A presentation by Vegard Dahl at the 2017 meeting of the Scandinavian Society of Anaestesiology and Intensive Care Medicine. All available content from SSAI2017: https://scanfoam.org/ssai2017/ Delivered in collaboration between scanFOAM, SSAI & SFAI.

1. Remifentanil in labour analgesia –
where are we in 2017 – an update.
Vegard Dahl, Head of Dept of
Anaesthesia and Intensive Care,
Professor, Akershus University Hospital,
Norway
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2. Disclosures
• None…
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3. Agenda
• Pharmacology
• Does it work?
• Whys use it at all?
• Conclusion
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4. Remifentanil - Pharma
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5. Pharmacology
• Highly lipid soluble µ-receptor agonist opioid
• 70% proteinbound
• Esther linkage - undergoes rapid hydrolysis to
remifentanil acid by tissue and plasma estherase,
T1/2: 1-5min
• Context sensitive half-life 3-4 minutes
• Potency = 2x fentanyl, 100-200x morphine
• Lower plasma concentration in pregnants versus
non-pregnants – large variability
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6. Fetal exposure
• Uterine vein/Maternal artery ratio: 0.88
• Umbilical artery/umbilical vein ratio: 0.29
– Redistribution, rapid fetal metabolism
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7. Is it in use??
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8. SSAI Malmø 2017

9. RemiPCA SAFE Network©
Regimen
Concentration of Remifentanil: 20mcg/ml (2mg Remifentanil in 100ml NaCl 0,9%)
Bolus: 10-30 μg
Lockout interval: 2 min
No additional infusion of remifentanil. No application of any other opioid or analgesic
drug.
https://www.google.com/maps/d/viewer?mid=1BrSGgixaIx0JjdvPPBPbHjzlkUA&usp=s
haring
2017: 7800 deliveries
26.6%
Hypoxia
26% Sedation
17% Nausea
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10. SSAI Malmø 2017
Labor or Delivery
Opioids cross the placenta and may produce respiratory depression and psycho-
physiologic effects in neonates.
An opioid antagonist, such as naloxone, must be available for reversal of opioid-
induced respiratory depression in the neonate. ULTIVA is not recommended for use in
pregnant women during or immediately prior to labor, when other analgesic techniques are
more appropriate. Opioid analgesics, including ULTIVA, can prolong labor through actions
which temporarily reduce the strength, duration, and frequency of uterine contractions.
However, this effect is not consistent and may be offset by an increased rate of cervical
dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during
labor for signs of excess sedation and respiratory depression.
USA
2015: 36%
occasionally

11. Bhatia K. Unknowns in the use of remifentanil PCA for labour analgesia.
Anaesthesia. 2013;68(6):641-2.
Birnbach DJ, Ranasinghe JS. Is remifentanil a safe and effective alternative to neuraxial
labor analgesia? It all depends. Anesth Analg. 2014;118(3):491-3.
Bonner JC, McClymont W. Respiratory arrest in an obstetric patient using remifentanil
patient-controlled analgesia. Anaesthesia. 2012;67(5):538-40.
Daly O, Kelly KP, McCormack JG, Heidemann BH. Remifentanil PCA in labour.
Anaesthesia. 2013;68(7):780-1.
Devabhakthuni S. Efficacy and safety of remifentanil as an alternative labor
analgesic. Clin Med Insights Womens Health. 2013;6:37-49.
Freeman LM, Bloemenkamp KW, Franssen MT, et al. Patient controlled analgesia
with remifentanil versus epidural analgesia in labour: randomised multicentre
equivalence trial. BMJ. 2015;350(7997):11.
Kranke P, Girard T, Lavand'homme P, Melber A, Jokinen J, Muellenbach RM, et al. Must we
press on until a young mother dies? Remifentanil patient controlled analgesia in labour
may not be suited as a "poor man's epidural". BMC Pregnancy Childbirth. 2013;13:139.
Muchatuta NA, Kinsella SM. Remifentanil for labour analgesia: time to draw breath?
Anaesthesia. 2013;68(3):231-5.
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12. The ideal opioid delivery
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Time
Pain
intensity
and effect
Contraction pain
Pain relief
Does not exist!

