Quality improvement interventions to increase the uptake of magnesium sulphate in preterm deliveries for the prevention of cerebral palsy (PReCePT study): a cluster randomised controlled trial.

OBJECTIVE: To compare two quality improvement (QI) interventions to improve antenatal magnesium sulphate (MgSO4 ) uptake in preterm births for the prevention of cerebral palsy. DESIGN: Unblinded cluster randomised controlled trial. SETTING: Academic Health Sciences Network, England, 2018. SAMPLE: Maternity units with ≥10 preterm deliveries annually and MgSO4 uptake of ≤70%; 40 (27 NPP, 13 enhanced support) were included (randomisation stratified by MgSO4 uptake). METHODS: The National PReCePT Programme (NPP) gave maternity units QI materials (clinical guidance, training), regional support, and midwife backfill funding. Enhanced support units received this plus extra backfill funding and unit-level QI coaching. MAIN OUTCOME MEASURES: MgSO4 uptake was compared using routine data and multivariable linear regression. Net monetary benefit was estimated, based on implementation costs, lifetime quality-adjusted life-years and societal costs. The implementation process was assessed through qualitative interviews. RESULTS: MgSO4 uptake increased in all units, with no evidence of any difference between groups (0.84 percentage points lower uptake in the enhanced group, 95% CI -5.03 to 3.35). The probability of enhanced support being cost-effective was <30%. NPP midwives gave more than their funded hours for implementation. Units varied in their support needs. Enhanced support units reported better understanding, engagement and perinatal teamwork. CONCLUSIONS: PReCePT improved MgSO4 uptake in all maternity units. Enhanced support did not further improve uptake but may improve teamwork, and more accurately represented the time needed for implementation. Targeted enhanced support, sustainability of improvements and the possible indirect benefits of stronger teamwork associated with enhanced support should be explored further.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Comparison of doses of Nebulized Magnesium sulphate as an adjuvant treatment with salbutamol in children with Status Asthmaticus.

Objectives: To compare the response between different doses of nebulized magnesium sulphate along with Salbutamol in children between two to 12 years of age with status asthmaticus. Methods: This single blinded, randomized clinical trial was carried out at the Department of Pediatrics, Dr. Ziauddin University Hospital, Karachi, Pakistan during October 2021 to September 2022. A total of 104 children aged between 2-12 years, with the diagnosis of asthma having "Pediatric Rapid Assessment Measure (PRAM)" score>4 and with reactive airways were included. Children either received three back-to-back nebulization with salbutamol solution only (n=50) or salbutamol and MgSO4 with three different doses (250mg, 500mg or 750mg) after every 20 minutes for 60 minutes. The PRAM score was used as an assessment tool to clinically score asthma. Results: In a total of 104 children, 53 (51.0%) were girls. The mean age was 5.25±2.86 years. No statistically significant difference was found in PRAM scores at baseline (p=0.448) and at 20-minutes (p=0.072) but significant differences were observed at 40-minutes (p=0.009), 60-minutes (p=0.011), 120-minutes (p=0.010), 6-hours (=0.034), 12-hours (p=0.018), 18-hours (p=0.033) and at 24-hours (p=0.029). The reduction in PRAM scores from baseline to 24-hours following treatment among Salbutamol, Salbutamol+ MgSo4 250mg, Salbutamol+ MgSo4 500mg and Salbutamol+ MgSo4 750mg group were 6.53±1.09, 7.22±1.09, 6.85±1.43 and 7.57±1.06 respectively (p=0.007). Conclusion: While children with status asthmaticus managed using salbutamol, with or without nebulized MgSO4, showed improved clinical outcomes, combining salbutamol with higher dosages of nebulized MgSO4 resulted in even greater clinical improvement.Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT04929626.

Enoxaparin sodium combined with magnesium sulfate in the treatment of severe preeclampsia.

