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7/27/2019 Vasopressor in Septic Shock, Semarang 0ct 2011
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Vasoactive agent inseptic shock patients
dr samsirun halim SpPD KIC
PIT PAPDI Semarang 8 October 2011
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outline discussionintroduction definition septic shock hemodynamic change during septic shock type, indication and target vasopressor
guideline and evidence
conclusion
conclusion
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introduction
Septic shock is a medical emergency that is associate with mortality rate of40-70%
Prompt recognition and institution of effective therapy is required for optimaloutcome when the shock state persists after adequate fluid resuscitation , vasopresssortherapy is required to improve and maintain adequate tissue/organ perfusion
in attempt to improve survival and prevent the development of mod and mof With vasopressor is the best choice in septic shock is debatable.
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definition septic shock
ACCP/SCCM consensus confererence comitte 1992........ sepsis-induced hypotension( SBP < 90 mmHg or areduction of "40 mmHg from baseline ) despite adequatefluid resuscitationalong with the presence of perfusionabnormalitiesthat may include but are not limited to lactic
acidosis, oliguria, or an acute alteration in mental status
Dellinger RP, Crit Care Med 2003;31;946-55
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Hemodynamic change in septis chock
A. normal
B. pre fluid resuscitation
Dellinger RP, Crit Care Med 2003;31;946-55
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hemodynamic change during septic shock
B. prefluid resuscitation
C. post fluid resuscitation
Dellinger RP, Crit Care Med 2003;31;946-55
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Septic shock .. A melting pot of shock etiologiesDellinger RP, Crit Care Med 2003;31;946-55
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mechanism action of catecolamin andeffect of stimulating receptor
vasopressor = raise BP
inotropic = raise cardiac output
!adrenergic = promoting vasoconstrition
"1= increasing HR and myocardial contractility
"2 = peripher vasodilatation
#= vasodilation mesenteric dan renalOvergaard CB, Circulation 2008;118;1047-56
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effects of vasoactive catecholamine Hollenberg SM, Crit Care Clin 2009;25;781-802
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dopamine recommended as the initial drug of choice by many clinicians it increases bothmyocardial contractility and SVR via !and "receptors May help maintain splanchnic circulation , urine output and renal function via
dopa receptor action
1-3 mcg/kg/min dopa receptor3-10 mcg/kg/min "receptor >10 mcg/kg/min!receptor
increases HR, can cause tachyarrytmias may also increase pcwp via pulmonary artery vasoconstriction Hollenberg SM, Crit Care Clin 2009;25;781-802
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norepinephrine
potent!adrenergic agonist, less "agonist effect
MAP $by vasoconstrition, CO and SV $10-15% > potent than dopamine and > effective reversinghypotension
Hollenberg SM, Crit Care Clin 2009;25;781-802
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Phenylephrine
selective!1-adrenergic agonistBP$by vasoconstriction
rapid onset, short duration, primary vascular effect -->actractive agent in management septic shock
concern reduce COHollenberg SM, Crit Care Clin 2009;25;781-802
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epinefrine
potent!-adrenergic and "adrenergic
MAP$by $CO and $SVR $DO2 but $O2 consumption $lactacte level%regional blood flow --> splanchnic perfusion
Hollenberg SM, Crit Care Clin 2009;25;781-802
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vasopressin peptide hormon, synthesized hypothalamus, store in the
pituitary glandreleased response to %blood volume, intravasculer volume,$plasma osmolality
constrict VSM directly via V1 receptor
$response of vasculature to cathecolamin
inhibit NO production by VSM
Hollenberg SM, Crit Care Clin 2009;25;781-802
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Type, indication, doses, mechanism of action, major side effect ofcatecolamine
Overgaard CB, Circulation 2008;118;1047-56
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Type, indication, doses, mechanism of action, major side effect ofcatecolamine
Overgaard CB, Circulation 2008;118;1047-56
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Perfusion Goals in Patients with Septic Shock
HemodynamicsPCWP 10-20 mmHg MAP >60 mmHg CI > 3 L/min/m2
Organ perfusion
CNS - improved sensorium Skin - warm, well perfused Renal - UOP > 1cc/kg/hr O2 delivery adequacy
SpO2 > 95% - Lactate < 2 mM/L
Hgb >10 gm/dl
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Effects of perfusion pressure on tissue perfusion in septic shock
LeDoux, Astiz ME, et all Crit Care Med 2000;28;2729-32
