Septic shock that requires
therapy with
adrenergic agents is associated with high rates of mortality. Inappropriately normal or low serum concentrations of
vasopressin contribute to the development of
hypotension during
sepsis. We critically evaluated the role of administering exogenous
vasopressin to patients with
septic shock. A computerized search of MEDLINE from January 1966--December 2003 and a manual search of relevant journals for abstracts were conducted. Eleven retrospective, six prospective cohort, and four prospective randomized studies were identified. Most studies evaluated short-term infusions of
vasopressin at 0.08 U/minute or less as add-on
therapy in patients requiring
adrenergic agents. The results show that starting
vasopressin in patients with
septic shock increases systemic vascular resistance and arterial blood pressure, thus reducing the dosage requirements of
adrenergic agents. These effects are rapid and sustained. Substantial enhancement of urine production, likely due to increased glomerular filtration rate, was shown in several studies. A few studies demonstrated clinically significant reduced cardiac output or cardiac index after
vasopressin was begun, necessitating cautious use in patients with cardiac dysfunction.
Vasopressin was associated with
ischemia of the mesenteric mucosa, skin, and myocardium; elevated hepatic
transaminase and
bilirubin concentrations;
hyponatremia; and
thrombocytopenia. Limiting the dosage to 0.03 U/minut or less may minimize the development of these adverse effects.
Vasopressin 0.03 U/minute or less should be considered if response to one or two
adrenergic agents is inadequate or as a method to reduce the dosage of
adrenergic agents. At present,
vasopressin therapy should not be started as first-line
therapy. Additional studies are needed to determine the optimum dosage, duration, and place in
therapy of
vasopressin relative to
adrenergic agents. A multicenter, comparative study of
vasopressin 0.03 U/minute as add-on
therapy is under way and should provide mortality data.