Anesthesia of Anesthesia of patients with patients with motor neuron motor neuron

diseasediseasePresentation by: SC Presentation by: SC 廖伯峰廖伯峰

江毅彥 江毅彥

HistoryHistory

53 y/o Female53 y/o Female Alcohol(+), Smoking (+) 1/2 PPDAlcohol(+), Smoking (+) 1/2 PPD General appearance: weaknessGeneral appearance: weakness Vital sign: T/P/R=36.2/84/18, BP:120/60 Vital sign: T/P/R=36.2/84/18, BP:120/60

mmHg, mmHg, Chest: Symmetric expansion. Chest: Symmetric expansion. Extremities: Movable but weaknessExtremities: Movable but weakness

HistoryHistory

1.Breast tumor r/o ductal adenocarcin1.Breast tumor r/o ductal adenocarcinoma oma

2. 2. Amyotrophic lateral sclerosis(2001~)Amyotrophic lateral sclerosis(2001~) 3. Gastric ulcer3. Gastric ulcer 4. Alcoholic with chronic pancreatitis4. Alcoholic with chronic pancreatitis

CN I: not performedCN I: not performed CN II: visual field – intact; visual acuity — not performeCN II: visual field – intact; visual acuity — not performe

dd CN III, IV & VI: EOM — fullCN III, IV & VI: EOM — full CN V: facial sensation — intactCN V: facial sensation — intact CN VII: facial palsy (-)CN VII: facial palsy (-) CN VIII: intactCN VIII: intact CN IX & X: gag reflex ( + /+ )CN IX & X: gag reflex ( + /+ ) CN XI: decreased muscle power of SCM and trapezious CN XI: decreased muscle power of SCM and trapezious

musclemuscle CN XII: tongue deviation (-), no atrophy or fasciculationCN XII: tongue deviation (-), no atrophy or fasciculation Reflex: Babinski’s sign (-), Hoffman sign (-)Reflex: Babinski’s sign (-), Hoffman sign (-)

Spirometry(2001)Spirometry(2001)

ObservedObserved PredictedPredicted %predicte%predictedd

FVC(L)FVC(L) 2.962.96 2.772.77 106.7106.7

FEVFEV1.01.0(L)(L) 2.602.60 2.372.37 109.7109.7

%FEV%FEV1.01.0 (%)(%)

87.887.8 85.285.2

VC(L)VC(L) 2.832.83 2.772.77 102.0102.0

RV(L)RV(L) 1.681.68 1.731.73 97.497.4•Normal standard spirometry • Normal diffusion capacity

Spirometry(2004)Spirometry(2004)

ObservedObserved PredictedPredicted %predicte%predictedd

FVC(L)FVC(L) 2.782.78 2.642.64 105.3105.3

FEVFEV1.01.0(L)(L) 2.192.19 2.232.23 98.298.2

%FEV%FEV1.01.0 (%)(%)

78.878.8 84.484.4

* Normal screening spirometry

About motor neuron About motor neuron diseasedisease

Selectivity of neuronal cell death—motor Selectivity of neuronal cell death—motor neuron onlyneuron only

(except 1.ocular motility 2.parasympathet(except 1.ocular motility 2.parasympathetic neuron in sacral spinal cord)ic neuron in sacral spinal cord)

Light microscopy: sensory, coordination oLight microscopy: sensory, coordination of movement, cognitive process remain intf movement, cognitive process remain intactact

Immunostaining: ubiquitin also in nonmoImmunostaining: ubiquitin also in nonmotor systems—marker for degenerationtor systems—marker for degeneration

Glucose metabolismGlucose metabolism

About motor neuron About motor neuron diseasedisease

Lower motor neuronLower motor neuron (LMN): axons (LMN): axons synapse directly on skeletal muscles synapse directly on skeletal muscles

Upper motor neuronUpper motor neuron (UMN): motor (UMN): motor

cortex →pyramidal tract →LMNcortex →pyramidal tract →LMN

LMN loss LMN loss signs:signs:

1)1) Flaccid Flaccid paralysisparalysis

2)2) Fasciculations Fasciculations

3)3) Hypotonia Hypotonia

4)4) Hyporeflexia, Hyporeflexia, areflexiaareflexia

UMN loss signUMN loss signs:s:

1)1) Initially weak anInitially weak and flaccidd flaccid

2)2) Eventually spastiEventually spasticc

3)3) HypertoniaHypertonia4)4) HyperreflexiaHyperreflexia5)5) Babinski signBabinski sign

