Regional Blood Flow Spectral Parameters as Predictors of Epidural-Related Maternal Fever: A Prospective Observational Study

doi:10.21203/rs.3.rs-4063247/v1

Background

Epidural-related maternal fever (ERMF) is a common phenomenon that appears to be unique to laboring women and presents diagnostic and therapeutic dilemmas for anesthesiologists. It is crucial to identify and predict the occurrence of ERMF at an early stage to improve the outcomes for mothers and infants.

Method

A total of 103 women who had vaginal deliveries with epidural labor analgesia (ELA) were recruited into the study. Pulsed-wave Doppler (PWD) ultrasound was used to measure peak systolic velocity (PSV, cm/s) and end-diastolic velocity (EDV, cm/s) in the regions of the anterior and posterior tibial arteries. Measurements were taken 1 minute before induction of analgesia and at 5-minute intervals for the subsequent 30 minutes. The change of PSV (△PSV) and EDV (△EDV) at 30 minutes relative to baseline after induction of analgesia was calculated. Participants were categorized into two groups based on their body temperature during labor and delivery: febrile and afebrile. The study compared the differences in blood flow spectral parameters between the two groups.

Results

Of the 103 study participants, 73 were ultimately included for analysis. Thirteen participants (17.8%) in the study developed ERMF. PSV was significantly higher in the febrile group than the non-febrile group at 10 min after ELA (P < 0.05). In contrast, EDV showed a significant difference between the two groups at 15 min after ELA (P < 0.01). Based on linear correlation analysis, there was a positive correlation between PSV and EDV at 30 minutes after analgesia induction and the peak labor temperature (P < 0.001). Receiver operating characteristic (ROC) curve analysis identified a cut-off value of 43.35 and an area under the curve (AUC) of 0.701 for △PSV in the anterior tibial artery region (95% CI 0.525 to 0.878, P = 0.025) and a cut-off value of 29.94 and an AUC of 0.733 for △EDV (95% CI 0.590 to 0.877, P = 0.001). The cut-off value for △PSV in the region of the posterior tibial artery was 39.96 with an AUC of 0.687 (95% CI 0.514 to 0.860, P = 0.034), and the cut-off value for △EDV was 33.10 with an AUC of 0.713 (95% CI 0.558 to 0.869, P = 0.007).

Conclusion

Regional blood flow spectral parameters after epidural analgesia induction can predict the occurrence of ERMF by indirectly reflecting the degree of sympathetic activity inhibition. Specifically, the amount of change in peak systolic velocity and end-diastolic velocity relative to baseline parameters 30 min after ELA induction was the most predictive.

Trial registration

The research was conducted in accordance with the Declaration of Helsinki, and approved by the Women and Children’s Hospital, School of Medicine, Xiamen university Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (reference number: ChiCTR2400080507,31/01/2024).

Epidural-related maternal fever

Epidural labor analgesia

Pulsed-wave Doppler ultrasound

Peak systolic velocity

End-diastolic velocity

Epidural-related maternal fever (ERMF) is a common phenomenon that appears to be unique to parturient women, posing diagnostic and therapeutic dilemmas for anesthesiologists¹. For parturients, intrapartum fever can impair uterine contractions, affect labor curves, and increase the rate of vaginal births as well as cesarean sections^2,3. Maternal fever can also precipitate adverse neonatal effects. A recent large propensity score-matched cohort study of 37,786 women found that maternal epidural analgesia-associated fever was associated with neonatal infection, including sepsis, unspecified infection, and pneumonia⁴. It is, therefore, crucial to identify and predict the occurrence of ERMF at an early stage to improve maternal and neonatal outcomes.

There is no consensus on the pathophysiology of ERMF. Two widely accepted theories are the sterile inflammatory hypothesis and the thermoregulatory hypothesis^5,2. Epidural labor analgesia blocks the sympathetic nerve supply to the cutaneous vasculature, impairing body temperature regulation. Mullington et al. have demonstrated that epidural analgesia can cause an imbalance in thermoregulation, increasing body temperature by blocking sympathetic pathways and reducing heat loss⁵. As such, the extent of the sympathetic blockade in epidural labor analgesia, which may play an essential role in the development of ERMF, is a potential research direction.

