presentation on various neurological and neuromuscular disease and anesthetic consideration.

1. ANAESTHESIA FOR NEUROLOGICAL
AND NEUROMUSCULAR DISEASE
DR SHWETA
DR KANIKA
DEPT. OF ANAESTHESIOLOGY
KING GEORGE MEDICAL COLLEGE ,LUCKNOW

2. • EPILEPSY
• CEREBROVASCULAR DISEASE/ STROKE
• MULTIPLE SCLEROSIS
• PARKINSON’S DISEASE
• ALZHEIMERS DISEASE
• MOTOR NEURON DISEASE
• POLIOMYELITIS
• GULLAINE BARRE SYNDROME
• CEREBRAL PALSY
NEUROLOGICAL
DISEASE
• MYASTHENIA GRAVIS
• MUSCULAR DYSTROPHIES
• CHANNELOPATHIES
• MALIGNANT HYPERTHERMIA
NEUROMUSCULAR
DISEASE

3. SEIZURE DISORDER
• Seizure is caused by
transient , paroxysmal,
and synchronised
discharge of group of
neurons in brain.
• Epilepsy is defined as
recurrent unprovoked
seizures.
Partial
• simple
• complex
Generalised
• Tonic
• Clonic
• GTCS
• myoclonic
• Abscence

4. MECHANISM OF ACTION OF AEDs
• Increase GABA activity
Increased frequency of Cl channel opening :
– Benzodiazepines (binds to BZ2 receptors);
– Tiagabine (prevents reuptake);
– Gabapentin (prevents reuptake).
Increased mean Cl channel opening duration : Barbiturates.
• Blocks GABA transaminase (blocking GABA catabolism within the
neuron) : Vigabatrin.
• Glutamate antagonist : Topiramate (at AMPA receptor).
• Reduction of inward voltage-gated positive currents
– Phenytoin (Na+ channel);
– Carbamazepine (Na+ channel);
– Ethosuximide (Ca2+ channel).
• Increased outward voltage-gated positive currents
– Sodium valproate (K+ channel);
– Pleotropic sites of action: Sodium valproate (1, 2, 3 and 4)*;
lamotrigine (2 and 3)*; topiramate (1, 2, and 3)

5. EFFECTS OF ANTIEPILEPTICS ON
ANAESTHETIC DRUGS
DRUG INTERACTION DUE TO ALTERED METABOLISM
ENZYME INDUCERS
• PHENYTOIN VALPROATE
• CARBAMAZEPINE>> OXCARBAZEPINE
• PHENOBARBITONE
• PRIMIDONE
• TOPIRAMATE
ENZYME INHIBITORS
DRUG INTERCTIONS RELATED TO PROTEIN BINDING
PHENYTOIN VALPROATE CARBAMAZEPINE

6. EFFECT OF ANAESTHETIC AGENTS ON
EPILEPSY
ANAESTHETIC AGENTS PROCONVULSANT ANTICONVULSANT
INHALATIONAL AGENTS
NITROUS OXIDE
HALOTHANE
ISOFLURANE
SEVOFLURANE
DESFLURANE
ENFLURANE
+
+
++
++
-
++
-
++
+++
-
-
+
INDUCING AGENTS
THIOPENTONE
METHOHEXITAL
ETOMIDATE
BENZODIAZEPINES
KETAMINE
PROPOFOL
OPIOIDS
++
+++
+++
-
++
++
+++
+++
+++
+++
+++
+
++
-

7. • NEUROMUSCULAR :
– None of the neuromuscular blocking agents appear to
have any pro-convulsant or anticonvulsant effects
– LAUDANOSINE: metabolite of atracurium, induce seizure
activity esp in hepatic failure
• LOCAL ANAESTHETIC: generalized convulsions at higher
doses, resulting from an accidental i.v. administration or rapid
systemic absorption from a highly vascular area.
• ANTIEMETICS: avoid dopamine antagonist like
metaclopramide

8. • Preoperative assessement:
– History ( manifestation , severity and control of disease)
– Medications( drugs and dosage)
– Investigations ( hemogram, LFT, KFT, serum electrolyte)
• Avoid prolonged disruption of AEDs
• Avail intravenous forms of AEDs in OT.
• Avoid prolonged fasting.
• Careful selection of anaesthetic drugs.
• Avoid hyperventilation.

10. MULTIPLE SCLEROSIS
• Autoimmune destruction of myelin
sheath within CNS nerve
conduction failure
• Females, 20-40 years & >60 years.
• Etiology : unknown
• Diagnosis based on combination of
clinical and laboratory tests
• Treatement :
– combinations of
immunosuppression modalities.
IFN, Glatiramer, Mitoxantrone,
Natalizumab, Cladribine,
Fingolimod
– Corticosteroids for acute phase
– Dantrolene, Diazepam, Baclofen,
Carbamazepine for muscle spasm,
chronic pain, seizures & dysthesia

11. MS: ANAESTHETIC CONCERNS
• Preoperative assessement includes details of symptoms and
neurological examination.
• Surgery and anaesthesia may aggravate MS.
• Continue immunosuppressive medications in perioperative
period.
• Minimize changes in homeostasis( fluid / temperature).
• Intravenous induction and inhaled anaesthetic safe.
• Careful cardiovascular monitoring .
• Avoid Sch. Nondepolarising NM blockers safe.
• REGIONAL anaesthesia: EPIDURALS in low dose safe but
SPINAL anaesthesia aggravate symptoms.
• Need of Post operative ventilation???

