MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children.


There are few data on the role of nebulised magnesium sulphate (MgSO4) in the management of acute asthma in children. Those studies that have been published are underpowered, and use different methods, interventions and comparisons. Thus, no firm conclusions can be drawn.
OBJECTIVES: Does the use of nebulised MgSO4, when given as an adjunct to standard therapy in acute severe asthma in children, result in a clinical improvement when compared with standard treatment alone?
DESIGN: Patients were randomised to receive three doses of MgSO4 or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour. The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation.
SETTING: Emergency departments and children`s assessment units at 30 hospitals in the UK. 
PARTICIPANTS: Children aged 2-15 years with acute severe asthma.
INTERVENTIONS: Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years) or 5 mg (ages >/= 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals. MAIN OUTCOME MEASURES: The primary outcome measure was the ASS after 1 hour of treatment. Secondary measures included `stepping down` of treatment at 1 hour, number and frequency of additional salbutamol administrations, length of stay in hospital, requirement for intravenous bronchodilator treatment, and intubation and/or admission to a paediatric intensive care unit. Data on paediatric quality of life, time off school/nursery, health-care resource usage and time off work were collected 1 month after randomisation.
RESULTS: A total of 508 children were recruited into the study; 252 received MgSO4 and 256 received placebo along with the standard treatment. There were no differences in baseline characteristics. There was a small, but statistically significant difference in ASS at T60 in those children who received nebulised MgSO4 {0.25 [95% confidence interval (CI) 0.02 to 0.48]; p = 0.034} and this difference was sustained for up to 240 minutes [0.20 (95% CI 0.01 to 0.40), p = 0.042]. The clinical significance of this gain is uncertain. Assessing treatment-covariate interactions, there is evidence of a larger effect in those children with more severe asthma exacerbations ( p = 0.034) and those with a shorter duration of symptoms ( p = 0.049). There were no significant differences in the secondary outcomes measured. Adverse events (AEs) were reported in 19% of children in the magnesium group and 20% in the placebo group. There were no clinically significant serious AEs in either group. The results of the base-case economic analyses are accompanied by considerable uncertainty, but suggest that, from an NHS and Personal Social Services perspective, the addition of magnesium to standard treatment may be cost-effective compared with standard treatment only. The results of economic evaluation show that the probability of magnesium being cost-effective is over 60% at cost-effectiveness thresholds of pound1000 per unit decrement in ASS and pound20,000 per quality-adjusted life-year (QALY) gained, respectively; it is noted that for some parameter variations this probability is much lower, reflecting the labile nature of the cost-effectiveness ratio in light of the small differences in benefits and costs shown in the trial and the relation between the main outcome measure (ASS) and preference based measures of quality of life used in cost-utility analysis (European Quality of Life-5 Dimensions; EQ-5D).
CONCLUSIONS: This study supports the use of nebulised isotonic MgSO4 at the dose of 151 mg given three times in the first hour of treatment as an adjuvant to standard treatment when a child presents with an acute episode of severe asthma. No harm is done by adding magnesium to salbutamol and ipratropium bromide, and in some individuals it may be clinically helpful. The response is likely to be more marked in those children with more severe attacks and with a shorter duration of exacerbation. Although the study was not powered to demonstrate this fully, the data certainly support the hypotheses that nebulised magnesium has a greater clinical effect in children who have more severe exacerbation with shorter duration of symptoms.

 

The Multiple Uses of Aromatherapy.


Cuts and Scrapes

A spray of diluted essential oils makes an excellent antiseptic. The germ-killing abilities of essential oils high in terpenes, such as tea tree, lavender, eucalyptus and lemon, increase when a 2-percent solution is sprayed through the air. The antiseptic quality of tea tree actually increase in the presence of blood and pus. Superficial cuts, scrapes and burns may also be treated with a salve. Although studies show that oils are antiseptic when diluted in an alcohol base instead of oil, this may sting in cases of an open wound. Tea tree, lavender, helichrysum, cistus, eucalyptus, rose geranium, sandalwood and rose repair skin damage and encourage new cell growth for faster healing.

Antiseptic Skin Spray
15 drops tea tree or eucalyptus
10 drops helichrysum
5 drops lavender
2 ounces distilled water
1/2 ounce grain alcohol or goldenseal tincture

Combine and shake well before each use to help disperse the oils. Spray as needed on minor cuts, burns and abrasions to prevent infection and speed healing.

Fungal Infections
Treat fungal infection with tea tree, lavender, eucalyptus, myrrh and geranium. Small amounts of peppermint relieve itching. Soak a compress in these essential oils diluted in vinegar, which also deters fungus, and apply to the affected area. A fungal powder is also appropriate to keep the area as dry as possible.

