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Delivery of anesthesia in the obstetric population warrants unique considerations, as two patients, the mother and the neonate, are exposed to the pharmacologic and physiologic effects of the chosen anesthetic agents and technique. A spinal anesthetic offers distinct advantages over general anesthesia by minimizing fetal exposure to anesthetics and potential respiratory depression. Furthermore, there is benefit to the mother by reducing the potential for nausea, vomiting, and aspiration that may occur with induction of general anesthesia in a full-stomach parturient. It is commonplace for intrathecal opioids to be added as an adjunct to the local anesthetic when administering a spinal anesthetic. However, the potential advantages of opioid administration, such morphine and/or fentanyl, are balanced by the potential risks. In this issue of the journal, Thornton and colleagues  describe the effects of fentanyl when added to a mixture of intrathecally administered bupivacaine plus morphine for cesarean section. The authors’ work in studying the effects of the added fentanyl is of vital importance because current clinical evidence offers inconsistent results.
Since the initial use of intrathecal opioids in the late 1970s, the practice has grown in popularity as it has been shown to provide significant analgesia in the postoperative period . Hydrophilic opioids (i.e., morphine) and lipophilic opioids (i.e., fentanyl) demonstrate different kinetics and analgesic profiles, with each opioid presenting unique risks and benefits. Hydrophilic opioids traverse the spinal cord slowly and bind to specific opioid receptors in the spinal cord. They also penetrate the dura and epidural adipose tissue slowly, thus resulting in delayed clearance from the cerebrospinal fluid (CSF). Lipophilic opioids quickly penetrate the spinal cord to bind to specific and non-specific receptors. Distribution into epidural adipose tissue and entry into the systemic circulation is also more rapid. Therefore, an intrathecal dose of fentanyl has a rapid onset (10–20 min) and short duration of analgesic action (4–6 hrs); in contrast, morphine has a slower onset (30–60 min) and a much longer, dose-dependent duration of action (13–33 hrs) . The difference in the therapeutic profile between these opioids allows the option for intrathecal administration of a combination of both fentanyl and morphine with the local anesthetic. The fentanyl dose would supplement the local anesthetic effects and provide dense segmental analgesia during a lower abdominal surgery, such as a cesarean section, while morphine would provide long-duration postoperative analgesia.
However, as the authors highlight in their discussion, the evidence supporting the addition of fentanyl to a bupivacaine/morphine spinal anesthetic is inconsistent. The results of the double-blind study by Thorton and colleagues showed that the addition of fentanyl did not improve the onset, or the density of the spinal anesthetic, as no additional intravenous (i.v.) opioids were required for rescue analgesia . Furthermore, early postoperative pain control was not improved by the addition of fentanyl, and more opioid-related side effects were reported in this group.
The study focused primarily on healthy patients with uncomplicated pregnancies; the results may differ from those in patients with complicated, multiparous pregnancies or patients with chronic pain. It would be particularly interesting to determine the time of sensory dermatomal regression from the spinal as it relates to the duration of surgery. Since fentanyl has been shown to have a synergistic effect to bupivacaine in spinal anesthesia , there might be a benefit during a “long” cesarean section or in patients with chronic pain. However, it is also reasonable to suspect that as an adjunct to morphine, fentanyl’s benefit would likely be marginal, as current support in the literature is lacking.
Side effects and complications due to intrathecal opioids have been well described. Without clinically significant benefit of utilizing two different intrathecal opioids during a caesarian section, the mother and fetus may accrue unnecessary additional risk. As Thornton and colleagues’ report , a higher incidence of nausea, vomiting, and pruritus was noted in the patients receiving the combination of fentanyl plus morphine. Evidence suggests that low doses of intrathecal fentanyl plus local anesthetics do not affect neonatal APGAR scores [4, 5]. However, when fentanyl is combined with intrathecal morphine, it is not clear if that still holds true. Furthermore, intrathecal fentanyl has been associated with uterine hyperactivity leading to fetal bradycardia , and, as a result, fetal demise has been reported . Lastly, addition of opioids to the local anesthetic would also require pharmaceutical compounding. Although hospital regulations and preparation of a spinal tray differ among institutions, local anesthetics are not pre-compounded with opioids and additions to the anesthetic solution would likely occur in the operating room in anticipation of the surgery. With each medication addition to the spinal mixture, there is a rare but significant risk for contamination, wrong medication errors, and/or wrong dose errors.
In summary, the study by Thornton and colleagues is clinically significant, as it demonstrates a lack of benefit to the common practice of combining intrathecal fentanyl and morphine when administering a spinal anesthetic for cesarean section. Although there is evidence to support intrathecal opioid use, co-administration of multiple opioids may subject the mother and fetus to additional harm without offsetting benefits. Sometimes, less is really more!
Conflict of interest
Nothing to declare