Mathews, Kusum S.

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.

5565 Background: The goal of this study was to determine the recurrence rates (R) of patients with grade 1 and 2 stage 1A and IB ovarian tumors treated with and without chemotherapy. Methods: We conducted a five-center retrospective study of patients with Stage 1A/B grade 1 and 2 ovarian carcinoma. All women underwent comprehensive staging including a minimum of unilateral salpingo-ophorectomy, unilateral pelvic and para-aortic lymphadenectomy, and omentectomy. Clear cell histologies were classified as grade 3 and excluded. The minimum cancer-free survivor follow-up was 3 years. Results: We identified 82 patients with Stage 1A/B grade 1 and 2 who met criteria for the study. The median age was 58 yrs (range 29 to 83) and the median follow-up was 5.3 yrs (range 3 to 11 yrs). The majority were of endometrioid histology (51), followed by mucinous (19), papillary serous (11), and mixed (1). Recurrences were of endometrioid (4), mucinous (1), or papillary serous (1) histology. For Stage 1A, overall recurrence rate was 9% (6/67). The overall recurrence rates for Stage 1A, grade1 tumors was 6% and among grade 2 tumors 12% (p=0.40). Among Stage 1A patients not treated with chemotherapy, there was a 7% (2/29) and 9.5% (2/21) recurrence rate for grade 1 and grade 2 tumors, respectively. For the grade 1 tumors, both patients are alive with disease at 3 and 5 yrs. For the grade 2 tumors, one is alive without evidence of disease at 7 yrs and the other died from disease at 4 yrs. Time to recurrence (TTR) was 2.3 yrs for grade 1 tumors and 2.6 yrs for grade 2 tumors. For Stage 1A patients treated with a platinum chemotherapy regimen, there were no recurrences (0/5) for grade 1 tumors and a 16% (2/12) recurrence rate for grade 2 tumors. Of the recurrences, one patient died from disease at 1.4 yrs and the other is alive with stable disease at 6 yrs. Time to recurrence was 2.85 yrs for grade 2 tumors. For grade 1 or 2, Stage 1A tumors, recurrence rates and time to recurrence were not effected by chemotherapy administration (R, p=0.55 and p=0.54, respectively; TTR, grade 2, p=0.85). No recurrences were observed in the 15 patients with Stage IB, grade 1 and 2 tumors. Conclusions: In comprehensively staged patients with Stage 1A/B, grade 1 and 2, low recurrence rates suggest adjuvant chemotherapy may not be indicated. No significant financial relationships to disclose.