Magnesium Sulfate Group Research Articles

Magnesium pre-treatment reduces neuronal apoptosis in newborn rats in hypoxia–ischemia

Hypoxic–ischemic brain damage has significant mortality and morbidity in newborns. Although the role of magnesium in neonatal hypoxic–ischemic brain injury related to N-methyl- d-aspartate receptors has been widely studied; the effects of magnesium on neuronal apoptosis have not been known exactly in hypoxia–ischemia. The aim of this study was to investigate the effects of magnesium on neuronal apoptosis in the 7-day-old rat hypoxia–ischemia model. Seven-day-old rats were administered magnesium sulfate (group 1; n=9) or saline (group 2; n=9) intraperitoneally before hypoxia–ischemia. Additionally 18 seven-day-old rats were given magnesium sulfate (group 3; n=9) or saline (group 4; n=9) after hypoxic–ischemic insult. Neuronal apoptosis was investigated by the dUDP-biotin nick end-labeling (TUNEL) method following 3-day recovery in all subjects. In evaluating TUNEL-positive cells, we firstly calculated the areas (mm 2) of brain regions, hippocampus, striatum, cortex, in right and left hemispheres in subjects by IMAGE analysis. The numerical density was calculated as the number of cells per square millimeter by counting all TUNEL-positive cells. Afterwards, the ratio of right side numeric density to sum of right and left side numeric densities (right Apoptosis Index) was calculated for every brain region in rats receiving magnesium and compared to vehicle groups. The right Apoptosis Index of the hippocampus in magnesium pre-treated rats (mean±S.D.; 36.6±22.1) was significantly lower than vehicle (61.0±16.0; P<0.05); whereas right apoptosis indices were not changed by magnesium pre-treatment in striatum and cortex. Additionally, magnesium sulfate administration following hypoxic–ischemic insult also had no effect on right apoptosis indices in all three brain regions. It is concluded that magnesium might have a role in preventing neuronal apoptosis due to neonatal hypoxic–ischemic brain injury.

Intravenous Magnesium Sulfate As An Adjunct In The Treatment Of Severe Asthmatic Patients Non-Responding To Conventional Therapy

Treatment of acute asthma is based on rapid reversal of bronchospasm and arresting airway inflammation. This study was done to determine the effect of intravenous MgSO4 for improvement of pulmonary fuction in patients with acute asthma non-responding to routine therapy. This randomized, double –blind controlled study was conducted on 48 patients, magnesium sulfate group , n=48 aged 12-85 years, 26 men, 22 women, and control (saline) group, n=33, aged 15-80 years, 17 men, 16 women, who had not responded to routine treatment. Peak expiratory flow rate (PEFR) was done before MgSO4 (25 mg/kg) and normal saline (100 ml) as a baseline criteria and after infusion of drugs at 30 mm and 3 hr. All patients were also given bronchodilators. The main outcome was PEER. Data were analyzed by X2 and t-test and differences between each point, were considered significant at P<0.05.The peak expiratory flow rate 3 hrs after baseline increased in MgSO4 group in comparison with saline group (82.60±5.8 veruss 47.8±87 p=0.002). the number of breating in MgSO4 was also increased at 30 mm and 3 hr after baseline. Cyanosis, diaphoresis and use of respiratory accessory muscles by patients were decreased in MgSO4 in comparison with saline group.According to the results, it is suggested that MgSO4 can be an adjunct agent for the treatment of patients with acute non-responding asthma

The effects of intrapartum magnesium sulfate therapy on fetal serum interleukin-1β, interleukin-6, and tumor necrosis factor-α at delivery: A randomized, placebo-controlled trial

Objective: Elevated levels of inflammatory cytokines in the fetus have been linked to neurologic morbidities in preterm neonates. Magnesium sulfate is currently being studied in clinical trials as a potential fetal neuroprotective agent. The purpose of this study was to determine whether intrapartum magnesium sulfate therapy has an effect on the umbilical venous concentrations of interleukin-1β, interleukin-6, and tumor necrosis factor-α at delivery. Study Design: Women with singleton gestations >32 weeks with no clinical indications for magnesium sulfate therapy (preeclampsia or tocolysis) and either clinical chorioamnionitis or prolonged rupture of membranes were recruited for the study. Consenting patients were randomly assigned, in a double-blinded fashion, to receive either magnesium sulfate (6-g load then 2 g/hr) or matched volumes of lactated Ringer’s solution until delivery. Fetal blood specimens were obtained by aspiration of the umbilical vein after cord clamping but before placental separation. Umbilical cytokine levels were measured with a sensitive and specific immunoassay. Results: Twenty-two patients were randomly assigned to groups and received either magnesium sulfate (n = 11) or placebo (n = 11). There were no differences in the demographic or clinical characteristics between groups. The umbilical venous ionized magnesium concentration was significantly higher in the magnesium sulfate group (2.32 ± 0.27 mg/dL vs 1.23 ± 0.15 mg/dL; P < .001). There were no statistically significant differences between groups with respect to umbilical levels of interleukin-1β (1.5 pg/mL [1.5-58] vs 1.5 pg/mL [1.5-10]; P = .5); interleukin-6 (8.5 pg/mL [1-1000] vs 11.2 pg/mL [1-113]; P = .9); or tumor necrosis factor-α (16 pg/mL [7.6-20.3] vs 16.6 pg/mL [8.3-22.2]; P = .5). Conclusion: In this pilot study the intrapartum administration of magnesium sulfate does not appear to affect the concentration of inflammatory cytokines in fetal blood at delivery. (Am J Obstet Gynecol 2001;184:1320-4.)

