Anaesthesia and neuromuscular block

Chapter 19 Anaesthesia and neuromuscular block

The administration of general anaesthetics and neuromuscular blocking drugs is generally confined to trained specialists. Nevertheless, non-specialists are involved in perioperative care and will benefit from an understanding of how these drugs act. Doctors from a variety of specialties use local anaesthetics and the pharmacology of these drugs is discussed in detail:

• General anaesthesia.

• Pharmacology of anaesthetics.

• Inhalation anaesthetics.

• Intravenous anaesthetics.

• Muscle relaxants: neuromuscular blocking drugs.

• Local anaesthetics.

• Obstetric analgesia and anaesthesia.

• Anaesthesia in patients already taking drugs.

• Anaesthesia in the diseased, the elderly and children; sedation in intensive therapy units.

General anaesthesia

Until the mid-19th century such surgery as was possible had to be undertaken at tremendous speed. Surgeons did their best for terrified patients by using alcohol, opium, cannabis, hemlock or hyoscine.¹ With the introduction of general anaesthesia, surgeons could operate for the first time with careful deliberation. The problem of inducing quick, safe and easily reversible unconsciousness for any desired length of time in humans began to be solved only in the 1840s when the long-known substances nitrous oxide, ether and chloroform were introduced in rapid succession.

The details surrounding the first use of surgical anaesthesia were submerged in bitter disputes on priority following an attempt to take out a patent for ether. The key events around this time were:

• 1842 – W E Clarke of Rochester, New York, administered ether for a dental extraction; however, the event was not made widely known at the time.

• 1844 – Horace Wells, a dentist in Hartford, Connecticut, introduced nitrous oxide to produce anaesthesia during dental extraction.

• 1846 – On 16 October William Morton, a Boston dentist, successfully demonstrated the anaesthetic properties of ether.

• 1846 – On 21 December Robert Liston performed the first surgical operation in England under ether anaesthesia.²

• 1847 – James Y Simpson, professor of midwifery at the University of Edinburgh, introduced chloroform for the relief of labour pain.

The next important developments in anaesthesia were in the 20th century when the appearance of new drugs, both as primary general anaesthetics and as adjuvants (muscle relaxants), new apparatus and clinical expertise in rendering prolonged anaesthesia safe enabled surgeons to increase their range. No longer was the duration and type of surgery determined by patients’ capacity to endure pain.

Phases of general anaesthesia

Balanced surgical anaesthesia (hypnosis, analgesia and muscle relaxation) with a single drug would require high doses that would cause adverse effects such as slow and unpleasant recovery, and depression of cardiovascular and respiratory function. In modern practice, different drugs are used to attain each objective so that adverse effects are minimised.

The perioperative period may be divided into three phases, and several factors determine the choice of drugs given in each of these. In brief:

Before surgery,

an assessment is made of:

• the patient’s physical and psychological condition

• any concurrent illness

• the relevance of any existing drug therapy.

All of these may influence the choice of anaesthetic technique and anaesthetic drugs.

During surgery,

drugs will be required to provide:

• unconsciousness

• muscular relaxation when necessary

• control of blood pressure, heart rate and respiration.

After surgery,

drugs will play a part in:

• reversal of neuromuscular block (if required)

• relief of pain, and nausea and vomiting

• other aspects of postoperative care, including intensive or high-dependency care.

Patients are often already taking drugs affecting the central nervous and cardiovascular systems, and there is considerable potential for interaction with anaesthetic drugs.

The techniques for giving anaesthetic drugs and the control of ventilation and oxygenation are of great importance, but are outside the scope of this book.

Before surgery (premedication)

The principal aims are to provide:

Anxiolysis and amnesia

A patient who is going to have a surgical operation is naturally apprehensive; this anxiety is reduced by reassurance and a clear explanation of what to expect. Very anxious patients will secrete a lot of adrenaline/epinephrine from the suprarenal medulla and this may make them more liable to cardiac arrhythmias with some anaesthetics. In the past, sedative premedication was given to virtually all patients undergoing surgery. This practice has changed dramatically because of the increasing proportion of operations undertaken as ‘day cases’ (in the USA 75% of all surgical procedures are undertaken as day cases) and the recognition that sedative premedication prolongs recovery. Sedative premedication is now reserved for those who are particularly anxious or those undergoing major surgery. Benzodiazepines, such as temazepam (10–30 mg for an adult), provide anxiolysis and amnesia for the immediate presurgical period.

