Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE: Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES: Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS: Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS: There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS: In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Plasmapheresis and Intravenous Immune Globulin Improve Neurologic Outcome of Central Pontine Myelinolysis Occurring Post Orthotopic Liver Transplant.

OBJECTIVE: To report 2 cases of central pontine myelinolysis (CPM) post liver transplantation in which treatment with plasmapheresis and intravenous immune globulin improved expected neurologic outcome. CASE SUMMARY: Two patients who underwent orthotopic liver transplant developed CPM early in their postoperative course. Magnetic resonance imaging of the brain demonstrated severe demyelination of either the pons or the midbrain, respectively. Both patients developed significant neurologic abnormalities, including acute mental status changes, severe muscle weakness, spasticity, and/or prolonged paralysis. Pretransplant laboratory results indicated serum sodium levels fluctuating between 115 mEq/L and 152 mEq/L. Both patients received 6 days of plasmapheresis (PP) followed by 5 consecutive days of intravenous immune globulin (IVIG). Significant neurologic improvement was experienced at 2 and 4 weeks, respectively, after therapy was initiated. Complete resolution of neurologic symptoms was evident at 1 year follow-up. DISCUSSION: Currently, specific guidelines or recommendations for the treatment of CPM are practically nonexistent. CPM remains a neurologic complication that is difficult to treat and may result in permanent significant neurologic sequelae. The etiology and pathogenesis of this disease are unclear, although aggressive osmolar correction, particularly in the setting of hyponatremia, is the main risk factor. While patients may eventually show some improvement with supportive care, progress is often protracted, and complete resolution of symptoms is exceedingly rare. The severity of the midbrain lesions juxtaposed against the rapidity of symptom resolution in these 2 patients alludes to a potential therapeutic benefit after initiation of therapy with PP and IVIG. CONCLUSIONS: These cases suggest that prompt recognition of CPM and initiation of PP and IVIG may help modulate its progress and improve long-term neurologic outcome.

Implementation of an enoxaparin protocol for venous thromboembolism prophylaxis in obese surgical intensive care unit patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious health care issue that affects a large number of people. Few standards exist for delineating the optimal dosing strategy for VTE prevention in obese patients, especially in the setting of major surgery or trauma. OBJECTIVE: To document the efficacy of a surgical intensive care unit (SICU)-specific, weight-based dosing protocol of enoxaparin 0.5 mg/kg given subcutaneously every 12 hours for VTE prophylaxis in morbidly obese (defined as body mass index [BMI] ≥35 kg/m(2) or weight ≥150 kg) SICU patients, using peak anti-factor Xa levels to determine therapeutic endpoints. METHODS: Data were collected retrospectively in an academic, university-based SICU on 23 morbidly obese patients who received weight-based enoxaparin for VTE prophylaxis from December 1, 2008, through June 30, 2010. RESULTS: A weight-based dosage range of enoxaparin 50-120 mg twice daily (median 60) was given to 23 patients. The mean BMI was 46.4 kg/m(2). The initial mean anti-factor Xa level (measured after the third dose) was 0.34 IU/mL (range 0.20-0.59). Patients received an average of 18 doses. Two cases required an increase or decrease in dosage based on anti-factor Xa levels. Morbidity related to this dosing included a single event of minor endotracheal bleeding and a single deep vein thrombosis that was likely present prior to treatment. CONCLUSIONS: Weight-based dosing with enoxaparin in morbidly obese SICU patients was effective in achieving anti-factor Xa levels within the appropriate prophylactic range. This regimen reduced the rate of VTE below expected levels and no additional adverse effects were reported.

Characterizing the free volume of ultrahigh molecular weight polyethylene to predict diffusion coefficients in orthopedic liners.

Liners used in orthopedic devices are often made from ultrahigh molecular weight polyethylene (UHMWPE). A general predictive capability for transport coefficients of small molecules in UHMWPE does not exist, making it difficult to assess properties associated with leaching or uptake of small molecules. To address this gap, we describe here how a form of the Vrentas-Duda free volume model can be used to predict upper-bound diffusion coefficients (D) of arbitrary molecules within UHMWPE on the basis of their size and shape. Within this framework, the free-volume microstructure of UHMWPE is defined by analysis of a curated set of model diffusants. We determined an upper limit on D for vitamin E, a common antioxidant added to UHMWPE, to be 7.1 × 10-12 cm2  s-1 . This means that a liner that contains 0.1 wt % or less Vitamin E and has <120 cm2 patient contacting surface area would elute <100 µg/day of vitamin E. Additionally, the model predicts that squalene and cholesterol-two pro-oxidizing biological compounds-do not penetrate over 820 µm into UHMWPE liners over the course of 5 years because their D is ≤7.1 × 10-12 cm2  s-1 . © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2393-2402, 2018.

Severe rash associated with dexmedetomidine use during mechanical ventilation.

Dexmedetomidine, a sedative administered by continuous infusion, is used to facilitate mechanical ventilation through alpha(2)-receptor activation. The drug's most common adverse reactions include hypotension, hypertension, nausea, bradycardia, and dry mouth. However, to our knowledge, no reports of dermatologic allergic reactions from dexmedetomidine use have been published. We describe a 22-year-old man who was intubated after being injured in a motor vehicle collision. He had been receiving propofol and fentanyl infusions for sedation during mechanical ventilation and was transitioning to dexmedetomidine. Within 4 hours of receiving dexmedetomidine 0.2 microg/kg/hour, the patient developed a wheal-and-flare rash encompassing 60% of his body surface area. The infusion was immediately discontinued; over the next 24 hours most of the rash receded, and within 48 hours of drug discontinuation the rash had completely resolved. According to the Naranjo adverse drug reaction probability scale, the likelihood that this rash was induced by dexmedetomidine was probable. Clinicians should be aware of this potential dermatologic adverse effect from dexmedetomidine, and patients receiving the drug should be closely monitored.