What is the evidence for administering dexmedetomidine in the epidural space for laboring patients?

Comment by InpharmD Researcher

Evidence from randomized trials and multiple systematic reviews indicates that dexmedetomidine, when administered via the epidural space as an adjuvant to local anesthetics for labor analgesia, improves pain control by reducing pain scores, prolonging the duration of analgesia, accelerating onset, and decreasing local anesthetic requirements. Maternal and neonatal safety outcomes are generally comparable to placebo or neuraxial opioids, with no consistent adverse effects on Apgar scores, umbilical cord pH, labor duration, or mode of delivery. Compared with opioids, epidural dexmedetomidine is associated with lower rates of pruritus and nausea/vomiting but a higher incidence of maternal bradycardia and, at higher concentrations, mild motor block or lower-limb weakness. The overall evidence supports epidural dexmedetomidine as an effective opioid-sparing adjuvant for labor analgesia, with careful dose selection needed to balance analgesic benefits against maternal hemodynamic and motor effects.

Dexmedetomidine epidural labor delivery obgyn pregnancy

Background

A 2024 systematic review and meta-analysis evaluated the efficacy and safety of dexmedetomidine used in epidural labor analgesia. This analysis incorporated data from eight randomized controlled trials, comprising a total of 846 participants. The primary aim was to assess the impact of dexmedetomidine on the visual analog scale (VAS) for pain within two hours following epidural initiation. Secondary outcomes examined included the duration of labor stages, Apgar scores, umbilical blood pH, analgesic consumption, and potential adverse reactions such as pruritus, nausea, vomiting, and maternal bradycardia. The findings from the meta-analysis demonstrated that the use of dexmedetomidine significantly improved VAS scores at multiple time points, specifically at 15, 30, 60, and 90 minutes post-epidural initiation. While the intervention showed a reduction in the incidence of pruritus compared to controls, there was an increased occurrence of maternal bradycardia associated with dexmedetomidine use. Notably, there were no significant differences observed in other measured outcomes, including Apgar scores and umbilical blood pH, suggesting that dexmedetomidine is a safe adjuvant in epidural labor analgesia for both the mother and fetus, with the exception of the noted increase in bradycardia. Data suggests that the intrathecal injection of either ropivacaine or bupivacaine, when combined with dexmedetomidine, has the potential to extend the duration of sensory block. Additionally, this combination was found to prolong the interval before the need for the first analgesic drug supplement. This finding suggests an effective strategy in prolonging pain relief in clinical settings where intrathecal anesthetics are used. [1]

A 2021 meta-analysis examined the analgesic effects and safety of epidural dexmedetomidine when used as an adjuvant to local anesthetics for labor analgesia. This comprehensive analysis synthesized data from nine randomized controlled trials encompassing 1,403 patients, predominantly conducted in China, with one study from Egypt. The selected trials compared epidural administration of dexmedetomidine with either placebo or opioids in parturients undergoing labor analgesia. The trials assessed a range of outcomes, including pain relief as measured by the VAS, mean arterial pressure (MAP), heart rate (HR), blood loss, and the incidence of nausea/vomiting, among others. The meta-analysis revealed that dexmedetomidine, compared to placebo, significantly relieved labor pain at various time points after the epidural block, including 15 minutes and 30 minutes post-block, as well as during fetal disengagement. However, heterogeneity was observed among the included studies for some outcomes. Additionally, compared to opioids, dexmedetomidine demonstrated a similar analgesic effect but was associated with a decreased incidence of nausea/vomiting and an increase in maternal bradycardia, with sensitivity analysis consistently confirming the reduction in nausea/vomiting across studies. Importantly, dexmedetomidine did not adversely affect maternal hemodynamic stability or neonatal outcomes, such as Apgar scores and umbilical artery parameters, indicating its potential as a safe alternative to opioids for epidural labor analgesia. Further high-quality studies were recommended to strengthen these findings. [2]

