HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE)
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1 HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE) ALGORITHM Des Patient Qualify fr Therapeutic Hypthermia (TH)? Is the Infant: 1) 35 weeks gestatinal age? 2) 6 hurs f age? AND AND 3) Indicating clinical signs f mderate r severe encephalpathy? * (See Table 1) AND 4) Shwing evidence f intrapartum hypxia with ONE f the fllwing: Prlnged resuscitatin: cntinued need fr PPV fr 10 minutes Apgar scre at 10 minutes 5 Bld gas (crd r pstnatal within 1 st hur f life) ph 7 & base deficit 16 mml/l Inclusin criteria Nenates 35 weeks (G.A) presenting n the first day f life with evidence f hypxic ischemic encephalpathy (HIE) Exclusin criteria Infants < 35 weeks (G.A.) Encephalpathic infants due t causes ther than hypxia ischemia Yes Cmmence Ttal Bdy Cling Gal temperature Order ceeg with aeeg capabilities Supprtive care N Maintain nrmthermia Supprtive Care! Attending physician may determine patient with mild HIE qualifies fr TH based upn verall clinical picture Initial Supprtive Care fr Infants with NE Fluid & Nutritin: NPO Ttal fluids: 40 ml/kg/day (D12.5W) Mnitr glucse (maintain bld glucse mg/dl) Mnitr electrlytes Cardirespiratry: Maintain MAP mmhg Cnsider ECHO Cnsider crtisl level Avid hyperxia and hypcarbia Neurlgic: Dcument neurlgic exam and severity f NE Assess fr clinical and electrgraphic seizures Treatment f seizures: Refer t Treatment f Nenatal Seizures after Acquired Brain Injury CCG - initial agent phenbarbital, next line fsphenytin Hematlgic: Assess fr clinical bleeding cnsider DIC screen Infectius Disease: If at risk f early nset sepsis: CBC, BCx Ampicillin & Clafran Liver and Renal Functin: Evidence f liver failure: Vitamin K daily x 3 dses Mnitr renal functin Page 1 f 11
2 TABLE OF CONTENTS Algrithm Target Ppulatin Backgrund Definitins Initial Evaluatin Clinical Management Labratry Studies Imaging Parent Caregiver Educatin n/a Fllw Up Related Dcuments References Clinical Imprvement Team TARGET POPULATION Inclusin Criteria: Intended fr nenates 35 weeks (G.A) presenting n the first day f life with evidence f hypxic ischemic encephalpathy (HIE) Exclusin Criteria: Infants < 35 weeks (G.A.) Encephalpathic infants due t causes ther than hypxia ischemia BACKGROUND DEFINITIONS Hypxic-ischemic encephalpathy (HIE) is a clinically defined syndrme f disturbed neurlgic functin in the first day f life in an infant, manifested by difficulty with initiating and maintaining respiratin, depressin f tne and reflexes, sub nrmal level f cnsciusness and ften seizures. This cnditin ccurs in 1-2/1000 newbrns and is a significant cause f nenatal mrtality and mrbidity. The risk f death r severe disability in survivrs f mderate-severe HIE is 60%. Induced mderate therapeutic hypthermia (33-34 C) has been shwn t be safe and decrease the incidence f death and disability with HIE. 1, 2, 3 INITIAL EVALUATION Eligibility Criteria fr Therapeutic Hypthermia1, 2, 3 1. Gestatinal Age 35 weeks AND 2. Infant less than 6 hurs f age (The decisin t start hypthermia after 6 hurs will be at the discretin f the nenatlgy attending) AND 3. Clinical signs cnsistent with encephalpathy (mderate, severe Table 1) AND 4. Evidence f intrapartum hypxia including ne f the fllwing: Page 2 f 11
