Comment: Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived

We thank Dr White for their insightful comments and findings associated with our recent article evaluating early initiation of vasopressin and the impact on new-onset arrhythmia (NOA) development in septic shock. ¹ Inclusion of our study, which is one of the largest to date evaluating this outcome, with other observational data identified by Huang and colleagues ² resulted in no observed association between early vasopressin use and NOA development. We are not overly surprised by this observation as an association between new-onset atrial fibrillation and adjunctive vasopressin use was not observed in a septic shock subgroup of a recent meta-analysis of randomized controlled trials. ³ While not directly comparable, the consistency of these observations may give clinicians added confidence in the finding and help mitigate concerns surrounding the moderate heterogeneity found by this new meta-analysis. Of course, it is pertinent to stress that clinicians be mindful of the limitations of the included observational studies.

The updated meta-analysis by Dr White observed early initiation of vasopressin was associated with decreased need for renal replacement therapy (RRT), shorter intensive care unit (ICU) length of stay (LOS), and reduced in-hospital mortality. These observations add to the variable data surrounding the effect of early vasopressin on clinical outcomes.^4-9 We agree with Dr White that cautious interpretation and further study of these observations are warranted. Taken together, we believe our study and the expanded meta-analysis by Dr White highlight the evolving discussion on optimizing vasopressor therapy in patients with septic shock, namely, vasopressor timing.

The impact of early vasopressor initiation on septic shock remains debated; however, recent data suggest earlier use may improve outcomes.^10-13 Arterial pH, lactate concentration, and catecholamine dose have each been implicated in the appropriate timing of vasopressin initiation.^14,15 Combined with growing support for minimizing catecholamine toxicity, sepsis phenotypes, vasopressin responders/non-responders, and biomarker-based therapies, the traditional approach to vasopressor utilization is changing.^16-19 Until further elucidated, clinicians may consider an early, multimodal approach to vasopressor selection in septic shock. ²⁰

Our study serves to add to the literature regarding vasopressor optimization, specifically that early vasopressin therapy may be beneficial in reducing the need for RRT, ICU LOS, NOA, and mortality. We hope our article further calls attention to the fact that there is much to be learned regarding the optimal approach to vasopressor therapy and how that approach impacts clinical outcomes.