High-dose Magnesium Sulfate Research Articles

Prolonged neuromuscular blockade and insufficient reversal after sugammadex administration in cesarean section under general anesthesia: a case report

BackgroundWe present a rare case of prolonged neuromuscular blockade and insufficient reversal after sugammadex administration in a pregnant patient being treated with magnesium sulfate and nifedipine undergoing cesarean section under general anesthesia.Case presentationA 37-year-old woman at 34 weeks gestation, weighing 42.5 kg, and receiving magnesium sulfate 94 mg/kg for preeclampsia and nifedipine 20 mg, underwent cesarean section under general anesthesia for abruptio placentae. Her trachea was intubated after administering rocuronium 0.94 mg/kg. Postoperatively, sugammadex 4.7 mg/kg was administered at post-tetanic count 2, 163 min after rocuronium administration. However, 9 min after sugammadex administration, the train-of-four ratio only reached 0.7. Fifteen min after sugammadex administration, extubation was successfully performed when the train-of-four ratio reached 0.9 after administration of atropine 0.5 mg and neostigmine 1.0 mg.ConclusionsCaution is required in pregnant women on high-dose magnesium sulfate with nifedipine, which may cause prolongation of neuromuscular blockade and insufficient reversal.

Magnesium sulphate and perinatal mortality and morbidity in very-low-birthweight infants born between 24 and 32 weeks of gestation in Japan

ObjectiveMaternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose–response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation. Study designA retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate. ResultsJapanese maternal and neonatal databases were linked using six key parameters from 2003 to 2007. Of 298,514 deliveries, 9101 were very-low-birthweight infants. Among these, full matching was possible for 5562 infants. Of the fully-matched infants, 3763 were born between 24 and 32 weeks of gestation, and 1813 (48%) were followed-up beyond 18 months. A multivariate analysis of the data, including gestational age, sex, fetal growth restriction, antenatal steroids and low pH (<7.1), showed that the low-dose group had no beneficial effects in terms of a reduction in mortality or incidence of brain damage (cerebral palsy or mental retardation). The high-dose group showed a significantly higher mortality rate [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.2–2.9]. A stratified subgroup analysis of infants born between 28 and 32 weeks of gestation showed that survivors in the low-dose group had significantly lower rates of cerebral palsy (OR 0.4, 95% CI 0.2–0.98) and brain damage (OR 0.2, 95% CI 0.1–0.9), while the high-dose group did not show any significant changes. ConclusionThis study found that antepartum exposure to magnesium sulphate did not reduce the infant mortality rate or influence neurological outcomes. However, among infants born between 28 and 32 weeks of gestation, rates of cerebral palsy and brain damage were found to be significantly lower among survivors in the low-dose group.

High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study.

To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma. Prospective, randomized, open-label study. Twenty-nine-bed pediatric emergency department located in a children's hospital in Asuncion, Paraguay. All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma. Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications. Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events. The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4 hr), for non-infectious mediated asthma, expedites discharges from the emergency department with significant reduction in healthcare cost.

Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour.

Different treatment regimens of magnesium sulphate for tocolysis in women in preterm labour.

High-dose magnesium sulfate infusion protocol for status asthmaticus: a safety and pharmacokinetics cohort study

To assess the safety and pharmacokinetics of high-dose magnesium sulfate (MgSO(4)) infusion in pediatric patients with status asthmaticus. A prospective cohort study within a 20-bed pediatric intensive care unit in an academic community hospital. Patients 2-18 years of age admitted with status asthmaticus between 10/2009 and 8/2010 were included in the study. All patients received standard therapy for asthma, while the treatment group received an intravenous magnesium sulfate bolus of 50-75 mg/kg (0.2-0.3 mmol/kg) followed by 40 mg/kg/h (0.16 mmol/kg/h) for 4 h. Patients were monitored for cardiorespiratory complications. The treatment group underwent four blood draws to assess pharmacokinetic parameters. Nineteen patients were in the treatment group and 38 patients in the control group after exclusion criteria and consenting were completed. No clinically significant differences were found between groups. There were no interventions or discontinuations of MgSO(4) due to adverse events. In the treatment group, three patients had mild infusion-related reactions. Heart rate and respiratory rate were statistically significantly lower in the magnesium treatment group. The continuous infusions of MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and ionized magnesium levels similar to levels required to produce smooth muscle relaxation in other clinical settings. Further studies are needed to investigate the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment for severe asthma treatment and determine the SrMg level required to maintain airway smooth muscle relaxation.

