Background & Aims
Surgery often introduces patients to opioids for the first time. We aimed to compare the short-term emotional effects of three opioids; morphine, oxycodone, and fentanyl, administered before induction of general anesthesia. In Norwegian hospitals, an opioid is frequently administered to the patients before the hypnotic used to induce general anesthesia, assuming a stress-reducing and well-being-enhancing effect. However, results from a quality control study conducted by our team on 269 surgery patients on the operating table show that the opioid analgesic remifentanil induced only a weak reduction of anxiety, and the majority of patients reported feeling worse or equally good, but not better, after the infusion (Eikemo et al., 2023, Anaesthesia). These findings have led us to conduct a more comprehensive, randomized, double-blind trial comparing three opioid analgesics (morphine, oxycodone and fentanyl) administered before general anesthesia.
Methods
In this double-blind, 3-arm randomized controlled trial, we measured pre-surgery well-being in 200 ASA 1 and 2 Norwegian-speaking patients (aged 18-85) undergoing non-cancer surgery with general anesthesia. Exclusion criteria were allergic reactions to opioids and body mass index less than 18 or greater than 35 kg/m2. Outcome measures included ten subjective state measures, such as feeling good and feeling anxious, rated on an 11-point (0-10) NRS (anchors `not´ – `very´) immediately before and 3-5 minutes after drug injection. To assess the impact of the three opioids on feeling good and feeling anxious, replicating and extending our prior study, we used mixed ANOVAs with the factors drug (oxycodone, morphine, fentanyl), time (pre/post), and drug×time. We also tested the overarching hypothesis that the subjective effects of the three opioids would differ through a generalized mixed model using a cumulative link mixed model with the factors drug and questionnaire item, and drug×item.
Results
Data were collected Nov 2021 to Dec 2022 at Kongsberg Hospital. Of 207 included patients, 200 were randomized (60% women, mean age 48.7, SD 14, 80.9 kg, SD 16.7) to receive morphine (69), oxycodone (65) and fentanyl (66). ANOVAs of feeling anxious and good revealed a significant effect of time (anxiety was modestly reduced by all opioids: 2.44 (SD 2.69) pre and 1.88 (SD 2.35) post; p = 0.028; feeling good was also reduced: 7.81 (SD 1.95) pre and 7.33 (SD 2.49) post; p = 0.035). There was no significant main effect of drug or drug×time interaction (p’s>0.306). The generalized mixed model revealed a significant interaction drug×item (LR chi-square-test (df) = 43 (18), reflecting higher ratings of dizziness, sedation, drug high and euphoria after fentanyl compared to morphine. Post-drug ratings of feeling relaxed, drug liking and disliking were similar across the three drug groups.
Conclusions
Our study assessed the acute subjective effects of three opioids: morphine, oxycodone, and fentanyl, administered in the minutes before induction of general anesthesia. Contrary to the general assumption that opioids enhance well-being but replicating our earlier results, we show a decrease in ‘feeling good’ after opioids. Patients also reported reduced anxiety. Importantly, no significant drug*time effect was observed. Comparison of the three drugs revealed higher responses to fentanyl compared to morphine for dizziness, sedation, drug high and euphoria, but comparable drug effects for other items, such as feeling relaxed or sad. These results challenge the prevailing belief in the emotional benefits of pre-surgical opioid administration.
References
Eikemo, M., Meier, I. M., Løseth, G. E., Trøstheim, M., Ørstavik, N., Jensen, E. N., Garland, E. L., Berna, C., Ernst, G., & Leknes, S. (2023). Opioid analgesic effects on subjective well?being in the operating theatre*. Anaesthesia, 78(9), 1102–1111. https://doi.org/10.1111/anae.16069
Presenting Author
Siri Gurandsrud Karlsen
Poster Authors
Topics
- Evidence, Clinical Trials, Systematic Review, Guidelines, and Implementation Science