Pharmacy Critical Care

CRITICAL CARE PHARMACY HANDBOOK 2010
CLINICAL PHARMACY WORKING COMMITTEE (CRITICAL CARE SUBSPECIALTY) PHARMACEUTICAL SERVICES DIVISION, MINISTRY OF HEALTH
LIST OF CONTENTS Page CHAPTER 1 : THE ROLE OF PHARMACIST IN CRITICAL CARE Datin Fadilah CHAPTER 2 : 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 PROTOCOLS
Dilution Protocols Masrahayu, Rahela, Maznuraini DVT Prophylaxis Thong Stress Ulcer Prophylaxis Ros Sakinah Antibiotic Guidelines for Infections in Intensive Care Unit Neuromuscular Blocking Agents in Critically Ill Patients Martina Sedative Agents in Critically Ill Patients Azrina Fluid Management in Critically Ill Patients Pn Rohana Medication Administration through Enteral Feeding TubesNgua Prokinetic Agents Ngua : Pls get the doc from Pn. Siti Hir and add into this file
CHAPTER 3 : 3.1 3.2 3.3
DOSING
Renal Dosing Pn Nik Mah, Pn Nurdita Liver Dosing Shafie Special Dosing in Obese Patients Siti Hir
CHAPTER 4 : 4.2
NUTRITION
Parenteral Nutrition in Critically Ill Patients Mazni
CHAPTER 5 : 5.1 5.2
OTHERS
Drug Causing Haematological Disorder Irma Poisoning Hasni
APPENDICES: Appendix 1: Drugs that may unmask/exacerbate Myasthenia Gravis- Ain Appendix 2: Categories of Safe & Unsafe Drugs in the Acute Porphyrias- Ain
Appendix 3: Drugs and Chemicals in Glucose-6-Phosphate Dehydrogenase Deficiency Appendix 4 : Drug-Disease Interactions Pn Yam (Appendix 3 & 4)
CHAPTER 1 THE ROLE OF PHARMACIST IN CRITICAL CARE
CHAPTER 2 PROTOCOLS 2.1 Dilution Protocols 2.1.1 Antiarrhythmic Agents

a. Digoxin 500mcg/2ml ( Lanoxin ) Below 25C, Protect from light Already in solution Immediate use is recommended D5% NS For direct IV injection can be administered undiluted or diluted with a 4 fold or greater volume of diluents. The use of less than a 4 fold volume of diluents could lead to precipitation of digoxin. ( eg. 2ml ampoule with 500mcg in 500ml of diluents for infusion) METHOD OF ADMINISTRATION IV infusion (over 10-20 mins or longer-Product Information Lanoxin Injection). ( To be given at least 2 hours - BNF) Intramuscular route are not recommended. The IM route is painful and associate with muscle necrosis. REMARKS Rapid injection is not recommended; it may cause systemic and coronary arteriolar constriction. Mixing digoxin with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended. REFERENCES: 1. Product information ( Lanoxin Injection). 2. Micromedex Healthcare series. 3. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs.13 th edition. Lawrence A. Trissel. 2005. 4. British National Formulary (BNF). 55 edition. March 2008. IV bolus (2 seconds ) IV bolus into central or large peripheral vein. If given into an IV line, it should be injected as proximally as possible, and followed by a rapid saline flush (5ml of NS ). Administer with cardiac monitoring. 1. Product information Adenocor. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. b. Adenosine 6mg/2ml ( Adenocor ) Below 25C ( Do not refrigerate ) Already in solution. NA
DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION
DILUENTS FOR INFUSION
NA
DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION DILUENTS FOR INFUSION
c.
Amiodarone
d. Isoproterenol Hydrochloride 1mg/5ml ( Isuprel ) 20C - 25C. Protect from light. Already in solution. NA NS ( for IV bolus only ) D5% ( for IV bolus and IV infusion ) IV bolus : dilute 0.2mg ( 1ml ) to 10 ml NS or D5%.
150mg/3ml ( Cordarone ) Below 25C. Already in solution. NA D5%
IV ( Central line ) METHOD OF ADMINISTRATION Loading Dose : Dilute 300mg in 50 mL D5%, run over 1 hour. Maintenance Dose : Dilute 600mg in 500mL D5% run over 23 hours. IV infusion : dilute 2mg ( 10ml ) in 500 ml D5%. IM : use undiluted ( 0.2mg ) SC : use undiluted ( 0.2mg ) Intracardiac : use undiluted ( 0.02mg ) Do not use concentrations of less than 2 ampoules ( 300mg) in 500 ml. Incompatible with NS. Do not add any other products to the infusion solution. REMARKS Must be administered via the central venous route. Concentration up to 10 times greater have been used when limitation of volume is essential Rate over 30mcg/min have been used in advanced stages of shock. If heart rate exceed 110 beats /min,decrease or temporarily discontinue the infusion. Do not use if is pinkish or darker than slightly yellow or contain precipitate. 1. Product information Cordarone. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. 1. Product information Isuprel. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
REFERENCES:
DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION DILUENTS FOR INFUSION METHOD OF ADMINISTRATION REMARKS REFERENCES:
a. Streptokinase 1 500 000 IU ( Streptase ) 2C - 25C. 5ml NS. 24 hours at 2C - 8C. NS D5% IV infusion : dilute up to 20 - 250mL NS or D5% over 60 mins. Avoid IM use. 1. Product information Streptase. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
2.1.2
DRUG
Antibiotics
a. Amikacin b. Ampicilin c. Azithromycin
STRENGTH/UNIT
250mg/2ml 500mg/2ml
500mg
500mg (Zithromax)
15C - 30C
STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION
Below 25C, Protect from light, Do not freeze Already in solution
Below 25C
5ml Water for Injection use within 1 hour NS Infusion concentration should not exceed 30mg/ml.
NA
4.8ml Water for Injection 24 hours at room temperature 1 week in refrigerator NS 1/2NS D5% Lactated Ringer's Injection Infusion concentration: 1mg/ml - 2mg/ml
D5% NS D5% 1/2 NS D5% 1/4 NS Lactated Ringer's Injection
METHOD OF ADMINISTRATION
IV infusion : Adults and paed over 30 to 60 minutes. Infant over 1 to 2 hours. IM injection in large muscle mass. Amikacin should not be mixed with other antibiotics in the same solution and must be administered separately.
IV Bolus : 3 - 5 min IV Infusion : 30 - 60 min IM (Dissolve 500mg in 1.8ml Water for Injection) Rapid infusion may cause seizures.
IV infusion 1mg/ml over 3 hours IV infusion 2mg/ml over 1 hour
REMARKS
Should not be given as IV bolus or IM
REFERENCES
1. Product information Amikozit. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
1. Product information Pamecil. 2. Micromedex Healthcare series. 3. BNF 50, September 2005.
1. Product information Zithromax. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
DRUG STRENGTH/UNIT STORAGE RECONSTITUITION
d. Cefepime
e. Cefotaxime
f.
Ceftazidime
1gm (Maxipime) 15C - 30C 10ml Water for Injection, D5%, NS 24 hours at room temperature
1gm 15C - 30C , Protect from light 10ml Water for Injection Not to be stored above 25C Not longer than 24 hours NS D5%
1gm , 2gm ( Fortum ) Below 25C, Protect from light 10ml Water for Injection ( both 1gm and 2gm) 18 hours at below 25C 1 week in refrigerator NS D5%
STABILITY AFTER RECONSTITUITION
1 week in refrigerator NS
DILUENTS FOR INFUSION METHOD OF ADMINISTRATION
D5% Infusion concentration: 1mg/ml - 40mg/ml IV infusion over 30 minutes IM ( Dissolve 1gm in 3ml Water for Injection, D5%, 1%
IV bolus over 3-5 minutes. IV infusion: 100ml over
IV bolus over 3-5 minutes. IV infusion: diluent up
Lidocaine )
50 - 60 minutes. IM ( Dissolve 1gm in 4ml Water for Injection )
to 50ml over 30 minutes. IM ( Dissolve 1gm in 3ml Water for Injection ) IV preferable for dose exceeds1gm. May be used in peritoneal dialysis and CAPD. Concentration : 125 250mg for 2L of dialysis fluid 1. Product information Fortum. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. i. Ciprofloxacin
IV preferable for dose exceed 1gm REMARKS IV preferable for patient with severe or life-threatening infection.
REFERENCES
1. Product information Maxipime. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. g. Ceftriaxone
1. Product information Rekaxime. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. h. Cefuroxime 750mg, 1.5gm (Zinacef ) 25C 6ml Water for Injection for 750mg
DRUG STRENGTH/UNIT STORAGE 500mg ( Rocephin ) Below 30C 100mg/50ml, 200mg/ 100ml ( Ciprobay ) Below 25C, Do not freeze Already in solution
RECONSTITUITION
5ml of solvent
15ml Water for Injection for 1.5gm 5 hours at room temperature 48 hours in refrigerator NS NS D5% Ringer lactate NA
6 hours at room temperature 24 hours in refrigerator NS
0.45%NS D5% D5%
IV bolus over 2-4 minutes. IV infusion: 50 to 100ml over at least 30 minutes. IM ( Dissolve 500mg in 2ml 1% Lidocaine ) Neonates : IV infusion should at least 60 minutes. REMARKS Dose exceed 1gm not be given by IM. Only use Calcium-free infusion solutions. 1. Product information Rocephin. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. j. Amoxicillin and Clavulanate Potassium 1.2gm
IV bolus over 3-5 minutes. IV infusion : 50 to 100ml over 30 minutes. IM ( Dissolve 750mg in 3ml Water for Injection )
IV Infusion over 60 minutes
Slow infusion into a large vein minimize local IV site reactions Ciprofloxacin solution can be infused directly or mixing with compatible infusion diluents. 1. Product information Ciprobay 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. l. Sulfamethoxazole and Trimethoprim 480mg/5ml Below 30C, Do not refrigerate. Protect from light. Already in solution NA
REFERENCES
1. Product information Zinacef. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. k. Cloxacillin
500mg Below 25C.
Below 25C. WFI Solution should be made up to full infusion volume, immediately after reconstitution. WFI NS 10ml Water for Injection. 30 minutes after reconstitution. NS
NS D5%
D5%
10
IV Infusion: 50-100ml over 30-40 minutes METHOD OF ADMINISTRATION IV Infusion complete within 4 hours of reconstitution.
IV bolus over 3-5 minutes. IV Infusion over 2030 minutes IM ( Dissolve 500mg in 2.5ml Water for Injection )
IV Infusion over 60-90 minutes
1 amp(5ml) to 125ml, 2amp(10ml) to 250ml, 3amp(15ml) to 500ml diluent. Less stable in infusions containing glucose, dextran or bicarbonate. Fluid restriction required, 1amp(5ml) to 75ml diluent. Infusion commenced within 30 minutes after preparation. Duration of infusion not exceed 1.5 hours. 1. Product information Monoclox 1. Product information DBL 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
o. Imipenem with cilastatin 500mg 15 - 30C 10ml of diluent for infusion 4 hours at room temperature 24 hours in refrigerator NS D5% NS D5% D10% D5%NS Mannitol 5% and 10%
REMARKS
REFERENCES
1. Product information Moxied-CLV 2. 2. BNF 50, September 2005.
m. Fusidic Acid 500mg ( Fucidin) 15 - 20C 10ml of buffer solution provided. NA NS D5% **
n.
Gentamicin
80mg/2ml Below 25C Already in solution. NA
11
IV Infusion: 250 -500ml over 2-4 hours
IV infusion : 100-200ml over 30 minutes.
IV infusion : 500mg in 100m diluent for infusion. Rate depend on dose. Dose 500mg over 20 - 30 minutes , 500mg over 40 -60 minutes. Must use the same diluent for reconstitution and as infusion solution. Reconstitution of Tienam : add 10 ml of appropriate infusion solution to vial. Shake well and transfer the suspension to infusion solution container. Repeat with additional 10ml infusion solution to ensure complete transfer of vial contents to infusion solution. Resulting mixture should be agitated until clear.
Give through central venous line to minimize venospams and thrombophlebitis. If superficial vein used, infusion over 6 hours. Never be injected undiluted. REMARKS Must not be given intramuscularly or subcutaneously. ** Precipitation may occur in infusion solution pH below 7.4 ( more acidic samples of dextrose 5% ) 1. 2. 3. REFERENCES Product information Fucidin. Micromedex Healthcare series. BNF 50, September 2005.
For extended-interval doses, an infusion period of 60 minutes recommended. Administer other antibiotic at least 1 hour before or after gentamycin.
1.
p.
Meropenem
Product information Garasent. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005. q. Metronidazole 500mg/100ml 15 - 30C. Protect from light
1. 2. 3.
4.
Product information Tienam. 2. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005. r. Linezolid
500mg , 1gm ( Meronem ) Below 30C 500mg - 10ml , 1gm - 20ml of NS or D5% NS : 2 hours at RT, 18 hours in refrigerator. D5% : 1 hours at RT, 8 hours in refrigerator.
600mg/300ml ( Zyvox) 15 - 30C. Protect from light.Keep in overwrap until ready to use. Already in solution NA
Already in solution NA
12
NA NS
NA
D5%
IV bolus : 10ml of WFI per 500mg over 5 minutes. METHOD OF ADMINISTRATION IV infusion : 50-200ml over 15 - 30 minutes.
IV infusion : 100ml over 20 30 minutes.
IV infusion : 30 -120 minutes.
REMARKS
Recommended to use freshly prepared solution of Meropenem. 1. Product information Meronem. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
Avoid contact between drug and aluminium in infusion set.
Do not mix or infuse with other medications. Yellow color of the injection may intensify over time without affecting potency. 1. Micromedex Healthcare series. 2. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. 2. 3.
REFERENCES
Product information . Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
s. DRUG STRENGTH/UNIT STORAGE RECONSTITUITION
Polymixin B
500,000 units 15 - 30C 500mg - 10ml , 1gm - 20ml of NS or D5%
t. Sulbactam Sodium/Ampicilin Sodium 1.5gm Below 25C 3.2ml Water for Injection Stability at 25C and 4C depends on concentration of solution prepared. For IM administration, used within 1 hour of reconstitution.
u. Sulbactam Sodium/Cefoperazone Sodium 1gm ( Sulperazon) Below 25C 3.4ml Water for Injection, NS, D5% Stability at 25C and 4C depends on concentration of solution prepared. For IM administration, used within 1 hour of reconstitution.
72 hours in refrigerator.
13
D5%
Water for Injection NS Water for Injection NS D5%
D5% Lactated ringer
IV infusion : 300-500ml over 60 - 90 minutes. METHOD OF ADMINISTRATION IM : 2ml Water for Injection, NS, 1% procaine solution. Intrathecal : 10ml physiological solution
IV bolus : slowly over 10 -15 minutes IV infusion : 50-100ml over 15 - 30 minutes. IM : 3.2ml Water for Injection or 2% Lidocaine IV infusion : dilute using diluents (NS,Water for Injection, Lactated ringer) to a maximum concentration of 45mg/ml. IV infusion : dilute using D5% to a maximum concentration of 30mg/ml. Administer within 2 hours.
IV bolus : over minimum 3 minutes IV infusion : 20ml over 15 - 60 minutes. IM : 3.2ml Water for Injection, and further diluted with 2% Lidocaine. Must use the same diluent for reconstitution and as infusion solution.
Intrathecal is for meningeal infection. REMARKS May cause extravasation. Monitor the IV site, rotate infusion site frequently.
REFERENCES
1. Micromedex Healthcare series. 2. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. 2. 3.
Product information Easyn. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information Easyn. 2. Micromedex Healthcare series
v. Piperacillin / Tazobactam
4.5gm ( Tazocin ) Below 25C 20ml of Water for Injection, NS 24 hours at room temperature 48 hours in refrigerator
w.
Vancomycin 500mg
Below 25C. Protect from light. 10ml Water for Injection. Freshly prepared prior to use.
14
Water for Injection NS DILUENTS FOR INFUSION D5%
NS D5%
Slow Iv injection : 3 - 5 mins METHOD OF ADMINISTRATION IV Infusion :- 50 ml - 150ml for 20 - 30 mins. IM : 2.25g with 4ml WFI
IV Infusion : dilute with infusion fluid up to 5mg/ml over 1 hour.
IV infusion concentration can increased to 10mg/ml in fluid restriction, but increased risk of infusion-related effects. Rate of administration not exceed 10mg/min for doses over 500mg. Use continuous infusion if intermittent not feasible. If Red-man syndrome appears, slow infusion rate to 1 - 2 hours and increase dilution volume.
IV infusion : maximum infusion volume with WFI is 50ml. REMARKS During IV infusion, discontinue primary infusion solution.
REFERENCES
1. Product information Tazocin. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
1. 2. 3. 4.
Product information Vancotex. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005
2.1.3
DRUG
Antifungal
a. Amphotericin B b. Fluconazole c. Voriconazole
STRENGTH/UNIT STORAGE
500mg ( Fungizone) Stored in refrigerator Protected against exposure to light 10ml Water for Injection
100mg/50ml ( Diflucan ) Below 30C, Do not refrigerate. Already in solution
200mg ( Vfend) 15-30C
RECONSTITUITION
19ml Water for Injection.
15
24 hours at room temperature 1 week in refrigerator D5%
NA
24 hours at 2- 8C
NS Ringer's Solution
NS D5% Compound Sodium Lactate
Infusion concentration is 0.1mg/ml
Hartmann's solution
D20%
Slow Intravenous infusion : 2 - 6 hours METHOD OF ADMINISTRATION
IV Infusion over 1-2 hours
IV infusion: dilute to concentration of 0.5-5mg/ml over 1 -2 hours.
Test dose : 1mg in 20ml D5% , administer over 20-30 minutes Do not reconstitute with NS Begin infusion immediately after dilution and protect from light. REMARKS
Infusion rate do not exceed 200mg/hr Fluconazole is formulated in 0.9% sodium chloride solution, each 100mg containing 7.5mmol of sodium. Patient requiring sodium or fluid restriction, consideration given to rate of fluid administration.
Maximum rate :3mg/kg/hour.
REFERENCES
1. Product information Fungizone. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
1. 2. 3.
4.
Product information Diflucan. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005.
1. 2. 3.
4.
Product information Vfend. 2. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005.
2.1.4 Antiviral
Acyclovir 250mg Below 25C, Protect from light 10ml Water for Injection
16
12 hours at room temperature STABILITY AFTER RECONSTITUITION Do not refrigerate
D5% NS
Infusion concentration should be approximately 7mg/ml or less.
IV infusion (over 1 hour) METHOD OF ADMINISTRATION
Should not be given intramuscularly, subcutaneously, locally or intra-ocularly. REMARKS Rapid infusion is not recommended to avoid possible renal tubular damage. Product information Klovireks-L. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005.
REFERENCES
2.1.5
Anticoagulants
DRUG Heparin 1000 IU/ml , 5000 IU/ml. 15C - 30 C. Protect from light. Already in solution. Fondaparinux ( Arixtra ) 2.5mg/0.5ml Enoxaparin Sodium ( Clexane ) 40mg/0.4ml , 60mg/0.6ml Below 25C. Already in solution.
STRENGTH/UNIT STORAGE RECONSTITUITION
Below 25C. Do not freeze. Already in solution.
17
NA NA NA
NS
NA
NA
D5%
IV infusion : minimum volume 250ml D5%. Subcutaneous. Should be avoided in children below 2 years old and not used in neonates.
Subcutaneous.
Subcutaneous.
Must not be administered by IM. Do not mix with other injections or infusions. Prefilled syringe is designed with an automatic needle protection system to prevent needle stick injuries. 1. Product information Arixtra. 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 4. BNF 50, September 2005.
Do not administer by IM route. Pre-filled syringes are ready-to-use.
REMARKS
Do not administer IM due to pain, irritation and hematoma formation.
1. 2.
Product information Heparinol. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005.
1. 2. 3.
3. REFERENCES
4.
4.
Product information Clexane. Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 BNF 50, September 2005.
2.1.6
DRUG
Antiepileptics
a. Phenytoin b. Phenobarbitone 200mg/ml Protect from light Already in solution c. Sodium Valproate
STRENGTH/UNIT STORAGE RECONSTITUITION
250mg/ Dilantin Between 15C to 30C (Do not freeze) Already in solution
400mg (Epilim) Below 25C Reconstitute with solvent provided
18
24 hours at 2C to 8C NA NS Dilute with 50-100ml NS to make a 1mg/ml solution. Max concentration is 10mg/ml. NA NS D5% IV infusion: Dilute with at least an equal volume of fluid. IV: Over 3 to 5 minutes. Not to exceed 60mg/min. IV infusion: eg. Emergency in status epilepticus IM S/C NS D5% Dilute with at least 50ml of NS or D5%
IV: Rate not exceeding 50mg/minute. Sensitive patient eg. Elderly with cardiovascular condition should receive more slowly (eg. 20mg/minute) METHOD OF ADMINISTRATION Recommended to give through a 0.22-0.5 micron in-line filter due to high potential of precipitation. Finish infusion within 1 hour after mixing the solution. IM administration is approved but not recommended due to erratic absorption REMARKS The solution is vesicant. Avoid extravasation. 1. Product information (Dilantin Injection). 2. Micromedex Healthcare series. 3. Britisn National Formulary 56 4. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
IV infusion: Administer as 60 minutes infusion. Not to exceed 20mg/min IV: (Loading dose) single doses up to 15mg/kg has been administered as rapid infusion over 5-10 minutes.
Avoid intra-arterial injection
Divide total daily dose if exceeds 250 mg/day
REFERENCES
1. Product information (Phenobarbital Sodium Injection). 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information (Epilim Injection). 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
d.
Diazepam
e.
Thiopentone (Thiopental) 500 mg (Pentotex) Below 25C
10mg/2ml (Valium) Room temperature Already in solution
19
NA
Use immediately. Discard any unused portion after 24 hours. WFI
Recommended to give alone DILUENTS FOR INFUSION But stable in NS, D5%. Use immediately after mixing. Dilute 10 mg with 200-250ml NS or D5% IM METHOD OF ADMINISTRATION IV injection: Rate not exceeding 5mg/min IV infusion: Rate not exceeding 5mg/min Infusion rate exceeding 5mg/ min may cause apnea, venous thrombosis, REMARKS thrombophlebitis and hypotension. Avoid extravasation.
NS D5%
IV slow: Over 20 to 40 seconds of 2.5% solution. (occasionally as 0.5% solution) IV infusion: as 0.2-0.4% solution. Thiopental sodium preparation may be given rectally as solution or suspension
1. REFERENCES 2. 3. 4.
Product information ( Diazepam Injection). Micromedex Healthcare series. Britisn National Formulary 56 Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
1. Product information ( Pentotex Injection). 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
2.1.7
Antihypertensive
a. Frusemide 20mg/2ml Below 25C. Protect from light. Do not use if solutions yellow in colour. Refrigeration may result in precipitation. However, resolubilization at room temperature or Isosorbide Dinitrate 10mg/10ml Below 30C.
DRUG STRENGTH/UNIT STORAGE
20
warming may be performed without affecting the stability of frusemide. RECONSTITUITION STABILITY AFTER RECONSTITUITION Already in solution 24 hours. Protect from light. NS Lactated Ringer's D5% DILUENTS FOR INFUSION . Already in solution 24 hours.
NS D5% Recommended concentration: 0.1mg/ml ( 10mg/amp in 100 ml diluents for infusion) OR 0.2 mg/ml ( 10mg/amp in 50 ml diluents for infusion). Continuous IV infusion. It should always be administered as an intravenous admixture and should never be injected directly. 1-10mg/hr Isosorbide dinitrate adsorbed to some extent by PVC infusion containers. Preferably use glass or polyethylene container. 1. Micromedex Healthcare series. 2. British National Formulary (BNF). 55 edition. March 2008. 3. Product information Isosorbide Injection - Isoket. (Schwardz Pharma).
IM Direct IV injection (slowly over 1-2 mins)for doses<120mg IV infusion or continuous IV infusion: rate of infusion should not exceed 4mg/min. Unstable in acidic media but very stable in basic media. REMARKS
1. 2. 3. 4. 5.
REFERENCES
Micromedex Healthcare series. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. British National Formulary (BNF). 55 edition. March 2008. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps. Product information Frusemide Injection - AKOSET. (Duopharma).
c.
Labetalol 25mg/5ml Below 30C. Protected from light. Already in solution
d.
Hydralazine 20mg Below 30C. Protected from light. Dissolve with 1ml water for injection
21
Within 24 hours. Within 24 hours. NS D5% Slow IV Injection: 10ml NS IV Infusion: 500ml NS or Ringer's solution
Recommended concentration: 1mg/ml. Suggested volume: 200ml (200mg/40ml labetalol injection into 160ml of compatible diluent ) IV bolus injection - slowly over 2 minutes. May repeat 40-80mg at 10 min intervals, up to 300mg total dose.
IM, Slow IV Injection over 1 min. 1020mg 4-6 hours as needed. IV Infusion: Initially 200mcg300mcg/min; maintenance 50150mcg/min
Continuous IV infusion - initial rate of 2mg/min, titrate to response up to 300mg total dose. Incompatible with Sodium Bicarbonate and alkaline solution. Precipitation may occur.
D5% decrease stability of Hydralazine
REMARKS
REFERENCES
1. Micromedex Healthcare series. 2. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 3. British National Formulary (BNF). 55 edition. March 2008. 4. Product information Labetalol Injection (Trandate). 5. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps.
1. Micromedex Healthcare series. 2. British National Formulary (BNF). 55 edition. March 2008. 3. Product information Hydralazine Injection (Apresoline). 4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps.
2.1.8
DRUG
Gastrointestinal
a. Ranitidine 50mg/2ml Below 30C, Protect from light. Solution is a clear, colorless to yellow solution; slight darkening does not affect potency. b. Esomeprazole
STRENGTH/UNIT STORAGE
Below 30C. Protect from light. However, can be stored exposed to normal in door light outside the box for up to 24 hours.
22
RECONSTITUITION
Already in solution
5ml of NS (The degradation of reconstituted solution is highly pH dependent. It must only be reconstituted in the specified volume of NS). Reconstituted solution for injection: With 5ml of NS and store within 12 hours at room temperature. Refrigeration is not required. Reconstitution solution for infusion: With 5ml of NS, Lactate Ringer's, D5% then further dilute to final volume of 50ml solution. Storage for 6hours (D5%) and 12 hours (NS and Lactate Ringer's) in room temperature. Refrigeration is not required. NS Lactate Ringer's D5%
Within 48 hours at room temperature.
DILUENTS FOR INFUSION -
D5% NS Intermittent bolus injection: dilute to maximum of 2.5mg/ml Intermittent infusion: dilute to maximum of 0.5mg/ml IM: Injection is administered undiluted. IV: must be diluted. May be administered IVP or IVPB or continuous IV infusion. Direct IV injection/IVP: 50mg diluted to a total of 20 ml with compatible infusion solution and given over at least 5 mins. (Administration not greater than 4ml/min.) Intermittent infusion/ IV PB : 50mg added to 100ml of compatible solution and administer over 15-20 mins. (Administration not greater than 5-7ml/min). Continuous IV infusion: 150mg diluted in 250ml of compatible IV solution and infused at 6.25mg/hr for 24hrs
IV injection: over a period of at least 3 mins.
IV infusion: over a period of 10-30 mins.
REMARKS 1. 2. 3. REFERENCES 4. 5. Product information Gastril Injection. (Duopharma). Micromedex Healthcare series Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005. Drug Information Handbook. 13th edition. 20052006. Lexi-comps British National Formulary (BNF). 55 edition. March 2008.
The stability of esomeprazole in aqueous solution is strongly dependent upon pH. The rate of degradation increase in response of decreasing pH. 1. Product information Nexium Injection. (AstraZeneca). 2. Micromedex Healthcare series. 3. British National Formulary (BNF). 55 edition. March 2008.
2.1.9 Inotropes
DRUG STRENGTH/UNIT STORAGE a. Adrenaline b. Dobutamine
1.8mg/1ml 15C - 30C. Protect from light.
250mg/20ml Below 25C, Protect from light
23
Already in solution RECONSTITUITION Already in solution Within 24hrs at room temperature and refrigerate. Oxidation turns drug pink, then a brown color; solution should not be used if they are discoloured or contain a precipitate. IV: NS IV:D5% Recommended: IV infusion: 1mg in 250ml of NS Intratracheal: dilute in NS or WFI. Absorption is greater with distilled water, but causes more adverse effects on PaO2. Within 24 hours. A pink discoloration may form due to slight oxidation of the drug but no significant drug loss within recommended times. If refrigerated, solution can be stored up to 48 hours. D5% NS Must be diluted to a concentration of not more than 5mg/ml before use. If higher concentration is used eg 500mg dobutamine in 50 cc diluents of infusion. It should be protected from light. Recommended: ( eg. 250mg-500mg of dobutamine in 500 cc diluents of infusion) SC, IM, slow IV injection, IV infusion, intracardiac injection, intratracheal injection. IM injection into the buttocks should be avoided. IV infusion (mcg/min): 1-10mcg/min Central line administration if IV infusion. Avoid extravasation. REMARKS Incompatible with bicarbonate solution and other alkaline solutions. 1. Product information Adrenaline Injection BP. (Duopharma) 2. Micromedex Healthcare series. 3. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005. 4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps 5. British National Formulary (BNF). 55 edition. March 2008. Do not add to 5% sodium bicarbonate or other strongly alkaline solution. Should not be used in conjunction with other agents or diluent containing sodium bisulphites and ethanol. 1. Product information Mobitil Injection. (Duopharma) 2. Micromedex Healthcare series. 3. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005. 4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps 5. British National Formulary (BNF). 55 edition. March 2008. IV infusion (mcg/kg/min)
REFERENCES
c.
Dopamine
d.
Noradrenaline 4mg/4ml
200mg/5ml Below 25C. Protected from light
Below 25C, Protect from light
24
Already in solution RECONSTITUITION Already in solution Within 24 hours. Do not use the injection if it is darker than slightly yellow or discoloured in any other way. D5% NS Injection should be diluted before administration. DILUENTS FOR INFUSION Recommended: 200mg or 400mg of dopamine in 250ml or 500ml diluents for infusion. (Micromedex, Handbook of Injectable Drugs). Max concentration: 3.2mg/ml (BNF) Within 24 hours with protection from light. Solution gradually darkens with exposure to light or air. Do not use if it is discoloured or contains a precipitate. D5% D5%in NS NS alone is not recommended.(Product Information Levophed Injection). (Lack of oxidation protection). Must be diluted before infusion. Recommended: a. 4-8mg in 250-1000ml of diluents for infusion. ( Micromedex). (Handbook of Injectable drugs). b. 4mg in 50ml of diluents for infusion. (BNF) IV infusion (mcg/kg/min)
IV infusion (mcg/kg/min) METHOD OF ADMINISTRATION Do not add dopamine in any alkaline solution. It is inactivated in alkaline solution. Incompatible with bicarbonate It is also sensitive to oxidizing agent and iron salts. Avoid extravasation. Administer into the large vein. REMARKS
IV infusion must be given into a large vein. Avoid extravasation. Avoid contact with iron salts, alkalis, or oxidizing agents.(Product Information Levophed). Incompatible with bicarbonate solution. 1. Product information Loxin Injection (Duopharma) 2. Micromedex Healthcare series. 3. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005. 4. Drug Information Handbook. 13th edition. 2005-2006. Lexi-comps 5. British National Formulary (BNF). 55 edition. March 2008.
1. 2. 3. REFERENCES 4. 5.
Product information Loxin Injection (Duopharma) Micromedex Healthcare series. Pocket Guide to Injectable Drugs. Companion to the handbook on Injectable Drugs. 13 th edition. Lawrence A. Trissel. 2005. Drug Information Handbook. 13th edition. 20052006. Lexi-comps British National Formulary (BNF). 55 edition. March 2008.
2.1.10 Miscellaneous
DRUG STRENGTH/UNIT a. Parentrovite b. Potassium chloride c. Pralidoxime
5ml x 2 ampoules (1 pair) (P-Trovite)
10% W/V, 10ml
500mg/20ml (Pampara)
25
Protect from light Already in solution N/A
Below 25C Already in solution NA NS (for the treatment of hypokalemia) Maximum concentration recommended for peripheral line is 6g/L. (can dilute up to 3 gm KCL in 500ml NS). For fluid restricted patient with central line, maximum concentration recommended is 11g/L.
Below 28C, Protect from light, Already in solution NA For IV intermittent: as 5% to 10% solution (the product is 2.5% in strenght, so can be readily administered) For IV infusion: Dilute in 100ml NS
Compatible with commonly used intravenous solutions
The content of each ampoule (No 1 and No 2) should be mixed prior to injection. METHOD OF ADMINISTRATION Although compatible with commonly used intravenous solutions, it is recommended parentrovite is given by slow injection
For fluid restricted patient with central line, maximum concentration recommended is 11g/L.
IV intermittent : over 5 to 10 minutes. IIV infusion: over 15 to 30 minutes S/C IM
REMARKS Product information (P-trovitel).
Use with caution in patients with cardiac disease
Maximum recommended daily dose is 12 gm 1. Product information (Pampara injection). 2. Micromedex Healthcare series. 3. British National Formulary 56. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
REFERENCES
1. Product information (Potassium chloride 10% W/v 10ml). 2. Micromedex Healthcare series. 3. British National Formulary 56. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
DRUG
d.
N-Acetylcysteine 2gm/10ml
e.
Piracetam
f.
Desmopressin
1gm/5ml
4mcg/ml (Minirin)
STRENGTH/UNIT
5gm/25ml
26
Below 25C, Already in solution NA D5% (Preferable) NS
15C to 25C Already in solution NA
2C to 8C Already in solution NA NS IV infusion: Dilute in 50ml NS
PCM poisoning: 150mg/kg in 200ml, then 50mg/kg in 500ml followed by 100mg/kg in 1000ml. PCM poisoning: IV infusion of 150mg/kg over 15 to 60 minutes, then IV infusion of 50mg/kg over 4 hours followed by IV infusion of 100mg/kg over 16 hours. Prevention of radiocontrastinduced renal dysfunction (unlabeled use): IV infusion For PCM poisoning patient less than 40kg and those requiring fluid restriction, the volume of diluent could be adjusted as needed to avoid fluid overload. 1. Product information (Hidonac NAcetylcysteine). 2. Micromedex Healthcare series. 3. Britisn National Formulary 56 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 1. Product information (Nootropil Injection). 2. Micromedex Healthcare series.
S/C IM IV infusion over 15 to 30 minutes
NA
REMARKS
1. 2. 3. 4.
Product information ( Minirin injection). Britisn National Formulary 56 Micromedex Healthcare series Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
REFERENCES
g.
Haloperidol 5mg/ml
h.
Calcium gluconate 10ml Below 30C.
i.
Dantrolene
20 mg (Dantrium) Below 30 C. Do not refrigerate. Protect from light. 60ml WFI (shake until solution is clear)
Below 25C. Protect from light. Already in solution
Already in solution
27
If necessary transfer individual vials into a larger volume sterile IV plastic bag. Do not transfer into glass bottle. Precipitation may occur. STABILITY AFTER RECONSTITUITION NA D5% IV infusion : Dose of 0.5mg100mg in 50ml-100ml D5% NA D5% NS IV infusion: Dilute to a maximum concentration of 50mg/ml (eg. 1gm in 20ml) IV slow bolus: Maximum rate of 50mg/minute IV infusion: The diluted solution of 50mg/ml to be infused over 1 hour IV push: In malignant hyperthemia crisis IV infusion: Over 1 hour in prevention of malignant hyperthemia Use within 6 hours at room temperature. NOT to be mixed with other intravenous infusions.
IM METHOD OF ADMINISTRATION IV bolus IV infusion of 50ml-100ml diluted solution with the rate of 3-25mg/hour Decanoate form should never be administered IV (IM only)
REMARKS
Has rarely been given by IM and S/C, but not recommended because the risk of tissue necrosis. 1. Product information (Calcium gluconate injection) 2. Britisn National Formulary 56 3. Micromedex Healthcare series. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
Solution is high pH and there is possibility for tissue necrosis, avoid extravasation. 1. Product information (Dantrium Intravenous) 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook,
1. Product information
(Manace injection 5mg) 2. Britisn National Formulary 56 3. Micromedex Healthcare series. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
REFERENCES
j.
Mannitol
20% (100gm/500ml) Between 15C to 30C. Do not freeze. Already in solution.
Potassium dihydrogen phosphate 10mmol/10ml (1.361g) Below 25C.
k.
Human Normal Immunoglobulin Intragam 3g (50ml) 2C to 8C. Do not freeze. Once removed from refrigeration, store below 25C and use within 3 months Already in solution
l.
RECONSTITUITION
Already in solution
28
NA
NA D5% NS Must be diluted before use
NA Can be administered undiluted Or can be diluted with up to 2 parts of NS or D5%
NA
IV doses should be incorporated into patient's maintenance IV fluid. Intermittent IV infusion should be reserved for severe depletion patient under ECG monitoring. IV infusion, slow: administer over 6 to 12 hours. Minimum infusion time is 4 hours. IV infusion: can be given undiluted. Start infusion at the rate of 1ml/minute. After 15 minutes, the rate can be gradually increased to a maximum of 3 to 4ml/minute. Reducing the rate in elderly and in patients with preexisting renal disease should be considered. Infusion which is too rapid may cause flushing and changes in heart rate and blood pressure. Prolonged administration (over 6 hours) using larger dose (greater than 0.4g/kg) may result in thrombophlebitis at the infusion site. Product information (Intragam).
Test dose (to assess adequate renal function): IV over 3-5 minutes METHOD OF ADMINISTRATION IV infusion (eg. Cerebral edema or increased intraocular pressure): over more than 30 minutes Use a filter when infuse mannitol solution of concentration of 20% or more. REMARKS
Incompatible with calcium or magnesium containing solutions.
1. 2. REFERENCES
Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
1. Product information (Potassium Dihydrogen Phosphate injection) 2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
DRUG STRENGTH/UNI T STORAGE RECONSTITUITI ON
m. Hydrocortisone 100mg Below 25C 2ml WFI
n.
Methylprednisolone
o.
1gm (Solu-Medrol) Below 25C Reconstitute with the diluent (15.6ml WFI+ Benzyl alcohol) provided
Dexamethasone sodium phosphate 8mg/2ml
Below 25C, Protect from light. Already in solution
29
Use immediately after reconstitute D5% NS
48 hours at temperature below 25C D5% NS
NA
D5% NS IV infusion: Dilute content of vial with 50-100ml of diluents Diluted solution is stable for 24 hours in room temperature or 2 days in fridge
IV infusion: Reconstituted solution is then further diluted to 1mg/ml
IM IV injection: Over 30 seconds to several minutes depending on the dose IV infusion: Over 20 to 30 minutes METHOD OF ADMINISTRATI ON
IM IV bolus: The reconstitued solution can be given undiluted. Preferred for emergency. Only for low dose (<125mg) - over 5 to 15 minutes and moderate dose (below 250mg) - over 15 to 30 minutes. Maximum concentration: 125mg/ml IV infusion : Dilute the reconstitued solution with D5% or NS. For high dose (more than 250mg) - over at least 30 minutes. Dose of more than 1 gm - over 1 hour Special notes: For acute spinal cord injury, start with IV bolus. After 45 minutes pause, followed by IV infusion of 5.4mg/kg/hour for 23 hours.
IM IV injection: Administer as IV bolus over 5-10 minutes or can be administered through tubing IV infusion: Of diluted solution
REMARKS
none
Rapid IV bolus injection is associated with high incidence of perianal discomfort 1. Product information (Penatone Injection). British National Formulary 56 3. Micromedex Healthcare series. 4. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005 r. Sodium bicarbonate
REFERENCES
1.Product information 1. Product information (Solumedrol) ( Stricort 100mg) 2. Lexi-Comp's Drug Information 2.Lexi-Comp's Drug Handbook, 12th Edition, Charles Information Handbook, F, Lacy, et al.2003 12th Edition, Charles F, 3. Britisn National Formulary 56 Lacy, et al.2003 4. Micromedex Healthcare series. 3. British National Formulary 56 q. Tranexamic acid p. Vitamin K (Phytomenadione) 10mg/ml (Kisan) 1g/10ml Below 25C. Protect from light. Aiready in solution
8.4% (10mmol/10ml) Below 25C. Protect from light. Aiready in solution
Between 15C to 30C. Protect from light. Aiready in solution
RECONSTITUITION
30
NA
NA NS D5%
NA WFI NS D5% S/C: Dilute to isotonicity (1.5%) by adding 1ml of 8.4% solution into 4.6ml WFI or NS or D5%
NS DILUENTS FOR INFUSION D5%
IM Slow IV: Reserved for potentially fatal haemorrhage. Maximum per dose-20 mg and maximum total doses - 40mg. IV injection at rate not exceeding 1mg/minute. IV infusion S/C
Slow IV: Do not inject more rapidly than 1ml/min IV continous infusion: eg. Local fibrinolysis - 25 to 50mg/kg over 24 hours or post operation on heart -1mg/kg/hour for 5 to 6 hours.
IV: of undiluted solution. Rate not exceeding 10mEq/minute (equivalent to 10ml/minute) IV: of diluted solution S/C: Of diluted to 1.5% solution.
REMARKS
Injectable solution may be given orally, undiluted.
Sodium bicarbonate solution 8.4% contains 1 mEq/ml bicarbonate (and sodium) 1. Product information ( Tren Injection) 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 4. Micromedex Healthcare series 5. Martindale 32nd Edition 1. Product information ( Sodium Bicarbonate 8.4% injection) 2. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 3. Micromedex Healthcare series
REFERENCES
1. Product information ( Kisan 10mg/ml) 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 4. Micromedex Healthcare series
s.
Magnesium Sulphate 2.465 g/ 5ml Below 25C.
t.
Nimodipine
10mg/50ml (Nimotop) Below 30C. Already in solution
Aiready in solution
31
NA NS D5% Lactated Ringer
N/A Solution is for direct infusion. See Method Of Administration
IV: 1 ampoule (5ml) diluted with at least 7.5ml of compatible solution IM: dilution is not required but each ampoule (5ml) can be diluted with 5ml of compatible solution. IV infusion: administer as continous IV infusion via CENTRAL catheter using infusion pump. It should be given via three-way stopcock together with 40ml/hr of either NS or D5% or Lactated Ringer. Solution must not be added to an infusion bag or bottle. Nimodipine is absorbed by PVC so the PE tube provided must be used.
IM: of undiluted or diluted solution. IV bolus: of diluted solution at rate not exceeding 150mg/minute METHOD OF ADMINISTRATION IV infusion: rate not exceeding 2g/hour 500mg MgSO4 = 4.06 mEq Mg = 49.3 mg elemental Magnesium
REMARKS 1. 2. 3. 4. 5. Product information ( Magnesium Sulphate Concentrated Injection) British National Formulary 56 Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 Micromedex Healthcare series Martindale 32nd Edition
Mannitol, human albumin or blood are suitable for co-infusion 1. 2. Product information (Nimotop) British National Formulary 56.
REFERENCES
2.1.11 Muscle Relaxant

