Daily Anesthesiology Research Analysis

BACKGROUND: The current gold standard for diagnosing malignant hyperthermia (MH) is an in-vitro contracture test (IVCT), which has many limitations. Here, we evaluate a newly developed test, the Ca2+ wave frequency assay (CaWFa), which aimed to directly measure Ca2+ release from the ryanodine receptors (RyR1) of single muscle fibres. METHODS: A small segment of muscle (50 mg) was sectioned from 30 patients undergoing routine IVCT muscle biopsies and mechanically skinned single muscle fibres were isolated. Using Ca2+-dependent fluorescence and confocal microscopy we were able to examine RyR1 sensitivity of single fibres challenged with graded concentrations of halothane and caffeine. The induction of regenerative Ca2+ waves and wave frequencies were compared with IVCT results to assess diagnostic sensitivity and specificity. RESULTS: The proportion of muscle fibres that responded with regenerative Ca2+ waves on exposure to 0.5 mM and 1 mM halothane was higher in muscle from MHS patients compared with MHN patients (36.5% vs 0% and 77.5% vs 23.1%, respectively). Ca2+ wave frequency was also elevated in the MHS fibres compared to MHN in halothane at all tested concentrations. No difference in Ca2+ wave onset or frequency were demonstrated between groups exposed to caffeine. Using CaWFa, an onset concentration of 1 mM halothane in combination with a wave frequency threshold of 1.57 waves/minute achieved 92% sensitivity and 88% specificity. CONCLUSIONS: The CaWFa effectively discriminates MHS from MHN muscle in response to halothane, offering a comparable sensitivity and specificity to the IVCT. The CaWFa shows promising potential as a minimally invasive alternative to IVCT for diagnosing MH susceptibility.

BACKGROUND: Postoperative delirium (POD) is a prevalent complication in elderly surgical patients. It is associated with long-term cognitive impairment and increased dementia risk. However, reliable tools to predict POD are currently lacking. METHODS: We enrolled 316 arthroplasty patients (aged ≥ 65 years) in this study. Preoperative assessments comprised neuropsychological tests (i.e., Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]), molecular biomarkers of serum/cerebrospinal fluid (CSF), and saccadic tasks. POD was diagnosed by expertized persons based on the Confusion Assessment Method test. We compared the effectiveness of abovementioned three types of assessments in predicting the occurrence of POD. RESULTS: The incidence of POD was 8.2% (26/316). MMSE and MoCA scales, serum neurofilament light chain (NfL) levels, and five saccadic parameters values (reaction time, primary saccade error, saccadic gains in pro-saccades; peak velocity in anti-saccades and memory guided saccades) differed significantly (p < 0.05) between POD and non-POD participants. The logistic regression classifier model revealed higher predictive accuracy when using saccadic parameters (area under the receiver operating characteristic curve [AUROC] = 0.81, 95% confidence interval [CI]: 0.70-0.92) than that by using MMSE and MoCA scores (AUROC = 0.64, 95% CI: 0.53-0.76), or NfL levels (AUROC = 0.61, 95% CI: 0.50-0.72). The multilayer perceptron machine learning classifier model further increased the accuracy (AUROC = 0.89, 95% CI: 0.82-0.94) by using saccadic parameters to predict POD occurrence. CONCLUSION: Saccadic parameters exhibited higher accuracy in predicting the occurrence of POD than MMSE and MoCA scores and molecular test results. Therefore, saccadic parameters may serve as a complementary behavioral biomarker for predicting the occurrence of POD in elderly arthroplasty patients.

BACKGROUND: Optimal target of mean arterial pressure (MAP) remains controversial in sepsis management. Critical closing pressure (Pcc), the arterial pressure at which blood flow ceases, is the key determinant of vascular waterfall phenomenon. Tissue perfusion pressure (TPP), the difference between MAP and Pcc, represents the driving pressure for arterial blood flow. We evaluated the prognostic value of Pcc and TPP for improving risk stratification in sepsis. METHODS: This retrospective cohort study included adult patients with sepsis in 18 hospitals between August 2013 to October 2022 from two independent datasets (the SEPSIS-EDT registry and the critical care database of PUMCH). Pcc was estimated via linear regression of hourly MAP against product of heart rate and pulse pressure, while TPP was calculated as MAP minus Pcc. Patients were categorized into four groups based on the optimal thresholds for mean Pcc and TPP within 24 hours of sepsis diagnosis: Low TPP-Low Pcc, Low TPP-High Pcc, High TPP-Low Pcc, and High TPP-High Pcc. Clinical outcomes included mortality rates and development of acute kidney injury (AKI) within two and seven days of sepsis diagnosis. External validation was performed using MIMIC-IV cohort. RESULTS: A total of 6,769 patients (mean age 61; 61.0% men) were included. ICU mortality was highest in the Low TPP-Low Pcc group and lowest in the High TPP-High Pcc group (35.1% vs. 20.1%; risk difference: 15.0%, 95% confidence interval: 10.2-19.8%). Similar patterns were observed for other outcomes. After adjustment for MAP, increased Pcc with concomitant reduced TPP showed a significant U-shaped association with both mortality and AKI development (P < 0.001). The findings were consistent in the MIMIC-IV cohort. CONCLUSION: While MAP remains central to sepsis management, Pcc and TPP provide complementary prognostic information. Incorporating these parameters into clinical assessment may improve risk stratification and optimize blood pressure management.