We hypothesize that the degree of sympathetic blockade induced by epidural labor analgesia may be related to the development of ERMF. To test this hypothesis, we designed this prospective observational study to quantify the degree of sympathetic blockade using spectral parameters of blood flow obtained by Pulsed-wave Doppler (PWD) ultrasound (US) to predict ERMF. PWD US is one of the most commonly used diagnostic methods for noninvasive vascular examination in clinical practice. Eicke et al. have demonstrated that Doppler ultrasound can quantify sympathetically induced changes in peripheral vascular resistance⁶. Prior studies have utilized regional hemodynamic parameters to evaluate the efficacy of peripheral nerve blocks based on this mechanism^7,8. Acquisition of an objective ultrasound-based indicator will assist clinicians in identifying individuals at risk for ERMF early.

Research Design and Ethics

This research was conducted as a single-center, prospective observational study at a tertiary care teaching hospital from January to March 2024. The aim was to assess the feasibility of using regional blood flow spectral parameters as predictors for ERMF. Ethical approval for the study was granted by the institutional ethics committee (approval number: KY-2024-009-K01), and the study was registered with the China Clinical Trials Registry (reference number: ChiCTR2400080507,31/01/2024). The methodology and procedures were thoroughly explained to all participants, ensuring complete understanding. Following this, written informed consent was obtained from each participant, adhering to ethical standards and research governance.

Recruitment of Subjects

Participants in this study were parturients who had epidural analgesia during labor at the Women and Children’s Hospital, School of Medicine, Xiamen university. PASS 14.0 software was employed to determine an appropriate sample size, considering the established principles for studies of this nature. The end-diastolic flow velocity (EDV) was the primary measure of interest. Drawing on previous literature findings and a pilot study⁹, the anticipated area under the receiver operating characteristic (AUROC) for predicting ERMF was established at 0.8. Given the local ERMF incidence rate of approximately 20% and an estimated attrition rate of 10%, it was calculated that a minimum of 60 participants would be required. This sample size was necessary to achieve a statistical power of 90%, with a Type I error probability set at 0.05¹⁰.

Inclusion Criteria:

(1) Individuals aged between 25 to 35 years, having a singleton, full-term birth.²

(2) Had a vaginal delivery.

(3) Consented to participate in the study, verified by the signing of an informed consent document.

Exclusion Criteria:

(1) A preexisting severe cardiorespiratory condition.

(2) Any pregnancy complications that could potentially influence autonomic functions, such as gestational diabetes or gestational hypertension.

(3) A documented history of peripheral vascular disease.

(4) The presence of an active infectious disease, fever, or a basal body temperature of 37.5°C or higher prior to delivery.

(5) Any contraindications to receiving epidural analgesia during labor.

(6) Severe cognitive or psychiatric disorders that could impair study participation or consent.

(7) The use of medications during the ultrasound parameter measurement phase that could affect peripheral vasoconstriction, including nifedipine.

(8) Any other medical or health conditions deemed by the anesthesiologist to render the individual unsuitable for inclusion in this study.

Epidural Labor Analgesia Technical Protocol

Upon the onset of regular uterine contractions, participants were admitted to the labor room. The anesthesiologist discussed ELA's advantages and potential risks with the participants before the study commenced. The delivery room temperature was regulated to remain between 24–26°C, with careful attention paid to maintaining the participant's bilateral lower extremities warm. Peripheral intravenous access was secured, and a Lactated Ringer's solution was infused at 2–5 mL/kg/h. An experienced attending anesthesiologist performed the epidural insertions. Continuous real-time monitoring of vital signs was done, including noninvasive blood pressure (NIBP), electrocardiogram (ECG), oxygen saturation (SPO₂), and fetal heart rate. For the procedure, participants were positioned in the left lateral decubitus position. The epidural catheter insertion site was selected at the L2/L3 or L3/L4 intervertebral space. The "water resistance disappearing" technique was employed to confirm entry into the epidural space. Upon a successful insertion of the spinal needle, a catheter was inserted into the lumber epidural space to a depth of approximately 3–4 cm. A test dose of 3mL of 1.5% lidocaine was administered. The participants were then monitored for 3–5 for any signs of local anesthetic toxicity or total spinal anesthesia.

