for the Neonatal ICU Pathophysiology Disclosure Learning Objectives Global Ischemia 10/16/2017 Why are we here today?

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Disclosure Clinical Manger and Nurse Educator for Bard Medical and the Arctic Sun for the Neonatal ICU Learning Objectives Upon completion of this module, the participant will be able to: Discuss the role of Targeted Temperature Management (TTM) Review TTM evidence based practice in neonates Discuss patient management during TTM Why are we here today? Global Ischemia Pathophysiology Neonates: from birth through the first 28 days of life. FDA. (2014). Guidance for Industry and FDA Staff, 1 12. Transient (5 30 minutes) complete or nearly complete lack of blood flow Lack of blood supply leads to ischemia If blood flow is not restored within 30 minutes, widespread necrosis occurs Polderman, KH. (2004). Int Care Med. 30(4), 556 575. 1

Gestational Age Plays an Important Role Complex negative cascade of reactions at cellular level Chain of events is called secondary injury or reperfusion injury May begin minutes after injury and continue up to 72 hours or longer At what gestational age would you consider cooling? Polderman, KH. (2008). Lancet. 371, 1955 60. Rocha Ferriera. (2016). N Plasticity. 2016: 1 16. What is the therapeutic window of opportunity? Blood + Oxygen Primary Energy Failure Latent Phase (30 min) Secondary Energy Failure (6 12 hours) Tertiary Energy Failure ( 3 days) BP BP Reperfusion Hours and Days Cause of disruption? Rocha Ferriera. (2016). N Plasticity. 2016: 1 16. Mechanism of Action Hypothermia Reduces Cytotoxic amino acid accumulation and nitric oxide 1 Secondary energy failure 1 Energy utilization 1 Metabolism 1 Inhibits Free radical activity 1,3 Cell death 2,3 1. Wisnowski, JE. (2015). J Cere Blood Flow and Metab. 0, 1 12. 2. Newmyer. (2015). Current Treatment Opt in Pediatrics, 1: 38 47. 3. Jacobs, SE. (2013). Cochrane Neonatal Review. 1, 2. Trends in Neonatal TTM Babies 36 weeks gestation, and aged 6 hr are eligible for treatment with cooling How does your hospital decide who and when to cool? Consider cooling beginning at 35 weeks NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, (6), 73. 2

Passive Cooling and Transport Commence continuous rectal temperature monitoring. Document initial temperature (axilla if rectal thermometer not available) Turn incubator off, open portholes, document rectal / axilla temperature every 15 min Wait 30 min Temperature falling? Yes Yes Baby temperature No Baby temperature No >33 o C >34 o C No Yes Add 1 blanket Remove blanket if present. Consider using a fan. Contact transport consultant for advice * *Do not use ice packs for cooling as severe hypothermia can result. Do not use active cooling (e.g. fan) unless rectal temperature is monitored. NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, (6), 75. Assessments and Diagnostics There is no clear diagnostic test Abnormal findings in the first few days after birth may be a useful predictor that insult has occurred in the perinatal period All neonates should have a detailed examination Shankaran, (2009). Jour of Ntrauma. 26(3), 437 443. Key Clinical Considerations Gestational age 1 Metabolic acidosis 2,3 Early onset of abnormal behavior 3 How does your hospital categorize abnormal behavior? Multisystem organ dysfunction 2,3 1. Rocha Ferriera. (2016). N Plasticity. 2016: 1 16. 2. Antonucci. (2014). J Pediatr Neonat Indiv Med. 3(2), 1 14. 3. Shankaran. (2009). J Ntrauma. 26(3), 437 443. Common Tools Events categorized as: mild, moderate, or severe 1,2 Metabolic acidosis 1,2 Apgar Score 1,2 1. Antonucci. (2014). J Pediatr Neonat Indiv Med. 3(2), 1 14. 2. NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, (6), 159 162. Selective Head vs. Whole Body Cooling Trial N Cooling method Year Gunn 22 Selective head 1998 Shankaran 19 Whole body 2002 Akisu 21 Selective head 2003 Cool Cap 234 Selective head 2005 Eicher 65 Head and whole body 2005 NICHD NRN 208 Whole body 2005 Lin 58 Selective head 2006 TOBY 325 Whole body 2009 neo.neuro 111 Whole body 2010 Zhou et al 194 Selective head 2010 ICE 221 Whole body 2011 Jacobs, SE. (2013). Cochrane Neonatal Review. 1, 2. 3

