School of Medicine and Health Sciences Poster Presentations
Are Repeat Outpatient Ketamine Infusions Associated with Cognitive Dysfunction?
Poster Number
192
Document Type
Poster
Publication Date
3-2016
Abstract
Introduction:
Outpatient ketamine infusions can be effective in relieving severe neuropathic pain for a period of weeks or months. The NMDA receptor is involved in learning and memory and antagonists such as ketamine may be associated with cognitive impairment (1,2). The objective of this study is to investigate whether repeat outpatient ketamine infusions are associated with cognitive dysfunction as measured by the Manos 10-point clock test, a validated screening tool for cognitive dysfunction(3).
Methods:
With IRB approval, patients undergoing repeat outpatient ketamine infusions were asked to complete a Manos 10 point clock test before and after each ketamine infusion and on the follow up clinic visit 2 to 4 weeks after the last infusion. The clock is scored using the Manos 10 point clock drawing criteria. Intact cognition was a score of 10, probable cognitive deficit, less than 8, and severely impaired at less than 4.
Statistical analysis was done in two parts to evaluate the primary and secondary questions.
Mean clock score, BMI, age, and ketamine dose were calculated across days 1-3 and times
(pre,post), so there would only be 1 clock score and 1 covariate score for BMI, age, and dose for each subject at each episode. For the primary question of whether there is a change in cognition associated with additional episodes of care, we used fixed effects mixed model regression, with clock scores as the dependent variable. We were particularly interested in the adjusted effect of episode of care with later episodes’ clock scores being compared to episode 1. A significant effect would indicate that cognition changes over time within subjects. For the secondary questions, in order to determine whether the clock score pattern across episodes differed by age, ketamine dose, BMI, race, sex, or the presence of opioids or antidepressants, we used a random effects mixed model including each of the above variables as covariates, along with episode. If the term was significant, it meant that the pattern of clock scores across episodes of care differed across levels of the indicator variable.
Results:
Each patient was given ketamine infusions for 3 consecutive days constituting one episode. These episodes were repeated 4 to 16 weeks apart. Data from 60 patients, who collectively had 124+ repeat episodes, were collected. In the final adjusted fixed effects model, episodes 4 (p=.037) and 6 (p=.039) both had significantly lower clock scores than episode one. In the random effects mixed model, ketamine dose (mg/kg) was significantly positively associated with clock scores (p=.008): for each .1 mg/kg increase in dose, the clock score was .23 points higher. Other findings with the random effects model assessed use of adjuvant medications in the setting of the infusions. Clock scores among patients receiving
opioids were significantly lower than those for patients without opioids starting with episode 4. Also those who did use antidepressants concurrently, had clock scores that declined more across episodes than those without antidepressants.
Conclusion:
Ketamine use may be associated with decreased cognition. In our study, patients with neuropathic pain receiving repeat outpatient infusions showed lower cognitive test scores after the 4th episode likely due to outliers in the data given the small sample size for each episode after the 4th episode of infusion. Analysis with the random effects model showed that dose had a positive correlation with cognitive test scores, while concurrent use of opioids or antidepressants had a negative correlation.
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Open Access
1
Are Repeat Outpatient Ketamine Infusions Associated with Cognitive Dysfunction?
Introduction:
Outpatient ketamine infusions can be effective in relieving severe neuropathic pain for a period of weeks or months. The NMDA receptor is involved in learning and memory and antagonists such as ketamine may be associated with cognitive impairment (1,2). The objective of this study is to investigate whether repeat outpatient ketamine infusions are associated with cognitive dysfunction as measured by the Manos 10-point clock test, a validated screening tool for cognitive dysfunction(3).
Methods:
With IRB approval, patients undergoing repeat outpatient ketamine infusions were asked to complete a Manos 10 point clock test before and after each ketamine infusion and on the follow up clinic visit 2 to 4 weeks after the last infusion. The clock is scored using the Manos 10 point clock drawing criteria. Intact cognition was a score of 10, probable cognitive deficit, less than 8, and severely impaired at less than 4.
Statistical analysis was done in two parts to evaluate the primary and secondary questions.
Mean clock score, BMI, age, and ketamine dose were calculated across days 1-3 and times
(pre,post), so there would only be 1 clock score and 1 covariate score for BMI, age, and dose for each subject at each episode. For the primary question of whether there is a change in cognition associated with additional episodes of care, we used fixed effects mixed model regression, with clock scores as the dependent variable. We were particularly interested in the adjusted effect of episode of care with later episodes’ clock scores being compared to episode 1. A significant effect would indicate that cognition changes over time within subjects. For the secondary questions, in order to determine whether the clock score pattern across episodes differed by age, ketamine dose, BMI, race, sex, or the presence of opioids or antidepressants, we used a random effects mixed model including each of the above variables as covariates, along with episode. If the term was significant, it meant that the pattern of clock scores across episodes of care differed across levels of the indicator variable.
Results:
Each patient was given ketamine infusions for 3 consecutive days constituting one episode. These episodes were repeated 4 to 16 weeks apart. Data from 60 patients, who collectively had 124+ repeat episodes, were collected. In the final adjusted fixed effects model, episodes 4 (p=.037) and 6 (p=.039) both had significantly lower clock scores than episode one. In the random effects mixed model, ketamine dose (mg/kg) was significantly positively associated with clock scores (p=.008): for each .1 mg/kg increase in dose, the clock score was .23 points higher. Other findings with the random effects model assessed use of adjuvant medications in the setting of the infusions. Clock scores among patients receiving
opioids were significantly lower than those for patients without opioids starting with episode 4. Also those who did use antidepressants concurrently, had clock scores that declined more across episodes than those without antidepressants.
Conclusion:
Ketamine use may be associated with decreased cognition. In our study, patients with neuropathic pain receiving repeat outpatient infusions showed lower cognitive test scores after the 4th episode likely due to outliers in the data given the small sample size for each episode after the 4th episode of infusion. Analysis with the random effects model showed that dose had a positive correlation with cognitive test scores, while concurrent use of opioids or antidepressants had a negative correlation.
Comments
Presented at: GW Research Days 2016