The patient-controlled epidural analgesia pump (DDB-I-A1, Apollo, China) was prepared with a mixture containing 0.08% ropivacaine and 0.4 µg/mL sufentanil, totaling 100 mL¹¹. The analgesic pump was set to deliver an initial bolus of 12–15 mL, followed by a maintenance infusion of 8–10 mL/h, with a patient-controlled bolus of 6 mL and a lockout interval of 20 minutes. A blunt needle was used to ensure the anesthesia coverage extended from the T10 to S4 dermatomes. Effective labor analgesia was defined as a visual analog scale (VAS) score of less than 4. If a subject's VAS score exceeded 4 after 30 minutes from the initial epidural dose, the analgesia was considered inadequate. In this case, an additional 8 mL of 0.125% ropivacaine was injected, and the participant was excluded from the study. Participants who required vasoactive drugs to manage hemodynamic instability during measurements were also excluded from the study.

Data Collection

Baseline information on subjects was documented, including weight, height, gestational age, duration of labor, hemorrhage, side effects, oxytocin dosage, basal body temperature, and any other medications taken during the study. Blood flow spectrum images were acquired while subjects were in the left or right lateral position to avoid the influence of the expanded uterus compressing blood vessels on ultrasound data. Ultrasound measurements of the right lower extremity were uniformly performed on all participants using a PWD US system (MX7, Mindray, China) with a 3–12 MHz high-frequency linear array transducer probe to reduce variability.

The anterior tibial artery (ATA) was scanned just above the ankle joint on the anteromedial aspect of the tibia, while the posterior tibial artery (PTA) was scanned at the medial malleolus. The color Doppler image of the artery's longitudinal axis was obtained, ensuring visibility of both the anterior and posterior tunica intima at the vessel's largest diameter. The sampling line was aligned as closely as possible with the blood flow direction, the Doppler angle was kept below 60 degrees, and the sample volume was adjusted to fit the vessel walls. The scale and baseline were optimized for the PWD scan. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were recorded using automated tracing(Supplementary Figs. 1).

Data was captured one minute prior to induction of epidural analgesia (PSV₀) and then at five-minute intervals for thirty minutes post-induction (PSV₅-PSV₃₀). The difference relative to baseline in blood flow parameters in the ATA and PTA was calculated (△PSV = PSV₃₀-PSV₀; △EDV = EDV₃₀-EDV₀). These measurements were performed by a certified physician trained in ultrasonography at the Second Affiliated Hospital, Zhejiang University School of Medicine. Throughout labor, the participants' temperatures were measured every hour using an infrared ear thermometer, continuing until two hours after the conclusion of the second stage of labor. Following UK guidelines, ERMF was defined as a maternal temperature reading of 38°C on one occasion or two consecutive readings of 37.5°C spaced one hour apart¹².

2.5 Statistical Analyses

Statistical analyses were performed utilizing SPSS software, version 22.0 (IBM Corp., Armonk, NY, USA). Graphical representations were generated with GraphPad Prism version 8.0 for macOS (GraphPad Software, San Diego, CA, USA) and R version 3.6.1 (R Core Team, 2019). The normality of data distributions was evaluated using the Kolmogorov-Smirnov test. Data adhering to a normal distribution were expressed as the mean ± standard deviation (SD). For comparisons between two independent groups, the t-test was applied. Generalized estimating equation was used to assess differences both between and within groups across multiple time points. For continuous data that deviated from normal distribution, the median and interquartile range [IQR] were used as descriptive statistics, and the Mann-Whitney U test was used for group comparisons. Categorical data were expressed as counts or percentages, and the χ² test or Fisher's exact test was used when deemed suitable for between-group comparison. A P-value < 0.05 indicated statistical significance. The correlation between two variables was analyzed using Spearman's rank correlation coefficient. Receiver Operating Characteristic (ROC) curves were plotted to ascertain the sensitivity, specificity, and threshold values of lower extremity arterial ultrasound flow spectral parameters for the prediction of ERMF. The Youden index on the ROC curves identified the optimal threshold value. The area under the curve (AUC) and 95% confidence intervals (CIs) were calculated and reported to provide a complete statistical assessment.

