Pertemuan Ilmiah Tahunan (PIT) XVIII IPD

FKUB-RSSA Malang 2019

DISKUSI KASUS
TERINTEGRASI

Nur Samsu

Divisi Ginjal dan Hipertensi

Departemen Ilmu Penyakit Dalam FKUB
RSU Dr Saiful Anwar Malang
 Pemeriksaan Fisik dan
Penunjang
 Vital Sign :
GCS : 345
TD : 80/50 mmHg
HR : 112 bpm
RR : 28 tpm
Tax : 38,6 C
SpO2 : 97 % NC 2 lpm
BB : 52 kg
Urine Output : 150cc/8 jam
Rhonki (+/+) kasar mediobasal
 Laboratory Findings
LAB VALUE NORMAL LAB VALUE NORMAL

Leucocyte 14,740 4.700 – 11.300 /µL Natrium 148 136-145 mmol/L

Hemoglobine 10,6 11,4 - 15,1 g/dl Kalium 3,93 3,5-5,0 mmol/L
PCV 31,4 38 - 42% Chlorida 125 98-106 mmol/L
Thrombocyte 227.000 142.000 – Ureum 114 20-40 mg/dL
424.000 /µL
MCV 93,5 80-93 fl Creatinine 1,86 <1,2 mg/dL
MCH 28,6 27-31 pg RBS 156 < 200 mg/dl
Eo/Bas/Neu/Li 0,2/0/75,8/19, 0-4/0-1/51-67/25- PTT 12,4 11,2
mf/Mon 4/4,6 33/2-5
SGOT 164 0-40 U/L INR 1,02
SGPT 39 0-41 U/L APTT 22,5 25,8

Albumin 2,88 3.5-5.5 g/dL

 Apa penyebab kondisi Acute Kidney Injury
pada pasien ini?
 Criteria of AKI
The Acute Kidney Injury
Network Classification ( AKIN)

Critical Care 11:R31 (2007)

 Penyebab utama AKI
Pre-renal Renal Post-renal

Cause: Hypovolemia Nephritic syndrome Nephrotic syndrome Cause: Obstruction

• Sepsis • Azotemia • Massive proteinuria • BPH
• Shock • Hematuria • Severe edema • Cancer
• Heart Failure • Red cell cast • Hyperlipidemia • Stone
• hypertension • Hyperchlesterolemia
• Mild edema • No hematuria, azotemia
• Mild proteinuria or HTN at onset

MPGN MCD  Acute GN 5%

PIGN MGN • Interstitial nephritis 10%
RPGN FSGS • Tubular necrosis 85%
IgA nephropathy DN (Toxin 35%, Ischemia 50%)
Alport syndrome SLE
Amyloidosis

BUN < 20 May present as polyuria

BUN > 20 Urine is dilute
Urine is concentrated w/ high urine [Na+] &
Urine [Na +] high (> 20 mEq/L) Unconcentrated urine
Urine [Na +] low (< 10 mEq/L) ↑ FENa+
↓ FENa+ Cells/casts  tubular injury
 AKI Causes: Sepsis
ICU LENGTH OF STAY HOSPITAL LENGTH OF STAY
6 25
Non-Septic AKI Non-Septic AKI
5 Septic AKI Septic AKI
20
4
15
Days

Days
3
10
2

1 5

0 0
None Risk Injury Failure None Risk Injury Failure
RIFLE Category RIFLE Category

Sepsis accounted for 32.4% of all hospitalized patients with AKI.

Over 42% of all sepsis diagnoses also had an AKI diagnosis.
Sepsis is the most common cause of AKI in the ICU.

Bagshaw SM, George C, Bellomo R et al. Crit Care. 2008;12:R47.

