Magnesium has been known for its antioxidative and antiinflammatory properties in many studies. In this study two dosing regimens of magnesium were compared with a placebo control group in order to investigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma patients. Inflammatory and oxidative factors were measured in this trial.
45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into 2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g of MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate injections levels of tumor necrosis factor alpha (TNF-α), total antioxidant power and lipid peroxidation were measured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were also determined.
Repeated measurements illustrated that there was no significant difference in TNF-α, total antioxidant power and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour post infusion of high dose group was lower than that of control group (p = 0.024). Patient’s mortality (28 day) was similar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing any complications.
No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive patients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to prevent microalbuminuria.
Magnesium; Microalbumin; TNF-α; Oxidative stress; Trauma; Critical care
The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients.
Twenty male chronic obstructive pulmonary disease patients (66.2±8.3 years old, FEV1: 49.3±19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864
Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (-734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l).
The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.
Pulmonary Disease; Chronic Obstructive; Magnesium; Cardiopulmonary Exercise Test; Spirometry; Blood Pressure; Circulatory and Respiratory Physiology
Background and Purpose
Although magnesium is neuroprotective in animal stroke models, no clinical benefit was confirmed in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial of acute stroke patients. The Magnetic Resonance in IMAGES (MR IMAGES) substudy investigated the effects of magnesium on the imaging surrogate outcome of infarct growth.
IMAGES trial patients in participating centers were randomized to receive either intravenous magnesium or placebo within 12 hours of stroke onset. Infarct growth was defined as volume difference between baseline DWI and day 90 FLAIR lesions. Patients who died were imputed the largest infarct growth observed.
Among the 90 patients included in the primary analysis, there was no difference in infarct growth (median absolute growth p=0.639; median percentage growth p=0.616; proportion with any growth p=0.212) between the 46 treated with magnesium and 44 with placebo). Infarct growth correlated with NIHSS score change from baseline to day 90. There was a trend showing baseline serum glucose correlated with infarct growth with magnesium treatment but not in the placebo group. The mismatch frequency was reduced from 73% to 47% by increasing the mismatch threshold from >20% to >100% of core volume.
Infarct growth, confirmed here as a surrogate for clinical progression, was similar between magnesium and placebo treatment, paralleling the main IMAGES trial clinical outcomes. Glucose was a covariate for infarct growth with magnesium treatment. A more stringent mismatch threshold to define penumbra more appropriately would have excluded half of the patients in this sub-12 hour stroke study.
Stroke; Magnesium; Magnetic resonance imaging; Diffusion weighted imaging; Glucose; Surrogate endpoint
Background: Hypothermia may be an effective treatment for stroke or acute myocardial infarction; however, it provokes vigorous shivering, which causes potentially dangerous hemodynamic responses and prevents further hypothermia. Magnesium is an attractive antishivering agent because it is used for treatment of postoperative shivering and provides protection against ischemic injury in animal models. We tested the hypothesis that magnesium reduces the threshold (triggering core temperature) and gain of shivering without substantial sedation or muscle weakness.
Methods: We studied nine healthy male volunteers (18-40 yr) on two randomly assigned treatment days: 1) Control and 2) Magnesium (80 mg·kg-1 followed by infusion at 2 g·h-1). Lactated Ringer's solution (4°C) was infused via a central venous catheter over a period of approximately 2 hours to decrease tympanic membrane temperature ≈1.5°C·h-1. A significant and persistent increase in oxygen consumption identified the threshold. The gain of shivering was determined by the slope of oxygen consumption vs. core temperature regression. Sedation was evaluated using verbal rating score (VRS, 0-10) and bispectral index of the EEG (BIS). Peripheral muscle strength was evaluated using dynamometry and spirometry. Data were analyzed using repeated-measures ANOVA; P<0.05 was statistically significant.
Results: Magnesium reduced the shivering threshold (36.3±0.4 [mean±SD] vs. 36.6±0.3°C, P=0.040). It did not affect the gain of shivering (Control: 437±289, Magnesium: 573±370 ml·min-1·°C-1, P=0.344). The magnesium bolus did not produce significant sedation or appreciably reduce muscle strength.
