The course of general anaesthesia can be divided into three phases: (1) induction, (2) maintenance, and (3) emergence. Inhalational anaesthetics are particularly useful in the induction of paediatric patients unwilling to accept an intravenous line or in patients of any age group with potentially difficult airways. In contrast, adults often prefer rapid induction with intravenous agents, although the non-pungency and rapid onset of sevoflurane have made a single-breath induction practical for adults. Regardless of the patient’s age, anaesthesia is often maintained with inhalational agents. A total intravenous technique is indicated if contraindications to inhalational agents exist, e.g. malignant hyperthermia, or if the specific surgical procedure requires total intravenous anaesthesia, e.g. laryngoscope or rigid bronchoscopy.

INTRODUCTION
The induction of general anaesthesia involves the transition from the awake state to unconsciousness. The first report of inhalation induction was published in 1847 by William Morton after his famous demonstration of the potential of ether as an anaesthetic at the Massachusetts General Hospital. For almost the first 100 years of general anaesthesia there was little alternative available to the volatile induction and maintenance of anaesthesia (VIMA). However, early agents were weak, highly irritant and slow acting. When the ultra short acting barbiturate thiopentone was introduced into clinical practice, the volatile induction technique fell out of favour due to the smoother and more rapid induction with thiopentone. Early intravenous induction agents were pharmacokinetically unsuitable for maintenance of anaesthesia and volatile agents were therefore still required. Due to developments in inhalational as well as intravenous agents, modern anaesthetic practice consists of:

1. Volatile induction and maintenance of anaesthesia (VIMA).
2. Intravenous (and, rarely, intramuscular) induction followed by volatile maintenance.
3. Total intravenous anaesthesia (TIVA).

VIMA
Background
Halothane was introduced into clinical practice in 1957 and was since then used for inhalational induction and maintenance. However, halothane still had a number of shortcomings as an induction agent as it is slow to induce patients compared to the intravenous route, and for many patients its pungent smell is unacceptable. Halothane was mainly used for inducing children as well as adults where intravenous induction was contra-indicated.

With the introduction of sevoflurane in the early nineties, a new agent appeared that can compete favourably with the intravenous agents in both its speed of action and quality of induction. For an agent to be suitable for VIMA, it should possess the following properties:

• A low MAC (thereby excluding nitrous oxide).
• A low blood /gas solubility, allowing rapid induction, titration as well as emergence.
• A non-pungent odour and minimal airway irritation, even at high concentrations, so that high inspired concentrations can be delivered to induce anaesthesia rapidly (thereby excluding desflurane).

Sevoflurane fulfills these requirements, and, further, due to its low potential for organ toxicity and a relatively stable cardiovascular profile, it is suitable for single agent VIMA. Difficulties in the transition from intravenous induction to volatile maintenance include apnoea after induction and thus a decrease in uptake of the volatile agent, as well as initial cardiovascular depression and hypotension from the intravenous agent followed by excessive stimulation if the patient is not deep enough from the volatile agent by the time the intravenous agent has redistributed. This can result in coughing, laryngospasm, a pressor response, or even awareness.

VIMA is recommended in the following situations:

1. Difficult airways - intravenous induction is contra-indicated in a patient where the ability to maintain the airway is in doubt. This includes a potentially difficult intubation due to tumours, trauma, infections, congenital abnormalities and inadequate neck extension or mouth opening.
2. In patients where it is desirable to maintain spontaneous ventilation, e.g. patients with large goitres or mediastinal tumours that could collapse the airways if spontaneous ventilation is abolished. In patients with bronchopleural fistulae, spontaneous ventilation should be maintained until a double-lumen tube is placed.
3. Paediatric patients.
4. Patients with difficult intravenous access or needle phobia.
5. Short day-case procedures.
6. Minimally invasive procedures with little post-operative pain.
7. Mentally retarded or psychiatric patients.
8. Elderly patients with cardiovascular disease.

Contra-indications for VIMA:

1. Risk of aspiration, e.g. full stomach, pregnancy, emergency procedures -thus patients requiring a rapid sequence induction.
2. Patient refusal.

