Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Distribution of perioperative stroke in cardiac surgery.

BACKGROUND AND PURPOSE: The recent literature suggests that a cardiac origin in ischaemic stroke is more frequent than previously assumed. However, it is not always clear which patients benefit from additional cardiac investigations if obvious cardiac pathology is absent. METHODS: A single-center retrospective observational study was performed with 7454 consecutive patients admitted to the intensive care unit after cardiac surgery in the period 2006-2015 and who had postoperative brain imaging. Cerebral imaging was studied for the occurrence of stroke including subtype and involved vascular territory. It was assumed that all perioperative thromboembolic strokes are of cardiac origin. Data obtained from a hospital cohort of consecutive patients who received a diagnosis of ischaemic stroke were used for comparison. RESULTS: Thromboembolic stroke occurred in 135 cardiac surgery patients in 56 (41%) of whom the posterior cerebral circulation was involved. In the control group, 100 out of 503 strokes (20%) were located in the posterior cerebral circulation. The relative risk for a posterior location for stroke after cardiac surgery compared to patients with ischaemic stroke without prior cardiac surgery was 2.09; 95% confidence interval 1.60-2.72. CONCLUSIONS: Thromboembolic stroke after cardiac surgery occurs twice as often in the posterior cerebral circulation compared to ischaemic strokes in the general population. If confirmed in general stroke cohorts, the consequence of this finding may be that in patients with an ischaemic stroke that involves the posterior cerebral circulation the chance of a cardiac origin is increased and therefore might trigger additional cardiac investigations such as long-term heart rhythm monitoring or echocardiography.

Predictors of short-term and long-term mortality in critically ill patients admitted to the intensive care unit following allogeneic stem cell transplantation.

Historically, the mortality of patients admitted to the ICU after allogeneic stem cell transplantation (alloSCT) is high. Advancements in transplantation procedures, infectious monitoring and supportive care may have improved the outcome. This study aimed to determine short-term and long-term mortality after ICU admission of patients after alloSCT and to identify prognostic clinical and transplantation-related determinants present at ICU admission for long-term outcome. A multicenter cohort study was performed to determine 30-day and 1-year mortality within 2 years following alloSCT. A total of 251 patients were included. The 30-day and 1-year mortality was 55% and 80%, respectively. Platelet count <25 × 109/L (OR: 2.26, CI: 1.02-5.01) and serum bilirubin >19 µmol/L (OR: 2.47 CI: 1.08-5.65) at admission, other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 4.59, CI: 1.49-14.1) and vasoactive medication within 24 h (OR: 2.35, CI: 1.28-4.31) were associated with increased 30-day mortality. Other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 1.9, CI: 1.13-3.19), serum bilirubin >77 (OR: 2.05, CI: 1.28-3.30) and vasoactive medication within 24 h (OR: 1.65, CI: 1.12-2.43) were associated with increased 1-year mortality. Neutropenia was associated with decreased 30-day and 1-year mortality (OR: 0.29, CI: 0.14-0.59 and OR: 0.70, CI: 0.48-0.98). Myeloablative conditioning and T cell-depleted transplantation were not associated with increased mortality.

Effect of magnesium on cognition after aneurysmal subarachnoid haemorrhage in a randomized trial.

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.

HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage.

RATIONALE: Delayed cerebral ischemia (DCI) is a major complication after aneurysmal subarachnoid hemorrhage (SAH). One option to treat delayed cerebral ischemia is to use induced hypertension, but its efficacy on the eventual outcome has not been proven in a randomized clinical trial. This article describes the design of the HIMALAIA trial (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA), designed to assess the effectiveness of induced hypertension on neurological outcome in patients with DCI after SAH. AIMS: To investigate whether induced hypertension improves the functional outcome in patients with delayed cerebral ischemia after SAH. DESIGN: The HIMALAIA trial is a multicenter, singe-blinded, randomized controlled trial in patients with DCI after a recent SAH. Eligible patients will be randomized to either induced hypertension (n = 120) or to no induced hypertension (n = 120). In selected centers, the efficacy of induced hypertension in augmenting cerebral blood flow will be measured by means of cerebral perfusion computerized tomography scanning. Follow-up assessments will be performed at 3 and 12 months after randomization by trial nurses who are blinded to the treatment allocation and management. We will include patients during five years. STUDY OUTCOMES: The primary outcome is the proportion of subarachnoid hemorrhage patients with delayed cerebral ischemia with poor outcome three-months after randomization, defined as a modified Rankin scale of more than 3. Secondary outcome measures are related to treatment failure, functional outcome, adverse events, and cerebral hemodynamics. The HIMALAIA trial is registered at clinicaltrials.gov under identifier NCT01613235.

