over 2-3 hours) followed by lasix (1mg/kg), can be given in cases of severe edema. May repeat every 8 hours. NOTES

128 NOTES

129

Hydronephrosis
DEFINITION Distention of the intrarenal collecting system; sometimes referred to as pelviectasis or caliectasis if the renal calices are dilated. PREVALENCE Most common prenatally detected congenital anomaly- up to 1% live births Majority of cases of antenatal hydronephrosis are not clinically significant Hydronephrosis occurs twice as often in males than females WORKUP Infants with hydronephrosis identified antenatally should have an ultrasound in the postnatal period. In general, infants should have a postnatal renal ultrasound in the first 2-7 days of life depending on the severity of prenatal findings. Postnatal ultrasound should be avoided in the first two days of life due to the fact that hydronephrosis may not be detected because of physiologic volume depletion and relative oliguria. Fetuses with severe bilateral hydroureteronephrosis prenatally from bladder outlet obstruction can be associated with severe impaired renal function and require urgent evaluation on the first postnatal day. Infants who had persistent antenatal hydronephrosis and then a normal ultrasound in the first few days of life, require a repeat study between 2 weeks to 3 months of age. Infants with persistent hydronephrosis documented postnatally should have the following workup: Cath UA, urine culture BMP VCUG If the VCUG is positive then start prophylactic antibiotics- Amoxicillin10 mg/kg/day If the VCUG is negative and pt with moderate to severe hydronephrosis, start antibiotic prophylaxis and proceed with Mag 3 lasix renogram after 6 weeks of age to detect possible obstruction CAUSES Transient/Physiologic Vesicoureteral reflux UPJ obstruction UPJ obstruction(Ureteropelvic junction) UVJ (Ureterovesicular junction)- if ureter dilated

130 PUV (Posterior urethral valves)- if bilateral with dilated ureters and thickened bladder NOTES

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132

Infectious Disease

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134

Meningitis
CLINICAL MANIFESTATIONS Infants have nonspecific findings: fever, irritability, cyanosis, grunting, lethargy, poor feeding, or a high pitched cry. Seizures and a bulging fontanel may occur and are highly suggestive of meningitis. After 1 year of age, signs of meningeal irritation may occur, including headache, stiff neck, occasional photophobia, or positive Kernigs and Brudzinskis sign. Determine whether the patient has any underlying chronic medical conditions (prematurity, Sickle cell, HIV, trauma, etc) PHYSICAL EXAM A complete physical exam should be performed paying attention to the childs appearance and activity (lethargic, irritable, consolable), perfusion, vital signs, skin (petechiae, purpura), and joints. Laboratory Data Routine Blood and urine cultures CBC with diff BMP to monitor for SIADH, and then q8-12hours initially. Obtain serum glucose before LP CRP If Clinically Indicated CXR PT/PTT, fibrinogen, FSP ABG Aspirates of purpuric lesions, joints, abscesses, effusions Throat Culture and sensitivities Stool culture Head imaging should be considered prior to lumbar puncture when focal neurologic signs are present, especially pupillary signs or cardiovascular instability.

135 BACTERIAL CAUSES OF MENINGITIS Age Group Newborn Pathogens Group B Streptococcus E. Coli Listeria monocytogenes Klebsiella pneumonia Enterococcus sp. Salmonella sp. Group B Streptococcus Listeria monocytogenes Strep. pneumoniae Neisseria meningitides E. Coli H. Influenzae Strep. pneumoniae N. meningitides H. influenzae

4-12 weeks

Over 12 weeks

CEREBROSPINAL FLUID ANALYSIS Indices Cell Count Cell Type Glucose (mg/dl) Protein (mg/dl) Normal 0-5 Lymphs >40 or > serum glucose Preterm: 65-150 Term: 20-170 Child: 5-40 Negative Bacterial 100-20,000 PMN <40 or < serum glucose Elevated Viral 10-3,000 Lymphs Normal Fungal TB

Lymphs Decreased

Lymphs/Monos Decreased

Elevated but less than 200

Elevated

Markedly Elevated

Positive Negative Varies Negative Gram Stain In partially treated bacterial meningitis, CSF findings may resemble viral meningitis. Bactogens may be helpful in these cases Mean WBCs in a term neonate is 8 (range of 0-22) In viral meningitis, PMNs predominate initially, then lymphocytes appear. A repeat lumbar puncture should be done 24-48hours after admission in most cases of neonatal meningitis, if a resistant pneumococcus is isolated, or if there has been no improvement.

136 MANAGEMENT The goal should be to stabilize the patient with concomitant evaluation for hypoxia, dehydration, increased intracranial pressure, acidosis, DIC and electrolyte abnormalities. Antibiotic therapy should be guided by the patients age, CSF analysis, and any underlying medical conditions (i.e. shunts, indwelling catheters, renal or liver disease). Initial antibiotic regimens should be broad spectrum and based on most likely organism. In infants, consider acyclovir for possible HSV infection. For risk factors for HSV infection see section on Infant with fever of unknown source. If considering Rickettsial disease, add doxycycline. ANTIBIOTIC THERAPY FOR MENINGITIS Regimens Ampicillin and Gentamicin Or Ampicillin and Cefotaxime (Claforan) 1 to 3 months Ampicillin and Ceftriaxone (Rocephin) Or Ampicillin and Cefotaxime Infants over 3 months, children, and Ceftriaxone adolescents Or Cefotaxime Add Vancomycin if risk factors for resistant-pneumococcus present (daycare attendance, age <2 years, smoke exposure, or antibiotics within the previous month), ill appearing, abnormal CSF with positive gram stain, or shunt in place. COMPLICATIONS SIADH Septic Shock and DIC/Coagulopathy Cerebral Edema Neurologic findings, both transient and persistent, such as deficits in cranial nerves (especially VI) and hearing. Subdural effusions and empyema Hydrocephalus: communicating versus obstructive Bacteremia with resultant septic arthritis, pericarditis, and pneumonia Seizures: evaluation (EEG and CT scan) should be considered for any seizures after 48-72 hours or focal seizures. NOTES Age Newborn Infant

137 NOTES

138

Shunt Infections
Ventriculoperitoneal shunts, placed for hydrocephalus, have reported incidence of infection between 2.4-9.4 percent. Most infections occur within one month of the placement of the shunt but can occur later. Skin flora account for the majority of infections with coagulase negative staph leading the list. However, gram negative organisms are also possible pathogens. CLINICAL MANIFESTATIONS Fever, irritability, CNS changes Shunt malfunction resulting in increased intracranial pressure and vomiting Peritoneal signs can develop Never underestimate the importance of the parents history; if parent feels there is something wrong with the shunt then it should be evaluated.

The diagnosis is made by obtaining a sample of CSF. The ability to pump the shunt reservoir is not a reliable indication of shunt infection or malfunction. Neurosurgery consultation is the general rule prior to tapping the shunt. A lumbar puncture can be performed as long as there is no obstruction. Thus a head CT and shunt series are generally obtained when evaluating a child for an infected shunt. CT scan may reveal a shunt malfunction, which is a predisposing cause, but a normal CT does not rule out infection. TREATMENT Vancomycin (60mg/kg/day divided Q6 hours) and ceftazadime (150 mg/kg/day divided Q8 hours) are generally recommended until the organism is identified. Removal of the shunt and/or intrashunt aminoglycosides are other treatment options in resistant cases. Vancomycin peak levels of 30-45 mcg/mL and trough levels of 15-20 mcg/mL are often needed for adequate treatment. NOTES

139

Infant with fever of uncertain source

Management of the infant with fever is largely dependent on the infant s age and clinical exam. Any toxic or ill appearing infant should have appropriate lab evaluation, hospital admission, and empiric antibiotics. Any infant with fever should have a careful exam to locate a source of infection. The following vital signs should be measured and recorded: temperature, heart rate, blood pressure, and respiratory rate. Many consider pulse ox to be the fifth vital sign. If a source of infection is identified, then the patient should be managed accordingly. If no source is located, lab evaluation is necessary to evaluate for UTI, occult bacteremia, meningitis or other serious bacterial illnesses (SBI) that may not be immediately evident on physical exam. Well appearing infants may have an SBI. RISK FACTORS FOR SBI History of prematurity Perinatal antibiotics Treated for unexplained jaundice History of previous rehospitalization Chronic illness Intrapartum history of mother with fever, Group B Streptococcus or antibiotic treatment RISK FACTORS FOR POSSIBLE HSV INFECTIONS IN INFANTS Primary maternal HSV infection at delivery Known exposure to HSV infected persons Fetal scalp electrodes Maternal history of STDs or unexplained fever at delivery CSF pleocytosis with a negative gram stain Failure of fever to abate within 24-48 hrs after starting antibiotics Unexplained CNS signs such as a seizure INFANTS LESS THAN 60 DAYS Generally, infants less than 60 days with a rectal temperature over 100.4 and no source, should have a complete sepsis work-up which includes CBC, CRP, blood culture x 2, cath U/A, urine Gram stain and culture, and a lumbar puncture. Vital signs should be measured and recorded. Also to be considered are stool studies if diarrhea is present, chest x-ray if respiratory signs are present, and viral cultures in selected patients and as appropriate to season. Consider laboratory evaluation for neonatal HSV infections in infants less than 30 days- if risk factors are present.

