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
Details
Lead Sponsor:
Polish Mother Memorial Hospital Research Institute