Vasopressor in Septic Shock, Semarang 0ct 2011

Vasoactive agent in septic shock patients dr samsirun halim SpPD KIC

PIT PAPDI Semarang 8 October 2011

outline discussion !   introduction ! ! ! ! !

  definition septic shock   hemodynamic change during septic shock   type, indication and target vasopressor   guideline and evidence   conclusion

!   conclusion

introduction !  

Septic shock is a medical emergency that is associate with mortality rate of 40-70%

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Prompt recognition and institution of effective therapy is required for optimal outcome

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when the shock state persists after adequate fluid resuscitation , vasopresssor therapy is required to improve and maintain adequate tissue/organ perfusion in attempt to improve survival and prevent the development of mod and mof

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With vasopressor is the best choice in septic shock is debatable.

definition septic shock !   ACCP/SCCM consensus confererence comitte 1992 !   ........ sepsis-induced hypotension ( SBP < 90 mmHg or a

reduction of ≥40 mmHg from baseline ) despite adequate fluid resuscitation along with the presence of perfusion abnormalities that 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

Hemodynamic change in septis chock

Dellinger RP, Crit Care Med 2003;31;946-55

A. normal

B. pre fluid resuscitation

hemodynamic change during septic shock

Dellinger RP, Crit Care Med 2003;31;946-55

B. prefluid resuscitation

C. post fluid resuscitation

Septic shock .. A melting pot of shock etiologies

Dellinger RP, Crit Care Med 2003;31;946-55

mechanism action of catecolamin and effect of stimulating receptor

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  vasopressor = raise BP   inotropic = raise cardiac output   α adrenergic = promoting vasoconstrition   β1= increasing HR and myocardial contractility   β2 = peripher vasodilatation   δ= vasodilation mesenteric dan renal Overgaard CB, Circulation 2008;118;1047-56

effects of vasoactive catecholamine

Hollenberg SM, Crit Care Clin 2009;25;781-802

dopamine !  

recommended as the initial drug of choice by many clinicians it increases both myocardial contractility and SVR via α and β receptors

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May help maintain splanchnic circulation , urine output and renal function via dopa receptor action

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1-3 mcg/kg/min dopa receptor 3-10 mcg/kg/min β receptor >10 mcg/kg/min α receptor

increases HR, can cause tachyarrytmias may also increase pcwp via pulmonary artery vasoconstriction

Hollenberg SM, Crit Care Clin 2009;25;781-802

norepinephrine !   potent α adrenergic agonist, less β agonist effect !   MAP ↑ by vasoconstrition, CO and SV ↑10-15% !   > potent than dopamine and > effective reversing hypotension

Hollenberg SM, Crit Care Clin 2009;25;781-802

Phenylephrine !   selective α1-adrenergic agonist !   BP↑ by vasoconstriction !   rapid onset, short duration, primary vascular effect --> actractive agent in management septic shock

!   concern reduce CO Hollenberg SM, Crit Care Clin 2009;25;781-802

epinefrine ! ! ! ! !

  potent α-adrenergic and β 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

vasopressin !   peptide hormon, synthesized hypothalamus, store in the pituitary gland

!   released 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

Type, indication, doses, mechanism of action, major side effect of catecolamine

Overgaard CB, Circulation 2008;118;1047-56

Type, indication, doses, mechanism of action, major side effect of catecolamine

Overgaard CB, Circulation 2008;118;1047-56

Perfusion Goals in Patients with Septic Shock ! 

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Hemodynamics !   PCWP 10-20 mmHg

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MAP >60 mmHg CI > 3 L/min/m2

Organ perfusion

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CNS - improved sensorium Skin - warm, well perfused Renal - UOP > 1cc/kg/hr

O2 delivery adequacy

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SpO2 > 95% Hgb >10 gm/dl

- Lactate < 2 mM/L

Effects of perfusion pressure on tissue perfusion in septic shock

LeDoux, Astiz ME, et all Crit Care Med 2000;28;2729-32

guideline and evidence

NE or dopamine for the treatment of hyperdynamic septic shock Martin C, Papazian L, Perrin G. Chest 1993,103:1826-31

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32 patients hyperdynamic septic shock following fluid administration

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Dopa achieved goal only 5/16 ( 31%) vs 15/16 (93%) NE

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

10 of 11 not respond DOPA respond to NE no deleterious effect of NE on urine output , but study only 6 houres

Comparison of Dopamine and NE in the treatment of Shock de Becker D, Biston P, Devriendt J, NEJM 2010;362:779-789

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RCT 1679 pts: Dopa 858, NE 821

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RESULTS :

Dopa -20ug/kg/’, NE - 0,19ug/kg/’ + Epinefrin/vasopresin outcome 1st : 28 d mortality, 2nd : number days w.o organ support and occurence adverse events

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NO difference in mortality DOPA 52,5% vs NE 48,5% DOPA more arytmogenic 24,1% vs 12,4%

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

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  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 with increases mortality rates in shock

NE plus Dobutamine vs epinephrine alone for management of septic shock : a randomised trial Annane D,et all Lancet 2007. 370 ; 676-84

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RCT multicentre 330 pts Epi 161 vs NE + dobu 169 ---> MAP 70 mmHG 1st outcome 28 days mortality RESULT

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mortality E (40%) vs NE + dobu (34%) p=0,31 there is no evidence in efficacy and safety between epinephrine alone and NE plus dobutamine for the management of septic shock

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 was found

Effects of dopamine, NE and Epinephrine on the Splanchnic 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 Med 2003; 31:1659-1667!

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 had no significant effect on HR, mAP,CI,SVR,DO2 and VO2 but improved gastric mucosal perfusion based on gastric intramucosal pCO2 and pH measurement

phenylephrine !   Reinelt et al. Crit Care Med 1999,27 : 325-331 !   reported reduced splanchnic blood flow and oxygen delivery in six septic shock patients treated with phenylephrine compared with NE

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 Med 2003; 31:1752-1758!

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 to offer any benefit over norepinephrin

!   the routine administration of vasopressin alone as a

vasopressor agent in septic shock requires more clinical research trial.

Vasopressin vs NE infusion in patients with septic shock Russel 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% vs 35,7 % p .05

!   low doses vasopressin does not reduce mortality rates

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 has more arrytmogenic

!   Epinefrine and vasopressin is the second choice because reduced the splancnic perfusion

thank you