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Disclaimer

Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct. Readers must therefore always check the product information and clinical procedures with the most up to date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations. The authors and the publishers do not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work. Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breastfeeding.

Neurological and muscular disorders

Chapter:
Neurological and muscular disorders
DOI:
10.1093/med/9780199584048.003.0011

  • Andrew Teasdale

    Epilepsy [link]

  • Cerebrovascular disease [link]

  • Parkinson's disease [link]

  • Anaesthesia in spinal cord lesions [link]

  • Myasthenia gravis [link]

  • Multiple sclerosis [link]

  • Guillain–Barré syndrome [link]

  • Motor neuron disease (amyotrophic lateral sclerosis)  [link]

  • Dystrophia myotonica [link]

  • Muscular dystrophy [link]

  • Jane Halsall

    Malignant hyperthermia [link]

Epilepsy

Epilepsy is a disorder characterised by chaotic brain dysfunction leading to symptoms ranging from behavioural disorder through to life-threatening convulsions. Most epileptic patients will be on seizure-modifying drug therapy.

General considerations

  1. Maintain GI function to avoid metabolic disturbance and interference with drug therapy.

  2. Make provision for therapy if oral antiepileptic medication cannot be given.

Preoperative assessment

  1. Nature, timing, and frequency of seizures should be recorded.

  2. Full drug history, including timing of antiepileptic therapy should be noted.

  3. The effect of the condition on lifestyle and the eligibility to hold a driver's licence should be noted.

Investigations

  1. Electrolyte and glucose measurement. Disturbance will alter seizure potential.

Conduct of anaesthesia

  1. Avoid prolonged fasting.

  2. Sedative premedication, if necessary, may be achieved with benzodiazepines. Long-acting drugs such as diazepam (10mg PO) or lorazepam (2–4mg PO) are useful.

  3. Maintain antiepileptic therapy up to the time of surgery.

  4. All currently used anaesthetic agents are anticonvulsant in conventional doses. Thiopental is powerfully anticonvulsant and may be a preferred induction agent in the poorly controlled epileptic.

  5. Muscle relaxation is best achieved by drugs without a steroid nucleus (e.g. atracurium, cisatracurium) since enzyme induction by all commonly used anticonvulsant drugs (especially phenytoin, carbamazepine, and the barbiturates) will lead to rapid metabolism of vecuronium and rocuronium.

  6. Avoid hyperventilation and consequent hypocarbia since this will lower seizure threshold.

  7. Regional anaesthesia may assist in preservation of, or early return to, oral intake. Be aware of maximum local anaesthetic doses.

  8. Use antiemetic agents unlikely to produce dystonias (e.g. cyclizine 50mg IV/IM, domperidone 30–60mg PR, ondansetron 4mg IV).

  9. Record any epileptiform activity in the perioperative period carefully. The misdiagnosis of postoperative shivering/dystonic movements on induction as epilepsy may have profound implications.

  10. Day case anaesthesia is suitable for those with well-controlled epilepsy (seizure free for 1yr or nocturnal seizures only). Patients should be warned of the potential for perioperative convulsions.

Drug issues

The following drugs should be used with caution in epileptics:

Drug

Notes

Methohexital

Reported to produce seizures in children. Increased EEG evidence of spike activity during administration. No longer marketed in the UK

Ketamine

Avoided because of cerebral excitatory effects although it has been used without incident in many epileptics

Etomidate

Associated with a high incidence of myoclonus (not centrally mediated). May be confused with epileptic activity

Antiemetics: phenothiazines (e.g. prochlorperazine), central dopamine antagonists (e.g. metoclopramide), butyrophenones

(e.g. droperidol)

High incidence of dystonic reactions may lead to confusion with epileptic activity

Inhalational agents: enflurane

Associated with abnormal EEG activity after administration—especially in presence of hyperventilation

Neuromuscular blockers: steroid based (e.g. vecuronium, rocuronium)

Pharmacodynamic resistance due to enzyme activation

Propofol

  1. Propofol is reported to be associated with abnormal movements during both induction and emergence from anaesthesia. This is unlikely to represent true seizure activity (EEG studies fail to demonstrate epileptiform activity during these episodes).

  2. Epileptic patients may be prone to seizures during the rapid emergence from propofol anaesthesia.

  3. Profound suppression of abnormal EEG activity is usually noted during propofol infusion.

  4. Propofol has also been reported to be effective in status epilepticus in ICU.

Caution is advised in the administration of propofol to epileptics (particularly those holding driving licences) unless there is an overwhelming clinical need for its administration. Co-induction with benzodiazepine (e.g. midazolam 2–3mg IV) may reduce its potential to produce abnormal movements and reduce the potential for postoperative seizure.

Driving and epilepsy

At present, UK law mandates the withdrawal of a driving licence from an epileptic until 12 months from the last seizure. The implications of a single convulsion in the postoperative period on a previously well-controlled epileptic cannot be overstated. Up-to-date advice on fitness to drive is available from the DVLA (Driver and Vehicle Licensing Agency: http://www.dvla.gov.uk).

What if oral or nasogastric therapy is not possible?

The following drugs are available in parenteral or rectal formulations. In general, IM administration of antiepileptic medication should be avoided because of unpredictable absorption postoperatively and the irritant nature of the formulations.

Drug levels should be measured during parenteral therapy or after changing the route of administration.

Drug

Notes

Carbamazepine

125mg rectal, equivalent to 100mg oral. Maximum 1g daily in four divided doses

Phenobarbital

200mg IM repeated 6-hourly. Child 15mg/kg. IV administration associated with sedation. Slow infusion of dilute preparation recommended

Phenytoin

Loading dose 15mg/kg IV at rate of no greater than 50mg/min. Maintenance dose (same IV as oral) twice daily. Infusion usually under ECG and BP control

Fosphenytoin

A prodrug of phenytoin. Less irritation and cardiovascular instability on injection. Absorbed very slowly after IM injection although non-irritant. Dose—same dose (in phenytoin equivalents*) and frequency as oral phenytoin

Sodium valproate

IV dose same as oral dose, twice daily. Dose to be injected over 3–5min

Clonazepam

IV infusion in high-dependency area only—facilities for airway control available. Child (any age) 500µg. Adult 1mg

* (see [link])

Cerebrovascular disease1

Stroke is the third leading cause of death in the industrialised world (after heart disease and cancer). Cerebrovascular disease is manifested by either global cerebral dysfunction (multi-infarct dementia) or focal ischaemic disorder ranging from transient ischaemic attack to major stroke.

Transient ischaemic attacks (TIA)

  1. These are defined as focal neurological deficits that occur suddenly and last for several minutes to hours but never more than 24hr. Residual neurological deficit does not occur.

  2. They are thought to be related to embolism of platelet and fibrin aggregates released from areas of atherosclerotic plaque. The risk of stroke in untreated patients is said to be ∼5% per annum with a mortality of ∼30% per episode.

  3. Patients with a history of TIA should be investigated and assessed by a specialist vascular service if practical. Doppler flow studies, with or without angiography, are indicated in all cases of recurrent TIA or those that have occurred despite aspirin therapy.

  4. Delay of all but urgent or emergency surgery is warranted until Doppler studies are performed. At present only those with a history of TIA with good recovery and a surgically accessible lesion of either >80% stenosis or ‘ragged’ plaque are routinely referred for carotid surgery. Crescendo TIA is considered by some as an indication for urgent carotid surgery.

General considerations

Cerebrovascular disease is associated with hypertension, diabetes, obesity, and smoking. The incidence rises with age. Medical management is based on the treatment of the underlying disorder, cessation of smoking, and antiplatelet/anticoagulant therapy.

Signs of concurrent cardiac and renal dysfunction should be sought.

When to operate

  1. Operation within 6wk of a cerebral event is associated with an up to 20-fold increase in the risk of postoperative stroke.

  2. Hemiplegia of <6–9 months’ duration is associated with exaggerated hyperkalaemic response to suxamethonium.

It therefore seems prudent to delay all but life-saving surgery for at least 6wk following a cerebral event and preferably to wait 3–6 months before considering elective surgery.

Preoperative assessment

  1. Measure blood pressure (both arms) and test blood glucose. The therapeutic aims are for normotension and normoglycaemia.

  2. Take a full drug history—continue antihypertensive drugs until operation.

  3. Warfarin should be discontinued and substituted with heparin (unfractionated or LMWH as per local protocol) if necessary.

  4. Aspirin is discontinued only if the consequences of haemorrhage are significant (e.g. tonsillectomy, neurosurgery) (see pp. [link][link]).

