Medical School, Royal Perth Hospital Unit, University of Western Australia, Australia.
Harry Perkins Institute for Medical Research, University of Western Australia, Australia.
Prostaglandins Other Lipid Mediat. 2020 Aug;149:106427. doi: 10.1016/j.prostaglandins.2020.106427. Epub 2020 Feb 19.
Dexamethasone is commonly given as an antiemetic during surgical procedures. It has immunosuppressive effects and can affect key enzymes involved in the synthesis of specialised lipid mediators of inflammation resolution (SPM) that direct inflammation resolution and have anti-nociceptive actions. This study examined the effect of dexamethasone on plasma SPM, and the relationship between SPM and perceived pain in women undergoing surgery.
Plasma SPM were measured in samples obtained from two double-blind controlled interventions. The first, included 51 women mean age 53 ± 1.5 years, undergoing breast surgery allocated to either intravenous saline, or dexamethasone (4 mg or 8 mg) after induction of anaesthesia. The second study included 31 women of mean age 44 ± 0.5 years undergoing laparoscopic gynecological surgery that were allocated to either saline, or dexamethasone (4 mg). SPM (18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2) were measured in plasma collected prior to induction of anaesthesia and at 24 h, and 6 weeks post-surgery. Pain was assessed using a verbal analogue scale at discharge from the post-anaesthesia recovery unit. The data from each study was combined to examine the effect of dexamethasone on plasma SPM. The relationship between pain score and SPM was examined using ordinal logistic regression.
The SPM 18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2 were detectable in all plasma samples. There was no significant difference in any SPM due to dexamethasone over the duration of the study. There was a fall in 17-HDHA between baseline and 24 h in both the dexamethasone and saline groups (P = 0.003) but no change in the downstream SPM (RvD1, 17R-RvD1 and RvD2) or 18-HEPE and RvE2. Pain score was negatively related to levels of RvE2 measured prior to induction of anaesthesia (rho = -0.2991, P = 0.006) and positively related to BMI (rho = 0.279, P = 0.011). In ordinal logistic regression the odds ratio for RvE2 was 0.931 (CI 0.880, 0.986; P = 0.014); after adjusting for the effect of BMI indicating that an increase in RvE2 of 1 pg/ml would result in a 6.9 % fall in pain score. Allocation to a dexamethasone group did not influence the pain score or the relationship between RvE2 and pain score.
Dexamethasone administered as an anti-emetic does not affect plasma SPM levels. An elevated RvE2 level prior to surgery is predictive of a lower perceived pain score post-anaesthesia.
地塞米松常用于手术过程中的止吐剂。它具有免疫抑制作用，可影响参与炎症消退特殊脂质介质（SPM）合成的关键酶，这些酶可直接影响炎症消退，并具有抗伤害作用。本研究旨在探讨地塞米松对血浆 SPM 的影响，以及 SPM 与接受手术的女性感知疼痛之间的关系。
从两项双盲对照干预研究中获得的样本中测量了血浆 SPM。第一项研究纳入了 51 名年龄 53 ± 1.5 岁的女性，她们接受乳房手术，在麻醉诱导后分别接受静脉注射生理盐水或地塞米松（4mg 或 8mg）。第二项研究纳入了 31 名年龄 44 ± 0.5 岁的女性，她们接受腹腔镜妇科手术，分别接受生理盐水或地塞米松（4mg）。在麻醉诱导前和术后 24 小时及 6 周采集血浆，测量 SPM（18-HEPE、17-HDHA、RvE2、RvD1 17R-RvD1 和 RvD2）。使用视觉模拟评分法在麻醉后恢复室出院时评估疼痛。将每项研究的数据合并，以研究地塞米松对血浆 SPM 的影响。使用有序逻辑回归分析疼痛评分与 SPM 之间的关系。
所有血浆样本中均检测到 SPM 18-HEPE、17-HDHA、RvE2、RvD1 17R-RvD1 和 RvD2。在研究期间，地塞米松对任何 SPM 均无显著影响。地塞米松组和生理盐水组的 17-HDHA 在基线和 24 小时之间均有下降（P = 0.003），但下游 SPM（RvD1、17R-RvD1 和 RvD2）或 18-HEPE 和 RvE2 没有变化。疼痛评分与麻醉诱导前测量的 RvE2 水平呈负相关（rho = -0.2991，P = 0.006），与 BMI 呈正相关（rho = 0.279，P = 0.011）。在有序逻辑回归中，RvE2 的优势比为 0.931（CI 0.880，0.986；P = 0.014）；调整 BMI 影响后，RvE2 增加 1pg/ml，疼痛评分降低 6.9%。分配到地塞米松组并不影响疼痛评分或 RvE2 与疼痛评分之间的关系。
作为止吐剂的地塞米松不会影响血浆 SPM 水平。手术前 RvE2 水平升高可预测麻醉后疼痛评分降低。
