Sepsis: Is There Room for Vasopressin? Cheryl L. Holmes, James A. Russell, and Keith R. Walley University of British Columbia Program of Critical Care Medicine and the McDonald Research Laboratories, St. Paul’s Hospital, Vancouver, B.C. Canada Abstract. Cardiovascular dysfunction contributes impor- tantly to the high mortality of septic shock, which remains in excess of 50%. Non-survivors are characterized by an inade- quate response to fluid resuscitation and catecholamine in- fusions. A number of recent reports suggest that vaso- pressin, a non-catecholamine vasopressor, may contribute usefully to the cardiovascular management of septic shock and other forms of vasodilatory shock. Here we review the clinical studies to date of vasopressin use in septic shock and other vasodilatory shock. We then review the known physiol- ogy of vasopressin to help understand why vasopressin may be beneficial in this setting. In general, humans having se- vere vasodilatory shock demonstrate low endogenous vaso- pressin blood concentration. Low-dose vasopressin infusion in this setting increases blood vasopressin concentration to that observed in hypotension of other causes, results in an increase in mean arterial pressure, and reduces the need for additional a-adrenergic vasopressor infusions. Current studies in low numbers of patients suggest that low-dose vasopressin may increase urine output in this setting. Vaso- pressin infusion increases blood pressure by V1 receptor stimulation on vascular smooth muscle. This vasoconstrictor effect is less pronounced in the cerebral, coronary, and renal circulations. Diminished vasoconstriction in some regional circulations may be contributed to by nitric oxide-mediated vasodilation resulting from oxytocin receptor stimulation by low-dose vasopressin. Thus, low-dose vasopressin infu- sion may be a useful adjunct to fluid resuscitation and catecholamine infusion in severe septic shock and other forms of vasodilatory shock. Keywords. sepsis, shock, vasopressin, hemodynamics Introduction Septic shock is the most common cause of death in intensive care units [1] and the thirteenth most com- mon cause of all deaths in North America from 1979 to 1987 [2]. Cardiovascular dysfunction contributes im- portantly to the high mortality of septic shock, which remains in excess of 50% [3]. Current cardiovascular management of septic shock involves fluid administra- tion and use of inotropes and vasopressor agents [2]. Non-survivors of septic shock are characterized by persistent vasodilation [4] and failure to increase mean arterial pressure and cardiac output in response to resuscitation [5,6]. Thus, the goals of cardiovascular management of septic shock are to maintain an ade- quate arterial perfusing pressure, cardiac output, and oxygen delivery to vital organs. Catecholamines are most often used to achieve these goals. Recent studies favor norepinephrine as an effec- tive vasopressor to maintain an adequate mean arterial pressure during septic shock [7]. However, a wide array of catecholamines, including norepinephrine, epineph- rine, phenylephrine, dopamine, dopexamine, dobuta- mine, and others are used in the cardiovascular man- agement of septic shock. All of these catecholamines have important adverse effects. Alpha-adrenergic ef- fects of norepinephrine and other catecholamines de- crease cardiac output and oxygen delivery. Regionally, at higher doses, a-agonists can significantly decrease renal and mesenteric blood flow and may contribute to renal, gut, and other organ failure in septic shock [8]. Arrhythmias may result from b-adrenergic effects. Over a short time, vascular and cardiac responsiveness to a- and b-adrenergic agonists diminishes [9,10]. In view of these concerns, recent studies have ex- amined vasopressor agents acting via alternative path- ways. For example, nitric oxide synthase (NOS) inhibi- tors increase blood pressure in patients having septic shock. Unfortunately, non-selective NOS inhibition de- trimentally reduces cardiac output and increases mor- tality [11]. In contrast, a number of preliminary reports of the use of vasopressin in septic shock and other forms of vasodilatory shock are encouraging. Here we review this preliminary data and, based on this, specu- late that a clear role for vasopressin in the cardiovas- cular management of septic shock will be identified in upcoming clinical trials. Human Trials of Low-Dose Vasopressin In 1991 Morrison, Doepfner, and Park commented on the possible use of vasopressin to treat septic shock in Support: Keith R. Walley is a BC Lung Association/St. Paul’s Hospital Foundation Scientist Address correspondence to: Keith R. Walley, M.D., McDonald Research Laboratories, St. Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. Phone: 604-806-8136; Fax: 604- 806-8351 Email: kwalley@mrl.ubc.ca 169 Sepsis 2000;4:169–175 © 2001 Kluwer Academic Publishers. Manufactured in The Netherlands.