Nicholas Jakowenko, PharmD, BCCCP
Clinical Staff Pharmacist
Mayo Clinic
Rochester, Minnesota
Disclosure information not submitted.
Joseph Murata, PharmD
Clinical Pharmacist
Banner Thunderbird Medical Center, United States
Disclosure information not submitted.
Brian Kopp, BCCCP, BCPS, PharmD
Clinical Pharmacist
Banner University Medical Center Tucson, United States
Disclosure information not submitted.
Brian Erstad, BCPS, PharmD, MCCM
Professor & Head
University of Arizona College of Pharmacy
Tucson, Arizona
Disclosure information not submitted.
Title: Influence of Timing and Catecholamine Requirements on Vasopressin Responsiveness in Septic Shock.
Introduction/Hypothesis: The Surviving Sepsis Campaign guidelines suggest adding arginine vasopressin (AVP) to norepinephrine (NE) to decrease NE dosage and help achieve goal mean arterial pressure (MAP). There is a paucity of data to guide the optimal timing and NE dose at which to initiate AVP in septic shock.
Methods: This was a multicenter, retrospective cohort study in adult patients with septic shock that evaluated the impact of AVP initiation timing and baseline NE requirements on hemodynamic responsiveness. Responsiveness was defined as a ≥ 50% reduction in NE dose equivalents without a reduction in MAP at 4 hours after AVP initiation. Patients were categorized according to whether they were started on AVP < 4 or ≥ 4 hours after vasopressor initiation and baseline NE dose equivalents (< 15, 15-40, or ≥ 40 mcg/min). The primary outcomes were the effects of AVP initiation timing and baseline NE requirements on AVP responsiveness. Multivariate analyses and logistic regression were performed to identify other factors associated with AVP responsiveness.
Results: A total of 300 patients were included with 74 patients being classified as responders and 226 patients as non-responders. Baseline characteristics between groups were similar except for higher rates of atrial fibrillation, lower pH, and slightly higher NE requirements in the non-responder group. Timing of AVP initiation was not associated with any differences in response rates (p=0.29). Multivariate logistic regression analyses did not demonstrate an effect of baseline NE requirements on AVP responsiveness (OR, 0.67; 95% CI, 0.45-1.01). However, patients requiring ≥ 40 mcg/min of NE equivalents had lower response rates (16.2% responders vs. 30.1% non-responders; p=0.023). Furthermore, stress dose steroid use during AVP therapy was associated with reduced response rates (OR, 0.56; 95% CI, 0.32-0.98).
Conclusion: Timing of AVP initiation after starting vasopressors was not associated with hemodynamic responsiveness according to our study's definition. Initiation of AVP at ≥ 40 mcg/min of NE equivalents was associated with lower response rates. However, logistic regression indicated that baseline NE requirements overall were not an independent predictor of AVP responsiveness.