Correlation Between Analgesic and Sedative Drug Withdrawal and Salivary Cortisol Levels in Children in PICUs : A Prospective Cohort Study

ABSTRACT Background and Objective Opioids and benzodiazepines are the most widely utilized sedative‐analgesic agents in pediatric intensive care units (PICUs). However, prolonged exposure to these drugs may lead to drug tolerance and dependence, whereas abrupt discontinuation or rapid dose reduction can precipitate withdrawal symptoms, which increase the risk of complications such as medical device dislodgement, exacerbated patient discomfort, and prolonged mechanical ventilation dependency and hospital stays. Studies have revealed that up to 94% of children in PICUs develop iatrogenic withdrawal syndrome (IWS), but there is currently no gold standard for a definitive diagnosis of IWS. This study aims to explore the correlation between salivary cortisol levels, sedation‐analgesia status, and the occurrence of IWS in critically ill children. Methods A total of 118 critically ill children who were exposed to sedative and/or analgesic drugs for a continuous period of ≥ 5 days at Yuying Children's Hospital, Affiliated Second Hospital of Wenzhou Medical University, from October 2022 to September 2024, were screened, and 106 patients were included in the study. Based on the Sofia observation withdrawal symptoms scale (SOS) score, 42 patients were divided into the IWS group (SOS ≥ 4) and 64 patients into the non‐IWS group (SOS < 4). The usage of sedative and analgesic drugs was compared between the two groups, as well as the salivary cortisol concentrations at 24, 48, and 72 h after drug withdrawal. The influencing factors of IWS occurrence and the predictive value of related indicators were analyzed. Results The cumulative doses of sedative and analgesic drugs administered in the IWS group were statistically significantly higher than those in the non‐IWS group ( p < 0.05). The median salivary cortisol concentration in the IWS group was significantly higher at 24 h after drug discontinuation compared with the non‐IWS group. Logistic results of binary regression analysis showed that a higher level of salivary cortisol at 24 h after discontinuation was an independent predictor for the occurrence of IWS ( p < 0.05). Receiver operating characteristic (ROC) curve analysis indicated an area under the curve of 0.857 (95% confidence interval (CI): 0.782–0.932) with sensitivity and specificity of 88.1% and 84.4%, respectively. Conclusions A statistically significant correlation was observed between salivary cortisol levels, the cumulative dosage of sedative‐analgesic drugs, and the occurrence of IWS. Higher levels of salivary cortisol are a predictor of IWS occurrence. Detecting salivary cortisol levels has clinical application for early diagnosis of IWS and judgment of withdrawal severity in critically ill children.