3.1 Demographic Data

Out of 103 parturients initially enrolled in the study, 11 were excluded for the following reasons: gestational diabetes mellitus, gestational hypertension, the use of contraindicated medications, and acute infectious diseases. During labor, 19 parturients were removed from the study: three due to inadequate epidural analgesia, seven proceeded to cesarean section, eight presented with suboptimal arterial visualization, and one was temporarily withdrawn from the study. Finally, data were collected from 73 participants. Among these, 13 (17.8%) developed a fever and were classified as the febrile group, while 60 (82.2%) remained afebrile (Figure 1). Table 1 presents a summary of the primary demographic data and obstetric characteristics. The baseline demographics showed no significant differences between the febrile and afebrile groups (P > 0.05). However, the duration of both the total labor process and the second stage of labor was significantly longer in the febrile group compared to the afebrile group (P < 0.05).

3.2 Regional Blood Flow Spectral Parameters in the Febrile and Afebrile Groups

The baseline spectral parameters of ultrasound blood flow did not differ significantly between the febrile and afebrile patients (P > 0.05) (Figure 2). Following the administration of epidural local anesthetics (ELA), there was a significant increase in the blood flow spectral parameters—peak systolic velocity (PSV) and end-diastolic velocity (EDV)—for both the anterior tibial artery (ATA) and the posterior tibial artery (PTA) at 5 minutes post-anesthesia. This elevation continued progressively, with statistically significant deviations from the baseline observed at all subsequent time points (P < 0.05). Moreover, at 10 minutes post-ELA, the PSV values for ATA and PTA were significantly higher in the febrile group than those in the afebrile group (P < 0.05). Furthermore, the EDV for ATA and PTA in the febrile group displayed significant elevations at 15 minutes post-anesthesia when contrasted with the afebrile group (P < 0.01).

3.3 Spearman Correlation Analysis

Post-epidural labor analgesia, there was a tendency for core body temperature to increase incrementally, reaching a peak towards the end of the second stage of labor. Subsequently, the temperature began to fall as the labor process concluded. Similarly, PSV and EDV of both lower extremity arteries showed a gradual rise following analgesia. To investigate the relationship between these variables, we conducted a Spearman correlation analysis focusing on PSV₃₀ and EDV₃₀ concerning T_peak, as presented in Table 2. The analysis revealed a positive correlation between PSV₃₀ and EDV₃₀with Tpeak, as shown in Figure 3.

3.4 ROC Curve Predicts Epidural-Related Maternal Fever

Using the changes in blood flow parameters post-analgesia, ROC curves were generated for the rate of change in the ATA and PTA 30 minutes after analgesia to predict ERMF (Figure 4). Utilizing the Youden index, we identified the optimal cut-off value and calculated the AUC, and the corresponding sensitivity and specificity for the ERMF prediction. The detailed statistics are shown in Table 3.

In this research, we evaluated the degree of sympathetic blockade induced by ELA by quantifying blood flow spectral parameters using PWD US. The aim was to determine the predictive value of these parameters for the onset of ERMF. To our knowledge, this is the first study to examine the link between blood flow spectral parameters and ERMF. We measured regional blood flow spectral parameters in the anterior and posterior tibial arteries, which indicate sympathetic nervous system activity. These vessels' superficial and consistent anatomical positioning facilitates longitudinal ultrasound scanning, allowing for precise and reliable measurements.