Analgesia

is indicated if the patient is in pain before surgery, or the analgesia can be given pre-emptively to prevent postoperative pain. Severe preoperative pain is treated with a parenteral opioid such as morphine. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are commonly given orally before operation to prevent postoperative pain after minor surgery. For moderate or major surgery, these drugs are supplemented with an opioid towards the end of the procedure.

Timing

Premedication is given about an hour before surgery.

Gastric contents

Pulmonary aspiration of gastric contents can cause severe pneumonitis. Patients at risk of aspiration are those with full stomachs, in the third trimester of pregnancy or with an incompetent gastro-oesophageal sphincter. A single dose of an antacid, e.g. sodium citrate, may be given before a general anaesthetic to neutralise gastric acid in high-risk patients. Alternatively or additionally, a histamine H₂-receptor blocker, e.g. ranitidine, or proton pump inhibitor, e.g. omeprazole, will reduce gastric secretion volume as well as acidity. Metoclopramide usefully hastens gastric emptying, increases the tone of the lower oesophageal sphincter and is an antiemetic.

During surgery

The aim is to induce unconsciousness, analgesia and muscle relaxation – the anaesthetic triad. Total muscular relaxation (paralysis) is required for some surgical procedures, e.g. intra-abdominal surgery, but most surgery can be undertaken without neuromuscular blockade. A typical general anaesthetic consists of:

Induction

1. Usually intravenous: pre-oxygenation followed by a small dose of an opioid, e.g. fentanyl or alfentanil to provide analgesia and sedation, followed by propofol or, less commonly, thiopental, etomidate or ketamine to induce anaesthesia. Airway patency is maintained with a supraglottic airway device (e.g. laryngeal mask airway (LMA)), a tracheal tube or, for very short procedures, an oral airway and facemask. Insertion of a tracheal tube usually requires paralysis with a neuromuscular blocker and is undertaken if there is a risk of pulmonary aspiration from regurgitated gastric contents or from blood.

2. Inhalational induction, usually with sevoflurane, is undertaken less commonly. It is used in children, particularly if intravenous access is difficult, and in patients at risk from upper airway obstruction.

Maintenance

1. Most commonly with oxygen and air, or nitrous oxide and oxygen, plus a volatile agent, e.g. sevoflurane, desflurane or isoflurane. Additional doses of a neuromuscular blocker or opioid are given as required.

2. A continuous intravenous infusion of propofol can be used to maintain anaesthesia. This technique of total intravenous anaesthesia is relatively common because the quality of recovery may be better than after inhalational anaesthesia. The propofol infusion is often combined with an infusion of remifentanil, an ultra-short-acting opioid.

When appropriate, peripheral nerve block with a local anaesthetic, or neural axis block, e.g. spinal or epidural, provides intraoperative analgesia and muscle relaxation. These local anaesthetic techniques provide excellent postoperative analgesia.

After surgery

The anaesthetist ensures that the effects of neuromuscular blocking drugs and opioid-induced respiratory depression have either worn off or have been adequately reversed by an antagonist; the patient is not left alone until conscious, with protective reflexes restored, and with a stable circulation.

Relief of pain

after surgery can be achieved with several techniques. An epidural infusion of a mixture of local anaesthetic and opioid provides excellent pain relief after major surgery such as laparotomy. Parenteral morphine, given intermittently by a nurse or a patient-controlled system, will also relieve moderate or severe pain but has the attendant risk of nausea, vomiting, sedation and respiratory depression. The addition of regular paracetamol and a NSAID, given orally or parenterally (the rectal route is used much less commonly now), will provide additional pain relief and reduce the requirement for morphine.

Postoperative nausea and vomiting

(PONV) is common after laparotomy and major gynaecological surgery, e.g. abdominal hysterectomy. The use of propofol, particularly when given to maintain anaesthesia, has reduced the incidence of PONV. Antiemetics, such as cyclizine, metoclopramide and ondansetron, may be helpful. Dexamethasone also reduces the incidence of PONV. Many anaesthetists use a combination of two or three of these drugs, a strategy which has been shown to be particularly effective.

Some special techniques

Dissociative anaesthesia

is a state of profound analgesia and anterograde amnesia with minimal hypnosis during which the eyes may remain open; it can be produced by ketamine (see p. 301). It is particularly useful where modern equipment is lacking or where access to the patient is limited, e.g. in prehospital or military settings.

