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Association Between Intravenous Magnesium Therapy in the Emergency Department and Subsequent Hospitalization Among Pediatric Patients With Refractory Acute Asthma: Secondary Analysis of a Randomized Clinical Trial.
Schuh, S, Freedman, SB, Zemek, R, Plint, AC, Johnson, DW, Ducharme, F, Gravel, J, Thompson, G, Curtis, S, Stephens, D, et al
JAMA network open. 2021;(7):e2117542
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IMPORTANCE Despite guidelines recommending administration of intravenous (IV) magnesium sulfate for refractory pediatric asthma, the number of asthma-related hospitalizations has remained stable, and IV magnesium therapy is independently associated with hospitalization. OBJECTIVE To examine the association between IV magnesium therapy administered in the emergency department (ED) and subsequent hospitalization among pediatric patients with refractory acute asthma after adjustment for patient-level variables. DESIGN, SETTING, AND PARTICIPANTS This post hoc secondary analysis of a double-blind randomized clinical trial of children with acute asthma treated from September 26, 2011, to November 19, 2019, at 7 Canadian tertiary care pediatric EDs was conducted between September and November 2020. In the randomized clinical trial, 816 otherwise healthy children aged 2 to 17 years with Pediatric Respiratory Assessment Measure (PRAM) scores of 5 points or higher after initial therapy with systemic corticosteroids and inhaled albuterol with ipratropium bromide were randomly assigned to 3 nebulized treatments of albuterol plus either magnesium sulfate or 5.5% saline placebo. EXPOSURES Intravenous magnesium sulfate therapy (40-75 mg/kg). MAIN OUTCOMES AND MEASURES The association between IV magnesium therapy in the ED and subsequent hospitalization for asthma was assessed using multivariable logistic regression analysis. Analyses were adjusted for year epoch at enrollment, receipt of IV magnesium, PRAM score after initial therapy and at ED disposition, age, sex, duration of respiratory distress, previous intensive care unit admission for asthma, hospitalizations for asthma within the past year, atopy, and receipt of oral corticosteroids within 48 hours before arrival in the ED, nebulized magnesium, and additional albuterol after inhaled magnesium or placebo, with site as a random effect. RESULTS Among the 816 participants, the median age was 5 years (interquartile range, 3-7 years), 517 (63.4%) were boys, and 364 (44.6%) were hospitalized. A total of 215 children (26.3%) received IV magnesium, and 190 (88.4%) of these children were hospitalized compared with 174 of 601 children (29.0%) who did not receive IV magnesium. Multivariable factors associated with hospitalization were IV magnesium receipt from 2011 to 2016 (odds ratio [OR], 22.67; 95% CI, 6.26-82.06; P < .001) and from 2017 to 2019 (OR, 4.19; 95% CI, 1.99-8.86; P < .001), use of additional albuterol (OR, 5.94; 95% CI, 3.52-10.01; P < .001), and increase in PRAM score at disposition (per 1-U increase: OR, 2.24; 95% CI, 1.89-2.65; P < .001). In children with a disposition PRAM score of 3 or lower, receipt of IV magnesium therapy was associated with hospitalization (OR, 8.52; 95% CI, 2.96-24.41; P < .001). CONCLUSIONS AND RELEVANCE After adjustment for patient-level characteristics, receipt of IV magnesium therapy after initial asthma treatment in the ED was associated with subsequent hospitalization. This association also existed among children with mild asthma at ED disposition. Evidence of a benefit of IV magnesium regarding hospitalization may clarify its use in the treatment of refractory pediatric asthma. TRIAL REGISTRATION ClinicalTrials.gov: NCT01429415.
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A Safety and Efficacy Comparison of a New Sulfate-Based Tablet Bowel Preparation Versus a PEG and Ascorbate Comparator in Adult Subjects Undergoing Colonoscopy.
