Among patients in septic shock and other forms of distributive shock, the addition of the antidiuretic hormone vasopressin to standard anti-hypotensive treatment is associated with a lower risk for atrial fibrillation (AF), researchers report.
In a meta-analysis that included 23 randomized clinical trials involving more than 3,000 patients in distributive shock, adding vasopressin to catecholamine vasopressors led to a statistically significant reduction in AF risk (relative risk 0.77, 95% CI 0.67 to 0.88).
Sepsis is the most common cause of distributive shock, but the condition can also occur after cardiovascular surgery, spinal cord injury, anaphylaxis, and prolonged shock.
AF is a common adverse event among patients in distributive shock, and is associated with an increased risk for death, morbidity, and longer hospital stays.
The endogenous peptide hormone vasopressin can be used as a vasopressor, and its use may result in adverse events including AF, organ injury, and death by reducing the requirement for catecholamines.
“The theoretical basis for vasopressin administration stems from research identifying relative vasopressin deficiency in patients with distributive shock,” William McIntyre, MD, of McMaster University in Ontario, Canada, and colleagues, wrote in the study online in the Journal of the American Medical Association.
In an effort to determine if blood pressure support combining vasopressin with catecholamine vasopressors could reduce the need for catecholaminergic drugs leading to fewer treatment-related side effects, the researchers constructed a random-effects model using combined data from the 23 randomized trials identified through database searches.
A total of 3,088 patients were enrolled in the trials (mean age of 61.1, 45.3% women). Most studies were single center and included patients with septic shock, and 15 of the 23 trials were not blinded.
The primary outcome was AF, and secondary outcomes included mortality, requirement for renal-replacement therapy, myocardial injury, ventricular arrhythmia, stroke, and length of stay in the intensive care unit.
Among the main findings:
- High-quality evidence supported a lower risk of AF associated with vasopressin treatment (RR 0.77 [95% CI 0.67 to 0.88]; risk difference [RD] −0.06, 95% CI −0.13 to 0.01)
- The overall RR estimate for mortality was 0.89 (95% CI 0.82 to 0.97; RD −0.04, 95% CI −0.07 to 0.00])
- When limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI 0.84 to 1.11)
- The overall RR estimate for renal-replacement therapy was 0.74 (95% CI 0.51 to 1.08; RD −0.07, 95% CI −0.12 to −0.01], but in trials limited to a low risk of bias the RR was 0.70 (95% CI 0.53 to 0.92, P=0.77 for interaction)
“To our knowledge, this systematic review is the first on the topic to include atrial fibrillation as an outcome,” the researchers wrote. “Prior reviews assessed arrhythmia, but this outcome has limited utility due to the variety of conditions that could be found under this heading.”
The reduction in AF associated with vasopressin was consistent for sepsis and post-cardiac surgery shock and in sensitivity analyses restricted to studies at low risk of bias.
The researchers hypothesized that vasopressin may reduce AF by “sparing the adrenergic stimulation provided by catecholaminergic vasopressors.”
“This could have manifested in fewer patients developing atrial fibrillation or may have caused atrial fibrillation to be shorter in duration and lower in rate and, in consequence, less likely to be detected.”
The review included data from the recently published Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery (VANCS) and Effects of Early Vasopressin versus Norepinephrine on Kidney Failure in Patients with Septic Shock (VANISH) trials.
Limitations to the analysis, the researchers said, included poor quality of reporting in some studies, which made it difficult to judge risk bias, and differences in vasopressor initiation, titration, and weaning from trial to trial.
McIntyre reported receiving grant funding from the Canadian Stroke Prevention Intervention Network and being a trainee member of the Cardiac Arrhythmia Network of Canada. Other co-authors reported relationships with Tenax Therapeutics, Orion Pharma, Ferring Pharmaceuticals, GlaxoSmithKline, Bristol-Myers Squibb/Pfizer, Amomed Pharma, Medtronic, and the Canadian Institutes of Health Research.