Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study
Authors: Fong Clare , Kueh Wern Lunn , Lew Sennen Jin Wen , Ho Benjamin Choon Heng , Wong Yu-Lin , Lau Yie Hui , Chia Yew Woon , Tan Hui Ling , Seet Ying Hao Christopher , Siow Wen Ting , MacLaren Graeme , Agrawal Rohit , Lim Tian Jin , Lim Shir Lynn , Lim Toon Wei , Ho Vui Kian , Soh Chai Rick , Sewa Duu Wen , Loo Chian Min , Khan Faheem Ahmed , Tan Chee Keat , Gokhale Roshni Sadashiv , Siau Chuin , Lim Noelle Louise Siew Hua , Yim Chik-Foo , Venkatachalam Jonathen , Venkatesan Kumaresh , Chia Naville Chi Hock , Liew Mei Fong , Li Guihong , Li Li , Myat Su Mon , Zena Zena , Zhuo Shuling , Yueh Ling Ling , Tan Caroline Shu Fang , Ma Jing , Yeo Siew Lian , Chan Yiong Huak , Phua Jason ,   for SICM-NICER group
Published: March 2024

Abstract
Background
Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches.

Methods
This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality.

Results
There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987–19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351–60.298) were both found to be independent predictors of hospital mortality on multivariable analysis.

Conclusions
Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.