Author Year Country

Study Design

Sample Size

(2017)

USA

RCT

PEDro=10

N=14

Population: TBI; Placebo (n=7): Mean Age=9.7yr; Median GCS=6. Probenecid + N-Acetylcysteine (NAC;n=7): Mean Age=8.6yr; Median GCS=6.

Intervention: Patients initially received comprehensive standard care with the aim of stabilization and mitigation of complications secondary to TBI injuries. Once stable, patients received probenecid (25 mg/kg load, then 10 mg/kg/dose every 6 h for 11 doses) and N-acetylcysteine (NAC) (140 mg/kg load, then 70 mg/kg/dose every 4 h for 17 doses) or placebo through a naso/orogastic tube. CSF and serum sample were collected over 4 days; prior and 1 hr after the first dose, and daily prior to drug administration).

Outcome Measure: NAC CSF Concentration, Glasgow Outcome Scale (GOS), Length of Stay (LOS), Physiological Parameters.

1.        NAC CSF concentrations were detectable 6 h after treatment, and continued to increase until they peaked at 72 hours. CSF NAC concentrations returned to baseline after 96h.

2.        No difference between GOS scores were observed between groups after treatment or at 3 mo follow-up.

3.        Median paediatric intensive care unit and hospital LOS were not significantly different between groups.

4.        Temperature, mean arterial pressure, and ICP were not different between groups.

Natale et al. (2007)

Canada

RCT

PEDro=5

N=6

Population: TBI; Magnesium Sulfate Group (MgSO₄, n=4): Mean Age=8.9yr; Gender: Male=2, Female=2; Mean Time Post Injury=43.8 hr; Mean Highest GCS=4.5. Placebo Group (n=2): Mean Age=5.7yr; Gender: Male=0, Female=2; Mean Time Post Injury=21.5 hr; Mean Highest GCS=9.

Intervention: Patients were randomized to receive either MgSO₄ or a placebo. A dosage of 50 mg/kg up to 4 g of MgSO₄ was administered in an appropriate volume of saline to create a concentration of 50 mg/ml. This was followed by a continuous intravenous MgSO₄ at a dosage of 8.3 mg/kg/hr for 24 hr. The placebo group received saline only, also for 24 hr. Intracranial Pressure (ICP) levels were measured every 5 min during the first 45 min of treatment, every 15 min after 90 min, every 30 min after 150 min then every 2 hr until the transfusion was complete. Assessments were conducted throughout the study period.

Outcome Measure: ICP levels, Cerebral Perfusion Pressure (CPP) levels, Mean Arterial Pressure (MAP) levels, Cerebral Blood Flow Velocity (CBFV).

1.        ICP and CPP levels did not significantly change during bolus dosage nor continuous infusion of MgSO₄ when compared to baseline.

2.        MAP levels were significantly higher during the 14-24 hr infusion period for the MgSO₄ group compared to baseline (82 mmHg versus 93 mmHg, p<0.050).

3.        CBFV among all patients with severe TBI did not reach the critically low level of 10 cm/sec and no deleterious effect of MgSO₄ on CBFV was detected.

Podolsky-Gondim et al. (2018)

Brazil

Retrospective

N=66

Population:  TBI Group (N=66): Mean Age=10.9y (3 – 17yr); Gender: Male=77.3%, Female=22.7%; Mean time post injury=acute; GCS=9.48 (4.39).

Intervention: Retrospective chart review of a trauma centre investigating the effect of coagulopathy on neurological outcome post-TBI. Records examined inpatient stay, 1-month, and 6-month follow-up.

Outcomes: ICP monitoring, coagulopathy rate, predictors of unfavorable Glasgow Outcomes Scale-Extended (GOS-E)

1.        32 of 66 (48.4%) received invasive ICP monitoring and in 16 of 66 (24.2%) ICP monitoring was the only neurosurgical intervention.

2.        Four patients underwent consecutive decompressive craniectomy.

3.        Coagulopathy was present in 34.8% of patients.

4.        At 1-month follow-up, 71.2% of patients had favorable outcomes on the GOS-E, and 77.3% at 6-months.

5.        Predictors of unfavorable GOS-E included: adolescence, low GCS, abnormal prothrombin time, fibrinogen levels, thrombocyte count, and neuroimaging findings of brain edema or bleeding (p<0.05).

Canada

Case Control

N=128

Population: TBI; Patients Transfused (n=53­­): Mean Age=3.5yr; Gender: Male=32, Female=21; Median GCS=3. Patients not Transfused (n=67­­): Mean Age=11.3yr; Gender: Male=47, Female=20; Median GCS=6.

Intervention: Patients with severe TBI were retrospectively identified to investigate the association between blood transfusions, anemia and patient outcomes.

Outcome Measure: Adverse Outcomes, Mortality.

1.       For those who received transfusions, the mean number of transfusions received was 1.67.

2.       Multivariable regression analysis did not reveal significant association between blood transfusion and anemia with adverse outcomes. However, non-accidental trauma suspected (Odds ratio=9.01; p<0.050) and Pediatric Risk of Mortality (PRISM) III score (Odds ratio=1.32; p<0.050) were significantly associated with mortality.