Updates in Pediatric Anesthesia

Transcription

1 Updates in Pediatric Anesthesia MAY 12, 2017 BRIAN GILLISS MD PEDIATRIC ANESTHESIA KAISER SAN FRANCISCO SELECTED SLIDES DRAFTED BY KAREN BOCKLI MD NEONATOLOGY, KAISER SAN FRANCISCO

2 Disclosure Kaiser Permanente South San Francisco has determined that the speaker (Dr. Gilliss, Dr. Bockli) and the planning committee (Dr. Becker, Dr. Yap, Dr. Ginsberg, Rebecca Bayrer, Heather Miller) for this activity do not have any relevant financial relationships. Kaiser Permanente South San Francisco takes responsibility for the content, quality, and scientific integrity of this CME Activity. Kaiser Permanente does not endorse any brand-name products.

3 Objectives Review new literature on pediatric anesthesia and discuss implications to current practice. Address new concern of FDA release statement on exposure to anesthesia for our pediatric population. Manage pediatric emergencies according to latest guidelines. Diagnose pediatric emergence delirium and apply latest treatment recommendations.

4 Recent Literature Not much to say... Implementation of Cognitive Aids SPA Pedi Crisis Cards Sugammadex in children... except about neurotoxicity

5 Recent Literature Clebone. Anesth Analg Mar;124(3):

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9 Recent Literature Volume 27 (2) Roughly 6 trials have been done (n~20-80), all with rocuronium Mixed surgical, oncology, CHD, neonates Case reports in myasthenia, myotonic dystrophy, and Duchenne s Typical time to reversal 30s-90s Anaphylaxis rate 0.3%, almost entirely within 4min What about emergent reintubation?

10 Discussion of KP SSF practice What cases do you do/transfer? ENT: myringotomy, T&A, sleep endoscopy, hearing tests ortho/podiatry: elbow CRPP, club foot Urology: circumcision, orchiopexy Gen Surg: appy IR: line revisions ED: intubation, difficult PIV, LP assistance How do you do your T&A? Premed, decadron, tylenol, precedex, zofran, opiate

11 Discussion of KP SSF practice What do you do for difficult IV access? Do you do regional/caudals? How young is too young? Who are your resources? Brian Gilliss cell KP-Oak pedi on call KP-SC pedi on call

12 Emergence Delirium How do you prevent it? How do you treat it?

13 Pediatric Emergencies Use the pedi crisis cards! What are you likely to see? Laryngospasm Bronchospasm Emergence delirium (airway fire)

14 Anesthetics and Neonates. Are the FDA Warnings Warranted? GAS Trial results Panda Trial Long-term differences in language and cognitive function after childhood exposure to anesthesia

15 FDA Warnings Repeated or lengthy (>3 hours) use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women in the 3 rd trimester may affect the child s developing brain.- December 2016 Last advisory meeting in recommendations were considered but no warnings were made

16 FDA Warnings FDA is requiring warnings to be added to the labels of general anesthetic and sedation drugs for children <3 years of age No specific anesthetic or sedation drug has been shown to be safer than any other Repeated or lengthy use (>3 hours) Desflurane Halothane Ketamine Methohexital Pentobarbital Etomidate Isoflurane Lorazepam Midazolam injection Propofol Sevoflurane

17 GAS Trial Aim: To determine if general anesthesia in infancy is safe Does general anesthesia and awake-regional anesthesia in infancy have the same neurodevelopmental outcome Primary Outcome: Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient score at five years of age. Secondary Outcome Neurodevelopmental outcome at 2 years of age

18 Study Design Prospective, observer blind, international, multi-site randomized Regional anesthesia vs general anesthesia 28 hospitals in Australia, Italy, the US, the UK, Canada, the Netherlands, and New Zealand Infants up to 60 weeks of age Exclusion criteria: congenital heart disease, vent before surgery, chromosomal abnormalities, previous exposure to GA or benzos, PVL, grade 3 or 4 IVH.

