a b s t r a c t

Background: electrical cardioversion (ECV) is the recommended treatment for atrial fibrillation (AFib) in critically ill patients, despite lacking data showing hemodynamic benefits of restoring sinus rhythm in this setting. The aim of this study was to assess the hemodynamic effect of successful ECV in a cohort of hemodynamically unstable critically ill patients.

Methods and results: This study included 66 successful ECV performed in hemodynamically unstable critically ill patients with new-onset AFib. The primary outcome was the requirement of norepinephrine and inotropes 6 h after successful ECV in relation to baseline. Baseline norepinephrine dose was 0.19 +- 0.02 ug/kg/min, and 67% of patients were treated with positive inotropic drugs. Six hours after ECV, 33 patients (50%) were considered he- modynamic non-responders. Overall, the mean norepinephrine dose at 6 h was 0.17 +- 0.02 ug/kg/min (P = 0.051 compared to baseline) and 61% of patients were on inotropes (P = 0.13 compared to baseline). During the 6-hour period after ECV the mean norepinephrine dose temporary increased to 0.20 +- 0.02 ug/kg/min (P = 0.033 compared to baseline).

Conclusions: ECV is associated with a large proportion of hemodynamic non-responders and a numerically mod- est, non-significant Hemodynamic improvement in critically ill patients with new-onset AFib.

(C) 2020

Introduction

The management atrial fibrillation (AFib) in critically ill patients is particularly challenging for several reasons [1]. First, patients with AFib are in general more severely ill and have a higher burden of comor- bidities compared to patients in sinus rhythm. AFib has an additional detrimental impact of in-hospital and post-discharge survival rates of these patients [2,3]. Second, therapeutic options to tackle arrhythmia are limited and most Pharmacologic options are not recommended by current guidelines [4]. Accordingly, the recommended treatment for AFib and other forms of supraventricular tachycardia consists mostly of electrical cardioversion (ECV) in patients with hemodynamical insta- bility [4].

The rationale for those recommendations resides in the assumption that restoration of sinus rhythm rapidly eliminates the deleterious

* Corresponding author at: Cardiac Care Unit, Department of Cardiology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

E-mail addresses: [email protected] (M. Arrigo), [email protected] (A. Mebazaa), [email protected] (D. Bettex), [email protected] (A. Rudiger).

effects of tachycardia and atrioventricular dissociation on left- ventricular filling which may restore hemodynamic stability. However, data supporting these assumptions are lacking in critically ill patients. The aim of this study was to assess the hemodynamic effect of successful ECV in a cohort of hemodynamically unstable critically ill patients.

Methods

This study was performed in the cardiosurgical ICU at the University Hospital Zurich, Switzerland. A detailed description of the study design has been previously published [5]. Briefly, consecutive patients with new-onset AFib treated by ECV were included. The original cohort in- cluded 144 ECV. For the purpose of this study, we excluded unsuccessful ECV (N = 42) and those performed in Hemodynamically stable patients (N = 36). Unsuccessful ECV was pre-specified as failure to achieve a conversion into sinus rhythm for at least 30 s. Hemodynamic instability was pre-specified as noradrenaline requirements greater than or equal to 0.1 ug/kg/min or a need for positive inotropic drug [5].

The primary outcome of this study was the requirement of norepi- nephrine and inotropes 6 h after successful ECV in relation to baseline. Secondary outcome was the maximum dose of norepinephrine during

https://doi.org/10.1016/j.ajem.2020.02.027

0735-6757/(C) 2020

M. Arrigo et al. / American Journal of Emergency Medicine 38 (2020) 1192–1194 1193

Table 1

Baseline characteristics of the study population.

Legend: BMI body mass index, SAPS Simplified Acute Physiology Score, SvO₂ mixed-venous or Central venous oxygen saturation. Respiratory failure was defined as a need for mechanical ventilation. Renal failure was defined as serum creatinine greater than or equal to 200 umol/L or a need for renal replacement therapy.

the 6-hour period after ECV. Patients not achieving a reduction in the norepinephrine dose or a weaning from inotropes at 6 h after ECV were considered hemodynamic non-responders.

The study was performed in accordance with Good Clinical Practice and the Declaration of Helsinki 2002, approved by the local ethical com- mittee (KEK-ZH 2014-0389). Due to the nature of the study, patient’s in- formed consent was waived by the ethical committee.

Values are given as mean +- SEM, median (quartiles) or percentage, as appropriate. Noradrenaline doses before and after ECV were com- pared with the related samples Wilcoxon Signed Rank Test, the use of inotropes before and after ECV with the McNemar test. Independent groups were compared with the Mann-Whitney U test or the Fisher’s exact test, as appropriate. Missing values of patients that died during follow-up (n = 3) were replaced by the last recorded value (carrying forward) to reduce bias. The null hypothesis was rejected with a two- sided P-value b 0.05. All analyses were performed with the use of IBM SPSS Statistics, version 25 (IBM, Armonk, NY).

