Intravenous anaesthetics

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controlled infusion (TCI) provides a convenient method for giving a continuous infusion of propofol.

Central nervous system. Propofol causes dose-dependent cortical depression and is an anticonvulsant. It depresses laryngeal reflexes more than barbiturates, which is an advantage when inserting a laryngeal mask airway.

Cardiovascular system. Propofol reduces vascular tone, which lowers systemic vascular resistance and central venous pressure. The heart rate remains unchanged and the result is a fall in blood pressure to about 70-80% of the preinduction level and a small reduction in cardiac output.

Respiratory system. Unless it is undertaken very slowly, induction with propofol causes transient apnoea. On resumption of respiration there is a reduction in tidal volume and increase in rate.

Metabolism. Propofol is conjugated in the liver by glucuronidation making it more water soluble; 88% then appears in the urine and 2% in the faeces.

Thiopental (thiopentone)

Thiopental is a very short-acting barbiturate, which induces anaesthesia smoothly, within one arm-tobrain circulation time. The typical induction dose is 3-5mg/kg. Rapid distribution (initial t1^ 4min) allows swift recovery after a single dose. The terminal t'/2 of thiopental is 11 h and repeated doses or continuous infusion lead to significant accumulation in fat and very prolonged recovery. Thiopental is metabolised in the liver. The incidence of nausea and vomiting after thiopental is slightly higher than after propofol. The pH of thiopental is 11 and considerable local damage results if it extravasates. Accidental intra-arterial injection will also cause serious injury distal to the injection site.

Central nervous system. Thiopental has no analgesic activity and may be antanalgesic. It is a potent anticonvulsant. Cerebral metabolic rate of oxygen consumption (CMROz) is reduced, which leads to cerebral vasoconstriction with a concomitant reduction in cerebral blood flow and intracranial pressure.

Cardiovascular system. Thiopental reduces vascular tone, causing hypotension and a slight compensatory increase in heart rate. Antihypertensives or diuretics may augment the hypotensive effect.

Respiratory system. Thiopental reduces respiratory rate and tidal volume.

Methohexitone is a barbiturate similar to thiopental but its terminal t1/, is considerably shorter. Since the introduction of propofol, its use is almost entirely confined to inducing anaesthesia for electrocontro-vulsive therapy (ECT). Propofol shortens seizure duration and may reduce the efficacy of ECT.

Etomidate is a carboxylated imidazole, which is formulated in a mixture of water and propylene glycol. It causes pain on injection and excitatory muscle movements are common on induction of anaesthesia. It is associated with a 20% incidence of nausea and vomiting. Etomidate causes adrenocortical suppression by inhibiting 11 (3- and 17 (3-hydroxylase and for this reason is not used for prolonged infusion; single bolus doses cause shortlived, clinically insignificant adrenocortical suppression. Despite all these disadvantages it remains in common use, particularly for emergency anaesthesia, because it causes less cardiovascular depression and hypotension than thiopental or propofol.

Ketamine

Ketamine is a phencyclidine (hallucinogen) derivative and an antagonist of the NMDA-receptor.4 In anaesthetic doses it produces a trance-like state known as dissociative anaesthesia (sedation, amnesia, dissociation, analgesia).

Advantages. Anaesthesia persists for up to 15 min after a single intravenous injection and is characterised by profound analgesia. Ketamine may be used as the sole analgesic agent for diagnostic and minor surgical interventions. In contrast to most other anaesthetic drugs, ketamine usually produces a tachycardia and increases blood pressure and cardiac output. This effect makes it a popular choice for inducing anaesthesia in shocked patients. The

4 N-methyl-D-aspartate.

cardiovascular effects of ketamine are accompanied by an increase in plasma noradrenaline (norepinephrine) concentration. Because pharyngeal and laryngeal reflexes are only slightly impaired, the airway may be less at risk than with other general anaesthetic techniques. It is a potent bronchodilator and is sometimes used to treat severe bronchospasm in those asthmatics requiring mechanical ventilation. (See also Dissociative anaesthesia, p. 348.)

Disadvantages. Ketamine produces no muscular relaxation. It increases intracranial and intraocular pressure. Hallucinations can occur during recovery (the emergence reaction), but they are minimised if ketamine is used solely as an induction agent and followed by a conventional inhalational anaesthetic. Their incidence is reduced by administration of a benzodiazepine both as a premedication and after the procedure.

Uses. Subanaesthetic doses of ketamine can be used to provide analgesia for painful procedures of short duration such as the dressing of burns, radio-therapeutic procedures, marrow sampling and minor orthopaedic procedures. Ketamine can be used for induction of anaesthesia prior to administration of inhalational anaesthetics, or for both induction and maintenance of anaesthesia for short-lasting diagnostic and surgical interventions, including dental procedures that do not require skeletal muscle relaxation. It is of particular value for children requiring frequent repeated anaesthetics.

Dosage and administration. Premedication with atropine will reduce the salivary secretions produced by ketamine and a benzodiazepine will reduce the incidence of hallucinations.

Induction. Intravenous route: 1-2 mg/kg by slow intravenous injection over a period of 60 seconds. A dose of 2 mg/kg produces surgical anaesthesia within 1-2 min, which will last 5-10 min. Intramuscular route: 5-10 mg/kg by deep intramuscular injection. This dose produces surgical anaesthesia within 3-5 min and may be expected to last up to 25 min.

Maintenance. Following induction, serial doses of 50% of the original intravenous dose or 25% of the intramuscular dose is given to prevent movement in response to surgical stimuli. Tonic and clonic movements resembling seizures occur in some patients. These do not indicate a light plane of anaesthesia or a need for additional doses of the anaesthetic.

A dose of 0.5 mg/kg i.m. or i.v. provides excellent analgesia and may be supplemented by further doses of 0.25 mg/kg.

Recovery. Return to consciousness is gradual. Emergence reactions with delirium may occur. Their incidence is reduced by benzodiazepine premedication and by avoiding unnecessary disturbance of the patient during recovery.

Contraindications include: moderate to severe hypertension, congestive cardiac failure or a history of stroke; acute or chronic alcohol intoxication, cerebral trauma, intracerebral mass or haemorrhage or other causes of raised intracranial pressure; eye injury and increased intraocular pressure; psychiatric disorders such as a schizophrenia and acute psychoses.

Precautions. Ketamine should be used under the supervision of a clinician experienced in tracheal intubation, should this become necessary. Pulse and blood pressure must be monitored closely. Supplementary opioid analgesia is often required in surgical procedures causing visceral pain.

Use in pregnancy. Ketamine is contraindicated in pregnancy before term, since it has oxytocic activity. It is also contraindicated in patients with eclampsia or pre-eclampsia. It may be used for assisted vaginal delivery by an experienced anaesthetist. Ketamine is better suited for use during caesarean section; it causes less fetal and neonatal depression than other anaesthetics.

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