Vasopressors and inotropes are used in septic shock in patients who remain hypotensive despite adequate fluid resuscitation. The goal is to increase blood pressure to optimize perfusion to organs. Generally, goal-directed therapy to supra-normal oxygen transport variables cannot be recommended due to lack of benefit. Traditionally, vasopressors and inotropes in septic shock have been started in a step-wise fashion starting with dopamine. Recent data suggest that there may be true differences among vasopressors and inotropes on local tissue perfusion as measured by regional hemodynamic and oxygen transport. When started early in septic shock, norepinephrine decreases mortality, optimizes hemodynamic variables, and improves systemic and regional (eg, renal, gastric mucosal, splanchnic) perfusion. Epinephrine causes a greater increase in cardiac index (CI) and oxygen delivery (DO2) and increases gastric mucosal flow, but increases lactic acid and may not adequately preserve splanchnic circulation owing to its predominant vasoconstrictive alpha (α) effects. Epinephrine may be particularly useful when used earlier in the course of septic shock in young patients and those who do not have any known cardiac abnormalities. Unlike epinephrine, dopamine does not preferentially increase the proportion of CI that preferentially goes to the splanchnic circulation. Dopamine is further limited because it cannot increase CI by more than 35% and is accompanied by tachycardia or tachydysrhythmias. Dopamine, as opposed to norepinephrine, may worsen splanchnic oxygen consumption (VO2) and oxygen extraction ratio (O2ER). Low-dose dopamine has not been shown to consistently increase the glomerular filtration rate or prevent renal failure, and, indeed, worsens splanchnic tissue oxygen use. Routine use of concurrently administered dopamine with vasopressors is not recommended. Phenylephrine should be used when a pure vasoconstrictor is desired in patients who may not require or do not tolerate the beta (β) effects of dopamine or norepinephrine with or without dobutamine. Patients with high filling pressure and hypotension may benefit from the combination of phenylephrine and dobutamine. Investigational approaches to vasopressor-refractory hypotension in septic shock include the use of vasopressin and corticosteroids.
Rudis MI, Basha MA, Zarowitz BJ. Is it time to reposition vasopressors and inotropes in sepsis?Crit Care Med. 1996;24(3):525-537.
2.
MacGregor DA, Smith TE, Prielipp RC, Butterworth JF, James RL, Scuderi PE. Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology. 2000;92(2):338-346.
3.
Meier-Hellmann A, Bredle DL, Specht M, Spies C, Hannemann L, Reinhart K.The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock. Intensive Care Med. 1997;23(1):31-37.
4.
Olson D, Pohlman A, Hall JB. Administration of low-dose dopamine to nonoliguric patients with sepsis syndrome does not raise intramucosal gastric pH nor improve creatinine clearance. Am J Respir Crit Care Med. 1996;154(6 pt 1):1664-1670.
5.
Dive A, Foret F, Jamart J, Bulpa P, Installe E.Effect of dopamine on gastrointestinal motility during critical illness. Intensive Care Med. 2000;26(7):901-907.
6.
Meier-Hellmann A, Sakka S, Reinhart K.Aspects in monitoring and treatment of gastrointestinal underperfusion in sepsis. Diagnosis and therapy of gastrointestinal underperfusion in sepsis. Anasthesiol Intensivmed Notfallmed Schmerzther. 1998;33(suppl 2):S60-S69.
7.
Meier-Hellmann A, Sakka SG, Reinhart K.Catecholamines and splanchnic perfusion. Schweiz Med Wochenschr. 2000;130(50):1942-1947.
8.
Yu M.A peek at renal blood flow, renal function, and oxygen consumption with epinephrine and dopamine therapy. Crit Care Med. 2000;28(5):1661-1663.
9.
Jindal N, Hollenberg SM, Dellinger RP. Pharmacologic issues in the management of septic shock. Crit Care Clin. 2000;16(2):233-249.
10.