140 ADMISSION CRITERIA All infants 0-30 days of age with fever of uncertain source (FUS) should be hospitalized Infants 31-60 days of age with FUS should be evaluated for low risk vs. high risk criteria for SBI Any infant 31-60 days of age with FUS identified as high risk clinically or by laboratory data should be hospitalized Infants 31-60 days of age with FUS identified as low risk may be managed as outpatients or inpatients HIGH RISK CRITERIA FOR SBI WBC < 5,000 or > 15,000 Bands > 1500 Urinalysis > 10 WBCs/hpf or positive Gram stain Abnormal CSF indices When diarrhea present, > 5 WBCs/hpf on stool specimen CRP > 10mg/dl if less than 4 weeks of age MEDICATIONS All infants 0-30 days with FUS should be treated with IV ampicillin plus a third generation cephalosporin or gentamicin Recommendations for treatment of infants 31-60 with FUS vary depending on laboratory and clinical findings Inpatient and outpatient low risk infants may be managed without antibiotics pending culture results and or change in clinical status. If decision is made to treat with antibiotics, IM rocephin may be given after all cultures (blood, urine, and CSF) are obtained and follow up arranged. Any infant 31 60 days of age with FUS identified as high risk should be hospitalized and receive an IV third generation cephalosporin. Consider adding IV ampicillin for severely ill infants or with findings suggestive of urinary tract infection. INFANTS BETWEEN 60 DAYS AND 36 MONTHS If child appears toxic- admit to hospital and perform full sepsis workup with IV antibiotics If temp < 102.2 and child appears well- no diagnostic test or antibiotics needed unless clinically indicated. Tylenol for fever- Close follow-up. Return if fever persists for >48 hours or rise in temp curve. If temperature > 102.2 evaluate pt for high risk verses low risk with CBC, CRP, U/A Gram stain and culture. Chest x-ray if respiratory symptoms present. Viral studies in selected patients and as appropriate to season. If pt meets high risk, give

141 Rocephin and send blood culture. LP should be performed first if there is any concern for meningitis on physical exam. Follow up in the clinic the next day. In addition- management of the outpatient must include a reliable family. The infant should be seen by an attending that will be responsible for insuring proper follow up. The infant should be monitored for several hours and reexamined prior to being released home.

These are only guidelines that must be individualized based on clinical experiences and circumstances. NOTES

142

Urinary Tract Infections

Urinary tract infections are a frequent source of fever in young children and the most common serious bacterial infection in infants and young children. Diagnosis of UTI requires a urine culture. A urinalysis should not be used to exclude or diagnose a UTI. A gram stain will improve the sensitivity and specificity of the urinalysis as well as aid in empiric antibiotic selection. DEFINTION Definitive diagnosis is by urine culture- significance of positive culture influenced by collection method, colony count, single vs. multiple organisms and proper handling of sample A suprapubic specimen with any gram negative or > 1000 gram positive colony forming units has > 99% probability for a UTI A catheter specimen with greater than 1000 colony forming units is suspicious for a UTI, a specimen with >10,000 is likely a UTI, and a specimen with >100,000 has a 95% probability for a UTI Clean catch specimens with greater than 100,000 cfu in a girl has 90% probability for a UTI. A clean catch specimen with > 10,000 cfu in a boy is likely a UTI. Pyelonephritis Significant fever Abdominal /flank pain Vomiting Ill appearing Dehydration

Cystitis Dysuria Frequency Urgency Enuresis Abdominal pain Temp < 38.5 C

RISK FACTORS FOR UTI Uncircumcised Male Fever > 102.2 Bacterial colonization Urinary stasis Obstruction Urinary reflux Foreign body Dysfunctional voiding Previous UTI Sexual practice/abuse

143 ORGANISMS ASSOCIATED WITH UTI Gram negative Escherichia coli- most common organism. Causative agent in >80% of first UTIs. Klebsiella species-second most common organism. Seen more in very young infants. Proteus- more common in males Enterobacter species Pseudomonas species Gram positive Enterococci - most common in infants < 30 days of age Group B Strep- newborns Staph saprophyticus- most common in teenage girls-sexually active Coagulase negative staph Staph aureus CLINICAL SIGNS AND SYMPTOMS OF UTI BY AGE Newborn Vomiting Temp instability Failure to Thrive Jaundice Infant Vomiting Fever Failure to Thrive Diarrhea Strong urine odor Irritability School Age Vomiting Fever Abdominal pain Dysuria Frequency Urgency Enuresis

MANAGEMENT A detailed and thorough history and physical exam is important in the management of urinary tract infections. Pay close attention to blood pressure, growth curve, abdominal exam, sacrum, and GU exam. Blood cultures should be obtained in all toxic patients, infants, and those with suspected pyelonephritis. In the hospitalized pt, obtain electrolytes, BUN, Cr, CRP and start patient on IVFs maintenance at a minimum. It is not recommended that routine follow up urine cultures be conducted during the initial course of inpatient or outpatient therapy. INDICATIONS FOR HOSPITALIZATION Ill appearing, dehydrated, or toxic patients Any patient with renal complications such as hypertension, elevated creatinine, anuria, or known underlying uropathy Patients with unreliable or non-compliant families All infants < 30 days of age Infants 31-60 days of age identified as high risk by laboratory data

144 Consider in all children < 5 yrs of age with pyelonephritis (not absolute indication) TREATMENT OPTIONS Inpatient Parenteral Antibiotics: CephalosporinsCeftriaxone, cefuroxime, cefotaxime- If 0-30 days of age, combine with ampicillin. If 31-60 days of age, consider adding ampicillin. Treat for total duration of 2-3 weeks. Change to PO once patient afebrile > 48hrs, taking po well, and labs trending down. Outpatient IM Rocephin followed by PO antibiotics based on sensitivities. Treat for total of 2-3 weeks.

Pyelonephritis

Cystitis

Prophylaxis

PO antibiotics based on sensitivities. Treat for 7-10 days. Amoxicillin (10mg/kg qhs) Septra (2mg/kg TMP qhs) Nitrofurantoin (2mg/kg qhs)

INDICATIONS FOR IMAGING Renal Ultrasound All patients with first time pyelonephritis should receive a renal ultrasound regardless of age or sex. Renal ultrasound is not reliable as a diagnostic test for reflux, pyelonephritis or renal scarring. Voiding Cystourethrogram (VCUG) All children with first UTI at any age with any of the following: abnormal ultrasound, hypertension, poor growth, family history of vesicoureteral reflux Consider in any patient with pyelonephritis regardless of age All children with recurrent UTI without known risk factors The VCUG may be done within the therapeutic course or during hospitalization once the fever has resolved. The classic fluoroscopy VCUG allows for grading of reflux and delineation of anatomy. If the VCUG is delayed, prophylactic antibiotics should be started at the end of the treatment course until the study can be done. Radionucleotide Cystogram (RNC)

145 A radionucleotide cystogram also called a nuclear cystogram is recommended for follow up studies because it involves less radiation than the standard VCUG but offers little anatomic detail Renal Cortical Scan- (DMSA or Glucoheptonate) Primary role is identifying renal scars- uses DMSA or glucoheptonate. Requires IV injection of radioisotope with imaging 2 hours later. Sedation usually required. GRADING SYSTEM OF VESICOURTERAL REFLUX Grade I- Into distal ureter Grade II- Up ureter into pelvis and calyces. No dilatation, normal calyceal fornices. Grade III- Mild dilatation of pelvis, calyces, and ureter Grade IV- Ureter and pelvis are moderately dilated, and the calyces are blunted Grade V- Gross dilatation and tortuosity of ureter, pelvis, and calyces with significant calyceal blunting The role of prophylaxis is evolving and may vary with age of the child, severity of the initial illness, and the results of the imaging studies. Recent studies suggest prophylaxis is no longer required for grades I-III. NOTES

146

Catheter Related Sepsis

A major complication of indwelling catheters is infection with bacteria or fungi. Infections can range from exit site cellulitis to bacteremia with or without shock. MAJOR PATHOGENS Gram positive bacteria-coagulase negative Staph (i.e. S. epidermidis) is the most common cause. S. aureus, both MSSA and MRSA, are also common. Streptococcus species are also found. Gram negative bacilli-E. coli, Klebsiella, Acinetobacter, Enterobacter, Pseudomonas, and others Fungi-Candida species, others are rare DIAGNOSIS Blood cultures should be obtained when CVC infection is suspected. Two sets of cultures should be obtained with at least one set drawn percutaneously. If there is greater quantitative growth from the central culture than the peripheral this suggests that the CVC is the etiology. Positive culture from cellulitic area or any drainage from local site Positive culture of the catheter tip if removed. Greater than 15 colonies of organism reflect infection rather than contamination. Order cultures for fungus and anaerobes as indicated. MANAGEMENT Management depends on the type of infection, the clinical status of the patient, and whether it is necessary or desirable to salvage the central line. Exit Site Cellulitis In the immunocompetent host who appears nontoxic and has localized cellulitis without evidence of rapid progression, it may be appropriate to obtain local cultures and begin oral antibiotics. Close follow-up is indicated and hospitalization should be considered if blood culture is positive and/or cellulitis is progressing. Neutropenic or immunocompromised hosts require a sepsis work-up, hospitalization and empiric IV antibiotics. Failure to respond as manifested by persistent fever or progressing cellulitis should prompt further evaluation for unusual organisms. Skin biopsy/aspiration should be strongly considered if patients do no respond to IV therapy. Tunnel Infection or Port Abscess Tunnel infection is defined as erythema, tenderness and induration overlying the subcutaneous tunnel tract which extends for more than 2 cm from the exit site.

147 Do appropriate cultures (blood, skin, drainage) and place on empiric IV antibiotics Catheter removal is usually necessary as these infections rarely respond to antibiotics After catheter removal antibiotics are generally continued for 7-10 days

Catheter Related Sepsis In many cases, it can be managed with antibiotics through the CVC. Empiric therapy should include Vancomycin and an aminoglycoside or Fortaz pending appropriate culture results. CVC should be removed Severe clinical presentation (i.e. shock) Certain organisms (S. aureus, Pseudomonas, fungi) or multiple organisms Failure to respond clinically and clear bacteremia in 48-72 hours Insertion site infection Neutropenia Complications arise (septic thrombophlebitis, valvular heart disease, endocarditis, metastatic abscesses) Antibiotic Lock Therapy: involves instilling a high concentration of an antibiotic into the catheter lumen then locking them in for a period of time when the catheter is not in use This can be used when it is important to salvage the tunneled central venous catheter Response varies with site of infection and organism (coagulase negative Staph shows best response) Best when done in conjunction with systemic antibiotics Recurrence can be as high as 20% Therapy is generally continued for 2 weeks Protocols for antibiotic/ethanol locks for catheter-related infections as well as protocols for the management of CVL occlusion exist. Please ask for these at the nurses station or the pharmacy. NOTES

