Vasopressin Loading for Refractory Septic Shock: A Preliminary Analysis of a Case Series

Abstract

Background: Vasopressin is one of the strong vasopressor agents associated with ischemic events. Responses to the administration of vasopressin differ among patients with septic shock. Although the administration of a high dose of vasopressin needs to be avoided, the effects of bolus loading have not yet been examined. Since the half-life of vasopressin is longer than that of catecholamines, we hypothesized that vasopressin loading may be effective for predicting responses to its continuous administration.Methods: We retrospectively analyzed consecutive cases of septic shock for which vasopressin was introduced with loading under noradrenaline at >0.2 μg/kg/min during the study period. Vasopressin was administered in a 1 U bolus followed by its continuous administration at 1 U/h. The proportion of patients with a negative catecholamine index (CAI) change 6 h after the introduction of vasopressin was set as the primary outcome. We defined non-responders for exploration as those with a mean arterial pressure change <18 mmHg 1 min after vasopressin loading, among whom none had a change in CAI <0.Results: Twenty-one consecutive cases were examined in the present study, and included 14 responders and 7 non-responders. The primary outcome accounted for 71.4% of responders and 0% of non-responders, with a significant difference (p = 0.0039). Median CAI changes 2, 4, and 6 h after the administration of vasopressin were 0, −5, and −10 in responders and +20, +10, and +10 in non-responders, respectively. CAI was not reduced in any non-responder. Outcomes including mortality were not significantly different between responders and non-responders. Digital ischemia (1/21) and mesenteric ischemia (1/21) were observed.Conclusions: Vasopressin loading may predict responses to its continuous administration in septic shock patients. Further investigations involving a safety analysis are needed.

Surviving Sepsis Campaign Research Priorities 2023

“…Often the response to vasopressor agents is not taken into account when defining these subphenotypes, even though different trajectories are associated with different outcomes (156). Selecting patients responding to vasopressin may be achieved with the use of a loading dose (157), but this is less likely to occur with other vasopressor agents. It also needs to be determined whether perfusion targets should be adjusted to the phase of sepsis (158).…”

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases

“…This is analogous to broad-spectrum and early antimicrobials in suspected and confirmed sepsis. Some studies pointed out that whether vasopressin was used or not could be based on the hemodynamic response after 1 U bolus vasopressin is administered [ 28 ] or a machine learning prediction model [ 29 ]. On the contrary, Jakowenko et al found that early vasopressin initiation was not associated with responsiveness at 4 h post-catecholamine initiation, suggesting that it may be reasonable to implement the 2021 SSC guidelines [ 30 ].…”

Evaluation of vasopressin use in the management of refractory shock in patients admitted to the intensive care unit

“…However, it is noteworthy that the half-life of the drug is 10 to 35 min, requiring a longer time to reach steady state and adequate pharmacological response. For this reason, bolus administration is often used in medical practice due to the severity of refractoriness cases (Nakamura et al 2021).…”