Ketamine

Ketamine is a cyclohexamine derivative presented as a clear solution in multi-dose vials, at a concentration of 100 mg/ml. The solution has a pH of around 4 and can cause pain on injection when used by extravascular routes.

Central nervous system: Ketamine produces a state of dissociative anesthesia (superficial sleep combined with profound analgesia and amnesia), completely unlike other forms of anesthesia. It appears to provide good somatic analgesia but poor visceral analgesia. During dissociative anesthesia, eyelid and corneal reflexes remain intact and the eyes remain open. Ocular lubricants should be used to prevent corneal desiccation. Ketamine stimulates the CNS, and may induce seizures in some patients, particularly if administered on its own. Dogs are particularly susceptible to this effect. For this reason, there is little, if any, justification for sole administration of ketamine.

Cardiovascular effects: Ketamine is unique amongst anesthetic agents in its effects on the cardiovascular system. In vitro it has direct negative inotropic effects, resulting in reduced myocardial contractility and cardiac output, but in vivo this effect is offset by concurrent stimulation of the sympathetic nervous system, usually resulting in an overall increase in cardiac output and arterial blood pressure. All other anesthetic agents will tend to depress these physiological variables. However, the argument that ketamine may be safer for critical cases due to its cardiovascular sparing properties may be invalid, since these patients are often already exhibiting maximal sympathetic tone to maintain perfusion of vital organs, and when ketamine is administered its direct negative inotropic effects may not be counterbalanced by a further increase in sympathetic output. This could then result in decreased cardiac output and arterial blood pressure. Ketamine appears to have minimal effects on peripheral vascular resistance. Due to the increase in arterial blood pressure, ketamine can cause elevations in intracranial pressure. This is not significant in normal patients, but may be problematic in those with intracranial pathology, e.g. brain tumours, or following head trauma.

Respiratory effects: Ketamine commonly produces a characteristic respiratory pattern, termed apneustic breathing – slow inspiration, followed by a pause, followed by rapid expiration. Although this is unusual, it tends to have little effect on blood gas values, although hypoxaemia and hypercapnia may occur unpredictably in some animals. Ketamine maintains pharyngeal and laryngeal reflexes better than other anesthetic agents, but it cannot be relied upon to provide airway protection since these reflexes are still depressed. It also increases salivation and respiratory secretions, and for this reason some authorities recommend concurrent antimuscarinic administration. This appears unnecessary when ketamine is combined with an α2 adrenoceptor agonist.

Musculoskeletal effects: Ketamine increases muscle tone and may cause rigidity if administered on its own, so is usually combined with drugs with good muscle relaxant properties (benzodiazepines, alpha2 adrenoceptor agonists).

Analgesia: At anesthetic doses, ketamine provides good somatic analgesia but poor visceral analgesia. Thus, if it is used as the major part of an anesthetic protocol for abdominal surgery, for example, ketamine must be combined with an agent that provides visceral analgesia: alpha2 agonists are often used to achieve this. Recently, there has been growing interest in the use of low doses of ketamine administered by constant rate infusion to provide analgesia. Further details may be found in Chapter 7.

The main advantage of ketamine in small animal anesthesia is that it can be given by either intravenous or intramuscular routes, and so, is particularly useful for fractious patients, especially cats, where it may be impossible to achieve intravenous access. The subcutaneous route can be used but is slightly less predictable. Although ‘Alfaxan’ can also be given by the intramuscular route, the volume required is much larger than that for ketamine, which is a major advantage of the latter. Intramuscular ketamine often provokes a pain response, however, due to the low pH of the solution. The drug is also absorbed across mucous membranes, and so can be squirted into the mouth of vicious cats, and will still work (although to a lesser extent than when administered intravenously or intramuscularly – an additional dose may have to be given intravenous or intramuscular once the cat is manageable). However, there is little doubt that ketamine is best administered intravenously, as it can be titrated to effect. Prolonged recovery can occur following large doses intramuscularly.

As a highly lipid-soluble drug, ketamine provides rapid onset of anesthesia when administered intravenously (although slightly slower than thiopental or propofol). Onset is slower with intramuscular use, but still occurs within 5-10 min.

Ketamine undergoes extensive hepatic metabolism in the dog, but is mainly excreted unchanged via the kidney in cats.

Ketamine – Summary

Indications

Induction of general anesthesia:

• where intravenous access is not possible

• high-risk patients Analgesia

Side effects

Cardiovascular stimulation

CNS stimulation (seizures)

Muscle hypertonicity

Contra – indications

Inability to secure airway

Raised intracranial pressure

Arterial hypertension