Magnesium sulfate as a vehicle for nebulized salbutamol in acute asthma

Purpose: Magnesium sulfate is thought to be an effective bronchodilator when administered intravenously to patients with acute severe asthma, and it can be safely administered via inhalation to patients with stable asthma. Our goal was to determine if isotonic magnesium sulfate could be used as a vehicle for nebulized salbutamol for patients with acute asthma. Methods: We enrolled 35 patients with acute asthma in a randomized, double-blind, controlled trial. After measurement of peak expiratory flow, patients received 2.5 mg salbutamol plus either 3 mL normal saline solution (n = 16) or isotonic magnesium sulfate (n = 19) through a jet nebulizer. Peak flow was reassessed 10 and 20 minutes after treatment. Results: Peak flow at baseline was similar in the two groups. Ten minutes after baseline, the mean (± SD) percentage increase in peak flow was greater in the magnesium sulfate-salbutamol group (61% ± 45%) than in the normal saline-salbutamol group (31% ± 28%; difference = 30%; 95% confidence interval [CI] for the difference: 3% to 56%; P = 0.03). At 20 minutes, the percentage increase in peak flow was 57% greater in the magnesium sulfate group (95% CI: 4% to 110%, P = 0.04). There was a significant inverse correlation between baseline peak flow (percent of predicted) and the percentage increase in peak flow at 20 minutes in the magnesium sulfate group ( r = −0.82, P <0.0001), but not in the saline group ( r = −0.12, P = 0.67). Conclusion: In patients with acute asthma, isotonic magnesium sulfate, as a vehicle for nebulized salbutamol, increased the peak flow response to treatment in comparison with salbutamol plus normal saline.

Oral nicardipine versus intravenous magnesium sulfate for the treatment of preterm labor

Objective: The aim of this study was to compare the efficacy and safety of oral nicardipine in acute therapy for preterm labor with those of parenteral magnesium sulfate. Study Design: Patients between 24 and 34 weeks’ gestation with documented preterm labor were randomly assigned to receive oral nicardipine (n = 57) or intravenous magnesium sulfate (n = 65) as initial tocolytic therapy. Patients in the nicardipine group received a 40-mg loading dose and then 20 mg every 2 hours as needed to stop contractions (total 80 mg). Patients in the magnesium sulfate group received a 6-g bolus followed by 2 to 4 g/h to provide uterine quiescence. Patients could be switched to another tocolytic regimen if they continued to have contractions after 6 hours of therapy. The main outcome variables examined were time to uterine quiescence, time gained in utero, recurrence of preterm labor, failure of tocolysis, and pertinent maternal and neonatal outcomes. Results: There were no significant differences in maternal demographic characteristics between the groups. Among patients who responded with uterine quiescence within 6 hours, there was a significant decrease in the time to uterine quiescence in the nicardipine group (P < .01). Patients in the magnesium sulfate group were more likely to have recurrence of preterm labor necessitating further tocolytic attempts (P = .048). The patients in the magnesium sulfate group had more adverse side effects, mainly nausea and vomiting (P = .004). There were no differences in birth weight, estimated gestational age at delivery, or neonatal complications between the 2 groups. Conclusions: Oral nicardipine is an effective, safe, and well-tolerated tocolytic agent. In this prospective clinical trial patients randomly assigned to receive oral nicardipine had arrest of preterm labor more rapidly than did those randomly assigned to receive parenteral magnesium sulfate. Patients who received magnesium sulfate were more likely to have adverse medication effects and recurrent preterm labor. (Am J Obstet Gynecol 1999;181:1432-7.)

