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