19 Study Design RA group received either an awake-spinal anesthetic, an awake caudal anesthetic or a combined spinalcaudal anesthetic GA group received sevoflurane for induction and maintenance 2 year assessment- Bayley-III Cognitive, Motor, and Language 5 Year assessment will be the Wechsler Preschool and Primary Scale of Intelligence Third addition 598 infants needed to enroll in total

20 Study Design Analyzed by treatment actually received and also secondarily by intention to treat Looking for toxicity

21 Results Lancet January 16; 387(10015):

22 Demographic Data Lancet January 16; 387(10015):

23 Demographic Data Assessment Details Family Demographics at 2 years Paid employment is main income Family Structure, 2 caregivers together Corrected at age assessment wks Number of Hospitalizations since operation RA Arm APP N=287 ga Arm APP N=356 RA Arm ITT N=361 ga Arm ITT N= (90%) 267 (8%) 274 (90%) 268 (88%) 226 (91%) 274 (90%) 277 (90%) 275 (90%) (69%) 206 (68%) 210 (68%) 207 (68%) 1 51 (20%) 64 (21%) 69 (22%) 64 (21%) 2 14 (6%) 18 (6%) 16 (5%) 18 (6%) Lancet January 16; 387(10015):

24 Demographic Data Assessment Details The child has had an intervention for neurodevelopmental issues RA Arm APP N=287 ga Arm APP N=356 RA Arm ITT N=361 Speech therapy 22 (9%) 27 (9%) 28 (9%) 27 (9%) Physiotherapy 22 (9%) 27 (9%) 26 (8%) 27 (9%) Occupational therapy 9 (4%) 12 (4%) 12 (4%) 12 (4%) Psychology 1 (<1%) 6 (2%) 1 (<1%) 6 (2%) ga Arm ITT N=358 Developmental medicine/early intervention Child had a head injury that involved loss of consciousness Child had other seizures (not febrile) 8 (3%) 7 (2%) 9 (3%) 7 (2%) 7 (3%) 4 (1%) 7 (2%) 4 (1%) 1 (<1%) 4 (1%) 1 (<1%) 4 (1%) Lancet January 16; 387(10015):

25 Results at 2 years Lancet January 16; 387(10015):

26 Results at 2 years Proportion below 1 and 2 SD Lancet January 16; 387(10015):

27 Results at 2 years Child is legally blind RA Arm APP N=287 ga Arm APP N=356 RA Arm ITT N=361 1 (2%) 0 1 (2%) 4 (1%) Cerebral Palsy 1 (<1%) 4 (1%) 1 (0%) 4 (1%) ga Arm ITT N=358 Autism Spectrum Disorder 2 (1%) 4 (1%) 1 (0%) 4 (1%) Lancet January 16; 387(10015):

28 Discussion Strong evidence for equivalence between RA and GA in infancy in terms of neurodevelopmental outcome at 2 years of age. Just under an hour of anesthesia in infancy does not cause clinically significant adverse neurodevelopmental outcome compared to awake regional anesthesia

29 Discussion Limitations Loss to follow up 14% 2 year outcome is not a perfect predictor of long term outcome due to the considerable variability in developmental timing in young children 5 year assessment and results will be known after 2018 Reporting secondary outcome >80% of participants were male 55% were premature infants 70 of the babies in the awake regional group converted to general anesthetic

30 Discussion Single relatively short exposure Less than 90 minutes in 61% of exposed patients Less than 2 hours in 85% of exposed patients Vast majority of anesthetics in young children are fairly brief duration Results likely pertinent to large portion of exposed infants

31 Conclusion Exposure to just under an hour of sevoflurane general anesthesia does not increase the risk of adverse neurodevelopmental outcome at 2 years of age

32 The Pediatric Anesthesia Neurodevelopmental Assessment Study (PANDA) Study Sibling matched cohort study Primary outcome: global cognitive function: IQ Secondary outcome: behavior and abnormal domain-specific neurocognitive functions

33 Methods Sibling matched cohort design Inclusion criteria: Children who had a single general anesthetic before 36 months for elective inguinal hernia surgery American Society of Anesthesiologists Physical Status 1 as health or limited systemic disease >36 weeks gestation at birth Unexposed biologically related siblings Assessment of IQ and behavior at 8-15 years Allowing time for any neurocognitive impairment to become evident Comprehensive assessment

