OAA Large Project Grant
The successful applicant for the OAA Large Project Grant was:
Principal Applicant
Dr Gareth Ackland
Honorary Consultant, Anaesthesia and Critical Care Medicine, University College
Hospital, London
Title
Elucidating the molecular mechanism underlying epidural related maternal fever
Amount
£59,627
Scientific Abstract
Local anaesthetics not only reduce pain during labour, but may also be responsible for epidural-related maternal fever [. This occurs in ~30% women, and is associated with complications including suspicious fetal cardiotocography, increased instrumental delivery and neonatal brain injury. Labouring women who develop a fever are often prescribed antibiotics - perhaps unnecessarily. Local anaesthetics exert cellular metabolic effects via the mitochondria. In addition to producing energy, mitochondria generate reactive oxygen species (ROS) which - at low levels - act as signalling molecules to regulate various cellular processes. Mitochondrial dysfunction generates excess ROS, which activates the inflammasome, an intracellular complex that generates cytokines which trigger inflammation and fever. We hypothesize that the local anaesthetic (bupivicaine) used in epidurals causes mitochondrial dysfunction, leading to excess ROS, which activates the inflammasome to produce cytokines and hence ERMF. By assessing mitochondrial and immune function in both labouring women before, and after, epidural analgesia is established - in addition to women not receiving epidural analgesia - we will elucidate the molecular mechanism underlying ERMF. These data will help develop novel biomarkers for fever during labour that is generated by infection or ERMF, thereby refining clinical management and avoiding unnecessary clinical interventions and/or adverse outcomes.
First year report from Dr G Ackland (364 KB)
