Peter D. LeRoux

Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review.

Objective:In this study, available medical literature were reviewed to determine whether brain hypoxia as measured by brain tissue oxygen (Bto2) levels is associated with increased risk of poor outcome after traumatic brain injury (TBI). A secondary objective was to examine the safety profile of a direct BtO2 probe. Data Source and Extraction:Clinical studies published between 1993 and 2008 were identified from electronic databases, Index Medicus, bibliographies of pertinent articles, and expert consultation. The following inclusion criteria were applied for outcome analysis: 1) more than 10 patients described, 2) use of a direct Bto2 monitor, 3) brain hypoxia defined as Bto2 <10 mm Hg for >15 or 30 minutes, 4) 6-month outcome data, and 5) clear reporting of patient outcome associated with Bto2. For the analysis, each selected article had to have adequate data to determine odds ratios (ORs) and confidence intervals (CIs). Thirteen studies met the initial inclusion criteria and three were included in the final outcome analysis. Safety data were abstracted from any report where it was mentioned. Data Synthesis:The three studies included 150 evaluable patients with severe TBI (Glasgow Coma Scale ≤8). Brain hypoxia was identified in 71 (47%) of these patients. Among the patients with brain hypoxia, 52 (73%) had unfavorable outcome including 39 (55%) who died. In the absence of brain hypoxia, 34 (43%) patients had an unfavorable outcome, including 17 (22%) who died. Overall brain hypoxia (Bto2 <10 mm Hg >15 minutes) was associated with worse outcome (OR 4.0; 95% CI 1.9–8.2) and increased mortality (OR 4.6; 95% CI 2.2–9.6). We reviewed published safety data; in 292 patients monitored with a Bto2 probe, only two adverse events were reported. Conclusion:Summary results indicate that brain hypoxia (<10 mm Hg) is associated with worse outcome after severe TBI and that Bto2 probes are safe. These results imply that treating patients to increase Bto2 may improve outcome after severe TBI. This question will require further study.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension

Background: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO2) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. Methods: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO2 monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO2, ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. Results: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO2 (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO2 (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. Conclusions: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Intraventricular hemorrhage in blunt head trauma: an analysis of 43 cases.

Before the advent of computed tomography, intraventricular hemorrhage (IVH) from any source was thought rare and invariably fatal. Although intraventricular blood is readily identifiable with computed tomography, there has been little systematic study of its significance in blunt head trauma. Forty-three patients with traumatic IVH were prospectively identified in 1 year at Harborview Medical Center (University of Washington). Most were victims of motor vehicle accidents and suffered severe head injuries. IVH occurred alone in two patients; superficial contusions and subarachnoid hemorrhage were the most common associated finding. Blood was present in only one or both lateral ventricles in 25 patients; only the 3rd or 4th ventricles in 4 and all ventricles in 14 instances. There were 3 intracerebral hematomas and 14 basal ganglion hemorrhages. All of the former and half of the latter communicated with the adjacent lateral ventricle. Extra-axial hematomas appeared more common when only the lateral ventricles were involved, whereas corpus callosum or brain-stem hemorrhage appeared more likely when all the ventricles were involved. Acute hydrocephalus was rare, and ventricular drainage was needed in only four cases. Intracranial pressure (ICP) was elevated (> 15 mm Hg) in 46% of patients. The amount of IVH was related inversely with the Glasgow Coma Scale, but not with increased ICP. The presence of IVH indicated a poor outcome, with only half of the patients being independent at a 6-month follow-up. Poor outcome was associated with increasing age, low admission Glasgow Coma Scale, the presence of space occupying lesions if only the lateral ventricles were involved, and hemorrhage in all four ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1–4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1–4.4) for panel members and 4.5 (95% CI 4.3–4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1–4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9–4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019–0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Brain Lactate Metabolism in Humans With Subarachnoid Hemorrhage

Background and Purpose— Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Methods— Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO2) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO2 and CMD pyruvate and categorized as hypoxic (PbtO2 <20 mm Hg) versus nonhypoxic and hyperglycolytic (CMD pyruvate >119 &mgr;mol/L) versus nonhyperglycolytic. Results— Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%–80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%–98%) than brain hypoxia (11%; interquartile range, 4%–75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%–95%] in nonsurvivors versus 9% [interquartile range 3%–17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%–87%] versus 88% [interquartile range, 27%–99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0–3 1.49; CI, 1.08–2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59–1.03; P=0.08). Conclusions— Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure.

