Time to administer polymyxin B hemoperfusion and hemodynamics in patients with septic shock requiring high-dose norepinephrine: a predetermined analysis of a prospective cohort study

Abstract

Background: Delayed administration of polymyxin B hemoperfusion (PMX-HP) for septic shock could diminish its efficacy in real-world clinical settings. Methods: BEAT-SHOCK (BEst Available Treatment for septic SHOCK) registry is a prospective registry consisting of 309 adult patients with septic shock requiring high-dose norepinephrine (≥ 0.2 μg/kg/min). This predetermined analysis included 82 patients treated with PMX-HP. They were grouped according to the median time from intensive care unit (ICU) admission to administration of PMX-HP: the early administration group (n = 40) and the late administration group (n = 42). The primary outcome was short-term hemodynamic status, including mean arterial pressure and vasoactive-inotropic score (VIS; calculated from doses of dopamine, dobutamine, norepinephrine, epinephrine, vasopressin, milrinone, and levosimendan) within 48 h after ICU admission. Results: The median time from ICU admission to administration of PMX-HP was 265 min (interquartile range [IQR]: 113–480). The median ages were 70 (IQR: 59–81) and 72 (IQR: 64–80) years (P = 0.77), and 21/40 (53%) and 25/42 (60%) patients were male (P = 0.52) in the early and late administration groups, respectively. The dose of norepinephrine at ICU admission was 0.33 (IQR: 0.24–0.47) and 0.30 (IQR: 0.22–0.34) μg/kg/min in the early and late administration groups, respectively (P = 0.17). Within 48 h after ICU admission, mean arterial pressure was significantly higher at 6 h and 8 h, and VIS was significantly lower at 8 h and thereafter in the early administration group. Within a 28-day period, there were 23 (IQR: 21–25) and 21 (IQR: 0–24) vasopressor/inotrope-free days (P = 0.027), and 18 (IQR: 1–23) and 14 (IQR: 0–19) ICU-free days (P = 0.025) in the early and late administration groups, respectively. The cumulative mortality at 90 days was 15.3% in the early administration group and 31.3% in the late administration group (adjusted hazard ratio 0.38; 95% confidence interval 0.13–1.09). Conclusions: In patients with septic shock, early administration of PMX-HP was associated with higher mean arterial pressure and lower VIS within 48 h after ICU admission. Additionally, it may be associated with an improved clinical course, represented by more ICU-free and vasopressor/inotrope-free days. Trial registration UMIN Clinical Trial Registry on 1 November 2019 (registration no. UMIN000038302).