Prehľad. I. Hypoxia ischémia (HI) II. Patofyziológia HI Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza. Perinatálna hypoxia Klinika

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1 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia Zobrazovacie metódy Neurologický nález Microcephalia (od 3.mesiaca) a Follow-up Kombinácia

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3 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Portman score Shah score RH kritériá SNAP-PE II Ambalavanam kritériá

4 Portman score for organ dysfunction in the immediate neonatal period after asphyxia body Apgar v 5. min > BE v 1. h / 5. min. z a./ k. < > 19 CTG N Decelerácie variab. 6 bodov - ťažká morbidita 5b mierna - stredná morbidita Decelerácie : variab. ťaž. / atypic neskoré Prolong. bradykard. Portman RJ, AJOG, 1990 Jan;162(1):

5 Shah score for postasfyxia morbidity PROGNOSTICKÉ SKÓRE (Shah) - 3 parametre: NMS > 1 min Ventilácia > 20 min BD > 16 mmol/l v prvých 4h*1 Prediktory úmrtia alebo ťažkej poruchy:» 0 sk: 46% (95% CI, 33%-58%)» 1 sk.: 64% (95% CI, 54%-73%)» 2 sk.: 76% (95% CI, 66%-85%)» 3 sk.: 93% (95% CI, 81%-99%) Shah PS.; APAM 2006; 160:729

6 Riadená hypotermia - indikačné kritériá 1. všeobecné 2. ťažká asfyxia 3. HIE klinicky stačí 1 kritérium klinické (v 10. min.života) Apgar < 6 ventilácia maskou / ETK laboratórne (do 60.min.života) ph < 7.00 BE 16 mmol/l laktát > 10 mmol/l* elektrofyziologicky (aeeg)!!!???

7 SNAPPE II Stredný TK 20 19b b 3O 0b Min TT 35 15b 35 35,6 8b 35,6 0b PO2 / FiO2 0,3 28b 0,3 0,99 16b 1,0 2,49 5b 2,49 0b ph 7,1 16b 7,1 7,19 7b 7,2 0b kŕče + 19b - 0b Diuréza 0,1 18b 0,1 0,9 5b 1,0 0b Apgar 5.min 7 18b 7 0b p. hmotn b b b Hypotrofia 5 per 12b 5 per 0b

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9 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika kŕče HIE II / III NBRS

10 Prognóza HIE po RH The best interests of the child Perinatálna hypoxia Klinika (HIE, kŕče, apnoe, multiorgánové dysfunkcie) Závažnosť HIE II * 3 / III extrémne (>17 sc podľa Thomsona) *1 Kŕče * 4 skoré ( h) status epi (>30 min) ťažko kontrolovateľné kŕče (>48 h) *2 Multiorgánové zlyhanie Trvanie: prolongovaná ventilácia perzistentná oligúria poruchy kŕmenia,... dlho trvajúca intenzívna starostlivosť po 2. týždni / pri prepustení: abnormálny neurologický nález, apnoe, antikonvulzíva, neschopnosť pitia ( < 6 dní vymiznutie HIE II alebo abnormálneho neurologického nálezu = dobrá prognóza) Medscape, August 2013

11 Exitus / závažné postihnutie pri strednej až závažnej HIE Prakesh S. Shah. Arch Pediatr Adolesc Med. 2007;161(10):

12 Shah, Semin Fetal Neonatal Med 2010 Oct;15(5):

13 Edwards AD. BMJ 2010;340:c363 Exitus / závažné postihnutie pri strednej až závažnej HIE

14 Edwards AD, BMJ 2010;340:c363. A meta-analysis of data from 3 hypothermia trials found that the primary outcome of death and disability at 18 months was significantly reduced by cooling in neonates: HIE II/III: RR 0.81, 95% CI 0.71 to 0.93; P=0.002; NNT 9 with moderate HIE: RR 0.73, 95% CI 0.58 to 0.92; P=0.008 but not in those with severe HIE: 0.87, 95% CI 0.75 to 1.01; P=0.07

15 Exitus / závažné postihnutie pri strednej až závažnej HIE Jacobs Susan E., Arch Pediatr Adolesc Med. 2011;165(8):

16 Jacobs Susan E., Arch Pediatr Adolesc Med. 2011;165(8):

17 Jacobs Susan E., Arch Pediatr Adolesc Med. 2011;165(8):

18 Tagin MA, Arch Pediatr Adolesc Med. 2012;166(6): Exitus / závažné postihnutie pri strednej až závažnej HIE

19 Tagin MA, Arch Pediatr Adolesc Med. 2012;166(6):558. survival with normal neurological function (1.63; ) death or major neurodevelopmental disability (0.76; 95% CI, ) moderate HIE NNT 6; RR 0.67; 95% CI, severe HIE NNT 7; RR 0.83;

20 Jacobs SE. The Cochrane Library, 2013, Issue 1

21 Jacobs SE. The Cochrane Library, 2013, Issue 1

22 Jacobs SE. The Cochrane Library, 2013, Issue 1

23 Low E, Arch Dis Child Fetal Neonatal Ed 2012;97:F using full-montage video-eeg, also found that therapeutic hypothermia provided a benefit, with reduced electrographic seizure burden, only in neonates with moderate HIE