Objective: To observe the treatment of severe preeclampsia in newborns with enoxaparin sodium combined with magnesium sulfate. Methods: A retrospective analysis was conducted on the clinical data of 80 patients with severe preeclampsia admitted to Hefei Second People's Hospital, China from January 2019 to December 2020. Treatment records showed that 40 cases received magnesium sulfate treatment (single group), and 40 cases received enoxaparin sodium combined with magnesium sulfate treatment (combination group). Levels of D-dimer, soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PLGF), Apgar scores of newborns delivered before and after treatment were compared. Gestation weeks and incidence of adverse reactions were analyzed. Results: After treatment, levels of D-dimer, sfit-1 and adverse reactions in the combination group were significantly lower than those in the single group (P<0.05), and the level of PLGF, newborn Apgar score and length of gestation were significantly higher than those in the single group (P<0.05). Conclusion: Compared to magnesium sulfate alone, the combination of enoxaparin sodium and magnesium sulfate in the treatment of pregnant women with severe preeclampsia can more effectively regulate the cytokine level of patients, improve pregnancy outcome, and improve neonatal Apgar score. The incidence of adverse reactions is low, making it a safe and efficient treatment modality.

Magnesium sulphate reduces tertiary gliosis but does not improve EEG recovery or white or grey matter cell survival after asphyxia in preterm fetal sheep.

Maternal magnesium sulphate (MgSO4 ) treatment is widely recommended before preterm birth for neuroprotection. However, this is controversial because there is limited evidence that MgSO4 provides long-term neuroprotection. Preterm fetal sheep (104 days gestation; term is 147 days) were assigned randomly to receive sham occlusion with saline infusion (n = 6) or i.v. infusion with MgSO4 (n = 7) or vehicle (saline, n = 6) from 24 h before hypoxia-ischaemia induced by umbilical cord occlusion until 24 h after occlusion. Sheep were killed after 21 days of recovery, for fetal brain histology. Functionally, MgSO4 did not improve long-term EEG recovery. Histologically, in the premotor cortex and striatum, MgSO4 infusion attenuated post-occlusion astrocytosis (GFAP+ ) and microgliosis but did not affect numbers of amoeboid microglia or improve neuronal survival. In the periventricular and intragyral white matter, MgSO4 was associated with fewer total (Olig-2+ ) oligodendrocytes compared with vehicle + occlusion. Numbers of mature (CC1+ ) oligodendrocytes were reduced to a similar extent in both occlusion groups compared with sham occlusion. In contrast, MgSO4 was associated with an intermediate improvement in myelin density in the intragyral and periventricular white matter tracts. In conclusion, a clinically comparable dose of MgSO4 was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival. KEY POINTS: Magnesium sulphate is widely recommended before preterm birth for neuroprotection; however, there is limited evidence that magnesium sulphate provides long-term neuroprotection. In preterm fetal sheep exposed to hypoxia-ischaemia (HI), MgSO4 was associated with attenuated astrocytosis and microgliosis in the premotor cortex and striatum but did not improve neuronal survival after recovery to term-equivalent age, 21 days after HI. Magnesium sulphate was associated with loss of total oligodendrocytes in the periventricular and intragyral white matter tracts, whereas mature, myelinating oligodendrocytes were reduced to a similar extent in both occlusion groups. In the same regions, MgSO4 was associated with an intermediate improvement in myelin density. Functionally, MgSO4 did not improve long-term recovery of EEG power, frequency or sleep stage cycling. A clinically comparable dose of MgSO4 was associated with moderate improvements in white and grey matter gliosis and myelin density but did not improve EEG maturation or neuronal or oligodendrocyte survival.

Neuroprotective effects of magnesium against stress induced by hydrogen peroxide in Wistar rat.

INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of diverse disease states. The present study was designed to examine the effects of magnesium sulphate (MgSO4) against hydrogen peroxide (H2O2) induced behaviour impairment and oxidative damage in rats. MATERIAL AND METHODS: Eighteen rats were equally divided into three groups. The first group was kept as a control. In the second group, H2O2 was given in drinking water at 3% during 5 days. In the third group, rats were subjected to daily administration of H2O2 and MgSO4 (100 mg/kg; b.w) for 5 days. Animals were subjected to behavioural tests (elevated plus maze and open field). At the end of experiment, brains were extracted for oxidative stress biomarkers assessment including levels of malondialdéhyde and hydrogen peroxide and activities of superoxide dismutase and catalase. RESULTS: Our findings showed that H2O2 treated rat exhibited anxiogenic behaviour and the genesis of free radicals in the brain. Magnesium showed amelioration against oxidative stress and significant decrease in anxiety levels. DISCUSSION AND CONCLUSION: Stress is a powerful process that disrupts brain homeostasis by inducing oxidative stress and its appear that magnesium may have potential therapeutic benefits by reducing oxidative stress and inducing anxiolytic effect.

