Intranasal Dexmedetomidine for Prevention of Intrapartum Fever

Intranasal Dexmedetomidine and Labor Analgesia-Related Intrapartum Fever: A Randomized Controlled Trial

Brief Title: Intranasal Dexmedetomidine for Prevention of Intrapartum Fever This study aims to evaluate the effect of intranasal dexmedetomidine (Dex) administered before neuraxial labor analgesia on the incidence of intrapartum fever in women undergoing vaginal delivery.

This prospective, randomized, double-blind, placebo-controlled trial will enroll 446 parturients scheduled for vaginal delivery with neuraxial labor analgesia at Chengdu Jinjiang Maternal and Child Health Hospital from 2026 to 2027. Participants will be randomly assigned in a 1:1 ratio to receive either intranasal Dex (50 μg) or an equal volume of normal saline before the initiation of labor analgesia.

Primary Outcome Measure:

Incidence of intrapartum fever (temperature ≥ 38.0℃) from initiation of labor analgesia to 2 hours postpartum

Secondary Outcome Measures:

Temperature-related outcomes: Incidence of fever at thresholds of ≥ 37.5℃ and ≥ 38.5℃; hourly temperature trends assessed by continuous wireless axillary monitoring Analgesic effect: NRS pain scores before labor analgesia and at 30 minutes, 1 hour, and 3 hours after analgesia Sedative effect: Ramsay Sedation Scale scores at the same time points Maternal safety: Incidence of bradycardia (heart rate < 60 bpm), hypotension (systolic blood pressure < 90 mmHg or < 20% of baseline), nausea, vomiting, oversedation (Ramsay ≥ 4), and respiratory depression (SpO₂ < 90%) Labor characteristics: Duration of first, second, and third stages of labor, total labor duration, and duration of labor analgesia Delivery outcomes: Mode of delivery (spontaneous vaginal delivery or cesarean section) and total consumption of local anesthetics Neonatal outcomes: Apgar scores at 1, 5, and 10 minutes, and NICU admission rate We hypothesize that intranasal Dex administered before labor analgesia will significantly reduce the incidence of intrapartum fever compared to placebo. This study is expected to provide a novel, non-invasive, and effective strategy for preventing epidural-related maternal fever, thereby improving maternal safety and perinatal outcomes in women undergoing vaginal delivery.

Study Overview

• Status: Not yet recruiting
• Conditions: Intrapartum Fever
• Intervention / Treatment: Drug: Placebo; Drug: Dexmedetomidine

Detailed Description

Background: Labor analgesia-related intrapartum fever (LRIF), defined as maternal temperature ≥ 38.0°C following labor analgesia, occurs in 15-25% of parturients and is associated with adverse maternal and neonatal outcomes. Dexmedetomidine (Dex) possesses anti-inflammatory properties, and intranasal administration offers rapid onset, high bioavailability, and non-invasiveness. However, its effect on LRIF has not been evaluated in high-quality prospective studies.

Study Design: This is a prospective, randomized, double-blind, placebo-controlled, single-center trial conducted at Chengdu Jinjiang Maternal and Child Health Hospital (2026-2027).

Intervention: Participants are randomized 1:1 to receive intranasal dexmedetomidine (50 μg, 25 μg per nostril) or intranasal normal saline (equal volume) immediately before labor analgesia. Labor analgesia follows a standardized combined spinal-epidural protocol with patient-controlled epidural analgesia.

Randomization and Blinding: A computer-generated random sequence with block size of 4 is used. Allocation is concealed in sequentially numbered, opaque, sealed envelopes. Double-blinding is implemented: participants, outcome assessors, data managers, and statisticians are blinded to group allocation. The attending anesthesiologist is unblinded but does not participate in any follow-up or outcome assessment.

Data Collection: Temperature is monitored continuously using wireless axillary sensors from analgesia initiation to 2 hours postpartum, ensuring capture of hourly temperature trends and fever events. Pain scores (NRS) and sedation levels (Ramsay Sedation Scale) are assessed at predefined time points: before analgesia, and at 30 min, 1 h, and 3 h after analgesia initiation. Data are extracted from electronic health records and case report forms, with double data entry and source data verification for primary outcome events.

Statistical Analysis: The primary analysis follows the modified intention-to-treat principle. The primary outcome (incidence of LRIF) will be analyzed using chi-square test, with risk ratio and 95% CI reported. Continuous variables will be compared using t-tests or rank-sum tests as appropriate. Logistic regression will be performed to adjust for potential confounders. A two-sided P-value < 0.05 is considered statistically significant.

Ethics: The study has been approved by the Ethics Committee of Chengdu Jinjiang Maternal and Child Health Hospital (Approval No. 202509). Written informed consent will be obtained from all participants.

