Early-Onset Ventilator-Associated Pneumonia in Patients with Severe Traumatic Brain Injury: Incidence, Risk Factors, and Consequences in Cerebral Oxygenation and Outcome.

BACKGROUND: Early-onset ventilator-associated pneumonia (EOVAP) occurs frequently in severe traumatic brain-injured patients, but potential consequences on cerebral oxygenation and outcome have been poorly studied. The objective of this study was to describe the incidence, risk factors for, and consequences on cerebral oxygenation and outcome of EOVAP after severe traumatic brain injury (TBI). METHODS: We conducted a retrospective, observational study including all intubated TBI admitted in the trauma center. An EOVAP was defined as a clinical pulmonary infection score >6, and then confirmed by an invasive method. Patient characteristics, computed tomography (CT) scan results, and outcome were extracted from a prospective register of all intubated TBI admitted in the intensive care unit (ICU). Data concerning the cerebral oxygenation monitoring by PbtO2 and characteristics of EOVAP were retrieved from patient files. Multivariate logistic regression models were developed to determine the risk factors of EOVAP and to describe the factors independently associated with poor outcome at 1-year follow-up. RESULTS: During 7 years, 175 patients with severe TBI were included. The overall incidence of EOVAP was 60.6% (47.4/1000 days of ventilation). Significant risk factors of EOVAP were: therapeutic hypothermia (OR 3.4; 95% CI [1.2-10.0]), thoracic AIS score ≥3 (OR 2.4; 95% CI [1.1-5.7]), and gastric aspiration (OR 5.2, 95% CI [1.7-15.9]). Prophylactic antibiotics administration was a protective factor against EOVAP (OR 0.3, 95% CI [0.1-0.8]). EOVAP had negative consequences on cerebral oxygenation. The PbtO2 was lower during EOVAP: 23.5 versus 26.4 mmHg (p <0.0001), and there were more brain hypoxia episodes: 32 versus 27% (p = 0.03). Finally, after adjusting for confounders, an EOVAP was an independent factor associated with unfavorable neurologic functional outcome at the 1-year follow-up (OR 2.71; 95% CI [1.01-7.25]). CONCLUSIONS: EOVAP is frequent after a severe TBI (overall rate: 61%), with therapeutic hypothermia, severe thoracic lesion, and gastric aspiration as main risk factors. EOVAP had a negative impact on cerebral oxygenation measured by PbtO2 and was independently associated with unfavorable outcome at 1-year follow-up. This suggests that all precautions available should be taken to prevent EOVAP in this population.

Early neurological wake-up test in intubated brain-injured patients: A long-term, single-centre experience.

BACKGROUND: In prehospital setting, a severe traumatic brain injury (TBI) requires tracheal intubation, sedation and mechanical ventilation pending the initial imagery. An early neurological wake-up test (ENWT), soon after the initial imaging assessment, allows a rapid neurological reassessment. This strategy authorises an initial clinical examination of reference with which will be compared the later examinations. The main objective of this study was to describe the characteristics of the patients who underwent an ENWT, and to determine its causes of failure. METHODS: We conducted a retrospective, observational, single-centre study including all intubated TBI admitted in the trauma centre. An ENWT was defined as cessation of sedation within 24h after TBI. Data concerning patient characteristics, CT-scan results, and outcomes were extracted from a prospective register of all intubated TBI admitted in the ICU. Characteristic of ENWT and causes of failure were retrieved from patient files. A multivariate logistic regression model was developed to determine the risk factors of ENWT failure. RESULTS: During 7 years, 242 patients with intubated TBI were included. An ENWT was started in 96 patients, for an overall rate at 40%. The ENWT was stopped in 38 patients (39.5%), mostly due to neurological deterioration in 27 cases (71%) or respiratory distress in 10 cases (26%). Significant predictors of ENWT failure were: the presence of subdural hematoma with a thickness >5mm on first imagery (OR=3.2; 95%CI [1.01-10.28]), and an initial GCS score <5 (OR=7.4; 95%CI [1.92-28.43]). Prevalence of poor outcome at 1year was lesser in patients with successful ENWT compared to those with failure or absence of ENWT: 4% vs. 48% and 49% (p<0.0001). CONCLUSIONS: The ENWT is achieved in 40% of patients, with a success rate of 60.5%. In presence of a subdural hematoma with a thickness >5mm or an initial GCS score <5, an ENWT failure may be expected.

Impairment of cardiac metabolism and sympathetic innervation after aneurysmal subarachnoid hemorrhage: a nuclear medicine imaging study.

