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ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 2  |  Page : 197-202  

Comparative evaluation of intrathecal dexmedetomidine and fentanyl as an adjuvant for combined spinal–epidural analgesia for labor


1 Department of Anaesthesiology, Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India
2 Department of Obstetrics and Gynecology, Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India

Date of Submission20-Apr-2022
Date of Decision06-Jul-2022
Date of Acceptance11-Jul-2022
Date of Web Publication19-Aug-2022

Correspondence Address:
Dr. Akash Deep
80PG Boys Hostel, Maharani Laxmi Bai Medical College Campus, Jhansi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.aer_73_22

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   Abstract 

Background: Combined spinal–epidural technique is a widely accepted and popular modality for labor analgesia. Opioids are being used as adjuvants since long time. Dexmedetomidine is a new drug that is being used as an intrathecal adjuvant. Aim: The study aims to compare the safety and efficacy of fentanyl and dexmedetomidine as intrathecal adjuvants in labor analgesia. Settings and Design: This was a continuous, prospective, randomized controlled trial with 120 parturients. Materials and Methods: After ethical approval and written consent, participants were divided randomly into two groups: Group A – bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + 20 μg of dexmedetomidine in 1 mL saline intrathecally (total volume: 3 mL) and Group B – bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + 15 μg of fentanyl in 1 mL saline intrathecally (total volume: 3 mL). Primary outcomes were satisfactory analgesia, mode of delivery, and neonatal outcome. Participants were monitored for the onset and duration of analgesia, degree of motor block, and maternal and fetal side effects. Results: A total of 108 parturients reported sufficient analgesia (Group A: 57; Group B: 51), and 74 patients delivered vaginally (Group A: 41; Group B: 44). The rates of normal vaginal delivery were higher in Group B. Group A reported earlier onset of analgesia (61.26 ± 18.23 s) that lasted for longer duration (124.16 ± 26.23 min) than in Group B. There were no serious side effects in any of the groups. Fetal ultrasound revealed attenuation of fetal heart rate variability. The heart rate of newborns was also found to be low in Group A. Conclusion: Chances of vaginal delivery are higher with intrathecal fentanyl as an adjuvant. Intensity and duration of analgesia are better with intrathecal dexmedetomidine.

Keywords: Dexmedetomidine, fentanyl, labor analgesia


How to cite this article:
Jain A, Mittal A, Sharma S, Deep A. Comparative evaluation of intrathecal dexmedetomidine and fentanyl as an adjuvant for combined spinal–epidural analgesia for labor. Anesth Essays Res 2022;16:197-202

How to cite this URL:
Jain A, Mittal A, Sharma S, Deep A. Comparative evaluation of intrathecal dexmedetomidine and fentanyl as an adjuvant for combined spinal–epidural analgesia for labor. Anesth Essays Res [serial online] 2022 [cited 2022 Dec 5];16:197-202. Available from: https://www.aeronline.org/text.asp?2022/16/2/197/354094


   Introduction Top


Labor is one of the most painful physiological conditions experienced by women in their lives. Labor pain ranks second or third among all painful conditions and consistently scores more than 7 on a 10-point scale.[1],[2] Since the medieval era, clinicians have been adopting methods to reduce the intensity of labor pain. The modern era of labor analgesia began with the “etherization of labor” by James Young Simpson, who successfully administered labor analgesia to a woman with a deformed pelvis.[3] At that time, the concept of labor analgesia was strongly condemned. Later, in 1853, John Snow delivered Britain's Queen Victoria by administering chloroform for labor analgesia.[4] In the 20th century, labor analgesia gained popularity, and by the 21st century, it has become an integral part of pain practice. Labor analgesia is beneficial for both the mother and the fetus. The duration of hospital stay and the levels of inflammatory markers were far lower in pregnant women who received labor analgesia than in those who did not.[5]

Since the beginning of the 21st century, regional analgesia has become the most widely used technique for labor pain globally. Epidural and spinal analgesia are the most common modalities used for labor analgesia. The intrathecal route provides instant analgesia; however, its duration is a limiting factor. In contrast, epidural analgesia takes at least 15 min to provide pain relief; however, using an indwelling epidural catheter can easily prolong its duration. With the limitations of both modalities considered, many dedicated centers are now combining spinal and epidural analgesia to provide early and prolonged pain relief. This combination is commonly known as walking epidural analgesia.[6],[7] With a reduced concentration of local anesthetic, this technique preserves sufficient motor function and allows patients to ambulate.

