In this post, Dr. Kirsten Weerdenburg reviews a recent article looking at the value of isolated loss of consciousness in children with blunt head injury as a predictor for clinically significant brain injury on CT.
Lee, Lois K., et al. “Isolated loss of consciousness in children with minor blunt head trauma.” JAMA pediatrics 168.9 (2014): 837-843.
Why this paper is important?
Loss of consciousness (LOC) is an element on history that frequently influences computed tomography (CT) use in the emergency department (ED) evaluation of children with blunt head trauma. There is great concern, awareness and scrutiny, however, of the non-negligible risk of lethal radiation-induced malignancy that the use of CT carries.
In 2009, the Pediatric Emergency Care Applied Research Network (PECARN) published their derivation and validation of two age-specific prediction rules with six variables for clinically important traumatic brain injury (ciTBI), as detailed below (1).
- For children aged <2 years: LOC >5 seconds, altered mental status, non-frontal scalp hematoma, severe mechanism of injury, palpable skull fracture, acting abnormally per parent
- For children aged ≥2 years: any LOC, altered mental status, vomiting, signs of basilar skull fracture, severe mechanism of injury, severe headache
In addition to this rule, there have been many other studies attempting to derive clinical prediction rules for CT evaluation after blunt head trauma. It has been recently found, however, that only physician practice and the PECARN rule are able to identify all ciTBI. PECARN is slightly more specific than physician judgment, and other clinical prediction rules have been found insufficiently sensitive (2).
LOC is a risk factor included in the PECARN rule (1), and has been identified in several multivariate analyses as a predictor for traumatic brain injury (TBI). In addition, longer duration of LOC in a patient’s history increases clinician concern (3) and frequently influences the use of CT after blunt head trauma (4). What has yet to be clarified is the importance of isolated LOC without other symptoms or signs of traumatic brain injury (TBI) as a predictor for ciTBI.
Population: Children aged 0-18 years presenting to the emergency department with a Glasgow Coma Scale (GSC) of 14 or 15 within 24 hours of a blunt head injury.
- Exclusions: trivial mechanism, no signs or symptoms of head injury except scalp abrasions or lacerations, penetrating trauma, significant comorbidities, preexisting neurologic disorders complicating assessment, neuroimaging obtained at transferring hospital, missing data on any of the PECARN predictors.
Exposure: History of LOC after minor blunt head trauma.
Control: No history of LOC after minor blunt head trauma.
- ciTBI – death, neurosurgical intervention, intubation longer than 24 hours, hospitalization for ≥2 nights
- TBI on CT – traumatic brain injury, skull fracture depressed at least the width of the table of the skull
Planned subanalysis of a large prospective observational cohort study.
Of the 42 412 children enrolled in the study, 1 719 children were excluded due to missing information about a history of LOC. In the 40 693 remaining children, there were the following findings:
- 6 286 children (15.4%) had a LOC after their head injury
- 3 797 children (27.8%) had history of LOC recorded by the treating clinician as one of the most important indications influencing their decision to obtain a CT scan
- Prevalence of ciTBI was 2.5% with any LOC and 0.5% with no LOC (rate difference 2.0%, 95% CI, 1.7-2.5)
- Risk ratio for ciTBIin isolated LOC compared with LOC with other PECARN predictors:
- Children aged <2 years: 0.13 (95% CI, 0.005-0.72)
- Children aged ≥2 years: 0.10 (95% CI, 0.06-0.19)
- ciTBI with isolated LOC (no other PECARN clinical predictors): 13 of 2780 children (0.5%; 95% CI, 0.2-0.8).
- ciTBI with expanded definition of isolated LOC (no other age-specific PECARN predictors and no other clinical factors associated previously with TBI: seizures, amnesia, neurologic deficit, any scalp hematoma, any traumatic scalp finding): 1 of 576 children (0.2%; 95% CI, 0.0-1.0).
In children presenting to the ED after a minor blunt head trauma, a history of isolated LOC is common and an important factor influencing CT evaluation, yet these children are at very low risk for ciTBI and do not routinely require evaluation with CT in the absence of other signs and symptoms of clinically important brain injury.
