Repetitorium Kinderanästhesie 4./5. July 2014

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2 Repetitorium Kinderanästhesie 4./5. July 2014

3 Regional and general anaesthesia in paediatric patients? Martin Jöhr Paediatric Anaesthesia Department of Anaesthesia Kantonsspital CH-6000 Luzern 16 Switzerland

4 . nothing. deep sedation or general anaesthesia is needed

5 pain or agitation? prophylactic pain medication with LA is a very attractive concept

6 1-79 ssociation of Paediatric Anaesthetists of Great Britain and Ireland

7 General adapted to the child high success rate familiar airway instrumentation neurotoxicity potential vital parameters Regional only for analgesia failure rate limited duration postoperative analgesia absent neurotoxicity stable vital signs (?)

8 General remarks Reduction of exposure Potential problems Conclusions

9 Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits University of Virginia Jevtovic-Todorovic V et al. J Neurosci (2003) 23:

10 numerous research papers review articles expert statements

11 Midazolam, N 2 O, isoflurane 7 day-old rats midazolam, N 2 O, isoflurane 6 hours exposition 3 weeks later apoptotic neurodegeneration midazolam 3, 6 und 9 mg/kg no effect N 2 O % no effect Jevtovic-Todorovic V et al. J Neurosci (2003) 23:

12 Midazolam, N 2 O, isoflurane normal growth, normal development day 28: are able to find and to climb on a visible platform learn much more slowly to find a hidden platform Jevtovic-Todorovic V et al. J Neurosci (2003) 23:

13 Midazolam, N 2 O, isoflurane Our findings indicate that exposure to an anesthetic cocktail (midazolam, isoflurane, N 2 O) that is commonly used in pediatric anesthesia triggers apoptosis... resulting in deletion of many neurons from the developing brain... Our findings indicate that an anesthetic protocol that does not alter somatic development or induce sensomotor impairments in rats does result in learning/memory deficits that are subtle enough to be easily overlooked. Jevtovic-Todorovic V et al. J Neurosci (2003) 23:

14 6 h isoflurane => apoptosis in primates control isoflurane Brambrink AM et al. Anesthesiology (2010) 112:

15 6 h isoflurane => apoptosis in primates % maximal growth rate of the brain monkey birth human 6 days 6 months Brambrink AM et al. Anesthesiology (2010) 112:

16 6 h isoflurane => apoptosis in primates 6 day-old monkeys 5 hours isoflurane apoptosis 52% glia cells 48% neurons 6.3% of all oligodendrocytes disappear => myelin production Brambrink AM et al. An Neurol (2012) 72:

17 Findings transferable to infants? species duration monitoring

18 There is little doubt: commonly used anaesthetics have the potential to induce apoptotic brain degeneration in humans too

19 There is little doubt: commonly used anaesthetics have the potential to induce apoptotic brain degeneration in humans too exclusively dependent on the anaesthetic action? only apoptosis or even more profound changes? the clinical relevance in humans?

20 Learning difficulties? learning difficulties (%) multiple anaesthetics single anaesthetic no age (years) retrospective ( ) anaesthetic, < 4 y halothane/n 2 O children => 593 anaesthetics Minnesota Wilder RT, Flick RP et al. Anesthesiology (2009) 110:

21 Academic performance Birth cohort ( ) in Denmark hernia repair in early infancy with hernia repair controls no difference academic performance at y Hansen TG et al. Anesthesiology (2011) 114:

22 Academic performance Large Danish databases surgery for pyloric stenosis before 3 months of age 779 pyloric stenosis controls surgery for cleft lip and palate - isolated cleft lip - isolated cleft palate - cleft lip and palate no difference most relevant predictor gender > Hansen TG et al. Paediatr Anaesth (2013) Oct 23:

23 FDA IARS ESA

24 General remarks Reduction of exposure Potential problems Conclusions

25 Neurotoxicity with local anaesthetics 3- and 7-day-old rats spinal anaesthesia levobupivacaine 0.5%; 2.5 mg/kg spinal block, normal recovery histology normal at 24 h and 7 days normal spinal cord function on day 35 Tony Yaksh San Diego California Hamurtekin E et al. Anesthesiology (2013) 119 July:142-55

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27 Awake regional anaesthesia 22G needle 1 mg tetracaine + 10 μg adrenaline number failure supplementation "high risk" malformation term neonate total Abajian JC (Burlington VT) et al. Anesth Analg (1984) 63:

28 Awake regional anaesthesia preterm and ex-preterm babies (n=575) spinal (n=339) caudal (n=236) successful awake regional 84.9% 90.1% supplementation 7.4% 6.0% conversion to GA 7.6% 3.9% total spinal n=8 n=1 Hoelzle M et al. Paediatr Anaesth (2010) 20: 620-4

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30 Haemodynamic stability blood pressure mmhg 2 700g term neonate 1.6 ml/kg bupivacaine 0.125% + E minutes 37/ Jöhr M et al. Paediatr Anaesth (2012) 22: 44-50

31 Epidural catheters "The national epidural audit" Llewellyn N, Moriarty A. Paediatr Anaesth (2007) 17: '633 epidural catheters permanent damage 9 severe complications 33 pressure sores towards a more restrictive use of these techniques Moriarty A. Paediatr Anaesth (2012) 22: 51-55

32 GAS Trial General anaesthesia Apoptosis - Spinal anaesthesia 722 infants <60 weeks postmenstrual age 27 institutions in 7 countries randomization: awake regional sevoflurane + RA recruitment completed in January 2013 neurodevelopmental outcome at 2 and 5 years final results by 2014 and 2017 coordinator Davidson AJ

