This study validated the existing multimodal TOR rules using the WinCOVID-19 Daegu registry data on OHCA patients. Among the nine existing TOR rules, KoCARC TOR rule I was found to be the best indicator of poor outcomes during the COVID-19 outbreak as evidenced by its highest specificity and PPV. To our best knowledge, this was the first study to determine the efficacy of these TOR guidelines for an emerging infectious disease.
Resuscitation of infected individuals greatly increases the risk of virus transmission to healthcare providers [1,6,16]. Current guidelines recommend emergency personnel to confirm the presence of COVID-19 in OHCA patients and wear high-level PPE, even in doubtful cases, before performing CPR. However, these measures may have limited benefits because COVID-19 has a very high rate of disease transmission and approximately 25% of the patients have asymptomatic infection . Therefore, the COVID-19 era is a challenging and confusing time for healthcare workers in the medical and emergency fields . Some OHCA patients were unexpectedly confirmed to be positive post-CPR or postmortem, contributing to emergency room shutdowns and temporary closures . As of September 2020, more than 20,000 people have been confirmed to have COVID-19 in South Korea, and 385 of these patients have died. In addition, more than 50% of these cases were in Daegu, the area of interest in this study, and its neighboring area Gyeongbuk . Further, more than 130 healthcare workers and medical staff have been infected. One physician died after treating two confirmed patients.
Our findings, although preliminary, showed that the survival outcomes of OHCA patients in Daegu during the peak of the COVID-19 outbreak (4.1%) were significantly lower than those reported nationwide (9.8%) or in the city (8.8%) in 2018 . Many variables were changed in the COVID-19 era, including prehospital ROSC and pre-hospital transport time (see Additional file 1). Although we could not describe the impact of the COVID-19 pandemic on the chain of survival and its negative effects on high-quality CPR, the risk-benefit ratio for CPR should be reconsidered . Despite that there were several factors associated with good prognosis in this study, including bystander CPR, EMS CPR, prehospital ROSC, and VF, no new factor was found for COVID-19. Other studies have also raised concerns on how CPR must be performed for IHCA patients with confirmed COVID-19. Considering the lower survival rate, physicians should establish goals of care or CPR preferences to reduce futile resuscitation by stratifying the survival probability of the IHCA patients, regardless of their COVID-19 status, at the time of hospital admission [5,19]. It is also important to consider prehospital TOR for out-of-hospital resuscitation in an infectious disease epidemic area.
The previous TOR rules can be divided into two sets of variables: one can be applied at the pre-hospital level and the other can be evaluated immediately after arriving at the ED. In this study, we selected and analyzed the external validation of all nine multimodal TOR rules for OHCA patients during the COVID-19 epidemic period. These rules were commonly selected depending on the country or region where the derivation and validation phases were conducted. These included the (1) International BLS (a combination of three criteria: arrest not being witnessed by EMTs, not receiving prehospital shock delivery, and not experiencing prehospital ROSC, Table 1) and ALS rules derived and validated in the United States and Europe ; (2) Goto and KANTO-SOS rules developed in Japan and Asian countries [13,14]; and (3) the Korean OHCA registry-based TOR models, KoCARC TOR rules, and two new TOR rules that were used in our previous studies [7,11]. The international BLS-TOR rules that can be enforced at the prehospital stage has high sensitivity and specificity, but also relatively high FPR (1-specificity) [9,15]. Therefore, a continuous development of the TOR model has been proposed [7,9]. A previous study that included acquired ECG asystole rhythm as a criterion also proposed a new TOR model applicable at the prehospital stage and another TOR model applicable immediately after arriving at the ED .
The previous four rules have been partially validated in other countries and in the setting of mechanical CPR or comprehensive post-resuscitation care [12,20-23]. Previous validations of the TOR rule reported survival rates of less than 1% among TOR rule–positive patients in North America. In contrast, high FPR of survival has been reported in Asian countries (28.7% in Singapore, 25.9% in Taiwan, and 30.4% in South Korea). This discrepancy may be due to different prehospital practices and a relatively higher prevalence of non-shockable rhythm in patients in Asian countries . However, the high false positive cases of survival in these Asian countries, where the withdrawal of life-sustaining treatment is not commonly applied, are likely to be biased. Kajino et al.  validated the TOR rules for predicting poor neurologic outcomes in a Japanese population and concluded that more specific TOR rules for each region should be developed, despite the good performance of the TOR rules in their study. However, even if the COVID-19 outbreak was not considered, these previous results implied that the extrapolation to and implementation of different TOR rules in regions with different organization of EMS treatment protocols, legislation, and socioeconomic characteristics might be problematic because the TOR rules would need to be adjusted to meet the regional situation.
In this study, we validated the existing multimodal TOR rules using the WinCOVID-19 Daegu registry data on OHCA patients. Our results indicated that of the 170 OHCA patients, we failed to screen one survivor of the seven survival discharges for the international BLS and KoCARC II rules. However, the remaining seven TOR rules were classified correctly. Current guidelines recommend that diagnostic tests that guide the cessation of life-saving efforts be accurate and reliable, with an FPV and FPR value close to 0% [7,9]. Among the nine rules, KoCARC TOR rule I was found to be the most effective indicator for poor outcomes, as indicated by the lowest FPV (0% with narrow 95% CI) and highest PPV (>99%). This rule included the combination of three factors, namely, not being witnessed by EMT, presenting with an asystole at the scene, and experiencing no prehospital shock or ROSC. It did not include the patient’s age or ED parameters, thereby making it easy to use in prehospital settings and applicable for OHCA patients in this current pandemic .
This study had several strengths and limitations. First, as with other multicenter observational studies, the integrity of the data could be biased. In addition, the observation period was only 2 months; hence, the effects on long-term survival outcomes, which are most important for OHCA research, remain unknown. In this regard, we will continue to conduct investigations until the COVID-19 pandemic has been effectively contained. Second, it has been speculated that poor survival outcomes are associated with fewer resuscitations and prolonged EMS scene and transport time to the hospital. Moreover, unfavorable neurological outcomes, as a primary outcome, is more suitable than survival to discharge. Because only four patients in our study displayed favorable neurological outcomes, we could not perform any secondary analyses or external validations. Third, the ratio of the survival outcomes was markedly lower in our study than that in previous Korean OHCA reports during the COVID-19 outbreak. This could be due to the direct adverse effects of COVID-19 on the cardiovascular system, prolonged EMS scene time, and differences in treatment in different hospitals . Fourth, the number of COVID-19 cases sharply decreased in April in Daegu. Thus, the sample size was too small for a large-scale multi-factor analysis. Finally, facility or regional differences in EMS resources, CPR quality, and post-cardiac arrest care might affect the survival outcomes during the COVID-19 outbreak. TOR rules in the COVID-19 era and socio-ethical issues must be discussed further, and a consensus process must be developed.