Norepinephrine in shock, toxic it’s not

From: AnesthesiaNow.com

Every day, clinicians treat hemodynamic instability as part of patient management. In a perioperative setting, hypotension is multifactorial owing to its many causes, which include anesthetic drugs, hemorrhage, hypovolemia, regional anesthesia effects, arrhythmias, pre-existing heart failure, and/or any combination of these. In this setting, hypotension is often transient and responds to volume administration, an α-adrenergic agent such as phenylephrine, or a mixed α- and β-adrenergic agent such as ephedrine. However, patients may also present with or develop more persistent hypotension and/or shock perioperatively that requires resuscitation with vasopressors and intravascular volume administration. An important question is: which vasopressor should be used initially to treat shock?

In critically ill patients, my personal bias has always been to use norepinephrine as the first-line agent, as its release from the sympathetic nervous system is normally an important physiologic response to shock. However, there is a clinical perception that norepinephrine increases mortality – a viewpoint often repeated in the clinical dogma of unknown origin suggesting that “Levophed (norepinephrine) leaves them dead”.

Clinicians instead seem to more commonly use dopamine as a first-line agent. However, patients with heart failure, a form of  shock, may have a diminished response to dopamine. [1] Norepinephrine, however, is a direct α1- and β1-adrenergic agonist stored in the sympathetic nerve terminal, and is also a potent vasoconstrictor and inotropic agent, which makes it an ideal agent to treat shock.

As reported in the New England Journal of Medicine, DeBacker et al [2] randomized 1679 patients as part of a European multicenter trial evaluating dopamine or norepinephrine as initial therapy to treat the hemodynamic instability associated with shock. Most of the patients in the study had septic shock (62%), while 17% had cardiogenic shock, and 16% hypovolemic shock. Although the overall 28-day mortality in the group receiving dopamine was 52.5% compared with 48.5% in norepinephrine-treated patients, this difference was not statistically different. However, arrhythmias were twice as frequent in the dopamine-treated group, and patients with cardiogenic shock who received dopamine had a significantly higher mortality rate. These data suggest that dopamine should no longer be considered as an initial therapeutic approach when treating shock. Other studies, including an observational evaluation of 1058 patients with shock, support this concept. [3,4]

We have used norepinephrine for many years as an initial therapy to treat hypotension perioperatively, especially following cardiac surgery, in critical care settings, and as an infusion to treat shock from multiple causes. [5,6] Although clinicians are frequently concerned about norepinephrine’s potential for renal vasoconstriction, this is not actually supported by clinical data. The current randomized study is particularly important because it provides data further suggesting that “Levophed leaves them dead” is incorrect. Perhaps our new modus operandi should be “norepinephrine in shock, toxic it’s not” or “use your head, give Levophed”.

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Jerrold H Levy, MD, FAHA

References:
1. Anderson FL, Port JD, Reid BB, et al. Effect of therapeutic dopamine administration on myocardial catecholamine and neuropeptide Y concentrations in the failing ventricles of patients with idiopathic dilated cardiomyopathy. J Cardiovasc Pharmacol 1992;20:800-806.

2. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779-789.

3. Patel GP, Grahe JS, Sperry M, et al. Efficacy and safety of dopamine versus norepinephrine in the management of septic shock. Shock 2009 [e-pub ahead of print].

4. Sakr Y, Reinhart K, Vincent JL, et al. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med 2006;34:589-597.

5. Levy JH, Tanaka KA, Bailey JM. Cardiac Surgical Pharmacology. In: Cardiac Surgery in the Adult. Edited by Cohn LH. New York, NY: McGraw Hill, 2008:77-110.

6. Levy JH, Adkinson NF, Jr. Anaphylaxis during cardiac surgery: implications for clinicians. Anesth Analg 2008;106:392-403.

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