The acute respiratory distress syndrome (ARDS) is a heterogenous clinical syndrome characterized by lung injury related to a local or systemic insult leading to acute hypoxemia and radiographic opacities.
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Fifty-five years after ARDS was first described by Drs. Ashbaugh and Petty, clinicians and scientists are still working to fully elucidate its heterogenous pathophysiology, test specific therapeutics, identify clinical risk factors, and most importantly, prevent its development.2.
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A number of “traditional” ARDS risk factors have been identified, but cardiac arrest is not listed among them.Fifty Years of Research in ARDS.ARDS: How It All Began|American Journal of Respiratory and Critical Care Medicine [Internet]. [cited 2022 May 17]; Available from: https://www.atsjournals.org/doi/abs/10.1164/rccm.201706-1281ED.
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In this issue of Resuscitation, Shih and coauthors add to the growing literature highlighting that ARDS is common after cardiac arrest and may be associated with worse outcome.
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They present a retrospective cohort analysis of 203 patients who suffered in-hospital cardiac arrest (IHCA) from 2014 to 2018 and sustained return of spontaneous circulation. Key among their reported findings are the following: 72% developed ARDS within 3 days, and those with ARDS had fewer alive-and-ventilator free days and higher hospital mortality compared to those without, though these differences did not persist after adjustment with a multivariable model.A previous study conducted by our group demonstrated comparable findings in a cohort of out-of-hospital cardiac arrest (OHCA) patients.
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In 600 mechanically ventilated patients who suffered OHCA and survived for 48 hours, 50% developed ARDS. ARDS was associated with higher hospital mortality, longer ICU stay, more ventilator days, and lower incidence of neurological recovery. The lower incidence of ARDS in our study compared with Shih et al. likely reflects the underlying conditions that contribute to out-of-hospital versus in-hospital cardiac arrest, different time windows in which development of ARDS was evaluated, and the slightly discrepant definitions used in each study. Both studies clearly highlight that ARDS is a major problem in the post-arrest population that warrants further study.Patients who suffer cardiac arrest often have numerous “traditional” risk factors for ARDS, including aspiration, chest wall and lung parenchymal trauma, and pulmonary infection.
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It remains unknown, but plausible, whether ischemia and reperfusion following cardiac arrest may contribute, as it does in other conditions such as lung transplantation.8.
Some of these risk factors might represent specific clinical phenotypes that lead to opportunities for understanding pathophysiologic mechanisms and identification of therapeutic targets. For example, prophylactic antibiotics have been demonstrated to reduce the incidence of early-onset ventilator pneumonia after OHCA, a major risk factor for ARDS.9.
We posit that cardiac arrest should indeed be included among ARDS risk factors with the goal of raising awareness among clinicians and further highlighting important research gaps. In fact, given the multitude of potential insults, ARDS following cardiac arrest may even be more common than is seen with “traditional” ARDS risk factors.
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With the high prevalence of ARDS, one may reasonably ask whether all post-arrest patients should be managed with lung-protective ventilation. Ventilation with low tidal volumes, a proven strategy for ARDS with a 9% absolute mortality reduction, has been demonstrated to improve outcome after OHCA, but not IHCA, a discrepancy which merits further study.10.
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We believe clinicians should vigilantly monitor for the development of ARDS, however, widespread, prophylactic adoption of lung protective ventilation in these patients could result in more ventilator dysynchrony, more sedative exposure and greater hypercapnia, which could impact neurological prognostication and outcomes. Some data suggest, however, that mild permissive hypercapnia is beneficial after cardiac arrest; a definitive, phase 3 randomized trial just completed enrollment.13.
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, Eastwood GM, Schneider AG, Suzuki S, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation [Internet] 2016; Available from: http://linkinghub.elsevier.com/retrieve/pii/S0300957216300053.
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This study has limitations. It was conducted at a single center, has a limited sample size, and began enrolling patients in 2014. The relatively small number of patients enrolled likely limited the authors’ abilities to detect differences in their adjusted primary outcome, alive-and-ventilator free days. While the older data set raises some question about whether cutting-edge ARDS or cardiac arrest therapies were used, a more contemporary data set might be even more problematic as the COVID-19 pandemic has dramatically changed the epidemiology of both in-hospital cardiac arrest and ARDS.
