Ketamine for Conscious Sedation in Pediatric Emergency Care

Rakhee B. Mistry; Milap C. Nahata, PharmD

Disclosures

Pharmacotherapy. 2005;25(8):1104-1111. 

In This Article

Pharmacology of Ketamine

Ketamine, which has been in use since 1970, is a nonbarbiturate phencyclidine derivative with potent sedative, hypnotic, analgesic, and amnestic properties.[8,9,10] Often referred to as a dissociative agent, ketamine causes a functional and electrophysiologic dissociation between the thalamoneocortical and limbic areas of the brain.[11,12] The ketamine dissociative state is unique in that it does not fit the standard definition of conscious sedation,[1] which requires responsiveness to verbal or tactile stimuli. Therefore, a separate sedation category—dissociative sedation—was introduced.[13] Dissociative sedation is defined as "a trancelike cataleptic state characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability."

Ketamine further differs from other agents in that it lacks the progressive dose-response relationship characteristic of most sedative and analgesic agents. Low doses of ketamine can provide analgesia and sedation, but once a critical threshold has been reached, the characteristic dissociative state appears with no observable level of depth. Administration of additional ketamine may not enhance or deepen the dissociative sedation as would other agents, such as opioids and sedative-hypnotics.[14]

The two most common routes of ketamine administration are the intravenous and intra-muscular routes. The oral route succumbs to first-pass metabolism and decreased absorption and thus requires higher doses. Ketamine is metabolized by hepatic N-methylation to norketamine, which has approximately one third the activity of the parent compound. Further metabolism results in hydroxylation; norketamine then undergoes urinary excretion. The concentration of norketamine is higher in children than adults,[12] suggesting faster metabolism and perhaps higher dosage requirements in children.

Ketamine produces a dose-related acceleration of heart rate and blood pressure thought to be caused by the release of endogenous catecholamines through its stimulatory effect on the sympathetic nervous system.[15] The indirect sympathomimetic effect of ketamine is assumed to dominate over its direct negative inotropic properties, therefore resulting in reduced risk of hypotension.[16] In addition, respiratory function is well maintained with ketamine. Functional residual capacity, minute ventilation, and tidal volume are unchanged, pulmonary compliance is improved, and bronchospasms are relieved due to the release of catecholamines.[17,18] Ketamine has demonstrated significant vagolytic properties; this partially accounts for its ability to cause bronchial smooth muscle relaxation.[12,19]

Although ketamine generally preserves airway patency, rare cases of pulmonary aspiration, apnea, arterial hypoxemia, and laryngospasm have been reported.[20,21,22] Ketamine is a potent sialagogue. It increases salivary and bronchial mucous gland secretions through stimulation of cholinergic receptors; therefore, an antisialagogue such as intramuscular atropine 10 µg/kg-0.1 mg/kg[7,10] or intramuscular glycopyrrolate 2-5 µg/kg[11] is often coadministered.[23] However, no difficulty occurred in 1100 children who received ketamine without atropine.[19]

Ketamine increases intracranial pressure and thus should be avoided in patients at risk for elevated intracranial pressure or those with a history of head trauma.[24,25] Paradoxical hypotension is also possible with ketamine due to a potential direct vasodilatory effect if catecholamine stores are depleted.[26,27] Increased pulmonary vascular resistance has been reported in adults; therefore, ketamine may be contraindicated in pediatric patients with pulmonary hypertension.[28]

Emergence phenomena, which are common in patients with psychiatric disorders, are a hallmark event of ketamine and have been described as vivid dreams, hallucinations, floating sensations, delirium, recovery agitation, and dysphoria. These phenomena seem to be dose related, are more common in patients older than 16 years and in females, and are thought to be caused by altered auditory and visual relays, which lead to misinterpretation of auditory and visual stimuli.[12,16,29] Prophylactic coadministration of a benzodiazepine is used to reduce such phenomena.[11,22,27]

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