1780 General Anaesthetics blood, then to the brain; recovery is a function of the zolam, and other anaesthetics such as etomidate, propofol, ful if the patient’s cooperation is required, as conscious- removal of the anaesthetic from the brain. With inject- or ketamine. Small doses of short-acting opioids, for ex- ness soon returns once the nitrous oxide is stopped. The able anaesthetics their activity is similarly dependent ample alfentanil, fentanyl, or remifentanil, given before or neuroleptic most commonly employed was droperidol and on their ability to penetrate the blood/brain barrier and at induction allow the use of smaller induction doses of it was usually used with fentanyl although other opioids recovery in turn is governed by their redistribution and some drugs used for anaesthesia, and this technique is par- have also been used. These procedures have since evolved ticularly suitable for poor-risk patients. into conscious sedation and monitored anaesthetic care excretion. The potency of inhalational anaesthetics is After induction, muscle relaxation with a rapidly acting techniques employing newer drugs. often expressed in terms of minimum alveolar concen- depolarising neuromuscular blocker such as suxamethoni- Ketamine used alone can produce a state of dissociative trations, known as MAC values. The MAC of an um aids intubation of the patient. Longer acting, compet- anaesthesia similar to that of neuroleptanalgesia in which anaesthetic is the concentration at 1 atmosphere that itive neuromuscular blockers may then be given to allow the patient may appear to be awake but is unconscious. will produce immobility in 50% of subjects exposed to procedures such as abdominal surgery to be carried out un- Marked analgesia and amnesia are produced, but there a noxious stimulus. Values given under the individual der lighter anaesthesia. For more detail, see Anaesthesia, may be an increase in muscle tone and emergence reac- monographs are based on use without nitrous oxide as p.1900. tions. Dissociative anaesthesia is considered suitable for the latter can reduce the MAC. Other factors including Maintenance of anaesthesia may be achieved with an use in various diagnostic procedures, dressing changes, age, body temperature, and concurrent medication inhalational anaesthetic, an intravenous anaesthetic, or an and in minor surgery not requiring muscle relaxation. such as opioid analgesics can also affect MAC values. intravenous opioid, either alone or in combination. Techniques using local anaesthetics are discussed on Opioid analgesics may also be given for analgesia as sup- p.1853. ◊ General references. plements during general anaesthesia (see also Balanced 1. Royston D, Cox F. Anaesthesia: the patient’s point of view. Lan- cet 2003; 362: 1648–58. Anaesthesia, under Anaesthetic Techniques, below). 2. García-Miguel FJ, et al. Preoperative assessment. Lancet 2003; Long-acting opioids such as morphine or papaveretum Alfadolone Acetate (BANM, rINNM) 362: 1749–57. may cause postoperative respiratory depression. The Acetato de alfadolona; Alfadolone, Acétate d’; Alfadoloni Acetas; 3. Buhre W, Rossaint R. Perioperative management and monitoring short-acting opioid fentanyl, and its congeners alfentanil in anaesthesia. Lancet 2003; 362: 1839–46. Alphadolone Acetate; GR-2/1574. 3α,21-Dihydroxy-5α-preg- 4. Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in post- and sufentanil, appear to produce fewer circulatory chang- nane-11,20-dione 21-acetate. operative recovery. Lancet 2003; 362: 1921–8. es and may be preferred to other opioids, especially in car- Альфадолона Ацетат 5. Sakai EM, et al. Inhalation anesthesiology and volatile liquid an- diovascular surgery; remifentanil may be valuable for its esthetics: focus on isoflurane, desflurane, and sevoflurane. Phar- C23H34O5 = 390.5. macotherapy 2005; 25: 1773–88. very short duration of action. Various combinations of an- CAS — 14107-37-0 (alfadolone); 23930-37-2 (alfadolone 6. Stachnik J. Inhaled anesthetic agents. Am J Health-Syst Pharm algesic techniques, including the use of pre-emptive anal- acetate). 2006; 63: 623–34. Correction. ibid. 2436. gesia, are used or are being investigated for the manage- 7. Nathan N, Odin I. Induction of anaesthesia: a guide to drug ment of surgical pain (see Postoperative Analgesia, p.4). choice. Drugs 2007; 67: 701–23. At the end of surgery drugs are sometimes given to accel- O Anaesthesia. Many drugs are involved in achieving and erate recovery by reversal of the effects of the various OH H3C maintaining conditions suitable for surgery. Conventional agents used during anaesthesia. The neuromuscular block O H general anaesthesia may be divided into a number of stages produced by competitive neuromuscular blockers may be including: reversed with anticholinesterases such as neostigmine and H3C H • premedication edrophonium but atropine or glycopyrronium are also • induction needed to prevent bradycardia and other muscarinic ac- H H tions developing. The opioid antagonist naloxone has been • muscle relaxation and intubation HO • maintenance given to reverse opioid-induced respiratory depression. H However, it may antagonise the analgesic effects of the •analgesia opioids in the control of postoperative pain and the in- (alfadolone) •reversal creasing use of short-acting intravenous opioid analgesics A brief outline of the drugs typically used in each stage should reduce the need for its use. Flumazenil is a benzo- Pharmacopoeias. In BP(Vet). follows. diazepine antagonist that is used to reverse the central sed- BP(Vet) 2008 (Alfadolone Acetate). A white to creamy white For premedication, benzodiazepines and some phenothi- ative effects of benzodiazepines in anaesthetic procedures. powder. Practically insoluble