Xie, Guozhen

Background: Propofol is a first-line sedative for critically ill adults receiving invasive mechanical ventilation (IMV). However, it can contribute to hemodynamic instability, especially in the setting of intubation. The magnitude, timing, risk factors, and variability of sedation-associated mean arterial pressure (MAP) changes remain poorly characterized in ICU settings. Objectives: To quantify MAP changes following propofol sedation, identify risk factors for hemodynamic instability, and characterize associated interventions. Methods: We included adults (≥18 years old) across 11 ICUs in the Mayo Clinic Enterprise who required IMV and received ≥6 consecutive hours of propofol infusion between 05/05/2018 and 07/31/2024. The primary outcome was MAP change within 2-hours following sedation. Secondary outcomes included vasopressor use and hypotension (MAP ≤60 mmHg). Mixed-effects modeling was utilized to account for individual patient differences. The main model used a “neutral” adjustment, estimating a 5 mmHg MAP increase per 0.05 mcg/kg/min of norepinephrine equivalents, reduced to 3 mmHg per 0.05 mcg/kg/min after reaching a dose of 0.20 mcg/kg/min. Those on any vasopressors prior to propofol sedation initiation were analyzed separately. Results: Across 16,418 patients, 25.2% were on vasopressors before sedation initiation. Among the remaining 12,281 patients, 40.3% required vasopressors and 7.7% experienced hypotension within 2 hours of sedation ( Image 1 ). Post-intubation sedation was associated with a MAP reduction within the first 30 minutes (-6.58 mmHg; 95% CI: -6.85 to -6.32; P<0.001; Images 2 and 3 ). There was substantial inter-patient variability in both baseline MAP (9.5% variation attributable to between-patient differences) and MAP decline after sedation (40.9% between-patient differences). Higher SOFA scores (-0.31 mmHg per point), older age (-0.04 mmHg per year), and male sex (-0.47 mmHg) were associated with lower MAP. Patients with higher illness severity experienced progressively greater MAP changes over time (-0.20 mmHg per hour per increasing SOFA point; P<0.001). Conclusions: Propofol sedation is associated with clinically significant hemodynamic effects requiring intervention in the early post-intubation period. The marked inter-patient variability in hemodynamic responses highlights the importance of personalized management approaches. Risk stratification may help identify patients who could benefit from preemptive hemodynamic optimization.

IMPORTANCE: Propofol is a first-line sedative for adults receiving invasive mechanical ventilation (IMV). However, it can contribute to hemodynamic instability, especially during intubation. The magnitude, timing, risk factors, and variability of sedation-associated mean arterial pressure (MAP) changes remain poorly characterized in ICU settings. OBJECTIVES: To quantify MAP changes following propofol sedation, identify risk factors for hemodynamic instability, and characterize associated interventions. DESIGN: Retrospective cohort study. The primary outcome was MAP change within 2 hours following sedation. Secondary outcomes included vasopressor use and hypotension (MAP ≤ 60 mm Hg). Mixed-effects modeling was used to account for individual patient differences. SETTING AND PARTICIPANTS: Adults (≥ 18 yrs old) who required IMV and received greater than or equal to 6 consecutive hours of propofol infusion, between May 5th, 2018, and July 31st, 2024, in 11 ICUs across the Mayo Clinic, spanning 5 hospitals in 4 states. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in MAP within 2 hours following the initiation of propofol-based sedation. RESULTS: Across 16,418 patients, 25.2% were on vasopressors before sedation initiation. Among the remaining 12,281 patients, 40.3% required vasopressors and 7.7% experienced hypotension within 2 hours of sedation. Propofol-based sedation was associated with a MAP reduction within the first 30 minutes (–6.58 mm Hg; 95% CI, –6.85 to –6.32; p < 0.001). There was substantial interpatient variability in both baseline MAP, and MAP decline after sedation (9.5 and 40.9% between-patient differences, respectively). Higher Sequential Organ Failure Assessment (SOFA) scores (–0.31 mm Hg/point), older age (–0.04 mm Hg/yr), and male sex (–0.47 mm Hg) were associated with lower MAP. Patients with higher illness severity experienced progressively greater MAP decline over time (–0.20 mm Hg/hr/SOFA point; p < 0.001). CONCLUSIONS AND RELEVANCE: Propofol-based sedation was associated with clinically significant hemodynamic effects requiring intervention in the early post-intubation period. The marked interpatient variability in hemodynamic responses highlights the importance of personalized management approaches, including risk stratification based on age, sex, and illness severity.