3 Prlnged resuscitatin: cntinued need fr psitive pressure ventilatin; required at birth and cntinued fr greater than r equal t 10 minutes. Apgar scre at 10 minutes t 5. *Bld gas [arterial crd gas, venus crd gas, r pstnatal (within 60 min) arterial bld gas ph 7 and base deficit 16 mml/l]. * Nte: aeeg may be additinal tl t determine degree f encephalpathy. * Attending physician may decide t initiate therapeutic hypthermia fr infants with mild HIE based upn cmplete clinical picture. 4 Sarnat Staging f Encephalpathy Mderate/Severe Encephalpathy will be defined as either clinical seizures r the presence f 3 f 6 categries frm mderate r severe clumn in Table 1 belw. Table 1. Stages f Encephalpathy Stage 1/Mild Stage 2/Mderate Stage 3/Severe Level f Cnsciusness * Nrmal Lethargic/Obtunded (Reduced respnse t stimulatin) Stuper r cma (Absent respnse t stimulatin) Spntaneus Activity * Nrmal Decreased Activity N Activity Muscle Tne * Hypertnia Hyptnia (fcal r general) Flaccid Psture * Nrmal Distal flexin, r cmplete extensin r frg-legged Reflexes Mr Suck Autnmic system * Pupils Respiratins Heart Rate Exaggerated mr Weak/incmplete Weak Cnstricted Peridic Breathing Bradycardia Decerebrate Absent Absent Deviated, dilated, NR Apnea Variable Seizures Absent May be present May be present * May be affected by hypthermia, narctics, and/r sedatives. CLINICAL MANAGEMENT Management at Birth Hspital and During Transprt 1. Start Passive Cling Immediately Advise referring prvider t turn ff exgenus heat surce (turn ff radiant warmer). 5 Earlier cling is assciated with better utcmes. 6 We d nt recmmend that active cling cmmence befre the arrival f the transprt team. 2. Cntinuus Temperature Mnitring Cntinuus temperature mnitring (rectal prbe) is preferred. Intermittent axillary temperatures are acceptable if skills and/r equipment are nt available fr cntinuus rectal temperature. Page 3 f 11
4 Target cre bdy temperature f 33.5 C (range C) (Usually achieved by turning ff exgenus heat surce). 3. Assess severity f HIE (prir t sedatives/narctics; see Table 1) 4. Obtain a bld gas and glucse Avid Hypglycemia: Glucse target: mg/dl 7 Avid hyperxemia 8, 9 and hypcarbia10, NPO, start IVF with D10W at 60ml/kg/day 6. Maintain adequate circulating vlume and bld pressure (MAP target 40-50mmHg) 7. Cnsider CBC, LFTs and DIC panel if bleeding present Elevated AST/ALT shrtly after birth may reflect insult hurs befre birth 8. Seizure Management phenbarbital 20mg/kg x 1 fr clinical seizures, repeat 10mg/kg up t 2 times if still seizing 9. On transprt: Cling: Flight fr Life has prtcl fr active and passive cling 12 Ventilatin: Avid hyperxemia 8, 9 and hypcarbia10, 11 Intrpic supprt 10. Request fr referring prvider t send placenta t pathlgy fr review if available the referring institutin Initial NICU Management Cardi respiratry stabilizatin: Alteratins in heart rate and bld pressure are cmmn during cling hypthermia decreases cardiac utput and HR Usual heart rate with cre temperature C, can be as lw as bpm Attempt t maintain MAP between 40-50mmHg a. Lss f cerebral autregulatin makes hypertensin and hyptensin hazardus Treatment with vlume replacement and/r intrpes shuld be cnsidered if MAP < 40 mmhg With persistent shck, cnsider adrenal insufficiency and btain crtisl level: if lw (< mml/l), treat with hydrcrtisne 2mg/kg q 8 IV. Cnsider echcardigram which may identify pr cardiac cntractility r under perfusin fr etilgy f refractry shck. Avid hyperxemia 8, 9 and hypcarbia10, 11 Cmmence Ttal Bdy Cling: Target cre temperature C Assess neurlgic status: Determine Sarnat scre Dcument in H&P (neurlgical exam t include features listed in Table 1). Place n cntinuus EEG (ceeg) with aeeg capabilities: Assess and Dcument aeeg findings. Cntinue ceeg with aeeg recrding during treatment anf thrugh rewarming*: assess ccurrence f seizures and mnitr severity f encephalpathy (Refer t bedside card fr basics f aeeg). * Cnsider discntinuing cnventinal EEG (ceeg) in patients with mild HIE with nrmal tracing and n evidence f seizures after 24 hurs IV antiepileptic drugs (AEDs) (phenbarbital) may cause transient suppressin f EEG activity. Ideally aeeg shuld be perfrmed befre administering AEDs. Page 4 f 11
