Clinical PaperProphylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management☆
Introduction
Targeted temperature management (TTM) as an element of post-resuscitation cardiac arrest care has been associated with improvements in post-discharge neurological function, favorable discharge disposition, and reduced mortality.1, 2, 3, 4 Despite widespread adoption of TTM in this patient population, our understanding of its complications and their impact on clinical outcomes has been slow to evolve.5, 6, 7, 8, 9, 10
Infections, especially early-onset pneumonia, are common complications after cardiac arrest, with or without TTM, though temperature management is believed to exacerbate this problem.11, 12, 13, 14, 15, 16 A two-center study focusing on early-onset pneumonia reported an incidence of 65% among cardiac arrest survivors, many of whom were treated with TTM.17 A more recent multicenter randomized study of TTM after cardiac arrest reported pneumonia occurred in 52% of patients treated at 33 °C and 46% of patients at 36 °C (p = 0.09).18 The incidence of pneumonia during TTM after cardiac arrest exceeds the 9–27% incidence in the general medical–surgical critical care population.19
Prophylactic antibiotics (PRO) have been shown to reduce the incidence of early-onset pneumonia among comatose patients requiring intubation by up to 64% but there are no prospective studies evaluating the effect of PRO on pneumonia incidence or functional outcome in cardiac arrest survivors treated with TTM.20, 21 The objective of this study was to determine if PRO were associated with a lower incidence of pneumonia and improved functional outcome compared to no prophylactic antibiotics (no-PRO) by retrospectively examining the Northern Hypothermia Network registry and to establish effect size to design a prospective randomized trial.
Section snippets
Methods
This retrospective cohort study examined data from the Northern Hypothermia Network, a multinational, web-based registry of post-resuscitation cardiac arrest care with contributions from 38 hospitals in the United States and Europe (Denmark, Germany, Iceland, Luxembourg, Norway, and Sweden). Forty-five percent of the centers were University hospitals, which contributed 73% of the patients. Local institutional review boards approved patient participation, and when required, the national data
Results
Data from 1240 patients were evaluated (Table 1). Patients were 61.0 (±15.8) years of age and predominantly male (71.9%). Patients were treated to target temperatures of 32 °C (n = 73, 5.9%), 33 °C (n = 1061, 85.8%), or 34 °C (n = 103, 8.3%). Maintenance of the target temperature was accomplished with surface cooling in 80% of patients. Serious infection information was available for 1206 (97.3%) patients. Pneumonia was the most common infection which occurred in 40.4% of patients.
Antibiotics were
Discussion
This analysis of a large, multinational registry of cardiac arrest survivors managed with TTM at 32–34 °C demonstrated that patients treated with PRO had less pneumonia, less sepsis, and fewer serious infections, but a similar ICU LOS and incidence of good functional outcome when compared to those who did not receive PRO. In the multivariable models, PRO were independently associated with a lower incidence of pneumonia but were not associated with good functional outcome.
TTM is promising therapy
Conclusions
This large, retrospective study of cardiac arrest survivors treated with TTM to 32–34 °C identified that antibiotic prophylaxis was associated with a 4-fold decrease in the incidence of pneumonia, but not with improved functional outcome. These findings warrant further validation and exploration in a prospective, randomized study.
Conflicts of Interest
No financial support was provided to complete this work.
Kjetil Sunde, MD, PhD has received travel fees and honoraria from Bard Medical. Niklas Nielsen, MD, PhD has received funding for lectures from Bard Medical. Sten Rubertsson, MD, PhD is a consultant for Physiocontrol. For the remaining authors, no conflicts were declared.
Acknowledgements
The Northern Hypothermia Network was supported, in part, by the Scandinavian Critical Care Trials Group and the Scandinavian Society of Anesthesiology and Intensive Care, the Stig and Ragna Gorthon Foundation, the Torsten Birger Segerfalk Foundation, the Laerdal Foundation, the Gyllenstierna Krapperup Foundation (Nyhamnslage, Sweden), and the Skåne County Council's research and development foundation.