  5. Document the nature of any ischaemic events and any residual neurological deficit. These may range from transient blindness (amaurosis fugax) to dense hemiplegia. This will help in differentiating new lesions arising in the perioperative period that may require urgent therapy.

  6. Ask about precipitating events. Vertebrobasilar insufficiency is most likely to be precipitated by postural changes and neck positioning.

Conduct of anaesthesia

  1. Ensure that antihypertensive medication (with the possible exception of ACE inhibitors for major surgery or when thoracic epidurals are planned) is continued to the time of operation. ACE inhibitors may predispose to profound, resistant hypotension under anaesthesia.

  2. Thromboprophylaxis is advisable unless contraindicated (e.g. low-dose LMWH).

  3. Ensure that pressor and depressor agents are available prior to induction. Use agents with which you are familiar. Maintain blood pressure as close as practical to preoperative levels to maintain cerebral blood flow. Useful pressors are ephedrine/metaraminol; useful depressors are opiods/labetalol/esmolol/GTN.

  4. Blood pressure may ‘swing’ excessively during surgery due to the interactions of anaesthesia, antihypertensives, and the surgical stimulation on a relatively rigid vascular system. IV fluid replacement should be proactive rather than reactive, with large-bore IV access and invasive central pressure monitoring if large fluid shifts are expected.

  5. Ensure that neck positioning is neutral and avoids movements associated with syncope.

  6. Induction of anaesthesia may result in dangerous hypotension followed by extreme hypertension on intubation. Careful IV induction is indicated. Cover for intubation may be provided by opioids (e.g. alfentanil 500–1000µg or fentanyl 150–250µg).

  7. Avoid hyperventilation. Hypocarbia is associated with reduced cerebral blood flow and therefore cerebral ischaemia. The combination of hypotension and hypocarbia must be avoided.

  8. Examine the patient early in the postoperative period to determine any change in neurological status. New neurological signs will require urgent referral to a neurologist/vascular surgeon and urgent treatment if possible.

Parkinson's disease

General considerations

  1. Parkinsonism is a syndrome characterised by tremor, bradykinesia, rigidity, and postural instability. The aetiology of Parkinson's disease is unknown, but parkinsonism may be precipitated by drugs (especially neuroleptic agents) or be post-traumatic/postencephalitic.

  2. Parkinsonism is due to an imbalance of the mutually antagonistic dopaminergic and cholinergic systems of the basal ganglia. Pigmented cells in the substantia nigra are lost, leading to reduced dopaminergic activity. There is no reduction in cholinergic activity.

  3. Drug therapy of parkinsonism is aimed at restoring this balance by either increasing dopamine or dopamine-like activity or reducing cholinergic activity within the brain.

  4. Drug therapy in parkinsonism is limited by severe side effects (nausea and confusion), especially in the elderly. Up to 20% of patients will remain unresponsive to drug therapy.

Drug therapies

Dopaminergic drugs

  1. l-dopa is an inactive form of dopamine, which is converted by decarboxylases to dopamine within the brain. It is more useful in patients with bradykinesia and rigidity than tremor and is usually administered with decarboxylase inhibitors (e.g. benserazide, carbidopa) that do not cross into the brain, reducing peripheral conversion into dopamine.

  2. Monoamine oxidase B (MAO-B) inhibitors (e.g. selegiline) act by reducing central breakdown of dopamine. Selegiline has fewer drug interactions than the non-specific MAO inhibitors, but may cause a hypertensive response to pethidine and dangerous CNS excitability with SSRI and tricyclic antidepressants (see [link]).

  3. Ergot derivatives such as bromocriptine, cabergoline, lisuride, and pergolide act by direct stimulation of dopamine receptors. They are usually reserved for adjuvant therapy in those already on l-dopa or those intolerant of the side effects of l-dopa.

  4. Entacapone is an adjuvant agent capable of reducing the dose of l-dopa and increasing the duration of its effect. It is usually reserved for those experiencing ‘end of dose’ deterioration after long-term dopaminergic therapy.

  5. Other adjuvant dopaminergic agents are ropinirole, pramipexole, amantadine, apomorphine, and tolcapone.

  6. There are no parenteral dopaminergic agents currently available for use in parkinsonism.

Anticholinergic (antimuscarinic) drugs

  1. The most commonly used agents in this group are benzatropine, procyclidine, benzhexol (trihexyphenidyl), and orphenadrine.

  2. These agents are indicated as first-line therapy only when symptoms are mild and tremor predominates. Rigidity and sialorrhoea may be improved by these agents but bradykinesia will not be affected.

  3. This class of drug is useful for drug-induced parkinsonism but not in tardive dyskinesia.

  4. Parenteral formulations exist for procyclidine and benzatropine, making these useful for acute drug-induced dystonias.

Surgical therapies

Surgery for treatment of Parkinson's-induced disability is increasing in popularity. It is normally performed in the awake patient using stereotactic guided probes.

  1. Thalamotomy is used in those with tremor as the predominant disability, especially if the tremor is unilateral. Anterior thalamotomy is sometimes used for rigidity.

  2. Pallidotomy is primarily for those with rigidity and bradykinesia, although the tremor (if present) may also be reduced.

  3. Deep brain stimulation using implantable devices is becoming more commonplace. There is no literature at present relating to incidental anaesthesia in patients with these devices, but it would seem prudent to contact the manufacturer or team responsible for insertion of the device before using diathermy. If diathermy is necessary, bipolar should be used, as far as practical from the device or lead. Device function should be checked after surgery.

Preoperative assessment

Ideally, patients with severe disease should be under the care of a physician with a special interest in Parkinson's disease, who should be involved in the perioperative care.

The following assessment is of particular interest:

  1. A history of dysphagia or excessive salivation (sialorrhoea) is evidence of increased risk of aspiration and possible failure to maintain an airway in the perioperative period. Gastro-oesophageal reflux is common in this group of patients.

  2. Postural hypotension may be evidence of both dysautonomia and drug-induced hypovolaemia and should warn of possible hypotension on induction or position changes during surgery.

  3. Drug-induced arrhythmias, especially ventricular premature beats, are common, although they are usually not clinically significant.

  4. Respiratory function may be compromised by bradykinesia and muscle rigidity as well as by sputum retention. Chest radiograph, lung function tests, and blood gases may be indicated.

  5. Difficulty in voiding may necessitate urinary catheterisation. Postoperative urinary retention may be a potent cause of postoperative confusion.

  6. The severity of the underlying disease should be determined and other likely problems anticipated, e.g. akinesia, muscle rigidity, tremor, confusion, depression, hallucinations, and speech impairment.

Drug interactions

Most patients with severe disease are on several maintenance drugs, many of which have potentially serious interactions.

Drug interactions in parkinsonism

Class of drug

Interaction

Notes

Pethidine

Hypertension and muscle rigidity with selegiline

May resemble malignant hyperpyrexia

Synthetic opioids, e.g. fentanyl, alfentanil

Muscle rigidity

More apparent in high doses

Inhalational agents

Potentiate l-dopa- induced arrhythmias

Avoid use of halothane if ventricular arrhythmia present on preop ECG

Antiemetics, e.g. metoclopramide, droperidol, prochlorperazine

May produce extrapyramidal side effects or worsen parkinsonian symptoms

Metoclopramide may increase plasma concentration of l-dopa—use domperidone/ondansetron

Antipsychotics, e.g. phenothiazines, butyrophenones, piperazine, derivatives

May produce extra-pyramidal side effects or worsen Parkinson's symptoms

Better to use atypical

antipsychotics such as sulpiride, clozapine, risperidone.

Antidepressants: tricyclics (e.g. amitriptyline), serotonin reuptake inhibitors (e.g. fluoxetine)

Potentiate l-dopa-induced arrhythmias (tricyclics only).

Hypertensive crises and cerebral excitation with selegiline (tricyclics and SSRIs)

Antihypertensives (all classes)

Marked antihypertensive effect in treated and untreated parkinsonism. Related to postural hypotension and relative hypovolaemia

Most marked with clonidine and reserpine

Conduct of anaesthesia

  1. Treatment for parkinsonism should be continued up to the start of anaesthesia. Distressing symptoms may develop as little as 3hr after a missed dose. Acute withdrawal of drugs may precipitate neuroleptic malignant syndrome. See [link].

  2. Premedication is usually unnecessary unless distressing sialorrhoea is present. Consider glycopyrronium (200–400µg IM) as an antisialogogue.

  3. The presence of preoperative sialorrhoea or dysphagia is a sign of gastrointestinal dysfunction. Airway control with intubation by rapid sequence induction may be indicated.