A 2023 systematic review and meta-analysis evaluated the efficacy and safety of neuraxial dexmedetomidine compared to neuraxial opioids for labor analgesia. This review synthesized findings from sixteen randomized controlled trials, encompassing 1,669 participants. Nine randomized controlled trials administered dexmedetomidine intrathecally, while seven studies administered dexmedetomidine via the epidural space. The local anesthetics used were either ropivacaine or bupivacaine with varying concentrations and doses. Findings from the review indicated that neuraxial dexmedetomidine significantly prolonged the duration of analgesia by an average of 47.58 minutes compared to opioids, with a reduction in pain scores and faster analgesic onset. Dexmedetomidine also demonstrated a lower incidence of pruritus and postoperative nausea and vomiting, without influencing the duration of the first and second stages of labor or modes of delivery. The study observed no significant difference in maternal or neonatal outcomes such as APGAR scores, although umbilical cord pH was marginally higher in the dexmedetomidine group. Despite these findings, the review highlighted some limitations, including high risk of bias, substantial heterogeneity, and varying definitions of analgesic duration across studies. These factors necessitate cautious interpretation before clinical application. [3]

Across two prospective randomized studies, epidural dexmedetomidine was evaluated as an adjuvant to ropivacaine for labor analgesia, with both investigations supporting its analgesic efficacy and generally favorable safety profile. A 2017 single-center, single-blinded trial (n=100) examined fixed concentrations of dexmedetomidine (0.25–1 µg/mL) combined with 0.1% ropivacaine and found that concentrations between 0.25 and 0.75 µg/mL provided effective analgesia with stable hemodynamics and neonatal outcomes, while 1 µg/mL was associated with a higher incidence of motor block. Building on this, a 2022 prospective dose-finding trial (n=120) using lower dexmedetomidine concentrations (0–0.5 µg/mL) with 0.075% ropivacaine quantified the dose–response relationship, estimating a median effective dose (ED50) of 0.085 µg/mL and an the 95% effective dose (ED95) of 0.357 µg/mL for achieving effective analgesia, without significant differences in sensory block level, motor block, cesarean delivery rate, or Apgar scores across groups; however, prolongation of the first stage of labor was observed at 0.5 µg/mL. Collectively, these studies suggest that low-to-moderate concentrations of epidural dexmedetomidine can enhance labor analgesia when combined with ropivacaine, while higher concentrations may increase the risk of motor block or labor prolongation, highlighting the importance of dose optimization. [4], [5]

References: [1] Zhang D, Sun Y, Li J. Application of Dexmedetomidine in Epidural Labor Analgesia: A Systematic Review and Meta-Analysis on Randomized Controlled Trials. Clin J Pain. 2024;40(1):57-65. Published 2024 Jan 1. doi:10.1097/AJP.0000000000001166
[2] Li N, Hu L, Li C, Pan X, Tang Y. Effect of Epidural Dexmedetomidine as an Adjuvant to Local Anesthetics for Labor Analgesia: A Meta-Analysis of Randomized Controlled Trials. Evid Based Complement Alternat Med. 2021;2021:4886970. Published 2021 Oct 27. doi:10.1155/2021/4886970
[3] Cedeno E, Vo MAJL, Tubog TD. Dexmedetomidine versus Opioids on Labor Analgesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AANA J. 2023;91(6):437-445.
[4] Wangping Z, Ming R. Optimal Dose of Epidural Dexmedetomidine Added to Ropivacaine for Epidural Labor Analgesia: A Pilot Study. Evid Based Complement Alternat Med. 2017;2017:7924148. doi:10.1155/2017/7924148
[5] Ni JX, Feng JL, Yao SJ, et al. Determination of the Dose-Response Relationship of Epidural Dexmedetomidine Combined with Ropivacaine for Labor Analgesia. Drug Des Devel Ther. 2022;16:609-618. Published 2022 Mar 6. doi:10.2147/DDDT.S346842
Relevant Prescribing Information

PRECEDEX (dexmedetomidine hydrochloride) in 0.9% Sodium Chloride Injection (4 mcg/mL) is a sterile, nonpyrogenic ready to use solution suitable for intravenous infusion. [6]

References: [6] PRECEDEX (dexmedetomidine hydrochloride injection). Prescribing information. Hospira, Inc.; 2025
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What is the evidence for administering dexmedetomidine in the epidural space for laboring patients?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-5 for your response.


