Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

Abstract

IntroductionCardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.MethodsThis was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.ResultsWe enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).ConclusionsTroponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.Trial registrationControlled-trials.com ISRCTN94845869

What’s new in vasopressin?

“…A recent meta-analysis reported no evidence of increased SAEs when vasopressin was used to treat vasodilatory shock [2]. This is consistent with data from VASST, which reported no difference in SAEs between the treatment groups (10.3 % vasopressin vs. 10.5 % noradrenaline) [4] and specifically no difference in rates of cardiac ischaemia, assessed by more detailed examination of cardiac enzyme elevations and electrocardiograms in a subset of VASST [15].…”

Safe Use of Vasopressin and Angiotensin II for Patients with Circulatory Shock

“…Animal studies have implicated AVP as causing myocardial ischemia due to its coronary vasoconstriction . However, clinical studies did not show a difference in rates of myocardial infarction with AVP use, 9 and a post hoc analysis of VASST found no difference in troponin or electrocardiogram changes between patients who received AVP compared with those who received NE . Notably, though, patients with unstable coronary syndromes and those with underlying symptomatic heart failure were excluded from VASST.…”

“…17 However, clinical studies did not show a difference in rates of myocardial infarction with AVP use, 9 and a post hoc analysis of VASST found no difference in troponin or electrocardiogram changes between patients who received AVP compared with those who received NE. 18 Notably, though, patients with unstable coronary syndromes and those with underlying symptomatic heart failure were excluded from VASST. Overall, data indicating AVP reduces cardiac function or causes clinically significant bradycardia in patients with vasodilatory shock are refuted by higher quality studies.…”

Protocol for a randomised controlled trial of VAsopressin versus Noradrenaline as Initial therapy in Septic sHock (VANISH)

“…Importantly, vasopressin infusion in septic shock appeared safe. The overall serious adverse event (SAE) rate was the same in the vasopressin and noradrenaline groups (10.3% and 10.5%, respectively), and there was no difference in specific adverse events (AEs) including myocardial ischaemia19 or cardiac output 20. However, in the predefined stratum of less severe shock, there was a reduced mortality in the vasopressin group compared with the noradrenaline group (26.5% vs 35.7% 28-day mortality, respectively, p=0.05).…”