Advances in epidural labor analgesia: Effectiveness and treatment strategies of butorphanol

Abstract

In this editorial, we provide a critical review of the article by Tang et al published in the World J Clin Cases, focusing on the utilization of butorphanol for epidural analgesia during labor. Our discussion encompasses recent research developments in epidural labor analgesia, specifically highlighting the current status of clinical applications of butorphanol and associated treatment approaches. Epidural analgesia is widely acknowledged as the primary method for pain management during labor, offering effective and prolonged pain relief while allowing mothers to remain alert and actively participate in the delivery process. Among the various drugs utilized for epidural labor analgesia, butorphanol has received increasing attention due to its potential efficacy and distinctive pharmacological properties. As a synthetic opioid analgesic, butorphanol exhibits both agonistic and antagonistic activity on opioid receptors, striking a balance between analgesia and minimizing side effects. Nevertheless, the safety and efficacy of butorphanol in epidural labor analgesia remains controversial. While certain studies have reported positive outcomes with butorphanol, including effective pain relief and a reduced incidence of side effects, others have raised concerns about its safety and efficacy compared to traditional opioids or alternative analgesics. In addition, the optimal dosing strategy and regimen of butorphanol as an adjuvant in epidural labor analgesia still need to be verified. Through comprehensive synthesis and analysis of existing literature, we aim to evaluate the current evidence regarding the use of butorphanol for epidural labor analgesia, delineate areas of consensus and controversy, and propose future avenues for research and clinical practice in this domain.

Key Words: Butorphanol; Epidural analgesia; Labor analgesia; Opioids; Pain management

Core Tip: The clinical application and therapeutic approaches of butorphanol as a pharmacological adjunct for epidural labor analgesia warrant thorough discussion. While some studies endorse its effectiveness in providing pain relief, debates persist regarding its safety and comparative performance against alternative medications. Subsequent research and validation are imperative, particularly concerning its optimal utilization as an adjunct in epidural labor analgesia. This editorial aim to consolidate current research findings, offering supplementary insights for clinical implementation, and advocates for more extensive clinical investigations in the future to holistically assess the efficacy and safety of butorphanol in epidural labor analgesia.

INTRODUCTION

Epidural analgesia stands out as the most effective pain relief method during labor, offering simplicity in administration and reliable analgesic outcomes. Maximizing analgesic efficacy while minimizing adverse effects on both mother and baby remains a critical focus in obstetric research, encompassing considerations such as optimal administration techniques, drug selection, and the potential benefits of incorporating adjuncts to local anesthetics. The overarching objective is to enhance maternal well-being and refine labor pain management. However, relying solely on a single medication approach often falls short of achieving the desired analgesic outcomes. Presently, a common practice in epidural labor analgesia involves combining local anesthetics with analgesics to alleviate maternal discomfort. While opioid agonists are frequently utilized for this purpose, numerous studies have highlighted their propensity for adverse reactions that may hinder the labor and delivery process, manifesting as side effects like nausea, vomiting, and pruritus. Butorphanol, a synthetic potent opioid analgesic, acts through κ opioid receptors to induce spinal nerve analgesia and sedation, boasting an extended half-life. Consequently, butorphanol demonstrates robust analgesic properties with prolonged duration of action. Importantly, the drug exhibits lower respiratory depression risks compared to simple μ receptor agonists. Therefore, it is paramount to investigate the effectiveness and safety profile of butorphanol as a pharmacological adjunct in epidural labor analgesia.

CURRENT SITUATION OF LABOR ANALGESIA

Every childbirth is accompanied by the mother’s experience of pain, which can induce feelings of anxiety and nervousness, leading to reduced appetite and weakened uterine contractions, subsequently prolonging the delivery process. The physical and psychological stress caused by labor pain can further intensify maternal distress and potentially result in fetal distress[1]. In recent years, healthcare professionals have endeavored to mitigate or eliminate this pain through advancements in perinatal medicine, gradually integrating painless delivery techniques into clinical practice to alleviate or eradicate the discomfort associated with childbirth. Labor analgesia approaches encompass both non-pharmacological and pharmacological interventions.

Non-pharmacological interventions, such as guided labor, water immersion, acupuncture, and acupressure, aim to help women manage labor pain without invasive measures[1-3]. While these methods appear to offer a safer alternative to pharmacological approaches, the evidence supporting their efficacy is limited and outcomes vary. Consequently, pharmacological management remains the primary choice for labor analgesia[4]. Each pharmacological modality presents distinct analgesic effects and potential adverse reactions. For instance, inhalation anesthesia may alleviate labor pain but often induces nausea and vomiting, causing discomfort for the mother[5]. Local anesthesia, with its inconsistent pain relief efficacy, is now less commonly utilized in clinical settings. Intravenous anesthesia poses challenges due to its significant respiratory and circulatory depressant effects[6].

