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“The supreme question about a work of art is out of how deep a life does it spring”
James Joyce, Ulysses
Anaesthetic interventions and obstetric outcomes
Labouring under an illusion?
Dr Matt Wilson
University of Sheffield
“We are all born in the same way but we all die in different ways.”
JYS Papers 232-233: RCSE Archive
“It will be necessary to ascertain anaesthesia’s precise effect, both on the action of the uterus….its influence, if any, upon the child and whether it has a tendency other complications.”
James Young Simpson 1848
Epidural analgesia, it’s what we do!
NOAD 2011
118 Units
22.7% regional
Mortality 0
Morbidity ≤ 1%
Epidurals are good for you!
Effective
Satisfaction
Protective
Intervention
Hypotension
Neonatal effects
Dural puncture
Neurological injury
Impact on labour
Epidurals cause Caesarean Sections!
“Oh yes they do...!” “Oh no they don’t....!”
Retrospective studies
Non randomised
Mixed parity
Selection bias
Post hoc correction
Propensity Quintiles
Multivariate analysis
Epidurals
C Section
IVD
Oxytocin
2nd Stage
Epidural vs Non-epidural deliveries
Sentinel Event Studies
Impact or “Before & After”
Non-Adherence
Hawthorne effect
External validity
Assumed point change
Meta-analyses of impact studies
Cambic C R , Wong C A Br. J. Anaesth. 2010;105:i50-i60
© The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
Randomised Controlled Trials
Gold StandardBalanced
Placebo controlled
“Double” Blind
LimitationsConsent
Placebo unethical
Open label
Adherence
Gambling, David R.; Sharma, Shiv K.; Ramin, Susan M.; Lucas, Michael J.; Leveno, Kenneth J.; Wiley, Jackie; Sidawi, Elaine J.Anesthesiology. 89(6):1336-1344, December 1998.
Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 16
Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 17
Cambic C R , Wong C A Br. J. Anaesth. 2010;105:i50-i60
© The Author [2010]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
C-Section
1st Stage Duration
2nd Stage Duration
Reducing epidural impact on labour
Technique
Drug dose
Timing
CSE vs. Mobile
PCEA
↑Satisfaction
↓Workload
↓LA consumption
↓Motor-block
Number of women requiring “No unscheduled intervention”
Local anaesthetic dose
Outcomes
PCEA refinementsBackground Infusion
AMB
Computer Integration
Superior analgesia
↓LA consumption
↓Breakthrough/Intervention
Obstetric outcomes unchanged
Incidence of IVD CEI: 20%
PIEB: 7% (P 0.03)
Total levobupivacaine consumption, number of women requiring additional PCEA boluses, and mean number of PCEA boluses per patient were lower in the PIEB group (P 0.001)
Anesthesia & Analgesia:October 2011 - Volume 113 - Issue 4 - p 826–831
Wong C et al. NEJM 2005 352(7): 655-65
Delayed epidural analgesia
Copyright © 2011 Anesthesiology. Published by Lippincott Williams & Wilkins. 33
Marucci, Massimo; Cinnella, Gilda; Perchiazzi, Gaetano; Brienza, Nicola; Fiore, Tommaso
Anesthesiology. 106(5):1035-1045, May 2007.
Instrumental vaginal birth
Maternal mobility & posture
Mechanism
Uterine activity
Endocrine modulation
Prostaglandins
Oxytocin
Epinephrine
Pelvic alignment
Gravity
Mobility in 1st stage with epidural
Delivery mode: SVD
Lawrence A, Lewis L, Hofmeyr GJ, Dowswell T, Styles C. Maternal positions and mobility during first stage labour. Cochrane Database of Systematic Reviews 2009, Issue 2.
Position in the second stage of labour for women without epidural
Gupta JK, Hofmeyr GJ, Smyth RMD.
Cochrane Database of Systematic Reviews 2000, Issue 1. Art. No.: CD002006.
