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WHO Model Prescribing Information: Drugs Used in Anaesthesia
(1989; 60 pages) [French] View the PDF document
Table of Contents
View the documentPreface
View the documentIntroduction
Open this folder and view contentsPremedication
Open this folder and view contentsGeneral anaesthetics and oxygen
Open this folder and view contentsLocal anaesthetics
Open this folder and view contentsNon-opioid analgesics
Open this folder and view contentsOpioid analgesics and antagonists
Open this folder and view contentsMuscle relaxants and cholinesterase inhibitors
Open this folder and view contentsBlood substitutes
Open this folder and view contentsSolutions for correcting water and electrolyte imbalance
Open this folder and view contentsAntacid for use in obstetric practice
View the documentAnaesthesia at the District Hospital
View the documentSelected WHO publications of related interest
View the documentBack cover
 

Introduction

Sound theoretical and practical training followed by several years of supervised experience in the administration of anaesthetics is essential to develop the skills of the anaesthetist. Even within the recommended dosage range, anaesthetic agents can cause death when inappropriately used and only as a last resort should they be administered by non-specialized personnel.

Emergency care

Ideally, fully equipped emergency services should be provided in every health centre. Where this is not feasible, selected health workers should be trained in basic anaesthetic techniques. It is important that transportation facilities should be available to ensure that as many patients as possible are brought within reach of the nearest emergency service. In the absence of transportation, efforts should be made to bring a trained anaesthetist to the side of the patient. Before injured or seriously ill patients are transported, consideration must be given to the need for respiratory support, supplementary oxygen, control of bleeding, relief of pain, fluid replacement and immobilization of fractures. In order to maintain the circulatory volume of seriously injured patients until more effective measures can be taken, and to allow for rapid parenteral delivery of the necessary drugs, an infusion of isotonic saline should be set up as soon as possible. Provided the patient is not shocked and there is no evidence of head injury, morphine should be administered immediately to relieve severe pain.

Anaesthetic techniques

To produce a state of prolonged full surgical anaesthesia reliably and safely a variety of drugs is needed. Irrespective of whether a general or conduction (regional or local) anaesthetic technique is used, it is essential that facilities for intubation and mechanically assisted ventilation are available.

Whenever possible, anaesthesia, whether conduction or general, should be deferred for at least 4 hours from the time the patient last ingested either solids or liquids. Since trauma significantly delays gastric emptying time, regurgitation or vomiting may still occur even when this rule is observed. At all times a properly functioning suction machine, tested prior to anaesthesia, must be available.

Premedication

Pre-anaesthetic medication is generally advisable prior to both conduction and general anaesthetic procedures for the following reasons:

• Sedatives improve the course of subsequent anaesthesia in apprehensive patients. Diazepam, promethazine syrup and chloral hydrate are effective. Diazepam can be administered orally, intravenously or rectally. Promethazine syrup, which has antihistaminic and antiemetic properties as well as a sedative effect, is of particular value in children, as is chloral hydrate. Intramuscular injection of promethazine is preferred in adults.

• Potent analgesics such as morphine or pethidine should be administered preoperatively to patients in severe pain or to provide analgesia during and after surgery. Sedatives should then be withheld since they may cause restlessness or confusion.

• Anticholinergic drugs such as atropine are additionally used prior to general anaesthetic procedures. They inhibit excessive bronchial and salivary secretions induced, in particular, by ether and ketamine. Intramuscular administration is most effective, but oral administration is more convenient in children.

Conduction anaesthesia

Conduction anaesthesia has many applications. It is used very widely in dental practice; for brief and superficial interventions; for obstetric procedures; and for specialized techniques of regional anaesthesia calling for highly developed skills. It can be particularly useful when the patient is required to collaborate during the intervention.

Local infiltration

Many simple surgical procedures that neither involve the body cavities nor require muscle relaxation (but including lower-segment caesarean section) can be performed under local infiltration anaesthesia. The local anaesthetic drug of choice is 0.5% lidocaine with or without epinephrine. No more than 4 mg/kg of plain lidocaine or 7 mg/kg of lidocaine with epinephrine should be administered on any one occasion.

Regional block

Regional nerve blocks can provide safe and effective anaesthesia but their execution requires considerable training and practice. Nevertheless, where the necessary skills are available, techniques such as axillary or ankle blocks can be invaluable. Either lidocaine 1.0% or bupivacaine 0.5% is suitable.

Spinal anaesthesia

Spinal anaesthesia is one of the most useful of all anaesthetic techniques and can be used widely for surgery of the abdomen and lower limbs. Either lidocaine (5%) or bupivacaine (0.75%) can be used but the latter is often chosen because of its longer duration of action.

General anaesthesia

Induction

Anaesthesia may be induced with an intravenous barbiturate, intravenous or intramuscular ketamine, or an inhalational agent. The first two methods are more pleasant for the patient but they are absolutely contraindicated when the anaesthetist is not confident of maintaining an airway.

