Critical Care Alert: Termination-of-resuscitation Rule in the ED Following Refractory Out-of-Hospital Cardiac Arrest

Article
Goto Y, Funada A, Maeda T, et al. Termination-of-resuscitation rule in the emergency department for patients with refractory out-of-hospital cardiac arrest: a nationwide, population-based observational study. Crit Care. 2022;26:137.

Background
In 2010, the international consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science with treatment recommendations (also known as CoSTR) endorsed the use of termination of resuscitation rules (TOR) for patients with out of hospital cardiac arrest (OHCA).^1,2 This was modified in 2020 to assist physicians with the decision to discontinue resuscitation of OHCA in the field or to transport the patient to a hospital. In some countries, such as Japan, the TOR rules legally cannot be implemented by EMS; all OHCA must be transported to a hospital. Goto’s TOR rule was developed in 2013, which states that upon reaching a hospital, resuscitation of these patients can be terminated if the three following criteria are met: arrest unwitnessed by bystanders, initial unshockable rhythm in the field, and no prehospital ROSC. However, when compared to other TOR rules, Goto’s TOR rule has been found to have low specificity.  In addition, there are no TOR rules that consider the duration of CPR by EMS providers. The modified Goto’s TOR rule for termination of resuscitation on hospital arrival includes the prior 3 criteria plus the duration of CPR by EMS ( > 20 minutes).

Objective
This study aimed to develop and validate a modified Goto’s TOR rule. They also validated the other TOR rules (Goto’s TOR, Korean Cardiac Arrest Research Consortium [KoCARC] I, and III rules).^3,4

Design
This study is a nationwide, population-based observational study including all adult patients (aged ≥ 18 years) who experienced OHCA and were resuscitated by EMS between 1 January 2016 and 31 December 2019 in Japan. There were multiple steps to the study. A decision rule (the modified Goto TOR) was developed via recursive partitioning (a form of decision tree analysis) and was validated with a previously separated validation cohort of patients. In addition to this analysis, multiple other TOR rules were included for external validation as well.

Exclusion Criteria

• Age < 18 years
• Physician on board the ambulance
• Unknown CPR duration by EMS
• Origin of cardiac arrest due to accidental hypothermia

Methods
The Fire and Disaster Management Agency (FDMA), which supervises Japan’s EMS system supplied de-identified information for this study.

The primary endpoint was the specificity, false-positive rate (FPR), and positive predictive value (PPV) of the modified Goto’s TOR rule for the prediction of one month mortality and unfavorable neurological outcome. Unfavorable neurological outcome was determined via the cerebral performance category (CPC).  A CPC category of 1 is good cerebral performance; category 2, moderate cerebral disability; category 3, severe cerebral disability; category 4, coma or vegetative state; and category 5, death. The secondary endpoints were the other TOR rules for predicting the one month mortality and unfavorable neurological outcome.

Outcomes

• 465,657 patients were included in this study.
• The patients were separated into two groups: the development group (2016–2017; n=231,363) and the validation group (2018–2019; n=234,294).
• In the development group (2016-2017), 27.5% (95% CI 27.3–27.6%) of patients fulfilled all four criteria of the modified Goto’s TOR criteria, and had a survival rate of 0.17%.
• In the validation group, 27.8% (95% CI 27.6–28.0%) of patients met criteria and had a 30 day survival rate of 0.21% (95% CI 0.18–0.25%), specificity of 99.1% (95% CI 98.9–99.2%), FPR of 0.9% (95% CI 0.8–1.1%), and PPV of 99.8% (95% CI 99.8–99.8%).
• The 27.8% of patients in the validation group who met criteria had 30 day good neurological outcome (CPC 1-2) of 0.05% (95% CI 0.03%-0.07%), specificity of 99.7% (95% CI 99.5%-99.8%), FPR of 0.3 (95% CI 0.2-0.4), and PPV of 99.9% (95% CI 99.9%-99.9%)

Key Results

• The modified Goto TOR demonstrated good test characteristics for identifying cardiac arrest patients who were not likely to survive or have good neurological outcome
• The specificity,PPV, and FPR of the modified Goto’s TOR rule for predicting one month mortality were significantly superior than the other three TOR rules (all P<0.001).

Limitations

• The modified Goto TOR was developed and validated among a specific patient population and EMS system, and care should be taken when extrapolating results to other patient populations.
• The authors did not have data on EtCO2 measurements for these patients. They are thus missing a key piece of information that is frequently used in making the decision to terminate resuscitation.
• The authors did not pre-specify what test characteristics would be acceptable prior to validation of the rule
• As an observational study, it cannot exclude confounders such as pre-existing comorbidities, location of the arrest, quality of bystander CPR or EMS-initiated CPR, and in-hospital treatments.

EM Takeaways

• The modified Goto's TOR rule has a 99.9% PPV of mortality or poor 1 month neurological outcome, which the authors state is within the acceptable range used by medical ethicists for defining medical futility.⁵
• While Japan has a different EMS system than the United States, this study demonstrates that prolonged OHCA continues to show poor patient outcomes, in regard to neurologic function and mortality.

References

1. Mancini ME, Soar J, Bhanji F, Billi JE, Dennett J, Finn J, et al. Part 12: education, implementation, and teams. 2010 International consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation. 2010;122:S539–81.
2. Soar J, Mancini ME, Bhanji F, Billi JE, Dennett J, Finn J, et al. Part 12: education, implementation, and teams: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation. 2010;81:e288-330.
3.  Yoon JC, Kim YJ, Ahn S, Jin YH, Lee SW, Song KJ, et al. Factors for modifying the termination of resuscitation rule in out-of-hospital cardiac arrest. Am Heart J. 2019;213:73–80.
4. Goto Y, Maeda T, Goto YN. Termination-of-resuscitation rule for emergency department physicians treating out-of-hospital cardiac arrest patients: an observational cohort study. Crit Care. 2013;17:R235.
5. Sasson C, Hegg AJ, Macy M, Park A, Kellermann A, McNally B. Prehospital termination of resuscitation in cases of refractory out-of-hospital cardiac arrest. JAMA. 2008;17:1432–8.