  4. Maintain normothermia to avoid shivering.

  5. There is no evidence that any anaesthetic technique is superior to any other.

  6. Analgesia: IV morphine is useful if regional or local analgesia is not possible (PCA may prove difficult for the patient). Oral analgesia may be difficult to administer with coexisting dysphagia (a nasogastric tube may be necessary).

Postoperative care

  1. In principle, the more disabled the patient preoperatively, the greater the need for postoperative high-dependency and respiratory care.

  2. Postoperative physiotherapy should be arranged if rigidity is disabling.

  3. Nasogastric tube insertion may be needed if GI dysfunction is present to allow early return of oral medication.

  4. Prolonged GI dysfunction postoperatively may lead to severe disability since no parenteral dopaminergic therapy is currently available.

Special considerations

Antiemetic therapy may prove problematic. The following are useful:

  1. Domperidone (10–20mg 4–6-hourly PO or 30–60mg 4–6-hourly PR). The drug of first choice for PONV in Parkinson's patients. It does not cross the blood–brain barrier to a significant degree and is thus not associated with significant extrapyramidal effects.

  2. Serotonin antagonists, e.g. ondansetron 4mg IV and granisetron 1mg IV slowly, may be useful rescue agents in PONV if domperidone alone is ineffective.

  3. Antihistamine derivatives (e.g. cyclizine 50mg IV/IM).

Further reading

Mason LJ, Cojocaru TT, Cole DJ. Surgical intervention and anesthetic management of the patient with Parkinson's disease (1996). International Anesthesiology Clinics, 34, 133–150.

Nicholson G, Pereira A, Hall G (2002). Review article: Parkinson's disease and anaesthesia. British Journal of Anaesthesia, 89, 904–916.

Stotz M et al. (2004). Case report: fulminant neuroleptic malignant syndrome after perioperative withdrawal of antiParkinsonian medication. British Journal of Anaesthesia, 93:, 868–871.

Anaesthesia in spinal cord lesions

There are ∼40 000 patients in the UK with spinal cord injuries. Most are young adults. Fertility in affected females approaches that of the non-injured population and obstetric services are regularly required.

Pathophysiology of spinal cord injury

Spinal injury can be divided into three distinct phases:

  1. The initial phase: very short (minutes) period of intense neuronal discharge caused by direct cord stimulation. This leads to extreme hypertension and arrhythmias, with risk of LVF, MI, and pulmonary oedema. Steroids usage in acute spinal cord injury remains controversial. If used, steroids must be given within 8hr of injury, in high dosage (e.g. 30mg/kg methylprednisone).

  2. Spinal shock follows rapidly and is characterised by hypotension and bradycardia due to loss of sympathetic tone. It is most common after high cord lesions (above T7). There is associated loss of muscle tone and reflexes below the level of the lesion. Vagal parasympathetic tone continues unopposed, causing profound bradycardia or asystole—especially on tracheal suction/intubation. This phase may last from 3d to 8wk. Paralytic ileus is common.

  3. Reflex phase: as neuronal ‘rewiring’ occurs, efferent sympathetic discharge returns, along with muscle tone and reflexes.

Autonomic dysreflexia

This is characterised by massive, disordered autonomic response to stimulation below the level of the lesion. It is rare in lesions lower than T7. Incidence increases with higher lesions. It may occur within 3wk of the original injury but is unlikely to be a problem after 9 months. The dysreflexia and its effects are thought to arise because of a loss of descending inhibitory control on regenerating presynaptic fibres.

Hypertension is the most common feature but is not universal. Other features include headache, flushing, pallor (may be manifest above the level of lesion), nausea, anxiety, sweating, bradycardia, and penile erection. Less commonly pupillary changes or Horner's syndrome occur. Dysreflexia may be complicated by seizures, pulmonary oedema, coma, and death and should be treated as a medical emergency. The stimulus required to precipitate the condition varies but is most commonly:

  1. Urological: bladder distension, UTI, catheter insertion

  2. Obstetric: labour, cervical dilation, etc.

  3. Bowel obstruction/faecal impaction

  4. Acute abdomen

  5. Fractures

  6. Rarely, minor trauma to skin, cutaneous infection (bedsores).

Management of dysreflexia

  1. Discover the cause if possible and treat.

  2. If no apparent cause, examine carefully for unrevealed trauma or infection, catheterise, and check for faecal impaction.

  3. If simple measures fail, consider:

    1. Phentolamine 2–10mg IV repeated if necessary.

    2. Transdermal GTN.

    3. Clonidine (150–300µg) if there is hypertension and spasticity.

    4. β-blockers are indicated only if there is associated tachycardia—esmolol 10mg IV repeated.

Systemic complications of spinal cord lesions

  1. Reduced blood volume—may be as little as 60ml/kg, a 20% reduction.

  2. Abnormal response to the Valsalva manoeuvre with continued drop in blood pressure (no plateau) and no overshoot with release.

  3. Profound postural hypotension with gradual improvement after initial injury (never to normal). Changes in cerebral autoregulation reduce its effect on CBF and consciousness in the non-anaesthetised patient.

  4. Lesions above C3—apnoea.

  5. Lesions at C3/4/5—possible diaphragmatic sparing, some respiratory capacity. Initial lesions may progress in height with shock and oedema, with recovery as the oedema improves, leading to a marked improvement in respiratory capacity.

  6. Below C5—phrenic sparing, intercostal paralysis. Recruitment of accessory muscles is necessary to improve respiratory capacity (this may take up to 6 months).

  7. Paralysis of abdominal muscles severely affects the ability to force expiration, reducing the ability to cough.

  8. The FVC is better in the horizontal or slight head-down position due to increased diaphragmatic excursion.

  9. Bronchial hypersecretion may occur.

  10. Poor thermoregulation due to isolation of central regulatory centres from information pathways, inability to use muscle to generate heat, and altered peripheral blood flow.

  11. Muscle spasms and spasticity occur due to intact reflexes below the level of the lesion. They can be caused by minor stimuli. Baclofen and diazepam may be used, the former increasingly via epidural infusion.

  12. Reduced bone density leading to increased risk of fractures. There is heterotopic calcification around the joints in up to 20% of patients.

  13. Poor peripheral perfusion—pressure sores and difficult venous access.

  14. Anaemia, usually mild.

  15. Tendency to thrombosis and pulmonary embolism. Some centres warfarinise tetraplegics 5d after initial presentation.

  16. There is delayed gastric emptying in tetraplegics (up to 5 times longer).

Suxamethonium in chronic spinal cord lesions

  1. After upper motor neuron denervation, the motor endplate effectively extends to cover the entire muscle cell membrane. With administration of suxamethonium, depolarisation occurs over this extended endplate, leading to massive potassium efflux and potential cardiac arrest.

  2. Recommendations vary as to the period of potential risk. Practically—avoid suxamethonium from 72hr following the initial injury. There are no reports of clinically significant hyperkalaemia with suxamethonium after 9 months.

Conduct of anaesthesia

Spinal shock phase

Surgery is usually confined to the management of life-threatening emergencies and coexisting injury. Anaesthesia should reflect this.

  1. Severe bradycardia or even asystole may complicate intubation—give atropine (300µg IV) or glycopyrronium (200µg IV) prior to intubation.

  2. Extreme care should be taken if cervical spine injury is suspected.

  3. Preload with fluid (500–1000ml crystalloid) to reduce hypotension.

  4. Central line insertion may be necessary to manage fluid balance and guide appropriate inotrope therapy.

Reflex phase

Previous anaesthetic history is vital—many procedures in these patients are multiple and repeated. Pay close attention to the following:

  1. Is there a sensory level and is it complete? (Risk of autonomic dysreflexia is greater in complete lesions.)

  2. If complete, is the proposed surgery below the sensory level? (Is anaesthesia necessary?)

  3. Has there been spinal instrumentation? (Potential problems with spinal/epidural anaesthesia.)

  4. Is the cervical spine stable/fused/instrumented? (Potential intubation difficulty.)

  5. Is postural hypotension present? (Likely to be worsened by anaesthesia.)

  6. Is there a history of autonomic dysreflexia (paroxysmal sweating and/or headache) and, if so, what precipitated it?

  7. In cervical lesions, what degree of respiratory support is necessary?

  8. Are there contractures, or pressure sores?

Investigations

  1. FBC—anaemia

  2. U&Es—renal impairment

  3. Liver function tests—possible impairment with chronic sepsis

  4. Pulmonary function tests (FVC)—mandatory with all cervical lesions due to potential respiratory failure.

Is anaesthesia necessary?

  1. In principle, if the planned procedure would require anaesthesia in a normal patient, it will be required for a cord-injured patient.