Attenuating the Pressor Response to Laryngoscopy and Endotracheal Intubation in Controlled Hypertensives: The Effect of Combining Lidocaine and Magnesium Sulphate.

BACKGROUND: Laryngoscopy and intubation result in a pressor response which may be deleterious especially in hypertensives, resulting in potentially harmful effects. Many drugs have been used to attenuate this undesirable pressor response to laryngoscopy and intubation in hypertensives; amongst them are magnesium alone in different doses or in combination with lidocaine. However, drug combinations have been found to be more effective than single drug therapy. OBJECTIVE: This study compared the different doses of magnesium sulphate and its combination with lidocaine for the attenuation of the pressor response. METHODS: A prospective, randomized, double-blinded study. Nighty-six controlled hypertensives (ASA physical status II) scheduled for elective surgery under general anaesthesia and who required endotracheal intubation were recruited and randomized into either Group I (they received 30mg/kg of IV MgSO4 plus 1.5mg/kg of 2% lidocaine) or Groups II and III who received 30mg/kg and 40mg/kg of IV MgSO4 alone, respectively. The outcome was the change in the systolic blood pressure (SBP) from the baseline following administration of study medication and after laryngoscopy and endotracheal intubation. The side effects of study medication and changes in serum magnesium level prior to and after 30 minutes of administering study medication were documented. RESULTS: The post-intubation SBP was attenuated in patients in groups I and III only. However, five patients in group III had hypotension. Serum magnesium levels were higher than their respective baseline values in all the groups. CONCLUSION: The combination of 1.5 mg/kg of 2% lidocaine and 30 mg/kg of MgSO4 is more effective than 30 mg/kg of MgSO4 alone and even MgSO4at the higher dose of 40 mg/kg.

CONTEXTE: La laryngoscopie et l'intubation entraînent une réponse pressive, qui peut être délétère, surtout chez les hypertendus, entraînant des effets potentiellement dangereux. De nombreux médicaments ont été utilisés pour atténuer cette réponse pressive indésirable à la laryngoscopie et à l'intubation chez les hypertendus, parmi lesquels le magnésium seul à différentes doses ou en association avec la lignocaïne. Cependant, les associations de médicaments se sont avérées plus efficaces qu'un traitement médicamenteux unique. OBJECTIF: Cette étude a comparé les différentes doses de sulfate de magnésium et son association avec la lidocaïne pour l'atténuation de la réponse pressive. MÉTHODES: Une étude prospective, randomisée, en double aveugle. Six hypertendus contrôlés (statut physique ASA II) prévus pour une chirurgie élective sous anesthésie générale et nécessitant une intubation endotrachéale ont été recrutés et randomisés dans le groupe I, ils ont reçu 30mg/kg de MgSO4 1V plus I,5mg/kg de lidocaïne à 2%, les groupes II et III ont reçu respectivement 30mg/kg et 40mg/kg de MgSO4 IV seul. Les résultats étaient les changements de la pression artérielle systolique (PAS) par rapport à la ligne de base après l'administration du médicament étudié et après la laryngoscopie et l'intubation endotrachéale. Les effets secondaires du médicament à l'étude et les changements du taux de magnésium sérique avant et après 30 minutes d'administration du médicament à l'étude ont été documentés. RÉSULTATS: La PAS après intubation a été atténuée chez les patients des groupes I et III seulement. Cependant, cinq patients du groupe III ont présenté une hypotension. Les niveaux de magnésium sérique étaient plus élevés que leurs valeurs de base respectives dans tous les groupes. CONCLUSION: L'association de 1,5 mg/kg de lidocaïne à 2 % et de 30 mg/kg de MgSO4 est plus efficace que 30 mg/kg de MgSO4 seul et même à la dose supérieure de 40 mg/kg. Mots clés: Sulfate de magnésium, Lidocaïne, Laryngoscopie et intubation endotrachéale, Réponse hémodynamique, Taux sériques de MgSO4.