Di Palma, JA, Bhandari, R, Cleveland, MV, Mishkin, DS, Tesoriero, J, Hall, S, McGowan, J
The American journal of gastroenterology. 2021;(2):319-328
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INTRODUCTION A new tablet-based bowel prep for colonoscopy has been developed containing poorly absorbed sulfate salts which act to retain water within the intestinal lumen resulting in a copious diarrhea, thereby cleansing the bowel. This study evaluated the safety and efficacy of these oral sulfate tablets (OST) compared with a US FDA-approved bowel prep solution containing PEG3350, electrolytes, and ascorbate (polyethylene glycol and ascorbate [PEG-EA]). METHODS Five hundred fifteen adult patients (mean 57y) were enrolled in this single-blind, multicenter, noninferiority study. Subjects were assigned either PEG-EA or OST to be administered in a split-dose regimen starting the evening before colonoscopy. PEG-EA was taken according to its approved labeling (1 L of prep solution with 16 oz. of additional water) in the evening and again in the morning. OST patients took a total of 24 tablets. OST patients were administered 12 tablets in the evening, and the following morning. Patients consumed 16 ounces of water with each dose of 12 tablets and drank an additional 32 oz. of water with each dose. Colonoscopies were performed by blinded investigators. Cleansing efficacy was evaluated globally and segmentally using a 4-point scale (Excellent-no more than small bits of feces/fluid which can be suctioned easily; achieves clear visualization of the entire colonic mucosa. Good-feces and fluid requiring washing and suctioning, but still achieves clear visualization of the entire colonic mucosa. Fair-enough feces even after washing and suctioning to prevent clear visualization of the entire colonic mucosa. Poor-large amounts of fecal residue and additional bowel preparation required). Scores of Good or Excellent were considered to be a success. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. RESULTS A high rate of cleansing success was seen with OST (92%), which was noninferior to PEG-EA (89%). Only a small proportion of subjects rated their expected gastrointestinal symptoms as severe (<5% for both preps). No clinically significant differences were seen between preps for chemistry and hematology parameters. No serious adverse experiences were reported with OST. DISCUSSION Sulfate tablets achieved a high level of cleansing in the study, comparable with US FDA-approved preps. OST was noninferior to PEG-EA in this study and achieved significantly more Excellent preps overall and in the proximal colon. The OST prep was well-tolerated, with a similar rate of spontaneously reported adverse experiences to PEG-EA and a low rate of severe expected gastrointestinal symptoms.
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Prenatal Tobacco Exposure and Childhood Neurodevelopment among Infants Born Prematurely.
Robbins, LS, Blanchard, CT, Sinkey, RG, Harris, SL, Tita, AT, Harper, LM
American journal of perinatology. 2021;(3):218-223
Abstract
OBJECTIVE Nicotine is an established neuroteratogen, and prenatal tobacco exposure alters the structure of the developing nervous system. An association between prenatal tobacco exposure and impaired neurologic function is less well established. We examine the association between prenatal tobacco exposure and childhood neurodevelopment among infants born preterm. STUDY DESIGN Secondary analysis of a multicenter randomized controlled trial assessing the benefits of magnesium sulfate for the prevention of cerebral palsy in preterm infants. Women were included if they delivered a singleton and nonanomalous infant before 37 weeks. Exposure was any self-reported prenatal tobacco use. Primary outcome was the original trial composite outcome of moderate or severe cerebral palsy at 2 years of age, or stillbirth, or infant death by 1 year of age. Secondary outcomes included components of the composite and mild cerebral palsy at 2 years, Bayley Scales of Infant Development II motor and mental scores, death before two years, and use of auditory aids or corrective lenses. Multivariable logistic regression models were performed to estimate adjusted odds ratios (aOR) with 95% confidence intervals. RESULTS Of 1,826 women included, 503 (27.5%) used tobacco. Tobacco users were more likely to be older, unmarried, and white; have a prior preterm birth; have received no prenatal care; and to use illicit drugs or alcohol. Gestational age at delivery, betamethasone exposure, and magnesium exposure were not different between groups. There were no differences in the composite primary outcome or in rates of cerebral palsy by tobacco use. Moderate developmental delay was more common among tobacco exposed in bivariate but not adjusted analysis (20.5 vs. 15.9%, p = 0.035). In adjusted analysis, tobacco exposure was associated with increased use of corrective lenses (5.0 vs. 2.9%, aOR: 2.28, 95% confidence interval: 1.28-4.07). CONCLUSION Prenatal tobacco exposure is not associated with neurodevelopmental impairment in infants born preterm. However, tobacco exposure may be associated with impaired vision. KEY POINTS · Tobacco exposure is not associated with impaired neurodevelopment in this preterm population.. · Prenatal tobacco exposure is associated with increased need for corrective lenses.. · Tobacco use in pregnancy may be a risk factor for poorer visual acuity in children..
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Association of Antenatal Corticosteroids and Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm Children.
Gentle, SJ, Carlo, WA, Tan, S, Gargano, M, Ambalavanan, N, Chawla, S, Bell, EF, Bann, CM, Hintz, SR, Heyne, RJ, et al
Obstetrics and gynecology. 2020;(6):1377-1386
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OBJECTIVE To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone. METHODS This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics. RESULTS Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups. CONCLUSION In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00063063.
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Low-dose Magnesium Sulfate Versus High Dose in the Early Management of Rapid Atrial Fibrillation: Randomized Controlled Double-blind Study (LOMAGHI Study).