 Glomerular Hypoperfusion
  ECF volume

  Effective volume
(CHF, sepsis, cirrhosis)

 Glomerular Hemodynamic: Contrast

 Vasoconstriction (pre glomerular) CSA
Ampho
 NSAID/ COX-2 inhibitor
 Contrast
 Amphotericin B NSAID ACE-I
ARB
 Cyclosporine/ tacrolimus
 Hypercalcemia
 Efferent vasodilatation
 ACE inhibitors/ ARBs
 Pathophysiology of prerenal AKI
Hypovolemia
RAA-axis
RBF maintained initially
through:
-Local myenteric reflex
-PG synthesis
-Actions of Ag II
Homeostatic goal:
Restore intravascular volume
and blood pressure to maintain
perfusion of essential organs
Decreased cardiac output
Systemic vasodilatation
Baroreceptor activation
Neurohormonal responses
Vasopressin Sympathetic
nervous system
Vasoconstriction
Mesangial cell contraction
Avid salt and water reabsorption
Reducing sweating
Thirst and salt appetite
Prerenal AKI
Dramatic reduction in renal Dramatic reduction in
Blood flow, glomerular filtration, splanchnic, skin, and
urine flow muskuloskeletal blood flow
 Bagaimana manajeman AKI serta
pemilihan antibiotik dan pemberian dosis
antibiotik pada kondisi seperti ini?
 AKI: Management Principles

 Determine exact diagnosis

 Remove offending agent/treat causes
 Prevent complications (i.e. hyperkalemia)
 Reverse oliguria/Improve renal blood flow (correction of
intravascular volume) -- RESUSCITATION
 Careful volume and electrolyte management
 Remove nephrotoxins, dose-adjust medications
 Provide nutrition (low K, low P)
 Initial Resuscitation

SvO2 = mixed venous oxygen saturation

Modificated by Rivers, NEJM 2001

 The Endothelial Glycocalyx

 Membrane coating endothelium

(“double barrier concept”)
 Affect endothelial permeability.
 Prevent leukocyte and platelet
adhesion.
 Decreases inflammation.
 Bounds plasma proteins and fluids.
 700 ~ 1000 mL of “non-circulatory” plasma
fixed within.
 Maintains “oncotic gradient”

Myburgh JA, Resuscitation fluids, NEJM, 369, 2013: 1243-1249 A: Healthy, B: Damaged
Surviving Sepsis Guidelines 2017
 Factors in Selecting Initial
Appropriate Therapy
 Patient features: Choose empiric therapy based on site and
severity of infection, and physician assessment of the likelihood
for deterioration and mortality.

 Local susceptibility and epidemiology: Choose empiric therapy

to cover the likely infecting pathogens based on patterns while considering
prior antibiotic therapy.
 Initial antibiotic therapy dosing and duration: Choose initial empiric
therapy that will deliver enough antibiotic to the site of infection and be well-
tolerated (consider antibiotic penetration).
 Combination vs. monotherapy: Initial antibiotic choice should give broad
enough coverage, avoid emergence of resistance, and have the potential
for synergy if necessary.
 A Clinical Issue of
Drug Dosage Adjustment
Renal Failure + Renal Failure +
No dosage adjustment Too-large dose reduction
or no treatment

OVERDOSAGE UNDERDOSAGE

Toxicity Lack of efficacy

The right dose must be prescribed, adjusted to renal function:
- not too large (overdosage)
- not too reduced (underdosage)
Target Concentration Strategy
Estimate Initial Dose
-Target level
-Loading dose
-Maintenance dose

Begin therapy

Assess therapy
-Patient response
-Drug level

Refine dose estimate and

Adjust dose
 Dose Modification for
Patients with Renal Insufficiency
Drugs requiring dose modification Drugs requiring dose modification

All antibiotics Lipid-lowering agents

HMG–CoA reductase inhibitors,
Antihypertensives benafibrate, clofibrate, fenofibrate
- Atenolol, nadolol, ACE Inhibitors
Hypoglycemia medications
Cardiac medications - Acarbose, chlorpropamide, glyburide,
- Digoxin, sotalol gliclazide, metformin, insulin

