1. The main aim of anaesthesia is the prevention of pain during surgery and at other times.
2. Anaesthesia involves a balanced approach, in which the individual patient’s psyche and pathophysiology are taken into account and drugs are used to modify and control any aspect as required.
3. The decision to use a particular drug or technique must be made after careful consideration of the pathophysiological features of the individual case and how these may affect the phar­macokinetic handling and tissue response to the drugs available.
4. Any associated disease or pathophysiological abnormality should wherever possible be treated or corrected before operation, and potentially dangerous physiological disturbances avoided during and after anaesthesia.
5. Anaesthetic drugs are relatively non-toxic but there are some important effects. Halothane is occasionally associated with hepatitis and methoxyflurane with kidney damage. Malignant hyperpyrexia, the aetiology of which is uncertain, is a rare but often fatal condition which can be triggered off by several anaesthetic drugs in genetically susceptible individuals.
6. Drugs used in anaesthesia can be involved in significant unwanted interactions with other drugs.
7. The treatment of respiratory failure is usually the responsibility of the anaesthetist. Although ventilatory assistance, physiotherapy, etc. are often the mainstay of treatment, drugs of different pharmacological classes are used.
8. Pain perception is an individual sensation. Symptomatic treatment of acute pain should not therefore be based on a concept of the painfulness of certain conditions, although some anal­gesics may be more appropriate for pain of certain conditions.
9. Strong analgesics for severe chronic pain should preferably be given orally, in adequate dosage, and on a regular individualised dosage schedule.

General Considerations

Although achieving insensibility to pain and to unpleasant surroundings has been the goal of much human activity since prehistoric times, it is only since 1846 with the introduction of ether by Morton that this could be done with any re­liable chance of success. Anaesthesia has devel­oped and been refined considerably since that time, and several important milestones are re­cognized and worthy of recall. These include the discovery of the local anaesthetic action of co­caine by Koller in 1884 and its use to produce spinal anaesthesia by Bier in 1898, the perfec­tion of endotracheal anaesthesia by Magill and Rowbotham about 1920, the introduction of the first barbiturate for induction of anaesthesia in 1932, and the introduction of curare in 1942.
In recent years, the specialty of anaesthesia has been broadened, and its scope is well de­scribed in a definition for the US Department of Labor (Dripps 1966):

Anesthesiology is a practice of medicine dealing with:

• The management of procedures for ren­dering a patient insensible to pain during surgical procedures.
• The support of life functions under the stress of anesthetic and surgical manipu­lations.
• The clinical management of the patient unconscious from whatever cause.
• The management of problems in pain re­lief.
• The management of problems in cardiac and respiratory resuscitation.
• The application of specific methods of inhalational therapy.
• The clinical management of various fluid electrolyte and metabolic disturbances.

The modern concept is one of ‘balanced an­aesthesia’, in which the whole of the patient’s psyche and pathophysiology are taken into ac­count and drugs are used to modify and control any aspect as required. Thus, as well as general anaesthetic agents, drugs of many classes – tran­quillisers, analgesics, muscle relaxants, drugs af­fecting the autonomic system etc. – all fall within the sphere of interest of the anaesthetist. ( Some of the more important of these will be discussed further at later part – Drugs Used in Anaesthesia .)

Never­theless, poisoned patients are often unnecessar­ily subjected to these potentially harmful meas­ures, and the literature is full of anecdotal accounts of miraculous recovery attributed to such treatment (Winchester et al. 1977). Prop­erly controlled clinical trials are difficult to carry out, and very few have been published. With the possible exception of forced alkaline di­uresis for poisoning with salicylate and long act­ing barbiturates such as phenobarbitone, none of these methods for enhancement of drug re­moval has ever been shown to reduce morbidity or mortality in poisoned patients (Todd 1984).

Indeed, some studies suggest the opposite result. This is not to say that such measures are never necessary, or indeed sometimes life saving, but a more critical appraisal of their role is required.

In some cases, the drug presumed to have been taken has never been chemically identi­fied, while, in others, haemodialysis has been carried out in patients with less than therapeutic plasma concentrations of the drug in question. Other studies have shown removal of only a very small and insignificant fraction of the ingested dose, sometimes amounting to the equivalent of less than 1 tablet or capsule (see, for example, Comstock et al. 1983; Heath et al. 1983). A mis­leading impression of efficacy may be gained by the use of nonspecific analytical methods for drug assay (Prescott 1974).

Other Binding Agents

Other agents have been used in attempts to bind unabsorbed drug in the gastrointestinal tract. Paraquat, a lethal weedkiller for which there is no known antidote, binds very strongly to Fuller’s earth and bentonite, and these ad­sorbents are used routinely in the treatment of paraquat poisoning.

Although bentonite may re­duce the normally slow absorption of paraquat in pure aqueous solution in rats (Smith et al. 1974), ail the evidence points to extremely rapid absorption of paraquat from commercial weed­killers in man. Our experience of paraquat poi poi­soning has been disastrous, with no apparent benefit from the early use of bentonite.

Cholestyramine binds acidic drugs and can reduce the absorption of paracetamol (aceta­minophen) taken at the same time. Like acti­vated charcoal, however, it is virtually useless when the delay between ingestion and admin­istration exceeds 1 hour (Dordoni et al. 1973).

1. Specific antidotal therapy is available for very few poisons. The mainstay of treatment of severe poisoning is intensive supportive therapy and good nursing care.

2. The great majority of poisoned patients recover with intensive supportive therapy alone, and enthusiastic claims for the success of other treatment often cannot be justified.

3. With some important exceptions, the management of poisoning is not altered by knowledge of plasma drug concentrations. There are many pitfalls in the interpretation of drug concen­trations in poisoned patients, especially when nonspecific analytical methods are used.

4. Gastric lavage and induction of nemesis soon after ingestion may be effective in removing unabsorbed drug, but are unreliable. Adsorbents such as activated charcoal are usually ineffec­tive in limiting absorption when given more than 1 hour after ingestion.

5. Poisoned patients are often subjected to unnecessary and potentially harmful haemodialysis, haemoperfusion and diuresis. The efficacy of these measures has been established for relatively few substances in terms of reduction in morbidity and mortality or removal of toxicologically significant amounts of active drug or poison.

6. The efficacy of methods for extracorporeal removal can be predicted from pharmacokinetic principles. It depends primarily on the volume of drug distribution, plasma protein binding, rate of transfer from peripheral to central compartments, and dialysis clearance relative to the endogenous total body clearance.

7. Haemoperfusion with activated charcoal or exchange resins is more effective than haemo­dialysis in removing drugs from the blood. Peritoneal dialysis is less effective than haemodi­alysis. Drugs with large volumes of distribution cannot be removed rapidly by any of these techniques, and indications for their use are limited.

8. Forced diuresis can only increase the renal clearance of reabsorbed compounds, and clearance may be dramatically increased by appropriate manipulation of urine pH. However, the renal excretion of most drugs is insignificant in relation to the metabolic clearance. Forced alkaline diuresis is largely restricted to salicylate and phenobarbitone poisoning.

9. Repeated oral activated charcoal effectively increases the body clearance of a number of drugs. It probably acts by irreversibly binding drug diffusing from the circulation to the gut lumen and may also interrupt the enterohepatic circulation.

10. The toxicity of a few drugs and poisons can be reversed by specific antidotal therapy. Mechanisms include pharmacological antagonism, inhibition of conversion to toxic metabolites, inactivation of highly reactive alkylating intermediates, chelation and binding with drug-specific antibodies.