Epidural anesthesia, a widely employed method in labor analgesia, stands out as a safe and effective intervention with minimal impact on both the mother and baby, offering a light motor block and blocks the nerve conduction of nociception, reduces the maternal stress response to pain without affecting hypothalamic gonadotropin secretion. Females using epidural analgesia have lower pain intensity and need for additional pain relief compared to intravenous infusions of opioid analgesics[7]. There is currently a great deal of concern among obstetricians regarding the adverse effects of epidural analgesia, particularly whether this technique affects the progression of labor or the rate of cesarean delivery. In response, two clinical studies have noted that women who received epidural analgesia rather than systemic opioids had a 90-minute reduction in the duration of the first stage of labor, with no negative effects on the fetus or neonate[8,9]. Recent guidelines suggest that maternal analgesic needs are a sufficient medical indication for epidural labor analgesia in the absence of medical contraindications. What the physician needs to do is to decide on the type of medication and the dosage to be used based on the mother’s physical condition and comorbidities, to maximize the relief of pain and to ensure the safety of the mother and the baby.

Studies have demonstrated that combining epidural local anesthetics with varying opioid dosages and concentrations can enhance the speed and duration of analgesia[10]. Adjuvant opioids can synergize with local anesthetics, reducing the minimum local analgesic concentration and overall dosage while maintaining analgesic efficacy[11]. Opioids, known for their potent and prolonged analgesic effects, when used in combination with local anesthetics, provide benefits such as rapid onset, sustained analgesia, and reduced adverse reactions. However, it is essential to note potential fetal and neonatal risks associated with opioid use in obstetric patients, including respiratory depression, neonatal reflex suppression, fetal heart rate changes, and potential impacts on Apgar scores[12].

In comparison to other opioids, butorphanol, a novel opioid receptor agonist-antagonist, has been observed to exhibit a lower incidence of respiratory depression at equivalent analgesic doses[13], highlighting its potential as a promising alternative in labor analgesia management.

BUTORPHANOL: EFFICACY AND COMPLICATIONS BLANCE

Butorphanol, a synthetic opioid analgesic, exhibits potent analgesic effects approximately six times greater than morphine[14]. Its primary mechanism of action involves stimulating the κ receptor to induce analgesia within the spinal cord, while also partially stimulating the δ receptor, thereby demonstrating dual functions of excitation and antagonism to the μ receptor. Additionally, when co-administered with μ-receptor agonists, butorphanol can exert μ-receptor antagonism, effectively reducing or counteracting side effects such as respiratory depression. Widely used to alleviate moderate to severe pain, butorphanol is valued for its rapid onset, sustained analgesic effect, low addiction potential, and relatively few side effects, particularly respiratory depression[15].

In recent years, butorphanol has garnered increased attention and application, finding use in painless diagnosis and treatment, surgical analgesia, labor analgesia, and acute pain management. Studies have revealed that preoperative administration of butorphanol via nasal drops or intravenous injection significantly reduces the required dose of sufentanil during surgery, while also diminishing postoperative pain levels and adverse effects, including postoperative cognitive dysfunction in elderly patients[16]. Similarly, its application in painless gastrointestinal endoscopy confers clear benefits due to its mild impact on the respiratory and circulatory systems, coupled with its effectiveness in relieving the stress response associated with mechanical traction. Research by Wang et al[17] indicates that adding butorphanol to propofol reduced the incidence of post-procedural visceral pain in patients undergoing gastroscopy and colonoscopy without significant respiratory depression and hemodynamic instability. These findings suggest that, compared to traditional opioids, the use of butorphanol in painless diagnosis and treatment results in fewer adverse events and increased patient comfort.

As an opioid receptor agonist-antagonist, butorphanol plays a pivotal role in alleviating drug injection discomfort, intraoperative and postoperative pain, and can also reduce the release of neurotransmitters and pain mediators, thereby achieving analgesic effects. Furthermore, butorphanol is considered safer for use during labor compared to other opioid agonists and has minimal impact on the Apgar score of newborns, making it a widely utilized option for postoperative analgesia in parturients[15]. Due to its effectiveness in relieving visceral pain, butorphanol can reduce the incidence of adverse drug reactions compared to other opioid agonists, consequently gaining favor as an adjuvant to epidural analgesia in labor management regimens[13].

