Remifentanil in labour analgesia where are we in 2017 an update.

Transcription

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

2 Disclosures None

3 Agenda Pharmacology Does it work? Whys use it at all? Conclusion

4 Remifentanil - Pharma

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, x morphine Lower plasma concentration in pregnants versus non-pregnants large variability

6 Fetal exposure Uterine vein/maternal artery ratio: 0.88 Umbilical artery/umbilical vein ratio: 0.29 Redistribution, rapid fetal metabolism

7 Is it in use??

8

9 RemiPCA SAFE Network Regimen Concentration of Remifentanil: 20mcg/ml (2mg Remifentanil in 100ml NaCl 0,9%) Bolus: μg Lockout interval: 2 min No additional infusion of remifentanil. No application of any other opioid or analgesic drug. haring 2017: 7800 deliveries 26.6% Hypoxia 26% Sedation 17% Nausea

10 USA 2015: 36% occasionally Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioidinduced 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.

11 Bhatia K. Unknowns in the use of remifentanil PCA for labour analgesia. Anaesthesia. 2013;68(6): Birnbach DJ, Ranasinghe JS. Is remifentanil a safe and effective alternative to neuraxial labor analgesia? It all depends. Anesth Analg. 2014;118(3): Bonner JC, McClymont W. Respiratory arrest in an obstetric patient using remifentanil patient-controlled analgesia. Anaesthesia. 2012;67(5): Daly O, Kelly KP, McCormack JG, Heidemann BH. Remifentanil PCA in labour. Anaesthesia. 2013;68(7): Devabhakthuni S. Efficacy and safety of remifentanil as an alternative labor analgesic. Clin Med Insights Womens Health. 2013;6: 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.

12 Pain intensity and effect The ideal opioid delivery Contraction pain Pain relief Does not exist! Time

13 Opioids and labour analgeisa

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15 Tramadol, meptazinol, pethidine, diamorphine, pentazocine, nalbuphine fentanyl IM,IV, Pca vs bolus.

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17 Van De Velde and Carvalho. IJOA 2016; 15: 66-74

18 Remi: 40µg/2mins Fenta: 20µg + loading Pet: 5 mg + loading

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):

20 Remifentanil provides better pain relief than other opioids, but only during the first two hours

21 Does it work?

22 From: M Van De Velde, B Carvalho: IJOA 2016; 25: 66-74

23 Efficacy of Remifentanil PCA as compared to CSE/Epidural 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.

24 . 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):e Oxygen saturation was significantly lower (SpO2 <92%) in women who used remifentanil (relative risk 1.5, 1.4 to 1.7).

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): 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): 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): Effect size difference: 3 cm

26 APRIL 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.

28 Always satisfied? Off course they are! Who wouldn t?

29 Optimal administration of remi?

30 Optimal administration of remi? Protocols varies (bolus dose, lock-out, background infusion, TCI, etc) Fixed bolus µg without background infusion, lock-out 2-3 minutes If background small dose < 0.05µg/kgxmin TCI? ng/ml New systems? VPIA? (Vital signs patient controlled intravenous analgesia)

31 SIA et al. IJOA correspondence 2014: 23: 196-8

32 Cont infusion or PCA? Shen MK, Wu ZF, Zhu AB, et al. Remifentanil for labour analgesia: a doubleblinded, randomised controlled trial of maternal and neonatal effects of patient-controlled analgesia versus continuous infusion ( µg/kgxmin) Anaesthesia. 2013;68(3): The results suggest that remifentanil PCA ( µg/kg) provides better pain relief and similar placental transfer compared with continuous infusion. (Author) Per protocol TCI Norwegian National Hospital (Oslo University Hospital): ng/ml + nurse controlled boluses) easier for anaesthesia personell?

33 Remifentanil TCI? Why not? Acta Anaesthesiol Scand Jul;57(6): doi: /aas Epub 2013 Mar 15. Remifentanil target-controlled infusion during second stage labour in high-risk parturients: a case series. Schwarz GL 1, 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).

34 Why use remifentanil?? The boss

35 In conclusion

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?

37 Then remifentanil is the best choice Continuous monitoring Including capnography or RR counting Well educated staff

38 Remifentanil PCA Is cheap Easy to administer Gives (some) pain relief

39 BUT.. Has a poor analgesic effect compared to the golden standard of regional analgesia May cause a lot of harm And..

40 Is too dangerous to be used as routine analgesia in the labour ward.. AND SHOULD BE RESERVED FOR THE SPECIAL OCCATIONS..

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42 Thank you!

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