Electroencephalographic Indices for Clinical Endpoints during Propofol Anesthesia in Infants: An Early-phase Propofol Biomarker-finding Study.

BACKGROUND: Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. METHODS: This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. RESULTS: Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 µg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) µg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). CONCLUSIONS: SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.

Implementation of an electroencephalogram-guided propofol anesthesia practice in a large academic pediatric hospital: A quality improvement project.

BACKGROUND: Propofol-based total intravenous anesthesia is gaining popularity in pediatric anesthesia. Electroencephalogram can be used to guide propofol dosing to the individual patient to mitigate against overdosing and adverse events. However, electroencephalogram interpretation and propofol pharmacokinetics are not sufficiently taught in training programs to confidently deploy electroencephalogram-guided total intravenous anesthesia. AIMS: We conducted a quality improvement project with the smart aim of increasing the percentage of electroencephalogram-guided total intravenous anesthesia cases in our main operating room from 0% to 80% over 18 months. Balancing measures were number of total intravenous anesthesia cases, emergence times, and perioperative emergency activations. METHODS: The project key drivers were education, equipment, and electronic health record modifications. Plan-Do-Study-Act cycles included: (1) providing journal articles, didactic lectures, intraoperative training, and teaching documents; (2) scheduling electroencephalogram-guided total intravenous anesthesia teachers to train faculty, staff, and fellows for specific cases and to assess case-based knowledge; (3) adding age-based propofol dosing tables and electroencephalogram parameters to the electronic health record (EPIC co, Verona, WI); (4) procuring electroencephalogram monitors (Sedline, Masimo Inc). Electroencephalogram-guided total intravenous anesthesia cases and balancing measures were identified from the electronic health record. The smart aim was evaluated by statistical process control chart. RESULTS: After the four Plan-Do-Study-Act cycles, electroencephalogram-guided total intravenous anesthesia increased from 5% to 75% and was sustained at 72% 9 months after project completion. Total intravenous anesthesia cases/mo and number of perioperative emergency activations did not change significantly from start to end of the project, while emergence time for electroencephalogram-guided total intravenous anesthesia was greater statistically but not clinically (total intravenous anesthesia without electroencephalogram [16 ± 10 min], total intravenous anesthesia with electroencephalogram [18 ± 9 min], sevoflurane [17 ± 9 min] p < .001). CONCLUSION: Quality improvement methods may be deployed to adopt electroencephalogram-guided total intravenous anesthesia in a large academic pediatric anesthesia practice. Keys to success include education, in operating room case training, scheduling teachers with learners, electronic health record modifications, and electroencephalogram devices and supplies.

Quantitative electroencephalogram in term neonates under different sleep states.

Electroencephalogram (EEG) can be used to assess depth of consciousness, but interpreting EEG can be challenging, especially in neonates whose EEG undergo rapid changes during the perinatal course. EEG can be processed into quantitative EEG (QEEG), but limited data exist on the range of QEEG for normal term neonates during wakefulness and sleep, baseline information that would be useful to determine changes during sedation or anesthesia. We aimed to determine the range of QEEG in neonates during awake, active sleep and quiet sleep states, and identified the ones best at discriminating between the three states. Normal neonatal EEG from 37 to 46 weeks were analyzed and classified as awake, quiet sleep, or active sleep. After processing and artifact removal, total power, power ratio, coherence, entropy, and spectral edge frequency (SEF) 50 and 90 were calculated. Descriptive statistics were used to summarize the QEEG in each of the three states. Receiver operating characteristic (ROC) curves were used to assess discriminatory ability of QEEG. 30 neonates were analyzed. QEEG were different between awake vs asleep states, but similar between active vs quiet sleep states. Entropy beta, delta2 power %, coherence delta2, and SEF50 were best at discriminating awake vs active sleep. Entropy beta had the highest AUC-ROC ≥ 0.84. Entropy beta, entropy delta1, theta power %, and SEF50 were best at discriminating awake vs quiet sleep. All had AUC-ROC ≥ 0.78. In active sleep vs quiet sleep, theta power % had highest AUC-ROC > 0.69, lower than the other comparisons. We determined the QEEG range in healthy neonates in different states of consciousness. Entropy beta and SEF50 were best at discriminating between awake and sleep states. QEEG were not as good at discriminating between quiet and active sleep. In the future, QEEG with high discriminatory power can be combined to further improve ability to differentiate between states of consciousness.

