The objective of this article is to discuss the pharmacology, side effects, and clinical application of vasoactive therapy in the management of adult septic shock.
Summary
Sepsis is one of the most common reasons for admission to an intensive care unit with the incidence estimated to be greater than 750 000 cases per year in the United States. Clinicians should understand the basic pharmacology of available vasoactive agents to allow for routine and complex management of septic shock.
Conclusion
While advances in research, identification, and early implementation of best practices for the treatment of sepsis has reduced mortality, rates remain high. Vasopressors and inotropes remain part of the core therapeutic modalities of sepsis management. Norepinephrine is the first-line vasopressor of choice for septic shock, though secondary vasopressors can be used depending on the patient’s circumstances.
LaguTRothbergMBShiehMS, et al.Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40(3):754–761.
2.
NguyenHBRiversEPAbrahamianFM, et al.Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006;48(1):28–54.
3.
SchorrC. Performance improvement in the management of sepsis. Crit Care Clin. 2009;25(4):857–867, x.
4.
AngusDCvan der PollT. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):2063.
5.
DellingerRPLevyMMRhodesA, et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.
6.
DellingerRPLevyMMCarletJM, et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(2):296–327.
7.
RhodesAEvansLEAlhazzaniW, et al.Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–377.
8.
VincentJLMartinezEOSilvaE. Evolving concepts in sepsis definitions. Crit Care Clin. 2009;25(4):665–675, vii.
9.
LevyMMFinkMPMarshallJC, et al.2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2003;31(4):1250–1256.
10.
SingerMDeutschmanCSSeymourCW, et al.The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810.
11.
BrownSMLanspaMJJonesJP, et al.Survival after shock requiring high-dose vasopressor therapy. Chest. 2013;143(3):664–671.
12.
SchmittingerCATorgersenCLucknerG, et al.Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med. 2012;38(6):950–958.
13.
HotchkissRSKarlIE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138–150.
14.
LandryDWOliverJA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001;345(8):588–595.
15.
VincentJLInceCBakkerJ. Clinical review: circulatory shock—an update: a tribute to professor Max Harry Weil. Crit Care. 2012;16(6):239.
16.
LevyBCollinSSennounN, et al.Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. 2010;36(12):2019–2029.
17.
LevyMMDellingerRPTownsendSR, et al.The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010;38(2):367–374.
18.
DellingerRPLevyMMRhodesA, et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.
19.
PinskyMR. Hemodynamic evaluation and monitoring in the ICU. Chest. 2007;132(6):2020–2029.
20.
BangashMNKongMLPearseRM. Use of inotropes and vasopressor agents in critically ill patients. Br J Pharmacol. 2012;165(7):2015–2033.
21.
HollenbergSM. Vasoactive drugs in circulatory shock. Am J Respir Crit Care Med. 2011;183(7):847–855.
22.
OvergaardCBDzavikV. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047–1056.
23.
CooperBE. Review and update on inotropes and vasopressors. AACN Adv Crit Care. 2008;19(1):5–13; quiz 4-5.
24.
HollenbergSM. Vasopressor support in septic shock. Chest. 2007;132(5):1678–1687.
25.
WilliamsonAPSeifenELindemannJP, et al.WB4101- and CEC-sensitive positive inotropic actions of phenylephrine in rat cardiac muscle. Am J Physiol. 1994;266(6 pt 2):H2462–H2467.
26.
MissaleCNashSRRobinsonSW, et al.Dopamine receptors: from structure to function. Physiol Rev. 1998;78(1):189–225.
27.
WeilMHHouleDBBrownEBJr, et al.Vasopressor agents; influence of acidosis on cardiac and vascular responsiveness. Calif Med. 1958;88(6):437–440.
28.
AsfarPTeboulJLRadermacherP. High versus low blood-pressure target in septic shock. N Engl J Med. 2014;371(3):283–284.
LevyB.Bench-to-bedside review: is there a place for epinephrine in septic shock?Crit Care. 2005;9(6):561–565.
31.
LamontagneFMeadeMOHebertPC, et al.Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med. 2016;42(4):542–550.
32.
Cardenas-GarciaJSchaubKFBelchikovYG, et al.Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med. 2015;10(9):581–585.
33.
De BackerDBistonPDevriendtJ, et al.Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779–789.
34.
BeloeilHMazoitJXBenhamouD, et al.Norepinephrine kinetics and dynamics in septic shock and trauma patients. Br J Anaesth. 2005;95(6):782–788.
35.