DRUG a. Suxamethonium b. Rocuronium c. Pancuronium 4mg/ 2ml (Pavulon)
25mg/ 2.5 ml (Esmeron) STRENGTH/UNIT 100mg/ 2ml 50mg/ 5ml
32
Between 2C to 8C. Protect from light STORAGE Multiple-dose vial solution are stable at room temperature for 14 days Already in solution NA
Between 2C to 8C. Protect from light.
Between 2C to 8C.
RECONSTITUITION STABILITY AFTER RECONSTITUITION
Already in solution NA NS
Already in solution.
N/A NS D5%
NS D5% DILUENTS FOR INFUSION Normally prepared as 1-2mg/ ml solution
D5% WFI Dilute to a concentration of 0.5mg/ ml or 2mg/ml. Up to 5mg/ml. IV bolus: of indiluted IV infusion
IM: Total dose not exceeding 150mg IV injection: over 10 to 30 seconds. Without dilution IV infusion: Ranged from 0.5 mg10mg/ minute. Normally at the rate of 2.5-4.3mg/ minute. Suxamethonium Chloride = Succinylcholine chloride 1. Product information ( Suxamethonium Chloride Fresinius Injection). 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 4. Micromedex Healthcare series
IV bolus: of the undiluted solution. Can be administered through the line of a running infusion. IV infusion.
REMARKS
If stored at room temperature, rocuronium should be used within 60 days
1. Product information
(Rocuronium bromide Injection - Esmeron). 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 4. Micromedex Healthcare series
REFERENCES
1. Product information (Pavulon). 2. LexiComp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 3. Micromede x Healthcare series
DRUG
d.
Atracurium
e.
Vecuronium
25mg/ 2.5ml STRENGTH/UNIT 50mg/ 5ml
4mg (Norcuron) 10mg
33
STORAGE
Between 2C to 8C. Protect from light.
Below 25C. Protect from light. Norcuron 4mg: with 1ml WFI (to make 4mg/ml solution) or with 4ml WFI (to make1mg/ml solution)
RECONSTITUITION
Already in solution Norcuron 10mg: with 5ml WFI (to make 2mg/ml solution) or with 10ml WFI (to make 1mg/ml solution) 12 hours at 15C to 25C. But product leaflet recommends to discard any unused portion. D5% NS Dilute reconstituted vial to 0.1-0.2mg/ml.
NA
NS D5% DILUENTS FOR INFUSION Solution may be prepared in a range of 0.2mg/ml to 5mg/ml. Common as 0.2mg/ml and 0.5mg/ml. Stability: 24 hrs in NS, 8 hrs in D5% at 30C
IV bolus: of reconstituted solution IV infusion: of diluted solution. Concentration of 1mg/ml may be used for IV infusion in fluid-restricted patient
IV injection: of indiluted METHOD OF ADMINISTRATION IV infusion
Not for IM due to tissue irritation. REMARKS 1. Product information ( Atralex Injection). 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 4. Micromedex Healthcare series Product information (Norcuron). 2. British National Formulary 56 3. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
REFERENCES
2.1.12 Respiratory
DRUG
a. Potassium chloride
10% W/V, 10ml
b.
Pralidoxime
c.
Salbutamol
500mg/20ml (Pampara) STRENGTH/UNIT
0.5mg/ml 5mg/5ml
34
Below 25C Below 28C, Protect from light, Already in solution NA Already in solution NA For IV intermittent: as 5% to 10% solution (the product is 2.5% in strenght, so can be readily administered) For IV infusion: Dilute in 100ml NS
Below 30C, Protect form light Already in solution
NA NS D5% WFI WFI can be used to dilute Ventolin 0.5mg/ml to facilitate injection IV infusion: Dilute 5mg/5ml salbutamol in 500ml Ns or D5% to produce 10mcg/ml solution.
NS (for the treatment of hypokalemia) Maximum concentration recommended for peripheral line is 6g/L. (can dilute up to 3 gm KCL in 500ml NS). For fluid restricted patient with central line, maximum concentration recommended is 11g/L.
IV intermittent : over 5 to 10 minutes. IV infusion (Maximum rate is 3 gm/hour) IIV infusion: over 15 to 30 minutes S/C IM REMARKS Use with caution in patients with cardiac disease 1. 2. REFERENCES 3. 4. Product information ( Potassium chloride 10% W/v 10ml). Micromedex Healthcare series. British National Formulary 56. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003 Maximum recommended daily dose is 12 gm 1. Product information (Pampara injection). 2. Micromedex Healthcare series. 3. British National Formulary 56. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
S/C IM IV slow bolus IV infusion
1. Product information (Ventolin injection). 2. Micromedex Healthcare series. 3. British National Formulary 56.
DRUG STRENGTH/UNIT
d.
Terbutaline
e.
Aminophylline
0.5mg/ml
250mg/5ml
35
Below 25C STORAGE Below 25C
Already in solution N/A D5%
Already in solution NA NS D5%
NS DILUENTS FOR INFUSION For premature labour: Dilute in D5% to a concentration 100mcg/ml and give via syringe pump. If pump not available, dilute to a concentration of 10mcg/ml. S/C: For bronchodilation. METHOD OF ADMINISTRATION IV infusion: For tocolysis acute (unlabeled used), duration of infusion is at least 12 hours. Dilute with NS to a concentration of 1mg/ml. Max concentration is 25mg/ml
IV slow injection IV infusion: LD: Over 20-30 minutes. Rate not exceeding 25mg/minute.
REMARKS 1. 2. REFERENCES 3. 4. Product information (Terbutaline injection- Baltic). Micromedex Healthcare series. British National Formulary 56. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
Dose of aminophylline = dose of theophylline/ 0.8 1. Product information (Aminophyllin IVFresenius injection). 2. Micromedex Healthcare series. 3. British National Formulary 56. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
2.1.13 Sedative
DRUG a. Fentanyl b. Dexmedetomidine Hydrochloride c. Propofol
36
STRENGTH/UNIT
0.1mg/2ml Below 25C. Protect from light.
200mg/2ml (Precedex)
200mg/20ml (Fresofol 1% emulsion) Below 25C. Do not freeze. Shake before use.
Between 15C to 30C .
STORAGE
Already in solution
Already in solution After dilution, store at 2-8C and use within 24 hours. NS Must be diluted before use for both LD and maintenance dose. Dilution is the same for LD and MD: 2ml of dexmedetomidine add into 48ml NS.
Already in solution
NA NS D5%
NA
NS D5% Minimum concentration is 2mg propofol /1ml diluent. Do not dilute less than 2mg/ml. Dilute in glass bottle. Shake before use Also compatible with lidocaine 1% (not exceeding 20mg lidocaine /200mg propofol)
IV slow over 1-2 minutes METHOD OF ADMINISTRATION IV infusion IM
IV infusion (using a controlled infusion device) LD: 1mcg/kg over 10 minutes followed by infusion of 0.20.7mcg/kg/hr (titrate accordingly) Contious infusion not to exceed 24 hours. Safety and effectiveness have not been evaluated in infusions over 24 hours. 1. Product information (Precedex) 2. Micromedex Healthcare series. 3. Lexi-Comp's Drug Information Handbook, 13th Edition, Charles F, Lacy, et al.2005
IV bolus IV infusion For IV infusion, both diluted or undiluted solution can be used. Duration of administration must not exceed 7 days.
REMARKS
Muscle rigidity may occur with rapid IV administration 1. Product information (Fentanyl Citrate Injection). 2. Britisn National Formulary 52 3. Micromedex Healthcare series. 4. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
REFERENCES
1. Product information (Fresofol 1% MCT/LCT emulsion). 2. Britisn National Formulary 52 3. Micromedex Healthcare series.
DRUG STRENGTH/UNIT
d.
Midazolam
e.
Morphine
5mg/ml , 15mg/3ml (Dormicum)
10mg/ml
37
Below 25C. Protect from light. STORAGE Room temperature
Already in solution NA NS D5% Concentration of dilution: 15mg midazolam per 100-1000ml diluent (source: Dormicum product insert) Concentration of dilution: The 5mg/ml formulation should be diluted to a concentration 0.5mg/ml (source: Micromedex) IV bolus (at a rate of 1mg over 30 seconds. Elderly: dose of 2-2.5mg over 5-10 minutes)
Already in solution. NA D5% Usual concentration for IV infusion is 0.11mg/ml For IV slow, a strenght of 2.5 to 15mg may be diluted in 4-5ml WFI
IV slow (over 2-5 minutes) IV infusion IM S/C
IV infusion IM
None REMARKS 1. 2. 3. 4. Product information (Dormicum). Britisn National Formulary 52 Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
Rapid S/C administration may cause local tissue irritation 1. 2. 3. 4. Product information (Dormicum). Britisn National Formulary 52 Micromedex Healthcare series. Lexi-Comp's Drug Information Handbook, 12th Edition, Charles F, Lacy, et al.2003
REFERENCES
2.2
Deep Vein Thrombosis Prophylaxis
2.2.1 INTRODUCTION
38
The occurrence of deep vein thrombosis in hospitalised patients is depending upon various risk factors. In orthopaedic patients undergoing surgery, up to 76.5% incidence of DVT has been reported.1 Meanwhile approximately 10 to 40% among medical or general surgical patients and 40 to 60% of patients having major orthopedic surgery, and was not placed on DVT prophylaxis are confirmed as having hospital-acquired DVT.2 One quarter to one third of these thrombi involve the proximal deep veins, and these thrombi are much more likely to produce symptoms and result in pulmonary embolism (PE). 3In a study of 51,645 hospitalized patients, the prevalence of acute PE was 1%, and PE was believed to have caused or contributed to death in 37% of these cases4. To prevent the occurrence of DVT and subsequent pulmonary embolism which can be fatal, thromboprophylaxis is recommended. The 2 methods of prophylaxis are either pharmacological or mechanical and are described under methods of prophylaxis.
2.2.2 DEFINITIONS Deep vein thrombosis (DVT) is defined as a clot that occurs in the deep veins of the extremities. Further subclassifications include symptomatic versus asymptomatic and proximal (above the knee) versus distal (below the knee). 5 Pulmonary embolism is defined as being a clot usually originating from a DVT that travels to the pulmonary vasculature where it becomes an embolism and thereby impedes gas exchange distal to embolism. 5 Venous thromboembolism (VTE) is defined as an event due to thrombosis of a vein and includes DVT or PE. 5 Thrombophlebitis is the inflammation of a vein around which a DVT has occurred. This condition can be painful and chronic. This term is synonymous with postphlebitic or postthrombotic syndrome. 5 Immobilized : restricted to bed or chair with no instruction or ability to ambulate. 5
2.2.3 INDICATIONS FOR PROPHYLAXIS All adult inpatients will be assessed for their risk of VTE that include the background history and acute or subacute precipitating factors which are shown in table 1. Clinicians will need to use their own judgment in addition to the guideline to determine the best method of reducing the risk of VTE in
39
each individual patient. It is the combined responsibility of the physician and other healthcare staff including the clinical pharmacist and nursing staff to ensure all patients at risk for VTE have received appropriate prophylaxis when needed.1 Table 1 : Venous Thromboembolism Risk Factors 6
Background Factors
Age Marked obesity ( BMI >30 ) Immobility ( bed rest longer than 4 days. ) Pregnancy Puerperium High dose estrogens Previous DVT or PE Thrombophilia - Deficiency of antithrombin, protein-C or protein-S - activated protein-C resistance - antiphospholipid antibody or Lupus anticoagulant. Precipitating Factors Trauma or surgery, especially of pelvis, hip, lower limb. Malignancy , especially pelvic , abdominal , metastatic Heart failure Recent myocardial infarction Paralysis of lower limb(s) Severe infection Inflammatory bowel disease Nephrotic syndrome Polycythemia Paraproteinemia Paroxysmal nocturnal hemoglobinurea Bechets disease. Burns
a. Low-risk groups 1 patients with minor trauma or minor medical illness at any age, in the absence of thrombophilia, previous DVT or PE.
40
patients undergoing minor surgery (duration under 30 minutes) at any age, in the absence of other risk factors. patients undergoing major surgery (duration over 30 minutes) who are aged under 40 years and have no additional risk factors. b. Moderate risk groups 1 patients undergoing major general, urological, gynaecological, cardiothoracic, vascular, or neurological surgery who are aged > 39 years or with other risk factors. patients immobilised with acute medical illness. major trauma minor surgery or trauma or illness in patients with previous deep vein thrombosis, pulmonary embolism, or thrombophilia. c. High-risk groups1 fracture or major orthopaedic surgery of pelvis, hip, or lower limb. major pelvic or abdominal surgery for cancer. major surgery, trauma, or illness in patients with previous deep vein thrombosis, pulmonary embolism, or thrombophilia. lower limb paralysis (for example, hemiplegic stroke, paraplegia). critical lower limb ischaemia or major lower limb amputation. 2.2.4 METHODS OF PROPHYLAXIS There are two method of prophylaxis of DVT, which are 1 a. Pharmacological methods : b. Standard heparin (usually in low dosage) Low molecular weight heparins Oral anticoagulant such as warfarin Aspirin
Mechanical methods - increase venous outflow and/or reduce stasis within the leg veins : - Graduated compression stockings (GCS) - Intermittent pneumatic compression (IPC) devices - Venous foot pump (VFP)
* Below is a summary table for recommendation of method prophylaxis regarding the type of risk and procedure.
41
Table 2: Recommended DVT prophylaxis for surgical procedures and medical conditions 8
Surgery/Condition General Surgerylowrisk: minor procedures, <40 years old, no additional risks General Surgery moderate risk: minor procedure but with risk factor, nonmajor surgery age 40-60 with no risks, or major surgery <40 years with no risks Recommended Prophylaxis None Early ambulation Comments
Heparin , LMWH , ES, or IPC
Heparin 5000 7500 iu bd OR
LMWH (daily dose according to manufacturer) with IPC or ES.

