Rare diseases in everyday practice « Google anaesthesia » ? F Veyckemans Clin univ. St Luc Brussels, Belgium

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

Conflict of interest Responsible for the website tyniurl.com/m-rares Syndromes & Maladies rares en pédiatrie: anesthésie with Prof J-L Scholtes (Brussels)

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

What is a rare disease? < 1/2000 in the general population but depends on country population clustering clinical recruitment e.g., Duchenne microdeletion ch 22

The anaesthesiologist’s perspective 1)care for a « rare disease » patient during a brief but often critical period of time 2) consider a disease is rare at the first time we meet it !

The anaesthetist’s queries 1) what is it ? malformative syndrome metabolic disease muscle disease 2) any increased anaesthetic risk ? 3) any special issue(s) regarding perianaesthetic care ?

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

Sources of information (1) On the disease : Books -Inborn metabolic diseases, 5 th ed, Saudubray & coll (Springer, 2012). -Smith’s recognizable patterns of human malformations 6 th ed, KL Jones (Elsevier Saunders, 2006) -Atlas of Metabolic Diseases 2 nd ed WL Nyhan & coll (Hodder Arnold, 2005)

Sources of information (1) On the disease : Internet * Google * Orphanet  name : expert summary + peer reviewed * OMIM : omim.org online Mendelian inheritance * GARD: Genetic & Rare Diseases information center * NORD * pubmed * disease-related website: parents’ groups

Sources of information (2) Anaesthetic management of the disease Books -Anesthesia for genetic, metabolic & dysmorphic syndromes of childhood Baum & O’Flaherty (Lippincott, Williams & Wilkins, 2007) -Genetic syndromes : recognition and perioperative aspects. B Bissonnette, B Dalens.. (McGraw-Hill, 2006) -most Textbooks on Paediatric Anaesthesia contain a chapter on the most common rare diseases or syndromes

Sources of information (2) Anaesthetic management of the disease Internet: « disease and anaesthesia » * Pubmed * Google * Orphanet  name  emergency care * VIRTANES  maladies rares de l’enfant Or discussion lists : PAC

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

Different names for the same disease Treacher-Collins = Franceschetti-Klein = mandibulofacial dysostosis

Different diseases with similar name e.g., Hecht-Beals syndrome = congenital arachnodactyly with contractures CCA syndrome  marfanoid syndrome Hecht syndrome = Dutch-Kentucky syndrome = trimus pseudocamptodactyly syndrome = distal arthrogryposis type 7  difficult airway

Genetics are complex

one gene  one protein  one function  one phenotype

Genetics are complex one gene other controller/inhibitor genes  inactivation of chromosome one protein RNAm  one function  environmental factors one phenotype

Genetics are complex  one phenotype can result from different mutations/genes  mutation(s) of one gene  different phenotypes  variable penetrance of some mutations  many mutations are sporadic  no familial history  results often not available in time

Validity of the information ? * Google -ranking of links according to a complex algoritm not to quality of data -check : source of data ? Wikipedia date of last update

Validity of the information? Case reports - often isolated cases - relative scientific value  no problem : luck ?  complication : cause-effect vs association ? poor management ? -date : old drugs ? + description of the disease from the anaesthetist’s point of view (date ?)

Validity of the information ? Ideal: case series « data from case series for a rare condition may be the best evidence a clinician can rely on » The Oxford Levels of Evidence 2, 2013 Oxford Centre for Evidence-Based Medicine

Validity of the information ? Medical progress often results in -prolonged survival -modification of evolution (gene therapy, transplantation)

Validity of the information ! -child’s parents -child’s paediatrician: personal contact !  specific information on this child

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

My way To summarize informations evaluate anaesthetic risk plan anaesthesia

NARCO acronym Neuromuscular Airway Respiratory Cardiovascular Others Malviya S, Voepel-Lewis T, Chiravuri SD et al. Does an objective system- based approach improve assessment of perioperative risk in children? A preliminary evaluation of the NARCO. Br J Anaesth 2011; 106: 352-6

Basic questions Neuromuscular: developmental delay ? seizures : controlled or not ? spasticity, contractures, hypotonia ? medical treatment ? Airway : difficult intubation/ventilation ? risk for regurgitation/inhalation ? obstructive sleep apnoea ? Respiratory : reactive airway ? restrictive or obstructive syndrome ? chronic lung infection ?

Basic questions Cardiovascular : congenital heart disease ? dysrythmias ? cardiomyopathy ? Others : special diet ? tolerates fasting ? previous anaesthesia ? psychological issues ?

Example : Willi-Prader syndrome - 1/10,000 - deletion of 15 q11-q13 of paternal origin - mental retardation - morbid obesity - behaviour problems - hypogenitalism - epilepsy - rumination, mericism

Example : Willi-Prader syndrome N mental retardation, epilepsy, behavioural problems hyperphagia A small mouth, micrognathia R central & obstructive sleep apnoea, gastrooesophageal reflux, scoliosis decreased response to hypoxaemia/hypercarbia C systemic hypertension, cor pulmonale O obese, short stature  pain threshold central adrenal insufficiency during stress (60 %) spontaneous annual death rate: 3%

Example : Willi-Prader syndrome N mental retardation, epilepsy, behavioural problems hyperphagia A small mouth, micrognathia R central & obstructive sleep apnoea, gastrooesophageal reflux, scoliosis decreased response to hypoxaemia/hypercarbia C systemic hypertension, cor pulmonale O obese, short stature  pain threshold central adrenal insufficiency during stress (60 %) annual death rate: 3% Difficult veins Cardiac echo Short fasting Night oximetry IV hydrocortisone recovery Postop monitoring Mask fit, intubation treatment

This patient is also a child ! Do not overlook the basics : -personal history -allergies ? -haemostasis ? -upper airway: infection ? difficult airway? -passive smoking ? -easy veins ? -BP, auscultation

Outline definition & queries sources of information pitfalls to prepare anaesthesia conclusion

Conclusion (1) check the name seek information : disease / anaesthesia - textbooks - internet : time of update ? Orphanet  Orphanaesthesia ? standard but focused preop examination summarize with NARCO

Conclusion (2) -a few keys to help manage a child with a rare disease -increase interest in rare diseases -suggestion : creation of a national/APA registry of anaesthetics for patients with a rare disease  source of information

APRICOT Anaesthesia Practice In Children Observational Trial European prospective multicenter observational study: Epidemiology of severe critical events JOIN THE NETWORK