Girbes AR, Patten MT, McCloskey BV, Groeneveld AB, Hoogenberg K.The renal and neurohumoral effects of the addition of low-dose dopamine in septic critically ill patients. Intensive Care Med. 2000;26(11):1685-1689.
11.
Ichai C, Soubielle J, Carles M, Giunti C, Grimaud D.Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: a single-blind randomized study. Crit Care Med. 2000;28(4):921-928.
12.
Lherm T, Troche G, Rossignol M, Bordes P, Zazzo JF. Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines. Intensive Care Med. 1996;22(3):213-219.
13.
Ichai C, Passeron C, Carles M, Bouregba M, Grimaud D.Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: a single-blind, prospective, controlled study. Crit Care Med. 2000;28(5):1329-1335.
14.
Klahr S, Miller SB. Acute oliguria. N Engl J Med. 1998;338(10):671-675.
15.
Day NP, Phu NH, Mai NT, et al. Effects of dopamine and epinephrine infusions on renal hemodynamics in severe malaria and severe sepsis. Crit Care Med. 2000;28(5):1353-1362.
16.
Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J.Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet. 2000;356(9248):2139-2143.
17.
Kellum JA, Bellomo R.Low-dose dopamine: what benefit?Crit Care Med. 2000;28(3):907-908.
18.
Reinhart K, Sakka SG, Meier-Hellmann A.Haemodynamic management of a patient with septic shock. Eur J Anaesthesiol. 2000;17(1):6-17.
19.
Martin C, Viviand X, Arnaud S, Vialet R, Rougnon T.Effects of norepinephrine plus dobutamine or norepinephrine alone on left ventricular performance of septic shock patients. Crit Care Med. 1999;27(9):1708-1713.
20.
Martin C, Viviand X, Leone M, Thirion X.Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28(8):2758-2765.
21.
Dasta JF. Norepinephrine in septic shock: renewed interest in an old drug. Drug Intell Clin Pharm. 1990;24(2):153-156.
22.
Redl-Wenzl EM, Armbruster C, Edelmann G, et al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med. 1993;19(3):151-154.
23.
Marik PE, Mohedin M.The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA. 1994;272(17):1354-1357.
24.
Groeneveld AB, Girbes AR, Thijs LG. Treating septic shock with norepinephrine. Crit Care Med. 1999;27(9):2022-2023.
25.
Gregory JS, Bonfiglio MF, Dasta JF, Reilley TE, Townsend MC, Flancbaum L.Experience with phenylephrine as a component of the pharmacologic support of septic shock. Crit Care Med. 1991;19(11):1395-1400.
26.
Richer M, Robert S, Lebel M.Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man. Crit Care Med. 1996;24(7):1150-1156.
27.
Lucas CE. A new look at dopamine and norepinephrine for hyperdynamic septic shock. Chest. 1994;105(1):7-8.
28.
Ruokonen E, Takala J, Kari A, Saxen H, Mertsola J, Hansen EJ. Regional blood flow and oxygen transport in septic shock. Crit Care Med. 1993;21(9):1296-1303.
29.
Martin C, Papazian L, Perrin G, Saux P, Gouin F.Norepinephrine or dopamine for the treatment of hyperdynamic septic shock?Chest. 1993;103(6):1826-1831.
30.
Abid O, Akca S, Haji-Michael P, Vincent JL. Strong vasopressor support may be futile in the intensive care unit patient with multiple organ failure. Crit Care Med. 2000;28(4):947-949.
31.
Yamazaki T, Shimada Y, Taenaka N, Oshumi H, Takezawa J, Yoshiya I.Circulatory responses to afterloading with phenylephrine in hyperdynamic sepsis. Crit Care Med. 1982;10(7):432-435.
32.
Flancbaum L, Dick M, Dasta J, Sinha R, Choban P.A dose-response study of phenylephrine in critically ill, septic surgical patients. Eur J Clin Pharmacol. 1997;51(6):461-465.
33.