12. • DRUG INTERACTIONS:
– Cardiotoxicity from immunosupressants
– Altered response to ms relaxants.
– Baclofen increases sensitivity to nondepolarising MR.
– Anticonvulsants produce resistance to nondepolarising
MR.

13. GULLAINE BARRE SYNDROME
• GBS is an acute frequently severe and fulminant radiculopathy
• With the marked decline in the incidence of polio, Guillain-Barré
syndrome is now the most common cause of acute flaccid paralysis
in healthy people
• Autoimmune in nature
• Incidence : one case per million per month.
• Males are at higher risk( 1.5 times)
• Adults more frequently affected than children
• The main modalities of therapy for Guillain-Barré syndrome include
– Plasmapheresis
– Administration of intravenous immune globulin

14. SUBTYPES OF GBS
SUBTYPE FEATURES ELECTRODIAGNOSIS PATHOLOGY
Acute inflammatory
Demyelinatimg
polyneuropathy
(AIDP)
ADULTS> CHILDREN
RAPID RECOVERY
ANTI GM1
ANTIBODIES
DEMYELINATING First attack on
schwann cell
surface( myelin
damage) secondary
axonal damage
Acute motor axonal
neuropathy(AMAN)
Children and young
adults, may be
seasonal, rapid
recovery anti-GD1a
antibodies
AXONAL 1st attack at motor
nodes of ranvier.
Extent of damage
highly variable
Acute motor
sensory axonal
neuropthy(AMSAN)
Adults, uncommon,
slow recovery
AXONAL Same as AMAN but
sensory fibres also
affected
Miller fisher
syndrome
Adults and children,
uncommon, triad of
areflexia , ataxia
and
ophthalmoplegiaG
Q-1b antibodies
DEMYELINATING Resembles AIDP

15. DIAGNOSTIC CRITERIA
• PROGRESSIVE WEAKNESS OF 2 OR MORE LIMBS
DUE TO NEUROPATHY
• AREFLEXIA
• DISEASE COURSE <4 WEEKS
• EXCLUSION OF OYHER CAUSES ( VASCULITIS,
TOXINS, BOTULISM, DIPTHERIA PORPHYRIA etc.
REQUIRED
CRITERIA
• Symmetric weakness
• Mild sensory involvement
• Cranial nerve involvement
• Abscence of fever
• Typical csf profile
• Electrophysiological evidence of
demyelination.
SUPPORTIVE
CRITERIA

16. GULLAINE BARRE SYNDROME
• There is risk for autonomic dysfunction, respiratory failure,
and aspiration.
• Great care should be taken to maintain circulatory stability,
including adequate cardiac preload and afterload.
• Exaggerated responses to indirect-acting vasopressors.
• Careful hemodynamic monitoring.
• Regional anaesthesia is not contraindicated.
• Succinylcholine should not be used (risk of hyperkalemia).
• A non-depolarizing muscle relaxant with minimal circulatory
effects, such as cisatracurium or vecuronium, may be used if
needed.
• Noxious stimulation, such as direct laryngoscopy, can cause
exaggerated increases in blood pressure.
• Compensatory cardiovascular responses may be absent to
changes in posture, blood loss, or positive airway pressure
may be absent.

17. POLIOMYELITIS
• Poliomyelitis is caused by an enterovirus that initially infect
the reticuloendothelial system.
• After being eliminated from our country, clinician will see
patients with postpolio sequelae much more commonly than
those with acute polio.
• Postpolio sequelae manifest as fatigue, skeletal muscle
weakness, joint pain, cold intolerance, dysphagia, and sleep
and breathing problems.

18. PATHOPHYSIOLOGY

20. • DIAGNOSIS : Virus
recovery from throat
washing, stool culture,
blood culture, and CSF
culture. Viral studies in
stool specimens are
essential for the diagnosis
of poliomyelitis.
• CSF examinantion :
pleocytosis/ Raised csf
proteins
• TREATEMENT: supportive

21. ANAESTHETIC CONCERNS
• Sensitivity to the sedative effects of anesthetics.
• Delayed awakening from general anesthesia.
• Sensitivity to nondepolarizing muscle relaxants.
• Careful positioning.
• Postoperative shivering may be profound, since these
individuals are very sensitive to cold.
• Postoperative pain perception may be abnormal.
• Outpatient surgery may not be appropriate for many
postpolio patients since they are at increased risk of
complications.