Sedation and amnesia

without analgesia is provided by intravenous midazolam or, less commonly nowadays, by diazepam. These drugs can be used alone for procedures causing mild discomfort, e.g. endoscopy, and with a local anaesthetic where more pain is expected, e.g. removal of impacted wisdom teeth. Benzodiazepines produce anterograde, but not retrograde, amnesia. By definition, the sedated patient remains responsive and cooperative. (For a general account of benzodiazepines and the competitive antagonist flumazenil, see Ch. 20.)

Benzodiazepines can cause respiratory depression and apnoea, especially in the elderly and in patients with respiratory insufficiency. The combination of an opioid and a benzodiazepine is particularly dangerous. Benzodiazepines depress laryngeal reflexes and place the patient at risk of inhalation of oral secretions or dental debris. A continuous infusion of low-dose propofol provides very effective sedation that can be rapidly titrated to produce the desired effect. Use of propofol in this way should be undertaken only by those with advanced airway skills, such as anaesthetists and some emergency physicians.

Entonox,

a 50:50 mixture of nitrous oxide and oxygen, is breathed by the patient using a demand valve. It is particularly useful in the prehospital environment and for brief procedures, such as splinting limbs.

Pharmacology of anaesthetics

All successful general anaesthetics are given intravenously or by inhalation because these routes enable closest control over blood concentrations and thus of effect on the brain.

Mode of action

General anaesthetics act on the brain, primarily on the midbrain reticular activating system, and the spinal cord. Many anaesthetics are lipid soluble and there is good correlation between this and anaesthetic effectiveness (the Overton–Meyer hypothesis); the more lipid soluble tend to be the more potent anaesthetics, but such a correlation is not invariable. Some anaesthetic agents are not lipid soluble and many lipid-soluble substances are not anaesthetics.

Until recently it was thought that the principal site of action of general anaesthetics was relatively non-specific action in the neuronal lipid bilayer membrane. The current view is that anaesthetic agents interact with proteins to alter the activity of specific neuronal ion channels, particularly the fast neurotransmitter receptors such as nicotinic acetylcholine, γ-aminobutyric acid (GABA) and glutamate receptors. The suppression of motor responses to painful stimuli by anaesthetics is mediated mainly by the spinal cord, whereas hypnosis and amnesia are mediated within the brain.

Comparison of the efficacy of inhalational anaesthetics is made by measuring the minimum alveolar concentration (MAC) in oxygen required to prevent movement in response to a standard surgical skin incision in 50% of subjects. The MAC of the volatile agent is reduced by the co-administration of nitrous oxide.

Inhalation anaesthetics

The preferred inhalation anaesthetics are those that are minimally irritant and non-flammable, and comprise nitrous oxide and the fluorinated hydrocarbons, e.g. sevoflurane.

Pharmacokinetics (volatile liquids, gases)

The depth of anaesthesia is correlated with the tension (partial pressure) of anaesthetic drug in brain tissue. This is driven by the development of a series of tension gradients from the high partial pressure delivered to the alveoli and decreasing through the blood to the brain and other tissues. The gradients are dependent on the blood/gas and tissue/gas solubility coefficients, as well as on alveolar ventilation and organ blood flow.

An anaesthetic that has high solubility in blood, i.e. a high blood/gas partition coefficient, will provide a slow induction and adjustment of the depth of anaesthesia. Here, the blood acts as a reservoir (store) for the drug so that it does not enter the brain readily until the blood reservoir is filled. A rapid induction can be obtained by increasing the concentration of drug inhaled initially and by hyperventilating the patient.

Anaesthetics with low solubility in blood, i.e. a low blood/gas partition coefficient (nitrous oxide, desflurane, sevoflurane), provide rapid induction of anaesthesia because the blood reservoir is small and anaesthetic is available to pass into the brain sooner.

