key: cord-0752508-h2ytd890
authors: El-Zein, Rayan S.; Chan, Maya L.; Su, Lillian; Chan, Paul S.
title: Outcomes of Pediatric Patients with COVID-19 and In-Hospital Cardiopulmonary Resuscitation
date: 2022-02-25
journal: Resuscitation
DOI: 10.1016/j.resuscitation.2022.02.018
sha: 88ba80fb364a0087dcaccbbc23122cc63f6dab28
doc_id: 752508
cord_uid: h2ytd890

BACKGROUND: Early studies found low survival rates for adults with COVID-19 infection and in-hospital cardiac arrest (IHCA). We evaluated the association of COVID-19 infection on survival outcomes in pediatric patients undergoing cardiopulmonary resuscitation (CPR). METHODS: Within Get-With-The-Guidelines®-Resuscitation, we identified pediatric patients who underwent CPR for an IHCA or bradycardia with poor perfusion between March and December, 2020. We compared survival outcomes (survival to discharge and return of spontaneous circulation for ≥20 minutes [ROSC]) between patients with suspected/confirmed COVID-19 infection and non-COVID-19 patients using multivariable hierarchical regression, with hospital site as a random effect and patient and cardiac arrest variables with a significant (p<0.05) bivariate association as fixed effects. RESULTS: Overall, 1328 pediatric in-hospital CPR events were identified (590 IHCA, 738 bradycardia with poor perfusion), of which 46 (32 IHCA, 14 bradycardia) had suspected/confirmed COVID-19 infection. Rates of survival to discharge were similar between those with and without COVID-19 infection (39.1% vs. 44.9%; adjusted RR, 1.14 [95% CI: 0.55-2.36]), and these estimates were similar for those with IHCA and bradycardia with poor perfusion (adjusted RRs of 1.03 and 1.05; interaction p=0.96). Rates of ROSC were also similar between pediatric patients with and without COVID-19 overall (67.4% vs. 76.9%; adjusted RR, 0.87 [0.43, 1.77]), and for the subgroups with IHCA or bradycardia requiring CPR (adjusted RRs of 0.95 and 0.86, interaction p=0.26). CONCLUSIONS: In a large multicenter national registry of CPR events, COVID-19 infection was not associated with lower rates of ROSC or survival to hospital discharge in pediatric patients undergoing CPR.

Although coronavirus disease 2019 (COVID-19) has been described primarily as a mild disease in children, rates of pediatric hospitalizations of patients with COVID-19 are on the rise. 1 The hospital course of pediatric patients may be complicated by clinical decompensation and potentially progress to in-hospital cardiac arrest (IHCA), yet little information is currently available on outcomes of pediatric patients with COVID-19 undergoing cardiopulmonary resuscitation (CPR).

In adults with COVID-19 infection, previous reports have described low survival rates for those with IHCA. [2] [3] [4] Besides the physiologic effects of COVID-19 infection, other potential reasons for lower survival in adults with IHCA include delays in CPR initiation due to requirements of donning personal protective equipment, shorter duration of resuscitation efforts, and overall decrease in CPR quality. 5, 6 Although it would be reasonable to believe that pediatric patients with COVID-19 who undergo CPR would have lower survival than children without COVID-19, there is a need for empirical data to quantify the extent of lower survival with COVID-19 infection in this population. Accordingly, within a large national registry, we examined the association of COVID-19 infection on survival outcomes for pediatric patients who underwent CPR.

The study was approved by Saint Luke's Hospital's IRB, which waived the requirement for informed consent as the study involved deidentified data.

Get With The Guidelines ® (GWTG)-Resuscitation is a large, prospective, quality improvement registry of IHCA and CPR events. The registry design has been previously described. 7 In brief, trained hospital personnel identify all patients without do-not-resuscitate orders who undergo cardiopulmonary resuscitation. Cases are identified by centralized collection of cardiac arrest flow sheets, reviews of hospital paging system logs, and routine checks of code carts and pharmacy tracer drug records. 7 Standardized Utstein-style definitions are used for all patient variables and outcomes to facilitate uniform reporting across hospitals. 8, 9 Within GWTG-Resuscitation, we identified patients under 18 years of age between March 1 and December 31, 2020, with an in-hospital CPR event due to a pulseless IHCA or bradycardia with poor perfusion requiring CPR. The independent variable was whether the pediatric patient had suspected/confirmed COVID-19 infection at the time of their CPR event.

Our primary outcome was survival to discharge, and the secondary outcome was sustained return of spontaneous circulation for >20 minutes (ROSC).

Baseline characteristics of patients with and without COVID-19 were compared using Fisher's exact test for categorical variables and student's t-test for continuous variables.

