Intravenous remifentanil for labour analgesia: is it effective, safe, and feasible?

Guasch Arévalo, E.; Brogly, N.
doi:10.1016/j.redare.2023.03.005
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; the demand for labour analgesia has become widespread&#44; given that pain control and quality of life are priorities for both women and the doctors who treat them&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In Spain&#44; neuraxial analgesia in any of its variants &#40;epidural&#44; intradural&#44; or combined&#41; is the most widely used analgesic modality - possibly because its efficacy-safety balance is superior to all other options - and it is now considered the gold-standard in this context&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Some women&#44; however&#44; are not candidates for neuraxial analgesia due to medical contraindication or other reasons&#44; and can be offered other&#44; albeit less effective&#44; analgesic modalities to alleviate labour pain&#46; One such option is patient controlled analgesia with intravenous remifentanil &#40;rPCA&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The use of remifentanil in PCA for labour pain has been documented since 2000&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Remifentanil is a &#956; opioid receptor agonist with a latency of 30&#8722;60&#160;s and a peak effect at 2&#46;5&#160;min&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It is rapidly metabolized by plasma esterases and has a very short context-sensitive half-life &#40;T<span class="elsevierStyleInf">1&#47;2</span> &#945;&#58; 0&#46;5&#8211;1&#46;5&#160;min&#44; T<span class="elsevierStyleInf">1&#47;2</span> &#946;&#58; 5&#8722;8&#160;min&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a> It has no cumulative effect in infusion&#44; can be administered over long periods&#44; and is eliminated within 3&#8722;10&#160;min regardless of the duration of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Remifentanil can be maintained throughout the cervical dilation phase until delivery&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">These characteristics give the drug several potential advantages for women in labour&#46; However&#44; the pain of uterine contractions is intermittent&#44; and with rPCA pain control is delayed by 10&#8211;20&#160;s&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> of 10 randomized clinical trials found no differences between rPCA and epidural analgesia in terms of foetal impact &#40;Apgar score &#60;7 at 5&#160;min of life&#41; and patient satisfaction&#59; however&#44; rPCA appears to be associated with a lower incidence of intrapartum fever&#44; and a significantly higher incidence of maternal respiratory depression&#46; Pain control with rPCA is rapid and does not appear to affect the duration of the first or second phase of labour or the incidence of caesarean section&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;15</span></a> There are no data on complications&#44; such as a higher or lower incidence of uterine atony and postpartum haemorrhage&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Several studies indicate that&#44; although remifentanil easily and quickly passes through the placental barrier&#44; its effect on neonatal respiratory depression is insignificant due to its rapid metabolism&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Let us briefly analyse the 3 factors that have motivated this editorial&#58; efficacy&#44; safety&#44; and resource management&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Efficacy</span><p id="par0035" class="elsevierStylePara elsevierViewall">The use of rPCA has been compared with meperidine and neuraxial analgesia&#46; The RESPITE study<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> compares rPCA with intramuscular meperidine&#46; The efficacy results were inconclusive&#44; although the fact that many women &#40;&#62;60&#37;&#41; refused to participate in the study shows a clear preference for neuraxial analgesia&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A recently created&#44; continuously updated registry of cases in which rPCA was administered and any side effects observed<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> brings together data from 31 European countries regarding the efficacy and serious side effects of rPCA for labour pain&#46; An audit of 5&#44;740 cases registered between 2010 and 2015 showed that 27&#46;3&#37; of women presented episodes of hypoxia &#40;oxygen saturation &#60;94&#37;&#41;&#44; 25&#46;8&#37; presented sedation&#44; 16&#46;9&#37; nausea and vomiting&#44; 2&#46;8&#37; presented pruritus&#44; and neonatal resuscitation was required in 0&#46;3&#37; of cases&#46; No serious complications&#44; defined as a respiratory depression requiring assisted ventilation or a cardiac arrest&#44; were recorded if the number of cases per centre exceeded 10 per year&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">In Northern Ireland&#44; rPCA was the most widely used analgesia modality between 2005 and 2014 &#40;8170&#47;25&#44;617 women analysed&#41;&#44; and was associated with an incidence of instrumental delivery or caesarean section similar to that observed in patients receiving epidural analgesia&#44; with no differences in neonatal outcomes&#46; Onset of