key: cord-0908944-y18nru1d authors: Couper, Keith; Taylor-Phillips, Sian; Grove, Amy; Freeman, Karoline; Osokogu, Osemeke; Court, Rachel; Mehrabian, Amin; Morley, Peter T.; Nolan, Jerry P.; Soar, Jasmeet; Perkins, Gavin D. title: COVID-19 in cardiac arrest and infection risk to rescuers: a systematic review date: 2020-04-20 journal: Resuscitation DOI: 10.1016/j.resuscitation.2020.04.022 sha: bcb4095d11abe084f2cc5f6ece6ae9058c6f9c49 doc_id: 908944 cord_uid: y18nru1d Abstract Background There may be a risk of COVID-19 transmission to rescuers delivering treatment for cardiac arrest. The aim of this review was to identify the potential risk of transmission associated with key interventions (chest compressions, defibrillation, cardiopulmonary resuscitation) to inform international treatment recommendations. Methods We undertook a systematic review comprising three questions: 1) aerosol generation associated with key interventions; 2) risk of airborne infection transmission associated with key interventions; and 3) the effect of different personal protective equipment strategies. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organisation COVID-19 database on 24th March 2020. Eligibility criteria were developed individually for each question. We assessed risk of bias for individual studies, and used the GRADE process to assess evidence certainty by outcome. Results We included eleven studies: two cohort studies, one case control study, five case reports, and three manikin randomised controlled trials. We did not find any direct evidence that chest compressions or defibrillation either are or are not associated with aerosol generation or transmission of infection. Data from manikin studies indicates that donning of personal protective equipment delays treatment delivery. Studies provided only indirect evidence, with no study describing patients with COVID-19. Evidence certainty was low or very low for all outcomes. Conclusion It is uncertain whether chest compressions or defibrillation cause aerosol generation or transmission of COVID-19 to rescuers. There is very limited evidence and a rapid need for further studies. Review registration: PROSPERO CRD42020175594 Background: There may be a risk of COVID-19 transmission to rescuers delivering treatment 32 for cardiac arrest. The aim of this review was to identify the potential risk of transmission 33 associated with key interventions (chest compressions, defibrillation, cardiopulmonary 34 resuscitation) to inform international treatment recommendations. Methods: We undertook a systematic review comprising three questions: 1) aerosol 37 generation associated with key interventions; 2) risk of airborne infection transmission 38 associated with key interventions; and 3) the effect of different personal protective 39 equipment strategies. We searched MEDLINE, Embase, Cochrane Central Register of 40 Controlled Trials, and the World Health Organisation COVID-19 database on 24 th March 41 2020. Eligibility criteria were developed individually for each question. We assessed risk of 42 bias for individual studies, and used the GRADE process to assess evidence certainty by 43 outcome. Results: We included eleven studies: two cohort studies, one case control study, five case 46 reports, and three manikin randomised controlled trials. We did not find any direct evidence 47 that chest compressions or defibrillation either are or are not associated with aerosol 48 generation or transmission of infection. Data from manikin studies indicates that donning of 49 personal protective equipment delays treatment delivery. Studies provided only indirect 50 evidence, with no study describing patients with COVID-19. Evidence certainty was low or 51 very low for all outcomes. 52 53 Conclusion: It is uncertain whether chest compressions or defibrillation cause aerosol 54 generation or transmission of COVID-19 to rescuers. There is very limited evidence and a 55 rapid need for further studies. 56 57 Review registration: PROSPERO CRD42020175594 58 59 Introduction 61 62 The World Health Organization (WHO) declared a Severe Acute Respiratory Syndrome 63 Coronavirus two (SARS-CoV-2) pandemic on 11 Current resuscitation guidelines highlight the importance of rescuer safety. 7 Delaying the 80 delivery of chest compressions and defibrillation for up to several minutes for healthcare 81 workers to don personal protective equipment (PPE) will reduce the likelihood of patient 82 survival. [8] [9] [10] In contrast, the delivery of aerosol generating procedures to a patient infected 83 with COVID-19 may place healthcare workers at risk. Driven by concern amongst the clinical 84 community as to the optimum approach in cardiac arrest, the International Liaison 85 Committee on Resuscitation (ILCOR) identified the urgent need for a review of current 86 evidence to inform international resuscitation treatment recommendations in patients with 87 known or suspected COVID-19. 88 89 90 Methods 91 92 We undertook a systematic review to explore three key questions relating to the 93 transmission of COVID-19 in relation to chest compressions, defibrillation and CPR (box 94 one). In view of the urgent need for evidence to inform international policy, the review was 95 completed in four-days. Our review was prospectively registered with PROSPERO 96 (CRD42020175594) and is written in accordance with the PRISMA statement. 