  2. Minor peripheral surgery below a complete sensory level is likely to be safe without anaesthesia.

  3. Even with minor peripheral surgery, minimal stimulation may provoke muscular spasm that may require anaesthesia to resolve. Local anaesthetic infiltration may prevent its occurrence.

  4. Care should be taken with high lesions (T5 and above) or patients with a history of autonomic dysreflexia undergoing urological procedures.

  5. If the decision is made to proceed without anaesthesia, IV access is mandatory and ECG, NIBP, and pulse oximeter should be applied.

  6. An anaesthetist should be present on ‘standby’ for such procedures.

General anaesthesia

  1. Monitoring should be applied prior to induction and blood pressure measured before and after every position change. Invasive monitoring should be performed with the same considerations as normal.

  2. Despite the theoretical risk of gastro-oesophageal reflux there appears to be no increased risk of aspiration. If intubation is necessary for the desired procedure, anticholinergic pre-treatment is recommended.

  3. Those with cervical cord lesions are likely to require assistance with ventilation under general anaesthesia. If IPPV is performed in tetraplegics, blood pressure may drop precipitously. Fluid preloading and vasopressors (e.g. ephedrine) may be required.

  4. With the exception of paralysis to facilitate intubation, neuromuscular blockade is unlikely to be necessary unless troublesome muscular spasm is present.

  5. Care should be taken to preserve body temperature (wrapping or forced-air warming blankets). Position with respect to pressure areas.

  6. Fluid management may be difficult as blood volume is usually low, and with high cord lesions reflex compensation for blood loss is absent. Fluid preloading coupled with aggressive replacement of blood losses with warmed fluid is recommended.

Centroneuraxial anaesthesia

Advantages

  1. Prevents autonomic dysreflexia.

  2. Unlikely to cause cardiovascular instability since sympathetic tone is already low prior to blockade.

  3. No reported adverse effect of spinal injection of local anaesthetics or opioids on neurological outcome.

  4. Avoids risks of general anaesthesia.

  5. Spinal anaesthesia is more common than epidural anaesthesia as it is technically easier and more reliable in preventing autonomic dysreflexia. Use standard doses of local anaesthetic agents (bupivacaine ‘heavy’ or plain). Intrathecal opioids appear to confer no advantage.

Disadvantages

  1. May be technically difficult to perform. Spinal anaesthesia is usually possible, but epidural techniques are likely to fail in the presence of spinal instrumentation or previous spinal surgery.

  2. There is difficulty in determining the success or level of blockade in complete lesions. Incomplete lesions are tested as usual.

Postoperative care

  1. Tetraplegics are best nursed supine or only slightly head up due to improved ventilatory function in this position.

  2. Temperature should be monitored and hypothermia actively treated.

  3. Analgesia should be provided by conventional means.

  4. Dysreflexia may occur and require drug treatment after removal of precipitating causes (such as pain and urinary retention).

Obstetric anaesthesia

Effect of pregnancy on spinal cord injury

  1. Exaggerated postural hypotension and worsened response to caval occlusion.

  2. Reduced respiratory reserve with increased risk of respiratory failure and pneumonia. Increased oxygen demand.

  3. Increased anaemia due to haemodilution.

  4. Labour is a potent cause of autonomic dysreflexia in those with lesions above T5 (dysreflexia may be the first sign of labour in such patients).

Effect of spinal injury on pregnancy

  1. Increased risk of infection (urinary infection and pressure sores).

  2. Increased risk of premature labour (increasing risk with higher level injury).

  3. Increased risk of thromboembolic complications.

  4. Labour pains will not be felt in complete lesions above T5. Lesion between T5 and T10—some awareness of some contractions.

Management of labour

  1. All cord-injured patients should be reviewed early in pregnancy and a plan formulated for the likely need for analgesia. The relative risks and difficulties of epidural catheter insertion should be predicted and discussed with the patient. A plan for anaesthesia in the event of Caesarean section should also be formulated and recorded in the patient notes.

  2. Epidural analgesia is usually possible in those with high cord lesions without vertebral instrumentation at the level of catheter insertion.

  3. Spinal anaesthesia is usually possible for elective Caesarean section and may be achievable with both single-shot and microcatheter techniques, irrespective of the presence of spinal instrumentation.

  4. General anaesthesia may proceed with the precautions outlined above.

Epidural analgesia in labour

  1. The most effective preventive measure for autonomic dysreflexia is adequate epidural analgesia. Those with high lesions may have an epidural commenced prior to induction of labour.

  2. Hypotension is not usually a problem after adequate fluid preloading (at least 1 litre of crystalloid or colloid). However, hypotension from any cause should be treated aggressively in those with high lesions due to the lack of compensatory mechanisms and a tendency to progressive hypotension. Aortocaval compression should be avoided by careful positioning for the same reasons.

  3. Autonomic dysreflexia has been reported up to 48hr after delivery. If successful block is achieved it would appear prudent to leave the epidural in situ for this time.

  4. Failure to establish adequate epidural blockade may necessitate drug treatment of autonomic dysreflexia (see above).

Further reading

Hambly PR, Martin B (1998). Anaesthesia for chronic spinal cord lesions. Anaesthesia, 53, 273–289.

Myasthenia gravis

Myasthenia gravis is characterised by muscle weakness and fatigability. It is caused by autoimmune disruption of postsynaptic acetylcholine receptors at the neuromuscular junction, with up to 80% of functional receptors lost. The disease may occur at any age but is most common in young adult women. It may be associated with thymus hyperplasia with ∼15% of affected patients having thymomas.

  1. Symptoms range from mild ptosis to life-threatening bulbar palsy and respiratory insufficiency.

  2. Management is usually with oral anticholinesterase medication with or without steroid therapy.

  3. Severe disease may require immunosuppressant therapy, plasmapheresis, or immunoglobulin infusion.

General considerations

  1. All patients with myasthenia are sensitive to the effects of non-depolarising muscle relaxants.

  2. Plasmapheresis depletes plasma esterase levels, prolonging the effect of suxamethonium, mivacurium, ester-linked local anaesthetics, and remifentanil.

  3. Suxamethonium may have an altered effect—patients may be resistant to depolarisation due to reduced receptor activity, requiring increased dose. This, in conjunction with treatment-induced plasma esterase deficiency, leads to an increased risk of non-depolarising (Phase II) block.

Preoperative assessment

  1. Assess the degree of weakness and the duration of symptoms. Those with isolated ocular symptoms of long standing are unlikely to have progressive disease. Those with poorly controlled symptoms should have their condition optimised.

  2. Any degree of bulbar palsy is predictive of the need for both intra- and postoperative airway protection.

  3. Those who have significant respiratory impairment are more likely to require postoperative ventilation.

  4. Take a full drug history and determine the effect of a missed dose of anticholinesterase. Those with severe disease may be very sensitive to dose omission.

Conduct of anaesthesia

  1. Maintain anticholinesterase therapy up to the time of induction. Although theoretical inhibition of neuromuscular blockade is possible, this has never been reported.

  2. Premedication should be minimal.

  3. Avoid use of neuromuscular blocking drugs if possible. Intubation/ ventilation is often achievable using non-paralysing techniques.

  4. Non-depolarising drugs should be used sparingly. Monitor the response with a nerve stimulator. Initial doses of ∼10–20% of normal are usually adequate.

  5. Consider topical LA to the airway.

  6. Short- and intermediate-duration non-depolarising drugs such as atracurium, mivacurium, vecuronium and rocuronium are preferable to longer-acting drugs.

  7. Reversal of neuromuscular blocking drugs should be achievable with standard doses of neostigmine if preoperative symptom control has been good (see below). Avoidance of reversal is preferred since further doses of anticholinesterase may introduce the risk of overdose (cholinergic crisis). Drugs with spontaneous reversal such as atracurium are optimal.

  8. Reversal of neuromuscular blockade using new agents such as sugammadex has been suggested as complete reversal of any drug-induced blockade by rocuronium or vecuronium may be achieved without the need for neostigmine. It may also reduce the confusion between postoperative weakness due to disease and neuromuscular blockade.

  9. Consider insertion of a nasogastric tube if difficulty with bulbar function is anticipated and early return of oral therapy required.

  10. Extubation is possible if neuromuscular function is assessed as adequate using nerve stimulation. Beware of preoperative bulbar function abnormality. The best predictor of safe extubation is >5s head lift.

  11. Regional anaesthesia may reduce the need for postoperative opioids and the risks of respiratory depression.

  12. Facilities for postoperative ventilation should be available.

Principles of perioperative cholinesterase management

  1. An easy conversion for oral pyridostigmine to parenteral (IV, IM, or SC) neostigmine is to equate every 30mg of oral pyridostigmine to 1mg of parenteral neostigmine.

