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Neonatal Hypoxic Ischemic Brain Injury Management in the First Hours Dongli Song, MD, PhD Santa Clara Valley Medical Center Neonatology History • Baby girl F, born to a 35 year old G5P4 mother with good antenatal care. This pregnancy complicated by GDM, diet control. • Blood group O positive; Hep B neg: HIV neg: RPR neg: Rubella immune: GBS negative • Mom admitted at 37+2 weeks with active vaginal bleeding. US showed placenta abruption. Pediatric team get called to the DR stat • Infant was delivered via stat c/s. • At delivery, she was floppy with no respiratory effort and no heart rate. • Bag and mask ventilation started immediately, HR > 100 bpm at 3 min, and some respiration effort noted at 5 min. She was intubated at 7 min for poor sustained respiration. Color improved but remained floppy at 10 min. Apgar score 0@1 min; 4@ 5 min; 5@ 10 min. What should you ask OB/L&D staff in the DR? Get cord blood gas Answer: ask OB/L&D staff to send cord blood gas. Cord arterial gas: pH 6.8, PCO2 103, Bicarb 15 and BD19.7 • Cord blood gas provides critical information regarding the severity and/or duration of hypoxic ischemic insults prior to delivery. • Cord arterial gas (from UA) is a part of the criteria for hypothermia treatment. • If cord blood gas is not available, get infant ABG within first hour of life. Physical examination • Weight 3720gms (>90%), OFC 35.5 cm (90%), Length 54.4 (>90%) • Temperature 36.5oC • HR 190bpm, BP 37/23 mmHg. • Pale and poor perfused • On ventilator with periodic respiration effort • No significant dysmorphic features Neurological examination • Does this infant display encephalopathy? • How could the neurological examination have been done/documented to show this? Neurological examination A systemic detailed neuro exam were performed and documented: • Level of Consciousness: poor eye opening to stimulation, no sustained alertness • Movements and Tone: minimal spontaneous activity, hypotonia • Brainstem/Autonomic Functions: pupils constricted but reactive, no suck, no gag • Reflexes: incomplete Moro, no DTR NICHD Exam Criteria for Hypothermia Moderate Encephalopathy Severe Encephalopathy 1. Consciousness Lethargic Stupor/coma 2. Activity Decreased No Activity 3. Posture Distal Flexion Decerebrate Hypotonia (focal or general) Flaccid 5. Primitive Reflexes Suck Moro Weak Incomplete Absent Absent 6. Autonomic Pupils Heart Rate Respirations Constricted Bradycardia Periodic Fixed; Unequal Variable HR Apnea 4. Tone Lab tests Your initial lab work should include following: A. Check blood glucose B. CBC C. BCx D. Chem 7 E. LFTs F. Coagulation tests Lab tests Answer: All above. • Correcting hypoglycemia is critical for brain protection. • Mom had placenta abruption, HCT and platelet count will help to determine if blood product transfusion is indicated. • Increase in creatinine indicates kidney injury, and elevation of LFTs and coagulopathy indicates liver damage. Lab results • Cord arterial gas: pH 6.8, PCO2 103, Bicarb 15 and BD 19.7. • Blood glucose 15 • CBC: WBC 17.7k, HCT 30%, platelet count 141K • Creatinine 1.3 • AST 945, ALT 220 • PT/PTT/INR significant prolonged Antepartum Risk Factors • Socioeconomic Status • Family History • Infertility treatment • Maternal thyroid disease • • • • • • Severe pre-eclampsia Bleeding in pregnancy Viral illness Abnormal placenta IUGR Postmaturity Intrapartum Risk Factors • Operative vaginal delivery or emergency Csection • Maternal fever • Occipito-posterior presentation • Acute intrapartum events: cord prolapse, abruptio placentae… Heterogeneous cause Badawi N. et al. BMJ.1998 Hypothermia treatment One hour later, fluid boluses were given, hypoglycemia was corrected and FFP transfusion was started. Infant started to have spontaneous respiration effort and movements and her tone improved. Your next treatment plan include: A. Start hypothermia treatment ASAP B. Obtain brain imagine to confirm hypoxic-ischemic brain injury before start hypothermia treatment C. Continue monitoring. Hypothermia will not be indicated if infant’s condition significantly improved at 6hr of life. Hypothermia treatment Answer: A and B Diagnosis of Neonatal Encephalopathy is