The effect of magnesium sulfate on fetal heart rate parameters: A randomized, placebo-controlled trial

Objective: We sought to determine the effect of magnesium sulfate on fetal heart rate baseline value, variability, and acceleration-deceleration pattern. Study Design: Normal, nonlaboring pregnant patients at >30 weeks’ gestation were recruited. Baseline fetal heart rate monitoring for 1 hour was performed. After an 800-kcal meal, patients were randomized to receive either an intravenous loading dose of 6 g of magnesium sulfate in 100 mL of isotonic sodium chloride solution or 100 mL of isotonic sodium chloride solution alone. Subsequently, patients in the magnesium sulfate group received a 2-g/h intravenous infusion for 3 hours at a rate of 125 mL/h. Patients randomized to the sodium chloride solution group received a sodium chloride solution infusion at a similar rate (unlabeled intravenous bags). Maternal blood was drawn at 0, 1, and 3 hours for determination of total and ionized magnesium and calcium, electrolyte, and glucose levels. One hour of fetal heart rate monitoring was repeated at 1 and 3 hours of infusion. Tracings were interpreted without identifiers (of time or group) by using the National Institute of Child Health and Human Development fetal heart rate monitoring guidelines. Results: Magnesium sulfate administration resulted in decreased fetal heart rate baseline values and variability in the third hour. The fetal heart rate baseline value was 134.4 ± 6.3 versus 136.6 ± 6.4 beats/min before infusion ( P > .05), 134.4 ± 7.1 versus 135.1 ± 6.6 beats/min in the first hour ( P > .05), and 134.6 ± 7.1 versus 132.3 ± 7.6 beats/min in the third hour ( P < .05) in the sodium chloride solution group versus the magnesium sulfate group, respectively. Fetal heart rate variability (grades 1-5) was 2.75 ± 0.33 versus 2.82 ± 0.29 before infusion ( P > .05), 2.81 ± 0.30 versus 2.84 ± 0.28 in the first hour ( P > .05), and 2.71 ± 0.52 versus 2.67 ± 0.36 in the third hour in the sodium chloride solution group versus the magnesium sulfate group, respectively ( P < .05). Magnesium sulfate blocked the positive correlation between gestational age and number of accelerations found in control subjects. No significant decelerations were identified. Conclusions: Prolonged administration of magnesium sulfate was associated with decreased fetal heart rate baseline values and variability. Given the small magnitude of these changes, the clinical significance of these findings is questionable. Magnesium sulfate inhibition of the increasing number of accelerations with gestational age needs to be considered when fetal well-being is assessed. (Am J Obstet Gynecol 1999;181:1122-7.)

Efficacy of Magnesium Sulphate and Phenytoin in the Management of Eclampsia

Fifty pregnant women admitted with diagnosis of eclampsia were randomly allocated to magnesium sulphate (Group A) or phenytoin sodium (Group B) treatment group. Incidence of recurrence of seizures maternal as well as perinatal morbidity and mortality were compared in both the groups. Mean maternal age, parity and gestational age was similar in both the groups. Mean birth weight was significantly lower in Group B compared to Group A. Seizure frequency prior to hospitalization was 5.4 +/- 4.7 in Group A and 4.8-3.6 in Group B. Mean time interval between occurrence of first seizure and hospitalization was 9.6 +/- 3.5 hours in Group A and 11.8 +/- 9.3 hours in Group B, the difference was not statistically significant. Women treated with phenytoin had a higher incidence of recurrent seizures (10/25-40%) than those treated with magnesium sulphate (2/25-8%). Majority of the women treated with phenytoin (6/10-60%) had single convulsion after initiation of anticonvulsant therapy and 1 woman of each group had recurrent convulsions (75). There was no significant difference in perinatal outcome in both the groups. Maternal morbidity was comparable in both the groups and there was no maternal death in either of the groups.

Maternal Magnesium Sulfate and the Development of Neonatal Periventricular Leucomalacia and Intraventricular Hemorrhage