INTRODUCTION: Although aneurysmal subarachnoid hemorrhage (SAH) is often complicated by myocardial injury, whether this neurogenic cardiomyopathy is associated with the modification of cardiac metabolism is unknown. This study sought to explore, by positron emission tomography/computed tomography, the presence of altered cardiac glucose metabolism after SAH. METHODS: During a 16-month period, 30 SAH acute phase patients underwent myocardial (18)F- fluorodesoxyglucose positron emission tomography ((18)F-FDGPET), (99m)Tc-tetrofosmin and (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy, respectively, assessing glucose metabolism, cardiac perfusion, and sympathetic innervation. Patients with initial abnormalities were followed monthly for two months for (18)F-FDG, and six months later for (123)I-mIBG. RESULTS: In this SAH population, acute cardiac metabolic disturbance was observed in 83% of patients (n = 25), and sympathetic innervation disturbance affected 90% (n = 27). Myocardial perfusion was normal for all patients. The topography and extent of metabolic defects and innervation abnormalities largely overlapped. Follow-up showed rapid improvement of glucose metabolism in one or two months. Normalization of sympathetic innervation was slower; only 27% of patients (n = 8) exhibited normal (123)I-mIBG scintigraphy after six months. Presence of initial altered cardiac metabolism was not associated with more unfavorable cardiac or neurological outcomes. CONCLUSIONS: These findings support the hypothesis of neurogenic myocardial stunning after SAH. In hemodynamically stable acute phase SAH patients, cardiomyopathy is characterized by diffuse and heterogeneous (18)F-FDG and (123)I-mIBG uptake defect. TRIAL REGISTRATION: Clinicaltrials.gov NCT01218191. Registered 6 October 2010.

Noninvasive detection of elevated intracranial pressure using a portable ultrasound system.

OBJECTIVE: The aim of this study is to prospectively compare the accuracies of transcranial color-coded sonography (TCCS) and transcranial Doppler (TCD) in the diagnosis of elevated intracranial pressure. METHODS: A prospective, blinded, head-to-head comparison of TCD and TCCS methods using intracranial pressure (ICP) measured continuously via an intraparenchymal catheter as the reference standard in 2 groups of 20 neurocritical care patients each: high ICP (group 1) and normal ICP (group 2). Middle cerebral artery (MCA) pulsatility index (PI) recordings from all patients' sonographic reports were selected based on the highest left or right recorded MCA PI. Transcranial Doppler was performed using a dedicated TCD device, and TCCS was performed using a portable ultrasound system. RESULTS: The PI values obtained did not differ significantly between the 2 methods (group 1, P = .46; group 2, P = .11). Linear regression analysis identified a significant relationship between PI obtained with both methods (r = 0.897; P < .0001). The duration of PI measurement was statistically longer with TCCS than TCD (group 1, P < .01; group 2, P < .01). Diagnostic accuracies were good and similar for both methods (TCD area under curve, 0.901; TCCS area under curve 0.870; P = .69). CONCLUSIONS: This work is a pilot study comparing TCCS and TCD in the detection of elevated ICP. This study suggests that a bedside portable ultrasound system may be useful to determine MCA PI with accuracy similar to that of a dedicated TCD device.

B-type natriuretic peptide release and left ventricular filling pressure assessed by echocardiographic study after subarachnoid hemorrhage: a prospective study in non-cardiac patients.

INTRODUCTION: Serum B-type natriuretic peptide (BNP) is frequently elevated after subarachnoid hemorrhage (SAH), but whether this high BNP level is related to transient elevation of left ventricular filling pressure (LVFP) is unknown. However, in patients with preexistent cardiac pathologies, it is impossible to differentiate between BNP elevation caused by chronic cardiac abnormalities and BNP related to acute neurocardiac injury. METHODS: All adult patients with SAH admitted to our intensive care unit were eligible. Patients were excluded for the following reasons: admission >48 hours after aneurysm rupture, pre-existing hypertension, or cardiac disease. Levels of BNP and cardiac troponin Ic were measured daily for 7 days. Echocardiography was performed by a blinded cardiologist on days 1, 2, and 7. Doppler signals from the mitral inflow, tissue Doppler, and the color M-mode-derived flow propagation velocity (FPV) were obtained to assess echo-estimated LVFP. RESULTS: During a 3-year period, sixty-six consecutive patients with SAH were admitted. Thirty one patients were studied. The BNP level was >100 ng/L in 25 patients (80%) during the first 3 days, with a peak on day 2 (median, 126 ng/L) followed by a gradual decrease (median variation days 1 to 7, 70%). All patients had an ejection fraction >50%. Early transmitral velocity/tissue Doppler mitral annular early diastolic velocity was low: 5.4 (+/- 1.5) on day 1, 5.8 (+/- 1.2) on day 2, and 5.1 (+/- 0.9) on day 7. Early transmitral velocity/FPV was also low: 1.27 (+/- 0.4), 1.25 (+/- 0.3), and 1.1 (+/- 0.2) on days 1, 2, and 7, respectively. Cardiac troponin Ic levels ranged from 0 to 3.67 microg/L and were correlated with BNP (r = 0.63, P < 0.01). CONCLUSIONS: BNP rises gradually over two days and return to normal within a week after SAH. Its release is associated with myocardial necrosis, but is unrelated to elevated LVFP assessed by echocardiography.