Ambulatory labor analgesia provides several advantages, such as less maternal exhaustion, reduced chances of instrumental deliveries, rare need for urinary catheterization, fewer impacts on maternal hemodynamics, better maternal satisfaction, and reduced workload for hospital staff.[6],[8],[9]

Ropivacaine and bupivacaine are commonly used local anesthetic drugs for walking epidural analgesia.[8] To reduce the chances of motor block, the concentration of local anesthetics is reduced through an intrathecal block, with adjuvants added. Adjuvants effectively supplement the sensory blockade and accelerate its onset. Opioids are the most common intrathecal adjuvants. Among various opioids, fentanyl is the preferred adjuvant because of its fewer side effects and intermediate duration of action.[9] Fentanyl has been used extensively in labor analgesia to potentiate the sensory block; however, fentanyl crosses the placenta and has side effects such as pruritus.[10]

Dexmedetomidine is a highly selective alpha-2 adrenergic agonist that has intrinsic analgesic properties and has been used intrathecally to prolong postoperative analgesia.[11],[12] The placental transfer is minimal; therefore, little or no effect on the fetus should be observed. Dexmedetomidine modulates the release of catecholamines and therefore has the advantage of controlling blood pressure. However, in some cases, dexmedetomidine causes bradycardia and hypotension in the mother, which could be deleterious.[13]

The present study aimed to compare the efficacy of intrathecal fentanyl and dexmedetomidine as adjuvants to low-dose bupivacaine. Here, we analyzed and compared the onset and duration of sensory block, quality of analgesia during labor, labor progression, and maternal and fetal side effects of these adjuvant drugs.


   Materials and Methods Top


Study design and subjects

The current study was undertaken as a continuous, prospective, double-blind, randomized control trial after approval from the institute ethics committee (reference number of approval: 329/IEC/I/2021). Informed and written consent was obtained from all participants regarding their participation in the study and subsequent data use for the current research work. All experimental protocols and procedures were approved by the institute ethics committee and followed the guidelines laid down in the Declaration of Helsinki (2018). Participants were 120 full-term pregnant females who were admitted to the obstetric department for safe confinement. The site of the study was dedicated labor room of the obstetrics department of a tertiary care teaching hospital. Labor room is equipped with multipara monitor, ultrasound, anesthesia work station, and resuscitation equipment. The study commenced in August 2021, and the last participant was enrolled on February 24, 2022.

The inclusion criteria were as follows:

  1. Prebooked patients who had given consent for labor analgesia
  2. Age: 20–40 years
  3. Body mass index <35 kg.m−2
  4. American Society of Anesthesiology Classification Status I or II.


The exclusion criteria were as follows:

  1. Any condition that contraindicates administration of central neuraxial blockade (such as coagulopathy or hypovolemic shock)
  2. Gestational age <36 weeks
  3. Obstetric complications such as preeclampsia, pregnancy-induced hypertension, gestational diabetes, or cephalopelvic disproportion
  4. Patients in the second stage of labor or on oxytocin infusion.


Sample size

The sample size for the current study was calculated using power analysis. The power of the study was set to 0.9, and the two-sided type I error was set at 0.05. The exact sample size was 98, which was arbitrarily increased to 120.

Intervention and evaluation

All participants who met the inclusion criteria were randomized into two groups (A and B) using computer-generated randomization. Under aseptic precautions, labor analgesia was administered through a combined spinal–epidural technique using an 18G Tuohy needle and a 27G spinal needle (Portex® CSEcure Combined Spinal Epidural Needle manufactured by Smith India Pvt. Ltd.) in the left lateral position. The drugs and volumes administered were as follows:

  1. Group A: Bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + 20 μg dexmedetomidine in 1 mL saline intrathecally (total volume: 3 mL)
  2. Group B: Bupivacaine 2.5 mg (0.5 mL diluted to 2 mL) + fentanyl (15 μg) in 1 mL saline intrathecally (total volume: 3 mL).


The syringes were masked, and the drug administration and subsequent patient monitoring were performed by the medical team who does not know about the composition. In both groups, epidural top-up was administered through the catheter upon the patient request. The drug used was 0.125% bupivacaine. Whenever the Visual Analog Scale (VAS) score reached 3, 5 mL was administered per request.

