An International, Multicenter, Observational Study of Cerebral Oxygenation During Infant and Neonatal Anesthesia

Vanessa A. Olbrecht, M.D., M.B.A.; Justin Skowno, F.C.A., F.A.N.Z.C.A.; Vanessa Marchesini, M.D.; Lili Ding, Ph.D.; Yifei Jiang, M.D., Ph.D.; Christopher G. Ward, M.D.; Gaofeng Yu, M.D.; Huacheng Liu, M.D., Ph.D.; Bernadette Schurink, M.D.; Laszlo Vutskits, M.D., Ph.D.; Jurgen C. de Graaff, M.D., Ph.D.; Francis X. McGowan, Jr., M.D.; Britta S. von Ungern-Sternberg, M.D., Ph.D., D.E.A.A., F.A.N.Z.C.A.; Charles Dean Kurth, M.D.; Andrew Davidson, M.B.B.S., M.D., F.A.N.Z.C.A.


Anesthesiology. 2018;128(1):85-96. 

In This Article

Abstract and Introduction


Background: General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia–ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants.

Methods: This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%).

Results: The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze.

Conclusions: Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.


NEUROLOGIC injury during pediatric anesthesia and surgery has always been a significant concern, especially during cardiovascular and neonatal surgery.[1,2] During the past few years, there has been concern for potential neurologic injury during anesthesia in infants without congenital heart disease related to potential neurotoxicity of anesthetic drugs[3] and cerebral hypoxia–ischemia related to hypotension and hypoxia during surgery.[4] Determining the incidence of low cerebral saturation during anesthesia in infants and neonates, as well as associated physiologic factors, such as hypotension and hypoxemia, could improve anesthetic safety, because these mechanisms may be preventable causes of neurologic injury.

In pediatric anesthesia, current standard monitoring includes electrocardiogram to monitor heart rate (HR) and rhythm, pulse oximetry saturation (SpO2), arterial pressure, respiratory rate, and end-tidal carbon dioxide (ETCO2). Real-time measurement of cerebral tissue hemoglobin oxygenation using near infrared spectroscopy (NIRS) is widely used in cardiac anesthesia and neonatal and pediatric intensive care units but is infrequently deployed outside of these areas. NIRS noninvasively measures cerebral oxygen saturation (rScO2) in a tissue volume approximately 1 to 2 cm below the sensor reflecting a weighted average saturation in gas-exchanging vessels (arterioles, venules, and capillaries).[5] Low regional cerebral rScO2 (less than 50% for greater than 7 h in neonatal intensive care patients[6] and less than 45% for greater than 3 h in pediatric cardiac intensive care)[7] has been linked to adverse neurodevelopmental outcomes and to cerebral ischemic lesions on magnetic resonance imaging in neonatal and pediatric cardiac intensive care. In piglet models of hypoxia–ischemia, low regional cerebral rScO2 (less than 50%) results in decreased brain tissue energetics, electroencephalogram slowing, brain ischemic lesions, and neurobehavioral impairment.[8] In pediatric cardiac surgery, rScO2 monitoring is regarded as the standard of care by many institutions,[9] because perioperative rScO2 has been associated with neurologic lesions and neurodevelopmental outcomes.[7,10,11]

Several studies have recently examined regional cerebral oxygenation in infants during pediatric, noncardiac, surgical procedures.[12–15] In children under age 2 yr, rScO2 usually increased with sevoflurane induction of anesthesia, although decreased rScO2 during induction was associated with very low mean arterial pressure and younger age.[12] These studies suggest that unrecognized cerebral desaturation during anesthesia of infants occurs not infrequently and is often associated with hypotension. However, these studies were conducted at a single center in low numbers of patients, reflecting local anesthesia practice for the definition and treatment of arterial pressure, as well as ventilation and arterial oxygenation. Thus, these observations may not be generalizable to infant anesthesia practices across the world.

In the present prospective, multicenter, observational study, we sought to determine the incidence of low regional cerebral oxygenation during anesthesia in a large cohort of infants receiving general anesthesia for noncardiac surgery in centers located in Australia, the United States, China, and Italy. Our secondary aims were to describe regional cerebral oxygenation during surgery and to identify factors associated with cerebral desaturation.