5 Labratry tests t cnsider: CBC if bleeding r cncern fr sepsis CMP t assess renal functin, evidence f transaminitis and electrlytes ABG t assess fr adequate ventilatin and presence f acidsis Lactate: cnsider fr refractry metablic acidsis Bld culture if cncern fr sepsis, if nt yet btained Sepsis management: Antibitics are nt indicated in all cases f HIE. Fr thse with cncern fr infectin in additin t HIE, evaluatin and treatment f infectin per standard f care is warranted, with the fllwing cnsideratins: Avidance f aminglycside is suggested due t increased risk f ttxicity and ptential fr nephrtxicity. Gentamicin can be substituted with ceftaxime. 13 Discntinuatin f antibitics at hurs if culture negative shuld be cnsidered t avid untward effects f antibitics. Fluid & acid/base management: Refer t LexiCmp fr ampicillin and ceftaxime dsing infrmatin. NPO; IVF: D12.5W at 40ml/kg/day. Frequent mnitring f urine utput and serum sdium trends. If urine utput < 1ml/kg/hur btain electrlytes q4-6 hurs and cnsider decreasing IVF t <40ml/kg/day while maintaining sufficient glucse infusin rate (GIR). Cnsider diuretics t facilitate adequate urine utput if vlume verlad is cntributing t rgan dysfunctin. Cnsider sdium bicarbnate fr refractry acidsis in adequately ventilating infant with shck and/r cagulapathy. N evidence t supprt lng term benefit f sdium bicarbnate in this ppulatin. Electrlyte management: Risk f hypnatremia: decreased urine utput due t Syndrme f Inapprpriate Antidiuretic Hrmne Secretin (SIADH) and acute tubular necrsis (ATN) Frequent glucse mnitring (risk f hyp r hyperglycemia). Magnesium-shuld be maintained within nrmal range ( mg/dl). 14 Seizure management: Pain/sedatin management: Refer t Nenatal Seizures after Acquired Brain Injury clinical pathway Pain/stress may have adverse effects in infants with HIE. Initial Fentanyl drip at 1mcg/kg/hur in ventilated infants; 0.5mcg/kg/hur in nn-ventilated infants. Titrate t effect. Nrmal heart rate may reflect stress r hypvlemia. Subsequent ICU Management Cardi Respiratry Management: Per ICU [at risk fr primary pulmnary hypertensin (PPHN), and r hypxic respiratry failure] Cnsider echcardigram Page 5 f 11
6 See abve sectin n cardirespiratry management Renal: Acute tubular necrsis and r SIADH may affect urine utput. Clse mnitring f urine utput is essential t avid fluid verlad and cerebral edema. Fluid/Nutritin: Dextrse t keep bld glucse within nrmal range Ttal fluids t maintain adequate circulating vlume, glucse and sdium Hypxia ischemia may impair gut functin and increase risk fr necrtizing enterclitis, cautius advancement in feedings recmmended NPO except rare instances in nn-ventilated, alert, infant wh is able t PO feed limited vlumes Neurlgy: Cntinued Seizure Management: prmpt treatment f seizures is indicated The clinical features f HIE evlves ver days, perfrm daily neurlgic exam and dcument changes in neurlgic exam Cnsider Neurlgy cnsult Hematlgy: Risk fr disseminated intravascular cagulatin (DIC), if bleeding r petechiae present, measure platelets, hematcrit and bleeding times Liver failure: Risk fr liver failure Cnsider repeat dse f Vitamin K n DOL 2 & 3 Check transaminases hurs after birth, if abnrmal cnsider repeating in 12 t 24 hurs Access: Cnsider arterial and venus access as clinically indicated Rewarming: Cmmences at 72 hurs Warm 0.5 C every hur t gal f 36.5 C Peripheral vasdilatin during this time may drp CO and BP Cntinue aeeg r ceeg during rewarming phase Occupatinal and Physical Therapy: Cnsult nce apprpriate Mnitring and Assessment f aeeg: 1. Mnitr general neurlgic status: backgrund pattern 2. Mnitr fr seizures 3. Backgrund at 48 hurs crrelates with lng term neurlgic utcme15, Can be perfrmed simultaneusly with ceeg 5. Dcument at admissin and daily Basics f reading aeeg 17 : 1. Backgrund Pattern: Describes the dminant type f electrical activity in the aeeg trace. Page 6 f 11