Comparison of epidural dexmedetomidine to fentanyl in reducing ropivacaine dose in Programmed Intermittent Epidural Bolus plus Patient Controlled Epidural Analgesia during labor: A randomized, double-blind, controlled study
Design

Randomized, double-blind, controlled study

N= 165

Objective To evaluate the efficacy of epidural dexmedetomidine at doses of 0.3, 0.4, or 0.5 µg/ml compared to fentanyl at 2 µg/ml as adjuvants to epidural 0.125% ropivacaine in reducing the mean hourly dose requirement of ropivacaine during labor
Study Groups

Fentanyl 2 µg/ml (n= 40)

Dexmedetomidine 0.3 µg/ml (n= 39)

Dexmedetomidine 0.4 µg/ml (n= 45)

Dexmedetomidine 0.5 µg/ml (n= 41)

Inclusion Criteria Nulliparous parturients with healthy singleton pregnancies, gestational age ≥37 weeks, ASA Physical Status II, spontaneous onset of labor, latent phase of labor with cervical dilation of 2–5 cm, and painful contractions requiring labor epidural analgesia
Exclusion Criteria Patients with preeclampsia or hypertension, preexisting or gestational diabetes, BMI > 35 kg/m2, contraindications to local anesthetics, dexmedetomidine, and fentanyl
Methods Patients were randomized to receive either 2 µg/ml fentanyl or 0.3, 0.4, or 0.5 µg/ml dexmedetomidine as adjuvants to 0.125% ropivacaine.
Duration Not specified
Outcome Measures Mean hourly amount of ropivacaine administered, frequency of patient-controlled epidural analgesia (PCEA)
Baseline Characteristics   Fentanyl 2 µg/ml (n = 40) Dexmedetomidine 0.3 µg/ml (n = 39)

Dexmedetomidine 0.4 µg/ml (n = 45)

Dexmedetomidine 0.5 µg/ml (n = 41)
Age, years 27.6 ± 3.7 28.3 ± 3.7 27.4 ± 3.4 28.8 ± 3.5
BMI, kg/m2 26.1 ± 3.0 27.5 ± 2.4 27.0 ± 3.2 27.2 ± 2.4
Gestational age, weeks 39.3 ± 1.1 39.3 ± 1.0 39.1 ± 1.0 39.5 ± 2.0
Cervical dilation at epidural placement, cm 2.1 ± 0.3 2.2 ± 0.4 2.2 ± 0.4 2.1 ± 0.4
Results   Fentanyl 2 µg/ml Dexmedetomidine 0.3 µg/ml Dexmedetomidine 0.4 µg/ml Dexmedetomidine 0.5 µg/ml p-value
Mean hourly ropivacaine consumption, ml/h 16.2 ± 3.3 14.0 ± 3.1 13.1 ± 3.7 12.1 ± 2.5 <0.0001
Frequency of PCEA boluses 3 (1, 3) 0 (0, 2) 0.5 (0, 2) 0 (0, 2) <0.001
Patient required PCEA 33 (82.5%) 17 (44.6%) 20 (44.4%) 9 (22.0%) 0.005
Adverse Events The incidence of pruritus in the fentanyl group was 17.5%, whereas no patient experienced pruritus in any of the dexmedetomidine groups. There was a significant difference in Bromage score among groups, with higher motor block in the 0.5 µg/ml dexmedetomidine group. 
Study Author Conclusions Epidural dexmedetomidine (0.3 and 0.4 µg/ml) was superior to standard dose epidural fentanyl in reducing the mean hourly amount of ropivacaine administered and minimizing opioid-related side effects. Further large and multicenter studies are necessary to confirm the benefits of dexmedetomidine as an alternative to opioids for routine use in labor analgesia. 
Critique The study was well-designed with a randomized, double-blind approach, providing strong evidence for the efficacy of dexmedetomidine. However, the sample size may not have been sufficient to detect differences in secondary outcomes or side effects. The study did not clarify the dose-response relationship of dexmedetomidine on epidural ropivacaine, and larger studies are needed to confirm the findings and assess the safety of dexmedetomidine as a neuraxial adjuvant. 
References:
[1] Pang RY, Shen YH, Jin XQ, et al. Comparison of epidural dexmedetomidine to fentanyl in reducing ropivacaine dose in Programmed Intermittent Epidural Bolus plus Patient Controlled Epidural Analgesia during labor: A randomized, double-blind, controlled study. Front Med (Lausanne). 2022;9:935643. Published 2022 Oct 17. doi:10.3389/fmed.2022.935643
Epidural-Related Fever and Cesarean Delivery: Comparing Ropivacaine/Dexmedetomidine and Ropivacaine/Sufentanil: A Single-Center Randomized Controlled Study in 695 Women
Design