Outcome and adverse effects

Primary outcomes were satisfactory analgesia, mode of delivery, and neonatal outcome. The effectiveness of labor analgesia was assessed using the VAS for a subjective rating of pain. Motor block was tested using the modified Bromage score as suggested by Breen et al.[6]

Criteria

  1. Complete block (unable to move feet or knees)
  2. Almost complete block (able to move feet only)
  3. Partial block (just able to move knees)
  4. Detectable weakness of hip flexion while supine (full flexion of knees)
  5. No detectable weakness of hip flexion while supine
  6. Able to perform partial knee bend.


The success of labor analgesia was defined as a reduction in the VAS score to 2 or less. The number of parturients who did not achieve a VAS score <3 by 20 min qualified as a failure and they were administered epidural top-up. The time of block onset was defined as the period between the administration of labor analgesia and the time when the VAS score dropped below 3 during active uterine contraction.

The duration of analgesia was calculated as the time elapsed from the onset of the block to the first epidural top-up on the patients' demand, from intrathecal injection to when the VAS was again recorded more than 3. The first top-up of 10 mL of 0.125% bupivacaine was administered at this point. Repeat top-ups of the same dosage were administered as and when necessary to keep the VAS score <3 until delivery.

All maternal side effects, such as hypotension, bradycardia, pruritus, nausea, and vomiting, were noted. The mother and newborns were followed up for 6 weeks postdelivery to evaluate any delayed adverse effects in the mother or fetus.

Progression of labor

Successful outcome was defined by successful normal vaginal delivery within 9 h.

Monitoring

The hemodynamic status of the parturients was continuously monitored through pulse oximetry and noninvasive blood pressure monitoring every 5 min. Hypotension was defined as a >20% reduction in blood pressure, and bradycardia was defined as a heart rate of <60 bpm. Injection of ephedrine (4 mg intravenous [i.v.]) was used to treat maternal hypotension. Fetal heart rate was continuously monitored using a cardiotocograph. Fetal activity and uterine blood flow were monitored using repeated ultrasound at intervals of 10 min for the initial 1 h and every 30 min thereafter. Neonatal outcome was assessed by APGAR score at the 1 min and 5 min after delivery.[14] The intubation requirement and overall outcome of neonate at 28 days were quantified separately.

Statistical analysis

In the current study, the quantitative variables are expressed as range and mean ± standard deviation. The qualitative variables are expressed as proportions, and the range varies for continuous data. Student's t-test and Chi-square test were used to compare the quantitative categorical variables. An analysis of variance test was used to compare continuous variables. Statistical calculations were performed using SPSS for Windows (version 22; IBM SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.


   Results Top


The study was undertaken between August 2021 and February 2022. A total of 152 parturients fulfilled the inclusion criteria, of whom 131 patients provided consent and were subsequently enrolled in the study after applying the inclusion criteria. Eleven patients were excluded based on the exclusion criteria. After reaching the preselected sample size of 120 patients, the enrolment was stopped, as shown in the CONSORT flow diagram [Figure 1]. The demographic and baseline variables are shown in [Table 1] and were statistically similar.
Figure 1: CONSORT flow diagram

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Table 1: Demographic and baseline parameters among participants

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A total of 111 patients reported sufficient analgesia (Group A: 57; Group B: 54), and 74 patients delivered vaginally (Group A: 41; Group B: 44), indicating an overall success rate of 61.66%; however, the success rate was significantly higher in Group B [Table 2]. The rates of forceps-assisted vaginal delivery and cesarean delivery were higher in Group A.
Table 2: Mode of delivery among participants

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The analysis of the quality of the block revealed an earlier onset of analgesia in Group A than in Group B. The differences were statistically significant. The duration of analgesia was also higher in Group A. The analysis of motor block reveals a higher degree of motor block in Group A than that in Group B [Table 3]. Monitoring VAS score during contractions reports a higher VAS score in Group B than in Group A [Figure 2].
Figure 2: VAS among the two groups. VAS = Visual Analog Scale

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Table 3: Quality of block among the participants

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Both methods were found to be safe with no serious side effects. The analysis of adverse effects revealed that pruritus was the most common side effect (however, it was seen only in Group B), followed by hypotension, bradycardia, shivering, and nausea [Table 4]. Fetal ultrasound and Doppler analysis revealed no differences in the umbilical artery and uterine blood flow. However, there was attenuation in heart rate variability with reduced pulsatility index in Group A. The analysis of fetal parameters also proved that both techniques were safe, and in both groups, all newborns were found to be safe and healthy after 6 weeks of delivery. The immediate response after delivery, however, revealed a slightly reduced APGAR score at 1 min in Group A, and the heart rate of newborns was also found to be low in Group A. The first cry was delayed in 37.5% of newborns in Group A and 35.2% of newborns in Group B.
Table 4: Incidence of maternal and fetal side effects in both the groups

