Translational Medicine & Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Department of Anaesthesia and Perioperative Medicine, University College London Hospitals NHS Trust, London, UK; Department of Anesthesiology, Perioperative Medicine and Pain Management, Miller School of Medicine, University of Miami, Miami, FL, USA.
Br J Anaesth. 2019 Jan;122(1):92-102. doi: 10.1016/j.bja.2018.09.024. Epub 2018 Oct 30.
Epidural-related maternal fever (ERMF) has been reported in ∼26% of labouring women. The underlying mechanisms remain unclear. We hypothesised that ERMF is promoted by bupivacaine disrupting cytokine production/release from mononuclear leucocytes [mononuclear fraction (MNF)]. We examined whether bupivacaine (i) reduces caspase-1 activity and release of the anti-pyrogenic cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), and (ii) is pro-inflammatory through mitochondrial injury/IL-1β.
In labouring women, blood samples were obtained before/after epidural analgesia was implemented. Maternal temperature was recorded hourly for the first 4 h of epidural analgesia. Time-matched samples/temperatures were obtained from labouring women without epidural analgesia, pregnant non-labouring, and non-pregnant women. The primary clinical outcome was change in maternal temperature over 4 h after the onset of siting epidural catheter/enrolment. The secondary clinical outcome was development of ERMF (temperature ≥ 38°C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity, intracellular IL-1ra, and plasma IL-1ra/IL-1β ratio was quantified in MNF from labouring women or THP-1 monocytes (using flow cytometry, respirometry, or enzyme-linked immunosorbent assay).
Maternal temperature increased by 0.06°C h [95% confidence interval (CI): 0.03-0.09; P=0.003; n=38] after labour epidural placement. ERMF only occurred in women receiving epidural analgesia (five of 38; 13.2%). Bupivacaine did not alter MNF or THP-1 apoptosis compared with saline control, but reduced caspase-1 activity by 11% (95% CI: 5-17; n=10) in MNF from women in established labour. Bupivacaine increased intracellular MNF IL-1ra by 25% (95% CI: 10-41; P<0.001; n=10) compared with saline-control. Epidural analgesia reduced plasma IL-1ra/IL-1β ratio (mean reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural analgesia.
Impaired release of anti-pyrogenic IL-1ra might explain ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote ERMF.
硬膜外相关产妇发热（ERMF）在约 26%的分娩妇女中发生。其潜在机制尚不清楚。我们假设 ERMF 是由布比卡因破坏单核白细胞[单核细胞分数（MNF）]中细胞因子的产生/释放所促进的。我们研究了布比卡因（i）是否降低半胱天冬酶-1 活性和抗发热细胞因子白细胞介素（IL）-1 受体拮抗剂（IL-1ra）的释放，以及（ii）是否通过线粒体损伤/IL-1β 引发炎症。
在分娩妇女中，在实施硬膜外镇痛之前/之后采集血样。在硬膜外镇痛的前 4 小时内，每小时记录一次产妇体温。从没有硬膜外镇痛、妊娠非分娩和非妊娠妇女中获得与分娩妇女时间匹配的样本/温度。主要临床结局是从放置硬膜外导管/入组开始 4 小时后产妇体温的变化。次要临床结局是 ERMF 的发展（体温≥38°C）。在来自分娩妇女或 THP-1 单核细胞的 MNF 中，用流式细胞术、呼吸测量法或酶联免疫吸附试验来量化布比卡因/盐水对细胞凋亡、半胱天冬酶-1 活性、细胞内 IL-1ra 和血浆 IL-1ra/IL-1β 比值的影响。
分娩后硬膜外放置后，产妇体温每小时升高 0.06°C（95%置信区间：0.03-0.09；P=0.003；n=38）。只有接受硬膜外镇痛的妇女（38 例中的 5 例；13.2%）发生 ERMF。与生理盐水对照相比，布比卡因并未改变 MNF 或 THP-1 的凋亡，但降低了已建立分娩妇女 MNF 中的半胱天冬酶-1 活性 11%（95%置信区间：5-17；n=10）。与生理盐水对照相比，布比卡因使 MNF 中的细胞内 IL-1ra 增加了 25%（95%置信区间：10-41；P<0.001；n=10）。与没有硬膜外镇痛的妇女相比，硬膜外镇痛降低了血浆 IL-1ra/IL-1β 比值（平均降低：14；95%置信区间：7-30；n=30）。
抗发热性 IL-1ra 释放受损可能从机制上解释 ERMF。分娩期间布比卡因的免疫调节作用可能会促进 ERMF 的发生。
Zotero 插件