The two most common side effects that do occur are dizziness and mild dysphoria, sometimes referred to as psychotomimetic reactions. Mild dysphoric events are far shorter and less severe than true emergence reactions.⁶ The incidence of these ranges from 3 percent to 15 percent, depending on the study’s definition, reporting, and dose.^2,4,6 They typically occur immediately after administration and quickly resolve. An approach where the patient receives a short explanation of the drug’s occasional tendency to cause brief feelings of unreality has, anecdotally, reduced the incidence of dysphoric reactions.^5,6 This is likely because patients who expect such feelings are far less alarmed when they do occur and view them as a brief side effect rather than an unexpected event that could portend an unintentional overdose. Interestingly, a recent study compared LDK intravenous push over 5 minutes to a 15-minute short infusion in 100 mL of normal saline; dysphoria was significantly reduced in the short infusion group, while no differences were seen in analgesia. This would seem to confirm the anecdotal experience that slower administration decreases side effects.⁹

Dizziness is, by far, the most common adverse drug event, reported in roughly 20 percent of patients in randomized controlled trials polling patients about side effects.⁴ Generally, this incidence increases in a dose-dependent fashion in the literature. However, this may have as much to do with differing trial designs as it does with drug effects.

In one large (n=530), retrospective, consecutive case series, 6 percent of patients experienced an adverse event documented in the chart.⁶ Seven patients (1.5 percent) developed transient hypoxia. Four of those also received hydromorphone, and all but one (chronic obstructive pulmonary disease requiring bilevel positive airway pressure) resolved with 2 L of oxygen via nasal cannula. Eighteen patients (3.5 percent) developed psychotomimetic/dysphoric disturbances, but only three received benzodiazepines. The disposition was unaltered in all. Five patients (1 percent) experienced emesis. While this study was limited by its retrospective design, its strength is that, presumably, only clinically relevant adverse drug events were documented. Most important, any incidents of true emergence phenomenon, laryngospasm, apnea, or cardiac arrest would certainly have been detected if they occurred. None were detected in this or any other study.⁶

Discussion

A comprehensive review of the literature reveals that LDK is safe to use. It is most efficacious between 0.15 and 0.30 mg/kg as an intravenous push, but slow infusions show promise. More than 10 studies, not all reviewed here, uniformly demonstrate that LDK is noninferior to morphine when compared head-to-head. Benign side effects are common and include dizziness and dysphoria, as opposed to the nausea and respiratory depression seen from morphine. LDK is indicated any time patients are in pain but is especially appropriate for opioid-tolerant patients, recovering addicts, or patients with a tenuous respiratory status or hypotension. Because of LDK’s opiate-potentiating effects, it is also appropriate and safe to use in patients with acute pain refractory to opioid treatment.⁴