Factors affecting use of magnesium sulphate for pre-eclampsia or eclampsia: a qualitative evidence synthesis.

BACKGROUND: Hypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO4 remains underused, particularly in low- and middle-income countries (LMICs). OBJECTIVE: This qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO4 to prevent or treat pre-eclampsia/eclampsia. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021. SELECTION CRITERIA: Primary qualitative and mixed-methods studies on factors affecting use of MgSO4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO4 . MAIN RESULTS: We included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation. CONCLUSIONS: These findings can inform policy and guideline development and improve implementation of MgSO4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used. TWEETABLE ABSTRACT: Global qualitative review identifies factors affecting underutilisation of MgSO4 for pre-eclampsia and eclampsia.

Could soluble minerals be hazardous to human health? Evidence from fibrous epsomite.

From a toxicological point of view, particulates and fibres with high solubility in water and/or in biological environments have not been considered in detail and the knowledge to date in this area is very scarce. In this study, the water-soluble natural epsomite fibres from Perticara Mine (Italy) were investigated using SEM-EDS, XRPD, ICP-AES and alpha spectrometry measurements which were combined and integrated to characterise the fibres' morphology, crystal chemistry and mineralogy. The morphological and morphometric results showed that most of the fibres are of inhalable size (Dae 5.09 µm) and can be potentially adsorbed from all parts of the respiratory tract. Chemical analysis reveals significant amounts of toxic elements (As, Co, Fe, Mn, Ni, Sr, Ti, Zn) and surprisingly high contents of radioactive isotopes (210Po and 228Th) in epsomite crystals, making the inhalation of these fibres potentially hazardous to human health. Through this study, we want to focus on soluble minerals, such as epsomite, which can be present in both natural and anthropic environments and have never been considered from the point of view of their potential hazard.

Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study With Magnesium.

OBJECTIVES: Calcium and magnesium are concentration-dependent pro- and anticoagulant cofactors, and magnesium behaves similarly to calcium in the presence of citrate. The authors hypothesized that magnesium can cause clot formation (primary objective) when mixed with coagulation factor-containing blood products diluted with different crystalloids in a rapid- infuser reservoir. A secondary objective was the observation of any infuser alarms and stops in the event of clotting. DESIGN: An experimental in vitro study with blood products, crystalloids, magnesium, and calcium in a rapid infuser with a reservoir using a closed-loop system. SETTING: Anesthesia research laboratory at an urban academic tertiary medical center PARTICIPANTS: Not applicable. INTERVENTIONS: Exposure of fresh frozen plasma (FFP) and packed red blood cells alone (control) or in combination with either normal saline (NS), lactated Ringer's solution (LR), or Plasma-Lyte A (PL) to increasing concentrations of magnesium sulphate (MgSO4) up to 1 g. After each incremental MgSO4 change, the authors applied a specific pump-flow sequence in a closed-loop system with a rapid-infuser reservoir, and if no clot was observed, the authors incrementally added calcium chloride (CaCl2) up to 1 g. MEASUREMENTS AND MAIN RESULTS: Observation of macroscopic clot and time to event, as well as occurrence and type of any pump alarms or stops. LR experiments resulted in clot observation in the reservoir by a dedicated observer after MgSO4 275 ± 206 mg (95% confidence interval [CI], 9-541). Adding MgSO4 1 g in the NS, PL, or the control experiments did not result in clot observation. Only when CaCl2 166.7 ± 51.64 mg (95% CI, 112.0-22.01) was added to the combination of blood products alone or mixed with NS and PL, clotting occurred. The mean FFP volume was 281 ± 48.6 mL (range, 204-340 mL) and was not different between groups (p = 0.44). Pump alarms and stops were inconsistent. CONCLUSIONS: The addition of magnesium to a combination of LR with coagulation factor- containing blood products consistently resulted in a visible blood clot in the rapid-infuser reservoir in the authors' experimental setup. In addition to MgSO4 1 g in the control, NS, and PL experiments, CaCl2 is needed before a clot can be observed.