13. Opioids and labour analgeisa…
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14. SSAI Malmø 2017

15. Tramadol,
meptazinol,
pethidine,
diamorphine,
pentazocine,
nalbuphine
fentanyl
IM,IV, Pca vs bolus.
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16. SSAI Malmø 2017

17. Van De Velde and Carvalho. IJOA 2016; 15: 66-74
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18. Remi: 40µg/2mins
Fenta: 20µg + loading
Pet: 5 mg + loading
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19. Other opioids better?
• CONCLUSIONS: Intravenous patient-controlled analgesia with either remifentanil or fentanyl provides a
moderate degree of labour analgesia, whereas transient maternal oxygen desaturation is observed more
commonly with remifentanil. Fentanyl is associated with a higher need for neonatal resuscitation. Marwah R,
Hassan S, Carvalho JC, Balki M. Remifentanil versus fentanyl for intravenous patient-controlled labour analgesia: an observational study.
Canadian Journal of Anaesthesia. 2012;59(3):246-54.
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20. Remifentanil provides better
pain relief than other opioids,
but only during the first two
hours
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21. Does it work?
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22. From: M Van De
Velde, B Carvalho:
IJOA 2016; 25: 66-74
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23. In women in labour, patient controlled analgesia with remifentanil is not equivalent to
epidural analgesia with respect to scores on satisfaction with pain relief. Satisfaction
with pain relief was significantly higher in women who were allocated to and received
epidural analgesia. TRIAL REGISTRATION: Netherlands Trial Register NTR2551.
CONCLUSION: In terms of labor duration, average VAS pain scores, and maternal overall
satisfaction score with analgesia, CSE analgesia is superior to that provided by epidural
analgesia or PCIA with remifentanil for pain relief in early labor in nulliparous women.
However, there were no differences in the mode of delivery, side effects or neonatal
outcomes between the three techniques.
Efficacy of Remifentanil PCA as compared to CSE/Epidural
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24. Oxygen saturation was significantly lower (SpO2 <92%) in women who used
remifentanil (relative risk 1.5, 1.4 to 1.7).
. Remifentanil IVPCA provides poorer efficacy on labor analgesia than epidural
analgesia, with more sedation on parturients and a trend of newborn acidosis.
Lin R, Tao Y, Yu Y, Xu Z, Su J, Liu Z. Intravenous remifentanil versus epidural
ropivacaine with sufentanil for labour analgesia: a retrospective study. PLoS ONE
[Electronic Resource]. 2014;9(11):e112283.
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25. Meta Analyses
• This meta-analysis suggests that remifentanil PCIA is not superior to epidural analgesia in analgesic
efficacy during labor. Given the wide CIs of the pooled results for secondary maternal and neonatal
outcomes, definite conclusions cannot be drawn for those outcomes. Further studies are still warranted to
validate these conclusions. Liu ZQ, Chen XB, Li HB, Qiu MT, Duan T. A comparison of remifentanil parturient-controlled intravenous analgesia with
epidural analgesia: a meta-analysis of randomized controlled trials. Anesth Analg. 2014;118(3):598-603.
• CONCLUSION: During labour, remifentanil-PCA provided superior analgesia and higher patient satisfaction
compared with pethidine with a comparable degree of adverse events. Epidural analgesia provided
superior pain relief in comparison with remifentanil. Due to a low number of reported adverse events, the
safety issue of remifentanil use in labour remains an open question that needs to be addressed in future
trials. Schnabel A, Hahn N, Broscheit J, Muellenbach RM, Rieger L, Roewer N, et al. Remifentanil for labour analgesia: a meta-analysis of
randomised controlled trials. European Journal of Anaesthesiology. 2012;29(4):177-85.
• Conclusions: Pooled assessment of remifentanil intervention seems an attractive strategy for controlling
labor pain in health term parturients, but it is not supported by strong evidence. Current evidence
suggests that it may produce effective analgesia by only a modest level. HealthMED. 2012;6(7):2407-18.
Effect size difference: 3 cm
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26. SSAI Malmø 2017
APRIL 2017
20 RCT’s, 3569 women