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Much work remains. First, we must work to better understand the impact of ARDS on cardiac arrest outcomes. Extracerebral organ dysfunction remains a major contributor to morbidity and mortality and likely impacts decisions to provide or withdraw life sustaining therapy.
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Second, we must elucidate the pathophysiology of post-arrest ARDS, including disentangling the complex interplay between hydrostatic lung edema and endothelial and epithelial lung injury. Then, we must identify biological phenotypes and targets for pharmacologic interventions and other novel therapies.20.
Fourth, we must further develop strategies to prevent ARDS in this high-risk population. These may include novel approaches to airway decontamination, temporary mechanical circulatory support and selective perfusion, and cocktails aimed to mitigate the effects of ischemia–reperfusion injury. In closing, improving how we care for these fragile patients will require research and strategies to mitigate multiorgan injury balanced with the imperative to optimize neurological outcomes.Conflict of Interest Statement
The authors report no conflicts of interest.
NJJ receives funding for unrelated work from the US National Institutes of Health, the US Centers for Disease Control and Prevention, the US Department of Defense, and University of Washington Royalty Research Fund.
NJJ was lead author on a similar publication focused on out-of-hospital arrest, published in Resuscitation: Johnson NJ, Caldwell E, Carlbom DJ, Gaieski DF, Prekker ME, Rea TD, Sayre M, Hough CL. The acute respiratory distress syndrome after out-of-hospital cardiac arrest: Incidence, risk factors, and outcomes. Resuscitation. 2019 Feb;135:37-44. PMID: 30654012.
References
- Acute respiratory distress syndrome: the Berlin Definition.JAMA J Am Med Assoc. 2012; 307: 2526-2533
- Acute respiratory distress in adults.Lancet Lond Engl. 1967; 2: 319-323
Fifty Years of Research in ARDS.ARDS: How It All Began|American Journal of Respiratory and Critical Care Medicine [Internet]. [cited 2022 May 17]; Available from: https://www.atsjournals.org/doi/abs/10.1164/rccm.201706-1281ED.
- The Berlin definition of ARDS: An expanded rationale, justification, and supplementary material.Intensive Care Med. 2012; 38: 1573-1582
Shih JA, Robertson HK, Issa MS, et al. Acute Respiratory Distress Syndrome after In-Hospital Cardiac Arrest. Resuscitation 2022;177:78–84.
- The acute respiratory distress syndrome after out-of-hospital cardiac arrest: Incidence, risk factors, and outcomes.Resuscitation. 2019; 135: 37-44
- Ventilator Management and Respiratory Care After Cardiac Arrest: Oxygenation, Ventilation, Infection, and Injury.Chest. 2018; 153: 1466-1477
- Mechanisms of lung ischemia-reperfusion injury.Curr Opin Organ Transplant. 2016; 21: 246-252
- Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest.N Engl J Med. 2019; 381: 1831-1842
- Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308
- Favorable neurocognitive outcome with low tidal volume ventilation after cardiac arrest.Am J Respir Crit Care Med. 2017; 195: 1198-1206
- The association between tidal volume and neurological outcome following in-hospital cardiac arrest.Resuscitation. 2018; 124: 106-111
- Initial arterial carbon dioxide tension is associated with neurological outcome after resuscitation from cardiac arrest.Resuscitation. 2017; 114: 53-58
- Post-resuscitation arterial oxygen and carbon dioxide and outcomes after out-of-hospital cardiac arrest.Resuscitation. 2017; 120
Eastwood GM, Schneider AG, Suzuki S, et al. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation [Internet] 2016; Available from: http://linkinghub.elsevier.com/retrieve/pii/S0300957216300053.
- Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest.Resuscitation. 2013; 84: 927-934
- In-hospital cardiac arrest in patients with coronavirus 2019.Resuscitation. 2021; 160
- A Multicenter Evaluation of Survival After In-Hospital Cardiac Arrest in Coronavirus Disease 2019 Patients.Crit Care Explor. 2021; 3: e0425
- Multiple organ dysfunction after return of spontaneous circulation in postcardiac arrest syndrome.Crit Care Med. 2013; 41: 1492-1501
- Personalized medicine for ARDS: the 2035 research agenda.Intensive Care Med. 2016; 42: 756-767
Article info
Publication history
Published online: June 10, 2022
Accepted:
June 2,
2022
Received:
May 31,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
