Appropriate Dosage of Vasopressor in Neonates and Infants

Improvements in surgical techniques and perioperative care in the neonate have resulted in a significant improvement in survival rates, with the mortality rate for neonatal noncardiac surgery being less than 5% in 2013, compared to 72% in 1947. As survival rates have improved, the question of long-term prognosis, especially concerning delayed cranial nerve development and subsequent quality of life, has emerged. In 48% of full-term infants undergoing non-cardiac surgery in the neonatal period for major congenital conditions (diaphragmatic hernia, esophageal atresia, abdominal wall defects, congenital megacolon, etc.) and 75% of preterm infants, brain damage is identified on post-operative brain MRI, and developmental testing reveals cognitive impairment in 3-56% and motor impairment in 0-77%.

motor disorders in 3-56% and 0-77%. Cognitive and motor deficits are known to occur in 45% of patients undergoing non-cardiac surgery for congenital conditions, excluding neurodevelopmental disorders caused by the concomitant congenital genetic disease itself.

Cerebral perfusion is regulated by arterial baroreflex, cerebral blood flow autoregulation, and flow metabolism, which are immature in the neonate and are lost under general anesthesia. This can lead to intraoperative changes in blood pressure, carbon dioxide concentration, intraventricular hemorrhage, and lateral ventricular hemorrhagic infarction, which can cause brain damage.

According to the Anaesthesia Practice in Children Observational Trial study, 32% of children undergoing general anesthesia and surgery develop hypotension that requires inotropes. The goal of maintaining arterial blood pressure at a constant level in infants during surgery is to maintain blood flow to vital organs, including the brain. However, there is a lack of evidence on what blood pressure should be maintained to maintain adequate cerebral perfusion in infants and how much hypotension is acceptable. The current definition of normal blood pressure in infants is based on birth weight and gestational age. For example, if the gestational age is 36 weeks, the recommendation is to maintain a mean arterial pressure of 36 mm Hg or higher. However, studies have shown that mean arterial pressure below this level does not affect prognosis as long as adequate perfusion is maintained. Furthermore, raising blood pressure to maintain normotension based on gestational age may lead to intraventricular hemorrhage. A recent study was published to determine the appropriate dose of ephedrine in infants with intraoperative hypotension and found that a higher dose (1.2 mg/kg) than the adult dose (0.1 mg/kg) was required to raise blood pressure, but the study was limited by the lack of confirmation of how raising blood pressure changes cerebral blood flow. Therefore, in this study, the investigators aimed to determine the changes in cerebral blood flow according to the dose of ephedrine infusion in neonates and infants as measured by the changes in blood flow in the internal carotid artery using transcranial ultrasound and to suggest blood pressure standards and ephedrine dosage for maintaining adequate cerebral blood flow in neonates and infants.

• Recovery of cerebral blood flow within 2 minutes [Time frame: within 2 minutes after ephedrine injection]
• Recovery of cerebral blood flow within 5 minutes [Time frame: within 5 minutes after ephedrine injection]
• Recovery of mean arterial pressure within 10 minutes [Time frame: within 10 minutes after ephedrine injection]
• Additional durg dose [Time frame: within 10 minutes after ephedrine injection]
• electroencephalogram [Time frame: from the induction of anesthesia to initiation of surgery]
• cerebral oxygen saturation [Time frame: from the induction of anesthesia to initiation of surgery]
• fluid responsiveness [Time frame: from the induction of anesthesia to initiation of surgery]