The main findings of the present study are as follows: (1) patients with OHCA who were < 69 years old and achieved prehospital ROSC without adrenaline use had a high favorable neurological survival rate at 1 month (70.8%) in this population; (2) the time from collapse to first shock was a crucial factor for patients aged ≥ 69 years who achieved prehospital ROSC without adrenaline use; and (3) in addition to the presence of bystander CPR, earlier transportation to hospital had a great effect on the favorable neurological survival rate in patients aged 69–80 years, particularly when the first shock was delayed (≥ 10 min). This prediction model may provide valuable support for decision-making in patients with witnessed OHCA and an initial shockable rhythm in the emergency department.
Prehospital predictors of outcomes in patients with OHCA
Previous studies proposed useful predictive scoring models for patients with OHCA3,4,5. The ROSC after cardiac arrest score was developed from the German Resuscitation Registry to predict the probability of ROSC with AUCs of 0.71 and 0.73 in the development and validation cohorts, respectively, in patients with OHCA by using sex, age, the presence of bystander witness, initial rhythm, location of cardiac arrest, etiology of cardiac arrest, and time until arrival of professionals3. Similarly, using Utstein templates for patient data collection, the Utstein-based ROSC score was developed to identify the probability of ROSC and survival to hospital admission of OHCAs with an AUC of 0.83 by using age, sex, etiology, location, bystander CPR, rhythm, and time to EMS arrival4. Recently, in patients with OHCA in Asia, the prehospital ROSC score was developed with an AUC of 0.81 by including variables such as age, time to EMS arrival, initial rhythm, witnessed arrest, and prehospital drug administration5.
The aforementioned three risk-scoring models were developed to estimate the probability of ROSC in patients with OHCA, but post-cardiac arrest brain injury is commonly observed in this patient population even when resuscitation is performed20. Approximately 80% of patients who are admitted to an intensive care unit after resuscitation from OHCA are comatose21, and most of them experience severe neurological disability or death22, Thus, the prediction model for neurological outcomes is important to inform patients’ relatives of the correct prognosis and avoid excessive care in patients with irreversible post-cardiac arrest brain injury20. In addition, patients with witnessed arrest and/or an initial shockable rhythm have more favorable outcomes than those without9,10. Previous studies indicated that early defibrillation is associated with favorable outcomes in patients with witnessed OHCA and a shockable rhythm11. Thus, patients with witnessed OHCA and an initial shockable rhythm may have unique prehospital predictors of favorable outcomes. Several prediction models have been developed to estimate favorable neurological survival. The OHCA score, derived from patients with OHCA admitted to a French intensive care unit, can provide a probability of survival with good neurological function, with an AUC of 0.82, using estimated no-flow and low-flow intervals and blood lactate and creatinine levels23. However, this prediction model included only patients who achieved successful resuscitation and had blood examination data (i.e., lactate and creatinine levels). In this context, the Cardiac Arrest Survival Score was developed as a simple clinical tool to predict favorable neurological survival at hospital discharge24. This prediction model offers the probability of survival with good neurological function, with an AUC of 0.88, using factors such as age, initial rhythm, bystander CPR, adrenaline use, previous disease, place, amiodarone, witness, prehospital ROSC, time from collapse to CPR, and CPR time24. These calculation systems may be clinically useful25, and decision tree models are also practical for stratifying patient risks and trajectories without a calculator. Goto et al. demonstrated that patients with OHCA can be stratified (from 0.3 to 23.2% of favorable neurological survival probability at 30 days) using four prehospital variables (initial shockable rhythm, age, witnessed arrest, and witnessed by EMS personnel)12. Nevertheless, dedicated prediction models for patients with witnessed OHCA and an initial shockable rhythm have not yet been fully evaluated. Although a machine learning-based prognostic model for patients with OHCA and an initial shockable rhythm has been investigated, its clinical applicability may be challenging26. Therefore, we aimed to develop a decision tree model for stratifying favorable neurological survival prediction in patients with witnessed OHCA and an initial shockable rhythm using prehospital factors.
