Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study

doi:10.1378/chest.15-0959

Chest

Volume 149, Issue 1, January 2016, Pages 74-83

Contents of this study were presented at the ATS International Conference, May 15-20, 2015, Denver, CO.

https://doi.org/10.1378/chest.15-0959 Get rights and content

Background

Atrial fibrillation (AF) during sepsis is associated with increased morbidity and mortality, but practice patterns and outcomes associated with rate- and rhythm-targeted treatments for AF during sepsis are unclear.

Methods

This was a retrospective cohort study using enhanced billing data from approximately 20% of United States hospitals. We identified factors associated with IV AF treatments (β-blockers [BBs], calcium channel blockers [CCBs], digoxin, or amiodarone) during sepsis. We used propensity score matching and instrumental variable approaches to compare mortality between AF treatments.

Results

Among 39,693 patients with AF during sepsis, mean age was 77 ± 11 years, 49% were women, and 76% were white. CCBs were the most commonly selected initial AF treatment during sepsis (14,202 patients [36%]), followed by BBs (11,290 [28%]), digoxin (7,937 [20%]), and amiodarone (6,264 [16%]). Initial AF treatment selection differed according to geographic location, hospital teaching status, and physician specialty. In propensity-matched analyses, BBs were associated with lower hospital mortality when compared with CCBs (n = 18,720; relative risk [RR], 0.92; 95% CI, 0.86-0.97), digoxin (n = 13,994; RR, 0.79; 95% CI, 0.75-0.85), and amiodarone (n = 5,378; RR, 0.64; 95% CI, 0.61-0.69). Instrumental variable analysis showed similar results (adjusted RR fifth quintile vs first quintile of hospital BB use rate, 0.67; 95% CI, 0.58-0.79). Results were similar among subgroups with new-onset or preexisting AF, heart failure, vasopressor-dependent shock, or hypertension.

Conclusions

Although CCBs were the most frequently used IV medications for AF during sepsis, BBs were associated with superior clinical outcomes in all subgroups analyzed. Our findings provide rationale for clinical trials comparing the effectiveness of AF rate- and rhythm-targeted treatments during sepsis.

Section snippets

Sepsis Cases

We identified a cohort of adult patients (aged ≥ 18 years) from an enhanced administrative database (Premier, Inc) with an initial sepsis hospitalization during the years 2010 to 2013. Patients included in Premier represent approximately 20% of hospitalized patients in nonfederal hospitals in the United States (see e-Appendix 1 for further details). Patients admitted with sepsis were identified through use of high positive predictive value (> 90%)¹⁸ explicit sepsis International Classification

Sepsis Cohort

Among 541,144 patients hospitalized with sepsis, we identified 113,511 (21%) with both sepsis and AF. Most patients with AF and sepsis (59,845 [60%]) did not receive IV therapy. We analyzed 39,693 patients with AF and sepsis (35%) who received IV rate- or rhythm-control AF treatment (Fig 1). Patients with sepsis and AF were 77 ± 11 years of age, 49% were women, and 76% were white. Among patients who received IV AF treatment during sepsis, CCBs were the most frequently used initial medications

Discussion

We examined practice patterns and outcomes associated with initial choice of IV therapy for rate or rhythm control in AF that occurred during sepsis. Although CCBs were the most commonly administered IV AF medication class during sepsis, selection of initial AF medications varied widely. After matching on observed patient characteristics, BB use during AF was associated with improved hospital mortality as compared with CCBs, digoxin, or amiodarone. Our findings did not show significant effect

Acknowledgments

Author contributions: A. J. W. takes responsibility for the content of the manuscript, including data and analysis. A. J. W. contributed to study conception, design, interpretation of the data, and drafting of the manuscript; S. R. E. and M. R. W. contributed to data analysis, interpretation, and editing of manuscript for intellectual content; E. J. B. contributed to study design, interpretation, and editing of manuscript for important intellectual content.

Financial/nonfiancial disclosures:

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Cited by (59)