BUTORPHANOL AS AN ADJUVANT IN EPIDURAL ANALGESIA

The pathophysiological mechanism of uterine spasmodic pain during delivery differs from incision pain, primarily stemming from visceral pain. Hence, the selection of labor analgesia treatment schemes should be tailored accordingly. To minimize the impact on both the parturient and fetus, the goal is to administer the lowest concentration and dosage within a specified timeframe, ensuring a smooth labor process while maintaining painless conditions. Butorphanol, known for its robust visceral pain-relieving properties, acts as a κ receptor agonist that can mitigate the intense cervical irritation arising from uterine dilation, making it a promising candidate for effective pain relief during labor. In a study by Cai et al[18] investigating the optimization of analgesic regimens for postoperative uterine pain in women undergoing repeat cesarean sections, the combination of tramadol and butorphanol in patients utilizing self-controlled intravenous analgesia postoperatively yielded substantial reductions in mean visual analog scale (VAS) scores for uterine spasmodic pain compared to sufentanil. This combination also demonstrated superior analgesic efficacy at rest, as well as at 6 hours and 12 hours postoperatively[18].

Nevertheless, there is a lack of sufficient studies confirming the safety and efficacy of using butorphanol as a pharmacological adjuvant in epidural labor analgesia. Current research indicates that safety evaluation parameters encompass the Apgar score post-delivery, maternal adverse reactions to drugs, and the incidence of unplanned cesarean sections. Effectiveness evaluation criteria include the duration of each labor stage and the mother’s VAS score. Incorporating butorphanol alongside local anesthetics effectively alleviates parturients’ pain across all labor stages, shortens the first stage of labor, and does not elevate unintended adverse effects.

Notably, there is a dearth of established standards for the appropriate dosage of this analgesic regimen, and the impact of varying doses of butorphanol on maternal labor remains unclear. Some researchers advocate for low doses of both ropivacaine and butorphanol, which not only reduce the incidence of instrumental delivery and labor complications in women receiving epidural analgesia but also provide high-quality pain relief[19]. Conversely, certain studies suggest no discernible difference in the effectiveness and safety of butorphanol compared to other opioid analgesics in epidural analgesia. Therefore, further validation through rigorous randomized controlled trials is imperative to explore the effects of different butorphanol doses during labor and delivery. Adjusting the balance between local anesthetics and butorphanol to identify a safe dosage with optimal analgesic efficacy and minimal adverse effects is crucial for refining this protocol.

EDITORIAL COMMENTS

This editorial also serves to comment on the article by Tang et al[20] published in the World J Clin Case. The authors delve into the crucial question of whether butorphanol is a safe and effective option for epidural labor analgesia. By examining data from prominent databases such as PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, and Google Scholar, Tang et al[20] conducted a comparative analysis of randomized controlled trials involving butorphanol and other opioids combined with local anesthetics for epidural labor pain management. With a study cohort of 1311 patients, the authors decisively addressed this inquiry through a meticulous meta-analysis.

While epidural analgesia plays a vital role in pain management during labor globally, recent guidelines underscore its association with adverse outcomes like prolonged labor and increased likelihood of surgical delivery[21,22]. Hence, refining the administration of epidural analgesia holds promise for improved outcomes. Butorphanol, targeting κ receptors implicated in visceral pain regulation, has gained traction as an effective remedy for labor pain in recent years[15,23]. However, the definitive safety and efficacy profile of butorphanol for epidural analgesia remains elusive. Meta-analyses are increasingly pivotal in medical literature, with researchers recognizing their significance in advancing clinical interventions. In this context, Tang et al[20] offer evidence-based insights through their meta-analysis on the safety and efficacy of butorphanol as an epidural analgesic during labor.

In summary, the authors employed a robust methodology, including rigorous criteria for inclusion and exclusion, resulting in credible information on the safety and efficacy of butorphanol as an epidural analgesic for labor, positioning epidural butorphanol as a commendable analgesic choice for laboring patients.

CONCLUSION

Labor pain can have detrimental effects on both the fetus and the mother, potentially leading to maternal-fetal physiological imbalances and fetal distress in severe cases. Epidural analgesia stands out as the most efficacious method for managing labor pain. However, several critical considerations warrant attention, including determining the optimal epidural medication regimen for effective analgesia, understanding the differential impact of various dosing strategies on mothers and infants, and tailoring the dosing regimen to specific populations. Future clinical studies are imperative to address these outstanding issues comprehensively. Paramount to all is ensuring the safety of both mother and baby, as well as enhancing the mother’s overall delivery experience. Combined with current evidence, low-dose bupropion in epidural labor analgesia has better analgesic effects while ensuring safety for mothers and infants. However, more clinical trials are needed to further define the optimal dose of bupropion for epidural labor analgesia. It is essential to advocate for an optimal epidural analgesia administration plan, enhance the quality of labor analgesia through a multidisciplinary integrated treatment approach, reduce the incidence of unplanned cesarean sections, minimize unnecessary interventions during labor, and uphold the well-being of mothers and infants.