* LMWH and heparin has comparable efficacy for DVT prophylaxis.8,9 The clinical advantages of LMWH over LDUH is its once-daily administration and the lower risk of heparin-induced thrombocytopenia (HIT), BUT LMWH is more costly.10 Heparin , LMWH Heparin 5000 7500 iu tds OR LMWH (daily dose according to manufacturer) *In high-risk general surgery patients, higher doses of LMWH provide greater protection than lower doses.3
General Surgeryhigh risk: non-major surgery over age 60 or over age 40 with risks.
General Surgeryvery high risk: major surgery over age 40 plus prior VTE, cancer or hypercoagulable state Elective Hip Replacement
LMWH combined with ES or IPC
LMWH (daily dose according to manufacturer
*May consider post discharge LMWH or perioperative warfarin LMWH or warfarin May combine with ES or IPC; start LMWH 12 hours before surgery, 12-24 hours after surgery, or 4-6 hours after surgery at half the dose for initial dose for at least 10 days. Start warfarin preoperatively or immediately after surgery, target INR 2. 0-3. 0. Extended prophylaxis is recommended for up to 28 to 35 days after surgery. 8
42
Surgery/Condition Elective Knee Replacement
Recommended Prophylaxis LMWH or warfarin
Comments Both LMWH and warfarin resulted in significantly fewer proximal DVTs compared with LDUH or IPC (p<0.006 for each comparison).11 Pooled data from 5 trials that directly compared LMWH with warfarin showed rates of proximal DVT of 3.4% and 4.8%, respectively.8
Hip Fracture Surgery Neurosurgery Trauma Acute Spinal Cord Injury Ischemic Stroke
LMWH or warfarin IPC, LDUH or LMWH LMWH with ES or IPC LMWH LDUH, LMWH Start LMWH post-surgery If high risk of bleeding, may use ES and/or IPC alone. Continue LMWH during rehabilitation or convert to warfarin (target INR 2.5) If contraindication to anticoagulant, use ES or IPC. Two studies directly comparing LDUH (5000 U three times daily) to LMWH (enoxaparin 40 mg once daily), using venography for diagnosis, found greater reduction in DVT with LMWH.8 A meta-analysis of studies of hospitalized patients with conditions other than myocardial infarction or ischemic stroke given VTE prophylaxis with unfractionated or low molecular weight heparin showed no significant difference was found between LMWH and LDUH in incidence of DVT, PE, or mortality; however, major hemorrhage was lower with LMWH than with LDUH (RR 0.48, 95% CI: 0.23-1.00).12
ES INR IPC
: elastic stockings : international normalized ratio : intermittent pneumatic compression
LDUH: low-dose unfractionated heparin LMWH: low molecular weight heparin VTE : venous thromboembolis. administration problem, thus it is not
* warfarin is hardly use in critical care due to recommended as first line
43
Table 3: MEDICATIONS USED TO PREVENT DVT

Medication Class Unfractionated heparin Heparin Moderate risk SC Heparin 5000units twice daily High risk SC Heparin 5000units 8 hourly Low molecular weight heparin
Medication Dosage
Enoxaparin 20 mg SC daily (moderate risk surgery) OR 40 mg SC daily (can go up to 30 mg SC q12h for high risk general surgery, major trauma or acute spinal cord injury) 14 Morbid obese (> 150 kg): can increase to SC 60 mg 12 hourly 13 Dose renal adjustment ( CrCL < 30 ml/min )14 Prophylaxis dose : SC 20 mg daily Therapeutic dose : 1 mg/kg daily
Fondaparinux Adult (>50 kg) 2.5 mg SC once daily Initiate dose after hemostasis has been established, 6 8 hours postoperatively. 16
Duration
5 days OR until hospital discharge if this is earlier than 5 days.
Surgical case14 7 10 days or longer if there is a risk of DVT and until patient ambulatory.
Orthopedic and abdominal surgery15 5 9 days after surgery.
Medical case14 6 14 days
In patient undergoing hip fracture surgery 9 24 days ( consider the risk )
Medical patients with DVT risk Duration of 6 to 14 days . Monitoring Platelet count Recommendation : the platelet count is monitored in patients receiving heparin for more than five days, and that heparin is stopped immediately if Platelet count Risk of thrombocytopenia (happen between 5th and the 21st day following the beginning of enoxaparin therapy.) If it significant decrease (30 to 50% of initial count), the treatment should be discontinued Full blood count, serum creatinine, and occult blood testing of stools are recommended. PT and APTT are insensitive measures. 16
Medication Class
Unfractionated heparin Heparin thrombocytopenia occurs.
Low molecular weight heparin
Medication
Enoxaparin and switch to other alternative.
Fondaparinux
Contraindication16
- bleeding disorders - a history of allergy either to enoxaparin, heparin or other low molecular weight heparin 1
- Hypersensitivity to fondaparinux - severe renal impairment (CLCr < 30 mL/min) - body weight < 50 kg (prophylaxis) - active major bleeding - bacterial endocarditis - thrombocytopenia
Precaution16
Hypersensitivity to drug.
May cause thrombocytopenia. Discontinue and consider alternative if platelet are < 100,000/mm3 or /and thrombosis develop.
Recent or anticipated neuraxial anesthesia (epidural or spinal anesthesia) are at risk of spinal or epidural hematoma and subsequent paralysis. Consider risk versus benefit.
Same with enoxaparin
Not to be use interchangeable (unit-for-unit) with heparin, LMWH or heparinoids.
Risk of thrombocytopenia
Use caution in patient with moderate renal dysfunction
In neonate suggest use preservative free as some preparation content large amount benzyl alcohol (> 100 mg/kg/day) that can cause fatal toxicity (gasping syndrome).
Caution in patient with renal failure; dosage adjustment need for ClCr < 30 mL/min.
Patient with severe hepatic impairment with elevation in prothrombin time.
Not recommended prior to and during percutaneous coronary prevention (PCI) for reperfusion in STEMI patients, due to increasesd risk for guiding catheter thrombosis.
Medication Class
Unfractionated heparin Heparin
Medication
Enoxaparin
Fondaparinux
Avoid administration 24 hours before and 48 hours after coronary artery bypass graft (CABG) surgery. Side effect Thrombocytopenia occurs in about 3-4% of patients given prophylactic heparin. Allergic reactions (including skin necrosis), raised serum transaminase concentrations, and osteoporosis with long term use (especially in pregnancy) 1 1 to 10% risk16 CNS : fever, confusion, pain Dermatology : erythema, bruising, hematoma at site of injection GI : nausea, diarrhea Hematologic : hemorrhage, thrombocytopenia Hepatic : ALT/ALP increase > 10% - Fever, nausea, anemia16
1- 10% Edema, hypotension, insomnia, dizziness, headache, confusion, rash, purpura, bullous eruption, hypokalemia, constipation, vomiting, diarrhea, dyspepsia, moderate thrombocytopenia, increase in liver enzyme. 16 Increased effect/toxicity if use with anicoagulants, antiplatelet agents, drotecogin alfa, NSAIDs, salicylates and thrombolytic agents. 16
Drug interaction
Increased effect/toxicity if use with anticoagulant, thrombolytics, dextran and drug affect platelet function ( eg aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel), cephalosporins which contain MTT chain and parenteral penicillins (may inhibit platelet aggregation). 16 Decreased effect if use with Nitroglycerin (IV) that may occur in high dosages. 16
Increased effect/toxicity if use with anticoagulant, thrombolytics, dextran and drug affect platelet function ( eg aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel), cephalosporins which conatain MTT chain and parenteral penicillins (may inhibit platelet aggregation). 16
Special instruction
There is an increased risk of wound haematomas, which can be minimised by avoiding injections
To avoid loss of medicinal product when using prefill syringe do not expel the air bubble from the syringe before
Medication Class
Unfractionated heparin Heparin close to wounds. 1
Medication
Enoxaparin
Fondaparinux the injection. 15
IV administration (first dose in STEMI patients only) either directly or use small volume (2550 ml) 0.9% saline minibag and administer through existing IV line over 1 -2 minute. Then flush with saline after injection to ensure all medicinal product is administered.15
References 1. College of surgeons Malaysia. 1999 . Consensus On Prophylaxis Of Venous Thromboembolism. Academy of medicine Malaysia. Wiig, JN, Solhaug, JH, Bilberg, T, et al 1995. Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery: multicentre trials 20 mg and 40 mg enoxaparin versus dextran. Eur J Surg 161,663-668 Geerts WH, GP, Pineo Heit JA, Bergqvist D, Lassen MR, Colwell CW, & Ray JGl. 2009. Prevention of venous thromboembolism. Chest seventh ACCP Consensus Conference on Antithrombotic Therapy. Stein PD, Henry JW. 1995. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 108,978-981 Thambi M, Galanter B. 2006. VTE/Deep vein thrombosis prophylaxis. University of Illinios Medical Centre. Thromboembolic Risk Factors ( THRIFT ) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. BMJ 1992; 305: 567 - 74. Kleinbart J, Williams MV and Rask KR. Chapter 31. Prevention of Venous Thromboembolism Emory University Schools of Medicine and Public Health. www.ahrg.gov. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA, et al. 2001. Prevention of venous thromboembolism. 156S-158S. Chest Sixth ACCP Consensus Conference on Antithrombotic Therapy. Palmer AJ, Schramm W, Kirchhof B, Bergemann R. 1997.Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials. Haemostasis 27:65-74. Warkentin, TE, Levine, MN, Hirsh, J, et al 1995 Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332,13301335 Freedman KB, Brookenthal KR, Fitzgerald RH, Jr. , Williams S, Lonner JH. 2000. A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty. J Bone Joint Surg 82A:929-938. Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, Juillard-Delsart D, et al. 2000. Prevention of venous thromboembolism in internal medicine with unfractionated or lowmolecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83:1419.
2. 3. 4.
5.
6.
7.
8. 9. 10. 11. 12.
13. 14. 15. 16.

Author 1. 2. 3. 4. 5.
Duplaga BA, Rivers CW, Nutescu E. 2001. Dosing and monitoring of low-molecular-weight heparins in special populations. Pharmacotherapy 21:218-34. Enoxaparin (Clexane) product leaflet, Sanofi-Aventis Fondaparinux (Arixtra) product leaflet, GloxiSmithKline Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States
Dr Arbayah Rais, Head of Dept Anesthetist, Selayang Hospital Fadilah Othman, Chief Pharmacist (Senior Clinical Pharmacist), Pharmacy Dept. Selayang Hospital Dr Haslinda Anesthetist ICU, Selayang Hospital Norliza Mat Ariffin, Pharmacist, Pharmacy Dept. Selayang Hospital Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.3
STRESS ULCER PROPHYLAXIS 2.3.1 INTRODUCTION Stress-related mucosal disease (SRMD) is an acute condition which erosion of the gastric mucosa occur secondary to a physiologic stress.1 It can be manifestation by bleeding which can be considered equivalent to overt gastroduodenal bleeding that result in hemodynamic instability (measured through a drop in blood pressure or an increase in heart rate) and subsequent need for red blood cell transfusions or surgical intervention of the gastric ulcers.2, (I suggest this sentence be rephrase cos it is too long and as a reader I cannot grasp its full meaning comment from MartinaRos Sakinah please look into it). 2, 3
The etiology of stress-related mucosal disease (SRMD) or stress related ulcer is multifactorial and complex. Patients with head injury or burns represent those at highest risk of SRMD, likely due to gastric acid secretion resulting from vagal stimulation. Other critically ill patients appear to develop SRMD as a result of diminishes mucosal defenses and hypoperfusion. 4 The longer the gastric pH remains below 4 the greater the risk of hemorrhage. Clinical trials have estimates clinically important bleeding occur in 3% to 6% of intensive care unit (ICU) patients with the most common risk factors ( ie those who are ventilated or have coagulopathy). 5, 6 Work by Cook and colleagues ascribed the risk of overt bleeding to be 4.4 % and clinically significant bleeding to be 1.5%. 5 There is a strong relationship between duration of mechanical ventilation, duration of intensive care stay and incidence of ulceration: patient without coagulopathy and mechanical ventilation had an incidence of bleeding of 0.1%. 5
2.3.2
INDICATION OF PROPHYLAXIS a. High risk patient - All patients to receive prophylaxis mechanical ventilation > 48 hours coagulopathy History of previous GI hemorrhage Current outpatient PUD treatment or prophylaxis - Central nervous system (CNS) injury ( subarachnoid hemorrhage (SAH) / cardiovascular attack (CVA) hemorrhagic or ischemic) Sepsis with or without organ dysfunction Vasopressor/inotropic prescription
b. Moderate risk patient - consider prophylaxis - Chronic non steroidal antiinflamatory drug (NSAID) or aspirin use - High dose prolonged steroid treatment - ICU stay > 10 days c. Low risk patient or tolerating per oral diet/Full gastric enteral feeds
No prophylaxis or discontinue prophylaxis 2.3.3 NUTRITIONAL GUIDELINE AND STRESS ULCERS The administration of gastric nutrition reduces, but does not eliminate the risk of GI hemorrhage. Any patient predicted to be mechanically ventilated > 48 hours and without a contraindication to gastric enteral nutrition, is encouraged to have nasogastric nutrition initiated within 72 hours of admission when a nasoenteric tube is in situ.
2.3.4
PROPHYLAXIS SMRD AGENT Many agents are available for use in patients at risk for stress-related mucosal disease. These agents include histamine type 2 receptor antagonists (H2RAs), proton pump inhibitors (PPIs), sucralfate, antacids, and prostaglandin analogs. Common products, usual dosage ranges, and considerations are shown in the Table 1. Current studies reveal that histamine type 2 receptor antagonists are the most widely used first-line agents; however proton pump inhibitors are widely used and their diverse routes of administration and favorable side effect profile are desirable features.13 The largest randomized controlled trial to date involved 1200 mechanically ventilated patients has determined that ranitidine was significantly better than sucralfate in reducing clinically important SRMD bleeding (odds ratio [ OR]: 0.44; 95% confidence interval [CI] : 0.21-0.92). 7 Multiple studies have examined the effects of proton inhibitors (PPIs) in ICU patients, but all have been small and many measured intermediate endpoints. 7 Some studies have been observational with PPI therapy alone, whereas others have compared PPI therapy with placebo or histamine-2 receptor antagonist (H2RA) therapy. Conclusions that can be gathered currently are that acid suppression achieved with PPI therapy is, on average, superior to that achieved with H2RAs, and that the clinical benefit of PPIs for reducing SRMD bleeding appears to be at least similar to that achieved with H2RAs. Current trends indicate increasing awareness and use of acid suppression in the population, with H2RAs representing first-line agents and PPIs gaining use. The most common complication of stress ulcer prophylaxis is pneumonia. 10 The hypothesis is based upon the concept that higher pH relates to overgrowth of gastric microbes and leads to upper tracheal colonization. This concept partnered with microspiration of intubated patients lying supine may increase the nosocomial pneumonia rate. The ability to reliably maintain a pH < 4 will decrease the rate of pneumonia. Several studies comparing the pneumonia rate when comparing sucralfate, antacids and H2RA show ether improvement or
insignificant trends toward decreasing rate with sucralfate. 10 However, due to the current incidence of outpatient ulcer and reflux reduction therapy and the complexity of administering sucralfate, overall benefit appears to be small.
Table 1: MEDICATION USED TO PREVENT SRMD 14

Medication class Histamine Type 2 Receptor Antagonists Ranitidine Adult Oral : 150 mg bd IV : 50 mg Q8H Esomeprazole 40 mg daily (IV, nasogastric tube, PO) Proton pump inhibitors
Medication Dosage
Omeprazole 20-40 mg daily (PO, nasogastric/jejunal, duodenal tube)
Pantoprazole 40 mg daily (IV,nasogastric tube, PO)
Adjust for creatinine clearance (CrCl) < 50 ml/min.
Patient who develops significant GI hemorrhage receiving prophylaxis : IV Omeprazole / Pantoprazole / Esomeprazole
80 mg loading dose followed by 8 mg/hr for 3 days Oral : 150 mg every 24 hour
- consider endoscopic evaluation - When no evidence of bleeding for 24 hours, convert to intermittent dosing schedule.
IV : 50 mg every 18-24 hours; adjust dose cautiously if needed
*Defined as bleeding that requires transfusion, causes hemodynamic changes and/or decrease in Hmeoglobin (Hgb) 1 gram
Hemodialysis : Adjust dosing schedule so that dose coincides with the end of hemodialysis.
The result of 16 randomized, controlled trials involving a total of > 3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. 11
Monitoring
AST, ALT, serum creatinine, sign
Hypersecretory
Medication class
Histamine Type 2 Receptor Antagonists Ranitidine and symptoms of PUD, occult blood with GI bleeding, renal function Esomeprazole
Proton pump inhibitors
Medication
Omeprazole
Pantoprazole disorders
Contraindication Precaution Use in caution in patient with hepatic impairment and renal impairment
Hypersensitivity to the component of the formulation Severe liver dysfunction may require dose adjustment Bioavailability may increase in the elderly, Asian population, and with hepatic dysfunction IV preparation contain edentate sodium (EDTA); use caution in patient who are at risk for zinc deficiency if other EDTA containing solution are co-administered Headache, diarrhea, flatulence, abdominal pain, abnormal liver function test
Side effect
Arrythmias, dizziness, headache, mental confusion, rash, anemia, thrombocytopenia, leucopenia, hepatic failure and pneumonia CYP450 effect Increase the effect : Cyclosporine
Headache, hypertension, pain, dizziness, flatulence, diarrhesa, constipation, urinary tract infection, anemia, pneumonia CYP450 effect
Headache, dizziness, diarrhea, abdominal pain, pneumonia
Drug interaction
CYP450 effect Increase the effect : HMG-CoA reductase inhibitor, Montelukast, phenytoin, warfarin, methotrexate Decrease effect ketoconazole, itraconazole,
Increase the effect : HMG-CoA reductase inhibitor, methotrexate, benzodiazepine, phenytoin
Decrease effect Warfarin, ketoconazole, itraconazole, cephalosporin, cycanocobalamin First line in treatment of SRMD
Decrease effect ketoconazole, itraconazole,
Special instruction
If patient on PPI for chronic disease (PUD treatment or prophylaxis) requiring this medication
Medication class
Histamine Type 2 Receptor Antagonists Ranitidine Esomeprazole
Proton pump inhibitors
Medication
Omeprazole
Pantoprazole
Stability of PPIs after reconstitution After reconstitution with 10 ml of isotonic sodium chloride solution, intravenous omeprazole / pantoprazole can be administered as a rapid injection over 2 minutes or it can be stores for up to 2 hours at room temperature.
Intravenous admixtures of pantoprazole can be prepared by mixing with 100 ml of isotonic sodium chloride solution, 5% dextrose in water, or lactated Ringers solution to achieve a final concentration of 0.4 mg/ml. This solution can be stored for up to 24 hours at room temperature. This admixture can be administered over 15 minutes. 12 References
1. Sesler JM. Stress-related mucosal disease in the intensive care unit: an update on prophylaxis. 2. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill 3. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics
and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999; 56:347-379. 4. Cho CH, Koo MWL, Garg GP, et al. Stress-induced gastric ulceration: Its aetiology and clinical implications, Scand J Gastroenterol. 1992;27:257-262. 5. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. N Eng J Med. 1994;330:337-381. 6. Brown RB, Klar J, Teres D, et al. Prospective study of clinical bleeding in intensive care unit patients. Crit Care Med. 1988;16:1171-1176. 7. Cook DJ, Guyatt G, Marshall J et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. 8. Jung R, Maclaren R. Proton pump inhibitor for stress ulcer prophylaxis in critically ill patients. Ann Pharmacother. 2002;36:1929-1937. 9. Redbuck JA, Welage LS et al. Prevention of stress ulceration: current trends in critical care. Crit care Med. 2004;32: 2008-2013. 10. Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer : meta analysis of randomized controlled trials. BMJ 2202;321(7269):1103-1106. 11. Morgan D. Crit care Med. 2002;30:S369-S372 12. Wyeth Pharmaceutical [package insert]. Philadelphia, Pa: Wyeth laboratories;2004 13. Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in critical care. Crit Care Med. 2004; 32:2008-2013. 14. Drug Information Handbook 17th Edition. 2008. Lexi Comp. United States Author 6. Dr Anselm Suresh Rao, Intensivist ICU, Selayang Hospital patients. Canadian Critical Care Trials Group. N Engl J Med. 1994; 330:377-381. AACN Adv Crit Care. 2007; 18:119-126.
7. 8. 9. 10.
Wong Kok Thong, Chief Pharmacist, Pharmacy Dept. Selayang Hospital Fadilah Othman, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital Zainon Abudin, Pharmacist, Pharmacy Dept. Selayang Hospital Siti Hajar Abdul Jalil, Pharmacist, Pharmacy Dept. Selayang Hospital 11. Masrahayu Moydin, Clinical Pharmacist, Pharmacy Dept. Selayang Hospital
2.4
ANTIBIOTIC GUIDELINE FROM INFECTIONS IN INTENSIVE CARE UNITS