11 97 98 Our first two research questions examined the association between key resuscitation 99 interventions (chest compressions, defibrillation, CPR) and aerosol generation and airborne 100 transmission of infection. Our third question examined the effect of different personal 101 protective equipment systems (supplementary information). Search strategy 104 The information specialist iteratively developed the search strategy in consultation with 105 other project team members and drawing on the strategy developed for a previous 106 review. 12 Study eligibility 119 We assessed study inclusion using pre-defined study criteria based on the research question 120 (see supplementary information). For all questions, we included randomised controlled 121 trials and non-randomised studies (e.g., interrupted time series, controlled before-and-after 122 studies, cohort studies). For questions one and two, we additionally included case reports 123 and case-series. For questions one and three we included cadaver studies, and for question 124 three included manikin studies. For all studies, we required that the study be set in the context of a cardiac arrest, with 127 delivery of chest compressions and/or defibrillation and/or CPR by any individual 128 (healthcare worker or lay person). For infection transmission, we included all types of 129 infection (viral/bacterial/fungal) with presumed airborne transmission. We imposed no date 130 or language restrictions provided there was an English language abstract. 131 132 Article selection 133 On search completion, we used EndNote X9 software to systematically identify and remove 134 duplicate citations. Titles/abstracts were reviewed independently by two reviewers from 135 the team (two of STP/AG/AM), and obviously irrelevant citations excluded. We 136 subsequently sourced full-text papers, with eligibility independently assessed by two 137 reviewers (AG/AM) against pre-specified criteria. At each stage, disagreements were 138 discussed and reconciled or referred to a third reviewer for adjudication (KC). Data extraction and analysis 141 A single reviewer from the team (one of STP/AG/KF/OO) extracted data from eligible full-142 text papers using a piloted data extraction form. Accuracy was assessed by a second 143 reviewer. We extracted key data from each study relevant to the specific research question, 144 including details of population, exposure, intervention/ comparator, outcome and type of 145 infection. Disagreements between reviewers were resolved by consensus, or consultation 146 with a third reviewer (KC). Where a publication was eligible for inclusion for more than one 147 research question, data were extracted into a single data extraction form record. Risk of bias assessment and assessment of certainty of evidence 150 A single reviewer from the team (one of STP/AG/KF/OO) assessed risk of bias of full-text 151 papers using quality assessment tools that were appropriate for each study design. We used 152 the modified Cochrane Collaboration Risk of Bias tool for randomised controlled trials; 15 the 153 Evidence Partners tool for case-control studies and cohort studies; 16, 17 and the Murad tool 154 for case reports and case series. 18 Assessment accuracy was evaluated by a second reviewer 155 (one of STP/AG/KF/OO). We used the GRADE system to assess certainty of evidence per 156 outcome (outcomes for each question are listed in box one). 19 157 158 Data analysis 159 We anticipated that identified studies would be heterogeneous. We assessed studies for 160 clinical, methodological, and statistical heterogeneity, Where not precluded by 161 heterogeneity, we intended to consider pooling data in a meta-analysis using a random-162 effects model. In the likely event that a meta-analysis was precluded, we planned a 163 narrative synthesis. Results Searches of databases and other sources identified 749 citations. Following removal of 168 duplicates and screening of titles/abstracts, we retrieved 38 full-text papers of which 11 169 were eligible for inclusion in the review (see Figure 1 ). In the two cohort studies, the authors compared SARS infection transmission in individuals 197 who were exposed and not exposed to specific interventions. 25, 27 Both studies were 198 undertaken in Canada and examined SARS transmission. In one study of 697 healthcare 199 workers, only nine individuals were exposed to chest compressions and four were exposed 200 to defibrillation. 27 In the other study of 43 healthcare workers, eight individuals were 201 exposed to CPR and defibrillation. Neither study identified a statistically significant 202 association between these exposures and infection transmission. Key study limitations were 203 the lack of clear definition of exposures and inability to account for multiple exposures. In the case-control study, 51 healthcare workers with probable SARS were compared with 206 477 healthcare workers without infection. 24 There was a correlation between giving chest 207 compressions and tracheal intubation, indicating that often healthcare workers who were 208 exposed to one were often exposed to the other. A multivariate analysis suggested that 209 exposure to chest compressions was associated with an increased odds of probable SARS 210 infection (odds ratio 4.52, 95% confidence interval 1.08 to 18.81 the study it is likely the nurse was also present in the room during airway manoeuvres. All studies and reports may be subject to recall bias, both in relation to the PPE worn and 227 the procedures undertaken. Evidence certainty was assessed as very low. Question three-personal protective equipment strategies 230 For question three, we included three manikin RCTs that recruited 104 participants. 