Amyotrophic lateral Amyotrophic lateral sclerosissclerosis

Amyotrophy:Amyotrophy:

biopsy →muscle biopsy →muscle atrophyatrophy

Lateral sclerosis: Lateral sclerosis:

lateral column. lateral column.

gliosis →firmnessgliosis →firmness Lou Gehrig's Lou Gehrig's

disease disease

loss of anterior horn cells, the anterior (ventral) spinal motor nerve roots

demonstrate atrophy

epidemiologyepidemiology

Prevelence:3 to 5 per 100,000Prevelence:3 to 5 per 100,000 Western pacificWestern pacific Sporadic (heavy metal?)Sporadic (heavy metal?) Inherited( AD): 5 to 10%Inherited( AD): 5 to 10% MalesMales 40 to 70 y/o (55)40 to 70 y/o (55) Median survival :3 to 5 yearsMedian survival :3 to 5 years

Amyotrophic lateral Amyotrophic lateral sclerosissclerosis

Upper and lower motor neuronUpper and lower motor neuron Progressive weaknessProgressive weakness Exclusion of alternative diagnosisExclusion of alternative diagnosis Bulbar, cervical, thoracic, Bulbar, cervical, thoracic,

lumbosacral motor neuronslumbosacral motor neurons 1 →possible 1 →possible 2 →probable2 →probable 3 →definite3 →definite

Clinical manifestationClinical manifestation

Asymmetric weakness, usually one of distally Asymmetric weakness, usually one of distally limb firstlimb first

Cramping with volitional movements, Cramping with volitional movements, typically in the morningtypically in the morning

Wasting and atrophy of muscleWasting and atrophy of muscle FasciculationFasciculation Hyperactivity of muscle stretch reflexesHyperactivity of muscle stretch reflexes Difficulty of chewing, swallowing, dysarthria, Difficulty of chewing, swallowing, dysarthria,

exaggeration of emotion expressionsexaggeration of emotion expressions Respiratory systemRespiratory system

Respiratory systemRespiratory system

BreathlessnessBreathlessness Nocturnal hypoventilation→ Nocturnal hypoventilation→

morning headache, daytime morning headache, daytime hypersomnolencehypersomnolence

Poor coughPoor cough Recurrent pulmonary aspirationRecurrent pulmonary aspiration Recurrent pneumoniaRecurrent pneumonia Respiratory failureRespiratory failure DieDie

PathogenesisPathogenesis

Not well defined Not well defined SOD1 mutation →free radical SOD1 mutation →free radical

accumulationsaccumulations Glutamate (EAAT2, astroglial cell)Glutamate (EAAT2, astroglial cell) VEGF↓VEGF↓

DiscussionDiscussion

Anesthesia in patients with Anesthesia in patients with ALSALS

Miller's anesthesiaMiller's anesthesia ,2005 ,2005 Anesthesia and Anesthesia and

neurosurgery, 2001neurosurgery, 2001

Responses to muscle relaxantsResponses to muscle relaxants Bulbar dysfunctionBulbar dysfunction Lung function: spirometryLung function: spirometry Regional anesthesia VS general Regional anesthesia VS general

anesthesiaanesthesia

Responses to muscle Responses to muscle relaxantsrelaxants

Predisposed to SCC-induced Predisposed to SCC-induced hyperkalehyperkalemiamia because of denervation and atrop because of denervation and atrophy of skeletal muscleshy of skeletal muscles

Patient with motor neuron disease are Patient with motor neuron disease are at risk for hyperkalemia when using Sat risk for hyperkalemia when using SCC because of CC because of upregulation upregulation of nAChRsof nAChRs

SCC is best avoidedSCC is best avoided

ALS patient, in addition, ALS patient, in addition, presynaptic ipresynaptic impairmentmpairment of neuromuscular transmi of neuromuscular transmission, explains their ssion, explains their hypersensitivity hypersensitivity tto nondepolarizing neuromuscular bloco nondepolarizing neuromuscular blockerskers

Increased sensitivity to nondepolarizinIncreased sensitivity to nondepolarizing muscle relaxants → either relaxants g muscle relaxants → either relaxants be be avoidedavoided altogether or altogether or shorter-acting shorter-acting relaxants be usedrelaxants be used

