Ketamine Infusions for Pediatric Sedation and Analgesia

Marcia L. Buck, PharmD, FCCP, FPPAG

Disclosures

Pediatr Pharm. 2016;22(6) 

In This Article

Clinical Experience

Postoperative Analgesia

The effectiveness of ketamine in children has been evaluated in a number of studies. Several recent papers have examined ketamine in unique patient populations. Asadi and colleagues compared the combination of ketamine and acetaminophen versus acetaminophen alone for post-operative pain control after pediatric adenotonsillectomy.[7] A total of 98 children between 3 and 12 years of age were enrolled in this randomized, triple-blind trial. Induction and maintenance anesthesia were the same in all patients, and each received intravenous acetaminophen at a dose of 15 mg/kg starting 15 minutes prior to the end of the case and every 6 hours afterwards for 24 hours. Patients received either ketamine 0.25 mg/kg or placebo 15 minutes before the end of the case. All patients received opioids as needed based on Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores. Patients in the ketamine/acetaminophen group had significantly lower pain scores at 30 minutes and 6 hours (3.4 ± 1.2 versus 4.04 ± 0.7 in the controls at 30 minutes, p = 0.003 and 2.98 ± 0.9 versus 3.37 ± 0.73, p = 0.02 at 6 hours). The difference in pain scores at 12 hours, as well as the incidence of nausea, vomiting, and opioid use were no different. The authors concluded that low-dose ketamine was beneficial in reducing post-operative pain without adverse effects.

Use in the Intensive Care Setting

Ketamine can be a useful addition to multimodal sedative/analgesic regimens in children requiring mechanical ventilation.[5,6,8,9] The increase in catecholamine concentrations resulting from its use produces bronchodilation at β2-adrenergic receptors which may be of benefit to children with bronchospasm or status asthmaticus. Although not yet studied in children, ketamine may also reduce the development of opioid tolerance or mitigate the symptoms of opioid withdrawal in infants and children given multimodal sedation and analgesia while intubated.

In the March 2016 issue of the Annals of Pharmacotherapy, Golding and colleagues published a review of the reports of ketamine continuous infusions for sedation or bronchospasm in children.[8] The authors identified three studies, three case series, and five case reports in both intubated and spontaneously breathing children. A total of 74 patients were included, with 72 receiving a loading dose between 0.2 and 2 mg/kg and an infusion ranging from 0.2 to 3.6 mg/kg/hr. The higher doses were typically used in patients treated for bronchospasm. Overall, the authors of these papers reported satisfactory sedation and analgesia, improved pulmonary compliance and oxygenation, and minimal adverse effects. There were two reports of nystagmus, one case of flushing, and one report of hypertension.

Of the papers included in this review, only two reports described the use of a ketamine infusion for sedation and analgesia during mechanical ventilation. In 1990, Tobias and colleagues described five children (7 months to 14 years of age) who received ketamine after developing adverse effects with opioids or benzodiazepines.[5] Four of the children were receiving mechanical ventilation. The patients each received a loading dose of 0.5 to 1 mg/kg over 2–3 minutes followed by an infusion of 0.6–0.9 mg/kg/hr. The duration of infusion ranged from 48 to 96 hours. No adverse effects were attributed to ketamine use; however, one patient developed elevated liver transaminases felt by the authors to be the result of postoperative hypoperfusion. An additional case report described an 11-year-old patient with meningococcal septic shock who developed hypotension and bradycardia with midazolam at a dose of 0.18 mg/kg/hr.[9] Ketamine was initiated at 0.24 mg/kg/hr and the midazolam infusion was decreased to 0.05 mg/kg/hr, resulting in stabilization of blood pressure. He remained on ketamine for 26 hours without adverse effects.

Use in Chronic Pain

In 2015, Sheehy and colleagues at the Children's National Health System published an intriguing longitudinal study of 63 children (median age 15 years) who received ketamine infusions for treatment of chronic pain.[10]The majority of the patients (37%) were being treated for complex regional pain syndromes, with the remaining patients treated for chronic headache or fibromyalgia. The most frequent location was the lower extremities, in 35% of patients. Treatment consisted of an infusion of 0.1–0.3 mg/kg/hr administered by a nurse and anesthesiologist in a clinic setting for 4 to 8 hours per day. Treatments could be provided for a maximum of 16 hours over a 3-day period. The primary objective of the study was the change in pain scores before and after treatment. The use of oral opioids was evaluated as a secondary outcome.

A total of 277 ketamine administrations were documented over 15-month period. Ketamine produced a significant reduction in pain scores compared to baseline (mean reduction -1.6 ± 0.24, p < 0.001). The reduction was most pronounced in patients with complex regional pain syndromes, compared to other diagnoses, and in patients with a history of trauma, chemotherapy-induced neuropathy, or postural orthostatic tachycardia syndrome (POTS). In 37% of the treatments, ketamine produced a 20% or greater reduction in pain scores compared to baseline. There was no significant difference in overall opioid use (mean change -0.1 ± 0.05 mg/kg/day in morphine-equivalent intake, p = 0.3). Ketamine was well tolerated, with no significant psychotropic or hemodynamic adverse effects. The authors concluded that ketamine infusions in the outpatient setting may be a beneficial option for patients who do not respond to or require high-dose opioid therapy. An additional case report described a 5-year-old with acute myeloid leukemia and graft versus host disease (GVHD) who was managed with hydromorphone and a ketamine infusion for over 5 months.[11] The dose was gradually increased to a maximum dose of 0.54 mg/kg/hr. An attempt to reduce the dose resulted in an increase in pain scores and a return to the previous dose. Following clinical improvement, both the opioid and ketamine were gradually weaned. Mild irritability and restlessness were noted after discontinuation of both drugs, but resolved within 3 days without intervention.

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