Cooling for Neonatal Hypoxic-Ischemic Encephalopathy Gaining Favor

WASHINGTON – Over the last decade, researchers have been steadily building a case for the use of cerebral and whole-body cooling to treat neonatal hypoxic-ischemic encephalopathy, said Dr. David Durand, director of neonatology at the Children’s Hospital and Research Center, Oakland, Calif.

“I think cooling is here to stay, in the [neonatal intensive care unit] and immediately out of the delivery room,” he said at the annual meeting of the American Academy for Cerebral Palsy and Developmental Medicine. “The consensus is pretty clear that cooling is no longer experimental.”

Cerebral cooling may aid in slowing the inflammation in the brain that leads to cell death in newborns who have moderate to severe hypoxic-ischemic encephalopathy, Dr. Durand said. In one study, cerebral cooling was shown to safely improve survival in 234 term infants with less-severe abnormalities on amplitude integrated electroencephalography (aEEG). The study found that death or severe disability occurred in 55% of the infants who were treated with cooling, compared with 66% of the controls, at 18 months’ follow-up (Lancet 2005;365:663-70).

Cooling should begin within 90 minutes of the acute event, and the brain must remain at 32°-34° C to offer adequate neuroprotection. If the cooling process is started later than 8 hours after birth, its neuroprotective value is lost completely, Dr. Durand said.

Previous studies have shown that neuronal death occurs in two phases after a reversible hypoxic-ischemic global insult. The first phase, “primary neuronal death,” is related to cellular hypoxia with exhaustion of the cell’s energy stores (Cochrane Database Syst. Rev. 2007 [doi:10.1002/14651858.CD003311.pub2]).

During the second phase – the next 6-48 hours – delayed neuronal death begins, according to the Cochrane review. Cerebral cooling that is applied during the first period of injury may help prevent the “secondary cascade,” Dr. Durand said. The second phase “is associated with encephalopathy and increased seizure activity, and accounts for a significant proportion of the final cell loss even after very severe insults,” he said.

Whole-body cooling also may be effective for these patients, Dr. Durand said. A randomized study of the use of cooling blankets at 33.5° C for 72 hours showed that death or severe disability occurred in 45 of the 102 infants (44%) who had the intervention, compared with 64 of the 103 patients (62%) in the control group. In all, 24 infants (24%) in the cooling group died, compared with 38 (37%) in the control group (N. Engl. J. Med. 2005;353:1574-84).

For babies who need a number of other tests, whole-body cooling provides easier access, Dr. Durand noted.

“Cooling is not all that hard to do [but] only should be done in a well-organized program,” he emphasized.

Other therapies for treatment of hypoxic-ischemic encephalopathy are also emerging. In one Chinese randomized trial, newborns who were treated with erythropoietin had less mortality or moderate/severe disability outcomes, compared with infants who were given conventional treatment. The infants were given either 300 U/kg (n = 52) or 500 U/kg (n = 31) every other day for 2 weeks, beginning less than 48 hours after birth. Death or moderate/severe disability occurred in 18 of 73 infants (24.6%) in the erythropoietin group, compared with 35 of 80 infants (43.8%) in the control group, with no adverse effects reported (Pediatrics 2009;124;e218-e226).

Dr. Durand said he had no relevant conflicts of interest.

WASHINGTON – Over the last decade, researchers have been steadily building a case for the use of cerebral and whole-body cooling to treat neonatal hypoxic-ischemic encephalopathy, said Dr. David Durand, director of neonatology at the Children’s Hospital and Research Center, Oakland, Calif.

“I think cooling is here to stay, in the [neonatal intensive care unit] and immediately out of the delivery room,” he said at the annual meeting of the American Academy for Cerebral Palsy and Developmental Medicine. “The consensus is pretty clear that cooling is no longer experimental.”

Cerebral cooling may aid in slowing the inflammation in the brain that leads to cell death in newborns who have moderate to severe hypoxic-ischemic encephalopathy, Dr. Durand said. In one study, cerebral cooling was shown to safely improve survival in 234 term infants with less-severe abnormalities on amplitude integrated electroencephalography (aEEG). The study found that death or severe disability occurred in 55% of the infants who were treated with cooling, compared with 66% of the controls, at 18 months’ follow-up (Lancet 2005;365:663-70).

Cooling should begin within 90 minutes of the acute event, and the brain must remain at 32°-34° C to offer adequate neuroprotection. If the cooling process is started later than 8 hours after birth, its neuroprotective value is lost completely, Dr. Durand said.

Previous studies have shown that neuronal death occurs in two phases after a reversible hypoxic-ischemic global insult. The first phase, “primary neuronal death,” is related to cellular hypoxia with exhaustion of the cell’s energy stores (Cochrane Database Syst. Rev. 2007 [doi:10.1002/14651858.CD003311.pub2]).