BACKGROUND Brain hypoxia (BH) can aggravate outcome after severe traumatic brain injury (TBI). Whether BH or reduced brain oxygen (Pbto2) is an independent outcome predictor or a marker of disease severity is not fully elucidated. OBJECTIVE To analyze the relationship between Pbto2, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) and to examine whether BH correlates with worse outcome independently of ICP and CPP. METHODS We studied 103 patients monitored with ICP and Pbto2 for > 24 hours. Durations of BH (Pbto2 < 15 mm Hg), ICP > 20 mm Hg, and CPP < 60 mm Hg were calculated with linear interpolation, and their associations with outcome within 30 days were analyzed. RESULTS Duration of BH was longer in patients with unfavorable (Glasgow Outcome Scale score, 1-3) than in those with favorable (Glasgow Outcome Scale, 4-5) outcome (8.3 ± 15.9 vs 1.7 ± 3.7 hours; P < .01). In patients with intracranial hypertension, those with BH had fewer favorable outcomes (46%) than those without (81%; P < .01); similarly, patients with low CPP and BH were less likely to have favorable outcome than those with low CPP but normal Pbto2 (39% vs 83%; P < .01). After ICP, CPP, age, Glasgow Coma Scale score, Marshall computed tomography grade, and Acute Physiology and Chronic Health Evaluation II score were controlled for, BH was independently associated with poor prognosis (adjusted odds ratio for favorable outcome, 0.89 per hour of BH; 95% confidence interval, 0.79-0.99; P = .04). CONCLUSION Brain hypoxia is associated with poor short-term outcome after severe traumatic brain injury independently of elevated ICP, low CPP, and injury severity. Pbto2 may be an important therapeutic target after severe traumatic brain injury. ABBREVIATIONS AOR: adjusted odds ratio APACHE II: Acute Physiology and Chronic Health Evaluation II CI: confidence interval CPP: cerebral perfusion pressure GCS: Glasgow Coma Scale ICP: intracranial pressure IQR: interquartile range MAP: mean arterial pressure TBI: traumatic brain injury

Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage.

BACKGROUND:Studies in traumatic brain injury suggest that monitoring techniques such as brain tissue oxygen (Pbto2) and cerebral microdialysis may complement conventional intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurements. OBJECTIVE:In this study of poor-grade (Hunt and Hess grade IV and V) subarachnoid hemorrhage (SAH) patients, we examined the prevalence of brain hypoxia and brain energy dysfunction in the presence of normal and abnormal ICP and CPP. METHODS:SAH patients who underwent multimodal neuromonitoring and cerebral microdialysis were studied. We examined the frequency of brain hypoxia and energy dysfunction in different ICP and CPP ranges and the relationship between Pbto2 and the lactate/pyruvate ratio (LPR). RESULTS:A total of 2394 samples from 19 patients were analyzed. There were 149 samples with severe brain hypoxia (Pbto2 ≤10 mm Hg) and 347 samples with brain energy dysfunction (LPR >40). The sensitivities of abnormal ICP or CPP for elevated LPR and reduced Pbto2 were poor (21.2% at best), and the LPR or Pbto2 was abnormal in many instances when ICP or CPP was normal. Severe brain hypoxia was often associated with an LPR greater than 40 (86% of samples). In contrast, mild brain hypoxia (≤20 mm Hg) and severe brain hypoxia were observed in only 53% and 36% of samples with brain energy dysfunction, respectively. CONCLUSION:Our data demonstrate that ICP and CPP monitoring may not always detect episodes of cerebral compromise in SAH patients. Our data suggest that several complementary monitors may be needed to optimize the care of poor-grade SAH patients.