Recovery from near drowning and postanoxic status epilepticus with controlled hypothermia.

A diver was resuscitated after cardiac arrest due to near drowning and was hypothermic on hospital arrival. During rewarming, status epilepticus occurred, previously identified as a predictor of poor outcome. The seizures responded well to treatment with antiepileptic drugs and controlled hypothermia. After six weeks, the patient had completely recovered. This case supports the hypothesis that hypothermia offers neuroprotection, even in the presence of status epilepticus. We recommend that near-drowning victims who are comatose after resuscitation for cardiac arrest be treated with controlled mild hypothermia for 12 to 24 hours.

Therapy failure following selection of enfuvirtide-resistant HIV-1 in cerebrospinal fluid.

We report the selection of enfuvirtide-resistant human immunodeficiency virus type 1 in cerebrospinal fluid, resulting in subsequent loss of viral suppression in the plasma. This case report emphasizes the potential danger of low-level penetration of entry inhibitors into the central nervous system.

Magnesium and headache after aneurysmal subarachnoid haemorrhage.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High mean fasting glucose levels independently predict poor outcome and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Hyperglycaemia has been related to poor outcome and delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Antiplatelet therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: 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. OBJECTIVES: To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH. SEARCH STRATEGY: 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. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: 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. OBJECTIVES: To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. SEARCH STRATEGY: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

Extent of atherosclerosis and prognosis of patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Atherosclerosis impairs the endothelial dependent vasodilatation and may change the diameter and plasticity of cerebral vessels. The aim of this study was to investigate if an index of the occurrence of atherosclerosis is associated with the risk of delayed cerebral ischemia or poor outcome after subarachnoid haemorrhage. METHODS: To assess the likelihood of atherosclerosis we used a modified version of the Framingham Heart Study Coronary Heart Disease Prediction Chart. The relation of this index to the occurrence of delayed cerebral ischemia was studied by means of survival analysis and to poor outcome by regression analysis. A multivariate analysis was used to investigate the independent contribution of the atherosclerosis index. RESULTS: Three hundred and twenty three patients were retrieved from our database from the period 1997 to 2004. The index of atherosclerosis related to a good clinical condition on admission (p = 0.01). A high risk of atherosclerosis independently predicted poor outcome (OR 4.3; 95%CI 1.6-12). This was not caused by an increase in the occurrence of delayed cerebral ischemia (HR 1.1; 95%CI 0.6-2.1), but, in part, by a marked decrease in recurrent bleeding in patients with no or minor atherosclerosis. CONCLUSIONS: An index of the occurrence of atherosclerosis is related to prognosis after subarachnoid haemorrhage. The use of the score may focus attention on patients at risk for poor outcome after subarachnoid haemorrhage.

