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Qubec A liberal transfusion strategy that raises the hemoglobin level to over 10 g/dl has only tended to improve the neurological recovery of patients with traumatic brain injury in a randomized study. The publication in New England Journal of Medicine (2024; DOI: 10.1056/NEJMoa2404360) in some aspects of functional independence and quality of life.

Most patients with traumatic brain injury develop anemia. Since the lack of red blood cells endangers the oxygen supply to the brain, the logical treatment is blood transfusions. However, previous studies have not shown any benefit for the patients.

On the contrary: In a study by the Canadian Critical Care Trials Group, a restrictive transfusion strategy in which patients only received red blood cell concentrates when their hemoglobin (Hb) had fallen below 7 g/dl had better results. Significantly fewer patients died in hospital (NEJM1999; DOI: 10.1056/NEJM199902113400601). A later study on children also found no benefits for a liberal transfusion strategy (NEJM2007; (DOI: 10.1056/NEJMoa066240).

However, these studies were carried out on patients who were being treated in an intensive care unit for various reasons. The proportion with traumatic brain injury was small. The Canadian Critical Care Trials Group has therefore carried out a new study (HEMOTION) that was limited to adult patients with traumatic brain injury. According to neurologists, these patients have the highest risk of suffering harm from the associated lack of oxygen if they suffer from anemia.

Between September 2017 and April 2023, 742 patients were randomized to the two strategies at 34 clinics in Canada, the UK, France and Brazil. The primary endpoint was an unfavorable outcome in the extended Glasgow Outcome Scale (GOS-E) after six months. In a so-called sliding dichotomy, the participants were divided into groups according to the initial GOS-E values ​​in order to better take into account the effect of the therapy on different severities of traumatic brain injury. The study also had numerous secondary endpoints on mortality, functional independence, quality of life and depression after six months.

Most patients were men (72.7%), the mean age was 48.7 years, and 73.2% had suffered severe head trauma with a mean motor Glasgow Coma Score of 4. The average Hb level on admission was 9.1 g/dl.

In the group with a liberal transfusion strategy, almost all patients (98.9%) received blood transfusions that increased the Hb value to 10.8 g/dl. In the group with a restrictive transfusion strategy, only one in three received blood transfusions (38.4%). A mean Hb value of 8.8 g/dl was achieved. The protocol was adhered to in a total of 722 patients.

As Franois Lauzier from the Université Laval in Quebec and his colleagues report, 249 of 364 patients (68.4%) in the group with the liberal strategy had an unfavorable outcome compared to 263 of 358 patients (73.5%) in the group with the restrictive strategy. The liberal strategy was therefore advantageous, but the adjusted difference of 5.4 percentage points, with a 95% confidence interval of -2.9 to 13.7 percentage points, missed statistical significance. An advantage of the liberal strategy was therefore not clearly proven.

A quarter of the patients did not survive the traumatic brain injury. There were no differences between the liberal strategy (26.8%) and the restrictive strategy (26.3%). Among the surviving patients, the liberal strategy achieved a slight but significant advantage of 4.34 points (0.22-8.45) in the Functional Independence Measure (which ranges from 18 to 126 points). Patients also rated their quality of life slightly better on the EuroQol visual analogue scale, which ranges from 0 to 100 (0.06 points; 0.01 to 0.10 points). There were also slight advantages in the EQ-5D-5L utility index score and the Qolibri score, but not in depression.

According to Lauzier, the blood transfusions have proven to be safe. Venous thromboembolic events occurred in 8.4% of patients in both groups. Acute respiratory distress syndrome was more common under the liberal strategy at 3.3% versus 0.8%.

Overall, no clear advantage of the liberal strategy can be derived from the data. Nevertheless, the press release headline states that more blood transfusions after a severe traumatic brain injury could mean better results. This is justified by the favorable results in the secondary endpoints. In contrast, the publication clearly states that the liberal transfusion strategy did not reduce the risk of an unfavorable neurological outcome after six months, measured with the GOS-E, in critically ill patients with traumatic brain injury.

Further studies are currently underway. The Belgian TRAIN study (NCT02968654) compares the threshold values ​​of 7 g/dl and 9 g/dl in patients with traumatic brain injury, subarachnoid hemorrhage and intracerebral hemorrhage. The North American-Australian SAHaRA study only includes patients with subarachnoid hemorrhage (NCT03309579). The US BOOST3 study is investigating the combination of better oxygenation of the brain with a reduction in intracranial pressure (NCT03754114). The Australian-New Zealand BONANZA study (ACTRN12619001328167) has a similar goal. © rme/aerzteblatt.de