22. CEREBRAL PALSY
• Originates from a non-progressive neurological insult sustained
perinatally or before 2 yrs of age.
• Predominantly affects the motor system, and the resultant spasticity
and hypertonicity are progressive.
• Infants generally have very low birth weight.
• Spastic: Lesion in cerebrum. Includes quadriplegia, diplegia,
hemiplegia.
• Dyskinetic: Lesion in basal ganglia.
• Ataxic: Lesion in cerebellum includes tremor, loss of balance, and
speech.
• Mixed: Includes spasticity and athetoid movements.

25. Cerebral palsy – preoperative
• Gastroesophageal Reflux: Impaired ability to handle
pharyngeal secretions, Increased salivation: Recurrent
pneumonia (chronic aspiration and inability to cough).
• Reactive airway disease is common.
• Neurological:Seizures are present in roughly 30% -
anticonvulsants.
• Musculo-skeletal:Poor nutrition, contractures, fragile bones
etc.

26. Peri-operative management
• Premedication includes sedatives, antiacids , anticonvulsants,
anticholinergics and anti emetics.
• Vascular access may be difficult.
• Careful positioning.
• Latex allergy has been reported.
• Lower M.A.C., sensitivity to inhalational agents.
• Temperature: risk of Hypothermia (↓ body fat, ↓ temp
regulation.
• Excessive secretions and or a history of gastro-oesophageal reflux
is a concern.
• ET size selection should be based on their age as this usually
provides the most appropriate fit.

27. • Resistance to non-depolarising muscle relaxants
• Elevated pain threshold, decreased central pain perception
• Emergence from anaesthesia may be delayed :
Hypothermia, Residual volatile anaesthetic agents
• Irritability on emergence from anaesthesia is common : Pain,
Urinary retention, Unfamiliar environment etc.

28. CEREBROVASCULAR DISEASE

29. CEREBROVASCULAR DISEASE

30. Occluded artery Clinical features
Anterior cerebral artery Contralateral leg weakness
Middle cerebral artery Contralateral hemiparesis and
hemisensory deficit (face and arm
more than leg)
Aphasia (dominant hemisphere)
Contralateral visual field defect
Posterior cerebral
artery
Contralateral visual field defect
Contralateral hemiparesis
Penetrating arteries Contralateral hemiparesis
Contralateral hemisensory deficits
Basilar artery Oculomotor deficits and/or ataxia
with crossed sensory and motor
deficits
Vertebral artery Lower cranial nerve deficits and/or
ataxia with crossed sensory deficits

32. ANAESTHETIC CONSIDERATION:
• Careful preoperative assessment, examination &
evaluation including drug history, precipitating events.
• Antihypertensive medication to be continued till the
time of operation.
• Thromboprophylaxis is advisable unless contraindicated.
• Pressor and depressor agents may be used to treat
unwanted changes in blood pressure during induction.
• Intravenous fluid replacement should be proactive rather
than reactive.
• Inducing agents with minimal hemodynamic effects ( esp
BP) prefered.
• Avoid hyperventilation.
• Examine the patient early in the postoperative period.

33. MOTOR NEURON DISEASE
• Degeneration of upper and/or
lower motor neurons i.e.
Amyotrophic Lateral Sclerosis
• Muscular weakness and
atrophy.
• Steady, asymmetric
progression.
• Sensory systems, voluntary eye
movements, and urinary
sphincters are spared.

34. AMYOTROPHIC LATERAL SCLEROSIS
ANAESTHETIC CONCERN
• Increased Sensitivity to NDMRs
– Reduction in choline acetyltransferase (involved in
synthesis of ACh) occurs secondary to degeneration of
anterior horn cells.
• Avoid Sux
– Hyperkalemic response in degenerating muscles.
• GA documented to cause ventilatory depression post-
operatively, even without use of muscle relaxants
– Respiratory complications are common and a major cause
for concern.
• Regional anaesthesia to be avoided in pts with motor
neuron disease, including ALS, for the fear of exacerbating the
disease

35. ALZHEIMER'S DISEASE
• Most common cause of Dementia in old age patients .
• Autosomal dominant mode.
• Diffuse amyloid rich senile plaques & neurofibrillary tangles-
hallmark findings.
• C/f: cognitive impairment such as dementia, apraxia, aphasia,
agnosia.
• Drug therapy includes Cholinesterase inhibitors- rivastigmine,
Donepezil, tacrine, Galantamine.

36. Anaesthetic consideration
• Monitored & Regional anaesthesia- challenging options.
• Shorter acting sedative-hypnotic drugs.
• Cautious use of anticholinergics- glycopyrrolate>> atropine.
• Cautious use of Muscle relaxants- prolonged action of Sch &
relative resistance to NDMR.

