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Headline
New-onset atrial fibrillation in ICU patients is associated with poor outcomes and, although evidence for its management is limited, beta-blockers and amiodarone appear similarly effective, and superior to digoxin and calcium-channel blockers.
Abstract
Background:
New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care.
Objectives:
In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation.
Methods:
We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK.
Results:
Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses.
Conclusions:
Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior.
Future work:
Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken.
Trial registration:
Current Controlled Trials ISRCTN13252515.
Funding:
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.
Contents
- Plain English summary
- Scientific summary
- Chapter 1. Background
- Chapter 2. Scoping review of treatments for new-onset atrial fibrillation
- Chapter 3. Database analysis part 1: RISK-II database
- Chapter 4. Database analysis part 2: intensive care unit databases
- Chapter 5. Expert panel
- Chapter 6. Discussion
- Chapter 7. Conclusions
- Acknowledgements
- References
- Appendix 1. Search strategy
- Appendix 2. Risk-of-bias assessment
- Appendix 3. Data extraction tables for single-group studies
- Appendix 4. Excluded studies
- Appendix 5. RISK-II supplementary material
- Appendix 6. Intensive care unit databases supplementary material
- Appendix 7. Critical Care Health Informatics Collaborative database analysis
- Appendix 8. Expert panel details
- List of abbreviations
About the Series
Declared competing interests of authors: Peter Watkinson worked part time for Sensyne Health (Oxford, UK); has received grant funding from the National Institute for Health Research (NIHR) and Sensyne Health outside the submitted work; was a member of the Health Technology Assessment (HTA) Elective and Emergency Specialist Care (EESC) Methods Group (2014–17), HTA EESC Panel (2013–18), HTA Prioritisation Committee B (in hospital) (2018–19) and NIHR Invention for Innovation (i4i) Programme for Product Development Awards Committee (2018 to present); and is supported by the NIHR Biomedical Research Centre, Oxford. Kathryn Rowan was a member of the Department of Health and Social Care/UK Research and Innovation COVID-19 Rapid Response Research Initiative and the College of Experts 2020, and was a Health Services and Delivery Research (HSDR) Programme Funding Committee Member (2014–19), HSDR Rapid Service Evaluation Themed Call Committee Member (2017), HSDR Commissioned Board Member (2016) and HTA Trauma Themed Call Board Member (2007–8). Duncan Young received a salary from the University of Oxford (Oxford, UK) during the duration of the work. Jonathan Bedford is funded by an award to the University of Oxford, NIHR Doctoral Research Fellowship 300224.
Article history
The research reported in this issue of the journal was funded by the HTA programme as project number 17/71/04. The contractual start date was in February 2019. The draft report began editorial review in December 2020 and was accepted for publication in April 2021. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.
Last reviewed: December 2020; Accepted: April 2021.
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