A retrospective review of the risk factors affecting the therapeutic serum concentrations of magnesium sulfate in pre-eclamptic patients.

WHAT IS KNOWN AND OBJECTIVE: To identify factors that may affect the therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis in pre-eclamptic patients. METHODS: One hundred and two women with PE with severe features were identified categorized into two groups: subtherapeutic and therapeutic group. Multivariate logistic regression analysis and receiver operation characteristic curve analysis were conducted for the risk factors influencing the serum magnesium concentration. RESULTS: Among 102 eligible patients, 63 (62%) patients did not attain ideal therapeutic serum magnesium levels. Those patients had elevated albumin levels (p < 0.05), higher creatinine clearance (Ccr) (p < 0.001), and higher body mass index (BMI) (p < 0.001). Logistic regression analysis identified BMI and Ccr as independent risk factors for subtherapeutic serum magnesium concentration (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for BMI than for Ccr in predicting subtherapeutic serum magnesium levels (0.787 vs. 0.774). WHAT IS NEW AND CONCLUSION: Maternal body weight and renal function were independent risk factors for subtherapeutic serum magnesium concentration in the early stage after administration.

Antenatal magnesium sulphate for preventing cerebral palsy: An economic evaluation of the impact of a quality improvement program.

Previous work demonstrated that implementing a quality improvement (QI) program improves the uptake of guideline-recommended antenatal magnesium sulphate, a critical intervention known to reduce cerebral palsy risk. Here we estimate potential cost savings attributable to the improved uptake. By expanding coverage from 63 to 83% of eligible women, we estimated that five children potentially would not have received a diagnosis of cerebral palsy, a potential cost saving of $AU4.8 million in lifetime healthcare costs. Our findings strengthen the case for embedding QI approaches in perinatal care to reduce the incidence of cerebral palsy.

Prevention of Shivering Post Subarachnoid Block: Comparison between Different Doses of Intravenous Magnesium Sulphate.

Background and Objectives: Shivering is a common complication of subarachnoid block (SAB). Magnesium sulphate has been proven to be effective in preventing shivering. The aim of this study was to compare the effectiveness and adverse effects in hemodynamic parameters between 50 mg/kg and 30 mg/kg of intravenous magnesium sulphate for prevention of shivering post-subarachnoid block. Materials and Methods: Eighty-six patients scheduled for surgery under SAB, aged between 18 to 65 years old with American Society of Anesthesiologists physical status I and II were randomised into two groups. Group A received a bolus of 50 mg/kg, while Group B received 30 mg/kg of intravenous magnesium sulphate, given over a 20 min duration following SAB. Shivering grade was recorded intraoperatively according to the Crossley and Mahajan shivering scale. Mean arterial pressure (MAP), heart rate, tympanic temperature, oxygen saturation and the use of vasopressors were recorded. Results: Forty-five percent of patients in Group A and 20% of patients in Group B did not exhibit shivering (p-value < 0.01). High-grade shivering was observed in 12.5% in Group A and 40% in Group B, respectively (p-value 0.02). The MAP trend was lower in Group B (p-value < 0.01), but the incidence of hypotension was not significant in both groups. The use of vasopressors was also similar between groups. Group B showed a lower oxygen saturation trend (p-value 0.04). The trends of heart rate and tympanic temperature were not significant in both groups. No patients had episodes of bradycardia or oxygen desaturation. Conclusions: In this study, intravenous magnesium sulphate 50 mg/kg is the lowest effective dose for prevention and treatment of high-grade shivering post-SAB without significant hemodynamic adverse events.

Safety and efficacy of Magnesium Sulfate in the management of Tetanus: A systematic review.

