General anaesthesia

General anaesthesia

Several different types of drug are given together during general anaesthesia. Anaesthesia is induced with either a volatile drug given by inhalation or with an intravenously administered drug; anaesthesia is maintained with an intravenous or inhalational anaesthetic. Analgesics, usually short-acting opioids, are also used. The use of neuromuscular blocking drugs necessitates intermittent positive-pressure ventilation. Following surgery, anticholinesterases can be given to reverse the effects of neuromuscular blocking drugs; specific antagonists can be used to reverse central and respiratory depression caused by some drugs used in surgery. A local anaesthetic can be used to reduce pain at the injection site. The required dose of induction agent may be less if the patient has been premedicated with a sedative agent or an opioid analgesic has been used.

Intravenous anaesthetics

Intravenous anaesthetics may be used either to induce anaesthesia or for maintenance of anaesthesia throughout surgery. Intravenous anaesthetics nearly all produce their effect in one arm-brain circulation time and can cause apnoea and hypotension, and so adequate resuscitative facilities must be available. They are contra-indicated if the anaesthetist is not confident of being able to maintain the airway (e.g. in the presence of a tumour in the pharynx or larynx). Extreme care is required in surgery of the mouth, pharynx, or larynx and in patients with acute circulatory failure (shock) or fixed cardiac output.

Barbiturates

THIOPENTAL SODIUM:

Indications: induction of general anaesthesia; anaesthesia of short duration; reduction of raised intracranial pressure if ventilation controlled; status epilepticus.

Contraindications: Respiratory obstruction, acute asthma, severe shock and dystrophia myotonica. Porphyria. Patients with hypersensitivity reactions to barbiturates. Breastfeeding should be temporarily suspended or breast milk expressed before induction of anaesthesia.

Dose and Administration: Induction of general anaesthesia, by slow intravenous injection usually as a 2.5% (25 mg/mL) solution, adult over 18 years, fit and premedicated, initially 100–150 mg (reduced in elderly or debilitated) over 10–15 seconds (longer in elderly or debilitated), followed by further quantity if necessary according to response after 30–60 seconds; or up to 4 mg/kg (max. 500 mg); child 1 month–18 years, initially up to 4 mg/kg, then 1 mg/kg repeated as necessary (max. total dose 7 mg/kg). Raised intracranial pressure, by slow intravenous injection, 1.5–3 mg/kg, repeated as required. Status epilepticus, by slow intravenous injection as a 2.5% (25 mg/mL) solution, adult over 18 years, 75–125 mg as a single dose; child 1 month–18 years,

initially up to 4 mg/kg by slow intravenous injection, then up to 8 mg/kg/hour by continuous intravenous infusion, adjusted according to

response.

Other intravenous anaesthetics

KETAMINE:

Indications: As an anaesthetic agent for diagnostic and surgical procedures. When used by intravenous or intramuscular injection, Ketamine is best suited for short procedures. For the induction of anaesthesia prior to the administration of other general anaesthetic agents.

Contraindications: persons in whom an elevation of blood pressure would constitute a serious hazard and in those who have shown hypersensitivity to the drug. Ketalar should not be used in patients with eclampsia or pre-eclampsia, severe coronary or myocardial disease, cerebrovascular accident or cerebral trauma.

Dose and Administration: By intramuscular injection, short procedures, initially 6.5–13 mg/kg, adjusted according to response (10 mg/kg usually produces 12–25 minutes of surgical anaesthesia). Diagnostic manoeuvres and procedures not involving intense pain, initially 4 mg/kg. By intravenous injection over at least 60 seconds, short procedures, initially 1–4.5 mg/kg, adjusted according to response (2 mg/kg usually produces 5–10 minutes of surgical anaesthesia). By intravenous infusion of a solution containing 1 mg/mL, longer procedures, induction, total dose of 0.5–2 mg/kg; maintenance, 10– 45 micrograms/kg/minute, rate adjusted according to response.

PROPOFOL:

Indications: For induction and maintenance of general anaesthesia. For sedation of artificially ventilated patients in the intensive care unit.

Contraindications: Hypersensitivity to propofol or to one of the excipients. Pregnancy (except in cases of abortion). Should not be used for general anaesthesia in children under the age of three years and for sedation of children under the age of 16 in the intensive care unit. Should not be used during lactation.

