NEUROMUSCULAR DISORDERS

Neuromuscular Pathology and Anesthetic  Management

Julia May 28, 2013

Readings:

›  Nurse Anesthesia. J Nagelhout. Chapter 30, pp 737.

›  Readings: Anesthesia and Coexisting diseases; Hines & Marshall. Pg 505-549

›  Clinical Anesthesiology. Morgan & Mahkail.

SCLERODERMA

›  Is a condition characterized by inflammation, vascular sclerosis, and fibrosis of the skin and viscera.

 ›            Injury to the vascular endothelium results in obliteration and leaking of cell proteins.

›  The leaking proteins affects the interstitial fluids.

›  This will produce edema, lymphatic obstruction, and ultimately fibrosis.

CREST SYNDROME

›  Ina few patients the disease evolves into the Crest Syndrome.

›  Calcinosis

›  Raynaud’s

›  Esophageal hypomotility

›  Sclerodactyly (tightness of the skin)

›  Telangiectasis (dilation of small vessels of the skin)

SCLERODERMA

›  Prognosis is poor with this disease and there is no effective treatment.

›  Onset of the disease is between the ages of 20-40yrs old, with women being more affected then men.

›  Treatment may include the administration of corticosteroids.

Physiologic Changes:

›  Skin and muscular system

›  Initial mild thickening and non-pitting edema.

›  Eventually the skin becomes taught, limiting mobility.

›  Skeletal muscle may exhibit weakness.

›  Nervous system

›  Thickening of the nerve sheaths may lead to cranial or peripheral neuropathy.

›  Cardiovascular

›  Patients may develop sclerosing of the small coronary vessels, conduction system and cardiac muscle.

›  Systemic and pulmonary hypertension.

›  May develop arrhythmia, conduction abnormalities and congestive heart failure.

›  Raynaud’s phenomenon is often associated and is the initial presentation.

›  Pulmonary

›  Major cause of morbidity and mortality.

›  Patient may develop pulmonary hypertension and diffuse pulmonary fibrosis.

›  Pulmonary compliance is decreased with increased airway pressures.

›  Kidneys

›  Renal artery involvement can lead to deceased renal blood flow and systemic hypertension.

›  Gastrointestinal

›  Dryness of the oral mucosa

›  Hypomotility of the lower esophagus and small intestine.

›  Dysphagia

›  These patients are prone to reflux.

Anesthetic Management

›  Assessment of organ system involvement.

›  The skin may be taught making tracheal intubation difficult.

›  FOB

›  Oral and nasal telangiectosis may lead to severe bleeding of the airway on intubation.

›  Cannulation of the artery for blood pressure monitoring may face the same challenges of Raynaud’s phenomenon.

›  These patients may be intravascularly depleted leading to hypotension on induction.

›  Increase gastric PH with H2 blockers.

›  Intra-operatively

›  Adequate ventilation with positive pressure ventilation.

›  Avoid acidosis and hypoxemia because it increases PVR.

SYSTEMIC LUPUS ERYTHEMATOSUS

›  SLE is a multisystem chronic inflammatory disease.

›  Characterized:

›  Antinuclear antibody production.

›  Manifesting most often in women.

›  Stress such as pregnancy, surgery or infection can exacerbate the symptoms.

›  SLE may also be drug induced

›   progression is slower and milder than the spontaneous form.

›  Drugs causing SLE

›  Procainamide, hydralazine, isoniazide, D-penicillamide, alpha-methyldopa.

›  Susceptible individuals are thought to be slow metabolizers (Slow acetylators)of the drugs.

Diagnosis

›  Screening test for lupus- antinuclear antibody test.

›  95% of the patients will test for this.

›  The most common antibody is directed against the nucleosomal DNA- histone complex.

›  Diagnosis is likely when the patient exhibits 3-4 manifestations:

›  Antinuclear antibodies,

›  Rash

›  Thrombocytopenia

›  Serositis, or nephritis

›  The common presentations are:

›  Arthralgia or non specific pattern of arthritis,

›  Vague CNS symptoms

›  History of rash or Raynaud's.

›  Weakly positive anitnuclear test.

