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Ketamine is a unique pharmaceutical agent in that it provides sedation, amnesia, analgesia, and anxiolysis. Its safe and effective use in pediatric PSA is well studied.25 It is the most commonly used anesthetic agent throughout the world. It has the best safety profile in terms of cardiorespiratory complications of any agent. Ketamine is a derivative of PCP that generates a functional and electrophysical dissociation between the brain's cortical and limbic systems. This results in a dissociative state whereby the patient is in a trance-like cataleptic condition in which sensory perceptions and memory are blunted. Although the patient appears awake, they are dissociated from their environment. Random tonic movements will occur and gentle physical restraint may be required.
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Ketamine is a positive inotrope. It increases the heart rate, blood pressure, cardiac output, and intracranial pressure. The blood pressure and heart rate may slightly increase with the use of ketamine. The systolic and diastolic blood pressure may increase up to 30 mmHg (average 15 mmHg). The heart rate may increase up to 30 beats per minute with an average of 15 beats per minute. These effects are believed due to decreased uptake of catecholamines at neural endplates.
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Ketamine's effect on the respiratory system includes bronchodilation, a slight increased respiratory rate, increased secretions, and potential laryngospasm. Ketamine is a potent bronchodilator. It does not depress airway reflexes like narcotics or benzodiazepines. The side effects of increased respiratory secretions can be blocked with atropine or glycopyrrolate. Administer atropine prior to or concurrently with ketamine in a dose of 0.01 mg/kg to a maximum of 0.3 to 0.5 mg. Administer glycopyrrolate before ketamine in a dose of 0.005 mg/kg to a maximum of 0.25 mg. Atropine administration is associated with less adverse respiratory events, less recovery agitation, and less vomiting during recovery than glycopyrrolate.26 Atropine also causes more side effects, compared to glycopyrrolate, because it crosses the blood–brain barrier.27,28 A recent trend is to not use an antisialogue as excessive respiratory secretions are uncommon and not associated with adverse respiratory events.29
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Ketamine may be administered by several routes. Rapid predictable effects are best seen with parenteral administration. Intravenous dosing (0.5 to 1.0 mg/kg slowly, up to 2 mg/kg) is approximately one-fourth of the intramuscular dosing (1 to 6 mg/kg, usually 2 to 4 mg/kg). A dissociative state is produced in less than a minute with intravenous administration and 2 to 10 minutes via the intramuscular route. Intravenous dosing may be repeated at 5 minutes with an additional 1 to 2 mg/kg. Intramuscular dosing may be repeated at 10 minutes with an additional 2 to 4 mg/kg if adequate sedation has not been achieved. Although ketamine may be given orally (5 to 6 mg/kg) or rectally (5 to 10 mg/kg), its titratability is poor, which makes its effectiveness much less predictable. Intramuscular dosing may be more commonly associated with laryngospasm when compared to intravenous administration.30
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Due to its safety profile, ketamine may be administered intravenously or intramuscularly. Intramuscular administration is preferable when intravenous access is difficult to establish, intravenous access is not required for another reason, and for procedures lasting 15 to 25 minutes due to its longer effects. Intravenous administration is preferable if intravenous access is required for another reason, intravenous access is easily obtained, for procedures lasting less than 10 minutes, and to decrease recovery time.31
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The lack of cardiorespiratory compromise of ketamine and the effectiveness of intramuscular administration make it an excellent agent for pediatric PSA. Patients tend to remain hemodynamically stable when using ketamine, reducing the need for intravenous access for fluid boluses and reversal agents. This is especially true in children where intravenous access can be a difficult procedure. A medication that can be safely administered intramuscularly not only simplifies PSA, but also improves patient and family satisfaction.
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Contraindications to the use of ketamine include age less than 3 months, procedures involving pharyngeal stimulation, known cardiovascular disease, concurrent head trauma with altered mental status, airway compromise including previous tracheal surgery/stenosis, glaucoma, known CNS mass lesions, increased intracranial pressure, penetrating globe injuries, active upper or lower respiratory disease, and porphyria. Preliminary information suggests that ketamine is safe to administer in head injury patients in the pediatric intensive care unit.32 Further study is required before this can become general practice in the Emergency Department.
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Patients will exhibit a slow emergence from the effects of ketamine over the course of 1 to 2 hours. Ketamine is metabolized and excreted by hepatic mechanisms. Place the patient in a quiet room that is free of excessive external stimuli to minimize the possibility of them becoming hyperactive or overstimulated by their surroundings. Ketamine-associated emesis is a commonly seen side effect.30,33–35 The rate of emesis is higher with intramuscular administration, with initial intravenous doses over 2.5 mg/kg, and with total doses ≥5.0 mg/kg.30,33 Although, a study of over 1000 children refuted this theory.34 The use of intravenous ondansetron (0.15 mg/kg, maximum 4 mg) decreased the rate of ketamine-associated emesis.35
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Emergence reactions are hallucinations that occur as the ketamine wears off and the patient awakens. They may be seen in up to 50% of adults and up to 10% of children given ketamine. The etiology of these emergence reactions is unknown. There is an association of emergence reactions with an age over 10 years, females, rapid intravenous administration, stimulation during the recovery period, and personality disorders. Rarely will a child less than 10 years of age develop an emergence reaction with hallucinations.
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The incidence of emergence reactions can be decreased. Administer the ketamine slowly intravenously. Place the patient in a dark, quiet room with minimal sensory stimulation during the recovery period. Treatment with benzodiazepines is indicated if an emergence reaction develops. The concurrent administration of midazolam in a dose of 0.025 to 0.050 mg/kg can reduce emergence reactions. One study found no advantage of combining midazolam with ketamine in preventing an emergence reaction.36 Another study found midazolam significantly reduced emergence reactions in adults.37 A recent review found no benefit and no harm in coadministering benzodiazepines.33 The concurrent use of midazolam is Physician-dependent, has no serious sequelae, and may reduce emergence reactions.
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The use of ketamine and propofol in combination has been coined “ketofol.” The reason these agents were combined was to provide appropriate sedation and analgesia while decreasing adverse events by using less of each individual agent. The combination of ketamine and propofol is effective for PSA.38–44 It provides a more rapid recovery than ketamine alone. The combination has similar complication rates, less adverse effects, and higher satisfaction scores than using higher doses of ketamine as a single agent.
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There is no established standard dosing. Prepare both the ketamine and the propofol as a 10 mg/mL solution. These agents can then be administered intravenously in a 1:1 ratio in aliquots of 1 to 3 mL every 2 minutes until the desired effect is achieved. Another option is to mix equal parts of both solutions into one syringe and administer the appropriate volume to deliver 0.5 mg/kg of each agent. Additional boluses can be administered to deliver 0.25 mg/kg of each agent every 2 to 3 minutes until the desired effect is achieved.