Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has been incompletely elucidated, but vasospasm probably is a contributing ...factor. Experimental studies have suggested that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties.
To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH.
We searched the Cochrane Stroke Group Trials Register (last searched April 2006), MEDLINE (1966 to March 2006) and EMBASE (1980 to March 2006). We handsearched two Russian journals (1990 to 2003), and contacted trialists and pharmaceutical companies in 1995 and 1996.
Randomised controlled trials comparing calcium antagonists with control, or a second calcium antagonist (magnesium sulphate) versus control in addition to another calcium antagonist (nimodipine) in both the intervention and control groups.
Two review authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information.
Sixteen trials, involving 3361 patients, were included in the review; three of the studies were of magnesium sulphate in addition to nimodipine. Overall, calcium antagonists reduced the risk of poor outcome: the relative risk (RR) was 0.81 (95% confidence interval (CI) 0.72 to 0.92); the corresponding number of patients needed to treat was 19 (95% CI 1 to 51). For oral nimodipine alone the RR was 0.67 (95% CI 0.55 to 0.81), for other calcium antagonists or intravenous administration of nimodipine the results were not statistically significant. Calcium antagonists reduced the occurrence of secondary ischaemia and showed a favourable trend for case fatality. For magnesium in addition to standard treatment with nimodipine, the RR was 0.75 (95% CI 0.57 to 1.00) for a poor outcome and 0.66 (95% CI 0.45 to 0.96) for clinical signs of secondary ischaemia.
Calcium antagonists reduce the risk of poor outcome and secondary ischaemia after aneurysmal SAH. The results for 'poor outcome' depend largely on a single large trial of oral nimodipine; the evidence for other calcium antagonists is inconclusive. The evidence for nimodipine is not beyond all doubt, but given the potential benefits and modest risks of this treatment, oral nimodipine is currently indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended for routine practice on the basis of the present evidence. Magnesium sulphate is a promising agent but more evidence is needed before definite conclusions can be drawn.
Many studies have assessed the relationships between seasonal or meteorological determinants and the occurrence of aneurysmal subarachnoid hemorrhage (SAH), but the data are conflicting. We ...systematically searched the literature and meta-analyzed data from all relevant articles when possible. We searched MEDLINE (1966–2011), EMBASE (1980–2011) and the Cochrane Library to identify all observational studies examining the relationship between seasonal and meteorological determinants (temperature, atmospheric pressure and relative humidity) and the occurrence of SAH. Two authors independently extracted data from articles that were included based on predefined criteria. We pooled relative risks (RR’s) with corresponding 95 % confidence intervals (CI’s) from the individual studies on season and month by means of the random effects method. We included 48 articles, totaling 72,694 patients. SAH occurred less often in summer than in winter (RR 0.89, 95 % CI 0.83–0.96), and was statistically significant more often in January than in the summer months of June–September. For atmospheric pressure seven of 17 studies found a significant association, six of 18 studies were significant for temperature, and three of 15 studies were significant for humidity, but the direction of these associations was conflicting and data on these determinants were too heterogeneous to pool. Seasons influence the occurrence of SAH, with SAH occurring less often in summer than in winter, and most often in January. The explanation for the seasonal differences remains uncertain, due to the lack of sound data on the influence of meteorological factors on SAH occurrence.
Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of ...secondary ischaemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischaemia.
To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH.
We searched the Cochrane Stroke Group Trials Register (last searched August 2006), MEDLINE (1966 to August 2006) and EMBASE databases (1980 to August 2006). We also searched reference lists of identified trials.
All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH.
Two review authors independently extracted the data and assessed trial quality. Relative risks (RR) were calculated with regard to poor outcome, case fatality, secondary ischaemia, haemorrhagic intracranial complications and aneurysmal rebleeding according to the intention-to-treat principle. In case of a statistically significant primary analysis, a worst case analysis was performed.
