Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Chronic hydrocephalus that requires shunting in aneurysmal subarachnoid haemorrhage [a-SAH]: its impact on clinical outcome.

BACKGROUND: Chronic hydrocephalus is a common occurrence following aneurismal subarachnoid haemorrhage [a-SAH] but its impact on neurological outcome has not been re reviewed systematically. PATIENTS AND METHODS: One hundred and eleven patients were recruited from a prospectively collected a-SAH registry over a 3-year period between 2002 and 2004. Their 6-month extended Glasgow Outcome Scale [GOSE] scores were correlated with routine clinical data and the need for CSF shunting [chronic hydrocephalus that required shunting, CHS]. RESULTS: Thirty patients with CHS were identified and they were associated with an initial poor WFNS grading [median 4 versus 2, p = 0.028]. Among patients with poor WFNS grading, CHS was associated with a better GOSE [median 4 versus 2, p = 0.041] and among patients with good WFNS grading, CHS paradoxically was associated with a poor GOSE [median 3.5 versus 7, p = 0.016]. CONCLUSION: The relationships between CHS and GOSE in a-SAH were complex. Their true clinical significance requires a more in-depth prospective study.

Cerebral hemisphere asymmetry in cerebrovascular regulation in ventilated traumatic brain injury.

Disturbances in cerebrovascular regulation in the form of diminished cerebral vasoreactivity (CVR) to carbon dioxide and an altered pressure autoregulatory response (PAR) are common after traumatic brain injury (TBI) and correlate with clinical outcome. Daily assessment of the state of cerebrovascular regulation may assist in the clinical management of TBI patients. This study examined 20 ventilated TBI patients. We employed blood flow velocity (BFV) measurement using transcranial Doppler ultrasonography to assess the impact of injury type (focal and diffuse) on cerebral hemisphere asymmetry in cerebrovascular regulation and to examine whether impairment in CVR and PAR correlate with clinical outcomes. Significant hemisphere asymmetries were found in BFV and PAR. Impairment in CVR was associated with unfavorable outcomes and bilateral CVR impairment predicted mortality.

Predicting one year clinical outcome in traumatic brain injury (TBI) at the beginning of rehabilitation.

Predicting long-term clinical outcome for patients with traumatic brain injury (TBI) at the beginning of rehabilitation provides essential information for counseling of the family and priority-setting for the limited resources in intensive rehabilitation. The objective of this study is to work out the probability of the one-year outcome at the beginning of rehabilitation. Sixty-eight patients with moderate-to-severe TBI and known one-year outcome were employed for outcome prediction using the logistic regression model. A large number of prospectively collected data at admission (age, Glasgow Coma Scale [GCS] Score, papillary response), during intensive care unit (ICU) management (duration of coma, intracranial pressure [ICP] and its progress) and at the beginning of rehabilitation (baseline Functional Independence Measure [FIM], Neuro-behavioral Cognitive Status Examination [NCSE] and Functional Movement Assessment [FMA]) were available for preliminary screening by univariate analysis. Six prognostic factors (age, GCS, duration of coma, baseline FIM, NCSC and FMA) were utilized for the final logistic regression model. Age, GCS and baseline FIM at the beginning of rehabilitation have been found to be independent predictors for one-year outcome. The accuracy of prediction for a good Glasgow Outcome Score is 68% and an outcome for disability (either moderate or severe) is 83%. Validation of this model using a new set of data is required.

Cerebral vasoreactivity: a comparison of color velocity imaging quantification and stable xenon-enhanced CT.

OBJECTIVE: Compromised cerebral vasoreactivity increases the risk of stroke. In this study, we sought to determine whether extracranial arterial blood flow volume measured on color velocity imaging quantification could be predictive of cerebral vasoreactivity after the administration of acetazolamide. SUBJECTS AND METHODS: Cerebral blood flow and extracranial arterial blood flow volume of 35 patients with symptomatic carotid occlusive disease were measured before and after the administration of acetazolamide on stable xenon CT and color velocity imaging quantification, respectively. The changes in unilateral extracranial arterial blood flow volume and respective hemispheric cerebral blood flow were compared. The mean difference in the percentage of change in flow volume, the 95% limit of agreement, and Cohen's kappa coefficient were calculated. RESULTS: A total of 64 unilateral extracranial arterial blood flow volume changes were successfully compared with the changes in the ipsilateral hemispheric cerebral blood flow. The mean difference in percentage of change in flow volume between the two techniques was 4.7%, with the 95% limit of agreement ranging from -90.2% to 99.7%. Cohen's kappa coefficient was 0.41 (95% confidence interval, 0.13-0.68; p = 0.001). CONCLUSION: The performance of color velocity imaging quantification for evaluating cerebral vasoreactivity is comparable to that of transcranial Doppler sonography. Because color velocity imaging quantification is not as limited as transcranial Doppler sonography, it could be an ideal complementary tool to transcranial Doppler sonography. More studies are required to define its clinical value.