Tetanus is a rare life-threatening condition often complicated by repetitive spasms, dysautonomia and neuromuscular respiratory failure contributing to high fatality rates in its severe form. Benzodiazepines used to treat muscle spasms pose a high risk of respiratory failure requiring mechanical ventilation, which is unaffordable and inaccessible for many. Magnesium sulfate, a cheap and widely available medication in all urban and rural health centres of LMICs for the treatment of eclampsia, can be used to control muscle spasms and dysautonomia. We thus conducted a systematic review of evidence to assess the safety and efficacy of magnesium sulfate in the treatment of tetanus. Any study published before April 15, 2021, discussing the efficacy and/or safety of MgSO4 infusion in the treatment of tetanus was systemically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our systematic review included data from 13 studies, three were randomised, double-blind and controlled trials. The remaining ten studies were observational; six prospective and four retrospective studies. Our review showed no mortality benefit associated with the use of magnesium sulfate. However, magnesium sulfate was found to be effective in reducing spasms along with diazepam, leading to better control of dysautonomia, reduced need for mechanical ventilation and shorter hospital stay by 3-7 days. The incidence of magnesium toxicity was very low in the studies included.

Translating antenatal magnesium sulphate neuroprotection for infants born <28 weeks' gestation into practice: A geographical cohort study.

BACKGROUND: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016-17, and earlier, in 1991-92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016-17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016-17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. RESULTS: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016-17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25-0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016-17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08-0.96; P = 0.043). CONCLUSIONS: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.

Factors contributing to favourable neonatal outcomes in early-onset severe preeclampsia.

We collected data from all the women with singleton pregnancies complicated by early-onset severe preeclampsia between 2008 and 2018 to identify the factor(s) that contributed to favourable neonatal outcome. Thirty women delivered the neonates with favourable outcome and the remaining 21 women delivered those with unfavourable outcome. Univariate logistic regression analysis revealed that gestational age at diagnosis ≥28 weeks (crude odds ratio [OR], 6.00), protocol-based management (crude OR 5.83), use of magnesium sulphate (crude OR, 6.00), gestational age at delivery ≥32 weeks (crude OR, 31.90), and birthweight ≥1000 g (crude OR, 10.36) were significantly associated with favourable neonatal outcome. Among these five factors, multivariate logistic regression analysis extracted gestational age at delivery ≥32 weeks (adjusted OR, 17.62) as an only independent factor contributing to favourable neonatal outcome. These data suggest that prolongation of pregnancy up to 32 weeks of gestation is a key factor to improve neonatal outcome in the expectant management of early-onset severe preeclampsia.This study was approved by the ethics committee of Otsu Red Cross Hospital (reference number: 363, date of approval: April 28th, 2016).Impact statementWhat is already known on this subject? It has been demonstrated that expectant management for the women with early-onset severe preeclampsia is associated with decreased neonatal morbidity as compared to the aggressive management, suggesting that prolongation of the pregnancy period contributes to improved neonatal outcomes.What do the results of this study add? Among multiple elements composing expectant management for the women with early-onset severe preeclampsia, 'gestational age at delivery ≥32 weeks' was extracted as an only independent factor that significantly contributes to favourable neonatal outcomes. Importantly, small for gestational age was not significantly associated with poor neonatal outcomes.What are the implications of these findings for clinical practice and/or further research? The obstetrician should aim to prolong the pregnancies complicated by early-onset severe preeclampsia up to 32 gestational weeks even in the presence of foetal growth restriction, as far as maternal conditions allow. Such management policy could contribute to improvement of the neonatal outcomes.

The efficacy of magnesium sulphate as an adjunct to local anaesthetics for perineal pain relief after episiotomy.