In Brief Objective Neonatal periventricular leucomalacia and intra-ventricular hemorrhage are strong correlates of cerebral palsy. Our objective was to evaluate the effect of maternal magnesium sulfate exposure on the incidence and severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. Methods Nine hundred eighteen consecutive inborn neonates with birth weights from 500 to 1750 g were divided primarily into two groups on the basis of maternal exposure to magnesium sulfate. The groups were divided secondarily into two clinical groups, a physician-initiated group, which consisted of neonates delivered for maternal or fetal indications, and a preterm delivery group, which included neonates delivered as a result of preterm labor or preterm premature rupture of membranes. These clinical groups were stratified further into magnesium sulfate–exposed and –unexposed subgroups. Neonatal neurosonograms were performed on days 3 and 7 of life and described as normal or abnormal. Abnormal sonograms included any periventricular leucomalacia or intraventricular hemorrhage. Severe lesions included periventricular leucomalacia, periventricular leucomalacia with intraventricular hemorrhage, or grades 3 or 4 intraventricular hemorrhage. The magnesium sulfate groups and the clinical groups with their magnesium sulfate strata were compared for the incidence and severity of abnormal sonograms. They also were compared for maternal and neonatal characteristics. Results Maternal magnesium sulfate exposure was not associated with reduction in the incidence of abnormal sonograms when compared with the unexposed group (27% compared with 33%, P = .06). However, fewer severe lesions were observed in the exposed group (14% compared with 21%, P = .004). When clinical groups were examined, magnesium sulfate was not associated with a decrease in abnormal sonograms (adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.78, 1.52, P = .40) or severe lesions (adjusted OR 1.11, 95% CI 0.73, 1.68, P = .42). Logistic regression analyses of magnesium sulfate exposure within clinical groups controlling for the confounding effects of maternal and neonatal characteristics revealed no protective effect of magnesium sulfate exposure on the incidence of abnormal sonograms (adjusted OR 1.01, 95% CI 0.70, 1.44, P = .97) or severe lesions (adjusted OR 1.01, 95% CI 0.70, 1.74, P = .69). Within clinical groups, the preterm delivery group exhibited an increased risk for abnormal sonograms (adjusted OR 1.63, 95% CI 1.01, 2.67, P = .05) and severe lesions (adjusted OR 9.79, 95% CI 3.27, 29.29, P = .001) when compared with the physician-initiated delivery group, independent of maternal magnesium sulfate exposure. Conclusion Maternal magnesium sulfate exposure had no protective effect on the incidence or severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. The prevalence of these lesions was correlated better with the clinical group of origin and indication for its use. Maternal magnesium sulfate exposure does not alter the incidence or severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates.

Maternal magnesium sulfate and the development of neonatal periventricular leucomalacia and intraventricular hemorrhage

Objective: Neonatal periventricular leucomalacia and intraventricular hemorrhage are strong correlates of cerebral palsy. Our objective was to evaluate the effect of maternal magnesium sulfate exposure on the incidence and severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. Methods: Nine hundred eighteen consecutive inborn neonates with birth weights from 500 to 1750 g were divided primarily into two groups on the basis of maternal exposure to magnesium sulfate. The groups were divided secondarily into two clinical groups, a physician-initiated group, which consisted of neonates delivered for maternal or fetal indications, and a preterm delivery group, which included neonates delivered as a result of preterm labor or preterm premature rupture of membranes. These clinical groups were stratified further into magnesium sulfate–exposed and –unexposed subgroups. Neonatal neurosonograms were performed on days 3 and 7 of life and described as normal or abnormal. Abnormal sonograms included any periventricular leucomalacia or intraventricular hemorrhage. Severe lesions included periventricular leucomalacia, periventricular leucomalacia with intraventricular hemorrhage, or grades 3 or 4 intraventricular hemorrhage. The magnesium sulfate groups and the clinical groups with their magnesium sulfate strata were compared for the incidence and severity of abnormal sonograms. They also were compared for maternal and neonatal characteristics. Results: Maternal magnesium sulfate exposure was not associated with reduction in the incidence of abnormal sonograms when compared with the unexposed group (27% compared with 33%, P = .06). However, fewer severe lesions were observed in the exposed group (14% compared with 21%, P = .004). When clinical groups were examined, magnesium sulfate was not associated with a decrease in abnormal sonograms (adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.78, 1.52, P = .40) or severe lesions (adjusted OR 1.11, 95% CI 0.73, 1.68, P = .42). Logistic regression analyses of magnesium sulfate exposure within clinical groups controlling for the confounding effects of maternal and neonatal characteristics revealed no protective effect of magnesium sulfate exposure on the incidence of abnormal sonograms (adjusted OR 1.01, 95% CI 0.70, 1.44, P = .97) or severe lesions (adjusted OR 1.01, 95% CI 0.70, 1.74, P = .69). Within clinical groups, the preterm delivery group exhibited an increased risk for abnormal sonograms (adjusted OR 1.63, 95% CI 1.01, 2.67, P = .05) and severe lesions (adjusted OR 9.79, 95% CI 3.27, 29.29, P = .001) when compared with the physician-initiated delivery group, independent of maternal magnesium sulfate exposure. Conclusion: Maternal magnesium sulfate exposure had no protective effect on the incidence or severity of periventricular leucomalacia and intraventricular hemorrhage in preterm neonates. The prevalence of these lesions was correlated better with the clinical group of origin and indication for its use.