Single-center, randomized controlled trial

N= 695

Objective To investigate the impact of two epidural analgesic combinations, ropivacaine/dexmedetomidine and ropivacaine/sufentanil, on the incidence of cesarean deliveries prompted by intrapartum hyperthermia
Study Groups

Dex group (n= 322)

Control group (C group, n= 326)

Inclusion Criteria Low-risk pregnant women with a singleton pregnancy, including primiparas and multiparas without medical or surgical comorbidities, spontaneous labor at a gestational age between 37 and 42 weeks, and willingness to receive epidural labor analgesia
Exclusion Criteria Contraindications to epidural analgesia, preterm labor (<37 weeks), severe cardiopulmonary disease, bradycardia, or pregnancy complicated by fetal growth restriction or oligohydramnios
Methods

Participants were randomized to receive 0.08% ropivacaine with either 0.5 µg/mL dexmedetomidine or 0.5 µg/mL sufentanil for labor epidural analgesia.The randomization process was safeguarded by supervision to maintain blinding among participants and healthcare providers involved in the study. Anesthesia and analgesia were administered and managed carefully to ensure that the analgesic solutions were prepared according to the randomized assignments, maintaining the study's double-blind nature. Maternal conditions such as blood pressure, ECG, and fetal heart rate were continuously monitored throughout the labor process. Body temperature was monitored every 60 minutes, and epidural-related fever was defined as a temperature ≥37.5°C.

Duration March 2024 to March 2025
Outcome Measures

Primary: Incidence of epidural-related fever

Secondary: Overall cesarean delivery rates, cesarean deliveries due to epidural-related fever, neonatal Apgar scores

Baseline Characteristics   Dex group (n=322) C group (n=326)
Age (years) 28.4±3.7 27.9±3.5
Height (cm) 162.6±5.1 162.6±5.1
Weight (kg) 75.1±10.5 74.8±11.8
Gestational age (weeks) 39.4±0.9 39.3±0.9
Multiparous [n (%)] 45 (14.0%) 37 (11.4%)
Results   Dex group (n=322) C group (n=326) P-value
Fever (temperature ≥37.5°C) 58 (18.0%) 93 (28.5%) 0.002
Cesarean section due to epidural analgesia-induced fever 3 (0.9%) 17 (5.2%) 0.02
Adverse Events No significant adverse events reported. One case of pruritus occurred in the sufentanil group.
Study Author Conclusions This study is the first to report another cause of cesarean delivery, specifically “cesarean delivery due to epidural-related fever”. In summary, epidural dexmedetomidine labor analgesia significantly reduced the epidural-related fever rate (18.0% vs 28.5%, P=0.002) and reduced the cesarean delivery rate due to epidural-related fever (0.9% vs 5.2%, P=0.020), without increasing neonatal adverse events. These findings support its use as an alternative adjuvant medication in epidural labor analgesia. 
Critique The study's strengths include its randomized controlled design and focus on a clinically relevant issue. However, limitations include its single-center nature, potential lack of generalizability, and the need for larger multicenter trials to confirm findings.
References:
[1] Che YJ, Chen D, Deng Z, Zhang W, Wu X. Epidural-Related Fever and Cesarean Delivery: Comparing Ropivacaine/Dexmedetomidine and Ropivacaine/Sufentanil: A Single-Center Randomized Controlled Study in 695 Women. Med Sci Monit. 2025;31:e948993. Published 2025 Oct 2. doi:10.12659/MSM.948993

Comparison of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia: a randomized controlled trial
Design

Randomized controlled trial

N= 80

Objective To compare the effects of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia
Study Groups

Dexmedetomidine (n= 36)

Sufentanil (n= 34)

