Too or Too Cold. Too Cold...Too Hot...Just Right. Temperature Control in Newborns. Temperature Balance in Newborns. Basics in the Delivery Room

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1 Too or Too Cold Neonatology Rediscovers Temperature Control Advances and Controversies in Clinical Pediatrics May 31, 2007 Terri A. Slagle Neonatology, CPMC Too Cold...Too Hot...Just Right Too Cold = Issues of resuscitation What we do and why Where we fail Too Hot = Approaches to improving outcome after perinatal asphyxia Hypothermia and impact on brain injuries Temperature Control in Newborns Temperature Balance in Newborns Man thrived earliest and most prolifically in areas of the world with a mean annual temperature close to 70 F William Silverman 1958 landmark study on temperature control neutral thermal environments reduce mortality 182 infants, day 1-5 Incubator at 37.1 C v 28.9 C Survival g 85% v 77%; <1000 g 50% v 14% Heat Loss Radiation Large surface area Convection Conduction Evaporation Wet Immature skin barrier Heat Production Metabolic process Impairments Shivering Non-shivering thermogenesis (brown fat) Limited amount in preterm Heat Loss Basics in the Delivery Room Place infant on a preheated radiant warmer Dry and remove wet linen Hat and warmed blankets If low resuscitation needs use mother as incubator Skin to skin with blanket over 1

2 What are We Aiming for? How Are We Doing? Not So Well! First Temperature of Term Infants (non-nicu ) The World Health Organization classifies a core body temperature for newborns (WHO 1997): o C as mild hypothermia or cold stress o C as moderate hypothermia < 32 o C as severe hypothermia 100% 80% 60% 40% 20% 0% > First Temperature 35 & 36 week GA (non-nicu) <36 100% 80% >37.5 C/S 60% Instrument Spont vag % First Temperature in <35 weeks <36 20% 100% 0% 80% C/S Instrument Spont vag 60% 40% 20% > <36 0% C/S Instrument Spont vag Output of W Delivers 30 mw/cm 2 Why are We Failing? but 9.3 W of loss immediately after birth 750 gm = 600 cm 2 Or 9 W absorbed Admission Temperatures and Morbidities 15 NICHD centers, , 5,277 infants g ½ of infants <36º Lowest temps Smallest, most interventions, low Apgars Admit temp for each 1 temp : Mortality 28% Late sepsis 11% No impact IVH, NEC, vent days EPICure study in handout % > <35 Laptook, Peds, 3/07 electronic pages Reduce Heat Loss by using Barriers Resurgence of interest in 1990 s Space blankets Hard to evaluate infant Bubble wrap Hard to evaluate infant Bubble wrap was a barrier to the overhead radiant heat Plastic wrap (food grade, heat resistant) Plastic bags ( turkey bags ) Plastic Wraps Wrap infant without drying them (or use a bag) Barrier to evaporative losses Able to visualize infant Vohra et al. <28 wks showed 1.9 C advantage Many since agree 4 randomized trials; > 300 infants Benefits with minimal risks (mild increase temps) 2

3 Heat from Both Sides Preheated warm surface Warming packs Exothermic crystalline reaction Aim for 39+1 C Trials using packs vs. incubators with success; experience in transport or MRI Small trial; 24 infants wks with 1.6 C gain (Brennan) Temperature control imprecise if pack stored in warmed place temp may exceed 40 C Risk of skin injury in smallest infants Need to remove for X-rays (blurs image) Reminder not all are MRI compatible Warmer Delivery Room WHO delivery rooms should be at least 25 C (77 F) ASHE standards but no professional medical organization standards But for comfort of mother and the health care team this may be less than ideal Surgical gowns are waterproof Do you really want me sweating into the surgical site? Labor a hypermetabolic state Middle ground => warmer for tiniest infants Other Heat Considerations Hats -> clearly of value BUT tube or stockingnet hats of minimal valve Wool hats, plastic or other barrier lined hats Breeze control Location of the resuscitation cot relative to doors & air vents Sides of warmer up!!! Now a CPQCC outcome measure (California Perinatal Quality Care Collaborative) Someone in charge of heat in the delivery room Newborn Fetus Hypoxic-Ischemic Brain Injury at Term 1-2/1000 term births in developed countries 10-20% of infants die 20-30% left with significant permanent impairments Essentially no change in data for 20 years Current options => supportive care New frontier is neuro-protective Multiple strategies with hypothermia most advanced stages Hypoxic-Ischemic Brain Injuries Injury (may start in utero) Resuscitation -> restores blood flow and O2 Cell stabilizes 6-48 hr later -> cerebral energy failure Likely from mitochondrial dysfunction Amount of mitochondrial injury key to level of cell damage Apoptosis programmed cell death Cascade of proteolytic enzymes (caspases, cyteine proteases) Possible role of circulating factors Neuro-Protection 3