The advantages of VIMA with sevoflurane over halothane can be summarised briefly: sevoflurane is less arrhythmogenic and less of a cardiovascular depressant in children; it is nonpungent and lacks the irritant effect of halothane on the airway; it is accepted more readily and provides a smoother, faster and less traumatic induction; and sevoflurane neither impairs liver function, even with prolonged use, nor exacerbates pre-existing liver dysfunction. (However, it should be considered unsafe in patients with a history or suspicion of previous volatile associated hepatitis).

If halothane is used, a gradual induction technique in which the patient breathes increasing concentrations of anaesthetic is tolerated far better than high initial halothane concentrations.

With sevoflurane VIMA it is possible to insert a laryngeal mask or endotracheal tube without the use of muscle relaxants if these are not required for the procedure or could have detrimental effects (e.g. in certain patients with neuromuscular diseases).

The advantages of avoiding muscle relaxants in patients receiving VIMA include reduction in the risk of awareness and the avoidance of adverse reactions to these agents, prolonged blocks, drug interactions and inadequate reversal.

In cases where post-operative pain is expected or profound muscle relaxation is required, VIMA is supplemented with adjuvant agents.

The quality of recovery from VIMA with sevoflurane (clear headedness) exceeds that of TIVA with propofol and propofol, thiopentone or etomidate induction followed by maintenance with isoflurane. Discharge from the recovery room also occurs earlier. As with desflurane, this faster emergence has been associated with delirium in some paediatric patients, which can be successfully treated with 1-2ug/kg fentanyl.

INHALATIONAL ANAESTHETICS
There are many steps between the administration of an anaesthetic from a vaporizer and its deposition in the brain (Figure 1).

FIGURE 1: INHALATION ANAESTHETIC AGENTS MUST PASS THROUGH MANY BARRIERS BETWEEN THE ANAESTHESIA MACHINE AND THE BRAIN.

Comparing the different inhaled agents, a more rapid uptake of a particular anaesthetic agent, and thus a greater difference between its inspired and alveolar concentrations, produces a slower rate of induction by that agent.

Three factors affect anaesthetic uptake:
• Its solubility in blood.
• Alveolar blood flow.
• Partial pressure difference between alveolar gas and venous blood.

Solubility
Insoluble agents, such as nitrous oxide, are taken up by the blood less avidly than are soluble agents, such as halothane. As a consequence, the alveolar concentration of nitrous oxide rises faster than that of halothane, and induction is faster. The relative solubility of an anaesthetic in blood and air is expressed as the blood/gas partition coefficient (Table 1).

TABLE 1: PROPERTIES OF MODERN INHALATION ANAESTHETICS

1 MAC values for 30 to 55 year old human subjects expressed as a percentage of 1 atm. High altitude requires a higher inspired concentration of anaesthetic to achieve the same partial pressure.

Alveolar blood flow
Uptake is affected by alveolar blood flow, which, in the absence of pulmonary shunting, is essentially equal to cardiac output. If the cardiac output drops to zero, so will anaesthetic uptake. As cardiac output increases, anaesthetic uptake increases, the rise in alveolar partial pressure slows, and induction is delayed. The effect of changing cardiac output is less pronounced for insoluble anaesthetics, since so little is taken up regardless of alveolar blood flow. Lowoutput states predispose patients to overdosage with soluble agents, since the rate of rise in alveolar concentrations will be markedly increased. Higher than anticipated levels of volatile anaesthetics, which are also myocardial depressants (e.g. halothane), may create a positive feedback loop by lowering cardiac output even further.

Partial pressure difference between alveolar gas and blood The alveolar concentration of an inhaled anaesthetic that prevents movement in 50% of patients in response to a standardised stimulus (e.g. surgical incision) is the minimum alveolar concentration (MAC).

This is a useful measurement, because it mirrors brain partial pressure and allows comparisons of potency between agents. However, it should be considered as a statistical average with limited value in managing individual patients, especially during times of rapidly changing alveolar concentrations (e.g. induction). The MAC values for the commonly used inhalation agents are given in Table 1.