Seven RCTs were included in the review, totalling 1385 patients. Four of these trials met the criteria for good quality studies. For any antiplatelet agent there were reductions of a poor outcome (RR 0.79, 95% confidence interval (CI) 0.62 to 1.01) and secondary brain ischaemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial haemorrhagic complications (RR 1.36, 95% CI 0.59 to 3.12), but none of these differences were statistically significant. There was no effect on case fatality (RR 1.01, 95% CI 0.74 to 1.37) or aneurysmal rebleeding (RR 0.98, 95% CI 0.78 to 1.38). For individual antiplatelet agents, only ticlopidine was associated with statistically significant fewer occurrences of a poor outcome (RR 0.37, 95% CI 95% CI 0.14 to 0.98) but this estimate was based on only one small RCT.
This review shows a trend towards better outcome in patients treated with antiplatelet agents, possibly due to a reduction in secondary ischaemia. However, results were not statistically significant, thus no definite conclusions can be drawn. Also, antiplatelet agents could increase the risk of haemorrhagic complications. On the basis of the current evidence treatment with antiplatelet agents in order to prevent secondary ischaemia or poor outcome cannot be recommended.
In patients with aneurysmal subarachnoid haemorrhage (SAH), headache typically is severe and often requires treatment with opioids. Magnesium has analgesic effects in several conditions, but whether ...it reduces headache after SAH is unknown.
In a cohort of 108 SAH patients included in the randomised controlled trial Magnesium in Aneurysmal Subarachnoid Haemorrhage-II (MASH-II), severity of headache was regularly assessed on an 11-point scale until day 10 after SAH. Headache was treated according to a standardised protocol with acetaminophen, codeine, tramadol or piritramide. Serum magnesium levels were assessed every other day. Differences in mean headache scores between patients with mean high (>1.0 mmol/l) and normal (< or =1.0 mmol/l) magnesium levels were analysed with a Student t test. Crude and adjusted ORs for the use of codeine, tramadol and piritramide for patients with high versus normal magnesium levels were calculated with logistic regression.
The 61 patients with high magnesium levels had lower mean headache scores (4.1) than the 47 patients with normal magnesium levels (4.9; mean difference, 0.8; 95% CI 0.1 to 1.6) and required less tramadol (adjusted OR, 0.3; 95% CI 0.1 to 0.7) or piritramide (adjusted OR 0.2; 95% CI 0.1 to 0.5). There were no differences in the use of acetaminophen or codeine.
In SAH patients, elevated serum magnesium levels are associated with slightly less severe headache and less frequent use of opioids. These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome.
Background and purpose
In randomized trials magnesium supplementation did not improve clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) on handicap scales. After aSAH, many patients ...have cognitive problems that may not translate into handicap. The effect of magnesium on cognitive outcome after aSAH was studied.
Methods
In total, 209 patients who had been included in the Magnesium for Aneurysmal Subarachnoid Haemorrhage (MASH‐2) trial in the University Medical Centre of Utrecht were studied. Patients had been randomized to 64 mmol magnesium sulfate daily or placebo during hospitalization. Three months after aSAH patients underwent a neuropsychological examination (NPE) consisting of six neuropsychological tests or a brief cognitive assessment. Poisson and linear regression analyses were used to analyse the effect of magnesium on cognition.
Results
In the magnesium group 53 (49.5%) of the 107 patients and in the placebo group 51 (50.0%) of the 102 patients scored lower than the median cognitive score relative risk 0.99, 95% confidence interval (CI) 0.76–1.30. Linear regression analyses showed no significant relationship between intervention and cognition (B = 0.05, 95% CI −0.15 to 0.33).
Conclusions
Treatment with magnesium has no effect on cognitive outcome after aSAH.
Hyperglycaemia has been related to poor outcome and delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH).
This study aimed to assess whether in patients with aSAH, levels ...of mean fasting glucose within the first week predict poor outcome and DCI better than single admission glucose levels alone.
Data on non-diabetic patients admitted within 48 h after aSAH with at least two fasting glucose assessments in the first week were retrieved from a prospective database (n = 265). The association of admission glucose or mean fasting glucose, dichotomised at the median levels, with outcome was assessed using logistic regression, and for DCI using Cox regression. To explore whether the association between glucose levels and outcome was mediated by DCI, we adjusted for DCI.
