A Textbook of Clinical Pharmacology and Therapeutics

152 ANAESTHETICS AND MUSCLE RELAXANTS

by plasma cholinesterase, reversal with an anticholinesterase
may not always be necessary, and recovery occurs within
20 minutes. It is useful for short procedures requiring muscle
relaxation (e.g. oesophagoscopy) and avoids the side effects of
suxamethonium.

DEPOLARIZING AGENTS

SUXAMETHONIUM

Use

Suxamethonium(known as succinylcholine in the USA) is the
dicholine ester of succinic acid and thus structurally resem-
bles two molecules of acetylcholine linked together. Solutions
ofsuxamethoniumare unstable at room temperature and
must be stored at 4°C. Suxamethoniumadministered intra-
venously produces paralysis within one minute with good
tracheal intubating conditions. Therefore suxamethoniumis
particularly useful when it is important to intubate the trachea
rapidly, as in patients at risk of aspiration of gastric contents
and patients who may be difficult to intubate for anatomical
reasons. Suxamethoniumis also used to obtain short-duration
muscle relaxation as needed during bronchoscopy, orthopaedic
manipulation and electroconvulsive therapy. The drug is
metabolized rapidly by plasma cholinesterase, and recovery
begins within three minutes and is complete within 15 min-
utes. The use of an anticholinesterase, such as neostigmine, is
contraindicated because it inhibits plasma cholinesterase, reduc-
ing the rate of elimination of suxamethonium.

Adverse reactions

• In about 1 in 2800 of the population, a genetically
  determined abnormal plasma pseudocholinesterase is
  present which has poor metabolic activity (see Chapter 14).
  Suxamethoniumundergoes slow hydrolysis by non-
  specific esterases in these patients, producing prolonged
  apnoea, sometimes lasting for severalhours. Acquired
  deficiency of cholinesterase may be caused by renal
  disease, liver disease, carcinomatosis, starvation,
  pregnancy and cholinesterase inhibitors. However, unlike
  the genetic poor metabolizers, these acquired disorders
  only prolong suxamethoniumapnoea by several minutes
  rather than several hours.


• Muscle fasciculations are often produced several seconds
  after injection of suxamethonium, and are associated with
  muscular pains after anaesthesia.


• Malignant hyperthermia is a rare disorder, see below.


• Muscarinic effects involve bradycardia or asystole.


• An increase in intragastric pressure occurs, but seldom
  causes regurgitation of stomach contents provided the lower
  oesophageal sphincter is normal and there is no history of
  oesophageal reflux.


• There is increased intra-ocular pressure and should not be
  used in glaucoma and open eye injuries.


• Increased plasma Kconcentration, due to potassium
  released from muscle. This is increased if the muscle cells

are damaged: suxamethoniumis contraindicated in patients

with neuropathies, muscular dystrophy, myopathies or

severe burns in whom fatal dysrhythmias have been

reported.

• Anaphylactic reactions are rare.

Key points

Suxamethonium is a depolarizing muscle relaxant.

• It has the most rapid onset of action.


• Its action is not reversed by anticholinesterases.


• Paralysis is usually preceded by painful muscle
  fasciculations. Therefore it should be given immediately
  after induction. Myalgia after surgery may occur.


• Premedication with atropine reduces bradycardia and
  hypersalivation.


• Prolonged paralysis occurs in patients with low plasma
  cholinesterase (genetically determined).


• It is contraindicated in patients with neuropathies,
  myopathies or severe burns, due to risk of hyperkalaemia.

MALIGNANT HYPERTHERMIA

This is a rare complication of anaesthesia. Predisposition is

inherited as an autosomal dominant, the protein abnormality

residing in a sarcoplasmic reticulum calcium channel (the

‘ryanodine receptor’). If untreated, the mortality is 80%. All of

the volatile anaesthetic agents and suxamethonium have been

implicated in its causation. It consists of a rapid increase in

body temperature of approximately 2°C per hour accompan-

ied by tachycardia, increased carbon dioxide production and

generalized muscle rigidity. Severe acidosis, hypoxia, hyper-

carbia and hyperkalaemia can lead to serious dysrhythmias.

Treatment includes the following:

• Anaesthetic should be discontinued and 100% oxygen
  administered via a vapour-free breathing system.


• Dantroleneshould be administered intravenously. This
  blocks the ryanodine receptor, preventing intracellular
  calcium mobilization and relieving muscle spasm.


• Hyperkalaemia should be corrected.


• Employ cooling measures such as tepid sponging, ice
  packs and cold fluids.

LOCAL ANAESTHETICS

INTRODUCTION

Local and regional techniques can be used to provide anaes-

thesia for many surgical procedures. They can also provide

good-quality post-operative analgesia, especially when using

continuous epidural infusions. A local anaesthetic may be the

method of choice for patients with severe cardiorespiratory

disease, as the risks of general anaesthesia and systemic nar-

cotic analgesics are avoided. Local anaesthetic techniques