Epidural-Related Fever and Cesarean Delivery: Comparing Ropivacaine/Dexmedetomidine and Ropivacaine/Sufentanil: A Single-Center Randomized Controlled Study in 695 Women

Introduction

The Chinese Expert Consensus on Labor Analgesia recommends an epidural labor analgesia regimen consisting of ropivacaine combined with sufentanil [1]. It has been observed that approximately 20% of parturients receiving epidural labor analgesia develop epidural-related fever [2,3]. The commonly used definition for intrapartum hyperthermia is a core body temperature reaching or exceeding 38°C on a single occasion, or reaching or exceeding 37.5°C on 2 consecutive occasions 2 hours apart during labor. The definition of epidural-related fever varies across studies; some define it as exceeding 38°C, while others define it as exceeding 37.5°C, with no consensus reached [4]. The mechanism of epidural-related fever remains unclear. The literature indicates that infection is the primary consideration for maternal fever during the intrapartum period [5]; however, no evidence of infection is found in many febrile parturients. Currently, 2 main mechanistic theories exist: sympathetic blockade and immunomodulation [6–10]. In the first, epidural labor analgesia affects the maternal thermoregulatory mechanism, leading to an imbalance between heat production and dissipation, thereby causing an increase in maternal body temperature [11]. In the second, local anesthetics may trigger epidural-related fever through immunomodulation and cellular damage [12]. Because it is impossible to differentiate epidural-related fever from fever caused by infections such as chorioamnionitis, the clinical management of epidural-related fever is the same as that for intrapartum infection. Epidural-related fever increases the difficulty of obstetric management, including necessitating antibiotic administration and supportive treatment [3,13], and increasing the rate of emergency cesarean delivery [14,15]. Intrapartum hyperthermia (not limited to epidural-related fever) can lead to low Apgar scores at 1 and 5 minutes, assisted ventilation, neonatal seizures, and hypotonia [16], and also increases the fetal ventricular rate in utero, thereby increasing the cesarean delivery rate [14]. The literature suggests [17] that premature rupture of membranes, more than 6 vaginal examinations, prolonged labor, and prolonged duration from membrane rupture to delivery are all risk factors that increase the likelihood of epidural-related fever. Currently, there is extensive research on epidural dexmedetomidine for epidural labor analgesia and cesarean delivery. Pre-spinal administration of dexmedetomidine is safe for both parturients and fetuses undergoing cesarean delivery [18–22]; epidural dexmedetomidine for labor analgesia is also safe for mothers and neonates [23–26], and its analgesic efficacy has been demonstrated to be superior to that of sufentanil [27–29].

Therefore, the focus of this study is not on the analgesic effect of dexmedetomidine but rather on epidural-related fever. There is currently too little literature on reducing intrapartum fever. One retrospective study [30] indicated that parturients receiving intrapartum magnesium sulfate treatment were less likely to develop maternal fever, but substantial prospective studies are needed for confirmation. It is known that prophylactic antibiotic use does not reduce the fever rate [5]. Using programmed intermittent epidural bolus (PIEB) reduced the incidence of epidural-related fever in 1 study [31]; however, that study excluded parturients with comorbidities and parturients who developed fever during epidural labor analgesia and required conversion to cesarean delivery. Epidural ropivacaine combined with dexmedetomidine can reduce the incidence of epidural-related fever without increasing adverse events [32], according to 1 study, but that study excluded multiparous women and parturients who developed fever during epidural labor analgesia and required conversion to cesarean delivery. Therefore, the present study considers actual clinical situations, such as parturients with comorbidities, multiparous women, and parturients developing fever after epidural labor analgesia and requiring conversion to cesarean delivery.

Currently, with the vigorous promotion of labor analgesia and the increasing number of advanced maternal age parturients, reducing the intrapartum fever rate and lowering the cesarean delivery rate are of significant importance for improving the success rate of vaginal delivery, reducing additional clinical burdens, and minimizing interference with the clinical management of the parturient’s labor process [33]. Therefore, this study aimed to compare the incidence of cesarean delivery due to intrapartum hyperthermia in 695 women given labor epidural analgesia with 0.08% ropivacaine and 0.5 μg/mL dexmedetomidine or 0.08% ropivacaine and 0.5 μg/mL sufentanil.

