Intravenous Anaesthetic Agents

Intravenous anaesthetic agents have been used since the early 1930's. Intravenous agents for anaesthesia are useful as they rapidly induce anaesthesia. Added to this they can also be used for maintenance of anaesthesia and they are associated with rapid removal from the circulation ending the anaesthesia. Intravenous (IV) anaesthetics are usually used for induction of anaesthesia and maintenance is achieved by inhalational anaesthetics supplemented with IV agents. Total intravenous anaesthesia can also be used in which only IV anaesthetic agents are used throughout however the depth of anaesthesia can be great and care is needed.

Once an IV anaesthetic agent is given the plasma levels will rise rapidly and then slowly decline. Nearly all agents lead to anaesthetic affect within one arm-brain circulation. Once the drug crosses the blood brain barrier anaesthesia is produced. Anaesthetic agents are affected by protein binding, cardiac output, lipid solubility and speed of intravenous injection.

This depends on removal of the IV agent from the receptor sites beyond the blood brain barrier. For IV anaesthetic agents this mostly depends on redistribution to other tissues e.g. liver, kidney and muscle. Some agents will also be metabolised (usually by the liver) or less often renally excreted. Usually all three of these occur at differing rates.

• Shocked patients
• Significant hepatic impairment
• Ill patients
• Debilitated patients

The following sections will look at some of the commonest IV anaesthetic agents namely: thiopental, propofol, ketamine, etomidate and midazolam.

Phenobarbital was used for IV anaesthesia in the 1920's but its affects were unpredictable and recovery from anaesthesia was also lengthy. Thus it is no longer used for anaesthesia although it is still used in status epilepticus. Thiopental is one of the most commonly used IV anaesthetic agents around the world. It is lipid soluble so levels in the brain rise rapidly and it can accumulate over long periods (thus for short procedures ideally).

Method of action

Binds to GABA receptors and enhances both the affects and also mimics the action of GABA thus suppressing synaptic responses

Pharmacological affects when given intravenously

• Anaesthesia within 30 seconds of injection
• Hypnosis
• Poor analgesic
• Depressed myocardial contractility
• Peripheral vasodilatation
• Reduced ventilatory drive - few seconds of apnoea usually seen
• Poor muscle relaxation
• Rapid recovery (due to redistribution) but some sedative affects may last for 24 hours

Uses

• Induction or maintenance of anaesthesia
• Treatment of status epilepticus
• Reduction of intracranial pressure

Administration

• Available as 2.5 or 5% solution
• 5% solution more toxic thus use not recommended
• Antecubital fossa should be avoided as extravasation may cause medial nerve damage
• Test volume of 1-2 ml usually given
• Cannula should be flushed before vecuronium or atracurium given as can precipitate
• Accumulates with repeated doses

Cautions and contraindications

• Hypovolaemia or shock
• Cardiovascular disease e.g. valvular stenosis, constrictive pericarditis
• Opioids - may enhance respiratory depression
• Asthma
• Severe hepatic disease
• Adrenocortical insufficiency
• Muscle disease e.g. myasthenia gravis, myotonic dystrophy (exaggerated respiratory depression)
• Absolute contraindications include - upper airway obstruction, definite hypersensitivity and porphyria

Adverse reactions

• Hypotension - enhanced in hypovolaemia or shock or if reduced cardiac output
• Arrhythmias
• Respiratory depression - risk increased if patient given opioids beforehand
• Thrombophlebitis
• Tissue necrosis if extravasated
• Arterial injection - patient has immediate burning pain and this can result in ischaemia or gangrene
• Laryngeal spasm - especially if foreign body present in airway
• Bronchospasm - especially if asthmatic
• Allergic reactions - from urticaria to fatal anaphylactoid reactions

Pregnancy

Thiopental crosses the placenta and if excessive fetal levels are achieved then respiratory or cardiovascular depression may occur. Contra-indicated in breast feeding.

This is a relatively new agent having only come on to the market in the mid 1980's. It is extremely lipid soluble and is associated with rapid recovery. Recovery relates to metabolism in the liver and probably other extrahepatic sites.