- Kupperman N, Holmes JF, Dayan PS, et al. Pediatric Emergency Care Applied Research Network (PECARN). Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study. Lancet. 2009;374(9696):1160-70.
- Easter JS, Bakes K, Dhaliwal J, et al. Comparison of PECARN, CATCH, and CHALICE rules for children with minor head injury: a prospective cohort study. Ann Emerg Med. 2014 Aug;64(2):145-52.
- Dunning J, Daly JP, Lomas JP, et al. Derivation of the children’s head injury algorithm for the prediction of important clinical events decision rule for head injury in children. Arch Dis Child. 2006;91(11):885-91.
- Haydel MJ, Shembekar AD. Prediction of intracranial injury in children aged five years and older with loss of consciousness after minor head injury due to nontrivial mechanisms. Ann Emerg Med. 2003;42(4):507-14.
The following is a critical appraisal by Dr. Weerdenberg-Yeh. Download it as a PDF here.
Are the results valid?
- Was there a clearly defined, focused research question? What was the study question?
- Yes, there was a clearly defined, focused research question: “What is the risk of ciTBIs in children with isolated loss of consciousness (LOC)?”
- How was the exposed cohort selected? Was there a well-defined selection procedure for inclusion into the cohort? What proportion of eligible subjects was actually included?
- The exposed cohort was selected from the group of children who presented with a GCS of 14 or 15 within 24 hours of a blunt head injury. The examining physician had indicated that there was a suspected or actual history of LOC on a structured data collection form.
- There was a well-defined selection procedure, which included history of LOC if there was any period of unconsciousness reported after the traumatic event. As this was a planned subanalysis of a large prospective observational cohort study, the investigators enrolled 42 412 children from the parent study, excluded 1 719 children due to missing information about LOC, and finally included 6 286 (15.4%) children with a history of LOC.
- How was the non-exposed cohort selected? Was this cohort drawn from the same source population as the exposed cohort? Was there a well-defined selection procedure for inclusion into the cohort? What proportion of eligible subjects was actually included?
- The non-exposed cohort was selected from the same group of children as the exposed cohort, but for this group, the examining physician indicated that there was no known history of LOC. There was a well-defined selection procedure for inclusion, which was when there was no history of LOC. Again, in this planned sub analysis of a large prospective observational cohort study, of the eligible children, 34 407 (84.6%) children did not have a history of LOC.
- How were the main exposures ascertained? Were the exposures clear, specific and measureable? Any likelihood of exposure misclassification?
- The main exposure of LOC was ascertained by the physician on history. The exposure was clear, specific and measurable, as it had to either be present, suspected, not present, or unknown. The exposure could have been misclassified if the patient had amnesia after the traumatic event or if it was unwitnessed, and the patient or parent was unaware of a history of LOC.
- Was the cohort free of the disease (outcome) at the start of follow up? Were only people at risk of the outcome included?
- This detail was discussed in the parent paper.
- Was the duration of follow up adequate (i.e. long enough for main outcomes to occur)?
- This detail was discussed in the parent paper.
- Was follow-up complete? Were efforts made to limit the loss to follow-up? What was the rate of attrition and was loss to follow-up similar in the exposed and non-exposed cohorts?
- This detail was discussed in the parent paper.
- What were the primary and secondary outcomes of the study? How well were the outcomes measured? Was the outcome clear, specific and measurable? Were surrogate outcomes used?
- The main outcomes were ciTBI and TBI on CT. ciTBI was defined as (1) death from intracranial injury, (2) any neurosurgical intervention, (3) intubation longer than 24 hours for head injury, or (4) hospitalization for 2 nights or longer owing to head injury. TBI on CT included any traumatic intracranial injury and skull fractures depressed at least the width of the table of the skull. There was no secondary outcome measured. The outcomes were measured well, and were clear, specific and measurable. No surrogate outcomes were used.