Inclusion Criteria Nulliparous women with ASA grade I–II, aged 20–35 years, weight 55–85 kg, gestation ≥37 weeks
Exclusion Criteria History of severe cardiopulmonary disease, bradycardia, cervical dilatation >3 cm, contraindications to epidural analgesia, undergoing cesarean section or labor induction
Methods Double-blind study with two groups: one group received 0.5 µg/mL dexmedetomidine with 0.1% ropivacaine, another group received 0.5 µg/mL sufentanil with 0.1% ropivacaine. Hemodynamic parameters and pain assessed using a visual analog scale. Epidural analgesia initiated at 2 cm cervical dilation. Continuous infusion via patient-controlled-analgesia pump at 6 mL/h. Rescue bolus of 6 mL administered when VAS score ≥5. 
Duration August 2016 to December 2016
Outcome Measures PDuration of first-stage labor, analgesic effect, Ramsay Sedation Scale, total analgesic consumption, side effects
Baseline Characteristics   Dexmedetomidine (n=36) Sufentanil (n=34)
Age, years 27.3±3.6 26.7±3.1
Weight, kg 70.8±4.7 69.5±5.4
Height, cm 159.3±2.9 160.4±3.2
Gestational age, weeks 39.8±1.2 40.1±1.3
Results   Dexmedetomidine (n=36) Sufentanil (n=34) p-value
VAS after cervical dilation >3 cm Lower Higher <0.05
Duration of first stage, minutes 378.5±52.6 406.5±58.2 0.042
Ramsay Sedation Scale 2.8±0.6 2.4±0.5 0.002
Total analgesics, mL 71.5±12.2 78.1±10.5 0.021
Adverse Events No significant differences in side effects between groups. Incidence of hypotension, shivering, nausea, vomiting, hypoxemia, and bradycardia was similar. No pruritus or motor block observed in dexmedetomidine group. 
Study Author Conclusions Dexmedetomidine is superior to sufentanil in analgesic effect and duration in first-stage labor during epidural analgesia when combined with 0.1% ropivacaine. 
Critique The study demonstrated the superior analgesic effect of dexmedetomidine over sufentanil with fewer side effects. However, the study is limited by its small sample size and the fact that dexmedetomidine is not licensed for epidural use by the FDA, necessitating further research with larger samples to confirm these findings. 
References:
[1] Zhang T, Yu Y, Zhang W, Zhu J. Comparison of dexmedetomidine and sufentanil as adjuvants to local anesthetic for epidural labor analgesia: a randomized controlled trial. Drug Des Devel Ther. 2019;13:1171-1175. Published 2019 Apr 11. doi:10.2147/DDDT.S197431
Effect of different doses of epidural dexmedetomidine on reducing visceral traction reaction for cesarean section: a double-blind randomized controlled trial
Design

Double-blind, randomized, placebo-controlled trial

N= 184

Objective To evaluate the effect of different doses of epidural dexmedetomidine on reducing visceral traction reaction for cesarean section under epidural anesthesia
Study Groups

Group R (n= 46)

Group RD0.5 (n= 46)

Group RD0.75 (n= 46)

Group RD1 (n= 46)

Inclusion Criteria Nulliparas with singleton pregnancy; ASA physical status I or II; aged 18–39 years; height 150–180 cm; gestational age ≥37 weeks scheduled for cesarean section under EA
Exclusion Criteria Contraindications to epidural anesthesia, hepatic or renal insufficiency, hypertension, cardiopulmonary disease, placenta previa, intrauterine fetal distress, preoperative heart rate <50 bpm or rhythm abnormalities, allergy or intolerance to any study medications, chronic opioid use, any previous EA or lower abdominal surgery
Methods

In this study, nulliparous women undergoing anesthesia for surgery were randomly divided into four groups to receive different concentrations of ropivacaine and dexmedetomidine: Group R received 0.75% ropivacaine alone; Group RD0.5 received 0.75% ropivacaine with 0.5 µg/kg dexmedetomidine; Group RD0.75 received 0.75% ropivacaine with 0.75 µg/kg dexmedetomidine; and Group RD1 received 0.75% ropivacaine with 1 µg/kg dexmedetomidine. Each group received a total drug volume of 12 mL. The randomization was conducted via a schedule prepared by the protocol statistician, with the allocation concealed in an opaque card provided to the anesthesiologist responsible for preparing the solutions. The anesthetic procedures were carried out with participants in a right lateral decubitus position, where an epidural was administered using a Tuohy needle followed by a test dose, and subsequently, the premixed solutions were injected. Sensory block onset was targeted at T6 bilaterally within 30 minutes, with supplementary ropivacaine if needed. If further analgesia was required or in cases of visceral traction reactions beyond Grade 2, or by patient request, 5 µg sufentanil was provided intravenously post-fetal extraction or the procedure was converted to general anesthesia.

