Specific Factors Associated with Iatrogenic Withdrawal Syndrome in Children After Cardiac Surgery

Background/Objectives: Iatrogenic withdrawal syndrome (IWS) is common but underrecognized in critically ill children, and data from pediatric cardiac intensive care units (pCICUs) remain limited. This study determined the frequency of IWS after cardiac surgery and the factors associated with it. Methods: Retrospective, single-center cohort study of all pediatric patients admitted to a pCICU after cardiac surgery over 15 months. IWS screening was performed using the Withdrawal Assessment Tool-1 (WAT-1) at least three times daily post-extubation. IWS was defined as at least one WAT-1 score of 3 or higher. A prespecified multivariable logistic regression model with ten perioperative variables was fitted in the complete-case population. A subgroup analysis in ventilated children examined sedative and analgesic exposure, including the grouped duration of remifentanil infusion, in an adjusted model. Results: Of 311 patients, 294 (94.5%) were screened, and IWS occurred in 136 patients (46.3%, 95% CI 40.6-52.0). In the complete-case population (n = 286), univentricular physiology (OR 2.51, p = 0.044), suspected postoperative infection (OR 5.28, p = 0.023), and invasive ventilation for 10-100 h (OR 2.75, p = 0.021) or beyond 100 h (OR 5.29, p = 0.003) were independently associated with IWS, whereas postoperative lactatemia (>2 mmol/L for >6 h) was associated with lower odds (OR 0.39, p = 0.039). In mechanically ventilated children (n = 162), after adjustment, no sedative or analgesic exposure was significantly associated with IWS, while odds were substantially higher in patients receiving remifentanil beyond 48 h (OR 2.64, p = 0.114) and midazolam (OR 3.95, p = 0.057). Conclusions: In our institution, IWS was highly frequent after pediatric cardiac surgery, in particular in patients with univentricular physiology. In sedated patients, midazolam and prolonged remifentanil showed substantially higher, though not statistically significant, odds of developing IWS. These hypothesis-generating associations require prospective confirmation.