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

Clinical Studies

Data regarding the efficacy and adverse effects of ketamine from various studies are presented in Table 1 and Table 2 . Inclusion criteria for most of the studies reviewed consisted of informed consent from parents and guardians, and patients aged 18 years or younger who were undergoing various procedures in the emergency department when some form of sedation was desirable. For almost all studies, exclusion criteria consisted of acute or chronic pulmonary infection or cardiovascular disease, hypertension, head injury, central nervous system mass lesions, hydrocephalus and other conditions associated with intracranial hypertension, glaucoma, previous adverse reaction to ketamine, psychosis, thyroid disorder, porphyria, and meal intake within 3 hours of the operation.

Research personnel consisted of a practitioner responsible for treatment of the patient and administration of drugs for sedation, and nurses responsible for constant monitoring of vital signs and assisting with any supportive or resuscitation measures. Discharge criteria, as set forth by the American Academy of Pediatrics,[1] consisted of satisfactory and stable cardiovascular function and airway patency, patient easily arousable with protective reflexes intact, patient able to talk and to sit up unaided, presedation level of responsiveness or a level as close to that as possible for an impaired child, and adequate state of hydration.

Two clinical studies used solely the intravenous route for ketamine administration.[10,30] In one of these studies, adequate sedation was achieved in only 50% of patients with the initial bolus dose of ketamine 1.0 mg/kg; however, 1.5 mg/kg was adequate in 94% of patients.[30] No deleterious cardiopulmonary effects were noted with either dose. Hypersalivation was reported in one patient; no antisialagogue was given for prophylaxis or treatment. Oxygen saturation remained above 93% in all patients. The authors stated that four children who cried during the recovery period may have been experiencing emergence reactions, although no sequelae were reported. Two (6.6%) children vomited, which was close to the 8.5% rate of emesis reported in an earlier study.[27]

The other study sought to determine whether emergence reactions associated with ketamine occurred more frequently in older than younger children.[10] No clinically important difference in the number or severity of reactions occurred in relation to age. Since severe, unpleasant reactions were uncommon and of short duration in older children, the authors concluded that emergence reactions should not be an excluding factor for ketamine administration in older children.

One study reported safe use of intramuscular ketamine by qualified nonanesthetist staff for short, painful procedures in emergency departments.[7] In another study, intramuscular ketamine 4-5 mg/kg produced adequate sedation in 93-100% of children, suggesting that this dose range is optimal for sedation.[14] However, one study used intramuscular ketamine 3 mg/kg; the author speculated that higher doses may be needed if adjunctive local anesthesia is withheld.[19] Neither the 3- nor the 4-mg/kg dose resulted in general anesthesia.

In one study, transient airway complications were noted in 1.4% of 1022 patients, with no indication of hypotension or more than a mild increase in blood pressure in any patient.[22] No adverse effects with sequelae were documented, and the probability of such a complication was considered extremely low (95% confidence interval [CI] 0-0.3%). The authors stated that stimulation of the posterior pharynx was a relative contraindication to ketamine due to four cases of laryngospasm reported in the study. Episodes of apnea were observed within 4-5 minutes of intramuscular ketamine administration, which coincided with peak concentrations of ketamine in the central nervous system. Data from this study also indicated that the risk of clinical aspiration with ketamine was minimal.

In a subsequent study[31] based on the 1022 patients in the above study,[22] emesis was associated with increasing age (p<0.001). Recovery agitation was associated with the presence of an underlying medical condition (p=0.004) and was inversely associated with increasing age (p<0.001). No study variable was predictive of ketamine-associated airway complications, and no significant ketamine dose relationship with airway complications, emesis, or recovery agitation was found. Thus, it would be difficult to make clinical decisions regarding selection of patients for ketamine administration based on these results.

