The Cardiopulmonary Effects of Vasopressin Compared With Norepinephrine in Septic Shock


      Vasopressin is known to be an effective vasopressor in the treatment of septic shock, but uncertainty remains about its effect on other hemodynamic parameters.


      We examined the cardiopulmonary effects of vasopressin compared with norepinephrine in 779 adult patients with septic shock recruited to the Vasopressin and Septic Shock Trial. More detailed cardiac output data were analyzed for a subset of 241 patients managed with a pulmonary artery catheter, and data were collected for the first 96 h after randomization. We compared the effects of vasopressin vs norepinephrine in all patients and according to severity of shock (< 15 or ≥ 15 μg/min of norepinephrine) and cardiac output at baseline.


      Equal BPs were maintained in both treatment groups, with a significant reduction in norepinephrine requirements in the patients treated with vasopressin. The major hemodynamic difference between the two groups was a significant reduction in heart rate in the patients treated with vasopressin (P <.0001), and this was most pronounced in the less severe shock stratum (treatment × shock stratum interaction, P =.03). There were no other major cardiopulmonary differences between treatment groups, including no difference in cardiac index or stroke volume index between patients treated with vasopressin and those treated with norepinephrine. There was significantly greater use of inotropic drugs in the vasopressin group than in the norepinephrine group.


      Vasopressin treatment in septic shock is associated with a significant reduction in heart rate but no change in cardiac output or other measures of perfusion.

      Trial registry

      ISRCTN Register; No.:ISRCTN94845869; URL:
      To read this article in full you will need to make a payment