Cerebral blood flow (CBF)-directed management of ventilated head-injured patients.

OBJECTIVE: Ischaemic brain damage has been shown to be an important contributing factor causing head injury fatality. Maintenance of an adequate cerebral perfusion pressure is difficult in patients with elevated intracranial pressure (ICP) and deranged cerebral vasoreactivity. Thirty-five cases of ventilated moderate-to-severe head-injured patients were prospectively studied, correlating their cerebral haemodynamic abnormalities, neurochemical disturbances (using microdialysis methodology) and clinical outcome. METHODS: Cerebral haemodynamic abnormalities were defined and classified by transcranial Doppler ultrasonography (TCD) and stable xenon-CT cerebral blood flow measurements (XeCT) into their status of CO2 reactivity, pressure autoregulation, hyperaemia or non-hyperaemia. Two-hour episodes of these abnormalities with and without haemodynamic intervention were followed in their changes in ICP, CPP, intracerebral metabolites and finally their clinical outcome. RESULTS: Loss of CO2 reactivity was associated with a significantly higher ICP, increasing intracerebral metabolites (lactate, glutamate and glycerol) and invariably a fatal outcome. Impaired pressure autoregulation was also associated with an elevated ICP, but no significant difference in intracerebral metabolites and incidence of favourable clinical outcome. Patients with intact CO2 reactivity and impaired pressure autoregulation were treated with an elevated CPP in 32 episodes, resulting in a significant reduction in ICP, intracerebral glutamate and glycerol and non-survival. In patients with intact CO2 reactivity and impaired pressure autoregulation, eleven episodes of hyperaemia were identified by XeCT. A modest 20%, blood pressure reduction resulted in a trend towards a reduction of ICP, intracerebral glutamate and glycerol and non-survival. CONCLUSIONS: The need for haemodynamic intervention in this group of ventilated patients with moderate-to-severe head inury can be made logical when these abnormalities are identified daily. The success of management was reflected by a stable or improved ICP, CPP, intracerebral metabolic deranagement and survival.

Re-defining the ischemic threshold for jugular venous oxygen saturation--a microdialysis study in patients with severe head injury.

Neurological change is more likely to occur when jugular venous oxygen saturation (SjvO2) is less than 50%. However, the value indicating cellular damage has not been clearly defined. We determined the critical SjvO2 value below which intracerebral extracellular metabolic abnormalities occurred in 25 patients with severe head injury. All patients received standard treatment with normoventilation and maintenance of intracranial pressure < 20 mmHg. SjvO2 was measured from the dominant jugular bulb using a calibrated fibreoptic catheter. Intracerebral metabolic monitoring was performed by collecting perfusate from a microdialysis probe placed in the frontal lobe anterior to the intracranial catheter. Excitotoxin (glutamate) and other extracellular metabolites (lactate, glucose and glycerol) were measured frequently using enzymatic and colorimetric methods. We observed biphasic relationships between SjvO2 and all intracerebral metabolites. Analysis of variance showed that there were rapid increases in glutamate, glycerol and lactate when SjvO2 dropped below 40, 43 and 45% respectively. Extracellular glucose decreased when SjvO2 dropped below 42%. Our findings suggested that the ischemic threshold for SjvO2 in patients with severe head injury is 45%, below which secondary brain damage occurred.

Effect of ischemic preconditioning on brain tissue gases and pH during temporary cerebral artery occlusion.