Adapted from National Antibiotic Guideline 2008, MOH Malaysia
Infection/ condition & Likely Organism Preferred
Suggested Treatment Alternative
Comments
A. Severe Sepsis or Septic Shock Where Site Of Infection Is Not Identified Severe sepsis or septic shock Cefepime 2g IV q12h; Meropenem 1g IV q8h; (site of infection is unknown) Gram-negative bacilli Gram-positive cocci OR Piperacillin/Tazobactam 4.5g IV q8h OR Imipenem 500mg IV q6h
Current evidence suggests that carbapenems, 4th generation cephalosporins or Piperacillin/ Tazobactam are equally effective in treatment of septic shock. If melioidosis cannot be ruled out, carbapenem should be used as the empirical agent.
Methicillin-resistant S.aureus Penicillin-resistant S. pneumoniae Ampicillin-resistant Enterococci Candida
PLUS OPTIONAL Vancomycin1 1g IV q12h
Empirical use of Vancomycin1 is only justified in areas with high endemic levels of MRSA or high levels of penicillin-resistant S.pneumoniae
PLUS OPTIONAL Fluconazole 400 - 800mg IV q24h
PLUS OPTIONAL Amphotericin B 0.6 -1.0mg/kg IV q24h
Empirical antifungal agents should not be used on a routine basis. Reference 1,2
B. Severe Community-Acquired Pneumonia Requiring Mechanical Ventilation
Infection/ condition & Likely Organism Preferred Severe community-acquired pneumonia requiring mechanical ventilation S. pneumoniae H. influenzae S. aureus K. pneumoniae M. pneumoniae L. pneumophilia C. pneumoniae *B.pseudomallei
Comments
3rd gen. Cephalosporins, e.g; Ceftriaxone 2g IV q24h
-lactam/-lactamase inhibitors, eg;

Amoxycillin/Clavulanate 1.2g IV q8h
Reference 3,4,5
PLUS Erythromycin 500mg IV q6h OR Azithromycin 500mg IV q24h * If risk factors present, consider Ceftazidime (Please Refer to Page 95(LRTI))
PLUS Erythromycin 500mg IV q6h OR Azithromycin 500mg IV q24h
C. Severe Nosocomial Pneumonia Requiring Mechanical Ventilation (Including Ventilator-Associated Pneumonia) Nosocomial pneumonia requiring mechanical ventilation (including VAP) Low risk for infection with multidrug resistant (MDR) organisms < 5 days S. pneumoniae S. aureus H. influenzae E. coli
3rd gen. Cephalosporins, e.g; Ceftriaxone 2g IV q24h; OR

Amoxycillin/Clavulanate 1.2g IV q8h
S. aureus is more common in diabetes mellitus, head trauma. Monotherapy is recommended for early onset HAP/VAP/HCAP. Reference 6,7

Ampicillin/Sulbactam 1.5g IV q6h
K. pneumoniae Enterobacter spp. Proteus spp. Serratia marcescens
Infection/ condition & Likely Organism Preferred High risk for infection with multidrug resistant (MDR) organisms P. aeruginosa
Comments
Piperacillin/Tazobactam 4.5g IV q6h OR Cefepime 2g IV q12h PLUS Amikacin1 15mg/kg/24h IV OR Ciprofloxacin 400mg IV q8h
Imipenem 500mg IV q6h OR Meropenem 1g IV q8h PLUS Amikacin1 15mg/kg/24h IV OR Ciprofloxacin 400mg IV q8h
Use combination therapy if MDR pathogen is suspected.
Aminoglycoside can be stopped after 5-7 days in patients on combination therapy who are responding to treatment.
Acinetobacter spp. K. pneumoniae (ESBL)
Cefoperazone/Sulbactam 2g IV q12h Meropenem 1g IV q8h OR Imipenem 500mg IV q6h PLUS (if MRSA is suspected) Vancomycin1 1g IV q12h
-lactam/-lactamase inhibitors, eg; Ampicillin/Sulbactam 1.5g IV q6h
Methicillin-Resistant S. aureus
Refer Appendix 1 (Clinical Pharmacokinetic Guidelines: Aminoglycosides & Vancomycin)
References: 1. 2. Crit Care Med 2003; 31:1250-1256 Crit Care Med 2004; 32(11)S495 S512 3. Am J Respir Crit Care Med 2002, 166:717-723 6. Am J Respir Crit Care Med. 2005;171:388-416 4. Clin Infect Dis 2003;37:1405-33 Curr Anaes and 7. Crit Care 2005;16:209-219 5. Curr Opin Crit Care 2004; 10:59-64
2.5
NEUROMUSCULAR BLOCKING AGENTS IN CRITICALLY ILL PATIENTS 2.5.1 INTRODUCTION The use of neuromuscular blocking agents in the ICU remains a problematic issue, especially since the indications for the pharmacologic paralysis of ICU patients are unclear. The current recommendations are that muscle relaxants be used to facilitate mechanical ventilation in patients whom sedation alone is inadequate in providing effective mechanical ventilation. The decision to treat a patient in the ICU with neuromuscular blocking agents is a difficult one that is guided more commonly by individual practitioner preference than by standards based on evidence-based medicine.1 2.5.2 NEUROMUSCULAR TRANSMISSION AND BLOCKADE2 The neuromuscular junction consists of the nerve terminal, the synaptic cleft, and the motor endplate. Acetylcholine (ACh) is released into the synaptic cleft when nerve impulses reach the nerve terminal and diffuses across the synaptic cleft to the motor endplate. Attachment of Ach to the nicotinic (not muscarinic) receptors on skeletal muscle causes a conformational change in the receptor that increases myocyte cell membrane permeability to sodium, potassium, chloride and calcium ions and releases calcium from the sarcoplasmic reticulum, leading to transmission of an action potential. Depolarization terminates when Ach unbinds from the receptor. Ach either diffuses back into the nerve terminal or is broken down by acetylcholinesterase. Neuromuscular blocking agents are structurally related to Ach and act by interfering with the binding of Ach to the motor endplate. They are divided into depolarizing or nondepolarizing agents based upon their mechanism of action. Depolarizing NMBAs bind to cholinergic receptors on the motor endplate, causing initial depolarization on the endplate membrane followed by blockade of neuromuscular transmission. Because calcium is not resequestered in the sarcoplasmic reticulum, muscles are refractory to repeat depolarization until depolarizing NMBAs diffuse from the receptor to the circulation and are hydrolyzed by plasma pseudocholinesterase. Nondepolarizing NMBAs competitively inhibit the Ach receptor on the motor endplate. Drug binding to the Ach receptor either prevents the conformational change in the receptor or physically obstructs the ion channels so that an endplate potential is not generated.
2.5.3
NEUROMUSCULAR BLOCKING AGENTS
Atracurium Atracurium is an intermediate acting NMBA with minimal cardiovascular adverse effects and is associated with histamine release at higher doses. Atracurium has been administered to various critically ill populations, including those with liver failure, brain injury or multiple organ dysfunction syndrome (MODS), to facilitate mechanical ventilation. Recovery of normal neuromuscular activity usually occurred within one to two hours after stopping the infusions and is independent of organ function. Long term infusions have been associated with the development of tolerance, necessitating significant dose increases or conversion to other NMBAs. Atracurium has been associated with persistent neuromuscular weakness as have other NMBAs.1
Pancuronium Pancuronium is a long acting, nondepolarizing compound which has vagolytic effects (more than 90% of ICU patients will have an increase in heart rate of 10 beats/min), which limits its use in patients who cannot tolerate an increase in heart rate. In patients with renal failure or cirrhosis, neuromuscular blocking effects of pancuronium are prolonged because of its increased elimination half-life and the decreased clearance of its 3hydroxypancuronium metabolite that has one-third to one-half the activity of pancuronium.1
Rocuronium Rocuronium is a nondepolarizing NMBA with a monoquaternary steroidal chemistry that has an intermediate duration of action and has a very rapid onset of action, with maximum neuromuscular blockade within 4 minutes. The metabolite of rocuronium which is 17-des-acetylrocuronium has only 5 10% activity compared with the parent compound1 and rocuronium is metabolized minimally in the liver.3
Vecuronium Vecuronium is an intermediate acting NMBA that has a structural analogue of pancuronium and is not vagolytic. Because of up to 35% of a dose is renally excreted, patients with renal failure will have decreased dose requirements. Similarly, because up to 50% of an injected dose is excreted in bile, patients with hepatic insufficiency will also have decreased drug requirements to maintain adequate blockade. The 3-desacetylvecuronium metabolite has 50% of the pharmacologic activity of the parent compound, patients with organ dysfunction may have increased plasma concentrations of both the parent compound and the active metabolite, which contributes to the prolongation of blockade if the dose is not adjusted. Vecuronium has been reported to be more commonly associated with prolonged blockade
once discontinued, compared with other NMBAs and therefore it is being used with decreased frequency in ICU.3 Table 1: Neuromuscular Blocking Agents Atracurium Dose 1.Adjunct to general anaesthesia (for surgery or intubation) Initial : IV injection : 0.3 0.6 mg/kg 4,5 Maintenance : IV injection : 0.1 0.2 mg/kg 4,5 OR IV infusion : 5 10 mcg/kg/min (300 600 mcg/kg/hr) 4,5 2.Intensive care Initial : IV injection : 0.3 0.6 mg/kg 4,5 Maintenance : IV infusion : 4.5 29.5 mcg/kg/min (usual : 11 13 mcg/kg/min)
4,5
Rocuronium 1.Surgery procedures (Intubation) Initial : IV injection : 0.6 mg/kg 4,6 Maintenance : IV injection : 0.15 mg/kg (Elderly : 0.075 0.1 mg/kg)4,6 OR IV infusion : 0.3 0.6 mg/kg/h (Elderly : 0.4 mg/kg/h) 4,6 2.Intensive care Initial : IV injection : 0.6 mg/kg 4,6 Maintenance : IV infusion : 0.3 0.6 mg/kg/h for first hour then adjusted according to response
4,6
Pancuronium 1.Neuromuscular blockade Initial : IV injection : 0.06 0.1 mg/kg or 0.05 mg/kg after initial dose of succinylcholine for intubation 3 Maintenance : IV injection 0.01 mg/kg 60 100 min after initial dose, then 0.01 mg/kg every 25 60 min 3 2.Intensive care IV injection : 0.05 0.1 mg/kg bolus followed by 0.8 1.7 mcg/kg/min once recovery from bolus seen or 0.1 0.2 mg/kg every 1-3 hours
3
Onset Duration Monitoring
2 3 min
1 2 min (within 4 min) 3

3
2 3 min
20 35 min
~ 30 min
60 100 min
Vital signs (heart rate, blood pressure,
Peripheral nerve stimulator measuring
Heart rate, blood pressure, assisted
Atracurium respiratory rate); renal function and liver function 3 Contraindicatio ns Hypersensitivity to atracurium besylate or any component of the formulation 3 Reduce initial dose and inject slowly over 1 2 min in patients in whom substantial histamine release will be potentially hazardous (patients with clinically important cardiovascular disease) 3 Increased sensitivity in patients with myasthenia gravis and Eaton-Lambert syndrome 3 Side effects 1 10% : Cardiovascular : Bradycardia, flushing, hypotension, tachycardia3 <1% : Broncheal secretions, erythema, itching, urticaria, wheezing 3
Rocuronium twitch response; heart rate, blood pressure, assisted ventilation status 3 Hypersensitivity to rocuronium or any component of the formulation 3 Use with caution in patients with valvular heart disease, pulmonary disease, hepatic impairment; ventilation must be supported during neuromuscular blockade 3 Increased sensitivity in patients with myasthenia gravis and Eaton-Lambert syndrome 3
Pancuronium ventilation status

3
Hypersensitivity to pancuronium or any component of the formulation 3 Ventilation must be supported during neuromuscular blockade 3 Use with caution in patients with renal and/or hepatic impairment (adjust dose appropriately)
Precautions
Increased sensitivity in patients with myasthenia gravis and Eaton-Lambert syndrome 3
>1% : Cardiovascular : Transient hypertension and hypotension 3 <1% (Limited to important or lifethreatening): Abnormal ECG, anaphylaxis, arrhythmia, bronchospasm, edema, hiccups, nausea, rash, rhonchi, shock, tachycardia,
Frequency not defined : Cardiovascular : elevation in pulse rate, elevated blood pressure and cardiac output, tachycardia, edema, skin flushing, circulatory collapse3 Dermatologic : Rash, itching, erythema, burning sensation along the vein3 Gastrointestinal :
Atracurium
Rocuronium wheezing, vomiting

3
Pancuronium excessive salivation3 Neuromuscular & skeletal : profound muscle weakness3 Respiratory : wheezing, bronchospasm3
Drug interaction
Increased effect : Aminoglycosides, beta blocker, calcium channel blocker, clindamycin, imipenem, quinolones, tetracycline, vancomycin, macrolides, loop diuretics (frusemide), ketamine, magnesium sulphate, procainamide, quinidine. May increase risk of myopathy when used with high-dose corticosteroids for extended periods3 Decreased effect : Carbamazepine (chronic use), phenytoin (chronic use), theophylline, sympathomimetics 3
References :
o ASHP Therapeutic Guidelines for sustained neuromuscular blockade in the adult critically ill patient. Approved by the ASHP Board of Directors on November 17, 2001. Am J Health Syst Pharm. 2002; 59:179-195.
Hanson, CW. Pharmacology of neuromuscular blocking agents in the intensive care unit. Crit Care Clin 1994; 10:779
Drug Information Handbook 14th International Edition. 2006 - 2007. Lexi Comp. United States British National Formularies 54th Edition. September 2007. United Kingdom GlaxoSmithKline [TracriumTM package insert]. GlaxoSmithKline Manufacturing S.p.A., Parma, Italy ;2005
o o
Organon [Esmeron package insert]. N.V. Organon, Oss, Holland ; 2002
2.6
SEDATIVE AGENTS IN CRITICALLY ILL PATIENTS 2.6.1 INTRODUCTION Sedatives and analgesics are often used to facilitate patient tolerance of invasive mechanical ventilation.1 Patients undergoing mechanical ventilation experience significant stress superimposed on their acute medical problem, ranging from anxiety about their surroundings and condition to distress with potential pain from necessary nursing care and procedures. 3 The goals of sedation and analgesia in this context include decreasing pain and anxiety, reducing the stress response, and facilitating nursing care. Recent evidence indicates that the choice of sedating agents, frequency of administration and regular assessment of sedation contribute to patient outcomes2 such as length of stay in the ICU, days of mechanical ventilation, and rate of self-extubation.1 Titrating the dose of sedative medication based on a sedation scale will help prevent over-sedation and treat under-sedation. Under-sedated patients may become agitated and distressed and are at risk of adverse events such as extubation4 while over-sedation can contribute to hypotension, venous thrombosis, prolonged ventilation, an increased risk of pneumonia and a prolonged stay in ICU.2 Improving sedation management through sedation protocols and interventions such as daily interruption of sedation is an increasing focus of quality improvement initiatives in critical care.4 In 2000, Kress and co-workers showed that daily withholding of sedative agents led to reduced length of ICU stay, less ventilator time, fewer ICU complications and fewer neurological investigations. Subsequent studies by the same group demonstrated daily sedation withholding to be safe in patients with ischaemic heart disease and that it reduces the psychological sequelae of critical illness. Sedation withholding is now part of the Ventilator Care Bundle, as outlined by the UK Department of Health and recommended by the Surviving Sepsis Campaign.2 Assessment of sedation level is carried out mainly by nurses or critical care physicians by assessing patient responses to simple stimuli.2 Sedation-agitation scales can be used to identify and quantify agitation, and to grade the depth of sedation.5 Sedation scales such as the Revised Riker Sedation and Agitation Scale, Ramsay Scale or the Richmond Agitated-Sedation Scale are widely used.2 The Malaysian Ministry of Health ICU Management Protocol suggested that patients are to be assessed for sedation and agitation based on the revised Riker
Sedation and Agitation Scale every 4 hours and titrate the sedative infusion rate with the aim of keeping the sedation score between -1 to +1.6 Exceptions to keeping the sedation score between -1 and +16 :

Head injured on cerebral protection : sedation score -3 Severe sepsis on high inotropic support : sedation score of at least -1 ARDS on high ventilatory support : sedation score of at least -2 Tetanus : sedation score of at least -2
Revised Riker Sedation Agitation Scale6 Score +3 Description Agitated and restless Definition When awaken or otherwise, pulling at ETT, trying to remove catheters or requires physical restraints Anxious but mildly agitated. Attempts to sit up but calms down with verbal instructions Awake, calm and easily follows commands
+2 +1 0 -1
Awake but mildly agitated Awake and calm
Aroused by voice and remains Awakens easily to verbal stimuli. Remains calm awake, calm and easily follows command Aroused by movement Awakens to loud verbal stimuli or gentle shaking. Has eye contact for at least 10 seconds but drifts off to sleep OR Awakens to loud verbal stimuli or gentle shaking and follows simple commands
-2 -3
Aroused by painful stimuli Unarousable
Localising or flexion to pain. communicate or follow commands
Does
not
Extension, minimal or no response to painful stimuli
2.6.2
SEDATIVE AGENTS Benzodiazepines7
Benzodiazepines binds to a specific receptor site of the GABA receptor, and thus the degree of modulation is limited, which explains the ceiling effect of their CNS depression. It has been suggested that a benzodiazepine receptor occupancy of 20% provides anxiolysis, whereas an occupancy of 30% to 50% is associated with sedation, and 60% is required for hypnosis. Midazolam is the most commonly used benzodiazepine for ICU sedation. It is a short acting, water soluble benzodiazepine that undergoes extensive oxidation in the liver to form water soluble hydroxylated metabolites, which are excreted in urine. However, the primary metabolite, namely 1-hydroxymethylmidazolam, has mild CNS depressant activity and may accumulate in the critically ill patient especially in the case of kidney failure. Medications that interfere with the cytochrome P450 enzyme will decrease metabolization of midazolam. During short term infusions, midazolam is generally safe and effective sedative agent. However, during continuous infusions, accumulation of midazolam can occur because of the large volume distribution and its high lipophilicity. It was shown that older patients require much lower plasma concentrations of benzodiazepine to achieve level of sedation comparable to those in younger patients
Propofol7 Propofol is a unique sedative-hypnotic agentwith a rapid onset and offset action. Like the benzodiazepines, propofol acts on the GABA receptor, although the site of action on this receptor is different. It is available for intravenous administration dissolved in fat emulsion has extremely rapid distribution and metabolization (by hepatic conjugation) responsible for promptly patient arousal after a single dose or interruption of drug infusion. Its metabolites are excreted by kidneys. Its formulation causes a transiently elevation on triglyceride level and has some allergic properties. It has respiratory and cardiovascular depressant effects, with minimal influence on heart rate, and is still very expensive what limits its routine use in ICU. Hepatic and renal diseases have little impact on the pharmacokinetics of propofol. Propofol infusion syndrome is a rare but serious and potentially fatal adverse effect, typically seen with infusion rates >5 mg/kg/h for more than 48 hours. This syndrome is characterized by dysrythmias, heart failure, metabolic acidosis, hyperkalemia and rhabdomyolisis, and it carries a mortality rate of up to 85%. In order to minimize the risk of this syndrome, propofol dosage should be under 4 mg/kg/h for a maximum of 7 days.
Dexmedetomidine7 Dexmedetomidine is a centrally acting 2-agonist with sedative and analgesic properties. The sedative properties are facilitated through the locus coeruleus site in the CNS and the analgesic effects may occur via activation of the 2 receptors by accentuating the action of opioids. It causes no significant effect on respiratory drive, even when used with opioids. Most studies involving dexmedetomidine have evaluated postoperative ICU patients and demonstrated efficacy for short-term sedation and analgesic sparing. Although dexmedetomidine is labeled in some countries only for sedation of less than 24 hours, the drug has not been extensively studied as an agent for long-term administration to critically ill, mechanically ventilated patients.
Table 1: Drug doses Midazolam Dose Initial dose : 0.01 - 0.05 mg/kg (~0.5 - 4 mg for a typical adult)9 Maintenance dose : 0.02 0.1 mg/kg/h or 1 7 mg/h9 Propofol 1) Monitored anaesthesia care sedation (healthy adults <55 y.o)(dih & mdx) Initial dose : 100 150 mcg/kg/min (6 9 mg/kg/h) IV infusion or 0.5 mg/kg slow IV injection for 3 5 min9,10 Maintenance dose : 25 75 mcg/kg/min (1.5 4.5 mg/kg/h) IV infusion or 10 20 mg incremental IV bolus doses9,10 Dexmedetomidin e Initial dose : 1 mcg/kg over 10 mins9,10 Maintenance dose : 0.2 0.7 mcg/kg/h for a maximum of 24 hours9,10
Midazolam
Propofol 2) Sedation for mechanically ventilated ICU patient Initial dose : 5 mcg/kg/min (0.3 mg/kg/h) IV infusion for 5 min then titrate in 5 10 mcg/kg/min (0.3 0.6 mg/kg/h) increments to achieve desired sedation level9,10 Maintenance dose : 5 50 mcg/kg/min (0.3 3 mg/kg/h) or higher9,10
Dexmedetomidin e
Onset Duration
1- 5 min9 15 30 min9
9-51 sec (average 30 sec)9 3 10 min (dose and rate dependent)9 Important depressant effect9,10 Important depressant effect9,10 None
9
Rapid9
Cardiac effects
Minimal depressant effect9,10 Important depressant effect9,10 None9 Respiratory and cardiovascular status, blood pressure9
Important depressant effect9,10 Minimal depressant effect9,10 Yes

9
Respiratory effects Analgesia Monitoring
Anaphylactic reactions, cardiorespiratory depression, fever, propofol infusion syndrome,
Level of sedation, heart rate, respiration, rhythm9
Midazolam
Propofol increased intracranial pressure or impaired cerebral circulation especially in neurosurgical patients10
Dexmedetomidin e
Contraindication
Hypersensitivity to midazolam and its components including benzyl alcohol (crosssensitivity with other benzodiazepines may exist)9 Narrow-angle glaucoma and pregnancy9
Hypersensitivity to propofol, fospropofol or its components9 Allergy to eggs, egg products, soybeans or soy products10
Hypersensitivity to dexmedetomidine and its components9 Use outside of intensive care setting10
Precaution
May cause severe respiratory depression, respiratory arrest or apnea9 May cause hypotension hemodynamic events are more common in paediatric patients or patients with hemodynamic instability9 Hypotension and/or respiratory depression may occur frequently in patients who have
Use slower rate of induction in elderly9 Do not administer with blood or blood products through the same IV catheter9 Abrupt discontinuation can result in rapid awakening, anxiety, agitation and resistance to mechanical ventilation9
Use cautiously in elderly patients; hypotension and/or bradycardia may be more pronounced10 Use caution in patients with heart block, severe ventricular dysfunction, hypovolemia, diabetes and chronic hypertension9
Midazolam received narcotic analgesics9 Side effects COMMON10 Gastrointestinal : Nausea & vomiting Neurologic : Excessive somnolence, headache Respiratory : Cough Other : Hiccoughs SERIOUS10 Cardiovascular : Cardiac arrest, usually in combination with CNS depressant drug; hypotensive episode Endocrine metabolic : Desaturation of blood in paediatric patients Neurologic : Involuntary movement Psychiatric : Agitation Respiratory : Apnea, respiratory arrest with CNS depressant drug, respiratory
Propofol
Dexmedetomidin e
COMMON10 Gastrointestinal : Nausea & vomiting Musculoskeletal : Involuntary movement SERIOUS