20 trials (6135 participants)
“Upright” positions, was associated with:
Duration 2nd stage
Severe pain 2nd stage,
Abnormal FHR patterns
Assisted delivery (RR 0.80, 95% CI 0.69 to 0.92)
Episiotomy
↑ Estimated blood loss 500 ml (RR 1.63, 95% CI 1.29 to 2.05)
↑ 2° tear
No difference in the risk of:
IVD: (RR 0.77, 95% CI 0.46-1.28)
Caesarean: (RR 0.57, 95% CI 0.28-1.16)
Heterogeneity, small studies, uncertainty
Posture in 2nd Stage with an epidural?
NIHR Health Technology Assessment ProgramISRCTN 35706297
Singleton, cephalic, term, nulliparae
Mobile epidural
Upright Lying Down
Enter 2nd Stage
Power: 0.9 To detect a RR SVD 0.6
N=3237Reporting 2015
Missing the bigger picture?
George Santayana
The Life of Reason
“Those who do not remember the past are doomed to repeat it”
Population pressure
An irreversible trend?
“Ageing” maternal population
Previous Caesarean Section
Abnormal placentation
Maternal choice
Obstetric practice
Maternal Age
Maternal age
The effect of previous C-Section
Planned vs. unplanned
Immovable obstacles
Weight watchers
Obesity a risk factor for adverse pregnancy outcomes.
UK parturient population:
33% BMI>25
23% BMI>30
Linear association between maternal BMI and risk of caesarean section in term deliveries
BJOG: An International Journal of Obstetrics & GynaecologyVolume 113, Issue 10, pages 1173-1177, 13 SEP 2006
Irresistible forces: pharmacogenetics
118 OPRM1 Gene (Opioid μ receptor)
Response to neuraxial opioids
ED50 spinal fentanyl Hz 304A:6.8 μg
Htz 304G:17.7 μg
Modulation of pain perception
ADRβ2
Labour progress
Clinical implications?
How to avoid the effects of epidural analgesia on labour….
Don’t put one in!
Non-pharmacological
Immersion
Acupuncture/acupressure
Hypnosis/Cognitive strategies
TENS
Aromatherapy
Complementary and alternative therapies for pain management in labour. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003521.
14 trials 1537 women
Acupuncture: 3 trials (n=496) ↓Pain relief (RR 0.7, 95% CI 0.49-1.0)
Self Hypnosis: 5 trials (n=729) ↓Pharmacological analgesia
↓ Epidural (RR 0.30, 95% CI 0.22 to 0.40)
↑Satisfaction
Insufficient evidence Audioanalgesia, acupressure, aromatherapy
No evidence Massage, Other complimentary Rx
21st ideal opioid analgesia for childbirth
Effective
Safe
°Responsive
°Side effects
Inexpensive
Rapid onset
Demand device?
PharmacologyRedistribution
Metabolism
Accumulation
Patient Controlled Analgesia (PCA) in labour
Established technology
No ideal drug
Restricted
Epidural contraindicated
Fetal non-viability
Remifentanil
Ultra-short acting μ agonist
Novel metabolism
Rapid offset
t1/2 ≈ 3mins
Non-cumulative
Bolus effect peak 2.5min
Effect site concentration
Remifentanil
Alfentanil
Sufentanil
Pethidine
180
Parturients
52
Remifentanil
40µg l/o 2mins
53
Meperidine
49.5 mg 5mg l/o 10 min
54
Fentanyl
50µg20µg l/o 5min
21
Exclusions
Douma M R et al. Br. J. Anaesth. 2010;104:209-215
OutcomesI VAS pain2 Maternal: Sedation, SaO2, Satisfaction,
Fetal: Apgars, NACS, Cord gases
Mean VAS pain scores as a function of time for meperidine, remifentanil, and fentanyl.
