Elsevier

Resuscitation

Volume 89, April 2015, Pages 36-42
Resuscitation

Clinical Paper
Sinus bradycardia during hypothermia in comatose survivors of out-of-hospital cardiac arrest – A new early marker of favorable outcome?

https://doi.org/10.1016/j.resuscitation.2014.12.031Get rights and content

Abstract

Background

Bradycardia is a common finding in patients undergoing therapeutic hypothermia (TH) following out-of-hospital cardiac arrest (OHCA), presumably as a normal physiological response to low body temperature. We hypothesized that a normal physiological response with sinus bradycardia (SB) indicates less neurological damage and therefore would be associated with lower mortality.

Methods

We studied 234 consecutive comatose survivors of OHCA with presumed cardiac etiology and shockable primary rhythm, who underwent a full 24-h TH-protocol (33 °C) at a tertiary heart center (years: 2004–2010). Primary endpoint was 180-day mortality; secondary endpoint was favorable neurological outcome (180-day cerebral performance category: 1–2).

Results

SB, defined as sinus rhythm <50 beats per minute during TH, was present in 115 (49%) patients. Baseline characteristics including sex, witnessed arrest, bystander cardiopulmonary resuscitation and time to return of spontaneous circulation were not different between SB- and no-SB patients. However, SB-patients were younger, 57 ± 14 vs. 63 ± 14 years, p < 0.001 and less frequently had known heart failure (7% vs. 20%, p < 0.01).

Patients experiencing SB during the hypothermia phase of TH had a 17% 180-day mortality rate compared to 38% in no-SB patients (p < 0.001), corresponding to a 180-day hazard ratio (HRadjusted = 0.45 (0.23–0.88, p = 0.02)) in the multivariable analysis. Similarly, SB during hypothermia was directly associated with lower odds of unfavorable neurological outcome (ORunadjusted = 0.42 (0.23–0.75, p < 0.01).

Conclusion

Sinus bradycardia during therapeutic hypothermia is independently associated with a lower 180-day mortality rate and may thus be a novel, early marker of favorable outcome in comatose survivors of OHCA.

Introduction

Therapeutic hypothermia (TH) is widely used and has been supported by guidelines as a neuro-protective treatment strategy in comatose survivors of out-of-hospital cardiac arrest (OHCA) for more than a decade.1, 2

It is recognized that the main cause of short-term mortality in comatose OHCA patients is extensive anoxic neurological injury.3 Early cerebral prognostication is challenging, especially in the era of TH, where prognostic tools are useful only 72 h after normothermia is obtained.3, 4 Initial shockable rhythm, witnessed arrest, bystander cardiopulmonary resuscitation (CPR) and shorter time to return of spontaneous circulation (ROSC) are known pre-hospital factors associated with favorable outcome, however the accuracy of these circumstances is often uncertain and provide only little prognostic value on the individual level.4 Early markers of favorable outcome during the post-resuscitation care could be useful in providing information to relatives in the days following the arrest and potentially to guide clinical decision making, prioritizing intensive care resources to the benefit of patients with good chances of recovery and to avoid futile treatment in cases where a permanent vegetative state can be expected.

While the initial rhythm, shockable vs. non-shockable, is an important prognostic factor5 also heart rate and cardiac rhythms during the post-resuscitation care may provide prognostic information. Heart rate is known to be of significant prognostic importance in both the general population, patients with known ischemic heart disease, hypertension and heart failure, however the prognostic implications of heart rate in acute circumstances e.g. in OHCA patients during and after TH remains to be established.6, 7

We hypothesized that a normal physiological response to hypothermia by developing sinus bradycardia (SB) <50 beats per minute (bpm) would be associated with lower mortality as a sign of less neurological damage. We assessed the prevalence of SB during hypothermia and its association to outcome in comatose survivors of OHCA and report the prevalence of common cardiac rhythms throughout the post-resuscitation care.

Section snippets

Materials and methods

We retrospectively enrolled consecutive comatose survivors of OHCA with presumed cardiac etiology admitted to a single tertiary heart center in Denmark between 1st June 2004 and 31st October 2010, after the local implementation of TH. The Capital Region of Denmark covers approximately 1.9 million citizens; of those nearly 600.000 live in central Copenhagen. Patients admitted after OHCA to Copenhagen University Hospital, Rigshospitalet were patients suffering cardiac arrest in central Copenhagen

Results

Of 403 consecutive comatose survivors of OHCA with suspected cardiac etiology, 270 (67%) patients underwent a full 24-h TH-protocol, the majority of whom were resuscitated from a shockable initial rhythm (n = 234, 87%), defining the study population (Fig. 1). Incident SB was present in 115 (49%) patients during the hypothermia phase. Patients experiencing SB were younger (57 ± 14 vs. 63 ± 14 years, p < 0.001) and fewer had pre-existing congestive heart failure (20% vs. 7%, p < 0.01) compared to patients

Discussion

Incident SB during TH is associated with a lower mortality rate. Development of SB during hypothermia is a normal physiological response to lowering of the body temperature, and SB may thus be a useful marker of less severe anoxic brain injury and thereby a good prognosis. These findings may provide useful information and early identification of patients with a favorable outcome, if confirmed in future studies.

In this consecutive cohort of comatose OHCA patients with shockable rhythm, the

Limitations

Due to the observational nature of this study, a causal relation of SB and a lower mortality rate cannot be proven. Data on prescription medicine, including heart rate modulating drugs such as β-blockers, were not available for analysis. However baseline characteristics with an indication for beta-blockers such as hypertension and ischemic heart disease did not differ between SB- and no-SB patients and congestive heart failure was more prevalent in no-SB patients. When including these

Conclusion

Sinus bradycardia during TH is independently associated with lower 180-day mortality in a large cohort of consecutive comatose survivors of out-of-hospital cardiac arrest. Sinus bradycardia or lower heart rates during TH may be a novel, very early marker of favorable outcome in comatose survivors of OHCA.

Funding sources

The Interreg IVA ØKS program supported the study as part of the grant for establishing the Center for Resuscitation Science in the Oresund Region (NYPS ID: 167157), including author JHT, CH, HS, NN and JK. The Danish Heart Foundation supported the study as part of a grant for co-funding of the Center for Resuscitation Science in the Oresund Region (see above), grant no: 13-04-R94-A4516-22755 and supported the study as part of grant for author JHT's salary in his Ph.D. study (grant no:

Conflict of interest statement

The authors state no other conflict of interests.

References (21)

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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.12.031.

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