10
COMMON10 Gastrointestinal : Nausea, xerostomia SERIOUS10 Cardiovascular : Atrial fibrillation, bradyarrythmia, cardiac dysrythmia, hypertension, hypotension, tachycardia Respiratory : Apnea, bronchospasm, dyspnea, hypercapnia, hypoventilation, pleural effusion, pulmonary congestion, respiratory acidosis
Cardiovascular : Bradyarrhythmia, heart failure Gastrointestinal : Pancreatitis Immunologic : Anaphylaxis Neurologic : Seizure Respiratory : Apnea, respiratory acidosis
Midazolam depression, respiratory obstruction Drug Interaction10 Atazanavir (contraindicated, theoretical) Carbamazepine (moderate, probable) Clarithromycin (moderate, probable) Codeine (major, probable) Dantrolene (major, theoretical) Diltiazem (moderate, probable) Efavirenz (contraindicated, theoretical) Fluconazole (moderate, established) Theophylline (moderate, probable) Voriconazole (moderate, established)
Propofol
Dexmedetomidin e
Bupivacaine (major, probable) Lidocaine (major, probable) Succinylcholine (moderate, probable)
Tapentadol (major, theoretical)
References :
1. Arroliga A, Frutos-Viva F, Hall J, Esteban A, Apezteguia C, Soto L,Anzueto A. 2005. Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest 128:496 506 2. Reschreiter H, Maiden M, Kapila A. 2008. Sedation practice in the intensive care unit: a UK national survey. Critical Care 12:R125 3. Schweickert WD, Kress JP. 2008. Strategies to optimize analgesia and sedation. Critical Care 12(Suppl 3):S6 4. Jackson DL, Proudfoot CW, Cann KF, Walsh TS. 2009. The incidence of suboptimal sedation in the ICU: a systematic review. Critical Care 13:R204 5. Sessler CN, Grap MJ, Ramsay MAE. 2008. Evaluating and monitoring analgesia and sedation in the intensive care unit. Critical Care 12(Suppl 3):S2 6. Management Protocols in ICU. 2006. Program Anestesia & Cawangan Kualiti Penjagaan Kesihatan, Bahagian Perkembangan Perubatan, Kementerian Kesihatan Malaysia. 7. Gommerz D, Bakker J. 2008. Medications for analgesia and sedation in the intensive care unit: an overview. Critical Care 12(Suppl 3):S4 8. Sessler CN, Wilhelm W. 2008. Analgesia and sedation in the intensive care unit: an overview of the issues. Critical Care 12(Suppl 3):S1 9. Drug Information Handbook 14th International Edition. 2006-2007. Lexi Comp. United States 10. MICROMEDEX Healthcare Series Vol. 143. 2010 Thomson Reuters. United States
2.7
MANAGEMENT OF ELECTROLYTES IMBALANCE IN CRITICALLY ILL PATIENTS 2.7.1 POTASSIUM (3.5 4.5 mmol/L )
Potassium is one of the body's major ions. Nearly 98% of the body's potassium is intracellular. The ratio of intracellular to extracellular potassium is important in determining the cellular membrane potential. Small changes in the extracellular potassium level can have profound effects on the function of the cardiovascular and neuromuscular systems.
a. Hypokalemia i) Sign and Symptoms of Hypokalemia (usually present when K<2.5mmol/L) Malaise, fatigue Neuromuscular disturbances: Weakness, hyporeflexia, paraesthesias, cramps, restlessness leg syndrome, rhabdomylysis, paralysis. Gastrointestinal: Constipation, ileus Polyuria, polydipsia, metabolic alkalosis ECG changes: small or inverted T waves, prominent U wave, depressed ST segments, prolonged PR interval. Arrhytmias: First and second degree heart block, atrial fibrillation, ventricular tachycardia, ventricular fibrillation.
ii) Correction of Hypokalemia

If K+ <2.5 mmol/L or <3mmol/L if on digoxin or presence of lifethreatening symptoms Give KCL 2G diluted to 100 mls N/S through a central line over an hour. Max. rate 0.4 mmol/kg/hour (20-30 mmol/hour) (1G KCL= 13.3mmol K+ )
If no life threatening symptoms, K+ <3.5 mmol/L
Give KCL 1G diluted to 50mls N/S over an hour or oral/NG KCl 20-40 mmol q6h
iii)
Potassium Correction Formula = (4.5 Current K+) x 0.4 + Body Weight + 1 x Body Weight 13.4 13.4
= g KCL
b. Hyperkalemia i) Sign And Symptoms of Hyperkalemia (Hyperkalemia is an emergency. The first sign of hyperkalemia may be death. Usually occur when K>6.5 mmol/L) Neuromuscular manisfestations : Bradycardia, prolongation of AV conduction, complete heart block, wide complex tachycardia, ventricular fibrillation and asystole. Urgent 12-lead ECG; possible changes are: Tall tented T waves, small P waves, depressed ST segments, widened QRS complexes, sine wave (biphasic waves, pre-cardiac arrest)
ECG has limitation in predicting cardiac toxicity. Thus, patient should be treated even in the absence of ECG changes
ii) Correction of Hyperkalemia