Narcotics Diuretics
- Codeine, meperidine AVOID potassium-sparing diuretics in
patients with creatinine clearance < 30
Psychotropics ml/min
- Lithium, gabapentin, trazodone,
paroxetine, primidone, topiramate, Miscellaneous
vigabatrin Allopurinol, colchicine, histamine2
receptor antagonists, diclofenac,
ketorolac, terbutaline
GR Matzke et al.: Drug dosing in kidney disease. Kidney International (2011) 80, 1122–1137
 Need Proper Antibiotic Dosing
(Normal Renal Function)
 Ciprofloxacin 400mg q8h
 Levofloxacin 750mg qd
 Imipenem 1 gm q 8H or 500 mg q 6H;
 Meropenem 1 gm q 6-8H
 Piperacillin / Tazobactam 4,5 gm q 6H
 Cafepime 2 gm 1 8-12H
 Ceftazidime 2 gm q 8H
 Gentamicin or Tobramycin 7mg/kg/day or
Amikacin 20 mg/kg/day
 Linezolid 600mg q 12 h
 Vancomycin 15 mg/kg q12h
Selected drug dosages for patients with renal failure
Normal t ½ in Adjustment for renal failure
Agent M&E t1/2 (hr) ESRD M GFR (ml/min)
(hr) > 50 10-50 <10
Ampicillin Renal; also 0.8-1.5 7-20 IE 6 6-12 12-16
hepatic
Cefotaxim Renal; also 1 2.6 IE 6-8 8-12 12-24
hepatic
Chloramp Renal; hepatic 2-4 3-7 No adjustment necessary
Gentamicin Renal 2 24-48 DR 60-90% 30-70% 20-30%
IE 8-12 12 24
Rifampin Hepatic 2-5 2-5 No adjustment necessary
Sulfametho Hepatic; also 9-11 20-50 IE 24 24-72 72-96
xazole renal
Vancomycin Renal 6-8 200-250 IE 24-72 72-240 240
 Clearance (Cl)
Dose in renal insufficiency :

1. Cltot Pts X Normal Dose

Cltot N

2. Cltot N X Normal Dosing Interval

Cltot Pts

Cltot= kliren total

 De-escalation Approach to
Antimicrobial Utilization
Serious hospital acquired infection suspected

Begin empirical antibacterial treatment with a

combination agents targeting the most common
pathogen based on local data

De-escalation Antibacterial based on results of

clinical microbiology data

Search for superinfection

N Significant clinical
Abscess formation,
improvement after 48-96
Non infectious caused of
hours
fever
Y

Discontinue antibacterial after 7-13 days course based on

site of infection and clinical response
Kollef, Drugs 2003:63 (20):2157
KASUS 2
 Pemeriksaan Fisik :
 Vital Sign :
Kesadaran : Composmentis
TD : 110/70 mmHg
Nadi : 120x/menit
Respirasi : 40x/menit
Suhu : 37,6°C
SpO2 : 98%
BB : 42 kg
Urine Output : 120 cc/ 8 jam

 Status Generalis :
Mata : sklera ikterik (+)
Thoraks : cardiomegaly
Abdomen : slightly distended, epigastric pain
Ekstremitas : Edema +/+ inferior
 Laboratory Findings
Jenis Pemeriksaan Hasil Satuan Nilai Rujukan
Darah Rutin
Leukosit 20.600 /µL 3800-10600
Eritrosit 3.8 Juta/µL 4.4-5.9
Hb 13,9 g/dl 13.2-17.3
Ht 24,6 % 40-52
Trombosit 81.000 Ribu/µL 150000-450000

LAB VALUE NORMAL LAB VALUE NORMAL

OT 68 0-40 U/L Ureum 46,1 20-40 mg/dL

PT 57 0-41 U/L Creatinine 2,4 <1,2 mg/dL
Bil T 2,5 < 1 mg/dl Natrium 125 136-145 mmol/L
Bil D 2,1 < 0,75 mg/dl Kalium 5,5 3,5-5,0 mmol/L
Bil I 0,4 < 0,25 mg/dl Chlorida 100 98-106 mmol/L
 Bagaimana manajemen cairan pada
pasien tersebut?
 Fluid Resuscitation
 Primary importance is “How much”
 Further consideration is “What fluid”

