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In common with other mu agonists, methadone can cause respiratory depression, although this is unlikely when used at clinical doses in conscious cats and dogs. Respiratory depression may occur when given i.v. during general anaesthesia due to increased depth of anaesthesia. Vomiting is rare, although methadone will cause constriction of GI sphincters (such as the pyloric sphincter) and may cause a reduction in GI motility when given over a long period. Methadone crosses the placenta and may exert sedative effects in neonates born to bitches treated prior to parturition. Severe adverse effects can be treated with naloxone.

Other CNS depressants (e.g. anaesthetics, antihistamines, barbiturates, phenothiazines, tranquillizers) may cause increased CNS or respiratory depression when used concurrently with narcotic analgesics.

Not recommended for animals whose eyes are at risk of perforation or who have raised intraocular pressure. The evidence that ketamine increases intracranial pressure is weak.

Cardiovascular depression, rather than stimulation, and arrhythmias may arise in animals with a high sympathetic nervous system tone (e.g. animals in shock or severe cardiovascular disease). Tachycardias can also arise after administration of high i.v. doses. Respiratory depression may be marked in some animals. Ketamine may result in 'spacey', abnormal behaviour for 1–2 hours during recovery. Prolonged administration of ketamine by infusion may result in drug accumulation and prolonged recovery.

Do not give to cats by CRI during the perioperative period due to the negative haemodynamic effects. Do not give lidocaine solutions containing adrenaline i.v. Do not use solutions containing adrenaline for complete ring block of an extremity because of the danger of ischaemic necrosis.

Depression, seizures, muscle fasciculations, vomiting, bradycardia and hypotension. If reactions are severe, decrease or discontinue administration. Seizures may be controlled with i.v. diazepam. Monitor the ECG carefully during therapy. Cats tend to be more sensitive to the CNS effects. The propellant used in unauthorized aerosol preparations (e.g. Xylocaine spray) is alleged to have caused laryngeal oedema in cats and should not be used to desensitize the larynx prior to intubation.

Cimetidine and propranolol may prolong serum lidocaine clearance if administered concurrently. Other antiarrhythmics may cause increased myocardial depression.