C. Dean Kurth

Arterial and venous contributions to near-infrared cerebral oximetry.

BackgroundCerebral 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. MethodsTwenty 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. ResultsAmong 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 × −17, r = 0.47), Sjo2 (y = 0.77 × +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 = &agr; Sao2 + &bgr; Sjo2 with &agr; and &bgr; being arterial and venous contributions). The contribution was similar among conditions but differed significantly among subjects (range, ≈ 40:60 to ≈ 0:100, arterial:venous). ConclusionsCerebral 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.

Brain magnetic resonance imaging abnormalities after the Norwood procedure using regional cerebral perfusion

OBJECTIVES Neurologic deficits are common after the Norwood procedure for hypoplastic left heart syndrome. Because of the association of deep hypothermic circulatory arrest with adverse neurologic outcome, regional low-flow cerebral perfusion has been used to limit the period of intraoperative brain ischemia. To evaluate the impact of this technique on brain ischemia, we performed serial brain magnetic resonance imaging in a cohort of infants before and after the Norwood operation using regional cerebral perfusion. METHODS Twenty-two term neonates with hypoplastic left heart syndrome were studied with brain magnetic resonance imaging before and at a median of 9.5 days after the Norwood operation. Results were compared with preoperative, intraoperative, and postoperative risk factors to identify predictors of neurologic injury. RESULTS Preoperative magnetic resonance imaging (n = 22) demonstrated ischemic lesions in 23% of patients. Postoperative magnetic resonance imaging (n = 15) demonstrated new or worsened ischemic lesions in 73% of patients, with periventricular leukomalacia and focal ischemic lesions occurring most commonly. Prolonged low postoperative cerebral oximetry (<45% for >180 minutes) was associated with the development of new or worsened ischemia on postoperative magnetic resonance imaging (P = .029). CONCLUSIONS Ischemic lesions occur commonly in neonates with hypoplastic left heart syndrome before surgery. Despite the adoption of regional cerebral perfusion, postoperative cerebral ischemic lesions are frequent, occurring in the majority of infants after the Norwood operation. Long-term follow-up is necessary to assess the functional impact of these lesions.

Use of intranasal fentanyl in children undergoing myringotomy and tube placement during halothane and sevoflurane anesthesia.

BackgroundMany 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. MethodsIn phase 1, 26 children with American Society of Anesthesiologists (ASA) physical status I or II who were scheduled for BMT received intranasal fentanyl, 2 &mgr;g/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 &mgr;g/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. ResultsIn 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. ConclusionsSerum 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.

A multiwavelength frequency-domain near-infrared cerebral oximeter.

This study tests a multiwavelength frequency-domain near-infrared oximeter (fdNIRS) in an in vitro model of the human brain. The model is a solid plastic structure containing a vascular network perfused with blood in which haemoglobin oxygen saturation (SO2) was measured by co-oximetry, providing a standard for comparison. Plastic shells of varying thickness (0.5-2 cm), with a vascular network of their own and encircling the brain model, were also added to simulate extracranial tissues of the infant, child and adult. The fdNIRS oximeter utilizes frequency-domain technology to monitor phaseshifts at 754 nm, 785 nm and 816 nm relative to a 780 nm reference to derive SO2 through photon transport and Beer-Lambert equations. We found a linear relationship between fdNIRS SO2 and co-oximetry SO2 with excellent correlation (r2 > or = 0.95) that fitted the line of identity in all experiments (n = 7). The bias of fdNIRS oximetry was -2% and the precision was 6%. Blood temperature and fdNIRS source-detector distance did not affect fdNIRS oximetry. Low haemoglobin concentration (6 g dl(-1)) altered the fdNIRS versus co-oximetry line slope and intercept, producing a 15% error at the extremes of SO2. The infant- and child-like shells overlying the brain model did not alter fdNIRS oximetry, whereas the adult-like shell yielded an error as high as 32%. In conclusion, fdNIRS accurately measures SO2 in an in vitro brain model, although low haemoglobin concentration and extracranial tissue of adult thickness influence accuracy.

Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets.

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.

The effects of neonatal isoflurane exposure in mice on brain cell viability, adult behavior, learning, and memory.

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 Paco2, 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.