Comparison of Postoperative Respiratory Monitoring by Acoustic and Transthoracic Impedance Technologies in Pediatric Patients at Risk of Respiratory Depression.

BACKGROUND: In children, postoperative respiratory rate (RR) monitoring by transthoracic impedance (TI), capnography, and manual counting has limitations. The rainbow acoustic monitor (RAM) measures continuous RR noninvasively by a different methodology. Our primary aim was to compare the degree of agreement and accuracy of RR measurements as determined by RAM and TI to that of manual counting. Secondary aims include tolerance and analysis of alarm events. METHODS: Sixty-two children (2-16 years old) were admitted after tonsillectomy or receiving postoperative patient/parental-controlled analgesia. RR was measured at regular intervals by RAM, TI, and manual count. Each TI or RAM alarm resulted in a clinical evaluation to categorize as a true or false alarm. To assess accuracy and degree of agreement of RR measured by RAM or TI compared with manual counting, a Bland-Altman analysis was utilized showing the average difference and the limits of agreement. Sensitivity and specificity of RR alarms by TI and RAM are presented. RESULTS: Fifty-eight posttonsillectomy children and 4 patient/parental-controlled analgesia users aged 6.5 ± 3.4 years and weighting 35.3 ± 22.7 kg (body mass index percentile 76.6 ± 30.8) were included. The average monitoring time per patient was 15.9 ± 4.8 hours. RAM was tolerated 87% of the total monitoring time. The manual RR count was significantly different from TI (P = .007) with an average difference ± SD of 1.39 ± 10.6 but were not significantly different from RAM (P = .81) with an average difference ± SD of 0.17 ± 6.8. The proportion of time when RR measurements differed by ≥4 breaths was 22% by TI and was 11% by RAM. Overall, 276 alarms were detected (mean alarms/patient = 4.5). The mean number of alarms per patient were 1.58 ± 2.49 and 2.87 ± 4.32 for RAM and TI, respectively. The mean number of false alarms was 0.18 ± 0.71 for RAM and 1.00 ± 2.78 for TI. The RAM was found to have 46.6% sensitivity (95% confidence interval [CI], 0.29-0.64), 95.9% specificity (95% CI, 0.90-1.00), 88.9% positive predictive value (95% CI, 0.73-1.00), and 72.1% negative predictive value (95% CI, 0.61-0.84), whereas the TI monitor had 68.5% sensitivity (95% CI, 0.53-0.84), 72.0% specificity (95% CI, 0.60-0.84), 59.0% positive (95% CI, 0.44-0.74), and 79.5% negative predictive value (95% CI, 0.69-0.90). CONCLUSIONS: In children at risk of postoperative respiratory depression, RR assessment by RAM was not different to manual counting. RAM was well tolerated, had a lower incidence of false alarms, and had better specificity and positive predictive value than TI. Rigorous evaluation of the negative predictive value is essential to determine the role of postoperative respiratory monitoring with RAM.

Trending and accuracy of noninvasive hemoglobin monitoring in pediatric perioperative patients.

BACKGROUND: Rainbow Pulse CO-Oximetry technology (Masimo Corporation, Irvine, CA) provides continuous and noninvasive measurement of arterial hemoglobin concentration (SpHb). We assessed the trending and accuracy of SpHb by this innovative monitoring compared with Hb concentration obtained with conventional laboratory techniques (Hb) in children undergoing surgical procedures with potential for substantial blood loss. METHODS: Hb concentrations were recorded from Pulse CO-Oximetry and a conventional hematology analyzer. Regression analysis and 4-quadrant plot were used to evaluate the trending for changes in SpHb and Hb measurements (ΔSpHb and ΔHb). Bias, precision, and limits of agreement of SpHb and of in vivo adjusted SpHb (SpHb - first bias to HB) compared with Hb were calculated. RESULTS: One hundred fifty-eight SpHb-Hb data pairs and 105 delta pairs (ΔSpHb and ΔHb) from 46 patients aged 2 months to 17 years with Hb ranging from 16.7 to 7.9 g/dL were collected. To evaluate trending, the delta pairs (ΔSpHb and ΔHb) were plotted, which revealed a positive correlation (ΔSpHb = 0.022 + 0.76ΔHb) with correlation coefficient r = 0.76, 95% CI [confidence interval] = 0.57-0.86. The bias and precision of SpHb to Hb and in vivo adjusted SpHb were 0.4 ± 1.3 g/dL and 0.1 ± 1.2 g/dL, respectively; the limits of agreement were -2.0 to 3.2 g/dL before in vivo adjustment and -2.4 to 2.2 g/dL after in vivo adjustment (P value = 0.04). The mean percent bias (from the reference Hb concentration) decreased from 4.1% ± 11.9% to 0.7% ± 11.3% (P value = 0.01). No drift in bias over time was observed during the study procedure. Of patient demographic and physiological factors tested for correlation with the SpHb, only perfusion index at sensor site showed a weak correlation. CONCLUSIONS: The accuracy of SpHb in children with normal Hb and mild anemia is similar to that previously reported in adults and is independent of patient demographic and physiological states except for a weak correlation with perfusion index. The trending of SpHb and Hb in children with normal Hb and mild anemia showed a positive correlation. Further studies are necessary in children with moderate and severe anemia.