Antifungal Powder
1/4 cup bentonite clay
1 tablespoon goldenseal root powder
12 drops (1/8 teaspoon) each essential oils of:
tea tree
clove
geranium

Combine all the ingredients and powder the affected area liberally. For fungal conditions, such as athlete’s foot, an aromatic foot bath is a great treat.

Soak Those Pups
5 drops tea tree oil
5 drops sage
2 drops peppermint

Fill a portable basin or tub with hot water-or, better yet, sage tea. Add essential oils to water and soak for at least 15 minutes. For feet that sweat excessively, finish with a foot powder.

Rashes Caused by Poisonous Plants
The menthol in peppermint relieves the painful burning and itching of poison oak, ivy or sumac. A 2- to 3- percent dilution (12-24 drops per ounce) in vinegar or witch hazel provides blessed relief to nerve endings. Four cups of quick-cooking oats (they dissolve best) wrapped in a muslin cloth and/or one cup Epsom salts may also be added to a lukewarm bath, or mix a smaller amount and sponge on. Lavender and a few menthol crystals added to a tincture of jewelweed or sassafras are also helpful during the first stages of a reaction. Oil-based products aren’t usually recommended, although some people find that a lotion relieves itching during the later, dry stage of poison oak, ivy and sumac.

Poison Oak/Ivy/Sumac Remedy
3 drops each:
lavender
helichrysum
Roman chamomile
geranium
cypress
1/2 teaspoon salt
1 tablespoon water
1 tablespoon vinegar
1/2 teaspoon menthol crystals
1 ounce calendula tincture

Combine ingredients. Apply externally as needed. When healing begins, apply externally 6 drops each stoechas lavender and cistus (diluted to 2 percent) in aloe gel or juice.
Herbal Adjuncts-Take liver herbs such as milk thistle, burdock and dandelion; avoid sweets and fruits. Take vitamin C and pantothenic acid.

Inflammation and Burns
For inflammation, immediately apply a cold herbal compress with an anti-inflammatory oil, such as chamomile, lavender or marjoram. The first step in treating burns and sunburns is to quickly immerse the area in cold water containing a few drops of one of these essential oils, or to apply a cold compress that has been soaked in that water. Lavender oil and aloe-vera juice promote new cell growth, reduce inflammation and stop infection. Aloe, which is so healing it has even been used successfully to treat radiation burns, also contains the natural “aspirin,” salicylic acid.

Sunburn Spray
50 drops (1/2 teaspoon) lavender oil
4 ounces aloe-vera juice
1 teaspoon vitamin E oil
1 tablespoon vinegar

Combine ingredients. Store in a spritzer bottle, and shake well before using. Use as often as needed to reduce pain and speed healing. Keep the bottle in the refrigerator for extra cooling relief.

Insect Bites and Other Critter Attacks
For mosquito or other insect bites that don’t require much attention, a simple dab of essential oil of lavender or tea tree provides relief. Chamomile and lavender essential oils reduce swelling, itching and inflammation, and together with tinctures of echinacea and plantain often prevent an allergic response. (If an allergic reaction does occur, take 1/2 teaspoon of echinacea tincture internally.)

First-Aid Remedy
3 drops each:
lavender
tea tree
German chamomile
helichrysum
1 ounce calendula infused oil

Mix together. This remedy is excellent for skin irritation, bites, stings, burns, inflammation, bruises or scrapes.

Adding essential oil and tincture to clay keeps the medicine reconstituted, preserved and ready for an emergency. As the clay dries it pulls toxins from stings and bites to the skin’s surface to keep them from spreading, while also pulling out pus or embedded splinters.

Clay Poultice
12 drops lavender essential oil
1 tablespoon bentonite clay
1 teaspoon each tincture of:
echinacea root
chamomile flowers
plantain leaves

Put clay in the container to be stored. Add the tinctures slowly, stirring as the clay absorbs them. Add lavender oil, stirring to distribute it evenly. Store poultice in a container with a tight lid to slow dehydration; it will last at least several months. If the mixture does dry out, add distilled water to reconstitute it.

Nothing is more annoying than trying to enjoy the outdoors while shooing away pesky insects. Many people don’t care for the smell of citronella, a traditional repellant, but this formula smells great.

Insect-Aside Bug Repellant
5 drops eucalyptus
2 drops orange
4 drops lavender
2 drops lemon
8 drops cedar
1 drop peppermint
1 drop clove
1 drop cinnamon
2 ounces carrier oil

Mix together and apply liberally. Keep out of eyes.