The Effect of Magnesium Sulphate on Hemodynamics and Its Efficacy in Attenuating the Response to Endotracheal Intubation in Patients with Coronary Artery Disease

Laryngoscopy and endotracheal intubation may produce adverse hemodynamic effects.Magnesium has direct vasodilating properties on coronary arteries and inhibits catecholamine release, thus attenuating the hemodynamic effects during endotracheal intubation. We studied 36 patients with coronary artery disease (CAD) scheduled for elective coronary artery bypass grafting to evaluate the hemodynamic effects of magnesium and its efficacy in attenuating the response to endotracheal intubation. Patients received either 0.1 mL/kg (50%) magnesium sulfate (50 mg/kg) (Group A, n = 19) or isotonic sodium chloride solution (Group B, n = 17) before the induction of anesthesia and 0.05 mL/kg of isotonic sodium chloride solution (Group A) or lidocaine 2% (1 mg/kg) (Group B) before intubation. The hemodynamic variables were recorded before induction, after the trial drug, after induction, and after endotracheal intubation. Automatic ST segment analysis was performed throughout the study period. Magnesium sulfate administration was associated with increased cardiac index (P < 0.01), a minimal increase in heart rate, and a significant decrease in mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P < 0.001). None of the patients in the magnesium group had significant ST depression compared with three patients in the control group. The magnesium group patients had a significantly lesser increase in MAP (P < 0.05) and SVR (P < 0.01) compared with the control group patients who received lidocaine before endotracheal intubation. Thus, magnesium is an useful adjuvant to attenuate endotracheal intubation response in patients with CAD. Implications: Endotracheal intubation produces adverse hemodynamic effects, which may be more detrimental in patients with coronary artery disease than in healthy patients. The present study shows that magnesium administered before endotracheal intubation can attenuate this response better than lidocaine. (Anesth Analg 1998;87:808-11)

The Effect of Magnesium Sulphate on Hemodynamics and Its Efficacy in Attenuating the Response to Endotracheal Intubation in Patients with Coronary Artery Disease

Laryngoscopy and endotracheal intubation may produce adverse hemodynamic effects. Magnesium has direct vasodilating properties on coronary arteries and inhibits catecholamine release, thus attenuating the hemodynamic effects during endotracheal intubation. We studied 36 patients with coronary artery disease (CAD) scheduled for elective coronary artery bypass grafting to evaluate the hemodynamic effects of magnesium and its efficacy in attenuating the response to endotracheal intubation. Patients received either 0.1 mL/kg (50%) magnesium sulfate (50 mg/kg) (Group A, n = 19) or isotonic sodium chloride solution (Group B, n = 17) before the induction of anesthesia and 0.05 mL/kg of isotonic sodium chloride solution (Group A) or lidocaine 2% (1 mg/kg) (Group B) before intubation. The hemodynamic variables were recorded before induction, after the trial drug, after induction, and after endotracheal intubation. Automatic ST segment analysis was performed throughout the study period. Magnesium sulfate administration was associated with increased cardiac index (P < 0.01), a minimal increase in heart rate, and a significant decrease in mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P < 0.001). None of the patients in the magnesium group had significant ST depression compared with three patients in the control group. The magnesium group patients had a significantly lesser increase in MAP (P < 0.05) and SVR (P < 0.01) compared with the control group patients who received lidocaine before endotracheal intubation. Thus, magnesium is an useful adjuvant to attenuate endotracheal intubation response in patients with CAD. Endotracheal intubation produces adverse hemodynamic effects, which may be more detrimental in patients with coronary artery disease than in healthy patients. The present study shows that magnesium administered before endotracheal intubation can attenuate this response better than lidocaine.

The effect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: A randomized, double-blind, placebo-controlled trial: Witlin A.G.; Friedman S.A.; Sibai B.M. USA Am J Obstet Gynecol 1997 176/3 (623–627)

Abstract OBJECTIVE: The primary outcome was to determine whether magnesium sulfate therapy prolongs the duration of labor in women with mild preeclampsia. Secondary outcomes were to assess the side effects associated with magnesium sulfate therapy: hours and maximum dose of oxytocin, incidence of progression to severe preeclampsia, incidence of cesarean delivery, change in maternal hematocrit, incidence of postpartum hemorrhage, incidence of maternal infection, and Apgar scores. STUDY DESIGN: Women with a diagnosis of mild preeclampsia at term were randomized to receive standard therapy during labor and for 12 hours post partum with either magnesium sulfate ( n = 67) or a matching placebo solution ( n = 68). RESULTS: There was no difference between magnesium sulfate and placebo with respect to the primary outcome variables: total length of labor (median 17.8 hours vs 16.5 hours, p = 0.7) and length of the active phase of labor (median 5.4 hours vs 6.0 hours, p = 0.5). In addition, no difference was observed in the secondary outcome variables: hours of oxytocin use, change in hematocrit, frequency of maternal infection, progression to severe preeclampsia, incidence of cesarean delivery, and Apgar scores. Although not statistically significant, the incidence of postpartum hemorrhage was approximately fourfold greater in the magnesium sulfate group (relative risk 4.1, 95% confidence interval 0.5 to 35.4). There was a significant difference in the maximum dose of oxytocin used (13.9 ± 8.6 mU/min with magnesium sulfate vs 11.0 ± 7.6 mU/min with placebo, p = 0.036). CONCLUSION: The use of magnesium sulfate during labor in women with mild preeclampsia at term does not affect any component of labor but did necessitate a higher dose of oxytocin. (Am J Obstet Gynecol 1997;176:623-7.)