Material and Methods

INCLUSION AND EXCLUSION CRITERIA:

The dexmedetomidine group (Dex group, n=347) received 0.08% ropivacaine +0.5 μg/ml dexmedetomidine for epidural labor analgesia. The control group (sufentanil group) (C group, n=348) received 0.08% ropivacaine +0.5 μg/ml sufentanil for epidural labor analgesia. The following inclusion criteria were applied: (1) Low-risk pregnant women with a singleton pregnancy, including primiparas and multiparas without medical or surgical comorbidities (who met the criteria for vaginal delivery; multiparas with a history of cesarean section were excluded); including primiparas and multiparas with comorbidities such as gestational diabetes mellitus, hypertension, thyroid dysfunction, and anemia; (2) Spontaneous labor at a gestational age between 37 and 42 weeks, with the fetus in a cephalic presentation and a desire for vaginal delivery; (3) Willingness to receive epidural labor analgesia and to sign the informed consent form. The exclusion criteria were: (1) Contraindications to epidural analgesia; (2) Preterm labor (<37 weeks), grand multiparas, and primiparas and multiparas with severe cardiopulmonary disease, bradycardia, or pregnancy complicated by fetal growth restriction or oligohydramnios that might be related to placental insufficiency; (3) Primiparas and multiparas with fever before labor or a baseline body temperature higher than or equal to 37.5°C and primiparas and multiparas with acute genital tract or upper respiratory tract infections (Figure 1).

RANDOMIZATION AND BLINDING:

The randomization schedule was created by a statistician using computer-generated random numbers produced by SPSS software (version 23). These random numbers were then ranked, and participants were allocated to the 2 groups in a 1: 1 ratio based on their rank numbers. For this study, ranks 1–347 were assigned to Group 1 (the dexmedetomidine group), and ranks 348–695 were assigned to Group 2 (the sufentanil group). The randomization schedule was strictly safeguarded against disclosure through mutual supervision by 2 individuals: an anesthesiology nurse not involved in the study and the research lead. Anesthesiologists, obstetricians, and midwives remained unaware of group assignments. If disclosure of the randomization schedule occurred before data collection, affected cases were re-randomized. To maintain double-blinding, group assignments and study identification numbers were sealed in opaque envelopes managed by a separate anesthesiology nurse (uninvolved in the study and unaware of allocations). When epidural labor analgesia was requested, this nurse prepared the corresponding analgesic solution according to the randomization sequence. The anesthesiologist then performed epidural catheter insertion and connected the analgesic pump but remained blinded to group assignments during epidural labor analgesia management. Data collectors and outcome assessors were also kept blinded to group allocations. Only after data collection completion could group assignments be unmasked using the randomization schedule and participants’ identification numbers.

ANTENATAL MANAGEMENT AND EPIDURAL ANALGESIA TECHNIQUES:

Upon admission to the delivery room, maternal conditions (non-invasive blood pressure, electrocardiogram, pulse oximetry) were continuously monitored, and uterine contractions and fetal heart rate were monitored using an SRF18B6 device (Guangzhou Sanrui Medical Equipment Co., Ltd.). Body temperature was recorded every 60 minutes from the onset of labor using a Mi Ear Thermometer (Kerton Electronic Medical Equipment Co., Ltd.). Once cervical dilation reached 2–3 cm and the parturient requested epidural labor analgesia, the obstetrician and anesthesiologist assessed the patient and initiated epidural labor analgesia. The midwife established peripheral intravenous access. The delivery room temperature was maintained at approximately 24°C. Epidural puncture was performed at the L2–3 interspace, and a catheter was advanced 3–4 cm cephalad. A test dose of 1.5% lidocaine (3 mL) was administered epidurally. If no adverse reactions occurred within 5 minutes, the catheter was fixed and connected to a PIEB pump (TR-1–100, Henan Tuoren Medical Equipment Group Co., Ltd.) with the following parameters: PIEB set to deliver 6–8 mL every 60 minutes, patient-controlled bolus of 3–4 mL, lockout time of 20 minutes, and a maximum dose of 18 mL/h. The control group (C group) received 0.08% ropivacaine (Ruiyang Pharmaceutical Co., Ltd.) combined with 0.5 μg/mL sufentanil (Jiangsu Enhua Pharmaceutical Co., Ltd.), while the dexmedetomidine group (Dex group) received 0.08% ropivacaine combined with 0.5 μg/mL dexmedetomidine (Yangtze River Pharmaceutical Group Co., Ltd.). Visual Analogue Scale (VAS) pain scores and adverse reactions were assessed hourly. If the VAS pain score exceeded 6, an additional 3–4 mL bolus was administered via the patient-controlled analgesia pump. If patient-controlled analgesia failed to relieve breakthrough pain, a manual epidural bolus of 6–8 mL of 0.08% ropivacaine was administered. Due to concerns among obstetric midwives at this institution that epidural labor analgesia might prolong the second stage of labor, the analgesic pump was discontinued at full cervical dilation (10 cm). Consequently, this study only included parturients who developed hyperthermia during the first stage of labor.