Previous studies have demonstrated that a brief period of ischemia protect against subsequent severe ischemic insults to the brain, i.e. preconditioning. We evaluated the effects of ischemic preconditioning, produced by 2 min proximal temporary artery occlusion, on brain tissue gases and acidity during clipping of cerebral aneurysm. Twelve patients with aneurysmal subarachnoid hemorrhage were recruited. All patients received standard anesthetics. After craniotomy, a calibrated multiparameter catheter was inserted to measure oxygen (PtO2) tension, carbon dioxide (PtCO2) tension and pH (pHt) in tissue at risk of ischemia during temporary artery occlusion. In patients assigned to the preconditioning group, proximal artery was occluded initially for 2 min and was allowed to reperfuse for 30 min. All patients underwent cerebral artery occlusion for clipping of aneurysm. The rate of change in PtO2, PtCO2 and pHt after artery occlusion were compared between groups using unpaired t test. Baseline brain tissue gases and pHt were similar between groups. Following artery occlusion, the decline in PtO2 and pHt were significantly slower in the preconditioning group compared with the routine care group. These results suggested that ischemic preconditioning attenuates tissue hypoxia during subsequent artery occlusion. Brief occlusion of the proximal artery may be a simple maneuver for brain protection during complex cerebrovascular surgery.

Magnesium sulfate for brain protection during temporary cerebral artery occlusion.

We evaluated the effects of magnesium sulfate on brain tissue oxygen (PtO2) tension, carbon dioxide (PtCO2) tension and pH (pHt) in patients undergoing temporary artery occlusion for clipping of cerebral aneurysm. We studied 18 patients with aneurysmal subarachnoid hemorrhage. All patients received standard anesthetics using target controlled infusion of propofol (3 microg/ml) and remifentanil (10 ng/ml). After craniotomy, a calibrated multiparameter sensor (Neurotrend, Diametrics Medical, Minneapolis, MN) was inserted to measure PtO2, PtCO2 and pHt in tissue at risk of ischemia during temporary artery occlusion. Patients were then randomly allocated to receive either intravenous saline or magnesium 20 mmol over 10 min followed by an infusion 4 mmol/h. Plasma magnesium concentration, brain tissue gases and pHt were determined at baseline, 30 min after study drug infusion and 4 min after temporary clipping. Data were analyzed by factorial ANOVA with repeated measures. Intergroup difference was compared with unpaired t test. P value < 0.05 was considered significant. Patient characteristics, baseline brain tissue gases and pHt did not differ between groups. Magnesium infusion increased PtO2 by 34%. Following temporary artery occlusion, PtO2 and pHt decreased and PtCO2 increased in both groups. However, tissue hypoxia was less severe and the rate of PtO2 decline was slower in the magnesium group. Our data suggested that magnesium enhances tissue oxygenation and attenuates hypoxia during temporary artery occlusion.

Monitoring of autoregulation using intracerebral microdialysis in patients with severe head injury.

We evaluated the performance of continuous intracerebral microdialysis to indicate the autoregulatory reserve in 36 severely head-injured patients. All patients received standard treatment with intracranial pressure (ICP) monitoring. A microdialysis probe was placed in the frontal cortex anterior to the ICP catheter. Perfusate was collected frequently and extracellular concentration of glutamate was measured online using enzymatic method. Autoregulatory index was calculated by comparing glutamate concentration with CPP using Pearson's correlation. A correlation coefficient (r) < 0.5 is considered as loss of autoregulation, whereas r values approach 0 indicate preserved autoregulation. The change of autoregulatory status over time was correlated with outcome at 6 months. Three patterns of autoregulatory profiles were identified. Patients with intact autoregulation had satisfactory outcome. Transient impairment of autoregulation may result in favorable outcome if patients responded to treatment. However, persistent loss of autoregulation was associated with poor outcome (P < 0.001). The correlation between extracellular glutamate concentration (by microdialysis) and CPP is a useful index of autoregulation in head-injured patients. It predicts clinical outcome and may be used to guide therapy.

Cerebral haemodynamic assessment in patients with thalamic haemorrhage: a pilot study with continuous compliance monitoring.

OBJECTIVE: Thalamic brain haemorrhage is a common disabling and potentially fatal condition. However, management is mainly supportive, very rarely do neurosurgeons resort to evacuation of the haematoma. We hypothesised that cerebral haemodynamic abnormalities in the forms of lost pressure autoregulatory response (PAR) and/or impaired cerebral vasoreactivity (CVR) to carbon dioxide may indicate the haematoma should be aspirated to prevent further brain damage. MATERIAL AND METHODS: Patients with thalamic haemorrhage were selected on clinical ground for intracranial pressure (ICP) monitoring and intensive care management. Spiegelberg double lumen intraventricular balloon catheter was inserted as any other fluid-filled ICP monitoring technique, on the side of the haematoma. Data of ICP, arterial blood pressure (ABP), cerebral perfusion pressure (CPP) and intracranial compliance were collected on a minute basis. Hourly averages were used for analysis. To assess PAR and CVR, blood flow velocity (BFV) in both middle cerebral arteries were measured continuously by transcranial Doppler (TCD) ultrasonography. RESULTS: Six patients with medium (15-25 ml) to large (>25 ml) haematoma volume were subjected to ultrasoud-guided aspiration. 51 CVR and 53 PAR tests were performed. 80820 sets of data were prospectively collected. Progressive reduction in ICP and sustained improvement in compliance and BFV were observed after aspiration. Impairment in PAR and/or CVR was consistent with clinical deterioration in four patients. Such disturbance was normalised after aspiration. Increments in BFV and improvement in compliance were demonstrated. CONCLUSIONS: Cerebral haemodynamic abnormalities in thalamic haematomas can be demonstrated by the non-invasive TCD ultrasonograpy. These abnormalities can be corrected by aspiration of the haematoma, and hence improve intracranial compliance.