Systemic Manifestations of SLE

›  SLE of the CNS

›  Can affect any area of the CNS

›  Cognitive dysfunction, mood disorders, schizophrenia, and organic psychosis.

›  Pericarditis or pericardial effusions

›  Chest pain and pleural friction rub

›  Pulmonary SLE

›  Lupus pneumonia characterized by diffuse pulmonary infiltrates.

›  PFT’s show a restrictive type of disease.

›  Recurring atelectasis can result in “Shrinking Lung” syndrome.

›  Renal abnormalities

›  Glomerular nephritis with proteinuria.

›  Resulting in hypoalbuminemia

›  Severe forms can lead to oliguric renal failure.

Anesthetic Management:

›  Management is influenced by the drug treatment used.

›  Nsaids, corticosteroids, antimalaria drugs.

›  Magnitude of the organ involvement

›  Laryngeal involvement, such as cricoarytnoid arthritis, mucosal  ulcers and recurrent laryngeal nerve is present in 30% of the patients.

Review of MNT:

›  Muscle contraction:

›  Occurs when the electrical signal is transmitted between the presynaptic neuron and the post synaptic neuron.

›  The junction between the two is referred to as the Junctional (synaptic) cleft.

›  The motor neurotransmitter= ACh

What occurs presynaptic:

q  An action potential occurs.

q  Calcium is released.

q  This stimulates the release of Ach.

q  Breakdown and synthesis of Ach occurs here.

q   Enzyme choline acetyltrasnferase (CAT) catalyzes acetylcoenzyme A (Acetyl-coA) + Choline= Ach + Co-A

Neuromuscular Junction:

q  Fluid filled area.

q  Ach is released here.

q  Calcium is fused to Ach vesicles (Quanta) until it ruptures.

q  This is the site were drugs work.

Postjunctional Membrane:

q  Contain nerve endings that are closely approximated.

q   Also known as the motor end plate.

q   Calcium binds to the receptors here

q  You have an influx of NA+ and Calcium, outward K+.

q  The resting membrane potential becomes depolarized.

q  Action potential occurs.

›  1. Presynaptic( Eaton-lambert)

›  2. Sarcolemma

›  3. Synaptic vesicles

›  4. Ach nicotinic receptor (Myasthenia gravis)

›  5. Mitochondria

›  6. Synaptic cleft

›  7. Postjunctional membrane (NM blockers)

›  8. NMJ (Botox)

Skeletal Muscle Pathophysiology:

›  Causes of skeletal muscle disorders

›  Autoimmune

›  Defect in muscle protein

›  Pharmacologic effects.

›  Safety in anesthesia

›  Requires knowledge of Pathophysiology

›  Condition or state the patient is in.

›  Drug therapy being used

›  Preoperative

›  Perform thorough preop assessment

›  Know the degree of respiratory, cardiac and muscle involvement.

›  Intraop

›  How does the patient’s drug therapy affect the anesthetic

›  Post-op

›  May require post-op ventilation

›  Pain management

MYASTHENIA GRAVIS

›  Cause:

›  Autoimmune destruction or inactivation of the post-synaptic Ach receptor.

›  This leads to a decrease in the receptors and loss of the folds on the synaptic vesicles.

›  85% antibody to Ach receptors

›  65% Hyperplastic Thymus gland.

›  10%Thymus

›  10% other

›  Characteristics

›  Episodes of remission/exacerbation

›  Exacerbation can be generalized or confined to a muscle group.

›  Ocular muscles: Diplopia or Ptosis

›  Bulbar involvement: Laryngeal weakness, and dysphasia.

›  Characteristics

›  Proximal muscles (Severe ds): Involves the neck, shoulders & respiratory muscles.

›  With MG. Muscle strength improves with rest.

›  Exacerbation is enhanced: Stress, Pregnancy, surgery & infection.

Treatment:

›  Anticholinesterase

›  Pyridostigmine

›  Most common

›  Given Po and has a duration of 3-4hrs.

›  Side effects

›  Cholinergic crisis: Salivation, diarrhea, muscle weakness, miosis and bradycardia

How can you tell between myasthenic crisis and cholinergic crisis?

›  Edrophonium (Tensilon) Test

›  Used to determine whether weakness is caused from too much drug treatment or myasthenic crisis.

