Sepsis

• 2 or more sirs with infection (+)

• Infection + SIRS with 1 or more criteria : (2002)
– Edema (+) or fluid balance (+) (> 20 mL/kg in 24 hrs);
– Hyperglycemia (fasting glucose > 120 mg/dL) on non-
diabetes patient
– Inflamatory variable: plasma C-reactive protein > 2 SD
above normal or
– procalcitonin plasma > 2 SD above normal;
– Mixed venous oxygen saturation (SVO2) > 70%; and
– Cardiac index > 3.5
• Gfgfgsrgrt
 Severe Sepsis

• Sepsis within organ dysfunction, tissue

hypoperfusion, and hypotension

Septic Shock
• Sepsis with acute circulation failure
– Persistent arterial hypotension (SBP < 90 mm
Hg),
– MAP < 60 mmHg, or
– SBP decrease > 40 mm Hg from baseline
• Even fluid resuscitation adequate.
• uiiudtutyut
N.E.J.M, vol 347:966-967, Sept 26,2002, No. 13
The Role of Vasopressor in Septic
shock
 Vasopressor Agent

• Vasopressor agents sering kali digunakan pada

pasien dengan syok septik dimana pemberian cairan
(fluid resuscitation) tidak dapat memperbaiki
hipotensi.
Ref.: Shama VK, et al. The International Sepsis Forum’s controvercies in sepsis: my initial
vasopressor agents in septic shock is norepinephrine rather than dopamine.

• Vasopressor agent
 memulihkan dengan cepat perfusi jaringan
dengan meningkatkan MAP (mean arterial pressure)
menjadi 65-75 mm Hg
Ref. Guntur H. The Role of Norepinephrine in Septic Shock Patients, Dexa Media, No.1,
Vol.21, Jan-Mar 2008
Vasopressor Agent

• Early Goal-Directed Therapy (EGDT):

Emanuel Rivers, et.al, N Engl J Med, Vol 345, No. 19. Nov 2001
RESULT :
– Of the 263 enrolled patients in Hospital, Mortality
was 30.5% in the group assigned to EGDT vs
45,5% in the group assigned to standard therapy
(P=0.009)
– Less severe organ disfuction : 13.0±6.3 (EGDT) vs
15.9 ±6.4 (standart therapy)
 EARLY GOAL DIRECTED THERAPY IN SEVERE SEPSIS AND
SEPTIC SHOCK Revisited
Ronny M.Otero, et.al, Chest 2006,130,1579 - 1595

CVP :Central Venous Pressure

Suspected Infection MAP : Mean Arterial Pressure
ScvO2 : Central Venous Oxygen Saturation

The High Risk Patient :

SBP < 90 mmHg after 20 – 40 cc/kg Volume challenge
Or Lactic acid > 4 mmol/liter

Antibiotics within 1 hour and source control

<8 mmHg
CVP Crystalloid

Decreased 8-12 mmHg

Oxygen
Consumption <65 mmHg Vasoactive Agents
MAP
>90 mmHg
≥65- ≤ 90 mmHg

<70% Transfusion of red cells Until hematocrit 30%

ScvO2
<70%
Inotropic Agents
≥70%

Goal Achieved
Vasopressor Agent

CARA KERJA Vasopressor Agents

Merangsang reseptor ,  adrenergic, Dopaminergic

 Arteriole Vasokontriksi
perifer

 1 Miocard Kontraksi jantung meningkat

SA-Node Kecepatan pacu jantung meningkat
AV-Node Konduksi meningkat

2 Arteriole Vasodilatasi
Bronchus Bronchodilatasi

Dopaminergis Dilatasi arteri ginjal

& mesenterium
 Norepinephrine or Dopamine
for treatment of septic shock?
 Norepinephrine or Dopamine?
Reinhart K, Jena. Vasopressor Agents. Programme Abstrak book:25. An International
Symposium Sepsis 2007. Institute Pasteur, Paris, France, 2007
Aktivitas vasopressor
pada reseptor

Efek Hemodinamika

Rating menunjukkan derajat efek dari penurunan ringan (-) sampai peningkatan mencolok (2+)
CO: Cardiac output; MAP: Mean Arterial Pressure; SVR: Systemic Vascular Resistance

NE adalah  adrenergik agonis yang poten dan juga memiliki efek 1

adrenergik agonis  meningkatkan MAP dan SVR lebih baik vs Dopamine
 Efek Hemodinamik Norepinephrine
vs Dopamine
Martin C., et al. Norepinephrine or Dopamine for hyperdinamic septic
shock, Chest 1993 Jun:103(6):1826-31

• NE meningkatkan MAP & SVRI lebih baik vs Dopamine

• Dopamine 25 mcg/kg/min meningkatkan Heart Rate , NE tidak meningkatkan
heart rate
n = 32 pasien, NE 1.5±1.2 mcg/kg/mnt (n=16); Dopamine 2,5-25 mcg/kg/mnt (n=16) + NE 5mcg/kg/mnt
 Norepinephrine lebih efektif vs dopamine
pada hyperdinamic septic shock
Martin C., et al. Norepinephrine or Dopamine for hyperdinamic septic
shock, Chest 1993 Jun:103(6):1826-31

100 Parameter Keberhasilan:

(P<0.001) - Systemic vascular resistance index > 1,100
dynes/cm5.m2 and/ or mean systemic
% Keberhasilan terapi

80
93% blood pressure ≥ 80 mmHg
60 - Cardiac index ≥ 4 L/min/m2
31% - Oxygen delivery > 550 ml/min/m2
40 - Oxygen uptake > 150 ml/min/m2
20 Norepinephrine (dosis 1.5±1.2 mcg/kg/mnt)