During induction of anaesthesia the blood is taking up anaesthetic selectively and rapidly, and the resulting loss of volume in the alveoli leads to a flow of anaesthetic into the lungs that is independent of respiratory activity. When the anaesthetic is discontinued the reverse occurs and it moves from the blood into the alveoli. In the case of nitrous oxide, this can account for as much as 10% of the expired volume and so can significantly lower the alveolar oxygen concentration. Mild hypoxia occurs and lasts for as long as 10 min. Oxygen is given to these patients during the last few minutes of anaesthesia and the early post-anaesthetic period. This phenomenon, diffusion hypoxia, occurs with all gaseous anaesthetics, but is most prominent with gases that are relatively insoluble in blood, for they will diffuse out most rapidly when the drug is no longer inhaled, i.e. just as induction is faster, so is elimination. Nitrous oxide is especially powerful in this respect because it is used at concentrations of up to 70%.

Nitrous oxide

Nitrous oxide (1844) is a gas with a slightly sweetish smell that is neither flammable nor explosive. It produces light anaesthesia without demonstrably depressing the respiratory or vasomotor centre provided that normal oxygen tension is maintained.

Advantages

Nitrous oxide reduces the requirement for other more potent and intrinsically more toxic anaesthetics. It has a strong analgesic action; inhalation of 50% nitrous oxide in oxygen (Entonox) may have similar effects to standard doses of morphine. Induction is rapid and not unpleasant, although transient excitement may occur, as with all anaesthetics. Recovery time rarely exceeds 4 min even after prolonged administration.

Disadvantages

Nitrous oxide is expensive to buy and to transport. It must be used in conjunction with more potent anaesthetics to produce full surgical anaesthesia.

Uses

Nitrous oxide is used to maintain surgical anaesthesia in combination with other anaesthetic agents, e.g. isoflurane or propofol, and, if required, muscle relaxants. Entonox provides analgesia for obstetric practice and for emergency treatment of injuries.

Dosage and administration

For the maintenance of anaesthesia, nitrous oxide must always be mixed with at least 30% oxygen. For analgesia, a concentration of 50% nitrous oxide with 50% oxygen usually suffices.

Contraindications

Any closed, distensible, air-filled space expands during administration of nitrous oxide, which moves into it from the blood. It is therefore contraindicated in patients with: demonstrable collections of air in the pleural, pericardial or peritoneal spaces; intestinal obstruction; arterial air embolism; decompression sickness; severe chronic obstructive airway disease; emphysema. Nitrous oxide will cause pressure changes in closed, non-compliant spaces such as the middle ear, nasal sinuses and the eye.

Precautions

Continued administration of oxygen may be necessary during recovery, especially in elderly patients (see diffusion hypoxia, above).

Adverse effects

The incidence of nausea and vomiting increases with the duration of anaesthesia. Exposure to nitrous oxide for more than 4 h can cause megaloblastic changes in the bone marrow. Because prolonged and repeated exposure of staff, as well as of patients, may be associated with bone marrow depression and teratogenic risk, scavenging systems are used to minimise ambient concentrations in operating theatres.

Halogenated anaesthetics

Halothane was the first halogenated agent to be used widely, but in the developed world it has been largely superseded by isoflurane, sevoflurane and desflurane. A description of isoflurane is provided, and of the others in so far as they differ. The MAC in oxygen of some volatile anaesthetics is:

Isoflurane 1.2%

Sevoflurane 2.0%

Desflurane 6.0%

Halothane 0.74%.

Isoflurane

Isoflurane is a volatile colourless liquid that is not flammable at normal anaesthetic concentrations. It is relatively insoluble and has a lower blood/gas coefficient than halothane or enflurane, which enables rapid adjustment of the depth of anaesthesia. It has a pungent odour and can cause bronchial irritation, making inhalational induction unpleasant. Isoflurane is minimally metabolised (0.2%), and none of the breakdown products has been related to anaesthetic toxicity.

Respiratory effects

Isoflurane causes respiratory depression and diminishes the ventilatory response to carbon dioxide. Although it irritates the upper airway, it is a bronchodilator.

Cardiovascular effects

Anaesthetic concentrations of isoflurane, i.e. 1–1.5 MAC, cause only slight impairment of myocardial contractility. Isoflurane causes peripheral vasodilation and reduces blood pressure. It does not sensitise the heart to catecholamines. In low concentrations (< 1 MAC), cerebral blood flow, intracranial pressure and cerebral autoregulation are maintained. Isoflurane is a potent coronary vasodilator and in the presence of a coronary artery stenosis it may cause redistribution of blood away from an area of inadequate perfusion to one of normal perfusion. This phenomenon of ‘coronary steal’ may cause regional myocardial ischaemia.