Cerebral oxygen saturation before congenital heart surgery

BACKGROUND In congenital heart disease (CHD), neurologic abnormalities suggestive of hypoxia-ischemia are often apparent before cardiac surgery. To evaluate preoperative cerebral oxygenation, this study determined cerebral O2 saturation (ScO2) in CHD and healthy children. METHODS Ninety-one CHD and 19 healthy children aged less than 7 years were studied before surgical or radiologic procedures. Arterial saturation (SaO2) and ScO2 were measured by pulse-oximetry and near infrared cerebral oximetry. Cerebral O2 extraction (CEO2) was calculated (SaO2-ScO2). SaO2, ScO2, and CEO2 were compared among diagnoses. Multivariable regression was performed between ScO2 and clinical variables. RESULTS In healthy subjects, ScO2 (68%+/-10%) and CEO2 (30%+/-11%) were similar to patients with ventricular septal defect, aortic coarctation, and single ventricle after Fontan operation. ScO2 was significantly decreased in patients with patent ductus arteriosus (53%+/-8%), tetralogy of Fallot (57%+/-12%), hypoplastic left heart syndrome (46%+/-8%), pulmonary atresia (38%+/-6%), and single ventricle after aortopulmonary shunt (50%+/-7%), or bidirectional Glenn operation (43%+/-6%). CEO2 was significantly different only in patent ductus arteriosus (46%+/-8%) and hypoplastic left heart syndrome (38%+/-12%). In multivariable regression, only SaO2 was related to ScO2 (R = 0.63, p < 0.001). CONCLUSIONS Cerebral oxygenation in CHD varies with anatomy and arterial saturation, and in some patients, it is very low compared with healthy subjects.

Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs

OBJECTIVES Deep hypothermic circulatory arrest (DHCA) widely used during neonatal heart surgery, carries a risk of brain damage. In adult normothermic ischemia, brain cells in certain regions die, some by necrosis and others by apoptosis (programmed cell death). This study characterized regional brain cell death after DHCA in newborn pigs. METHODS Eighteen piglets underwent 90 minutes of DHCA and survived 6 hours, 2 days, or 1 week. Six piglets underwent surgery alone or deep hypothermic cardiopulmonary bypass and survived 2 days. Three piglets received no intervention (control). Brain injury was assessed by neurologic and histologic examination and correlated with perioperative factors. Apoptosis and necrosis were identified by light microscopic analysis of cell structure and in situ DNA fragmentation (TUNEL). RESULTS All groups subjected to DHCA had brain injury by neurologic and histologic examination, whereas the other groups did not. DHCA damaged neurons in the neocortex and hippocampus and occasionally in the striatum and cerebellum. Damaged neurons in the neocortex were mainly apoptotic and in the hippocampus, a mixture of necrotic and apoptotic neurons. Apoptosis and necrosis were apparent in all DHCA groups even though neurologic deficits improved over the weeks survival. Neocortical and hippocampal damage correlated with blood glucose, hematocrit, and arterial PO(2) during and after cardiopulmonary bypass. CONCLUSIONS In neonates, neocortical and hippocampal neurons are selectively vulnerable to death after DHCA. Both apoptosis and necrosis contribute to neuronal death, beginning early in reperfusion and continuing for days. These data suggest the need for several neuroprotective strategies tailored to the region and death process, initiated during the operation and continued after the operation.

The physiologic effects of isoflurane anesthesia in neonatal mice

In neonatal rodents, isoflurane has been shown to confer neurological protection during hypoxia-ischemia and to precipitate neurodegeneration after prolonged exposure. Whether neuroprotection or neurotoxicity result from a direct effect of isoflurane on the brain or an indirect effect through hemodynamic or metabolic changes remains unknown. We recorded arterial blood pressure, heart rate, blood gases, and glucose in 10-day-old mice during 60 min of isoflurane anesthesia with spontaneous or mechanical ventilation, as well as during 60 min of hypoxia-ischemia with isoflurane anesthesia or without anesthesia. During isoflurane anesthesia, hypoglycemia and metabolic acidosis occurred with spontaneous and mechanical ventilation. During hypoxia-ischemia, isoflurane was fatal with spontaneous breathing but survivable with mechanical ventilation, with arterial blood pressure and heart rate being similar to that observed in unanesthetized animals. Minimum alveolar concentration (MAC) was 2.3% in 10-day-old mice. In summary, isoflurane anesthesia precipitated hypoglycemia, which may have contributed to the neurodegeneration observed in neonatal rodents. Use of 0.8 MAC isoflurane for evaluation of neuroprotection during hypoxia-ischemia requires mechanical ventilation and glucose supplementation in this model.

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanils use as an anesthetic for children. IMPLICATIONS This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanils use as an anesthetic for children.