Our findings revealed significant differences in PSV and EDV between the febrile and afebrile groups at 10 and 15 minutes post-ELA, respectively (P < 0.01). Sympathetic nerves solely innervate the blood vessels in the human limbs. During ELA, the blockade of sympathetic nerve fibers precedes motor and sensory block as the local anesthetic permeates the epidural space. This blockade triggers a vasodilatory effect, influencing local blood flow velocity, a phenomenon detectable through the spectral parameters assessed by PWD US^8,13. Previous research has employed the pulse perfusion index (PI) as an indicator for ERMF. Sun et al. found that individuals who developed a fever during labor exhibited significantly higher PI values commencing 10 minutes post-ELA, corroborating the time our study detected intergroup disparities⁹.

The thermoregulatory hypothesis posits that epidural labor analgesia (ELA) may interfere with maternal thermoregulation². Typically, during pregnancy, there is an enhanced sympathetic activation, a characteristic feature in normotensive women, further augmented by increased vasodilatory sympathetic activity compared to the nonpregnant state¹⁴. Conditions such as preeclampsia are believed to arise from an imbalance between excessive sympathetic activation and the vasodilatory responses that are typical during pregnancy^15,16. Consequently, preserving the equilibrium of the sympathetic nervous system is crucial throughout pregnancy. Labor and delivery are characterized by intense uterine contractions and considerable physical exertion, leading to elevated heat production⁵. In the case of fever, skin vasodilation during this period is mediated by sympathetic cholinergic fibers, facilitating 'active vasodilation' and thus promoting increased heat loss^5,17,18. We hypothesize that ELA might disrupt this delicate balance by inducing a 'chemical blockade' of the sympathetic nervous system, thus compromising the enhanced cooling mechanisms that are critical during labor.

Our hypothesis suggests that variations in the degree of sympathetic blockade may be a pathogenic factor contributing to ERMF, prompting us to analyze the correlation between blood flow spectral parameters and the participant’s body temperature. Prior research has documented a progressive rise in body temperature during labor, culminating at the termination of the second stage^9,19,20.We noted a similar gradual increase in blood flow spectral parameters following analgesia. Although our measurements were confined to a 30-minute post-analgesia window, and we cannot confirm these as peak values, the consistent analgesic level at 30 minutes indicates a relatively stable impact of the local anesthetic on sympathetic tone⁹. A positive correlation between PSV₃₀, EDV₃₀, and the peak body temperature during labor supports our initial hypothesis that a more pronounced sympathetic blockade intensifies the disturbance in autonomic function equilibrium and impedes heat dissipation, leading to a higher body temperature increase. Our findings highlight the potential involvement of the thermoregulatory hypothesis in ERMF development².

It is imperative to note the considerable individual variability in the ATA and PTA's baseline blood flow spectral parameters. Focusing on the relative changes in these parameters pre- and post-analgesia is more informative than the absolute values alone. A significant strength of this study is incorporating the change of these parameters with the incidence of ERMF in an ROC analysis to determine the AUC. The results demonstrate that the ΔEDV has a superior predictive value compared to the ΔPSV. (AUC: ATA ΔPSV 0.701; ATA ΔEDV 0.733; PTA ΔPSV 0.687; PTA ΔEDV 0.713). The reason may be that EDV better reflects vascular compliance and distal vascular resistance, whereas PSV is mainly influenced by cardiac functional status and vascular anatomy, and therefore EDV is more representative of the degree of sympathetic blockade. While the predictive sensitivity of these indicators is not exceedingly high, it is crucial to recognize that ERMF development is multifactorial, and disturbances in thermoregulation from epidural analgesia are only a part of the pathophysiological narrative and do not fully account for it^1,2,21. The data indicate that ΔPSV and ΔEDV in the ATA and PTA regions possess potential predictive merits for the occurrence of ERMF.

In clinical practice, direct measurement of SNA is not achievable; instead, we infer its activity through indirect methods. The previous study showed a PI with an AUC of 0.818 for ERMF prediction, higher than our study⁹. This variation may result from different anesthetic concentrations and doses used in the studies. Some participants were treated with ropivacaine at concentrations up to 0.15%. Lower concentrations of local anesthetics might lead to lesser sympathetic blockade than higher concentrations^22,23. Although PI is convenient clinically, its reliability can be significantly affected by uterine contractions during labor²⁴. Our study introduces a new predictor by utilizing changes in ultrasound spectral parameters (PSV, EDV), which could offer a more objective quantitative measure and minimize the influence of confounding factors.

