SYSTEMIC EFFECTS OF KETAMINE

ANAESTHESIOLOGY:

                                       SYSTEMIC EFFECTS OF KETAMINE:

Ketamine is a dissociative anaesthetic drug derived from phencyclidine first in 1962 and introduced for use in 1965. It is on the World Health Association list of Essential Medicines. It is used for anaesthetic purpose especially in countries where anaesthetic equipments and trained staff are in short supply.

      It differs from other intravenous anaesthetic drugs in many respects and produces dissociative anaesthesia rather than generalized depression of the central nervous system. Pharmacologically, it is classified as NMDA (N-methyl-D-Aspartate) Receptor antagonists but does have some activity at other receptors. By blocking these receptors, it induces a trance-like cataleptic state with retention of protective airway reflexes, and cardiopulmonary stability. At sub-anaesthetic doses, ketamine produces a dissociative state characterized by a sense of detachment from one’s physical body (depersonalization) and detachment from the external world (derealisation). At higher doses, it induces an extreme dissociative state known as ‘K-hole’ characterised by depersonalisation, derealisation, disorientation, temporary memory loss, vivid hallucinations and euphoria.

     Some of the characteristics that make ketamine a suitable agent for anaesthesia include: retention of protective airway reflexes, cardiopulmonary stability and analgesic property. Even though transient apnoea may occur after intravenous injection, ventilation is usually well maintained thereafter. The pharyngeal and laryngeal reflexes and a patent airway are maintained well in comparison with other intravenous anaesthetics. There is even dilatation of the bronchial muscles as well. These properties make ketamine suitable for patients who have asthma, chronic obstructive pulmonary disease and other airway diseases when undergoing general anaesthesia. It also makes ketamine the anaesthetic of choice when reliable ventilation equipments are not available. However, normal precautions must still be taken in standard setting to protect the airway and prevent aspiration.

    Ketamine have positive ionotropic effect on the heart which may be related to increased calcium influx mediated by cyclic adenosine monophosphate and increased myocardial sensitivity to epinephrine. During ketamine anaesthesia, arterial blood pressure is increased by up to 25%, the heart rate by approximately 20%, cardiac output may increase and also the myocardial oxygen demand. Ketamine is therefore the anaesthetic of choice for patients in traumatic shock (emergency) who are at risk of hypotension. It is sometimes used for emergency surgery when the patient’s fluid volume status is unknown and cannot be readily determined e.g hypovolaemic shock patients after road traffic accident. Ketamine is especially useful in difficult locations like accident site or emergency surgery in field conditions like war zones.

      Ketamine is also a potent analgesic. It is about the only sedation induction intravenous anaesthetic agent with analgesic properties.  It can be used at sub-anaesthetic doses to relieve acute pain. It may also be used as an intravenous coanalgesic with opiates to manage otherwise intractable pain particularly if this pain is neuropathic (pain due to vascular insufficiency or shingles are good examples). As part of a cream, gel or liquid, ketamine can be used for topical application for nerve pain. Low dose ketamine is also used for the treatment of complex regional pain syndrome. The dissociative anaesthetic effect of ketamine has also been applied for postoperative pain mananagement.

       Ketamine is extremely lipid soluble and induces anaesthesia in about 30 to 60 seconds after intravenous injection. A single average dose for induction (2mg/kg) produces unconsciousness for about 10 to 15 minutes. Vivid and often unpleasant nightmares or hallucinations may occur during recovery from ketamine anaesthesia for up to 24 hours. Also, agitation on recovery from the drug (emergence reaction or emergence phenomena or delirium) is also observed. Due to hallucinations it may cause, ketamine is not typically used as a primary anaesthetic. The incidence of emergence delirium and hallucinations are reduced by avoidance of verbal and tactile stimulation during the recovery period or by concomitant administration of opioids, butyrophenones, benzodiazepines or physostigmine.

     With ketamine, the cerebral metabolic rate is increased in several regions of the brain and cerebral blood flow, cerebral blood volume and intracranial pressure increases. It may be safe in head injury and infact neuroprotective by increasing cerebral perfusion pressure.

   In the gastrointestinal system, ketamine causes hyper salivation (ptyalism). There is drooling and increased oral secretions. Anticholinergics such as atropine or diphenhydramine which thickens the secretions should be avoided. Apart from the rare hyper salivation, vomiting can occur during recovery in 10% of cases with intravenous and 20% of cases with intramuscular use of the drug.

    Skeletal muscle tone is used increased with ketamine. There is skeletal muscle hypertonicity and rigidity.

   In the eye, ketamine causes transient increase in intra-ocular pressure. However, eye movements often persist during surgical anaesthesia.

    In some intensive care units, ketamine has been used in cases of prolonged seizures. Some evidence indicates the NMDA-blocking effect of the drug protects neurones from glutamatergic damage during prolonged seizures.

  Ketamine has also been tried as an etheogen i.e. psychoactive drug use for spiritual or religious effect. It is said to generate ‘the divine within’.

    Due to the detached, dream-like state ketamine creates, the user may find it difficult to move and may therefore be abused as a ‘date rape’ drug.

    
 After intravenous administration, only approximately 12% of ketamine is protein bound.  Ketamine crosses the placenta readily. Therefore foetal concentrations are approximately equal to those in the mother. Its metabolism occurs predominantly in the liver by demethylation   and hydroxylation of the cyclohexanone ring generating metabolites such as norketamine which is also pharmacologically active. Approximately 80% of the injected dose is excreted renally as glucuronides. The elimination half life is about 2 hours. The elimination is slower if benzodiazepines, halothane or barbiturates are administered concurrently. Ketamine may interact with amiodarone or droxidopa.

   In conclusion ketamine remains a vital anaesthetic agent especially in developing countries for its good cardiopulmonary stability and has potential for abuse.