148

MRSA Infections in Children

Staphylococcus aureus causes a wide variety of infections in children, from skin infections such as impetigo and furuncles to more serious conditions such as pneumonia, osteomyelitis, arthritis, endocarditis, and sepsis. The rise of community based methicillin resistant Staph Aureus infections in healthy children poses a significant challenge in managing these infections. TYPICAL COMMUNITY ACQUIRED MRSA INFECTIONS Skin and soft tissue infections- mostly skin abscesses, boils Folliculitis/pustular lesions Furuncle/carbuncle Insect/spider bite, cellulitis Drainage of purulent collections is usually indicated. Obtain specimen for culture and susceptibility testing prior to starting antibiotic therapy. RISK FACTORS FOR HEALTH CARE ASSOCIATED MRSA Hospitalization in the past year Surgery in the past year Permanent indwelling catheter or percutaneous medical device Dialysis Long term care ANTIBIOTIC SUSCEPTIBILITY PATTERNS Most CA-MRSA isolates are resistant to macrolides but remain susceptible to clindamycin and trimethoprim-sulfamethoxazole.. In vitro resistance to erythromycin but susceptibility to clindamycin by routine testing may not predict clinical effectiveness of clindamycin because of a property associated with erythromycin resistant CA-MRSA called inducible resistance to clindamycin. Treatment failures with clindamycin have occurred with MRSA isolates that possess clindamycin inducible resistance. Clindamycin inducible resistance can be detected by the D-Test. TESTING STAPH AUREUS FOR SUSCEPTIBILITY TO CLINDAMYCIN If lab reports. Erythro susceptible, Clinda susceptible Erythro resistant, Clinda resistant Erythro resistant, Clinda susceptible Negative D test Positive D test Then interpret as.. Clinda susceptible Clinda resistant Unknown; request D test Clinda susceptible Clinda resistant

149 ANTIBIOTIC THERAPY FOR COMMUNITY STAPH AUREUS INFECTIONS Outpatient- Skin and soft tissue infections without severe illness Empiric-Clindamycin if the prevalent community MRSA is clindamycin susceptible or the patient is penicillin allergic otherwise may use empiric augmentin, cephalexin Culture proven MRSA Clindamycin- Ensure D-test negative if erythromycin resistant Trimethoprim-sulfamethoxazole Linezolid (very expensive) Inpatient-Suspected invasive illness and/or severe illness Empiric-Vancomycin, Linezolid (if intolerant of vancomycin) plus gentamicin. Will need to check for metastatic spread- echo, CT chest/abd/pelvis, renal ultrasound If admitted but without serious illness- clindamycin CONSIDERATIONS IN DECOLONIZATION TO PREVENT RECURRENCE Efficacy is unproven Suggested criteria for decolonization Multiple (>2) infections in the patient or within the household, infections caused by culture-proven S Aureus with similar susceptibilities COMMON PROTOCOL Keep fingernails clean and cut short, change towels, washcloths, underwear, and sleepwear daily. Wear cotton undergarments. Bactroban to anterior nares BID for 2 weeks- Be aware that resistance to mupirocin is increasing worldwide and there are no studies that find topical antibiotics to be useful for eradicating nasal MRSA. Betadine skin cleanser (7.5%)- Povidine-iodine- Lather and sit for 3 minutes three times per week for 3 weeks Chlorox rinse- 1 tsp per gallon of water- 2 times per week NOTES

150

Hematology/Oncology

151

152

Emergency Treatment of Bleeding Disorders

Abnormal bleeding can be caused by platelet dysfunction, thrombocytopenia, or any disorder in the coagulation cascade. The most common defects encountered are caused by Hemophilia, Christmas Disease, ITP, DIC, Von Willebrands Disease, and malignancy. Treatment of hemorrhage demands knowledge of why a person is bleeding, site of bleeding, and what therapeutic options are available. The following are types of hemorrhage which require immediate care: Central nervous system bleeds can present with headache, vomiting, retinal hemorrhages, focal neurologic findings, or meningeal signs Major organ hemorrhage presents with signs specific to that organ Retroperitoneal hemorrhage should be considered in any patient with known coagulopathy who complains of abdominal pain, severe hip pain, the inability to perform a straight-leg raise, or who has paresthesia of the anterior thigh Retropharyngeal hemorrhage should be considered in any known hemophiliac with pharyngitis, dysphagia, respiratory compromise, or abnormal lateral neck films Wet purpura or gross mucous membrane hemorrhage Deep muscle (e.g., quadriceps) hemorrhage presents with an enlarging, tender muscle IMMUNE THROMBOCYTOPENIC PURPURA (ITP) General Information Peak incidence around 2-7 years, typically is self-limited, and usually presents with bruising and petechiae, but may have gross bleeding Platelet count typically is less than 20,000/cc3. A lymphocytosis may be present from a recent viral infection. Do not have hepatosplenomegaly or lymphadenopathy. In the presence of anemia and/or neutropenia, consider leukemic process as etiology. For the vast majority of patients with ITP, no treatment is necessary. Less than 1% of patients will have serious/life threatening bleeding with ITP. If necessary, the following treatments may be employed: WinRho-Rh immunoglobulin for patients who are Rh positive. Should expect some hemolysis and drop in hemoglobin of 1-2 gm/dL. Discuss dosing with hematologist. IVIG at 1 g/kg/day x 2. See IVIG Administration Protocol in the Appendices. Steroids-Discuss with hematologist before initiating.

153 Treatment of CNS Hemorrhage IV Immunoglobulin or Rh immune globulin: There are many preparations of IVIG commercially available (Gammagard, Gamimune N, Sandoglobulin, etc.), each with specific administration rates. However, the dosage is the same for all. In the emergency situation, 1 gm/kg/day should be given. This dose may be repeated 24 hours later if necessary. Alternatively, 500 mg/kg/day can be given Q day for 4 to 5 days (see chapter on IVIG administration). Rh immune globulin can only be used if the patient is Rh positive (if HgB 10, give 250 IU/kg/dose; if HgB <10, give 125-200 IU/kg/dose). Platelet Transfusion: In general, transfusion of platelets in acute ITP is not indicated. However, in the emergency situation, they do play an important role. Steroids: May be useful for intracranial midline shifts with CNS hemorrhage Plasmapheresis: Transient benefit Emergency splenectomy: Will increase platelet count in 80% of ITP patients. If patient is stable, use conservative measures first. Always consult neurosurgeons in patients with a CNS hemorrhage FACTOR VIII DEFICIENCY (HEMOPHILIA A) Patients with Hemophilia A will have prolonged PTT but normal PT and bleeding time. Factor VIII activity is reduced. Factor VIII may be administered by using fresh frozen plasma, cryoprecipitate, and commercially prepared factor VIII concentrate. Recombinant factor VIII concentrate is the treatment of choice in persons with Hemophilia A due to low risk of infection. Management of Bleeding One unit of factor VIII/kg will raise the plasma activity level 2%. So to raise the plasma level from 0 to 100% activity, you should give 50 units/kg of factor VIII. In treating major hemorrhage or providing hemostasis for surgery, the initial dose should be followed by continuous replacement either as bolus doses of 25 units/kg every 6-12 hours or by continuous infusion. Desired Factor Activity Levels for Specific Situations Type of Hemorhage Desired Factor Level Life Threatening Bleeds CNS 100% Major Surgery/Trauma Retropharyngeal Retroperitoneal Spontaneous Joint Bleed 40-60% Spontaneous Muscle Bleed 40-60% Severe Abdominal Pain 40-80% Simple Dental Extraction 40%

154 Example: A child with Hemophilia A, who weighs 18 kg, has a bleed into his knee. What amount of factor VIII should be administered? Current factor VIII activity (always assume 0% in a severe bleed): 0% Desired factor VIII activity (from chart above): 40% 1 unit/kg of Factor will increase serum activity by 2%, thus 20 units/kg will raise the activity level to 40% 20 units/kg x 18 kg= 360 units of Factor VIII should be administered Always round up the dose to the vial size available. If your calculated dose is 360 units and the vial size is 510, give the whole vial. Oral Bleeding If the child has oral bleeding from trauma or dental extraction, you may want to use aminocaproic (Amikar), a fibrinolytic blocking agent. The initial dose is 100-200 mg/kg followed by 100 mg/kg Q4-6 hours. It can be given intravenously or orally. Amikar is contraindicated with hepatic disease or hematuria. Maximum dose is 30 grams/24 hours. An alternative is tranexamic acid or Cyklokapron, which is also used for oral bleeding. The dosage is 25 mg/kg given QID. Doses should be adjusted accordingly in the presence of impaired renal function. FACTOR IX DEFICIENCY (CHRISTMAS DISEASE) Patients with factor IX deficiency will have a prolonged PTT and low Factor IX activity. Potential sites of bleeding are similar to Factor VIII deficiency. Factor IX concentrates are commercially available and are generally placed in one of three categories: Recombinant Factor IX: Benefix. This is the treatment of choice. Prothrombin Complex Concentrates (PCCs) including Profilnine, Konyne. PCCs contain not only Factor IX, but also Factors II, VII, and X. They should be used only when a limited number of administrations is expected. Because of the presence of the other factors, there is a significant thrombogenic potential with repeated doses. Pure Factor IX concentrates such as Alphanine. Alphanine contains only trace amounts of Factors II, VII, X, and can be safely used in a situation where repeated administration is necessary. Cryoprecipitate has no Factor IX, but FFP has one unit of Factor IX per milliliter. Management of Bleeding Goals for desired Factor IX activity levels are the same as in Factor VIII deficiency (see table above). PCCs will raise the activity 1.5% for each unit/kg administered. Alphanine will raise activity by 1% for each unit/kg. Benefix raises the activity by 0.8% for each unit/kg.

