Journal Watch By Aimee Aysenne, MD, MPH, and Chitra Venkatasubramanian MBBS, MD, MSc
The treatment of TBI has been recently
reviewed in several articles. BOOST-II is
a multicenter, phase II randomized study
evaluating the feasibility of monitoring
and treating the partial pressure of brain
tissue oxygenation. This was a highly
successful trial, leading to early cessation.
The second article is a retrospective study
evaluating potential recovery after TBI, even
in the setting of severe injury, especially in a
pediatric population. Both of these articles
give us hope for continuing to push the limits
of neurocritical care and early aggressive
measures for our severe TBI patients.
BOOST-II: Reduction of brain tissue
hypoxia in severe TBI
David O. Okonkwo, et al. Critical Care Medicine
2017; 45: 1907-1914.
Methods: BOOST-II is a NIH funded phase
II, two-arm, single blind, multicenter
RCT assessing the safety and efficacy of a
management protocol optimizing Pbt02
after severe TBI. The primary outcome was
reducing the total burden of brain hypoxia (Pbt02 < 20 mm Hg).
All patients included had indications for invasive ICP monitoring.
Intraparenchymal ICP and Pbt02 monitors were inserted about 2
cm from cortical surface into the subcortical white matter in the
least affected frontal lobe in the control and treatment groups.
Standard therapy was according to the third edition of the Brain
Trauma Foundation’s guidelines. A three-tiered approach to ICP
and PbtO2 management was used when ICP was ≥ 20 mm Hg
and/or PbtO2 < 20 mm Hg. Tier 1 started within 15 minutes for
ICP and five minutes for PbtO ; Tier 2 was activated when ICP was
≥ 20 mm Hg and/or PbtO2 < 20 mm Hg for >60 minutes, and Tier
3 was optional. In the control group, only tiered ICP therapy was
used, and the PbtO2 values were not accessible to treatment team.
For the intervention group (ICP + Pbt02), stepwise treatments to
correct either ICP, Pbt02 or both was used. Secondary outcome was
six month blinded in-person/telephone assessment of GOS-E and
Disability rating scale (DRS).
Results: 119 patients (57 treatment arm) with similar baseline
demographics and injury severity were enrolled. The trial was
stopped early after successful demonstration of primary outcome
in a smaller sample size. The mean age was 37 years (±17.3), 79
percent males with mean GCS 3.7 (±1.5). Monitors were inserted
by 9.05 (± 5.22 hours) and average of 80.3 hours (± 42.6) of
valid data was obtained. Adherence to the protocol was similar
(13 percent deviation in treatment vs. 11 percent in ICP group).
The treatment group had 66 percent less duration of hypoxia, 72
percent less severe brain hypoxia and 77 percent less duration of
hypoxia. All p values were significant. ICP was similar between
groups. Six month GOS-E showed a trend toward lower mortality
and better outcomes, but none were statistically significant due
to sample size. No increase in adverse events (e.g., infection,
hemorrhage, respiratory) was noted from monitor placement.
Comments: BOOST-II showed that multimodal ICP + Pbt02
monitoring and therapy is feasible and better at reducing brain
tissue hypoxia compared to ICP monitoring and treatment alone,
with a trend toward improved outcomes. Highlights of this trial
were a) feasibility of executing a multicenter trial with good
adherence to a complex management protocol in a very severe TBI
population; b) safety; c) physiological validation of the existence
of brain tissue hypoxia and its adverse effect on TBI outcome;
and d) supporting the hypothesis that Pbt02 directed therapy can
reduce secondary brain injury after TBI. BOOST-III is now funded,
and we eagerly anticipate the results of this.
Pediatric patients are more likely to survive and have good
functional outcome after TBI than adults
Emami P et al. J Neurosurg 2017 Mar; 126 (3): 760-767.
Methods: This retrospective cohort study of severe TBI patients
analyzed differences in survival and early outcome between
pediatric (< 15 years) and adult (16-55 years) patients. Patients
were identified through the Trauma Register of the German
Trauma Society. Patients from this registry were included if they
had severe TBI defined as an Abbreviated Injury Scale of the head
(AIShead) of > 3, documentation of GCS and Eppendorf-Cologne
Scale (ECS) scores recorded prior to resuscitation and on hospital
admission, and outcome documentation. Patients missing data
were excluded. Patients were subdivided into pediatric (0-15 years)
and adult (16-55 years). Neurologic exams prior to resuscitation
and on hospital admission included the GCS, and pupillary
exam was documented with the ECS. Results were presented as
means for continuous variables, medians with IQRs for time to
death, ISS and GCS, and as percentages for categorical variables.
A multivariable logistic regression was performed to assess the
relative importance of GCS score, pupil parameters and TBI, with
hospital death as the dependent variable.
Results: 9,959 patients were included in this study with 888
pediatric patients. Mean ages were 9 and 34, respectively. Median
ISS for pediatric and adult patients were 21 and 25, respectively
(p < 0.001), and median prehospital GCS scores were 9 and 8.
The overall percentage of deaths and deaths within 24 hours of
admission was higher in adults than children. Pediatric patients
were more likely to have a good outcome defined as GOS 4 or
5, despite significantly higher rates of CPR in pediatric patients.
Ventilator days, ICU LOS and hospital LOS were all significantly
lower in pediatric patients (p < 0.001). Absence of motor response
and no pupillary reaction to light were associated with higher
mortality. More pediatric patients (53 percent) died than adults (50
percent) when GCS was 3. Risk of death continuously rose with
increasing ECS scores, and at the maximal ECS score of 8 (bilaterally
fixed and dilated pupils, no motor response), mortality was high in
both groups (85 percent for adults, 81 percent for pediatric).
Comments: Pediatric patients had significantly lower overall
mortality, ventilator days, and ICU and hospital LOS when
compared to adults. Pediatric patients also had a higher rate
of good early functional outcome as measured by the GOS. Of
note, for the worst possible GCS score (3), mortality was only 53
percent (pediatric) and 50 percent (adult); for the worst ECS score
(8 – denoting no motor response and bilateral fixed and dilated
pupils), mortality was 80 percent (pediatric) and 85 percent
(adult). This suggests that even in the most severe cases of TBI,
15-20 percent of patients may survive. Implications of this study
are that aggressive early care even in the setting of bilateral fixed
pupils and no motor response may be warranted, particularly
in younger patients, as mortality in this group is not as high as
Aimee Aysenne, MD
MBBS, MD, MSc