What s the latest news in Neonatal TTM? Monitor and maintain body temperature 1 4 Cooling should be initiated and conducted under clearly defined protocols 1,3 Commence cooling within 6 hours of birth, continue cooling for 72 hours 3,4 Rewarm over at least 4 hours 3 Maintain normothermia for 24 hours 2 Avoid hyperthermia 2,3 1. AHA. (2015). Circulation: Part 13 Neo Resusc. 123, 13 16. 2. NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, (6), 73 364. 3. Wylie et al (2015). European Resuscitation Council. 249 263. 4. NICE. (2010). Nat Inst for Health and Clin Exc, 1 9. < 6 hours Time to Initiation 36.5 37 C 33.5 34.5 C Four Phases * 24 hours Normothermia 36.5 37.5 C 72 hours 0.5 C per hour Maintenance * Duration to follow institutional and society guidelines Antonucci. (2014). Jour of Pediatr Neonat Individual Med, 3(2), 1 14. Mosalli, R. (2012). Jour of Clinical Neonatology, 1(2), 101 106. NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, (6), 73 364. Shankaran, (2009). Jour of Ntrauma, 26(3): 437 443. What is your goal for managing temperature? Physiological Effects of Cooling and Nursing Considerations Cardiovascular in HR; normal HR could be considered abnormal during cooling 1 1 o C = 15 bpm 1 Peripheral vasoconstriction (consider vascular access) 1 Renal Pay attention to intake and output 3 Diuresis 2,4 1. Mosalli, R. (2012). Jour of Clinical Neonatology. 1(2), 101 106. 2. Bader MK, Littlejohn LR (2009). AANN CC for N Nurs. 237 246. 3. Nunnally, ME. (2010). Mount Prospect: SCCM. 21 27. 4. Guanci, MM., Mathiesen, C. (2009). Foun of N Nurs. 237 246. Physiological Effects of Cooling and Nursing Considerations Respiratory Most infants will require assisted ventilation during cooling Secretions tend to be more sticky More frequent suction with saline and regular repositioning might be necessary O 2 consumption and CO 2 production Mosalli, R. (2012). Jour of Clinical Neonatology. 1(2), 101 106. Physiological Effects of Cooling and Nursing Considerations Gastrointestinal Impaired bowel function / motility 1 Endocrine Altered glucose metabolism 1,2 Hematological Impaired platelet function: monitor for bleeding 1 Impaired clotting cascade 1 Decreased WBC count 1 Other Drug metabolism prolonged 1 1. Mehta, S. (2010). PA: HMP Communications. 603 612. 2. Nunnally, ME. (2010). Mount Prospect: SCCM. 21 27. 4

Skin Care and Assessment Routine assessment of skin is integral 1 Monitor skin integrity of all dependent areas with repositioning and be alert for: Pressure ulcers from devices are the most common pressurerelated injuries in the neonatal period 1 Injury and erythema 1 Subcutaneous fat necrosis 1,2 Cyanosis 3 Strohm 2 1. AWHONN. (2013). Neonatal Skin Care: EBG. Third Ed, 1 104. 2. Strohm. (2011). Amer Academy Pediatr. 128 (2): e450 452. 3. Mosalli, R. (2012). Jour of Clinical Neonatology. 1(2), 101 106. Do neonates shiver? Neonate Temperature Immature central thermoregulatory control Most metabolic heat is lost from the skin surface How is heat loss different in neonates? Sessler, D. (2009). Anesthesiology. 109(2), 318 338. Neonatal Heat Loss 70% of heat produced by the brain 1,* Heat lost to cooler objects in room and water evaporating from skin 2 In cold environment, whether in incubator or not, excessive heat may be lost 2 Sources of Heat Generation Brown adipose tissue 1 Non shivering thermogenesis (NST) 1 Primary defense against cold 3 Doubles heat production in neonates 3 Requires adequate oxygenation 1 Skeletal muscles 1 Seizures 2 Swimming movements with arms 2 Bicycling their legs 2 Shivering 1 * According to the literature, unintentional hypothermia may be harmful to sick neonates, depending on the underlying condition. 1. Jacobs, SE. (2013) Cochrane Neonatal Review. 1, 2. 2. NHS Networks, (2015 17). Nat Assoc Neonatal Nurses, 6, 154. 1. Asakura, H (2004). J Nippon Med Sch. 71(6): 360 370. 2. NHS Networks. (2015 17). Nat Assoc Neonatal Nurses. (6), 286. 3. Sessler, D. (2009). Anesthesiology. 109(2), 318 338. 5

