Author: Thomas Rosenthal
Surgical patients who receive analgesic doses of ketamine together with dexmedetomidine should be closely monitored before and immediately after they leave the hospital because of the potential neurocognitive and behavioral effects of the drug combination, a study has found.
“At analgesic doses required for pain relief, ketamine administered in combination with dexmedetomidine impairs thinking, behavior and memory,” said Amie Hayley, PhD, a senior research fellow at Swinburne University of Technology, in Victoria, Australia, who was the lead author of the study. “These effects occur both during the treatment period as the drugs are being administered and for up to two hours after treatment has concluded.”
Dr. Hayley and her colleagues at Monash Health, also in Victoria, Australia, explored the neurocognitive effects of ketamine alone and in combination with either dexmedetomidine or fentanyl on 39 patients. The patients received a ketamine bolus of 0.3 mg/kg, followed by a ketamine infusion of 0.15 mg/kg per hour for three hours. One hour and 30 minutes after receiving the ketamine dose, 19 patients received a dexmedetomidine infusion of 0.7 mcg/kg per hour (KET/DEX arm) and 20 received three 25-mcg fentanyl injections over 1.5 hours (KET/FENT arm).
Receiving only ketamine significantly reduced patients’ psychomotor speed, as well as the accuracy of responses to both simple and complex questions (all P<0.0001). In addition, recall and recognition memory also were impaired, but the ketamine did not alter executive functions, said Dr. Hayley, who presented the findings at the Society of Critical Care Medicine’s 2019 Critical Care Congress (abstract 100).
In contrast, those in the KET/FENT arm saw only a modest acute deficit in psychomotor accuracy and speed (all P<0.05).
“Group comparison at medication coadministration revealed comparatively greater neurocognitive deficits under the KET/DEX condition (all P<0.05),” Dr. Hayley said. “The concomitant administration of a ketamine bolus and dexmedetomidine infusion resulted in marked impairment on skills relating to psychomotor speed, attention, response inhibition, cognitive flexibility, mental processing and memory.”
Dr. Hayley said it was possible “the addition of dexmedetomidine enhances the pharmacodynamic effects of ketamine at these doses, producing synergistic analgesic and sedative effects, which have downstream implications for overt neurocognitive and behavioral abilities.”
One might be able to attribute the variations in neurocognitive performance with KET/DEX to the residual exacerbation of the alpha-2 adrenergic–mediated effects of dexmedetomidine, which would increase sedation, rather than through direct intoxication, she said.
Dr. Hayley said the findings are the first to demonstrate the residual neurocognitive and behavioral effects of ketamine when used with dexmedetomidine, and suggested a potential synergistic effect of these drugs when combined at analgesic doses. “This may have significant clinical implications regarding optimal patient care, both during the acute treatment phase and throughout the postoperative observation period,” she said.
The study’s findings are particularly important when a patient is being prepared for routine discharge from the hospital after surgery, according to Dr. Hayley. “In particular, it means that patients should be closely monitored before they leave the hospital in case they are still affected by the medications, and suggests that additional assessments may need to be undertaken to evaluate a patient’s home-readiness after leaving the hospital site and upon returning home,” she said.
“Dr. Hayley and colleagues have demonstrated that some of the most commonly used sedative-hypnotics and analgesics in critical care units can adversely affect short-term cognitive abilities, particularly when combined,” explained Eric S. Schwenk, MD, an associate professor of anesthesiology at Jefferson University Hospitals, in Philadelphia, who was not part of the study but was asked to comment.
A comprehensive sedation assessment should be done before surgery and again before discharge, according to Dr. Hayley. “Thus, consideration should be given to a patient’s mental capacity and functional performance when determining appropriate treatment options in order to lessen potential aftereffects and to ensure appropriate functional outcomes prior to patient discharge and after the patient returns home from their hospital stay.”
Dr. Schwenk agreed: “These results may lead some intensivists to think twice before ordering these drugs in patients with preexisting cognitive dysfunction, especially the elderly.”
Dr. Schwenk noted, “The study did not look beyond the short term, so conclusions about long-term effects cannot be made. The study, while a good contribution to the field, should not dissuade anesthesiologists and others from using ketamine or dexmedetomidine in appropriate situations, as both agents have unique pharmacological profiles and provide excellent analgesia.”
Dr. Hayley added, “These results prompt us to recommend immediate replication studies in patient populations, which have significant potential for optimizing patient care during the acute and postoperative period under these treatment regimens.”