Continuous ketamine infusion may be a safe and effective adjunct to sedation in mechanically ventilated critically ill patients, and could be a potential alternative to the continuous infusion of benzodiazepines.
“Ketamine is a rapid-acting anesthetic with both sedative and analgesic properties,” said Lara Groetzinger, PharmD, of the medical ICU of the University of Pittsburgh Medical Center’s Presbyterian Hospital, and the lead researcher. “Its unique mechanism of action provides an option for patients who are mechanically ventilated and require both sedation and analgesia.” The study was presented at the Society of Critical Care Medicine’s 2016 Critical Care Congress (abstract 586).
Dr. Groetzinger said continuous infusion of benzodiazepines has been associated with negative outcomes, such as increased duration of mechanical ventilation and ICU length of stay, possibly related to the deep sedation and delirium associated with these agents.
Benefits of Ketamine
“Ketamine produces a dissociated anesthetic state, and unlike certain benzodiazepines, its duration of action is not prolonged in the presence of active metabolites and clearance is not affected by decreased renal function, which is common in the critically ill population,” Dr. Groetzinger said. “Ketamine also has potent analgesic properties, making it a good analgosedative agent. Ketamine also possesses positive hemodynamic qualities, by not decreasing blood pressure, and desirable respiratory effects, specifically bronchodilation.”
The study collected data between July 1, 2014, and June 30, 2015, from 43 mechanically ventilated patients receiving continuous ketamine infusions as an adjunct to sedation. The average age of the patients was 45 years; the group was 67% male.
The study analyzed patients’ demographics, ketamine dose, concomitant sedative dosing and hemodynamic parameters. Additionally, the Riker Sedation-Agitation Scale was used to assess sedation in all patients, who were screened every two hours. Ketamine was started on average at 0.16 mg/kg per hour (range, 0.05-1 mg/kg/h) for 3.6 days (range, 0.3-21.6 days), with a mean dose of 0.44 mg/kg per hour (range, 0.05-2 mg/kg/h). The study found a nonsignificant increase in both mean arterial blood pressure from 77 to 81 mm Hg (P=0.15) and heart rate (P=0.97), compared with baseline values, during the initial 24 hours of ketamine infusion.
Despite these findings, the study stopped short of recommending ketamine, saying more studies are needed to find an alternative to benzodiazepines. No outcome studies have compared ketamine with benzodiazepines or any other sedative, such as propofol or dexmedetomidine, in this patient population.
Interesting but Not Actionable
“While the risks associated with benzodiazepine use are reasonably well described, there is not enough evidence currently to definitely say that ketamine is more or less harmful, or that ketamine provides better outcomes than other sedatives. There are case reports and case series of ketamine’s use in these patients, but no studies have compared clinical outcomes in ICU patients sedated with ketamine to other agents,” Dr. Groetzinger said.
“Our data are descriptive at best, providing some insight regarding potential dosing strategies and adverse effects to watch out for,” she also said. “We did not evaluate any patient outcomes associated with the use of ketamine in these patients. The bottom line is more information is needed.”
There is insufficient evidence to confirm that ketamine should be used instead of other sedatives. Although ketamine has favorable properties, the lack of well-designed trials renders it difficult to make this assertion, Dr. Groetzinger said. “Further study is warranted to explore the optimal dosing and patient population for the use of ketamine as a therapeutic adjunct or alternative for sedation in mechanically ventilated patients.
“The choice of sedative for mechanically ventilated patients should be driven by patient-specific properties, including sedation goals and the pharmacology of the drug in that patient,” Dr. Groetzinger said.