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Background: Arginine vasopressin (AVP) is suggested as an adjunct to norepinephrine in patients with septic shock. Guidelines recommend an AVP dosage up to 0.03 units/min, but 0.04 units/min is commonly used in practice based on initial studies. This study was designed to compare the incidence of hemodynamic response between initial fixed-dosage AVP 0.03 units/min and AVP 0.04 units/min., Methods: This retrospective, multi-hospital health system, cohort study included adult patients with septic shock receiving AVP as an adjunct to catecholamine vasopressors. Patients were excluded if they received an initial dosage other than 0.03 units/min or 0.04 units/min, or AVP was titrated within the first 6 hours of therapy. The primary outcome was hemodynamic response, defined as a mean arterial pressure ≥65 mm Hg and a decrease in catecholamine dosage at 6 hours after AVP initiation. Inverse probability of treatment weighting (IPTW) based on the propensity score for initial AVP dosage receipt was utilized to estimate adjusted exposure effects., Results: Of the 1536 patients included in the observed data, there was a nearly even split between initial AVP dosage of 0.03 units/min (n = 842 [54.8%]) and 0.04 units/min (n = 694 [45.2%]). Observed patients receiving AVP 0.03 units/min were more frequently treated at the main campus academic medical center (96.3% vs. 52.2%, p < 0.01) and in a medical intensive care unit (87.4% vs. 39.8%, p < 0.01). The IPTW analysis included 1379 patients with achievement of baseline covariate balance. There was no evidence for a difference between groups in the incidence of hemodynamic response (0.03 units/min 50.0% vs. 0.04 units/min 53.1%, adjusted relative risk 1.06 [95% CI 0.94, 1.20])., Conclusions: Initial AVP dosing varied by hospital and unit type. Although commonly used, an initial AVP dosage of 0.04 units/min was not associated with a higher incidence of early hemodynamic response to AVP in patients with septic shock.

Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.

Study Objectives: Patients with septic shock often require vasoactive agents for hemodynamic support; however, the optimal approach to discontinuing these agents once patients reach the recovery phase is currently unknown. The objective of this evaluation was to compare the incidence of hypotension within 24 hours based on the discontinuation order of norepinephrine (NE) and vasopressin (AVP) in patients in the recovery phase of septic shock., Design: Retrospective cohort study., Setting: The medical, surgical, and neurosciences intensive care units (ICUs) at a large tertiary care academic medical center., Patients: A total of 585 adults in the recovery phase of septic shock who received fixed-dose AVP for at least 6 hours as an adjunct to NE between September 2011 and August 2015 were included. Of these patients, 155 had AVP discontinued first, and 430 had NE discontinued first., Measurements and Main Results: Hypotension was evaluated during the 24-hour period after discontinuation of the first vasoactive agent and was defined as mean arterial pressure less than 60 mm Hg with one or more of the following interventions: increased remaining vasoactive agent dose by 25%, reinstitution of the discontinued agent, or administration of at least 1 L of fluid bolus. Time to hypotension was evaluated with survival analysis, and risk of hypotension was evaluated with multivariable Cox proportional hazards regression. No significant difference between groups was noted in the incidence of hypotension within 24 hours (55% in the AVP discontinued first group vs 50% in the NE discontinued first group, p=0.28) or ICU mortality (45.2% vs 40.0%, p=0.26). After adjustment for baseline factors with multivariable Cox proportional hazards regression, having AVP discontinued first was independently associated with an increased risk of hypotension with a time-varying effect that decreased over time (HR(t) = e [1.16-0.08*t] , p<0.001)., Conclusion: In patients recovering from septic shock treated with concomitant AVP and NE, no significant difference was noted in the incidence of hypotension based on discontinuation order of these agents., (© 2018 Pharmacotherapy Publications, Inc.)

Study Objectives: To determine whether vasopressin is detectable in the continuous venovenous hemodialysis (CVVHD) effluent of patients receiving exogenous arginine vasopressin, and to determine whether treatment-specific factors are associated with vasopressin levels in CVVHD effluent. DESIGN. Prospective observational study. SETTING. Intensive care units of a tertiary care academic medical center. PATIENTS. Twenty-seven adults with vasodilatory shock who received a stable-dose continuous intravenous infusion of arginine vasopressin with concomitant uninterrupted CVVHD for at least 4 hours between September 2008 and May 2010. MEASUREMENTS AND MAIN RESULTS. Vasopressin levels in CVVHD effluent were assessed by radioimmunoassay. Statistical analysis was performed with analysis of variance and Pearson correlation. A multivariate linear regression was used to assess for independent factors associated with vasopressin levels in CVVHD effluent. The CVVHD effluent of all patients was assessed for vasopressin levels. The median exogenous arginine vasopressin dose was 0.03 unit/minute (range 0.02-0.18 unit/min), whereas the median CVVHD effluent flow rate was 22.6 ml/kg/hour (interquartile range [IQR] 21.5-26.8 ml/kg/hr). Vasopressin was detectable in all effluent samples (median 88.8 pg/ml, IQR 36.4-113.7 pg/ml). There were no significant differences in CVVHD effluent vasopressin levels among CVVHD filter types (p=0.39). The CVVHD effluent vasopressin levels correlated with exogenous arginine vasopressin dose (r2=0.49, p<0.001). After adjustment for CVVHD effluent flow rate and administration of corticosteroids, with multivariate linear regression, only exogenous arginine vasopressin dose was independently associated with CVVHD effluent vasopressin level. CONCLUSION. Vasopressin is detectable in CVVHD effluent, suggesting that it is removed by CVVHD. In addition, exogenous arginine vasopressin infusion dose is independently associated with CVVHD effluent vasopressin level.

Purpose: There are little data regarding the discontinuation of vasoactive medications in patients recovering from septic shock. We designed this retrospective cohort study to evaluate the incidence of hypotension based on the order of removal of norepinephrine (NE) and vasopressin (AVP) in patients receiving concomitant NE and AVP infusions for the treatment of septic shock., Materials and Methods: Consecutive patients receiving concomitant NE and AVP infusions for septic shock admitted to the intensive care units of a tertiary care academic medical center were evaluated., Results: Of 50 included patients, the first vasoactive medication discontinued was NE in 32 patients and AVP in 18 patients. The groups had similar Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores at shock onset and at the time of discontinuation of the first agent. Five patients who had NE discontinued first (16%) versus 10 patients who had AVP discontinued first (56%) developed hypotension within 24 hours (unadjusted relative risk, 3.6; 95% confidence interval, 1.5-4.5; P = .008). In a multivariate analysis, only discontinuation of AVP first was independently associated with hypotension (adjusted relative risk, 5.9; 95% confidence interval, 1.7-21.0; P = .006)., Conclusions: Discontinuation of AVP before NE may lead to a higher incidence of hypotension in patients recovering from septic shock receiving concomitant AVP and NE., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)