Attenuated hemodynamic response to adjunct vasopressin in obese septic shock patients: a physiological or dose-dependent effect?

INTRODUCTION: Obesity is increasingly prevalent in ICU patients, often requiring adjusted dosing due to altered drug pharmacodynamics. Arginine vasopressin (AVP) is used adjunctively to norepinephrine (NE) in septic shock, but its hemodynamic efficacy may vary with body mass index (BMI), potentially influencing NE-sparing effects. METHODS: ). NE and AVP doses were recorded every 15 minutes. Multivariable linear mixed-effect models assessed between-group differences in NE trajectories within two and five hours after AVP initiation and the interaction between BMI and time, followed by a secondary analysis including AVP dosing. RESULTS: Thirty-three percent were normal weight, 34.5% overweight and 32.5% obese. The model-estimated NE dose decreased by 6.1% (95%CI 1.7-10.6) per hour in normal weight patients, remained stable in overweight patients (-2.0%, 95%CI -6.3-2.4), and increased by 5.5% (95%CI 1.0-10.0) per hour in obese patients. The three-way interaction of AVP dose, time and BMI was significant (p<0.001), with higher AVP dose being associated with a decrease in NE requirements in normal weight patients but not in overweight and obese patients. BMI-adjusted AVP dosing did not significantly alter NE requirements compared to fixed dose (all p>0.70). CONCLUSIONS: In septic shock patients, obesity is associated with increased NE requirement after AVP initiation, in contrast to the reduction observed in normal weight patients. Obesity-related resistance to AVP may be driven by intrinsic physiological factors rather than insufficient dosing.