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   Discussion Top


Effective labor pain relief prevents maternal exhaustion and enhances cooperation in the mother, making labor a tolerable and pleasant experience. Combined spinal–epidural analgesia has emerged as the methodology of choice for labor analgesia.[6],[15],[16] Also called walking epidural analgesia, combined spinal and epidural analgesia grants the advantage of early onset and prolonged duration of action; moreover, if the conditions demand, the block can also be intensified for cesarean delivery.[8] However, for labor analgesia, the intensity of the block needs to be balanced to avoid any motor block, which acts as a limiting factor for successful normal vaginal delivery. In clinical practice, adjuvants have been used in spinal anesthesia for a long time and are now gaining popularity in labor spinal analgesia.[17]

Opioids have long been used as adjuvants. μ-agonist opioids, such as morphine, tramadol, fentanyl, and sufentanil, are commonly injected with hyperbaric bupivacaine as an adjuvant. In labor analgesia/anesthesia, whether epidural or intrathecal, fentanyl is the most common adjuvant.[9] Wong et al. investigated the efficacy of various doses of fentanyl as an adjuvant for labor spinal analgesia; they concluded that 15 μg was a safe and effective dose of fentanyl. This forms the basis of using a 15 μg dose of fentanyl in the current study.[18],[19]

The α2 agonist is another class that has gained popularity as adjuvant therapy. Among the two commonly used α2 agonists, dexmedetomidine is preferred over clonidine as an adjuvant. Several studies have used variable doses of dexmedetomidine i.v. and epidurally in labor without any adverse effects on the mother or fetus.[20],[21] Ezz Gehan et al. used 20 μg dexmedetomidine intrathecally, which formed the basis of the dexmedetomidine dose in this study.[20]

In the current study, the authors found a better success rate with fentanyl; however, maternal analgesia was better with dexmedetomidine. The probable reason for this is a higher degree of motor blockade and enhanced alteration in fetal heart rate compared with fentanyl. This result corresponds with that of Li et al., who also reported a higher cesarean section rate with dexmedetomidine.[21]

As regards hemodynamic parameters, the authors observed a significant decrease in heart rate compared to baseline values in both groups, with more significant decreases in heart rate and an increased need for atropine in patients receiving intrathecal dexmedetomidine than in patients receiving intrathecal fentanyl. In addition, the incidence of fetal bradycardia was higher with dexmedetomidine administration. The findings of the current study correspond to those of Gupta et al., who compared dexmedetomidine with buprenorphine as an adjuvant.[22]

According to the published literature, this is the first study to evaluate fetal movement and fetal umbilical blood flow using ultrasound with Doppler. The results showed that dexmedetomidine reduced fetal movements, which can be explained by its sedative action even at low doses. This reduced fetal movement could have contributed to the reduced spontaneous delivery rate in the patients who received dexmedetomidine. This finding has been consistently reported in several studies. Although dexmedetomidine does not affect uterine or umbilical blood flow, it was found to attenuate the increase in fetal heart rate secondary to fetal movements, which can also be explained by the pharmacodynamics of α2 agonists.[23],[24] This reduced heart rate variability makes monitoring difficult and contributes to increased cesarean section rates with dexmedetomidine.

Intrathecal fentanyl was associated with the side effects of pruritus and nausea in the current study, and several previous studies have reported these side effects with intrathecal fentanyl.[19],[25] If these minor side effects that were not found to be bothersome for the patient are weighed against the significantly increased cesarean section rate with dexmedetomidine, the former should be selected as an adjuvant for labor analgesia owing to its safety and effectiveness.

The authors performed the current study in a prospective manner, elimination selection bias by randomization, and ensured blinding by masking the syringe for the administration of the intrathecal drug. However, the current study is not free of limitations; the main limitations of the current study are as follows:

  1. The study was performed in a single center
  2. The study group included healthy parturients, and the study findings may not reciprocate in parturients with some or other diseases
  3. Two drugs were only used.


The authors suggest performing a multicenter prospective study in future using other adjuvants to find out best-suited intrathecal adjuvant for labor analgesia.


   Conclusion Top


Walking epidural using intrathecal adjuvant is a safe and effective method for labor analgesia. Intensity and duration of block are higher with intrathecal dexmedetomidine. Normal vaginal delivery chances are higher with fentanyl. Fentanyl should be preferred over dexmedetomidine as an intrathecal adjuvant for labor analgesia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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