1 / 26

What is Hot and What is Cold in Newborn Hypoxic–Ischemic Brain Injury

What is Hot and What is Cold in Newborn Hypoxic–Ischemic Brain Injury. Sidhartha Tan, MD Clinical Professor Department of Pediatrics NorthShore University HealthSystem and University of Chicago. Cold is Hot. Hypothermia has shown to be partially neuroprotective in term HIE.

tariq
Download Presentation

What is Hot and What is Cold in Newborn Hypoxic–Ischemic Brain Injury

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. What is Hot and What is Cold in Newborn Hypoxic–Ischemic Brain Injury Sidhartha Tan, MD Clinical Professor Department of Pediatrics NorthShore University HealthSystem and University of Chicago

  2. Cold is Hot • Hypothermia has shown to be partially neuroprotective in term HIE. • Three big trials have been conducted, • CoolCap, NICHD, TOBY. • Total of 767 newborn infants randomized. • ICE trial 221 infants and neo.nEuro trial 129 infants.

  3. Three Trials’ Results • TOBY trial and CoolCap trial did not show any reduction in death and disability, the primary outcome. • Only the NICHD trial showed reduction. • Meta-analysis showed reduction of 0.81 (0.71-0.93). • ICE trial confirms the smaller studies of hypothermia with RR 0.77.

  4. Hypothermia • Needs to be given as early as possible. • Needs to be given for a long time. • Different methods of cooling and target temperatures are equally effective. • Decrease in secondary outcomes: severe disability, cerebral palsy, PDI<70, MDI<70, blindness but not deafness.

  5. Chance of Normal Outcome • Normal neurological outcome: No CP, MDI, PDI>84, normal vision and hearing. • CoolCap and NICHD showed no difference. • Only TOBY trial showed significant increase. • Meta-analysis showed risk ratio 1.53 (1.22-1.93).

  6. Smaller Trials • Meta-analysis of smaller trials (10) showed significant decrease in mortality, RR 0.78. • Only the Uganda study showed increase in mortality, suggesting among other things that hypothermia alone without other NICU support is harmful.

  7. Severity of Encephalopathy • Hypothermia has effect on moderate encephalopathy • Not significant in the severe group but trend in positive direction. • Small study neo.nEURO.network shows effect in severe group and no effect in moderate group, 129 infants.

  8. Unfavorable Outcomes • Unfavorable outcome increases in control group with hypothermia. • Hypothermia delays EEG recovery from animal data. • Subcutaneous fat necrosis and hypercalcemia – case reports • Cooling requires rectal temperature monitoring. Unmonitored, 2/5 found to be overcooled. Ice caps require insulation but cause wide fluctuation in temperature. • Sedation and anelgesia often needed to reduce shivering.

  9. Number Needed to treat • 9 for death or disability (5-25). • 9 for severe disability. • 8 for cerebral palsy. • 8 for intact survival. • 14 for survival.

  10. Unknown things about Hypothermia • Long term benefits unknown • How long how deep • When is it too severe. • When is it too late.

  11. Hypothermia and ECMO • Some patients with HIE also have profound hypoxemia requiring ECMO. • Case series of 5 patients out of 117 cooled patients that required ECMO after hypothermia (7-64 hr age). • 5 out of 5 had thrombocytopenia requiring platelet transfusions, prolonged coagulation, 3/5 other blood products. • 4 out of the 5 infants had transient bradycardia, hypotension, oliguria. • 3 out of 5 had normal MDI/PDI, one had tone problems at 3 months and lost to f/u, 1 had severe deficits with hydrocephalus. Massaro et al, J Pediatr 2010;157:499-501

  12. Old is Cold

  13. ST analysis • Fetal cardiotachography with ST analysis was no different than fetal cardiotachography alone in predicting metabolic acidosis. • Study shows low incidence of HIE in both monitored groups (4 out of 5,681 deliveries). Westerhuis et al,,Obstet Gynecol 2010;115:1173–80

  14. Apgar Score at 10 min • 27% of the 208 infants in NICD trial had Apgar score of 0-2 at 10 min. • Death or disability incidence: • Apgar 0 76% • Apgar 1 82% • Apgar 2 80% • Caution in making a decision of terminating resuscitation on basis of Apgar at 10 min. Laptook et al, Pediatrics 2009;124:1619–1626.

