Loading Dose Of Magnesium Sulfate Research Articles

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia

Objectives. To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia.Study Desiqn. Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05.Results. There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states.Conclusions. The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.

The effects of magnesium sulfate on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats

The study was performed to evaluate whether magnesium sulfate could alter the degree of disruption of the blood-brain barrier (BBB) caused by hyperosmotic mannitol. Wistar adult female rats were infused with 25% mannitol into the left internal carotid artery. Each animal received intraperitoneally a 300 mg/kg loading dose of magnesium sulfate, dissolved in 0.9% saline, followed by a further 100 mg/kg dose. In the other group, intracarotid infusion of magnesium sulfate was performed at a dose of 150 mg/kg 10 min before mannitol administration. Evans blue (EB) dye was used as a marker of BBB disruption. The measured serum glucose and magnesium levels increased after mannitol and/or magnesium administration when compared with their initial values before treatment (P < 0.01). Water content of the left hemisphere was significantly increased by hyperosmotic mannitol (P < 0.01). The increased water content in the mannitol-perfused hemisphere was significantly decreased by magnesium treatment (P < 0.05). The content of EB dye in the mannitol-perfused hemisphere markedly increased when compared with the right hemisphere of the same brain (P < 0.01). The EB dye content in the mannitol-perfused hemisphere following both intraperitoneal and intraarterial administration of magnesium decreased when compared with mannitol alone (P < 0.01). We conclude that although magnesium sulfate administration by both intracarotid arterial and intraperitoneal routes attenuates BBB disruption caused by hyperosmolar mannitol, particularly intraperitoneal route of magnesium sulfate administration may provide a useful strategy to limit the transient osmotic opening of the BBB.

THIS MONTH IN ANESTHESIOLOGY

THIS MONTH IN ANESTHESIOLOGY

A Comparison of Magnesium Sulfate and Nimodipine for the Prevention of Eclampsia

Magnesium sulfate has been used for some time in the United States to prevent eclampsia. It dilates cerebral blood vessels and can reduce ischemia by preventing cerebral vasospasm. If eclampsia is in fact a result of cerebral ischemia, the calcium-channel blocker nimodipine, a specific cerebral vasodilator, would seem to be an ideal alternative treatment. Nimodipine can be given orally, has little toxicity, and lowers blood pressure. This unblinded trial randomized women with severe preeclampsia, for whom delivery had been decided on, to receive either 60 mg of nimodipine by mouth every 4 hours or a 6-g loading dose of magnesium sulfate followed by an infusion of 2 g per hour. An alternative was to administer 4 g at the outset to be followed by an infusion of 1 g per hour. Treatment continued for up to 24 hours antepartum. Participants were accessed from 14 centers in 8 countries. The 819 women randomized to receive nimodipine and the 831 given magnesium sulfate were comparable demographically and clinically, except for slightly higher baseline systolic blood pressure in the magnesium sulfate group. Mean arterial pressure fell by 8% on average within 1 hour of the start of treatment, and the reduction was maintained at 3 hours. Nimodipine-treated patients were significantly likelier to have a seizure than those given magnesium (2.6% vs. 0.8%). The crude relative risk of a seizure with nimodipine was 3.0. The majority of seizures in this group and all those in the magnesium sulfate group occurred in the antepartum period. The group difference in seizure risk was significant only in the postpartum period. Women given magnesium more often required hydralazine to control blood pressure and more frequently had postpartum bleeding. In addition, respiratory problems were more numerous in these patients. Rates of eclampsia were 1.4% in the nimodipine group and 0.5% in women given magnesium sulfate. This study shows that magnesium sulfate is a more effective means of preventing eclampsia in women with severe preeclampsia than is nimodipine. The findings suggest that eclampsia might be a result of cerebral overperfusion rather than decreased blood flow.