  2. Reversal of neuromuscular blockade is possible with neostigmine if indicated by nerve stimulator—in general, no twitches on train of four means no reversal possible.

  3. Initial dosage of neostigmine should be used under nerve stimulator control, starting with a 2.5–5mg bolus and increasing if necessary with a 1mg bolus every 2–3min to a maximum equivalent dose to the oral pyridostigmine dose (1:30). For example, if the pyridostigmine dose is 120mg 3–4-hourly, then the maximum neostigmine dose should be 4mg (to be repeated after 2–4hr if necessary).

  4. Consider the use of sugammadex (see above).

Rapid sequence induction

  1. Suxamethonium may be used if indicated—doses of 1.5mg/kg are usually effective.

  2. If doubt exists as to the ease of intubation, consider awake techniques.

  3. If suxamethonium is used, do not use any other neuromuscular blockade until muscle function has returned and no fade is present.

Postoperative care

  1. Rapid return of drug therapy is mandatory. Use NG tube if necessary.

  2. In the event of gastrointestinal failure, parenteral therapy is indicated.

Preoperative predictors of need for postoperative ventilation

  1. Major body cavity surgery.

  2. Duration of disease >6yr.

  3. A history of coexisting chronic respiratory disease.

  4. Dose requirements of pyridostigmine >750mg/d.

  5. A preoperative vital capacity of <2.9l.

  6. The best monitors of postoperative respiratory capacity are:

  7. Repeated peak flow measurements.

  8. Vital capacity should be at least twice tidal volume to allow for cough.

Blood gases and pulse oximetry may be normal up to the point of respiratory failure.

Special considerations

Thymectomy

  1. Consensus now favours thymectomy in all adults with generalised myasthenia gravis. Remission rates are high and improvement of symptoms is almost universally attainable (96% gain benefit regardless of preoperative characteristics).

  2. Best results are achieved in those with normal or hyperplastic thymus.

  3. The approach most commonly used is trans-sternal. Transcervical approaches provide less satisfactory access for surgery.

  4. Thoracoscopic thymectomy is gaining acceptance, although its reputed benefit of reduced complications and need for postoperative ventilation is yet to be proven.

  5. Anaesthetic management follows the same general principles outlined above, although all patients need postoperative care in HDU or require ventilation for a short period in the early postoperative period.

  6. Fewer than 8% of patients requiring sternotomy for thymectomy need ventilation for >3hr postoperatively.

  7. Almost all patients will require a degree of muscle relaxation if preoperative preparation has been optimal. Postoperative analgesia can be achieved satisfactorily with epidural or PCA.

Eaton–Lambert syndrome

Eaton–Lambert syndrome (myasthenic syndrome) is a proximal muscle weakness associated with cancer (most often small cell carcinoma of the lung).

  1. The condition is thought to be due to a reduction in the release of acetylcholine (prejunctional failure).

  2. It is not reversed by anticholinesterase therapy and muscle weakness is improved by exercise.

  3. Associated dysautonomia may manifest as dry mouth, impaired accommodation, urinary hesitance, and constipation.

  4. Unlike myasthenia gravis, patients with myasthenic syndrome are sensitive to both depolarising and non-depolarising neuromuscular blocking drugs.

  5. Reduced doses should be used if the disease is suspected. Maintain a high index of suspicion in those undergoing procedures related to diagnosis and management of carcinoma of the lung.

Specific drugs of interest in myasthenia gravis

Drug

Interaction

Notes

Non-depolarising neuromuscular blocking agents

Marked sensitivity

Avoid use if possible. Start with 10% normal dosage. Always monitor neuromuscular function. Use short-and intermediate-acting agents only

Suxamethonium

Resistance to depolarisation and delayed onset of action

No reported clinical ill effects using 1.5mg/kg. Delayed recovery in patients with induced esterase deficiency (plasmapheresis, anticholinesterase treatment). Follow with non-depolarising agents only when full recovery of neuromuscular function noted

Inhalational anaesthetics

All inhalational agents reduce neuromuscular transmission by up to 50%

Avoiding need for neuromuscular blocking agents

IV anaesthetics

No discernible clinical effect on neuromuscular transmission

Total IV anaesthesia with propofol may be useful if neuromuscular function is precarious

Local anaesthetics

Prolonged action and increased toxicity in ester-linked agents with anticholinesterase therapy and plasmapheresis. Exacerbation of myasthenia reported

Use minimum dosage required for adequate block. Monitor respiratory function as with general anaesthesia

Drugs dependent on esterases for elimination

Prolonged effect and increased toxicity if patient on plasmapheresis or (theoretically) anticholinesterase therapy

Suxamethonium, remifentanil, mivacurium, ester-linked local anaesthetics, esmolol, etc.

Antibiotics

Neuromuscular blocking effects may become clinically important

Avoid aminoglycosides (e.g. gentamicin). Similar effects reported with erythromycin and ciprofloxacin

Miscellaneous

All the following agents have a reported effect on neuromuscular transmission: procainamide, β-blockers (especially propranolol), phenytoin, magnesium

Pyridostigmine

Adult: 30–120mg at suitable intervals (usually 4–6-hourly). Do not exceed total daily dose of 720mg Child: <6yr initial dose 30mg; 6–12yr initial dose 60mg. Total daily dose 30–360mg Neonate: 5–10mg every 4hr, 30–60min before feeds

Useful duration of action. No parenteral preparation available. Less potent and slower onset than neostigmine

Neostigmine (oral)

Adult: 15–30mg PO at suitable intervals (up to 2-hourly). Total daily dose 75–300mg Child: <6yr initial dose 7.5mg PO; 6–12yr initial dose 15mg PO. Total daily dose 15–90mg Neonate: 1–5mg PO 4-hourly, 30min before feeds

More marked GI effects than pyridostigmine. Useful if parenteral therapy indicated but more likely to require antimuscarinic (atropine or glycopyrronium) cover if used by this route

Neostigmine (SC/IM)

Adult: 1–2.5mg at suitable intervals (usually 2–4-hourly). Total daily dose 5–20mg Child: 200–500µg 4-hourly Neonate: 50–250µg 4-hourly

IV usage increases side effects and has reduced duration of action. If IV usage is necessary, anticholinergic agents (atropine/glycopyrronium) should be administered

Edrophonium

Adult: 2mg by IV injection followed after 30s by 8mg if no adverse reaction Child: 20µg/kg IV followed by 80µg/kg after 30s if no adverse reaction

Use limited to diagnosis of myasthenia and differentiation of myasthenic and cholinergic crises

Distigmine

Adult: 5mg daily 30min before breakfast. Maximum 20mg daily

Very long acting with risk of cholinergic crisis due to dosage accumulation. Not recommended in small children or neonates

Further reading

Baraka A (1992). Anaesthesia and myasthenia gravis. Canadian Journal of Anaesthesia, 39, 476–486.

Krucylak PE, Naunheim KS (1999). Preoperative preparation and anesthetic management of patients with myasthenia gravis. Seminars in Thoracic and Cardiovascular Surgery, 11, 47–53.

Mirakhur RK (2009) Sugammadex in clinical practice. Anaesthesia, 64, 45–54.

Wainwright AP, Brodrick PM (1987). Suxamethonium in myasthenia gravis. Anaesthesia, 42, 950–957.

Multiple sclerosis

An acquired disease of the central nervous system characterised by demyelinated plaques within the brain and spinal cord. The onset of symptoms usually occurs in early adulthood with 20–30% of cases following a benign course and 5% a rapid deterioration. It is most common in geographical clusters within Europe, North America, and New Zealand.

General considerations

This is an incurable disease, but steroids and interferon have been associated with improved symptom-free intervals. Most patients suffer from associated depression. Baclofen and dantrolene are useful for painful muscle spasm.

  1. Symptoms range from isolated visual disturbance and nystagmus to limb weakness and paralysis.

  2. Respiratory failure due to both respiratory muscle failure and bulbar palsy may be a feature in end-stage disease.

  3. Symptoms are characterised by symptomatic episodes of variable severity with periods of remission for several years.

  4. Permanent weakness and symptoms develop in some patients, leading to increasingly severe disability.

  5. Demyelinated nerve fibres are sensitive to heat. A temperature rise of 0.5°C may cause a marked deterioration in symptoms.

Preoperative assessment and investigation

  1. Preoperative evaluation must include a history of the type of symptoms suffered and a detailed neurological examination. This will allow comparison with postoperative state to elucidate any new lesions.

  2. Respiratory function may be affected. Bulbar palsy causes increased risk of aspiration and reduced airway reflexes in the postoperative period.