Magnesium sulfate solution dramatically improves immediate recovery of rats from hypoxia

This study in rats investigated the effects of 0.5 mEq/1 kg body weight of magnesium sulfate solution upon hypoxic left cardiac ventricular pressure (Part 1), optimal timing for injection of magnesium sulfate solution for successful resuscitation (Part 2) and survival benefits of magnesium sulfate after 8 or 12 min of hypoxia (Part 3) in rats resuscitated by single bolus arterial reperfusion using 2 ml of arterial blood and 6–9 μg epinephrine. A total of 153 pentobarbital anesthetized rats were subjected to 8 or 12 min 0.75% O 2:99.25% N 2 hypoxia in order to induce cardiac arrest. In Part 1, 13 rats (six control and seven injected with magnesium sulfate solution) were subjected to 12 min hypoxia and cardiac left ventricular pressure (LVP) was measured. In Part 2, 47 rats were exposed to 12 min of hypoxia. Normal saline or magnesium sulfate solution was injected prior to hypoxia, at 2 or 4 min of hypoxia, to find the optimal timing of magnesium sulfate injection for successful resuscitation by arterial reperfusion. In Part 3, 90 rats were studied to determine 7-day survival. Two control groups were injected with saline during 8 min (29 rats) or 12 min (18 rats) of hypoxia and two groups received magnesium sulfate solution during 8 min (14 rats) and 12 min (29 rats) of hypoxia. Magnesium sulfate fully reversed the hypoxic increase of LVP and improved survival after 12 min of hypoxia from approximately 15 (control) to 100% if given during the first 2.5 min of hypoxia. The main cause of the progressive resuscitation failure after 8 or 12 min control hypoxia was a progressive increase in acute cardiac failure. Although magnesium sulfate solution significantly improved immediate recovery after hypoxia (8 and 12 min), mortality due to reperfusion injury (para or tetraplegia) was observed in 62% of rats surviving longer than 1 day after 8 min and 100% after 12 min hypoxia (in control rats—50 and 100%, respectively). The overall survival after hypoxia, with or without reperfusion injury, was relatively low: 28% in control groups after 8 min and 17% after 12 min. In the magnesium sulfate groups these numbers were only slightly higher, 36 and 21%, respectively. It is concluded that in conjunction with arterial reperfusion magnesium sulfate infusion is very effective in improving acute cardiac recovery after 8–12 min of hypoxia. The likely mechanism of magnesium sulfate action is decreased incidence of ventricular fibrillation (VF) and asystole, and possibly myocardial relaxation during and after hypoxia, a property which may qualify MgSO 4 as an ischemic preconditioning agent. Poor long-term survival rates of rats exposed to hypoxia and resuscitated by intraarterial reperfusion do not support its use in resuscitation.

Administration of magnesium sulphate before rocuronium: effects on speed of onset and duration of neuromuscular block

The speeds of onset of pancuronium, atracurium and vecuronium are increased by prior administration of magnesium sulphate. A prospective, randomized, double-blind, controlled, clinical study was performed to examine the effects of prior i.v. administration of magnesium sulphate 60 mg kg-1 on the neuromuscular blocking effects of rocuronium 0.6 mg kg-1 during isoflurane anaesthesia. Neuromuscular function was measured electromyographically (Relaxograph) in 30 patients who received either magnesium sulphate 60 mg kg-1 or normal saline, 1-min before rocuronium 0.6 mg kg-1. Mean onset times were similar in the two groups (magnesium sulphate 71 (SD 20) s; normal saline 75 (23) s), but times to initial, 10% and 25% recovery from neuromuscular block were significantly longer in the magnesium sulphate group (42.1 (16.3), 49.0 (12.4) and 56.5 (13.2) min, respectively) than in the saline group (25.1 (9.1), 33.0 (11.1) and 35.6 (13.2) min, respectively) (P < 0.05 in all three cases). Administration of magnesium sulphate was not associated with adverse haemodynamic effects. Prior administration of magnesium sulphate, under the study conditions described, prolonged rocuronium-induced neuromuscular block but did not increase speed of onset.

Comparative study of different anticonvulsants in eclampsia.

