Inpatient Insights
Liberal blood transfusion appears more favorable for acute brain injury patients
Blood transfusions are commonly administered to patients with acute brain injury, but the optimal hemoglobin transfusion threshold is uncertain in these patients. Members of the TRAIN Randomized Clinical Trial Study Group conducted a multicenter, phase 3, parallel-group, open-label randomized clinical trial to assess the impact on neurological outcome of two different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. The study, published online in JAMA on October 9, 2024, was conducted in 72 ICUs across 22 countries.
Over 800 patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected ICU stay of at least 72 hours were enrolled in the study and randomly assigned to undergo a liberal (triggered by hemoglobin <9 g/dL) or a restrictive (triggered by hemoglobin <7 g/dL) transfusion strategy over a 28-day period. The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between one and five, at 180 days following randomization.
The liberal strategy group received a median of 2 units of blood, and the restrictive strategy group received a median of 0 units of blood. At 180 days after randomization, 62.6% of patients in the liberal strategy group had an unfavorable neurological outcome compared with 72.6% of patients in the restrictive strategy group. In the liberal strategy group, 8.8% of patients had at least one cerebral ischemic event compared with 13.5% of patients in the restrictive strategy group. The researchers concluded that a liberal transfusion strategy compared with a restrictive strategy resulted in a lower rate of unfavorable neurological outcome among patients with acute brain injury. ■
Does antihypertensive drug treatment increase the risk of hemodialysis hypotension?
Antihypertensive medications are often prescribed to manage hypertension in hemodialysis patients, and intradialytic hypotension is a common complication in these patients.
A global group of researchers based in Italy, the United States, the Netherlands, and Germany conducted a study to emulate a randomized clinical trial investigating the risk of hemodialysis hypotension in over 4,000 incident hemodialysis patients.
The study, published in the October 2024 issue of the Clinical Journal of the American Society of Nephrology included patients who started antihypertensive drug treatment between January 2016 and December 2019.
The results indicated that calcium channel blocker use (reference medication) was associated with an hemodialysis hypotension incidence rate of 7.4 events per person-year, whereas use of b- and a–b-blockers were strongly associated with a higher likelihood of hemodialysis hypotension.
The use of ACE inhibitors or ARBs and diuretics were also associated with a higher likelihood of hemodialysis hypotension compared with calcium channel blocker use.
The researchers concluded that their observational findings with a large cohort of patients suggest that calcium channel blockers have the lowest risk of hemodialysis hypotension in hemodialysis patients and that b- and a–b-blockers, ACE inhibitors, ARBs, and diuretics may increase the risk of hemodialysis hypotension and should be avoided in hemodialysis patients. They suggest that pragmatic trials comparing hypertensive drugs in this population be performed. ■
Ziresovir may be effective for hospitalized infants with RSV
RSV is a leading cause of severe illness in infants. Although RSV vaccines have been approved for use in adults 60 or older and in people who are pregnant, none are currently approved for use in children, and the only FDA-approved therapy for RSV in infants is aerosolized ribavirin, which has limited efficacy, an unfavorable safety profile, and potential teratogenic effect. Results of a phase 2 trial suggested that ziresovir may have efficacy in the treatment of infants hospitalized with RSV infection, and as a follow-up to this study, members of the AIRFLO Study Group conducted a phase 3, multicenter, double-blind, randomized, placebo-controlled trial in China. The study, published in the September 26, 2024, issue of NEJM, enrolled participants 1 to 24 months old who were hospitalized with RSV infection.
Participants were randomly assigned, in a 2:1 ratio, to receive ziresovir (at a dose of 10 mg to 40 mg, according to body weight) or placebo, administered twice daily, for 5 days. The primary end point was the change from baseline to day 3 (defined as 48 hours after the first administration) in the Wang bronchiolitis clinical score (total scores range from 0 to 12, with higher scores indicating greater severity of signs and symptoms).
The reduction from baseline in the Wang bronchiolitis clinical score at day 3 was significantly greater in patients given ziresovir than with placebo and the reduction in the RSV viral load at day 5 was also greater in the ziresovir group than in the placebo group. Improvements were observed in prespecified subgroups, including in participants with a baseline bronchiolitis score of at least 8 and in those 6 months old or younger. The incidence of adverse events was 16% with ziresovir and 13% with placebo, with the most common adverse events being diarrhea (in 4% and 2% of the participants, respectively), an elevated liver-enzyme level (in 3% and 3%, respectively), and rash (in 2% and 1%, respectively). The researchers suggested that these initial findings warrant further evaluation in an international, phase 3 trial of ziresovir treatment for RSV infection. ■
Is I.V. thrombolysis after dabigatran reversal safe for patients with acute ischemic stroke?
I.V. thrombolysis is the standard of care for systemic reperfusion in patients with acute ischemic stroke. However, treatment with dabigatran, a direct thrombin inhibitor that has been approved for stroke prevention in patients with nonvalvular AFib, represents a contraindication to I.V. thrombolysis for acute ischemic stroke, especially without specific coagulation tests. The anticoagulation effects of dabigatran can be reversed by administration of idarucizumab. Evidence from earlier studies indicate that I.V. thrombolysis after dabigatran reversal with idarucizumab may be safe and effective for patients with acute ischemic stroke, but there is no randomized evidence to support this practice. Researchers in Greece conducted a national registry-based study to evaluate the safety and efficacy of idarucizumab pretreatment in patients with acute ischemic stroke receiving I.V. thrombolysis.
The study, published in the October 8, 2024, issue of Neurology, aimed to document the rates of symptomatic intracranial hemorrhage, any intracranial hemorrhage, 3-month mortality, and the proportion of excellent and good functional outcome at 3 months among patients with acute ischemic stroke who received I.V. thrombolysis after dabigatran reversal with idarucizumab. The researchers also compared these results with those of I.V. thrombolysis-treated patients without dabigatran pretreatment.
The results indicated that the risk of symptomatic intracranial hemorrhage, any intracranial hemorrhage, and 3-month mortality did not differ between patients receiving I.V. thrombolysis with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome. The authors suggested that randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of I.V. thrombolysis in this specific population. ■