In Response.

Abstract

We thank Dr Tulchinsky1 for highlighting his possible concerns regarding the safety of mixing multiple drugs and administration of bupivacaine dose <13 mg during spinal anesthesia for cesarean delivery (CD). As referenced in our review, there is practice variation among the Society of Obstetric Anesthesiology and Perinatology (SOAP) survey respondents. We absolutely believe that the risks of drug side effects, drug errors, and bacterial contamination have to be balanced against possible benefits. Additionally, clinical practice variation often means that the best evidence is not being followed. Indeed, this prompted us to conduct this systematic review.2 The question we set to answer was as follows: What is the evidence of the benefit of intrathecal fentanyl for CD? If there is no benefit in efficacy or quality of spinal anesthesia, then the practice of adding fentanyl to the intrathecal drugs administered for CD anesthesia is not supported and should be abandoned. We found that adding fentanyl to intrathecal bupivacaine reduced the need for an intraoperative conversion to general anesthesia (GA), reduced intraoperative supplemental analgesia, and reduced nausea and vomiting. These benefits should be balanced against the side effect of pruritus. While nausea and vomiting make the experience of childbirth unpleasant, the need for GA is a safety concern as an unplanned conversion to GA exposes the mother to the risk of failed intubation and aspiration. Similarly, intravenous drugs used for supplementing the inadequate spinal block can impair maternal recall, participation in the birth, and cross the placenta, leading to a range of adverse fetal outcomes such as diminished maternal bonding or breastfeeding and respiratory depression. While the efficacy of intrathecal morphine for postoperative analgesia is well established, we wanted to know if the use of a second opioid (fentanyl) is justifiable. We were surprised to find only 2 studies with a total of 100 participants for this comparison. The pooled data showed a lower need for intraoperative supplemental analgesia when intrathecal fentanyl was used (number needed to treat [NNT] = 9.2). Further, Techanivate et al3 found a lower incidence of shivering in the intrathecal fentanyl group (NNT = 3.3). These findings need further confirmation, considering the small sample size for this comparison. Indeed, by challenging current practices and conducting systematic reviews of the evidence, such as ours, it allows clinicians to identify dogma and persistent knowledge gaps. However, until more studies become available, the current evidence base suggests the benefit of adding both fentanyl and morphine to intrathecal bupivacaine. Thus, our results refute Dr Tulchinsky’s assertion that the unnecessary complexity of multiple drug combinations or “mixology” is unwarranted. Regarding drug contamination and errors, Patel and Loveridge4 in 2015 qualitatively and quantitatively reviewed the obstetric neuraxial drug administration errors. They found 29 reported cases; most common effect was failure of the neuraxial technique. There were 4 reported deaths, all due to the accidental intrathecal administration of tranexamic acid. Interestingly, no reported neuraxial drug administration errors involved opioid medication. Therefore, we did not find evidence for the assertion that mixology or adding opioids to bupivacaine for spinal anesthesia causes serious drug errors in clinical practice. Further, better approaches to reduce the risk of bacterial and particulate contamination have been described that include wiping the ampules with an antiseptic and using filter needles for drawing up the drugs.5 Thus, we would advocate these strategies to avoid contamination rather than using a less effective drug mixture producing an inferior quality block. The point raised by Dr Tulchinsky about bupivacaine dose is an important one. We firmly believe that reducing the dose of bupivacaine for CD has little role in modern day anesthesia, especially with the availability of very effective strategies such as phenylephrine infusions to counteract hypotension.6 Not using an adequate dose of bupivacaine could lead to failure of spinal anesthesia. Nevertheless, we also believe that we should not use a “one-size-fits-all” approach in terms of bupivacaine doses. A bupivacaine dose of ≥13 mg for all patients, as advocated by Dr Tulchinsky, maybe excessive for some patients that can lead to a high spinal block with associated side effects such as bradycardia, numbness/weakness of hands, and shortness of breath. At least 10 different studies have assessed the effective dose 95 (ED95) of bupivacaine for the CD that ranges from 8.8 to 15 mg.7 There are 2 main reasons for this variability. First, the ED95 dose is calculated using statistical modeling that inherently comes with the uncertainty of estimates. Second, the dose requirement varies based on patient factors such as height, weight, and gestational age. Of the 4 studies (included in our review) that used a dose of 7.5 mg, 3 of them were from India and 1 from Singapore. It is well known that the average height of women in India and Singapore is significantly lower than the most western countries. So, a bupivacaine dose of 7.5 mg for these women may actually be adequate. All the remaining included studies used a bupivacaine dose of ≥10 mg. In conclusion, we present evidence that intrathecal fentanyl added to bupivacaine reduces intraoperative supplemental analgesia and nausea/vomiting and find no evidence of serious drug errors.2,4 While the evidence base for the benefit of adding fentanyl to the intrathecal bupivacaine–morphine mixture is less robust until further is available, it is our opinion that clinicians should use both opioids, fentanyl, and morphine in spinal anesthesia for CD. Strategies to reduce risk of drug error and bacterial contamination during the preparation of intrathecal drugs, as described in the literature, should be rigorously practiced.4,5 Vishal Uppal, MBBS, MSc, FRCADolores M. McKeen, MD, MSc, FRCPCDepartment of Anesthesia, Perioperative Medicine and Pain ManagementDalhousie University, Nova Scotia Health Authority and IWK Health CentreHalifax, Nova Scotia, Canada[email protected]