Douma M R et al. Br. J. Anaesth. 2010;104:209-215
© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
Douma M R et al. Br. J. Anaesth. 2010;104:209-215
© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: [email protected]
Maternal/neonatal effects
Pethidine Fentanyl Remifentanil
SpO2 <95% 33% 56% 37%
Satisfaction (1-10) 7 7.3 8.1
APGAR5 9.7 9.6 9.9
NACS 120 min 37.2 36.7 37.8
Cord BE -7.23 -6.67 -5.41
Epidural 34% 15% 13%
Remifentanil vs. Pethidine
Superior analgesia
Maternal satisfaction
Sedation similar
Fetal effects equivalent
Heart Rate
APGAR 5
Cord pH
NACS
Epidural conversion rate
Study & Remi technique N Comparator Conversion Comparator
ConversionRemifentanil
% %
Blair11 (Infusion 0.25-0.5 µg/kg/min) 21 None na 19
Thurlow12 (PCA 20 µg, lockout 3 min) 36 im pethidine 17 38
Blair10 (PCA 40 µg, lockout 2 min) 39 Pethidine PCA 32 10
Evron13 (Infusion 0.27-0.93 µg/kg/min) 88 Pethidine infusion 39 11
Volikas4 (PCA 0.5 µg/kg lockout 2) 50 None n/a 10
Balki19(Bolus 0.25 µg plus infusion) 20 Variable bolus/infusion n/a 5
Douma20 (PCA 40 µg, lockout 2 min) 20 Epidural n/a 10
Douma21 (PCA 40 µg, lockout 2 min) 159 (3 arms) PCA pethidine 34 13
Mean 30.5 15.2
Median 32 12
Hypothesis
Remifentanil PCA reduces progression to epidural analgesia, relative to intramuscular pethidine.
Epidural IVD
RESPITEA Randomised Controlled Trial of Remifentanil intravenous
Patient Controlled analgesia (PCA) versus intramuscular pethidine for pain relief in labour
ISRCTN29654603
EUDRACT # 2012-005257-22
Antenatal information to all women
Singleton, term, cephalic.
Established labour
Request opioid
Consent, Randomisation
Pethidine Remifentanil PCA
% progress to epidural analgesia
Delivery
Primary end point
Sample
Assumed RR=0.5
Power=0.9
N required = 320
Target =400
Secondary outcomes
MaternalPain relief (VAS)
Side effectsSedation
Respiratory depression
Nausea
Birth mode
Satisfaction
Fetal/NeonatalDistress Delivery
APGAR 5
Acidosis
Resuscitation
SCBU admission
Participating units
Birmingham
Bradford
York
Wolverhampton
N. Staffs
Frimley Park
Northwick Park
BHR, Romford
Poole
UCLan
www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/respite/index.aspx
A Comparison of Remifentanil Parturient-Controlled Intravenous Analgesia with Epidural Analgesia: A Meta-Analysis of Randomized Controlled Trials
Liu, Zhi-Qiang MD, PhD*; Chen, Xiu-Bin MD*; Li, Hai-Bing MD*; Qiu, Man-Tang MD, PhD†; Duan, Tao MD, PhD‡
Remifentanil PCIA
Higher vas pain scores than epidural analgesia 1 hour (MD = 1.9 cm; 95% CI, 0.5–3.3; I2 = 94%)
2 hours (MD = 3.0 cm; 95% CI, 0.7–5.2; I2 = 89%)
No difference incidence of nausea, vomiting, pruritus, or umbilical artery pH values
Anesthesia & Analgesia:March 2014 118 - Issue 3 - p 598–603
Anaesthetic interventions in labour
Intra-partum research
Recruitment
Costly
InfrastructureCTU, PPI, MREC
External validity
Generalisability
NHS Priority
NIHR Evaluation, Trials and Studies (NETS) programmes- from 2012
NETSCC
Public Health Research
Established: 2008
Health Technology Assessment
Established: 1993
Health Services and Delivery Research
Established 2012
Efficacy and Mechanism EvaluationFunded by the MRC Managed by NIHR
Established: 2008
Translating science into better health
We choose….“and do the other things, not because they are easy, but because they are hard, because that goal will serve to organise and measure the best of our energies and skills…”
Address at Rice University, September 12 1962
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