Reinelt H, Radermacher P, Kiefer P, et al. Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999;27(2):325-331.
34.
Yu M, Levy MM, Smith P, Takiguchi SA, Miyasaki A, Myers SA. Effect of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study. Crit Care Med. 1993;21(6):830-838.
35.
Haywood GA, Tighe D, Moss R, et al. Goal directed therapy with dobutamine in a porcine model of septic shock: effects on systemic and renal oxygen transport. Postgrad Med J. 1991;67(suppl 1):S36-S39.
36.
Parrillo JE. Myocardial depression during septic shock in humans. Crit Care Med. 1990;18(10):1183-1184.
37.
Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D.Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330(24):1717-1722.
38.
De Backer D, Moraine JJ, Berre J, Kahn RJ, Vincent JL. Effects of dobutamine on oxygen consumption in septic patients. Direct versus indirect determinations. Am J Respir Crit Care Med. 1994;150(1):95-100.
39.
Klem C, Dasta JF, Reilley TE, Flancbaum LJ. Variability in dobutamine pharmacokinetics in unstable critically ill surgical patients. Crit Care Med. 1994;22(12):1926-1932.
40.
Shoemaker WC, Appel PL, Kram HB. Oxygen transport measurements to evaluate tissue perfusion and titrate therapy: dobutamine and dopamine effects. Crit Care Med. 1991;19(5):672-688.
41.
Duranteau J, Sitbon P, Teboul JL, et al. Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med. 1999;27(5):893-900.
42.
Neviere R, Mathieu D, Chagnon JL, Lebleu N, Wattel F.The contrasting effects of dobutamine and dopamine on gastric mucosal perfusion in septic patients. Am J Respir Crit Care Med. 1996;154(6 pt 1):1684-1688.
43.
Gutierrez G, Clark C, Brown SD, Price K, Ortiz L, Nelson C.Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients. Am J Respir Crit Care Med. 1994;150(2):324-329.
44.
Reinelt H, Radermacher P, Fischer G, et al. Effects of a dobutamine-induced increase in splanchnic blood flow on hepatic metabolic activity in patients with septic shock. Anesthesiology. 1997;86(4):818-824.
45.
Parviainen I, Ruokonen E, Takala J.Dobutamine-induced dissociation between changes in splanchnic blood flow and gastric intramucosal pH after cardiac surgery. Br J Anaesth. 1995;74(3):277-282.
46.
Levy B, Bollaert PE, Lucchelli JP, Sadoune LO, Nace L, Larcan A.Dobutamine improves the adequacy of gastric mucosal perfusion in epinephrine-treated septic shock. Crit Care Med. 1997;25(10):1649-1654.
47.
Tuchschmidt J, Fried J, Astiz M, Rackow E.Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest. 1992;102(1):216-220.
48.
Dickerson RN, Lima JJ, Kuhl DA, Brown RO, Hak LJ. Effect of sustained endotoxemia on alpha1-adrenergic responsiveness in parenterally fed rats. Pharmacotherapy. 1998;18(1):170-174.
49.
Bollaert PE, Bauer P, Audibert G, Lambert H, Larcan A.Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine-resistant septic shock. Chest. 1990;98(4):949-953.
50.
Mackenzie SJ, Kapadia F, Nimmo GR, Armstrong IR, Grant IS. Adrenaline in treatment of septic shock: effects on haemodynamics and oxygen transport. Intensive Care Med. 1991;17(1):36-39.
51.
Lipman J, Roux A, Kraus P.Vasoconstrictor effects of adrenaline in human septic shock. Anaesth Intensive Care. 1991;19(1):61-65.
52.
Silverman HJ, Penaranda R, Orens JB, Lee NH. Impaired beta-adrenergic receptor stimulation of cyclic adenosine monophosphate in human septic shock: association with myocardial hyporesponsiveness to catecholamines. Crit Care Med. 1993;21(1):31-39.
53.