Conclusions: Magnesium significantly reduced the shivering threshold; however, due to the modest absolute reduction, this finding is considered to be clinically unimportant for induction of therapeutic hypothermia.
Magnesium; Temperature; Thermoregulation; Therapeutic hypothermia; Brain protection; Cardiac protection; Shivering
Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy.
In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age.
A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event.
Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.)
Magnesium ion gates the N-methyl-D-aspartate (NMDA) receptor and may protect the brain from NMDA receptor-mediated asphyxial injury. The present study evaluated the neuroprotective role of magnesium in birth asphyxia.
Material and Methods:
Forty term neonates with severe birth asphyxia were randomized to either the study group or the control group. Neonates in the study group received magnesium sulfate in a dose of 250 mg/kg initially within half an hour of birth followed by 125 mg/kg at 24 and 48 h of birth. Cranial computed tomography (CT) scan and electroencephalography (EEG) were performed for all the babies. Denver II was used for developmental assessment at the age of 6 months.
Two babies in each group died of severe hypoxic ischemic encephalopathy. EEG abnormalities occurred in 43.75% of the cases in the control group compared with 31.25% in the study group. CT scan abnormalities were present in 62.5% of the control group compared with 37.5% of the cases in the study group. The Denver II assessment at 6 months revealed that there were five babies that were either abnormal or suspect in the control group compared with three in the study group.
Magnesium is well tolerated and does appear to have beneficial effects in babies with severe asphyxia. More data is however needed and a large multicenter trial should be conducted.
Asphyxia; magnesium; neuroprotection
Hypomagnesaemia is a common complication after cardiopulmonary bypass (CPB) and predisposes to the development of cardiac arrhythmias. Previous studies showed that intravenous magnesium reduces the incidence of postoperative cardiac arrhythmias but it also inhibits platelet function. Our aim was to compare the postoperative blood loss in patients not receiving magnesium after CPB with the group who received magnesium and to compare the requirement of blood, fresh frozen plasma (FFP) and platelets within 24 hours after surgery. This prospective randomized controlled study was conducted in 80 adult patients on oral aspirin undergoing elective CABG requiring CPB. Group A patients had not received magnesium infusion after recovery from CPB. Group B patients received magnesium infusion after recovery from CPB. Postoperative bleeding was assessed in both the groups. All the data were statistically analyzed. There was a insignificant increase in 24 hours postoperative drainage in magnesium recipient group compared to control group (p>0.05). Requirements of blood and blood products to maintain haematocrit and coagulation profile revealed insignificant (p > 0.05). Increase in requirement of PRC, FFP and platelets in magnesium recipient patients than the control group. Incidence of atrial fibrillation (Gr A 2.5%, Gr B 2.5%) and atrial extrasystoles (Gr A 2.5%, Gr B 10%) revealed comparable (p > 0.05) between the groups, but incidence of ventricular arrhythmias were significantly (p<0.05) high in the patients of Gr A(17.5%) than Gr B(5%). To conclude, magnesium may be administered to patients who continue pre-operative aspirin to undergo on-pump CABG surgery.
Aspirin; Magnesium; CPB; CABG; Postoperative bleeding
Heart manipulation during off-pump coronary artery bypass surgery may cause hemodynamic instability, and temporary coronary arterial occlusion may lead to myocardial ischemia. To reduce this, perioperative β-blocking agents or calcium antagonists can be administrated. The effects of perioperative administration of magnesium on myocardial function were studied in patients undergoing coronary artery bypass grafting.
The aim of the study was to evaluate the effects of preoperative magnesium administration on perioperative hemodynamia, ventricular arrhythmias and myocardial protection.
MATERIALS AND METHODS:
We reviewed 2 groups of patients undergoing off-pump coronary artery bypass surgery – 24 patients (control group) that had not received preoperative intravenous infusion of magnesium and 23 patients (treatment group) that had received preoperative intravenous magnesium sulfate.
The results demonstrated that it had reduced the heart rate, changes of ST segments, the need of β-blocking agents and the use of intra-operative intra-aortic balloon pump and the inotropic usage.
This treatment may provide hemodynamic optimization during off-pump coronary artery bypass.
