key: cord-330837-pwwgmtjr
authors: Lim, Zheng Jie; Reddy, Mallikarjuna Ponnapa; Afroz, Afsana; Billah, Baki; Shekar, Kiran; Subramaniam, Ashwin
title: Incidence and outcome of out-of-hospital cardiac arrests in the COVID-19 era: A systematic review and meta-analysis
date: 2020-11-01
journal: Resuscitation
DOI: 10.1016/j.resuscitation.2020.10.025
sha: 
doc_id: 330837
cord_uid: pwwgmtjr

BACKGROUND: The impact of COVID-19 on pre-hospital and hospital services and hence on the prevalence and outcomes of out-of-hospital cardiac arrests (OHCA) remain unclear. The review aimed to evaluate the influence of the COVID-19 pandemic on the incidence, process, and outcomes of OHCA. METHODS: A systematic review of PubMed, EMBASE, and pre-print websites was performed. Studies reporting comparative data on OHCA within the same jurisdiction, before and during the COVID-19 pandemic were included. Study quality was assessed based on the Newcastle-Ottawa Scale. RESULTS: Ten studies reporting data from 35,379 OHCA events were included. There was a 120% increase in OHCA events since the pandemic. Time from OHCA to ambulance arrival was longer during the pandemic (p = 0.036). While mortality (OR = 0.67, 95%-CI 0.49-0.91) and supraglottic airway use (OR = 0.36, 95%-CI 0.27-0.46) was higher during the pandemic, automated external defibrillator use (OR = 1.78 95%-CI 1.06-2.98), return of spontaneous circulation (OR = 1.63, 95%-CI 1.18-2.26) and intubation (OR = 1.87, 95%-CI 1.12-3.13) was more common before the pandemic. More patients survived to hospital admission (OR = 1.75, 95%-CI 1.42-2.17) and discharge (OR = 1.65, 95%-CI 1.28-2.12) before the pandemic. Bystander CPR (OR = 1.08, 95%-CI 0.86-1.35), unwitnessed OHCA (OR = 0.84, 95%-CI 0.66-1.07), paramedic-resuscitation attempts (OR = 1.19 95%-CI 1.00-1.42) and mechanical CPR device use (OR = 1.57 95%-CI 0.55-4.55) did not defer significantly. CONCLUSIONS: The incidence and mortality following OHCA was higher during the COVID-19 pandemic. There were significant variations in resuscitation practices during the pandemic. Research to define optimal processes of pre-hospital care during a pandemic is urgently required. REVIEW REGISTRATION: PROSPERO (CRD42020203371).

The novel coronavirus disease 2019 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been associated with more than 39 million cases and 1 million deaths worldwide as of October 16 th 2020 [1] . Health systems are under significant sustained stress with many parts of world experiencing second and subsequent waves of infection. The understanding of how the pandemic affects overall population health and access to health care; the nature and extent of disruptions it causes to pre-hospital and in hospital health care delivery is still evolving.

For example, an increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported since the very early phase of the COVID-19 epidemic [2] . A recent population-based crosssectional study reported that out-of-hospital cardiac arrests had increased 3-fold during the 2020 COVID-19 period when compared with during the comparison period in 2019 [3] . Patients with OHCA during 2020 were older, more likely to have comorbidities and substantially less likely to have return and sustained return of spontaneous circulation [3] .

The chain of survival refers to a series of actions such as early access, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced life support and early post resuscitative care. These actions should be optimally executed to reduce the mortality associated with OHCA.

Like any chain, the chain of survival is only as strong as its weakest link [4] . A pandemic can disrupt this chain of survival in multiple ways and influence patient outcomes.

The study hypothesis was that the incidence of OHCA and the associated mortality was higher during the COVID-19 pandemic period when compared to an earlier period. In this systematic review and meta-analysis, the authors aimed to determine the influence of the COVID-19 pandemic on the incidence, processes of care and mortality among OHCA patients.

To evaluate the effect of the COVID-19 pandemic, the studies with direct comparison to an earlier time frame (termed "before pandemic") were selected. This enabled a direct comparison between the two-time frames to help understand any differences in incidences.