37. PARKINSON'S DISEASE
• Neurodegenerative disorder in the elderly patients causing
loss of Dopaminergic neurons in basal ganglia.
• Dopamine deficiency causes activaion of GABA neurons
resulting in cortical inhibition.
• C/f : tremors,abnormal gait & posture,dyskinesia.
• Increase in glutamate neurotransmission causes increased
cholinergic activity- sialorrhoea,seborrhoea,bladder
dysfunction,dysphagia.
• Lewy bodies-hallmark finding.

38. • T/t- Levodopa remains mainstay drug, combined with
carbidopa.
• Dopamine agonists- bromocriptine, pergolide, cabergoline,
ropinirole, pramepixole, Amantadine, apomorphine.
• Dopamine metabolism inhibitors-
– MAO-B inhibitor: selegelline.
– COMT inhibitor: entacapone, tolcapone.
• Centrally acting anticholinergics- Trihexphenidyl, Benztropine.

39. ANAESTHETIC CONCERNS
• Preop thorough assessment of neurological disabilities & medications.
• Continue antiparkinsonian medication till the day of surgery,
apomorphine- s/c or i/v intraoperatively.
• Premedication- prone for aspiration pnuemonitis.
– avoid metoclopramide, droperidol ,phenothiazines.
• Opioid- acute dystonias,chest wall rigidity.
• Ketamine-controversial??
• Autonomic dysfunction chr. by orthostatic hypotension.
• Cautious use of volatile anaesthetics.
• DRUG INTERCTIONS: reaction with meperidine in pt recieving
selegelline, risk of Neurolept malignant syndrome.
• Post op care: need for respiratory support ,hallucinations & mental
confusion.

41. DRUG COMMENT
INTRAVENOUS INDUCING AGENTS
PROPOFOL
THIOPENTONE
ETOMIDATE
AVOID FOR STEREOTACTIC PROCEDURES
SAFE
SAFE
VOLATILE ANAESTHETIC
HALOTHANE
ISOFLURANE
SEVOFLURANE
DESFLURANE
Possible arrhythmias
Probably safe
Probably safe
Probably safe
NEUROMUSCULAR BLOCKING AGENTS
DEPOLARISING
NONDEPOLARISING
Possible hyperkalemia
Probably safe
ANALGESICS
MORPHINE
PETHIDINE
FENTANYL
ALFENTANYL
Possible muscle rigidity
Avoid in patients on selegiline
Possible muscle rigidity
Possible dystonic reactions

42. NEUROLEPTIC MALIGNANT
SYNDROME
• Result from relative lack of dopamine:
– dopamine receptor blockade.
– inadequate dopamine production.
• Supporting evidence:
– Neuroleptic drugs block dopamine receptors.
– Occurs with other dopamine blocking drugs.
– Occurs on sudden withdrawal of antiparkinsonian therapy.
– Responds to dopamine agonists.
• Essential evidence:
– Recent or current therapy with dopamine blocking drug
• Neuroleptic (ANTIDOPAMINERGIC)
• other drug eg metoclopramide
– recently stopped a dopamine agonist eg L-dopa.

43. PATHOPHYSIOLOGY
BLOCKADE OF DOPAMINERGIC FIBRES IN CENTRAL NERVOUS SYSTEM
CORPUS STRIATUM
MUSCLE RIGIDITY AND CONTRACTION
THERMOREGULATORY CENTRES IN
PREOPTIC NUCLEI OF ANTERIOR
HYPOTHALAMUS
PYREXIA
NIGROSTRIATAL & MESOCORTICAL
SYSTEM
MENTAL STATUS CHANGES
SPINAL CORD
AUTONOMIC DISTURBANCES

44. HYPERTHERMIA
Oral temperature >
38°C (100.4°F) in the
absence of another
known cause
EXTRAPYRAMIDAL
EFFECTS(>2)
Choreiform movements
Cogwheel rigidity
Dyskinesia
Dysphagia
Festinating gait
Lead pipe muscle rigidity
Oculogyric crisis
Opisthotonous
Sialorrhoea
Trismus
AUTONOMIC
DYSFUNCTION(>2)
Hypertension (diastolic
blood pressure at least 20
mm Hg
above baseline)
Incontinence
Prominent diaphoresis
Tachycardia (heart rate at
least 30 bpm above
baseline)
Tachypnoea (respiration >
25 breaths/min)
DIAGNOSTIC CRITERIA

45. MANAGEMENT
• Discontinuation of the offending neuroleptic agent
• ABC, FLUID RESUSCUTATION
• Cooling measures
• Pharmacotherapy
Bromocriptine
1. 2.5 mg q8h up to 5 mg q4h
2. continue for 7–10 days after resolution then taper over 1–2 weeks (except depot
preparations)
Dantrolene
1. 2–3 mg/kg
2. extreme rigidity, very high fever (> 40oC), unable to tolerate oral treatment
Benzodiazepines
1. to control agitation/delirium
ECT
1. refractory to adequate trial of dopamine agonist/supportive care
2. after resolution of acute features
1. remain catatonic or
2. develop ECT-responsive psychotic features
3. suspected acute lethal catatonia

46. MYASTHENIA GRAVIS
• Myasthenia gravis is caused by autoimmune disruption of
postsynaptic acetylcholine receptors at the neuromuscular
junction.
• Hallmarks are weakness and rapid exhaustion of voluntary
skeletal muscles.
• Muscle strength characteristically improves with rest,
deteriorates rapidly with exertion.
• Laryngeal and pharyngeal muscle weakness may lead to
aspiration, problems clearing secretions, difficulty chewing.
• Disease course marked by exacerbations and remissions :
– Infection, stress, surgery, pregnancy have unpredictable
effects, but often cause exacerbations.
– Antibiotics can aggravate weakness.