4 Hypoxic-Ischemic Brain Injuries Evolving process Insult -> Recovery -> Reperfusion Impaired cerebral blood flow sets in motion Interrupted placental flow, gas exchange across placenta, O2 delivery Cascade of biochemical events Depleted high energy phosphate reserves (ATP) lactic acid (makes cells less functional) Accumulation of Ca ++, Na +, H 2 0 in cells Depolarized membranes release of neurotransmitters such as glutamate Free fatty acids ripe for peroxidation if have O2 free radicals Impacts of Hypothermia Inhibit glutamine release Cerebral metabolism (preserves ATP) Estimates 5-7% in metabolism for each 1 C Tissue lactic acid accumulation Intracellular acidosis Nitric oxide production Leukotrienes Reduction in apoptosis (later death) is greater than the acute necrosis Building Evidence for Hypothermia 1980 s animal work => sheep, piglets, rats 2-4 C cooling Used before / during / after hypoxic-ischemic insult Variable results but general support for less tissue injury with cooling Best if cool before the insult Worst if severe injury, delay in cooling, no sedation so got shivering Building Evidence for Hypothermia Outcomes from cold water drowning Adults: out of hospital cardiac arrests Cooling results in improved neurologic outcomes Pilot trials of post stroke Avoid hyperthermia Nordic Cooling Trial after Stroke underway Hypothermia Side Effects Cold stress and injuries have many side effects Bradycardia and arrhythmia Acidosis Bleeding (+/- thrombocytopenia) Hypotension Persistent pulmonary hypertension Hepatic dysfunction Hypoglycemia Hypocalcemia Hematuria / oliguria Be aware of history! Pilot Studies on Cooling Newborns None large enough to determine benefit or truly substantiate safety (see handout for list of studies) No severe side effects Outcome is bleak and have little to offer Intriguing -> multicenter trials (rare event) Obstacles: how to define the real infants at risk 4

5 Targeting Highest Risk Infants 36 weeks of greater < 6 hours of age ph <7.0 or base deficit > 16 cord artery or < 1 hr of age ph <7.15 or deficit but high risk event like prolapsed cord, abruption, uterine rupture and need for resuscitation (Apgar of <5 at 10 minutes) Evidence of encephalopathy or seizures Lethargy, stupor or coma & hypotonia, abnormal reflexes, absent/weak suck Use of amplitude integrated EEG (aeeg) Whole Body Cooling Cooling blankets, water circulation No overhead heat source Rationale is need to get deep structures of brain cooled and cap will give a gradient Head Cooling (Cool-Cap) Cap with circulated water On radiant warmer aiming for rectal temp Cool Cap Trial Gluckman, Lancet 2005; 365:663, 25 centers wk infants moderate to severe encephalopathy, <6 hrs age Cool cap + body cooling to C rectal for 72 hrs Similar adverse systemic issues Outcome: 18 mo death or severe disability OR 0.61 trend in favor of cooling (95% CI ) Moderate HIE and no seizures (aeeg) OR 0.46 in favor of cooling (95% CI ) Whole Body Hypothermia Study Group Shankaran, NEJM 2005; 353:1574, 15 centers wk infants encephalopathy criteria a little looser but < 6 hours Body cooling to 33.5 C esophageal for 72 hrs Similar adverse systemic issues Outcome: 18 mo death or severe disability 44% v 62% OR 0.72 in favor of cooling (95% CI ) Death rate 24% cooled v 37% of control (p=0.08) Rate of CP among survivors decreased 19% v 30% OR 0.68 trend for cooling (95% CI ) NICHD network Is Cooling Ready for Prime Time? Impacts of cooling studies may underestimate impact (average enrollment = 5 hours of age) -> should we let asphyxiated infants stay cold from DR? Transport infants Australian trial looking at cooling during transport (ICE study using Hot- Cold gel packs) Should heavy sedation / paralysis be used? Shivering data from animal studies Is this still research trial or are we ready to label it innovative therapy? Consent would be advised in either. 5

6 Hypothermia Promising therapy in selected infants Whole body cooling might be preferable means Call early to get infants evaluated as potentials for the treatment Watch for new information 6