Statistical analyses were performed using the Review Manager 5.4 (Cochrane Collaboration) and

Stata/MP 15.1 (Statacorp). Numerical data was summarized using mean and standard deviation and categorical data using proportion and percentage. To enable an analysis of results between studies, median values were converted to means, derived using an estimation formula [9] .

Between-group differences were compared using Fischer's exact test. An analysis of nonparametric values was conducted using the Kruskal Wallace test. A p-value <0.05 was considered statistically significant. The Mentel-Haenszel random-effects model demonstrate better properties in the presence of heterogeneity accounting for both within-study and betweenstudy variances which was considered for the pooled odds ratio (OR). Results were presented in Forest plots. Heterogeneity was tested by using the χ² test on Cochran's Q statistic, which was calculated by means of H and I² indices. The I² index estimates the percentage of total variation across studies based on true between-study variances rather than on chance. Conventionally, I 2 values of 0-25% indicate low heterogeneity, 26-75% indicate moderate heterogeneity, and 76-100% indicate substantial heterogeneity.

A total of 209 studies were obtained from the living systematic review, with 23 full-text articles assessed for eligibility. Ten studies across five countries (Australia, France, Italy, Spain and USA) were included in the qualitative and statistical analysis [3, [10] [11] [12] [13] [14] [15] [16] [17] [18] . Six studies were fair [10, 12, 13, [15] [16] [17] and four studies were of good quality based on NOS [3, 11, 14, 18] ( Supplementary table 1) . Six studies compared the COVID-19 pandemic with the same period in 2019 [3, 10, 13, 15, 17, 18] . One study compared OHCA during the COVID-19 pandemic against OHCA earlier in the year [16] . While one study compared data collected during COVID-19 pandemic with data from 2011-2019 [13] , the remaining studies compared COVID-19 data against the time periods of 2016-2019 [12] , 2017-2018 [14] and 2017-2019 [11] . The mean age reported among nine studies was 70.8 years during the COVID-19 pandemic, and 65.6 years before the pandemic. Time from call to ambulance arrival was significantly higher during the pandemic (p=0.036). The incidence and outcomes of OHCA of each study is outlined in table 1. The incidence proportion of OHCA due to a medical cause was similar before and during the pandemic (90.0% (12, [3, 10-12, 15, 17] . This is illustrated in Figure 3a .

Bystander CPR (Figure 3b ) was reported in all ten studies in a total of 7,908/19,549 patients (40.5%) before pandemic and 2,850/7,322 patients (38.9%) during the pandemic (p<0.001) [3, [10] [11] [12] [13] [15] [16] [17] [18] . Bystander CPR occurred more frequently before the pandemic but was not statistically significant (OR=1.08 95% CI 0.86-1.35; p=0.51; I 2 =88%).

Unwitnessed OHCA (Figure 3c ) was reported in eight studies across 11,794/20,048 patients (58.8%) before the pandemic and 4,328/6,995 patients (61.9%) during the pandemic (p<0.001) [3, [10] [11] [12] [13] [14] [15] 18] . Unwitnessed OHCA occurred less often before the pandemic, however, was not statistically significant (OR=0.84 95% CI 0.66-1.07; p=0.17; I 2 =89%).

Resuscitation was attempted by paramedics in six studies in a total of 3,182/6,415 patients (49.6%) before the pandemic and 5,053/9,399 patients (53.8%) during the pandemic (p<0.001) [3, 10, 11, [15] [16] [17] . While there was no difference in the number of arrests who had resuscitation attempted in the two timeframes (OR=1.19 95% CI 1.00-1.42; p=0.05; I 2 =73%), only one study reported an increase in frequency of resuscitation attempts during the pandemic (Figure 3d ) [3] . the pandemic (p<0.001) [3, 10, 11, 13, 17, 18] . Shockable rhythm or shocked events occurred more frequently before the pandemic (OR=1.57 95% CI 1.17-2.09; p=0.002; I 2 =78%).

There were more OHCA occurring at home during the pandemic (Figure 3g ). Across six studies, 4,837/6,645 OHCA occurred at home before the pandemic (72.8%) compared to 1,997/2,376 arrests (84.0%) during the pandemic (p<0.001) [10, 11, 13, 14, 17, 18] . OHCA more frequently occurred at home during the pandemic (OR=0.51 95% CI 0.40-0.66; p<0.0001; I 2 =68%).