A low dose (‘Dhaka’) magnesium sulphate regime for eclampsia

Eclampsia remains a common cause of maternal death in Bangladesh. Early experience of magnesium sulphate use for eclampsia in Bangladesh was based on a lower dose regime, tailored for use in the smaller woman. a) To determine the recurrent convulsion rate with the low dose "Dhaka" magnesium sulphate regime (recognizing the limitations of sample size). b) To identify whether toxicity occurs with this regime. c) To measure serum level of magnesium with this regime. This prospective study included 65 eclamptic patients receiving lower dose magnesium sulphate therapy at Dhaka Medical College Hospital from 25 March 1998-15 June 1998. The loading dose of magnesium sulphate was 10 gm. Following this 2.5 gm was given intramuscularly 4 hourly, for 24 hours after administration of the first dose. Four blood samples were collected for serum magnesium levels. Patients were monitored hourly by observing their respiratory rate, knee jerks and urinary output. Findings were matched with serum magnesium levels. The range of serum magnesium levels was 1.74 to 6 mg/dl with mean (s.d.) values of 3.87 (0.78). Only five (9%) patients had diminished knee jerks 6, 10, 12, 12 and 15 hours after administration of the loading dose. But at those times the serum magnesium levels were 3.2 mg/dl, 3.8/dl, 3.4 mg/dl and 3.3 mg/dl respectively. Of the 65 patients, only one developed recurrent convulsions. This was 3 hours after the loading dose and was controlled by diazepam treatment and maintenance magnesium sulphate. Half of the standard dose of magnesium sulphate appeared to be sufficient to control convulsions effectively and serum levels of magnesium remained lower than levels which produce toxicity.

Population pharmacokinetics of magnesium in preeclampsia

Objective: The purpose of this study was to determine the population pharmacokinetics of magnesium from sparse observational data in patients with preeclampsia. Study Design: Serum magnesium concentrations (1-11 per patient) were obtained retrospectively from the records of 116 patients with preeclampsia who had a loading dose of magnesium sulfate (16 or 20 mmol), followed by a maintenance dose (1 mmol/h) over an average of 28 hours. Population clearance, volume of distribution, and the baseline magnesium concentration were estimated using the NONMEM program. Results: The following population typical values, together with the interpatient variability (expressed as coefficient of variation) were obtained with the use of a 1-compartment model: systemic clearance, 4.28 L/h (37.3%); volume of distribution, 32.3 L (32.1%); baseline concentration, 0.811 mmol/L (18.5%). The average half-life was 5.2 hours. Clonus was not obtunded in 4 patients whose serum magnesium concentrations were similar to the average concentration of 1.7 mmol/L. The variability remaining unexplained after the population model was fitted to the data was 6.5% to 10.8%. Conclusion: This study extended knowledge of the pharmacokinetic disposition of magnesium in preeclampsia. The results are potentially useful for the calculation of loading and maintenance doses, particularly when the relationship between serum concentration and effect in preeclampsia is clarified. (Am J Obstet Gynecol 2001;185:593-9.)

A low dose ('Dhaka') magnesium sulphate regime for eclampsia: Clinical findings and serum magnesium levels

Background. Eclampsia remains a common cause of maternal death in Bangladesh. Early experience of magnesium sulphate use for eclampsia in Bangladesh was based on a lower dose regime, tailored for use in the smaller woman. Objectives. a) To determine the recurrent convulsion rate with the low dose 'Dhaka' magnesium sulphate regime (recognizing the limitations of sample size). b) To identify whether toxicity occurs with this regime. c) To measure serum level of magnesium with this regime. Methods. This prospective study included 65 eclamptic patients receiving lower dose magnesium sulphate therapy at Dhaka Medical College Hospital from 25 March 1998-15 June 1998. The loading dose of magnesium sulphate was 10 gm. Following this 2.5 gm was given intramuscularly 4 hourly, for 24 hours after administration of the first dose. Four blood samples were collected for serum magnesium levels. Patients were monitored hourly by observing their respiratory rate, knee jerks and urinary output. Findings were matched with s...

A prospective, randomized, controlled trial of high and low maintenance doses of magnesium sulfate for acute tocolysis

Objective: This study was undertaken to compare a high-dose protocol for magnesium sulfate tocolytic therapy with a low-dose regimen with respect to time needed to achieve tocolysis. Study Design: Patients between 24 and 34 weeks' gestation with preterm labor were included. Patients with ruptured membranes or nonreassuring fetal assessments were excluded. Gravid women received a 4-g loading dose of magnesium sulfate and were prospectively randomly assigned to receive a maintenance dose of 2 or 5 g/h. Results: The median times to tocolysis were 120 minutes (semi-interquartile range, 30 minutes) in the low-dose group and 90 minutes (semi-interquartile range, 28 minutes) in the high-dose group (P <.001). Conclusion: Patients treated with a higher maintenance dose of magnesium sulfate had a higher frequency of side effects; however, tocolysis was achieved more rapidly and they required shorter admissions to the labor and delivery unit without increased maternal or neonatal morbidity. (Am J Obstet Gynecol 2000;182:1477-82.)

