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Canadian Journal of Cardiology

Arrhythmic Events and Mortality in Patients With Cardiogenic Shock on Inotropic Support: Results of the DOREMI Randomized Trial

Published:September 20, 2022DOI:https://doi.org/10.1016/j.cjca.2022.09.013

      Abstract

      Background

      Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias.

      Methods

      The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes.

      Results

      Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality.

      Conclusions

      Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events.

      Résumé

      Contexte

      Le soutien inotrope est couramment utilisé dans la prise en charge du choc cardiogénique (CC). Les données existantes au sujet de l’incidence et de la signification des épisodes d’arythmie chez les patients en choc cardiogénique sous soutien inotrope présentent un risque élevé de biais.

      Méthodologie

      Dans le cadre de l’essai à double insu DOREMI (Dobutamine Compared to Milrinone), les patients ont été répartis aléatoirement entre un groupe de traitement par dobutamine et un groupe de traitement par milrinone. Les patients ayant présenté des épisodes arythmiques (définis comme des arythmies ayant nécessité une intervention ou des arythmies ventriculaires soutenues) ont été comparés à des patients sans épisode arythmique afin de déterminer les facteurs associés à la survenue de ces épisodes et d’établir le lien avec la mortalité en milieu hospitalier et avec des issues secondaires.

      Résultats

      Quatre-vingt-douze patients (47,9 %) ont présenté des épisodes arythmiques, qui sont survenus autant dans le groupe traité par dobutamine que dans celui traité par milrinone (P = 0,563). La nécessité d’avoir recours à des vasopresseurs au moment d’amorcer le traitement par inotrope et des antécédents de fibrillation auriculaire étaient positivement corrélés aux épisodes arythmiques, alors qu’une dysfonction ventriculaire droite prédominante, des antécédents d’infarctus du myocarde et une fraction d’éjection du ventricule gauche plus élevée étaient négativement corrélés aux épisodes arythmiques. Les épisodes d’arythmie supraventriculaire n’étaient pas corrélés à la mortalité (risque relatif [RR] : 0,97; intervalle de confiance [IC] à 95 % : 0,68 à 1,40; P = 0,879), mais ils étaient corrélés positivement aux arrêts cardiaques ayant nécessité une réanimation et à la durée de l’hospitalisation. Les épisodes d’arythmie ventriculaire étaient positivement corrélés à la mortalité (RR : 1,66; IC à 95 % : 1,13 à 2,43; P = 0,026) et aux arrêts cardiaques ayant nécessité une réanimation. Les épisodes arythmiques étaient traités le plus souvent par amiodarone (97 %) et par cardioversion électrique (27 %), et ces traitements n’étaient pas corrélés à la mortalité.

      Conclusions

      Des épisodes arythmiques cliniquement pertinents surviennent chez environ la moitié des patients présentant un CC traités par dobutamine ou par milrinone, et ces épisodes sont associés à des issues cliniques défavorables. Cinq facteurs pourraient aider à cibler les patients les plus susceptibles de présenter des épisodes arythmiques.

      Graphical abstract

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      Linked Article

      • Inotropes and Arrhythmias: Are We Doing Harm or Guilt by Association?
        Canadian Journal of Cardiology
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          Inotropic agents are ubiquitous in the pharmacologic management of cardiogenic shock. The 2 most commonly used agents in North America are milrinone, a phosphodiesterase-3 inhibitor, and dobutamine, a predominately β-1 receptor agonist with mild β-2 and α-1 agonism.1-3 The use of these agents has been associated with increased incidence of arrhythmias, some of which may be caused by proarrhythmic effects of the agents themselves, but—equally—the arrhythmias may be a consequence of the underlying cardiac condition.
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