1258: USE OF CAUSAL INFERENCE TO COMPARE NOREPINEPHRINE- AND VASOPRESSIN-RELATED ICU MORTALITY

Abstract

Introduction: The choice of vasopressor has been studied extensively in septic shock, however limited data exists in other shock types. Norepinephrine and vasopressin were compared in a retrospective study of the cardiac surgery population. Vasopressin as first-line treatment of post-cardiac surgery vasoplegic shock was found to improve clinical outcomes. However, the study was associated with biases which limits its validity. As there are no prospective studies, we use causal inference to analyze retrospective data. An observational study allows individual observation under one treatment scenario, while a counterfactual outcome is unknown. Targeted Maximum Likelihood Estimation (TMLE) models counterfactual outcomes with limited confounding by generating a pseudo-population. By adjusting for common causes of death, we were able to compare mortality outcomes between norepinephrine and vasopressin. Methods: An anonymous, publicly available database was analyzed using pre-existing IRB approval. The eICU Collaborative Research Database contains data on over 200,000 ICU admissions. The analysis used 27,388 patients with 25 initial features. Missing values greater than 50% were dropped. Machine Learning Extensions Library (MLxtend) was used to select features sequentially. The primary outcome was ICU mortality. Imputation was performed using Sklearn Iterative Imputuer, data scaled using Sklearn Standard Scaler. Our primary model was TMLE with Logistic Regression. We analyzed vasopressin and norepinephrine administration, accounting for their co-administration by using them as covariates. Net fluid balance, Apache IV, albumin, admission weight, age, diabetes, and metastatic cancer were confounder covariates for both groups. Before analysis, a causal diagram was constructed based on these covariates. Our primary metric was Average Treatment Effect (ATE). Results: Mortality analysis on the norepinephrine group showed an ATE of -0.179, 95% CI [-0.188, -0.167]. Vasopressin showed an ATE of 0.03 (95% CI [0.01,0.051]). Compared to vasopressin, norepinephrine showed a reduction in mortality. Conclusions: We found that norepinephrine was associated with decreased mortality compared to vasopressin in this setting. We hope this study’s results will help guide prospective studies moving forward.