Duration December 2020 to July 2021
Outcome Measures

Primary: Incidence of visceral traction reaction

Secondary: Ramsay Sedation Scale, incidence of shivering, thirst, hypotension, bradycardia, nausea or vomiting, Apgar scores

Baseline Characteristics   Group R (n= 46) Group RD0.5 (n= 46) Group RD0.75 (n= 46) Group RD1 (n= 46)
Age (years) 31 ± 4 30 ± 3 30 ± 4 29 ± 5
Weight (kg) 68 ± 8 69 ± 9 69 ± 8 71 ± 8
Gestation(weeks) 39 ± 1 39 ± 1 39 ± 1 39 ± 1
Operation time (min) 38 ± 6 40 ± 7 40 ± 8 40 ± 7
Results   R (n= 46) RD0.5 (n= 46) RD0.75 (n= 46) RD1 (n= 46)
Overall treatment effect

28/54/43/14

1

-

89/35/10/4

0.14 (0.08–0.28)

< 0.001

97/24/12/5

0.12 (0.06–0.24)

< 0.001

107/25/5/1

0.07 (0.04–0.15)

< 0.001

T2 (fetal delivery)

8/17/16/5

1

-

21/18/5/2

0.26 (0.12–0.56)

< 0.001

24/13/7/2

0.23 (0.11–0.52)

< 0.001

29/13/3/1

0.14 (0.06–0.30)

< 0.001

T3 (uterus suture)

10/22/12/2

1

-

36/10/0/0

0.10 (0.04–0.23)

< 0.001

39/5/1/1

0.07 (0.03–0.18)

< 0.001

39/6/1/0

0.07 (0.03–0.17)

< 0.001

T4 (peritoneal closure)

9/15/15/7

1

-

32/7/5/2

0.11 (0.04–0.26)

< 0.001

34/6/4/2

0.09 (0.03–0.22)

< 0.001

39/6/1/0

0.04 (0.01–0.11)

< 0.001

Visceral Traction Reaction†

Grade:0/1/2/3(n)*

Odds ratio (95% CI)‡

p value 

*Data are expressed as a number

† Visceral Traction Reaction: 0, no discomfort in stomach or perineum, no nausea, vomiting, or intestinal tympanites; 1, mild discomfort, no visceral pain, vomiting, or nausea; 2, mild visceral pain, nausea; 3, Serious visceral pain, nausea and vomiting, intestinal tympanites

‡Odds ratio (95% CI): treatment differences in visceral traction reaction of Group RD0.5, Group RD0.75, and Group RD1 compared with Group R respectively

Adverse Events Higher incidence of thirst in group RD0.75 and RD1 compared to group R and RD0.5 (p < 0.001). Incidence of hypotension, bradycardia, nausea or vomiting was comparable among groups. Shivering rate in group RD0.5, RD0.75, and RD1 were significantly lower than in group R (p < 0.001). 
Study Author Conclusions

It is suggested that 0.5 μg/kg epidural dexmedetomidine can be used as adjuvant to epidural ropivacaine during cesarean section, because of its alleviating visceral traction reaction, moderate sedating, and reducing shivering without thirst increase.

Critique The study was well-designed with a double-blind, randomized, placebo-controlled approach, which strengthens the validity of the findings. However, the observational nature of some data could introduce bias, and the lack of laboratory indicators limits the depth of analysis. Additionally, the study did not measure the blood concentration of dexmedetomidine in maternal and infants, which could provide more insight into the safety profile.
References:
[1] Liu M, Wang B, Prudence B, Chen X. Effect of different doses of epidural dexmedetomidine on reducing visceral traction reaction for cesarean section: a double-blind randomized controlled trial. J Anesth. 2023;37(3):371-378. doi:10.1007/s00540-023-03166-8
Impact of Dexmedetomidine-Ropivacaine versus Sufentanil-Ropivacaine Combination for Epidural Labour Analgesia on Neonatal Outcomes: A Pilot Randomised Clinical Trial
Design