47. • Diseases considered AI in origin often coexist
– Decreased thyroid function
– RA
– SLE
– Pernicious Anemia
• Clinical Classification OSSERMAN’S GRADING
– Class 1: ocular symptoms only
– Class 1A: ocular symptoms with EMG evidence of
peripheral muscle involvement
– Class 2A: mild generalized symptoms
– Class 2B: more severe and rapidly progressive symptoms
– Class 3: acute and severe bulbar symptoms
– Class 4: late in the course of disease with severe bulbar
symptoms and marked generalized weakness

49. PATHOPHYSIOLOGY

50. TYPE ETIOLOGY ONSET SEX COURSE THYMUS
NEONATAL Passage of ab
from myasthenic
mothers across
placenta
Neonatal Both Transient Normal
CONGENITAL Congenital end
plate pathology
Genetic
autosomal
recessive pattern
0-2 years M>F Nonfluctuating
compatible with
long survival
normal
JUVENILLE Autoimmune 2-20 years F > m Slowly progressive Hyperplasia
ADULT Autoimmune 20-40
years
F > m Maximum severity Hyperplasia
within 3-5
years
ELDERLY Autoimmune >40 years M > F Rapid progressive
High mortality
Thymoma

51. Therapy - Myasthenia Gravis
• Immunosuppressants: Steroids , Azathioprine,Cyclosporine
• Plasmapheresis, iv immunoglobulin
– Acute exacerbations, i.e. in immediate post-operative
period if anticholinesterases have been withheld and
symptoms are severe
– Plasmapheresis + IVIG for 5 days -> rapid improvement,
may last for weeks
• Thymectomy
• Anticholinesterase drugs
– Pyridostigmine, po duration of 2-4 hours
– Excessive administration -> Cholinergic Crisis
• SLUDGE: Salivation, lacrimation, urination, defecation, +
miosis + bradycardia + bronchospasm
• Profound weakness: due to excess Ach at NMJ ->
persistent depolarization

52. CHOLINERGIC CRISIS VS MUSCARINIC CRISIS
MUSCARINIC CRISIS CHOLINERGIC CRISIS
An exacerbation of the myasthenic
symptoms caused by
undermedication
with anticholinesterases
an acute exacerbation of muscleweakness
caused by
overmedication
with cholinergic anticholinesterase drugs
Generalised muscle weakness
Pupils - miosis
TENSILON TEST : improvement in
symptoms
Muscle weakness + parasympathomimetic
effects
Pupils – mydriasis
Further deterioration
Atropine + supportive Neostigmine + supportive

55. ANAESTHETIC CONCERNS
• Plasmapheresis depletes plasma
esterase levels, thus prolonging the
effect of drugs eliminated by these
enzyme systems (suxamethonium,
mivacurium, ester-linked local
anaesthetics).
• Sch may have an altered effect and
patients may be resistant to
depolarization due to reduced
receptor activity, requiring increased
dose. This, in conjunction with
treatment-induced plasma esterase
deficiency, leads to an increased risk of
non-depolarizing (Phase II) block.

56. PREOPERATIVE ASSESSEMENT:
• Assess the degree of weakness and the duration of
symptoms.
• Any degree of bulbar palsy is predictive of the need for both
intra- and postoperative airway protection.
• Perform lung function tests—FVC <50% predicted (or <2.9
litres) or those who have coexisting respiratory disease are
more likely to require postoperative ventilation.
• Take a full drug history and determine the effect of a missed
dose of anticholinesterase on the patient.
• Continue anticholinesterase therapy.
• Premedication should be minimal.
• Facilities for postoperative ventilation should be available.

57. PERIOPERATIVE CONSIDERATION:
• Sch may be used if indicated—doses of 1.5 mg/kg are usually
effective.
• If doubt exists as to the difficulty of intubation, awake
techniques may be useful.
• If sch is used, do not use any neuromuscular blockade drug
until muscle activity has returned and no fade is present.
• Non-depolarizing drugs should be used sparingly
• Use reduced doses of relaxant (10% normal) under nerve
stimulator control.
• Use of rocuronium & reversal with sugammadex is
alternative.
• Reversal of neuromuscular blocking drugs should be
achievable with standard doses of neostigmine.
• Careful Extubation.

