Skip to main content
Top
Published in: Critical Care 6/2008

Open Access 01-12-2008 | Research

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial

Authors: Andrea Morelli, Christian Ertmer, Sebastian Rehberg, Matthias Lange, Alessandra Orecchioni, Amalia Laderchi, Alessandra Bachetoni, Mariadomenica D'Alessandro, Hugo Van Aken, Paolo Pietropaoli, Martin Westphal

Published in: Critical Care | Issue 6/2008

Login to get access

Abstract

Introduction

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock.

Methods

We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance.

Results

No differences were found in any of the investigated parameters.

Conclusions

The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

Trial registration

ClinicalTrial.gov NCT00639015
Appendix
Available only for authorised users
Literature
1.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Taylor Thompson B, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/CCM.0b013e31817d7ee4CrossRefPubMed Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Taylor Thompson B, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/CCM.0b013e31817d7ee4CrossRefPubMed
2.
go back to reference Reinelt H, Radermacher P, Kiefer P, Fischer G, Wachter U, Vogt J, Georgieff M: Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med 1999, 27: 325-331. 10.1097/00003246-199902000-00039CrossRefPubMed Reinelt H, Radermacher P, Kiefer P, Fischer G, Wachter U, Vogt J, Georgieff M: Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med 1999, 27: 325-331. 10.1097/00003246-199902000-00039CrossRefPubMed
3.
go back to reference Beale RJ, Hollenberg SM, Vincent JL, Parrillo JE: Vasopressor and inotropic support in septic shock: an evidence-based review. Crit Care Med 2004,32(11 Suppl):S455-S465. 10.1097/01.CCM.0000142909.86238.B1CrossRefPubMed Beale RJ, Hollenberg SM, Vincent JL, Parrillo JE: Vasopressor and inotropic support in septic shock: an evidence-based review. Crit Care Med 2004,32(11 Suppl):S455-S465. 10.1097/01.CCM.0000142909.86238.B1CrossRefPubMed
4.
go back to reference 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: 1395-1400. 10.1097/00003246-199111000-00016CrossRefPubMed 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: 1395-1400. 10.1097/00003246-199111000-00016CrossRefPubMed
5.
go back to reference 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: 461-465. 10.1007/s002280050231CrossRefPubMed 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: 461-465. 10.1007/s002280050231CrossRefPubMed
6.
go back to reference Hofmann BB, Lefkowitz RJ: Catecholamines and sympathomimetic drugs. In Goodman and Gilman's the pharmacological basis of therapeutics. Edited by: Alfred Gilman, Louis S Goodman, Brian B Hoffman, Robert J Lefkowitz. New York: Pergamon; 1991:187-220. Hofmann BB, Lefkowitz RJ: Catecholamines and sympathomimetic drugs. In Goodman and Gilman's the pharmacological basis of therapeutics. Edited by: Alfred Gilman, Louis S Goodman, Brian B Hoffman, Robert J Lefkowitz. New York: Pergamon; 1991:187-220.
7.
go back to reference Krejci V, Hiltebrand LB, Sigurdsson GH MD: Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med 2006, 34: 1456-1463. 10.1097/01.CCM.0000215834.48023.57CrossRefPubMed Krejci V, Hiltebrand LB, Sigurdsson GH MD: Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis. Crit Care Med 2006, 34: 1456-1463. 10.1097/01.CCM.0000215834.48023.57CrossRefPubMed
8.
go back to reference Morelli A, Lange M, Ertmer C, Dünser M, Rehberg S, Bachetoni A, D'Alessandro M, Van Aken H, Guarracino F, Pietropaoli P, Traber DL, Westphal M: Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock 2008, 29: 446-451.PubMed Morelli A, Lange M, Ertmer C, Dünser M, Rehberg S, Bachetoni A, D'Alessandro M, Van Aken H, Guarracino F, Pietropaoli P, Traber DL, Westphal M: Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock 2008, 29: 446-451.PubMed
9.
go back to reference Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed
10.
go back to reference Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Child EW: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007, 35: 2016-2024. 10.1097/01.CCM.0000281637.08984.6ECrossRefPubMed Rivers EP, Kruse JA, Jacobsen G, Shah K, Loomba M, Otero R, Child EW: The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. Crit Care Med 2007, 35: 2016-2024. 10.1097/01.CCM.0000281637.08984.6ECrossRefPubMed