24 RH neovplyvní kŕče pri HIE III a pri závažnom MRI náleze Srinivasakumar Preethi,Pediatr2013;163:465-70

25 EPO neovplyvní outcome pri HIE III Zhu, PEDIATRICS Volume 124, Number 2, August 2009

26 Srinivasakumar Preethi. J Pediatr 2013;163: reduced electrographic seizure burden in neonates with moderate HIE but not in those with severe clinically HIE, not in those with severe MRI injury LIMITATIONS Not prospectively randomized Controls: before the initiation of clinical therapeutic hypothermia or were admitted beyond the 6-hour

27 Neurologická prognóza pre HIE III (nezávisle od RH) Klebermass-Schrehof K., Dresden 2014

28 Death or survival with severe disability % (N) ALL MODERATE SEVERE 83 % (48) 51% (27) 60% (9) 91 % (39 ) 62% (21) Control Hypoth 32% (6) Simbruner, NZ, 2010

29 Simbruner G,. Pediatrics 2010;126:e771-8 In contrast, Simbruner et al reported that hypothermia is strongly neuroprotective even in severe HIE.

30 Jacobs SE. The Cochrane Library, 2013, Issue 1

31 Jacobs SE. The Cochrane Library, 2013, Issue 1

32 Jacobs SE. The Cochrane Library, 2013, Issue 1

33 Jacobs SE. Cochrane Database Syst Rev. 2013;1:CD Cooling reduces mortality without increasing major disability in survivors TH is effective for moderate or severe HIE!? Further trials appropriate techniques of cooling, patient selection duration of cooling and method of providing

34 Soll RF, Neonatology Nov 2013;104(4):260-2 The updated review of Jacobs SE. Cochrane Database Syst Rev. Jan TH is effective for moderate or severe HIE MRI abnormalities after cooling (RR 0.73, 95% CI ) MRI abnormalities are highly predictive of poor developmental outcome

35 ? Horn AR. Acta Paediatr 2013, 102(8):378

36 Horn A.R. BMC Pediatrics 2013, 13:52 Interpretácia a využitie Thompson scóre Thompson score 5 v hodine identifikovalo všetkých novorodencov s abnormálnym aeeg v 3. a/alebo 6. hodine toto môže byť dostatočnou indikáciou na to, aby sa volalo centrum s chladením pre rozhodnutie o ďalšom postupe Thompson score 7 v hodine bolo viac senzitívnym prediktorom strednej až závažnej HIE v 72. hodine ako aeeg v 6. hodine kritérium pre riadenú hypotermiu Thompson score 17 v hodine by mohlo byť vylučovacím kritériom???

37 RH holandská štúdia -kŕče Groenendaal F., Neonatology; 2013;104:15-21, Dresden,

38 Prognóza HIE po RH The best interests of the child Perinatálna hypoxia Klinika (HIE, kŕče, apnoe, multiorgánové dysfunkcie) Závažnosť HIE II / III extrémne (>17 sc podľa Thomsona) *1 Kŕče skoré ( h) status epi (>30 min) ťažko kontrolovateľné kŕče (>48 h) *2 Multiorgánové zlyhanie prolongovaná ventilácia perzistentná oligúria poruchy kŕmenia,... Trvanie: dlho trvajúca intenzívna starostlivosť po 2. týždni / pri prepustení: abnormálny neurologický nález, apnoe, antikonvulzíva, neschopnosť pitia perzistencia HIE III po 72 hod zvyšuje riziko smrti a poškodenia ( < 6 dní vymiznutie HIE II nálezu = dobrá prognóza) alebo abnormálneho neurologického Shankaran Medscape, August 2013

39 asymmetrical tonic neck reflex (ATNR)

40 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium (validné na Dg HII ale nie na outcome???) ph v UA S100B a NSE (neuron špecifická enoláza) prvých 72h CK-BB CSF: laktát, camp Chalak LF. J Pediatr Mar;164(3): e1

41 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia aeeg funkcie mozgového kmeňa evokované potenciály

42 Perinatálna hypoxia Klinika Laboratórium Prognóza HIE po RH The best interests of the child Elektrofyziologické vyšetrenia aeeg (dg aj prognóza!!!) Závažné patologické aeeg (BS / LV / FT) prvých 24 hod: normálna background activity a neprítomnosť kŕčov dobrá prognóza po 48 hod: patologická background activity a kŕče zlá prognóza funkcie mozgového kmeňa evokované potenciály silná predikcia Shankaran, Dresden 2014 Hamrick S.E.G., Brain injury, NEOPREP 2012 Thoresen M. Pediatrics Jul;126(1):e131-9

