Case Presentations Anamika B. Mukherjee, MD September 13, 2017
Nothing to disclose Disclosures
Learning Objectives Use the CPQCC Toolkit for therapeutic hypothermia to apply the guidelines for screening HIE infants for therapeutic hypothermia Understand which newborns should receive therapeutic hypothermia and when Review the process for stabilizing infants with asphyxia
Case Baby girl F, born to a 35 year old G 5 P 4 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 placental abruption
NICU Team attends the delivery... Infant was delivered via emergency C-section the baby was floppy with no respiratory effort, cyanotic and had no detectable heart rate Bag and mask ventilation started immediately, HR > 100 bpm at 5 min, and intermittent spontaneous breathes noted at 5 min. She was intubated at 7 min of life for poor sustained respiration. Color improved, HR 110 bpm but baby 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 assessment 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 36.5 o C HR 170 bpm, BP 37/23 mmhg. Pale and poor perfusion Intubated on mechanical SIMV with periodic respiratory effort No significant dysmorphic features What is your assessment and what should be done next?
Goals of Resuscitation Avoid hypoxia and hyperoxia Initiate low concentration FiO2 and increase FiO2 to 1.0 if chest compressions required; wean FiO2 as soon as HR recovers Avoid hyperthermia in the delivery room in moderate severe HIE; hyperthermia is associated with adverse neurologic outcomes Avoid hypoglycemia and hyperglycemia Recognize and treat seizures
Lab tests Your initial lab work should include following: A. Check blood glucose B. CBC C. Blood Culture D. Basic metabolic panel 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
One hour later, fluid boluses were given, blood pressure improved, hypoglycemia was corrected. 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 imaging to confirm hypoxic-ischemic brain injury before starting hypothermia treatment C. Continue monitoring. Hypothermia will not be indicated if infant s condition significantly improved at 6hr of life.
Early Screening and Identification of Candidates for Neonatal Therapeutic Hypothermia Toolkit Released February 2015 Priya Jegatheesan, MD, Anna Morgan, MD, Thomas Shimotake, MD, Dongli Song, MD, PhD and Krisa Van Meurs, MD on behalf of the Perinatal Quality Improvement Panel (PQIP), California Perinatal Quality Care Collaborative (CPQCC) download \Toolkit @ www.cpqcc.org
Neurological examination Does this infant display encephalopathy? How should the neurological examination be done/documented to show this?
Diagnosis of Neonatal Encephalopathy is Clinical Careful history and neurological exam Laboratory studies to exclude mimics of hypoxia-ischemia Metabolic abnormalities including inborn errors of metabolism Infection Acute bilirubin encephalopathy Stroke
Neonatal Neurologic Exam Most challenging aspect for community providers Experience helps signs of neonatal encephalopathy and/or asphyxia can be subtle/subclinical Observation over time, NE may be progressive Serial exams are necessary Document accurate timing of exam Non-focal or normal inadequate Staging system (modified Sarnat) Important in deciding course of management Sarnat stage correlates with childhood outcomes
NE Staging predicts outcomes Table showing degree of encephalopathy to establish the pretest probability of poor outcome Presence of moderate to severe NE best predictor of death/severe handicap at 2.5 years (sensitivity=96%) Levene MI, Lancet 1986 Severity of NE and the presence of seizures can predict 30 month neurodevelopmental outcome, as early as DOL#1. Miller SP, AJOG 2004
Modified Sarnat Exam Level of consciousness Hyperalert Lethargic stuporous Tone Normal Hypotonia Flaccid Posture Mild distal flexion Strong distal flexion decerebrate Activity Normal Decreased none Primitive reflexes suck Moro Autonomic function pupils heart rate respiration weak strong dilated Tachycardia Normal weak or absent Incomplete constricted Bradycardia periodic absent absent variable Variable apnea Modified from Sarnat and Sarnat, Arch Neurol, 1976