National pediatric anesthesia safety quality improvement program in the United States.

BACKGROUND: As pediatric anesthesia has become safer over the years, it is difficult to quantify these safety advances at any 1 institution. Safety analytics (SA) and quality improvement (QI) are used to study and achieve high levels of safety in nonhealth care industries. We describe the development of a multiinstitutional program in the United States, known as Wake-Up Safe (WUS), to determine the rate of serious adverse events (SAE) in pediatric anesthesia and to apply SA and QI in the pediatric anesthesia departments to decrease the SAE rate. METHODS: QI was used to design and implement WUS in 2008. The key drivers in the design were an organizational structure; an information system for the SAE; SA to characterize the SAE; QI to imbed high-reliability care; communications to disseminate the learnings; and engaged leadership in each department. Interventions for the key drivers, included Participation Agreements, Patient Safety Organization designation, IRB approval, Data Management Co., membership fee, SAE standard templates, SA and QI workshops, and department leadership meetings. RESULTS: WUS has 19 institutions, 39 member anesthesiologists, 734 SAE, and 736,365 anesthetics as of March, 2013. The initial members joined at year 1, and initial SAE were recorded by year 2. The SAE rate is 1.4 per 1000 anesthetics. Of SAE, respiratory was most common, followed by cardiac arrest, care escalation, and cardiovascular, collectively 76% of SAE. In care escalation, medication errors and equipment dysfunction were 89%. Of member anesthesiologists, 70% were trained in SA and QI by March 2013; virtually, none had SA and QI expertise before joining WUS. CONCLUSION: WUS documented the incidence and types of SAE nationally in pediatric anesthesiology. Education and application of QI and SA in anesthesia departments are key strategies to improve perioperative safety by WUS.

Quality and safety in pediatric anesthesia: how can guidelines, checklists, and initiatives improve the outcome?

PURPOSE OF REVIEW: Cognitive aids are tangible or intangible instruments that guide users in decision-making and in the completion of a complex series of tasks. Common examples include mnemonics, checklists, and algorithms. Cognitive aids constitute very effective approaches to achieve well tolerated, high quality healthcare because they promote highly reliable processes that reduce the likelihood of failure. This review describes recent advances in quality improvement for pediatric anesthesiology with emphasis on application of cognitive aids to impact patient safety and outcomes. RECENT FINDINGS: Quality improvement encourages the examination of systems to create stable processes and ultimately high-value care. Quality improvement initiatives in pediatric anesthesiology have been shown to improve outcomes and the delivery of efficient and effective care at many institutions. The use of checklists, in particular, improves adherence to evidence-based care in crisis situations, decreases catheter-associated bloodstream infections, reduces blood product utilization, and improves communication during the patient handoff process. Use of this simple tool has been associated with decreased morbidity, fewer medical errors, improved provider satisfaction, and decreased mortality in nonanesthesia disciplines as well. SUMMARY: Successful quality improvement initiatives utilize cognitive aids such as checklists and have been shown to optimize pediatric patient experience and anesthesia outcomes and reduce perioperative complications.

Accuracy of acoustic respiration rate monitoring in pediatric patients.