43 Validita patologického aeeg v 6-24 h (BS, FT, CLV) Spitzmiller RE. Journal of Child Neurology, 2007

44 Jacobs SE. The Cochrane Library, 2013, Issue 1

45 * Jacobs SE. The Cochrane Library, 2013, Issue 1

46 * Jacobs SE. The Cochrane Library, 2013, Issue 1

47

48

49 TTNT: PPV of abn trace (BS, LV or FT) to poor outcome Thoresen M., Pediatrics 2010;126:e131 e139

50 Glass H.C.: Neo Pharmacol Conf, La Jolla, USA, 2013

51 Evolution of aeeg backround with hypotermia by severity of MRI injury Nash KB. Neurology 2011;76:

52 HIE II + abnormal aeeg Klebermass-Schrehof K., Dresden 2014

53 HIE III + abnormal aeeg NT HT Klebermass-Schrehof K., Dresden 2014

54 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia Zobrazovacie metódy Doppler (prvé hodiny 24. hod) relatívne pomer EDBFV : PSBFV (dg aj prognóza!!!) IR < 0,5 nepriaznivý vývoj

55 Prehľad I. Prognóza Zobrazovacie metódy UZV* bezprostredne (vylúčenie ICH, VVCH, infekcie a prítomnosť edemu mozgu prognóza): generalizovane echogenicita nezreteľné sulky úzke komory za 2-7 dní: echogenicita bazálnych ganglií (viditeľnosť na UZV = zlá prognóza!!!) echogenicita periventrikulárne a v parenchýme 1-3 týždne: parenchymálne cysty > 6 týždne: ventrikulomegália kortikálna atrófia Fox G, Neonatology 2010

56 Prehľad V. Prognóza Zobrazovacie metódy MRI (vylúčenie ICH, VVCH, inf. a fokálny infart) Konvencionárna MR-T1 a T2 (3.deň; optim deň života) DW MR (3.-6 h; optim deň života; normalizácia 7. deň) HIE II.-III.: (zlá prognóza) týždeň abnormality. baz. ganglií, capsula int. (PLIC)*, PV-WM cortical grey-white differentiation loss neskoré ventrikulomegália, kortikálna atrófia, stenčovanie sa CC perzistencia abnormalít a atrófia BG a WM oneskorená myelinizácia Senzitivita:90% Špecificita:100% Pozitívna prediktívna hodnota:100% MR proton spektroskopy (behom 24h) Vysoký pomer Lactat / Choline Nízky pomer N-Acetyl-Asparate / Choline Gomella TC. Neonat, 2013, Fox G, Neonatology 2010

57 Riadená HT: MRI > CT Inder T.E. IPOKRaTES 2012

58 Validita late MRI Klebermass-Schrehof K., Dresden 2014

59

60

61

62

63

64 Záchyt HIE na DW a na T1/T2 McKinstry RC et al Neurology 2002

65 Conv. vs DW MRI Groenendaal F, IPOKRaTES, 2014, Porto

66

67

68

69

70 Miller J Pediatr 146: 453, 2005

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72 Groenendaal F, IPOKRaTES, 2014, Porto

73 Groenendaal F, IPOKRaTES, 2014, Porto

74

75 Senzitivita a špecificita van Laerhoven H, Pediatrics Vol. 131 No. 1, 2013 pp

76 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia Zobrazovacie metódy Neurologický nález (NN) Po 72 h vymyznutie HIE III = dobrá prognóza Po týždni Norm. NN = veľmi dobrá prodnóza Pred prepustením Norm. NN + spont. pitie a = dobrá prodnóza Shankaran S. J Pediatr Apr;160(4): e3. Finer NN. J Pediatr. 1981;98(1):112. Gomelle TC. Neonatology, 2013

77 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia Zobrazovacie metódy Neurologický nález Microcephalia (v 3.mesiaci) alebo Pretrvávanie abnormálneho NN (v 12. mesiaci) Gomelle TC. Neonatology, 2013

78 Shankaran S., Dresden 2014

79 Prehľad I. Hypoxia ischémia (HI) II. Patofyziológia HI III. Riadená hypotermia (RH) IV. Intenzívna starostlivosť V. Prognóza Perinatálna hypoxia Klinika Laboratórium Elektrofyziologické vyšetrenia Zobrazovacie metódy Neurologický nález Microcephalia (v 3.mesiaci) alebo Pretrvávanie abnormálneho NN (v 12. mesiaci) KOMBINÁCIA Gomelle TC. Neonatology, 2013

80 Klebermass-Schrehof K., 5th Symposium Asphyxia & Hypothermia, Dresden 2014

81 ??? hibernizovať najťažšie formy HIE III??? HIE III Diskrepancia v metaanalýzach HIE II / HIE III!!! 85% HIE III po RH zomrie alebo zostane poškodený (Perlman, 2011) Na EPO reaguje len HIE II (Zhu,2009) RH nie je efektívna na vymiznutie aeeg kŕčov u HIE III ani u záv. MRI, Neovplyvniteľné kŕče sú príznakom zlej prognózy (Srinivasakumar, 2013) Riadená hypotermia je efektívna len v prípade HIE I a II (Medscape August 2013) Školský vek... Dospelosť longer-term morbidity!!!???

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