58. DRUGS INTERACTIONS
NONDEPOLARIZING NM BLOCKERS INCREASED SENSTIVITY
SUCCINYLCHOLINE RESISTANCE TO BLOCKADE AND DELAYED
ONSET
INHALATIONAL AGENTS REDUCE NEUROMUSCULAR
TRANSMISSION
INTRAVEINOUS AGENTS NO EFFECT
LOCAL ANESTTHETICS PROLONGED ACTION AND INCREASED
TOXICITY OF ESTER LINKED AGENTS WITH
ANTICHOLINESTERASE THERAPY &
PLASMAPHERESIS
ANTIBIOTICS NEUROMUSCULAR BLOCKADE INCREASES
WITH AMINOGLYCOSIDES,
ERYTHROMYCIN etc.

59. MYASTHENIA SYNDROME
LAMBERT EATON MYASTHENIC
SYNDROME
• Proximal muscle weakness associated with cancer (most often
small cell carcinoma of the lung).
• Due to a reduction in the release of acetylcholine
(prejunctional failure).
• It is not reversed by anticholinesterase therapy and muscle
weakness is improved by exercise.
• Associated with dys-autonomia .
• Sensitive to both depolarizing and non-depolarizing
neuromuscular agents.

60. MYASTHENIC SYNDROME MYASTHENIA GRAVIS
Manifestations Proximal limb weakness
Strength improves with exercise
Muscle pain common
Reflexes -/ decreased
Extraocular, bulbar and facial
muscle weakness
Fatigue with exercise
Muscle pain uncommon
Reflexes normal
Gender Male>female female >male
Coexisting
pathology
Small cell carcinoma Thymoma
Response to
muscle
relaxant
Sensitive to scholine &
nondepolarising agents
Poor response to
anticholinesterase
Resistant to scholine
Sensitive to nondepolarising
agents
Good response to
anticholinesterase

61. DISORDERS OF MUSCLES
• Congenital Muscular
Dystrophies
– Myotonic
– Duchenne, Becker
• Acquired Myopathies
– Cushing’s Syndrome
– Dermatomyositis
– Polymyositis

62. MYOTONIC DYSTROPHY
• Most common muscle
dystrophy in ADULTS
• Characterized by persistent
contractures of skeletal
muscles after voluntary
contraction or following
electrical stimulation
• Abnormality in the
intracellular ATP system that
fails to return calcium to the
sarcoplasmic reticulum
• SWAN NECK / HATCHET
FACE

63. ASSSOCIATED ORGAN DYSFUNCTION
• Cardiac Involvement
– Mitral valve prolapse – 20% of individuals
– Deterioration of the His-Purkinje system lead to arrhythmias
• 1st degree AV block very common
• Pulmonary Pathology
– Restrictive lung disease
– Impaired responses to hypoxia and hypercarbia
• Cataracts( CHRISTMAS TREE ) very common
• GI abnormalities
– Gastric atony
– Intestinal hyper-motility
– Pharyngeal muscle weakness with impaired airway protection
– Cholelithiasis

64. ANAESTHETIC CONCERNS
• Eventually develop extremely compromised respiratory
function.
– Pulmonary Aspiration, Pneumonia
– Chronic Alveolar hypoventilation because of impaired
neuromuscular function -> chronic hypercapnoea.
– Decreased FRC, VC, MIP.
• Avoid premedication with sedatives – very sensitive to
respiratory depressant effects of narcotics and
benzodiazepines.
• Avoid Etomidate.
– May cause myoclonus and precipitate contractures.
• Avoid Sux.
– Produces an exaggerated contracture.
• Susceptible to MH.

65. • Avoid Anticholinesterases – may precipitate contracture by
increasing ACh available at NMJ.
• Keep room warm – shivering may lead to contractures.
• Exaggerated effects of myocardial depression from inhaled
agents- even Asymptomatic pts have some degree of
cardiomyopathy.
• Anesthesia and surgery could theoretically aggravate co-
existing cardiac conduction blockade by increasing vagal tone.
or causing transient hypoxia of the conduction system.
• Pregnancy:
– Exacerbation of symptoms is likely.
– Uterine atony and retained placental often complicate
vaginal delivery.

66. MUSCULAR DYSTROPHY
• X-linked:
– Duchenne's
– Becker's.
• Autosomal recessive:
– limb-girdle
– childhood
– congenital.
• Autosomal dominant:
– facioscapulohumeral
– oculopharyngeal.

67. DUCHENNE’S AND BECKERS
MUSCULAR DYSTROPHY
• X linked recessive disorder
• Most common muscle
dystrophy seen in
children(& most severe)
• Males> females,
• Affects Dystrophin gene
(present in skeletal , smooth
& cardiac muscle)
• DIAGNOSIS : CPK levels &
muscle biopsy &
electrodiagnostic testing

70. ASSOCIATED COMORBIDITIES
• MENTAL RETARDATION
• RESPIRATORY INSUFFICIENCY:
– Most common cause of death in DMD.
– Early involvement of expiratory muscles with sparing of
diaphragm.
– Scoliosis ( with every 10* of scoliosis FVC decreases by
4%).
– Ineffective cough retained secretions leading to
infection.
• CARDIAC INVOLVEMENT:
– DCM in early course.
– Systolic dysfunction in later phase of disease.
– MR due to papillary muscle dysfunction.