22, 29, 30 231 One study was individually randomised, 30 and the other two were crossover RCTs. 22 The outcome of infection transmission was not evaluated in any study. No studies examined infection rates with different types of PPE. The outcome of PPE effectiveness was evaluated in one randomised crossover trial that 241 examined the performance of different N95 (or higher-level) mask types (cup-type, fold-242 type, valve-type) during chest compressions (see Table 2 ). 29 The primary outcome was the 243 adequate protection rate (APR) defined as the proportion of participants achieving a good 244 fit. During chest compression delivery, the APR differed between study arms (cup-type: difference between groups). For all mask types, APR was lower during chest compression 247 delivery than at baseline. The outcome of CPR quality was evaluated in three studies, two studies reported time taken 250 to deliver key interventions, 28, 30 and one study by Shin and colleagues (2017), examined 251 CPR quality 29 with and without PPE (see Table 2 pool data between studies because of the likelihood that healthcare workers were exposed 280 to multiple aerosol generating procedures and owing to the very low rates of disease 281 transmission. For example, in one study, only one healthcare worker was infected in both 282 the chest compression exposed and defibrillation exposed groups. Our confidence in any 283 pooled estimates would be very low. Since completing the review, we identified via ongoing literature scanning a retrospective 286 cohort study of 72 healthcare workers (28 infected with COVID-19; 44 not infected) that met 287 inclusion criteria for question two. 31 Healthcare workers experienced multiple potential 288 exposures as part of their clinical duties. single non-infected individual was exposed to CPR. 289 The risk of COVID-19 transmission in individuals exposed to CPR was not significant (relative 290 risk 0.63, 95% confidence interval 0.06 to 7.08). Whilst this additional study does not alter 291 the findings of our review, it highlights the rapid publication of much needed new data 292 about COVID-19. Our finding that there is no direct evidence that chest compressions and defibrillation either 295 are or are not aerosol generating procedures is important. However, this absence of 296 evidence should not be interpreted as providing evidence that these procedures are not 297 aerosol generating. From a physiological perspective, the generation of aerosols by chest compressions is 300 clinically plausible, because changes in thoracic pressure during chest compressions 301 generate airflow and small exhaled tidal volumes. 32 Evidence from the physiotherapy 302 literature shows that manual chest physiotherapy techniques do generate aerosols. 33 In 303 contrast, for defibrillation, 32 the mechanism for aerosol generation during defibrillation is 304 less clear. However, tonic muscle spasms caused by defibrillation could conceivably 305 generate a small amount of airflow. For policy makers, there is a need to balance the known risk of treatment delays if PPE is 308 donned before chest compressions and defibrillation are delivered, against the unknown, 309 but potential, risk of COVID-19 transmission to rescuers. This risk may also extend beyond 310 the rescuer, with additional risk of onward transmission to other healthcare workers, 311 patients, and the wider community. 34 The known risk associated with treatment delay relate 312 to the time taken to don PPE and the challenges of delivering effective treatment whilst 313 wearing PPE. [8] [9] [10] 28 Importantly, we found evidence that delivery of chest compressions may 314 reduce the effectiveness of face masks. 29 315 316 This review highlights the urgent need for research to identify and quantify aerosol 317 generation associated with chest compressions and defibrillation. This could be undertaken 318 using observations in clinical settings, or cadaver or animal models. Such work is essential to 319 better understand the potential risk to the rescuer when undertaking these procedures. 320 321 The aim of this review was to identify the available evidence relating to aerosol generation, 322 infection transmission and protection afforded by personal protective equipment. Beyond 323 this specific focus, interpretation of the evidence to guide clinical practice guidelines will 324 need careful consideration of the prevalence of COVID-19 in specific settings, the likelihood 325 that the resuscitation provider has already been exposed (e.g. close household contact), the 326 availability of personal protective equipment, the time taken to train staff in its use, and the 327 values and preferences of the wider community where any guidance will be implemented. 328 In addition the balance of risks and benefits for specific interventions will vary; for example, 329 early defibrillation for a witnessed cardiac arrest compared with cardiopulmonary 330 resuscitation for cardiac arrest secondary to refractory hypoxia. As identified in this review, 331 cardiopulmonary resuscitation is also a complex intervention comprising ventilation, chest 332 compressions, drug therapy and defibrillation, which become difficult to separate out 333 without reducing overall clinical effectiveness. Finally, with over one million out of hospital 334 cardiac arrests each year around the world and the critical importance of the community's 335 willingness to commence chest compressions and defibrillation, long term unintended 336 consequences of restrictive policies need to be considered and necessitate clear 337 communication strategies with local communities. Our review has three key limitations. Firstly, in order to provide an urgent review of 340 evidence to meet the needs of the international resuscitation community, we were unable 341 to undertake simultaneous independent data extraction and risk of bias assessments. 