Beta-Blocker Therapy in Severe Traumatic Brain Injury: A Prospective Randomized Controlled Trial. Khalili H, Ahl R, Paydar S, et al. World J Surg. 2020 Jun;44(6):1844-1853.
In 2017, EAST published a Practice Management Guideline conditionally recommending beta blockade in acute TBI based on overall low-quality evidence. Subsequently in 2018, the AAST conducted a multi-institutional trial in which adult TBI patients who required intensive care unit admission were compared based on beta-blocker administration. On multivariate regression, the investigators found that beta-blocker administration decreased mortality. The Beta-Blocker Therapy in Severe Traumatic Brain Injury: A Prospective Randomized Controlled Trial provides the first randomized study of the benefits of beta blockade in select TBI patients.
In this single-center, randomized controlled trial, patients with a severe TBI (intracranial AIS ≥3) were randomized to 20 mg of propranolol twice daily or no intervention. Severe blunt TBI without extracranial injuries requiring intervention were included. Eligible patients were randomized 24-hours after admission if they were hemodynamically stable, and had no ongoing transfusion requirements. Patients randomized to beta blockade received 20 mg of propranolol twice daily for up to ten days or until discharge. Unfortunately, due to funding issues a placebo was not administered in the control group. Importantly, treating physicians were not blinded to therapy and single-doses of beta-blockers were not accounted for.
222 patients were eligible for enrollment and randomization. 120 patients did not receive beta-blocker therapy and 102 were prescribed the intervention. Only three patients in the beta-blocker group were excluded from the final analysis due to cessation of therapy secondary to bradycardia. No patients ceased therapy due to hypotension. The two cohorts had similar baseline characteristics and demographics. 16.7% of patients allocated to the conventional treatment group died compared to 8.1% in the intervention group (p = 0.06). After limiting the analysis only to patients suffering from isolated severe TBI, 154 patients were available for analysis. Compared to those who did not receive propranolol, patients administered propranolol had a significantly reduced mortality (4.4% vs. 18.6%, p = 0.01) Furthermore, they showed improved Glasgow Outcome Scores at six-month follow up. Upon regression analysis the investigators determined that patients that did not receive beta blockade were three times as likely to die (p = 0.04).
Currently, the American Brain Trauma Foundation Guidelines make no specific recommendation to guide the use of beta blockade in acute TBI. This study adds to the existing and increasingly robust body of literature supporting beta blockade in TBI. The traditional concern of beta-blockers precipitating hypotension and bronchoconstriction leading to hypotension and hypoxia and subsequent secondary brain injury appears to be largely unfounded, and are outweighed by the potential benefits of blunting the catecholamine surge strongly associated with TBI. Although the exact mechanism(s) of beta-blocker benefit in TBI remain to be elucidated, the findings of both decreased mortality and significantly improved neurologic outcomes at 6 months in this trial are striking. These results, along with the low risk profile, strongly support the increased routine administration of beta-blockers to stable patients with isolated severe TBI. However, the small overall sample size and resultant under powering also calls for the performance of a larger, multicenter, and placebo-controlled randomized trial to confirm the benefits and better identify risks and any important sub-groups who may not benefit from early beta-blocker administration.
Predictors of Retained Hemothorax in Trauma: Results of an EAST Multi-Institutional Trial. Prakash PS, Moore SA, Rezende-Neto JB, et al. J Trauma Acute Care Surg. 2020 Jul 8.
Retained hemothorax (RH) is a frequent and challenging clinical problem following blunt or penetrating thoracic trauma. Therapeutic interventions such as tube thoracostomy, fibrinolytic therapy and video-assisted thoracoscopy (VATS) are the mainstays of therapy. The natural history of retained hemothorax and the factors that predict the progression to retained hemothorax remain largely unknown. In this EAST multi-institutional trial investigators describe the natural history of CT-diagnosed hemothoraces and characterize predictors of RH.
During the two-year study period, investigators identified 1,033 patients with a hemothorax on initial presentation. Due to the need for CT volumetric analysis, only patients whose initial hemothorax was diagnosed on chest CT were included in this study (n=698). Hemothoraces identified on plain film and immediately treated or intervened on empirically without imaging were excluded (n=335). Of those identified on axial imaging, 53% (n=369) of these patients were managed with initial tube thoracostomy. The remaining patients were observed (n=329). Patients undergoing tube thoracostomy tended to be severely injured males with a median of five rib fractures associated with underlying pulmonary contusions. The median volume on initial CT was 101mL. Median chest tube size was 32 French. Chest tube size was not associated with the development of a retained hemothorax. Notably, less than 5% of patients under went percutaneous thoracostomy as the initial management strategy. Initial tube thoracostomy successfully treated nearly three-quarters of the patients (71%). 29% of patients developed a retained hemothorax. Repeat axial imaging was the primary modality to diagnosed RH. Of these patients 67% required an additional intervention. 30% of patients underwent additional thoracostomy tube placement, 28% operative intervention the majority of which was VATS. Patients managed operatively had lower treatment failure rates and were less likely to require additional procedures. Patients with RH had overall worse outcomes and had worse functional outcomes at discharge. On multivariate analysis predictors of RH were: chest AIS, penetrating mechanism, hematocrit on presentation and estimated volume on axial imaging. For every 100mL of hemothorax on axial imaging there is a 15% increased risk in RT.
Hemothorax size on initial chest CT was the strongest predictor of retained hemothorax. The investigators used the Mergo Formula for volumetric assessment of the pleural space. Patients with a CT-estimated volume of <300mL were significantly less likely to develop a retained hemothorax. This cut off is beneficial to help determine which patient may benefit from early intervention versus observation alone. Interestingly, in this study the rate of subsequent empyema in the setting of both hemothorax and retained hemothorax was less than 1%, notably less than prior studies. Taken together, these data suggest that a small traumatic hemothorax, less than 300 mL (treated with observation or thoracostomy), has a very low likelihood of progression to a retained hemothorax (~10%) and the majority can be successfully observed. It is important to note however, that investigators did not report the rate of RH in the hemothorax group that was managed with initial observation alone. This study supports the previously published EAST Practice Management Guideline on the Management of Hemothorax and Occult Pneumothorax recommendation that VATS should be the intervention of choice for the treatment of a retained hemothorax in lieu of a second tube thoracostomy or thrombolytic therapy.