Dose and Administration: Induction of anaesthesia, by intravenous injection or infusion, 1.5–2.5 mg/kg (1–1.5 mg in those over 55 years) at a rate of 20– 40 mg every 10 seconds until response; child over 1 month, administer slowly until response (usual dose in child over 8 years 2.5 mg/kg, may need more in younger child e.g. 2.5–4 mg/kg). Maintenance of anaesthesia, by intravenous infusion, 4–12 mg/kg/hour or by intravenous injection, 25–50 mg repeated according to response; child over 3 years, by intravenous infusion, 9– 15 mg/kg/hour.

Inhalational anaesthetics

Inhalational anaesthetics may be gases or volatile liquids. They can be used both for induction and maintenance of anaesthesia and can also be used following induction with an intravenous anaesthetic. Volatile liquid anaesthetics are administered using calibrated vaporisers, using air, oxygen, or nitrous oxide– oxygen mixtures as the carrier gas; all can trigger malignant hyperthermia and are contra-indicated in those susceptible to malignant hyperthermia. To prevent hypoxia inhalational anaesthetics must be given with concentrations of oxygen greater than 21%.

ISOFLURANE:

Indications: Isoflurane may be used for induction and maintenance of general anesthesia. Adequate data have not been developed to establish its application in obstetrical anesthesia.

Contraindications: Known sensitivity to Isoflurane, USP or to other halogenated agents. Known or suspected genetic susceptibility to malignant hyperthermia.

Dose and Administration: Induction of anaesthesia, using specifically calibrated vaporiser, in oxygen or nitrous oxide–oxygen, increased gradually from 0.5% to 3%. Maintenance of anaesthesia, using specifically calibrated vaporiser, 1–2.5% in nitrous oxide–oxygen; an additional 0.5–1% may be required when given with oxygen alone; caesarean section, 0.5–0.75% in nitrous oxide–oxygen.

SEVOFLURANE:

Indications: Sevoflurane is indicated for induction and maintenance of general anesthesia in adult and pediatric patients.

Contraindications: Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.

Dose and Administration: Induction of anaesthesia, using a specifically calibrated vaporiser, in oxygen or nitrous oxide–oxygen, adjusted according to response, adult up to 5%; child 1 month–18 years up to 8%. Maintenance of anaesthesia, using a specifically calibrated vaporiser, in oxygen or nitrous oxide– oxygen, adjusted according to response, adult and child over 1 month 0.5–3%.

Antimuscarinic drugs

Antimuscarinic drugs are used as premedicants to dry bronchial and salivary secretions which are increased by intubation, by surgery to the upper airways, and by some inhalational anaesthetics. They are also used before or with neostigmine to prevent bradycardia, excessive salivation, and other muscarinic actions of neostigmine. They also prevent bradycardia and hypotension associated with drugs such as propofol and suxamethonium.

Atropine sulphate: used for premedication but still has an emergency role in the treatment of vagotonic side-effects. For its role in acute arrhythmias after myocardial infarction,

Hyoscine hydrobromide reduces secretions and also provides a degree of amnesia, sedation and anti-emesis. Unlike atropine it may produce bradycardia rather than tachycardia. In some patients, especially the elderly, hyoscine may cause the central anticholinergic syndrome (excitement, ataxia, hallucinations, behavioural abnormalities, and drowsiness)

GLYCOPYRRONIUM BROMIDE (Glycopyrrolate):

Indications: indicated for use as a preoperative antimuscarinic to reduce salivary, tracheobronchial, and pharyngeal secretions; to reduce the volume and free acidity of gastric secretions; and to block cardiac vagal inhibitory reflexes during induction of anesthesia and intubation. may be used intraoperatively to counteract surgically or drug- induced or vagal reflexes associated arrhythmias. Glycopyrrolate protects against the peripheral muscarinic effects (e.g., bradycardia and excessive secretions) of cholinergic agents such as neostigmine and pyridostigmine given to reverse the neuromuscular blockade due to non-depolarizing muscle relaxants.

Contraindications: Known hypersensitivity to glycopyrrolate or any of its inactive ingredients.