Dose evaluation for long-term magnesium treatment in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Magnesium is a neuroprotective agent that might prevent or reverse delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). We are presently running a randomized, placebo-controlled, double blind trial with magnesium sulphate (64 mmol/day intravenously). We studied whether this treatment regime resulted in our target serum magnesium levels of 1.0-2.0 mmol/L. METHODS: Magnesium sulphate was administered intravenously as soon as possible after admission and continued until 14 days after occlusion of the aneurysm. Serum magnesium measurements were done at baseline and at least every 2 days during administration of trial medication. For comparison we used the serum magnesium levels of the placebo-treated patients. RESULTS: Magnesium therapy was begun in 94 patients. The mean magnesium level in the treatment period was 1.47 +/- 0.32 mmol/L. In 81 patients serum magnesium stayed within target levels during the entire treatment period. One patient had a serum magnesium level below 1.0 mmol/L (0.91 mmol/L) in a single measurement and 10 patients had serum magnesium levels above 2.0 mmol/L at one or more measurements. In six patients magnesium therapy was discontinued: in three because of nausea, headache, or both in combination with serum magnesium levels above 2.0 mmol/L and in the other three because of hypotension, phlebitis and renal failure. CONCLUSIONS: With an intravenous dosage schedule of 64 mmol magnesium sulphate a day, serum magnesium levels of 1.0-2.0 mmol/L can easily be maintained without severe side effects for an extended period in a vast majority of patients with SAH.

Magnetic resonance imaging in experimental subarachnoid haemorrhage.

BACKGROUND: We developed an MRI protocol to measure cerebrovascular diameter and blood flow velocity, and if we could detect cerebrovascular alterations after SAH and their impact on cerebral ischaemia. METHOD: SAH was induced in 15 Wistar rats by means of the endovascular filament method; 6 other rats served as control. MRI measurements were performed on a 4.7T NMR spectrometer 1 and 48 hours after SAH and 9 days thereafter. Diffusion-weighted and T2-weighted images were acquired to detect cerebral ischaemia. The arterial spin labelling method was used to measure CBF. MR angiography was used to measure vessel diameter and blood flow velocity, from which the arterial blood flow was calculated. FINDINGS: The ischemic lesion volume increased between 1 and 48 hours after SAH from 0.039 to 0.26 ml (P = 0.003). CBF decreased from 53.6 to 39.1 ml/100 g/min. The vessel diameter had narrowed, the blood flow velocity diminished as did the arterial blood flow in most vessels, but only the vasoconstriction in the right proximal ICA reached significance (0.49 mm to 0.43 mm, P = 0.016). Baseline values were restored at day 9. CONCLUSIONS: We showed that it is feasible to detect alterations of in-vivo vessel diameter and blood flow velocities and their consequences for brain damage after experimental SAH in the rat. The growth of the infarct volume between day 0 and 2 after SAH and the parallel vasoconstriction suggest that delayed cerebral ischaemia after SAH occurs in rats and that this may be caused by vasoconstriction.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage (SAH). Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm and have neuroprotective properties. Several types of calcium antagonists have been studied in several clinical trials. OBJECTIVES: To determine whether calcium antagonists improve outcome in patients with aneurysmal SAH. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (September 2003). In addition, we searched MEDLINE (1966 to October 2003) and EMBASE (1980 to October 2003), handsearched two Russian journals (1990 to 2003) and contacted trialists and pharmaceutical companies (in 1995 and 1996) to identify further studies. SELECTION CRITERIA: All unconfounded, truly randomised controlled trials comparing any calcium antagonist with control. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We analysed 12 trials totalling 2844 patients with SAH (1396 in the treatment group and 1448 in the control group). The drugs analysed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), AT877 (one trial, 276 patients) and magnesium (one trial, 40 patients). Overall, calcium antagonists reduced the risk of poor outcome: relative risk (RR) 0.82 (95% confidence interval (CI) 0.72 to 0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event was 20. For oral nimodipine alone the RR was 0.70 (0.58 to 0.84). The RR of death on treatment with calcium antagonists was 0.90 (95% CI 0.76 to 1.07), that of clinical signs of secondary ischaemia 0.67 (95% CI 0.60 to 0.76), and that of CT or MR confirmed infarction 0.80 (95% CI 0.71 to 0.89). AUTHORS' CONCLUSIONS: 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 with oral nimodipine; the evidence for nicardipine, AT877 and magnesium is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks of this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) 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.

[Diagnostic image (171). A man with a painful red ear. Relapsing polychondritis]. / Diagnose in beeld (171). Een man met een pijnlijke, rode oorschelp. Recidiverende polychondritis.

A 50-year-old man presented with a painful and red swollen right ear, fever, iridocyclitis and a peripheral facial nerve palsy, due to relapsing polychondritis. Immunosuppressive therapy was successful.