Feasibility of Short-Term Infusion of Magnesium Sulfate in Pediatric Patients With Status Asthmaticus

This report describes the feasibility of high-dose magnesium sulfate infusion in pediatric patients with status asthmaticus. Retrospective chart review over a 3-year period of all patients younger than 18 years of age with status asthmaticus who underwent a high-dose magnesium sulfate infusion for 4 hours. All patients were breathing spontaneously but were refractory to conventional therapy. The magnesium sulfate infusion regimen was 50 mg/kg (for patients weighing >30 kg) or 75 mg/kg (for those weighing ≤30 kg) over a period of 30 to 45 minutes, followed by a continuous infusion of 40 mg/kg/hr for 4 hours. Information regarding vital and clinical respiratory signs, serum magnesium (SrMg), ionized magnesium (iMg), electrocardiograms, and cardiac troponin levels were retrieved. We analyzed the relationship between SrMg and iMg by using linear regression analysis. Nineteen patients were included. At the end of the infusion, SrMg levels were 4.4 ± 0.8 mg/dL, and iMg levels were 0.95 ± 0.2 mmol/L. SrMg levels only moderately predicted iMg (r(2) = 0.541). There were no reports of hypotension, respiratory failure, neurological problems, or nausea. Discomfort at the site of infusion was reported in three cases. Troponin levels (n = 12) and electrocardiograms (n = 12), when available, were noted at the end of the infusion and were normal in all patients p=0.01. In this case series, short-term high-dose administration of magnesium sulfate in the context of status asthmaticus was feasible, and we did not observe clinical complications with its use. Total SrMg was inadequate to reflect the active form of magnesium, iMg. The dose used achieved theoretical therapeutic levels of iMg.

Magnesium and the inflammatory response: potential pathophysiological implications in the management of patients with aneurysmal subarachnoid hemorrhage?

Cerebral vasospasm and delayed cerebral ischemia remain an unsolved problem in patients with aneurysmal subarachnoid hemorrhage (SAH). In theory, high-dose magnesium sulfate (MgSO(4)) therapy offers vascular and neuroprotective benefits and is therefore currently under evaluation. The intensity of the inflammatory response after SAH is associated with the outcome. The aim of the current study was to evaluate a possible link between the inflammatory response and MgSO(4) therapy, since magnesium (Mg(2+)) has anti-inflammatory properties. In 15 patients with SAH, inflammatory cytokine levels in the cerebrospinal fluid (CSF) and peripheral blood were determined daily using an enzyme-linked immunosorbent assay between day 4 and day 12. Eight patients were treated with standard therapy alone (group 1) and seven patients were treated with an additional, high-dose of MgSO(4) (group 2). Serum Mg(2+) levels in group 2 were significantly higher compared to group 1: 1.48 ± 0.04 mmol/L versus 0.90 ± 0.01 mmol/L, ρ<0.001. Interleukin-6 (IL-6) in the CSF was significantly lower in group 2 compared to group 1: 6680 ± 989 vs.11079 ± 1277 pg/mL, ρ = 0.021. A trend towards lower systemic IL-6 levels was found in group 2: 58 ± 7 versus 104 ± 21 pg/mL, ρ = 0.052. Systemic IL-1β levels were significantly lower in group 2: 0.66 ± 0.11 and 0.15 ± 0.01 pg/mL (ρ<0.001), while the CSF levels did not differ. Tumor necrosis factor-α levels did not differ between the two groups. Although there were more patients with favorable outcome in group 2, the difference was not statistically significant. This was probably due to the small sample size. The results indicate a suppression of inflammatory cytokine release, in particular IL-6, in patients treated with high-dose MgSO(4). These results call for further studies of the effect of Mg(2+) on the inflammatory signaling pathway with regard to delayed cerebral ischemia following SAH.

Immediate clinical outcomes in preterm neonates receiving antenatal magnesium for neuroprotection