Bulbar dysfunctionBulbar dysfunction

In late stage of the disease, reduced respiratIn late stage of the disease, reduced respiratory muscle reserve and abnormal airway prory muscle reserve and abnormal airway protective reflexes → increased risk for otective reflexes → increased risk for respirarespiratory depressiontory depression and and aspirationaspiration secondary to secondary to the use of sedative and anesthetic drugsthe use of sedative and anesthetic drugs

Aspiration prophylaxis should be considereAspiration prophylaxis should be considered: no evidenced: no evidence

Placement of a feeding tubePlacement of a feeding tube

Lung functionLung function

Respiratory muscle weakness frequentRespiratory muscle weakness frequently developsly develops

Pre-OP ventilatory impairment may hePre-OP ventilatory impairment may help predict anesthetic risk → one small lp predict anesthetic risk → one small study: study: 40%40% FVC/FEV FVC/FEV11

Ventilatory support in the immediate pVentilatory support in the immediate post-OP period may be necessaryost-OP period may be necessary

Regional VS general Regional VS general anesthesiaanesthesia

Epidural anesthesia used in ALS patienEpidural anesthesia used in ALS patients without reported untoward effectts without reported untoward effect

Regional anesthesia is preferable to GRegional anesthesia is preferable to GAA

RA may facilitate progression of neuroRA may facilitate progression of neurodegenerative disease: evidence is anecdegenerative disease: evidence is anecdotaldotal

There is evidence of sympathetic There is evidence of sympathetic hyperactivity and autonomic failure hyperactivity and autonomic failure accompanied by reduced baroreflex accompanied by reduced baroreflex sensitivitysensitivity

Handbook For Anesthesia Handbook For Anesthesia And Co-Existing DiseaseAnd Co-Existing Disease, 20, 20

0202Pre-OP assessmentPre-OP assessment History and Examination: general History and Examination: general

details, bulbar function, respiratory details, bulbar function, respiratory functionfunction

Investigations: to confirm diagnosis, Investigations: to confirm diagnosis, routine works, chest radiography, routine works, chest radiography, LFT,ABG, tests of diaphragmatic LFT,ABG, tests of diaphragmatic function, videofluoroscopyfunction, videofluoroscopy

Pre-OP managementPre-OP management

PremedicationPremedication Opioid: should be Opioid: should be

avoidedavoided Small dose of Small dose of

benzodiazepine benzodiazepine Prophylaxis Prophylaxis

against pulmonary against pulmonary aspiration (i.e. an aspiration (i.e. an HH22-receptor -receptor antagonist)antagonist)

MonitoringMonitoring ECGECG BPBP SpOSpO22

EtCOEtCO22

Neuromuscular Neuromuscular function function monitoringmonitoring

Induction and maintenance Induction and maintenance of anesthesiaof anesthesia

Tracheal Tracheal extubationextubation should be should be performed with the patient performed with the patient fully fully awakeawake to ensure maximal function of to ensure maximal function of the laryngeal reflexesthe laryngeal reflexes

Regional anesthesia: if appropriate, Regional anesthesia: if appropriate, better than GA, better than GA, level of blocklevel of block not to not to compromise an already weak compromise an already weak respiratory musculaturerespiratory musculature

Post-OP managementPost-OP management

Effective post-OP pain relief without Effective post-OP pain relief without the use of agents that depress the use of agents that depress respiratoryrespiratory

Post-OP ventilation may be required Post-OP ventilation may be required and weaning may be prolongedand weaning may be prolonged

Case report ⅠCase report Ⅰ

46 y/o woman with emergency operati46 y/o woman with emergency operation for ileuson for ileus

65 y/o woman with emergency operati65 y/o woman with emergency operation for gastric fistula malfunctionon for gastric fistula malfunction

63 y/o man scheduled for a surgery of r63 y/o man scheduled for a surgery of rectal cancerectal cancer

49 y/o man scheduled for gastrectomy49 y/o man scheduled for gastrectomy

Spinal or/and epidural anesthesia Spinal or/and epidural anesthesia without muscle relaxantswithout muscle relaxants

IV propofol(3mg/kg) and sevoflurane IV propofol(3mg/kg) and sevoflurane (5%) + inhalation of 2-3% (5%) + inhalation of 2-3% sevoflurane and single IV sevoflurane and single IV vecuronium 1 mgvecuronium 1 mg

GA with sevoflurane and epidural GA with sevoflurane and epidural anesthesia with lidocaine + anesthesia with lidocaine + vecuroniumvecuronium

Case report ⅡCase report Ⅱ

Patient undergoing abdominal Patient undergoing abdominal hysterectomyhysterectomy

Epidural anesthesia with 2% Epidural anesthesia with 2% lidocaine + continuous infusion of lidocaine + continuous infusion of low dose propofol for sedationlow dose propofol for sedation

Epidural Epidural morphinemorphine provides provides excellent post-OP pain relief without excellent post-OP pain relief without respiratory complicationrespiratory complication

Chen LK, Chang Y, Liu CC, Hou WY.