Bouida, W, Beltaief, K, Msolli, MA, Azaiez, N, Ben Soltane, H, Sekma, A, Trabelsi, I, Boubaker, H, Grissa, MH, Methemem, M, et al
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2019;(2):183-191
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OBJECTIVES We aim to determine the benefit of two different doses magnesium sulfate (MgSO4 ) compared to placebo in rate control of rapid atrial fibrillation (AF) managed in the emergency department (ED). METHODS We undertook a randomized, controlled, double-blind clinical trial in three university hospital EDs between August 2009 and December 2014. Patients > 18 years with rapid AF (>120 beats/min) were enrolled and randomized to 9 g of intravenous MgSO4 (high-dose group, n = 153), 4.5 g of intravenous MgSO4 (low-dose group, n = 148), or serum saline infusion (placebo group, n = 149), given in addition to atrioventricular (AV) nodal blocking agents. The primary outcome was the reduction of baseline ventricular rate (VR) to 90 beats/min or less or reduction of VR by 20% or greater from baseline (therapeutic response). Secondary outcome included resolution time (defined as the elapsed time from start of treatment to therapeutic response), sinus rhythm conversion rate, and adverse events within the first 24 hours. RESULTS At 4 hours, therapeutic response rate was higher in low- and high-MgSO4 groups compared to placebo group; the absolute differences were, respectively, 20.5% (risk ratio [RR] = 2.31, 95% confidence interval [CI] = 1.45-3.69) and +15.8% (RR = 1.89, 95% CI = 1.20-2.99). At 24 hours, compared to placebo group, therapeutic response difference was +14.1% (RR = 9.74, 95% CI = 2.87-17.05) with low-dose MgSO4 and +10.3% (RR = 3.22, 95% CI = 1.45-7.17) with high-dose MgSO4 . The lowest resolution time was observed in the low-dose MgSO4 group (5.2 ± 2 hours) compared to 6.1 ± 1.9 hours in the high-dose MgSO4 group and 8.4 ± 2.5 hours in the placebo group. Rhythm control rate at 24 hours was significantly higher in the low-dose MgSO4 group (22.9%) compared to the high-dose MgSO4 group (13.0%, p = 0.03) and the placebo group (10.7%). Adverse effects were minor and significantly more frequent with high-dose MgSO4 . CONCLUSIONS Intravenous MgSO4 appears to have a synergistic effect when combined with other AV nodal blockers resulting in improved rate control. Similar efficacy was observed with 4.5 and 9 g of MgSO4 but a dose of 9 g was associated with more side effects.
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Antenatal Exposure to Magnesium Sulfate and Spontaneous Intestinal Perforation and Necrotizing Enterocolitis in Extremely Preterm Neonates.
Shalabi, M, Mohamed, A, Lemyre, B, Aziz, K, Faucher, D, Shah, PS, ,
American journal of perinatology. 2017;(12):1227-1233
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Which intravenous bronchodilators are being administered to children presenting with acute severe wheeze in the UK and Ireland?
Morris, I, Lyttle, MD, O'Sullivan, R, Sargant, N, Doull, IJ, Powell, CV, ,
Thorax. 2015;(1):88-91
Abstract
During a prospective 10-week assessment period, 3238 children aged 1-16 years presented with acute wheeze to Paediatric Emergency Research in the UK and Ireland centres. 110 (3.3%) received intravenous bronchodilators. Intravenous magnesium sulfate (MgSO4) was used in 67 (60.9%), salbutamol in 61 (55.5%) and aminophylline in 52 (47.3%) of cases. In 35 cases (31.8%), two drugs were used together, and in 18 cases (16.4%), all three drugs were administered. When used sequentially the most common order was salbutamol, then MgSO4, then aminophylline. Overall, 30 different intravenous treatment regimens were used varying in drugs, dose, rate and duration.
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Effects of intravenous infusion of hydrogen-rich fluid combined with intra-cisternal infusion of magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.
Takeuchi, S, Mori, K, Arimoto, H, Fujii, K, Nagatani, K, Tomura, S, Otani, N, Osada, H, Wada, K
BMC neurology. 2014;:176
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BACKGROUND The failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage. METHODS This study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers. DISCUSSION The present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy. TRIAL REGISTRATION UMIN-CTR: UMIN000014696.
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School-age outcomes of very preterm infants after antenatal treatment with magnesium sulfate vs placebo.