DEFINITION OF EPIDURAL-RELATED FEVER:

Regarding the definition of epidural-related fever, although most studies use 38°C as the criterion for epidural-related fever, controversy remains regarding whether 37.5°C or 38°C should be selected as the diagnostic threshold for fever during labor analgesia. Greenwell et al [34] found that among low-risk parturients receiving epidural labor analgesia, even a modest elevation in maternal temperature was an independent predictor of adverse neonatal outcomes. The proportion of infants experiencing adverse consequences increased directly with the degree of maternal temperature elevation. Therefore, this study adopted 37.5°C as the criterion for epidural-related fever.

DEFINITION OF MATERNAL COMORBIDITIES:

Maternal comorbidities were defined as follows: hypertensive disorders of pregnancy included preeclampsia and chronic hypertension (of any cause). Diabetes included pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus, diagnosed via a 75 g oral glucose tolerance test at 24–28 weeks of gestation. Thyroid dysfunction was diagnosed based on thyroid function tests during prenatal care. Anemia was defined as a hemoglobin concentration below 110 g/L.

INDICATIONS FOR INTRAPARTUM CAESAREAN DELIVERY:

Decisions regarding artificial rupture of membranes, oxytocin augmentation, and the timing of intrapartum cesarean delivery were made by obstetricians based on labor management guidelines. All indications for intrapartum cesarean delivery were recorded by obstetricians according to standard definitions [35] (Figure 2). Ideally, cesarean delivery indications should be categorized as fetal, maternal, or non-medically indicated. However, due to the complexity and overlap of clinical scenarios, these distinctions are difficult to define and implement. The cesarean delivery indications [35] differentiate between fetal causes (without oxytocin use) and dystocia. Indications for cesarean delivery during spontaneous labor were categorized as fetal causes (without oxytocin use), dystocia, or maternal request for cesarean delivery. This study introduced the concept of “cesarean delivery due to epidural-related fever”. Fetal causes (without oxytocin use) were defined as suspected fetal distress without oxytocin use. Dystocia (Dys) was defined as labor progression slower than 1 cm/hour (ineffective uterine action, IUA) or initial progression faster than 1 cm/hour followed by arrest (effective uterine action, EUA). Dys/IUA was further subdivided on the basis of inability to treat adequately with oxytocin (ITT), fetal intolerance (FI), overcontracting (OC), and poor response to oxytocin (PR), into: (1) inability to reach the maximum oxytocin dose due to fetal intolerance (Dys/IUA/ITT/FI); (2) inability to adequately treat uterine hyperstimulation with oxytocin (Dys/IUA/ITT/OC); (3) poor response to oxytocin (Dys/IUA/PR), defined as failure to achieve labor progression faster than 1 cm/hour despite reaching the maximum recommended oxytocin dose; (4) no oxytocin use (Dys/IUA/No Oxytocin), defined as slow labor progression (<1 cm/hour) without oxytocin use due to various clinical reasons. EUA labor was further subdivided on the basis of cephalopelvic disproportion (CPD) and malposition (Mal), into cephalopelvic disproportion (Dys/EUA/CPD) or malposition (Dys/EUA/Mal). If no other cesarean delivery indications were present, cesarean delivery at the request of the parturient or her family was recorded as “maternal request for cesarean delivery”. Cesarean delivery due to epidural-related fever was defined as cesarean delivery due to maternal fever (≥37.5°C) causing fetal heart rate >160 bpm and fetal distress, in the absence of other cesarean delivery indications or maternal request. Clinically, we observed that most parturients with epidural-related fever experienced elevated maternal temperature, leading to elevated fetal temperature. Some fetuses exhibited persistently elevated heart rates, such as >180 bpm, resulting in fetal distress and cesarean delivery to ensure fetal safety. Fetal temperature is typically 0.12–3.2°C higher than maternal temperature [36].