71. ANAESTHETIC CONSIDERATION
• Perioperative complications disproportionate to severity of
disease.
• Preoperative cardiology and pulmonary assessement.
• Increased risk of aspiration , premedication with prokinetics
and anti emetics.
• Premedication with antisialogogue.
• Careful intravenous induction of anaesthesia with balanced
opioid/ induction agent.
• Masseter spasm may be seen.

72. • Potent inhalational anaesthetics should be carefully used
due to risk of myocardial depression. Hence TIVA preferred.
• Sch should be avoided.
• Non-depolarizing neuromuscular blockers are safe. Nerve
stimulator monitoring should be used.
• Malignant hyperpyrexia has been associated with muscular
dystrophy.
• Respiratory depressant effects of all anaesthetic drugs are
enhanced and postoperative respiratory function should be
monitored carefully.
• Some may need prolonged ventilatory support.
• Regional analgesia is safer than GA.

73. CHANNELOPATHIES
Disturbance in the transfer of ions across the sarcolemma.
1) Familial periodic paralysis
– Hyperkalemic Periodic Paralysis.
– Hypokalemic Periodic Paralysis
2) Ligand Gated Calcium Channelopathy
Malignant Hyperthermia

74. MALIGNANT HYPERTHERMIA
• It is a pharmacogenetic clinical syndrome that in its classic
form occurs during anesthesia with a triggering agents with
rapidly increasing body temperature (by as much as 1°C/5
min) and extreme acidosis
• TRIGGERING AGENTS
– DEPOLARISING MUSCLE RELAXANTS, the only currently
used of which is succinylcholine.
– INHALATION AGENTS ether, halothane, enflurane,
isoflurane, desflurane, sevoflurane.

75. Two classic clinical manifestations of fulminant MH syndrome :
– Rigidity after induction with thiopental and succinylcholine
but successful intubation, followed rapidly by the
symptoms .
– Normal response to induction of anesthesia and
uneventful anesthetic course until onset of the following
symptoms:
• Unexplained sinus tachycardia or ventricular
arrhythmias, or both.
• Tachypnea if spontaneous ventilation is present.
• Unexplained decrease in O2 saturation (because of a
decrease in venous O2 saturation).
• Increased in end-tidal PCO2 with adequate ventilation
(and in most cases unchanged ventilation).
• Unexpected metabolic and respiratory acidosis.
• Central venous desaturation.
• Increase in body temperature above 38.8°C with no
obvious cause.

76. MALIGNANT HYPERTHERMIA
MORE SPECIFIC SIGNS
• Generalised muscle
rigidity
• Rapidly unexplained
increase in end tidal CO2
• Rapidly developing fever
• Increased serum creatine
phosphate
• Cola coloured urine
LESS SPECIFIC SIGNS
• Tachycardia
• Tachypnoea
• Arrhythmias
• Hypertension /
hypotension
• Metabolic acidosis
• Hyperkalemia
• Coagulopathy
• Cyanosis

77. Criteria Used in the Malignant
Hyperthermia Scale Clinical Grading
• Process I: Muscle rigidity
– Generalized rigidity
– Masseter rigidity
• Process II: Myonecrosis
– Elevated CK >20,000 (after
succinylcholine administration)
– Elevated CK >10,000 (without
exposure to succinylcholine)
– Cola-colored urine
– Myoglobin in urine >60 µg/L
– Blood/plasma/serum K+ >6
mEg/ml
15
15
15
15
10
5
3

78. • Process III: Respiratory acidosis
– PetCO2 >55 with controlled ventilation
– PaCO2 >60 with controlled ventilation
– PetCO2 >60 with spontaneous
ventilation
– Inappropriate hypercarbia
– Inappropriate tachypnoea
• Process IV: Temperature increase
– Rapid increase in temperature 15
– Inappropriate temperature >38.8°C in
perioperative period
• Process V: Cardiac involvement
– Inappropriate tachycardia
– Ventricular tachycardia or fibrillation
15
15
15
15
10
15
10
3
3

79. PATHOPHYSIOLOGY

81. TREATMENT
• Discontinue all anesthetic agents and hyperventilate with 100%
oxygen.
• Administer dantrolene (2.5 mg/kg intravenously) to a total dose of
10 mg/kg IV every 5 to 10 minutes until symptoms subside.
• Correct the metabolic acidosis with frequent monitoring of blood
gases and Ph.
• Control fever by administering iced fluids, cooling the body surface,
cooling body cavities with sterile iced fluids. Cooling should be
halted at 38°C to 39°C to prevent inadvertent hypothermia
• Monitor urinary output and establish diuresis to protect the kidney
from probable myoglobinuria.
• Further therapy is guided by blood gases, electrolytes,
temperature, arrhythmia, muscle tone, and urinary output.
• Treatment of hyperkalemia with glucose and insulin should be slow.
The most effective way to lower serum potassium is reversal of MH
by effective doses of dantrolene.
• Analyze coagulation studies (e.g., international normalized ratio,
platelet count, prothrombin time, fibrinogen, fibrin split or
degradation products).