Few “creepy crawlies” can survive the following blend. Use for skin fungus, scabies or other nonspecific critters.

Cootie Oil
10 drops thyme linalol
3 drops lemon
5 drops lavender
5 drops rosemary
1 drop clove bud
1 drop cinnamon bark
2 ounces carrier oil

Combine ingredients. Apply as needed.

Herbal Adjuncts – Jewelweed leaves, garlic, black-walnut hulls and the lichen usnea are all specific against fungus, and can be used as an external wash or soak.

Source: www.oawhealth.com

 

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.


Background

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO4) in acute asthma in children. We assessed the effect of MgSO4 treatment in children with severe acute asthma.

Methods

In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2—16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO4 (250 mmol/L; 151 mg per dose; MgSO4 group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.

Findings

Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO4and 256 to placebo. Mean ASS at 60 min was lower in the MgSO4 group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference −0·25, 95% CI −0·48 to −0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.

Interpretation

Overall, nebulised isotonic MgSO4, given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO2<92%) at presentation and those with preceding symptoms lasting less than 6 h.

Source: lancet

 

Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial.


Background

Previous studies suggested intravenous or nebulised magnesium sulphate (MgSO4) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO4 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 MgSO4 (2 g in 20 min) or nebulised MgSO4 (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 MgSO4 were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO4 and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO4, 357 (91%) patients allocated intravenous MgSO4, and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO4 compared with controls or between those treated with nebulised MgSO4 and intravenous MgSO4. Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO4 group than it was in the nebulised MgSO4 group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO4 did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO4 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 MgSO4 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.

Source: lancet

 

 

FDA Warns Against Prolonged Use of Magnesium Sulfate to Stop Preterm Labor.


The FDA is changing the label of magnesium sulfate to warn against its use for more than 5 to 7 days to stop preterm labor. Long-term use can lead to hypocalcemia, osteopenia, and fractures in the infant. In addition, the drug’s pregnancy category is being changed from A to D, indicating “positive evidence of human fetal risk.”

The FDA reemphasizes that magnesium sulfate is not approved to stop preterm labor. It is unknown whether a shorter treatment duration would result in harm to the fetus.

The warning comes after the FDA reviewed epidemiologic data and 18 cases of skeletal abnormalities in infants exposed to magnesium sulfate in utero (average duration of exposure, 10 weeks). The epidemiologic data indicate that laboratory results normalize within days of birth, but long-term clinical effects on bone health aren’t known.

Asked to comment, Allison Bryant of Journal Watch Women’s Healthwrote: “The use of magnesium sulfate as a tocolytic persists in many institutions. In addition, data suggesting its effectiveness in providing neuroprotection for fetuses exposed in utero and born at early gestational ages have led to a resurgence in use. However, there are no data suggesting value to using magnesium sulfate for tocolysis for longer than 48 hours, for neuroprotection beyond when delivery is felt to be imminent, or for seizure prophylaxis in the setting of preeclampsia beyond 24 hours postpartum. Therefore, this FDA warning is unlikely to greatly alter current clinical practice.”

Source: FDA 

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis.


A disturbed balance between angiogenic and antiangiogenic growth factors is a highly accepted mechanism in the pathogenesis of pregnancy-induced hypertension and proteinuria, which is clinically known as preeclampsia (PE). We investigated the effect of magnesium sulfate (MgSO4) therapy on vascular endothelial growth factor (VEGF), placental growth factor (PlGF), nitric oxide (NO) metabolites, soluble fm-like tyrosine kinase-1 (sFlt-1) and endoglin levels in PE rats and the effect of this treatment on the feto-maternal outcome. The PE group showed hypertension, proteinuria and decreased number and weight of live pups relative to the control group. This result was associated with increased sFlt-1, VEGF receptor-2 (VEGFR-2), VEGFR-3 and endoglin levels but decreased NO metabolites. MgSO4 therapy ameliorated systolic hypertension and proteinuria and decreased sFlt-1, VEGFR-2, VEGFR-3 and endoglin levels but increased NO metabolites in the treated group. Physiological and biochemical changes and improved pup weight and viability were observed in the treated group. The vasodilator action of MgSO4 and increased NO production are expected to increase placental blood flow and help fetal nutrition and development. Relief of placental ischemia decreases the production of antiangiogenic growth factors and restores the bioavailability of angiogenic factors (PlGF and VEGF). These changes resulted in better fetal outcome and an improved clinical picture of PE. These findings are promising and encourage further study of the mechanism of action of MgSO4 to support its widespread use in the prevention and management of the etiopathological changes underlying the vast majority of the manifestations and complications of PE.

Source: Hypertension Research/nature.