C. Dean Kurth

BACKGROUND: Cerebral oximetry is a noninvasive bedside technology using near-infrared light to monitor cerebral oxygen saturation (Sco2) in an uncertain mixture of arteries, capillaries, and veins. The present study used frequency domain near-infrared spectroscopy to determine the ratio of arterial and venous blood monitored by cerebral oximetry during normoxia, hypoxia, and hypocapnia. METHODS: Twenty anesthetized children aged < 8 yr with congenital heart disease of varying arterial oxygen saturation (Sao2) were studied during cardiac catheterization. Sco2, Sao2, and jugular bulb oxygen saturation (Sjo2) were measured by frequency domain near-infrared spectroscopy and blood oximetry at normocapnia room air, normocapnia 100% inspired O2, and hypocapnia room air. RESULTS: Among subject conditions, Sao2 ranged from 68% to 100%, Sjo2 from 27% to 96%, and Sco2 from 29% to 92%. Sco2 was significantly related to Sao2 (y = 0. 85 x -17, r = 0.47), Sjo2 (y = 0.77 x +13, r = 0.70), and the combination (Sco2 = 0.46 Sao2 + 0.56 Sjo2 - 17, R = 0.71). The arterial and venous contribution to cerebral oximetry was 16 +/- 21% and 84 +/- 21%, respectively (where Sco2 = alpha Sao2 + beta Sjo2 with alpha and beta being arterial and venous contributions). The contribution was similar among conditions but differed significantly among subjects (range, approximately 40:60 to approximately 0:100, arterial:venous). CONCLUSIONS: Cerebral oximetry monitors an arterial/venous ratio of 16:84, similar in normoxia, hypoxia, and hypocapnia. Because of biologic variation in cerebral arterial/venous ratios, use of a fixed ratio is not a good method to validate the technology.

BACKGROUND: Many children are restless, disoriented, and inconsolable immediately after bilateral myringotomy and tympanosotomy tube placement (BMT). Rapid emergence from sevoflurane anesthesia and postoperative pain may increase emergence agitation. The authors first determined serum fentanyl concentrations in a two-phase study of intranasal fentanyl. The second phase was a prospective, placebo-controlled, double-blind study to determine the efficacy of intranasal fentanyl in reducing emergence agitation after sevoflurane or halothane anesthesia. METHODS: In phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 microg/kg, during a standardized anesthetic. Serum fentanyl concentrations in blood samples drawn at emergence and at postanesthesia care unit (PACU) discharge were determined by radioimmunoassay. In phase 2, 265 children with ASA physical status I or II were randomized to receive sevoflurane or halothane anesthesia along with either intranasal fentanyl (2 microg/kg) or saline. Postoperative agitation, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, and satisfaction of PACU nurses and parents with the anesthetic technique were evaluated. RESULTS: In phase 1, the mean fentanyl concentrations at 10 +/- 4 min (mean +/- SD) and 34 +/- 9 min after administering intranasal fentanyl were 0.80 +/- 0.28 and 0.64 +/- 0.25 ng/ml, respectively. In phase 2, the incidence of severe agitation, highest CHEOPS scores, and heart rate in the PACU were decreased with intranasal fentanyl. There were no differences between sevoflurane and halothane in these measures and in times to hospital discharge. The incidence of postoperative vomiting, hypoxemia, and slow respiratory rates were not increased with fentanyl. CONCLUSIONS: Serum fentanyl concentrations after intranasal administration exceed the minimum effective steady state concentration for analgesia in adults. The use of intranasal fentanyl during halothane or sevoflurane anesthesia for BMT is associated with diminished postoperative agitation without an increase in vomiting, hypoxemia, or discharge times.

BACKGROUND: Volatile anesthetics, such as isoflurane, are widely used in infants and neonates. Neurodegeneration and neurocognitive impairment after exposure to isoflurane, midazolam, and nitrous oxide in neonatal rats have raised concerns regarding the safety of pediatric anesthesia. In neonatal mice, prolonged isoflurane exposure triggers hypoglycemia, which could be responsible for the neurocognitive impairment. We examined the effects of neonatal isoflurane exposure and blood glucose on brain cell viability, spontaneous locomotor activity, as well as spatial learning and memory in mice. METHODS: Seven-day-old mice were randomly assigned to 6 h of 1.5% isoflurane with or without injections of dextrose or normal saline, or to 6 h of room air without injections (no anesthesia). Arterial blood gases and glucose were measured. After 2 h, 18 h, or 11 wk postexposure, cellular viability was assessed in brain sections stained with Fluoro-Jade B, caspase 3, or NeuN. Nine weeks postexposure, spontaneous locomotor activity was assessed, and spatial learning and memory were evaluated in the Morris water maze using hidden and reduced platform trials. RESULTS: Apoptotic cellular degeneration increased in several brain regions early after isoflurane exposure, compared with no anesthesia. Despite neonatal cell loss, however, adult neuronal density was unaltered in two brain regions significantly affected by the neonatal degeneration. In adulthood, spontaneous locomotor activity and spatial learning and memory performance were similar in all groups, regardless of neonatal isoflurane exposure. Neonatal isoflurane exposure led to an 18% mortality, and transiently increased Paco(2), lactate, and base deficit, and decreased blood glucose levels. However, hypoglycemia did not seem responsible for the neurodegeneration, as dextrose supplementation failed to prevent neuronal loss. CONCLUSIONS: Prolonged isoflurane exposure in neonatal mice led to increased immediate brain cell degeneration, however, no significant reductions in adult neuronal density or deficits in spontaneous locomotion, spatial learning, or memory function were observed.

Detection of cerebral hypoxia-ischemia remains problematic in neonates. Near-infrared spectroscopy, a noninvasive bedside technology has potential, although thresholds for cerebral hypoxia-ischemia have not been defined. This study determined hypoxic-ischemic thresholds for cerebral oxygen saturation (SCO2) in terms of EEG, brain ATP, and lactate concentrations, and compared these values with CBF and sagittal sinus oxygen saturation (SVO2). Sixty anesthetized piglets were equipped with near-infrared spectroscopy, EEG, laser-Doppler flowmetry, and a sagittal sinus catheter. After baseline, SCO2 levels of less than 20%, 20% to 29%, 30% to 39%, 40% to 49%, 50% to 59%, 60% to 79%, or 80% or greater were recorded for 30 minutes of normoxic normocapnia, hypercapnic hyperoxia, or bilateral carotid occlusion with or without arterial hypoxia. Brain ATP and lactate concentrations were measured biochemically. Logistic and linear regression determined the SCO2, CBF, and SVO2 thresholds for abnormal EEG, ATP, and lactate findings. Baseline SCO2 was 68 + 5%. The SCO2 thresholds for increased lactate, minor and major EEG change, and decreased ATP were 44 +/- 1%, 42 +/- 5%, 37 +/- 1%, and 33 +/- 1%. The SCO2 correlated linearly with SVO2 (r = 0.98) and CBF (r = 0.89), with corresponding SVO2 thresholds of 23%, 20%, 13%, and 8%, and CBF thresholds (% baseline) of 56%, 52%, 42%, and 36%. Thus, cerebral hypoxia-ischemia near-infrared spectroscopy thresholds for functional impairment are SCO2 33% to 44%, a range that is well below baseline SCO2 of 68%, suggesting a buffer between normal and dysfunction that also exists for CBF and SVO2.