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Pharmacodynamics
- acts on N-methyl-d-aspartate receptor and µ receptor
- dissociative anaesthesia - characterized by:
- catalepsy
- = a characteristic akinetic state
with a loss of orthostatic reflexes but without impairment of consciousness,
in which the extremities appear to be paralysed by motor and sensory failure
- light sedation
- amnesia
- amnesia for events following apparent recovery common
- marked analgesia
- analgesic effect appears to be largely related to the blocking of the
affective-emotional rather than the somatic component of pain perception
- analgesia produced even by sub-anaesthetic doses persists well into the
post-op period
- minimal respiratory depression
- rate of onset of anaesthesia slower than after barbiturates
- may be difficult to get a clear
end-point indicative of onset of sleep as patients appear to gaze sightlessly
into space and may not close their eyes for several mins. Eyelash, corneal and
laryngeal reflexes remain unimpaired. There is usually increased muscle tone
accompanied by grimacing or involuntary muscle movement and tremor but no response to
auditory stimuli
- both cerebral blood flow and cerebral oxygen consumption increased.
Accompanied by raised ICP. Rise in ICP and blood flow can be abolished by
hypocarbia produced by controlled ventilation
- increases HR and BP indirectly by vasomotor stimulation through sympathetic
NS (releases catecholamines from nerve endings)
- has myocardial depressant properties and should be avoided in patients with
high cervical cord lesions in whom vasoconstriction will not occur
- recovery:
- consciousness returns 10-15 min after dose of 2 mg/kg
- difficult to determine exact moment of recovery of consciousness. Muscle
tone reverts to normal first, after which there may be a period in which the
patient seems "distant". Final apparent return of full consciousness
may be sudden and may occur from a few mins to more than an hour after first
evidence of recovery of consciousness
- diplopia and other visual disturbance common on awakening
- emergence phenomena (eg vivid dreams and hallucinations)
Pharmacokinetics
- hepatic microsomal metabolism to norketamine which has 20-30% of activity
of parent
- data are sparse for patients with liver or renal failure
Use in ICU
- not recommended for routine sedation but may be useful in difficult
situations
- bronchodilator properties may useful in asthmatics who require sedation for
mechanical ventilation but there are no controlled data supporting its use
- patients who have been critically ill for a prolonged period may have
exhausted their catecholamine stores. In these patients the myocardial
depressant effect will not be counteracted by a vasoconstrictor effect and
the blood pressure may fall
Doses
- usual adult IV induction dose is 2 mg/kg but most patients will fall asleep
with doses as low as 1 mg/kg
- Sedation
- subhypnotic doses (<5 µg/kg/min) may be useful for patients who
are difficult to sedate with narcotic and benzodiazepine infusions
- at this low dose usual adverse effects (eg tachycardia,
hypertension, increased ICP and emergence reactions) do not seem to
occur
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Further reading
Liu LL, Gropper MA. Postoperative analgesia and
sedation in the adult intensive care unit. A guide to drug selection. Drugs,
2003; 63(8):755-67
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