Cerebral metabolic rate of oxygen and amplitude-integrated electroencephalography during early reperfusion after hypoxia-ischemia in piglets.

The therapeutic window following perinatal hypoxia-ischemia is brief, and early clinical signs of injury can be subtle. Electroencephalography (EEG) represents the most promising early diagnostic of hypoxia-ischemia; however, some studies have questioned the sensitivity and specificity of EEG. The present study investigated the use of both near-infrared spectroscopy (NIRS) measurements of the cerebral metabolic rate of oxygen (CMRO(2)) and amplitude-integrated EEG (aEEG) to detect the severity of hypoxia-ischemia after 1 h of reperfusion in newborn piglets (10 insult, 3 control). The CMRO(2) was measured before and after 1 h of reperfusion from hypoxia-ischemia, the duration of which was varied from piglet to piglet with a range of 3-24 min, under fentanyl/nitrous oxide anesthesia to mimic awake-like levels of cerebral metabolism. EEG data were collected throughout the study. On average, the CMRO(2) and mean aEEG background signals were significantly depressed following the insult (P < 0.05). Mean CMRO(2) and mean aEEG background were 2.61 +/- 0.11 ml O(2).min(-1).100 g(-1) and 20.4 +/- 2.7 microV before the insult and 1.58 +/- 0.09 ml O(2).min(-1).100 g(-1) and 11.8 +/- 2.9 microV after 1 h of reperfusion, respectively. Both CMRO(2) and aEEG displayed statistically significant correlations with duration of ischemia (P < 0.05; r = 0.71 and r = 0.89, respectively); however, only CMRO(2) was sensitive to milder injuries (<5 min). This study highlights the potential for combining NIRS measures of CMRO(2) with EEG in the neonatal intensive care unit to improve early detection of perinatal hypoxia-ischemia.

[1]  K. Zierler Equations for Measuring Blood Flow by External Monitoring of Radioisotopes , 1965, Circulation research.

[2]  D. Maynard,et al.  Device for continuous monitoring of cerebral activity in resuscitated patients. , 1969, British medical journal.

[3]  D. Ingvar,et al.  Correlation between dominant EEG frequency, cerebral oxygen uptake and blood flow. , 1976, Electroencephalography and clinical neurophysiology.

[4]  B. Siesjö,et al.  Brain energy metabolism , 1978 .

[5]  N Monod,et al.  Neonatal Electroencephalography During the First Twenty-Four Hours of Life in Full-Term Newborn Infants , 1986, Neuropediatrics.

[6]  C. Poser,et al.  Arterial Behavior and Blood Circulation in the Brain , 1987 .

[7]  Ira J. Rampil,et al.  1653 and Isoflurane Produce Similar Dose‐related Changes in the Electroencephalogram of Pigs , 1988, Anesthesiology.

[8]  A. Gunn,et al.  Outcome after ischemia in the developing sheep brain: An electroencephalographic and histological study , 1992, Annals of neurology.

[9]  G. Bernert,et al.  Near-Infrared spectroscopy in newborn infants , 1992, Brain and Development.

[10]  C. Cooper,et al.  Absolute quantification of deoxyhaemoglobin concentration in tissue near infrared spectroscopy. , 1994, Physics in medicine and biology.

[11]  R. Koehler,et al.  Interaction of Fentanyl and Nitrous Oxide on Peripheral and Cerebral Hemodynamics in Newborn Lambs , 1994, Anesthesiology.

[12]  D. Delpy,et al.  Quantification of adult cerebral hemodynamics by near-infrared spectroscopy. , 1994, Journal of applied physiology.

[13]  N. Sims,et al.  Biochemical changes associated with selective neuronal death following short-term cerebral ischaemia. , 1995, The international journal of biochemistry & cell biology.

[14]  A. Barkovich,et al.  Magnetic resonance imaging in perinatal asphyxia. , 1995, Archives of disease in childhood. Fetal and neonatal edition.

[15]  I. Rosén,et al.  Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. , 1995, Archives of disease in childhood. Fetal and neonatal edition.

[16]  P. Steen,et al.  A Piglet Survival Model of Posthypoxic Encephalopathy , 1996, Pediatric Research.

[17]  B S Carter,et al.  Prospective validation of a scoring system for predicting neonatal morbidity after acute perinatal asphyxia. , 1998, The Journal of pediatrics.

[18]  C. W. Yoxall,et al.  Measurement of Cerebral Oxygen Consumption in the Human Neonate Using Near Infrared Spectroscopy: Cerebral Oxygen Consumption Increases with Advancing Gestational Age , 1998, Pediatric Research.

[19]  Identification of term infants at risk for neonatal morbidity. , 1998, The Journal of pediatrics.