Airway management differed before and during the pandemic as reported in four studies [3, 11, 12, 14] . More patients were intubated before the pandemic (51.5% (5,589/10,848) versus 47.3% Survival to hospital admission, reported in six studies, occurred in 1,739/6,467 (26.9%) patients before the pandemic and 389/2,168 (17.9%) during the pandemic (p<0.001) [10, 11, 13, 14, 17, 18] . Patients were more likely to survive to hospital admission before the pandemic (OR=1.75 95% CI 1.42-2.17; p=<0.0001; I 2 =57%) ( Figure 3l ). Similarly, survival to hospital discharge occurred in 551/6,556 (8.4%) of patients before the pandemic and 141/2,207 patients (6.4%) during the pandemic (p=0.002), demonstrating that survival to hospital discharge occurred more frequently before the pandemic (OR=1.65 95% CI 1.28-2.12; p<0.001; I 2 =30%) ( Figure 3m ) [10, 11, 13, 14, 17, 18] .

J o u r n a l P r e -p r o o f DISCUSSION Across the selected studies, we observed a more than two-fold increase in OHCA incidence during the COVID-19 pandemic, with an overall significant increase in mortality. Our analysis found several disruptions to the chain of survival in OHCA victims during the pandemic and this may have at least in part contributed to the outcomes seen. There was reduced bystander CPR and AED use, along with increased supraglottic airway management by paramedic personnel.

Also, time from call to ambulance arrival was longer during the pandemic.

The majority of OHCA was attributed to medical causes and was more frequently the reason for arrest. Public health measures may have role in reduction seen in the incidence of non-medical causes for OHCA. This is potentially due to a complex interplay of heightened financial difficulties, social isolation, uncertainty about the future, redistribution of the health workforce and the disruption to clinical services due to the pandemic-related lockdown, resulting in a delay in receiving care [19, 20] . There was not only a substantial reduction in the use of pre-hospital services to transport STEMI patients to hospitals [10] , but also a significant reduction in cardiology admissions [21] and STEMI activations [22] in 2020. Conversely, trauma causes of OHCA were less frequently observed, which is consistent with national lockdowns restricting mass gathering recreational and sporting events [23] . This may have also resulted in reduced road traffic accidents [24] .

Despite most OHCA events occurring at home, a higher frequency of unwitnessed OHCA was observed. This may be explained by strict self-quarantine measures adopted, resulting in vulnerable populations such as the elderly being isolated from family members who would otherwise visit frequently. With "stay home" measures, it is unsurprising that significantly more cardiac arrests occurred at home, where quarantine isolation may have enforced living in different areas at home or different houses from family members [10] . It could be postulated that although OHCA events occurred at home where family may be present, they may be less likely to commence CPR due to psychological and emotional effects of the sudden event [25] .

Bystander CPR was more frequent before the pandemic. While there is an ongoing fear of contracting COVID-19 during CPR administration [26] , limited evidence exists surrounding the J o u r n a l P r e -p r o o f transmission of infection from patient to rescuer [27] . Although likely underreporting and/or identification of SARS-CoV-2 virus, the overall low prevalence of confirmed COVID-19 cases among OHCA during the pandemic suggests that any concerns regarding bystander CPR may be unwarranted especially in jurisdictions wherein risks of community transmission may be minimal. It should be noted, however, that CPR has the potential to generate aerosols [28] and safety of bystanders and pre-hospital healthcare workers is equally important. Community education, advanced healthcare planning and people wearing bands to indicate their wish not to receive CPR may go a long way in promoting dignity and comfort of the person who has suffered an OHCA and who has a poor chance of survival even outside a pandemic. During a pandemic it may of even greater relevance when health services are stretched, and an element of risk exists to responders providing CPR and ACLS.