Antenatal magnesium sulfate can potentially reduce the risk of cerebral palsy in neonates delivered between 24 and 32 weeks of gestational age. Some studies using high-dose magnesium sulfate for neuroprotection have reported increased perinatal mortality. A retrospective study was conducted on 475 neonates born between 24 and 32 weeks of gestational age. Serum magnesium level in the first 24 h of life was used to stratify the neonates treated with antenatal magnesium into four subgroups: A (<2.5 mEq/L), B (≥2.5 to <3.5 mEq/L), C (≥3.5 to <4.5 mEq/L), and D (≥4.5 mEq/L). Primary outcome of survival without intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) along with secondary outcomes, such as Apgar scores, resuscitation, intubation, broncho-pulmonary dysplasia, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), time to reach full feeds, length of stay (LOS), and mortality during immediate neonatal period were studied. Of the 475 neonates included in the study, 289 (61%) received antenatal magnesium sulfate. Primary outcome of survival without IVH and/or PVL among the preterm neonates was 70.9% in those receiving and 74.2% in those not receiving antenatal magnesium (P=0.25). There were higher incidences of ROP (P=0.02), PDA (P=0.01), greater time to reach full feeds (P=0.03), and increased LOS (P=0.01) in neonates who had received antenatal magnesium. These findings were not statistically significant when the data were corrected for gestational age and birth weight. Among the subgroups, there was a significantly increased mortality rate (P<0.05) with increasing magnesium levels (5% vs. 16.9%, P<0.05 in groups A vs. D) and a trend toward higher intubation rate (P=0.1) and PDA (P=0.14). Antenatal magnesium is safe in the immediate postnatal period; however, in the subset of preterm neonates with serum magnesium levels >4.5 mEq/L, there is increased mortality independent of birth weight and gestational age. Identification of these neonates and appropriate dosing for their antenatal neuroprotection needs to be studied.

Magnesium Sulfate Therapy for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Object As magnesium is a potent cerebral vasodilator, we have investigated routine supplementation of magnesium (as a potent cerebral vasodilator) in patients presented with aneurysmal subarachnoid hemorrhage (ASAH) to determine whether there has been a reduction in the incidence of cerebral vasospasm. Materials and Methods A prospective randomized, placebo-controlled, clinical trial of high-dose magnesium sulfate (MgSO4) therapy after ASAH was performed in 83 patients. MgSO4 was administered intravenously as soon as possible after admission and continued until 10 days after occlusion of the aneurysm. Blood magnesium levels were obtained daily during MgSO4 therapy. Outcome measures including the evidence of vasospasm on clinical examination using transcranial Doppler ultrasonographic recordings, or control angiogram within 10 days after occlusion of the aneurysm, were obtained. The clinical outcomes were recorded using Glasgow Outcome Scale (GOS) at 3 months. Results Eighty-three patients were enrolled in the study: 40 (12 male and 28 female patients) received MgSO4 therapy and 43 (20 male and 23 female patients) comprised placebo-treated patients. The mean ages of the patients in these groups were 54 and 53 and the mean Fisher, Hunt and Hess grades were 3.02±0.97, 2.50±1.03 and 2.95±0.95, 2.32±0.96 in the treatment and control groups, respectively. The mean serum magnesium and calcium levels were 1.54±0.72, 8.24±0.94 and 0.88±0.13, 8.64±0.13 in the treatment and control groups, respectively. Ten out of 40 patients who received MgSO4 therapy developed symptomatic vasospasm, confirmed by angiography and transcranial Doppler ultrasonography, compared with 14 of 43 patients among the control group (P=0.54). The mean GOS were 3.80±1.5 and 4.11±1.43 in the treatment and control groups, respectively P=0.78. Conclusions From our study, it appears that MgSO4 therapy has no statistically significant beneficial role in the prevention of cerebral vasospasm after ASAH. We did observe, however, that the ultimate GOS was better in the treatment group than in the control group. To assess the safety and effectiveness of high-dosage MgSO4 therapy or the adverse effects, large randomized, placebo-controlled, and double-blind clinical trials are needed.

Does magnesium sulfate reduce the short- and long-term requirements for pain relief after caesarean delivery? A double-blind placebo-controlled trial

The purpose of this study was to determine whether magnesium sulfate decreases postoperative pain and analgesic consumption. Women who underwent elective cesarean delivery were randomized into groups according to high-dose magnesium sulfate (50 mg/kg load and 2 g/h), low-dose magnesium sulfate (25 mg/kg load and 1 g/h), or placebo. Before the delivery, the dose of patient-controlled opioid that was used and the visual analogs of pain during the first 48 hours after delivery and at 6 weeks were assessed. Forty-two women were assigned randomly to the high-dose arm; 38 women were assigned to the low-dose magnesium arms, and 40 women were assigned to the control arm. The cumulative opioid use (P = .636); pain scores at 6, 12, 24, and 48 hours at rest (P = .786) and with movement (P = .179); the use of analgesics after hospital discharge (P = .711); and wound pain with movement (P = .429) or pressure (P = .144) after 6 weeks were similar. Magnesium sulfate does not reduce the severity of short-term or long-term (6 weeks) pain after cesarean delivery.