155 DISSEMINATED INTRAVASCULAR COAGULATION (DIC) DIC can be described as a paradoxical, consumptive coagulopathy, where there is a cycle of thrombus formation and lysis that consumes clotting factors. It should not be considered a disease, but rather a process that can be initiated by a variety of stimuli. Clinical presentations can include bleeding, petechiae, gangrene, or thrombus formation. There may be evidence of ischemia in a major organ, such as brain or kidney. Often there is no obvious clinical evidence, but the underlying diagnosis prompts a laboratory evaluation, which confirms DIC. Some common causes of DIC include: Shock or sepsis Malignancy; especially acute promyelocytic leukemia Severe trauma, crush injury, or burns TTP, collagen vascular diseases Laboratory Evaluation Anemia with red cell fragmentation (schistocytes, bite cells). LOOK AT THE SMEAR!!! Platelet count less than 100,000/mm3 (commonly even less than 30,000/m3) D-dimers are elevated PT/PTT prolonged Prolonged thrombin time Decreased fibrinogen (<200) with acute DIC. The fibrinogen can be normal in diseases that are associated with chronic DIC, such as acute promyelocytic leukemia. Factors VIII and V are reduced in DIC, and these assays can be helpful in difficult cases where the diagnosis of DIC is unclear Management Successful treatment of DIC is primarily dependent on appropriate treatment of the underlying disease, such as fluid replacement, treatment of shock, correction of acid-base imbalances Fresh frozen plasma provides replacement of clotting proteins, but its primary role is to replace anticoagulants, such as antithrombin III, protein C, and protein S. The dose is 10 cc/kg and may be repeated as needed. Platelet transfusion may be necessary Exchange transfusion can be used to quickly correct the physiologic deficiencies Heparin therapy is controversial, and is not typically necessary in most cases of DIC. However, in patients with serious thrombotic complications (brain, renal, etc.) heparin therapy may play a role. If it to be used, a bolus dose of 100 U/kg is given followed by a continuous infusion of 100 U/kg given over 6 hours. Steroids should not be used unless the underlying condition may be benefited or if shock is present

156 NOTES

157

Fever in Immunocompromised Children

Children may be immunocompromised for a variety of reasons. The most common form of immunodeficiency is secondary to chemotherapy (CRX) in the patient with a malignancy. CRX most commonly causes neutropenia but also affects immunoglobulin production and cell mediated immunity. Also, CRX can interrupt skin and mucous membrane integrity allowing an entry site for microorganisms to invade systemically. Finally, many hematology-oncology patients (e.g., Hodgkins disease, chronic ITP, sickle cell disease, hemolytic anemias) will be functionally or anatomically asplenic, rendering them more susceptible to encapsulated organisms. The following are guidelines for the evaluation and treatment of patients who are immunocompromised and febrile. HISTORY History of present illness and comprehensive ROS to help define the source of infection Underlying disease Recent therapy (e.g., radiation or chemotherapymeds and dates received) Exposures, especially to varicella Presence of an indwelling catheter; previous infection of catheter PHYSICAL EXAM It must be remembered in the neutropenic patient that the signs of inflammation may be muted or absent. Dull TMs may be the only sign of a severe otitis media. Proceed with care! Thorough sinopulmonary exam to include ears, sinuses, teeth, throat, and lungs GI tract with particular attention to the RLQ (typhlitis) and the perianal area (NO RECTAL TEMPS OR SUPPOSITORIES) Hepatomegaly and splenomegaly as evidence of fungal or viral infections Integument looking for cellulitis, abscess, septic emboli (small erythematous or hemorrhagic papules) or varicella-zoster and examination of indwelling catheter site Pain alone may be a sign/location of an infection LABORATORY EVALUATION CBC with differential Blood culture from all central lines. U/A and C&S, urine gram stain if indicated Chest X-ray in any patient with respiratory symptoms or young age. Obtain PA and lateral in radiology department if at all possible. Consider sinus CT, chest CT, abdominal CT, pleural tap, etc. as indicated by H&P Consider viral titers/PCR for CMV, EBV Nasopharyngeal swab for RSV, adenovirus, influenza if indicated

158 TREATMENT OF THE FEBRILE, NEUTROPENIC PATIENT Neutropenia is defined as an absolute neutrophil count (ANC) less than 1000. ANC is calculated by multiplying the percent neutrophils plus percent bands times the total white blood cell count {i.e., ANC=(WBC) (%bands + %neutrophils)}. A temperature over 100.5F x 2 in 24 hours or 101F x 1 is defined as a fever in the immunocompromised patient. After evaluation is completed and cultures have been obtained, begin empiric antibiotics covering the most likely organisms. Organisms Requiring Coverage In all patients consider gram negatives (including Pseudomonas) and gram positives (e.g., Staph and Strep) If indwelling catheter: Staph epi and MRSA If GI symptoms or chronic sinusitis: anaerobes If interstitial pneumonia: pneumocystis If prolonged neutropenia, steroids, prolonged broad spectrum antibiotics, consider fungus. Treatment If the patient shows signs of early septic shock, administer O2, fluid bolus and monitor vital signs and I/O carefully Empiric antibiotics should be administered within an hour of presentation. In an ill appearing patient, do not wait for screening labs prior to starting antibiotics. Empiric therapy (i.e., no source is evident) must include Gram negative coverage Due to increased frequency of Gram positive line infections, initial Gram positive coverage may be indicated Patients who have mucositis, previous Gram positive line infection, or appear toxic need initial Gram positive coverage along with Gram negative coverage AML patients with fever/neutropenia need initial Gram positive/Gram negative coverage Example single agent Gram negative coverage: ceftazidime Example single agent Gram negative, Gram positive, anaerobic coverage: meropenem Metronidazole or clindamycin should be used if there is the possibility of anaerobic infection (abscess, oral or GI pathology, sinus) If pneumonitis is suspected, utilize empiric therapy as above plus therapeutic TMP-SMX and possibly macrolide When fungus is suspected use caspofungin All patients should be under neutropenic precautions NOTES

159

Thrombotic Disorders
Questions about management regarding deep vein thrombosis (DVT) and pulmonary embolus (PE) can often be answered by calling 1-800-NO-CLOTS. A patient can be predisposed to developing thrombosis by both inherited disorders as well as acquired risk factors. Risk Factors for Thrombosis Acquired Central Venous Line Congenital Heart Disease Trauma TPN Infection Surgery and Immobilization Oral Contraceptive Use Obesity Nephrotic Syndrome Inflammatory Bowel Disease Diabetes Mellitus Systemic Lupus Erythematosus Antiphospholipid Syndrome (Lupus Anticoagulant, Anticardiolipin Ab) Inherited Antithrombin III Deficiency Protein C Deficiency Protein S Deficiency Factor V Leiden Mutation (Activated Protein C Resistance) Prothrombin Gene Defect Increased Factor VIII Increased Fibrinogen, Dysfibrinogenemia Plasminogen Deficiency Homocysteinuria MTHFR mutation

CLINICAL PRESENTATION Swelling, pain, and/or discoloration of affected limb Inability to draw blood from a central line Swelling of face and neck in the superior vena-cava syndrome Pulmonary embolism may present as dyspnea, tachypnea, hypoxia, cough, unexplained tachypnea or syncope, hemoptysis, or chest pain (pleuritic) Fever occurs in up to 20% of PE, mimicking pneumonia EVALUATION OF DVT/PE Compression Doppler Ultrasound: Is the best and least invasive test for DVT. Sensitivity is approximately 90%, although sensitivity is decreased with calf vein thrombosis. If the Doppler ultrasound is negative, yet high clinical suspicion remains, a venogram or MRI may be diagnostic. Chest X-Ray: Findings are generally non-specific, although most patients with a PE will have abnormalities present (atelectasis, effusion, or infiltrate) BNP (Brain natriuretic peptide) has a sensitivity and specificity of only 60-62%. Elevations of BNP may be associated with adverse outcomes.

160 D-dimer: If low probability of PE and D-dimer less than 500 ng/dL then PE is very unlikely. If D-dimer is greater than 500 ng/dL then the sensitivity for PE is over 95%, however specificity is low with the D-dimer test. Ventilation-Perfusion (V/Q) Scan: A normal scan essentially rules out a PE. A high probability scan has 95% specificity, but only 40% sensitivity. However, most patients with a PE will have a low or intermediate probability scan. Helical or Spiral CT: A spiral CT scan has a sensitivity of 70-90%, thus if there is high clinical suspicion for PE further testing is warranted. A negative spiral CT has good negative predictive value. Pulmonary Angiography: This is the gold standard test for PE, although it is invasive and 5% of patients will have complications due to catheter insertion or dye reactions. Echocardiography: Only useful in massive PE where rapid diagnosis is necessary to justify use of thrombolytic therapy THERAPY FOR THROMBOEMBOLISM Thrombolytic therapy is indicated in patients with hemodynamic instability (hypotension), severe hypoxia, or right ventricle dysfunction associated with massive PE. Anticoagulation therapy with low molecular weight heparin (LMWH, Lovenox) or heparin is also used for patients with a DVT/PE, regardless of whether thrombolytic therapy is utilized. It is recommended, however, that heparin therapy not be initiated until after thrombolytic therapy is complete. Relative contraindications to lytic therapy include history of stroke, transient ischemic attack, neurologic disease, and hypertension. Systemic Thrombolytic Therapy1 Medication Dose and Route Comments Tissue Plasminogen Loading: None Monitor fibrinogen, TCT, Activator (tPA) Maintenance: 0.1-0.6 PT, APTT. Agent of choice mg/kg/hr for 6 hours in children due to fibrin Max dose: 100mg given specificity and low over 6 hours. immunogenicity. Expensive product. 1 Start heparin therapy immediately after completion of thrombolytic therapy. A loading dose of heparin may be omitted. The length of time for optimal maintenance is uncertain. Values provided are starting suggestions; some patients may respond to longer or shorter courses.