DATA COLLECTION:

Data were collected from patient medical records, recording: maternal age, gestational age, height, weight, the proportion of multiparous women, the proportion of women with comorbidities, the time from the initiation of epidural labor analgesia to the onset of fever in febrile patients, analgesic dosage, the proportion of patients using oxytocin, body temperature upon entering the delivery room for labor admission, maternal body temperature during the delivery process (tympanic membrane temperature), VAS pain score before epidural analgesia, the maximum VAS pain score during labor, the total intrapartum cesarean delivery rate, the duration of labor stages (first stage and second stage), the proportion of neonates with an Apgar score ≤7 at 1 minute, the proportion of neonates with an Apgar score ≤7 at 5 minutes, the proportion of neonates transferred to the pediatric department for treatment, indications for intrapartum cesarean delivery, the proportion of cesarean deliveries due to maternal request, and the proportion of cesarean deliveries due to epidural-related fever. Adverse events included hypotension, bradycardia, restricted lower limb movement, and pruritus. If hypotension occurred (systolic blood pressure ≤90 mmHg or diastolic blood pressure ≤60 mmHg), ephedrine 6 mg was administered as an intravenous bolus; if bradycardia occurred (heart rate ≤50 beats per minute), atropine 0.25 mg was administered as an intravenous bolus. During maternal labor under epidural analgesia, respiration, heart rate, and blood pressure were monitored; an anesthesiologist provided continuous supervision throughout the entire period to ensure maternal safety.

SAMPLE SIZE CALCULATION:

The primary outcome was epidural-related fever. Based on an intrapartum fever incidence of approximately 20% [2,3], this study defined epidural-related fever as a maternal temperature ≥37.5°C. The sample size was calculated using the 2-sample proportion comparison formula, assuming a fever rate of 20% with sufentanil as the adjuvant and 10% with dexmedetomidine based on relevant literature [27,28]. A type I error (α) of 0.05 and a type II error (β) of 0.1 were used, with a 1: 1 allocation ratio. Power Analysis & Sample Size (PASS) 11.0 software was used to calculate a sample size of n1=n2=266. Assuming a 10% data loss rate, the final sample size was n1=n2=296, leading to a planned recruitment of 600 parturients.

Sample size calculation formula:

STATISTICAL ANALYSIS:

SPSS 23.0 software was used for statistical analysis. Maternal age, gestational age, height, weight, admission temperature, and durations of first and second stages of labor demonstrated normal distribution with equal variances. These parameters were analyzed using t-test and are presented as mean±standard deviation. The time interval from epidural analgesia to fever onset (hours), pre-analgesia VAS pain scores, maximum intrapartum VAS pain scores, and total analgesic dosage (in mL) exhibited non-normal distributions. These variables were compared using the non-parametric Mann-Whitney U test for independent samples and are reported as median with interquartile range. Proportions of multiparous women, comorbidities, oxytocin use, intrapartum fever, cesarean delivery rate, Apgar scores ≤7 at 1 and 5 minutes, neonatal transfers to pediatric care, indications for intrapartum cesarean delivery, cesarean deliveries due to maternal request, and cesarean deliveries due to epidural-related fever were analyzed using chi-square or Fisher’s exact tests. Categorical variables are presented as numbers (percentages). All statistical tests were 2-sided, with P<0.05 considered statistically significant.

Results

COMPARISON OF DEMOGRAPHIC CHARACTERISTICS AND EPIDURAL LABOR ANALGESIA BETWEEN THE 2 PARTURIENT GROUPS:

Table 1 summarizes the demographic characteristics and epidural analgesia details for the 2 groups. There were no significant differences in demographic characteristics between the groups. The proportion of oxytocin use, time from epidural analgesia initiation to fever onset, pre-analgesia VAS pain scores, maximum VAS pain scores during labor, and analgesic doses were similar between the 2 groups.