During the second phase – the next 6-48 hours – delayed neuronal death begins, according to the Cochrane review. Cerebral cooling that is applied during the first period of injury may help prevent the “secondary cascade,” Dr. Durand said. The second phase “is associated with encephalopathy and increased seizure activity, and accounts for a significant proportion of the final cell loss even after very severe insults,” he said.

Whole-body cooling also may be effective for these patients, Dr. Durand said. A randomized study of the use of cooling blankets at 33.5° C for 72 hours showed that death or severe disability occurred in 45 of the 102 infants (44%) who had the intervention, compared with 64 of the 103 patients (62%) in the control group. In all, 24 infants (24%) in the cooling group died, compared with 38 (37%) in the control group (N. Engl. J. Med. 2005;353:1574-84).

For babies who need a number of other tests, whole-body cooling provides easier access, Dr. Durand noted.

“Cooling is not all that hard to do [but] only should be done in a well-organized program,” he emphasized.

Other therapies for treatment of hypoxic-ischemic encephalopathy are also emerging. In one Chinese randomized trial, newborns who were treated with erythropoietin had less mortality or moderate/severe disability outcomes, compared with infants who were given conventional treatment. The infants were given either 300 U/kg (n = 52) or 500 U/kg (n = 31) every other day for 2 weeks, beginning less than 48 hours after birth. Death or moderate/severe disability occurred in 18 of 73 infants (24.6%) in the erythropoietin group, compared with 35 of 80 infants (43.8%) in the control group, with no adverse effects reported (Pediatrics 2009;124;e218-e226).

Dr. Durand said he had no relevant conflicts of interest.

WASHINGTON – Over the last decade, researchers have been steadily building a case for the use of cerebral and whole-body cooling to treat neonatal hypoxic-ischemic encephalopathy, said Dr. David Durand, director of neonatology at the Children’s Hospital and Research Center, Oakland, Calif.

“I think cooling is here to stay, in the [neonatal intensive care unit] and immediately out of the delivery room,” he said at the annual meeting of the American Academy for Cerebral Palsy and Developmental Medicine. “The consensus is pretty clear that cooling is no longer experimental.”

Cerebral cooling may aid in slowing the inflammation in the brain that leads to cell death in newborns who have moderate to severe hypoxic-ischemic encephalopathy, Dr. Durand said. In one study, cerebral cooling was shown to safely improve survival in 234 term infants with less-severe abnormalities on amplitude integrated electroencephalography (aEEG). The study found that death or severe disability occurred in 55% of the infants who were treated with cooling, compared with 66% of the controls, at 18 months’ follow-up (Lancet 2005;365:663-70).

Cooling should begin within 90 minutes of the acute event, and the brain must remain at 32°-34° C to offer adequate neuroprotection. If the cooling process is started later than 8 hours after birth, its neuroprotective value is lost completely, Dr. Durand said.

Previous studies have shown that neuronal death occurs in two phases after a reversible hypoxic-ischemic global insult. The first phase, “primary neuronal death,” is related to cellular hypoxia with exhaustion of the cell’s energy stores (Cochrane Database Syst. Rev. 2007 [doi:10.1002/14651858.CD003311.pub2]).

During the second phase – the next 6-48 hours – delayed neuronal death begins, according to the Cochrane review. Cerebral cooling that is applied during the first period of injury may help prevent the “secondary cascade,” Dr. Durand said. The second phase “is associated with encephalopathy and increased seizure activity, and accounts for a significant proportion of the final cell loss even after very severe insults,” he said.

Whole-body cooling also may be effective for these patients, Dr. Durand said. A randomized study of the use of cooling blankets at 33.5° C for 72 hours showed that death or severe disability occurred in 45 of the 102 infants (44%) who had the intervention, compared with 64 of the 103 patients (62%) in the control group. In all, 24 infants (24%) in the cooling group died, compared with 38 (37%) in the control group (N. Engl. J. Med. 2005;353:1574-84).

For babies who need a number of other tests, whole-body cooling provides easier access, Dr. Durand noted.

“Cooling is not all that hard to do [but] only should be done in a well-organized program,” he emphasized.

Other therapies for treatment of hypoxic-ischemic encephalopathy are also emerging. In one Chinese randomized trial, newborns who were treated with erythropoietin had less mortality or moderate/severe disability outcomes, compared with infants who were given conventional treatment. The infants were given either 300 U/kg (n = 52) or 500 U/kg (n = 31) every other day for 2 weeks, beginning less than 48 hours after birth. Death or moderate/severe disability occurred in 18 of 73 infants (24.6%) in the erythropoietin group, compared with 35 of 80 infants (43.8%) in the control group, with no adverse effects reported (Pediatrics 2009;124;e218-e226).

Dr. Durand said he had no relevant conflicts of interest.