The effect of magnesium sulfate on maternal and fetal blood flow in pregnancy‐induced hypertension

The purpose of this study was to evaluate the effects of magnesium sulfate on maternal and fetal blood flow in pregnancy-induced hypertension. Twelve patients with pregnancy-induced hypertension were prospectively studied with transcranial pulsed Doppler and transabdominal color flow Doppler before and after infusion of a 6 gram intravenous loading dose of magnesium sulfate. The maternal vessels studied included the middle cerebral, common carotid, and internal carotid arteries. The fetal vessels studied included the middle cerebral, renal, and umbilical arteries. In addition the maternal circulation in the placental base plate was imaged. The results of this descriptive study suggest that a 6 gram loading dose of magnesium sulfate significantly vasodilates the vascular bed distal to the maternal middle cerebral artery, and increases blood velocity in this distribution. There was no significant change in pulsatility index or blood velocity in the central large vessels of the head and neck. There were no acute effects noted in the fetal or placental vessels evaluated.

Magnesium Bolus or Infusion Fails to Improve Expiratory Flow in Acute Asthma Exacerbations

Intravenous magnesium sulfate improves objective measures of expiratory flow in patients with acute severe exacerbations of asthma. Randomized, double-blind, placebo-controlled trial. Urban emergency department. Forty-eight asthmatic patients aged 18 to 60 years with initial peak expiratory flow rate (PEFR) < 200 L/min who failed to double their initial PEFR after two standardized albuterol treatments. Subjects were randomized to three groups: a loading dose of magnesium sulfate, 2 g IV over 20 min followed by 2 g/h over 4 h (infusion), magnesium sulfate, 2 g over 20 min followed by placebo infusion (bolus), or placebo loading dose and infusion (placebo). All subjects received standardized aminophylline and steroid therapy. The PEFR and FEV1 were measured at the start of the loading dose, and 20, 50, 80, 140, 200, and 260 min later using a water-displacement spirometer. Changes from baseline were compared by one-way analysis of variance for repeated measures. Magnesium sulfate administration did not at any time significantly improve either FEV1 (F = 0.036, p = 0.96) or PEFR (F = 0.51, p = 0.61). This study had the power to detect a PEFR difference of 26 L/min and a FEV1 difference of 0.19 L between groups (beta = 0.20, alpha = 0.05 two-tailed significance). Use of IV magnesium sulfate in addition to standard therapy does not provide clinically meaningful improvement of objective measures of expiratory flow in patients with moderate to severe asthma exacerbations.

Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: A randomized, placebo-controlled study

The purpose of this study was to determine the effect of a 6 gm intravenous bolus of magnesium sulfate on maternal brain blood flow velocity waveforms in patients with preeclampsia. Twelve patients with preeclampsia were randomized to two groups and studied with Doppler ultrasonography before and immediately after infusion of either a 6 gm intravenous loading dose of magnesium sulfate or a placebo. The middle cerebral, common carotid, and internal carotid arteries were studied. Magnesium sulfate significantly reduced the pulsatility index in the middle cerebral artery (change in pulsatility index = -0.16 + 0.09) when compared with the placebo (change in pulsatility index = -0.02 + 0.06), p = 0.01. There were no significant changes in the Doppler indexes of the carotid vessels. These data suggest that magnesium sulfate vasodilates the smaller-diameter intracranial vessels distal to the middle cerebral artery and may exert its main effect in the prophylaxis and treatment of eclampsia by relieving cerebral ischemia.

Angiotensin converting enzyme inhibitors and magnesium conservation in patients with congestive cardiac failure.