Doyle, LW, Anderson, PJ, Haslam, R, Lee, KJ, Crowther, C, ,
JAMA. 2014;(11):1105-13
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IMPORTANCE Antenatal magnesium sulfate given to pregnant women at imminent risk of very preterm delivery reduces the risk of cerebral palsy in early childhood, although its effects into school age have not been reported from randomized trials. OBJECTIVE To determine the association between exposure to antenatal magnesium sulfate and neurological, cognitive, academic, and behavioral outcomes at school age. DESIGN, SETTING, AND PARTICIPANTS The ACTOMgSO4 was a randomized clinical trial conducted in 16 centers in Australia and New Zealand, comparing magnesium sulfate with placebo given to pregnant women (n = 535 magnesium; n = 527 placebo) for whom imminent birth was planned or expected before 30 weeks' gestation. Children who survived from the 14 centers who participated in the school-age follow-up (n = 443 magnesium; n = 424 placebo) were invited for an assessment at 6 to 11 years of age between 2005 and 2011. MAIN OUTCOMES AND MEASURES Mortality, cerebral palsy, motor function, IQ, basic academic skills, attention and executive function, behavior, growth, and functional outcomes. Main analyses were imputed for missing data. RESULTS Of the 1255 fetuses known to be alive at randomization, the mortality rate to school age was 14% (88/629) in the magnesium sulfate group and 18% (110/626) in the placebo group (risk ratio [RR], 0.80; 95% CI, 0.62-1.03, P = .08). Of 867 survivors available for follow-up, outcomes at school age (corrected age 6-11 years) were determined for 669 (77%). Comparing the magnesium sulfate and placebo groups revealed no statistically significant difference in proportions with cerebral palsy (23/295 [8%] and 21/314 [7%], respectively; odds ratio [OR], 1.26; 95% CI, 0.84-1.91; P = .27) or abnormal motor function (80/297 [27%] and 80/300 [27%], respectively; OR, 1.16; 95% CI, 0.88-1.52; P = .28). There was also little difference between groups on any of the cognitive, behavioral, growth, or functional outcomes. CONCLUSIONS AND RELEVANCE Magnesium sulfate given to pregnant women at imminent risk of birth before 30 weeks' gestation was not associated with neurological, cognitive, behavioral, growth, or functional outcomes in their children at school age, although a mortality advantage cannot be excluded. The lack of long-term benefit requires confirmation in additional studies. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12606000252516.
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Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial.
Goodacre, S, Cohen, J, Bradburn, M, Gray, A, Benger, J, Coats, T, ,
The Lancet. Respiratory medicine. 2013;(4):293-300
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BACKGROUND Previous studies suggested intravenous or nebulised magnesium sulphate (MgSO(4)) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO(4) improve symptoms of breathlessness and reduce the need for hospital admission in adults with severe acute asthma. METHODS In our double-blind, placebo-controlled trial, we enrolled adults (aged ≥16 years) with severe acute asthma at emergency departments of 34 hospitals in the UK. We excluded patients with life-threatening features or contraindication to study drugs. We used a central randomisation system to allocate participants to intravenous MgSO(4) (2 g in 20 min) or nebulised MgSO(4) (three 500 mg doses in 1 h) alongside standard therapy including salbutamol, or placebo control plus standard therapy alone. We assessed two primary outcome measures in all eligible participants who started treatment, according to assigned treatment group: the proportion of patients admitted to hospital within 7 days and breathlessness measured on a 100 mm visual analogue scale (VAS) in the 2 h after initiation of treatment. We adjusted for multiple testing using Simes's method. The trial stopped before recruitment was completed because funding expired. This study is registered, number ISRCTN04417063. FINDINGS Between July 30, 2008, and June 30, 2012, we recruited 1109 (92%) of 1200 patients proposed by the power calculation. 261 (79%) of 332 patients allocated nebulised MgSO(4) were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO(4) and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO(4), 357 (91%) patients allocated intravenous MgSO(4), and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO(4) compared with controls or between those treated with nebulised MgSO(4) and intravenous MgSO(4). Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO(4) group than it was in the nebulised MgSO(4) group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO(4) did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO(4) was associated with an odds ratio of 0·73 (95% CI 0·51 to 1·04; p=0·083) for hospital admission and a change in VAS breathlessness of 2·6 mm (-1·6 to 6·8; p=0·231) compared with placebo; nebulised MgSO(4) was associated with an odds ratio of 0·96 (0·65 to 1·40; p=0·819) for hospital admission and a change in VAS breathlessness of -2·6 mm (-7·0 to 1·8; p=0·253) compared with placebo. INTERPRETATION Our findings suggest nebulised MgSO(4) has no role in the management of severe acute asthma in adults and at best suggest only a limited role for intravenous MgSO(4) in this setting. FUNDING UK National Institute for Health Research Health Technology Assessment Programme.