Management of babies who qualify for possible cooling Identify patients to discuss with regional cooling center within 1 hour of birth After initial resuscitation and stabilization, perform screening evaluation If screening criteria are met, call the regional cooling center Discuss if the patient is appropriate to remain for observation vs. transport for cooling If determined to be a candidate for cooling by regional cooling center, begin passive cooling Turn down/off external heat sources and avoid hyperthermia Document the time and do not actively cool patients Monitor core (rectal) temp closely Target rectal temp= 33-34⁰C or axillary temp=32-33⁰c Check temp continuously/frequently (q 15 minutes) Use flow sheet (appendix H) Core temp may still fall <33.5⁰C with passive cooling. Be prepared to respond Maintain adequate sedation
Management of babies who qualify for possible cooling (cont) Secure vascular access Before peripheral vasoconstriction occurs with cooling Umbilical venous and arterial access preferred Periph IV at a minimum Maintain adequate sedation Keep comfortable/minimize cold stress and avoid shivering during passive cooling i.v. morphine Treat only clinical seizures no prophylactic antiepileptic drugs Lorazepam (Ativan): 0.1 mg/kg/dose IV, repeat 1X prn for suspected seizures Phenobarbital: 20 mg/kg/ IV load, for obvious seizures Monitor electrolytes closely fluctuations often seen in CA, K, Mg levels with cooling
Exclusion Criteria Infants 36 weeks gestation (based > 34 weeks considered for cooling at the discretion of the cooling center) Infants without evidence or clinical history of HIE Inability to initiate cooling by 6 hours of age Congenital or chromosomal anomaly Refusal of consent by parent or physician Severe intrauterine growth restriction (weight 1800 grams) Infants in extremis for which no additional intensive therapy will be offered by attending neonatologist
Decision to Initiate hypothermia Evidence of moderate or severe encephalopathy (abnormalities in 3 categories) on Sarnat exam Laboratory/historical criteria for HIE are met Add LLUCH blood gas and historical date Newborns with laboratory or historical data making them potentially eligible with a normal initial Sarnat exam should be examined hourly for changes in the Sarnat exam
NICHD Trial Protocol for Whole-Body Hypothermia and Re-Warming Inclusion Criteria: Infants will be evaluated using two steps Biochemical criteria (Step 1A), Clinical (Step 1B), Neurological (Step 2) Infants must meet BOTH Steps (1 and 2) and not meet any exclusion criteria to be eligible for therapeutic hypothermia Clinical and Biochemical criteria History of an acute perinatal event Apgar score 5 at 10 minutes of life Cord ph or any postnatal blood gas ph of 7.0 at 1 hour Base deficit on cord gas or any postnatal blood gas of 16 meq/l at 1 hour Continued need for mechanical ventilation imitated at birth and continued for at least 10 minutes Shankaran S et al., NICHD Trial, NEJM 2005
STEP 1B: IF BLOOD GAS IS NOT AVAILABLE (Or ph 7.01-7.15 or Base Deficit 10-15 meq/l) Acute perinatal event (i.e. abruptio placenta, cord prolapse, severe fetal heart rate abnormalities such as variable or late decelerations), Moderate to severe encephalopathy (one or more at any time) within 6 hours of birth): lethargy or obtundation, stupor or coma (not due to anti-epileptic medications and maternal magnesium sulfate exposure) hypotonia or hypertonia (not due to anti-epileptic medications and maternal magnesium sulfate exposure) Increased, decreased or absent reflexes (e.g. DTR, gag, grasp, absent or weak suck) Autonomic dysfunction (decreased or absent respirations, low resting HR < 100 bpm with rare accelerations to 120 bpm, pupillary constriction (even in dim light, fixed and dilated pupils clinical seizures abnormal aeeg background and/or electrographic seizures AND Apgar score 5 at 10 minutes of life OR Continued need for ventilation initiated at birth and continued for at least 10 minutes
4 hours after hypothermia initiated... Infant develops bradycardia HR 70s What should you do? What are the most common side effects of hypothermia?
