Norepinephrine Dosing in Obese Patients: Impact of Weight-Based Dosing on Short- and Long-Term Mortality

Abstract

SESSION TITLE: Sepsis & Septic Shock SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, October 29, 2017 at 01:30 PM - 03:00 PM PURPOSE: Obesity is thought to be protective in septic shock. Norepinephrine (NE) is frequently dosed by a weight-based regimen, and potentially higher doses of NE are used in the obese population. The interaction of body mass index (BMI) with NE dosing and their influence on clinical outcomes has been only limitedly explored. METHODS: Historical cohort study of all adult septic shock patients requiring NE admitted between 2010 through 2015 to all intensive care units (ICU) at Mayo Clinic Rochester. Patients with BMI 25-39.9 kg/m2 were classified into overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2) and obesity class II (35-39.9 kg/m2). Patients with normal BMI (18.5-24.9 kg/m2) formed the control group. Patients with chronic respiratory failure, repeat ICU admissions, ICU stay <1day, lactate <2 mmol/L and BMI <18.5 and ≥ 40 kg/m2 were excluded. The primary outcome was in-hospital mortality and secondary outcomes included new cardiac arrhythmias, acute kidney injury (AKI) and one-year mortality. Odds ratios (OR) [95% confidence intervals (CI)] were used to represent univariate and multivariate outcomes respectively. A two-tailed p<0.05 was considered significant. RESULTS: During this 6-year period, 4774 patients met our study criteria - BMI 18.5-24.9, 25-29.9, 30-34.9 and 35-39.9 kg/m2 had 1406 (29%), 1608 (34%), 1151 (24%) and 609 (13%) patients respectively. The baseline characteristics revealed significant inter-group differences in age, race, gender and baseline creatinine, but no differences in comorbidity burden, severity of illness or use of corticosteroids in the ICU. Median NE dose increased linearly with increase in BMI cohorts - 5 gm (interquartile range [IQR] 1-13) (BMI 18.5-24.9 kg/m2), 5.3 gm (IQR 2-14) (BMI 25-29.9 kg/m2), 6 gm (IQR 2-16) (BMI 30-34.9 kg/m2) and 7 gm (IQR 2-18) (BMI 35-39.9 kg/m2), p<0.001. There was no difference in number, type or total doses of additional vasoactive medications. In-hospital (29%, 24%, 22%, 22%; p<0.001) and one-year mortality (46%, 53%, 53%, 51%; p=0.001) were significantly different between patients with BMI 18.5-24.9, 25-29.9, 30-34.9 and 35-39.9 kg/m2 respectively. Unadjusted log10NE levels were associated with higher in-hospital mortality (OR 2.9 [95%CI 2.6-3.3]; p<0.001), AKI (OR 1.8 [95% CI 1.6-1.9]; p<0.001), cardiac arrhythmias (OR 1.4 [95% CI 1.3-1.5]; p<0.001) and one-year mortality (OR 1.8 [95% CI 1.6-2]; p<0.001). After adjusting for age, gender, BMI, comorbidity burden, severity of illness, cardiac injury, AKI, cardiac arrhythmia and use of mechanical ventilation, log10NE was an independent predictor of in-hospital (OR 2.2 [95% CI 1.9-2.7]; p<0.001) and one-year mortality (OR 1.4 [95% CI 1.2-1.7]; p<0.001). CONCLUSIONS: Total NE use was independently associated with worse short and long-term mortality, AKI and cardiac arrhythmias in patients independent of BMI. CLINICAL IMPLICATIONS: Alternative strategies to weight-based NE dosing are recommended in obese patients. DISCLOSURE: The following authors have nothing to disclose: Aditya Kotecha, Saraschandra Vallabhajosyula, Dinesh Apala, Erin Frazee, Vivek Iyer No Product/Research Disclosure Information