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1. Background
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Cerebral palsy is a term which includes a number of different diseases or condition that can arise any time during brain development. Approximately 45% of all cases of cerebral palsy are associated with preterm birth (Australian Cerebral Palsy Register Report December 2009) with the rate of cerebral palsy amongst neonatal survivors born at less than 28 weeks gestation up to 30 times higher compared with infants born at term.
Theoretically magnesium sulphate (MgSO4) might be neuroprotective due to effects on cellular metabolism, cell death or injury or blood flow to the brain. The first case control study was published fifteen years ago and the evidence has been growing ever since (Nelson et al, 1995). The current Cochrane review concludes that antenatal MgSO4 given to women at risk of preterm birth substantially reduces the risk of cerebral palsy in their child (RR 0.68 95% confidence interval 0.54 to 0.87; five trials, 6145 infants). This Cochrane review contains five trials: Mittendorf et al, 2002; The Magpie Trial 2002; Crowther et al, 2003; Marret et al, 2007; Rouse et al, 2008. Two meta-analysis were published recently (Costantine et al; Doyle et al). National Clinical Practice Guidelines were released in March 2010.
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2. Recommendations for use
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The use of MgSO4 is recommended for neuroprotection of the fetus/infant/child:
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- when women are at risk of imminent preterm birth before 30 weeks gestation
- when preterm birth before 30 weeks gestation is planned or definitely expected within 24 hours.
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The use of MgSO4 is recommended:
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- regardless of the number of babies in utero
- regardless of the anticipated mode of birth
- whether or not antenatal corticosteroids have been given.
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3. Guideline
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3.1 Dose
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When birth is planned, commence MgSO4 as close to four hours before birth as possible.
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Loading dose: using a 10mL vial of magnesium sulphate prepare 4gram (i.e. 8mL) of magnesium sulphate 50% in a 10mL syringe, configure the pump to accept the 10mL syringe and set the pump to 32mL an hour for 15 minutes.
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Maintenance rate: once the loading dose has been completed, using the 50mL vial of magnesium sulphate, prepare 50mL of magnesium sulphate 50% in a 50mL syringe, re-set the pump to accept 50mL syringe and set the pump to administer the maintenance rate of 1g/hr (2mL/hour) or as ordered.
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Continue regimen until birth or for 24 hours, whichever comes first.
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3.2 Urgent delivery/birth
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In situations where urgent delivery is necessary because of actual or imminent maternal or fetal compromise then delivery should not be delayed to administer MgSO4.
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3.3 Repeat doses
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In the event that birth does not occur after giving MgSO4 for neuroprotection of the infant, and preterm birth (less than 30 weeks gestation) again appears imminent (planned or definitely expected within 24 hours), a repeat dose of MgSO4 may be considered.
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3.4 Monitoring
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3.4.1 Magnesium level monitoring
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Measurement of magnesium levels will facilitate management where there are signs of toxicity or in the presence of renal impairment.
Serum magnesium concentrations should be checked every 6 hours in the antepartum and intrapartum phase (therapeutic level of magnesium: 1.7 to 3.5 mmol/L).
Magnesium is excreted by the kidneys and regular monitoring of serum levels should be conducted in women with oliguria (urine output <100mL over 4 hours) or urea >10mmol/L and those with renal impairment.
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| | | | | | | ECG changes (P-Q interval prolongation, widen QRS complex)
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| | Reduction in deep tendon reflexes
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| | Loss of deep tendon reflexes
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| | Sinoatrial and atrioventricular blockade. Respiratory paralysis and CNS depression
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Note: If serum magnesium level is >3.5mmol/L, cease infusion and consult with obstetrician.
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3.4.2 Clinical observations
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During administration of the loading or bolus dose:
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- 5 minutely blood pressure and pulse (x 4 readings)
- observe for the development of side effects
- check patellar reflexes after administration.
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During administration of the maintenance infusion:
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- ½ hourly blood pressure, pulse, and respiratory rate (pre-treatment respiratory rate should be ≥ 16 per minute). These may be undertaken hourly post-birth.
- 1 hourly patellar reflexes
- 1 hourly urine measures, 4 hourly testing of urinary protein
- 2 hourly temperature
- continuous electronic fetal monitoring from 26 weeks gestation until clinical review/discussion by medical staff. Between 24- 26 weeks gestation, individualised management with regard to fetal monitoring will be considered
- maintain strict fluid balance chart.
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Record patellar reflexes as:
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- A = Absent
- N = Normal
- B = Brisk
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Request magnesium level and review management if:
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- respiratory rate < 12 breaths/minute
- urine output < 100mLs in 4 hours
- loss of patellar reflexes
- further seizures occur.
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3.5 Response to magnesium toxicity
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The following clinical signs of magnesium toxicity must be reviewed by a consultant obstetrician/anaesthetist:
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- urine output <100mL in 4 hours
- absent patellar reflexes
- respiratory depression.
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The antidote for magnesium toxicity is: calcium gluconate (10mL of 10% solution over 10 minutes) by slow intravenous injection. The patient requires ECG monitoring during and after administration due to the potential for cardiac arrhythmias.
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Note: Resuscitation and ventilator support should be available during and after dose administration of both magnesium sulphate and calcium gluconate.
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| CEASE Magnesium infusion in the following emergencies: |
- respiratory arrest: call: Code Blue - Adult and Child (intranet-only)
- cardiac arrest: call: Code Blue - Adult and Child (intranet-only).
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3.6 Potential interactions
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There is a potential theoretical interaction between MgSO4 and nifedipine resulting in hypotension and neuromuscular blockade effects. This is seldom reported in clinical practice (Snyder & Cardwell, 1989; Ben-Ami et al, 1994). If hypotension occurs, nifedipine and MgSO4 administration should be ceased.
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4. References
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4.1 References
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Magnesium Sulphate: Neuroprotection of Preterm Infants: References - links to a separate page.
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4.2 Evidence table
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Magnesium Sulphate: Neuroprotection of Preterm Infants: Evidence Table - links to a separate page.
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Published: 4 May 2010
| Edited: 12 May 2010
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Royal Women's Hospital Clinical Practice Guidelines (CPGs) are intended to provide guidance to health care professionals, based on a thorough evaluation of research evidence, on the practical assessment and management of specific clinical issues or situations. The guidelines allow some flexibility on the part of the health care professional based on the needs of the specific patient for whom they are caring.
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