Dose and Administration: Premedication, by intramuscular or intravenous injection, 200–400 micrograms or 4–5 micrograms/kg (max. 400 micrograms); child by intramuscular or by intravenous injection, 4–8 micrograms/kg (max. 200 micrograms). Intra-operative use, by intravenous injection, 200– 400 micrograms or 4–5 micrograms/kg (max. 400 micrograms), repeated if necessary; child under 18 years 4–8 micrograms/kg (max. 200 micrograms), repeated if necessary. Control of muscarinic side-effects of neostigmine in reversal of non-depolarising neuromuscular block, by intravenous injection, 200 micrograms per 1 mg of neostigmine, or 10–15 micrograms/kg; child 10 micrograms/kg.

Sedative and analgesic peri-operative drugs

These drugs are given to allay fear and anxiety in the pre-operative period (including the night before an operation), to relieve pain and discomfort when present, and to augment the action of subsequent anaesthetic agents. A number of the drugs used also provide some degree of pre-operative amnesia. The choice will vary with the individual patient, the nature of the operative procedure, the anaesthetic to be used, and other prevailing circumstances such as outpatients, obstetrics, and recovery facilities. The choice also varies between elective and emergency operations.

Anxiolytics and neuroleptics

Benzodiazepines possess useful properties for premedication including relief of anxiety, sedation, and amnesia; short-acting benzodiazepines taken by mouth are the most common premedicants. They have no analgesic effect so an opioid analgesic may sometimes be required for pain.

Benzodiazepines can alleviate anxiety at doses that do not necessarily cause excessive sedation and they are of particular value during short procedures or during operations under local anaesthesia (including dentistry). Amnesia reduces the likelihood of any unpleasant memories of the procedure (although benzodiazepines, particularly when used for more profound sedation, can sometimes induce sexual fantasies). Benzodiazepines are also used in intensive care units for sedation, particularly in those receiving assisted ventilation

Opioid analgesics

Opioid analgesics given in small doses before or with induction reduce the dose requirement of some drugs used during anaesthesia. Alfentanil, fentanyl, and remifentanil are particularly useful because they act within 1–2 minutes and have short durations of action. The initial doses of alfentanil or fentanyl are followed either by successive intravenous injections or by an intravenous infusion; prolonged infusions increase the duration of effect. Repeated intra-operative doses of alfentanil or fentanyl should be given with care since the resulting respiratory depression can persist postoperatively and occasionally it may become apparent for the first time postoperatively when monitoring of the patient might be less intensive. Alfentanil, fentanyl, and remifentanil can cause muscle rigidity, particularly of the chest wall or jaw; this can be managed by the use of neuromuscular blocking drugs

Neuromuscular blocking drugs

Neuromuscular blocking drugs used in anaesthesia are also known as muscle relaxants. By specific blockade of the neuromuscular junction they enable light levels of anaesthesia to be employed with adequate relaxation of the muscles of the abdomen and diaphragm. They also relax the vocal cords and allow the passage of a tracheal tube. Their action differs from the muscle relaxants acting on the spinal cord or brain which are used in musculoskeletal disorders. Patients

who have received a neuromuscular blocking drug should always have their respiration assisted or controlled until the drug has been inactivated or antagonised. They should also receive sufficient concomitant inhalational or intravenous anaesthetic, or sedative drugs to prevent awareness.

Non-depolarising neuromuscular blocking drugs

Non-depolarising neuromuscular blocking drugs (also known as competitive muscle relaxants) compete with acetylcholine for receptor sites at the neuromuscular junction and their action may be reversed with anticholinesterases such as neostigmine. Non-depolarising neuromuscular blocking drugs have a slower onset of action than suxamethonium. These drugs can be classified by their duration of action as short-acting (15–30 minutes), intermediate-acting (30–40 minutes) and long-acting (60–120 minutes), although duration of action is dose-dependent. Drugs with a shorter or intermediate duration of action, such as atracurium and vecuronium, are more widely employed than those with a longer duration of action such as pancuronium.

ATRACURIUM BESILATE (Atracurium besylate):

Indications: highly selective, competitive or non-depolarising neuromuscular blocking agent (short to intermediate duration). It is used as an adjunct to general anaesthesia or sedation in the intensive care unit (ICU), to relax skeletal muscles, and to facilitate tracheal intubation and mechanical ventilation.

Contraindications: Atracurium is contraindicated in patients’ known to be hypersensitive to atracurium, cisatracurium or benzenesulfonic acid.