COMPARISON RESULTS OF EPIDURAL-RELATED FEVER, DURATION OF LABOR, AND NEONATAL OUTCOMES:

Table 2 summarizes epidural-related fever, duration of labor, and neonatal outcomes; the epidural-related fever rate in the dexmedetomidine group, analyzed using the fundamental formula of the chi-square test, was found to be significantly lower (18.0% vs 28.5%, P = 0.002); between the 2 groups. There were no significant differences in body temperature (in °C) upon admission to the delivery room, duration of labor stages (first stage and second stage), proportion of neonates with an Apgar score ≤7 at 1 minute, proportion of neonates with an Apgar score ≤7 at 5 minutes, or number of neonates transferred to the pediatric department for treatment (Table 2).

COMPARISON RESULTS OF INTRAPARTUM CESAREAN DELIVERY RATES BETWEEN THE 2 GROUPS:

Table 3 displays the proportions of indications for intrapartum cesarean delivery in the 2 groups. This study is the first to propose the concept of “cesarean delivery due to epidural-related fever”, defined as follows: after epidural labor analgesia, epidural-related fever occurs; analgesia is adequate (VAS score ≤5 points); other indications for cesarean delivery such as fetal causes, dystocia, or cephalopelvic disproportion are excluded; fetal heart rate is >160 beats per minute and persists for at least 1 hour; fetal heart rate decelerations are detected on cardiotocography; fetal distress occurs; and conversion to cesarean delivery is performed for fetal safety. The proportion of parturients converted to cesarean delivery due to epidural-related fever was significantly lower in the dexmedetomidine group (0.9% vs 5.2%, P=0.020). There was, however, no significant difference in the overall cesarean delivery rate between the 2 groups (25.5% vs 25.2%, P=0.927). There were no differences in other indications for intrapartum cesarean delivery between the 2 groups. Finally, there was no difference in the proportion of cesarean deliveries due to maternal request between the 2 groups (Table 3).

Both groups had a modified Bromage score of 0 during epidural analgesia, with no cases of hypotension or bradycardia. One case of pruritus occurred in the sufentanil group, with no other adverse reactions.

