Introduction: Organ failure is the key determinant of severity in acute pancreatitis, while increased serum chloride was associated with increased organ failure in critically ill patients. This study aimed to investigate the association between the trajectory of early serum chloride and prolonged organ failure in patients with predicted severe AP (pSAP).
Methods: This is a secondary analysis using data from two multicenter trials that enrolled patients with pSAP. All patients enrolled in the CLEVER-AP trial1 (training cohort) and patients who had serum chloride measured during the first 5 days from the TRACE trial2 (validation cohort) were included. Group-based trajectory modeling was applied to serum chloride to develop trajectory sub-phenotypes. Patients in the validation cohort were classified into sub-phenotypes by minimizing the squared residual error between their chloride measurements and each trajectory's predicted values. The multivariate logistic regression model was used to analyze the association between trajectory sub-phenotypes and a composite outcome of prolonged organ failure or death defined by the presence of organ failure on day 7 or death before day 7.
Results: There were 259 patients in the training cohort and 345 patients in the validation cohort. Three chloride trajectory sub-phenotypes were developed: group A had a persistently low chloride level. The chloride in Group B was high at baseline and then decreased over time. Group C had a persistently high chloride level. There were significant differences in the incidence of the composite outcome among the three groups in the training cohort (11.2%, 22.5%, 62.5% from group A to C; P＜0.001). Taking group A as the reference, group C was significantly associated with increased incidence of the composite outcome (adjusted odds ratio [aOR]: 15.83, 95%CI: 4.95-50.58; p <0.001). Notably, the validation cohort successfully replicated the associations identified in the training cohort (incidence of the composite outcome: 45.4%, 51.65%, and 72.3% from group A to C; P＜0.001).
Conclusion: Chloride trajectory sub-phenotypes were consistent across independent cohorts with distinct outcomes. Persistently high serum chloride levels were associated with a higher risk of prolonged organ failure or death in patients with pSAP. Chloride restriction might be a promising strategy in this population.