Dissociative Agents

Introduction

Dissociative Anaesthetics interrupt signals from conciousness centers rather then a generalised center depression. The patients eyes remain open with a slow nystagmus, and hypertonus and spontaneous movements may occur. Examples include phencyclidine, ketamine and tiletamine.

Mechanism of Action

Dissociative agents are highly lipid soluble, allowing for their rapid onset of action. They produce a dose related anaesthetic and analgesic effect. It is currently thought that the most likely mechanism of action is antagonism of the N-methyl-D-aspartate (NMDA) receptor. They appear to have a greater somatic analgesic effect compared with visceral pain. NMDA receptors in the CNS are receptors for exitatory amino acids, such as glutamate and aspartate. NMDA antagonists block the NMDA receptor and hence reduce CNS activity. However, they have no effect unless the excitatory transmitters are at work.

Pharmacolocical considerations

Dissociative agents can be given via intravenous or intramuscular route. They under go hepatic metabolism and excreted via the kidney.

Contraindications and Side effects

Central Nervous System

• Dissociative agents significantly increase cerebral blood flow, intracranial pressure (ICP) and cerebrospinal fluid (CSF) pressure.

Cardiovascular System

• Tachycardia and increased arterial blood pressure are seen due to sympathetic activity.
• Increased myocardial oxygen consumption and cardiac work.
• These cardiovascular effects can be limited by the admisitration of benzodiazepines or alpha-2 agonists prior to the agent being given.

Respiratory System

• There may be an initial fall in respiratory rate but this soon normalises.
• Agents can increase salivation and respiratory tract secretions but this can be partly controlled by antimuscarnic administration.

Uses

Dissociative agents are used to provide analgesia, both peri- and post-operatively. They can also be used as the primary anaesthetic agent in combination with other agents in cats and horses. It can also be used in combination for short procedures in ruminants.

Drugs in this Group

Ketamine

Ketamine is the most commonly used dissociative anaesthetic. It has the lowest potency and shortest duration of action of the three agents. It is available as a 10, 50 and 100mg/ml solution. It is often used in combination with morphine and lidocaine in a continuous-rate infusion or MLK drip.

Ketamine is an NMDA antagonist. It is given by constant rate infusion or as a bolus for intra-operative analgesia. Both visceral and somatic analgesia is provided, and the drug inhibits central sensitisation and therefore reduces long-term pain. Ketamine also has anaesthetic properties and is used to provide chemical restraint.

Tiletamine

Tiletamine is available in combination with the benzodiazepine, zolamzepam as a 1:1 combination in powder form which can be made into a highly concentrated solution used for darting wild animals.

Phencyclidine

Phencyclidine was the first dissociative agent used in veterinary patients, it is no longer available for clinical use. However, it is the most potent of the three agents.