There have been significant practice variations during the pandemic. For instance, there was an increase in use of supraglottic airway which may at least in part driven by risks of endotracheal intubation. The international liaison committee on resuscitation (ILCOR) recommends the use of supraglottic airways as first line for adults with OHCA (weak recommendation, very low certainty of evidence). However, the aerosol risks of supraglottic airway use when resuscitating patients with COVID-19 remian unclear anda supraglottic airway may potentially cause a false sense of security amongst healthcare providers [28] [29] [30] . Similarly, although ILCOR recommends the use of mechanical chest compression devices (weak recommendation, very low certainty of evidence), it is interesting to note that there was no difference in the use of mechanical CPR devices during the pandemic [28] .

Interestingly, the frequency of a shockable rhythm/shocked events and ROSC was higher before the pandemic. This may reflect disruptions in the chain of survival, where the probability of ROSC diminishes significantly with time and it is unclear whether increased non-shockable rhythm is a consequence of delayed response or underlying pathophysiology [31] . Additionally, this may be related to the delay from call to ambulance arrival that is observed in this study. The quantitative increase in OHCA calls and the need to properly apply personal protective equipment and disinfect ambulances between calls likely contributed to the delay in response and regrettably contributed to the observed increase in OHCA mortality [10] . This may also be compounded by the increased frequency of unwitnessed OHCA and reduction in bystander CPR.

As a result, patients may be found long after cardiac arrest where they may no longer be in a shockable rhythm.

The absolute increase in OHCA incidence and corresponding rise in mortality was reported in our analysis. Direct COVID-19 deaths would account for a proportion of these deaths [3, 13] , while indirect factors such as lockdown and behavioral changes for fear of infection or reluctance to burden health systems may have resulted in delays in presenting to hospital [10, 13] . Worldwide, a decrease in acute hospital presentations have been observed, with reports of reduced ST-elevation myocardial infarction presentations in Spain, Italy and USA [32] .

Emergency department presentations have also decreased following the implementation of lockdown measures in the UK, Germany and USA [33, 34] . Emergency medicine services may also be overwhelmed with the surge in OHCA calls, resulting in a strain in pre-hospital services [15] .

There are several limitations that need to be acknowledged. Firstly, most of the included studies were from the early phase of the pandemic from countries that were significantly affected and had little time to prepare. Moreover, some degree of lockdown in many of the countries, due to the fear of contracting the virus, which implied that many people continued to avoid health care facilities. Hence the result may still be representative during the pandemic. Secondly, postmortem testing to confirm COVID-19 was not reported, hence the direct causation of COVID-19 infection and OHCA or its indirect association due to unattended comorbid diseases during this pandemic was not readily available. Thirdly, there was limited information about the previous medical history or comorbidities of these OHCA patients. Finally, it would been helpful to map the OHCA event curve against that of the epidemiological pandemic curve (based upon hospital confirmed cases) in each of the reporting areas to observe any correlations between the incidence of COVID-19 and OHCA event rates, however this data was not provided in the studies. This information would be critical in helping systems better prepare for future resurgences in COVID-19 cases.

The incidence and mortality of OHCA during the COVID-19 pandemic was significantly higher as compared to time periods before the pandemic. Multiple factors may have contributed to the increased mortality, including increased time from call to ambulance arrival and the reduced frequency of unwitnessed events, bystander CPR and AED use. There were significant practice changes during the pandemic. Urgent research to improve pre-hospital care during a pandemic is required.

-Zheng Jie LIM: This author has conceived the project idea, conducted the systematic review, statistical analysis, assisted with data analysis, wrote the initial drafts of the manuscript, created tables and figures and finalized the manuscript.

-Mallikarjuna REDDY: This author has conducted the systematic review, assisted with data analysis, wrote the initial drafts of the manuscript and finalized the manuscript. ROSC: Return of spontaneous circulation; AED: Automatic external defibrillator. * The study did not compare the incidence of OHCA between 2019 and 2020 and was thus excluded from this analysis. # Out of resuscitations attempted by emergency medical services. ^ Marijon et al looked at two different timeframes and compared the incidence and outcomes of OHCA against data from the pandemic period in 2020.

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Prof Shekar acknowledges research support from Metro North Hospital and Health Service. We would like to acknowledge the work of pre-hospital health professionals in providing excellent health care during the COVID-19 pandemic.J o u r n a l P r e -p r o o f

Competing interests: All authors declare no support from any organization for the submitted work, no competing interests with regards to the submitted work