161 Anticoagulation Therapy for DVT or PE Medication Dose and Route Comments Enoxaparin/Low Molecular Treatment: Monitor anti-factor Xa level Weight Heparin <2 month or <5 kg: 1.5 4 hrs after 3rd dose and 4 hrs (Lovenox) mg/kg/dose SQ Q12 hrs after dose adjustments (see >2 months or >5 kg: 1.0 below). Therapeutic Xa mg/kg/dose SQ Q12 hrs level is 0.5-1.0 u/mL; Max dose: 150 mg prophylactic Xa level is 0.20.4 u/mL. Potential Prophylaxis: advantages over heparin are <2 months: 0.75 less monitoring, less HIT mg/kg/dose SQ Q12 hrs syndrome, and possibly less >2 months: 0.5 mg/kg/dose osteoporosis with long term SQ Q12 hrs use. Advantages over warfarin are lack of drug/food interactions. Heparin Load: 75 units/kg IV over Adjust heparin to maintain 10 min PTT between 60-85 seconds Maintenance: (approx. equal to anti-factor <1 yr: 28 units/kg/hr IV Xa level of 0.3-0.7). Obtain >1 yr: 20 units/kg/hr IV PTT 4 hrs after bolus or any change in infusion rate. Older children and adults: Once therapeutic obtain Load: 80 units/kg daily CBC and PTT. Maintenance: 18units/kg/hr Max dose: 10,000 units

Monitoring Anti-Factor Xa Levels in Pediatric Patients Anti-Factor Xa Hold Next Dose? Dose Change? Repeat Anti-Factor Level Xa level? <0.35 units/mL No Increase by 25% 4 hrs after next dose 0.35-0.49 units/mL No Increase by 10% 4 hrs after next dose 0.5-1.0 units/mL No No Next day, then 1 wk later, and monthly thereafter (all 4 hrs after dose) 1.1-1.5 units/mL No Decrease by 20% Before next dose 1.6-2.0 units/mL 3 hours Decrease by 30% Before next dose, then 4 hrs after next dose >2.0 units/mL Until anti-Xa 0.5 Decrease by 40% Before next dose, if units/mL not <0.5 units/mL repeat Q12 hours

162 EVALUATION Children are more likely to have abnormalities within the coagulation cascade than adults. Thus, all children deserve a work-up for the etiology of their thrombo-embolic event. The timing of this work-up is controversial, as some tests may be abnormal because of the recent event. However, it is probably best to initiate the work-up at the time of the event and repeat the abnormal tests once anticoagulation therapy is terminated. A hematology consult is warranted in all children with a thromboembolic event, but tests that may be helpful are presented below. It is often helpful to evaluate the childs parents as well.

Laboratory Evaluation of a Thromboembolic Event Protein C Activity, Protein S Activity Protein C and S Antigen Activate Protein C Resistance (surrogate marker for Factor V Leiden Mutation) Antithrombin III Prothrombin Gene Defect ANA Fasting Homocysteine Factor VIII Activity Level D-dimer MTHFR gene Lipoprotein (A) Anti-cardiolipin Dilute Russell Viper Venom TREATMENT OF ANTICOAGULANT INDUCED BLEEDING

Protamine sulfate is used to reverse heparin and LMWH therapy when an immediate effect is required. The same protocol for protamine administration for the reversal of heparin is used for LMWH. Prior to lumbar punctures or epidural procedures, at least two doses of LMWH should be withheld and, if possible, determine anti-factor Xa levels prior to the procedure. Reversal of Heparin Therapy1 Time Since Last Heparin Dose Protamine Dose <30 minutes 1.0 mg/units of heparin 30-60 minutes 0.5-0.75 mg/units of heparin 60-120 minutes 0.375-0.5 mg/units of heparin >120 minutes 0.25-0.375 mg/units of heparin Maximum dose of 50 mg. Infusion rate of 10 mg/mL solution should not exceed 5 mg/min. Hypersensitivity reactions may occur in patients with known reactions to fish or protamine containing insulin.
1

163 TREATMENT OF BLOCKED CATHETERS Thrombolytics are used in low doses to restore catheter patency. Streptokinase should not be used to reestablish patency due to potential allergic reactions with repeated doses. tPA is currently the treatment of choice. Fill the IV line with the dose of tPA as indicated in the table below. Allow tPA to dwell for 1-2 hours. Attempt to aspirate the volume of tPA instilled into the line PLUS 2 mL of blood (0.2 mL in nursery patients). This will assure the drug was removed from the line and not pushed into the systemic circulation. Procedure may be repeated one time if necessary. Guidelines for Local Instillation of tPA in Central Venous Lines1 Weight Single-Lumen Double-Lumen SC Port CVL CVL 10 KG 0.5 mg in 0.5 mL 0.5 mg in 0.5 mL 0.5 mg in 0.5 mL NS NS; treat one lumen NS at a time >10 KG 2 mg in 2 mL NS 2 mg in 2 mL NS; 2 mg in 2 mL NS treat one lumen at a time 1 Also see pharmacy preprinted order sets for catheter occlusions which should be located in each nursing station. NOTES

164

Sickle Cell Disease

PAIN CRISIS Pain associated with a vaso-occlusive crisis is due to ischemia secondary to occlusion in the microvasculature. Clinical Diagnosis Children less than five years may present with dactylitis, a swelling of the hands and feet. This may be a patients initial presentation with sickle cell disease. As the child gets older, pain may change to any locality. Common sites are the abdomen, back, and long bones. Patients with vaso-occlusive crisis may have a low-grade temperature. However, any temperature over 101 requires a complete history and physical in search of a source, appropriate cultures, and administration of parenteral antibiotics. A thorough history and physical should be performed to try to discover a possible triggering event for the painful crisis (e.g., infection, dehydration, etc.). Always consider that a patient with sickle cell disease can have pain that is not related to sickle cell disease (e.g., pneumonia, osteomyelitis, pancreatitis, appendicitis, etc.) Laboratory Evaluation Laboratory evaluation should include CBC with differential and reticulocyte count If the patient requires admission, electrolytes, BUN, creatinine, and liver enzymes should be checked Blood cultures (if febrile), CXR (if pain is located to the thorax), and type and cross should be obtained if clinically indicated Check oxygen saturation Treatment Fluid hydration at 1800-2000cc/m2 /day (or approximately 1.25 to 1.5 maintenance) using D5 NS with appropriate amount of KCl added. Monitor fluids and electrolytes closely, as renal salt wasting occurs commonly in children with sickle cell disease, and fluid overload predisposes to ACS. Avoid the use of meperidine Do not give supplemental oxygen unless the patient is hypoxic Do not use Ketorolac for greater than 5 days

165 MILD PAIN: Usually can be managed at home with Ibuprofen 10 mg/kg PO Q6-8 hours plus acetaminophen 10-15 mg/kg (+/- codeine 1 mg/kg) PO Q4-6 hours PRN Encourage 1 maintenance fluid intake MODERATE PAIN: Usually managed in the clinic or emergency department. Ketorolac 1 mg/kg IV load (Max: 15 mg if <50 kg, 30 mg if >50 kg) plus acetaminophen with codeine 1 mg/kg of codeine PO. OR Ketorolac 1 mg/kg IV load (Max: 15 mg if <50 kg, 30 mg if >50 kg) plus morphine 0.05-0.1 mg/kg/dose (Max: 10 mg) IV Q3-4 hours Reassess in 30-60 minutes and give rescue dose of morphine every 30 minutes for breakthrough pain. If no pain relief or sedation, rescue dose should be 50% of initial dose. If mildly sedated but still in pain, the rescue dose should be 25% of initial dose. Bolus 10-20 cc/kg of isotonic fluids, then give 1 maintenance fluids either PO or IV If the patient has not improved after 6 to 8 hours, admission will be required If able to discharge, send home on ibuprofen and acetaminophen with codeine at above doses around the clock for 24 to 48 hours SEVERE PAIN: Ketorolac 0.5 mg/kg Q6 hours (Max: 15 mg if <50 kg, 30 mg if >50 kg) plus morphine 0.05-0.1 mg/kg (Max: 10 mg) IV Q3-4 hours. Give rescue dose of morphine every 30 minutes for breakthrough pain. If no pain relief or sedation, rescue dose should be 50% of initial dose. If mildly sedated but still in pain, the rescue dose should be 25% of initial dose. If three or more rescue doses are required within a 24 hour period, increase the maintenance morphine dose by 2550%. Any patient receiving IV narcotics should have a continuous pulse oximeter. OR Ketorolac 0.5 mg/kg Q6 hours (Max: 15 mg if <50 kg, 30 mg if >50 kg) plus morphine PCA (see table below). Start PCA after pain controlled with boluses as above.

166 Morphine PCA1 Adjustments Increase 4 hour Limit by 10-20% if patient reaching the limit and pain not controlled Increase PCA bolus dose and/or basal rate by 10-20% if patient requiring frequent PCA boluses or frequent pushing of PCA button 1 Any patient receiving IV narcotics should have a continuous pulse oximeter. Bolus 10-20 cc/kg of isotonic fluids, then give 1 maintenance fluids either IV or PO. Be aware that excess fluids may precipitate or exacerbate acute chest syndrome. All patients should have a form of incentive spirometry and a stool softener (i.e., colace) Opiates tend to cause itching due to histamine release and can cause nausea/vomiting. Diphenhydramine, nalbuphine (10-20 mcg/kg/dose IV Q4-6 hrs PRN), or naloxone (5-10 mcg/kg/dose IV Q6 hrs PRN) should be used PRN for itching. Promethazine should be used for nausea/vomiting. CEREBROVASCULAR ACCIDENTS Strokes and other cerebrovascular events are major causes of mortality and morbidity in HgbSS patients. Most events are caused by thrombotic phenomena, but strokes can also be due to hemorrhage, especially in the young adult. Diagnostic clues to a thrombotic cerebrovascular accident (CVA) include hemiparesis, slurred speech, alteration in mental status, and seizure. Laboratory Evaluation CBC with differential CMP Reticulocyte count MRI/MRA without contrast. If unable to obtain stat MRI/MRA, a head CT without contrast should be ordered. EEG if indicated Lumbar puncture if indicated Type and cross for exchange transfusion RBC phenotype Quantitative hemoglobin electrophoresis Starting Dose Basal Rate: 0.01-0.04 mg/kg/hr PCA Bolus: 0.18-0.04 mg/kg/dose Lock Out: 6-15 minutes 4 Hour Lock Limit: 0.24-0.5 mg/kg

167 Treatment Consult hematology-oncology attending. Treatment consists of exchange transfusion with the goal of reducing HgS to less than 30% and total hemoglobin to 10 gm/dL. Give sickle negative, leukodepleted, and if available, antigen matched PRBC. If antigen matched blood is not available, PRBC should be C, E, and Kell negative as well as sickle negative and leukodepleted. The Red Cross can perform an automated exchange transfusion on patients over 18kg. PRIAPISM Priapism is a persistent, painful erection due to vascular engorgement of the corpora cavernosa by sickled blood. Without adequate treatment, priapism leads to impotence in 80% of patients. Management Acute Reversible Priapism: Typically resolves in less than 2-4 hours (stuttering priapism). This is usually managed at home with frequent emptying of bladder, warm baths, increased oral intake of fluids, and analgesics. If not resolved within 2 hrs, patient should alert their physician. Acute Prolonged Priapism: Requires admission, consult hematology-oncology attending Intravenous fluid hydration at 2500 cc/m2/day Analgesics as used in a pain crisis Consider foley catheter if patient not adequately emptying bladder on his own Consider simple transfusion if the above measures are not successful Some centers recommend aspiration and irrigation with epinephrine within 12 hours Surgical management is controversial, but if detumescence has not occurred within 24 hours, then surgical intervention with Winter shunt should be considered. Consider pseudoephedrine 30 mg PO QHS (<10 years of age) or 60 mg PO (>10 years of age) for priapism prophylaxis APLASTIC CRISIS An aplastic crisis is a decreasing hemoglobin, approximately 1 gm per day, with a simultaneous fall in reticulocytosis (retic count 2%). It may follow a viral prodrome; commonly associated with an infection with parvovirus B19. Fatigue, dizziness, pallor, tachycardia, or heart failure may all be signs of an aplastic crisis. The patient may also have coexisting splenic sequestration.