The MAC values for different anaesthetics are roughly additive, e.g. a mixture of 0.5 MAC of nitrous oxide (53%) and 0.5 MAC of halothane (0.37%) approximates the degree of central nervous depression of 1.0 MAC of isoflurane (1.2%). 65% of nitrous oxide decreases the MAC of volatile anaesthetics by approximately 50%. Roughly:

• 1.3 MAC of any of the volatile anaesthetics (e.g. for halothane: 1.3 x 0.74% = 0.96%) has been found to prevent movement in about 95% of patients;
• 0.3-0.4 MAC is associated with awakening from anaesthesia (MAC awake).

MAC can be altered by several physiological and pharmacological variables. The change in MAC with age is striking: MAC increases from birth until two to three months of age, thereafter steadily declining with aging, although there are slight increases at puberty. A 6% decrease in MAC per decade of age, regardless of the volatile anaesthetic, is reported. MAC is relatively unaffected by species, sex or duration of anaesthesia.

Recovery
Recovery from anaesthesia depends on lowering anaesthetic concentration in brain tissue. The most important route for elimination of inhalational anaesthetics is the alveolus. Many of the factors that speed accelerate induction also speed accelerate recovery: elimination of rebreathing, high fresh gas flows, low anaesthetic-circuit volume, low absorption by the anaesthetic circuit, decreased solubility, high cerebral blood flow, and increased ventilation.

Nitrous oxide elimination is so rapid that it dilutes alveolar oxygen and CO₂. The resulting diffusion hypoxia is prevented by administering 100% oxygen for 5-10 minutes after discontinuing nitrous oxide. The rate of recovery is usually faster than induction because tissues that have not reached equilibrium will continue to take up anaesthetic agents until the alveolar partial pressure falls below tissue partial pressure. This redistribution does not occur to the same extent after prolonged anaesthesia and, therefore, the speed of recovery also depends on the length of time of the anaesthetic.

The newest generation of inhalational agents includes sevoflurane, desflurane and xenon. These agents have distinct advantages over the older anaesthetics but are more expensive. The clinical pharmacology of the most commonly used inhalational agents is summarised in Table 2.

TABLE 2: CLINICAL PHARMACOLOGY OF INHALATIONAL ANAESTHETICS

	Nitrous Oxide	Halothane	Enflurane	Isoflurane	Desflurane	Sevoflurane
Cardiovascular     Blood pressure     Heart rate     Systemic vascular resistance     Cardiac output1	N/C N/C N/C N/C	N/C		N/C	N/C or N/C or	N/C
Respiratory     Tidal volume     Respiratory rate     Resting PaCO2	N/C
Cerebral     Blood flow     Intracranial pressure     Cerebral metabolic rate2     Seizures
Neuromuscular     Nondepolarizing blockade
Renal     Renal blood flow     Glomerular filtration rate     Urinary output					? ?	? ?
Hepatic     Blood flow
Metabolism3	0.004%	15-20%	2-5%	0.2%	<0.1%	2-3%
Trigger of malignant hyperthermia	-	+	+	+	+	+

1 Controlled ventilation.
2 CMRO2 would increase with enflurane-induced seizure.
3 Percentage of absorbed anaesthetic undergoing metabolism.
N/C = no change; ? = uncertain.

Additional comments regarding the most commonly used inhalational agents follow.

Nitrous oxide
Nitrous oxide is essentially odourless and relatively inexpensive. Myocardial depression may be unmasked in patients with coronary artery disease or severe hypovolemia. The hypoxic drive is markedly depressed by even small amounts of nitrous oxide - this is of great importance in the recovery room where patients with low arterial oxygen tension may go unrecognized. Nitrous oxide has been implicated as a cause of postoperative nausea and vomiting. Prolonged exposure to nitrous oxide can result in bone marrow depression (after as little as 4 hours of anaesthesia) and neurological deficits (peripheral neuropathy). Because of possible teratogenic effects, nitrous oxide should be avoided in pregnancy.