Department of Anesthesiology, National Taiwan University Hospital, Taipei, R.O.C.

Case report Case report ⅢⅢ

General anaesthesia in a patient with moGeneral anaesthesia in a patient with motor neuron diseasetor neuron disease

2004 European Academy of anaesthesi2004 European Academy of anaesthesiologyology

56 y/o man with pancreatic carcinoma 56 y/o man with pancreatic carcinoma scheduled for elective Whipple’s surgscheduled for elective Whipple’s surgeryery

5-h operation → 8-h after, patient recovered 5-h operation → 8-h after, patient recovered consciousness and ventilated with CPAP → consciousness and ventilated with CPAP → 5-h after, extubated with normal breathing p5-h after, extubated with normal breathing pattern → attern → 3-h after3-h after, , secondary surgerysecondary surgery → 3-h → 3-h operation → 3-h after……operation → 3-h after……

Without SCC: several complicationsWithout SCC: several complications Low-doseLow-dose cisatracurium: may be a good choi cisatracurium: may be a good choi

cece

For major surgery, using low-dose of For major surgery, using low-dose of cisatracurium and propofol is cisatracurium and propofol is possiblepossible

RepeatedRepeated surgery may lead to a surgery may lead to a considerable increase in respiratory considerable increase in respiratory complicationscomplications

Spirometry should be performed and Spirometry should be performed and the use of neuromuscular monitoring the use of neuromuscular monitoring when planning GAwhen planning GA

Case report ⅣCase report Ⅳ

Use of rapacuronium in a child with spiUse of rapacuronium in a child with spinal muscular atrophynal muscular atrophy

Paediatric anaesthesia 2001Paediatric anaesthesia 2001 18 month-old girl with SMA diagnosed 18 month-old girl with SMA diagnosed

at 6 m/o at 6 m/o Scheduled for placement of a percutanScheduled for placement of a percutan

eous jejunostomy tubeeous jejunostomy tube

Thiopental sodium, alfentanil, Thiopental sodium, alfentanil, lidocaine for induction, and mask lidocaine for induction, and mask ventilation with 2% ventilation with 2% isofluraneisoflurane

Rapacuronium Rapacuronium 9 mg (1 mg/kg) for 9 mg (1 mg/kg) for emergency airway controlemergency airway control

Within 10 min, partial recovery of Within 10 min, partial recovery of the diaphragm was observed → 20 the diaphragm was observed → 20 min after, TOF responses → 75 min min after, TOF responses → 75 min after, operation doneafter, operation done

Reversal with neostigmine 0.6 mg Reversal with neostigmine 0.6 mg and glycopyrrolate 0.12 mg IVand glycopyrrolate 0.12 mg IV

Guidelines are entirely Guidelines are entirely based onbased on experience with the adult form of experience with the adult form of anterior horn cell degeneration anterior horn cell degeneration ((ALSALS))

Induction with Induction with propofolpropofol in in combination with combination with sevoflurane sevoflurane might might have avoided laryngospasm and the have avoided laryngospasm and the use of muscle relaxantsuse of muscle relaxants

A A lesser doselesser dose might have been might have been sufficient to break laryngospasmsufficient to break laryngospasm

TOF : a good monitor?TOF : a good monitor?

ConclusionConclusion

SCCSCC is best avoided, reported to is best avoided, reported to cause rhabdomyolysis and cause rhabdomyolysis and hyperkalemia from denervated hyperkalemia from denervated musclesmuscles

Use of neuromuscular monitoring Use of neuromuscular monitoring when planning GA: TOF ?when planning GA: TOF ?

Muscle relaxants should Muscle relaxants should be avoidedbe avoided altogether or altogether or shorter-acting/low-shorter-acting/low-dosedose muscle relaxants be used muscle relaxants be used