Ketamine as Single Dose Analgesics on Acute Postoperative Pain in Both Genders Following Surgical Removals of Third Molars

Statement of problem: Ketamine is an unique dissociative drug which in low doses acts as an analgesic drug on different pain types and, corresponding to dose, as a sedative and an anesthetic. The dose-response profile of different low ketamine doses on acute postoperative pain in females versus males has not been established.

Purpose: The aim of the study was to test different single ketamine doses on female and male patients suffering from postoperative pain following third molar surgery.

Materials and Methods: This pilot trial was done as a randomized, double-blind, and parallel group study consisting of 128 non-paid Caucasian patients of both sexes with a mean age 24 years (range 19-31 years). Patient consent and Norwegian Ethical Committee approval was obtained prior to trial. Entry level was moderate pain intensity (PI) defined as = or > 4 on a numerical rating scale (0-10 NRS) following third molar surgery. The patients were randomly allocated according to gender in 8 groups (n=16) to receive different single doses of racemic ketamine i.v. Treatments consisted of ketamine 0.5 mg/kg b.w., 0.3 mg/kg b.w., 0.1 mg/kg b.w., and placebo (saline only) to females and males. All test drugs were administered as 5 ml bolus injection over 2 minutes. Primary outcome variable was sum PI (SUMPI) for an observation period of 30 minutes. In case of missing data or rescue drug intake the last valid PI score was carried forward.

Data analysis: Data were analyzed by One Way ANOVA with post hoc tests (Bonferroni). Analysis between genders was done with independent samples T-test (PASW Statistics ver. 18).

Results: Statistical analysis showed that among females SUMPI over 30 minutes after 0.5 mg/kg ketamine was not significantly different (P > or = 0.05) from that after 0.3 mg/kg, but was significantly lower (0.05) than SUMPI after 0.1 mg/kg. SUMPI after all active doses in females were significantly lower than that after placebo. In males 0.5

mg/kg ketamine was not significantly different from 0.3 mg/kg or 0.1 mg/kg. 0.3 mg/kg ketamine was not significantly different from 0.1 mg/kg. Both 0.5 mg/kg and 0.3 mg/kg ketamine were significantly different from placebo. Ketamine 0.1 mg/kg was not significantly different from placebo. Analyses between genders showed apparently no significant difference between SUMPI of equal doses of ketamine. The trial indicates that there is an apparently more pronounced dose response profile of the analgesic effect of i.v. ketamine in low doses within females than in males. For this secondary variable little variation was shown between the groups when males were treated. An expected variation reflecting observed differences in the analgesic effect of the different ketamine doses was seen in females. It may be argued against this trial that the results may have been influenced by the relatively low number of patients within each group. Another factor explaining the results may be that ketamine causes more psychotomimetic effects in males than in females.

Conclusion: The trial suggests that there may be differences between females and males with respect to the analgesic effect of i.v. ketamine in low doses. This possible gender difference may have clinical impact on the pain being treated in a clinical setting.

 

References:

 

Kronenberg RH. Ketamine as an analgesic: parenteral, oral, rectal, subcutaneous, transdermal and intranasal administration. J Pain Palliat Care Pharmacother 2002;16:27-35.

 

Morgan CJ, Perry EB, Cho HS, Krystal HJ, D'Souza DC. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology (Berl) 2006;187:405-14.