      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Alberti C
        • Brun-Buisson C
        • Goodman SV
        • European Sepsis Group
        • et al.
        Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients.
        Am J Respir Crit Care Med. 2003; 168: 77-84
        • Dellinger RP
        • Levy MM
        • Carlet JM
        • International Surviving Sepsis Campaign Guidelines Committee
        • American Association of Critical-Care Nurses
        • American College of Chest Physicians
        • American College of Emergency Physicians
        • Canadian Critical Care Society
        • European Society of Clinical Microbiology and Infectious Diseases
        • European Society of Intensive Care Medicine
        • European Respiratory Society
        • International Sepsis Forum
        • Japanese Association for Acute Medicine
        • Japanese Society of Intensive Care Medicine
        • Society of Critical Care Medicine
        • Society of Hospital Medicine
        • Surgical Infection Society
        • World Federation of Societies of Intensive and Critical Care Medicine
        • et al.
        Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.
        Crit Care Med. 2008; 36: 296-327
        • Landry DW
        • Levin HR
        • Gallant EM
        • et al.
        Vasopressin deficiency contributes to the vasodilation of septic shock.
        Circulation. 1997; 95: 1122-1125
        • Landry DW
        • Levin HR
        • Gallant EM
        • et al.
        Vasopressin pressor hypersensitivity in vasodilatory septic shock.
        Crit Care Med. 1997; 25: 1279-1282
        • Malay MB
        • Ashton Jr, RC
        • Landry DW
        • et al.
        Townsend RN Low-dose vasopressin in the treatment of vasodilatory septic shock.
        J Trauma. 1999; 47: 699-703
        • Patel BM
        • Chittock DR
        • Russell JA
        • Walley KR
        Beneficial effects of short-term vasopressin infusion during severe septic shock.
        Anesthesiology. 2002; 96: 576-582
        • Dünser MW
        • Mayr AJ
        • Ulmer H
        • et al.
        Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study.
        Circulation. 2003; 107: 2313-2319
        • Lauzier F
        • Lévy B
        • Lamarre P
        • Lesur O
        Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial.
        Intensive Care Med. 2006; 32: 1782-1789
        • Morelli A
        • Ertmer C
        • Rehberg S
        • et al.
        Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study.
        Crit Care. 2009; 13: R130
        • Holmes CL
        • Walley KR
        • Chittock DR
        • Lehman T
        • Russell JA
        The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series.
        Intensive Care Med. 2001; 27: 1416-1421
        • Torgersen C
        • Dünser MW
        • Schmittinger CA
        • et al.
        Current approach to the haemodynamic management of septic shock patients in European intensive care units: a cross-sectional, self-reported questionnaire-based survey.
        Eur J Anaesthesiol. 2011; 28: 284-290
        • Krejci V
        • Hiltebrand LB
        • Sigurdsson GH
        Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis.
        Crit Care Med. 2006; 34: 1456-1463
        • Hayes MA
        • Yau EH
        • Hinds CJ
        • Watson JD
        Symmetrical peripheral gangrene: association with noradrenaline administration.
        Intensive Care Med. 1992; 18: 433-436
        • Russell JA
        • Walley KR
        • Singer J
        • VASST Investigators
        • et al.
        Vasopressin versus norepinephrine infusion in patients with septic shock.
        N Engl J Med. 2008; 358: 877-887
        • Bone RC
        • Sibbald WJ
        • Sprung CL
        The ACCP-SCCM consensus conference on sepsis and organ failure.
        Chest. 1992; 101: 1481-1483
        • Shoemaker WC
        • Appel PL
        • Kram HB
        • Waxman K
        • Lee TS
        Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.
        Chest. 1988; 94: 1176-1186
        • Abraham E
        • Bland RD
        • Cobo JC
        • Shoemaker WC
        Sequential cardiorespiratory patterns associated with outcome in septic shock.
        Chest. 1984; 85: 75-80
        • Rivers E
        • Nguyen B
        • Havstad S
        • Early Goal-Directed Therapy Collaborative Group
        • et al.
        Early goal-directed therapy in the treatment of severe sepsis and septic shock.
        N Engl J Med. 2001; 345: 1368-1377
        • 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: 1717-1722
        • Parker MM
        • Shelhamer JH
        • Natanson C
        • Alling DW
        • Parrillo JE
        Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis.
        Crit Care Med. 1987; 15: 923-929
        • Dünser MW
        • Ruokonen E
        • Pettilä V
        • 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: R181
        • Roy WL
        • Edelist G
        • Gilbert B
        Myocardial ischemia during non-cardiac surgical procedures in patients with coronary-artery disease.
        Anesthesiology. 1979; 51: 393-397
        • Robinson BF
        Relation of heart rate and systolic blood pressure to the onset of pain in angina pectoris.
        Circulation. 1967; 35: 1073-1083
        • Mehta S
        • Granton J
        • Cook D
        • et al.
        Troponin and CKMB trends in patients with septic shock randomized to vasopressin (VP) or Norepinephrine (NE).
        Am J Respir Crit Care Med. 2009; 179: A1564
        • Gordon AC
        • Mehta S
        • Lapinsky S
        • et al.
        Comparison of vasopressin- versus norepinephrine-associated ischemic ECG changes in septic shock.
        Intensive Care Med. 2009; 35: S114
        • Brame AL
        • Singer M
        Stressing the obvious? An allostatic look at critical illness.
        Crit Care Med. 2010; 38: S600-S607
        • Rudiger A
        Beta-block the septic heart.
        Crit Care Med. 2010; 38: S608-S612
      1. National Institutes of Health Clinical Center. Heart rate control with esmolol in septic shock. NCT01231698. Bethesda, MD: National Institutes of Health. Accessed January 30 2012.

        • Rehberg S
        • Ertmer C
        • Vincent JL
        • et al.
        Role of selective V1a receptor agonism in ovine septic shock.
        Crit Care Med. 2011; 39: 119-125
        • Takala J
        Should we target blood pressure in sepsis?.
        Crit Care Med. 2010; 38: S613-S619
        • Morelli A
        • Donati A
        • Ertmer C
        • et al.
        Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.
        Crit Care. 2011; 15: R217
        • Holmes CL
        • Patel BM
        • Russell JA
        • Walley KR
        Physiology of vasopressin relevant to management of septic shock.
        Chest. 2001; 120: 989-1002