Potentials of magnesium treatment in subarachnoid haemorrhage.

Subarachnoid hemorrhage from a ruptured aneurysm is a subset of stroke. The young age (median 55 years) and poor outcome (50% of patients die; 30% of survivors remain dependent) explain why in the population the loss of productive life years from aneurysmal subarachnoid hemorrhage (SAH) is as large as that from brain infarcts, the most common type of stroke. Ischemia plays an important role in the pathophysiological process after SAH. A period of global cerebral ischemia firstly occurs in the acute phase, immediately after rupture of the aneurysm, due to acute vasoconstriction and elevated intracranial pressure, which leads to a drop in perfusion pressure. This is quite distinct from the secondly, delayed cerebral ischemia (DCI), which is focal or multi-focal. DCI usually occurs between 4 and 10 days after the initial bleeding, has a gradual onset and is multi-focal, and is an important cause of death and dependency after SAH. The interval between the bleeding and the onset of ischemia provides an opportunity for preventive treatment. Magnesium is readily available, inexpensive and has a well-established clinical profile in obstetrical and cardiovascular practice. It is beneficial in the treatment of eclampsia, a disease with a pathophysiology comparable to DCI after subarachnoid hemorrhage. Neuroprotective mechanisms of magnesium include inhibition of the release of excitatory amino-acids and blockade of the NMDA-glutamate receptor. Magnesium is also a non-competitive antagonist of voltage dependent calcium channels, has cerebrovascular dilatory activity and is an important co-factor of cellular ATPases, including the Na/K-ATPase. Magnesium can reverse delayed cerebral vasospasm and reduces the extent of acute ischemic cerebral lesions after experimental subarachnoid hemorrhage in rats. In this article we discuss the neuroprotective potency of magnesium in SAH by describing the pathophysiology of ischaemia after SAH and the many ways magnesium may interfere with this.

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment.

BACKGROUND: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of magnesium. Our aim was to find a dosage schedule of magnesium sulphate to maintain a serum magnesium level of 1.0-2.0 mmol/L for 14 days to cover the period of DCI. METHODS: We prospectively studied 14 patients admitted within 48 hours after aneurysmal subarachnoid haemorrhage (SAH) to our hospital. Magnesium sulphate was administrated intravenously for 14 days, using 3 different dosage schedules. Group A (n=3) received a bolus injection of 16 mmol magnesium sulphate followed by a continuous infusion of 16 mmol/daily; group B (n=6) a continuous infusion of 30 mmol/daily; and group C (n=5) a continuous infusion of 64 mmol/daily. Serum magnesium was measured at least every two days and all patients were under continuous observation during magnesium treatment. Renal magnesium excretion was measured only in group C. FINDINGS: In treatment group A the mean serum magnesium level during treatment was 1.03+/-0.14 (range 0.82-1.34) mmol/L, in group B 1.10+/-0.15 (range 0.87-1.43) mmol/L, and in group C 1.38+/-0.18 (range 1.11-1.98) mmol/L. The renal magnesium excretion in group C was equal to the administrated doses within 48 hours after treatment had started. All patients in group A reported a flushing sensation during the bolus injection; no other side effects were noted. INTERPRETATION: With a continuous intravenous dosage of 64 mmol/L per day, serum magnesium levels maintained within the range of 1.0-2.0 mmol/L for 14 days.

An arachnoid cyst presenting as an intramedullary tumour.

A case of thoracic intradural extramedullary arachnoid cyst is presented in which an intramedullary low grade glioma was suspected preoperatively. The cyst was widely fenestrated and postoperatively, the patient experienced considerable improvement in her symptoms. As postoperative MRI studies also showed resolution of the intramedullary changes we regard the intramedullary changes as a result of the cyst, without the existence of primary medullary pathology. To our knowledge an arachnoid cyst, to date, has not been described as the cause of syringomyelia. As radiological findings can be misleading, extramedullary pathology, located more cranially, should be ruled out when treating cystic medullary changes.