33 GAS Trial General anaesthesia Apoptosis - Spinal anaesthesia 722 infants preliminary <60 weeks postmenstrual early outcomes age 27 APA institutions Cambridge in 7 (June), countries ESPA Geneva (September) randomization: awake regional sevoflurane + RA close recruitment to 20% completed failure rate in in January the awake 2013 regional group marked neurodevelopmental hypotension common outcome in at the 2 and GA 5 + years RA group no substantial reduction in risk of apnoea final results by 2014 and 2017 coordinator Davidson AJ

34 . the wrong questions. Anesthetists rather than anesthetics are the threat to baby brains. being unable to swim is not the problem of the water. Weiss M, Bissonnette B, Engelhardt T, Soriano S Paediatr Anaesth (2013) 23 October: blood pressure and perfusion hyperoxia and hypoxia hypocapnia optimal dosing

35 General remarks Reduction of exposure Potential problems Conclusions

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37 Conclusions The experience of the anaesthesiologist and the age of the patient are the main predictors of complications. There is little doubt that early exposure to anaesthetic drugs confers the potential of neurodegenerative changes in the developing brain. The clinical impact of these findings remains largely unclear, and good and skilled practice in paediatric anaesthesia is of paramount importance.

38 Conclusions The experience of the anaesthesiologist and the age of the patient are the main predictors of complications... improvement of the outcome by the aggregation of marginal gains.. There is little doubt that early exposure to anaesthetic drugs confers the potential of neurodegenerative changes in the A regional block for analgesia combined with a reduced dose of the general anaesthetic is still a very attractive concept developing brain. The clinical impact of these findings remains largely unclear, and good and skilled practice in paediatric anaesthesia is of paramount importance.

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41 Anästhesie und Lernstörungen? incidence of developmental and behavioral disorders Kontrolle 1 OP 1,1 Retrospektiv ( ) Medicaid Datenbank Geschwisterkohorte 2 OP 2,9 3 OP 4, OP vor 3 J ohne OP 304 OP DiMaggio C et al. Anesth Analg (2011) 113:

42 Sectio und Lernstörungen? Lernschwierigkeiten (%) vaginale Geburt Sectio Narkose Sectio RA Alter (Jahre) Retrospektiv ( ) Sectio Kinder => 193 Sectio Narkose 304 Sectio RA Minnesota Sprung J, Flick RP et al. Anesthesiology (2009) 111:

43 Anästhesie und Lernstörungen? incidence of developmental and behavioral disorders Hernie 2,3 (1,3-4,1) Retrospektiv ( ) Medicaid Datenbank Kontrolle RR Hernien-OP vor 3 J Geburten => 383 Hernie 5050 Kontrollen DiMaggio C et al. J Neurosurg Anesthesiol (2009) 21:

44 Anästhesie und Lernstörungen? Pediatric Anesthesia NeuroDevelopment Assessment PANDA Projekt Aufwändige Testung von exponierten und nicht exponierten Geschwistern Erste Daten von 28 Kindern Lun LS, Li G, DiMaggio C et al. Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project Neurosurg Anesthesiol (2012) 24 (Oct) :382-8

45 Zwillingsregister in Holland Daten von eineiigen Zwillingspaaren - Narkose im Alter von 0-3 Jahren - Testung im Alter von 12 Jahren Narkose vor 3 Jahren => mehr kognitive Probleme Aber kein Unterschied zum nicht exponierten Zwilling Hypothese: Notwendigkeit einer Narkose ist ein Hinweis auf eine erhöhte Vulnerabilität des Organismus Bartels M et al. Twin Res Hum Genet (2009) 12:

46 Anästhesie und Academic performance Dänische Datenbanken mit großen Zahlen Lippen- und Gaumenspalten - isolierte Lippenspalte - isolierte Gaumenspalte - Lippenkiefergaumenspalte Pylorusstenose-OP in den ersten 3 Monaten Wichtigster Prädiktor gender > Frühstücksgespräche

47 GAS Trial General anesthesia Apoptosis - Spinal anesthesia 660 Neugeborene mit Leistenhernie Multizenterstudie Randomisiert: Spinalanästhesie Sevofluran Entwicklung im Alter von 2 und 5 Jahren Rekrutierung bis 2012 Erste Resultate 2014 und 2017 Koordinator Davidson AJ

48 Neurodegeneration gibt es aber man kann sie kompensieren 7 d alte Ratten 4h 1 MAC Sevo kognitives Defizit Normaler Käfig Normaler Käfig enriched environment 4 Wochen 4 Wochen normal Shih J et al. Anesthesiology (2012) 116:

49 Plastizität des Gehirns Davidson AJ. Anesthesiology (2012) 116: 507-9

50 Plastizität des Gehirns Ständige Anpassung an neue Umstände Wir wachen anders auf als wir einschlafen Welche Rolle Anästhetika spielen, ist unklar Davidson AJ. Anesthesiology (2012) 116: 507-9

51 Neurodegeneration gibt es Keine grundlegende Änderung der Praxis Opioide zur Analgesie Lokalanästhetika Hypnotika bedarfsgerecht dosiert Davidson AJ. Anesthesiology (2012) 116: 507-9

52 FDA IARS

53 Enriched environment Ratten 7 Tage alt 4 h Sevofluran 1 MAC normaler Käfig Im Alter von 8 Wochen Kognitive Testung nach 4 Wochen stimulierende Umgebung vor allem Kurzzeitgedächtnis beeinträchtigt keine negativen Auswirkungen der Narkose Shih J et al. Anesthesiology (2012) 116 März:

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55 FDA IARS

56 Avoiding airway instrumentation % difficult intubation years; Dresden y 1-5 y 5-17 y intubations in children => 36 difficult intubations Schmidt J, Koch T Anesthesiology (2008) 109: A1244