168 Management Transfusions are the mainstay of therapy if the patient is symptomatic and/or the hemoglobin is less than 5 gm/dL without evidence of erythroid recovery. The principle is to increase their hemoglobin without putting them into fluid overload. If anemia is severe (Hgb <5), give 5 cc PRBCs/kg over 3-4 hrs. Assess the patient and then give another 5 cc/kg if needed. If signs of fluid overload, a dose of Lasix 1 mg/kg can be given. Once the patients hemoglobin is above 7, larger aliquots (10 cc/kg) may be used if necessary. Remember not to transfuse to a hemoglobin over 12 gm/dL. SPLENIC SEQUESTRATION CRISIS A sequestration crisis is a relatively sudden entrapment of RBCs in an enlarged spleen associated with hemoglobin 2 gm/dL below baseline. There is usually an increased reticulocyte count and an increased indirect bilirubin. Physical exam reveals an enlarged spleen. Signs of intravascular depletion, such as tachycardia or shock, may also be present. Laboratory evaluation should include a CBC, total bilirubin, liver enzymes, and reticulocyte count. Management Transfuse if the patient is symptomatic or hemoglobin is <5 gm/dL (or <7-8 gm/dL in patients with a higher baseline, e.g., HbSC). Give 5 cc/kg over 3-4 hours and repeat if needed. The goal is to obtain a hemoglobin of 8-9 gm/dL. Do not over transfuse as the hemoglobin will rise 1-2 gm/dL once sequestered RBCs are released from the spleen. If the patient is hemodynamically unstable, it is necessary to rapidly stabilize the patient with intravascular fluids/PRBCs and emergently consult a surgeon for splenectomy Splenectomy is the treatment of choice for recurrent sequestrations or a single severe episode SICKLE CELL DISEASE AND FEVER (TEMP 101 F) The child with sickle cell disease and fever should never be taken lightly. It must be remembered that children with sickle cell disease are at increased risk for bacterial infections due to encapsulated organisms, such as pneumococcus and H. influenzae. There is a 15-35% mortality rate for pneumococcal sepsis in sickle cell patients. Management in Clinic or ED Patient should be rapidly triaged and evaluated Laboratory evaluation should include CBC with differential, reticulocyte count, and blood culture. Other labs, including CMP, urinalysis, CSF studies, stool studies, and CXR should be obtained when clinically indicated.

169 Antibiotics should be administered promptly. Use ceftriaxone 75 mg/kg (2gm max) IV. If allergic to cephalosporins but not penicillins, use ampicillin/sulbactam 50 mg/kg/dose IV Q8 hours. If allergic to cephalosporins and penicillins, use clindamycin 10 mg/kg/dose (600 mg Max) Q6 hours plus gentamicin 2.5 mg/kg/dose IV Q8 hours. If in shock, unstable vitals, or CNS infection add vancomycin 10-15 mg/kg/dose (1 gram Max) IV Q 8 hours Patient should be admitted or at a minimum observed for 6 hours in the clinic/ED setting (see below for admission criteria) If discharged home, the patient should be seen the following day and given a second dose of ceftriaxone Admission Criteria Age less than 1 years Temperature over 102.2F Hypotension {SBP <70 mmHg + (2)(age in years)} Poor perfusion WBC >30,000 or less than 5,000 Platelet <100,000 Hemoglobin <5 gm/dL History of pneumococcal sepsis or bacteremia or other serious bacterial infection Dehydration Infiltrate on CXR or O2 saturations below baseline Allergic to penicillins or cephalosporins Other acute complications (severe pain, splenic sequestration, acute chest syndrome, stroke, priapism, or aplastic crisis) Poor compliance or follow-up Inpatient Management CBC and reticulocyte count should be obtained daily. Other labs should be checked as clinically indicated. Patient should be assessed frequently with attention to vital signs. PO intake plus IV rate should be 1 to 1.5 times maintenance Antibiotics should be continued until cultures are negative. Give ceftriaxone 75 mg/kg/day IV Q24 hours, or cefotaxime 50 mg/kg/dose IV Q8 hours if less than 50 kg or cefotaxime 1-2 grams/dose IV Q8 hours if over 50 kg (Max dose 12 grams/24 hours). Acetaminophen 15 mg/kg/dose PO Q4-6 hours, and/or ibuprofen 10 mg/kg/dose PO Q8 hours PRN fever control Add vancomycin 10-15 mg/kg/dose IV Q8 hours if critically ill (1 gram max single dose)

170 Patient may be discharged when they are clinically stable, afebrile for 24 hours, blood and other cultures are negative at 48 hours, and tolerating PO fluids and medications ACUTE CHEST SYNDROME

Acute chest syndrome is defined as a new infiltrate on chest x-ray, with pulmonary symptoms (chest pain, cough, hypoxia, tachypnea, retractions, etc.) and/or fever. There is a multifactorial etiology and pathophysiology, including infection, infarction, pulmonary edema, fat embolization, hypoventilation and atelectasis. Evaluation CXR CBC with differential, reticulocyte count, blood cultures, and sputum cultures (if obtainable) Type and cross leukodepleted, sickle negative, antigen matched PRBCs Pulse oximetry

Management
CBC and reticulocyte count should be obtained daily. Monitor electrolytes if on IV fluids Repeat CXR if acutely worsens PO intake plus IV fluids should equal 1 times maintenance (fluid overload can make acute chest syndrome worse) Give ceftriaxone 75 mg/kg/day Q24 hours (2 grams max dose). May give cefotaxime 50 mg/kg/dose IV Q8 hours if less than 50 kg or cefotaxime 1-2 grams/dose IV Q8 hours if over 50 kg (Max dose 12 grams/24 hours). Also give azithromycin 10 mg/kg/day IV/PO on day one and 5 mg/kg/day IV/PO on days 2 through 5 (other macrolides may be used instead) If critically ill, add vancomycin 10-15 mg/kg/dose IV Q8 hours (1 gram max single dose) Use supplemental oxygen if needed for sats <92% or below patients baseline Give bronchodilator therapy with albuterol with PEP Q4-6 hours Simple transfusion with 10 cc/kg of PRBCs over 3-4 hours if severely ill, deteriorates during hospitalization or does not improve within 12-24 of hospitalization (do not transfuse above a hemoglobin of 12 gm/dL) Exchange transfusion will be necessary if critically ill or starting hemoglobin is too high Incentive spirometry 10 inhalations Q2 hours while awake or bubble therapy if too young for incentive spirometry Consider steroids if history of asthma, wheezing, prolonged expiratory phase, or deteriorating (remember to taper steroids over 7-10 days to prevent a rebound in pain)

171 Use pain medications as described in above section on pain management. Try to avoid over sedation which can lead to hypoventilation, atelectasis, and worsening acute chest syndrome. Likewise, try to avoid undertreating pain which can lead to splinting and worsening of acute chest syndrome. NOTES

172

Oncologic Emergencies
HYPERLEUKOCYTOSIS Elevated WBC in a patient with acute leukemia in which there is risk of increased viscosity, sludging and intracranial hemorrhage or pulmonary stasis. Risk increases significantly in ALL when WBC >500,000 and in AML when WBC >100,000. There is no increased risk when leukocytosis is due to mature cells as in infection or CML. Evaluation CBC Type and Cross match Tumor lysis labs (BMP, Ca, Phos, Uric Acid, U/A) Treatment Immediate leukoreduction: Arrange an emergency leukophoresis to be done by the American Red Cross (251-6000). Will need double lumen renal dialysis catheter placed by surgeons or PICU attending in femoral vein. Maintain plts > 75,000 to avoid CNS bleed Do not transfuse RBCs unless Hgb <7 gm% so viscosity is not increased further. If Hgb < 7.0, transfuse slowly in 5 cc/kg aliquots. Hydrate at 1 maintenance provided patient does not have signs or symptoms of elevated intracranial pressure. SUPERIOR VENA CAVA SYNDROME A Mediastinal mass which causes compression or occlusion of the SVC and/or trachea. Symptoms may include: stridor, dyspnea, plethora or cyanosis of the face/neck, distended veins of the neck and collaterals on the chest, headaches, decreased sensorium, papilledema. Usually associated with non Hodgkins lymphoma or leukemia/lymphoma. Management Keep patient upright Notify anesthesia and radiotherapy Do not paralyze for intubation Begin tumor lysis therapy Try to obtain a diagnosis via BM aspirate, pleural tap, etc RX with Rad Rx (2 Gray/d) until symptoms resolve May need prednisone 40-60 mg/m2/day