Another group found ketamine to be the first-line agent for sedation of children with fractures in the emergency department.[11] Sedation was adequate in 89% of 114 patients after intravenous or intramuscular administration of ketamine. The authors suggested that ketamine should be used only in an environment such as the emergency department, with one-on-one monitoring and board-certified physicians skilled in airway management directly involved in the care of the patient. In another study, the intramuscular route demonstrated slower onset but longer duration of action than the intravenous route.[8] Investigators have recommended that intravenous ketamine be given slowly over 30-60 seconds and be used for short procedures, and that the intramuscular route be used for longer, more complex procedures.[8,30]

One study assessed the efficacy and adverse effects of orally administered ketamine.[9] The authors found oral ketamine more effective than placebo regarding patient tolerance of lidocaine injection (p<0.001) and suturing (p=0.009). Also, a deeper degree of sedation was noted with ketamine than with placebo (p=0.012). No significant differences were found in vital signs or oxygen saturation changes between the groups. The authors suggested that the intravenous and intramuscular routes subject the patient to additional discomfort and pain, making the oral route the least anxiety-provoking for sedation in young children. However, oral ketamine is not commercially available in the United States.

A more recent study found that injection of a local anesthetic was better tolerated with concurrent oral ketamine than oral midazolam (p=0.029).[32] However, no difference between oral ketamine and oral midazolam was observed regarding tolerance of a topical local anesthetic. Oral ketamine resulted in an acceptable level of sedation faster than oral midazolam (20 vs 43 min). Emesis was more common (20% of patients) with ketamine, and dysphoria and behavioral disturbances within 2 weeks of discharge were more common with midazolam (p=0.048). The authors suggested that oral ketamine 10 mg/kg provided better sedation than oral midazolam 0.7 mg/kg.

A comparison of intramuscular ketamine with intranasal midazolam revealed that children given ketamine were less likely to cry or be restrained during their procedure than those given midazolam (12% vs 25%, p<0.01).[33] Difficulty in administering intranasal midazolam was noted in 66% of patients. No differences between groups were found regarding the recovery period. Ketamine was rated as the preferred drug by nurses, physicians, and parents.

Some studies used adjuvant midazolam with ketamine to reduce the frequency of emergence phenomena. In one study, adequate sedation was achieved in all 27 patients receiving intravenous ketamine plus midazolam versus 24 of 26 patients who were adequately sedated with intranasal midazolam alone.[34] Onset of sedation was quicker with intravenous ketamine plus midazolam than intranasal midazolam alone (3.2 vs 7.4 min, p<0.001). Physicians (95% vs 83%, p<0.35) and parents (95% vs 78%, p=0.10) were more satisfied with the combination than with intranasal midazolam alone. No patient in the group receiving intravenous ketamine plus midazolam experienced emergence phenomena.

However, another study found no correlation between the addition of midazolam to ketamine and frequency of emergence phenomena.[29] No difference was observed in the effectiveness or duration of sedation between intravenous ketamine and intravenous ketamine plus midazolam. Emesis was more frequent in the ketamine-only group (ketamine 19.4% vs ketamine-midazolam 9.6%; rate difference 9.8% [95% CI 1.4-18.2%]), whereas oxygen desaturation was more frequent in the ketamine plus midazolam group (ketamine 7.3% vs ketamine-midazolam 1.6%; rate difference 5.7%, [95% CI -10.6 to -0.9%]).

One study compared intramuscular ketamine with an intramuscular combination of meperidine, promethazine, and chlorpromazine.[5] Ketamine led to quicker onset of sedation (3 vs 18 min, p<0.01) and discharge from the emergency department (85 vs 113 min, p=0.01) than the combination. This resulted in less distress for the patients who received ketamine. Also, ketamine was associated with greater physician satisfaction than the meperidine-promethazine-chlorpromazine combination. Sedation was adequate in all 17 patients receiving ketamine and in 10 of 12 patients receiving meperidine-promethazine-chlorpromazine. No significant adverse reactions were noted in either group. These study results indicated that ketamine is a relatively safe agent for sedation, fulfills many criteria for an ideal sedative agent, and should be considered for use in children in the emergency department.

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