Conduct of anaesthesia

  1. General anaesthesia does not affect the course of multiple sclerosis.

  2. Regional anaesthesia does not affect neurological symptoms, but it may be medicolegally prudent to document discussion of relative risks before embarking on nerve or plexus blockade.

  3. Centroneuraxial blockade has been associated with recurrence of symptoms. However, this is reduced by use of minimal concentrations of local anaesthetic/opioid in combination.

  4. Epidural analgesia for labour is not contraindicated—keep LA concentration to a minimum. There is widespread use of spinal anaesthesia for Caesarean section in patients with multiple sclerosis in the UK.

  5. Suxamethonium is associated with a large efflux of potassium in debilitated patients and should be avoided.

  6. Response to non-depolarising drugs is normal, although caution and reduced dosages are indicated in those with severe disability.

  7. Careful cardiovascular monitoring is essential since autonomic instability leads to marked hypotensive responses to drugs and sensitivity to hypovolaemia.

  8. Temperature is important and should be monitored in all patients. Pyrexia must be avoided and should be treated aggressively with antipyretics (paracetamol 1g PR/PO), tepid sponging, and forced-air blowers. Hypothermia may delay recovery from anaesthesia.

Further reading

Drake E, Drake M, Bird J, Russell R (2006). Obstetric regional blocks for women with multiple sclerosis: a survey of UK experience. International Journal of Obstetric Anesthesia, 15, 115–123.

Guillain–Barré syndrome

Guillain–Barré syndrome is an immune-mediated progressive demyelinating disorder characterised by acute or subacute proximal skeletal muscle paralysis. The syndrome is often preceded by limb paraesthesia/back pain and in more than half of affected patients by a viral illness. No single viral agent has been implicated.

More than 85% of patients achieve a full recovery, although this may take several months. The use of steroids in the management of this condition remains controversial.

  1. One-third of patients will require ventilatory support.

  2. The more rapid the onset of symptoms, the more likely the progression to respiratory failure. Impending respiratory failure may be evidenced by difficulty in swallowing and phonation due to pharyngeal muscle weakness.

  3. Inability to cough is a marker of severe respiratory impairment and usually indicates the need for intubation and ventilation.

  4. Autonomic dysfunction is common.

Conduct of anaesthesia

  1. Respiratory support is likely to be necessary, both during surgery and in the postoperative period.

  2. Autonomic dysfunction leads to potential severe hypotension during induction of anaesthesia, initiation of positive pressure ventilation, and postural changes under anaesthesia or recovery.

  3. Hydration should be maintained with wide-bore IV access and pressor agents (ephedrine 3–6mg bolus IV) prepared prior to induction.

  4. Tachycardia due to surgical stimulus may be extreme and atropine may elicit a paradoxical bradycardia.

  5. Suxamethonium should be avoided due to potential catastrophic potassium efflux. The risk of hyperkalaemia may persist for several months after clinical recovery.

  6. Non-depolarising muscle relaxants may not be needed and should be used cautiously.

  7. Epidural analgesia is useful and may avoid the need for systemic opioid analgesia. Epidural opioids have been used to manage distressing paraesthesia in these patients.

Motor neuron disease (amyotrophic lateral sclerosis)

Amyotrophic lateral sclerosis is one of a family of motor neuron diseases. It is a degenerative disorder of upper and lower motor neurons in the spinal cord. It manifests initially with weakness, atrophy, and fasciculation of peripheral muscles (usually those of the hand) and progresses to axial and bulbar weakness.

  1. Progression is relentless, with death from respiratory failure usually occurring within 3yr of diagnosis.

  2. Patients remain mentally competent up to the point of terminal respiratory failure, leading to ethical and moral difficulty in the provision of long-term ventilation.

Conduct of anaesthesia

  1. Bulbar palsy increases the risk of sputum retention and aspiration. Intubation may be necessary. Many patients with advanced disease will have a long-term tracheostomy for airway protection and episodes of mechanical ventilation.

  2. Respiratory support is likely to be necessary, both during surgery and in the postoperative period.

  3. Autonomic dysfunction leads to potentially severe hypotension during induction of anaesthesia, initiation of positive pressure ventilation, and postural changes under anaesthesia or recovery.

  4. Hydration should be maintained with wide-bore IV access if necessary and pressor agents (ephedrine/metaraminol) prepared prior to induction.

  5. Suxamethonium should be avoided due to potential catastrophic potassium efflux.

  6. Non-depolarising agents should be used in reduced dosage if necessary and their action monitored with a nerve stimulator.

Dystrophia myotonica

Dystrophia myotonica (myotonic dystrophy, myotonia atrophica) is the most common of the dystonias (1:20 000), the others being myotonia congenita and paramyotonia. It is an autosomal dominant disease, presenting in the second or third decade of life.

General considerations

  1. Persistent contraction of skeletal muscle follows stimulation. It is characterised by prefrontal balding and cataracts.

  2. The main clinical features are related to muscular atrophy, especially of facial, sternomastoid, and peripheral muscles.

  3. Progressive deterioration/atrophy of skeletal, cardiac, and smooth muscle over time leads to a deterioration in cardiorespiratory function and a (possibly severe) cardiomyopathy.

  4. Further respiratory deterioration occurs due to degeneration of the central nervous system, leading to central respiratory drive depression.

  5. Progressive bulbar palsy causes difficulty in swallowing/clearing secretions and an increased risk of aspiration.

  6. Degeneration of the cardiac conduction system causes dysrhythmia and atrioventricular block.

  7. Mitral valve prolapse occurs in ∼20% of patients.

  8. There is mental deterioration after the second decade.

  9. Endocrine dysfunction may lead to diabetes mellitus, hypothyroidism, adrenal insufficiency, and gonadal atrophy.

  10. Death usually occurs in the fifth or sixth decade.

  11. Pregnancy may aggravate the disease and Caesarean section is more common due to uterine muscle dysfunction.

  12. Therapy is supportive using antimyotonic medications such as procainamide, phenytoin, quinine, and mexiletine.

Preoperative assessment

  1. Assess respiratory reserve, including signs of bulbar palsy (difficulty with cough or swallowing).

  2. Seek signs of cardiac failure and dysrhythmia.

  3. Gastric emptying may be delayed. Premedication with an antacid (ranitidine 150–300mg PO) or a prokinetic (metoclopramide 10mg PO) may be indicated.

Investigations

  1. CXR, spirometry, and arterial blood gases if indicated by respiratory symptoms.

  2. ECG to exclude conduction defects and echocardiography for myocardial dysfunction.

  3. U&Es and glucose to exclude endocrine dysfunction.

Conduct of anaesthesia

  1. Suxamethonium produces prolonged muscle contraction (and potassium release) and should be avoided. Contraction may make intubation, ventilation, and surgery difficult.

  2. Non-depolarising drugs are safe to use but do not always cause muscle relaxation. Use of a nerve stimulator may provoke muscle contraction, leading to misdiagnosis of tetany.

  3. Reversal with neostigmine may also provoke contraction. Non-depolarising agents with short action and spontaneous reversal (atracurium, mivacurium) are preferred.

  4. Reversal of rocuronium and vecuronium is possible without the use of neostigmine using sugammadex.

  5. Intubation and maintenance of anaesthesia can often be achieved without the use of any muscle relaxant.

  6. Invasive arterial monitoring is indicated for significant cardiovascular impairment.

  7. Even small doses of induction agents can produce profound cardio-respiratory depression.

  8. Bulbar palsy increases the need for intubation under general anaesthesia.

  9. Regional anaesthesia does not prevent muscle contraction. Troublesome spasm may be helped by infiltration of local anaesthetic directly into the affected muscle. Quinine (600mg IV) and phenytoin (3–5mg/kg IV slowly) have been effective in some cases.

  10. High concentrations of inhaled anaesthetics should be avoided because of their effect on myocardial contraction and conduction.

  11. Patient warmth must be maintained. Postoperative shivering may provoke myotonia.

Postoperative care

  1. High-dependency care is indicated after anything but minor peripheral surgery. Discharge to low-dependency areas should be considered only if the patient is able to cough adequately and maintain oxygenation on air or simple supplemental oxygen.

  2. Analgesia is best provided, if possible, by regional or local block to avoid the systemic depressant effects of opioids.

Myotonia congenita

This develops in infancy and early childhood and is characterised by pharyngeal muscle spasm leading to difficulty in swallowing. It improves with age and patients have a normal life expectancy.

Paramyotonia

This is extremely rare. It is characterised by cold-induced contraction, only relieved by warming the affected muscle. Anaesthetic management is the same as for myotonic dystrophy. Patient warmth is paramount.

Further reading

Imison AR (2001). Anaesthesia and myotonia—an Australian experience. Anaesthesia and Intensive Care, 29, 34–37.