173 TUMOR LYSIS SYNDROME TLS occurs primarily in patients with rapidly dividing cells who present with large tumor burdens (high WBC, massive organomegaly, large mediastinal or other tumor mass). It may occur at diagnosis or upon initiating therapy. The most common abnormalities include: hyperuricemia, hyperkalemia, hyperphosphatemia with associated hypocalcemia. Many others may occur. In AML, especially APML, DIC is the most common tumor lysis consequence. Evaluation STAT BMP, Ca, Phos, Uric acid, U/A If there is abnormal involvement or elevated creatinine, obtain ultrasound of abdomen to rule out renal leukemic infiltration or ureteral obstruction. Frequency of monitoring labs depends upon the severity of lab abnormalities. Volume status may require CVP. In severe TLS, PICU transfer is warranted. Treatment Strict I & Os and daily weights Hydration at 2400-4000 cc/m2/day with fluids containing sodium bicarbonate 50 mEq/liter to maintain a urine pH between 6.5 and 7. If severely anemic, may need to transfuse 1st to avoid CHF. Allopurinol 10 mg/kg/day divided Q8 hours Aluminum hydroxide (Basogel) for prevention and treatment of hyperphosphatemia. Can also use Amphogel; Lo-phos. Renal irradiation if obstruction or infiltration is present and renal dysfunction occurs For hyperkalemia: albuterol 0.1-0.3 mg/kg by inhalation; furosemide 1 mg/kg; kayexalate 1-2 mg/kg/day divided Q4-6 hours PO (See also Fluids and Electrolytes in handbook) Dialysis if develops fluid overload or recalcitrant hyperkalemia For severe hyperuricemia, especially when anti-tumor therapy is necessary quickly, may use Rasburicase (Elitek) 0.15 mg/kg daily for one to five days If hyperphosphatemia or hypocalcemia are more severe than hyperuricemia, stop alkalinization NOTES

174

Transfusions
RED BLOOD CELLS RBCs are usually transfused in the form of packed RBCs (pRBC). The hct of pRBCs is 66% and the hgb is 22gm%. There are about 250 mL in each unit, thus each unit contains approx. 55 gm of hgb. Calculations Simple transfusion Vol cells (mL)= Est. blood volume x desired change in hct Hct of pRBC Or 10 mL/kg of pRBC will raise hgb approx 3gm% Wait four hours to repeat hgb/hct Exchange transfusion for severe anemia and CHF Exchange vol= Est. blood volume x desired hgb rise 22gm/dL-HgbR Where HgbR=hgb(initial) +hgb(desired) 2 PLATELETS A platelet pheresis is a single donor product. The total volume of a platelet pheresis averages 250-300 mL. Dose: Children <15 kg=10-15 mL/kg will raise platelet count by 50-100,000 Children >15 kg=1 pheresis pack Wait one hour to check platelet count. SPECIAL CONSIDERATIONS Prophylaxis against Graft vs. Host Disease (GVHD): All oncology patients and newborns are at risk for transfusion induced GVHD. All cellular blood products should be irradiated before transfusing. Cytomegalovirus: All oncology patients and newborns are at risk for transfusionrelated CMV. All immunosuppressed patients should receive only leukodepleted products. If leukodepleted blood products are not available, you MUST use CMV specific products.

175 Prophylaxis for transfusion reactions Sickle cell disease: Always use sickle-dex negative, leukodepleted, and antigen matched blood. If patient has not received pRBCs previously, send blood for RBC phenotype. NOTES

176

Appendices

177

178

Quick Calculations
Blood Pressure Norms Percentile for age (over 2 years old) <5th 50th 95th Systolic (mmHg) 70 + (2 x age in years) 90 + (2 x age in years) 100 + (2 x age in years) Diastolic (mmHg) 70 + (1.5 x age in years) 70 + (2 x age in years)

Glucose Infusion Rate Rate of infusion mg/kg/min = (%dextrose in soln x 10 x rate of infusion (ml/hr))/ 60 x wt in kg Serum Osmolality Serum osm= 2(Na) + (BUN/2.8) + (Glucose/18) Adjusted Sodium for Hyperglycemia Adjusted Na = Na x 1.6 (glucose/100 -1) Body Mass Index 13 + age abnormal Body surface area (actual) = square root of [wt (kg) x ht (cm)]/3600 Body surface estimated = [(wt(kg) x 4) +7] / (wt + 90) Fractional Excretion of Sodium FENa = (Urine Na x Serum Cr) x 100 (Urine Cr x Serum Na) Transfusing to a Desired Hemoglobin *Equation assumes 70cc/kg of total blood volume and pRBC hemoglobin concentration of 22 grams/dL pRBC volume (cc) = (Desired HgB Actual HgB)(wt in kg)(3.18) For example: A 34 kg Sickle Cell patient with acute chest syndrome has a HgB of 5.5. What volume of pRBC should be transfused to increase the patients HgB to 10.5? pRBC volume (cc) = (10.5 5.5)(3.4)(3.18) = 540cc

179

IVIG Administration Protocol

Common inpatient uses include ITP (1gram/kg), Kawasaki Disease (2grams/kg), and Stevens Johnson Syndrome (2gram/kg) It is recommended that the infusion of IVIG be initiated at a rate of 0.5ml/kg/hr. If infusion at this rate and concentration causes the patient no distress, the administration rate may be gradually doubled to a maximum rate of 4ml/kg/hr. It is recommended that antecubital veins be used, if possible. This may reduce the likelihood of the patient experiencing discomfort at the infusion site. Various minor reactions such as headache, fatigue, chills, backache, leg cramps, lightheadness, fever, urticaria, nausea, and vomiting may occur. Less common reactions include anaphylaxis, aseptic meningitis, hemolytic anemia, and noninfectious hepatitis IVIG should be used with caution if patients with known IgA deficiencies A rate of administration which is too rapid may cause flushing and changes in blood pressure. Slowing or stopping the infusion usually allows the symptoms to disappear promptly. Premedication with Benadryl and Tylenol may be useful

Initiate Infusion: Patient weight = _____ 0.5ml/kg/hr x 30 minutes, then 1ml/kg/hr x 30 minutes, then 2ml/kg/hr x 30 minutes, then 4ml/kg/hr end of infusion Example: 70kg patient 0.5ml x 70 = 35ml/hr for 30 minutes, then 1ml x 70 = 70ml/hr for 30 minutes, then 2ml x 70 = 140ml/hr for 30 minutes, then 4ml x 70 = 280ml/hr until end of infusion Vital signs Every 15 minutes x 1 hour, then Every 30 minutes x 2 hours, then Every hour until complete

180

Phone Directory
Practice Chapin Pediatrics 119 Amicks Ferry Road Chapin, SC 29036 Childrens Choice Pediatrics 6108 Garners Ferry Road Columbia, SC 29209 Carolina Pediatrics 2113 Adams Grove Rd. Suite 100 Columbia, SC 29203 Carolina Pediatrics 114 Gateway Corporate Blvd. Suite 210 Columbia, SC 29003 Carolina Pediatrics 7033 St. Andrews Rd., Suite 103 Columbia, SC 29212 Sterling Sharpe Pediatrics 4605 Monticello Rd. Columbia, SC 29203 Phone 932-2200 Fax 932-2225 Physicians Luke Bonnett, MD

647-1265

647-1266

John Carroll, MD Tom Brady, MD Philip Mubarak, MD Heather Kruger, MD

256-0531 256-0536

765-9052

376-4447

419-2647

Tanya Russo, MD

376-2838

407-1386

Heather Kruger, MD

252-7001 252-3886

252-5219

Brookland Community Peds 500 North 12th Street West Columbia, SC 29169

739-6982

939-1650

Dan Bodison, MD Kimberly Hightower, MD Lynn Wilson, MD Stuart Hamilton, MD Mary Parrish, MD Ruby Albert, MD Lyanna Yuchongtian, MD Patrice Chishom, MD Ragin Monteith, MD Adnan Qadeer, MD Luke Pruitt, MD Stuart Hamilton, MD Katherine Atkinson, MD

Pediatric & Adult Care of Batesburg-Leesville 120 West Church St., Suite E Leesville, SC 29006 Family Health Center P.O. Box 1806 Orangeburg, SC 29115 Lake Murray Pediatrics 448 Old Cherokee Road Lexington, SC 29203 Lexington Pediatrics 346 West Butler Street

532-2208

604-0207

531-6900 531-6963 520-5800

531-9629

Charles Kilgore, MD Stephanie Waters, MD Kyle Guyton, MD Joseph Delaney, MD

359-8855 359-3384

359-1257

Dwight Reynolds, MD Lillie Bates, MD

181 Lexington, SC 29072 Luberoff Pediatrics 109 Vista Oaks Drive Lexington, SC 29072 Medically Fragile Childrens Program 5 Medical Park Columbia, SC 29203 Medical Park Pediatrics and Adolescences 120 Highland Center Drive, Suite100 Columbia, SC 29203 Midlands Pediatrics 2712 Middleburg Drive, Suite 101 Columbia, SC 29204 Orangeburg Pediatric Clinic 940 Holly Street, NE Orangeburg, SC 29115 Pediatric Associates 14 Medical Park, Suite 410 Columbia, SC 29203 Pediatric Associates 1346 Haile Street Camden, SC 29020 Caroline Webber, MD Douglas Luberoff, MD

808-0523

358-0615

434-2300

254-2611

Julie Anderson, MD Cara ONeill, MD

788-0577 788-4016

788-5760

Susan Claytor, MD Randy Colby, MD

254-4257

525-7334

Clarence Dollison, MD Constance Yearling, MD Tracey MacPherson, MD Karen Connelly, MD Thomas Gue, MD Guy Castles, MD Trey Castles, MD Charlotte Lindler, MD Tom Joseph, MD Becky Riley, MD Ted Kalutz, MD Christine Sellers, MD Marguerite Charlton, MD

536-2725

534-1441

799-9044 799-9241 432-1931

256-8119

432-1176

Pediatric Associates 1165 Hwy. 1 South, Suite 100 Lugoff, SC 29078 Palmetto Pediatrics 74 Polo Road Columbia, SC 29223

438-3311

438-4020

788-4886

788-5020

Palmetto Pediatrics 3250 Harden St. Extension, Suite 100 Columbia, SC 29203 Palmetto Pediatrics 16 Woodcross Drive Columbia, SC 29212

779-4001 779-4039

252-9458

732-0140 732-0142

732-4848

Nada Hamzy, MD Rick Shrouds, MD Barry Cabiness, MD Sarah Grooms, MD Sylvia Brook,MD Jennifer Soroos, MD Teresa Baggett, MD Michael Barker, MD Debbie Greenhouse, MD Leigh Bartlett, MD Brad Painter, MD Lloyd Kapp, MD Kay Moore, MD Catherine Miller, MD Melissa Mills, MD Jerri Lynn Shealy, MD