Halothane
Halothane is the least expensive volatile anaesthetic. A dose-dependent reduction of arterial blood pressure is due to direct myocardial depression - 2.0 MAC of halothane results in a 50% decrease of blood pressure and cardiac output. Although halothane is a coronary artery vasodilator, coronary blood flow decreases due to the drop in systemic arterial pressure. Halothane sensitizes the heart to the dysrhythmogenic effects of adrenaline and doses above 1.5mg/kg should be avoided. The hypoxic drive is severely depressed (at 0.1 MAC) and the apnoeic threshold, the highest PaCO2 at which a patient remains apnoeic, rises. Halothane is a potent bronchodilator - probably the best under the currently available volatile anaesthetics. Patients exposed to multiple halothane anaesthetics at short intervals, middle-aged obese women, and persons with a familial predisposition to halothane toxicity, or a personal history of toxicity, are considered to be at increased risk for halothane hepatitis, although this condition is extremely rare (1 in 35000 cases). Halothane should be used with great caution in patients with intracranial mass lesions because of the possibility of intracranial hypertension.

Isoflurane
Isoflurane causes minimal cardiac depression in vivo. Dilation of normal coronary arteries could theoretically divert blood away from fixed stenotic lesions, resulting in coronary steal syndrome with regional myocardial ischaemia during episodes of tachycardia or drops in perfusion pressure. Adrenaline can be safely administered in doses up to 4.5ug/kg. Even low levels of isoflurane (0.1 MAC) blunt the normal ventilatory response to hypoxia and hypercapnia. Isoflurane reduces cerebral metabolic oxygen requirements, and at 2 MAC it produces an electrically silent electroencephalogram. EEG suppression probably provides some degree of brain protection during episodes of cerebral ischaemia.

Desflurane
Desflurane has an ultrashort duration of action due to a low blood/gas partition coefficient (0.42) and wake-up times are approximately half as long as those for isoflurane. Pungency and airway irritation make desflurane unsuitable for inhalational induction. Due to a high vapour pressure at 20°C (681mmHg), a special desflurane vaporizer had to be developed. Cardiac output remains relatively unchanged or slightly depressed at 1-2 MAC. Rapid increases in desflurane concentration lead to transient but sometimes worrisome elevations in heart rate, blood pressure and catecholamine levels, which can be attenuated by increasing the desflurane concentration slowly or by administering fentanyl, esmolol or clonidine. Desflurane does not increase coronary artery blood flow. Adrenaline can be safely administered in doses up to 4.5mg/kg. Desflurane undergoes minimal metabolism in humans. Although emergence is more rapid after desflurane than after isoflurane anaesthesia, switching from isoflurane to desflurane towards the end of anaesthesia does not significantly accelerate recovery, nor does faster emergence usually translate into faster discharge from the recovery room. Desflurane emergence has been associated with delirium in some paediatric patients.

Sevoflurane
The properties and advantages of sevoflurane, especially when used for VIMA have been discussed in more depth in the previous section.

Xenon
Xenon is presently not available in South Africa. The advantages of xenon include minimal cardiovascular effects, a low blood solubility with rapid induction and recovery and it is not a known triggering agent of malignant hyperthermia. Xenon is probably nontoxic with no metabolism, nonexplosive and environmentally friendly. Disadvantages are its high cost and low potency (MAC = 70%).

NONVOLATILE INDUCTION AGENTS
The nonvolatile induction of general anaesthesia includes the intravenous, intramuscular (e.g. ketamine) or rectal route (e.g. thiopentone or methohexital) of administration.

The intramuscular or rectal route is usually used in uncooperative patients where inhalational induction is contraindicated or not feasible - as soon as the patient is quiet, intravenous access can be secured.

Induction of anaesthesia in adult patients usually involves intravenous administration, and the development of EMLA (eutectic mixture of local anaesthetic) cream has increased the popularity of intravenous inductions in children. After intravenous, intramuscular or rectal induction, anaesthesia can be maintained with either intravenous or inhalational agents.

Specific indications for intravenous induction include patients with a risk of pulmonary aspiration - here a rapid sequence induction should be performed. In patients with malignant hyperthermia volatile agents are contraindicated, and total intravenous anaesthesia (TIVA) is required. Contraindications for intravenous induction include the potentially difficult airway or intubation, as mentioned above. The uses and dosages of the most commonly used nonvolatile anaesthetics are summarised in Table 3.