11.
go back to reference Parrillo JE: Septic shock – vasopressin, norepinephrine, and urgency. N Engl J Med 2008, 358: 954-956. 10.1056/NEJMe0800245CrossRefPubMed Parrillo JE: Septic shock – vasopressin, norepinephrine, and urgency. N Engl J Med 2008, 358: 954-956. 10.1056/NEJMe0800245CrossRefPubMed
12.
go back to reference Sakka SG, Reinhart K, Meier-Hellmann A: Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 2002, 122: 1715-1720. 10.1378/chest.122.5.1715CrossRefPubMed Sakka SG, Reinhart K, Meier-Hellmann A: Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest 2002, 122: 1715-1720. 10.1378/chest.122.5.1715CrossRefPubMed
13.
go back to reference Sakka SG, van Hout N: Relation between indocyanine green (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients. Intensive Care Med 2006, 32: 766-769. 10.1007/s00134-006-0109-6CrossRefPubMed Sakka SG, van Hout N: Relation between indocyanine green (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients. Intensive Care Med 2006, 32: 766-769. 10.1007/s00134-006-0109-6CrossRefPubMed
14.
go back to reference Creteur J, De Backer D, Vincent JL: Monitoring gastric mucosal carbon dioxide pressure using gas tonometry: in vitro and in vivo validation studies. Anesthesiology 1997, 87: 504-510. 10.1097/00000542-199709000-00008CrossRefPubMed Creteur J, De Backer D, Vincent JL: Monitoring gastric mucosal carbon dioxide pressure using gas tonometry: in vitro and in vivo validation studies. Anesthesiology 1997, 87: 504-510. 10.1097/00000542-199709000-00008CrossRefPubMed
15.
go back to reference Groeneveld AB, Kolkman JJ: Splanchnic tonometry: a review of physiology, methodology, and clinical applications. J Crit Care 1994, 9: 198-210. 10.1016/0883-9441(94)90016-7CrossRefPubMed Groeneveld AB, Kolkman JJ: Splanchnic tonometry: a review of physiology, methodology, and clinical applications. J Crit Care 1994, 9: 198-210. 10.1016/0883-9441(94)90016-7CrossRefPubMed
16.
go back to reference Winer BJ, Brown DR, Michels KM: Statistical principles in experimental design. 3rd edition. New York: McGraw-Hill; 1991. Winer BJ, Brown DR, Michels KM: Statistical principles in experimental design. 3rd edition. New York: McGraw-Hill; 1991.
17.
go back to reference Sander O, Welters ID, Foex P, Sear JW: Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications. Crit Care Med 2005, 33: 81-88. 10.1097/01.CCM.0000150028.64264.14CrossRefPubMed Sander O, Welters ID, Foex P, Sear JW: Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications. Crit Care Med 2005, 33: 81-88. 10.1097/01.CCM.0000150028.64264.14CrossRefPubMed
18.
go back to reference Schwarz B, Hofstötter H, Salak N, Pajk N, Knotzer H, Mayr A, Labek B, Kafka R, Ulmer H, Hasibeder W: Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension. Intensive Care Med 2001, 27: 593-601. 10.1007/s001340100856CrossRefPubMed Schwarz B, Hofstötter H, Salak N, Pajk N, Knotzer H, Mayr A, Labek B, Kafka R, Ulmer H, Hasibeder W: Effects of norepinephrine and phenylephrine on intestinal oxygen supply and mucosal tissue oxygen tension. Intensive Care Med 2001, 27: 593-601. 10.1007/s001340100856CrossRefPubMed
19.
go back to reference Zhang H, Smail N, Cabral A, Rogiers P, Vincent JL: Effects of norepinephrine on regional blood flow and oxygen extraction capabilities during endotoxin shock. Am J Respir Crit Care Med 1997, 155: 1965-1971.CrossRefPubMed Zhang H, Smail N, Cabral A, Rogiers P, Vincent JL: Effects of norepinephrine on regional blood flow and oxygen extraction capabilities during endotoxin shock. Am J Respir Crit Care Med 1997, 155: 1965-1971.CrossRefPubMed
20.
go back to reference Alia I, Esteban A, Gordo F, Lorente JA, Diaz C, Rodriguez JA, Frutos F: A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock. Chest 1999, 115: 453-461. 10.1378/chest.115.2.453CrossRefPubMed Alia I, Esteban A, Gordo F, Lorente JA, Diaz C, Rodriguez JA, Frutos F: A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock. Chest 1999, 115: 453-461. 10.1378/chest.115.2.453CrossRefPubMed
21.
go back to reference Meier-Hellmann A, Specht M, Hannemann L, Hassel H, Bredle DL, Reinhart K: Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis. Intensive Care Med 1996, 22: 1354-1359. 10.1007/BF01709551CrossRefPubMed Meier-Hellmann A, Specht M, Hannemann L, Hassel H, Bredle DL, Reinhart K: Splanchnic blood flow is greater in septic shock treated with norepinephrine than in severe sepsis. Intensive Care Med 1996, 22: 1354-1359. 10.1007/BF01709551CrossRefPubMed
