Out-of-hospital cardiac arrest termination of resuscitation (TOR) rules - Systematic Review of diagnostic accuracy: EIT 6303 (EIT642) TF SR

Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest: none

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees: MAS and GDP funded by the NIHR (UK) to review and update the UK termination of resuscitation guideline used by UK ambulance services.

CoSTR Citation

Lauridsen KG, Allan K, Greif R - on behalf of the International Liaison Committee on Resuscitation Education, Implementation and Teams Task Force.

Prehospital termination of resuscitation (TOR) rules Draft Consensus on Science with Treatment Recommendations. International Liaison Committee on Resuscitation (ILCOR) Education, Implementation and Teams Task Force, 2024, November 4. Available from: http://ilcor.org

Methodological Preamble (and Link to Published Systematic Review if applicable)

A systematic review on prehospital termination of resuscitation rules was first published as part of the 2020 ILCOR Consensus on Science with Treatment Recommendations (CoSTR).¹ The author group behind this ILCOR review subsequently published a systematic review summarizing the findings from the 2020 ILCOR CoSTR including an updated literature search until January 2024 and additional analyses including literature on cost-effectiveness.² Accordingly, this systematic review is based on the existing search strategy and include literature from January 1^st 2023 to ensure that no recent literature was missed. We conducted an adolopment of the recently published review and conducted data extraction and risk of bias assessment for any paper published after the existing review. In accordance with the previous ILCOR review, we considered papers for prehospital termination of resuscitation rules to be used by the emergency medical services personnel in the prehospital setting. Studies addressing termination of resuscitation among patients arriving at the Emergency Department by ambulance, and in-hospital termination of resuscitation were excluded.

PICOST

PROSPERO Registration CRD42019131010

Quality of evidence was assessed using the QUADAS-2 framework for systematic reviews of diagnostic accuracy studies. Risk of bias for each outcome (prediction of death and prediction of poor neurologic outcome) was assessed independently. Risk of bias was ultimately found to be the same for both outcomes and is reported per outcome, across the range of studies. The domains of patient selection, index test, reference standard, are also assessed in terms of concerns regarding applicability.

The quality of the review identified for adolopment was rated using the AMSTAR framework. Kasper G. Lauridsen had an intellectual conflict as co-author of the review and was therefore excluded from AMSTAR rating.

Consensus on Science

The 2020 ILCOR CoSTR identified 34 studies addressing the use of termination of resuscitation rules. This included 12 observational studies reporting derivation and internal validation on prediction of death in hospital (very low certainty evidence), 24 observational studies reporting external validation on prediction of death in hospital (very low certainty evidence), 6 observational studies reporting derivation and internal validation on prediction of poor neurological outcomes (very low certainty evidence), 11 observational studies reporting external validation on poor neurological outcomes (very low certainty evidence), and one clinical validation study reporting prediction of death in hospital (moderate evidence).¹ No meta-analysis was conducted for the 2020 CoSTR due to high risk of bias and heterogeneity.

The updated review by Smyth et al.² identified additional 10 studies that were all observational assessin.^3–12 The new studies identified by Smyth et al. were all observational studies reporting on validation of different TOR rules from historical cohorts. The studies are summarized in table 1-3 for the outcomes of No ROSC (Table 1), Death in hospital (Table 2), and Death or survival with unfavourable neurological outcome (Table 3) along with a description of the performance of the TOR rules being validated (several studies validated several scores and/ or the same score in different cohorts).

Table 1: Prediction of no return of spontaneous circulation

Table 2: Prediction of death in hospital

Table 3: Death or survival with unfavourable neurological outcome

Following the systematic review, we identified 3 additional studies for inclusion. Two studies investigating cost-effectiveness of different TOR rules^13,14 and one study on the derivation of a new TOR rule for pediatric OHCA.¹⁵ Khan et al. estimated quality-adjusted life years for survivors based on data from a systematic review applied on OHCA in the United Kingdom and identified that the most cost-effective strategies were the ERC TOR rule (incremental cost-effectiveness ratio (ICER) of £8,111), the Korean Cardiac Arrest Research Consortium 2 (KOC 2) TOR rule (ICER of £17,548), and the universal Basic Life Support (BLS) TOR rule (ICER of £19,498,216).¹⁴ The KOC 2 TOR rule was cost-effective at the established cost-effectiveness threshold of £20,000–£30,000 per QALY. Nazeha et al. investigated the cost-effectiveness following implementation of TOR rules in Singapore based on cases that were terminated in the field and all cases applicable for TOR although clinicians decided transport to hospital.¹³ The found that terminating CPR on all patients eligible for the TOR rule would result in 31 additional deaths per 10,000 patients compared to No TOR. If TOR is exercised for every eligible case, it could expect to save approximately $400,440 per QALY loss compared to No TOR, and $821,151 per QALY loss compared to Observed TOR.