In the overall cohort, we compared rates of survival to discharge between patients with and without COVID-19 infection by constructing multivariable hierarchical regression models, with hospital site as a random effect and COVID-19 status, location of arrest, and initial rhythm, regardless of statistical significance as fixed effects. Because of the sample size, we only included the following other variables with a bivariate association as fixed effects to avoid overparameterization: age, sex, race, initial cardiac arrest rhythm, location of cardiac arrest, comorbid conditions (prior heart failure or myocardial infarction, index admission heart failure or myocardial infarction, diabetes mellitus, baseline depression in central nervous system function, acute stroke, pneumonia, and metastatic or hematologic malignancy), medical conditions present within 24 hours of cardiac arrest (renal insufficiency, hepatic insufficiency, respiratory insufficiency, hypotension, septicemia, and metabolic or electrolyte abnormality), and interventions in place at the time of cardiac arrest (continuous intravenous vasopressor, assisted or mechanical ventilation, and hemodialysis). These models used a Poisson distribution with a log-link to estimate risk ratios (RRs). We then evaluated for an interaction between COVID-19 status and CPR event type (IHCA vs. bradycardia with poor perfusion) to determine if the association between COVID-19 and survival differed for IHCA and bradycardia events.

Finally, we repeated all analyses for the secondary outcome of ROSC.

For each analysis, the null hypothesis was evaluated at a 2-sided significance level of 0.05 and calculated 95% confidence intervals (CIs) using robust standard errors. All statistical analyses were conducted using SAS Version 9.1.3 (SAS Institute, Cary, NC).

Of 1328 pediatric in-hospital CPR events, 590 were pulseless IHCAs and 738 were bradycardia requiring CPR. Suspected/confirmed COVID-19 infection was present in 46 patients (17 confirmed, 6 suspected, and 23 were missing designation as confirmed or suspected 

Among pediatric patients requiring CPR during the pandemic months in 2020, COVID-19 infection was not associated with lower rates of ROSC or survival to discharge. This was the case overall, and for those with IHCA or bradycardia with poor perfusion. Our results on the association between COVID-19 infection and survival differ from those for IHCA in adult patients, which ranged from 0% to 14%. 10, 11 One reason for the difference in results is potentially less severe illness with COVID-19 in hospitalized pediatric patients undergoing CPR as compared to adults. In our study, there were no differences in rates of mechanical ventilation between pediatric patients requiring CPR with and without COVID-19 infection although there were higher rates of pneumonia and sepsis in pediatric patients with COVID-19. Less severe respiratory compromise in pediatric COVID-19 patients with a CPR event may account for the different associations of COVID-19 infection in pediatric and adult patients with CPR events. Although some have questioned whether CPR should even be initiated in adults with COVID-19 infection and IHCA, 12, 13 our findings suggest that end-of-life decisions for pediatric patients with a CPR event should not be influenced by COVID-19 status.

To the best of our knowledge, one other report has described clinical outcomes of pediatric IHCA and COVID-19. Utilizing the PediRES-Q database, Lauridsen et al. evaluated 28 pediatric patients with confirmed or suspected COVID-19 who suffered IHCA between March 1, 2020 and April 1, 2021. 14 In their COVID-19 cohort, rates of ROSC and survival to discharge were 50% and 25%, respectively, which are comparatively lower than the rates in our cohort (67% and 39%). In contrast to our study, patients with COVID-19 in that study was associated with lower rates of ROSC although rates of survival to discharge were not significantly different. Our study extends the findings of this prior study by confirming that rates of survival to discharge were similar between children with and without COVID-19 infection who undergo a CPR event and by also examining the association of COVID-19 infection with survival outcomes after CPR for children with bradycardia with poor perfusion. Reasons for different results for ROSC between that and our study are unclear, but likely are due to different study populations and possibly variables in model adjustment.

Our study has the following limitations. As GWTG-Resuscitation is a quality improvement registry, our findings may not be representative of all hospitals. It is possible that some patients who were suspected to have COVID-19 were later confirmed to be negative. However, among 46 patients in our study with suspected/confirmed COVID-19 infection, we found that 74% of those with data on confirmed vs. suspected COVID-19 infection had confirmed COVID-19 infection, although there was a missing data rate of 50% on this optional data field However, we found COVID-19 patients had higher rates of hypotension, pneumonia, and sepsis, which is consistent with active infection. Second, our sample of COVID-19 patients was small and may have been 

In a large multicenter national registry of CPR events, sCOVID-19 infection status was not associated with lower rates of ROSC or survival to hospital discharge in pediatric patients undergoing CPR. University of Pennsylvania serves as the data analytic center and has an agreement to prepare the data for research purposes.

Rayan El-Zein and Paul S. Chan conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Maya L. Chan carried out the analyses. Lillian Su critically reviewed the manuscript.

Anne 

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Abbreviations: CI, confidence interval; IHCA, in-hospital cardiac arrest

ROSC, return of spontaneous circulation for >20 minutes * Models for the overall cohort adjusted for COVID-19 status, initial rhythm, location of arrest, age group, pneumonia, sepsis, hypotension, and renal insufficiency

† Models for IHCA adjusted for: COVID-19 status, initial rhythm, location of arrest, pneumonia, sepsis, and hypotension. ‡ Model for bradycardia adjusted for: COVID-19 status, location of arrest, hypotension, and sepsis

Acknowledgments Funding/Support:  Dr. El-Zein is currently supported by the National Heart, Lung and Blood Institutes of Health under Award Number T32H110837. The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the National Institutes of Health. Sincerely, Rayan El-Zein