Association of Epidural-related Fever and Noninfectious Inflammation in Term Labor

Abstract

essential for the growth of some neoplastic cells including melanoma and hepatocellular carcinoma among others.Where does this leave us and what does all this have to do with the study by Vadillo-Ortega et al? First and most importantly, the balance between the protective and adverse effects of NO seems to be determined by the relative amount of NO and reactive radicals, yet the effects of these vary by tissue in ways not well understood. Second, a relative L-arginine deficiency does uncouple NOS and arginase pathways. Arginase upregulation seems to dominate during L-arginine deficiency resulting in NO deficiency and enhanced production of reactive oxygen species by NOS. Peroxynitrite is formed in place of NO and this leads to microvascular damage and impairs cytotrophoblast invasion. In contrast, the angiogenic/vasculogenic properties of NO likely promote cytotrophoblast endovascular invasion of uterine spiral arterials. Vadillo-Ortega et al attacked this NO deficiency by increasing the substrate through dietary arginine and seemed to demonstrate a beneficial effect, which likely would have resulted from recoupling of the NOS and arginase pathways. That being said, arginine supplementation may be a shotgun approach to what needs to be a sniper shot and therefore could well be associated with significant collateral damage since excessive NO production is not necessarily benign. Recent studies would suggest that a better approach would include both prevention of arginine deficiency but also suppression of the upregulation of arginase. As yet, however, specific ways to block arginase are awaiting discovery. As stated by Braam and Vehaar (Curr Pharm Des 2007;13:1727-1740, "Ideally, eNOS is sufficiently expressed, produces NO sufficiently and not abundantly, does not produce superoxide and is not scavenged by ROS; the produced NO then reaches its signaling target, mainly soluble guanylyl cyclase (sGC) and elicits a cellular responsey there is a great challenge ahead."

A cohort study of the impact of epidural analgesia on maternal and neonatal outcomes

“…Several studies have demonstrated elevated levels of interleukin‐6 ( IL‐6) in inflammatory etiologies of maternal fever . Riley et al compared rates of inflammatory markers and placental infection in women with and without epidural analgesia during labor，they found that the prevalence of infection was the same in the two groups, but women with an epidural were more likely to experience maternal fever and women with higher IL‐6 levels on admission were at increased risk of developing fever . The noninfectious inflammation hypothesis was also supported by a double‐blind, placebo‐controlled trial with antibiotics given before epidural analgesia and showed no difference in the rate of maternal fever or placental inflammation between groups .…”

“…A few studies have observed that women receiving epidural analgesia were at increased risk for intrapartum fever . Women with maternal pyrexia are more likely to receive antibiotics and undergo instrumental delivery and maternal pyrexia may also be associated with adverse neonatal outcomes including low Apgar scores, respiratory distress, hypotonia and neonatal seizures .…”

Endocan serum concentration in uninfected newborn infants

“…Similar results were reported by Aksoy et al [23] who did not find significant differences between newborns delivered vaginally compared to those delivered by C-section with spinal anesthesia, which was also the type of anesthesia used for C-section in our study group. Delivery mode and anesthesia were included as potential factors that may influence endocan levels by altering oxygenation and inflammatory status of the newborn [24][25][26].…”

Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms

“…Higher levels of maternal 34 and fetal 35 pro-inflammatory endogenous pyrogens that trigger fever have been measured in pregnant patients following epidural analgesia. 9,[34][35][36] However, Riley and colleagues reported that pregnant patients who subsequently developed ERMF had higher admission levels of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) prior to receiving epidural analgesia, 9 suggesting that prolonged epidural administration of bupivacaine may augment baseline elevated cytokine levels. 37 38 Conversely, anti-inflammatory glucocorticoids reduce ERMF, in part through reducing cytokine production.…”