Remifentanil PCIA for Labour Analgesia: Where does it belong?

Transcription

1 Remifentanil PCIA for Labour Analgesia: Where does it belong? Marc Van de Velde, MD, PhD, EDRA. Professor of Anaesthesia, Department Cardiovascular Sciences, Catholic University Leuven (KUL) Chair, Department of Anaesthesiology, University Hospitals Leuven (UZL), Leuven, Belgium OAA Committee member President of the Society of Anesthesia and Resuscitation of Belgium (SARB)

2 Conflicts of Interest Holder of the Baxter UZLeuven Anaesthesia Research Chair Co-Holder of the Noble Gas research fund supported by Air Liquide. Received financial support of the following companies for either research, consultancy or lectures (Active = current or within the last 3 years): Smiths Medical (active). Sintetica (active). Grunenthal (active). Nordic Pharma (active). MSD (active). Janssens Pharmaceutics (active). Heron (active). Halyard (active). Aquettant (active). Aspen (active). AstraZeneca. Glaxo Smith Kline. BBraun. Abbvie. Fresenius. GE. Chapter 20 Neuraxial Anaesthesia for Caesarean delivery Armstrong, Walters, Cheesman and O Sullivan

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4 For those working in the UK Do You offer in Your department remifentanil PCIA for labour analgesia: 1. As a routine and first line option. 2. Only as an alternative when neuraxial analgesia is contraindicated. 3. Not at all.

5 For those working overseas Do You offer in Your department remifentanil PCIA for labour analgesia: 1. As a routine and first line option. 2. Only as an alternative when neuraxial analgesia is contraindicated. 3. Not at all.

6 If You use remifentanil PCIA Do You have guaranteed one-to-one mdiwifery care: 1. Yes, always. 2. Yes, most of the time. 3. Yes, but often not. 4. No.

7 If You use remifentanil PCIA Do You monitor respiration using saturation monitoring: 1. Yes. 2. No.

8 If You use remifentanil PCIA Do You monitor respiration using capnography: 1. Yes. 2. No.

9 Use of remifentanil PCIA Alternative when neuraxial contraindicated. Belgium 40% of units. Scandinavia: up to 80% of units. UK up to 50% of units. First line treatment routine use. More and more units in the UK, Austria, Switserland, The Netherlands, Finland, Scandinavia,..

10 IJOA 2016, Van de Velde and Carvalho

11 PCIA remifentanil for labour analgesia. Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the current scientific basis to advocate routine use?

12 Quality of pain relief: adequate levels of pain reduction. Sustained throughout the entire labour process

13 Epidural versus pethidine and tramadol. Jain et al. Int J Obstet Gynecol Obstet 2003; 83,

14 Epidural versus pethidine and tramadol. Jain et al. Int J Obstet Gynecol Obstet 2003; 83,

15 Reduction in VAS scores with remifentanil Blair 2001 Volikas 2001 Volmanen 2002 Thurlow 2002 Volmanen 2005 Evron 2005 Blair 2005 Volikas 2005 Balki 2007 Volmanen 2008 D'Onofrio 2009 Douma 2010 Douma 2011 Ng 2011 Volmanen 2011 Tveit 2012 Marwah 2012 Ismail 2012 Epidural Most studies performed in early labour, following only minutes of labour and not in more advanced labour!!!!! High conversion rate: up to 40% Additional analgesia: % A er Before

16 VAS scores during prolonged infusion. Ng et al. Anaesthesia 2011; 66, Douma et al. IJOA 2011; 20,

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18 Leong et al. Anesth Analg 2011; 113,