Ischemia and arrhythmia; magnesium effects; off-pump coronary surgery
The objective was to evaluate whether intravenous magnesium sulfate (magnesium) alters levels of angiogenic factors in women with preeclampsia.
This was a prospective cohort study comparing women with preeclampsia treated with magnesium for seizure prophylaxis to those who were not. Serum levels of angiogenic factors, soluble fms-like tyrosine kinase 1, soluble endoglin and placental growth factor, were measured at the time of diagnosis and approximately 24 hours later. Secondary analysis compared women receiving magnesium for preeclampsia to women receiving magnesium for preterm labor. Analysis of covariance was used to compare levels at 24 hours, adjusting for levels at enrollment and potential confounders.
Angiogenic factor levels did not differ between preeclampsia groups with and without magnesium or between preeclampsia and preterm labor groups treated with magnesium (all P > 0.05).
Magnesium likely decreases seizure risk in preeclampsia by a mechanism other than altering angiogenic factor levels.
angiogenic factors; magnesium sulfate; preeclampsia; pregnancy; toxemia
Higher mortality was found in very old patients with acute ischemic stroke treated with intravenous recombinant tissue-plasminogen activator (rtPA) as compared to younger patients. The benefit of thrombolytic treatment in this particular subgroup is still a subject of debate. The purpose of this study was to compare stroke outcomes in Thai patients aged over 70 years treated with and without intravenous rtPA. This was a retrospective review of sequential cases and was not a randomized controlled study. One-hundred and five patients with acute ischemic stroke aged over 70 years who were treated with intravenous rtPA and 105 patients without rtPA treatment (control group) were included in the study. Patients’ base-line characteristics and study outcomes of interest were compared. There were significant differences in the base-line characteristics of the two groups. However, for the subgroup of patients aged over 80 years, these characteristics were similar. Those who were treated with intravenous rtPA had a higher rate of favorable outcomes (40% vs 16%; P=0.137) and a lower rate of mortality (22% vs 44%; P=0.128) than patients who did not receive rtPA treatment. In well-matched subgroups of patients aged over 80 years, our retrospective review revealed there was a trend of a higher rate of favorable outcome and lower mortality in patients receiving rtPA treatment. More study is needed to further confirm the suggested benefit of thrombolysis in Asian octogenarian acute stroke patients.
thrombolysis; stroke; aging; Asian; Thai
Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO4; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E2, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, p<0.01), and neurological severity score (p<0.05). Low-dose MgSO4 or nimesulide showed no significant neuroprotection. There was also significant suppression of cyclooxygenase-2, prostaglandin E2, myeloperoxidase, and caspase-3 expression in the combination treatment group, suggesting that the combination of the two drugs improved the neuroprotective effects of each individual drug. MgSO4 and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.
in vivo studies; ischemia; middle cerebral artery occlusion; therapeutic approach; stroke
Ischemic brain strokes consisttwo-thirdsof strokesand their complications bear a lot of disability for patient and society. In this study, we seek for effect of Erythropoietin on ischemic brain stroke's outcomes according to National Institutes of Health Stroke Scale (NIHSS) changes.
This study is a RCT (randomized clinical trial). All patients with focal neurologic deficit with primary suspicion of brain stroke undergone neuroimaging evaluations. After confirmation of new ischemic brain stroke, the patients with inclusion criteria’srandomized into two groups of cases and controls.
NIHSS was defined for each patient and all patients received a routine treatment protocol. Erythropoietin 16,000 IU as a bolus intravenous dose was given to case patients as soon as neuroimaging study confirmed new ischemic stroke and continued as 8000 IU each 12 h up to total dose of 56,000 IU during 3 days. Patients re-evaluated at days 14 and 28 and NIHSS was assessed by another neurologist blinded to patient's group. Finally, NIHSS changes of both groups compared with each other's.
Evaluations revealed that in days14 and 28 during follow-up, Erythropoietin was effective in NIHSS (P= 0.0001). This effect was of value in level of consciousness Commands (P= 0.024), facial palsy (P= 0.003), motor arm (P= 0.0001), motor leg (P= 0.0001), sensory (P= 0.009), and best language (P= 0.023).
