Optimal Vasopressin Initiation in Septic Shock: The OVISS Reinforcement Learning Study.

Summary

Using reinforcement learning on large multicenter EHR data, the OVISS study recommended initiating vasopressin earlier, in more patients, and at lower norepinephrine doses than typical practice, with an associated reduction in in-hospital mortality. The rule was externally validated across 227 US hospitals and showed superior expected outcomes versus clinician behavior.

Key Findings

• The RL-derived rule suggested vasopressin in 87% vs 31% of patients under usual care.
• Initiation occurred earlier (median 4 vs 5 hours from shock onset) and at lower norepinephrine doses (0.20 vs 0.37 µg/kg/min).
• Adherence to the rule was associated with lower hospital mortality (adjusted OR 0.81, 95% CI 0.73-0.91) across external datasets.

Clinical Implications

Consider earlier vasopressin initiation at lower norepinephrine doses for septic shock, guided by decision-support tools; prospective trials are needed before protocol changes.

Limitations

• Observational design with potential residual confounding and confounding by indication
• Reliance on EHR data quality; generalizability to non-US settings uncertain

Future Directions

Prospective pragmatic trials to test RL-guided vasopressor strategies; integration into EHR decision support with safety and fairness monitoring.