Muscle Biopsies and Anaesthesia

BCH Data2005-2008

So what is the problem? Links between muscular disorders and

anaesthetics MH risk and volatiles

25% linkage to CCD Weak linkage to minicore disease

Propofol and mitochondria? How can we decide what anaesthetic to

give in the absence of a confirmed diagnosis?

Anaesthetic Database and ICE lab results

Anaesthetic given and histological diagnosis

Searched anaesthetic database for all procedures including muscle biopsy where full data is available (2005 >) Pre op conditions Anaesthetic details

Searched ICE for muscle biopsy histology

Results 1 35 cases identified Histology available in 32 Median age 2 (IQR 0.5-8) 33 anaesthetised by Consultant 2 anaesthetised by SpR

Results 2: Anaesthetist’s reported diagnosis

DIAGNOSIS NUMBER

Myopathy 14 (of which 1 stated minicore)

Mitochondrial disorder 3

Other muscle problem 1

Neurological problem 2

Other problem 4

No factor recorded 11

Results 3: Anaesthetics Induction

Sevoflurane 17 Propofol 16 Ketamine 1 Spinal 1

Maintenance Volatile 30

Isoflurane 18 Sevoflurane 12

Propofol 2 Propofol / ketamine 1 Ketamine 1 Spinal 1

Results 4: local blocks Infiltration 25 Regional 6

Caudal 4 Epidural 1 (other surgery also)

Spinal 1

None stated 2

Results 5: Histology (32/35)

DIAGNOSIS NUMBERNon specific changes etc 11

Neurological problem 7 (2 may be mitochondrial cytopathy also)

Mitochondrial myopathy 4 (including 2 above)

Minicore disease 3

Muscular dystrophy 3

Central core disease 2

Other congenital myopathy 2

Other metabolic problem 2

Did the Pre-op diagnosis match the histology? Yes 10 No 12 Unstated 11 No report 3

For 2 CCD: no diagnosis recorded

For 3 MCD: 1 minicore, 1 cong. myopathy, 1 none recorded

Search of all cases on database where there is risk of MH

Central core disease 6 25% linkage

Induction: 2 propofol 4 sevo Maintenance: 1 propofol 5 volatile

Minicore disease 8 Weak linkage

Induction: 7 propofol 1 sevo Maintenance: 4 propofol 4 volatile

Duchenne Muscular Dystrophy Risk of rhabdomyolysis with volatiles? 17 cases recorded (9 spine surgery)

Induction: 14 propofol 3 sevo Maintenance: 8 propofol 9 volatile (2 both)

Conclusions and Questions ? Recording of pre existing conditions Pre op diagnosis wrong >50% of time CCD or MCD and potential MH

5/35 of muscle biopsies had this diagnosis 9/14 CCD or MCD patients received volatiles

9/17 DMD patients received volatiles What should we do for muscle biopsies where

diagnosis is unknown? What should we do for CCD, MCD and DMD

where diagnosis is known?

Anaesthesia for Muscle Biopsies

Rob AlcockRJAH Orthopaedic and General Hospital NHS Trust

What Should We Do for Muscle Biopsies Where Diagnosis is Unknown?

What Should We Do for CCD, MCD and DMD Where Diagnosis is Known?

What Neuromuscular Diseases are Out There? What are their Frequencies?

What Problems Might We Encounter? What are the Risks?

Anaesthesia for Muscle Biopsies

What conditions are biopsied? Muscular Dystrophies Congenital Myopathies Mitochondrial Myopathies Metabolic muscle disease Myositis and Dermatomyositis Periodic Paralysis Myotonias and Myotonic Dystrophy

Muscular Dystrophies Duchenne Muscular Dystophy (DMD)

1:5,000 Becker Muscular Dystrophy 1:18,000 Emery Dreyfuss Dystrophy 1: 100,000 Fascioscapulohumeral Dystrophy 1:20,000

Congenital Myopathies Incidence 1:1000 6000 in the W Midlands Main Symptom is Hypotonia Only 14% of Hypotonic infants

