Lars Eriksson: A clinical trial of S-ketamine analgesia in third molar surgery: Effects, safety and influence on inflammatory biomarkers

Abstract

Background and aims: Third molar surgery is a common surgical procedure and a well-established pain model in research, which is generally performed under local anaesthesia. Post-operative pain management is often solved with a combination of paracetamol and ibuprofen. In this thesis, our goal was to find a better alternative for pain management in the early post-operative period.  The overall aim was to study if preoperative IV S-ketamine (0.125mg/kg or 0.25mg/kg) can offer a more effective and safer transition from local anaesthesia to orally administered analgesia, to investigate whether surgery or S-ketamine have an impact on inflammatory biomarkers in plasma, and to examine differences in protein expression between saliva and plasma. 

Patients and methods: 168 patients participated in the study. Physiological variables, questionnaires, pain diaries, and self-reported side effects were all registered in the study. Biomarkers in plasma and saliva were analysed using a multiplex panel (Olink).

Results: There was a globally significant lower pain score in the group with high dose S-ketamine, and a longer time to first rescue medication. There were minor, clinically insignificant changes of SpO2 and pulse rate in the S-ketamine 0.25 mg/kg group.  Surgery significantly affected certain biomarkers (IL6, CST5, OSM, TGF-alpha, IL10, FGF-19, Flt3L, white blood cell count, neutrophil blood cell count, cortisol, and high sensitivity c-reactive protein). S-ketamine had no impact on the expression of biomarkers. Although major differences were observed in biomarker expression between saliva and plasma, the correlations were ultimately limited and weak.

Conclusion:  A single dose of S-ketamine 0.25 mg/kg IV reduces postoperative pain for up to 24h with a longer time to first rescue medication, compared to S -ketamine 0.125 mg/kg and placebo. Single dose S-ketamine 0.25 mg/kg IV gives a minor reduction of SpO2 and a minor increase of pulse rate at the end of infusion of S-ketamine. These changes are clinically insignificant. Third molar surgery causes an immune response within 2 hours expressed in plasma; infusion of S-ketamine 0.25 or 0.125 mg/kg does not cause any immune reaction. The immune response in saliva vs plasma differs and are not interchangeable.