34 Results 105 sibling pairs with complete data included in primary analysis Mean age was 10.6 years for exposed and 10.9 years for unexposed Exposed siblings were 90% male and 56% of unexposed siblings were male All exposed children received inhaled anesthetic agents. Mean duration of anesthesia was 84 minutes

35 Results No Difference in IQ amongst those exposed or unexposed No difference in secondary outcomes Mean scores of memory, attention, visuospatial function, executive Function, language, motor and processing speed, or behavior

36 Results Socioeconomic status was significantly associated with IQ in the combined exposed and unexposed cohort Further validating the use of a sibling matched cohort design No evidence that duration of anesthesia exposure of 120 minutes or longer was associated with larger differences in IQ between siblings

37 Limitations No data on repeated exposures, prolonged exposures, or vulnerable subgroups Sex imbalance Recruitment bias- higher mean IQ than population

38 Long-term differences in language and cognitive function after childhood exposure to anesthesia Examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills and behavior at age 10

39 Methods Analysis of Western Australian Pregnancy Cohort Study (Raine) Enrolled 2900 pregnant women at weeks gestation Collected detailed demographics and medical data prenatally and at birth from medical records and self reporting After birth, all children were assessed at 1, 2, 3, 5, 8, 10, 13, 16 years of age 10 year follow up- language, cognitive function, motor skills, and behavior were all tested

40 Results 2868 children born from children had no follow up and considered missing 321 exposed to anesthesia before age were unexposed 40 were exposed to multiple anesthetics, 141 exposed to a single anesthetic

41 Results Unexposed (n=2287) Exposed (n=321) P Value Boys 1126 (49.2%) 209 (65.1%) <0.001 Caucasian 1981 (86.6%) 296 (92.2%) <0.001 Household Income <7000$ 164 (7.2%) 23 (7.2%) $ 709 (31%) 111 (34.6%) $ 551 (24.1%) 59 (18.4%) >36000$ 687 (30.0%) 113 (35.2%)

42 Results Neuropsych Domain Neuropschy Test Score Unexposed Test Scores Mean Exposed Test Scores Mean Score Difference P value Language CELF Total CELF Receptive CELF Expressive Cognition CPM Total Written Oral

43 Results Neuropsych Domain Neuropsych Test Score Unexposed Test Scores Mean Exposed Test Scores Mean Score Difference Behavior CBCL Total CBCL Internalizing P value Motor Function CBCL Externalizing MAND NDI Score

44 Discussion Exposed children had an increased risk for long-term deficits in language and abstract reasoning at age 10 Increased risk even in children with a single exposure to anesthesia Not all cognitive domains are uniformly affected No differences in visual tracking and attention, fine or gross motor, or behavior

45 Discussion Strengths: Availability of battery of directly administered neuropsychological assessments Defined cohort

46 Limitations Retrospective analysis Lack of detailed anesthetic information- unable to review medical records Difference in demographics between exposed and unexposed group More exposed children were Caucasian and living in higher income households Higher proportion of boys in exposed group No access to medical records- unable to adjust for comorbid disease in either group Unable to assess anesthetic drug exposure and length

47 Conclusion In this cohort- children exposed to anesthesia before age 3 had an increased long term risk of clinical deficit in receptive and expressive language as well as abstract reasoning Developmental outcome affected by anesthesia may be confined to specific domains

48 Change in practice? Avoid non-essential surgery in infants Already being done?? Withholding anesthesia- in neonatal animals has shown deleterious effects of painful stimuli or stress Increasing stress hormones and increasing neuronal cell death Include risk of anesthesia in informed consent? Texas Children s Hospital cases per year <3 years of age The FDA warning will now be discussed before surgery with parents of all children <3 years of age who will be receiving an anesthetic Legal obligations to inform is unclear

49 Change in Practice? FDA warning will potentially delay necessary surgical and diagnostic procedures that require anesthesia, resulting in adverse outcomes for patients Proceed with caution: delay unnecessary operations until the infants are older if possible

50 Discussion

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