Purpose: To develop and validate an explainable machine learning (ML) tool to help clinicians predict the risk of propofol-associated hypertriglyceridemia in critically ill patients receiving propofol sedation. Methods: Patients from 11 intensive care units (ICUs) across five Mayo Clinic hospitals were included if they met the following criteria: a) ≥ 18 years of age, b) received propofol infusion while on invasive mechanical ventilation for ≥24 h, and c) had a triglyceride level measured. The primary outcome was hypertriglyceridemia (triglyceride >400 mg/dL) onset within 10 days of propofol initiation. Both COVID-inclusive and COVID-independent modeling pipelines were developed to ensure applicability post-pandemic. Decision thresholds were chosen to maintain model sensitivity >80%. Nested leave-one-site-out cross-validation (LOSO-CV) was used to externally evaluate pipeline performance. Model explainability was assessed using permutation importance and SHapley Additive exPlanations (SHAP). Results: Among 3922 included patients, 769 (19.6%) developed propofol-associated hypertriglyceridemia, and 879 (22.4%) had COVID-19 at ICU admission. During nested LOSO-CV, the COVID-inclusive pipeline achieved an average AUC-ROC of 0.71 (95% confidence interval [CI] 0.70–0.72), while the COVID-independent pipeline achieved an average AUC-ROC of 0.69 (95% CI 0.68–0.70). Age, initial propofol dose, and BMI were the top three most important features in both models. Conclusion: We developed an explainable ML-based tool with acceptable predictive performance for assessing the risk of propofol-associated hypertriglyceridemia in ICU patients. This tool can aid clinicians in identifying at-risk patients to guide triglyceride monitoring and optimize sedative selection.

Abstract Rationale Propofol is one of the first-line sedative-hypnotic agents for critically ill adults requiring mechanical ventilation. Although propofol can elevate triglyceride levels, and the latter is a risk factor for pancreatitis, the association between propofol and acute pancreatitis is unclear. Objectives We sought to determine the clinical impact and potential associations between propofol infusion, hypertriglyceridemia, and acute pancreatitis. Methods This is an observational multicenter study of adults (⩾18 yr old) who were admitted to an intensive care unit, who required mechanical ventilation and received continuous propofol infusion for at least 24 hours. The primary outcomes were the frequency of hypertriglyceridemia (&gt;400 mg/dl) and acute pancreatitis. Further analyses were done to determine the clinical impact of elevated triglyceride levels (i.e., sedation changes) and risk factors for pancreatitis development. Results Of 11,828 patients included, 33.2% (n = 3,922) had triglyceride levels measured, of whom 21.7% (n = 851) had hypertriglyceridemia at 4.5 days (SD = 6.8) after propofol initiation. Of those still requiring sedation, 70.4% (n = 576/818) received alternative sedatives after developing hypertriglyceridemia. Pancreatitis occurred in 1.2% of patients (n = 47/3,922) and was more frequent in those with hypertriglyceridemia (3.2%, 27/851; vs. 0.7%, 20/3,071; P &lt; 0.001). After adjustment for potential confounding variables, each 100 mg/dl increase in triglyceride levels was associated with an 11% increase in risk of pancreatitis. Propofol dose was not associated with pancreatitis development. Conclusions Acute pancreatitis is uncommon in patients receiving propofol infusion, and it occurs over a wide range of triglyceride levels, indicating a multifactorial pathophysiology. Hypertriglyceridemia frequently prompts the use of alternative sedatives. Further study is needed to determine how to best monitor and treat hypertriglyceridemia in critically ill patients receiving propofol infusion.

AbstractToxic epidermal necrolysis (TEN) is a rare but often lethal drug reaction involving the skin. Treatment is often centered around suppurative care, and the mortality rate remains unacceptably high, although the clinical and epidemiological features of TEN have been well documented for decades. Recent studies have placed an emphasis on certain medications in the pathophysiology of severe TEN, and our colleagues previously reported several cases of clinical improvement in TEN patients following hemodialysis. Here, we discuss the major considerations for initiating dialysis in TEN patients. By doing so, we hope to encourage others to explore this potential avenue for treating TEN, one of the most serious medical emergencies in the field of dermatology.