- Were outcomes measured similarly in exposed and non-exposed cohorts? Was outcome ascertainment influenced by knowledge of the exposure status (i.e. lack of blinding)?
Yes, outcomes were measured similarly in exposed and non-exposed cohorts, and outcome ascertainment was not influenced by knowledge of the exposure status.
- How comparable were the exposed and non-exposed cohorts? Have the authors identified all potentially important cofounders? Is there information on how the potential confounders are distributed between groups? What confounders were adjusted for and was the adjustment adequate? Is residual confounding a concern?
The exposed cohort with a history of LOC had more CT scans done, but otherwise it was comparable to the non-exposed cohort without a history of LOC. There were no potential confounders in this study.
Any other potential biases in this study?
- Potential for selection bias? None.
- Potential for information bias? None.
- Potential for confounding? None.
- Was there a clear rationale for the sample size estimation? This was discussed in the parent paper.
Are the analytic strategies clearly described? Were the data analytic methods appropriate for the research question and study design?
Yes, the analytic strategies were clearly described. The authors defined isolated LOC in 2 ways: (1) PECARN-isolated LOC – isolated LOC with no other PECARN ciTBI age-specific clinical predictors and (2) expanded-isolated LOC – isolated LOC with no other PECARN age-specific clinical predictors and no other clinical factors identified in other pediatric studies of TBI (excluding mechanism of injury). They divided the study cohort into children younger than 2 years and older than 2 years, as per the PECARN ciTBI rules. The investigators used appropriate data analytic methods for the research question and study design, as they calculated rates and risk.
What are the study results?
- How strong was the association between the exposure and outcome (e.g. rate ratio or hazard ratio or odds ratio)?
- For PECARN-isolated LOC, the rate of TBI on CT was 1.9% (95% CI, 1.4-2.6; 38 of 1993) and the rate of ciTBI was 0.5% (95% CI, 0.2-0.8; 13 of 2780).
- For expanded-isolated LOC, the rate of TBI on CT was 0.9% (95% CI, 0.2-2.7; 3 of 326) and the rate of ciTBI was 0.2% (95% CI, 0.0-1.0; 1 of 576).
- Risk ratio for ciTBI in isolated LOC compared with LOC with additional age-specific PECARN predictors:
- Children aged <2 years: 0.13 (95% CI, 0.005-0.72).
- Children aged ≥2 years: 0.10 (95% CI, 0.06-0.19).
How precise was the estimate of the association (i.e. confidence intervals)?
- The estimate of the risk ratio for ciTBI was precise for children aged ≥2 years as the confidence interval was small. This was not, however, the case for children aged <2 years, where there was a large confidence interval.
Can you apply the results to patient care?
- Were the study participants similar to the patient in your practice?
- Does your patient match the study inclusion criteria? Yes, many of the patients I see in practice match this study population.
- Were all clinically important outcomes considered?
- Do the results of this study fit with other available evidence?
- This evaluation of isolated LOC has not previously been investigated.
What are the major strengths of this study?
- Large population of children from multiple Pediatric Emergency Departments making it more generalizable.
- Prospective nature of the study reduces the possibility that results are biased by selecting subjects for the comparison group who may be more or less likely to have ciTBI or TBI on CT.
- Provides useful data on risk of ciTBI in the setting of isolated LOC.
- Highlights the importance of determining whether LOC occurred with or without other ciTBI risk factors when deciding on CT use, given the incremental increase for ciTBI with the addition of 1 PECARN predictor in conjunction with history of LOC, and its very strong influence on imaging decisions.
What are the major limitations of this study?
- Not all children had cranial CT imaging completed, meaning that the gold standard comparator was missing in some cases.
- Some children were missing data on the presence or absence of LOC or whether it was actually isolated; the authors were unable to determine the isolated LOC status in all enrolled children.
- Possibility of varying interpretations of history of LOC recorded on data collection forms by different clinicians.
- Relatively small sample size of children aged <2 years with isolated LOC, as well as a large confidence interval around the risk ratio for this age group, meaning we should be wary about applying this rule to this age group.
Are there any major ethical concerns with this study?