Administration of high-dose erythropoietin in first 24 h can be effective on reduction of ischemic stroke complication. A larger scale clinical trial is warranted.
Erythropoietin; national institutes of health stroke scale; neuroprotection; stroke
Background and Objective: Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase.
Methods: This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30 mg twice daily for 3 days (short-term group) or 10–14 days (long-term group). The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke.
Results: Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups. However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6±5.9% and 1.5±6.0% vs 8.3±5.2% and 5.7±6.4%; p<0.01 and p<0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10 m was significantly greater in the long-term group (98±67 vs 54±55 cm/sec; p<0.05).
Conclusion: Edaravone treatment for up to 14 days suppresses the progression of disuse muscle atrophy and improves leg locomotor function to a greater extent than shorter-term treatment in acute stroke patients. This suggests that the management of stroke may be improved with long-term edaravone therapy by providing myoprotective effects that ameliorate functional outcome in the chronic phase.
There has been longstanding controversy over the use of magnesium sulfate infusion in the medical management of aneurysmal subarachnoid hemorrhage (SAH). Several clinical trials evaluating the beneficial effects of magnesium on cerebral vasospasm and their poor outcome have been published. However, results from the majority of these studies have been inconclusive. This meta-analysis was performed to evaluate the effectiveness of magnesium on patient outcomes after aneurysmal SAH.
Materials and Methods:
PubMed and the Cochrane library were searched for controlled clinical trials assessing the efficacy of magnesium sulfate infusion after aneurysmal SAH. Eight studies consisting of 936 patients were included.
There was a decreased risk of poor outcome at 3–6 months after SAH in magnesium treatment groups when compared to placebo [0.78 (95% CI 0.66–0.93)]. Poor outcome was defined as severe disability, persistent vegetative state, or death, as measured by the Glasgow outcome scale (GOS), extended Glasgow outcome scale (GOSE) or modified Rankin scale (mRS). The risk of mortality after SAH was unaffected by magnesium treatment [RR 0.68 (95% CI 0.58–1.27)].
Magnesium sulfate infusion decreases risk of poor outcome after aneurysmal SAH. Current studies in the literature do not suggest a role for magnesium sulfate in mortality reduction after SAH.
Cerebral vasospasm; delayed cerebral ischemia; magnesium sulfate; subarachnoid hemorrhage
This randomised, placebo-controlled, double-blind study was designed to assess the effect of intravenous clonidine and magnesium sulphate on intraoperative haemodynamics, anaesthetic consumption and postoperative recovery. Seventy five patients undergoing elective upper limb orthopaedic surgery were randomised into three groups. Group C received clonidine 3 μg/kg as a bolus before induction and 1μg/kg/hour by infusion intraopertively. Group M received magnesium sulphate 30 mg/kg as a bolus before induction and 10 mg/kg/hour by infusion. Group P received same volume of isotonic saline. Anaesthesia was induced and maintained with fentanyl citrate and propofol. Muscular relaxation was achieved by vecuronium bromide. Induction time, recovery time and consumption of propofol as well as fentanyl citrate were recorded. Induction of anaesthesia was rapid with both clonidine and magnesium sulphate. Time of bispectral index (BIS) to reach 60 was significantly lower in Group C and Group M (P < 0.0001). Requirements of propofol and fentanyl were significantly less in Group C and Group M (P < 0.001). Postoperative recovery was slower in Group M compared with other two groups (P < 0.001). Perioperative use of both clonidine and magnesium sulphate significantly reduced the consumption of propofol and fentanyl citrate. Magnesium sulphate caused a delayed recovery.
Anaesthetic consumption; bispectral index; clonidine; magnesium sulphate
Magnesium has been used as an adjuvant by various routes, including intravenous, intrathecal, and epidural in different dosage regimens. The effect of single bolus dose of magnesium as an adjuvant to fentanyl for postoperative analgesia has not been studied. This prospective randomized controlled trial was done to evaluate the efficacy of single bolus administration of magnesium epidurally as an adjuvant to epidural fentanyl for postoperative analgesia in patients undergoing total hip replacement under combined spinal epidural anesthesia.
