ANAESTHESIA FOR NEUROLOGICAL AND NEUROMUSCULAR DISEASE

DR SHWETADR KANIKA

DEPT. OF ANAESTHESIOLOGYKING GEORGE MEDICAL COLLEGE ,LUCKNOW

• 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

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

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)

EFFECTS OF ANTIEPILEPTICS ON ANAESTHETIC DRUGS

DRUG INTERACTION DUE TO ALTERED METABOLISM

• PHENYTOIN VALPROATE• CARBAMAZEPINE>> OXCARBAZEPINE• PHENOBARBITONE• PRIMIDONE• TOPIRAMATE

ENZYME INDUCERS

ENZYME INHIBITORS

DRUG INTERCTIONS RELATED TO PROTEIN BINDING PHENYTOIN VALPROATE CARBAMAZEPINE

EFFECT OF ANAESTHETIC AGENTS ON EPILEPSY

ANAESTHETIC AGENTS PROCONVULSANT ANTICONVULSANT

INHALATIONAL AGENTS

NITROUS OXIDE HALOTHANE ISOFLURANESEVOFLURANEDESFLURANE ENFLURANE

++

++++-

++

-++

+++--+

INDUCING AGENTS

THIOPENTONEMETHOHEXITALETOMIDATEBENZODIAZEPINESKETAMINEPROPOFOLOPIOIDS

++++++++

-++++

+++

++++++++++++

+++-

• 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

• 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.

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

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???

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

MR.

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

SUBTYPES OF GBSSUBTYPE 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 ophthalmoplegiaGQ-1b antibodies

DEMYELINATING Resembles AIDP

DIAGNOSTIC CRITERIA

REQUIRED 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.

SUPPORTIVE

CRITERIA

•Symmetric weakness•Mild sensory involvement•Cranial nerve involvement•Abscence of fever•Typical csf profile•Electrophysiological evidence of demyelination.

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.

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.

PATHOPHYSIOLOGY

• 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

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.

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.

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.

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.

• 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.

CEREBROVASCULAR DISEASE

CEREBROVASCULAR DISEASE

Occluded artery Clinical features

Anterior cerebral artery Contralateral leg weakness

Middle cerebral artery Contralateral hemiparesis andhemisensory deficit (face and armmore than leg)Aphasia (dominant hemisphere)Contralateral visual field defect

Posterior cerebralartery

Contralateral visual field defectContralateral hemiparesis

Penetrating arteries Contralateral hemiparesisContralateral hemisensory deficits

Basilar artery Oculomotor deficits and/or ataxiawith crossed sensory and motordeficits

Vertebral artery Lower cranial nerve deficits and/orataxia with crossed sensory deficits

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.

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.

AMYOTROPHIC LATERAL SCLEROSISANAESTHETIC 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

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.

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.

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.

• 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.

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.

DRUG COMMENT

INTRAVENOUS INDUCING AGENTSPROPOFOLTHIOPENTONEETOMIDATE

AVOID FOR STEREOTACTIC PROCEDURESSAFESAFE

VOLATILE ANAESTHETICHALOTHANEISOFLURANESEVOFLURANEDESFLURANE

Possible arrhythmiasProbably safeProbably safeProbably safe

NEUROMUSCULAR BLOCKING AGENTSDEPOLARISINGNONDEPOLARISING

Possible hyperkalemiaProbably safe

ANALGESICSMORPHINEPETHIDINEFENTANYLALFENTANYL

Possible muscle rigidityAvoid in patients on selegilinePossible muscle rigidityPossible dystonic reactions

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.

PATHOPHYSIOLOGYBLOCKADE 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

HYPERTHERMIA

Oral temperature > 38°C (100.4°F) in the absence of

anotherknown cause

EXTRAPYRAMIDAL EFFECTS(>2)

Choreiform movementsCogwheel rigidity

DyskinesiaDysphagia

Festinating gaitLead pipe muscle rigidity

Oculogyric crisisOpisthotonous

SialorrhoeaTrismus

AUTONOMIC DYSFUNCTION(>2)

Hypertension (diastolic blood pressure at least

20 mm Hgabove baseline)

IncontinenceProminent diaphoresisTachycardia (heart rate at least 30 bpm above

baseline)Tachypnoea

(respiration > 25 breaths/min)

DIAGNOSTIC CRITERIA

MANAGEMENT• Discontinuation of the offending neuroleptic agent• ABC, FLUID RESUSCUTATION• Cooling measures• Pharmacotherapy

Bromocriptine1. 2.5 mg q8h up to 5 mg q4h2. continue for 7–10 days after resolution then taper over 1–2 weeks (except depot

preparations)Dantrolene3. 2–3 mg/kg4. extreme rigidity, very high fever (> 40oC), unable to tolerate oral treatmentBenzodiazepines1. to control agitation/deliriumECT5. refractory to adequate trial of dopamine agonist/supportive care6. after resolution of acute features

1. remain catatonic or2. develop ECT-responsive psychotic features

7. suspected acute lethal catatonia

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.

• 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

PATHOPHYSIOLOGY

TYPE ETIOLOGY ONSET SEX COURSE THYMUS

NEONATAL Passage of ab from myasthenic mothers across placenta

Neonatal Both Transient Normal

CONGENITAL Congenital end plate pathologyGenetic 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 progressiveHigh mortality

Thymoma

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– Treatment of Cholinergic Crisis: Atropine, Mechanical

Ventilation if needed

CHOLINERGIC CRISIS VS MUSCARINIC CRISISMUSCARINIC CRISIS CHOLINERGIC CRISIS

An exacerbation of the myasthenic symptoms caused byundermedicationwith anticholinesterases

an acute exacerbation of muscleweakness caused byovermedicationwith cholinergic anticholinesterase drugs

Generalised muscle weakness

Pupils - miosisTENSILON TEST : improvement in symptoms

Muscle weakness + parasympathomimetic effectsPupils – mydriasisFurther deterioration

Atropine + supportive Neostigmine + supportive

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.

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.

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.

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.

MYASTHENIA SYNDROMELAMBERT 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.

MYASTHENIC SYNDROME MYASTHENIA GRAVIS

Manifestations Proximal limb weakness

Strength improves with exerciseMuscle pain commonReflexes -/ decreased

Extraocular, bulbar and facial muscle weaknessFatigue with exerciseMuscle pain uncommonReflexes 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 scholineSensitive to nondepolarising agentsGood response to anticholinesterase

DISORDERS OF MUSCLES

• Congenital Muscular Dystrophies– Myotonic– Duchenne, Becker

• Acquired Myopathies– Cushing’s Syndrome– Dermatomyositis– Polymyositis

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

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

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.

• 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.

MUSCULAR DYSTROPHY

• X-linked:– Duchenne's– Becker's.

• Autosomal recessive:– limb-girdle– childhood– congenital.

• Autosomal dominant:– facioscapulohumeral– oculopharyngeal.

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

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.

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.

• 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.

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

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.

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.

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

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

1515

15

151053

• 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

151515

1510

1510

33

PATHOPHYSIOLOGY

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).

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 .

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

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 .

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

• 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.

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).

• 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.

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