Blood purification could tackle COVID-19?

Coronavirus disease 2019 (COVID-19) threatened human lives worldwide since first reported. The current challenge for global intensivists is to establish an effective treatment for severe COVID-19. Blood purification has been applied to the treatment of various critical illnesses. Theoretically, its technique also has an enormous possibility of treating severe COVID-19 in managing inflammatory cytokines and coagulopathy. Recent clinical studies have revealed the positive clinical effect of therapeutic plasma exchange. Other studies have also indicated the considerable potential of other blood purification techniques, such as Cytosorb, AN69 surface-treated membrane, and polymyxin b hemoperfusion. Further research is needed to elucidate the actual effects of these applications.

Impact of polymyxin B hemoperfusion therapy on high endotoxin activity level patients after successful infection source control: a prospective cohort study

We sought to evaluate the clinical implication of endotoxin levels in gram-negative bacilli (GNB)-induced abdominal septic shock patients with polymyxin B-hemoperfusion (PMX-HP) treatment. A prospective cohort of 60 patients who received surgical infectious source control for abdominal sepsis from January 2019 to December 2020 was included in the study. Endotoxin activity (EA) levels and Sequential Organ Failure Assessment (SOFA) scores were assessed immediately after surgery (baseline), 24, and 48 h post baseline. With receiver operating characteristic curves, the patients were stratified into two groups by the EA cut-off value (high-risk group vs low-risk group) and the clinical outcomes were compared. Logistic regression was performed to identify the clinical impact of PMX-HP on in-hospital death. Among the 31 high-risk patients (EA level ≥ 0.54), 16 patients (51.6%) received PMX-HP treatment and showed significant decreases in EA levels compared to patients who underwent conventional treatment only (− 0.34 vs − 0.12, p = 0.01). SOFA scores also showed significant improvement with PMX-HP treatment (12.8–8.9, p = 0.007). Fourteen in-hospital deaths occurred (45.2%), and PMX-HP treatment had a protective effect on in-hospital death (odds ratio (OR) 0.04, p = 0.03). In 29 low-risk patients (EA level < 0.54), seven patients (24.1%) received PMX-HP treatment and showed significant decreases in EA levels (0.46–0.16, p = 0.018). However, SOFA scores and in-hospital deaths were not improved by PMX-HP treatment. EA level significantly decreased after PMX-HP treatment and it may represent a therapeutic option to improve organ impairment and in-hospital death in septic shock patients with EA levels exceeding 0.54.

Effectiveness of polymyxin B hemoperfusion for sepsis depends on the baseline SOFA score: a nationwide observational study

Background Polymyxin B hemoperfusion (PMX) aims to treat septic shock by removing endotoxin from the patient’s blood. However, the relationship between the severity of the patient's organ damage and the survival benefit of PMX treatment is not clear. Methods We analyzed the efficacy of PMX on adult sepsis patients using the propensity score matching method and the Japanese Diagnosis Procedure Combination (DPC) national inpatient database from April 2018 to March 2020. We stratified the patients into five categories based on their baseline Sequential Organ Failure Assessment (SOFA) score and compared the mortality between PMX-treated and non-treated groups in each category. We also compared continuous hemodiafiltration (CHDF)-, ventilator- and noradrenaline-free days between the groups. Results Of 44,177 patients included in the study, 2191 received PMX. After 1:1 propensity score matching, we created matched cohorts of 2033 pairs. PMX significantly improved the survival of the patients in the SOFA score categories of 7–9 and 10–12. On the other hand, there was no significant difference in the survival rate in SOFA score categories of 0–6, 13–15, and 16–24. In analyzing organ support-free days, PMX was also beneficial in the 7–9 and 10–12 SOFA categories compared to other categories. Conclusion Analysis of a large-scale Japanese inpatient database found a significant association between PMX efficacy and baseline SOFA score. This result indicates higher efficacy in patients with medium SOFA scores in the range of 7–12. The result provides a promising hypothesis for selecting appropriate patients for PMX and should be validated in future RCTs.

Endotoxin Adsorbent Therapy in Severe COVID-19 Pneumonia

<b><i>Introduction:</i></b> Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. <b><i>Methods:</i></b> We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. <b><i>Results:</i></b> Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO₂/FiO₂ ratio and decreased EAA level after EA therapy. <b><i>Conclusions:</i></b> We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.

Effects of Polymyxin B Hemoperfusion on Septic Shock Patients Requiring Noradrenaline: Analysis of a Nationwide Administrative Database in Japan

<b><i>Introduction:</i></b> Polymyxin B hemoperfusion (PMX) reduces endotoxin in septic shock patients’ blood and can improve hemodynamics and organ functions. However, its effects on the reduction of septic shock mortality are controversial. <b><i>Methods:</i></b> Using the Japanese diagnosis procedure combination database from April 2016 to March 2019, we identified adult septic shock patients treated with noradrenaline. This study used propensity score matching to compare the outcome between PMX-treated and non-treated patients. The primary endpoint was 28-day mortality, counting from the day of noradrenaline initiation. The secondary endpoints were noradrenaline-, ventilator-, and continuous hemodiafiltration (CHDF)-free days at day 28. <b><i>Results:</i></b> Of 30,731 eligible patients, 4,766 received PMX. Propensity score matching produced a matched cohort of 4,141 pairs with well-balanced patient backgrounds. The 28-day survival rate was 77.9% in the PMX group and 71.1% in the control group (<i>p</i> &#x3c; 0.0001). Median days of noradrenalin-, CHDF-, and ventilator-free days were 2 days (<i>p</i> &#x3c; 0.0001), 2 days (<i>p</i> &#x3c; 0.0001), and 6 days (<i>p</i> &#x3c; 0.0001) longer in the PMX group than in the control group, respectively. When stratified with the maximum daily dose of noradrenaline, the PMX group showed a statistically significant survival benefit in the groups with noradrenaline dose &#x3c;20 mg/day but not in the noradrenaline group dose ≥20 mg/day. <b><i>Conclusion:</i></b> Analysis of large Japanese databases showed that septic shock patients who received noradrenaline might benefit from PMX treatment.