BACKGROUND: Episiotomy is a deliberate surgical incision of the perineum with the aim of increasing the vulval outlet to facilitate childbirth. However, it could be associated with some complications, such as pain, hemorrhage, and wound infection. It is a surgical procedure that requires adherence to basic surgical principles of providing adequate analgesia. AIM: To determine the efficacy of magnesium sulphate (MgSO4) as an adjunct to local anesthetics for analgesia during episiotomy repair among women that had vaginal delivery at Usmanu Danfodiyo University Teaching Hospital Sokoto, Sokoto, Nigeria. SUBJECT AND METHODS: This was a single-blind randomized clinical trial. Pregnant women who had episiotomy during the study period were randomized into two groups. Those in Group A had xylocaine administered alone, whereas those in Group B had xylocaine + MgSO4 administered for repair of episiotomy. Pain was assessed by numeric rating scale at commencement of the repair, at 2 and 6 h after the repair. Patient's level of satisfaction, request for additional analgesia, and side effects were also assessed. RESULTS: The pain score in the xylocaine + MgSO4 group was lower throughout the period of assessment. There was no significant difference in the pain scores between the two groups at 0 and 6 h. However, there was significant difference in the mean pain scores between the two groups at 2 h (P < 0.001). There was no significant difference in the level of satisfaction, request for additional analgesia, and side effects between the two groups. CONCLUSION: Both xylocaine alone and xylocaine with MgSO4 provide adequate perineal pain relief during episiotomy repair. MgSO4 improves the analgesic effect of xylocaine at 2 h after episiotomy repair without any significant side effect.

Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double-blind, randomised, placebo-controlled, multi-centre trial.

OBJECTIVE: To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis. DESIGN: Double-blind, randomised, placebo-controlled, multi-centre trial. SETTING: Fourteen Danish obstetric departments. POPULATION: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children. METHODS: Women were randomised to receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire. MAIN OUTCOME MEASURE: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP. RESULTS: The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65). CONCLUSIONS: Antenatal MgSO4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis. TWEETABLE ABSTRACT: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation.

Magnesium sulphate for fetal neuroprotection at imminent risk for preterm delivery: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Ordinary meta-analyses indicate that magnesium sulphate (MgSO4 ) treatment in women at imminent risk for preterm delivery decreases the offspring's risk of cerebral palsy (CP). However, repetitive testing of cumulative data calls for statistical caution, e.g. by trial sequential analysis (TSA), for which there are previously insufficient samples to draw a firm conclusion. Recently, a randomised controlled trial (RCT) provided additional data that potentially increased the sample size such that a new TSA might detect a statistically significant effect. OBJECTIVES: To assess the possible fetal neuroprotective effect of MgSO4 for women at imminent risk for preterm delivery in an updated systematic review with meta-analysis and TSA. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and ClinicalTrials.gov on 8 October 2019. The search strategy clustered terms describing the MgSO4 intervention and preterm delivery. SELECTION CRITERIA: RCTs. DATA COLLECTION AND ANALYSIS: Two reviewers extracted the data. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models. A TSA was applied to the primary outcome, CP. The quality of the evidence was assessed using GRADE. The protocol was registered in PROSPERO (registration: CRD42019151441). MAIN RESULTS: We identified six eligible trials (5917 women). MgSO4 intervention in women at imminent risk for preterm birth decreased the offspring's CP risk (meta-analysis RR 0.68, 95% CI 0.54-0.85; TSA RR 0.69, 95% CI 0.48-0.97). CONCLUSIONS: This systematic review with meta-analysis and TSA shows conclusively that MgSO4 , when given to women at imminent risk for preterm delivery, decreases the offspring's CP risk. TWEETABLE ABSTRACT: Antenatal magnesium sulphate decreases the risk of cerebral palsy in children born preterm.

Question 5: Magnesium Sulphate for Acute Asthma in children.

Most children who present to the emergency department with acute asthma, respond well to inhaled ß2-agonists (spacer or nebuliser), oxygen (if required) and systemic steroids. Guidelines across the world agree on this simple, straight forward evidenced based approach. In children with more severe asthma attacks and those who do not respond to initial treatment, the evidence base for the secondary level treatment is less clear. Many regimens exist for the next step. Intravenous Magnesium Sulphate (MgSO4) is now used frequently in these situations and some centres are starting to use nebulized MgSO4 as part of the initial maximal inhaled therapy options. This paper examines the role of MgSO4 in acute asthma in children. It focusses on how MgSO4 might work, what are the current recommendations for use and then what is the current evidence base to support its use. We have presented the evidence for the use of both nebulized and intravenous MgSO4. At the end of the paper we have suggested future directions for research in this area. Our aim is to present a synthesis of the current role of MgSO4 in the management of an acute asthma attack.