PMID- 30579413
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 1471-6771 (Electronic)
IS  - 0007-0912 (Linking)
VI  - 122
IP  - 1
DP  - 2019 Jan
TI  - Role of leucocyte caspase-1 activity in epidural-related maternal fever: a
      single-centre, observational, mechanistic cohort study.
PG  - 92-102
LID - S0007-0912(18)30770-0 [pii]
LID - 10.1016/j.bja.2018.09.024 [doi]
AB  - BACKGROUND: Epidural-related maternal fever (ERMF) has been reported in
      approximately 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-1beta. METHODS: 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 degrees
      C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity,
      intracellular IL-1ra, and plasma IL-1ra/IL-1beta ratio was quantified in MNF from
      labouring women or THP-1 monocytes (using flow cytometry, respirometry, or
      enzyme-linked immunosorbent assay). RESULTS: Maternal temperature increased by
      0.06 degrees C h(-1) [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-1beta ratio (mean
      reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural
      analgesia. CONCLUSIONS: Impaired release of anti-pyrogenic IL-1ra might explain
      ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote
      ERMF.
CI  - Copyright (c) 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All
      rights reserved.
FAU - Del Arroyo, A G
AU  - Del Arroyo AG
AD  - Translational Medicine & Therapeutics, William Harvey Research Institute, Barts
      and The London School of Medicine and Dentistry, Queen Mary University of London,
      London, UK.
FAU - Sanchez, J
AU  - Sanchez J
AD  - Translational Medicine & Therapeutics, William Harvey Research Institute, Barts
      and The London School of Medicine and Dentistry, Queen Mary University of London,
      London, UK.
FAU - Patel, S
AU  - Patel S
AD  - 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.
FAU - Phillips, S
AU  - Phillips S
AD  - Department of Anaesthesia and Perioperative Medicine, University College London
      Hospitals NHS Trust, London, UK.
FAU - Reyes, A
AU  - Reyes A
AD  - Department of Anaesthesia and Perioperative Medicine, University College London
      Hospitals NHS Trust, London, UK.
FAU - Cubillos, C
AU  - Cubillos C
AD  - IdiPAZ, Hospital La Paz Institute for Health Research, Madrid, Spain.
FAU - Fernando, R
AU  - Fernando R
AD  - Department of Anaesthesia and Perioperative Medicine, University College London
      Hospitals NHS Trust, London, UK.
FAU - David, A L
AU  - David AL
AD  - Institute for Women's Health, University College London, London, UK; NIHR
      University College London Hospitals Biomedical Research Centre, London, UK.
CN  - EPIFEVER Investigators
FAU - Sultan, P
AU  - Sultan P
AD  - Department of Anaesthesia and Perioperative Medicine, University College London
      Hospitals NHS Trust, London, UK.
FAU - Ackland, G L
AU  - Ackland GL
AD  - Translational Medicine & Therapeutics, William Harvey Research Institute, Barts
      and The London School of Medicine and Dentistry, Queen Mary University of London,
      London, UK. Electronic address: g.ackland@qmul.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20181030
PL  - England
TA  - Br J Anaesth
JT  - British journal of anaesthesia
JID - 0372541
RN  - 0 (Anesthetics, Local)
RN  - 0 (Cytokines)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - Y8335394RO (Bupivacaine)
SB  - IM
MH  - Adult
MH  - Analgesia, Epidural/*adverse effects/methods
MH  - Analgesia, Obstetrical/*adverse effects/methods
MH  - Anesthetics, Local/adverse effects/pharmacology
MH  - Apoptosis/drug effects
MH  - Body Temperature/drug effects
MH  - Bupivacaine/adverse effects/pharmacology
MH  - Caspase 1/*physiology
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Fever/*chemically induced/enzymology/physiopathology
MH  - Humans
MH  - Labor, Obstetric/metabolism
MH  - Leukocytes/enzymology
MH  - Obstetric Labor Complications/*chemically induced/enzymology/physiopathology
MH  - Pregnancy
MH  - Young Adult
OTO - NOTNLM
OT  - analgesia, epidural
OT  - bupivacaine
OT  - cytokines
OT  - interleukin-1
OT  - labour, obstetric
OT  - maternal fever
IR  - Reeve A
FIR - Reeve, A
IR  - Sodha S
FIR - Sodha, S
IR  - Ciechanowicz S
FIR - Ciechanowicz, S
IR  - Olearo E
FIR - Olearo, E
IR  - Dick J
FIR - Dick, J
IR  - Stewart A
FIR - Stewart, A
EDAT- 2018/12/24 06:00
MHDA- 2019/02/26 06:00
CRDT- 2018/12/24 06:00
PHST- 2018/01/10 00:00 [received]
PHST- 2018/09/03 00:00 [revised]
PHST- 2018/09/24 00:00 [accepted]
PHST- 2018/12/24 06:00 [entrez]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
AID - S0007-0912(18)30770-0 [pii]
AID - 10.1016/j.bja.2018.09.024 [doi]
PST - ppublish
SO  - Br J Anaesth. 2019 Jan;122(1):92-102. doi: 10.1016/j.bja.2018.09.024. Epub 2018
      Oct 30.