Daily Anesthesiology Research Analysis

BACKGROUND: Endotoxic septic shock, a subset of septic shock with high endotoxin activity and multiorgan failure, is associated with high risk of death. We sought to identify the effect of endotoxin removal from the blood with polymyxin B haemoadsorption on mortality. METHODS: We conducted an open-label, randomised, controlled, phase 3 trial at 19 US hospitals, enrolling adults (aged ≥18 years) with septic shock requiring vasopressors, with multiple organ dysfunction, and with endotoxin activity between 0·60 and 0·89 units. Patients were randomly assigned (2:1) to receive two sessions of polymyxin B plus standard of care or standard of care alone (control), with block randomisation stratified by site. Study personnel were masked to treatment allocation. Polymyxin B haemoadsorption was given via haemodialysis at a blood flow rate of 80-120 mL/min for 90-120 min per session, 22 h apart. The primary outcome was 28-day mortality in the intention-to-treat cohort. The safety cohort included all participants exposed to any amount of study treatment. Design and analysis followed a Bayesian framework, using a prior for the treatment effect based on a subgroup of the earlier EUPHRATES trial. 90-day mortality was the key secondary outcome. The trial was registered at ClinicalTrials.gov and is completed (NCT03901807). FINDINGS: Between Sept 30, 2019, and April 10, 2025, we screened 14 890 patients, of whom 157 were enrolled (106 assigned to polymyxin B and 51 to control; 66 [42%] women and 91 [58%] men). At 28 days, 41 (39%) patients in the polymyxin B group and 23 (45%) in the control group had died, yielding a posterior probability of benefit of 95·3% (APACHE-II adjusted odds ratio 0·67 [95% credible interval 0·39-1·08]). At 90 days, the posterior probability of benefit was 99·4% (0·54 [0·32-0·87]). Of 100 patients in the polymyxin B group assessed for safety, 30 (30%) had a serious adverse event compared with 11 (22%) of 51 patients in the control group (difference -8 percentage points [95% CI -22 to 6]). Two (2%) serious adverse events in the polymyxin B group were treatment-related, one related to polymyxin B and one to catheter placement. INTERPRETATION: In patients with endotoxic septic shock defined by high endotoxin activity and multiorgan failure, polymyxin B haemoadsorption was associated with a high probability of lower mortality at 28 days and 90 days. FUNDING: Spectral Medical.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a clinically defined, biologically heterogeneous condition with no proven disease-modifying therapies. Retrospective analyses have identified two biologically distinct subphenotypes (hyperinflammatory and hypoinflammatory) of ARDS, with differing outcomes and responses to therapy. Rapid identification of these subphenotypes in an actionable timeframe has previously not been possible. The PHIND study aimed to prospectively identify these subphenotypes and to demonstrate differing 60-day mortality. METHODS: The PHIND study was a prospective, multicentre, observational cohort study conducted in intensive care units (ICUs) within the National Health Service in the UK and the Health Service Executive in Ireland. Adult patients aged 18 years and older with ARDS or acute hypoxaemic respiratory failure (AHRF) were enrolled within 72 h of onset of the syndrome. Eligible patients were required to be receiving invasive mechanical ventilation, non-invasive ventilation, or high-flow nasal oxygen. Plasma interleukin (IL-6) and soluble TNF receptor-1 (TNFR1) were quantified at enrolment using a near-patient benchtop immunoanalyser (Randox multiSTAT) with a run time of approximately 1 h. Together with plasma bicarbonate measured from an arterial blood sample, these values were used to prospectively determine subphenotypes on an individual patient basis using a validated parsimonious logistic regression model. The primary outcome was 60-day mortality. The study was registered on ClinicalTrials.gov, NCT04009330. FINDINGS: Between Nov 22, 2019, and Sept 28, 2023, 1853 patients from 30 centres were screened for eligibility. Of these, 1328 were excluded and 525 were recruited into the study, with 512 individuals included. 308 (60%) patients were male, 204 (40%) were female, and mean age was 57·0 years (SD 15·1). 443 (87%) patients were white, 18 (4%) were Black, and 16 (3%) were Asian. 490 were subphenotyped using the near-patient assay: 89 (18%) were classified as hyperinflammatory and 401 (82%) as hypoinflammatory. The primary outcome of 60-day mortality was measured in 486 patients after four patients withdrew consent for confirmation of vital status. 60-day mortality was significantly higher in the hyperinflammatory group (45 [51%] of 88) than in the hypoinflammatory group (111 [28%] of 398; risk ratio 1·8 [95% CI 1·4-2·4], p<0·0001). After adjustment, hyperinflammatory patients had increased odds of 60-day mortality (adjusted odds ratio 2·7 [95% CI 1·6-4·4], p=0·0002). INTERPRETATION: Rapid identification of ARDS inflammatory subphenotypes using a near-patient assay was feasible and associated with many clinical characteristics and outcomes consistent with those described in earlier retrospective studies, including mortality, prevalence of sepsis, and incidence of metabolic acidosis. These findings support the implementation of precision medicine approaches in ARDS and the urgent need for prospective, subphenotype-stratified interventional trials. FUNDING: Innovate UK, Randox Laboratories, and Belfast Health & Social Care Trust.

Postmenstrual age (PMA) is the major risk factor for postanesthesia apnea. The authors hypothesized that modern anesthesia may reduce the at-risk PMA cutoff threshold. The aim of this individual participant data meta-analysis was to identify the PMA above which postanesthesia apnea risk is less than 1%. Individual participant data from 12 prospective studies undergoing open inguinal herniorrhaphy were analyzed. A total of 132 of 751 (17.6%) former preterm infants experienced postanesthesia apnea. The data indicate that the PMA cutoff at which the risk of postanesthesia apnea was approximately 10%, approximately 5%, and less than 1% was 53 weeks, 57 weeks, and 65 weeks, respectively, after general anesthesia and approximately 38 weeks, 40 weeks, and 45 weeks, respectively, after neuraxial anesthesia. Anemia was a risk factor only for infants more than 48 weeks PMA. Postanesthesia apnea onset was earlier and odds for occurrence were higher for general anesthesia without (odds ratio, 6; P = 0.008) and with caudal block (odds ratio, 2.94; P = 0.012) compared to neuraxial anesthesia. Anesthetic technique has important implications; neuraxial anesthesia appears to reduce the at-risk PMA for postanesthesia apnea compared with general anesthesia.