Muscle Biopsies and Anaesthesia

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Muscle Biopsies and Anaesthesia

• BCH Data
• 2005-2008

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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?

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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 gt)
• Pre op conditions
• Anaesthetic details
• Searched ICE for muscle biopsy histology

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Results 1

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

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Results 2 Anaesthetists 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
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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

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Results 4 local blocks

• Infiltration 25
• Regional 6
• Caudal 4
• Epidural 1 (other surgery also)
• Spinal 1
• None stated 2

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Results 5 Histology (32/35)
DIAGNOSIS NUMBER
Non 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
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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

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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

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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)

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Conclusions and Questions

• ? Recording of pre existing conditions
• Pre op diagnosis wrong gt50 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?

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Anaesthesia for Muscle Biopsies

• Rob Alcock
• RJAH Orthopaedic and General Hospital NHS Trust

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Anaesthesia for Muscle Biopsies

• 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?

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What conditions are biopsied?

• Muscular Dystrophies
• Congenital Myopathies
• Mitochondrial Myopathies
• Metabolic muscle disease
• Myositis and Dermatomyositis
• Periodic Paralysis
• Myotonias and Myotonic Dystrophy

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Muscular Dystrophies

• Duchenne Muscular Dystophy (DMD) 15,000
• Becker Muscular Dystrophy 118,000
• Emery Dreyfuss Dystrophy 1 100,000
• Fascioscapulohumeral Dystrophy 120,000

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Congenital Myopathies

• Incidence 11000
• 6000 in the W Midlands
• Main Symptom is Hypotonia
• Only 14 of Hypotonic infants

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Congenital Myopathies

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

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What Are We Worrying About?

• Malignant Hyperpyrexia
• Conditions Associated with Malignant Hyperpyrexia
• Muscular Dystrophy
• General Considerations

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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

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Masseter Spasm

• Defined as lasting gt 2 mins after Administration
  of Suxamethonium
• 30 may prove to have MH
• Wait
• Resort to Trigger Free Anaesthesia

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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

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Conditions Associated with MH

• Central Core Myopathy
• Minicore or Multiminicore Myopathy
• King Denborough syndrome

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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

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Muscular Dystrophy

• Malignant Hyperthermia Association of the United
  States (MHAUS)
• 3 Cases Life Threatening Hyperkaemia
• Duchenne Becker
• Following Use of Volatile Agents

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General Considerations

• Avoid Suxamethonium in Children with
  Neuromuscular Disease
• Avoid Hypothermia
• Cardiac Problems associated with Dystrophies?
• Respiratory muscle weakness

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What are the Risks?
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Fulminant MH Abortive MH
Overall Incidence
Incidence of Different Forms of MH in
Relation to Type of Anesthesia

• - Total Number of Anesthetics
  1251,063 117,435 116,303
• - General Anesthesia 1221,811 115,404
  114,403
• - Anesthesia with Inhalation Agent 184,488 16
  ,653 16,167
• - With Sux 161,961 14,506
  14,201
• Without Sux 1174,597 120,541
  118,379
• Anesthesia with Sux 1140,006 18,819
  18,297

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Anaesthesia for Biopsy?

• Randall et al Paediatric Anaesthesia
  20071722-27
• 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 lt 1

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Anaesthesia for Biopsy?

• Carr et al Can. J Anaes. 199542 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

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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?

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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!