BACKGROUND: Rainbow acoustic monitoring (RRa) utilizes acoustic technology to continuously and noninvasively determine respiratory rate from an adhesive sensor located on the neck. OBJECTIVE: We sought to validate the accuracy of RRa, by comparing it to capnography, impedance pneumography, and to a reference method of counting breaths in postsurgical children. METHODS: Continuous respiration rate data were recorded from RRa and capnography. In a subset of patients, intermittent respiration rate from thoracic impedance pneumography was also recorded. The reference method, counted respiratory rate by the retrospective analysis of the RRa, and capnographic waveforms while listening to recorded breath sounds were used to compare respiration rate of both capnography and RRa. Bias, precision, and limits of agreement of RRa compared with capnography and RRa and capnography compared with the reference method were calculated. Tolerance and reliability to the acoustic sensor and nasal cannula were also assessed. RESULTS: Thirty-nine of 40 patients (97.5%) demonstrated good tolerance of the acoustic sensor, whereas 25 of 40 patients (62.5%) demonstrated good tolerance of the nasal cannula. Intermittent thoracic impedance produced erroneous respiratory rates (>50 b·min(-1) from the other methods) on 47% of occasions. The bias ± SD and limits of agreement were -0.30 ± 3.5 b·min(-1) and -7.3 to 6.6 b·min(-1) for RRa compared with capnography; -0.1 ± 2.5 b·min(-1) and -5.0 to 5.0 b·min(-1) for RRa compared with the reference method; and 0.2 ± 3.4 b·min(-1) and -6.8 to 6.7 b·min(-1) for capnography compared with the reference method. CONCLUSIONS: When compared to nasal capnography, RRa showed good agreement and similar accuracy and precision but was better tolerated in postsurgical pediatric patients.

Quantification of serum fentanyl concentrations from umbilical cord blood during ex utero intrapartum therapy.

Fetal IM injection of fentanyl is frequently performed during ex utero intrapartum therapy (EXIT procedure). We quantified the concentration of fentanyl in umbilical vein blood. Thirteen samples from 13 subjects were analyzed. Medians and ranges are reported as follows. Weight of the newborn at delivery was 3000 g (2020-3715 g). The dose of fentanyl was 60 µg (45-65 µg). The time between IM administration of fentanyl and collection of the sample was 37 minutes (5-86 minutes). Fentanyl was detected in all of the samples, with a median serum concentration of 14.0 ng/mL (4.3-64.0 ng/mL).

Cerebral oxygen saturation-time threshold for hypoxic-ischemic injury in piglets.

BACKGROUND: Detection of cerebral hypoxia-ischemia (H-I) and prevention of brain injury remains problematic in critically ill neonates. Near-infrared spectroscopy (NIRS), a noninvasive bedside technology could fill this role, although NIRS cerebral O(2) saturation (Sc(O2)) viability-time thresholds for brain injury have not been determined. We investigated the relationship between H-I duration at Sc(O2) 35%, a viability threshold which causes neurophysiological impairment, to neurological outcome. METHODS: Forty-six fentanyl-midazolam anesthetized piglets were equipped with NIRS and cerebral function monitor (CFM) to record Sc(O2) and electrocortical activity (ECA). After carotid occlusion, inspired O(2) was adjusted to produce H-I (Sc(O2) 35% with decreased ECA) for 1, 2, 3, 4, 6 or 8 h in different groups, followed by survival to assess neurological outcome by behavioral and histological examination. RESULTS: For H-I lasting 1 or 2 h, ECA and Sc(O2) during reperfusion rapidly returned to normal and neurological outcomes were normal. For H-I more than 2-3 h, ECA was significantly decreased and Sc(O2) was significantly increased during reperfusion, suggesting continued depression of tissue O(2) metabolism. As H-I increased beyond 2 h, the incidence of neurological injury increased linearly, approximately 15% per h. CONCLUSION: A viability-time threshold for H-I injury is Sc(O2) of 35% for 2-3 h, heralded by abnormalities in NIRS and CFM during reperfusion. These findings suggest that NIRS and CFM might be used together to predict neurological outcome, and illustrate that there is a several hour window of opportunity during H-I to prevent neurological injury.

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 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.

Factors predictive of poor behavioral compliance during inhaled induction in children.