Muscular dystrophy

The muscular dystrophies comprise a range of congenital muscular disorders characterised by progressive weakness of affected muscle groups. They can be classified according to inheritance:

  1. X-linked: Duchenne's, Becker's

  2. Autosomal recessive: limb-girdle, childhood, congenital

  3. Autosomal dominant: facioscapulohumeral, oculopharyngeal.

Duchenne's muscular dystrophy

This is the most common and most severe form.

General considerations

  1. Sex-linked recessive trait, clinically apparent in males.

  2. Onset of symptoms of muscle weakness at 2–5yr.

  3. The patient is usually confined to a wheelchair by 12yr.

  4. Death usually by 25yr due to progressive cardiac failure or pneumonia.

  5. Cardiac: myocardial degeneration leading to heart failure and possible mitral valve prolapse. Evidence of heart failure is often apparent by 6yr (reduced R wave amplitude and wall motion abnormalities). Isolated degeneration of the left ventricle may lead to right outflow obstruction and right heart failure.

  6. Respiratory: progressive respiratory muscle weakness, leading to a restrictive ventilation pattern, inadequate cough, and eventual respiratory infection and failure.

  7. Possible vascular smooth muscle dysfunction, leading to increased bleeding during surgery.

  8. Associated progressive and severe kyphoscoliosis.

  9. Disease progression may be tracked by serum creatinine kinase levels. These are elevated early in the disease but reduce to below normal as muscles atrophy.

Other muscular dystrophies (Becker's, facioscapulohumeral, and limb-girdle dystrophy) are less severe than Duchenne's dystrophy, with onset at a later age and slower progression of the disease. Isolated ocular dystrophy is associated with a normal lifespan.

Preoperative assessment and investigations

  1. Patients are usually under the care of specialist paediatricians.

  2. CXR, spirometry, and blood gases may be indicated by respiratory symptoms.

  3. Echocardiography is mandatory if the patient is wheelchair bound—myocardial and valve function can be assessed.

  4. Reduced gut muscle tone leads to delayed gastric emptying and increased risk of aspiration.

Conduct of anaesthesia

  1. Antacid premedication (H2 receptor blocker or proton pump inhibitor) with a prokinetic such as metoclopramide may be useful to reduce risk of aspiration.

  2. An antisialogogue such as glycopyrronium may be needed if secretions are a problem.

  3. Careful IV induction of anaesthesia with balanced opioid/induction agent.

  4. Potent inhalational anaesthetics should be used cautiously in these patients because of the risk of myocardial depression.

  5. Suxamethonium should be avoided because of potassium efflux and potential cardiac arrest.

  6. Non-depolarising neuromuscular blockers are safe, although reduced doses are required. Nerve stimulator monitoring should be used.

  7. Respiratory depressant effects of all anaesthetic drugs are enhanced and postoperative respiratory function should be monitored carefully. Those with pre-existing sputum retention and inadequate cough are at high risk of postoperative respiratory failure and may need prolonged ventilatory support.

  8. Regional analgesia is useful to avoid opioid use and potential respiratory depression after painful surgery. Caudal epidural may be technically easier to perform than lumbar epidural in those with kyphoscoliosis.

Further reading

Almenrader N (2006). Spinal surgery in children with non-idiopathic scoliosis: is there a need for routine post operative ventilation? British Journal of Anaesthesia, 97, 851–857.

Malignant hyperthermia

Aetiology

  1. Malignant hyperthermia (MH) is a pharmacogenetic disease of skeletal muscle induced by exposure to all potent volatile anaesthetic agents and the depolarising muscle relaxant suxamethonium.

  2. It is inherited as an autosomal dominant condition and caused by loss of normal Ca2+ homeostasis at some point along the excitation–contraction coupling process on exposure to triggering agents. Any defect along this complex process could result in the clinical features of MH and may explain why differing chemical agents trigger MH and the heterogeneity seen in DNA studies.

  3. The most likely site is the triadic junction between the T tubules, involving the voltage sensor of the dihydropyridine receptor (DHPR), and the ryanodine receptor, a Ca2+ efflux channel on the sarcoplasmic reticulum (SR).

  4. About 70% of MH families are linked to the RYR1 gene located on chromosome 19q. Over 200 mutations have been identified in RYR1 but only 29 have evidence of causality. Other loci have been identified (e.g. chromosomes 1, 3, and 7) but only for small numbers of families.

Epidemiology

  1. Incidence is about 1:10 000–15 000 but difficult to estimate. All races are affected.

  2. Mortality rates have fallen dramatically from 70–80% to 2–3% due to increased awareness, improved monitoring standards, and the availability of dantrolene.

  3. Commonly seen in young adults, males > females, but this may be a lifestyle rather than a true sex difference.

  4. Used to be more frequent in minor operations, e.g. dental/ENT, due to anaesthetic technique, i.e. when suxamethonium and vapour were commonly used.

  5. Previous uneventful anaesthesia with triggering agents does not preclude MH; 75% of MH probands (index cases) have had previous anaesthesia prior to their MH crisis.

  6. Annual UK incidence of confirmed MH cases is falling (currently ∼10–15/yr) due to changes in anaesthetic techniques, e.g. decreased use of suxamethonium, increased use of TIVA and local anaesthesia. However, there is an increased referral rate due to increased index of suspicion.

Clinical presentation

  1. The clinical diagnosis can be difficult as the presentation of MH varies considerably and no one sign is unique to MH. It can be a florid dramatic life-threatening event or have an insidious onset. Rarely it can develop 2–3d postoperatively with massive myoglobinuria and/or renal failure due to severe rhabdomyolysis.

Clinical signs

  1. Signs of increased metabolism: tachycardia, dysrhythmias, increased CO2 production, metabolic acidosis, pyrexia, DIC. Often called a ‘metabolic storm’. Pyrexia develops as a consequence of metabolic stimulation, so it occurs after other signs. A pyrexia developing after recovery from normal anaesthesia is not indicative of MH.

  2. Muscle signs: masseter spasm after suxamethonium, generalised muscle rigidity, hyperkalaemia, high CK, myoglobinuria, renal failure.

  3. The two most important early signs are unexplained, unexpected, increasing heart rate and ETCO2.

Masseter muscle spasm

  1. Masseter muscle spasm (MMS) after suxamethonium defined as impeding intubation and persisting for ∼2min. 30% of patients presenting with MMS alone, even when anaesthesia has proceeded uneventfully, prove to be MH susceptible.

  2. If possible abandon surgery; if not convert to ‘MH safe’ technique (volatile free); allow approximately 15min to ensure that the patient is stabilised. Monitor ETCO2 and temperature, and consider an arterial line.

  3. Additional MH signs increase the likelihood of MH significantly: 50–60% if metabolic signs present, 70–80% if muscle signs present.

  4. Investigations that are particularly useful are the initial and 24hr creatine kinase (CK) and examination of the first voided specimen for myoglobinuria, indicating evidence of muscle damage.

  5. Prolonged severe muscle stiffness greatly in excess of the ‘normal scoline pains’ may occur.

  6. MMS may be the first indication of a previously unsuspected muscle disease, particularly the myotonic conditions. Perform resting CK and EMG. Consider neurological opinion.

Treatment of a crisis

See [link].

  1. ‘Guidelines for the treatment of an MH crisis’ is available from the AAGBI for display in theatres.

After treating a suspected MH crisis

  1. If MH was suspected clinically refer the patient to an MH unit with all the relevant clinical details/anaesthetic chart/laboratory results. The timing of various events is important.

  2. In the meantime warn the patient and family of the potential implications of MH.

  3. MH is not a diagnosis to be made lightly without adequate follow-up.

  4. Unless MH can be clearly excluded on clinical grounds the patient/family will be offered screening to confirm or refute the clinical diagnosis.

  5. The proband is always screened even if the clinical reaction is undoubted. If the proband cannot be screened (e.g. died or too young) the most appropriate relative is screened (e.g. parents of a young child).

Diagnosis of MH susceptibility

  1. Muscle biopsy using the in vitro contracture test (IVCT) remains the gold standard of MH diagnosis. This is an open invasive procedure usually performed under an ultrasound-guided femoral nerve block to remove 8–10 muscle specimens ∼3–4cm long from the vastus medialis muscle. As living samples are used, the patient has to travel to the MH centre.

  2. The IVCT follows a European MH Group (EMHG) protocol exposing muscle tissue to halothane and separately to caffeine under preset conditions in a dedicated laboratory.

  3. The diagnosis is considered positive if the muscle contracts in response to halothane and/or caffeine.

  4. There is a potential for ‘false positive’ MH diagnoses in order to ensure the accuracy of the MH negative diagnosis. The combined EMHG data indicate a specificity of 93.6% and sensitivity of 99%.