maternal respiratory depression was rapidly diagnosed thanks to the constant presence of a midwife&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Safety</span><p id="par0050" class="elsevierStylePara elsevierViewall">The side effects described are&#58; hypoxia&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> cardiac and respiratory arrest&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> pruritus&#44; nausea and vomiting&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> The most reliable data come from the aforementioned database&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> It is important the bear in mind that in terms of safety&#44; continuous monitoring does not replace surveillance&#44; and that the use of capnography does not exclude the possibility of maternal respiratory depression&#46; According to Logtenberg et al&#46; who performed a large study in the Netherlands&#44; maternal monitoring is essential to avoid complications<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> - an observation corroborated by Tveit et al&#46; in their prospective study&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Human and materials resources</span><p id="par0055" class="elsevierStylePara elsevierViewall">Providing women in labour with analgesia on demand should be considered a human right&#46; However&#44; before offering a specific analgesic modality&#44; such as neuraxial analgesia or rPCA&#44; the attending clinician must weigh up the advantages&#44; disadvantages and possible complications&#44; taking into account the hospital&#8217;s infrastructure&#44; staff&#44; and their competence to deal with such complications&#46; These requirements are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In terms of staffing&#44; a 1&#58;1 midwife-patient ratio is recommended&#44; although this is not always easy to achieve&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The difficulty of providing adequate nurse follow-up is further complicated by major fluctuations in the number of births over a given period and the difficulty of increasing staff numbers in parallel with these trends&#46; Respiratory monitoring alone&#44; including capnography&#44; does not replace the presence of a trained healthcare professional&#46; These are the issues that currently limit the widespread use of rPCA as a routine labour analgesia option&#44; and alternative analgesic options are required&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">According to the recommendations of the Royal College of Anaesthesiologists&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> units that provide rPCA for labour analgesia should have local policies and processes in place to ensure that it is used safely&#44; that midwives who care for women using rPCA are familiar with its use and have received specific training&#46; Unit staffing levels should permit continuous midwifery supervision of its use&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Some protocols clearly specify that the midwife should not leave the dilation room once rPCA has begun&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The need for maternal respiratory monitoring is an obstacle to widespread implementation of rPCA as an analgesic modality&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;27</span></a> Current guidelines recommend monitoring maternal status with electrocardiography and continuous pulse oximetry&#44; implementing measures to prevent or facilitate prompt diagnosis of respiratory depression during rPCA&#44; and providing resources for immediate maternal and neonatal resuscitation in order to improve prognosis if complications occur&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In conclusion&#44; we summarize the SEDAR recommendations&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;30</span></a> including the requirements&#44; protocol&#44; indications and contraindications of rPCA&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">&#8220;Remifentanil is a moderately effective analgesic alternative&#44; although it is associated with certain risks&#46; It must be used with strict safety protocols&#46;&#34;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">&#8220;Continuous one-to-one monitoring by a healthcare professional is essential when using rPCA&#44; since respiratory depression can occur at any time after the start of opioid analgesia&#46; Respiratory rate&#44; depth of sedation&#44; and pain should be assessed at regular intervals&#44; and the foetal heart rate should be monitored continuously&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">&#8220;When using rPCA&#44; SaO<span class="elsevierStyleInf">2</span>&#44; respiratory rate and depth of sedation should be monitored&#44; the patient should be given supplementary oxygen and be monitored continuously by a midwife &#40;one-to-one&#41;&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">&#34;The healthcare system must be flexible enough to offer this and other analgesic alternatives safely and effectively when demanded or required by the patient&#46;&#34;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interests</span><p id="par0105" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Requirements</span>&nbsp;\t\t\t\t\t\t\n
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