Early Propranolol After Traumatic Brain Injury is Associated With Lower Mortality.

Ko A, et al. Early propranolol after traumatic brain injury is associated with lower mortality. J Trauma Acute Care Surg. 2016 Apr;80(4):637-42.

BACKGROUND: β-Adrenergic receptor blockers (BBs) administered after trauma blunt the cascade of immune and inflammatory changes associated with injury. BBs are associated with improved outcomes after traumatic brain injury (TBI). Propranolol may be an ideal BB because of its nonselective inhibition and ability to cross the blood-brain barrier. We determined if early administration of propranolol after TBI is associated with lower mortality.

METHODS: All adults (age ≥ 18 years) with moderate-to-severe TBI (head Abbreviated Injury Scale [AIS] score, 3-5) requiring intensive care unit (ICU) admission at a Level I trauma center from January 1, 2013, to May 31, 2015, were prospectively entered into a database. Administration of early propranolol was dosed within 24 hours of admission at 1 mg intravenous every 6 hours. Patients who received early propranolol after TBI (EPAT) were compared with those who did not (non-EPAT). Data including demographics, hospital length of stay (LOS), ICU LOS, and mortality were collected.

RESULTS: Over 29 months, 440 patients with moderate-to-severe TBI met inclusion criteria. Early propranolol was administered to 25% (109 of 440) of the patients. The EPAT cohort was younger (49.6 years vs. 60.4 years, p < 0.001), had lower Glasgow Coma Scale (GCS) score (11.7 vs. 12.4, p = 0.003), had lower head AIS score (3.6 vs. 3.9, p = 0.001), had higher admission heart rate (95.8 beats/min vs. 88.4 beats/min, p = 0.002), and required more days on the ventilator (5.9 days vs. 2.6 days, p < 0.001). Similarities were noted in sex, Injury Severity Score (ISS), admission systolic blood pressure, hospital LOS, ICU LOS, and mortality rate. Multivariate regression showed that EPAT was independently associated with lower mortality (adjusted odds ratio, 0.25; p = 0.012).

CONCLUSION: After adjusting for predictors of mortality, early administration of propranolol after TBI was associated with improved survival. Future studies are needed to identify additional benefits and optimal dosing regimens.

LEVEL OF EVIDENCE: Therapeutic study, level IV.

More harm than good: Antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. (Petrillo)

Bhullar IS, Johnson D, Paul JP, Kerwin AJ, Tepas JJ 3rd, Frykberg ER. More harm than good: Antiseizure prophylaxis after traumatic brain injury does not decrease seizure rates but may inhibit functional recovery. J Trauma Acute Care Surg. 2014 Jan;76(1):54-61.

BACKGROUND: The purposes of this study were to examine the current Brain Trauma Foundation recommendation for antiseizure prophylaxis with phenytoin during the first 7 days after traumatic brain injury (TBI) in preventing seizures and to determine if this medication affects functional recovery at discharge.

METHODS: The records of adult (age ≥ 18 years) patients with blunt severe TBI who remained in the hospital at least 7 days after injury were retrospectively reviewed from January 2008 to January 2010. Clinical seizure rates during the first 7 days after injury and functional outcome at discharge were compared for the two groups based on antiseizure prophylaxis, no prophylaxis (NP) versus phenytoin prophylaxis (PP). Statistical analysis was performed using χ.

RESULTS: A total of 93 adult patients who met the previously mentioned criteria were identified (43 [46%] NP group vs. 50 [54%] PP group). The two groups were well matched. Contrary to expectation, more seizures occurred in the PP group as compared with the NP group; however, this did not reach significance (PP vs. NP, 2 [4%] vs. 1 [2.3%], p = 1). There was no significant difference in the two groups (PP vs. NP) as far as disposition are concerned, mortality caused by head injury (4 [8%] vs. 3 [7%], p = 1), discharge home (16 [32%] vs. 17 [40%], p = 0.7), and discharge to rehabilitation (30 [60%] vs. 23 [53%], p = 0.9). However, with PP, there was a significantly longer hospital stay (PP vs. NP, 36 vs. 25 days, p = 0.04) and significantly worse functional outcome at discharge based on Glasgow Outcome Scale (GOS) score (PP vs. NP, 2.9 vs. 3.4, p < 0.01) and modified Rankin Scale score (2.3 ± 1.7 vs. 3.1 ± 1.5, p = 0.02).