27. Results Weibel et al..
• Based on the current systematic review, there is
mostly low-quality evidence to inform practice
and future research may significantly alter the
current situation. The quality of evidence is
mainly limited by poor quality of the studies,
inconsistency, and imprecision. More research is
needed on maternal and neonatal safety
outcomes (maternal apnoe and respiratory
depression, Apgar score) and on the optimal
mode and regimen of remifentanil administration
to provide highets efficacy with reasonable
adverse effects for mother and their newborns.
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28. Always satisfied?
Off course they are! Who wouldn’t?
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29. Optimal administration of remi?
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30. Optimal administration of remi?
• Protocols varies (bolus dose, lock-out,
background infusion, TCI, etc)
• Fixed bolus 20-50 µg without background
infusion, lock-out 2-3 minutes
• If background – small dose < 0.05µg/kgxmin
• TCI? 0.5-1.5 ng/ml
• New systems? VPIA? (Vital signs patient
controlled intravenous analgesia)
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31. SIA et al. IJOA correspondence 2014: 23: 196-8
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32. Cont infusion or PCA?
• Shen MK, Wu ZF, Zhu AB, et al. Remifentanil for labour analgesia: a double-
blinded, randomised controlled trial of maternal and neonatal effects of
patient-controlled analgesia versus continuous infusion (0.005-0.2
µg/kgxmin) Anaesthesia. 2013;68(3):236-44. The results suggest that
remifentanil PCA (0.1-0.4 µg/kg) provides better pain relief and similar
placental transfer compared with continuous infusion. (Author)
• Per protocol TCI Norwegian National Hospital (Oslo University Hospital):
– 0.5 – 2 ng/ml + nurse controlled boluses) – easier for anaesthesia
personell?
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33. Remifentanil TCI?
• Why not?
• Acta Anaesthesiol Scand. 2013 Jul;57(6):802-8. doi: 10.1111/aas.12096. Epub 2013 Mar 15.
• Remifentanil target-controlled infusion during second stage labour in high-risk parturients:
a case series. Schwarz GL1, Volmanen P, Albrechtsen S, Bjoernestad E.
• 1ng/ml start, incremental doses of 0.5 ng/ml, titrated untill satisfied mother or side-effects
(1-6 ng/ml).
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34. Why use remifentanil ??
The boss
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35. In conclusion…
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36. When to use it?
• For parturients with contraindications to
regional analgesia
– Bleeding disorders
– Infections?
– Mother does not want regional
• In places with reduced anaesthesia service?
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37. Then remifentanil is the best choice
• Continuous monitoring
• Including capnography or RR counting
• Well educated staff
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38. Remifentanil PCA
• Is cheap
• Easy to administer
• Gives (some) pain relief
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39. BUT..
• Has a poor analgesic effect compared to the
golden standard of regional analgesia
• May cause a lot of harm
• And…..
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40. AND SHOULD BE RESERVED FOR
THE SPECIAL OCCATIONS..
Is too dangerous to be used as routine
analgesia in the labour ward..
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41. SSAI Malmø 2017

42. Thank you!
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43. Large randomized prospective trials are required before it may be recommended
for routine use in labouring women. © 2013 Elsevier Ltd.
Lim LFM, Leo S. Role of remifentanil in labour analgesia. Trends in Anaesthesia
and Critical Care. 2013;3(3):152-6.
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