Intravenous induction using thiopental or methohexital is rapid and excitement does not occur in patients sedated with diazepam. Neither agent can be used alone as an anaesthetic since large or repeated doses severely depress respiration and delay recovery. Before intubation is attempted, a muscle relaxant must be given or deep inhalational anaesthesia achieved.

Ketamine is used both intravenously and intramuscularly for induction, and for maintenance of anaesthesia of short duration that does not call for muscular relaxation. Diazepam or another benzodiazepine should be given beforehand in order to reduce the incidence of emergence reactions during recovery. Before intubation is attempted a muscle relaxant must be administered. Ketamine in low doses is also a potent analgesic. It is thus of particular value in children, when burns are dressed and during radiotherapeutic procedures and marrow sampling.

One of the volatile anaesthetics - ether, halothiane or trichloroethylene (with or without nitrous oxide) - must be used for induction when intravenous agents are contraindicated and particularly when intubation is likely to be difficult. Halothane is preferred in these circumstances. Because it is non-irritant, induction is smoother and more pleasant for the patient. Once anaesthesia is established ether may be substituted.

Inhalational techniques

Ether is the safest and most reliable anaesthetic in inexperienced hands. It must, however, be used with care since it is flammable in air and explosive when mixed with high concentrations of oxygen or nitrous oxide or mixtures of these. It produces good muscle relaxation and, if necessary, it can be used alone for induction and maintenance of anaesthesia in all branches of surgery.

Halothane may also be used for induction and maintenance of anaesthesia. Induction is smooth and rapid but, since halothane is cardiodepressant, the concentration that can be administered with safety to maintain anaesthesia is strictly limited. When it is used in abdominal surgery, muscle relaxants must also be given as soon as anaesthesia is established. It must always be administered from a calibrated vaporizer in order to reduce the risk of cardiorespiratory depression.

Trichloroethylene is a weak hypnotic agent but a potent analgesic. It can be used economically in conjunction with halothane in a draw-over system but it must never be used with a soda lime system for carbon dioxide absorption. In analgesic doses it can be used for the relief of pain in labour.

Nitrous oxide is costly and has to be transported and stored in cylinders. It is used widely in conjunction with other agents for induction and maintenance of anaesthesia. It should never be used alone for these purposes since it is a weak anaesthetic, but it allows the dosage of other anaesthetic agents to be reduced. In subanaesthetic doses (50% with oxygen) it is of value as an analgesic in obstetric procedures and in the emergency management of injured patients.

Oxygen should be added routinely to inhalational agents, even when air is used as the carrier gas, to protect against hypoxia. This is an essential precaution whenever halothane is used. When oxygen is not available, ether is the safest agent for maintenance of anaesthesia. Oxygen is most simply given with volatile anaesthetics (provided adequate precautions are taken when it is mixed with ether) using the economical draw-over technique, but it may also be used in an anaesthetic machine for compressed gases.

Muscle relaxants

Muscle relaxants are classified according to their mode of action as depolarizing or non-depolarizing neuromuscular blocking agents. Their use allows abdominal surgery to be carried out under light anaesthesia. They should never be given until it is certain that general anaesthesia has been established, and ventilation must be mechanically assisted until they have been completely inactivated.

Suxamethonium is the only widely used depolarizing muscle relaxant. It produces rapid, complete paralysis which is very short-lasting in most patients and is of particular value for laryngoscopy and intubation. Should paralysis be prolonged, ventilation must be assisted until muscle function is fully restored. Powder formulations of suxamethonium are recommended because they retain activity during storage. Liquid formulations must be kept under refrigeration during transportation and storage.

Gallamine and alcuronium are both non-depolarizing muscle relaxants with a duration of action of about 30 minutes. Their effects may be rapidly reversed after surgery by the anticholinesterase agent neostigmine, provided atropine is given to prevent excessive autonomic activity. Alcuronium has little effect on the cardiovascular system but the vagolytic action of gallamine tends to produce a tachycardia.

Pancuronium is another potent synthetic agent with a duration of action of about 30 minutes but it requires refrigerated storage as does the newer agent atracurium. Vecuronium, another relatively new and expensive non-depolarizing muscle relaxant, has the advantage of a shorter duration of action (15-20 minutes), which frequently averts the need for postoperative neostigmine. The powder formulation has a long shelf-life.

Analgesics

For relief of mild postoperative pain, acetylsalicylic add or paracetamol suffices. Opioid analgesics such as morphine and pethidine should be reserved for severe pain. Opioids are also used during prolonged operations to supplement general anaesthesia. When doses producing respiratory depression are used, vital functions must be closely monitored and assisted ventilation maintained until spontaneous breathing is fully restored. Naloxone, a specific opioid antagonist, helps to restore breathing but its effect is short-lasting and it counteracts the analgesic effect as well as the respiratory depression. To avoid unnecessarily high dosages, it can be given in small divided doses until the respiratory depressant effect of the opioid is overcome but, because its action is not long sustained, the patient will continue to need careful respiratory monitoring.