22.
go back to reference Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K: Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999, 27: 893-900. 10.1097/00003246-199905000-00021CrossRefPubMed Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K: Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999, 27: 893-900. 10.1097/00003246-199905000-00021CrossRefPubMed
23.
go back to reference Marik PE, Mohedin M: The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994, 272: 1354-1357. 10.1001/jama.272.17.1354CrossRefPubMed Marik PE, Mohedin M: The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994, 272: 1354-1357. 10.1001/jama.272.17.1354CrossRefPubMed
24.
go back to reference Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer PH, Nabet P, Larcan A: 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: 282-287. 10.1007/s001340050329CrossRefPubMed Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer PH, Nabet P, Larcan A: 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: 282-287. 10.1007/s001340050329CrossRefPubMed
25.
go back to reference Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ: Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 1987, 252: H291-H300.PubMed Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ: Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 1987, 252: H291-H300.PubMed
26.
go back to reference Zhang H, De Jongh R, De Backer D, Cherkaoui S, Vray B, Vincent JL: Effects of α- and β-adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock. Crit Care Med 2001, 29: 581-588. 10.1097/00003246-200103000-00020CrossRefPubMed Zhang H, De Jongh R, De Backer D, Cherkaoui S, Vray B, Vincent JL: Effects of α- and β-adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock. Crit Care Med 2001, 29: 581-588. 10.1097/00003246-200103000-00020CrossRefPubMed
27.
go back to reference Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, Williams MD: Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med 2005, 33: 2194-2201. 10.1097/01.CCM.0000182798.39709.84CrossRefPubMed Levy MM, Macias WL, Vincent JL, Russell JA, Silva E, Trzaskoma B, Williams MD: Early changes in organ function predict eventual survival in severe sepsis. Crit Care Med 2005, 33: 2194-2201. 10.1097/01.CCM.0000182798.39709.84CrossRefPubMed
28.
go back to reference Bersten AD, Rutten AJ: Renovascular interaction of epinephrine, dopamine and intraperitoneal sepsis. Crit Care Med 1995, 23: 537-544. 10.1097/00003246-199503000-00020CrossRefPubMed Bersten AD, Rutten AJ: Renovascular interaction of epinephrine, dopamine and intraperitoneal sepsis. Crit Care Med 1995, 23: 537-544. 10.1097/00003246-199503000-00020CrossRefPubMed
29.
go back to reference Bersten AD, Rutten AJ, Summersides G, Ilsley AH: Epinephrine infusion in sheep: systemic and renal hemodynamic effects. Crit Care Med 1994, 22: 994-1001. 10.1097/00003246-199406000-00019CrossRefPubMed Bersten AD, Rutten AJ, Summersides G, Ilsley AH: Epinephrine infusion in sheep: systemic and renal hemodynamic effects. Crit Care Med 1994, 22: 994-1001. 10.1097/00003246-199406000-00019CrossRefPubMed
30.
go back to reference Bellomo R, Kellum JA, Wisiniewsky SR, Pinsky MR: Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs. Am J Respir Crit Care Med 1999, 159: 1186-1192.CrossRefPubMed Bellomo R, Kellum JA, Wisiniewsky SR, Pinsky MR: Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs. Am J Respir Crit Care Med 1999, 159: 1186-1192.CrossRefPubMed
31.
go back to reference Bellomo R: Noradrenaline: friend or foe? Heart Lung Circ 2003, 12: S42-S48. 10.1046/j.1443-9506.2003.t01-7-.xCrossRefPubMed Bellomo R: Noradrenaline: friend or foe? Heart Lung Circ 2003, 12: S42-S48. 10.1046/j.1443-9506.2003.t01-7-.xCrossRefPubMed
Metadata
Title
Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial
Authors
Andrea Morelli
Christian Ertmer
Sebastian Rehberg
Matthias Lange
Alessandra Orecchioni
Amalia Laderchi
Alessandra Bachetoni
Mariadomenica D'Alessandro
Hugo Van Aken
Paolo Pietropaoli
Martin Westphal
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2008
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc7121

Other articles of this Issue 6/2008

Critical Care 6/2008 Go to the issue