Ketamine Infusions for Pediatric Sedation and Analgesia

Marcia L. Buck, PharmD, FCCP, FPPAG

Disclosures

Pediatr Pharm. 2016;22(6) 

In This Article

Adverse Effects

Emergence reactions occur in approximately 5–12% of patients receiving ketamine.[2,3] These reactions: dysphoria, agitation, anxiety, and other behavior changes, as well as hallucinations or nightmares are not correlated to patient age or dose. Most symptoms resolve quickly, but can continue for up to a week. Clinicians have traditionally administered a benzodiazepine with ketamine in an effort to reduce emergence reactions, based on an early study showing benefit. Newer research, including two controlled trials in children and a meta-analysis, have not found this to be effective and may place the patient at risk for adverse effects.[11] Benzodiazepines may be of benefit in children with a high level of anxiety at the time of the procedure. Emergence reactions may also be reduced if verbal and tactile stimulation is minimized; however, the effectiveness of this approach has not been well studied.

Nausea and vomiting are reported to occur in 8–25% of children given ketamine.[3,12] Higher rates have been associated with larger doses (an initial dose ≥ 2.5 mg/kg or total dose ≥ 5 mg/kg), IM administration, use with opioids, and increasing patient age. In a study of 8,282 pediatric patients, the peak age for emesis was 12 years. Ondansetron is often effective in reducing emesis. Other commonly reported adverse effects reported with ketamine include erythema or rash, injection site pain, transient diplopia or nystagmus, and tonic clonic movements that may resemble seizures.[3]

Several rare but potentially life-threatening adverse effects have been associated with ketamine use, including laryngospasm, apnea, impaired cardiac function, increased intracranial pressure, and diabetes insipidus. Recent analysis of more than 8,282 children given ketamine for procedural sedation identified a 0.3% incidence of laryngospasm.[13] There was no association with age or dose. Analysis of a case-control subset found no difference in the incidence of laryngospasm in patients given an anticholinergic (OR 0.22, 95% CI 0.02–3.2, p = 0.269). In contrast, concomitant benzodiazepine use resulted in a lower incidence (55% versus 38% in patients not given a benzodiazepine, OR 13.7, 95% 1.51–125, p = 0.02).

While most patients experience no change in cardiac function or increased function while receiving ketamine, the negative inotropic effect of ketamine on the myocardium outweighs its sympathomimetic effect in some patients. In a recent paper from Eken and colleagues, the effects of ketamine on cardiac function were measured in 22 children (mean age 3.5 ± 2.2 years) receiving procedural sedation during suturing of incisions on the face, scalp, or hand.[14] Cardiac contractility was measured prior to and 10 minutes after a 1.5 mg/kg IV ketamine dose. Ejection fraction was reduced in 14 patients (63.6%), with a mean reduction of 5.6 ± 3.1%. Systolic blood pressure was reduced in 10 of the 14 patients with a reduced ejection fraction. The mean decrease from baseline was -7.6 ± 10.9 mmHg. In contrast, 80% of the patients without a reduction in ejection fraction had an elevated systolic blood pressure. While the small sample size limits the conclusions which can be drawn, this paper may stimulate future research to aid in determining which children are more likely to experience adverse cardiac effects.

Ketamine has the potential to increase intracranial pressure (ICP), and it is recommended that ketamine not be used in the initial management of patients with an elevated ICP. Once stabilized, ketamine has been shown to reduce ICP and improve cerebral perfusion in both traumatic and non-traumatic brain injury. Alternative sedatives should be used in patients with cerebrospinal shunt malfunction, meningitis, intraventricular hemorrhage, or other causes of impaired CSF circulation.[2,3]

There are rare reports of diabetes insipidus (DI) occurring after ketamine use, including a recent case in a 2-year-old child with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and hypertrophic cardiomyopathy.[15] The patient was admitted for pneumonia and subsequent respiratory failure requiring intubation. A ketamine infusion was initiated for sedation and facilitation of mechanical ventilation. The patient developed symptoms of DI shortly after ketamine was started and was successfully managed with vasopressin. The authors suggested that inhibition of glutamate produced by ketamine may prevent arginine vasopressin release from the neurohypophysis and that patients receiving ketamine infusions should have close monitoring of serum sodium and urine output prior to, during, and after infusion.

Ketamine has been shown to produce neuronal apoptosis in immature animal models and in isolated human neuronal cells. While current research with ketamine for procedural sedation has not revealed a significant risk for adverse neurologic effects, there is limited information available on the potential cognitive effects of long-term use.[16,17] A recent study of 11 children receiving oral ketamine for chronic pain found no decline in neurocognitive testing over a 14-week period.[18]

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