Presentation on theme: "Hypoxic Ischemic Encephalopathy"— Presentation transcript:
1Hypoxic Ischemic Encephalopathy Neonatal Intensive Care NurseryNight Curriculum SeriesSource for image?
2Learning ObjectivesKnow the etiology of hypoxic-ischemic encephalopathy (HIE)Know the criteria used to diagnose HIEReview the clinical severity grading of HIEBe able to describe the pathophysiology of posthypoxic brain injuryBecome familiar with the assessment tools available to evaluate infants with HIEKnow how hypothermia is used for neuroprotection and the criteria for using itBecome familiar with the results of trials of allopurinol and opioids as neuroprotective agents
3Case ScenarioYou are paged to a code in the delivery room. Upon arrival, you are told that the patient is a 32 year old G2P1 woman whose last baby was delivered via C-section for breech presentation, but who wished to attempt a vaginal birth for this pregnancy. Right before you were paged, the woman, who is at term and had been in labor for the past 4 hours, suddenly complained of excruciating abdominal pain, became hypotensive, and fetal heart tones were lost. She is now under general anesthesia and the OB is performing an emergent C-section.
4Case Scenario What is the differential diagnosis? What are the implications of the maternal condition on the fetus?What should you expect in the immediate management of the newborn in the DR?
5Case ScenarioThe baby is delivered via C-section and is brought to the radiant warmer. Initial assessment reveals an unresponsive floppy infant with no respiratory effort and a heart rate of 80bpm. Resuscitation is undertaken. Subsequent Apgar scores are 1, 4, and 7 at 1, 5 and 10 minutes, respectively. The baby is transferred to the NICU for further care.
6Case ScenarioWhat complications should you expect from this delivery and what is the underlying pathophysiology?What diagnostic and prognostic studies should be done in the NICU?What treatments are available for this baby and what are the criteria to treat?
7DefinitionsHypoxia or Anoxia: A partial (hypoxia) or complete (anoxia) lack of oxygen in the brain or bloodAsphyxia: The state in which placental or pulmonary gas exchange is compromised or ceases altogetherIschemia: The reduction or cessation of bloodflow to an organ which compromises both oxygen and substrate delivery to the tissueHypoxic-Ischemic Encephalopathy: Abnormal neurologic behavior in the neonatal period arising as a result of a hypoxic-ischemic event.
8Etiology of HIE Maternal: Cardiac arrest Asphyxiation Severe anaphylaxisStatus epilepticusHypovolemic shockUteroplacental:Placental abruptionCord prolapseUterine ruptureHyperstimulation with oxytocic agentsFetal:Fetomaternal hemorrhageTwin to twin transfusionSevere isoimmune hemolytic diseaseCardiac arrhythmia
9Incidence of HIEOccurs in 1-6 per 1000 live term births in developed countries25% die or have multiple disabilities4% have mild to moderate forms of cerebral palsy10% have developmental delay (this is similar to the control population!)
10PathophysiologyThe immature brain is in some ways more resistant to hypoxic-ischemic events compared to older children & adultsThis may be due to:Lower cerebral metabolic rateImmaturity in the development of the balance of neurotransmittersPlasticity of the immature CNS
11PathophysiologyGestational age plays an important role in the susceptibility of CNS structures< 20 weeks: Insult leads to neuronal heterotopia or polymicrogyria26-36 weeks: Insult affects white matter, leading to periventricular leukomalaciaTerm: Insult affects primarily gray matter
12PathophysiologyOther factors that influence the distribution of CNS injury:Cellular susceptibility (neuron most susceptible)Vascular territories (watershed areas)Regional susceptibility (areas of higher metabolic rates, ie. Thalamus)Degree of asphyxia
14Pathophysiology Acute HIE leads to primary and secondary events: Primary neuronal damage: cytotoxic changes due to failure of microcirculation inhibition of energy-producing molecular processes ATPase membrane pump failure cytotoxic edema and free radical formation compromised cellular integritySecondary neuronal damage: May extend up to 72 hours or more after the acute insult and results in an inflammatory response and cell necrosis or apoptosis (fueled by reperfusion)
15Diagnosis There is no clear diagnostic test for HIE Abnormal findings on the neurologic exam in the first few days after birth is the single most useful predictor that brain insult has occurred in the perinatal periodEssential Criteria for Diagnosis of HIE:Metabolic acidosis (cord pH <7 or base deficit of >12)Early onset of encephalopathyMultisystem organ dysfunction
16Clinical Staging of HIE (Sarnat and Sarnat, 1976) HIE can be divided into Mild, Moderate, and Severe
17Systemic Complications of HIE Acute renal failure in up to 20% of asphyxiated term infantsMyocardial dysfunction and hypotension in 28-50% of term infantsElevated LFTs in 80-85% of term infantsCoagulation impairment is relatively common in severely asphyxiated infantsSupportive care required!!