Dose and Administration: Surgery or intubation, adult and child over 1 month, by intravenous injection, initially 300–600 micrograms/kg; maintenance, by intravenous injection, 100–200 micrograms/kg as required or by intravenous infusion, 5–10 micrograms/kg/minute (300–600 micrograms/kg/hour). Intensive care, adult and child over 1 month, by intravenous injection, initially 300–

600 micrograms/kg      (optional)    then       by     intravenous           infusion 4.5–
29.5 micrograms/kg/minute (usual dose 11–13 micrograms/kg/minute).

CISATRACURIUM:

Indications: indicated for use during surgical and other procedures and in intensive care. It can be used as an adjunct to general anaesthesia, or sedation in the Intensive Care Unit (ICU) to relax skeletal muscles, and to facilitate tracheal intubation and mechanical ventilation (intermediate duration).

Contraindications: Cisatracurium is contraindicated in patients’ known to be hypersensitive to atracurium, cisatracurium or benzenesulfonic acid.

Dose and Administration: Intubation, by intravenous injection, adult and child over 1 month, initially 150 micrograms/kg; maintenance, by intravenous injection, 30 micrograms/kg approx. every 20 minutes; child 2–12 years, 20 micrograms/kg approx. every 9 minutes; or maintenance, by intravenous

infusion, adult and child over 2 years, initially, 3 micrograms/kg/minute, then after stabilisation, 1–2 micrograms/kg/minute; dose reduced by up to 40% if used with isoflurane. Intensive care, by intravenous infusion, adult 0.5– 10.2 micrograms/kg/minute (usual dose 3 micrograms/kg/minute).

MIVACURIUM:

Indications: Mivacurium is a highly selective, short-acting, non-depolarising neuromuscular blocking agent with a fast recovery profile. Mivacurium is used as an adjunct to general anaesthesia to relax skeletal muscles and to facilitate tracheal intubation and mechanical ventilation.

Contraindications: Mivacurium is contraindicated in patients’ known to be hypersensitive. Also contraindicated in pregnancy since there is no information on the use of Mivacron in pregnant women and in patients known or suspected of being homozygous for the atypical plasma cholinesterase gene.

Dose and Administration: By intravenous injection, 70–250 micrograms/kg; maintenance 100 micrograms/kg every 15 minutes; child 2–6 months initially 150 micrograms/kg, 7 months–12 years initially 200 micrograms/kg; maintenance (child 2 months–12 years) 100 micrograms/kg every 6–9 minutes. Doses up to 150 micrograms/kg may be given over 5–15 seconds, higher doses should be given over 30 seconds. In patients with asthma, cardiovascular disease or those who are sensitive to falls in arterial blood pressure give over 60 seconds. By intravenous infusion, maintenance of block, 8–10 micrograms/kg/minute, adjusted if necessary every 3 minutes by 1 microgram/kg/minute to usual dose of 6–7 micrograms/kg/minute; child 2 months–12 years, usual dose 11– 14 micrograms/kg/minute.

ROCURONIUM BROMIDE:

Indications: Rocuronium is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation during routine and rapid sequence induction, and to provide skeletal muscle relaxation (intermediate duration) during surgery. Rocuronium is also indicated as an adjunct in the intensive care unit (ICU) to facilitate intubation and mechanical ventilation.

Contraindications: Hypersensitivity to rocuronium or to the bromide ion or to any of the excipients.

Dose and Administration: Intubation, adult and child over 1 month, by intravenous injection, initially 600 micrograms/kg; maintenance by intravenous injection, 150 micrograms/kg (elderly 75–100 micrograms/kg) or maintenance by

intravenous      infusion,      300–600 micrograms/kg/hour      (elderly      up      to
400 micrograms/kg/hour). Intensive care, by intravenous injection, adult initially

600 micrograms/kg;      maintenance        by       intravenous      infusion,        300–

600 micrograms/kg/hour for first hour, then adjusted according to response.