182 Palmetto Pediatrics 1404-A West Main Street Lexington, SC 29072 Pediatric Care Center 6614 Augusta Highway Leesville, SC 29070 Pediatrics of Newberry P.O Box 355 Newberry, SC 29108 Tanya Reid, MD 114 Gateway Corp. Blvd. Suite 320 Columbia, SC 29201 Ridge Pediatrics and Adolescent Center 338 East Columbia Avenue, Suite E Batesburg-Leesville, SC 29070 Sandhills Pediatrics 9 Medical Park, Suite 110 Columbia, SC 29203 358-2370 358-2376 Jim Dewar, MD Sonya Head, MD Patricia Risinger, MD

604-8400

604-8404

405-0220

405-0222

Karl Holtzer, MD

699-7555 622-3588 532-2877

462-3704

532-5430

Linda Crout Wingard, MD

252-1801 252-1816 252-1825

540-2877

Sandhills Pediatrics 7936 Broad River Road Irmo, SC 29063 Sandhills Pediatrics 110 Summit Centre Drive Columbia, SC 29229 Sandhills Pediatrics 4568 Sunset Blvd Lexington, SC 29072 Sumter Pediatrics 237 Church Street Sumter, SC 29150

407-0704

407-2529

744-9000 744-9004 520-5147

944-9008

520-5150

Laura Lidlie, MD Grant Willard, MD Laura Rickenmann, MD Bill Taylor, MD Marc Todd, MD Kevin Wessinger, MD Bruce Cope, MD Tye Whitaker, MD Melinda OLeary, MD Ted Dubose, MD Elizabeth Haile, MD Michael Finch, MD Christie Thomas, MD

775-6311 775-5620

778-5131

The Kids Group 206 Medical Circle, Suite 1B West Columbia, SC 29169 University Primary Care 2 Medical Park, Suite 203 Columbia, SC 29203 William Westerkam, MD

796-9200

796-9226

212-7130

212-7160

Melissa Arscott, MD Teresa Buschor, MD Earl Bryant, MD Timothy Key, MD James Durant, MD Mark Mitchiner, MD John Rowe, MD Carl Whetsell, MD Doug Dodds, MD Kristine McCorquodale, MD Deanne Geurkink, MD Carol Heebner, MD Eileen Walsh, MD

749-0181

749-3229

183 320 Harbison Blvd., Suite 290 Columbia, SC 29212

184

Hospital & Other Useful Numbers

Physicians 9 East 9 West Abdullah Sakarcan, MD Admissions Amy Richburg Annette Lynn Ashley Lynn Baptist Hospital Bernarda Strauss Black River Health Care Blood Bank Cardiac Diagnostics Cardiology Carla Roberts, MD Caughman Taylor, MD CENTA Medical Group Childrens First Medical Center, Chester, SC CHOC CHOC- Resident room Clarendon Hospital Critical Care Dan Brown David Amrol, MD Dental Clinic Developmental Pediatrics Edward Cheeseman Jr., MD Elijah Adkins, MD Endocrine Fairfield County Hospital Flossie Harvey Frederick Garner, M.D. Frederick Piehl, MD Genetics George Kotchmar, MD Greta Harper, MD Hematology/Oncology Infectious Disease James Glasser, MD James Stallworth, MD Phone 434-7161 434-7326 434-2394 434-6881 434-7553 540-1157 434-7606 865-4500 799-5390 433-4321 434-7611 434-7401 434-7940 434-3510 434-7387 256-2483 581-5000 434-6155 434-7055 435-5243 434-4603 748-7555 799-5022 434-6567 935-5604 434-6836 434-4555 434-7990 635-5548 434-4649 254-2495 256-4107 799-5390 434-7980 434-4603 434-3533 434-7995 434-4555 434-4666 Pager/Cell Fax 434-6034 434-6041 434-8607 Practice Pediatric Inpatient Unit Pediatric Inpatient Unit Pediatric Nephrology Admissions Dermatology Resident Coordinator Baptist Hospital Genetics Dr Garma, Dr Keith PHR Blood Bank Amy Arnold Pediatric Hem/Onc Pediatric Administration ENT Dr Umeh

654-9764

540-1050 434-3855

433-4230 5829 352-1408 2189 434-5952 434-2262 434-3094 434-8606 799-4624 581-5015 434-6979

Clarendon Hospital 748-1040 799-5860 935-5380 USC Dept. of Ophthalmology Pediatric Surgery Fairfield County Hospital Teacher Otorhinolaryngology Orthopaedic Surgery Infectious Diseases Pediatric Critical Care Pediatric Pulmonology Allergy/Immunology Dental Clinic

434-4599 434-4669 1281 253-6676 3228 352-0582 434-8607 434-3866 434-3094 434-7983 434-4599 434-3855

1547

Pediatric Surgery General Pediatrics

185 Janice Bacon, MD Jason Hawn, MD Jeffery Ehreth, MD Joey Delaney, MD Juan Camps, MD Julia Ballance, MD Kate Clarkson, M.D. Katie Stephenson, MD Kelly Lewis, RD Kevin McRedmond, MD L. B. Mauldin, M.D. Lab (Chem) Lab (ER) Lab (Histo) Lab (Micro) Lab (Molecular) Lab (Send Out) Lab (STAT) Laura Pirich, MD Lawrence Siegel, MD Lee Carson Lenwood Smith, MD Lexington Hospital Lib Jennings Lita Middleton Lowrys Pediatrics, Chester, SC Luther Williams, MD Malaka Jackson, MD Mark Locke, MD Mark McDonald, MD Mark Posey, PhD Matt Garber, M.D. Matt Wienecke, MD Medical Records Medically Fragile Michael Bykowsy, MD Midlands Audiology Midlands ENT Moncrief Natasha Ruth, MD Neonatal ICU Neonatology Nephrology 779-4928 434-8251 434-2833 434-5027 434-4555 434-7025 799-5390 434-4629 434-3745 434-3508 254-6391 434-2327 434-2222 434-6710 434-7623 434-4977 434-7609 434-2323 434-3625 935-7543 736-4560 434-8323 791-2000 434-7638 434-4320 581-2400 434-7974 434-7098 227-8161 434-4603 935-5347 434-4652 434-7972 434-7111 434-2300 765-9233 765-1919 254-2495 751-2210 434-7929 434-7151 434-6392 434-3572 654-0159 977-1062 352-0584 7226 654-5885 434-4699 434-3855 434-2834 434-3855 434-4599 434-3855 799-5391 434-3855 434-3094 799-0682 Obstetrics & Gynecology General Pediatrics Urology General Pediatrics Pediatric Surgery General Pediatrics Genetics (Pediatrics) General Pediatrics Clinical Dietitian Pediatric Hem/Onc Neurology

2333 7227 2359 931-9044 2771 2856 352-0784

352-1405 312-0237

434-3094 935-5380 434-8326

1007 434-3855 581-2401 434-2262 434-4669 434-3866 935-5380 434-2262

Pediatric Hem/Onc Developmental Peds Dermatology Neurological Surgery Lexington Hospital Social Worker Pediatric Residency Coordinator Dr Mello Pediatric Cardiology Pediatric Endocrinology Orthopaedic Surgery Pediatric Critical Care Developmental Peds General Pediatrics Pediatric Cardiology Medical Records Allergy/Immunology Midlands Audiology Moncrief Pediatrics Pediatric Rheumatology Neonatal ICU

799-0344

654-5798

751-2014 434-2262 434-6401 434-8607

186 Neurology Neurosurgery NP on call Newberry County Memorial Hospital Newborn Nursery Olga Rosa, MD Orangeburg Regional Medical Center Ozzie Shuler, MD Patty Leopard Pediatric Clinic Pediatric ER Pharmacy Pharmacist, PICU Pharmacist, Floor Pharmacist, NICU Pharmacist, CBD PICU Poison Control Privthi Reddy, MD Providence NE Psychiatry Pulmonology Rathna Amanarth, MD Rheumatology Richard Cartie, MD Robert Holleman, MD Robert Hubbird, MD Robin Stanfield, MD Ronnie Neuberg, MD Sara Lindsey, MD ScottThompson, M.D. Sharon Kaminer, MD Shaw Air Force Base Sheila Jones, MD Shuri Coleman Southside Pediatrics Staci Dupre Stephanie Cox Sumter Family Health Surgery 434-7961 352-1415 276-7570 434-6455 434-3823 395-2200 434-7973 4347945/7020 434-6155 434-6684 434-6421 434-6068 434-3821 Newberry County Memorial Hospital Newborn Nursery Forensic Pediatrics Orangeburg Regional Medical Center Pediatric Cardiology General Pediatrics Admin. Assistant Peds Outpatient Clinic Pediatric ER Pharmacy 434-7981

355-9296

654-0158

434-2262 434-3855 434-3855 434-4582

3408 4208 2269 1832 434-7475 777-1117 434-4555 865-4500 434-4300 748-7555 254-1006 434-5989 434-6490 434-4625 434-4603 434-7528 434-3511 434-8971 254-2495 434-1096 895-2273 296-5513 434-7453 642-9204 434-3522 434-4569 774-4500 434-4555 434-7901 434-4599 PICU Poison Control Pediatric Surgery Dr Heath, Dr Stuck 748-1040 254-2090 434-2262 352-1523 352-0583 1836 954-3925 7225 654-1074 434-8607 434-3866 434-3855 434-3094 434-3855 254-2148 434-2262 895-6080 Pediatric Gastroenterology Pediatric Intensive Care Pediatric Nephrology Pediatric Critical Care General Pediatrics Pediatric Hem/Onc General Pediatrics Otorhinolaryngology Pediatric Cardiology Shaw Air Force Base Pediatrics Pitts Radiology Caseworker Dr Collins, Dr Luther, Dr Tiffany Social Work Pediatric Residency Admin. Assistant Sumter Family Health

0529 648-3633 3961 434-3855

187 Susan Luberoff, MD Teen Clinic Tim Livingston, MD Trey Brown, MD USC SOM Library Victor Iskersky, MD William Giles 898-1470 434-4118 434-3796 748-7555 733-3344 434-6392 256-2483 255-3435 434-4123 434-7981 748-1040 ARC, Wilson Building Pediatric Neurology Pediatric Pulmonology Library SOM Neonatal-Perinatal Medicine ENT

241-0639 434-4309

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