Results

The study population for this study consisted of 66 successful ECV performed in hemodynamically unstable patients for new-onset AFib. Baseline characteristics summarized in Table 1 indicate a relevant bur- den of organ dysfunction. Median length of ICU stay was 14 days (7-24 days), ICU survival was 79%. Baseline norepinephrine dose was

0.19 +- 0.02 ug/kg/min, and 67% of patients were treated with positive inotropic drugs. Six hours after ECV, 33 patients (50%) were considered hemodynamic non-responders. Overall, the mean norepinephrine dose at 6 h was 0.17 +- 0.02 ug/kg/min (P = 0.051 compared to baseline) and 61% of patients were on inotropes (P = 0.13 compared to baseline). During the 6-hour period after ECV the mean norepinephrine dose tem- porary increased to 0.20 +- 0.02 ug/kg/min (P = 0.033 compared to baseline), Fig. 1.

No significant difference in organ dysfunction, anemia, inflamma- tion and other parameters of disease severity was found between he- modynamic responders and non-responders, Table 1. No significant

difference in the median interval between AFib onset and ECV was found between hemodynamic responders and non-responders (195 min vs. 165 min, P = 0.62). AFib relapse at 6 h was observed in 51% of the patients despite the use of amiodarone pre- and post- treatment in 61% and 39% of the ECV, respectively. No significant differ- ence in AFib relapse was observed between hemodynamic responders and non-responders (48% vs. 53%, P = 0.8).

Discussion

Our study shows a large proportion of hemodynamic non- responders and a numerically modest, statistically non-significant he- modynamic improvement associated with ECV in hemodynamically un- stable patients with new-onset AFib. Despite a single-arm study design, our data suggest that while in some critically ill patients, hemodynamic instability is induced by AFib, in a relevant proportion of cases hemody- namic instability and AFib are concomitantly present with marginal – if any – contribution of AFib to the Hemodynamic compromise. The

P = 0.051

P < 0.001

P = 0.033

0.25

0.20

Norepinephrine, ug/kg/min

0.15

0.10

0.05

0.00

Baseline Peak after ECV 6 hours after ECV

Fig. 1. Norepinephrine use before and after electrical cardioversion.

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distinction between the two groups is of paramount importance since the latter group is unlikely to benefit from any antiarrhythmic treat- ment, including ECV, but maybe erroneously exposed to harm such as sedation, hypotension and in non-intubated patients, hypoventilation, hypoxia, and aspiration. Further, the administration of Antiarrhythmic drugs may (further) impair inotropy and reduce stroke volume, wors- ening hemodynamic compromise. Even more notably – but very fre- quently neglected – conversion in sinus rhythm may precipitate hemodynamic instability and induce a profound low-cardiac output state. This is particularly true in patients with pre-existing cardiomyop- athy with severely reduced left ventricular ejection fraction. In these pa- tients, ECV immediately induces a reduction of the heart rate with limited – if any – possibility for an early compensatory increase in stroke volume due to the pre-existing cardiomyopathy. In addition, stunning of atrial cardiomyocytes after shock and electrical remodeling after a prolonged duration of AFib lead to insufficient atrial contraction and im- paired diastolic filling. Together, this results in an immediate net de- crease in cardiac output which may have a profound impact on hemodynamic parameters and organ perfusion. Our study showed a statistically relevant increase in the dose of norepinephrine during the post-ECV phase, that may reflect a short-term hemodynamic worsening induced by ECV. The expected positive effects induced by the restora- tion of sinus rhythm (i.e. atrioventricular synchrony, reverse remodel- ing) will occur at a later stage with no benefit in the first hours after ECV. Finally, the recommendations proposed by the guidelines assume a high efficacy of ECV to restore sinus rhythm. While the immediate res- toration of sinus rhythm may be achieved in ~90% of elective, ambula- tory patients using the optimal technique, the immediate success rate in critically ill patients is significantly lower (~70%), as previously showed by our group [5]. Several strategies to improve immediate suc- cess have been proposed but none of them has been adequately tested prospectively. Furthermore, recurrence of AFib is very frequent in criti- cally ill patients, with relapse rates N50% at 6 h, as shown by this study.

In conclusion, a reappraisal of the management of AFib in critically ill patients is warranted. We advocate a more restrictive use of antiar- rhythmic drugs and ECV in patients with hemodynamic instability, in particular in those patients in whom the causal role of arrhythmia in generating instability is unlikely. Patient history, physical examination, and echocardiography should be carefully considered in addition to he- modynamic parameters when considering ECV in this context. Further studies should address the open points and investigate which patients would benefit most from ECV, since our study could not show any dif- ference in baseline characteristics that may be used to identify hemody- namic responders of ECV. In the meantime, harm derived from unnecessary procedures should be avoided.

CRediT authorship contribution statement

Mattia Arrigo: Conceptualization, Formal analysis, Investigation, Writing – original draft. Alexandre Mebazaa: Conceptualization, Writ- ing – review & editing. Dominique Bettex: Investigation, Writing – re- view & editing. Alain Rudiger: Conceptualization, Investigation, Writing – review & editing.

References

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