Other effects

Isoflurane relaxes voluntary muscles and potentiates the effects of non-depolarising muscle relaxants. Isoflurane depresses cortical EEG activity and does not induce abnormal electrical activity or convulsions.

Sevoflurane

Sevoflurane is less chemically stable than the other volatile anaesthetics in current use. About 2.5% is metabolised in the body and it is degraded by contact with carbon dioxide absorbents, such as soda lime. The reaction with soda lime causes the formation of a vinyl ether (compound A), which may be nephrotoxic. Sevoflurane is less soluble than isoflurane and is very pleasant to breathe, which makes it an excellent choice for inhalational induction of anaesthesia, particularly in children. The respiratory and cardiovascular effects of sevoflurane are very similar to isoflurane, but sevoflurane does not cause ‘coronary steal’. In many hospitals, despite its higher cost, sevoflurane is displacing isoflurane as the most commonly used volatile anaesthetic.

Desflurane

Desflurane has the lowest blood/gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised; this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and cannot be administered with conventional vaporisers. It has a very pungent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia. Despite this limitation, its very rapid recovery characteristics, even after very prolonged anaesthesia, make it an increasingly popular choice for major surgery.

Halothane

Halothane has the highest blood/gas partition coefficient of the volatile anaesthetic agents and recovery from halothane anaesthesia is comparatively slow. It is pleasant to breathe. Halothane reduces cardiac output more than any of the other volatile anaesthetics. It sensitises the heart to the arrhythmic effects of catecholamines and hypercapnia; arrhythmias are common, in particular atrioventricular dissociation, nodal rhythm and ventricular extrasystoles. Halothane can trigger malignant hyperthermia in those who are genetically predisposed (see p. 309).

About 20% of halothane is metabolised and it induces hepatic enzymes, including those of anaesthetists and operating theatre staff. Hepatic damage occurs in a small proportion of exposed patients. Typically fever develops 2–3 days after anaesthesia, accompanied by anorexia, nausea and vomiting. In more severe cases this is followed by transient jaundice or, very rarely, fatal hepatic necrosis. Severe hepatitis is a complication of repeatedly administered halothane anaesthesia (incidence of 1 in 50 000) and follows immune sensitisation to an oxidative metabolite of halothane in susceptible individuals. This serious complication, along with the other disadvantages of halothane and the popularity of sevoflurane for inhalational induction, has almost eliminated its use in the developed world. It remains in common use in other parts of the world because it is comparatively inexpensive.

Oxygen in anaesthesia

Supplemental oxygen is always used with inhalational anaesthetics to prevent hypoxia, even when air is used as the carrier gas. The concentration of oxygen in inspired anaesthetic gases is usually at least 30%, but oxygen should not be used for prolonged periods at a greater concentration than is necessary to prevent hypoxaemia. After prolonged administration, concentrations greater than 80% have a toxic effect on the lungs, which presents initially as a mild substernal irritation, progressing to pulmonary exudation and atelectasis. Use of unnecessarily high concentrations of oxygen in incubators causes retrolental fibroplasia and permanent blindness in premature infants.

Intravenous anaesthetics

Intravenous anaesthetics should be given only by those fully trained in their use and who are experienced with a full range of techniques of managing the airway, including tracheal intubation.

Pharmacokinetics

Intravenous anaesthetics enable an extremely rapid induction because the blood concentration can be raised quickly, establishing a steep concentration gradient and expediting diffusion into the brain. The rate of transfer depends on the lipid solubility and arterial concentration of the unbound, non-ionised fraction of the drug. After a single induction dose of an intravenous anaesthetic, recovery occurs quite rapidly as the drug is redistributed around the body and the plasma concentration reduces. Recovery from a single dose of intravenous anaesthetic is thus dependent on redistribution rather than rate of metabolic breakdown. With the exception of propofol, repeated doses or infusions of intravenous anaesthetics will cause considerable accumulation and prolong recovery. Attempts to use thiopental as the sole anaesthetic in war casualties led to it being described as an ideal form of euthanasia.³

Only gold members can continue reading. Log In or Register to continue

Related

Stay updated, free articles. Join our Telegram channel

Tags: Clinical Pharmacology 11e

Jun 18, 2016 | Posted by admin in PHARMACY | Comments Off

Full access? Get Clinical Tree

Get Clinical Tree app for offline access

Get Clinical Tree app for offline access