›  An increase in weakness with 10mg indicates cholinergic crisis

›  An increase in strength indicates myasthenic crisis.

Other medical treatments for MG:

›  Thymectomy

›  The thymus produces T-Lymphocytes which aids in immunity

›  Plasmaphoresis

›  Removal of anti-bodies from the blood stream

›  Medications

›  Azathioprine (Imuran): Immunosuppressant

›  Steroids

›  Anticholinesterase

Preop Evaluation:

›  What surgery are they having?

›  Thymectomy: Indicates deterioration of disease.

›  Other: the patient may be optimized or in remission

›  Determine how severe the disease is.

›  Consider pretreatment with H2 blocker for aspiration prevention.

›  Consider omitting sedatives.

›  Edrophonium test

Intraop Management:

›  May use standard inhalational agents.

›  Avoid muscle relaxants.

›  Consider deep inhalation technique.

›  May require increased doses of Sux for resistance, but duration will also be increased.

›  They will have a sensitivity to NDMR.

Postop Care:

›  Post-op ventilation criteria: Following Thymecotmy

›  If disease is > 6mn

›  Presence of pulmonary disease

›  VC < 40cc/kg

›  Pyridostigmine dose > 750mg/d

Babies of MG Mothers:

›  Babies will have symptoms of MG for 1-3 weeks

›  May require post-op ventilation.

EATON-LAMBERT SYNDROME: (Myasthenic Syndrome)

›  Paraneoplastic disorder affecting the lower extremities.

›  Usually associated with small cell carcinoma.

›  Other causes: Met. Ca, sarcoidosis or autoimmune.

›  Muscle weakness generally improves with exercise.

›  Unaffected by anticholinesterase drugs.

›  There is a  prejunctional deficit in the release of Ach, which is thought to be related to antibodies on the calcium channels.

Signs & Symptoms:

›  Autonomic deficits:

›  failure of nicotinic cholinergic synaptic transmission.

›  Patients may be prone to orthostatic hypotension and cardiac irritability.

›  Gastroporesis  and urinary retention

›  Muscle weakness

›  Usually the trunk, pelvic and legs

›  Fatigue and difficulty walking

Anesthetic Considerations:

›  These patients are sensitive to both depolarizers and nondepolarizers.

›  Consider using deep inhalationals anesthesia.

›  If MR is required you will need to decrease the dose.

›  May use reversal agents

›  Consider post-op ventilation support

DUCHENES MUSCULAR DYSTROPHY

›  (Pseudo Hypertrophic Muscular dystrophy).

›  Is the most common and most severe childhood progressive NMD

›  Affects 3 per 10,000 births

›  Caused by an X-linked recessive gene.

›  Becomes apparent in males 2-5 yrs of age

Signs & Symptoms:

›  Waddling gait

›  Difficulty climbing stairs

›  Frequent falls

›  Involves proximal skeletal muscles of the pelvis.

Characteristics:

›  Progressive skeletal muscle weakness to eventually being debilitated in a wheel chair by 8-11 yrs of age.

›  Kyphoscloiosis

›  Skeletal muscle atrophy can lead to long bone fracture.

›  Serum Creatinine Kinase is 30-300 times normal.

›  Death can occur by ages 15-25

›  Skeletal muscle cell shows necrosis and phagocytes of the muscle fiber.

›  Left-Normal  Right-Dystrophic cell

Anesthetic Considerations:

›  Cardiac function

›  Degenerative cardiac muscle

›  EKG shows tall R-waves in V1, deep Q waves in limb leads, Short PR and ST

›  Mitral regurg due to papillary muscle dysfunction.

›  Respiratory function.

›  Decreased function

›  Decreased cough ability

›  Loss of pulmonary reserve

›  Increased secretions

›  Kyphoscoliosis: Restrictive or obstructive lung ds?

›  Most common cause of death

›  Planned surgery

›  Sux is contraindicated

›  Rhabdo, Hyperkalemia, cardiac arrest.

›  NDMR

›  Prolonged effect

›  Dantroline

›  Should be readily available for these patients are at risk for MH.

›  Plan for regional anesthesia when possible.