[20]  I. Roberts,et al.  Measurement of Cerebral Blood Flow in Newborn Infants Using Near Infrared Spectroscopy with Indocyanine Green , 1998, Pediatric Research.

[21]  L. D. de Vries,et al.  Amplitude integrated EEG 3 and 6 hours after birth in full term neonates with hypoxic–ischaemic encephalopathy , 1999, Archives of disease in childhood. Fetal and neonatal edition.

[22]  A. David Edwards,et al.  Assessment of Neonatal Encephalopathy by Amplitude-integrated Electroencephalography , 1999, Pediatrics.

[23]  R. Craen,et al.  Dynamic CT measurement of cerebral blood flow: a validation study. , 1999, AJNR. American journal of neuroradiology.

[24]  K. Blomgren,et al.  Impairment of mitochondrial respiration after cerebral hypoxia-ischemia in immature rats: relationship to activation of caspase-3 and neuronal injury. , 2000, Brain research. Developmental brain research.

[25]  E. Cady Magnetic resonance spectroscopy in neonatal hypoxic-ischaemic insults , 2001, Child's Nervous System.

[26]  Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green. , 2001, Physics in medicine and biology.

[27]  D. Delpy,et al.  Quantitative Near Infrared Spectroscopy Measurement of Cerebral Hemodynamics in Newborn Piglets , 2002, Pediatric Research.

[28]  V. Borutaite,et al.  Serial Review: Nitric Oxide in Mitochondria Guest Editors: Christoph Richter and Matthias Schweizer NITRIC OXIDE INHIBITION OF MITOCHONDRIAL RESPIRATION AND ITS ROLE IN CELL DEATH , 2002 .

[29]  Ting-Yim Lee,et al.  Near-Infrared Spectroscopy Measurement of Oxygen Extraction Fraction and Cerebral Metabolic Rate of Oxygen in Newborn Piglets , 2003, Pediatric Research.

[30]  J. Low Determining the contribution of asphyxia to brain damage in the neonate , 2004, The journal of obstetrics and gynaecology research.

[31]  L. D. de Vries,et al.  Role of cerebral function monitoring in the newborn , 2005, Archives of Disease in Childhood - Fetal and Neonatal Edition.

[32]  Carol L Wagner,et al.  Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. , 2005, Pediatric neurology.

[33]  S. Jacobs,et al.  Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. , 2005, The Journal of pediatrics.

[34]  D. Delpy,et al.  Measurement of CMRO2 in neonates undergoing intensive care using near infrared spectroscopy. , 2005, Advances in experimental medicine and biology.

[35]  A. du Plessis,et al.  Near-infrared spectroscopy in the fetus and neonate. , 2006, Clinics in perinatology.

[36]  Paul B. Colditz,et al.  Hypoxic/Ischemic models in newborn piglet: Comparison of constant FiO2 versus variable FiO2 delivery , 2006, Brain Research.

[37]  Ting-Yim Lee,et al.  Near-infrared spectroscopy measurements of cerebral blood flow and oxygen consumption following hypoxia-ischemia in newborn piglets , 2006 .

[38]  A. Brambrink,et al.  Brain protection by anesthetic agents , 2006, Current opinion in anaesthesiology.

[39]  Ingmar Rosén,et al.  Continuous brain-function monitoring: state of the art in clinical practice. , 2006, Seminars in fetal & neonatal medicine.

[40]  Ting-Yim Lee,et al.  Measurement of Cerebral Oxidative Metabolism with Near-Infrared Spectroscopy: A Validation Study , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  Eduardo D. Martín,et al.  Adenosine released by astrocytes contributes to hypoxia‐induced modulation of synaptic transmission , 2007, Glia.

[42]  N. Schor,et al.  Whole-Body Hypothermia for Neonates With Hypoxic–Ischemic Encephalopathy , 2007 .

[43]  A. Gunn,et al.  Timing of injury in the fetus and neonate , 2008, Current opinion in obstetrics & gynecology.

[44]  W. McGuire,et al.  Allopurinol for preventing mortality and morbidity in newborn infants with suspected hypoxic-ischaemic encephalopathy. , 2008, The Cochrane database of systematic reviews.

[45]  S. Donn,et al.  Should amplitude-integrated electroencephalography be used to identify infants suitable for hypothermic neuroprotection? , 2008, Journal of Perinatology.

[46]  Ting-Yim Lee,et al.  Assessing the Severity of Perinatal Hypoxia-Ischemia in Piglets Using Near-Infrared Spectroscopy to Measure the Cerebral Metabolic Rate of Oxygen , 2009, Pediatric Research.

[47]  Ting-Yim Lee,et al.  Changes in Cerebral Oxygen Consumption and High-Energy Phosphates During Early Recovery in Hypoxic-Ischemic Piglets: A Combined Near-Infrared and Magnetic Resonance Spectroscopy Study , 2009, Pediatric Research.