0 Dopamine (dosis 10-25 mcg/kg/mnt)

5/16 31 15/16 93

Tingkat keberhasilan terapi dengan Norepinephrine lebih baik

(93%) vs Dopamine (31%) dalam mengatasi septic shock
 Hospital mortality: Norepinephrine vs
Dopamine
Claude Martin, et al. Effect of norepinephrine on the
outcome of septic shock. Critical Care Med 2000 Vol.
28(8): 2558-2765

90%
80%
70%
60%

mortality
50%
40%
30%
20%
10%
0%
Hospital
Day 7 Day 28
Discharge
NE 28% 55% 62%
Dopamine 40% 82% 84%

Norepinephrine has significantly

NE : 0.5-5(p<.001) lower
mcg/kg/mnt (n=57)

hospital mortality than high dose Dopamine

Dopamine : 16-25 mcg/kg/mnt (n=40
 NE has beneficial effects on renal function

Claude Martin, et al. Renal Effects on NE used to treat septic

syock patients. Critical Care Medicine 1990, 18:282-285

In 24 patients , re-establishment of urine flow, decrease in serum creatinine and

increase in creatinine clearance  NE does not worsen Renal ischemia in septic
shock patients and even suggest to optimize effectively renal blood flow and renal
vascular resistance
 Renal function: Norepinephrine or Dopamine?

Use of dopamine in acute renal failure: A meta-analysis.

Clinical Investigations

Critical Care Medicine. 29(8):1526-1531, August 2001.

Kellum, John A. MD; M. Decker, Janine RN
Abstract:
Objective: To determine whether low-dose dopamine administration reduces the incidence or
severity of acute renal failure, need for dialysis, or mortality in patients with critical illness.
Data Sources and Study Selection : We performed a MEDLINE search of literature published
from 1966 to 2000 for studies addressing the use of dopamine in the prevention and/or
treatment of renal dysfunction.
Data Extraction : Data were abstracted regarding design characteristics, population,
intervention, and outcomes. Results of individual randomized clinical trials were pooled using
a fixed effects model and a Mantel-Haenszel weighted chi-square analysis.
Data Synthesis: We identified a total of 58 studies (n = 2149). Of these, outcome data were
reported in 24 studies (n = 1019) and 17 of these were randomized clinical trials (n = 854).
Dopamine did not prevent mortality, (relative risk, 0.90 [0.44-1.83];p = .92), onset of acute
renal failure (relative risk, 0.81 [0.55-1.19];p = .34), or need for dialysis, (relative risk, 0.83
[0.55-1.24];p = .42). There was sufficient statistical power to exclude any large (>50%) effect
of dopamine on the risk of acute renal failure or need for dialysis.
Conclusions: The use of low-dose dopamine for the treatment or prevention of acute
renal failure cannot be justified on the basis of available evidence and should be
eliminated from routine clinical use.
 Does Low dose Dopamin decreased the risk
of renal failure in at risk patient in ICU ?

Infusion of low dose dopamine did not reduce renal failure at risk
patients in the intensive care unit
Bellomo R, Chapman M, Finfer S, et al. Low­dose dopamine in patients with early renal
dysfunction:a placebo­controlled randomised trial. Australian and New Zealand Intensive
Care Society (ANZICS) Clinical Trial Group. Lancet 2000 Dec 23/30;356:2139–43.

Main Result
Dopamine Placebo

Peak Serum Creatinin 245 µmol/l 249 µmol/l

Urine Output after 1 hour 71 ml/h 72 ml/h
Urine Output after 24 hour 96 ml/h 92 ml/h
Urine Output after 48 hour 99 ml/h 109 ml/h
Need for renal replacement therapy 35 patients 40 patients

Conclusion
Infusion of low dose dopamine did not reduce the risk of renal failure in at
risk intensive care unit patients
Renal function:
Norepinephrine or Dopamine?
 Norepinephrine (RAIVAS) or Dopamine?

Bridges EJ, et al. Cardiocascular Aspects of Septic Syock. Critical Care Nurses
2005 Apr;25(2): 14-40

NOREPINEPHRINE :
• Meningkatkan MAP dan SVR (systemic Vascular Resistance)

DOPAMINE :
• Efek dopamine tergantung dari dosis yang diberikan.
• Dopamine dosis rendah (1-4 mcg/kg/min) TIDAK TERBUKTI dan TIDAK
DIREKOMENDASIKAN untuk proteksi ginjal
– Marik PE. Low Dose Dopamine: a systemic review. Intensive Care Med, 2002: 28:877-883
– Kellum J, Decker J. Use of dopamine in acute renal failure: a meta analysis. Critical Care Med 2003: 31:1526-1531)

• Dopamine 20 mcg/kg/min :  Tekanan Artrium Kanan , Heart Rate dan Takikardi

 Indikasi Raivas (1)

• Mengontrol tekanan darah pada keadaan

hipotensi akut, misalnya pada keadaan:

~ infark miokard
~ septikemia
~ reaksi transfusi
~ reaksi obat
 Indikasi Raivas (2)

• Mengontrol tekanan darah pada keadaan

hipotensi akut, misalnya pada keadaan:

~ pasca feokromositomektomi
~ pasca simpatektomi
~ poliomielitis
~ anestesi spinal
Indikasi Raivas (3)

• Sebagai terapi tambahan pada henti jantung

dan hipotensi berat.

• Untuk memperbaiki dan mempertahankan

tekanan darah yang adekuat setelah denyut
jantung dan ventilasi jantung efektif telah
dicapai dengan cara lain.