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21 Cochrane Database of Systematic Reviews Weibel S, Jelting Y, Afshari A, Pace NL, Eberhart LHJ, Jokinen J, Artmann T, Kranke P. Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour. Data collection and analysis CochraneDatabaseof SystematicReviews 2017, Issue 4. Art. No.: CD Two review authorsindependently assessed trialsfor inclusion, DOI: extracted / CD pub2. data, and appraised study quality. We contacted study authors for additional information other than incomplete outcome data. We performed random-effects metaanalysis. Patient-controlled analgesia with remifentanil versus alternative parenteral methodsfor pain management in labour (Review) To reduce the risk of random error in meta-analysis we performed trial sequential analysis. We included total zero event trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta-analysis. Weapplied the Gradesof Recommendation, Assessment, Development, and Evaluation (GRADE) approach to assessthequality of evidence. Main results Patient-controlled analgesia with remifentanil versusalternativeparenteral methodsfor pain management in labour (Review) Copyright 2017The CochraneCollaboration. Published by John Wiley & Sons, Ltd. Figure 2. Risk of bias summary: review authors judgements about each risk of bias item for each included study. TwentyRCTswith 3569womenwereincluded. Of those, 10trials(2983participants) comparedremifentanil (PCA) toan epidural, four trials(216 participants) to another opioid (IV/IM), threetrials(215 participants) to another opioid (PCA), two trials(135 participants) to remifentanil (continuousiv), and onetrial (20 participants) to remifentanil (PCA, different regimen). No trialswereidentified for theremaining comparisons. Weibel S, Jelting Y, Afshari A, Pace NL, Eberhart LHJ, Jokinen J, Artmann T, Kranke P Methodological quality of studieswasmoderate to poor. Weassessed risk of biasashigh for blinding issuesand incompleteoutcome datain 65% and 45% of theincluded studies, respectively. Thereisevidenceof effect that women in theremifentanil (PCA) group weremoresatisfied with pain relief than women in theother opioids(iv/im) group (standardised mean difference (SMD) 2.11, 95% confidence interval (CI) 0.72 to 3.49, four trials, very lowquality evidence), and that women werelesssatisfied compared to women in theepidural group (SMD -0.22, 95% CI to -0.04, seven trials, verylow-quality evidence). Thereisevidence of effect that remifentanil (PCA) provided stronger pain relief at one hour than other opioids administered IV/IM (SMD -1.58, 95% CI to -0.48, three trials, very low-quality evidence) or via PCA (SMD -0.51, 95% CI to -0.00, three trials, very low-quality evidence). Pain intensity was higher in the remifentanil (PCA) group compared to the epidural group (SMD 0.57, 95% CI 0.31 to 0.84, six trials, low-quality evidence). Datawerelimited on safety aspectsfor both thewomen and thenewborns. Only onestudy analysed maternal apnoeain acomparison of remifentanil (PCA) versus epidural and reported that half of the women in the remifentanil and none in the epidural group had an apnoea (very low-quality evidence). There is no evidence of effect that remifentanil (PCA) was associated with an increased risk for maternal respiratory Weibel depression S, Jeltingwhen Y, Afshari compared A, Pace tonl, epidural Eberhart analgesia(rr LHJ, Jokinen 0.91, J, Artmann 95% T, CIKranke 0.51 top. 1.62, ccc 0.01, threetrials, lowquality evidence) and Patient-controlled no reliableconclusion analgesia might with bereached remifentanil compared versus alternative to remifentanil parenteral (continuousiv) methods for(all pain study management armsincluded labour. zero events, two trials, low-quality CochraneDatabaseof evidence). InSystematicReviews one trial of remifentanil 2017, Issue (PCA) 4. Art. versusanother No.: CD opioid (IM) threeout of 18 women in the remifentanil and noneout DOI: / CD pub2. of 18 in thecontrol group had arespiratory depression (verylow-quality evidence). Thereisno evidence of effect that remifentanil (PCA) wasassociated with an increased risk for newbornswith Apgar scoreslessthan seven at fiveminutescompared to epidural analgesia(rr 1.26, 95% CI 0.62 to 2.57, ccc 0.01, fivetrials, low-quality evidence) and no reliableconclusion might be reached compared to another opioid (IV) and compared to remifentanil (PCA, different regimen) both

22 Remifentanil versus epidural. Volmanen et al. Acta Anaesth Scand 2008; 52, Douma et al. IJOA 2011; 20,

23 Freeman et al.

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26 THE BEST LABOUR PAIN RELIEF STRATEGY IS A NEURAXIAL BLOCK! IF ONE OPTS FOR OPIOID ANALGESIA OR NITROUS OXIDE PERHAPS REMIFENTANIL IS SLIGHTLY BETTER IN TERMS OF PAIN RELIEF.

27 PCIA remifentanil for labour analgesia Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the scientific basis to advocate routine use?

28 Maternal side-effects. Sedation. Nausea and vomiting. Pruritus. Respiratory depression and desaturation.

29 Respiratory depression and desaturation. Blair et al. Anaesthesia 2005; 60, Douma et al. IJOA 2011; 20, Douma et al. Brit J Anaesth 2010; 104,

30 Freeman et al. Freeman et al.

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32 Respiratory effects % respiratory depressed Respiratory effects: SaO2 < 90% SaO2 < 94% SaO2 < 95% RR < 12 RR < 8 Number of pa ents Pa ents with respiratory depression Respiratory depression

33 PAIN SCORES: EPIDURAL BETTER! Anesth Analg 2014

34 Anesth Analg 2014 Measured Saturation and capnography Only measurement during 1st hour of analgesia in both groups Continued measurement in remifentanil group Anesthetist constantly in the room If apnoe occurred: > 20 sec stimulation by vocal commands If apnoe occurred: > 40 sec stimulation by mild prodding

35 27 apneas in remi-group 9 resulted in saturation < 90% Anesth Analg 2014

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37 17y, Induction of labour. Entonox. At 3.55 pm PCIA remifentanil: 40 mcg/2 min, no infusion. At pm patient comfortable and awake. Midwife leaves room briefly. Family activates emergency button at pm: cyanose and unresponsive and apnoe. Pump and medication failures were ruled out.

38 30y, Induction of labour. PCIA remifentanil: 40 mcg/5 min, 2 mcg/min infusion. Following the start of PCIA: cardiorespiratory collaps with CPR and perimortem C-section. Remifentanil 10-fold higher concentration then prescribed and the patient received bolus of 400 mcg instead of 40 mcg.