The practical significance of this research is in defining critical values for the variability of blood flow spectral parameters. Maternal and fetal hyperthermia exposure is associated with adverse effects¹. The likelihood of ERMF increases when the ΔPSV of ATA and PTA is above 43.35 and 39.96, respectively, and the ΔEDV of ATA and PTA is above 29.94 and 33.10, respectively. Our findings also confirm that the total and second stages of labor are longer in febrile women, which is consistent with prior studies²⁵. Epidural analgesia, which blocks the sympathetic-motor nerve fibers, may reduce uterine contractility and extend labor. Prolonged labor and higher doses of local anesthetics are significant risk factors for maternal fever^1,23. Clinicians should monitor such patients closely, maintain labor progress, or consider lower anesthetic concentrations when feasible²⁰.

This study has its limitations. It was a prospective observational study with a small sample size, and single-center trials may not be as reliable as multicenter ones. The homogeneity of subjects also raises concerns about the applicability of these findings to parturients with conditions like gestational hypertension or gestational diabetes mellitus that could affect sympathetic nervous system. Future research should have an inclusive study population and pursue validation through more rigorous randomized controlled trials. Additionally, the anesthetic concentrations used were standard for our facility, and further studies are required to determine whether different concentrations affect the variability of these parameters.

In summary, the changes in regional blood flow spectral parameters post-epidural analgesia offer an indirect method to gauge the extent of sympathetic inhibition, which can predict the occurrence of ERMF. Notably, the changes in peak systolic velocity and end-diastolic velocity relative to the baseline, measured 30 minutes after ELA induction, emerged as the most predictive factors. These findings could enable clinicians to identify high-risk individuals more promptly, allowing for earlier interventions to enhance maternal and infant outcomes.

Ethics declarations

Ethical approval and consent to participate

This study was approved by the Ethics Committee of Women and Children's Hospital, School of Medicine, Xiamen University (KY-2024-009-K01). Written consent was obtained for all willing participants prior to registering for this study.

Consent for publication

Not applicable.

Data availability

The datasets used or analyzed in the study are available upon request from the corresponding author.

Conflict of interest

The authors declare that they have no conflict of interest.

Competing interests

The authors declare no competing interests.

Funding

None.

Contributions

F.S. designed the study and wrote the manuscript. P.L. performed the part of the experiment. Y.M.X. collected date. Y.C.L. analyzed the data revised the manuscript. J.X.J. supervised the study. All authors reviewed and approved the manuscript.