The role of haematoma aspiration in the management of patients with thalamic haemorrhage: a pilot study with continuous compliance monitoring.

OBJECTIVE: Thalamic brain haemorrhage is a common disabling and potentially fatal condition. Management is mainly supportive and very rarely do neurosurgeons have to resort to evacuation of the haematoma. We hypothesised that haematoma aspiration may help to improve the outcome of the group of patients with thalamic haemorrhage. MATERIAL AND METHODS: Patients with thalamic haemorrhage were selected on clinical group (intraventricular haemorrhage, hydrocephalus and haematoma size > 15 ml) for intracranial pressure (ICP) monitoring and management in the intensive care unit (ICU). A Spiegelberg double lumen intraventricular balloon catheter was inserted as a fluid-filled catheter on the side of the haematoma. Data of ICP, arterial blood pressure (ABP), cerebral perfusion pressure (CPP) and compliance were collected at one-minute intervals. Hourly averages were used for analysis. RESULTS: 94,448 set of data were collected from eight patients with thalamic haemorrhage. Significant reduction in ICP and improvement in intracranial compliance were detected. In patients with haematoma aspiration, intracranial compliance was improved within 48 hours of the procedure whereas ICP did not. CONCLUSIONS: This pilot study showed that haematoma aspiration in patients with thalamic haemorrhage could improve intracranial compliance. Whether this could be translated into clinical outcome benefits requires further study in a larger number of patients.

Is transcranial Doppler ultrasonography (TCD) good enough in determining CO2 reactivity and pressure autoregulation in head-injured patients?

Disturbance of cerebral haemodynamic status, cerebral vasoreactivity (CVR) to carbon dioxide (CO2) and pressure autoregulatory response (PAR) have been shown to be associated with severity of head injury and to correlate with neurological condition and clinical outcome. Information regarding impaired CVR and/or lost PAR has been shown to be of prognostic value in treating head-injured patients. The classic method of evaluating cerebral haemodynamic status requires an invasive measurement of cerebral blood flow (CBF) such as the technique of Kety and Schmidt or by the 133Xe inhalation method. Transcranial Doppler ultrasonography (TCD) is a simple and non-invasive method for its assessment. In this study, cerebral haemodynamic status as determined by TCD was compared with that of stable xenon-enhanced cerebral blood flow (XeCBF) which is generally regarded as a gold standard in CBF measurement with minimal complication, suggesting that employing CO2 and blood pressure challenge with TCD measurement to assess the CVR and PAR in head-injured patients, provides a relatively less invasive method and can be repeated at least daily to assess the cerebrovascular autoregulatory reserve.

Neurochemical changes in ventilated head-injured patients with cerebral perfusion pressure treatment failure.

The goal of intensive care management of patients with head injury is to provide them with a favourable physiological and metabolic environment for recovery of injury-compromised cells, and to prevent secondary brain insults. Clinical intracerebral microdialysis has enabled documentation of the metabolic derangement after head injury. Treatment targeted at this derangement has emphasized maintenance of optimal cerebral perfusion pressure (CPP). To determine the relationships between CPP and five clinically relevant intracerebral extracellular metabolites (glucose, lactate, glycerol, glutamate and pyruvate) in relation to different therapy intensities, 23 moderate to severe head-injury patients with hourly microdialysis samples were studied. These five metabolites were correlated with CPP and showed a biphasic relation at CPP of 65 to 67 mmHg, which was believed to be the critical CPP indicating irreversible brain damage. Relationship between intracerebral metabolites and CPP in relation to different therapy intensities was studied and suggests the critical CPP threshold in head-injured patients with high ICP and maximum therapy is elevated and should be maintained above 70 mmHg to prevent irreversible brain damage.