342 Instead, we performed single assessments followed by independent accuracy assessments. 343 Secondly, for expediency, we undertook a single search to cover all three questions. We gratefully acknowledge the support of Julia Geppert, Karoline Munro, and Emily 383 Watkins . 384 385 Page 13 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 Records identified through database searching (n = 688) Additional records identified through other sources Expert consultation (n = 3) Citation searching (n = 60) Records after duplicates removed (n = 545) Records screened (n = 545) Records excluded (n = 507) Full-text articles assessed for eligibility (n = 38) Full-text articles excluded, with reasons (n = 27) Non-eligible study design-e.g. review (n=6) Non-eligible exposure (n=14) No relevant outcome (n=4) No comparator group (n=3) Studies included in qualitative synthesis (n = 11) Studies included in quantitative synthesis (n = 0) World Health Organisation. Coronavirus disease (COVID-19) Pandemic Clinical Characteristics of 138 Hospitalized Patients With Coronavirus-Infected Pneumonia in Wuhan Modes of transmission of virus causing COVID-19: implications for IPC 394 precaution recommendations. Geneva: World Health Organization Infection prevention and control of epidemic-and pandemic-prone acute 398 respiratory infections in health care: WHO guidelines. Geneva: World Health Organization Guidance: COVID-19: infection prevention and control. GOV.UK, 2020 Aerosol generating procedures and risk of 405 transmission of acute respiratory infections to healthcare workers: a systematic review European Resuscitation Council Guidelines for Resuscitation 408 2015: Section 2. Adult basic life support and automated external defibrillation Delayed time to defibrillation after in-hospital 411 cardiac arrest Using simulation for training and to change protocol during the 413 outbreak of severe acute respiratory syndrome Predicting survival from out-of-hospital cardiac 415 arrest: a graphic model The PRISMA Group. Preferred Reporting Items for 417 Systematic Reviews and Meta-Analyses: The PRISMA Statement Aerosol-Generating Procedures and Risk of 419 Ottowa: Canadian Agency for Drugs 420 and Technologies in Health World Health Organisation Surviving Sepsis Campaign: guidelines on the management 426 of critically ill adults with Coronavirus Disease 2019 (COVID-19) The Cochrane Collaboration's tool for assessing risk of bias 429 in randomised trials Tool to Assess Risk of Bias in Case-Control Studies Tool to Assess Risk of Bias in Cohort Studies Methodological quality and synthesis of case series and 437 case reports GRADE guidelines: 1. Introduction-GRADE evidence profiles and 439 summary of findings tables Transmission of Panton-Valentine leukocidin-producing 441 Possible SARS coronavirus transmission during 443 cardiopulmonary resuscitation Nosocomial transmission of severe fever with thrombocytopenia 445 syndrome in Korea Transmission of tuberculosis during cardiopulmonary resuscitation Focus on breathing system filters Risk factors for SARS infection among hospital healthcare workers in 449 Beijing: A case control study SARS among critical care nurses Healthcare worker infected with Middle East 453 Respiratory Syndrome during cardiopulmonary resuscitation in Korea Risk factors for SARS transmission from patients requiring 456 intubation: a multicentre investigation in Toronto Respiratory protection during simulated 458 emergency pediatric life support: a randomized, controlled, crossover study Comparing the protective performances of 3 types of N95 461 filtering facepiece respirators during chest compressions: A randomized simulation study The "delay effect" of donning a gown during 464 cardiopulmonary resuscitation in a simulation model Risk Factors of Healthcare Workers with Corona Virus 466 Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China Does compression-only cardiopulmonary resuscitation generate 469 adequate passive ventilation during cardiac arrest? Evaluation of droplet dispersion during non-invasive 471 ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications 472 for management of pandemic influenza and other airborne infections. Health technology assessment Why did outbreaks of severe acute respiratory syndrome occur in some 475 hospital wards but not in others? JS 554 and GDP are Editors of Resuscitation and receive payment from the publisher Elsevier. JS is 555 chair of the ILCOR ALS Task Force, and GDP is co-chair of ILCOR Box one: research questions 530 Research question one In individuals in any setting, is delivery of 1) chest compressions, 2) defibrillation or 3) cardiopulmonary resuscitation associated with aerosol generation?Research question two In individuals in any setting wearing any/no personal protective equipment, is delivery of 1) chest compressions, 2) defibrillation or 3) cardiopulmonary resuscitation associated with transmission of infection?Research question three In individuals delivering chest compressions and/or defibrillation and/or CPR in any setting, does wearing of personal protective equipment compared with wearing any alternative system of personal protective equipment or no personal protective equipment affect infection with the same organism as the patient, personal protective equipment effectiveness, or quality of CPR?