TABLE 3: USES AND DOSAGES OF THE MOST COMMONLY USED NONVOLATILE ANAESTHETICS

IV = intravenous
IM = intramuscular

Barbiturates
Barbiturates are most commonly administered intravenously for induction of general anaesthesia, however, the rectal route is sometimes used in children. The duration of action is determined by redistribution, and not by metabolism or elimination.

Thiopentone is highly protein-bound (80%), and its great lipid solubility and high nonionized fraction (60%) account for maximal brain uptake within 30-60 seconds.

If the central compartment is contracted (e.g. hypovolemia), the serum albumin is low (e.g. severe liver disease) or the nonionized fraction is increased (e.g. acidosis), higher brain and heart concentrations will be achieved for a given dose.

Lower induction doses in elderly patients reflect the higher peak plasma levels due to slower redistribution. In contrast to the rapid initial distribution half-life of a few minutes, the elimination half-life of thiopentone ranges from 3 to 12 hours. Biotransformation involves hepatic oxidation.

Intravenous induction doses cause a fall in blood pressure and an elevation in heart rate. Peripheral capacitance vessels are dilated, with increased peripheral pooling of blood and decreased venous return.

Cardiac output is often maintained by a rise in heart rate and increased myocardial contractility from compensatory baroreceptor reflexes.

However, in the absence of an adequate baroreceptor response, as with hypovolemia, shock, congestive heart failure, ß-adrenergic blockade or fixed cardiac output (e.g. stenotic valvular lesions, cardiac tamponade or constrictive pericarditis), the use of barbiturates is contra-indicated due to a possible dramatic fall in cardiac output and blood pressure.

Patients with poorly controlled hypertension are particularly prone to wide swings in blood pressure. Adequate pre-operative hydration (10ml/kg crystalloid in a fasting patient) and a slow rate of injection attenuate the cardiovascular changes in most patients.

Barbiturates do not completely depress airway reflexes, and bronchospasm in asthmatic patients or laryngospasm in lightly anaesthetised patients is not uncommon following airway instrumentation. Apnoea usually follows an induction dose.

Barbiturates constrict the cerebral vasculature with a decrease in cerebral blood flow and intracranial pressure. Cerebral perfusion pressure is increased and cerebral oxygen consumption decreased. Barbiturates provide some brain protection from transient episodes of focal ischaemia (e.g. cerebral embolism) but probably not from global ischaemia (e.g. cardiac arrest). 50-100 mg intravenous thiopentone rapidly control most generalised seizures.

Acute intermittent porphyria or porphyria variegata are absolute contra-indications for the use of barbiturates, while relative contraindications include myxoedema, adrenal insufficiency, myasthenia gravis, myotonia dystrophica and severe liver disease.

Etomidate
Etomidate is characterised by a rapid onset of action. Redistribution is responsible for awakening. Etomidate is dissolved in propylene glycol - this solution often causes pain on administration that can be lessened by a prior injection of lignocaine. Etomidate induction is characterized by a 30-60% incidence of myoclonus - this can be decreased by the use of opioids. Biotransformation involves hepatic microsomal enzymes and plasma esterases.

Etomidate has minimal effects on the cardiovascular system, and myocardial contractility and cardiac output are usually unchanged. Etomidate is therefore a suitable agent for high risk patients due to cardiovascular disease.

Induction doses usually do not result in apnoea unless opioids have also been administered.

Cerebral metabolic rate, cerebral blood flow and intracranial pressure are decreased to the same extent as with thiopentone. Cerebral perfusion pressure is well maintained.

Postoperative nausea and vomiting are more common than with barbiturates.

Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis and long-term infusions lead to adrenocortical suppression.

Ketamine
Ketamine causes a state of dissociative anaesthesia - the patient appears conscious (with eye opening, swallowing, muscle contractures) but is unable to process or respond to sensory input.

Loss of consciousness occurs within one arm-to-brain-circulation (30-60 seconds) after intravenous administration and within 10-15 minutes after intramuscular injection. Awakening is due to redistribution after 15-30 minutes. Biotransformation involves the liver -induction of hepatic enzymes may explain the development of tolerance in patients who receive multiple doses of ketamine.