References (39)
- et al.
Infectious complications in survivors of cardiac arrest admitted to the medical intensive care unit
Resuscitation
(2004) - et al.
Factors associated with pneumonia in post-cardiac arrest patients receiving therapeutic hypothermia
Am J Emerg Med
(2014) - et al.
Recommended guidelines for reviewing, reporting, and conducting research on post-resuscitation care: the Utstein style
Resuscitation
(2005) - et al.
Assessment of outcome after severe brain damage
Lancet
(1975) - et al.
An appraisal of multivariable logistic models in the pulmonary and critical care literature
Chest
(2003) - et al.
Why do patients who have acute lung injury/acute respiratory distress syndrome die from multiple organ dysfunction syndrome? Implications for management
Clin Chest Med
(2006) - et al.
Epidemiology and outcomes of ventilator-associated pneumonia in a large US database
Chest
(2002) - et al.
Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Circulation
(2010) - et al.
Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation
Circulation
(2003) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest
N Engl J Med
(2002)
Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia
N Engl J Med
Assessment of adverse events and predictors of neurological recovery after therapeutic hypothermia
Ann Pharmacother
Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia
Crit Care Med
Managing the complications of mild therapeutic hypothermia in the cardiac arrest patient
J Intensive Care Med
Surface cooling after cardiac arrest: effectiveness, skin safety, and adverse events in routine clinical practice
Neurocrit Care
Main complications of mild induced hypothermia after cardiac arrest: a review article
J Cardiovasc Thorac Res
Safety profile and outcome of mild therapeutic hypothermia in patients following cardiac arrest: systematic review and meta-analysis
Emerg Med J
Infectious complications in out-of-hospital cardiac arrest patients in the therapeutic hypothermia era
Crit Care Med
Infections in the survivors of out-of-hospital cardiac arrest in the first 7 days
Intensive Care Med
Cited by (45)
Microbiological profile of nosocomial infections following cardiac arrest: Insights from the targeted temperature management (TTM) trial
2020, ResuscitationCitation Excerpt :In a systematic review, prophylaxis with an SDD regime has been shown to reduce nosocomial infections.20 Specifically in the group of cardiac arrest patients, prophylaxis was found to reduce the incidence of early pneumonia.11 This finding was partly confirmed in a prospective randomized pilot trial of 83 patients with cardiac arrest, in which prophylactic versus clinically driven antibiotics decreased the rate of positive cultures from the lower respiratory tract, although outcomes did not improve.5
About prevention of early ventilator-associated pneumonia after cardiac arrest
2020, Anaesthesia Critical Care and Pain MedicineFunctional outcomes associated with varying levels of targeted temperature management after out-of-hospital cardiac arrest — An INTCAR2 registry analysis
2020, ResuscitationCitation Excerpt :The overall incidence of adverse events was low in both groups, however pneumonia was the more common and occurred with similar frequency in both temperature groups. The high incidence of pneumonia during post-cardiac arrest care is described in other OHCA cohorts.3,27,28 More TTM-low patients had TTM discontinued due to hemodynamic instability, and the rate of TTM discontinuation in our study was higher than reported in the TTM-trial.3
Prophylactic antibiotic use following cardiac arrest: A systematic review and meta-analysis
2019, ResuscitationCitation Excerpt :The substantial heterogeneity (I2 = 61%) was driven by differences between the two randomised controlled trials, rather than differences between study design. Kim et al. and Gagnon et al. reported only median and interquartile range, so could not be included in the meta-analysis.22,24 However, in line with the results of the meta-analysis, these studies reported no difference between the control and intervention group.
A systematic review of safety and adverse effects in the practice of therapeutic hypothermia
2018, American Journal of Emergency Medicine
- ☆
These data were presented in part as an abstract at the 2014 Neurocritical Care Society Annual Meeting from September 11–14, 2014.