Sixty patients received combined spinal–epidural anesthesia with 2 mL of 0.5% hyperbaric bupivacaine intrathecally. After the surgery, patients were randomized into Group F [epidural fentanyl (1 μg/kg) in 10 mL saline] and Group FM [epidural magnesium (75 mg) along with fentanyl (1 μg/kg) in 10 mL saline]. Supplementary analgesia was provided by 50 mg intravenous tramadol if Verbal Rating Score (VRS) >4. Patient's first analgesic requirement and duration of analgesia were recorded.
The duration of analgesia was significantly longer for Group FM, 340±28.8 min, compared with Group F, 164±17.1 min (P=0.001). The frequency of rescue analgesics required in 24-h postoperative period in Group FM (2.3±0.5) was significantly less than that in Group F (4.3±0.5) (P=0.001). VRS was significantly lower in Group FM up to 4 h in the postoperative period (P=0.001). Bromage scale was statistically insignificant at all points of time.
The administration of magnesium (75 mg) as an adjuvant to epidural fentanyl (1 μg/ kg) for postoperative analgesia results in significantly lower VRS with prolonged duration of analgesia as compared with epidural fentanyl (1 μg/kg) alone. Concomitant administration of magnesium also reduces the requirement of breakthrough analgesics with no increased incidence of side effects.
Epidural; magnesium; N-methyl-d-aspartate receptor; post operative pain; rescue analgesia
With increasing usage of thrombolysis in the treatment of acute ischemic strokes within 4.5- hour window, it is becoming more important to recognize stroke mimics. Though the incidence of stroke mimics being thrombolysed is less than 3%, it is essential to diagnose them so as to avoid wrong thrombolytic treatment which carries potential complications of bleeding. We describe the case of a 17 year old girl with acute lymphoblastic leukemia, who developed stroke like episodes on two consecutive challenges with a chemotherapeutic regime which included intravenous and intrathecal methotrexate. She had MRI changes consistent with acute ischemic stroke on both occasions. Her deficits recovered completely and spontaneously, as did the MRI changes. She did not have any further episodes when methotrexate was excluded from the chemotherapeutic regime.
Leucoencephalopathy; methotrexate; stroke mimic
Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of α-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy.
Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups.
All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P < 0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered.
There were no significant differences detected in the 1) percentage of patients requiring pressor support, 2) the duration of postoperative pressor support, or 3) the amount of phenylephrine support needed between controls and magnesium treated patients. The percentage of patients requiring pressure support depended on the minimum systolic blood pressure ordered after surgery.
Carotid endarterectomy; Cerebral protection; Hypotension; Magnesium; Phenylephrine
Magnesium is an abundant intracellular cation that has been used for years in the treatment of hyper-tension and seizures associated with eclampsia of pregnancy as well as used as a tocolytic agent.1 Over sixty years ago, Haury showed that magnesium sulfate (MgSO4) could produce bronchodilation in asthmatics.2 However, interest in magnesium sulfate as a potential therapy for acute asthma surfaced in the late 1980s following a series of studies demonstrating that magnesium produced dose-dependent bronchodilation. The precise mechanism by which magnesium produces smooth muscle relaxation is not known, but it is thought to act by enhancing calcium uptake in the sarcoplasmic reticulum3 and/or as a calcium antagonist.4 In addition, magnesium is a cofactor regulating a number of enzymatic and cellular activities in the body, including adenyl cyclase and sodium-potassium ATP-ase, potentially enhancing the effects of β2-agonists.5 Other potential beneficial mechanisms in asthma include inhibition of acetylcholine release from cholinergic nerves6 and reduction of histamine release from mast cells.7
It is not clear whether magnesium acts as a functional antagonist to bronchoconstriction like the β2-agonists and theophylline or a specific antagonist like anticholinergics and antihistamines. Studies showing attenuation of the bronchoconstriction from histamine and methacholine would suggest functional antagonism.8,9 Some suggest that the response to intravenous magnesium sulfate is dependent upon achieving serum magnesium concentrations of 4–6 mg/dL (1.6–2.4 mmol/L).10 These values are similar to those that are employed to achieve tocolysis (4–8 mg/dL) and about one half those associated with severe toxicity of respiratory failure, cardiac arrhythmias and death (12–15 mg/ dL).1 It should be pointed out that studies have not reported lower magnesium concentrations in asthmatics than controls although one study reported correlation with bronchial hyperresponsiveness and intracellular magnesium concentrations in asthmatics. 11–13 Thus, it is unlikely that the bronchodilator response to magnesium is a result of restoring normal homeostasis but most likely a function of its direct antagonistic effects on intracellular calcium activity.