BACKGROUND: Preoperative identification of children at risk of emotional distress and poor behavioral compliance during inhaled induction of anesthesia allows targeted interventions to reduce distress, thereby enhancing the quality of the anesthetic experience. We sought to identify patient, procedural, and health care system factors predictive of poor behavioral compliance during induction. METHODS: We studied 861 developmentally appropriate children ages 1-13 yr, The American Society of Anesthesiologists physical status I to III, presenting for inhaled induction of anesthesia. All inductions were performed in an induction room with parent(s) present. Behavioral compliance was assessed using the Induction Compliance Checklist (ICC), an observational scale consisting of 10 behaviors scored as the number of behaviors observed during induction; ICC > or =4 was considered poor behavioral compliance. A multivariable ordinal logistic regression model for behavioral compliance was generated and the performance of the multivariable model was evaluated by the c statistic. RESULTS: Twenty-one percent of children exhibited poor behavioral compliance on induction. Factors increasing the odds of poor behavioral compliance were younger age (< 4 yr, P < 0.0001), shorter preoperative preparation time (P = 0.004), and high anxiety levels in the preoperative clinic (modified-Yale preoperative anxiety scale > 40; P = 0.016). Previous anesthesia experience increased the odds in school-age children (P = 0.046); this effect was ameliorated in children attending the preoperative tour (P = 0.018). The model using these factors demonstrated moderate discrimination between children with poor compliance and those with perfect compliance (ICC = 0) (c statistic = 0.75). CONCLUSIONS: Factors predictive of poor behavioral compliance were age, previous anesthesia, preoperative tour attendance, preoperative preparation time and anxiety levels in the preoperative clinic. These factors, bundled into a predictive algorithm, may help identify children who could benefit from behavioral or pharmacological interventions and avoid use of interventions to those at low risk.

Development and validation of a multiwavelength spatial domain near-infrared oximeter to detect cerebral hypoxia-ischemia.

Detection of cerebral hypoxia-ischemia in infants remains problematic, as current monitors in clinical practice are impractical, insensitive, or nonspecific. Our study develops a multiwavelength spatial domain construct for near-infrared spectroscopy (NIRS) to detect cerebral hypoxia-ischemia and evaluates the construct in several models. The NIRS probe contains photodiode detectors 2, 3, and 4 cm from a three-wavelength, light-emitting diode. A construct determines cerebral O(2) saturation based on spatial domain principles. Device performance and construct validity are examined in in-vitro models simulating the brain, and in piglets subjected to hypoxia, hypoxia-ischemia, and hyperoxic conditions using a weighted average of arterial and cerebral venous O(2) saturation measured by CO-oximetry. The results in the brain models verify key equations in the construct and demonstrate reliable performance of the device. In piglets, the device measures cerebral O(2) saturation with bias +/-4% and precision +/-8%. In conclusion, this NIRS device accurately detects cerebral hypoxia-ischemia and is of a design that is practical for clinical application.

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.

An MRI study of neurological injury before and after congenital heart surgery.

BACKGROUND: Neurological deficits are observed in patients with congenital heart disease (CHD) before and after neonatal surgery, the etiology being multifactorial. To understand the impact of preoperative events and to characterize the evaluation of neurological injury, we performed serial magnetic resonance imaging (MRI) studies of the brain in a cohort of neonates undergoing open-heart surgery. METHODS AND RESULTS: Twenty-four term neonates with CHD were studied prospectively with brain MRI: before surgery, within 2 weeks of surgery, and several months after surgery. Preoperative MRI examinations showed periventricular leukomalacia (PVL) in 4 patients (16%) and infarct in 2 subjects (8%). MR spectroscopy was performed in 19 subjects preoperatively and revealed elevated brain lactate in 53%. An early postoperative MRI (n=21) identified new PVL in 48%, new infarct in 19%, and new parenchymal hemorrhage in 33%. New lesions or worsening of preoperative lesions occurred in 67% of subjects. No patient- or procedure-related factors for the development of early postoperative lesions were identified. A late postoperative MRI (n=17) demonstrated resolution of early lesions in 8 and mild cerebral atrophy in 2. CONCLUSIONS: Mild ischemic lesions, primarily in the form of PVL, occur in a number of neonates with CHD before surgery and >50% of patients postoperatively. Resolution of these lesions is common 4 to 6 months after surgery. Longer-term follow-up is needed to determine the significance of perioperative ischemic lesions on functional outcome.