In sharp contrast to other anaesthetic agents, ketamine increases arterial blood pressure, heart rate and cardiac output.

Pulmonary artery pressure and myocardial work is increased. These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of noradrenaline and are often beneficial to patients with acute hypovolaemic shock.

Ketamine should be avoided in patients with:
• Coronary artery disease
• Uncontrolled hypertension
• Congestive heart failure
• Arterial aneurysms.

Exhaustion of catecholamine stores (e.g. severe end-stage shock) unmask the direct myocardial depressant effects of ketamine and cardiorespiratory arrest can be precipitated.

Ventilatory drive is minimally affected, although rapid intravenous bolus administration or pre-treatment with opioids occasionally produces apnoea. Ketamine is useful in asthmatic patients, because it is a potent bronchodilator. Although upper airway reflexes remain largely intact, patients at increased risk for aspiration pneumonia should be intubated. The increased salivation can be attenuated by premedication with an anticholinergic agent.

Ketamine is not suitable in patients with space-occupying intracranial lesions due to an increase in cerebral oxygen consumption, cerebral blood flow and intracranial pressure. The hallucinations, disturbing dreams and delirium during emergence and recovery are less common in children and in patients premedicated with benzodiazepines. Ketamine elevates the intra-ocular pressure and is therefore contraindicated in open eye injury. Ketamine produces intense somatic as well as visceral analgesia and after the induction an infusion of 1-4 mg/kg/hour can be administered. The infusion is discontinued 15-30 minutes before the end of the procedure. Postoperative nausea and vomiting is relatively common after ketamine administration.

Sympathetic antagonists (e.g. propanolol) unmask the direct myocardial depressant effects of ketamine. Ketamine produces myocardial depression when given to patients anaesthetised with halothane and, to a lesser extent, other volatile anaesthetics. The combination of theophylline and ketamine may predispose patients to seizures.

Propofol
Recovery from propofol is more rapid and accompanied by less hangover than recovery from any other intravenous induction agent. Together with its anti-emetic effect, this makes propofol a preferred agent for outpatient anaesthesia. Pain during administration can be lessened by prior injection of lignocaine, or mixing the lignocaine with propofol (2 ml of 1% lignocaine with 20 ml propofol). Since propofol formulations can support the growth of bacteria, good sterile technique is important in preparation and handling, including cleaning the rubber stopper or ampule neck surface with an alcohol swab prior to opening it. Administration should be completed within 6 hours of opening the ampule. Sepsis and death have been linked to contaminated propofol preparations.

The cardiovascular effects include a decrease in arterial blood pressure due to a drop in systemic vascular resistance, cardiac contractility and preload. Hypotension is more pronounced than with thiopentone and is exacerbated by large doses, rapid injection and old age. The total dose required can be reduced by lower rates of administration. Changes in heart rate and cardiac output are usually transient and insignificant in healthy patients, but may be severe enough to lead to asystole in patients at extremes of age or on negative chronotropic medication.

Apnoea usually follows an induction dose. Propofol-induced depression of upper airway reflexes makes intubation or laryngeal mask placement possible without the use of muscle relaxants. Propofol decreases cerebral blood flow and intracranial pressure. It is safe in epileptic patients. Propofol is not recommended in neonates and children under 3 years and is not registered for obstetric anaesthesia.

Benzodiazepines
Of the benzodiazepines, midazolam is most commonly used for intravenous induction.

Induction time with midazolam is relatively long and unpredictable, making it unsuitable for rapid-sequence inductions. Redistribution is responsible for awakening. The initial distribution half-life lasts 3-10 minutes. Biotransformation involves the liver - the elimination half -life of midazolam is 2 hours. Renal failure may lead to prolonged sedation in patients receiving midazolam due to the accumulation of a conjugated metabolite.

Benzodiazepines display minimal cardiovascular depressant effects even at induction doses and are therefore suitable for patients with poor cardiovascular reserve. However, the combination of opioids and benzodiazepines can markedly reduce arterial blood pressure and peripheral vascular resistance - this synergistic action is especially pronounced in patients with ischaemic or valvular heart disease. Although apnoea may be less common after benzodiazepine induction than after barbiturate induction, even small doses of midazolam and diazepam have resulted in respiratory arrest.