Blunt cerebrovascular injuries in severe traumatic brain injury: incidence, risk factors, and evolution.

OBJECTIVE Blunt cerebrovascular injuries (BCVIs) affect approximately 1% of patients with blunt trauma. An antithrombotic or anticoagulation therapy is recommended to prevent the occurrence or recurrence of neurovascular events. This treatment has to be carefully considered after severe traumatic brain injury (TBI), due to the risk of intracranial hemorrhage expansion. Thus, the physician in charge of the patient is confronted with a hemorrhagic and ischemic risk. The main objective of this study was to determine the incidence of BCVI after severe TBI. METHODS The authors conducted a prospective, observational, single-center study including all patients with severe TBI admitted in the trauma center. Diagnosis of BCVI was performed using a 64-channel multidetector CT. Characteristics of the patients, CT scan results, and outcomes were collected. A multivariate logistic regression model was developed to determine the risk factors of BCVI. Patients in whom BCVI was diagnosed were treated with systemic anticoagulation. RESULTS In total, 228 patients with severe TBI who were treated over a period of 7 years were included. The incidence of BCVI was 9.2%. The main risk factors were as follows: motorcycle crash (OR 8.2, 95% CI 1.9-34.8), fracture involving the carotid canal (OR 11.7, 95% CI 1.7-80.9), cervical spine injury (OR 13.5, 95% CI 3.1-59.4), thoracic trauma (OR 7.3, 95% CI 1.1-51.2), and hepatic lesion (OR 13.3, 95% CI 2.1-84.5). Among survivors, 82% of patients with BCVI received systemic anticoagulation therapy, beginning at a median of Day 1.5. The overall stroke rate was 19%. One patient had an intracranial hemorrhagic complication. CONCLUSIONS Blunt cerebrovascular injuries are frequent after severe TBI (incidence 9.2%). The main risk factors are high-velocity lesions and injuries near cervical arteries.

Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA).

Traumatic brain injury (TBI) is an important cause of death and disability. Safety and pharmacodynamics of 4-amino-tetrahydrobiopterin (VAS203), a nitric oxide (NO)-synthase inhibitor, were assessed in TBI in an exploratory Phase IIa study (NOSynthase Inhibition in TRAumatic brain injury=NOSTRA). The study included 32 patients with TBI in six European centers. In a first open Cohort, eight patients received three 12-h intravenous infusions of VAS203 followed by a 12-h infusion-free interval over 3 days (total dose 15 mg/kg). Patients in Cohorts 2 and 3 (24) were randomized 2:1 to receive either VAS203 or placebo as an infusion for 48 or 72 h, respectively (total dose 20 and 30 mg/kg). Effects of VAS203 on intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain metabolism using microdialysis, and the therapy intensity level (TIL) were end points. In addition, exploratory analysis of the extended Glasgow Outcome Score (eGOS) after 6 months was performed. Metabolites of VAS203 were detected in cerebral microdialysates. No significant differences between treatment and placebo groups were observed for ICP, CPP, and brain metabolism. TIL on day 6 was significantly decreased (p<0.04) in the VAS203 treated patients. The eGOS after 6 months was significantly higher in treated patients compared with placebo (p<0.01). VAS203 was not associated with hepatic, hematologic, or cardiac toxic effects. At the highest dose administered, four of eight patients receiving VAS203 showed transitory acute kidney injury (stage 2-3). In conclusion, the significant improvement in clinical outcome indicates VAS203-mediated neuroprotection after TBI. At the highest dose, VAS203 is associated with a risk of acute kidney injury.

Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis.

Ischemic Stroke of the Artery of Percheron with Normal Initial MRI: A Case Report.

The artery of Percheron is a solitary trunk representing an uncommon anatomic variant that provides bilateral arterial supply to the paramedian thalami and the rostral midbrain. Occlusion of this artery results in bilateral thalamic and mesencephalic infarctions. The clinical diagnosis is difficult because the complex anatomy causes large clinical variability. We report a case of a comatose patient with normal early head-computed tomography and magnetic resonance imaging. A bilateral paramedian thalamic infarct due to an occlusion of the artery of Percheron was revealed two days later by a new head computed tomography. To our knowledge, this is the first report in the literature of a symptomatic patient presenting an acute Percheron stroke with normal early brain magnetic resonance imaging. Our case indicates that a normal initial magnetic resonance imaging cannot formally eliminate the diagnosis of acute stroke of the artery of Percheron. We discuss the causes of noncontributive brain magnetic resonance imaging at the onset of this acute Percheron stroke and the alternative diagnosis and therapy methods.