Roberts, Russel J.

Objectives: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. Design: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Setting: Thirty-three hospital sites in the United States ( n = 32) and Jordan ( n = 1). Patients: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. Interventions: None. Measurements and Main Results: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851–5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 μg/min norepinephrine equivalents (3.4–18.1 μg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16–1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. Conclusions: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Objectives: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. Design: Multicenter prospective cohort study between September 2017 and February 2018. Settings: Thirty-four hospitals in the United States and Jordan. Patients: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. Interventions: None. Measurement and Main Results: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, −0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45−2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19−0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27−2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63−1.18). Conclusions: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

BackgroundClinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published.ObjectiveTo assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use.MethodsA scenario‐based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi‐square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups.ResultsAmong 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045).ConclusionSince vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.