7 Cntinuus: Lwer (minimum) amplitude arund 7 t 10 mcv and maximum amplitude f 10 t 25 (t 50) mcv. Discntinuus: Backgrund minimum amplitude variable, but belw 5 mcv, and maximum amplitude abve 10 mcv. Burst-suppressin: Discntinuus backgrund with minimum amplitude withut variability at 0 t 1 (2) mcv and bursts with amplitude >25 mcv. 2. Seizures: Epileptic seizure activity in the aeeg usually is seen as an abrupt rise in the minimum amplitude and a simultaneus rise in the maximum amplitude, ften fllwed by a shrt perid f decreased amplitude. Single seizure: A slitary seizure. Repetitive seizures: Single seizures appearing mre frequently than at 30 minute intervals. Status epilepticus: Cntinuusly nging seizure activity fr >30 minutes. Figure 1. Amplitude Integrated EEG Tracings 18 LABORATORY STUDIES IMAGING Radigraphic and Electrgraphic Evaluatin: 1. Neur Imaging: MRI Day 4-5 depending upn clinical stability Earlier MRI may be cnsidered t make decisins abut withdraw f intensive care Use f ttal bdy cling will imprve feasibility f earlier imaging if indicated 2. EEG: cntinuus 1-3 hur Ideally shuld be perfrmed 24 hurs after cling is terminated t determine backgrund activity fr prgnsticatin. Page 7 f 11
8 FOLLOW UP Neurlgy/Nenatal Brain Injury Clinic (lcated in the Hemphilia & Thrmbsis Center). Brain injury clinic crdinatr will track the patient fr discharge and arrange fllw-up (n need t alert anyne). First fllw-up with Neurlgy at 4-6 weeks after discharge. Page 8 f 11
9 References 1. Shankaran S, Laptk AR, Ehrenkranz RA, et al. Whle-bdy hypthermia fr nenates with hypxic-ischemic encephalpathy. N Engl J Med. 2005;353: di: /NEJMcps Gluckman PD, Wyatt JS, Azzpardi D, et al. Selective head cling with systemic hypthermia after nenatal encephalapthy: multicentre randmised trial. Lancet. 2005;365: Azzpardi D, Strhm B, Edwards AD, et al. Mderate hypthermia t treat perinatal asphyxial encephalpathy. N Engl J Med. 2009;361(14): di: /NEJMa Murray DM, O Cnnr CM, Ryan CA, Krtchikva I, Bylan GB. Early EEG grade and utcme at 5 years after mild nenatal hypxic ischemic encephalpathy. J Pediatr. 2016; di: /peds Laptk A, Tysn J, Shankaran S, et al. Elevated temperature after hypxic ischemic encephalpathy: risk factr fr adverse utcmes. J Pediatr. 2008; 122: di: /peds Relfsema V, bennet L, Gerge S, Wu D, eta l. Windw f pprtunity fr hypthermia fr pstischemic white matter injury in near-term fetal sheep. J Cereb Bld Flw Metab Aug; 24(8): Tam EW, Feigenbaum A, Addis JB, Blaser S, et al. Hypglycemia is assciated with increased risk fr brain injury and adverse neurdevelpmental utcme in nenates at risk fr encephalpathy. J Pediatr Jul ; 161(1): Sabir H, Jary S, Tley J, Liu X, Thrensen M. Increased inspired xygen in the first hurs f life is assciated with adverse utcme in newbrns treated fr perinatal asphyxia with therapeutic hypthermia. J Pediatr. 2012;161: di: /j.jpeds Kapadia V, Chalak LF, DuPnt TL, Rllins NK, Brin LP, Wyckff MH. Perinatal asphyxia with hyperxemia within the first hur f life is assciated with mderate t severe hypxic-ischemic encephalpathy. J Pediatr. 2013;163: di: /j.jpeds Pappas A, Shankaran S, Laptk AR, et al. Hypcarbia and adverse utcme in nenatal hypxic ischemic encephalpathy. J Pediatr. 