External validation of the simple NULL-PLEASE clinical score in predicting outcomes in men and women with out-of-hospital cardiac arrest
Authors: Byrne C , Barcella C , Krogager M L , Pareek M , Ringgren K B , Wissenberg M , Folke F , Gislason G , Kober L , Lippert F , Kjaergaard J , Hassager C , Torp-Pedersen C , Lip G Y H , Kragholm K 
Published: October 2022

Abstract

Background
The NULL-PLEASE score (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood pH &lt;7.2, Lactate &gt;7.0 mmol/L, End-stage renal disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) was developed to help identify patients with out-of-hospital cardiac arrest (OHCA) who are unlikely to survive. Although survival after OHCA differs between sexes, the performance of the NULL-PLEASE score according to sex has not been tested previously.

Purpose
To validate the NULL-PLEASE score separately in men and women in a nationwide setting.

Methods
Using Danish nationwide registry data from 2001–2019, we retrospectively identified male and female OHCA survivors with return of spontaneous circulation (ROSC) or ongoing cardiopulmonary resuscitation at hospital arrival. The primary outcome was 1-day mortality. Secondary outcomes were defined as 30-day mortality and the combination of 1-year mortality or anoxic brain damage. Logistic regression with a NULL-PLEASE score of 0 as reference was used for outcome risk estimation. The predictive ability of the score was assessed using area under the receiver operating characteristics (AUCROC) curves.

Results
A total of 2,601 men (median age 67 years (interquartile range (IQR) 56–76 years), and 1,280 women (median age 69 years (IQR 58–79 years) were included. One-day mortality was 31% in men and 42% in women; 30-day mortality was 56% and 71% in men and women, respectively; and 63% of men and 78% of women experienced the combined outcome. For patients with a NULL-PLEASE score ≥9, absolute risks were: 1-day mortality: 82.0% (95% confidence interval [CI]: 75.6–88.4%) for men and 79.1% (95% CI: 71.3–86.8%) for women; 30-day mortality: 98.6% (95% CI: 96.6–100.0) for men and 97.1% (95% CI: 94.0–100.0%) for women; and the combined outcome: 99.3% (95% CI: 97.9–100.0%) for men and 97.1% (95% CI: 94.0–100.0%) for women. AUCROC values for 1-day mortality were 0.827 (95% CI: 0.811–0.844) for men and 0.736 (95% CI: 0.710–0.763) for women. Results were similar for 30-day mortality and for the combined outcome. ROC curves for all outcomes are shown in Figure 1 (men) and Figure 2 (women). For a NULL-PLEASE score cut-point ≥3 to predict 1-day mortality, the positive predictive value was 91.8% in men and 91.1% in women, with a sensitivity of detecting patients who die of 47.3% in men and 51.8% in women. The corresponding negative predictive value for surviving more than 1 day was 54.6% in men and 37.7% in women, and the specificity of detecting patients who survive was 93.7% in men and 85.3% in women.

Conclusions
In a nationwide OHCA-cohort, the NULL-PLEASE score consistently appeared to perform better in men than in women for all outcomes. Nevertheless, its predictive ability was high among both sexes. Sex-specific differences should not be overlooked in clinical decision-making in patients surviving OHCA.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Danish Foundation TrygFonden