Acknowledgments

We thank Dr. Yupeng Wu for his assistance in the preparation of this manuscript

Goetzl L. Maternal fever in labor: etiologies, consequences, and clinical management. Am J Obstet Gynecol. 2023;228(5S):1274–82.
Patel S, Ciechanowicz S, Blumenfeld YJ, Sultan P. Epidural-related maternal fever: incidence, pathophysiology, outcomes, and management. Am J Obstet Gynecol. 2023;228(5S):1283–304.
Lieberman E, Cohen A, Lang J, Frigoletto F, Goetzl L. Maternal intrapartum temperature elevation as a risk factor for cesarean delivery and assisted vaginal delivery. Am J Public Health. 1999;89(4):506–10.
Jia L, Cao H, Guo Y, Shen Y, Zhang X, Feng Z, Liu J, Xie Z, Xu Z. Evaluation of Epidural Analgesia Use During Labor and Infection in Full-term Neonates Delivered Vaginally. JAMA Netw Open. 2021;4(9):e2123757.
Mullington CJ, Low DA, Strutton PH, Malhotra S. Body temperature, cutaneous heat loss and skin blood flow during epidural anaesthesia for emergency caesarean section. Anaesthesia. 2018;73(12):1500–6.
Eicke BM, Milke K, Schlereth T, Birklein F. Comparison of continuous wave Doppler ultrasound of the radial artery and laser Doppler flowmetry of the fingertips with sympathetic stimulation. J Neurol. 2004;251(8):958–62.
Lu B, Jiang J, Li X, Chen Q, Qin J, Chen Y, Chen J, Shen Q. Regional haemodynamic variables and perfusion index in the evaluation of sciatic nerve block: a prospective observational trial. BMJ Open. 2022;12(5):e057283.
Li J, Karmakar MK, Li X, Kwok WH, Ngan Kee WD. Regional hemodynamic changes after an axillary brachial plexus block: a pulsed-wave Doppler ultrasound study. Reg Anesth Pain Med. 2012;37(1):111–8.
Sun C, Ren S, Chen C, Liu Q, Lu P, Xia L, Shao D, Xu J. Pulse perfusion index for predicting intrapartum fever during epidural analgesia. J Clin Anesth. 2022;80:110852.
Obuchowski NA, McClish DK. Sample size determination for diagnostic accuracy studies involving binormal ROC curve indices. Stat Med. 1997;16(13):1529–42.
American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin 209: Obstetric Analgesia and Anesthesia. Obstet Gynecol. 2019;133(3):e208–25.
National Collaborating Centre for Women's and Children's Health (UK). Intrapartum Care: Care of Healthy Women and Their Babies During Childbirth. London: National Institute for Health and Care Excellence (UK); 2014.
Hermanns H, Werdehausen R, Hollmann MW, Stevens MF. Assessment of skin temperature during regional anaesthesia-What the anaesthesiologist should know. Acta Anaesthesiol Scand. 2018;62(9):1280–9.
Jarvis SS, Shibata S, Bivens TB, Okada Y, Casey BM, Levine BD, Fu Q. Sympathetic activation during early pregnancy in humans. J Physiol. 2012;590(15):3535–43.
Fischer T, Schobel HP, Frank H, Andreae M, Schneider KT, Heusser K. Pregnancy-induced sympathetic overactivity: a precursor of preeclampsia. Eur J Clin Invest. 2004;34(6):443–8.
Greenwall KM, Brislane Á, Matenchuk BA, Sivak A, Davenport MH, Steinback CD. Muscle sympathetic nerve activity during pregnancy: A systematic review and meta-analysis. Physiol Rep. 2023;11(5):e15626.
Fusi L, Steer PJ, Maresh MJ, Beard RW. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet. 1989;1(8649):1250–2.
Tsen LC. Too cold, too hot or just right? Temperature regulation during caesarean section. Anaesthesia. 2019;74(8):973–5.
Lavesson T, Källén K, Olofsson P. Fetal and maternal temperatures during labor and delivery: a prospective descriptive study. J Matern Fetal Neonatal Med. 2018;31(12):1533–41.
Goetzl L, Rivers J, Zighelboim I, Wali A, Badell M, Suresh MS. Intrapartum epidural analgesia and maternal temperature regulation. Obstet Gynecol. 2007;109(3):687–90.
Sultan P, Segal S. Epidural-Related Maternal Fever: Still a Hot Topic, But What Are the Burning Issues? Anesth Analg. 2020;130(2):318–20.
Zhou X, Li J, Deng S, Xu Z, Liu Z. Ropivacaine at different concentrations on intrapartum fever, IL-6 and TNF-α in parturient with epidural labor analgesia. Exp Ther Med. 2019;17(3):1631–6.
Yue HL, Shao LJ, Li J, Wang YN, Wang L, Han RQ. Effect of epidural analgesia with 0.075% ropivacaine versus 0.1% ropivacaine on the maternal temperature during labor: a randomized controlled study. Chin Med J (Engl). 2013;126(22):4301–5.
Ginosar Y, Weiniger CF, Meroz Y, Kurz V, Bdolah-Abram T, Babchenko A, Nitzan M, Davidson EM. Pulse oximeter perfusion index as an early indicator of sympathectomy after epidural anesthesia. Acta Anaesthesiol Scand. 2009;53(8):1018–26.
Callahan EC, Lee W, Aleshi P, George RB. Modern labor epidural analgesia: implications for labor outcomes and maternal-fetal health. Am J Obstet Gynecol. 2023;228(5S):1260–9.

