Cerebral Effect of Intratracheal Aerosolized Surfactant Versus Bolus Therapy in Preterm Lambs.
OBJECTIVE
Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome.


METHODS
Prospective randomized study.


METHODS
BioCruces Institute Animal Research Facility.


METHODS
Fourteen intensively monitored and mechanically ventilated preterm lambs.


METHODS
Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis.


RESULTS
In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress.


CONCLUSIONS
In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of surfactant administered as a standard bolus.
1Experimental Research Unit, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain. 2Neonatal Intensive Care Unit and Neonatology Group, BioCruces Health Research Institute, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain.
Carmen
C
Rey-Santano
Victoria E
VE
Mielgo
Jon
J
López-de-Heredia-y-Goya
Xabier
X
Murgia
Adolfo
A
Valls-i-Soler
D000336:Aerosols / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D001921:Brain / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D011446:Prospective Studies; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000662:veterinary; D012756:Sheep
D000336:Aerosols; D011663:Pulmonary Surfactants; D010100:Oxygen