Moran JL, O’Fathartaigh MS, Peisach AR, Chapman MJ, Leppard P.Epinephrine as an inotropic agent in septic shock: a dose-profile analysis. Crit Care Med. 1993;21(1):70-77.
54.
Levy B, Bollaert PE, Charpentier C, et al. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med. 1997;23(3):282-287.
55.
Day NP, Phu NH, Bethell DP, et al. The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection. Lancet. 1996;348(9022):219-223.
56.
Meier-Hellmann A, Reinhart K, Bredle DL, Specht M, Spies CD, Hannemann L.Epinephrine impairs splanchnic perfusion in septic shock. Crit Care Med. 1997;25(3):399-404.
57.
Uusaro A, Takala J.Vasoactive drugs and splanchnic perfusion in septic shock. Crit Care Med. 1998;26(8):1458-1460.
58.
Meier-Hellmann A, Bredle DL, Specht M, Hannemann L, Reinhart K.Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine. Crit Care Med. 1999;27(10):2166-2171.
59.
Levy B, Nace L, Bollaert PE, Dousset B, Mallie JP, Larcan A.Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock. Intensive Care Med. 1999;25(9):942-948.
60.
Kiefer P, Tugtekin I, Wiedeck H, et al. Effect of a dopexamine-induced increase in cardiac index on splanchnic hemodynamics in septic shock. Am J Respir Crit Care Med. 2000;161(3 pt 1):775-779.
61.
Kiefer P, Tugtekin I, Wiedeck H, et al. Effect of dopexamine on hepatic metabolic activity in patients with septic shock. Shock. 2001;15(6):427-431.
62.
Takala J, Meier-Hellmann A, Eddleston J, Hulstaert P, Sramek V.Effect of dopexamine on outcome after major abdominal surgery: a prospective, randomized, controlled multicenter study. European Multicenter Study Group on Dopexamine in Major Abdominal Surgery. Crit Care Med. 2000;28(10):3417-3423.
63.
Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95(5):1122-1125.
64.
Landry DW, Levin HR, Gallant EM, et al. Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med. 1997;25(8):1279-1282.
65.
Malay MB, Ashton RC Jr, Landry DW, Townsend RN. Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma. 1999;47(4):699-703.
66.
Bollaert PE. Stress doses of glucocorticoids in catecholamine dependency: a new therapy for a new syndrome?Intensive Care Med. 2000;26(1):3-5.
67.
Spijkstra JJ, Girbes AR. The continuing story of corticosteroids in the treatment of septic shock. Intensive Care Med. 2000;26(5):496-500.
68.
Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A.Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26(4):645-650.
69.
Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999;27(4):723-732.
70.
Annane D, Bellissant E, Sebille V, et al. Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve. Br J Clin Pharmacol. 1998;46(6):589-597.
71.
Oppert MRA, Graf KJ, Barckow D, Frei U, Eckardt KU. Plasma cortisol levels before and during “low-dose” hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock. Intensive Care Med. 2000;26:1747-1755.
72.
Bellissant E, Annane D.Effect of hydrocortisone on phenylephrine—mean arterial pressure dose-response relationship in septic shock. Clin Pharmacol Ther. 2000;68(3):293-303.
73.
Rosselet A, Feihl F, Markert M, Gnaegi A, Perret C, Liaudet L.Selective iNOS inhibition is superior to norepinephrine in the treatment of rat endotoxic shock. Am J Respir Crit Care Med. 1998;157(1):162-170.
74.
Griffiths MJ, Messent M, Curzen NP, Evans TW. Aminoguanidine selectively decreases cyclic GMP levels produced by inducible nitric oxide synthase. Am J Respir Crit Care Med. 1995;152(5 pt 1):1599-1604.
75.
Grover R, Zaccardelli D, Colice G, Guntupalli K, Watson D, Vincent JL. An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group. Crit Care Med. 1999;27(5):913-922.
76.
Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med. 1999;27(3):639-660.