Brain lesions in newborns exposed to high-dose magnesium sulfate during preterm labor

High-dosage, tocolytic magnesium sulfate (MgSO4) administered to pregnant women during preterm labor can be toxic, and sometimes lethal, for their newborns (Cochrane Database of Systematic Reviews (relative mortality risk 2.82, 95% confidence interval 1.2-6.6)). Based on the results of the Magnesium and Neurologic Endpoints Trial and the work of many others, a unifying triangular concept is proposed to account for the increased prevalence of brain lesions, with their likely resultant mortality, in neonates and infants exposed to high-dose MgSO4 in the context of preterm labor. We review the evidence that: (1) elevated circulating levels of serum ionized magnesium occurring in mothers, and therefore in their babies, at the time of delivery are associated with subsequent neonatal intraventricular hemorrhage (IVH); (2) neonatal IVH is strongly associated with lenticulostriate vasculopathy (LSV), an unusual mineralizing lesion involving the thalami and basal ganglia of the neonate; and, (3) exposure to 50 g or more of tocolytic MgSO4 during preterm labor is associated with the development of LSV.

Increased risk of perinatal death with high-dose magnesium sulfate

Increased risk of perinatal death with high-dose magnesium sulfate

Increased risk of perinatal death with high-dose magnesium sulfate

Increased risk of perinatal death with high-dose magnesium sulfate

Proarrhythmia With Class III Antiarrhythmic Drugs: Types, Risks, and Management

The nature of the proarrhythmic reactions induced by antiarrhythmic drugs is linked to the electrophysiologic effects of these agents. Torsades de pointes is the classic form of proarrhythmia observed during therapy with any drug that prolongs repolarization, for example, the class III agents. Its precise electrophysiologic mechanism is not fully elucidated, although the arrhythmia is generally considered to be due either to early afterdepolarization in the context of prolonged cardiac repolarization or to an increase in spatial or temporal dispersion of repolarization. Among the class III drugs the proarrhythmic risk appears to be lowest for amiodarone, probably due to its complex electrophysiologic profile that may create significant myocardial electrical homogeneity. In the case of d,l-sotalol, the incidence of torsades de pointes increases with dose and the baseline values of the QT interval. Where d-sotalol and other pure class III agents might fall into the varying spectrum of proarrhythmic potential remains unclear. That d-sotalol has been found to increase mortality in postinfarction patients with ventricular dysfunction (the Survival With Oral d-Sotalol [SWORD] trial) is a matter of considerable concern. It raises the possibility that such a phenomenon may be a common property of most, if not all, pure class III compounds. Accordingly, care must be taken to minimize the likelihood of proarrhythmia; in particular, therapy with a class III agent should only be initiated in the presence of a defined indication established on the basis of clinical trials. When class III antiarrhythmic drug-induced proarrhythmia occurs, immediate cessation of therapy with the responsible agent and correction of predisposing factors, such as electrolyte disorders or bradycardia, is mandatory. Intravenous administration of high-dose magnesium sulfate has been demonstrated to be effective in terminating and preventing new episodes of torsades de pointes. Temporary pacing may be necessary.

Favorable hemodynamic effects of magnesium sulfate in preeclampsia

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of magnesium sulfate in preeclamptic and preterm labor patients. STUDY DESIGN: Fifteen preeclamptic patients at 32.4 ± 3.3 (mean ± SD) weeks' gestation and 11 preterm labor patients (31.3 ± 2.8 weeks) were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance (BoMed, Irvine, Calif.) before and during high-dose magnesium sulfate bolus and infusion. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during magnesium sulfate infusion. All patients received a standard crystalloid infusion. Data analysis continued until the patient received epidural placement or other antihypertensive therapy or was delivered. RESULTS: At baseline the systemic vascular resistance index was 2465 ± 718 F · ohm/m 2 and the cardiac index was 3.6 ± 1.0 L/min/m 2 for the preeclamptic patients. These were significantly different compared with the preterm labor patients, who had a systemic vascular resistance index of 1377 ± 563 F · ohm/m 2 and 4.6 ± 1.2 L/min/m 2. Magnesium sulfate infusion resulted in a rapid, sustained fall in systemic vascular resistance and a rise in cardiac index in the preeclamptic patient. This effect was evident at least 4 hours after initiation of the bolus and infusion. In the preterm labor patients the hemodynamic effects of magnesium sulfate were minimal and were noted only during the magnesium sulfate bolus. CONCLUSION: Magnesium sulfate infusion appears to have a prolonged hemodynamic effect in the preeclamptic patient. Sustained reduction in systemic vascular resistance and an increase in cardiac index is found in patients with preeclampsia but not in preterm labor.

High-dose intravenous magnesium sulfate in the management of life-threatening status asthmaticus — authors' reply

High-dose intravenous magnesium sulfate in the management of life-threatening status asthmaticus — authors' reply