If K+ > 6 mmol/L with ECG abnormalities Give Calcium Gluconate 10% 20 ml IV over 3 min (may be repeated in 5 min) 5-10 units Actrapid in 100 ml 50% dextrose IV over 30-60 min. IV Frusemide 20mg to increase urine output. Resonium 15G q8h oral/N/G or 30G q8h enema/rectal. IV NaHCO3 50-100 mmol over 5-10 min (not to be given after calcium as Ca2+ bind HCO3. Lastly dialysis.
2.7.2 SODIUM ( 135 145 mmol/L) Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone (ADH), and renal handling of filtered sodium.
Clinically significant hyponatremia is relatively uncommon and is nonspecific in its presentation; therefore, the physician must consider the diagnosis in patients presenting with vague constitutional symptoms or with altered level of consciousness. Irreparable harm can befall the patient when abnormal serum sodium levels are corrected too quickly or too slowly. The physician must have a thorough understanding of the pathophysiology of hyponatremia to initiate safe and effective corrective therapy. The patient's fluid status must be accurately assessed upon presentation, as it guides the approach to correction. a. Hyponatremia i) Sign and Symptoms of Hyponatremia The clinical features of acute hyponatremia are related to osmotic water shifted that leads to increased ICF volume and brain cells swelling. Mild hyponatremia is usually asymptomatic. Serum Na of about 120 mmol/L may be associated with disturbed mental state, restlessness, confusion and irritability. As the Na approaches 110 mmol/L, seizures and coma may occur. ii) Correction of Hyponatremia
Total Na+ deficit (mmol) = (130 current Na+) x 60% of body weight in kg.
Volume (ml) required to replace total Na+ deficit using 0.9% N/S = Total Na+ deficit (mmol) 154 (mmol /L) x 1000
Volume (ml) required to replace total Na deficit using 3% N/S = Total Na+ deficit (mmol) 513 (mmol /L) Volume (ml) required to replace total Na deficit using 20 % N/S = Total Na+ deficit (mmol) 3400 (mmol/L) x 1000 x 1000
The volume calculated should be given within the calculated no. of hours = (130 current Na+) 0.5
The rate of rise in plasma Na should not exceed 0.5 mmol/L/ hour and the final plasma Na+ concentration should not exceed 130mmol/L.
b. Hypernatremia i) Sign and Synptoms of Hypernatremia Definition Na > 145mmol/L Features are tremulousness, irritability, ataxia, spasticity, mental confusion and coma ii) Correction of Hypernatremia
Free H2O replacement Water deficit (L) = 0.6 x BW in kg x ( measured Na - 1) 140 To be given over 48-72 hours Use Dextrose 5%.
2.7.3
MAGNESIUM ( 0.7 1 mmol/L) Magnesium plays an important role in neuromuscular function. Only 1 % is in ECF, 60% are found in bones and reminder in cells. Therefore, serum magnesium may not reflect total body magnesium content.
a.
Hypomagnesemia i) Sign & Symptoms of Hypomagnesemia Symptomatic magnesium depletion is associated with refractory hypokalemia, hypocalcemia and metabolic alkalosis. Features are : - Tremors, muscle twitching. - Positive Trousseaus and Chvosteks signs - Generalized weakness, confusion, ataxia - Vertical nystagmus - Tetany, seizures - ECG Mild to moderate: prolongation of QT or QU
intervals, bifid T waves, U wave, supraventricular and ventricular ectopics. Severe: PSVT, R-on-T phenomena, torsades de pointes, VT Hypomagnesaemia facilitates development of digoxin cardiotaxicity. ii) Correction of Hypomagnesemia 50% MgSo4 solution has osmolarity of 4000 mOsm/L, dilute to 10-20% solution before IV use. 1mg MgSo4 =4 mmol (8mEq) elemental Mg 1 ml 50% MgSo4 =0.5G=2 mmol (4 mEq) Mg2+
Without symptoms
IV 0.125G/kg MgSo4 x24h then 0.0625G/kg MgSo4 daily x3-5 days IV Mg SO4 20mmol in 40ml NS OVER 2 hours IV Mg SO4 10mmol in 20ml NS OVER hour
If Mg2+ <0.6 mmol/L with cardiac IV 0.05-0.07G/kg MgSo4 over 20 min then 0.03-0.05G/kg/h abnormalities/ asthma/ eclampsia/ 2+ tetanus/ pulmonary Keep serum Mg 2.0-3.5 mmol/L hypertension c. Hypermagnesemia i) Sign and Symptoms of Hypermagnesemia Magnesium levels of 2-4 mEq/L are associated with the following:
o o o o o
Nausea Vomiting Skin flushing Weakness Lightheadedness High magnesium levels are associated with depressed levels of consciousness, respiratory depression, and cardiac arrest. ii) Correction of Hypermagnesemia
Only in patients IV Calcium Gluconate 10% 30 mls over 3 minutes with impaired Diuresis if possible renal failure Dialysis
2.7.4
CALCIUM ( 2.1 2.65 mmol/L) Calcium regulation is critical for normal cell function, neural transmission, membrane stability, bone structure, blood coagulation, and intracellular signaling. The essential functions of this divalent cation continue to be elucidated, particularly in head injury/stroke and cardiopulmonary effects. Depending on the cause, unrecognized or poorly treated hypocalcemic emergencies can lead to significant morbidity or death
a.
Hypocalcemia Sign and Symptoms of Hypocalcemia Paraesthesia Circumoral numbness Cramp Tetany
Dystonia Convulsion Psychosis Chvosteks sign gentle tapping over facial nerve cause twitching of facial muscles. Trousseaus sign inflation of sphygmomanometer cuff above diastolic pressure for 5 min causes carpopaedal spasm. Papilloedema (severe) Prolonged Q-T interval on ECG Long-standing hypocalcemia may result in dry skin, coarse hair,
alopecia, brittle nails and hypoplastic teeth.
Correction of Hypocalcemia
10 mls 10% CaCl2 (to be given through central line) contains 272 mg elemental calcium 10 mls 10% Ca gluconate (can be given through peripheral line) contains 90 mg elemental calcium
Treatment directed at underlying cause:
If symptomatic (muscle spasm, laryngeal spasms or cardiac involvement)
If ionised Ca2+ <0.65 mmol/L or corrected Ca2+ <2.0 mmol/L
i)
IV 10-20mls 10% Ca gluconate over 10 min followed by 1-2 mg/kg/h x6-12h i.e. 30 mls 10% Ca gluconate diluted to 100 mls N/S run at 2540ml/h x6-12h ii) Give Mg if deficient iii) Daily maintenance dose of Ca 2-4G orally
b.
Hypercalcemia Sign and Symptoms of Hypercalcemia Neurology :- Depression, proximal myopathy, fatigue, confusion, stupor and coma. Renal :- Hypertension, renal colic (nephrolithiasis), polyuria and nocturia (nephrogenic diabetes insipidus), dehydration. Bones:- Pain, pathological fractures osteitis fibrosa cystics in hyperthyroidism (subperiosteal resorption, bone cysts).
Abdominal:- Nausea, vomiting, constipation, abdominal colic, peptic ulcer disease, pancreatitis.
General:- Soft tissue and corneal calcification (band keratopathy) ECG changes:- Shortened QT intervals.
Correction of Hypercalcemia
N/S or 1/2N/S at 250-500 ml/h to correct hypovolaemia Frusemide 40-80 mg I/V every 2 hours to maintain urine output 100200mls/hr.
2.7.5
PHOSPHATE ( 0.8 1.5 mmol/L) Phosphate is the most abundant intracellular anion and is essential for membrane structure, energy storage, and transport in all cells. In particular, phosphate is necessary to produce ATP, which provides energy for nearly all cell functions. Phosphate is an essential component of DNA and RNA. Phosphate is also necessary in red blood cells for production of 2,3-diphosphoglycerate (2,3-DPG), which facilitates release of oxygen from hemoglobin. Approximately 85% of the body's phosphorus is in bone as hydroxyapatite, while most of the remainder (15%) is present in soft tissue. Only 0.1% of phosphorus is present in extracellular fluid, and it is this fraction that is measured with a serum phosphorus level.
a. Hypophosphatemia Sign and Symptoms of Hypophosphatemia
Weakness is the most common symptom suggesting hypophosphatemia and may involve any muscular system to any extent.
o o o o
Diplopia Dysarthria Dysphagia Weakness of trunk or extremities, particularly the large muscle groups
Symptoms of respiratory insufficiency or myocardial depression may indicate hypophosphatemia. Neurologic symptoms may vary, ranging from simple paresthesias to profound alterations in mental status.
Correction of Hypophosphatemia
Add 2 ampuoles of KH2PO4 in 1 pint IVD OR IV KH2PO4 20mmol/L in 100ml NS OVER 6 hours OR IV KH2PO4 10mmol/L in 100ml NS OVER 4 hours
2.7.6
FLUID/IV DRIP SUMMARY
Na+ (mmol/L) D5% (500ml) Dextrose 5% Saline 0.9% (500ml) 0.9% NaCl (500ml) 0.45% NaCl (500ml) 3% NaCl (500ml) Hartmanns (500ml) Gelafundin (500ml) HES 6% Voluven (100ml) Venofundin (1000ml) Sterofundin 154
Cl(mmol/L) 154
K+ (mmol/L) -
Ca2+ (mmol/L) -
Osmolarity (mOsmol) 252 560
pH 3.2-6.5
Others Dextrose 50g 170 Kcal Dextrose 50g 170 Kcal
154 77 513 130 154 154 154 154 140
154 77 513 109 120 154 154 154 140
4 4
3 2.5
308 154 1026 273 274 310 308 309
5.0 5.0 5.0 6.0-7.5 7.1-7.7 4.0-7.0 5.5 4.0-6.5
Lactate 28mEq/L Gelatin 40g/L Starch 60g/L Hydroxyethyl Starch 130/0.4 6g Poly(O-2hydroxyethyl)star ch (HES) 60g
(1000ml)
2.8
MEDICATION ADMINISTRATION THROUGH ENTERAL FEEDING TUBES 2.8.1 Medication plan Temporarily discontinue medications that are not immediately necessary Consider giving medications by an alternate route such as transdermal, rectal, inhaled, intramuscular, subcutaneous, buccal, sublingual or intravenous whichever possible Enteral administration of medications Evaluate tube type, tube location in the GI tract, site of drug action and absorption and effects of food on drug absorption (e.g. sucralfate is not suitable for intestinal feeding tubes administration as it acts on the stomach) Drug that require administration on empty stomach, feeding should be stopped 30 minutes before and after dosing Liquid dosage forms is preferred whenever possible Tablets that could be crushed into fine powder and the contents of capsules can be mixed to a slurry in water and given through large-bore feeding tubes Feeding tubes should be flushed with at least 30 ml of water before and after administration of medication via the tube Medication should not be added to enteral formula to reduce the risk of microbial contamination and to avoid drug-nutrient incompatibilities 2.8.3 Medications that should not be crushed Formulation Sustained-release Enteric-coated Reason Crushing destroys the sustained-release tablets and microencapsulated drugs, resulting in erratic blood levels Do not crush well but break into small chunks that bond together when moist and clogging the tube Decreased the efficacy of the medication Increased stomach irritation Aerosolized particles may be harmful to the healthcare provider
2.8.2 .
Teratogenic, carcinogenic or cytotoxic medication
8.4
Consideration with Liquid Medications Medication dosage or frequency may need adjustment when switching from solid to liquid preparations (e.g. extended-release phenytoin capsules may be given once daily, however phenytoin suspension is an immediaterelease product that need to be dosed 2 to 4 times daily) Osmolality Many commercial liquids have osmolalities over 1000 mOsm/kg, the osmolality of GI secretions ranges from 100 to 400 mOsm/kg Diarrhea, cramping, abdominal distension and vomiting may occur after administration of hyperosmolar products through the feeding tube the effects may be reduced by diluting medication with 10-30 ml of sterile water before administration Osmolality of diluted mixture = (osmolality of drug / volume of drug) / total volume of mixture Contents of sorbitol many sweeteners including mannitol, lactose, saccharin and sucrose may cause or worsen diarrhea, the most likely excipient to cause GI problems is sorbitol sorbitol may cause gas and bloating at total daily doses of 10 gram, cramping and diarrhea may occur a total daily dose of 20 gram 2.8.5 Drug interaction and incompatibility and special consideration
Interaction / Incompatibility Syrups and other acidic medication (pH less than 4) may clump when mixed with enteral feeding formulas
Recommended intervention (s) Stopping the enteral feeding for 1 to 2 hours before and 2 hours after drug administration To avoid nutritional status compromise: minimize the time of feeding interruption by using once daily or twice daily dosing regimen Stopping the enteral feeding for 2 hours before and after each dose Flushing the tube before and after each phenytoin dose Phenytoin suspension given through
Phenytoin absorption decreases by 50% to 75% when given with enteral feeding
Interaction / Incompatibility
Recommended intervention (s) feeding tube may be diluted with 20-60 ml of water Close monitoring of serum concentrations is warranted Carbamazepine suspension may be diluted with an equal volume of sterile water or normal saline Close monitoring of serum concentrations is warranted Consider increasing the warfarin dose or using alternative anticoagulants Monitor prothrombin time Consider vitamin K contents in enteral formulas vitamin K may directly block warfarins effects in doses of 140-500 mcg.day Fluroquinoloes should not be given within 2 hours before or 4 hours after enteral formulas Avoid giving via enteral feeding tubes or concomitantly with enteral formulas parenteral route is preferred If to be given via entral tube crush tablets and mix in 20 to 60 ml sterile water immediately before administration Omeprazole and lansoprazole capsules (delayed-release) through large-bore nasogastric or gastrostomy tubes may be mixed with juices (apple, orange) mixing with water may cause clumping and lead to occlusion Omeprazole and lansoprazole capsules (delayed-release) through small-bore jejunostomy or gastrostomy tubes Dissolve in sodium bicarbonate 8.4% solution Esomeprazole granules (delayed-release) should be mixed with water Commercial immediate-release omperazole with sodium bicarbonate Should only be mixed with water Continuous enteral feeding should be held for 3 hours before and 1 hour after medication administration Lansoprazole disintegrating tablet (delayed-release) Dissolves on tongue or may be mixed with small amount of water in an oral syringe and injected through the NG
Carbamezepine absorption may decrease with enteral feeding
Warfarin effects may be decrease in patients receiving enteral feeding due to reduce absorption and vitamin K antagonism
Fluroquinolones antibtiotics may have an erratically changes in its pharmacokinetics in patients receiving enteral feeds
Proton-pump inhibitors these medications are acid labile and inactivated by gastric acid, specially formulated to maintain the acidity until it delivers to alkaline pH of the duodenum for absorption
Interaction / Incompatibility
Recommended intervention (s) tube Should not be given through feeding tube increased viscosity, tube occlusion Continuous enteral feeding should be held for 3 hours before and 1 hour after medication administration Bulk forming laxatives (e.g. methycellulose) Should not be given via feeding tubes Form semisolid mass that may occlude feeding tube when mixed with less than 250 ml fluid (still potentially block feeding tube when mixed properly) Consider using fiber-containing enteral nutrition
Laxatives
References: 1. Silberman H. Parenteral and Enteral Nutrition. 2nd ed. Norwalk, CT: Appleton & Lange; 1989, 11758. 2. Estoup M. Approaches and limitations of medication delivery in patients with enteral feeding tubes. Crit Care Nurse. 1994;14:6872,79. 3. Gora ML, et al. Considerations of drug therapy in patients receiving enteral nutrition. Nutr Clin Pract. 1989; 4:10510. 4. Thomson F.C., Naysmith, M.R. & Lindsay, A. Managing drug therapy in patients receiving enteral and parenteral nutrition. Hosp Pharmacist. 2000;7:15564. 5. Gilbar PJ. A guide to enteral drug administration in palliative care. J Pain Symptom Manage. 1999;17:197207. 6. Rombeau JL, Caldwell MD, eds. Clinical Nutrition: Enteral and Tube Feeding. 3rd ed. Philadelphia, PA: WB Saunders; 1997. 7. Janson DD, Chessman KH. Enteral nutrition. In: DiPiro JT et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York, NY: McGraw-Hill; 2002, 2495517. 8. Mitchell JF. Oral dosage forms that should not be crushed or chewed. Hosp Pharm. 2002; 37:21314. 9. Dickerson RN, Melnik G. Osmolality of oral drug solutions & suspensions. Am J Hosp Pharm. 1988;45:83234. 10.Jew RK, et al. Osmolality of commonly used medications and formulas in the neonatal intensive care unit. Nutr Clin Pract. 1997;12:15863. 11.Lutomski DM, et al. Sorbitol content of selected oral liquids. Ann Pharmacother. 1993;27:26974. 12.Burns PE, et al. Physical compatibility of enteral formulas with various common medications. J Am Diet Assoc. 1988;88:10946. 13.Cutie AJ, et al. Compatibility of enteral products with commonly employed drug additives. JPEN J Parenter Enter Nutr. 1983;7:18691. 14.Healy DP, et al. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother. 1996;40:610.
15.de Marie S, et al. Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections. Intensive Care Med. 1998;24:3436. 16.Wright DH, et al. Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. JPEN J Parenter Enter Nutr. 2000;24:428. 17.Cohn SM, et al. Enteric absorption of ciprofloxacin during tube feeding in the critically ill. J Antimicrob Chemother. 1996;38:8716. 18.Mueller BA, et al. Effect of enteral feeding with Ensure on oral bioavailabilities of ofloxacin and ciprofloxacin. Antimicrob Agents Chemother. 1994;38:21015. 19.Mimoz O, et al. Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients. Intensive Care Med. 1998;24:104751. 20. Cacek, A.T., DeVito, J.M. & Koonce, J.R. 1986. In vitro evaluation of nasogastric administration methods for phenytoin. Am. J. Hosp. Pharm. 43: 689-692. 21. Clark-Schmidt, A.L., Garnett, W.R., Lowe, DR et al. 1990. Loss of carbamazepine suspension through nasogastric feeding tubes. Am. J. Hosp. Pharm. 47: 2034-2037. 22. Williams, N.E. 2008. Medication administration through enteral feeding tubes. Am. J. Hosp. Pharm. 65(24): 2347-2357. 23. Beckwith, M.C., Feddema, S.S., Barton, R.G. & Graves, C. 2004. A guide to drug therapy in patients with enteral feeding tubes: dosage form selection and administration method. Hospital Pharmacy. 39(3): 225-237. CHAPTER 3: DOSING 3.1 RENAL DOSING Acute renal failure is common in critical care situations and is associated with significant morbidity and mortality. Rapid assessment of renal function is important in critical care for the following reasons: Emergency angiography (coronary or otherwise) Emergency dosing of drugs with narrow therapeutic window Severe CHF or volume overload condition Severe hyperkalemia Investigations have to be carried on in order to determine renal status or renal injury. Measurements included: Estimation of GFR Assessment of Proteinuria or other urine markers of renal injury Functional assessment of renal function (e.g. Fractional excretion of sodium) Urine volume Acute Renal Failure characterized by deterioration of renal function over a period of hours to days. The mortality rate for patients in the intensive care unit (ICU) is lower in those who have ARF, especially when ARF is severe enough to require dialysis treatment. In addition, evidence suggests that the relative risk of death is 4.9 in patients in the ICU who have renal failure that is not severe enough to require dialysis. The mortality rate in postoperative renal failure is 24 - 100% and about 50 - 70% in intensive care who require dialysis. Mortality rate has not decreased significantly over the past 50 years.
A prospective multicenter observational study (Beginning and Supportive Therapy for the Kidney (BEST) Study) had discovered the incidence of ARF among 29,269 subjects of critically ill ICU patients was 5.7% and 2/3 required dialysis. 30% of the total subjects studied already had pre-existing renal dysfunction. Overall mortality associated with ARF was 60.3%. The most common contributing factor is septic shock. This study defined ARF as oliguria and/or BUN > 84mg/dl (>30mmol/L).JAMA 294:813;2005 Cockcroft Gault Equation is most common method being used in estimating GFR:
(140-Age)xWeight (kg) 72xSCr
x (0.85 if female)
RIFLE criteria are one type of classification to determine the progression of renal damage. A study done on 5,383 intensive care unit patients, 67% developed acute renal injury. 12% of patient with R classification had mortality rate of 8.8%, 27% patient with I classification had mortality rate of 11.4% and 28% patient with F classification had mortality rate of 26.3%. More than 50% patients progressed from Rto Ior F had worse outcomes than non-progressed. (Hosteet al. Critical Care 10:R73, 2006et 2006) RIFLE Criteria - adopted from Bellomo et al Crit Care 8:R204; 2004
Standard guideline
Agent AMPICILLIN Usual Dosage Mild to moderate infection: 500mg to 2g ivpb q6h. Severe infection: 2g ivpb q4h (150-200mg/kg/day) Usual dose: 250mg to 1g po q6h (50-100mg/kg/ day). Renal Dosing >50/ q6h || 10-50/ q6-12h || <10/ q12-24 hours || Hemodialysis: Dose after dialysis || PD: 250mg q12h. >50/ no changes || 10-50/ q6-12h || <10/ q12h
AMPICILLIN (Oral)
Agent AMPICILLIN SULBACTAM (UNASYN) AUGMENTIN (Oral)
Usual Dosage Usual dose: 1.5 to 3g ivpb q6h
Renal Dosing >30/ q6-8h || 15-29/ q12h || 5-14/ q24h
Usual dose: 875mg po q12h or 250-500mg po q8h Mild infection (i.e. UTI): 500mg to 1g ivpb q8-12h. Usual dose: 1-2g ivpb q8-12h. Severe or life threatening: 2g ivpb q6-8h. Max 8g/day Usual oral dose: 500mg x 1, then 250mg po qd x 4 days. Chlamydia: 1gram po x 1. MAC prevention: 1200mg qwk or 500mg po TTW. PID or CAP: 500mg ivpb qd x 2 days or more than 500mg po qd. Uncomplicated gonococcal infection: 2 grams orally x1 *(see comments) IV: Usual dose: 8-10mg/kg/day divided q6h, q8h or q12h. PCP: 15-20mg/kg/day in 3 or 4 divided doses. Oral: UTI: 1 DS tab (160mg TMP/800mg SMX) po q12h. Usual: 500mg to 1g ivpb 8h. Severe: 1.5g ivpb q6h. Life threatening: 6-12g/day. Mild to moderate infection: 500mg to 2g ivpb q12h. Severe: 2g ivpb q8h. Usual dose: 1g ivpb q12h. Severe: 2-3g ivpb q12h. (Max 6g/day) Mild infection: 1g ivpb q6-8h Moderate-severe: 1g ivpb q4h or 2g ivpb q6-8h. Life-threatening: 2g ivpb q4h or 3g ivpb q6h.
>30/ no change || 10-30/ 250-500mg q12h || <10/ 250-500mg po q24h >30/ no change || 10-30/ 50% of usual dose q6-8h || <10/ 25% of usual dose q6-8h || HD/PD: see <10 guidelines. (HD: 500mg AD) Give loading dose of 1-2g before starting regimens above. No adjustments required in renal failure. Cannot be given IM. *Because of the high incidence of gastric upset with the 2 gram dose--this is the least preferred regimen for treatment of uncomplicated gonococcal infections.
AZACTAM
AZITHROMYCIN (ZITHROMAX)
BACTRIM
>30/ no change || 15-30/ 50% of usual dose q12h-alternatively: 8-10mg/kg/day divided q12h x 1-2 days, then 4-6mg/kg q24h. || <15/ not recommended by manufacturer. Alternatively: 8-10mg/kg/dose q48h or 4-6 mg/kg/day. >55/q6-8h || 35-54/q8h || 11-34/ 50% usual dose q12h || <10 ml/min/ 50% to full dose q24-48h. || Hemodialysis: 0.5-1 gram after dialysis >60/ 0.5-2g q12h || 30-60/ 0.5g-2g q24h || 11-29/ 0.5g-1g q24h || <10/ 250-500mg q24h or 0.5-2g q48h. || HD: 1g AD || PD: 1-2 grams q48h >30/ Usual dose || 10-30/ 50% of dose q12h || <10/ 25% of dose q12h.|| Hemodialysis or PD: 50% of usual dose q24h 10-50/ q8-12h || <10/ q24-48h || HD: give 1g after Dialysis: e.g. Give Cefoxitin 1g ivpb MW-F after dialysis + a supplemental dose on Sunday.
CEFAZOLIN
CEFEPIME (MAXIPIME)
CEFOTETAN (IV)
CEFOXITIN (IV)
Agent CEFOTAXIME (IV)
Usual Dosage Mild infection: 1-2g ivpb q12h. Moderate: 1-2g ivpb q8h; Severe: 2g ivpb q6-8h; Life threatening: 2g ivpb q4h (Max dose/day= 12g) Usual: 750mg to 1.5g ivpb q8h. Severe: 1.5g ivpb q6-8h.
Renal Dosing >50/ Usual dose || 10-50/ q8-12h || <10/ q24h || HD: 0.5 to 2g ivpb q24h AD. || PD: 1g ivpb q24h. >20/q8h || 10-20/ q12h || <10/ 750mg q24h. || Hemodialysis: Give single dose after dialysis or give 750mg q12h. || PD: 750mg1.5g q24h No changes req'd (usual oral doses are not significant). No dosage adjustments req'd in renal failure. PD: 750mg ivpb q12h Crcl 30-50/ q12h || 10-30/ q24h || <10/ q48h Keflex: 10-50/ q6-12h || <10/ q12-24h . Velosef: >20/ no change || 5-20/ 250mg q6h || < 5/ 250mg q12h >50/ no change || 10-50/ 50-75% of usual dose q12h || <10/50% of usual dose q12. Alternatives: [200mg ivpb or 250mg po q12h] or [400 mg ivpb or 500mg po q24h]. || HD/PD: 250-500mg po or 200-400mg ivpb q24h AD or 200mg ivpb or 250mg po q12h. Severe renal dysfunction: decrease dose or increase interval. [crcl < 30 ml/min: 500mg loading dose, then 250 mg once or twice daily.] No dosage adjustments required for renal failure
CEFUROXIME (IV)
CEFTIN (ORAL)
Usual dose: 250-500mg po q12h
CEFTRIAXONE (IV) CEFTAZIDIME (IV)
Usual dose: 1-2g ivpb q24h. Severe: 2g ivpb q12h Usual dose: 1g ivpb q8-12h. Severe: 2g ivpb q8-12h. (Max dose/day= 6 grams). Usual dose: 250-500mg po q6h; 500mg-1g q12h. Oral dosing: 250-750mg po q12h; cystic fibrosis: 750mg po q8h. IV dosing: 200-400mg ivpb q12h. Febrile neutrapenic pt: 400mg ivpb q8h Usual dose: 250-500mg orally q12h. Severe (Legionella): 5001000 mg po q12h. Helicobacter: 500mg po tid. Usual oral dose: 150-400mg po q6h. Usual IV dose: 600mg ivpb q6-8h or 900mg ivpb q8h. Maximum daily dose= 4800mg Usual dose: 250-500mg po q6h Usual dose: 100mg po bid x1 f/b 100mg qd or divided bid (if severe: 100mg po bid) or 100-200mg ivpb qd or divided doses q12h. Usual oral dose: 500mg to 1g po q12h or 250mg to 1g po q6h.
CEPHALEXIN KEFLEX/VELOSEF CIPROFLOXACIN (CIPRO)
CLARITHROMYCIN (BIAXIN)
CLINDAMYCIN (IV/PO)
DICLOXACILLIN (Oral) DOXYCYCLINE (VIBRAMYCIN)
No changes required for renal insufficiency. No dosage adjustments required for renal failure
ERYTHROMYCIN
>10/ No change || <10/ 50-75% of usual dose. Max 2 grams/day. || Hemo: no
Agent
Usual Dosage Usual IV dose: 250mg to 1g q6h. Max 4 g/day. supplement.
Renal Dosing
IMIPENEM (PRIMAXIN)
Mild to moderate infection: 250500mg ivpb q6-8h. Severe infection: 500mg to 1g ivpb q6-8h. Max dose/day= 50mg/kg/day or 4g/day Usual dose: 500mg po or ivpb q24h. UTI or pyelonephritis: 250mg po/ivpb q24h. IV: 1 gram or 15 mg/kg load IV, then 500mg or 7.5 mg/kg q6h (range: q6-12h --long T ). Oral: 250-750mg po tid. (occasionally bid). Max 4g/day. Mild to moderate infection: 500mg to 1g ivpb q4h or 1-2g ivpb q6h. Severe: 1-2g ivpb q4h Usual dose: 200-400mg po/IV q12h. Usual dose: 0.5 to 4 mu q4-6h. Severe infection: Dosing interval q2-3h (i.e. 3mu q3h). Max dose per day: up to 30 million units Usual dose: 250-500mg po q6h Group A strept URI: 1.2 mu IM x 1. Prophylaxis of recurrent rheumatic fever: 1.2mu q3-4wks. Early syphilis: 2.4mu x 1 (in 2 injection sites). Late syphilis (> 1yr): 2.4 mu (in 2 sites) qwk x 3.
31-70/ 500mg q6-8h || 21-30/ 500mg q8-12h max || 0-20/ 250-500mg q12h max. || HD: 250 mg AD + q12h. || PD: max dose= 1gram/day i.e. 500mg ivpb q12h. >50/ no change || 20-49/ 500mg x 1 then 250mg q24h || <19/HD/PD: 500mg x 1 then 250mg q48h > 10/ no change || <10/ 500mg ivpb q12h.
LEVOFLOXACIN (LEVAQUIN) METRONIDAZOLE (FLAGYL)
NAFCILLIN
No dosage changes req'd for renal failure. || Renal + Hepatic dysfcn: decrease dose by 50%. >50/ no change || 10-50/ usual dose q24h || <10/ 100-200mg q24h >50/ Usual dose || 10-50/ 75% of usual dose || <10/ 20-50% of usual dose. || Hemo/PD: 20-50% of dose usually q6h. Max dose in ESRD: 6 mu/day. >10/ No Changes || <10/ 250-500mg po q8h Administer by deep IM in the upper outer quadrant of the buttock. Not indicated as single drug tx of neurosyphilis, but may be given 1 time/wk x 3 weeks following IV tx. Levels: (time to peak): 12-24hrs. Levels are detectable for 1-4 wks. Higher doses increase duration not peak. Use a PCNprocaine/benzathine combination (bicillin) to achieve early peak levels in acute infections. [Supplied: 600,000 u/ml (1ml., 2ml, 4ml) Time to peak: 1-4 hrs. Duration: 15 to 24 hours. Supplied: 600,000 u/ml (1 ml, 2ml, 4ml). 300,000u/ml-10ml vial.
OFLOXACIN (FLOXIN) PENICILLIN G (Aqueous)
PEN VK (Oral) PENICILLIN G BENZATHINE Peak: 12-24hrs Duration: 1-4 wks.
PENICILLIN G PROCAINE Peak: 1-4 hrs Duration: 15-24 hours
Dosing: 0.6 to 4.8 mu/day in 1-2 dd. Uncomplicated gonorrhea: 1g probenecid f/b 4.8mu divided into 2 inj sites 30min later. Endocarditis (strept): 1.2 mu q6h x 2-4wks. Neurosyphilis: 2-4 mu/day + 500mg probenecid qid x 10-
Agent
Usual Dosage 14days(Note: IV Pcn is D.O.C)
Renal Dosing
PIPERACILLIN
Mild infection: 3-4g ivpb q6-8h Serious infection: 3-4g ivpb q4-6h (200-300mg/kg/day) Max 24g/day Mild infection: 3.375g ivpb q6h Moderate to severe: 3.375g ivpb q4h
>40/ No change || 20-40/ 4g q8h || <20/ 4g q12h || HD/PD: 2g q8h. || Alternatively: >50/q4-6h || 10-50/ q6-8h || <10/ q8h >40/ 3.375g q6h || 20-40/ 2.25g q6h || <20/ 2.25g q8h || HD: Max 2.25g q8h. 0.75g AD. || PD: 2.25g q8h
PIPERACILLINTAZOBACTAM (ZOSYN)
SYNERCID
7.5 mg/kg ivpb q8-12h (usually q8h). Dilute dose in 250ml D5W and infuse over 1 hour. Usual dose: 250-500mg po/iv q6h. Usual dose: 3.1g ivpb q4-6h 50-90/ q8-12h || 10-50/ q12-24h || <10/ q24h (use not recommended) >60/ 3.1g q4-6h || 30-60/q8-12h || 10-30/ q12-24h or 2g ivpb q8h || <10/ 2g q12h or 3.1g q24-48h || <10 + hepatic dysfcn/ 2g q24h || PD: 3.1g q12h || Hemodialysis: 2g q12h + 3.1g after dialysis.
TETRACYCLINE TIMENTIN
ANTIFUNGALS AMPHOTERICIN B Test dose: (optional): 1 mg/20-50 ml D5W over 10-30 min. Monitor temp, pulse, RR and BP q30min x 4 hours. Do not give premeds with test dose. Maintenance dose: Initially give 0.25-0.3 mg/kg/day. Increase as tolerated by an equivalent amountqd. Usual daily dose: 0.5-1 mg/kg/day or up to 1.5 mg/kg qod. For lifethreatening infection may give full dose the first day (usually 0.6-0.7 mg/kg IBW on Day # 1). Premedication: Prevention of fever/chills: Tylenol 650mg PO/PR + Benadryl 25-50mg PO/IVP 60min prior to maintenance infusion. May also add: Hydrocortisone 25-50mg IV/IM +/- Demerol 50mg IV. Renal dosing: <10/ q24-36h. During therapy if the BUN increases above 40 mg/dl or the serum creatinine exceeds 2.5-3 mg/dl, Hold Ampho B until renal function improves, then restart at a reduced dose or change to QOD dosing until Serum creatinine/BUN improve. Bladder irrigation: Add 30-50mg Ampho B to 1000ml (or less) sterile H2O administered intermittently or continuously for 2 to 14 days. (Note: use of D5W for Bladder irrigations is not recommended because of the possibility of enhancing microbial and fungal growth in the bladder). Oral: Oropharyngeal candidiasis: 200mg po x 1, f/b 100mg po qd. Esophageal candidiasis: 100-200 mg po qd (up to 400mg/day). Cryptococcal meningitis: 400mg po x 1, f/b 200mg po qd x 10-12 weeks (Suppression: 50-200mg po qd). Onychomycosis: 200-300mg qweek or 100-200mg po qod >50/ no change || <50 / 50% of usual dose. || Alternatively: 20 to 50/ give normal dose q48h. || <20 / 50% of usual dose q48h. || Hemodialysis: give 100-200mg after each dialysis. || CAPD: give 50% of usual dose at usual interval.
FLUCONAZOLE (DIFLUCAN)
Agent
Usual Dosage (further studies needed). IV: since oral absorbtion is rapid and essentially complete-IV dose=oral dose.
Renal Dosing
FLUCYTOSINE (ANCOBON