Management of new onset atrial fibrillation in critically unwell adult patients: a systematic review and narrative synthesis
2022, British Journal of Anaesthesia
Citation Excerpt :
In observational studies, diltiazem was more effective than metoprolol at achieving HR control, defined as HR <110 beats min−1 (42/55 [73%] vs 35/66 [53%]).47 Three observational studies reported outcomes for digoxin.35,42,44 Only Liu and colleagues42 reported outcomes for rates of cardioversion to SR with an efficacy of 15/27 (55.6%).
New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients.
Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, β-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported.
Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by β-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting β-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001).
There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and β-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies.
PROSPERO CRD42019121739.
Comparative effectiveness of common treatments for new-onset atrial fibrillation within the ICU: Accounting for physiological status
2022, Journal of Critical Care
New-onset atrial fibrillation (NOAF) is common in patients on an intensive care unit (ICU). Evidence guiding treatments is limited, though recent reports suggest beta blocker (BB) therapy is associated with reduced mortality.
We conducted a multicentre cohort study of adult patients admitted to 3 ICUs in the UK and 5 ICUs in the USA. We analysed the haemodynamic changes associated with NOAF. We analysed rate control, rhythm control, and hospital mortality associated with common NOAF treatments. We balanced admission and post-NOAF, pre-treatment covariates across treatment groups.
NOAF was followed by a systolic blood pressure reduction of 5 mmHg (p < 0.001). After adjustment, digoxin therapy was associated with inferior rate control versus amiodarone (adjusted hazard ratio (aHR) 0.56, [95% CI 0.34–0.92]). Calcium channel blocker (CCB) therapy was associated with inferior rhythm control versus amiodarone (aHR 0.59 (0.37–0.92). No difference was detected between BBs and amiodarone in rate control (aHR 1.15 [0.91–1.46]), rhythm control (aHR 0.85, [0.69–1.05]), or hospital mortality (aHR 1.03 [0.53–2.03]).
NOAF in ICU patients is followed by decreases in blood pressure. BBs and amiodarone are associated with similar cardiovascular control and appear superior to digoxin and CCBs. Accounting for key confounders removes previously reported mortality benefits associated with BB treatment.
Impact of rate control in hospitalized patients with atrial fibrillation and sepsis
2021, European Journal of Internal Medicine
Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials
2021, Chest
Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation.
Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation?
This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock ≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models.
Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95% CI, 0.54-0.85; P < .001). Unimportant heterogeneity was observed (I² = 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2% and 5.5, respectively.
The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality.
UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm;
Management of Ventricular Heart Rate in Atrial Fibrillation Patients With Sepsis
2021, Chest
Comparative Effectiveness of Heart Rate Control Medications for the Treatment of Sepsis-Associated Atrial Fibrillation
2021, Chest
Atrial fibrillation (AF) with rapid ventricular response frequently complicates the management of critically ill patients with sepsis and may necessitate the initiation of medication to avoid hemodynamic compromise. However, the optimal medication to achieve rate control for AF with rapid ventricular response in sepsis is unclear.
What is the comparative effectiveness of frequently used AF medications (β-blockers, calcium channel blockers, amiodarone, and digoxin) on heart rate (HR) reduction among critically ill patients with sepsis and AF with rapid ventricular response?
We conducted a multicenter retrospective cohort study among patients with sepsis and AF with rapid ventricular response (HR > 110 beats/min). We compared the rate control effectiveness of β-blockers to calcium channel blockers, amiodarone, and digoxin using multivariate-adjusted, time-varying exposures in competing risk models (for death and addition of another AF medication), adjusting for fixed and time-varying confounders.
Among 666 included patients, 50.6% initially received amiodarone, 10.1% received a β-blocker, 33.8% received a calcium channel blocker, and 5.6% received digoxin. The adjusted hazard ratio for HR of < 110 beats/min by 1 h was 0.50 (95% CI, 0.34-0.74) for amiodarone vs β-blocker, 0.37 (95% CI, 0.18-0.77) for digoxin vs β-blocker, and 0.75 (95% CI, 0.51-1.11) for calcium channel blocker vs β-blocker. By 6 h, the adjusted hazard ratio for HR < 110 beats/min was 0.67 (95% CI, 0.47-0.97) for amiodarone vs β-blocker, 0.60 (95% CI, 0.36-1.004) for digoxin vs β-blocker, and 1.03 (95% CI, 0.71-1.49) for calcium channel blocker vs β-blocker.
In a large cohort of patients with sepsis and AF with rapid ventricular response, a β-blocker treatment strategy was associated with improved HR control at 1 h, but generally similar HR control at 6 h compared with amiodarone, calcium channel blocker, or digoxin.

View all citing articles on Scopus

: FUNDING/SUPPORT: This study was supported by the National Institutes of Health [Grants K01HL116768 (A. J. W.) and 2R01HL092577 (E. J. B.)].

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Chest

Original Research: Critical CarePractice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study

Background

Methods

Results

Conclusions

Section snippets

Sepsis Cases

Sepsis Cohort

Discussion

Acknowledgments

Am Heart J

J Am Coll Cardiol

J Crit Care

Chest

J Am Coll Cardiol

J Am Coll Cardiol

Am Heart J

Am J Cardiol

Am J Cardiol

Int J Cardiol

J Am Coll Cardiol

Am Heart J

Trends in sepsis and infection sources in the United States. A population-based study

Ann Am Thorac Soc

Hospital deaths in patients with sepsis from 2 independent cohorts

JAMA

Incidence and prognosis of sustained arrhythmias in critically ill patients

Am J Respir Crit Care Med

Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis

JAMA

Paroxysmal atrial fibrillation in critically ill patients with sepsis

J Intensive Care Med

Supraventricular arrhythmias in intensive care unit patients: short and long-term consequences

Anesth Analg

Effectiveness of direct-current cardioversion for treatment of supraventricular tachyarrhythmias, in particular atrial fibrillation, in surgical intensive care patients

Crit Care Med

Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias

Crit Care Med

Original Research: Critical Care
Practice Patterns and Outcomes of Treatments for Atrial Fibrillation During Sepsis: A Propensity-Matched Cohort Study