Vasoactive agent in ! septic shock patients!

dr samsirun halim SpPD KIC!

PIT PAPDI Semarang 8 October 2011!

outline discussion ! ! " introduction !

! ! ! ! ! " denition 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%! Prompt recognition and institution of effective therapy is required for optimal outcome! when the shock state persists after adequate uid 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! With vasopressor is the best choice in septic shock is debatable.!

denition septic shock!

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

reduction of "40 mmHg from baseline ) despite adequate uid 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 uid resuscitation!

hemodynamic change during septic shock!

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

B. preuid resuscitation!

C. post uid 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!

! ! ! ! ! !

" vasopressor = raise BP! " inotropic = raise cardiac output! " ! adrenergic = promoting vasoconstrition! " "1= increasing HR and myocardial contractility! " "2 = peripher vasodilatation! " #= 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 ! and " receptors! May help maintain splanchnic circulation , urine output and renal function via dopa receptor action!

!" !" !" ! " ! "

1-3 mcg/kg/min dopa receptor! 3-10 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!

norepinephrine!
! " potent ! adrenergic agonist, less " 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 !1-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 !-adrenergic and " adrenergic ! " MAP$ by $CO and $SVR! " $DO2 but $O2 consumption! " $lactacte level ! " %regional blood ow --> 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!

!"
Hemodynamics! ! " PCWP 10-20 mmHg!

!"

!" !" !" !" !" !" !"

MAP >60 mmHg! CI > 3 L/min/m2! CNS - improved sensorium! Skin - warm, well perfused! Renal - UOP > 1cc/kg/hr! SpO2 > 95% Hgb >10 gm/dl! - Lactate < 2 mM/L!

Organ perfusion!

!"

O2 delivery adequacy!

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!

! " ! " ! " ! " ! "

32 patients hyperdynamic septic shock following uid 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!

Comparison of Dopamine and NE in the treatment of Shock! de 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 and occurence adverse events! RESULTS :!

!" !"

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

Does dopamine administration in shock inuence 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 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!

! ! ! !

" " " "

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 efcacy 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 signicant 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 ow 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 sufcient to substitute for

norepinephrin in the treatment of septic shock not appear to offer any benet over norepinephrin! vasopressor agent in septic shock requires more clinical research trial.!

! " the routine administration of vasopressin alone as a

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! more arrytmogenic!

! " Dopamine and NE is the rst choice although dopamine has ! " Epinefrine and vasopressin is the second choice because
reduced the splancnic perfusion!

thank you!