Validation of the present study compared with that of previous studies
In the present study, the presence of prehospital ROSC was the most important factor for achieving a favorable neurological outcome. This result is reasonable because previous studies have shown that prehospital ROSC is one of the strongest predictors of favorable outcomes9. The next-best predictor was the absence of prehospital adrenaline administration. In the current guidelines, the administration of prehospital adrenaline for patients with a shockable rhythm is weakly recommended when initial defibrillation attempts have failed27. A recent randomized controlled trial and large-scale meta-analysis showed that prehospital adrenaline administration improves the probability of survival to discharge but has no significant effect on favorable neurological outcomes28,29. Furthermore, a prospective, nonrandomized, observational propensity analysis reported that the administration of prehospital adrenaline is a significant negative predictor of favorable neurological survival (CPC 1–2: odds ratio 0.31 [95% CI 0.26–0.36]30. Although whether prehospital adrenaline is beneficial for patients with OHCA remains controversial, the presence of prehospital adrenaline use is a robust negative factor in achieving favorable neurological survival in this population.
Younger age and earlier defibrillation attempts are well-known risk factors for favorable outcomes31,32,33. In the present study, early defibrillation attempts (< 10 min) provided better neurological prognosis in patients aged 69–80 years old, and very early defibrillation attempts (< 3 min) were associated with neurologically favorable survival in older patients (> 81 years). Early defibrillation is a well-known predictor of favorable prognosis, while very early defibrillation (< 3 min) by EMS may be achieved only in specific situations, such as in patients who experience a cardiac arrest in the presence of EMS. Therefore, the findings on very early defibrillation should be interpreted with caution. Interestingly, this decision tree model suggested that the benefit of bystander CPR on favorable neurological survival was pronounced in patients aged 69–80 years without early defibrillation attempts (≥ 10 min). Furthermore, the factor “bystander CPR by citizen” was selected using recursive partitioning analysis regardless of inputting the categories of “chest compression by citizen,” “rescue breathing by citizen,” and “bystander CPR by citizen,” suggesting that the presence of “first aid” by citizen might be important for favorable neurological survival34,35,36,37.
Finally, this decision tree model showed that earlier transportation to a hospital considerably affected favorable neurological outcomes in patients receiving bystander CPR by citizens. The effect of transport time on favorable outcomes remains debatable in patients with OHCA38,39,40. A systematic review and meta-analysis reported that paramedic transport time is not significantly different between OHCAs with favorable and those with unfavorable neurological outcomes at hospital discharge (mean difference: + 17 min, 95% CI from − 10.37 to 44.37 min)38. However, residual confounding factors may have probably influenced this result38,39,40. Our study suggests that earlier transportation might be beneficial for favorable neurological survival, particularly in patients with witnessed OHCA, an initial shockable rhythm, prehospital ROSC, and bystander CPR, but without early defibrillation attempts.
Clinical implication
To the best of our knowledge, this is the first decision tree model that was developed particularly for patients with witnessed OHCA and an initial shockable rhythm to predict a favorable neurological prognosis. By using this prediction model, patient risks and prognosis can be promptly stratified based on prehospital factors without a calculator in the emergency room, as opposed to previous scoring models3,4,5,6,7,8, thereby aiding in decision-making for the further application of advanced medical support, such as veno-arterial extracorporeal membrane oxygenation. However, the decision depends on several factors, such as the preference of patient and family members, prognosis at baseline, and medical resources and the accuracy of the present model is not yet established. Therefore, the clinical decision should not be made uniformly. Further, our decision tree model implies that very early defibrillation (< 3 min) may contribute to better neurological prognosis, especially in older patients (> 81 years). In addition, earlier hospital transportation (> 36 min) might be beneficial for favorable neurological survival, particularly in those with prehospital ROSC and who are provided bystander CPR but without early defibrillation attempts. Further studies are warranted to confirm these findings.
Study limitations
The present study has several limitations. Because we obtained limited information from the FDMA database, important data, such as body mass index, comorbidities, and post-arrest care at a hospital (e.g., mechanical circulatory support, targeted temperature management, and coronary interventional therapies), were not available. In addition, some variables necessary to calculate previous predictable scoring models, such as blood lactate and creatinine levels, were missing. Because we defined short-term favorable neurological survival (at 1 month) as the primary endpoint, our prediction model may not be applicable for predicting long-term outcomes. However, a systematic review reported that long-term neurological outcome scores after OHCA are consistent with short-term outcomes at 30 days8. Therefore, our model may also predict long-term outcomes.
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