Dosing: 12.5 to 37.5 mg/kg po q6h (50 to 150mg/kg/day). Doses up to 250 mg/kg/day have been used in severe infections. Capsules should be taken a few at a time over 15 min to minimize N&V. Systemic mycosis: 200mg po qd with food (up to max of 400mg/day if unsatisfactory clinical response with lower dose). Doses >200mg are given in 2 divided doses. Onychomycosis: 200mg po bid for 1 week each month x 2 months (fingernails); x 3-4 months (toenails). Oropharyngeal candidiasis: 200mg (20ml)-oral solution-swish vigorously then swallow once daily x 1-2 weeks. Esophageal candidiasis: 100mg (10ml) oral soln-swish and swallow qd x 3 weeks. May increase to 200mg/day. Life-threatening infections: Loading dose: 200mg po tid should be given for the first 3 days of therapy, then 200400mg/day. Superficial mycoses(tinea corporus, cruris, pedis, capitis; cutaneous candidiasis): 250 mg po qd. Onychomycosis: (fingernails) 250mg po qd x 6 weeks or pulse dosing: 500mg po qd for 1st week of month x 2 months. (Toenails): 250mg po qd x 12 weeks or pulse dosing: 500mg po qd for 1st week of month x 4 months. Systemic mycosis: 250-500mg po qd.
>50 / no change || 10 to 50/ q12-24 hrs || <10 / q24-48 hrs. || Hemodialysis: Single doses after dialysis || CAPD: 500mg to 1 gram q24h
ITRACONAZOLE (SPORANOX)
No adjustments necessary in renal insufficiency.Duration of therapy: Oral candidiasis, Tinea Corporis, and Tinea Cruris: 15 days. Tinea Pedis: 30 days. Tinea Capitis: 4-8 weeks.[100mg capsule; 10 mg/ml oral soln]
TERBINAFINE (LAMISIL)
Specific guidelines are not available for renal or hepatic insufficiency. [250mg tab]
ANTIVIRALS ACYCLOVIR (ZOVIRAX) Mucocutaneous herpes simplex: IV: 5 mg/kg/dose q8h x 5-10 days. Encephalitis: 10mg/kg/dose IV 50 - 90/ 5 to 12.4 mg/kg q8h || 10-50 / 5-12.4 mg/kg q12-24h || <10 / 2.5 to 6 mg/kg q24h. Alternatively: (Oral): 10-25 / dose q8h || <10 /
Agent
Usual Dosage q8h. Primary HSV infection-genital (Oral tx): 200mg q4h while awake (5x/day) or 400mg po tid x 10 days. Recurrent genital: 400mg po tid x 5 days. Herpes Zoster: 800mg po q4h while awake (5x/day) x 7 days. If severe give 10-12 mg/kg IV q8h x 7-14 days. Chronic suppression (genital herpes): 400mg po bid. Zovirax ointment: apply " q3h (6 x/day).
Renal Dosing dose q12h. (IV): 25-50/ 5-10mg/kg q12h || 10-25/ 5-10mg/kg q24h || <10/ 2.5 to 5mg/kg IV q24h. || HD: dose after dialysis || CAPD: see < 10.
FAMCICLOVIR (FAMVIR)
Herpes Zoster: 500mg po q8h x 7 days. Recurrent herpes simplex(genital): 125 mg po bid x 5 days. Primary Genital herpes simplex: 250 mg po tid x 5-10 days. Genital-chronic suppression: 250 mg po bid. [125mg, 250mg, 500mg tablet] Herpes zoster: 1000mg po tid x 7 days. Primary genital herpes: 1000mg po bid x 10 days. Recurrent genital: 500mg po bid x 5 days. Genital-chronic suppression: 500mg po qd [500mg caplet] Parkinsons dx: 100mg po bid. Influenza A viral infection: 200mg/day in 1-2 divided doses.
>60/ no change || 40-59/ 500mg q12h || 1139/ 500mg q24h || <10/ 250 mg q48h || HD: 250mg after dialysis.
VALACYCLOVIR (VALTREX)
>50/ no change || 30-49/ 1 gram q12h || 1029/ 1 gram q24h || <10/ 500mg q24h. || HD: dose after dialysis. || CAPD: 500mg q24h.
AMANTADINE (SYMMETREL
50-60/ 200mg alternating c 100mg po qd || 30-50/ 100mg qd || 20-30/ 200mg twice weekly || 10-20/ 100mg 3x/week || <10/ 200 mg alternating c 100mg q7 days. || HD/PD: No supplemental dose req'd. > 10/ no change || <10/ 100mg po qd
RIMANTADINE (FLUMADINE)
Prophylaxis and treatment of influenza A virus. Dosing: 100mg po bid. [100mg tab; 50mg/5ml syrup]
H2 Antagonists Cimetidine (Tagamet) Active ulcer: Oral: 800 mg orally at bedtime or 300mg orally four times daily or 400 mg orally twice daily. IM/IV: 300mg every 6 hours or 37.5 mg/hr continuous infusion. Active bleed: 37.5 mg/hr continuous IV (maximum 2400mg/day). Maintanance CRCL (> 40ml/min) / 300mg q6-8h ; (2040 ml/min) / 300 mg q8h ; (5-20ml/min) / 200-300mg q12h; (< 5ml/min) / 200mg q12h.
Agent
Usual Dosage (duodenal ulcer prophylaxis): 400mg orally at bedtime. Gastric hypersecretory conditions: 300600mg every 6 hours.
Renal Dosing
Famotidine (Pepcid)
Usual dose (Acute): 40mg orally at bedtime or 20mg orally twice daily. Maintenance: 20 mg orally at bedtime. Hypersecretory conditions: 20mg orally every 6 hours. May increase up to 160mg orally every 6 hours
CRCL > 50 ml/min: No changes (40mg IV/PO qd or 20mg q12h.) || CRCL < 50 ml/min: Oral: 20mg qd or 40mg qod. IV: 20mg q24h. [Since CNS adverse effects have been reported in patients with moderate and severe renal insufficiency, to avoid excess accumulation of the drug in patients with moderate or severe renal insufficiency, the dose of PEPCID may be reduced to half the dose or the dosing interval may be prolonged to 36-48 hours as indicated by the patient's clinical response.] CRCL > 50 ml/min: Usual dose || CRCL 20-49 ml/min: 150mg qd. || CRCL < 20 ml/min: 150mg qod.
Nizatidine (Axid)
Usual: 300mg orally at bedtime or 150 mg orally twice daily. Maintenance: 150mg orally at bedtime. Supplied: [150, 300mg capsule] Usual dose: 150mg orally twice daily or 300mg orally at bedtime. Maintenance: 150mg orally at bedtime. Gastric hypersecretory conditions: 150mg orally 2 to 4 times daily. IVPB: 50mg every 6 to 8 hours (Maximum: 400mg/day) Continuous infusion: (preferred in actively bleeding patients): 6.25 mg/hr titrated to gastric pH >4 for prophylaxis or >7.0 for treatment.
Ranitidine (Zantac)
CRCL (ml/min) >50/ no change; 10-50: Administer at 75% of normal dose or administer 50mg IV or 150mg orally every 18-24 hours. CRCL <10 mL/minute: Administer at 50% of normal dose or administer 50mg IV every 18-24 hours or 150mg orally q24h. || Hemodialysis: Slightly dialyzable (5% to 20%). Give dose at end of dialysis session.
References 1. American Hospital Formulary Service. Drug Information. Bethesda, MD: ASHP, 1997. 2. Bartlett JG.1998 Pocket Book of Infectious Disease Therapy., Ninth Edition. Baltimore,MD: Williams&Wikins,1998. 3. Bennett, WM, Aronoff, GR et. al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults. Fourth Edition, 1999. 4. Drug Information Handbook, 5th Ed. 1997, Lexi-Comp inc.
Agent
Usual Dosage
Renal Dosing
5. Gilbert DN, Moellering RC, Sande MA. The Sanford Guide to Antimicrobial Therapy 2000. 30th ed. Hyde Park,VT: Antimicrobial Therapy, Inc.; 2000.
ANTIBIOTIC DOSING IN RENAL IMPAIRMENT DRUG NAME ABACAVIR ACYCLOVIR USUAL DOSE (Normal renal function) 300 mg PO q12h 5 - 10 mg/kg IV q8h CrCl (ml/min) no change > 50 25-50 24-10 0-9 HD > 10 0-10 >10 0-10 > 25 24-10 0-9 HD AMOXICILLIN 500 mg - 1 gm PO q12h > 30 24-10 <10 HD >15 15-5 <5 HD no dose change necessary > 30 30-10 < 10 HD no dose adjustment necessary normal dose q6 - 8h normal dose q8h normal dose q8h + supplemental dose after each HD DOSAGE ADJUSTMENT (in renal insufficiency) no change 5 - 10 mg/kg IV q8h 5-10 mg/kg IV q12h 5 - 10 mg/kg IV q24h 2.5 -5 mg/kg IV q24h 2.5 - 5 mg/kg IV q24h (give dose after dialysis on dialysis days) no adjustment necessary 200 mg PO q12h no adjustment necessary 200 - 400 mg PO q12h no adjustment necessary 800 mg PO q8 - 12h 400 - 800 mg PO q12h 800 mg PO q12h (give dose after dialysis on dialysis days) no dose adjustment necessary 250 - 875 mg PO q12h 250 - 875 mg PO q24h 250 - 875 mg PO q24h + 250 - 500 mg after each HD normal dose and interval 500 - 875 mg q24h 250 - 500 mg q24h 250 - 500 mg q24h + 250 - 500mg after each HD
200 mg PO q4h (5x daily) 400 mg PO q4 (5x daily) - 12h 800 mg PO q4 (5x daily) - 12h
AMOXICILLIN + CLAVULANATE
500 - 875 mg PO q12h
AMPHOTERICIN B
AMPICILLIN
0.25 - 1.5 mg/kg/day * not to exceed total daily dose of 1.5 mg/kg 250 mg - 2 gm IV q46h
DRUG NAME AMPICILLIN / SULBACTAM
USUAL DOSE (Normal renal function) 1.5 - 3 gms IV q6h
CrCl (ml/min) > 30 15-30 < 15 HD no change no change > 30 30-10 <10 HD
AMPRENAVIR AZITHROMYCIN AZTREONAM
1200 mg PO q12h 500 mg IV/PO once daily for 3 days 1 - 2 gms IV q8h
DOSAGE ADJUSTMENT (in renal insufficiency) normal dose IV q6h normal dose IV q12h normal dose IV q24h normal dose q24h + supplemental dose after each HD no change no change normal dose load with 1-2 gm, then 500 mg - 1 gm IV q8h load with 1-2 gm, then 250 - 500 mg IV q8h dose for CrCl < 10 + supplemental dose after HD no dose adjustment necessary 500 mg - 1 gm q12h 500 mg - 1 gm q24h 2 gm after each HD no dose adjustment necessary 1 - 2 gm q 24h 500 mg - 1 gm q24h 250 - 500 mg q24h dose for CrCl < 11 + 250 - 500 mg after each HD no dose adjustment necessary 2 gm IV q12h 2 gm IV q24h 1 gm IV q24h dose for CrCl < 11 + 1 gm after each HD no dose adjustment necessary 1 gm IV q12h 1 gm IV q24h 500 mg IV q24h dose for CrCl < 11 + 500 mg after each HD * adults with both renal and hepatic failure should not receive more than 2 gm/day
CEFAZOLIN
500 mg - 1 gm IV q8h
CEFEPIME
1 - 2 gm IV q12h
> 35 35-10 < 10 HD > 60 30 - 60 29-10 < 11 HD > 60 30-60 29-10 < 10 HD > 60 30 - 60 29-10 < 11 HD no change
2 gm IV q8h (meningitis)
1 gm IV q8h (neutropenic fever)
CEFTRIAXONE
1 - 2 gms IV q24h * max. dose = 4 gm/day 250 - 500 mg PO q12h 500 mg - 1 gm IV q8h
CEFUROXIME AXETIL CEFOTAXIME
> 10 < 10 > 35 35-10 < 10
normal dose 250 mg PO q24h no dose adjustment necessary 1 gm q12h 1 gm q24h
DRUG NAME CLARITHROMYCIN
USUAL DOSE (Normal renal function) 250 - 500 mg PO q12h
CrCl (ml/min) > 30 < 30
CLINDAMYCIN DICLOXACILLIN DIDANOSINE (ddI)
600 mg IV q8h OR 150 - 450 mg PO q6h 125 - 500 mg PO q6h > 60 kg: 200 mg PO q12h OR 400 mg PO q24h (tablets) <60kg: 125 mg PO q12h 250 mg PO q24h (tablets) OR 100 mg IV/PO q12h 600 mg PO q24h 250 - 500 mg PO q6 12h OR 15 - 20 mg/kg/day IV divided q6h 15 - 25 mg/kg/day
no change no change 50 26 - 49 25-10 < 10 HD no change no change no change
DOSAGE ADJUSTMENT (in renal insufficiency) normal dose If normal dose is 500 mg PO q12h: give load of 500 mg then 250 mg q12h If normal dose is 250 mg PO q12h, give 250 mg q24h no change no change > 60 kg: normal dose < 60 kg: normal dose > 60 kg: 100 mg PO q12h or 200 mg PO q24h (tablets) < 60 kg: 75 mg PO q12h or 150 mg PO q24h (tablets) > 60 kg: 150 mg PO q24h (tablet) < 60 kg: 100 mg PO q24h (tablet) > 60 kg: 100 mg PO q24h (tablet) < 60 kg: 75 mg PO q24h (tablet) dose for CrCl < 10 no change no change no change
DOXYCYCLINE EFAVIRENZ ERYTHROMYCIN
ETHAMBUTOL
FLUCONAZOLE
Loading Dose: 100 800 mg PO/IV q24h Maintenance Dose: 50 - 800 mg PO/IV q24h 50 - 150 mg/kg/day PO divided q6h
> 50 10-50 < 10 HD > 50 < 50 (no HD) HD > 40 20 - 40 20-10 < 10 HD >70 50-69 25-49 <25 HD
normal dose normal dose q24 -36h normal dose q48h normal dose after each HD normal dose 50% normal dose q24h load with 100 - 400 mg, then normal dose after each HD normal dose 12.5 - 37.5 mg/kg q12h 12.5 - 37.5 mg/kg q24h 12.5 - 37.5 mg/kg q24 - 48h If receiving HD q 48 - 72h then 20 - 50 mg/kg immediately after each HD 5 mg/kg q12h 2.5 mg/kg q12h 2.5 mg/kg q24h 1.25 mg/kg q24h 1.25 mg/kg 3x/week with doses given after HD
FLUCYTOSINE (5-FC)
GANCICLOVIR IV
Induction: 5 mg/kg IV q12h x 14 - 21 days
DRUG NAME
USUAL DOSE (Normal renal function) Maintenance: 5 mg/kg IV q24h
IMIPENEM (Refer to product information for complete prescribing information for patients requiring different total daily doses)
DOSAGE ADJUSTMENT (in renal insufficiency) 5 mg/kg q24h 2.5 mg/kg q24h 1.25 mg/kg q24h 0.625 mg/kg q24h 0.625 mg/kg 3x/week with doses given after HD 500 mg IV q6h (2 > 71 > 70 kg: 500 mg q6h 60 - 69 kg: 500 mg g/day) [Note that q8h 50 - 59 kg: 250 mg q6h 40 - 49 kg: meningitis dose is 250 mg q6h 30 - 39 kg: 250 mg q8h higher (up to 1g q 6h, 41 - 70 > 70 kg: 500 mg q8h 60 - 69 kg: 250 mg depending on renal q6h 50 - 59 kg: 250 mg q6h 40 - 49 kg: function- consult ID)] 250 mg q8h 21 - 40 > 70 kg: 250 mg q6h **In patients undergoing hemodialysis or with a Clcr of 6-20 ml/min, the 500mg IV q 12 hour dose should be reserved for treatment of severe infections. Patients with Clcr < 5 ml/min should not receive imipenem/cilastatin unless dialysis is going to be instituted within 48 hours. These patients may be at an increased risk of seizures. 800 mg PO q 8h 300 mg PO daily 100 - 200 mg PO (capsule / solution) q12h OR 200 mg IV q12h x 4 doses, then 200 mg IV q24h ***IV use NOT TO EXCEED 14 days*** 150 mg po q 12h no change no change PO: no change IV: > 30 IV: < 30 no change no change PO: no change normal dose not recommended due to injectable excipient 150 mg PO q12h 150 mg PO q24h 150 mg x 1,then 100 mg PO q24h 150 mg x 1, then 50 mg PO q24h 150 mg x 1, then 25 mg PO q24h 150 mg x 1, then 25 - 50 mg PO q24h
CrCl (ml/min) >70 50-69 25-49 <25 HD
INDINAVIR ISONIAZID ITRACONAZOLE
LAMIVUDINE
> 50 30-49 15-29 14-May <5 HD
LAMIVUDINE/ZIDO VUDINE (COMBIVIR) LEVOFLOXACIN
1 tablet PO q12h If normal dose 250 mg IV/PO q24h If normal dose 500 mg IV/PO q24h
not recommended in fixed combination for Clcr < 50 ml/min > 20 < 20 and HD > 50 20 - 49 < 20 and HD 250 mg q24h 250 mg q48h 500 mg q24h 500 mg q48h 500 mg x 1, then 250 mg q48h
DRUG NAME
USUAL DOSE (Normal renal function) If normal dose 750 mg IV/POq24 h (note that the 500 mg q 24h dosage schedule shown above should be used if the levofloxacin MIC is <0.5 ug/ml) 600 mg IV/PO q12h 1 gm IV q 8h - (note that meningitis dose is higher, 2g q 8h, with normal renal function) 500 mg IV/PO q12h 500 mg IV/PO q8h (C. difficile diarrhea) 2 gm IV q4-6h 1250 mg PO q12h 200 mg PO q12h 50-100 mg PO q12h
CrCl (ml/min) CVVHD > 50 20 - 49 < 20 and HD CVVHD
DOSAGE ADJUSTMENT (in renal insufficiency) 500 mg q 48h 750 mg q24h 750 mg q48h 750 mg X 1, then 500 mg q48h 750 mg q 48h
LINEZOLID MEROPENEM
no change >50 26-50 25-Oct <10 HD no change no change no change no change no change > 40 < 40 > 30 < 30 > 125 60 - 124 40 - 59 20 - 39 19-Oct < 10 & HD < 10 & ESLD > 50 Oct-50 < 10 HD >40 20-40 <20 HD >40 20-40 <20 HD
METRONIDAZOLE
no change normal dose normal dose q12h 50% normal dose q12h 50% normal dose q24h 50% normal dose q24h + 50% normal dose after each HD no change no change no change no change no change normal dose avoid use: therapeutic levels not attained in the urine normal dose normal dose PO q24h 3.0 - 4.0 million units q4h 1.8 - 2.0 million units q4h 1.3 - 1.5 million units q4h 800,000 - 1.0 million units q4h 800,000 - 1.0 million units q6h 500,000 - 800,000 units q6h 500,000 units q8h normal dose normal dose q24-36h normal dose q48h dose for CrCL < 10 ml/min normal dose 2.25 gm q6h 2.25 gm q8h 2.25 gm q8h + 1.125 gm supplemental dose after each HD normal dose 4.5 gm q8h 4.5 gm q12h 2.25 gm q8h + 1.125 gm supplemental
NAFCILLIN NELFINAVIR NEVIRAPINE NITROFURANTION
NORFLOXACIN PENICILLIN G
400 mg PO q12h 2.0 - 4.0 million units IV q4h
PENTAMIDINE
4 mg/kg IV or IM q24h
PIPERACILLIN/TAZ OBACTAM
Mild to Moderate Infections: 3.375 gm IV q6h
Severe/life threatening infections: 4.5 gm IV q6h
DRUG NAME
USUAL DOSE (Normal renal function) Pseudomonas aeruginosa infections*: 3.375 gm IV q4h. * Combination therapy with an aminoglycoside may be indicated, depending on piperacillin MIC and site of infection. Treatment of uncomplicated UTIs can be with "mild to moderate infection" dosages 7.5 mg/kg IV q8h 15-30 mg/kg/d (maximum 2 gm/day)
CrCl (ml/min) >40 20-40 <20 HD
DOSAGE ADJUSTMENT (in renal insufficiency) dose after each HD normal dose 3.375 gm q6h 3.375 gm q8h 2.25 gm q8h + 1.125 gm supplemental dose after each HD
QUINUPRISTIN/DA LFOPRISTIN PYRAZINAMIDE
no change > 10 <10 HD no change no change no change no change no change > 50 26-49 < 25 and HD > 80 50-80 Oct-49 < 10 HD < 10 > 30 15 - 30 < 15
no change normal dose 25-30 mg/kg three times weekly 25-30 mg/kg three times weekly, postdialysis no change no change no change no change no change normal dose normal dose q24h 50% normal dose q24h normal dose 1 gram loading dose, then 7.5 mg/kg q24h 1 gram loading dose, then 7.5 mg/kg q24-72h 7.5 mg/kg q72-96h give 50-75% of loading dose after each HD normal dose q24h normal dose normal dose divided q12h x 48-72h then 50% of normal daily dose given q24h NOT ADVISED
PYRIMETHAMINE RIFABUTIN RIFAMPIN RITONAVIR SAQUINAVIR STAVUDINE
25 - 75 mg PO q24h 300 mg PO q24h 600 mg IV/PO q12 24h 600 mg PO q12h 600 mg PO q8h > 60kg: 40 mg PO q12h < 60kg: 30 mg PO q12h 15 mg/kg/day IM
STREPTOMYCIN
TMP/SMX (Bactrim, Septra) 1SS tablet = 80 mg TMP; 1DS tablet =160 mg TMP;
Urinary Tract Infections: 5 mg/kg/day of trimethoprim
DRUG NAME 1 ampule(5 ml) = 80 mg TMP
VALACYCLOVIR
USUAL DOSE (Normal renal function) component given in divided doses Serious Systemic Infections: 8-10 mg/kg/day of trimethoprim component given in divided doses (q 6 -12hr) Pneumocystis carinii Pneumonia 15-20 mg/kg/day of trimethoprim component given q 68hr Primary Genital Herpes Simplex 1 gm PO q12hrs
CrCl (ml/min) HD
DOSAGE ADJUSTMENT (in renal insufficiency) NOT ADVISED-
> 30 29-Oct <10 HD > 30 < 29 HD > 50 30-49 29-Oct <10 HD
normal dose 1 g q24 hrs 500 mg q24 hrs 500 mg q24 hrs dosed post-dialysis normal dose 500 mg PO q24h dose for Clcr < 29, given after HD normal dose 1 gm PO q12h 1 gm PO q24h 500 mg PO q24h dose for Clcr < 10, given after HD INDUCTIO MAINTENANCE N 900 mg po 900 mg po q24h q12h 450 mg po 450 mg po q24h q12h 450 mg po 450 mg po q2days q24h 450 mg po 450 mg po twice weekly q2days do not use in patients on hemodialysis normal dose 0.75 mg q12h 0.75 mg q24h normal dose 100 mg q8h Ali Olyaei PharmD, 2005
Recurrent Herpes Simplex (genital) 500 mg PO q12h Herpes zoster: 1 gm PO q8h
VALGANCICLOVIR
900 mg po q12h > 60 40 - 59 25 - 39 24-Oct HD > 50 Oct-49 < 10 and HD > 26 < 25 and HD
ZALCITABINE (ddC)
0.75 mg PO Q8H
ZIDOVUDINE
200 mg PO q8h
REFERRENCES
Joshi MC. Dose Adjustment- An Important Issue in Critical Care. Internet Journal of Medical Update Vol1, No1, Jan-jun 2006 Mahendra Agraharkar, MD, FACP. Acute Renal Failure
3.2
LIVER DOSING
DRUGS Acyclovir Adenosine Adrenaline Alprazolam
DOSAGE ADJUSTMENT No adjustment No adjustment No adjustment Reduce dose by 50 % to 60% or avoid in cirrhosis. May precipitate coma in liver disease.
Amikacin Aminophylline
No adjustment Adjusted according to serum level measurement during the first 12 to 24 hours. Use with caution.
Amiodarone
Dosage adjustment should be considered, drug extensively metabolised by liver.
Amitryptylline
Increase sedative effect; avoid or use with caution in liver disease.
Amlodipine
Required dosage adjustment; 2.5mg od for hypertension, 5 mg od for angina.
Amoxycillin-Clavulanate (Augmentin) Ampicillin + Sulbactam (Unasyn) Amphotericin B Aspirin
No adjustment
No adjustment
No adjustment Avoid use in severe liver disease; may increase risk of gastrointestinal bleeding.
Atenolol Atracurium Atropine Atorvastatin
No adjustment No adjustment No adjustment Contraindicated in active liver disease and increase in serum transaminase
Azithromycin
Not necessary; use with caution due to potential hepatotoxicity (rare). Specific dosing guidelines for hepatic impairment have not been established.
Baclofen Budesonide Bupivacaine Calcium Polystyrene Sulfonate
No adjustment Reduced dose in moderate to severe case Reduced dose in severe case; use with caution No adjustment as drug not absorbed systematically.
References:
1. Micromedex (R) Healthcare Series. Vol 141
2. British Formulary 56, September 2008. 3. Drug Information Handbook. 15th Edition 2003. 4. Infectious Disease Handbook; Antimicrobial Therapy & Diagnostic test/Procedure. 5th Edition. Lexi-Comp.2003. 5. Anesthesiology & Critical Care Drug Handbook. 6th Edition.2005. Lexi-Com
6. Medical Toxicology. Richard C. Dart. .2004.pg 1914. Dantrolene. 7. www.rxlist.com/mevacor-drug.htm. Lovastatin Drug Information: Used, Side effect, Drug
Dosage. 8. Dexmedetomidine: a novel sedative-analgesic agent Ralph Gertler, MD, 1 H. Cleighton Brown, MD,1 Donald H. Mitchell, MD,1 and Erin N. Silvius, MD1 2001.
3.3
SPECIAL DOSING IN OBESE PATIENTS Obesity is defined by the CDC as a BMI of >30kg/m2, and morbid obesity is defined as a BMI of >40kg/m2. 3.3.1 Physiological changes in obesity Can alter pharmacodynamic and pharmacokinetic of a drug which includes: Dramatically increased adipose tissue Slightly increased lean tissue mass Increased cardiac output Increased glomerular filtration rate Fatty infiltration of liver
A higher proportion of body tissue can influence drug with lipophilic properties whereas increased organ mass, lean body mass, and blood volume in obesity can affect hydrophilic medications. Failure to adjust doses in obesity may result either in sub therapeutic failure or increased toxicity. 3.3.2 Reported dosing adjustment in obesity
Drugs Antimicrobials Acyclovir Aminoglycosides Amphotericin B Suggested dosing weight Additional dosing recommendation
IBW1 IBW + 0.4(ABW-IBW)1 ABW for conventional preparation; IBW for lipid preparation1 IBW + 0.3(ABW-IBW)2 IBW + 0.45(ABW-IBW)2 IBW1 Consider higher doses in obese patient1 ABW3 IBW2 ABW2 IBW3 IBW3 IBW3 ABW5
Beta-lactams Ciprofloxacin Erythromycin Fluconazole Ganciclovir Mycobacterial antibiotics Vancomycin Muscle relaxant Suxamethonium Atracurium Pancuronium Sedative Propofol
ABW = actual body weight
IBW = ideal body weight
Calculations:IBW (Ideal body weight): Male IBW (kg) = 50 kg + 2.3 (height in inches over 60 inches) Female IBW (kg) = 45.5 kg + 2.3 (height in inches over 60 inches) Creatinine clearance in obese patient4 Overestimation or underestimation of clearance can occur in obesity when considering actual body weight versus ideal body weight, respectively. The Cockcroft-Gault equation is commonly used to calculate glomerular filtration rate (GFR) in lean patients, however its use in obesity is questionable due to the disparity between muscle mass and body weight ratio observed in obesity. The Salazar-Corcoran equation takes into account multiple factors to provide a better estimation of ClCr in obesity including serum creatinine, gender, actual weight, age, and height.
3.3.3
Salazar-Corcoran Equation4: ClCr(Male) = (137-age)x[(0.285xWt)+(12.1xHt2)] (51xSCr)
ClCr(Female) = (146-age)x[(0.287xWt)+(9.74xHt2)] (60xSCr) Wt= actual body weight in kg Ht= height in meters SCr=serum creatinine in mg/dl Although some drugs have established dosing adjustments for obesity, it remains unknown for the majority of drugs if dosing adjustment is warranted.
References: 1. Optimal antibiotic dosing for obese patients a challenge for clinicians by Elizabeth Dodds Ashley, PharmD, BCPS Infectious Disease News June 2007
2. 3. 4. 5.
Antimicrobial Dosing in Obesity Rebecca Wurtz, GailItokazu, and Keith Rodvold Clinical Infectious Diseases1997;25:112C Uptodate 17.1 Pharmacokinetics Alterations in Obesity By Jane B. Lee, PharmD; P. Shane Winstead, PharmD;Aaron M. Cook, PharmD ORTHOPEDICS 2006; 29:984 MICROMEDEX(R) Healthcare Series Vol. 143
CHAPTER 4: NUTRITION 4.1 PARENTERAL NUTRITION IN CRITICALLY ILL PATIENTS ESPEN Guidelines on Parenteral Nutrition: Intensive Care (Adapted from Singer et al., 2009) Recommendations Indications Starvation and underfeeding in ICU patients is aasociated with increased morbidity and mortality Parenteral Nutrition (PN) should be initiated within 24 to 48 hours in all patients who are not expected to be on normal nutrition within 3 days when enteral nutrition (EN) is not feasible All patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary PN C C Grade
Requirements A complete PN formulation should be given to ICU patients to
Recommendations cover their needs fully The aim in acute illness is to provide energy as close as possible to the measured energy expenditure (to reduce negative energy balance) ICU patients should receive 25 kcal/kg/day increasing to target over the next 2-3 days (in the absence of indirect calorimetry)
Grade C B C
Carbohydrates The minimal amount required is about 2g/kg of glucose per day Hyperglycemia (glucose >10 mmol/L) contributes to death in critically ill patient and should be avoided to prevent infectious complications Lipids Lipids should be an integral part of PN for energy and to ensure essential fatty acid provision in long term ICU patients Intravenous lipid emulsions can be administered safely at a rate of 0.7 g/kg up to 1.5 g/kg over 12 to 24 hours The tolerance of mixed LCT/MCT lipid emulsions in standard use is sufficiently documented Olive oil-based PN is well tolerated in critically ill patients EPA and DHA containing lipid emulsions had demonstrable effects on cell membranes and inflammatory process. Fish oilenriched lipid emulsions probably decrease length of stay in crtitically ill patients B B
B B C B B
Amino Acids A balanced amino acid mixture should be infused at approximately 1.3-1.5 g/kg of ideal body weight per day in conjunction with an adequate energy supply In critically ill patients indicated for PN, the amino acid solution should contain 0.2-0.4 g/kg/day of L-glutamine (e.g. 0.3-0.6 g/kg/day alanyl-glutamine dipeptide) Micronutrients All PN prescriptions should include a daily dose of multivitamins and of trace elements Route A central venous access is required to administer the high osmolarity PN mixture Peripheral venous access may be considered for low osmolarity PN mixture (<850 mOsm/L) If peripherally administered PN does not allow full provision of the patients need, then PN should be administered via the central venous access B
C C C
Recommendations Mode PN admixtures should be administered as a complete all-inone bag
Grade
Reference: Singer, P., Berger, M.M., Van den Berghe, G., Biolo, G., Calder, P., Forbes, A., Griffiths, R., Kreyman, G., Leverve, X. & Pichard, C. 2009. ESPEN guidelines on parenteral nutrition: intensive care. Clinical Nutrition. (28). 387-400.
CHAPTER 5: OTHERS
5.1
DRUG CAUSING HAEMATOLOGICAL DISORDER Drugs may produce hematologic toxicity by one of three general mechanisms: direct drug (or a metabolite) toxicity toxicity due to a drug effect on a genetic abnormality in the bone marrow toxicity involving immune mechanisms.
The four major blood dyscrasias attributable to drugs are: agranulocytosis or leukopenia (loss of the white blood cells) aplastic anemia (loss of all the formed elements of the blood) thrombocytopenia (loss of the platelets)
hemolytic anemia (loss of the red blood cells).
The incidence of these adverse hematologic drug reactions, the relative importance of various etiologic chemicals, and their resultant morbidity and mortality vary.
5.1.1
Drugs Suspected of Inducing Agranulocytosis (Leukopenia) Drug-induced agranulocytosis is classified as Type 1 (due to an immune mechanism) and Type II (drug effect on bone marrow DNA synthesis). In Type I reactions, blood immunoglobins are directed against drug-related antigens located on circulating leukocytes. Allopurinol* Aminopyrine Chloramphenicol Chlordiazepoxide Chloroquine Chlorpromazine Indomethacin Mefenamic acid Penicillamine Phenylbutazone Phenytoin Quinidine Rifampicin Sulfonamides Thiazides Acetaminophen Acetazolamide Anticonvulsants Antimalarials Aspirin Captopril Cephalosporins Chlorthalidone Cimetidine Clindamycin Diazepam Diflunisal Doxycycline Fenoprofen Gentamicin Griseofulvin Hydralazine Ibuprofen Isoniazid Isotretinoin L-dopa Mercurial diuretics Methyldopa Naproxyn Nitrofurantoin Penicillins Phenothiazines Piroxicam Procainamide Propranolol Spironolactone Streptomycin Sulfonylureas Sulindac Tolmetin Vancomycin
* Underlined drugs are most significant
Many of these other drugs have been implicated in only one or a few case reports
5.1.2
Drugs Suspected of Inducing Aplastic Anemia Aplastic anemia is an unexpected peripheral-blood pancytopenia with variable bone marrow hypocellularity in the absence of underlying malignant or myeloproliferative disease. Severe aplastic anemia is seen with a bone marrow of less than 25% of normal cellularity or a bone marrow of less than 50% of normal cellularity with less than 30% of the hematopoietic cells and at least two of the following peripheral blood values: Granulocytes fewer than 500/mm3 Platelets fewer than 20,000/mm3 Anemia with reticulocytes fewer than 1%. 15 About 65% of people with aplastic anemia die within 4 months of diagnosis; few die after this 4-month period.'
Allopurinol* Aminopyrine Chloramphenicol Chloroquine Gold salts Indomethacin Mefenamic acid Phenylbutazone Propylthiouracil
Sulfonamides Acetaminophen Aspirin Benzene Captopril Chlordiazepoxide Chlorpromazine Fenoprofen Indoprofen
Naproxyn Organic solvents Phenytoin Piroxicam Sulfonylureas Sulindac Thiazides Thiocyanate
*Underlined drugs are most significant Many of these other drugs have been implicated in only one or a few case reports
5.1.3
Drugs Suspected of Inducing Thrombocytopenia
Drug-induced immune thrombocytopenia is characterized by acute purpura, confluent petechiae or ecchy-moses- particularly after mild trauma-and gastrointestinal, central nervous system, or urinary tract bleeding,all associated with a mild or severe lack of blood platelets. Drugs may induce marrow hypoplasia, destroy platelets directly, or be responsible for an immune reaction. Thrombocytopenia may be associated with several disease states (acute leukemia, Gaucher's disease, systemic lupus erythematosus, sarcoidosis); drug-induced thrombocytopenia usually remits 1 to 2 weeks after drug discontinuance.
Gold salts* Indomethacin Mefenamic acid Quinidine Quinine Thiazides Acetaminophen Aminopyrine Amiodarone
Aspirin Codeine Danazol Diclofenac Digitoxin Fenoprofen Heparin Ibuprofen
Isotretinoin Para-aminosalicyclic acid Phenytoin Piroxicam Ranitidine Sulindac Tolmetin
*Underlined drugs are most significant Many of these other drugs have been implicated in only one or a few case reports
5.1.4
Drugs Suspected of Inducing Hemolytic Anemia Aminopyrine* Methyldopa Quinidine Acetaminophen Aspirin Cephalosporins Diclofenac Ibuprofen L-dopa Mefenamic acid Naproxyn Penicillins Quinine Rifampicin Sulfonamides Sulindac Tetracyclines Thiopental
Chlorpromazine Phenytoin
Phenylbutazone
Volatile nitrites
*Underlined drugs are most significant. Many of these other drugs have been implicated in only one or a few case reports.
5.2
POISONING Dose & Duration Dilution Side Effects Contraindications Monitoring
Treatment Option
Organophosphate Poisoning
1. Prevention of absorption - Activated Charcoal Adult : 25 100 gm Child : 25 50 gm < 1 yr : 0.5 1 gm/kg Tx : Cont until pt clinical condition improve. 2. Treatment - Atropine Adult : 2 mg q5-10 min (IV) until atropinised Child : 0.05 mg/kg (IV), then 0.02-0.05 mg/kg q15-60 min until atropinised Tx : cont for 12 24 H Commnet from Martina Want to include the infusion dose? - Pralidoxime Adult : 30mg/kg (bolus), repeat at 4-6 H, Inf : 8mg/kg/H (Max : 12 gm/day) Child : 20 50 mg/kg, 10 20 mg/kg/H (Max : 2gm/dose) Dilute up to 20 mg/ml with WFI for IV inj. given over 5-10 min Inf : dilute in 100ml NS over 15-30 min Blurred vision, diplopis, dizziness, drowsiness,BP headache,transient LFT, impaired accommodation, N, tachycardia, Hypersensitvity to any component of the product GIVE only after patient is adequately atropinised Vital signs, ECG, urine output Given undiluted I/Tracheal : Dilute dose in 1-2 ml of NS Antimuscarinic effect e.g dry skin, dilated pupil, flushing, urinary retention,bronchial secretion, constipation, bradycardia etc Dilute 30 gm in 240 ml Impaired intestinal motility Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage Serum electrolyes, ECG, serum amylase
Hypersensivity, Myasthenia Gravis, paralytic ileus, pyloric stenosis and prostatic enlargement
Pulse rate, EKG, urine output, GI motility
Note : administer as soon as possible after exposure, however pt presenting late (26 days post exposure) may
Treatment Option
Dose & Duration