Table 1: Characteristics of Study Subjects (N = 73)

Variables	Febrile Group (N=13, 17.8%)	Afebrile Group (N=60, 82.2%)	P value
Age (years)	28.46±2.37	29.63±2.88	0.176
Weight (kg)	69.04±6.64	68.16±8.57	0.728
Height (cm)	164.00±5.29	162.73±4.80	0.400
Gestational Age (weeks)	40 [39-40]	39 [39-40]	0.268
Cervical Dilation at Epidural Request (cm)	2 [2-2.5]	2 [2-2]	0.888
Basal Body Temperature (°C)	36.42±0.21	36.44±0.19	0.691
Total Duration of Labor (h)	12.7±3.0	10.4±3.5	0.026
First Stage of Labor (h)	11.0±3.1	9.3±3.3	0.085
Second Stage of Labor (h)	1.5 [1.2-1.85]	0.6 [0.4-1.4]	0.002
Third Stage of Labor (min)	7.1±7.2	7.8±5.4	0.237
Oxytocin Before ELA
Using Oxytocin	8 (61.5%)	31 (51.7%)	0.518
Without Oxytocin	5 (38.5%)	29 (48.3%)	-
Premature Rupture of Membranes	1 (7.7%)	15 (25%)	0.273
Blood Loss (mL)	250 [205-290]	230 [200-280]	0.307

Data are presented as mean ± standard deviation, median [interquartile range], or n (%).

Table 2 Correlation analysis of blood flow spectral parameters 30 min after ELA with the peak temperature (T_peak) in labor
	Parameters	r	R²	95%CI	P value
ATA	PSV₃₀	0.3137	0.1525	0.0833 to 0.5123	0.0069
ATA	EDV₃₀	0.4928	0.2371	0.2900 to 0.6532	<0.0001
PTA	PSV₃₀	0.2953	0.1216	0.0631 to 0.4972	0.0112
PTA	EDV₃₀	0.4731	0.2610	0.2663 to 0.6383	<0.0001
Abbreviations: ATA, anterior tibial artery; PTA, posterior tibial artery; PSV₃₀, peak systolic velocity 30 min after epidural analgesia; EDV₃₀, end-diastolic velocity 30 min after epidural analgesia; CI, confidence interval; ELA, epidural labor analgesia;

Table 3 Cut-off values for the amount of change of blood flow spectral parameters for 30 minutes of epidural labor analgesia
	Parameters	AUC	95%CI	Cut-off	Sensitivity	Specificity	P value
ATA	△PSV	0.701	0.525 to 0.878	>43.35	0.692	0.700	0.025
ATA	△EDV	0.733	0.590 to 0.877	>29.94	0.692	0.750	0.001
PTA	△PSV	0.687	0.514 to 0.860	>39.96	0.769	0.667	0.034
PTA	△EDV	0.713	0.558 to 0.869	>33.10	0.538	0.883	0.007
Abbreviations: ATA, anterior tibial artery; PTA, posterior tibial artery; EDV, end-diastolic velocity; PSV, peak systolic velocity; AUC, area under the receiver operating characteristic curve; △PSV = PSV₃₀-PSV₀; △EDV= EDV₃₀-EDV₀; PSV₀, peak systolic velocity before ELA; EDV₀, end-diastolic velocity before ELA; PSV₃₀, peak systolic velocity 30 min after ELA; EDV₃₀, end-diastolic velocity 30 min after ELA

No competing interests reported.

SupplementaryFigure1.tif

Regional Blood Flow Spectral Parameters as Predictors of Epidural-Related Maternal Fever: A Prospective Observational Study

Status:

Version 1

Abstract

Background

Method

Results

Conclusion

Trial registration

Figures

INTRODUCTION

METHODS

Research Design and Ethics

Recruitment of Subjects

Inclusion Criteria:

Exclusion Criteria:

Epidural Labor Analgesia Technical Protocol

Data Collection

2.5 Statistical Analyses

RESULTS

DISCUSSION

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1