The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study

Background: Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. Methods: A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. Results: A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, −4 << 4 h had more survivors (229/304, 75.3%) than ≤−4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When −4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤−4 h had an odds ratio of 1.96 (1.07–3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94–2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than −4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. Conclusions: The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.