Depolarising neuromuscular blocking drugs

SUXAMETHONIUM CHLORIDE (Succinylcholine chloride):

Indications: Depolarising muscle relaxant of short duration. neuromuscular blockade (rapid onset, short duration)

Contraindications: family history of malignant hyperthermia, hyperkalaemia; major trauma, severe burns, neurological disease involving acute wasting of major muscle, prolonged immobilisation—risk of hyperkalaemia, personal or family history of congenital myotonic disease, Duchenne muscular dystrophy, low plasma-cholinesterase activity (including severe liver disease)

Dose and Administration: By intravenous injection, initially 1 mg/kg; maintenance, usually 0.5–1 mg/kg at 5–10 minute intervals; max. 500 mg/hour; neonate and infant under 1 year, 2 mg/kg; child over 1 year, 1 mg/kg. By intravenous infusion of a solution containing 1–2 mg/mL (0.1–0.2%), 2.5– 4 mg/minute; max. 500 mg/hour; child reduce infusion rate according to body-weight. By intramuscular injection, infant under 1 year, up to 4–5 mg/kg; child over 1 year, up to 4 mg/kg; max. 150 mg.

Anticholinesterases used in anaesthesia

Anticholinesterases reverse the effects of the non-depolarising (competitive) neuromuscular blocking drugs such as pancuronium but they prolong the action of the depolarising neuromuscular blocking drug suxamethonium.

Neostigmine: has a long duration of action. It is the specific drug for reversal of non-depolarising (competitive) blockade. It acts within one minute of intravenous injection and its effects last for 20 to 30 minutes; a second dose may then be necessary. Glycopyrronium or alternatively atropine, given before or with neostigmine, prevent bradycardia, excessive salivation, and other muscarinic effects of neostigmine

Antagonists for central and respiratory depression

Respiratory depression is a major concern with opioid analgesics and it may be treated by artificial ventilation or be reversed by Naloxone. Naloxone will immediately reverse opioid-induced respiratory depression but the dose may have to be repeated because of the short duration of action of naloxone; however, naloxone will also antagonise the analgesic effect.

NALOXONE HYDROCHLORIDE:

Indications: reversal of opioid-induced respiratory depression; reversal of neonatal respiratory depression resulting from opioid administration to mother during labour; overdosage with opioids.

Contraindications: contraindicated in patients with hypersensitivity to naloxone hydrochloride or to any of the excipients of this medicinal product.

Dose and Administration: By intravenous injection, 100–200 micrograms (1.5–3 micrograms/kg); if response inadequate, increments of 100 micrograms every 2 minutes; further doses by intramuscular injection after 1–2 hours if required; child by intravenous injection, 10 micrograms/kg; subsequent dose of 100 micrograms/kg if no response; if intravenous route not possible, may be given in divided doses by intramuscular or subcutaneous injection. neonate, reversal of respiratory and CNS depression resulting from opioid administration to mother during labour, by subcutaneous, intramuscular, or intravenous injection, 10 micrograms/kg, repeated every 2–3 minutes; alternatively by intramuscular injection, 200 micrograms (60 micrograms/kg) as a single dose at birth.

FLUMAZENIL:

Indications: indicated for the complete or partial reversal of the central sedative effects of benzodiazepines. It may therefore be used in anaesthesia and intensive care in the following situations: Termination of general anaesthesia induced and/or maintained with benzodiazepines. Reversal of benzodiazepine sedation in short diagnostic and therapeutic procedures. For the specific reversal of the central effects of benzodiazepines, to allow return to spontaneous respiration and consciousness, in patients in intensive care.

Contraindications: life-threatening condition (e.g. raised intracranial pressure, status epilepticus) controlled by benzodiazepines.

Dose and Administration: By intravenous injection, 200 micrograms over 15 seconds, then 100 micrograms at 60-second intervals if required; usual dose range, 300–600 micrograms; max. total dose 1 mg (2 mg in intensive care); question aetiology if no response to repeated doses. By intravenous infusion, if drowsiness recurs after injection, 100–400 micrograms/hour, adjusted according

to level of arousal.

Drugs for malignant hyperthermia

Malignant hyperthermia is a rare but potentially lethal complication of anaesthesia. It is characterised by a rapid rise in temperature, increased muscle rigidity, tachycardia, and acidosis. The most common triggers of malignant hyperthermia are the volatile anaesthetics. Suxamethonium has also been

implicated, but malignant hyperthermia is more likely if it is given following a volatile anaesthetic. Volatile anaesthetics and suxamethonium should be avoided during anaesthesia in patients at high risk of malignant hyperthermia. Dantrolene is used in the treatment of malignant hyperthermia. It acts on skeletal muscle cells by interfering with calcium efflux, thereby stopping the contractile process