›  Monitor for signs of M.H

›  Delayed respiratory depression for up to 36 hrs post-op.

›  Monitored unit

MALIGNANT HYPERTHERMIA

›  Life threatening uncommon hyper-metabolic state which is triggered by certain anesthetics.

›  Incidences.

›  Occurs in 52% of the patients under the age of 15 with a mean age of 18.3

›  Occurs in 1:50,000 adults, and 1:15,000. children

Pathophysiology:

›  Cause is unknown

›  Believed to be an inherited disorder.

›  There is a defect in calcium regulation.

›  Focus has been placed recently on the Ryanodine receptor which modulates calcium release from the SR.

What happens when a triggering agent is given?

›  Actin-myosin cross bridges are sustained.

›  Uptake of calcium requires energy and that energy increases muscle cell metabolism 2-3 fold.

›  ↑ metabolism = ↑ O2 consumption= ↑ Temp & CO2 → Depletion of ATP stores & ↑ lactic acid.

›  Triggering agents:

›  Sux

›  Inhalationals

›  K+ Salts

›  Non Triggering

›  Locals, Nitrous

›  Opioids, Barbiturates, Propofol & Ketamine

Neurological Diseases

›  Multiple Sclerosis (MS)

›  Amyotrophic Lateral sclerosis (ALS)

›  Guilliane Barre syndrome (Acute Demyelinating polyNeuropathy)

›  Myelin :

›  is an electrically-insulating dielectric phospholipid layer that surrounds only the axons of many neurons.

›  It main purpose is to increase the speed of impulses along the nerve cells.

›  In the brain the myelinated area is also known as the white matter.

›  Demyelination:

›  Refers to the loss of the myelin sheath insulating the nerve.

›  This is what is seen with disease such as, MS, ALS and Guiiliane Barre syndrome.

MULTIPLE SCLEROSIS

›  Demyelination of several sites of the brain and spinal cord with chronic inflammation and scarring.

›  DX

›  Early via MRI

Characteristics:

›  Autoimmune response initiated by a virus.

›  Occurs between the ages of 20-40yrs.

›  There are episodes of exacerbation and remission.

›  S/S: Motor weakness & Parasthesia, visual disturbances.

›  Increases in body temperature worsens symptoms.

Treatment:

›  Spasms:

›  Dantroline, Bachlofin & diazapam

›  Urinary retention:

›  Bethanechol

›  Decrease exacerbation:

›  ACTH, Gluccocorticois

›  Immunosuppressant:

›  Inteferon B, AZT, Cyclophosamide

Anesthetic Considerations:

›  Avoid elective surgery during relapse stages.

›  Council patients on the effects of stress on the disease.

›  Avoid sux

›  Avoid elevations in body temperature.

›  Increase in temp of 0.5 degree

›  Can decrease demyelinated nerve conduction.

›  Spinal anesthesia can exacerbate symptoms.

›  GA and epidural have not been shown to have e major effect.

AMYOTROPIC LATERAL SCLEROSIS

›  Most common and most rapidly progressing neurologic disease in adults.

›  Occurs during the 5^th and 6^th decade of life.

›  Muscle weakness, atrophy, fasciculation and spasms.

›  It progresses to involve the bulbar and skeletal muscles.

Anesthetic Management:

›  Aimed at keeping judicious respiratory care.

›  Avoid Sux

›  These patient's are more sensitive to NDMR.

›  Monitor respiratory status post-op.

›  Extubate fully awake.

GUILLIAN-BARRE SYNDROME:

›  (Acute demyelinating polyneuropathy).

›  Immune mediated.

›  Most common acute form of neuropathy.

›  Seen 2-4 weeks after a viral infection.

›  There is nerve infiltrated by lymphoid cells, with phagocytosis of myelin

›  The patient develops acute ascending paraysis.

›  Motor weakness and respiratory failure.

›  Bulbar involvement.

›  Remyelination occurs over 3-4 months, with full recovery in most cases.

Pathogenesis:

›  There is an immunologic response against myelin sheath of the PNS, especially the lower motor neurons.

›  Usually follows a viral infection.

›  Can also be seen in par-neoplastic disease such as:

›  Hodgkins lymphoma or HIV