Pharmacological affects when given intravenously

• Anaesthesia within 20 -40 seconds of injection
• More arterial hypotension compared with thiopentone (due mostly to vasodilatation)
• Reduced ventilatory drive - (longer than thiopental)
• Muscle tone reduced but movements can still occur

Uses

• Induction or maintenance of anaesthesia
• Sedation

Administration

Usually given as an infusion

Cautions and contraindications

• Hypovolaemia or shock
• Cardiovascular disease e.g. valvular stenosis, constrictive pericarditis
• Opioids - may enhance respiratory depression
• Severe hepatic disease
• Adrenocortical insufficiency
• Muscle disease e.g. myasthenia gravis (exaggerated respiratory depression)
• Absolute contraindications include - upper airway obstruction and definite hypersensitivity

Propofol is used for induction in children and adolescents for short sedation but not for long infusions, as on an ICU. Caution must be exercised however, as there is a risk of fatal effects including metabolic acidosis, cardiac failure, rhabdomyolysis, hyperlipidaemia and hepatomegaly.

Adverse reactions

• Hypotension - enhanced in hypovolaemia or shock or if reduced cardiac output
• Bradycardia (may need to give antimuscarinic)
• Respiratory depression with transient apnoea
• Excitatory phenomena - convulsions on giving propofol and during recovery
• Pain on injection (less if large vein used)
• Flushing
• Allergic reactions e.g. rash, anaphylaxis
• Thrombophlebitis
• Rarely - pancreatitis, pulmonary oedema, urine discoloration and sexual disinhibition have been reported

Pregnancy

Use of propofol in obstetrics and breast feeding mothers not recommend (can be used in terminations)

A rapid acting induction agent with a short duration of action (2-3 min) as rapidly redistributed. Cardiovascular and respiratory depression is less than thiopental and propofol. It is used for outpatient anaesthesia as recovery is rapid and in patients with cardiovascular compromise. There is no hangover affect making it useful for day case surgery.

Adverse affects

• Nausea and vomiting - worse than propofol
• Pain on injection
• Venous thrombosis post injection
• Extraneous movements (reduced by pre-med with benzodiazepine)
• Excitatory phenomena
• Emergence phenomena - restlessness and delirium during recovery
• Suppresses synthesis of cortisol - only a problem if continuous administration

Absolute contraindications

• Upper airway obstruction
• Porphyria
• Adrenal insufficiency

Different from other IV agents as causes dissociative anaesthesia rather than generalised CNS depression. Ketamine is extremely lipid soluble and associated with prolonged recovery and is rarely used now. Has the potential for abuse and dependence. Ketamine is commonly used in paediatrics for minor procedures e.g. burns dressing changes, laceration repair and other procedural sedation. It is also considered for induction of anaesthesia in children in certain circumstances e.g. bronchospasm or haemodynamic compromise.

Pharmacological affects when given intravenously

• Anaesthesia within 30 - 60 seconds of injection, for 10 -15 minutes
• Potent analgesic
• Amnesia for 1 hour after recovery
• Increased arterial pressure and heart rate
• Cardiac output increase with increased oxygen consumption by the myocardium
• Reduced ventilatory drive
• Muscle tone increased and spontaneous movements may occur
• Salivation increased

Uses

• Induction or maintenance of anaesthesia
• Useful in shocked patient

Administration

Can also produce anaesthesia when given intramuscularly

Cautions and contraindications

• Hypertension
• Ischaemic heart disease
• Avoid in patients with a psychotic tendency
• Absolute contraindications - airway obstruction and raised intracranial pressure

Adverse reactions

• Hypertension and tachycardia
• Extraneous muscle movements
• Emergence delirium, hallucinations and nightmares
• Salivation
• Increased intracranial pressure
• Skin rashes

Benzodiazepines do not cause true general anaesthesia as patient is still aware and not relaxed enough for surgery. Midazolam is a benzodiazepine which acts by potentiating neural inhibition mediated by GABA. Midazolam has a slow onset of action (2-3 min) and recovery is rapid. It provides sedation with amnesia giving the illusion of having had a general anaesthetic.

Actions on the central nervous system

• Anxiolytic
• Sedation
• Hypnosis
• Anterograde amnesia
• Anticonvulsant

Other actions include muscle relaxation

Midazolam has less adverse affects on the cardiovascular system compared with other anaesthetic agents

Uses

• Sedation
• Induction of anaesthesia

Cautions and contraindications

• Hepatic and renal impairment
• Cardiac or respiratory disease
• Myasthenia gravis
• Children
• Previous drug or alcohol abuse
• Absolute contraindications include - marked neuromuscular respiratory weakness, respiratory depression or pulmonary insufficiency

Adverse effects

• GIT disturbance
• Jaundice
• Hypotension
• Laryngospasm and bronchospasm
• Cardiac arrest
• Respiratory depression and arrest
• Dizzy
• Slowed reaction time
• Ataxia
• Confusion
• Dysarthria
• Impaired cognition
• Allergy - anaphylaxis