Discussion

This study incorporated dexmedetomidine as an adjuvant for epidural labor analgesia; the defined criterion for epidural-related fever was ≥37.5°C; the observation period was from the initiation of epidural analgesia to the end of the second stage of labor; compared with the sufentanil group’s rate of 28.5% (93/326), the dexmedetomidine group’s rate was 18.0% (58/322) (P=0.002), indicating a significant reduction in fever incidence; whereas according to the criterion of fever ≥38.0°C, the rates were: Dex group 5.9% (19/322) vs C group 8.9% (29/326) (P=0.146), showing no difference in fever incidence. Compared with literature regarding reduced fever rates, for fever ≥38.0°C, the fever rate in the Dex group was 5.9% (19/322), higher than the 4.1% (12/291) in Li et al’s study [32]; the C group’s rate of 8.9% (29/326) was also higher than the 5.8% (85/1454) in Fan Yuru’s study [31]. The primary reason is probably that this study more closely approximates real-world clinical practice, including multiparous women and patients with low-risk comorbidities, and additionally including parturients who underwent intrapartum conversion to cesarean delivery due to epidural-related fever or other reasons. These 2 cited studies [31,32] excluded parturients who converted to cesarean delivery during labor due to epidural-related fever or other causes, and parturients with antenatal comorbidities; consequently, their reported fever rates are lower than in the present study. Another study [15] reported a fever rate (sufentanil adjuvant) of 26.4% (42/159) for fever ≥38.0°C, substantially higher than our C group’s 8.9% (29/326). That study [15] also included parturients with comorbidities and those converted to cesarean delivery; in particular, it counted parturients who were febrile during both the second and third stages of labor, whereas the present study only calculated fever incidence during the first stage; thus, its fever rate is markedly higher than our study and other studies [31,34]. In our study, the proportion of febrile parturients (≥37.5°C) in the C group was 28.5% (93/326), higher than the 20.2% (42/208) in Wang Hui et al’s study [37]; analysis revealed that in Wang Hui et al’s study (≥37.5°C), they used 0.075% ropivacaine +0.5 μg/mL sufentanil; this difference may be attributable to their use of a lower concentration of local anesthetic and their exclusion of patients with pre-existing hypertension and diabetes, potentially explaining the disparity in fever rates between the 2 studies. Compared with another study [38] that defined fever as ≥37.5°C, the fever rate with sufentanil as the adjuvant was similar (25.7%, 93/371); that study included parturients with comorbidities but did not investigate dexmedetomidine. In the present study, since epidural catheters were placed in both groups, it seems unlikely that epidural puncture or catheter insertion alone triggered maternal fever-related inflammatory changes [12]. Furthermore, according to a study on orthopedic patients [39], the magnitude of systemic cytokine release after mere epidural space catheter insertion is unlikely to explain the magnitude of the systemic inflammatory response associated with epidural-related fever. The lower incidence of fever in the dexmedetomidine group suggests that epidural-related fever is not related to the epidural catheter itself, but rather to the medications administered epidurally. The precise mechanism underlying epidural-related fever during epidural labor analgesia remains unclear. Across different hospitals and regions, intrapartum fever rates vary substantially; in a US study report [34], the fever rate (≥37.5°C) among parturients receiving epidural labor analgesia was 44.8% (1246/2784), and the rate for ≥38.0°C was 19.2% (535/2784), significantly higher than the C group’s fever rates in this study (≥37.5°C: 28.5%; ≥38.0°C: 8.9%). Therefore, in clinical practice, other factors influence intrapartum hyperthermia; notably, the primary manifestation of clinical chorioamnionitis is fever, with diagnostic criteria including temperature reaching ≥38.0°C, accompanied by other clinical symptoms such as maternal/fetal tachycardia, uterine tenderness, foul-smelling amniotic fluid, and leukocytosis [13]. However, due to the complexity of clinical scenarios and the atypical presentations in some parturients, obstetricians face challenges in accurately distinguishing and diagnosing whether fever stems from epidural labor analgesia, chorioamnionitis, or other causes. This indicates that among parturients with comorbidities or those converted to cesarean delivery due to fever, a subset developed fever because of clinical chorioamnionitis infection, and a proportion underwent cesarean delivery specifically due to chorioamnionitis infection. Because chorioamnionitis and epidural analgesia are independent factors for intrapartum hyperthermia [40], the intrapartum incidence of clinical chorioamnionitis ranges from 5% to 12%, similar to the incidence of intrapartum fever [41–43]. A literature review on epidural labor analgesia and maternal fever notes [4] that when 37.5°C is used as the fever threshold, epidural labor analgesia correlates with maternal fever; however, when 38°C is used as the threshold and after controlling for the confounding factor of labor duration stratification, epidural labor analgesia ceases to be a risk factor for maternal fever. This may occur because prolonged labor increases analgesic duration, frequency of vaginal examinations, and duration of membrane rupture, all of which elevate opportunities for chorioamnionitis and intrauterine infection, thereby increasing the likelihood of maternal fever exceeding 38°C. Consequently, obstetricians should maintain heightened vigilance: once temperature exceeds 38°C, the fever may not be attributable to epidural labor analgesia, warranting further investigation into the etiology and prompt necessary intervention.

