The following is a summary of “Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials,” published in the October 2024 issue of Critical Care by Shah et al.
Despite numerous randomized controlled trials (RCTs) on resuscitation in septic shock, there is still no straightforward best approach.
Researchers conducted a retrospective study exploring whether differences in individual responses to resuscitation strategies might explain the mixed results seen in earlier trials.
They divided study 81 sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation groups. Machine learning models were trained to predict individual absolute risk differences (iARDs) in 90-day mortality, checking heterogeneity treatment effect (HTE) variability in validation cohorts while exploring patient characteristics and components of early goal-directed therapy (EGDT).
The results showed that a local-linear random forest model was the top performer in predicting individual absolute risk differences. The validation cohort showed treatment effect variability with significant interaction (P<0.001). For patients grouped by predicted risk, treatment response improved from –8% (95% CI: 1-19% to 4%) and relative risk reduction, 1.34 [0.89-2.01] in quintile 1, indicating potential harm, to 12% (95% CI: 1% to 23%) and 0.64 [0.42-0.96] in quintile 5, suggesting a benefit. Sensitivity analyses supported these results, and pre-intervention albumin was the main contributor to treatment effect variability, while individual early goal-directed therapy components yielded unclear results.
Investigators concluded that treatment responses to early goal-directed therapy varied among patients, with some experiencing significant benefits while others faced harm. Patient characteristics, particularly albumin levels, played a crucial role in identifying this variability in treatment effects.
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