Dennis G. Maki, MD, MACP
Does low-dose vasopressin reduce mortality more than norepinephrine in patients with septic shock who are being treated with catecholamines?
Randomized controlled trial.
Blinded (patients, clinicians, data analyst, and investigators).*
28 and 90 days after infusion started.
27 centers in Canada, Australia, and the USA.
802 patients > 16 years of age who had septic shock (≥ 2 diagnostic criteria for the systemic inflammatory response syndrome, suspected or proven infection, new organ dysfunction, and hypotension that was resistant to fluids [lack of response to 500 mL of normal saline or requiring vasopressors]). Exclusion criteria included ischemic syndromes, > 24 hours since meeting entry criteria, use of open-label vasopressin, anticipated poor prognosis, underlying chronic heart disease and shock, and lack of commitment to aggressive care.
Vasopressin (n = 406) or norepinephrine (n = 396). Infusions were started at 0.01 U/min and 5 µg/min, respectively, and increased every 10 minutes during the first hour to a maximum of 0.03 U/min and 15 µg/min, respectively. During the titration period, open-label vasopressors were titrated to an initial target mean arterial pressure of 65 to 75 mm Hg. Infusions were continued until the patient died, a serious adverse event occurred, or the patient no longer required open-label vasopressors.
All-cause mortality at 28 days. Secondary outcomes included 90-day mortality and serious adverse events (e.g., cardiac arrest, acute mesenteric ischemia). The study had 80% power to detect an absolute 10% between-group difference in mortality (α = 0.05).
97% of patients had infusions and were included in the intention-to-treat analysis (mean age 61 y, 61% men).
Groups did not differ for 28-day or 90-day mortality or for serious adverse events (Table).
Low-dose vasopressin did not reduce mortality more than norepinephrine in patients with septic shock who were receiving catecholamines.
Vasopressin vs norepinephrine infusion for septic shock†
†NS = not significant; other abbreviations defined in Glossary.
‡Based on 778 patients who received infusions; calculated using control event rate and adjusted odds ratios in article.
§Based on 771 patients who received infusions; calculated using control event rates and adjusted odds ratios in article.
||Based on 778 patients; calculated using event rates in article.
Dennis G. Maki. Low-dose vasopressin did not reduce mortality more than norepinephrine in septic shock. Ann Intern Med. 2008;149:JC3–14. doi: 10.7326/0003-4819-149-6-200809160-02014
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Published: Ann Intern Med. 2008;149(6):JC3-14.
Infectious Disease, Multi-Organ Failure and Sepsis, Pulmonary/Critical Care.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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