Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. OBJECTIVE: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. METHODS: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. RESULTS: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB- group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. CONCLUSION: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population.

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States. METHODS: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes. RESULTS: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66). CONCLUSIONS: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. INTERVENTIONS: None. MEASUREMENTS: Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. MAIN RESULTS: Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes. CONCLUSIONS: About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.

Nuclear lamin phosphorylation: an emerging role in gene regulation and pathogenesis of laminopathies.

Decades of studies have established that nuclear lamin polymers form the nuclear lamina, a protein meshwork that supports the nuclear envelope structure and tethers heterochromatin to the nuclear periphery. Much less is known about unpolymerized nuclear lamins in the nuclear interior, some of which are now known to undergo specific phosphorylation. A recent finding that phosphorylated lamins bind gene enhancer regions offers a new hypothesis that lamin phosphorylation may influence transcriptional regulation in the nuclear interior. In this review, we discuss the regulation, localization, and functions of phosphorylated lamins. We summarize kinases that phosphorylate lamins in a variety of biological contexts. Our discussion extends to laminopathies, a spectrum of degenerative disorders caused by lamin gene mutations, such as cardiomyopathies and progeria. We compare the prevailing hypothesis for laminopathy pathogenesis based on lamins' function at the nuclear lamina with an emerging hypothesis based on phosphorylated lamins' function in the nuclear interior.