The goldilocks zone: Vasopressin response is dependent on admission lactate and timing of initiation

Learning Objectives: Vasopressin (AVP) is often utilized in patients with refractory septic shock to augment mean arterial pressure (MAP). However, the most appropriate approach to utilizing this agent is still unknown. This evaluation aimed to elucidate specific cut off values of previously identified factors associated with a positive hemodynamic response to AVP in patients with septic shock. Methods: This was a single center, retrospective evaluation of 938 patients who received fixed-dose AVP for septic shock for at least 6 hours with concomitant catecholamines (CA) in the Medical, Surgical, or NeuroSciences ICU at a tertiary care center. Specific cut off points for lactate concentration, timing of AVP initiation from CA initiation, and baseline CA doses, which correlate with a positive MAP response to AVP were evaluated. AVP response was defined as a decrease in CA dose and achievement of MAP ≥ 65 mmHg 6 hours after AVP initiation. Results: There were 938 patients included: 426 responders (45%), 512 non-responders (55%). Compared to non-responders, responders were more likely to have AVP initiated within 12-48 hours of CA initiation (36.4% vs. 27.1%) and less likely to have AVP initiated within 12 hours of CA (50.2% vs. 60.4%). There was no difference between groups for initiation after 48 hours (13.4% vs. 12.5%; overall p = 0.005). Additionally, responders were more likely to have a lactate concentration ≤2 mmol/L at the time of AVP initiation compared to non-responders (39.4% vs. 25.4%; p < 0.001). There were no significant differences in responders and non-responders in regards to baseline CA dose requirements. When patients were divided into groups based on the timing of AVP initiation and their initial lactate concentration, the highest rate of AVP response was seen in patients that had both AVP initiated between 12-48 hours and an initial lactate concentration ≤2 mmol/L (p < 0.001). The lowest rates of AVP response occurred in patients with both AVP initiated within 12 hours of NE and with a lactate concentration > 2 mmol/L. Conclusions: Patients with septic shock who experienced a positive hemodynamic response to AVP were more likely to have AVP initiated within 12-48 hours of CA initiation compared to nonresponders. Additionally, responders were more likely to have a lactate concentration ≤2 mmol/L at the time of AVP initiation.