One hundred eclampsia patients were admitted in this hospital from January 1993 to November 1993 and they were subjected to different anticonvulsant regimes. There were 28 patients in lytic cocktail group, 16 in diazepam group, 16 in magnesium sulphate group and 40 patients in phenytoin sodium group. The results are compared in every aspect. Feto maternal outcome is best with magnesium sulphate regime followed by phenytoin sodium regime. They produce significantly better results than lytic cocktail and diazepam.

Lack of effect of antenatal indomethacin on fetal cerebral blood flow

OBJECTIVE: Our purpose was to investigate fetal cerebral blood flow and the incidence of intraventricular hemorrhage in patients undergoing tocolysis with either indomethacin or magnesium sulfate at <30 weeks' gestation. STUDY DESIGN: Consenting patients at <30 weeks' gestation with preterm labor were randomized to receive indomethacin or magnesium sulfate tocolysis. Magnesium sulfate was administered intravenously with an 8 gm loading dose given over the first hour, 4 gm over the second hour, and then a maintenance infusion of 2.5 gm per hour. The infusion was continued for approximately 12 hours after the cessation of uterine contractions. Patients randomized to receive indomethacin were given an initial dose of 50 to 100 mg orally or per rectum, followed by 25 to 50 mg orally every 4 to 6 hours for 24 to 48 hours. Oral tocolytic agents were not used after successful tocolysis. Betamethasone was administered to all patients. Patients underwent fetal cerebral Doppler studies during tocolytic therapy and at least 24 hours after completion of the treatment. RESULTS: Twelve patients were randomized to receive indomethacin and twelve patients were randomized to receive magnesium sulfate. Twenty-one fetuses underwent cerebral Doppler studies in triplicate during and after therapy. The mean gestational age at tocolysis was 27.5 ± 1.9 weeks for the indomethacin group and 26.4 ± 1.6 weeks for the magnesium sulfate group ( p = 0.14). The middle cerebral artery resistance index for fetuses during indomethacin treatment was 0.73 ± 0.09, whereas the resistance index after therapy was 0.75 ± 0.05 ( p = 0.49). The resistance index during magnesium sulfate tocolysis was 0.79 ± 0.04 and after therapy it was 0.76 ± 0.04 ( p = 0.18). There was no significant difference in the resistance index between the groups on or off therapy. In addition, the incidence of intraventricular hemorrhage was similar in both groups. CONCLUSION: These results suggest that indomethacin does not significantly affect fetal cerebral blood flow. If antenatal indomethacin in the preterm fetus increases the risk of intraventricular hemorrhage, it would appear to be by another mechanism. (Am J Obstet Gynecol 1997;176:1166-71.)

The effect of magnesium sulfate therapy on the duration of labor in women with mild preeclampsia at term: A randomized, double-blind, placebo-controlled trial

OBJECTIVE: The primary outcome was to determine whether magnesium sulfate therapy prolongs the duration of labor in women with mild preeclampsia. Secondary outcomes were to assess the side effects associated with magnesium sulfate therapy: hours and maximum dose of oxytocin, incidence of progression to severe preeclampsia, incidence of cesarean delivery, change in maternal hematocrit, incidence of postpartum hemorrhage, incidence of maternal infection, and Apgar scores. STUDY DESIGN: Women with a diagnosis of mild preeclampsia at term were randomized to receive standard therapy during labor and for 12 hours post partum with either magnesium sulfate ( n = 67) or a matching placebo solution ( n = 68). RESULTS: There was no difference between magnesium sulfate and placebo with respect to the primary outcome variables: total length of labor (median 17.8 hours vs 16.5 hours, p = 0.7) and length of the active phase of labor (median 5.4 hours vs 6.0 hours, p = 0.5). In addition, no difference was observed in the secondary outcome variables: hours of oxytocin use, change in hematocrit, frequency of maternal infection, progression to severe preeclampsia, incidence of cesarean delivery, and Apgar scores. Although not statistically significant, the incidence of postpartum hemorrhage was approximately fourfold greater in the magnesium sulfate group (relative risk 4.1, 95% confidence interval 0.5 to 35.4). There was a significant difference in the maximum dose of oxytocin used (13.9 ± 8.6 mU/min with magnesium sulfate vs 11.0 ± 7.6 mU/min with placebo, p = 0.036). CONCLUSION: The use of magnesium sulfate during labor in women with mild preeclampsia at term does not affect any component of labor but did necessitate a higher dose of oxytocin. (Am J Obstet Gynecol 1997;176:623-7.)

Effect of intravenous magnesium sulfate on cardiac arrhythmias in critically ill patients with low serum ionized magnesium.

