Public Defence: Marianne Myhre
Cand.med Marianne Myhre at Institute of Clinical Medicine will be defending the thesis “Analgesic, ventilatory, and cognitive effects of pregabalin and opioids. Studies in healthy volunteers and kidney donors.” for the degree of PhD (Philosophiae Doctor).
Foto: Ine Eriksen
Trial Lecture – time and place
See Trial Lecture.
- First opponent: Professor Ole Mathiesen, Zealand University Hospital
- Second opponent: Associate Professor Rolf Karlsten, Uppsala University Hospital
- Third member and chair of the evaluation committee: Associate Professor Signe Søvik, University of Oslo
Chair of the Defence
Associate Professor Pål Dag Line, University of Oslo
Professor Audun Stubhaug, University of Oslo
Multimodal postoperative pain treatment is often used for the treatment of postoperative pain emphasizing the importance of combining different drugs to achieve optimal pain relief and reduce opioid-related side effects. In the wake of this approach, pregabalin has gained popularity as an analgesic adjunct for acute postoperative pain, although the evidence for acute analgesic efficacy has been inconsistent. As yet, pregabalin is approved for neuropathic pain conditions, partial epilepsy disorders, and generalized anxiety and not for the use of acute postoperative pain. To prove the utility of pregabalin as add-on to a multimodal pain regime, the clinical benefit has to be demonstrated and total benefits must outweigh total harms.
In this thesis, we investigated the analgesic- and opioid-sparing effects of pregabalin. In an experimental cold pressor model in healthy volunteers, additive analgesic effects were demonstrated when pregabalin was combined with increasing doses of remifentanil. In a clinical study in patients undergoing laparoscopic donor nephrectomy, pregabalin did not reduce pain intensity compared to placebo, but showed significant opioid-sparing effects 0‒48 h after surgery. Hyperalgesia, pain-related sleep interference, and nausea were reduced with pregabalin in the early postoperative period.
The opioid-sparing effect may be of limited value if the side effects are not reduced accordingly. We found that pregabalin potentiates the ventilatory depressive effect of remifentanil in healthy volunteers. Furthermore, we explored the cognitive effects of pregabalin, and found that pregabalin negatively affected executive functioning under experimental and clinical conditions by impairing working memory and inhibition, measured as neuropsychological task performance. These potentially severe adverse effects warrant further studies. At present the efficacy and safety of perioperatively pregabalin is not sufficiently documented.
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