Some evidence suggests the neuroprotection of estrogen provided by the antioxidant activity of this compound. The main objective of this study was to determine the level of estradiol and its correlation with the activity of antioxidant enzymes, total antioxidant status and ferritin from ischemic stroke subjects. The study population consisted of 30 patients with acute ischemic stroke and 30 controls. There was no significant difference between estradiol in stroke and control group. The activity of superoxide dismutase and level of ferritin was higher in stroke compared with control group (P < .05, P < .001, resp.). There was no significant correlation between estradiol and glutathione peroxidase, glutathione reductase, catalase, total antioxidant status, and ferritin in stroke and control groups. We observed inverse correlation between estradiol with superoxide dismutase in males of stroke patients (r = −0.54, P = .029). Our results supported that endogenous estradiol of elderly men and women of stroke or control group has no antioxidant activity.
Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis.
RESEARCH DESIGN AND METHODS
We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points.
A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67–43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23–54.44]; P = 0.029).
High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.
Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke.
Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later.
Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies.
Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age.
We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale.
We evaluated 203 patients (≥65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 ± 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge.
These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.
Cerebral ischemic preconditioning; transient ischemic attack; elderly; stroke
Background and Purpose
Conventional therapies for ischemic stroke include thrombolytic therapy, prevention of inappropriate coagulation and thrombosis, and surgery to repair vascular abnormalities. Over 10 years have passed since the US Food and Drug Administration approved intravenous tissue plasminogen activator for use in acute stroke patients, but most major clinical trials have failed during the last 2 decades, including large clinical trials for secondary prevention and neuroprotection. These results suggest the presence of heterogeneity among stroke patients. Neuroimaging techniques now allow changes to be observed in patients from the acute to the recovery phase. The role of MRI in stroke evaluation and treatment is discussed herein.
Three MRI strategies are discussed with relevant examples. First, the following MRI strategies for acute ischemic stroke are presented: diffusion-perfusion mismatch, deoxygenation (oxygen extraction and cerebral metabolic rate of oxygen), and blood-brain barrier permeability derangement in selected patients for recanalization therapy. Second, multimodal MRI for identifying stroke mechanisms and the specific causes of stroke (i.e., patent foramen ovale, infective endocarditis, and nonbacterial thrombotic endocarditis) are presented, followed by MRI strategies for prevention of recurrent stroke: plaque images and flow dynamics for carotid intervention.
The studies reviewed herein suggest that using MRI to improve the understanding of individual pathophysiologies will further promote the development of rational stroke therapies tailored to the specifics of each case.
atherosclerosis; stroke; perfusion; personalized treatment; MRI
The concentration of magnesium in serum has been shown to fall to potentially dangerously low levels after several courses of treatment with cis-diamminedichloroplatinum II (cis-platin). The aims of this study were to examine the effects of magnesium supplementation on predicted outcome of treatment, rate of response to treatment and toxicity of treatment. Sixteen patients with testicular cancer were studied in detail over a 14 month period. One patient with an ovarian dysgerminoma was also included in the study. Eight patients were randomised to receive magnesium supplements both intravenous and oral; nine did not. The non-supplemented group showed significantly greater renal tubular damage as assessed by urine N-acetyl-B-D-glucosaminidase (NAG). There was a trend towards a reduction in treatment delays due to neutropenic episodes in the supplemented group, and serum magnesium concentrations remained significantly higher. Neither group showed differences in tumour growth rates or outcome. These results show that magnesium supplements are of considerable benefit and show no harmful effects in patients receiving cis-platin treatment. It is is suggested that magnesium supplements should be a routine part of the treatment regime, and that these should comprise both i.v. supplements during treatment and oral supplements between courses.