Magnesium affects cardiac function, although until the recent development of a new ion-selective electrode no method existed for measuring the physiologically active form of magnesium, free ions (iMg2+), in the blood. We investigated the antiarrhythmic effect of magnesium sulfate administered to critically ill patients with cardiac arrhythmias and reduced iMg2+ as determined using the ion-selective electrode. Eight patients with a low iMg2+ level (less than 0.40 mmol/L) were given intravenous magnesium sulfate (group L). Magnesium sulfate was also administered to patients with a normal iMg2+ level (more than 0.40 mmol/L) but who did not respond to conventional antiarrhythmic drugs (group N). Intravenous magnesium sulfate significantly increased the iMg2+ level in patients in group L from 0.35 +/- 0.06 mmol/L (mean +/- SD) to 0.54 +/- 0.09 mmol/L (p < 0.01), and had an antiarrhythmic effect in 7 of the 8 patients (88%). However, in group N patients, intravenous magnesium sulfate had an antiarrhythmic effect in only 1 of the 6 patients (17%) (p < 0.05 vs group L). These results suggest that intravenous magnesium sulfate may be effective in the acute management of cardiac arrhythmias in patients with a low serum iMg2+ level.

Magnesium Sulfate in Exacerbations of Chronic Obstructive Pulmonary Disease

Acute exacerbations of chronic obstructive pulmonary disease are commonly seen and difficult to treat. We sought to determine the bronchodilator efficacy of magnesium sulfate in this situation, as this compound is helpful in acute asthma. Subjects who came to either of two Veterans Affairs emergency departments were randomized in a double-blind fashion to receive either 1.2 g of magnesium sulfate or placebo over 20 minutes after they first received albuterol, 2.5 mg by nebulization. Peak expiratory flow, dyspnea scores, arterial hemoglobin oxygen saturation by pulse oximetry, maximal inspiratory and expiratory pressures, and vital signs were monitored for 45 minutes after the start of magnesium sulfate or placebo treatment. Seventy-two individuals were studied. The peak expiratory flow increased 16.6% +/- 27.7% (mean +/- SD) in both groups after the initial albuterol treatment, from 121.2 +/- 55.7 L/min to 136.9 +/- 63.9 L/min. The peak expiratory flow increased from 136.7 +/- 69.7 L/min at the start of the infusion to 162.3 +/- 76.6 L/min at 30 minutes and 161.3 +/- 78.7 L/min at 45 minutes with magnesium sulfate treatment. The peak expiratory flow was 137.0 +/- 58.6 L/min on initiation of the intravenous infusion, 143.0 +/- 72.7 L/min at 30 minutes, and 143.3 +/- 70.5 L/min at 45 minutes in the placebo group. The difference in peak expiratory flow from initiation of the infusion to 30 and 45 minutes later (calculated as means of the 30- and 45-minute values) was significantly different for the two groups (25.1 +/- 35.7 L/min vs 7.4 +/- 33.3 L/min; P = 0.3); the difference was also significant when expressed as percentage increase (22.4% +/- 28.5% vs 6.1% +/- 24.4%; P = .01). There was a statistically nonsignificantly trend toward a reduced need for hospitalization in the magnesium sulfate group as compared with the placebo group (28.1% vs 41.9%; P = .25). There were no significant changes in the other parameters with either treatment. Magnesium sulfate, 1.2 g over 20 minutes after beta-agonist administration, is safe and modestly efficacious in the treatment of acute exacerbations of chronic obstructive pulmonary disease, and its bronchodilator effect is greater than that of a beta-agonist given alone and lasts beyond the period of magnesium sulfate administration.

Ridogrel improves maternal/fetal homeostasis in an ovine model of pregnancy-induced hypertension

The effects of ridogrel (a thromboxane synthetase inhibitor / endoperoxide receptor antagonist) were assessed in an ovine model of pregnancy-induced hypertension. Maternal serum prostacyclin and thromboxane levels were quanitiated using RIA, and maternal and neonatal coagulation status was assessed. Pregnancy and neonatal outcome were recorded. Ridogrel,(E)-5-[[[3-pyridinyl)[3-(tri-fluoromethyl)phenyl]methylen]amin]oxy]pentanoic acid, was administered in one bolus dose at 0.1 or 1.0mg/kg IV, three hours following the onset of a 27 hour magnesium sulfate infusion given hypertensive ewes to prevent maternal seizures. At both doses, ridogrel improved neonatal outcome (0% neonatal mortality in each ridogrel group versus 67% neonatal mortality in the magnesium sulfate group), and ridogrel at 0.1mg/kg IV normalized birth weights. Abnormalities of maternal platelet function (abnormal or no response to collagen), occurring during the ovine syndrome, resolved following ridogrel treatment. Ridogrel's effects on maternal and neonatal coagulation were more dramatic at the 0.1mg/kg IV dose. Ridogrel appeared to be beneficial in this model of pregnancy-induced hypertension.