18Assessment Tools in HIE Amplitude-integrated EEG (aEEG)When performed early, it may reflect dysfunction rather than permanent injuryMost useful in infants who have moderate to severe encephalopathyMarginally abnormal or normal aEEG is very reassuring of good outcomeSeverely abnormal aEEG in infants with moderate HIE raises the probability of death or severe disability from 25% to 75%
19Assessment Tools in HIE Evoked PotentialsBrainstem auditory evoked potentials, visual evoked potentials and somatosensory evoked potentials can be used in full-term infants with HIEMore sensitive and specific than aEEG aloneHowever, not as available as aEEG and there is a lack of experience among pediatric neurologistsTherefore aEEG is preferred because of easy access, application, and interpretation
20Assessment Tools in HIE NeuroimagingCranial ultrasound: Not the best in assessing abnormalities in term infants. Echogenicity develops gradually over daysCT: Less sensitive than MRI for detecting changes in the central gray nucleiMRI: Most appropriate technique and is able to show different patterns of injury. Presence of signal abnormality in the internal capsule later in the first week has a very high predictive value for neurodevelopmental outcome
21Management - Hypothermia Has become standard of careWhole-body and head-cooling availableUnclear if one regimen is superior to the other - currently either one is utilized, based on availabilityAim to get core (rectal) temperature to 33-35º C for 72 hoursbased on Cool Cap and NICHD Neonatal Research Network trials
22Hypothermia - Mechanism of Action Reduces cerebral metabolism, prevents edemaDecreases energy utilizationReduces/suppresses cytotoxic amino acid accumulation and nitric oxideInhibits platelet-activating factor, inflammatory cascadeSuppresses free radical activityAttenuates secondary neuronal damageInhibits cell deathReduces extent of brain damageDEATH OR SEVERE DISABILITY AT 18 MONTHS OF AGE SIGNIFICANTLY REDUCED!!
23Criteria for Hypothermia Hypothermia is not effective for every babyCurrently only used in infants > 35 weeksTime interval between birth and initiation of treatment importantTreatment must be started within 6 hours of birth to be effective
24UCMC Criteria for Hypothermia Infant must be 35 weeks gestation or moreInfant must have 2 of the following:Apgar score of 5 or less at 10 minutesMechanical ventilation or resuscitation at 10 minutesCord or arterial pH <7 or base deficit of 12 or more within 60 minutes of birthCooling must be started within 6 hours of birthCore temp goal of 33-34ºC for 72 hours
25Pharmacologic Management AllopurinolSome trials have shown a decrease in mortality and a beneficial effect on free radical formation, cerebral blood flow and electrical brain activityMeta-analysis concluded that more trials need to be done using allopurinol as an adjunct to hypothermia to make a conclusion on its effectiveness in treating HIE
26Pharmacologic Management OpioidsA few studies have demonstrated that morphine and fentanyl may have a neuroprotective effect after HIE with less severe signs of brain damage on MRI at 7 days of life and better neurologic outcomes at 13 months of ageHowever, long term effects of these medications are not known and more prospective randomized trials are warranted.
27Gaps in Current Knowledge What is the contribution of the fetal inflammatory response?Are there gender and genetic influences?How can all drugs be delivered effectively across the blood-brain barrier?What additional evaluations should be performed at the time of delivery to enhance therapy?What are potential treatment strategies for infants who initially present beyond 6 hours of age?
28Questions1. The mother of a baby with suspected HIE inquires about the possibility of a brain insult in her infant. Of the following, the single most useful predictor of brain insult in this infant is the evidence of: A. Abnormal neurologic exam findings B. Cerebral edema on cranial US C. Elevated creatinine phosphokinase D. Hemodynamic and pulmonary imbalance E. Multisystem organ dysfunction
29Questions1. The mother of a baby with suspected HIE inquires about the possibility of a brain insult in her infant. Of the following, the single most useful predictor of brain insult in this infant is the evidence of: A. Abnormal neurologic exam findings B. Cerebral edema on cranial US C. Elevated creatinine phosphokinase D. Hemodynamic and pulmonary imbalance E. Multisystem organ dysfunction
30Questions2. The severity of HIE can be graded as mild, moderate, or severe, using a classification proposed by Sarnat and Sarnat. Of the following, the criterion most consistent with the diagnosis of mild HIE is:A. Absence of seizuresB. Low Apgar scoresC. Need for assisted ventilationD. Proximal muscle weaknessE. Obtunded state of consciousness
31Questions2. The severity of HIE can be graded as mild, moderate, or severe, using a classification proposed by Sarnat and Sarnat. Of the following, the criterion most consistent with the diagnosis of mild HIE is:A. Absence of seizuresB. Low Apgar scoresC. Need for assisted ventilationD. Proximal muscle weaknessE. Obtunded state of consciousness
32Questions3. Several ancillary tests have been proposed to improve the prediction of long-term outcome of infants who have suffered from HIE. Of the following, the most useful and practical test for determining the prognosis of HIE is:A. Cranial ultrasoundB. MRIC. EEGD. Near-infrared spectroscopyE. Somatosensory evoked potentials
33Questions3. Several ancillary tests have been proposed to improve the prediction of long-term outcome of infants who have suffered from HIE. Of the following, the most useful and practical test for determining the prognosis of HIE is:A. Cranial ultrasoundB. MRIC. EEGD. Near-infrared spectroscopyE. Somatosensory evoked potentials
34ReferencesAllan WC. The clinical spectrum and prediction of outcome in hypoxic-ischemic encephalopathy. Neoreviews 2002; 3; e108-e115Delivoria-Papadopoulos M, et al. Biochemical basis of hypoxic-ischemic encephalopathy. Neoreviews 2010; 11; e184-e193Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant, 9th edition. 2011, pMarro, PJ, et al. Pharmacology review: Neuroprotective treatments for hypoxic-ischemic injury. Neoreviews 2010; 11; e311-e315Shankaran S. Neonatal encephalopathy: Treatment with hypothermia. Neoreviews 2010; 11; e85-e92