To investigate whether angiotensin converting enzyme inhibitors reduce diuretic induced magnesium excretion in patients in congestive cardiac failure. Cohort analytic study. A London district general hospital. Thirty four patients with chronic congestive cardiac failure caused by ischaemic heart disease or cardiomyopathy selected consecutively from inpatients under the care of two consultant cardiologists. Nineteen patients (group 1) on diuretics alone were compared with 15 patients (group 2) taking diuretics plus either enalapril or captopril. All drug regimens were stable for at least three months before the study. Patients with impaired renal function (plasma creatinine greater than 120 mumol/l) were excluded. An intravenous loading dose of magnesium sulphate was given to minimise the variability in baseline magnesium state. Total urine magnesium excretion and creatinine clearance in 24 hour urine collections. Plasma magnesium was similar in the two groups. However, 24 hour urine magnesium excretion was significantly lower in group 2 than in group 1. Furthermore, creatinine clearance was also significantly lower in group 2 and correlated strongly with magnesium excretion. There was no such relation in group 1. There was no difference in fractional clearance of magnesium between groups. Angiotensin converting enzyme inhibitors have an important magnesium conserving action, possibly via their effect on glomerular filtration rate.

Adjusting the loading dose of magnesium sulfate for tocolysis

The purpose of this prospective study was to establish a method to calculate a loading dose of magnesium sulfate so as to achieve therapeutic levels of tocolysis more quickly. Fifty patients in preterm labor were enrolled. In the first phase 25 patients were studied so that the apparent volume of distribution for the loading dose of magnesium sulfate could be estimated and an adjusted loading dose could be calculated. The efficacy of this adjusted loading dose was then tested on a further 25 patients in the second phase. We found that the apparent volume of distribution could be accurately estimated and an adjusted loading dose calculated, with the use of ideal body weight, degree of underweight, and current use of (β-sympathomimetics. In the adjusted loading dose group therapeutic levels were achieved more often, with higher postloading magnesium levels and a greater decrease in contraction index immediately after the loading dose. We conclude that an adjusted loading dose can be calculated for magnesium sulfate to optimize tocolytic therapy.

The effect of magnesium sulfate on fetal heart rate variability and uterine activity

The effect of magnesium sulfate on fetal heart rate (FHR) variability and uterine activity is evaluated in 19 preeclamptic patients at term in active labor. Magnesium sulfate was given by intramuscular injection in nine patients and by intravenous infusion in 10 patients after an intravenous loading dose over a period of 15 minutes. No significant changes was noted in FHR variability. There was only a transient, mild decrease in the frequency of uterine contractions during the magnesium sulfate loading dose, and there was no significant change in the intensity of uterine contractions. The conclusion is that, when magnesium sulfate is used for treatment of mild preeclampsia in patients at term in established labor, there is no clinically significant effect on FHR variability or uterine activity.

Is Low Level of Serum Ionized Magnesium Responsible for Eclampsia?

Objective: To determine the level of serum ionized magnesium in eclampsia patient before and 24 hours after giving the loading dose of magnesium sulfate and if low, to determine the relationship between levels of ionized magnesium in serum and occurrence of eclamptic convulsions. Methods: Fifty eclampsia patients received a loading dose of 4 gm of magnesium sulfate, which was diluted with 12 ml of distilled water and then was given intravenously over a period of 10-15 minutes and it was followed by 3 gm of magnesium sulfate deep intramuscular injection in each buttock. Patient's venous blood samples were obtained before and 24hours after loading dose of magnesium sulfate and analyzed for ionized magnesium, sodium, potassium, and calcium level. Results: Level in eclampsia women is 0.47 (0.15-1.04) m mol/L and 0.74 (0.20-2.00) m mol/L before and 24 hours after treatment with loading dose of magnesium sulfate, respectively .This change is significant.( P value is &lt; 0.001) . Change in ionized magnesium level associated with change in diastolic and systolic blood pressure, mean arterial pressure and albuminuria .This changes are also significant (p&lt;.001). Conclusions: The evidence indicated that low level of ionized magnesium in serum may be the cause of eclamptic convulsion. Key words: Ionized magnesium, Eclampsia, magnesium sulfate. DOI: 10.3329/jbcps.v27i2.4250 J Bangladesh Coll Phys Surg 2009; 27: 76-81