2011;158: di: /j.jpeds Lingappan K, Kaiser JR, Srinivasan C, Gunn AJ. Relatinship between PCO2 and unfavrable utcme in infants with mderate-t-severe hypxic ischemic encephalpathy. Pediatric Research. 2016;80: di: /pr O Reilly D, Labrecque M, O Melia M, Bacic J, Hansen A, Sul JS. Passive cling during transprt f asphyxiated term newbrns. J Perinatlgy. 2013; 33: di: /jp Smit E, Liu X, Gill H, Sabir H, Jary S, Thresen M. Factrs assciated with permanent hearing impairment in infants treated with therapeutic hypthermia. J Pediatr. 2013;163: di: /j.jpeds Bhat MA, Char BA, Bhat JI, Ahmad SM, Ali SW, Mufti MU. Magnesium sulfate in severe perinatal asphyxia: a randmized, placeb-cntrlled trial. J Pediatr. 2009;123(5): di: /peds Epub 2009 Apr Ter Hst H, Smmer C, Bergman KA, Fck JM, van Weerden TW, Bs AF. Prgnstic significance f amplitude integrated EEG during the first 72 hurs after birth in severely asphyxiated nenates. Pediatric Research. 2004;55: di: /01.pdr c. 16. Azzpardi D; TOBY study grup. Predictive value f the amplitude integrated EEG in infants with hypxic ischaemic encephalpathy: data frm a randmised trial f therapeutic hypthermia. Arch Dis Child Fetal Nenatal Ed. 2014;99(1):F80-2. di: /archdischild Hellstrm-Westas L, Rsen I, de Vries LS, Greisen G. Amplitude-integrated EEG classificatin and interpretatin in preterm and term infants. Nereviews. 2006:7(2):e76-e87. di: /ne.7-2-e Thrensen M, Hellstrm-Westas L, Liu X, de Vries, LS. Effect f hypthermia n amplitude-integrated electrencephalpgram in infants with asphyxia. J Pediatr. 2010;126: di: /peds Page 9 f 11
10 CLINICAL IMPROVEMENT TEAM MEMBERS Cassidy Delaney, MD Nenatlgy Rbert Dietz, MD Nenatlgy James Barry, MD Nenatlgy Theresa Grver, MD Nenatlgy Michael Murphy, PharmD Clinical Pharmacist Sarah Nickels, PhD Clinical Effectiveness APPROVED BY Antimicrbial Stewardship Nvember 2, 2016 Pharmacy & Therapeutics Cmmittee Nvember 3, 2016 Clinical Care Guideline and Measures Review Cmmittee Nvember 29, 2016 Medicatin Safety Cmmittee nt applicable MANUAL/DEPARTMENT Clinical Care Guidelines/Quality ORIGINATION DATE Nvember 29, 2016 LAST DATE OF REVIEW OR REVISION Nvember 29, 2016 APPROVED BY Lalit Bajaj, MD, MPH Medical Directr, Clinical Effectiveness REVIEW REVISION SCHEDULE Scheduled fr full review n date here Nvember 29, Clinical pathways are intended fr infrmatinal purpses nly. They are current at the date f publicatin and are reviewed n a regular basis t align with the best available evidence. Sme infrmatin and links may nt be available t external viewers. External viewers are encuraged t cnsult ther available surces if needed t cnfirm and supplement the cntent presented in the clinical pathways. Clinical pathways are nt intended t take the place f a physician s r ther health care prvider s advice, and is nt intended t diagnse, treat, cure r prevent any disease r ther medical cnditin. The infrmatin shuld nt be used in place f a visit, call, cnsultatin r advice f a physician r ther health care prvider. Furthermre, the infrmatin is prvided fr use slely at yur wn risk. CHCO accepts n liability fr the cntent, r fr the cnsequences f any actins taken n the basis f the infrmatin prvided. The infrmatin prvided t yu and the actins taken theref are prvided n an as is basis withut any warranty f any kind, express r implied, frm CHCO. CHCO declares n affiliatin, spnsrship, nr any partnerships with any listed rganizatin, r its respective directrs, fficers, emplyees, agents, cntractrs, affiliates, and representatives. Page 10 f 11
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