Tx : until pt clinical condition improve
Dilution
Side Effects
laryngospasm
Contraindications
Monitoring
still benefit
Paraquat Poisoning
Prevention of absorption - Activated Charcoal Adult : 25 100 gm Child : 25 50 gm < 1 yr : 0.5 1 gm/kg Tx : Cont until pt clinical condition improve Dilute 30 gm in 240 ml Impaired intestinal motility Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage Serum electrolyes, ECG, serum amylase
- Fdbck from
Martina: Fullers earth?
Opiods Poisoning
1. Overdosage - Naloxone Adult : 0.4 2 mg q 2-3 min (bolus) (Max : 10 mg) Child : 0.01 mg/kg, then 0.1 mg/kg if no response Tx : up to 48H 2. Reversal of Opiod induced resp distress Maybe given undiluted Infusion : 4mg in 500ml in NS, D5 discrd inf after 24H Hyperyension, N, V, sweating, tachycardia, elevated PTT Hypersensitivity to naloxone Vital Signs
Treatment Option
- Naloxone
Dose & Duration

1.5 3 g/kg (IV), if needed increment of 0.1mg q2min, further dose IM after 1-2H prn
Dilution
Side Effects
Contraindications
Monitoring
Benzodiazepines Poisoning
1. Prevention of absorption - Activated Charcoal
Adult : 25 100 gm Child : 25 50 gm < 1 yr : 0.5 1 gm/kg Tx : Cont until pt clinical condition improve.
Dilute 30 gm in 240 ml
Impaired intestinal motility
Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage
Serum electrolyes, ECG, serum amylase
2. Treatment - Flumazenil
Adult : 0.2 mg (15 sec), then 0.1mg q1min prn, usual 0.3-0.6mg (Slow IV), Inf : 0.1-0.4 mg/H (Max : 2 mg) Child : 5g/kg every 60 sec, max 40 g/kg
Given undiluted or further dilute with D5,NS, NS Discard solution after 24H
N, V, Flushing, agitation, anxiety, transient BP, HR
Life threatening condition controlled by BDZ (e.g intracranial pressure, status epilepticus)
Airway, breathing, circulation, vital signs, ECG
Treatment Option
Dose & Duration

then 2-10 /kg/H Tx : until desired level of consciousness with max dose achieved
Dilution
Side Effects
Contraindications
Monitoring
Heparin and Derivatives Poisoning

Severe Haemorrhage - Protamine Sulfate Adult : 1mg /100U hep, (Max : 100 mg) Undiluted over 10 min Maybe further dilute with NS or D5.Rate <5mg/min inf over 2-3H Hypotension, bradycardia and dyspnoea None when use as indicated Airway, breathing, circulation, vital signs, Coagulation Profile, FBC
Child : 1mg/100U hep, 0.5mg/100U hep. If > 1H (slow IVstat), subs dose1mg/kg (Max : 50 mg) Tx : any dose over 100mg in 2H should be justified by coagulation studies
Warfarin Overdosage
1. Prevention of absorption - Activated Charcoal Adult : 25 100 gm Child : 25 50 gm Dilute 30 gm in 240 ml Impaired intestinal motility Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI Serum electrolyes, ECG, serum amylase
Treatment Option
Dose & Duration

< 1 yr : 0.5 1 gm/kg Tx : Cont until pt clinical condition improve.
Dilution
Side Effects
Contraindications
haemorrhage
Monitoring
Treatment - Vitamin K Adult : 10 mg (Max : 25 50 mg) Child : 1-5 mg (Max : 0.6 mg/kg) Dilute 10mg in 50ml D5 over 30 min or into Y site of fast running D5 Max 40mg over 24H Venous irritation, phlebitis, anaphylaxis Hypersensitivity to components Airway, breathing, circulation, vital signs, Coagulation Profile, FBC, INR
Tx : may repeat in 6-8H if initial response is not adequate
Paracetamol Poisoning
1. Prevention of absorption - Activated Charcoal Adult : 25 100 gm Child : 25 50 gm < 1 yr : 0.5 1 gm/kg Tx : Cont until pt clinical condition improve. Dilute 30 gm in 240 ml Impaired intestinal motility Absence of bowel sounds, GI perforation, intestinal obstruction, recent surgery, GI haemorrhage Serum electrolyes, ECG, serum amylase
Treatment Option
Dose & Duration
Dilution
Side Effects
Contraindications
Monitoring
2. Treatment - N-Acetylcysteine Adult : 150mg/kg over 15min, then 50mg/kg over 4H, then 100mg/kg over 16H Child : Same as adult Adult : Initial dilute in 200ml D5% given over 15min, then in 500ml over 4H, then in 1L over 16 H Child (<12y) : Dilution of adult given at the same rate of adult dose. Child (<20 kg) : Initial dilute as 3ml/kg over 15 min, then 7ml/kg over 4H, then 14/kg over 16H. Rash, anaphylaxis, bronchospasm, hypocalcaemia and ECG changes Hypersensitivity to acetylcysteine or any of its component Airway, breathing, circulation, vital signs, Ca2+ level, LFT, ECG
Tx : usually total infusion time is 21H
From Martina: Want to add what to do if these happens. Stop or not to stop NAC?
Notes : NAC therapy should begin within 8H of ingestion if possible. NAC efficacy decrease progressively from 8-16H post ingestion
References : 1. BNF 51, March 2006 2. Drug Doses, 13th Ed 2005, Frank Shann 3. Intravenous Medication 2008, 24th Ed, Betty LG, Adrienne RN
4. Micromedex (R) Healthcare Series Vol. 13
APPENDICES APPENDIX 1: DRUGS THAT MAY UNMASK/EXACERBATE MYASTHENIA GRAVIS

Anesthetic agents Chloroprocaine Diazepam Ether Halothane Ketamine Lidocaine Neuromuscular blocking agents Propanidid Procaine Antibiotics Aminoglycosides Amikacin Gentamicin Kanamycin Neomycin Netilmicin Paromomycin Spectinomycin Streptomycin Tobramycin Fluoroquinolones Ciprofloxacin Levofloxacin Norfloxacin Others Ampicillin Clarithromycin Clindamycin Colistin Erythromycin Lincomycin Quinine Telithromycin Tetracyclines Anticonvulsants Gabapentin Phenytoin Trimethadione Antipsychotics Chlorpromazine Lithium Phenothiazines Antirheumatic drugs Chloroquine Penicillamine Cardiovascular drugs Beta blockers Bretylium Procainamide Propafenone Quinidine Verapamil and calcium channel blockers Glucocorticoids Corticotropin Methylprednisolone Prednisone Neuromuscular blockers and muscle relaxants Botulinum toxin Magnesium sulfate and magnesium salts Methocarbamol Ophthalmologic drugs Betaxolol Echothiophate Timolol Tropicamide Proparacaine Other drugs Anticholinergics Carnitine Cholinesterase inhibitors Deferoxamine Diuretics Emetine (Ipecac syrup) Interferon alpha Iodinated contrast agents Narcotics Oral contraceptives Oxytocin Ritonavir and antiretroviral protease inhibitors Statins Thyroxine
* Drugs listed here should be used with caution in patients with myasthenia gravis. Aminoglycosides should be used only if absolutely necessary with close monitoring. Please refer to the text for further information. Ref: Uptodate 17.1
APPENDIX 2: CATEGORIES OF SAFE & UNSAFE DRUGS IN THE ACUTE PORYPHYRIAS
Categories of safe drugs in the Acute Porphyrias

Drugs Which are SAFE to use: Acetaminophen Acetazolamide Allopurinol Amiloridine Aspirin Atropine Bethanidine Bromides Bumetanide Chloral hydrate Cimetidine Corticosteroids Coumarins Fluoxetine Gabapentin Gentamycin Guanethidine Insulin Narcotic analgesics Ofloxacin Paracetamol Penicillins Phenothiazines Propranalol Streptomycin Succinylcholine Tetracycline Drugs which are PROBABLY SAFE to use: Adrenaline Amitriptyline Azathioprine Chloramphenicol Cisapride Colchicine Cyclosporin Cytarabine Dicumarol Chloroquine Digoxin Daunorubicin Doxazosin Estrogens (natural/endogenous) Ibuprophen Imipramine Indomethacin Labetalol Lithium Losartan Drugs which are PROBABLY SAFE to use: (cont.) Methenamine Methylphenidate Naproxen Neostigmine Nortriptyline Nitrous oxide Penicillamine Procaine Propanidid Propofol Propoxyphene Rauwolfia alkaloids 6-Thioguanine Thiouracils Thyroxine Tricyclic antidepressants Tubocurarine Vigabatrin Vitamin B Vitamin C
This list is NOT comprehensive and does not reflect all information and opinions about drug safety in the acute porphyrias. There is considerable evidence for classification of drugs in the "Safe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably Safe" category. Additional information concerning safe and unsafe drugs can be found in the text, including available websites. Reproduced with permission from Anderson, KE, et al. Disorders of heme synthesis: X-linked sidero-blastic anemia and the porphyrias. In: The metabolic and molecular bases of inherited disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds). McGraw-Hill Medical Publishing Division, New York. p 2991. Copyright 2000 The McGraw-Hill Companies.
Categories of Unsafe drugs in the Acute Porphyrias
Drugs which are UNSAFE ACE inhibitors Antipyrine Aminopyrine (amidopyrine) Aminoglutethamide Barbiturates (all) Nbutylscopolammoni um bromide Calcium channel blockers Carbamazepine Chlorpropamide Danazol Dapsone Diclofenac Enalapril Diphenylhydantoin Ethosuximide Ergot preparations Ethchlorvynol Ethinamate Felbamate Glutethimide Griseofulvin Ketoconazole Lamotrigine
Drugs which are UNSAFE (cont.) Mephenytoin Metoclopramide Meprobamate Methyprylon Nefazadone Nifedipine Novobiocin Phenazone Phenylbutazone Primidone Pargyline Progesterone (progestins) Rifampin Succinimides Sulfasalazine Sulfonamide antibiotics Sulfonmethane (sulfonal) Sulfonethylmethan e (trional) Sulfonylureas Trimethadione Valproic acid Tranylcypromine
Drugs which are POTENTIALLY UNSAFE Alfadolone acetate Alfaxolone Alkylating agents* Altretamine (hexamethylmelam ine) Benzodiazepines Busulfan Captopril Cephalosporins Chlorambucil Chlordiazepoxide Clonidine Cyclophosphamide Dacarbazine Deferoxamine Diazepam Diltiazem Colistin Dacarbazine Diphenhydramine EDTA Etomidate Estrogens (synthetic) Erythromycin 5-Fluorouracil Gold compounds Fluroxene
Drugs which are POTENTIALLY UNSAFE (cont.) Heavy metals (eg, Gold) Hydralazine Hyoscine Ketamine Lisinopril Mefenamic acid Melphalan Mifepristone Methyldopa Metyrapone Nalidixic acid Nikethamide Nitrazepam Nitrofurantoin o,p'-DDD Pentazocine Phenoxybenzamine Procarbazine Pyrazinamide Spironolactone Theophylline Tiagabine Tramadol Tricyclic antidepressants Troglitazone
This list is NOT comprehensive and does not reflect all information and opinions about drug safety in the acute porphyrias. There is considerable evidence for classification of drugs in the "Unsafe" category, but much less evidence, or conflicting evidence, for drugs in the "Probably Unsafe" category. Additional information concerning safe and unsafe drugs can be found in the text, including available websites. * Chlorambucil and Melphalan may be safer than the other alkylating agents listed here. Reproduced with permission from Anderson, KE, et al. Disorders of heme synthesis: X-linked sidero-blastic anemia and the porphyrias. In: The metabolic and molecular bases of inherited disease (Scriver, CR, Beaudet, AL, Sly, WS, Valle, D, eds). McGraw-Hill Medical Publishing Division, New York. p 2991. Copyright 2000 The McGraw-Hill Companies. Ref: Uptodate 17.1 APPENDIX 3: DRUGS AND CHEMICALS IN GLUCOSE-6-PHOSPHATE DEHYDROGENASE
Unsafe for class I, II, and III variants Acetanilid Dapsone Furazolidone Methylene blue Nalidixic acid Naphthalene (mothballs, henna) Niridazole Nitrofurantoin Phenazopyridine Phenylhydrazine Primaquine Sulfacetamide Sulfamethoxazole Sulfanilamide Sulfapyridine Thiazosulfone Toluidine blue Trinitrotoluene
Safe for class II and III variants* Acetaminophen Aminopyrine Ascorbic acid (except in very high doses) Aspirin Chloramphenicol Chloroquine Colchicine Diphenhydramine Isoniazid L-DOPA Menadione Paraaminobenzoic acid Phenacetin Phenytoin Probenecid Procainamide Pyrimethamine Quinidine Quinine Streptomycin Sulfamethoxpyridazine Sulfisoxazole Trimethoprim Tripelennamine Vitamin K
* Safety for class I variants is usually not known. Data from Beutler, E, Blood 1994; 84:3613. Reference: Uptodate 17.1
APPENDIX 4: DRUG-DISEASE INTERACTIONS Drug 1 Aminoglycosides Disease Myasthenia Gravis Remarks Cause significant increase in weakness, respiratory depression. Aminoglycoside-related postoperative respiratory depression caused the greatest frequency of drug-induced neuromuscular blockade Edema Management Avoid or use only if absolutely necessary with close monitoring Ref www.uptodate.com
Androgens (testosterone)
HF
Endocrine Society Guideline (US) recommend not to use in NYHA III, IV
Uptodate vs 17.1
Amiodarone
Thyroid disorders
the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases.
Thyroid function to be monitored.
Complex Drug-Drug-Disease Interactions Between Amiodarone, Warfarin, and the Thyroid GlandKurnik, Daniel MD; Loebstein, Ronen MD; Farfel, Zvi MD; Ezra, David MD; Halkin, Hillel MD; Olchovsky, David MD
Antiarrhythmic (sotalol, ibutilide) ACE inhibitors gold salts and interferon . Antimalarials Antipsychotics
HF
Negative inotropic, precipitate HF, proarrhythmic Occasional triggers of a psoriatic flare Exacerbate Parkinsonism
Amiodarone is the preferred choice in arrhythmias in HF

Use Cautiously
Uptodate vs 17.1
Skin Therapy Letter Editor: Dr. Stuart Maddin Vol. 4 No. 3
Psoriasis
6 7
Psoriasis Parkinsons
Not contraindicated. Use with caution
Neurology, Vol 66,
Drug
Disease disease
Remarks
Management
Ref Issue 6, March 2006
Beta Blockers
COPD, Asthma
Non selective beta blockers prevents bronchodilatation
-All beta blockers are contraindicated in severe disease -Non selective ones to be avoided in mild to moderate disease. Selective or combined alpha/beta to be used cautiously at low dose
Uptodate vs 17.1
9 10
Beta Blockers Beta Blockers
Diabetes Peripheral Vascular Disease, Raynauds phenomeno n Bradycardia, heart block
Facilitation of hypoglycaemia Non selective beta blockers implicated. Reduction in cardiac output and blockade of beta-2receptor-mediated skeletal muscle vasodilation contribute to the vascular insufficiency [ -ve Chronotropic effect. -maintenance of cardiac output depends on sympathetic drive May aggravate existing disease
Use cautiously Selective agents can be used cautiously
Uptodate vs 17.1 Uptodate vs 17.1
11
Beta blockers
Use cautiously
Uptodate vs 17.1
12
Beta Blockers
Psoriasis
Not contraindicated in psoriasis. However, when there is a clear relationship between the exacerbation of
Drug
Disease
Remarks
Management
the psoriasis and the intake of a beta blocker, it sometimes help to switch from a noncardioselective beta 2 blocker to a cardioselective beta 1 blocker.
Ref
13
Beta Blockers
Myasthenia gravis
Exacerbate
Use with caution
Uptodate vs 17.1
14
Chemotherapeuti c agents (cyclophosphamide, traztuzumab, bevacizumab, anthracyclinelike chemo agents CNS depressants,
HF
Cardiotoxic
Altenative administration schedule. Baseline and periodic monitoring of ECG and LVEF (with either ECHO) is recommended.
Uptodate vs 17.1
15
Myasthenia
Increase symptoms when used
Use cautiously
Uptodate vs 17.1
Drug opioids, muscle relaxants 16 Corticosteroids
Disease Gravis Psoriasis
Remarks together or at high doses Rebound that invariably follows their use. The flare-up may be even worse than the original attack.
Management
Ref
Avoid
17 18
COX-2 selective inhibitosr Calcium Channel Blockers
HF CHF
Exacerbation of HF Negative Inotropic, increase sympathetic activity by short acting dihydropyridines. Longer acting ones appears safe
Use with caution Avoid use of shorter acting dihydropyridines
Uptodate vs17.1
Efficacy and safety of calcium channel blockers in heart failure: focus on recent trials with second-generation dihydropyridines. AU de Vries RJ; van Veldhuisen DJ; Dunselman PH SO Am Heart J 2000 Feb;139(2 Pt 1):185-94.
19
Calcium channel blockers (short acting verapamil, diltiazem, nifedipine) Fluoroquinolones
2nd-3rd degree heart block
Negative Inotropic.
Avoid use of shorter acting dihydropyridines
20
Myasthenia
Exacerbate
Use with caution
Uptodate vs17.1
Drug
Disease gravis
Remarks
Management
Ref
21
Lithium
Psoriasis
Well recognised cause of exacerbation. It may even cause pustular or erythrodermic psoriasis in a significant proportion of affected patients.
Lithium does not aggravate a preexisting psoriasis in all cases, and therefore is not contraindicated in all patients with psoriasis.
22
Lignocaine and procaine may cause worsening if given iv Magnesium Sulfate Metformin NSAIDs, Aspirin
Myasthenia Gravis
Uptodate vs 17.1
23
Myasthenia Gravis HF Peptic Ulcers Asthma
Relatively contraindicated since it has inhibitory effect on acetylcholine release Increased risk of lactic acidosis Gastrotoxicity
Relative contraindication Use with caution Use with caution
Uptodate vs 17.1
24 25
Uptodate vs 17.1 Uptodate vs 17.1
26
NSAIDs, Aspirin
Acute exacerbation of airway inflammation. Less likely with COX-2 inhibitors Exacerbation and impaired
Avoid in aspirin sensitive asthma. Use with caution in others Use with caution
Uptodate vs 17.1
27
NSAIDs
HF
Uptodate vs 17.1
Drug
Disease
Remarks response to ACE-I
Management
Ref
28
NSAIDs
Psoriasis
Anecdotal reports suggest adversely affecting psoriasis
Consider discontinuing a NSAID if the patients psoriasis worsened on starting, and improved after stopping that drug
Uptodate vs 17.1
29 30
Neuromuscular Blocking Agents High Dose Prednisolone, glucocorticoids in high doses Penicillamine Phenytoin, Gabapentin Procainamide, quinidine, quinine, List is comprehensive -Refer Appendix 1
Myasthenia Gravis Myasthenia Gravis
Unmask or exacerbate MG Exacerbation during early stages of treatment
Titrate judiciously During crisis, use only if patients airway is protected Avoid Use cautiously Avoid
Uptodate version 17.1 Uptodate version 17.1
31 32 33
Myasthenia Gravis Myasthenia Gravis Myasthenia Gravis
Induces autoimmune Myasthenic syndrome. Reversible Rare cases of exacerbation Cause significant increase in weakness
Uptodate version 17.1 Uptodate version 17.1 Uptodate version 17.1
Drug 34 35 36 PDE-3 (Cilostazol) PDE-4 (Anagrelide) PDE-5 (sildenafil, vardenafil, tadalafil) Statins
Disease HF HF HF
Remarks Increased mortality +inotropic, vasodilatory, leading to fluid retention and heart failure Potentially hazardous in patients with HF with borderline BP. Avoid in IHD Unmasking subclinical MG due to myotoxicity, new and worsening MG Safety and efficacy has not been studied in these patients Exacerbate SLE
Management Contraindicated Avoid Use with caution
Ref Uptodate vs 17.1 Uptodate vs 17.1 Lexicomp
37
Myasthenia Gravis CHD SLE
Use cautiously
Uptodate version 17.1 Lexicomp Drugs Uptodate vs 17.1
38 39
Sildenafil Sulfonamide Antibiotics, Penicillin (but not the semi synthetic ones) Theophylline
Use with caution Avoid
40
Cardiac disease
Can reduce theophylline clearance by as much as 50%
Monitor level closely
Shannon: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th ed. Ch 65
41
Theophylline
Primary Hepatic
Can reduce theophylline clearance by as much as 50%
Monitor level closely
Shannon: Haddad and Winchester's Clinical Management
Drug
Disease Disease
Remarks
Management
Ref
of Poisoning and Drug Overdose, 4th ed. Ch 65
42
Theophylline
Cystic Fibrosis, Hyperthyroidism
Increase clearance
May need to increase dose
Shannon: Haddad and Winchester's Clinical Management of Poisoning and Drug Overdose, 4th ed. Ch 65 Drug labels
43
TNF blockers
HF
New onset or worsening preexisting HF
Use with caution in patients with HF or decreased left ventricular function; worsening and new-onset HF has been reported." In addition, infliximab is contraindicated at doses higher than 5 mg/kg in patients with moderate or severe HF (NYHA class III/IV)
44
TNF blockers
Psoriasis
45
Telithromycin
Myasthenia Gravis Thyroid
Possibility of emergence or worsening of psoriasis during treatment with TNF blockers, particularly pustular and palmoplantar forms of psoriasis. Black box warning on possibility of exacerbating or unmasking MG. Should not use. thyroid disorders may affect
Monitor
FDA ALERT [8/4/2009]
Uptodate version 17.1
46
Warfarin
Thyroid function should be
Complex Drug-Drug-Disease
Drug
Disease disorders
Remarks warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively
Management
Ref
Interactions Between Amiodarone, Warfarin, and the Thyroid Gland Kurnik, Daniel MD; Loebstein, Ronen MD; Farfel, Zvi MD; Ezra, David MD; Halkin, Hillel MD; Olchovsky, David MD
tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.
Refer to Appendix 2
47
Inexhaustive list (see Appendix 2) Inexhaustive list (see Appendix 3)
Acute Intermittent Porphyria G6PD deficiency
Can exacerbate disease
Uptodate 17.1
48
Can cause hemolysis
Refer to Appendix 3
Uptodate 17.1

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CRITICAL CARE PHARMACY HANDBOOK 2010

CHAPTER 3 : 3.1 3.2 3.3

Parenteral Nutrition in Critically Ill Patients Mazni

CHAPTER 5 : 5.1 5.2

Drug Causing Haematological Disorder Irma Poisoning Hasni

CHAPTER 1 THE ROLE OF PHARMACIST IN CRITICAL CARE

CHAPTER 2 PROTOCOLS 2.1 Dilution Protocols 2.1.1 Antiarrhythmic Agents

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION

DILUENTS FOR INFUSION

150mg/3ml ( Cordarone ) Below 25C. Already in solution. NA D5%

STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION

Below 25C, Protect from light, Do not freeze Already in solution

DILUENTS FOR INFUSION

D5% NS D5% 1/2 NS D5% 1/4 NS Lactated Ringer's Injection

IV infusion 1mg/ml over 3 hours IV infusion 2mg/ml over 1 hour

Should not be given as IV bolus or IM

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION

STABILITY AFTER RECONSTITUITION

DILUENTS FOR INFUSION METHOD OF ADMINISTRATION

IV bolus over 3-5 minutes. IV infusion: 100ml over

IV bolus over 3-5 minutes. IV infusion: diluent up

50 - 60 minutes. IM ( Dissolve 1gm in 4ml Water for Injection )

STABILITY AFTER RECONSTITUITION

6 hours at room temperature 24 hours in refrigerator NS

DILUENTS FOR INFUSION

0.45%NS D5% D5%

IV Infusion over 60 minutes

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION

500mg Below 25C.

DILUENTS FOR INFUSION

IV Infusion over 60-90 minutes

1. Product information Moxied-CLV 2. 2. BNF 50, September 2005.

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION

80mg/2ml Below 25C Already in solution. NA

STABILITY AFTER RECONSTITUITION

DILUENTS FOR INFUSION

IV Infusion: 250 -500ml over 2-4 hours

IV infusion : 100-200ml over 30 minutes.

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION

STABILITY AFTER RECONSTITUITION

DILUENTS FOR INFUSION

IV infusion : 100ml over 20 30 minutes.

IV infusion : 30 -120 minutes.

Avoid contact between drug and aluminium in infusion set.

s. DRUG STRENGTH/UNIT STORAGE RECONSTITUITION

500,000 units 15 - 30C 500mg - 10ml , 1gm - 20ml of NS or D5%

STABILITY AFTER RECONSTITUITION

Water for Injection NS Water for Injection NS D5%

DILUENTS FOR INFUSION

D5% Lactated ringer

1. Product information Easyn. 2. Micromedex Healthcare series

DRUG STRENGTH/UNIT STORAGE RECONSTITUITION STABILITY AFTER RECONSTITUITION

Water for Injection NS DILUENTS FOR INFUSION D5%

IV Infusion : dilute with infusion fluid up to 5mg/ml over 1 hour.

100mg/50ml ( Diflucan ) Below 30C, Do not refrigerate. Already in solution

200mg ( Vfend) 15-30C

19ml Water for Injection.

STABILITY AFTER RECONSTITUITION

24 hours at room temperature 1 week in refrigerator D5%

NS D5% Compound Sodium Lactate

DILUENTS FOR INFUSION

Infusion concentration is 0.1mg/ml

Slow Intravenous infusion : 2 - 6 hours METHOD OF ADMINISTRATION