Bradycardia Prolonged QT Thrombocytopenia Skin breakdown Hypocalcemia Hypokalemia Metabolic acidosis Coagulopathy Clotting PPHN Hypotension Adverse effects
aeeg at 4 hours of life
After 72 hours of hypothermia, rewarming has started the aeeg shows
Neonatal Seizures are Common Neonatal seizures are common and often suggest underlying brain injury or dysfunction 50-60% of patients in RCTs Seen commonly during the first 12 hours of life and during the rewarming phase of cooling Birth is most common time of life to have seizures 0.95/1000 term births in California (OSWHPD database) Glass HC, et al J Peds, 2008 Other estimates 0.7-2.7 / 1000 live births at term 57.5-132 / 1000 live birth in preterms
Detecting Seizures by Exam Neonatal seizures are often subtle or subclinical Only 21% of neonatal seizures on EEG had clinical signs Electrographic only events are common More in babies with frequent seizures, especially after anti-seizure treatment Average accuracy of seizure detections was 50% Doctors no better than bedside nurses Clancy, Epilepsia 1988 Scher, Pediatr Neurol 2003 Malone, Epilepsia 2009
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.
Effect of hypothermia on the hypoxic-ischemic cascade of events Lina F. Chalak Neoreviews 2016;17:e463-e470
Cooling Trials: Meta-analyses 11 RCT: n = 1505, combined death/disability at 18 months RRR = 0.75 (95% CI 0.68-0.83) NNTB7= 7 (95% CI 5 10) Control (%) Cooling (%) Death/moderate-severe disability 62 44 CP 30 19 Visual impairment 14 7 Hearing loss 6 4 Jacobs, Cochrane Reviews 2013
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
Alternative Approaches: What about longer cooling and / or deeper cooling? NICHD optimizing cooling trial: to determine whether longer cooling (120 hours) or deeper cooling (32.0C) or both is superior to cooling at 33.5C for 72 hours in babies with HIE Results Deeper cooling or longer cooling compared with hypothermia at 33.5C for 72 hours did not further reduce NICU deaths Cooling at 32C was associated with more inhaled nitric oxide use and ECMO therapy, and associated with higher incidence arrhythmia and anuria
Recognizing Neonatal Encephalopathy (NE) Not always obvious index of suspicion based on risk factors Expect 4:1 ratio of babies with acidosis/acute events to NE Send cord gases after every high risk delivery or NE case Obs as likely to be sued for not checking cord gases as for having bad ones Sometimes the gases indicate non-hi cause of NE exonerating OB
Case 38-weeks gestation male infant is delivered by emergency C-section for recurrent late decelerations and moderate variability. Infant is born apneic, floppy and cyanotic, HR 70 bpm Apgars are 2,3,8 at 1, 5 and 10 minutes Infant is intubated and placed on mechanical ventilation. Initial arterial blood gas obtained at 15 minutes of age: ph 6.8, PCO2 55, PO2 90, base excess -20. Baby has seizure-like activity with lip smacking and decorticate posturing. Neurologic exam: flaccid infant with absent deep tendon reflexes, absent suck and absent gag, The aeeg prior to any sedation or antiepileptic medication is severely suppressed. Would you cool this baby?
Case 2 You attend the delivery of a 34 weeks gestational age infant with history of fetal distress (poor variability and late decelerations) Apgar scores: 3/4/7 at 1/5/10 minutes The baby has minimal response to PPV via bag mask. The baby is then intubated FiO2 35% and transferred to the NICU. Initial ABG at 30 minutes of life; ph 6.9, PCO2 66, PO2 80, base excess - 18. At 1 hour of life, the infant develops repetitive jerking of the right upper extremity. Infant is lethargic with mild hypotonia and a weak suck, consistent with Sarnat stage II. The aeeg demonstrates low voltage and seizure activity. How would you proceed with the management of this infant?
Case 3 You are about to receive a 39 week gestational age male infant born at a community hospital for evaluation for therapeutic hypothermia. Birth history: Emergency C-section 2nd to maternal seizures with preeclampsia. APGARs: 0, 3, and 3 at 1, 5 and 10 minutes with a cord gas ph<7 and BE -16. Infant was intubated in the DR and initial gas at 1hr of life was ph 6.76/pCO2 112/pO2 93 and BE -17. Follow-up ABG 45 minutes later was 7.32/38/81/-6. aeeg showed continuous background and no seizures clinically or on aeeg. Neurologic exam: hyperalert infant with normal to increased tone, normal to increased reflexes, active suck and exaggerated Moro, consistent with Sarnat stage 1. How would you proceed in the management of this infant?
Questions?