Pharmacodynamic analysis of a fluid challenge with 4 ml kg⁻¹ over 10 or 20 min: a multicenter cross-over randomized clinical trial

Purpose: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg⁻¹. Methods: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg⁻¹ of crystalloids in 10 (FC₁₀) or 20 (FC₂₀) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (d_max), time when the d_max was observed (t_max), change from baseline at 1-min (d₁) and 5-min (d₅) after FC end. Results: After FC₁₀ and FC_20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The d_max and the t_max were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end. Conclusions: The infusion time of FC administration affects fluid responsiveness, being higher for FC₁₀ as compared to FC₂₀. The effect on flow variables of either FCs fades 5 min after the end of infusion.