EisenhoferGFinbergJP. Different metabolism of norepinephrine and epinephrine by catechol-O-methyltransferase and monoamine oxidase in rats. J Pharmacol Exp Ther. 1994;268(3):1242–1251.
36.
RadosevichJJPatanwalaAEErstadBL. Norepinephrine dosing in obese and nonobese patients with septic shock. Am J Crit Care. 2016;25(1):27–32.
37.
MartinCViviandXLeoneM, et al.Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28(8):2758–2765.
38.
HamzaouiOGeorgerJFMonnetX, et al.Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Crit Care. 2010;14(4):R142.
39.
MonnetXJabotJMaizelJ, et al.Norepinephrine increases cardiac preload and reduces preload dependency assessed by passive leg raising in septic shock patients. Crit Care Med. 2011;39(4):689–694.
40.
LoebHSWinslowEBRahimtoolaSH, et al.Acute hemodynamic effects of dopamine in patients with shock. Circulation. 1971;44(2):163–173.
41.
SakrYReinhartKVincentJL, et al.Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) study. Crit Care Med. 2006;34(3):589–597.
42.
AgrawalAGuptaAConsulS, et al.Comparative study of dopamine and norepinephrine in the management of septic shock. Saudi J Anaesth. 2011;5(2):162–166.
43.
De BackerDAldecoaCNjimiH, et al.Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012;40(3):725–730.
44.
DunserMWRuokonenEPettilaV, et al.Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care. 2009;13(6):R181.
45.
De BackerDCreteurJSilvaE, et al.Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best?Crit Care Med. 2003;31(6):1659–1667.
46.
AnnaneDVignonPRenaultA, et al.Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007;370(9588):676–684.
47.
BealeRJHollenbergSMVincentJL, et al.Vasopressor and inotropic support in septic shock: an evidence-based review. Crit Care Med. 2004;32(suppl 11):S455–S465.
48.
PatelBMChittockDRRussellJA, et al.Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology. 2002;96(3):576–582.
49.
BauerSRAloiJJAhrensCL, et al.Discontinuation of vasopressin before norepinephrine increases the incidence of hypotension in patients recovering from septic shock: a retrospective cohort study. J Crit Care. 2010;25(2):362 e7- e11.
50.
RussellJAWalleyKRSingerJ, et al.Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877–887.
51.
GordonACMasonAJThirunavukkarasuN, et al.Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA. 2016;316(5):509–518.
52.
HolmesCLWalleyKRChittockDR, et al.The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med. 2001;27(8):1416–1421.
53.
LeoneMAlbaneseJDelmasA, et al.Terlipressin in catecholamine-resistant septic shock patients. Shock. 2004;22(4):314–319.
54.
MorelliARoccoMContiG, et al.Effects of terlipressin on systemic and regional haemodynamics in catecholamine-treated hyperkinetic septic shock. Intensive Care Med. 2004;30(4):597–604.
55.
SingerM. Arginine vasopressin vs. terlipressin in the treatment of shock states. Best Pract Res Clin Anaesthesiol. 2008;22(2):359–368.
56.
GregoryJSBonfiglioMFDastaJF, et al.Experience with phenylephrine as a component of the pharmacologic support of septic shock. Critical Care Med. 1991;19(11):1395–1400.
57.
MorelliALangeMErtmerC, et al.Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock. 2008;29(4):446–451.
58.
VailEGershengornHBHuaM, et al.Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA. 2017;317(14):1433–1442.
59.
EnricoCKanoore EdulVSVazquezAR, et al.Systemic and microcirculatory effects of dobutamine in patients with septic shock. J Crit Care. 2012;27(6):630–638.
60.
PaciulloCAMcMahon HornerDHattonKW, et al.Methylene blue for the treatment of septic shock. Pharmacotherapy. 2010;30(7):702–715.
61.
KwokESHowesD. Use of methylene blue in sepsis: a systematic review. J Intensive Care Med. 2006;21(6):359–363.
62.
KirovMYEvgenovOVEvgenovNV, et al.Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med. 2001;29(10):1860–1867.
63.
RamsayRRDunfordCGillmanPK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol. 2007;152(6):946–951.
64.
ChawlaLSBusseLBrasha-MitchellE, et al.Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014;18(5):534.
65.
KhannaAEnglishSWWangXS, et al.Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419–430.
66.
SenchenkovaEYRussellJEsmonCT, et al.Roles of coagulation and fibrinolysis in angiotensin II-enhanced microvascular thrombosis. Microcirculation. 2014;21(5):401–407.