Clinical • Careful history and neurological exam • Laboratory studies to exclude “mimics” of hypoxiaischemia – Metabolic abnormalities • including inborn errors of metabolism – Infection – Acute bilirubin encephalopathy – Stroke Diagnosis – Neuro imaging HUS - may detect basal ganglia and thalamic injury, not sensitive to cortical injury. Most useful in detecting and following intracranial bleeding. CT - can detect diffuse cortical neuronal injury, most useful to r/o intracranial hemorrhage that requiring immediate surgical intervention. Concerns for radiation. MRI - is the study choice of assessing HI brain injury. It provides specific information regarding the injury pattern, severity and evolution. Neuro imaging is not an absolute requirement for initiating hypothermia treatment for HIE. Cortical Injury Chao, C. P. et al. Radiographics 2006;26:S159-S172 Copyright ©Radiological Society of North America, 2006 Basal Ganglia Injury Parent’s questions You talked to infant’s father and explained to him that the his baby is critically ill and may have suffered serious brain injury. He asked: • What causes her brain injury? • Is my baby going to die? • If she survived, will she be normal? • What can you do to save my baby? Significance • • • Incidence of HIE: 1-2/1000 live births *California: 4.5/1000 live births HIE is a major cause of infant mortality and morbidity with significant long term neurological deficits: 15 - 20% die in infancy and 20 -25% survived with some neurological abnormalities including cerebral palsy, cortical visual impairment, seizures, developmental delay and mental retardation. Hypothermia treatment • • • Neonatal encephalopathy is a neurological emergency. Brain injury evolves over time. Biphasic nature of cell death (Gluckman PD, et al 1992): Primary neuronal death (cell hypoxia/primary energy failure). Latent period – at least 6 hours. Secondary phase - delayed neuronal death begins. Mechanisms of ischemic brain injury Hypoxiaischemia Primary neuronal death Cytotoxic mechanisms 1 hour Hypothermia Modified from Gunn and Thoresen, 2006 Delayed neuronal death 6 hours Days Mechanisms of ischemic brain injury Ferriero D. NEJM 2004 INCLUSION ≥36wks GA and ≥ 1800gms Meet both Physiologic and Neurological Criteria No “Lethal” chromosomal or congenital anomalies NEUROLOGIC EXAM CRITERIA PHYSIOLOGIC CRITERIA Moderate Encephalopathy 3 of 6 findings below Cord or Baby’s ABG < 1 hour No gas <1hr OR pH 7.01-7.15 and BD 10-15.9 1. Lethargic 2. Inactive/decreased activity 3. Distal flexion 4. Hypotonia- focal or general 5. Weak suck/incomplete moro 6. Pupil constricted/ Bradycardia / periodic breathing pH ≤7.0 OR BD ≥ 16 Plus OR Severe Encephalopathy 3 of 6 findings below A MAJOR PERINATAL EVENT nonreassuring FHR cord prolapse/rupture, uterine rupture, maternal trauma, abruption, hemorrhage, CPR, AND Apgar ≤ 5 at 10 min, or PPV ≥ 10 min MEET PHYSIOLOGI C CRITERIA MEET AND NEUROLOGIC CRITERIA 1. Stupor/coma 2. No activity 3. Decerebrate 4. Flaccid tone 5. Absent suck/moro 6. Pupils dilated /unreactive /skew, variable HR, apnea OR Seizure Cooling Based on NICHD total body cooling protocol Clinical or Electrical Hypothermia treatment Whole Body Cooling cooling blanket > esophageal temp 33.5oC for 72hrs Select Head Cooling Cooling Cap > rectal temp 34-35 oC for 72hrs Hypothermia Trials: 50% Cooled Babies had Poor Outcomes Cooled Controls Died or severe disability 44-55% 62-66% Died 24-33% 38% Bayley MDI < 70 25-30% 39% Bayley PDI < 70 27-30% 35-41% NICHD and CoolCap trials, Lancet and NEJM 2005 Hypothermia treatment improves outcome Hypothermia treatment Potential adverse effects -Hypotension -Cardiac arrhythmia (mainly sinus bradycardia ) -Persistent acidosis -Increased oxygen consumption -Increased blood viscosity -Reduction in platelet count -Pulmonary hemorrhage -Sepsis -Necrotizing enterocolitis -no severe side effects have been reported so far Best patient care depends on • Close communication with family • Multidisciplinary care • Neurology– neurological examination (structured /routine), diagnosis, prognosis, follow up • Radiology – timing and interpretation • Physical and occupational therapy – evaluation, pre-discharge examination Thank you!