Stephanie Chi Ping Ng

Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage (IMASH) A Randomized, Double-Blinded, Placebo-Controlled, Multicenter Phase III Trial

Background and Purpose— Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. Methods— We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). Results— Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. Conclusions— The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis

IntroductionPrevious meta-analyses of magnesium sulphate infusion in the treatment of aneurysmal subarachnoid hemorrhage (SAH) have become outdated due to recently published clinical trials. Our aim was thus to perform an up-to-date systemic review and meta-analysis of published data on the use of magnesium sulphate infusion in aneurysmal SAH patients.MethodsA systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of magnesium sulphate infusion in aneurysmal SAH patients. The results were analyzed with regard to delayed cerebral ischemia (DCI), delayed cerebral infarction, and favorable neurological outcomes at three and six months. The risks of bias were assessed using the Jadad criteria, with a Jadad score >3 indicating a lower such risk. Meta-analyses are presented in terms of relative risk (RR) with 95% confidence intervals (CIs).ResultsSix eligible studies with 875 patients were reviewed. The pooled RR for DCI was 0.87 (95% CI, 0.36 to 2.09; P = 0.75). That for delayed cerebral infarction was 0.58 (95% CI, 0.35 to 0.97; P = 0.04), although this result did not persist if only randomized clinical trials with a lower risk of bias were included (RR 0.61, 95% CI, 0.31 to 1.22; P = 0.17). The pooled RR for a favorable outcome at three months was 1.14 (95% CI, 0.99 to 1.31; P = 0.07), and that for a favorable outcome at six months was 1.08 (95% CI, 0.94 to 1.24; P = 0.29).ConclusionsThe present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation.

Health-Related Quality of Life After Aneurysmal Subarachnoid Hemorrhage: Profile and Clinical Factors:

BACKGROUND:Health-related quality of life has recently been suggested as a supplement to the traditional neurological outcome measures from the patients perspective according to the World Health Organization model and may capture the effects of other factors such as posttraumatic stress disorder and neuroendocrine dysfunction. OBJECTIVE:To explore the profile and clinical factors of quality of life after aneurysmal subarachnoid hemorrhage using the data we obtained from the recently completed Intravenous Magnesium Sulphate After Aneurysmal Subarachnoid Hemorrhage (IMASH) trial. METHODS:This study was registered at www.strokecenter.org/trials and www.ClinicalTrials.gov (NCT00124150). Data from a patient cohort obtained with the Short Form-36 questionnaire completed at 6 months were used for analysis. RESULTS:Patients with aneurysmal subarachnoid hemorrhage demonstrated a decrease in quality of life according to the Short Form-36 at 6 months. The physical and mental health scores correlated with the Extended Glasgow Outcome Scale and had the potential to avoid the ceiling effect. Multiple regression analyses showed that the physical component scores were related to age, World Federation of Neurological Surgeons grade, and chronic hydrocephalus and that the mental component scores were not related to the traditional prognostic factors. CONCLUSION:Subarachnoid hemorrhage caused a decrease in quality of life. Chronic hydrocephalus is related to a decrease in physical health quality of life.

The comparative impact of video consultation on emergency neurosurgical referrals.

OBJECTIVE:Neurosurgical resources are concentrated in tertiary referral centers, whereas emergencies identified from district general hospitals are traditionally referred by telephone consultation (TC). Recent advances in communication technology offer the alternative options of teleradiology (TR) and video consultation (VC). This study aimed to determine the differences among these three consultation methods on the basis of their process-of-care indicators, clinical outcomes, and cost-effectiveness. METHODS:Patients with emergency neurosurgical conditions (head injury, stroke, and miscellaneous) from a district general hospital were randomized to three different modes of consultation: TC, TR, or VC. Process-of-care indicators (postresuscitation Glasgow Coma Scale score, consultation time required, diagnostic accuracy, and transfer decision and safety), 6-month clinical outcome, and cost-effectiveness of the three consultation modes were correlated. RESULTS:In a 3-year period, 710 patients were recruited and randomized to the three consultation modes (n = 235, 239, and 236, respectively). Demographic and clinical data were comparable. TR and VC showed a definite advantage in diagnostic accuracy over TC (89.1 and 87.7% versus 63.8%; P < 0.001). However, duration of the corresponding consultation process was longer for TR and VC than TC (1.01 and 1.3 h versus 0.70 h). A high failure rate (30%) was noted in VC. Thirty-three percent of patients were transferred to the neurosurgical center after consultation. The difference in consultation modes did not have an impact on transfer rate and safety. There was a trend toward more favorable outcome (61%; P = 0.12) and a reduced mortality (25%; P = 0.025) in TR compared with TC (54 and 34%, respectively) and VC (54 and 33%, respectively). The mean cost per patient in the VC group was slightly higher than the other two groups (TC versus TR versus VC = US

Ultra-early (within 24 Hours) aneurysm treatment after subarachnoid hemorrhage

14,000 versus US

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

14,400 versus US

The impact of ventricular catheter impregnated with antimicrobial agents on infections in patients with ventricular catheter: interim report.