CONCLUSION: PP may not decrease early posttraumatic seizure and may suppress functional outcome after blunt TBI. These results need to be verified with randomized studies before recommending changes in clinical practice and do not apply to penetrating trauma.

LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemiologic study, level III.

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Vancomycin and nephrotoxicity: Just another myth? (Petrillo)

Davies SW, Guidry CA, Petroze RT, Hranjec T, Sawyer RG. Vancomycin and nephrotoxicity: Just another myth? J Trauma Acute Care Surg. 2013 Oct;75(5):830-5.

BACKGROUND: Vancomycin is considered the drug of choice for methicillin-resistant Staphylococcus aureus infection; however, it has also been linked with nephrotoxicity in the past, sometimes leading to its substitution with linezolid. We hypothesized that patients treated with vancomycin for gram-positive (GP) infections would have an increased incidence of rise in creatinine and need for hemodialysis (HD) compared with patients receiving linezolid.

METHODS: This was a retrospective cohort study of a prospectively maintained database of all surgical patients treated with either vancomycin or linezolid for GP infections in a single intensive care unit from 2001 to 2008 and managed under a cycling antibiotic protocol. Patients were followed up until hospital discharge. Categorical and continuous variables were evaluated. Multivariable logistic regression was performed.

RESULTS: A total of 545 patients were treated for 1,046 GP infections (571 with vancomycin, 475 with linezolid) over 7 years. Patient demographics were similar between groups; however, the vancomycin group was associated with a longer treatment course (16.2 [0.5] days vs. 14.3 [0.5] days; p = 0.022). Unadjusted outcomes were similar between groups. Multivariable analysis revealed that Acute Physiology and Chronic Health Evaluation II score predicted an increase in creatinine levels greater than 1.0 following antibiotic therapy (relative risk [RR], 3.01; 95% confidence interval [CI], 1.22-7.42) and subsequent need for HD (RR, 3.07; 95% CI, 1.23-7.62). In addition, initial creatinine level predicted an increase in creatinine levels greater than 1.0 following antibiotic therapy (RR, 4.36; 95% CI, 1.46-12.99) and subsequent need for HD (RR, 10.83; 95% CI, 3.19-36.77). Linezolid was found to be protective regarding rise in creatinine levels greater than 1.0 following antibiotic therapy; however, this was only experienced when vancomycin trough levels greater than 20 were encountered (RR, 5.4;95% CI, 1.19-24.51).

CONCLUSION: These data suggest that vancomycin is minimally nephrotoxic and has a similar nephrotoxic profile as compared with linezolid when appropriate dosing is used, even among critically ill patients with complex infections.

LEVEL OF EVIDENCE: Therapeutic/care management, level II.

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Occult abusive injuries in infants with apparently isolated skull fractures. (Petrillo)

J Trauma Acute Care Surg. 2013 Jun;74(6):1553-1558. PMID: 23694887

BACKGROUND: There is currently no consensus about which screening studies should be undertaken to identify abusive injuries in infants with apparently isolated skull fractures. Our objective was to determine rates of screening, rates of injury identification, and rates of reporting to child protective services among infants who underwent subspecialty evaluation for abuse after presenting with an apparently isolated skull fracture.

METHODS: This was a retrospectively planned, secondary analysis of index children enrolled in a large network of children with concerns for physical abuse. For this analysis, we included infants (<12 months) who presented with signs and symptoms attributable to a skull fracture. We determined rates of skeletal survey, dedicated ophthalmologic examination and abdominal injury screening, rates of injury identification by testing and reports to child protective services.

RESULTS: A total of 215 infants underwent abuse consultation for apparently isolated skull fractures. Skeletal surveys were performed in 201 subjects (93.4%) and identified additional fractures in 12 (5.6%; 95% confidence interval, 2.9-9.6%). Patient age, trauma history, and fracture type (simple/complex) were not sensitive predictors of finding additional fractures on skeletal survey. Only one additional fracture was associated with clinical signs or symptoms. Dedicated ophthalmologic examination was undertaken in 100 subjects (46.5%); one child had retinal hemorrhages. Hepatic transaminases were obtained in 135 subjects (62.7%), and 5 subjects (2.3%) had abdominal computed tomography. No abdominal injuries were identified. A total of 146 subjects (67.9%) were reported to child protective services.

CONCLUSION: Infants with apparently isolated skull fractures are an important fraction of consultations for physical abuse. Additional fractures are identified in a small subset of the skeletal surveys completed in these children.

LEVEL OF EVIDENCE: Epidemiological study, level IV.

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