• Study Type: Interventional
• Enrollment (Estimated): 446
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bo Liu; Phone Number: +8618502846036; Email: liubojjfy@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610011
      • Chengdu Jinjiang District Women & Children Health Hospital
      • Contact: jianjun mao; Phone Number: +8615008460156; Email: jiafeijjfy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ASA physical status II or III
• Age ≥ 18 years
• Singleton pregnancy, cephalic presentation
• No contraindications to neuraxial anesthesia and voluntarily requesting labor analgesia

Exclusion Criteria:

• Maternal temperature ≥ 37.3°C before labor analgesia
• Allergy to α2-adrenergic receptor agonists
• Severe pregnancy complications or systemic diseases
• Use of analgesics, nonsteroidal anti-inflammatory drugs, or other medications that may affect body temperature within one week prior to enrollment
• Heart rate < 60 bpm or systolic blood pressure < 90 mmHg before labor analgesia
• Severe rhinitis or nasal deformity
• Premature rupture of membranes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Dexmedetomidine Group; Participants in this arm will receive a single dose of intranasal dexmedetomidine 50 μg (one spray of 25 μg per nostril, total two sprays) immediately before initiation of Combined Spinal-Epidural labor analgesia. Labor analgesia follows standard protocol using ropivacaine and sufentanil via patient-controlled epidural analgesia pump.	Drug: Dexmedetomidine; A single intranasal dose of dexmedetomidine 50 μg (25 μg per nostril) administered before combined spinal-epidural labor analgesia. Labor analgesia is maintained with ropivacaine and sufentanil via patient-controlled epidural analgesia pump.
Placebo Comparator: Placebo (Normal Saline) Group; Participants in this arm will receive a single dose of intranasal normal saline (one spray per nostril, total two sprays) immediately before initiation of Combined Spinal-Epidural labor analgesia. Labor analgesia follows standard protocol using ropivacaine and sufentanil via patient-controlled epidural analgesia pump.	Drug: Placebo; Intranasal normal saline (one spray per nostril, total two sprays) administered as a single dose before initiation of Combined Spinal-Epidural labor analgesia. Identical in appearance, color, odor, and packaging to the dexmedetomidine nasal spray to maintain blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Labor Analgesia-Related Intrapartum Fever (LRIF)	Proportion of participants with maternal temperature ≥ 38.0°C measured from initiation of labor analgesia to 2 hours postpartum. Temperature is continuously monitored using a wireless axillary sensor.	Up to 2 hours post-analgesia initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of fever at different thresholds	Proportion of participants with maternal temperature ≥ 37.5°C and ≥ 38.5°C during the same period.	Up to 2 hours post-analgesia initiation
Hourly temperature trends	Maternal temperature recorded every hour from initiation of labor analgesia to 2 hours postpartum.	Hourly, up to 2 hours post-analgesia initiation
Analgesic effect (NRS pain scores)	Numeric Rating Scale (NRS) pain scores, ranging from 0 (no pain) to 10 (worst possible pain), with higher scores indicating worse pain. Assessed before labor analgesia (T0), and at 30 minutes (T1), 1 hour (T2), and 3 hours (T3) after analgesia.	Baseline, 30 minutes, 1 hour, and 3 hours post-analgesia initiation
Sedative effect (Ramsay Sedation Scale)	Ramsay Sedation Scale scores, ranging from 1 (anxious, agitated, or restless) to 6 (no response to light glabellar tap or loud auditory stimulus), with higher scores indicating deeper sedation. Assessed at the same time points as pain scores.	Baseline, 30 minutes, 1 hour, and 3 hours post-analgesia initiation
Labor characteristics	Duration of first, second, and third stages of labor, total labor duration, and duration of labor analgesia.	Throughout labor and delivery
Mode of delivery	Spontaneous vaginal delivery or cesarean section.	At delivery
Total consumption of local anesthetics	Total dose (mg) of ropivacaine used during labor analgesia.	From analgesia initiation to delivery
Incidence of Hypotension	Proportion of participants with systolic blood pressure < 90 mmHg	Up to 2 hours post-analgesia initiation
Incidence of Bradycardia	Proportion of participants with heart rate < 60 bpm during labor analgesia.	Up to 2 hours post-analgesia initiation
Incidence of Nausea and Vomiting	Proportion of participants experiencing nausea or vomiting during labor analgesia.	Up to 2 hours post-analgesia initiation
Incidence of Oversedation	Proportion of participants with Ramsay Sedation Scale score ≥ 4 during labor analgesia.	Up to 2 hours post-analgesia initiation
Incidence of Respiratory Depression	Proportion of participants with SpO₂ < 90% during labor analgesia.	Up to 2 hours post-analgesia initiation
Neonatal Apgar Scores	Apgar (Appearance, Pulse, Grimace, Activity, Respiration) scores, ranging from 0 to 10, with higher scores indicating better neonatal condition. Assessed at 1 minute, 5 minutes, and 10 minutes after delivery.	1, 5, and 10 minutes post-delivery
NICU Admission Rate	Proportion of neonates admitted to the Neonatal Intensive Care Unit after delivery.	During neonatal hospitalization

Collaborators and Investigators

• Sponsor: Chengdu Jinjiang Maternity and Child Health Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: March 21, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Dexmedetomidine; labor analgesia; Intrapartum Fever
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Dexmedetomidine
• Other Study ID Numbers: 202509

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No