Hypothermia Enhanced by Magnesium Sulphate

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

New 2010 neonatal resuscitation guidelines state that offering therapeutic hypothermia (TH) should be a standard of care in managing neonates with perinatal hypoxic - ischemic insult and present with signs of moderate and/or severe hypoxic - ischemic encephalopathy (HIE) . Despite the evidence from several randomized control trial (RCT) proving its effectiveness, its effect is perceived insufficient or only modest. Thus today's research efforts are directed toward finding the new possibilities of enhancing the effects of hypothermia. List of agents with potential neuroprotective properties includes: erythropoetin, melatonin, topiramate, morphine, xenon, MgSO4. Given investigators previous experiences with preterm neonates exposed to MgSO4 prenatally or administered this drug after birth because of perinatal asphyxia, the investigators designed the trial which would evaluate the possibility of increasing the TH effect by combining this method with MgSO4. Until now there are several published studies evaluating the effectiveness of MgSO4 in the group of asphyxiated neonates, including one RCT. However, all of these studies were conducted before the era of TH Furthermore, irrespective of the potential benefits, safety of using MgSO4 during TH in the group of term neonates was not studied. It is particularly important in the light of the results presented by Mittendorf et.al. They studied the effects of prenatal aggressive treatment with MgSO4 on the outcome of preterm neonates showed that patients exposed to high doses of MgSO4 were at higher risk of severe intracranial bleeding. Other side effects of high serum magnesium levels are: vasodilatation, hypotension, cardiac arrhythmias, coagulopathy, and gastrointestinal disturbances. MgSO4 is a very attractive neuroprotective option,also because of its easy availability. Drug can be administered in the birth hospital while neonate is being prepared for the transport to TH center. Timing of the intervention is very important for neonates suffering from perinatal asphyxia. Both TH and administration of potentially neuroprotective drug should be started during "therapeutic window". It is the initial potentially reversible phase of hypoxic insult lasting about 6 hours. If the long-term follow up shows that MgSO4 has an additive neuroprotective effect and no significant side effects in the group of asphyxiated neonates treated with TH this relatively simple and not expensive intervention may be introduced into clinical practice

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Polish Mother Memorial Hospital Research Institute
• Collaborator: Poznan University of Medical Sciences
• Treatments: Magnesium Sulfate

Criteria

Inclusion Criteria:

Group A Infants > 36.0 weeks gestation* with at least ONE of the following: * for gestational age also use clinical assessment

• Apgar score of less than or equal to ≤5 at 10 (ten) minutes after birth

• continued need for resuscitation, including endotracheal or mask ventilation, at 10min after birth

• acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 min of birth less than (<) pH 7.00

• base deficit greater than or equal to (≥) 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)

Group B Newborn with moderate or severe encephalopathy with varying states of consciousness: lethargy, stupor, or coma and

One or more of below:

• hypotonia

• abnormal reflexes : oculomotor / pupillary

• suck: weak / absent

• clinical seizures - clinically confirmed

Group C integrated electroencephalogram (aEEG / CFM) (lasting at least 20 minutes), which indicates either a moderate / serious abnormalities in the background activity aEEG (a score of 2 or 3) or convulsions attacks.

Exclusion Criteria:

• major congenital maformation

• extremely poor prognosis : Apgar score 0 @ 15 minutes of life