Brain oxygen tension and outcome in patients with aneurysmal subarachnoid hemorrhage.

OBJECT Poor outcome is common after aneurysmal subarachnoid hemorrhage (SAH). Clinical studies suggest that cerebral hypoxia after traumatic brain injury is associated with poor outcome. In this study we examined the relationship between brain oxygen tension (PbtO(2)) and death after aneurysmal SAH. METHODS Forty-six patients, including 34 women and 12 men (Glasgow Coma Scale Score < or = 8 and median age 58.5 years) who underwent PbtO(2) monitoring were studied prospectively during a 2-year period in a neurosurgical intensive care unit at a University Level I Trauma Center. Brain oxygen tension, intracranial pressure (ICP), mean arterial pressure, cerebral perfusion pressure (CPP), and brain temperature were continuously monitored, and treatment was directed toward ICP, CPP, and PbtO(2) targets. The relationship between PbtO(2) and 1-month survival was examined. RESULTS Data were available from 5424 hours of PbtO(2) monitoring. For the entire cohort the mean ICP, CPP, and PbtO(2) were 13.85 +/- 2.40, 84.05 +/- 3.41, and 30.79 +/- 1.91 mm Hg, respectively. Twenty-five patients died (54%). The mean daily PbtO(2) was higher in survivors than nonsurvivors (33.94 +/- 2.74 vs 28.14 +/- 2.59 mm Hg; p = 0.05). In addition, survivors had significantly shorter episodes of compromised PbtO(2) (defined as 15-25 mm Hg) than nonsurvivors (125.85 +/- 15.44 vs 271.14 +/- 55.23 minutes; p < 0.01). Intracranial pressure was similar in survivors and nonsurvivors. In contrast, the average CPP was significantly lower in nonsurvivors than survivors (76.96 +/- 5.50 vs 92.49 +/- 2.75 mm Hg; p = 0.01). When PbtO(2) was stratified according to CPP level, survivors had higher PbtO(2) levels. Following logistic regression, the number of episodes of compromised PbtO(2) (odds ratio 1.1, 95% confidence interval 1.003-1.2) and number of episodes of cerebral hypoxia (< 15 mm Hg; odds ratio 1.3, 95% confidence interval 1.0-1.7) were more frequent in those who died. CONCLUSIONS Patient deaths after SAH may be associated with a lower mean PbtO(2) and longer periods of compromised cerebral oxygenation than in survivors. This knowledge may be used to help direct therapy.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

Background and Purpose— To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. Methods— After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. Results— Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. Conclusions— Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Surgical decompression without transposition for ulnar neuropathy: factors determining outcome.

Fifty-one surgical decompressions without nerve transposition for ulnar neuropathy were performed in 46 patients. All of the patients were men with an average age of 59 years at the time of surgery. The follow-up range was between 5 and 32 months (average, 17.8 months). The disease involved the nondominant arm in 24 patients (52%) and was bilateral in 5 (11%). In 23 cases (50%), no predisposing condition could be identified, whereas 15 patients (33%) abused alcohol and 8 patients (17%) had diabetes mellitus. Fifty-seven percent of the patients helped by surgery had symptoms for less than 1 year, whereas only 30% of patients with symptoms for more than 1 year had symptomatic improvement. The relative magnitude of the slowing of ulnar nerve conduction velocity across the elbow was not significantly correlated with the success of decompression in relieving symptoms. Ulnar nerve conduction velocities across the elbow were 36.13 +/- 11.76 m/s in those responding to surgery and 38.97 +/- 13.91 m/s in those not responding (c = 0.06, dF = 50, P less than 0.3). A total of 37 patients showed symptomatic improvement after decompression. Simple decompression of the ulnar nerve was performed under local anesthesia without transposition of the nerve. In all of these cases, compression of the nerve occurred predominantly in the epicondylar groove. Narrowing of the nerve in the groove was present in 28 cases (55%); scar tissue was found adhering to the nerve in 21 cases (41%); and two pseudoneuromas were found (4%). Forty-one operations (80%) resulted in symptomatic improvement, typically noted by the patient within the first month postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)