82. PREVENTION IN SUSCEPTIBLE
PATIENTS
• Screening with CAFFEINE CONTRACTURE TEST on muscle
biopsy- gold standard test.
• Avoid use of triggering agents.
• Prefer anaethetic workstation without prior use of inhaled
agents.
• Or, anaesthetic machines may be purged wih activated
charcoal.(Drain, remove, or disable anaesthetic vaporizers,
and changing tubing and CO2 absorbent and flowing oxygen at
10 L/min for 10 minutes or longer. )
• Dantrolene need not be given preoperatively .

83. Familial periodic paralysis
HYPERKALEMIC :
• Early onset, sometimes in infancy (autosomal dominant).
• Periodic paralysis with brief episodes of flaccid
weakness that resolve spontaneously
• Respiratory and cranial muscles are typically spared
• Genetic mutation that affects sodium channels causes
sustained sodium currents which don’t allow the
formation of action potentials during these brief attacks.
• ECG signs of hyperkalemia, also ectopic beats or
paroxysmal.
• Preo-perative management consists of potassium-free
dextrose-containing solutions.
• Avoid cold, hyperkalaemia and carbohydrate depletion
• Succinylcholine is contra-indicated

84. HYPOKALEMIC
• Most common type, onset during adolescence.
• Results from a mutation in a calcium channel.
• Attacks can be severe, resulting in respiratory compromise and
cardiac disturbances.
• Triggers are strenuous exercise, high carbohydrate intake, lowserum
potassium, mental stress, cold, trauma and infection.
• Maintain normal serum potassium, glucose and acid bases Status
peri-operatively.
• Adequate premedication needed to avoid stress.
• Maintain normothermia.
• Avoid overeating the day before surgery.
• Avoid intravenous fluids with dextrose and sodium .

85. METABOLIC & MITOCHONDRIAL
MYOPATHIES
• Heterogeneous group of disorders is now the commonest cause of
muscle weakness in children with an incidence of 1 in 4000
• Electron transport chain (ETC) function results in decreased ATP
production,and an increased production of free radicals.The acidosis
and excess free radicals further damage the mitochondria
• Mitochondrial DNA mutations include:-
– MELAS: mitochondrial encephalopathy, lactate acidosis
– MERRF: myoclonic epilepsy with red fibres syndrome
• The severest forms can present in the neonatal period with profound
weakness, liver and renal failure, and substantial neurological
impairment

86. • In acid maltase deficiency-severe respiratory deficiency,recurrent
aspiration pneumonia and pulmonary arterial hyper-tension might
occur
• In lipid storage deficiencies, patients are susceptible to hypo-
glycaemia, acidosis, general muscle weakness, rhabdomyolysis, and
progressive cardiac insufficiency
• Patients have exaggerated metabolic responses to prolongedfasting,
fever and illness.
• The patient is typically a floppy infant, a poor feeder with small
stature, displays developmental delay, is hypotonic or
hypoglycaemic, with or without positive family history.ECG and Echo
might reveal cardiomyopathy or conduction deficits, and ventricular
dilatation can compress the airway.

87. Anesthetic Considerations
• Evaluate pre-operative cardiac and respiratory status. Total AV
block requires pacing
• Evaluate metabolic status: glucose, lactate, liver enzymes and
serum creatinine. Overnight fasting can cause hypoglycaemia,
dehydration and mild metabolic acidosis
• Maintain intravenous infusion containing glucose and electrolyte
pre-operatively, avoid lactate-containing fluids
• Increased sensitivity to sedatives, barbiturates, and propofol.
• Variable sensitivity to nondepolarising muscle relaxants. Avoid
succinylcholine.
• Inhalation or total intravenous anaesthesia.
• Propofol may have an adverse effect on fatty acid oxidation and
impair mitochondrial respiratory chain function, and therefore put
patients with mitochondrial disorders and carnitine deficiency
syndromes at risk for a clinical scenario similar to propofol infusion
syndrome (PRIS).

88. • Alternative intravenous anaesthetics that are under
investigation include ketamine, etomidate, and
dexmedetomidine.
• Many clinicians now consider sevoflurane as the agent of choice
in these patients, how ever some respiratory chain disorders are
more sensitive to inhaled agents and require lower MAC.
• Adequate Pain management as the response to pain may
heighten the risk of lactic acidosis from depletion of energy
stores and increased oxygen demand.
• Prevent hypothermia.

89. THANK YOU