Discussion
We were able to successfully demonstrate that TCD ultrasonography and QPR are feasible as an early assessment tools in trauma patients. It was used across a variety of patients, mechanisms and types of brain injury without compromising care and represents the first study of its kind in the literature evaluating each component in tandem as a predictor of a positive CT scan. Given that 94% of the positive CT images led to either neurosurgical consultation or intervention, a portable early prediction tool such as the tested examination could augment prehospital triage and facilitate care in trauma centres.
Quantitative pupillometry
Pupillary changes are a critical component of the trauma assessment, predict changes in neurologic status and may be the only detectable sign of deterioration.15 Despite this, there is no standard on how pupil reactivity is measured—light, power, distance from the eye, and terminology (sluggish/brisk) are all variable and qualitative.16
Interobserver variability in estimation of pupil diameter is high, calling for a more quantitative assessment of the pupil.17 Even at robust trauma centres, with excellent and experienced nurses, size discrepancy between nursing measurements of the pupil and the QPR measurements commonly occurred and are troubling. Approximately 40% of the patients had over 1 mm of difference between clinical and quantitative exams. As a critical component of the neurologic examination, standardising and quantifying the examination may be beneficial.
In our study, the NPi was decreased in the CT positive group (below the normal cut-off value of 3). This corresponded to an OR of 2.9 for predicting brain injury and a specificity of 82.4%. Of all of the variables, a low NPi was the most predictive.
Transcranial Doppler
TCD serves as a non-invasive technique to describe intracerebral blood flow in haemorrhage, cerebral vasospasm, autoregulation and has been used to guide therapy.18–20 It commonly used in patients with subarachnoid haemorrhage but is not widely used in trauma. Up to 80% of the TBI patients can have TCD derangements in the early post-traumatic period and can therefore be useful in guiding management decisions.21 Elevations in the PI and decreases in the diastolic flow velocity (FVd) may reflect rising ICP, or downstream resistance, and increased flow velocity (FV) can diagnose vasospasm.22
Our data demonstrate that a ‘snap shot’ of MCA flow dynamics is feasible and predicative of TBI. MCA mean FV standards are well described, as are PI ((FVs-FVd)/FVm) ranges.23 Abnormal PI values in trauma patients range from 1.2 to 1.4 in the literature.20 ,24 ,25 We elected to use 1.3 as our threshold value.
PI was higher in the CT-positive group. The number of patients with a PI value of >1.3 was also significantly higher in the CT-positive group. EDV, contrary to most literature, did not predict a positive CT in our study.
The relationships between MCA velocities and various brain injuries are poorly defined and are dependent on systemic blood pressures, degree of ICP elevation, cerebral vasospasm (influenced by pCO2 levels) and degree of cerebral dysregulation. Despite this, we feel that TCD may have a role in early trauma evaluation and that an isolated PI of >1.3 should be followed up with early CT imaging.
Optic Nerve Sheath Diameter
The retrobulbar segment of the optic nerve sheath is a continuation of the subarachnoid space, and elevated intracranial pressure is transmitted behind the eye and can be visualised by ultrasound with relative ease.26 Sonographic assessment of optic nerve oedema using ONSD correlates with ICP with sensitivities of 74–95% and specificities of 74–100%.27 ONSD US has been shown to be consistent with regard to reproducibility, accuracy, interobserver agreement and has been validated against MRI as a gold standard.28 ‘Normal’ ONSD is a subject of debate, but it is generally agreed that an ONSD below 5 mm is considered normal.27 ,29 Prior studies all have small sample size, heterogeneous populations, lack of power and are limited in universal applicability (single expert user, etc).30 We evaluated ONSD as a portion of our non-invasive examination. This represents the largest ONSD data set in the trauma literature, with 100 patients imaged, 556 separate data points and multiple providers performing the ultrasound. We noted no statistical difference between the positive CT and negative CT groups for ONSD. While 15 patients in the positive CT group had an ICP monitor placed (36%), only 4 had opening pressures over 20. The ONSD in these patients averaged 5.6, 4.48, 5.2 and 5.03 mm for opening pressures of 28, 25, 30 and 20, respectively. This small number of patients precludes statistical analysis, but these ONSD values are less than expected for the elevation of ICP.