39 24y, Induction of labour because IUD. Paracetamol, codeine, entonox, diamorphine SC. PCIA remifentanil: 40 mcg/2 min, no infusion. Anti-reflux valve. Anesthetist present during the first 5 PCIA boluses that the patient administered. Anesthetist left the patient after 20 minutes. 15 minutes later: midwife left the room briefly. Family member alarmed: patient unresponsive, not breathing, GCS 3/15 and deep cyanosis, no pulse, CPR started, perimortem CS, death infant. 3 additional boluses were administered after anesthetist had left the room; drug dose and concentration was correct.

40 New, soon to be published information During defense: I would no longer offer this as a routine analgesia technique Another thesis of the same group (Freeman et al.) next month!

41 New, soon to be published information Acta Anesthesiol Belg: Under review! High % of apneas and desaturation not observed by midwifery staff! Engelen, Derks, Beenakkers. Click here to download Table Table 2 - re Table 2: Number of patients with desaturations and respiratory depressions SpO2 <80% n (%) SpO2 <94% n (%) RR <8/min n (%) Standard monitoring 1 (1%) 22 (25%) 0 Continuous monitoring 20 (33%) 58 (97%) 38 (63%) P-value

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44 Respiratory depression: a safety protocol. One to One midwifery care, uninterrupted! Safety precautions: Separate IV cannula Adequate staff training Written protocols Careful (Pharmacy?) preparation of solution. Monitoring: Saturation monitoring Capnography Ventilation monitoring Supplemental oxygen? Is this what we want and can achieve????

45 PCIA remifentanil for labour analgesia Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the scientific basis to advocate routine use?

46 Remifentanil sedation in second trimester pregnancies. Loss of beat-to-beat variability in the CTG! There have been cases of urgent C- section for opioid induced loss of FHR variability. Van de Velde et al. Anesth Analg 2006.

47 Remifentanil for general anesthesia: Prospective case series. Base Exc: base excess; ND: not done, UA: umbilical artery. Patient Apgar 1 Apgar 5 Apgar 10 Weight (g) Mask (min) UA ph UA pco2 Base Exc None None None ND ND ND None None None None Van de Velde et al. Int J Obstet Anesth 2004; 13,

48 Opioids and fetal acid-base status.

49 Opioids and fetal acid-base status. Reynolds et al. BJOG 2002; 109,

50 Remifentanil and fetal acid-base status. Douma et al. Brit J Anaesth 2010; 104, Douma et al. IJOA 2011; 20,

51 Remifentanil and fetal acid-base status. Only 7 studies looked at UA BE! Only 1 study looked specifically at sideeffects (n = 50, n = 37 for umbilical artery samples; Volikas et al. BJA 2005). UA BE: ± 5.02 (mean ± SD). 2/34 subjects UA BE worse then -10 meq/l.

52 PCIA remifentanil for labour analgesia Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the scientific basis to advocate routine use?

53 PCIA remifentanil for labour analgesia Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the scientific basis to advocate routine use?

54 Less C-sections with remi PCIA because less use of neuraxial analgesia Survey in BELGIUM: 65% labour neuraxial analgesia 2005 NOAD data in the UK: 23% labour neuraxial analgesia 2006 Survey in BELGIUM: C-section rate 18% 2005 NOAD data in the UK: C-section rate 24%

55 Remifentanil decreases uterine muscle activity following oxytocin infusion in vitro. n pd2 E max % Meperidine ± ± 7.8 Remifentanil ± ± 7.6 Alfentanil ± ± 8.9 Mepivacaine ± ± 7.3 Ropivacaine ± ± 3.7 Bupivacaine ± ± 7.4 Clonidine 10 ND 4.7 ± 10.4 Midazolam ± ± 11.0 The sensitivity (pd2) and maximal responses (Emax) of isolated pregnant rat uterine preparations to agents tested. Nacitarhan et al. Methods Find Exp Clin Pharmacol 2007; 29, Kayacan et al. Adv in Therap 2007; 24,

56 PCIA remifentanil for labour analgesia Quality of pain relief. Maternal side-effects. Foetal and neonatal side-effects. Off-license indication. Mode of delivery. Effects on uterine muscle activity. What is the scientific basis to advocate routine use?

57 What is the scientific basis to advocate routine use? IJOA 2016, Van de Velde and Carvalho

58 IJOA 2016, Van de Velde and Carvalho

59 What is the scientific basis to advocate routine use? Approximately 1000 prospective remi PCIA patients published. Most patients: remifentanil was stopped after minutes. In a high proportion nitrous oxide was coadministered. Large group requested epidural analgesia.

60 Conclusion. Remifentanil is worse in terms of pain relief and maternal and fœtal side-effects as compared to epidural analgesia. Remifentanil is marginally better then pethidine or entonox. Remifentanil has a 20 30% risk of respiratory depression and cases of near death have been described.

61 Conclusion. Do not start to use it. Stop if You are using it. If You persevere in risking your parturients lifes, try to avoid catasthrophy (and I can not guarantee success) by: One-to-one, uninterrupted, midwifery care. Use separate, dedicated IV cannulla. Monitor: Capnography Saturation Use supplementary oxygen if required. Use written protocols for use and preparation. Do not use if other opioids are already given.

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