16,300, respectively), but the differences were not statistically significant. CONCLUSION:Emergency neurosurgical consultation assisted by TR and VC achieved a higher diagnostic accuracy in comparison with conventional TC. Although VC did not show an advantage over TR in process-of-care indicators, clinical outcome, and cost, it has been proven to be a safe mode of consultation in emergency neurosurgery.

Plasma Magnesium Concentrations and Clinical Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients Post Hoc Analysis of Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage Trial

BACKGROUND The timing of definitive aneurysm treatment (coiling or clipping) in acute aneurysm subarachnoid hemorrhage was a subject of controversy. Although most vascular neurosurgeons agreed on early aneurysm treatment (within the first 72 hours), whether ultra-early aneurysm treatment (within the first 24 hours) was beneficial remained debatable. We aimed to investigate whether ultra-early aneurysm treatment is associated with better neurological outcome in all patients or only good-grade patients or only poor-grade patients. METHODS Two-hundred and seventy-six (84%) patients had hemorrhage onset time and aneurysm treatment time available for analysis. Values of P < 0.05 were taken as statistically significant, and P values between 0.05 and 0.10 were considered to be a trend. RESULTS For the 96 poor-grade (World Federation of Neurological Surgeons grading scale 4 to 5) patients, there was a significant association between Short Form-36 mental scores and ultra-early aneurysm treatment (50 ± 10 vs. 46 ± 10, P = 0.019) and a trend toward association between ultra-early surgery and favorable neurological outcome (odds ratio 2.4 [95% confidence interval 1.0 to 6.0], P = 0.062). A reduction in clinical rebleeding (12% vs. 22%, P = 0.168) was observed in patients undergoing ultra-early aneurysm treatment. CONCLUSIONS Aneurysm treatment performed within the 24-hour window may be associated with a better outcome and halve the clinical rebleeding risk in poor-grade aneurysmal subarachnoid hemorrhage patients.

Phase I–II clinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury

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.

Is Transcranial Doppler Ultrasonography (TCD) Good Enough in Determining CO2 Reactivity and Pressure Autoregulation in Head-Injured Patients?

INTRODUCTION Previous prospective study in our unit had shown that the use of dual antibiotic prophylaxis in patients with external ventricular drain was associated with decreased incidence of cerebrospinal fluid infection but complicated with opportunistic extracranial infection. In recent years, cerebrospinal fluid shunt catheters impregnated with antimicrobial agents have become available. Theoretically, these catheters provide antibiotic prophylaxis locally without the associated complications of systemic opportunistic infection. METHODS We carried out a prospective randomized, controlled clinical trial in a regional neurosurgical center in Hong Kong. We recruited patients admitted for emergency neurosurgical operation after informed consent was obtained from next-of-kin. Eligible patients were randomized to receive an antibiotic-impregnated ventricular catheter or plain ventricular catheter Dual prophylactic antibiotic coverage was given to the patients randomized for plain ventricular catheter only. Patients who received antibiotic impregnanted catheters were not treated with systematic prophylactic antibiotics. Here we present the analysis of 110 patients, recruited over a 2-year period, to receive antibiotic-impregnanted ventricular catheters versus non-impregnated ventricular cathethers with prophylactic antibiotic coverage. FINDINGS Fifty-two patients were randomized to antibiotic-impregnated ventricular catheter with no systemic antibiotic prophylaxis (Group A) and 58 patients were randomized to plain ventricular catheters with prophylactic dual antibiotics (Group B). There was no ventriculostomy-related infection in either groups of patients. There was also no statistical significant difference in incidences of extracranial infections between the two groups, p = 0.617. CONCLUSIONS In this analysis, antibiotic-impregnation of ventricular catheters was as effective as systemic antibiotics in the prevention of ventriculostomy infections, with the potential advantage of avoiding the systemic side-effects of prophylactic antibiotics.