We noted a higher than expected ONSD (>5 mm) in both the non-injured group and injured groups in the absence of elevated ICP. Patients in both groups commonly had scleral thickening or ultrasonic evidence of papilledema, again without evidence of elevated ICP clinically or radiographically. This has been described previously in trauma31 as a finding representing inflammation. It is possible that trauma and resuscitation increase the ONSD via unknown mechanisms (eg, inflammation or simple oedema) and are not necessarily reflective of elevated ICP or brain injury. It is also possible that this could be reflective of a neuropathologic process not able to be seen on CT scan caused by mild TBI. This warrants further study, as it clearly negatively impacts the utility of ONSD US as a bedside examination in trauma.
Full examination
We attempted to identify an additive effect of the entire non-invasive examination. Applying logistic regression to the tested variables (PI>1.3, NPi <3) and adding age and lactate, we attempted to create a preliminary predictive model to identify brain injury (positive head CT). ROC analysis for this model was 0.7181 (figure 1). As a means of comparison, GCS has been shown to have an ROC between 0.77 and 0.88 for predicting mortality in severe TBI32 ,33 and an ROC of 0.446–0.643 in mild TBI for predicting abnormal CT findings.34 This places the ROC for the tested variables in line with other prediction models. While not more accurate than GCS by ROC criteria, this test is more objective and in theory may be less subject to misinterpretation than the GCS.
Finally, we suggest a simple scoring heuristic predicting brain injury (figure 2). This tool should be regarded as highly preliminary. Using this scoring system, on a scale of 0–4, patients meeting the most severe criteria have a 99.5% chance of having a positive CT scan. A single positive value from the tested examination predicts an 82.3–88.7% chance of having a CT-verified brain injury.
Figure 2Suggested scoring heuristic for predicting a positive radiological finding in a patient with TBI. Note: this scoring rule is based on preliminary data, and requires validation in a larger data set.
While preliminary, a non-invasive imaging strategy such as this may have clinical utility. It could assist in triage to a trauma centre, arranging the order of events in the resuscitation bay, or alerting the team to a high likelihood of brain injury. Age plays a large role in this model, as does lactate. Without lactate as a variable, the ROC is less predictive at 0.61. We interpret this simply to imply that the model is not accurate unless the patient is severely injured, as evident by an elevated lactate. If a patient is healthy and not injured, a positive non-invasive neurologic examination has no clinical implication. An injured patient over 40, however, with a positive non-invasive examination, is at high risk of having a brain injury and should be triaged accordingly. On the contrary, the absence of any non-invasive findings does not rule out injury, and a high level of clinical suspicion must be maintained.
Feasibility
The tested examination is easy to perform accurately and carries no negative impact to the patient. The examination takes 11 min on average. Pupillometry and ONSD data were obtainable in almost all patients (97% and 96%, respectively). TCD was obtainable 79.2% of the time in the injured group, and 73.1% of the time in the non-injured group. This is consistent with the literature, where a TCD window is unobtainable 10–20% of the patients.22 As a testament to the portability of the examination, several tests were obtained in the operating room, while the patients were undergoing torso, abdominal or extremity operations.
Limitations
This study has several limitations. With half of the screened patients not enrolled (declined consent or non-availability of sonographer), there may be the addition of selection bias. Most ultrasound literature describes a convenience sample as clinical expertise is not universally available. Likewise, in our study, this limitation was primarily manpower driven.
Ultrasound is operator dependant adding variability to the data. We attempted to mitigate this in two ways. We had multiple providers perform the exams (most literature identifies single expert user performing all exams), and we took multiple images of each data point, allowing for internal review and QA.
Exams were performed without explicit knowledge of the patient's diagnosis or prognosis (in the trauma bay) in an effort to minimise any bias. Results were de-identified and assigned a study label, and only after de-identification were images measured and analysed. These methods should have distributed variability evenly and acted to ‘blind’ the study.
While it is the largest study of its kind, the clinical numbers are still small for robust statistical comparison. In the statistical analysis, the model to identify predictors of positive CT findings was based on non-missing data for all variables. Bootstrapping can not only overcome this somewhat but can also amplify bias. This scoring model, again, is highly preliminary. Further studies with larger numbers are necessary to validate this model.