“The supreme question about a work of art is out of · Epidural conversion rate Study & Remi...

“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: journals.permissions@oxfordjournal.org

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: journals.permissions@oxfordjournal.org

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: journals.permissions@oxfordjournal.org

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: journals.permissions@oxfordjournal.org

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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