Congenital Myopathies Nemaline Rod Myopathy 20% Central Core Myopathy 16% Centronuclear Myopathy 14% Minimulticore Myopathy 10% Disproportionate Fibre Type Myopathy 21% Rare Forms 19%

What Are We Worrying About? Malignant Hyperpyrexia Conditions Associated with Malignant

Hyperpyrexia Muscular Dystrophy General Considerations

Malignant Hyperpyrexia (MH) Spectrum of Pharmacogenetic Disorders Disorder of Calcium Homeostasis Triggered by Suxamethonium and Volatile

Anaesthetics Frequently associated with Ryanodine Ca Efflux

Channel on the Sarcoplasmic Reticulum Previous Uneventful Exposure to Triggers does

not rule out MH Diagnosed by In vitro Contracture Test

Masseter Spasm Defined as lasting > 2 mins after

Administration of Suxamethonium 30% may prove to have MH Wait Resort to Trigger Free Anaesthesia

Genetics of MH 19q11.2-13.2 Ryanodine (RyR1):- Release of

Ca2+ stores from sarcoplasmic reticulum

17q11.2-q24:- Altered sodium channel functioning 7q21.1 Dihydropyridine (DHP):- voltage sensor for

RyR1 1q32 CACNL1A3 gene encoding the alpha 1-

subunit of the voltage-gated DHP receptor that interacts with RyR1

Conditions Associated with MH Central Core Myopathy Minicore or Multiminicore Myopathy King Denborough syndrome

Central Core Myopathy The most common presentation is at birth or in

early childhood with weakness and hypotonia, slowly progressive.

Also present in adolescence as slowly progressive limb-girdle syndrome

Skeletal Abnormalities are Common Asymptomatic individuals may present with CK or

MH 25% of patients are susceptible to MH

Muscular Dystrophy Malignant Hyperthermia Association of the

United States (MHAUS) 3 Cases Life Threatening Hyperkaemia Duchenne & Becker Following Use of Volatile Agents

General Considerations Avoid Suxamethonium in Children with

Neuromuscular Disease Avoid Hypothermia Cardiac Problems associated with

Dystrophies? Respiratory muscle weakness

What are the Risks?

Incidence of Different Forms of MH in Relation to Type of Anesthesia

- Total Number of Anesthetics 1:251,063 1:17,435 1:16,303

- General Anesthesia 1:221,811 1:15,404 1:14,403

- Anesthesia with Inhalation Agent 1:84,488 1:6,653 1:6,167

- With Sux 1:61,961 1:4,506 1:4,201

-Without Sux 1:174,597 1:20,541 1:18,379

-Anesthesia with Sux 1:140,006 1:8,819 1:8,297

Fulminant MH Abortive MH Overall Incidence

Anaesthesia for Biopsy? Randall et al Paediatric Anaesthesia

2007;17:22-27 351 Patients with a Variety of NM Disorders 274 Received Volatile Agents 3 Received Sux! No Cases of MH or Rhabdomyolysis Conclusion: Risk of MH < 1%

Anaesthesia for Biopsy? Carr et al Can. J Anaes. 1995;42: 281-286 2,214 Pts with suspected MH Sensitivity

Undergoing Muscle Biopsy Trigger Free Anaesthesia 97% GA 1082 were positive 5 Patients had MH reactions

Mitocondrial Myopathies Case Reports of Resp and CV Depression,

Lactic Acidosis and Rhabdomyolysis after Prolonged Propofol Anaesthesia

Propofol is Highly Metabolised Volatiles are Minimally Metabolised Should Propofol be Avoided?

Conclusion Patients for Bx Should Ideally be

Anaesthetisd in the Absence of Volatiles. Patients with Known CCD, MCD and DMD

Should be Anaesthetised without Volatiles. Patients with Known Mitochondrial Disease

Should be Anaesthetised with Volatiles. No-one with NMD Should be given Sux!