The crude and multivariable adjusted odds ratios and 95% confidence intervals for poor outcome were 1.9 (1.1 to 3.2) and 1.6 (0.9 to 2.7) for high admission glucose and 3.5 (2.0 to 6.1) and 2.5 (1.4 to 4.6) for high mean fasting glucose. The crude and adjusted hazard ratios for DCI were 1.7 (1.1 to 2.5) and 1.4 (0.9 to 2.1) for high admission glucose and 2.0 (1.3 to 3.0) and 1.7 (1.1 to 2.7) for high mean fasting glucose. After adjusting for DCI, the odds ratios on poor outcome for high mean fasting glucose decreased only marginally.
Compared with high admission glucose, high mean fasting glucose, representing impaired glucose metabolism, is a better and independent predictor of poor outcome and DCI. DCI is not the key determinant in the relationship between high fasting glucose and poor outcome.
Summary Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed ...cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage. Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36). Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio RR 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·84–1·10). Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. Funding Netherlands Heart Foundation, UK Medical Research Council.
In a cohort of 337 patients with subarachnoid hemorrhage (SAH), we investigated the relationship between blood glucose levels, baseline characteristics, and outcome by means of Student's t-test and ...multivariate logistic regression. The mean glucose levels on admission and from day 1 to 10 were significantly higher in patients with poor condition on admission and in patients with poor outcome. In a multivariate analysis, glucose level on admission was not an independent predictor of outcome. Hyperglycemia may be a link in the association between poor condition on admission and poor outcome.
Summary Extracellular volume overload and hypertension are important contributors to the high risk of cardiovascular mortality in patients undergoing haemodialysis. Hypertension is present in more ...than 90% of patients at the initiation of haemodialysis and persists in more than two-thirds, despite use of several antihypertensive medications. High blood pressure is a risk factor for the development of left ventricular hypertrophy, heart failure, and mortality, although there are controversies with some study findings showing poor survival with low—but not high—blood pressure. The most frequent cause of hypertension in patients undergoing haemodialysis is volume overload, which is associated with poor cardiovascular outcomes itself independent of blood pressure. Although antihypertensive medications might not be successful to control blood pressure, extracellular volume reduction by persistent ultrafiltration and dietary salt restriction can produce favourable results with good blood pressure control. More frequent or longer haemodialysis can facilitate volume and blood pressure control. However, successful volume and blood pressure control is also possible in patients undergoing conventional haemodialysis.
Background: Magnesium therapy probably reduces the frequency of delayed cerebral ischaemia (DCI) in subarachnoid haemorrhage (SAH) but uncertainty remains about the optimal serum magnesium ...concentration. We assessed the relationship between serum magnesium concentrations achieved with magnesium sulphate therapy 64 mmol/day and the occurrence of DCI and poor outcome in patients with SAH. Methods: Differences in magnesium concentrations between patients with and without DCI and with and without poor outcome were calculated. Quartiles of last serum magnesium concentrations before the onset of DCI, or before the median day of DCI in patients without DCI, were related to the occurrence of DCI and poor outcome at 3 months using logistic regression. Results: Compared with the lowest quartile of serum magnesium concentration (1.10–1.28 mmol/l), the risk of DCI was decreased in each of the higher three quartiles (adjusted odds ratio (OR) in each quartile 0.2; lower 95% CI 0.0 to 0.1; upper limit 0.8 to 0.9). The OR for poor outcome was 1.8 (95% CI 0.5 to 6.9) in the second quartile, 1.0 (95% CI 0.2 to 4.5) in the third quartile and 4.9 (95% CI 1.2 to 19.7) in the highest quartile. Discussion: Magnesium sulphate 64 mmol/day results in a stable risk reduction of DCI over a broad range of achieved serum magnesium concentrations, and strict titration of the dosage therefore does not seem necessary. However, concentrations ⩽1.28 mmol/l could decrease the effect on DCI while concentrations ⩾1.62 might have a negative effect on clinical outcome.
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