in water and in petroleum spirit; soluble in alcohol; freely soluble in chloroform. azines such as promethazine or alimemazine may be given ANAESTHETIC TECHNIQUES. A balanced combination to sedate and relieve anxiety in apprehensive patients. Bu- Profile of drugs with different actions is often used to provide Alfadolone acetate has been used to enhance the solubility of al- tyrophenones such as droperidol have also been used. The the various components of general anaesthesia includ- benzodiazepines have useful amnesic and muscle-relaxant faxalone (below). It possesses some anaesthetic properties and is ing unconsciousness, muscle relaxation, and analgesia. considered to be about half as potent as alfaxalone. properties and short-acting oral forms are common in cur- This technique, termed balanced anaesthesia, has been rent regimens. The phenothiazines and butyrophenones reported to minimise intra-operative cardiovascular de- are rarely used now although their antiemetic actions may pression, to facilitate a rapid return of consciousness, be useful to control postoperative nausea and vomiting and to have a low incidence of postoperative adverse Alfaxalone (BAN, rINN) (see p.1700). Cloral hydrate is still used in some countries effects such as nausea and vomiting, and excitation. Alfaksaloni; Alfaxalon; Alfaxalona; Alfaxalonum; Alphaxalone; for pre-operative sedation. The use of barbiturates has Typically an opioid is given before or with induction GR-2/234. 3α-Hydroxy-5α-pregnane-11,20-dione. largely ceased. For sedation of children the oral route is and anaesthesia is induced using nitrous oxide and an Альфаксалон often preferred to injections, or the rectal route may be intravenous barbiturate such as thiopental. The opioid is C21H32O3 = 332.5. used in exceptional circumstances. then given in small incremental doses to achieve and CAS — 23930-19-0. Antimuscarinics such as atropine, glycopyrronium, and ATC — N01AX05. maintain adequate analgesia during surgery. Opioid ATC Vet — QN01AX05. hyoscine may be given to inhibit excessive bronchial and analgesics commonly used in this technique include salivary secretions induced by intubation and some anaes- morphine, fentanyl, sufentanil, and alfentanil; buprenor- thetics, although such use is less common nowadays. phine and nalbuphine have also been used. O CH3 Antimuscarinics are also given as premedicants to reduce In total intravenous anaesthesia (TIVA), induction and the intra-operative bradycardia and hypotension induced CH3 maintenance of anaesthesia is achieved with one or more O by drugs such as suxamethonium, halothane, or propofol anaesthetics given intravenously. This allows high in- or by vagal stimulation. Hyoscine also provides some spired oxygen concentrations in situations where hypoxae- CH3 H degree of amnesia. mia may otherwise occur, and is advantageous in surgery Opioids, including morphine and its derivatives, papaver- where delivery of inhaled anaesthetic may be difficult (for H H etum and pethidine, have been widely used before surgery example in bronchoscopy). Combinations used in TIVA to reduce anxiety, smooth induction of anaesthesia, reduce HO include propofol with alfentanil or fentanyl, and mida- H overall anaesthetic requirements, and provide pain relief zolam with alfentanil. Neuromuscular blockers are given during and after surgery. The routine use of opioids as pre- to produce muscle relaxation but there can be difficulty in Pharmacopoeias. In BP(Vet). medicants is now rare and generally restricted to patients assessing the depth of anaesthesia in patients who are par- BP(Vet) 2008 (Alfaxalone). A white to creamy white powder. already in pain. However, they continue to find a role at alysed for mechanical ventilation, and there have been re- Practically insoluble in water and in petroleum spirit; soluble in induction (below). ports of awareness during procedures under total intrave- alcohol; freely soluble in chloroform. Patients may also be given drugs that reduce the danger nous anaesthesia (see also Intraoperative Awareness under Profile from regurgitation and aspiration of gastric contents (see Precautions, above). Alfaxalone was formerly used with alfadolone acetate (above) under Aspiration Syndromes, p.1693), such as the hista- Although now largely obsolete, use of a neuroleptic with [‘Althesin’], as an intravenous anaesthetic for induction and mine H2-antagonists, cimetidine and ranitidine, and the an opioid analgesic produces an altered state of conscious- maintenance of general anaesthesia. proton pump inhibitor, omeprazole. Cardiovascular drugs ness known as neuroleptanalgesia in which the patient is Adverse reactions associated with polyethoxylated castor oil may be needed during surgery to control blood pressure calm and indifferent to the surroundings yet is responsive (present as a vehicle) led to the general withdrawal of alfaxalone and counteract arrhythmias. to commands. The technique was used for diagnostic or with alfadolone acetate from human use. It is still used in veteri- The aim of induction is to produce anaesthesia rapidly and therapeutic procedures such as minor surgery, endoscopy, nary medicine. smoothly. Induction may be achieved with intravenous or and changing dressings. Neuroleptanalgesia can be con- Porphyria. Alfaxalone:alfadolone has been associated with inhalational anaesthetics but intravenous induction may be verted to neuroleptanaesthesia by the concurrent admin- acute attacks of porphyria and is considered unsafe in porphyric more pleasant for the patient. Intravenous drugs used in- istration of nitrous oxide in oxygen; a muscle relaxant may patients. clude the barbiturate thiopental, the benzodiazepine mida- also be included. Neuroleptanaesthesia is particularly use-