Randomised, double-blind, pilot clinical trial

N=200

Objective To investigate the impact of dexmedetomidine-ropivacaine combination versus sufentanil-ropivacaine combination for epidural labour analgesia on neonatal and maternal outcomes and test the feasibility of a future large, randomised trial
Study Groups Dexmedetomidine group (n=100); Sufentanil group (n=100)
Inclusion Criteria Women aged ≥18 years with full-term single pregnancy scheduled for vaginal delivery with epidural analgesia.
Exclusion Criteria  Presence of contraindications to neuraxial analgesia, including history of infectious disease of the central nervous system, history of spinal or intraspinal disease, systemic infection, skin or soft tissue infection at the site of puncture and coagulopathy; presence of contraindications to dexmedetomidine use, such as prenatal bradycardia (heart rate180 mm Hg);  uncontrolled systemic disease with an American Society of Anesthesiologists physical status≥III; history of psychiatric disease (diagnosed before or during pregnancy by a psychiatrist) or epilepsy or allergy to study drugs.
Methods Participants were randomly assigned  in a 1:1 ratio to receive self-controlled epidural labour analgesia using ropivacaine supplemented with either dexmedetomidine (0.45 µg/mL for induction and 0.36 µg/mL for maintenance) or sufentanil (0.45 µg/mL for induction and 0.36 µg/mL for maintenance). Maternal and neonatal outcomes were assessed, and the feasibility of the protocol was evaluated.
Duration 16 March 2023 to 15 June 2023
Outcome Measures

Primary: Composite of neonatal morbidity (1- or 5 min Apgar score <7, umbilical artery PH <7.1, requirement for immediate assisted ventilation and admission to neonatal ward or ICU within 24 hours).

Secondary: Effect of analgesia, occurrence of adverse events, feasibility of protocol implementation.

Baseline Characteristics   Dexmedetomidine (n=100) Sufentanil (n=100) P value 
Cervical dilation at beginning, median (IQR), cm 1 (1, 1) 1 (1, 1) 0.275

Intervertebral space 

    L2–3

    L3–4

 

98 (98.0%)

2 (2.0%)

 

98 (98.0%)

2 (2.0%)

>0.999

 

  

Epidural loading dose, mean (SD), mL 13.5 (1.8) 13.6 (1.8) 0.721
Onset of analgesia, median (IQR),min* 10(8,15) 13(10,16) 0.009
Results   Dexmedetomidine (n=100) Sufentanil (n=100)

Estimated effects (95% CI)

P value

Composite neonatal morbidity (ITT analysis), % 14.0 (14.0) 17.0(17.0) RR=0.82 (0.43 to 1.58)     -
Composite neonatal morbidity (PP analysis), no. (%) 14(14.1)(n=99) 17(17.0)(n=100) RR=0.83(0.43 to 1.59)     -
Epidural analgesics for maintenance,median (IQR),mL 77.0 (38.5, 104.0) 55.0 (27.0, 82.0) MD=17 (4 to 29)  0.007
Maternal satisfaction to analgesia, median (IQR), point‡‡ 9 (8, 10) 9 (8, 10) MD=0 (0 to 0) 0.730
Persistent pain at 42 days, no. (%)§§ 17.0 (17.0)(2) 30.0(30.0)(3) RR=0.57 (0.34 to 0.96) 0.033

*Calculated as the dexmedetomidine group vs or minus the sufentanil group

‡‡Assessed on the first-day postpartum using an 11-point verbal numerical rating scale, where 0=very dissatisfied and 10=very satisfied

§§Defined as a numeric rating scale of pain ≥1 that persisted since childbirth

Adverse Events Pruritus was significantly lower in the dexmedetomidine group (0.0% vs 30.0%, p<0.001). Lower limb weakness was higher in the dexmedetomidine group (13.0% vs 1.0%, p<0.001). Other adverse events like hypotension and bradycardia did not differ significantly between groups. No severe adverse events occurred during the study period.
Study Author Conclusions Compared with sufentanil-ropivacaine combination, use of dexmedetomidine-ropivacaine combination for epidural labour analgesia was associated with an 18% decrease in composite neonatal endpoint and deserves further investigation. The dexmedetomidine-ropivacaine combination provided similar labour pain relief without pruritus but increased lower limb weakness. TThe conduct of a large, randomised trial using the same protocol requires careful re-evaluation.
Critique The study was well-designed as a double-blind, randomised trial, providing valuable preliminary data on the use of dexmedetomidine in epidural labour analgesia. However, the pilot nature and small sample size limit the power to detect significant differences in neonatal outcomes. The fixed concentration of dexmedetomidine may not represent the optimal dosing strategy, and the study's generalisability is limited by its single-centre design and focus on a Chinese population.
References:
[1] Jin KX, Deng CM, Ding T, Qu Y, Wang DX. Impact of dexmedetomidine-ropivacaine versus sufentanil-ropivacaine combination for epidural labour analgesia on neonatal outcomes: a pilot randomised clinical trial. BMJ Open. 2024;14(12):e090208. Published 2024 Dec 22. doi:10.1136/bmjopen-2024-090208