Probes to Measure Core Body Temperature in Neonates* Esophageal probes have been shown to display the most accurate temperature reading A rectal or esophageal temperature probe is recommended Monitoring a secondary source is recommended i.e. skin temperature sensor (neonates) When cooling to hypothermia, you may see a cold induced diuresis Closely monitor intake and output Summary It is important to properly manage neonatal patients receiving targeted temperature management You must be dedicated to patient management in order to effectively cool patients All sources of heat generation should be assessed and monitored * Different probes and placement may result in various forms of risk of harm to a patient. Follow the instructions for use and hospital SOPs and physician s orders. List of References AHA. (2015). Circulation: Part 13 Neonatal Resuscitation. 123, 13 16. Antonucci. (2014). J Pediatr Neonat Individual Med. 3(2), 1 14. Asakura, H. (2004). J Nippon Med Sch. 71(6): 360 370. AWHONN. (2013). Neonatal Skin Care: EBG. Third Ed, 1 104. Bader, (2009). AANN Core Curriculum for N Nurs. 237 246. FDA. (2014). Guidance for Industry and FDA Staff, 1 12. Guanci, MM. & Mathiesen, C. (2009). Foun of N Nurs. pp. 237 246. Gillam Krakauer. (2012). Pediatrics in Review. 33(9), 387 389. Jacobs, SE. (2013). Cochrane Neonatal Review. 1, 2. Lee, et al. (2015). Pediatr Emerg Care. 30(5), 315 318. Kang, et al. (2015). Frontiers in Pediatrics. 3(101),1 9. List of References Li, Y. (2012). Prog Neurobiol, 98(2), 145 165. Logitharajah, P. (2009). Pediatric Research. 66, 222 229. Marro. (2002). The American Academy of Pediatrics. 3: 1 11. Nunnally, ME. (2010). Mount Prospect: SCCM. 21 27. Mehta, S. (2010). PA: HMP Communications. 603 612. Mosalli, R. (2012). Journal of Clinical Neonatology, 1(2), 101 106. Newmyer, (2015). Current Treatment Options in Pediatrics, 1: 38 47. NHS Networks, (2015 17). NANN Guidelines, issue 6, 73 289. NICE. (2010). National Institute for Health and Clinical Excellence, 1 9. Nielsen N et al (2013). N Engl J Med. 369(23): 2197 206. Polderman, KH. (2008). Lancet. 371, 1955 60. List of References Ramenghi, (2012). Neonatalogy. XII, 1067 1078. Rocha Ferriera, (2016). N Plasticity, 2016: 1 16. Sessler, D. (2009). Anesthesiology. 109(2), 318 338. Shankaran, (2005). N Engl J Med. 353: 1574 84. Shankaran, (2009). J Ntrauma. 26(3): 437 443. Stiles, Jernigan. (2010). Npsychol Rev. 20(4), 327 348. Strohm, (2011). Amer Academy Pediatr. 128 (2): e450 452. Takenouchi, et al. (2012). Therapeutic Hypothermia For Neonatal Enc. 34(2), 165 170. Tan. (2014). Clin Perinatol. 41(1), 105 117. Wisnowski, JE. (2015). journal of Cerebral Blood Flow and Metabolism. 0, 1 12. Wylie et al (2015). European Resuscitation Council. 249 263. 6