“How much”
 Avoid the “Lethal Triad”
 Coagulopathy
 Consumption of clotting factor
 Dilution of platelets and clotting factors

 Hypothermia
 Perpetuates coagulopathy
 Most forgotten vital sign in resuscitation

 Acidosis
 Inadequate resuscitation and tissue perfusion
 Anaerobic metabolism and of lactic acid production
Goals of Resuscitation Fluid Therapy

 Restore blood Therapeutic end point

pressure
• CRT < 2 seconds
 Normalize systemic
• MAP 65 – 70 mmHg
The principle of fluid therapy is
perfusion
• Urine output > 0.5

to maintain tissue perfusion
Preserve organ
function
ml/kg/hour (adults); > 1
ml/kg/hour (children)
• Shock index = HR/SBP
(normal 0.5 – 0.7)
Volume  Fluids
 • CVP 8 to 12 mmHg
 Pressure  Vasopressor • O2 sat > 95%
 Flow  Inotrope • ScvO2 > 70%
 No therapeutic end point
is universally effective
“Hypoperfusion can be present in the absence
of significant hypotension.”
(Don’t only relay on BP for diagnosing shock)

CVP: Poor Target for Fluid Rx

No longer recommended as lone guiding

principles as they carry limited value for measuring
fluid responsiveness

use of dynamic variables (ie passive leg raise, pulse

pressure variation, stroke volume variation)
Deficit or Excess Blood Volume
Fluid Resuscitation
Marik PE, et al. Chest. 2008;134(1):172-178. Surviving Sepsis 2017 Guidelines
 Which fluid to Choose?

1: What is your goal for therapy?

 Maintenance
 Rehydration
 Volume resuscitation
2: Any baseline electrolyte abnormalities?
 Look at basic chemistry prior to ordering
fluids.
3: Where is the fluid going to go?
 Which Fluid to Choose?
 Hypovolemia: primary goal is volume expansion.
 Use the fluid that will put the most volume into the
intravascular space.
 Dehydration (= hyperosmolality): primary goal is
free water replacement.
 Use a hypotonic fluid usually 0.45% saline or D5W.
 Post-operative patients  pain can be powerful
stimulants of inappropriate ADH secretion
(SIADH).
 Giving hypotonic fluids can cause dangerous
hyponatremia.
 Advantages and Disadvantages
of Colloids and Crystalloids
Colloids
Advantages Disadvantages
1. Plasma volume expansion without 1. Anaphylaxis
concomitant ISF expansion
2. Greater intravascular volume expansion for 2. Expensive
a given volume
3. Longer duration of action 3. Albumin can aggravate myocardial
depression in shock patient, owing to albumin
4. Better tissue oxygenation binding to Ca++, which in turn decreases ionic
calcium
5. Less alveolar-arterial O2 gradient 4. Possible coagulopathy, impaired cross
matching
Crystalloids
1. Easily available 1. Weaker and shorter volume effect compared
to colloid
2. Composition resembling plasma (acetated 2. Decreased tissue oxygenation, owing to
ringer, lactated ringer) increased distance between microcirculation
3. Easy storage at room temperature and tissue
4. Free of anaphylactic reaction
5. Economical
Parenteral fluid and nutrition therapy, 2012
Pengaruh cairan koloid dan kristaloid terhadap volume kompartemen
cairan ekstraseluler
 Specific Considerations apply
to different categories of patients
 Bleeding pts required control of hemorrhage and transfusion
with RBCs and blood components as indicated
 Isotonic, balanced salt solutions are pragmatic initial
resuscitation fluid for the majority of acutely ill pts
 Consider saline in pts with hypovolemia and alkalosis
 Consider albumin during the early resuscitation of pts with
severe sepsis
 Saline or isotonic crystalloids are indicated in pts with
traumatic brain injury
 Albumin is not indicated in pts with traumatic brain injury
 HES is not indicated in pts with sepsis, risk for AKI
The right amount
of the right fluid
at the right time