Elsevier

Resuscitation

Volume 182, January 2023, 109652
Resuscitation

Clinical paper
External validation of the TiPS65 score for predicting good neurological outcomes in patients with out-of-hospital cardiac arrest treated with extracorporeal cardiopulmonary resuscitation

https://doi.org/10.1016/j.resuscitation.2022.11.018Get rights and content

Abstract

Aim

Estimating prognosis of patients treated with extracorporeal cardiopulmonary resuscitation (ECPR) is essential for selecting candidates. The TiPS65 score can predict neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) treated with ECPR. We aimed to perform an external validation of this score.

Methods

Data from the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry, a multicentred, nationwide, prospectively registered database, were analysed. All adult patients with OHCA and shockable rhythm and treated with ECPR between January 2018 to December 2019 were included. In the TiPS65 score, age, call-to-hospital arrival time, initial cardiac rhythm at hospital arrival, and initial pH value were used as predictors. The primary outcome was 30-day survival with favourable neurological outcomes (Cerebral Performance Category 1 or 2). Discrimination, using the C-statistic, and predictive performances of each score, such as sensitivity and specificity, were investigated.

Results

Of 590 included patients (517 [81.6%] men; median [interquartile range] age, 60 [50–69] years), 64 (10.8%) reported favourable neurological outcomes. The C-statistic of the TiPS65 score was 0.729 (95% confidence interval (CI): 0.672–0.786). When the cut-off of TiPS65 score was set to >1, the sensitivity and specificity were 0.906 (95%CI: 0.807–0.965) and 0.430 (95%CI: 0.387–0.473), respectively; conversely, when the cut-off was set to >3, they were 0.172 (95%CI: 0.089–0.287) and 0.971 (95%CI: 0.953–0.984), respectively.

Conclusions

The TiPS65 score shows reasonable discrimination and predictive performances. This score can be supportive in the decision-making process for the selection of eligible patients for ECPR in clinical settings.

Introduction

Extracorporeal cardiopulmonary resuscitation (ECPR) specifically refers to the deployment of veno-arterial extracorporeal membrane oxygenation (ECMO) before the return of spontaneous circulation (ROSC) during cardiac arrest, and it is considered as one of the advanced resuscitation procedures. Once initiated, the patient’s blood is drained from a central vein and returned to the aorta after being pumped through a membrane lung to provide gas exchange and blood flow to vital organs in the absence of spontaneous circulation.1 ECPR is expected to improve survival and neurological and functional recovery in patients with out-of-hospital cardiac arrest (OHCA), especially those with refractory ventricular fibrillation (VF).2, 3, 4, 5 However, ECPR requires significant financial and personnel resources6, 7 and is an invasive procedure that can cause serious adverse events such as bleeding, limb ischaemia, and infection.8, 9 Therefore, it is important to select appropriate candidates who are likely to be benefitted more from ECPR, rather than applying it to all patients with OHCA. Although an international expert consensus has recently been proposed,10 validated criteria for the selection of patients for ECPR are insufficient. If the prognosis of the patients treated with ECPR can be predicted, then this may help clinicians select the appropriate patients.

Clinical prediction models can be useful tools for estimating the prognosis of patients in emergency departments. Recently, the TiPS65 scoring system was developed for predicting the neurological outcomes of adult patients with OHCA treated with ECPR using a nationwide OHCA registry in Japan.11 It is a simplified score involving four variables, namely, time from call to hospital arrival, pH value, cardiac rhythm on hospital arrival, and age; the data that can be easily collected on hospital arrival. The TiPS65 scoring system showed good discrimination and calibration performance for predicting favourable neurological outcomes of patients with OHCA and shockable rhythm who were treated with ECPR.11 Although many other prognostic prediction models have been developed for patients with OHCA,12 very few have focused on patients requiring ECPR, and the existing models related to ECPR have included only patients with hypothermic cardiac arrest who underwent rewarming with ECPR.13, 14 Thus, TiPS65 is the only model that can predict outcomes in patients with OHCA treated with ECPR. However, this score has not yet been externally validated in other studies, and its reproducibility needs to be evaluated for further application. This study aimed to validate the predictive performance of the TiPS65 score using data different from the original study.

Section snippets

Methods

This study was reported according to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement.15 Study approval was granted by the Ethics Committee of the Kyoto University Graduate School of Medicine (R1045) and the participating hospitals. The requirement for individual patient consent was waived due to the observational nature of the study.

Patient characteristics

Of the 57,754 patients in the JAAM-OHCA registry, 590 patients treated with ECPR were included in the analysis (517 [87.6%] men; median [IQR] age, 60 [50–69] years) (Fig. 1; Table 2). Most patients had witnessed cardiac arrest (78.1%), and more than half had received bystander CPR (58.3%); 151 (26%) had survived the 30-day period, and 64 (10.8%) showed favourable neurological outcomes after 30 days. Other patient characteristics including pre- and in-hospital data are listed in Table 2. The

Key observations and strengths

In this multicentre cohort study, the TiPS65 score showed reasonable external validity for predicting the neurological outcomes of patients with OHCA treated with ECPR. The C-statistic of the model was 0.729 (95%CI: 0.672–0.786), which is comparable to the C-statistic reported in the original development study (0.741, 95%CI: 0.682–0.792). At a cut-off score of >1, the TiPS65 score showed high sensitivity (0.906, 95%CI: 0.807–0.965), while at a cut-off score of >3, it showed high specificity

Conclusion

We validated the TiPS65 score externally for predicting the neurological outcomes of patients with OHCA treated with ECPR; the score showed favourable discrimination and predictive performances. The use of this score is expected to be helpful in the decision-making process for initiating ECPR in actual clinical settings.

Funding

This study was supported by a scientific research grant from the JSPS KAKENHI of Japan (22H03313 (TI) and 22K09139 (TK)).

This study was also supported by a research fund from the ZOLL Foundation (Okada).

The funders have no role in the conduct of this study.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available as it is not permitted by the Ethics Committee. Data are available from the corresponding author on reasonable request.

Conflict of interests

Yohei Okada has received funding from the ZOLL Foundation, an overseas research scholarship from the Fukuda Foundation for Medical Technology, and the International Medical Research Foundation.

Other authors declare that they have no competing interests.

CRediT authorship contribution statement

Yuto Makino: Conceptualization, Methodology, Software, Resources, Formal analysis, Data curation, Writing – original draft, Writing – review & editing, Visualization. Yohei Okada: Conceptualization, Methodology, Writing – review & editing. Taro Irisawa: Investigation, Resources, Project administration. Tomoki Yamada: Investigation, Resources. Kazuhisa Yoshiya: Investigation, Resources. Changhwi Park: Investigation, Resources. Tetsuro Nishimura: Investigation, Resources. Takuya Ishibe:

Acknowledgements

We thank all EMS personnel for collecting Utstein data and Ms. Ikuko Nakamura and Yumiko Murai for supporting our study. Furthermore, we thank the JAAM and all personnel at the participating institutions for their contributions.

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