Comparison of Equipressor Doses of Norepinephrine, Epinephrine, and Phenylephrine on Septic Myocardial Dysfunction Nicolas Ducrocq, M.D.,* Antoine Kimmoun, M.D.,* Anna Furmaniuk, M.Sc.,† Zerin Hekalo, M.Sc.,† Fatiha Maskali, Ph.D.,‡ Sylvain Poussier, Ph.D.,‡ Pierre-Yves Marie, M.D., Ph.D.,§ Bruno Levy, M.D., Ph.D. ABSTRACT Background: Myocardial depression is a frequent event during septic shock and may mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data are scarce regarding the myocardial effects of vasopressors used to treat hypotension. In this study, the authors compared the effects of three commonly used vasopressors acting on different ad- renergic receptors on myocardial function in a rodent model of septic shock, as explored with conductance catheter and positron emission tomography. Methods: Septic shock was induced in rats by peritonitis. Eighteen hours after septic insult, vasopressors were titrated to increase mean arterial pressure by 20% compared with baseline values. Results: We observed that peritonitis was associated with arterial hypotension and systolodiastolic dysfunction. Nor- epinephrine and epinephrine improved mean arterial pres- sure, cardiac output, and preload recruitable stroke work, a load-independent measure of systolic function, as well as diastolic function and ventriculoarterial coupling. Heart rate, myocardial oxygen consumption, and arrhythmia inci- dence were furthermore increased in the epinephrine group. Conversely, phenylephrine, a peripheral -agonist, exhibited deleterious effects on systolodiastolic function and ventricu- loarterial coupling. Conductance catheter and positron emis- sion tomography yielded identical results with regard to myocardial function evolution under vasopressor treatment. Conclusions: Phenylephrine, a drug without -1 effects, was associated with decreased ventricular performance and ventriculoarterial uncoupling, whereas epinephrine and nor- epinephrine improved global hemodynamics and myocardial function in severely hypokinetic and hypotensive experimen- tal septic shock. Nevertheless, epinephrine was associated with increased myocardial oxygen consumption. Thus, nor- epinephrine appears to be a more reliable and safer strategy as a first-line therapy in this particular setting. C ARDIOVASCULAR dysfunction is a major contribu- tor in septic shock-induced mortality. 1 Septic shock is characterized by both an alteration in vascular tone 2 and a systolic and diastolic biventricular dysfunction. 3 In clinical practice, volume-resuscitated patients exhibit high cardiac output and low systemic resistance with myocardial depres- sion despite the high output. The overall incidence of global left ventricular hypokinesia in patients with septic shock and no previous cardiac history is 60%, a value much higher than previously described. 4 In 10 –20% of patients with septic shock, septic cardiomyopathy mimics a cardiogenic shock state with impaired cardiac output leading to death. 5 Cur- * Doctoral Student, Groupe Choc Contrat Avenir Inserm, U961, Faculte de Medecine, Nancy Universite, Nancy, France; Service Re ´animation Me ´dicale, CHU Nancy-Brabois, Vandoeuvre-les- Nancy, France. † Masters Degree Student, Groupe Choc Contrat Avenir Inserm, U961, Faculte de Medecine, Nancy Universite. ‡ Re- searcher, Service Me ´decine Nucle ´aire et Nancyclotep, CHU Nancy- Brabois. § Professor, Service Me ´decine Nucle ´aire et Nancyclotep, CHU Nancy-Brabois.  Professor, Groupe Choc Contrat Avenir In- serm, U961, Faculte de Medecine, Nancy Universite; Service Re ´ani- mation Me ´dicale, CHU Nancy-Brabois. Received from Groupe Choc Contrat Avenir Inserm, U961, Fac- ulte de Medecine. Nancy Universite, Nancy, France. Submitted for publication October 14, 2011. Accepted for publication January 9, 2012. Support was provided solely from institutional and/or depart- mental sources. Address correspondence to Dr. Levy: CHU Nancy-Brabois, Ser- vice de Re ´animation Me ´dicale, 54511 Vandoeuvre-les-Nancy Cedex, France. b.levy@chu-nancy.fr. Informaton on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. ANESTHESIOLOGY’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue. Copyright © 2012, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology 2012; 116:1083–91 What We Already Know about This Topic • Myocardial dysfunction occurs during septic shock What This Article Tells Us That Is New • Norepinephrine and epinephrine improved global hemody- namics and myocardial function during experimental septic shock but epinephrine increased myocardial oxygen con- sumption, whereas phenylephrine decreased ventricular performance  Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org). Anesthesiology, V 116 • No 5 May 2012 1083 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/116/5/1083/258035/0000542-201205000-00022.pdf by guest on 17 January 2024