Impact of a posttraumatic cerebral infarction on outcome in patients with TBI: the Italian multicenter cohort INCEPT study.

BACKGROUND: Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors. METHODS: This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models. RESULTS: We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups. CONCLUSIONS: PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS. TRIAL REGISTRATION: The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study.

BACKGROUND: Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. METHOD: This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. RESULTS: A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08-7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8-100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. CONCLUSIONS: This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.

Are optimal cerebral perfusion pressure and cerebrovascular autoregulation related to long-term outcome in patients with aneurysmal subarachnoid hemorrhage?

BACKGROUND AND OBJECTIVES: Continuous assessment of the cerebrovascular autoregulation (CVA) through use of the pressure reactivity index (PRx), a moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure, has been effective in optimizing cerebral perfusion pressure (CPPopt) in traumatic brain injured (TBI) patients. This study investigates the feasibility of measuring CPPopt in patients with aneurysmal subarachnoid hemorrhage (aSAH) by continuously assessing the CVA. METHODS: Twenty-nine aSAH patients were enrolled, and data from CVA status, CPPopt, and periods when CPP was below, within, or above CPPopt were computed daily. Outcome was assessed at 6 months with the Glasgow Outcome Scale. Mann-Whitney U test was used to analyze differences in the duration of impaired CVA and duration of CPP below CPPopt in patients with good and poor outcomes. Multivariable logistic regression analysis was used to identify independent predictors of outcome. RESULTS: CVA monitoring data were available for all 29 patients with a total monitoring time of 2757 h. The duration of impaired CVA was 36.5% (interquartile range: 24.6 to 49.8) of the total monitoring time in 15 patients with good outcome and 71.6% of the total monitoring time (51.2 to 80.0) in 14 patients with poor outcome (Mann-Whitney U test 3.295, P=0.0010). PRx-based CPPopt could be identified in 26 patients (89.6%) with a total monitoring time of 2691 h. The duration of CPP below the CPPopt range was 28.0% (interquartile range: 18.0 to 47.0) of the total monitoring time in patients with good outcome and 76.0% (48.5 to 82.5) in patients with poor outcome (Mann-Whitney U test 2.779, P=0.0054). Glasgow Coma Scale score and duration of impaired CVA were independently associated with 6-month outcome (Glasgow Coma Scale score odds ratio: 1.95, 95% confidence interval: 1.01-3.75; duration of impaired CVA odds ratio: 0.88, 95% confidence interval: 0.78-0.99). CONCLUSIONS: The assessment of CVA and CPPopt is feasible in aSAH patients and may provide important information regarding long-term outcome. A PRx above the 0.2 threshold and a CPP below the CPPopt range are associated with worse outcome.

Cerebrovascular reactivity and autonomic drive following traumatic brain injury.

INTRODUCTION: The autonomic nervous system exerts tonic control on cerebral vessels, which in turn determine the autoregulation of cerebral blood flow. We hypothesize that the impairment of cerebral autoregulation following traumatic brain injury might be related to the acute failure of the autonomic system. METHODS: This prospective, observational study included patients with severe traumatic brain injury requiring mechanical ventilation and invasive monitoring of intracranial pressure (ICP) and arterial blood pressure (ABP). Pressure reactivity index (PRx), a validated index of cerebrovascular reactivity, was continuously monitored using bedside computers. Autonomic drive was assessed by means of heart rate variability (HRV) using frequency domain analysis. FINDINGS: Eighteen TBI patients were included in the study. Cerebrovascular reactivity impairment (PRx above 0.2) and autonomic failure (low spectral power of HRV) are significantly and independently associated with fatal outcome (P = 0.032 and P < 0.001, respectively). We observed a significant correlation between PRx and HRV spectral power (P < 0.001). The high frequency component of HRV (HF, 0.15-0.4Hz) can be used to predict impaired autoregulation (PRx > 0.2), although sensitivity and specificity are low (ROC AUC = 0.67; P = 0.001). CONCLUSION: Following traumatic brain injury, autonomic failure and cerebrovascular autoregulation impairment are both associated with fatal outcome. Impairment of cerebrovascular autoregulation and autonomic drive are interdependent phenomena. With some refinements, HRV might become a tool for screening patients at risk for cerebral autoregulation derangement following TBI.