  5. If the proband is confirmed as MH susceptible by IVCT, they are screened for the 29 RYR1 mutations currently used for diagnostic purposes by the EMHG for DNA testing of MH.

  6. If a mutation is identified in the proband, family members can be offered an initial DNA blood test for the familial mutation; if a mutation carrier, they are classified as MH susceptible without a muscle biopsy; if mutation negative, a confirmatory biopsy is required for reasons of safety because MH is complex with a small incidence (∼5–10%) of discordant results within families.

  7. If a mutation is not identified in the proband, family members are offered IVCT only.

  8. Family screening is organised on the basis of the autosomal dominant pattern of inheritance, so relatives with a 50% risk are screened first, i.e. parents, siblings, and children; the latter are not screened until aged 10–12yr.

  9. The purpose of family screening is to identify the small number of individuals in a family who are susceptible to MH rather than labelling the whole family. Screening will involve only a small proportion of the family.

  10. Once identified as MH susceptible the MH unit can provide written information about MH, warning cards/discs, and information about the British MH Association (BMHA), a patient support charity.

  11. MH centres should co-ordinate family screening to ensure the appropriate method of testing is offered.

Anaesthesia for known or suspected MH-susceptible patients

  1. MH patients should not be denied necessary surgery solely because of MH.

  2. Preoperative questioning about personal and family anaesthetic history is essential to identify potential MH patients.

  3. It is not absolutely essential to screen suspected cases prior to surgery, providing careful individual assessment has been made of the risks involved.

  4. An MH ‘safe’ technique, i.e. avoiding suxamethonium and all anaesthetic volatile agents, may not pose any additional risk in many circumstances, but will do so in certain situations, e.g. when the preferred technique would have necessitated use of these agents.

  5. All local anaesthetic agents are safe.

  6. Dantrolene is not required prophylactically because of its side effects, but should be readily available.

  7. Standard monitoring is adequate, i.e. ECG, NIBP, SaO2, ETCO2. A baseline core temperature should be established before the procedure and monitored ∼4hr postoperatively.

  8. If no volatile-free machine is available, remove all vaporisers and circuitry from the machine and ventilator, including soda lime, and purge with oxygen for 20–30min. Use new circuits/soda lime/LMAs/ETT, etc.

  9. The MH unit can be contacted for further advice if required.

Anaesthesia for a patient with a known or suspected family history of MH

  1. Establish the family history and the relationship of your patient to the named proband or other tested family members. The MH centre will then be able to advise about the risk to your patient and need for further investigation.

  2. If anaesthesia is urgent and more details unavailable, proceed as for an MH-susceptible patient.

Suspicious previous anaesthetic history

  1. Unexplained/unexpected cardiac arrest/death during anaesthesia carries a 50% risk of MH.

  2. History of postoperative myoglobinuria (red/black urine).

  3. Renal failure in otherwise healthy patient.

  4. Postoperative pyrexia. Establish timing of the pyrexia in relation to surgery. If intraoperative/immediate recovery period was uneventful with the pyrexia developing later on the ward, MH is not implicated. If timing is unclear, the likelihood of MH is low but cannot be excluded.

  5. Take a thorough history of the event. If possible obtain old records and seek further advice from the MH centre. If surgery is urgent proceed as if MH susceptible and resolve problem later.

Obstetric patients

  1. Baby of susceptible parent:

    1. Has 50% chance of being affected if one parent is MH susceptible, so should be treated as potentially MH.

  2. Mother MH susceptible:

    1. Plans for any emergency situation should be prepared with obstetric anaesthetist prior to EDD.

    2. It is essential to anticipate airway problems and consider other options, e.g. awake intubation.

    3. Regional techniques preferred.

    4. For general anaesthesia use an MH-safe technique, substituting suxamethonium with a rapid-onset non-depolarising muscle relaxant, e.g. rocuronium, and maintaining anaesthesia with a propofol infusion.

    5. Ephedrine, oxytocin, and ergometrine can be used.

  3. Father MH susceptible (fetus at risk)

    1. Avoid MH-triggering agents which cross the placenta, i.e. inhalational agents, until after delivery of the baby.

    2. Suxamethonium, being highly charged, can be used as it does not cross the placenta to any great extent.

Associated conditions

  1. Central core disease (CCD) is a non-progressive inherited condition causing peripheral muscle weakness and occasionally musculoskeletal and cardiac problems. It is the only condition known to be associated with MH, but this is not invariable. CCD patients should be treated as potentially MH susceptible but offered screening because of the discordant association. Other muscle diseases are not thought to be related to MH but clearly cause anaesthetic problems in their own right.

  2. Heat stroke and King–Denborough syndrome remain controversial (see [link]).

  3. Neuroleptic malignant syndrome and sudden infant death syndrome are not associated with MH (see [link]).

Anaesthesia for the MH-susceptible patient

MH ‘triggering’ agents

Avoid suxamethonium and all anaesthetic vapours/volatiles

MH ‘safe’ agents

All induction agents including ketamine, all analgesics, all non-depolarising agents, all local anaesthetics

Atropine/glycopyrronium/neostigmine

Ephedrine and other vasopressors

Metoclopramide/droperidol Nitrous oxide, benzodiazepines

Monitoring

ECG, NIBP, ETCO2, core temperature

Check temp 2hr preop to establish baseline and 4–6hr postop

Anaesthetic equipment

If no vapour-free machine is available, remove the vaporisers and blow both the anaesthetic machine and the ventilator with oxygen for 20–30min. Use fresh clean tubing/masks/ET tubes/soda lime etc. If possible select a ventilator with little inner tubing, e.g. Nuffield Penlon

Dantrolene

This is not required prophylactically, as no reaction should occur. It is unpleasant for the patient and markedly prolongs the action of non-depolarising muscle relaxants. However, it should be readily available

MH centres and the British MH Association (BMHA)

  1. There is only one MH centre in the UK: Dr P.J. Halsall, MH Investigation Unit, Clinical Sciences Building, St James's University Hospital, Leeds LS9 7TF. Tel: 0113 2065274; Fax: 0113 2064140; Hotline: 07947 609601 (usually available for medical emergencies only).

  2. The British MH Association (BMHA) is a charitable patient support group which provides the ‘hotline’, warning cards/discs, translations for travel abroad, and newsletters, as well as fundraising for research. Secretary: Mrs A. Winks, 11 Gorse Close, Newthorpe, Nottingham NG16 2BZ. Tel: 01773 717901.

  3. There are 16 MH centres in Europe. Contact the European MH Group Secretary Dr P.J. Halsall (address above) for further details or see the EMHG website: http://www.emhg.org.

  4. For the USA and Canada contact MHAUS, 39 East State St, PO Box 1069, Sherburne, NY 13460, USA. Tel: in North America, 1-800-MH-Hyper; outside North America, 1-315-464-7079; http://www.mhaus.org. Hotline: 1-800-98-MHAUS.

  5. For Australia contact Dr Neil Street, Anaesthetic Dept, The New Children's Hospital, Westmead, NSW, PO Box 3515, Parramatta 2124. Tel: (02) 9845 0000; Fax: (02) 9845 3489.

  6. For New Zealand contact Dr Neil Pollock, Anaesthetic Dept, Palmerston North Hospital, Mid Central Health, Palmerston North Tel: (06) 3569169; Fax: (06) 3508566.

Further reading

Davis PJ, Brandon BW (2009). Editorial. The Association of Malignant Hyperthermia and Unusual Disease: when you're hot you're hot, or maybe not. Anesthesia and Analgesia, 109, 1001–1003.

Ellis FR, Halsall PJ, Christian AS (1990). Clinical presentation of suspected malignant hyperthermia during anaesthesia in 402 probands. Anaesthesia, 45, 838–841.

AAGBI. Guidelines for the Treatment of an MH Crisis. London: Association of Anaesthetists of Great Britain and Ireland. www.aagbi.org.

Halsall PJ, Hopkins PM (2003). Inherited disease and anaesthesia. In: Healy TEJ, Knight PR (eds), A Practice of Anaesthesia, 7th edn. London: Arnold, 363–376.

MacLennan DH, Phillips MS (1992). Malignant hyperthermia. Science, 256, 789–794.

Urwyler A, Deufel T, McCarthy TV, West SP for the European MH Group (2001). Guidelines for the molecular genetic testing of susceptibility to malignant hyperthermia. British Journal of Anaesthesia, 86, 283–287.

Notes:

1 Selim M (2007). Perioperative stroke. New England Journal of Medicine, 356, 706–713.