Benzodiazepines reduce cerebral oxygen consumption, cerebral blood flow and intracranial pressure but not to the extent the barbiturates do. They are effective in controlling generalized seizures. Benzodiazepines produce anterograde amnesia and are anxiolytic and sedative. They reduce the MAC of volatile anaesthetics by as much as 30%.

Benzodiazepines are more commonly used for premedication or sedation than for induction of general anaesthesia. Diazepam and lorazepam are seldom used for induction of anaesthesia (elimination half-life for diazepam is 30 hours, and for lorazepam 15 hours).

Flumazenil is a specific benzodiazepine-receptor antagonist that effectively reverses most of the central nervous system effects of benzodiazepines.

Droperidol
Droperidol was used for induction of anaesthesia but it is not available in South Africa anymore.

Opioids
Intra-operative opioids are most commonly used to produce analgesia.

Opioids display minimal cardiovascular depressant effects even at high doses and are therefore sometimes used as induction agents for patients with poor cardiovascular reserve. With the exception of pethidine, opioids do not depress cardiac contractility.

High doses of morphine, fentanyl, sufentanil, alfentanil and remifentanil are associated with a vagus-mediated bradycardia, and arterial blood pressure can drop as a result of bradycardia, venodilation and decreased sympathetic reflexes.

Opioids depress ventilation, particularly respiratory rate, and patients induced with opioids usually need postoperative ventilation, except when remifentanil is used.

The unique ester structure of remifentanil, and ultra-short-acting opioid, makes it susceptible to rapid ester hydrolysis by non-specific esterases in blood and tissue. The duration of a remifentanil infusion has little effect on wake-up time. Its contextsensitive half-time (the time required for the plasma drug concentration to decline by 50% after termination of an infusion) is approximately 3 minutes regardless of the duration of infusion, and is not affected by severe liver or renal disease.

As soon as the remifentanil infusion is stopped, a longer-acting opioid or alternative analgesic should be administrated for post-operative pain relief. High doses of opioids can induce chest wall rigidity severe enough to prevent adequate ventilation. This centrally mediated muscle contraction is effectively treated with muscle relaxants.

TABLE 4: DOSES OF COMMON OPIOIDS FOR INTRAVENOUS INTRAOPERATIVE ANAESTHESIA

*Note: The wide range of opioid doses reflects a large therapeutic index and depends upon which other anaesthetics are simultaneously administered. For obese patients, doses should be based on ideal body weight or lean body mass, not total body weight. Tolerance can develop rapidly (within 2 hrs) during IV infusion of opioids, necessitating higher infusion rates.

Opioids (e.g. alfentanil 15-25 µg/kg) can be administered 2-3 minutes before intubation to attenuate the pressor response of airway manipulation - this is especially useful in patients with hypertension.

Alfentanil, sufentanil and fentanyl are the most commonly used opioids for intra-operative and immediate postoperative pain relief. These drugs will be discussed in the August edition.

Several of the intravenous drugs are suitable for continuous infusions, either as single drugs or in combination, e.g. midazolam, propofol, ketamine, thiopentone, remifentanil, alfentanil, sufentanil, or fentanyl. With continuous infusions a relatively constant brain level is achieved and maintained, while with the intermittent intravenous bolus technique markedly high and low levels of drug are attained in the blood and brain.

No single anaesthetic technique provides ideal anaesthesia and the type of anaesthetic administered depends on the specific clinical situation and the anaesthetist’s choice.

REFERENCES:

1. Morgan GE, Mikhail MS. Clinical Anaesthesiology (third edition). London: Prentice-Hall International (UK) Limited, 2001:127-177.
2. Coetzee A. Van der Merwe W. ’n Inleiding tot Anestesiologie (second edition). Oxford University Press 1990:29-71.
3. Beeton A. A practical approach to VIMA. National Anaesthesia Congress & Refresher course 2000:6-10.
4. Lines D. Sevoflurane - an ideal induction agent? National Anaesthesia Congress & Refresher course 2000:12-20. 5. Propofol: Package insert.