  15. Can Serial Examination Prognosticate • Newborn infants who do not improve on serial examination have bad prognosis. • Amiel-Tyson neurological assessment at term vs Sarnat scoring. • Serial neurological examination in the first 3 days of life was not superior to Sarnat and worse than discharge exam for predicting outcome at 2 years. • Sarnat stage correlation 0.64 with Griffith’s score at 2 years for HIE. • The later the exam the better the prognosis. Murray et al, Developmental Medicine & Child Neurology 2010, 52: e55–e59. • Limitations: not all exams done by same observer, scoring was ordinally scored twice, correlation with ordinal scoring at 2 years.

  16. Biomarkers of HIE • Metabolic acidosis, Apgar scores, neonatal examination are not prognostic. • Serum biomarkers are needed. • Limitations with existing serum biomarkers. • Neuron specific enolase and S100B have not panned out. S100B has later rise after 48 hr.

  17. MRI Biomarkers of HIE • MRI is better than cranial ultrasound in the pre-hypothermia era for predicting 2 year outcome. Tworney et al, MR imaging of term infants with hypoxic-ischaemic encephalopathy .. Pediatr Radiol (2010) 40:1526–1535 • 6 died • 5 CP

  18. MRI Biomarkers of HIE • ADC of posterior limb of internal capsule<0.86 had unfavorable outcome. • ADC of PLIC >0.86 and >1.07 in lentiform nucleus predicted 100% with favorable outcome. Tworney et al, Pediatr Radiol (2010) 40:1526–1535

  19. MRI Biomarkers of HIE

  20. Perinatal Events and Early Magnetic Resonance Imaging in Therapeutic Hypothermia. Bonifacio, SL et al.J Pediatr. 2010 Oct 20. • Cohort study - 35 hypothermic neonates with 25 controls. • Whole body cooling, >36 weeks, moderate-severe encephalopathy • MRI 1.5T, median 5 days hypothermia group, 4 days control group, ~ 1 hr. • Hypothermia has less total, basal ganglia and thalamic scores for injury, and watershed lesions on MRI. • All babies with decreased fetal movement antenatally had MRI injury in both groups. • Limitations: Controls had higher encephalopathy score day 1 and MRI at earlier time; MRI could have been done earlier.

  21. MRI study of the TOBY trial. Rutherford, M et al.Lancet Neurol. 2010 January ; 9(1): 39–45. • 131 infants of 352 infants in the TOBY trial got MRI. • Subset of infants had more severe aEEG findings. • MRI was obtained at a median of 8 days (2-30). • 63% of MRI scans <8days had major abnormalities predictive of abnormal outcome. • 47% of MRI scans >8 days were predictive. • Predictive accuracy of moderate/severe lesions in basal ganglia and thalamus, severe WM lesions, or an abnormal PLIC, for death or severe disability was 84% in cooled and 81% in non-cooled group.

  22. MRI Biomarkers of HIE • MRI convenient to do post-hypothermia. • ADC and DWI are not that reliable at 4-7 days post-hypothermia. • MRI can be done with hypothermia. Wintermark et al. Early versus late MRI in asphyxiated newborns treated with hypothermia. Arch Dis Child Fetal Neonatal Ed 2011;96:F36–F44. • Early MRI studies on day 1 or 2-3 may be a biomarker of brain injury. The earlier the MRI the better.

  23. Summary • Hypothermia is the treatment of choice for HIE. • Start as early as possible. • Maintain rectal temperatures in defined range. • Combination therapy may be needed. • MRI emerging as a good biomarker. The earlier the MRI the better.

  24. TIMING Sentinel event? ANATOMICAL Early event? Intrapartum events? Maternal “Birth asphyxia” Placental Fetal

  25. THEORIES PROOFS

More Related