Shetty et al. derived a new pediatric TOR rule to predict no survival or unfavourable neurological outcome.¹⁵ The TOR rule was derived in a dataset from 2013-2019 and validated during 2020-2022. The specificity was 99.1% in the derivation cohort and 99.7% in the validation cohort (including the period of COVID-19).

Certainty of Evidence

Overall, the available evidence did not provide major changes to the trust in the TOR rule performances or the certainty of evidence for adult OHCA. Only one change was made for the critical outcome of clinical validation of a TOR rule to predict death in hospital. Based on review of Morrison 2014¹⁶ it was decided to downgrade for both imprecision and indirectness resulting in low-certainty evidence. The certainty of evidence across all outcomes for adult OHCA are presented in table 4.

Table 4: Certainty of evidence for adult OHCA

Pediatric out-of-hospital cardiac arrest

We assessed pediatric OHCA as a separate population. We identified evidence 3 studies assessing TOR rules in pediatric patients for the prediction of death. One study applying adult TOR rules in pediatric patients,⁵ derivation of the MIEMMS score,⁸ and derivation of the pToR score.¹⁵ Evidence was rated as very low certainty (downgraded for risk of bias, imprecision, and indirectness).

Treatment Recommendations

For adult out-of-hospital cardiac arrest, we suggest that emergency medical service systems may implement termination of resuscitation (TOR) rules to assist clinicians in deciding wehter to discontinue resuscitation efforts at the scene or to transport to hospital with ongoing CPR. We suggest that TOR rules may only be implemented following local validation of the TOR rule with acceptable specificity considering local culture, values, and setting (conditional recommendation, very-low certainty evidence).

For pediatric out-of-hospital cardiac arrest we suggest against the use of TOR rules to decide whether to terminate resuscitation efforts or not due to insufficient evidence (conditional recommendation, very-low certainty evidence).

Justification and Evidence to Decision Framework Highlights

The task force made a conditional recommendation for the use of termination of resuscitation (TOR) rules for adult OHCA in line with the last CoSTR on termination of resuscitation. The values in making this recommendation remain largely unchanged.

In making this recommendation, we recognise variation in patient values, resources available, and performance of TOR rules in different settings.

We note that the certainty of evidence is very low and limited by a lack of clinical validation studies.

The task force recognizes that application of TOR rules may result in missed survivors but has the potential to reduce variation in practice associated with clinician judgement and prevent premature terminations by clinicians.

We recognize that termination of resuscitation rules are already implemented in some EMS systems. In settings where EMS personnel will transport all patients to the hospital, the use of TOR rules may be associated with reduced costs. In contrast, the potential economic benefit in EMS systems with physician-staffed ambulances competent of terminating CPR may be absent.

The task force recognizes that the performance of TOR rules varies depending on the EMS system, the setting, and the survival rate in the population. Therefore, TOR rules should not be implemented without assessing the local validity of a TOR rule and the validity should be reassessed as survival outcomes change over time.

We considered pediatric OHCA as a separate population, and we value that missed survivors in this population may be valued differently from the adult population. Several missed survivors were seen when applying adult TOR rules to the pediatric population and the two TOR rules derived specifically for the pediatric population remains to be externally validated.

Knowledge Gaps

There is a paucity of evidence addressing use of TOR rules in clinical practice. Studies are required to address:

• Accuracy of TOR rules in clinical practice
• Compliance with OOH-TOR rules
• Implementation strategies of TOR rules for EMS based on evidence
• Societal perceptions and acceptability of TOR rules
• Validation of TOR rules specific for children
• Impact of TOR rules on non-heart-beating organ donation
• Risk associated with emergent transport of futile cases with ongoing resuscitation

Attachment: EIT 6303 Adolopment OH TOR rules Et D table

References

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