Dexmedetomidine reduced the intrapartum hyperthermia rate (≥37.5°C) but failed to reduce the overall cesarean delivery rate (25.5%, 82/322 vs 25.2%, 82/326, P=0.927). Neonatal outcomes between the 2 groups, such as the proportion with Apgar score ≤7 at 1 minute, proportion with Apgar score ≤7 at 5 minutes, and proportion of neonates transferred to pediatric care (Table 2), also showed no difference. This is similar to the proportion of intrapartum conversion to cesarean delivery (25.2%) seen in previous studies [14] (≥37.5°C). According to research [14,15,34], parturients developing intrapartum hyperthermia after receiving epidural labor analgesia exhibit an increased cesarean delivery rate and are associated with a higher risk of adverse neonatal outcomes, such as low Apgar scores at 1 and 5 minutes. However, this study found no reduction in the overall cesarean delivery rate. Yet, through clinical observation in recent years, we have noted that some parturients develop hyperthermia after epidural analgesia, with adequate analgesia (VAS score ≤5 points), absence of other cesarean indications, and no maternal/family request for cesarean delivery; as labor progresses, fetal heart rate exceeds 160 beats per minute, even reaching 180 beats per minute, indicating fetal distress; after obstetrician assessment, conversion to cesarean delivery occurs. Consequently, the present study is the first to propose the concept of “cesarean delivery due to epidural-related fever”. It is defined as follows: epidural-related fever occurs after epidural analgesia; analgesia is adequate (VAS score ≤5 points); other indications for cesarean delivery such as fetal causes, dystocia, or cephalopelvic disproportion are excluded; fetal heart rate is >160 beats per minute and persists for at least 1 hour; fetal heart rate decelerations are detected on cardiotocography; fetal distress occurs; conversion to cesarean delivery is performed for fetal safety. Based on indications for intrapartum cesarean delivery [35], after excluding fetal causes, dystocia, and maternal request, it was surprisingly found that the Dex group had a reduced cesarean rate (0.9% 3/322 vs 5.2% 17/326, P=0.020) (Table 3), consistent with our hypothesis that reducing the maternal epidural-related fever rate could subsequently reduce the cesarean delivery rate. Maternal hyperthermia during labor can cause maternal tachycardia, increased cardiac output, and elevated basal metabolic rate; maternal hyperthermia also leads to fetal hyperthermia, which in turn causes fetal tachycardia and increases the risk of adverse delivery outcomes such as fetal distress [44]; for parturients with intrapartum hyperthermia, particularly those with comorbidities like cardiopulmonary disease, hypertension, diabetes, or anemia, obstetric management becomes highly cautious. That is, obstetricians may broaden cesarean indications for febrile parturients to ensure maternal and fetal safety, and because of this, some febrile parturients who might not otherwise require cesarean delivery are persuaded to undergo the procedure. The literature has long indicated [14,15] that elevated temperature during epidural labor analgesia is a reason for higher cesarean rates. This also explains why the reduced hyperthermia rate in the dexmedetomidine group led to fewer cesarean deliveries in the present study. However, the overall cesarean delivery rate was not reduced, and neonatal outcomes showed no difference between the 2 groups. We analyzed potential reasons for this finding: (1) The sample size in this study may be insufficient; the small difference in cesarean rates between groups might only achieve statistical significance in larger studies. Therefore, larger multicenter trials are needed to assess epidural dexmedetomidine’s impact on cesarean rates. (2) Although obstetricians strictly follow cesarean indication guidelines [35], in clinical practice, cesarean rates vary substantially even among different obstetricians within the same institution [45]. The complexity of clinical scenarios, possibly due to differing interpretations of cesarean indications [35], may also contribute to cesarean rate variations. This could explain the lack of difference in overall cesarean rates between the 2 groups in this study; future studies should use simpler and standardized intrapartum cesarean indications to analyze whether cesarean delivery in parturients receiving epidural labor analgesia is attributable to epidural-related fever [46]. (3) Given China’s current low birth rate context, our hospital places exceptional emphasis on perioperative safety for mothers and neonates; consequently, obstetricians manage parturients with intrapartum hyperthermia more aggressively, including persuading earlier cesarean delivery and actively managing fever; they also intervene more proactively for suspected fetal distress; obstetricians preemptively intervene (eg, via cesarean) for febrile parturients, especially those with epidural-related fever, when anticipating potential distress rather than waiting for distress to necessitate emergency surgery. This may explain the lack of any difference in neonatal outcomes between groups. A previous report notes that controlling the duration of epidural-related fever (≥38.0°C) to under 90 minutes helps reduce neonatal morbidity [47].

This study also has certain limitations. First, in parturients with epidural-related fever, pathological examination of the placenta and amniotic fluid was not performed to confirm the diagnosis of chorioamnionitis and differentiate whether epidural-related fever was caused by epidural analgesia, chorioamnionitis, or other factors. Epidural-related fever remains a clinical phenomenon with an unclear mechanism; future research should primarily focus on differentiating epidural-related fever through placental pathological examination, followed by investigating its mechanisms and the roles of various inflammatory pathways and related signaling pathways. Second, this was a single-center study; the sample size and parturient population (predominantly northern Chinese) may not represent the broader Chinese population. Therefore, large-sample, multicenter randomized controlled trials should be conducted to further explore dexmedetomidine as a feasible alternative adjuvant in epidural labor analgesia, and to provide more robust evidence that epidural dexmedetomidine labor analgesia reduces hyperthermia rates and consequently lowers cesarean delivery rates. Third, since we clinically observed cases where parturients underwent emergency conversion to cesarean delivery due to hyperthermia and persistently elevated fetal heart rate, this study is the first to propose the concept of “cesarean delivery due to epidural-related fever”; therefore, the conclusion that epidural dexmedetomidine labor analgesia reduces cesarean rates should be applied with caution.

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.