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guideline and evidence
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NE or dopamine for the treatment of hyperdynamic septic shock Martin C, Papazian L, Perrin G. Chest 1993,103:1826-31
32 patients hyperdynamic septic shock following fluid administration
Patients received either Dopa ( 2,5-25 mcg/kg/mint) or NE (0,5-5mcg/kg/
mnt) with the goals of SVRI > 1100 dyne/m2, MAP >80mmHg, CI >4 L/min/m2, DO2 >550 ml/min/m2 dab VO2 >150mL/min/m2
Dopa achieved goal only 5/16 ( 31%) vs 15/16 (93%) NE
10 of 11 not respond DOPA respond to NE
no deleterious effect of NE on urine output , but study only 6 houres
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Comparison of Dopamine and NE in the treatment of Shockde Becker D, Biston P, Devriendt J, NEJM 2010;362:779-789
RCT 1679 pts: Dopa 858, NE 821
Dopa -20ug/kg/, NE - 0,19ug/kg/ + Epinefrin/vasopresin
outcome 1st : 28 d mortality, 2nd : number days w.o organ support andoccurence adverse events RESULTS :
NO difference in mortality DOPA 52,5% vs NE 48,5% DOPA more arytmogenic 24,1% vs 12,4%
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Does dopamine administration in shock influence outcome ?Results of Sepsis Occurrence in Acutely Ill Patients (SOAP) Study Sakr Y, Fleinhart K, Vincent JL. Crit Care Med 2006,34, 589-597
cohort, multicenter, observtional study, 3147 pts 33,6% shock----> 14,7% septic shock dopa 35,4%, non dopa 64,6%
mortality dopa in ICU 42,9%vs35% p.02
mortality hospital 48,9% vs 41,7% p=0.1
suggest dopamine administration maybe associated withincreases mortality rates in shock
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NE plus Dobutamine vs epinephrine alone for management of septicshock : a randomised trial Annane D,et all Lancet 2007. 370 ; 676-84
RCT multicentre 330 pts Epi 161 vs NE + dobu 169 ---> MAP 70 mmHG 1st outcome 28 days mortality
RESULT
mortality E (40%) vs NE + dobu (34%) p=0,31
there is no evidence in efficacy and safety between epinephrine aloneand NE plus dobutamine for the management of septic shock
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Low dose dopamine in patients with early renal dysfunction.A placebo -controlled randomised trial (ANZICS)Bellomo R, Chapman M et al. Lancet 2000;356:2139-43
328 pts randomised placebo - low dose dopamin ( 2ug/kg/)
No protective effect on renal function or other outcome wasfound
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Effects of dopamine, NE and Epinephrine on theSplanchnic Circulation in Septic Shock
Figure 2, page 1665, reproduced with permission from De Backer D, Creteur J, Silva E,
Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic
circulation in septic shock: Which is best? Crit Care Med2003; 31:1659-1667
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Epinephrine
Levy et al.Crit Care Med 1997;25 :1649-53 found that the addition of dobutamine 5 mcg/kg/min to epinephrine infusion in 20 septic patients hadno significant effect on HR, mAP,CI,SVR,DO2 and VO2but improved gastric mucosal perfusion based ongastric intramucosal pCO2 and pH measurement
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phenylephrine
Reinelt et al. Crit Care Med 1999,27 : 325-331
reported reduced splanchnic blood flow and oxygendelivery in six septic shock patients treated withphenylephrine compared with NE
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Circulating vasopressin levels during septic shock
Figure 2, page 1755 reproduced with permission from Sharshar T,
Blanchard A, Paillard M, et al. Circulating vasopressin levels in septic
shock. Crit Care Med2003; 31:1752-1758
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Vasopressin compared to NE in septic shock : Is Vasopressin more effective ?Macias L, Varon J, Fromm RE,Crit Care & Shock 2004:7:39-41
vasopressin at a dose sufficient to substitute for
norepinephrin in the treatment of septic shock not appear tooffer any benefit over norepinephrin
the routine administration of vasopressin alone as avasopressor agent in septic shock requires more clinicalresearch trial.
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Vasopressin vs NE infusion in patients with septic shockRussel JA, Walley KR, et al. NEJM 2008;358:877-87
RCT 778 pts, Vasopresin (0.01-0.03 U/min) vs NE 5-15mcg/min )
no differences in adverse events or survival rates
less severe septic shock ( NE < 15mcg/) mortallity 26.5% vs35,7 % p .05
low doses vasopressin does not reduce mortality rates
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Conclusion
Mortality in septic shock still high Vasopressor is used to increase BP to improve perfusion
prevent the mod and mof Dopamine and NE is the first choice although dopamine hasmore arrytmogenic
Epinefrine and vasopressin is the second choice becausereduced the splancnic perfusion
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thank you
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