Ancillary drugs used in anaesthesia

Various drugs may be needed to modify normal physiological functions or otherwise to maintain the patient in a satisfactory condition during surgery. These include:

• antidysrhythmic agents such as lidocaine, propranolol and verapamil

• hypotensive agents such as hydralazine and sodium nitroprusside for controlled reduction of blood pressure

• vasoactive agents including ephedrine or methoxamine to maintain blood pressure after spinal or epidural block

• osmotic diuretics such as mannitol hexanitrate to reduce intracranial pressure

• bronchodilators such as salbutamol and aminophylline.

Special precautions and close monitoring of the patient are often required when these drugs are administered. Certain vasoactive agents, and particularly sodium nitroprusside, can be given safely only by means of an infusion pump.

Fluid replacement therapy

Fluid requirements must be assessed before, during and after major surgery. Any preoperative loss of blood, plasma or gastrointestinal fluid must be replaced and account must also be taken of sweating, chronic malnutrition and preoperative starvation. Cumulative fluid losses can attain many litres. Replacement fluids should correspond as nearly as possible in volume and composition to those lost. When, as in emergency, adequate fluid replacement is impossible, general anaesthesia can become hazardous and conduction anaesthesia should be preferred.

Blood transfusion should be avoided, unless absolutely necessary, whenever screening for human immunodeficiency viruses and hepatitis B virus is impracticable. None the less, blood becomes essential to restore oxygen-carrying capacity when more than 15% of the circulating volume is lost, particularly in patients with pre-existing anaemia. Isotonic sodium chloride solution may be used for short-term volume replacement. Plasma expanders such as albumin concentrates (which carry no risk of human immunodeficiency virus or hepatitis B virus transmission) or less expensive substitutes such as dextran 70, polygeline or hetastarch may additionally be required.

During surgery extracellular fluid is sequestered in traumatized tissue. As a general rule one-third to one-half of the estimated 24 hour fluid requirement should be administered parenterally during a major operation in addition to the total measured fluid loss. Provided renal function is maintained, fluid is most simply replaced by intravenous administration of sodium chloride solution 9 mg/ml or the more physiologically appropriate compound solution of sodium lactate.

Isotonic glucose/saline mixtures (most commonly glucose 4%/saline 0.18%) are preferred in children to avoid the danger of sodium overload and hypoglycaemia. These solutions are also preferred both before and after major surgery. For an adult patient whose condition is stable, 2-3 litres of glucose/saline provide the average daily requirement of both water and sodium in a temperate climate.

When fluids are administered intravenously over long periods, potassium chloride is required to prevent potassium depletion. In order to avoid serious dysrhythmias, especially in patients with impaired renal function, the required dosage should be determined, whenever possible, by monitoring blood levels of potassium.

Anaesthesia during pregnancy

Throughout pregnancy the safety of the fetus as well as of the mother must be considered; there is a greater risk of vomiting and aspiration during induction, and airway obstruction is also more likely to occur as a result of localized oedema.

Thiopental is generally preferred for induction and anaesthesia may be maintained safely with halothane, nitrous oxide and oxygen. Suxamethonium may be used for intubation. When pregnancy is advanced the patient must be placed in the “wedge” position to avoid supine hypotension.

In obstetric practice intramuscular pethidine is effective in relieving the pain of early labour but it should be used only when naloxone can be administered to the neonate to reverse respiratory depression. A subanaesthetic concentration of nitrous oxide or trichloroethylene may be administered on demand during labour and delivery. Alternatively, pain may be relieved by epidural nerve block with bupivacaine.

The danger of aspiration of gastric contents is reduced by fasting and routine oral administration of antacids. Sodium citrate is commonly used before induction to neutralize the gastric contents. Magnesium trisilicate is less satisfactory since it is slow-acting and bulky and has been implicated as a cause of gastric aspiration. A histamine H2-receptor antagonist (cimetidine or ranitidine) may additionally be given either orally, at least 2 hours before surgery, or intravenously, immediately before induction, to reduce the acidity and volume of gastric secretions. The antiemetic metoclopramide is also used to promote gastric emptying and to increase tone in the lower oesophageal sphincter. However, its effects are antagonized by atropine.

In emergency, caesarean section must often be carried out under general anaesthesia. Because this can be unpredictably hazardous, spinal block is often preferred for elective caesarean section. This technique avoids drug-induced fetal depression and is of particular value in premature labour. It can also be used for procedures such as the removal of a retained placenta, where rapid onset of anaesthesia is of value. However, “postspinal headache” is particularly common in obstetric patients. Epidural nerve block is also used in many hospitals but should only be undertaken by a skilled anaesthetist.

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