Skip Navigation LinksHome > March 2007 - Volume 109 - Issue 3 > Intrapartum Epidural Analgesia and Maternal Temperature Regu...
Obstetrics & Gynecology:
doi: 10.1097/01.AOG.0000255976.14297.f6
Original Research

Intrapartum Epidural Analgesia and Maternal Temperature Regulation

Goetzl, Laura MD, MPH1; Rivers, Jose MD3; Zighelboim, Israel MD2; Wali, Ashutosh MD3; Badell, Martina MD4; Suresh, Maya S. MD3

Free Access
Article Outline
Collapse Box

Author Information

From the 1Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina; 2Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri; 3Department of Anesthesiology, Baylor College of Medicine, Houston, Texas; and 4Department of Obstetrics and Gynecology, Emory University, Atlanta, Georgia.

This study was supported by the National Institute of Child Health and Human Development, grant no. 1K12HD01426-01, and by the Berlex Foundation Scholar Award in Clinical Research.

Corresponding author: Laura Goetzl, MD, MPH, Department of Obstetrics & Gynecology, MUSC, 96 Jonathan Lucas Street, CSB 634, Charleston, SC 29425; e-mail: goetzl@musc.edu.

Collapse Box

Abstract

OBJECTIVE: To examine maternal temperature changes after epidural analgesia.

METHODS: A prospective cohort of nulliparas at term was monitored with hourly maternal tympanic temperatures after epidural analgesia (n=99). Temperature response after epidural analgesia was examined in the group as a whole. Subsequently, mean maternal temperature curves were compared between women who remained afebrile throughout labor (n=77) and women who developed intrapartum fever with body temperature greater than 100.4ºF (n=22). Baseline maternal characteristics were assessed.

RESULTS: Women who later developed intrapartum fever had a higher mean temperature within 1 hour after epidural analgesia. In contrast, women who remained afebrile had no increase in core temperature. During the first 4 hours after epidural analgesia initiation, women who later develop intrapartum fever have an increase in mean tympanic temperature of 0.33ºF per hour.

CONCLUSION: Epidural analgesia is not associated with increased temperature in the majority of women. Hyperthermia is an abnormal response confined to a minority subset, which occurs immediately after exposure. Our findings do not support a universal perturbation of maternal thermoregulation after epidural analgesia.

LEVEL OF EVIDENCE: II

The association between intrapartum epidural analgesia and maternal fever was first described in 19891 and has since been confirmed in multiple randomized controlled trials.2–4 Risk is largely confined to first-time mothers, who have the longest duration of exposure. The absolute risk of intrapartum temperature greater than 100.4ºF in nulliparas with epidural analgesia has been reported to range from 14.5% to 33%. The leading hypothesis regarding the mechanism of epidural fever has been an alteration in maternal thermoregulation.5 Two observational studies have prospectively followed maternal temperature after epidural analgesia with hourly temperature measurements. Fusi et al1 evaluated 18 women (13 nulliparas) after epidural analgesia and reported a significant rise in vaginal temperature after 6 hours. Camann et al6 evaluated 40 women (31 nulliparous) after epidural analgesia and reported a rise in mean maternal tympanic temperature of 0.6°C (1.1ºF) over baseline that was significant after 4 hours. Although these studies provided novel insights, the underlying assumption inherent in their study design was that maternal temperature response to epidural analgesia is uniform. The purpose of our study is to evaluate this assumption.

Back to Top | Article Outline

MATERIALS AND METHODS

Our study cohort consisted of full-term nulliparous women requesting epidural analgesia. The cohort was derived from the placebo arm of a recently published double-blind, placebo-controlled trial.7 Our investigations were approved by the Institutional Review Board at Baylor College of Medicine (Protocol H-11497). Inclusion criteria included nulliparity, full-term pregnancy (37 weeks or more), vertex presentation, singleton gestation, ability to provide informed consent, and request for epidural analgesia for control of labor pain. Subjects were excluded if their temperature at any time prior to epidural analgesia exceeded 99.4ºF. After epidural catheter placement maternal tympanic temperature was assessed hourly until delivery (Thermoscan Pro3000, Braun Medical, Kronberg, Germany). Room temperature was centrally maintained at 71.8±0.85ºF (TM99A, Cooper Instruments, Middlefield, CT), and independent temperature control was not available in labor rooms.

Statistical analysis was performed with SPSS 8.0 (SPSS Inc, Chicago, IL). Maternal temperatures were compared at each time point with the repeated measures analysis of variance. Rise in temperature over time was evaluated with repeated measures analysis of variance for a change over time. In addition, continuous variables were compared with the Student t test for normally distributed data and the Mann Whitney U test for nonparametric data. Rates were compared with the Fisher exact test. Two-tailed tests were used, and P<.05 was considered significant.

Back to Top | Article Outline

RESULTS

Among 101 nulliparous women, 99 had two or more tympanic temperature samplings before delivery and were included in the analysis. Fever (tympanic temperature greater than 100.4ºF) occurred in 22 (22.2%) at some point before delivery. Mean maternal tympanic temperature after epidural analgesia is shown in Figure 1. A rise in mean maternal tympanic temperature was observed over time, which became statistically significant 4 hours after initiation of epidural analgesia. The absolute rise in mean temperature over 8 hours was 1.3ºF. Of interest, the magnitude of the standard error bars indicates considerable variability. For subsequent analysis we stratified our cohort into those who eventually developed intrapartum fever and those who remained afebrile. The two groups were clinically indistinguishable with respect to their demographic characteristics, initial clinical indicators of infection, maternal temperature at epidural placement, white blood cell count, or group B streptococcus carriage rates (Table 1). Although not statistically significant, subjects who developed an intrapartum fever after epidural analgesia were on average 2.4 years older and carried infants who were 193 g heavier. During labor, intrapartum fever was most strongly associated with duration of exposure to epidural analgesia. Not surprisingly, fetal tachycardia was more frequent in febrile women because there is a strong known correlation between maternal temperature and fetal heart rate (r=0.91).1 No neonate born to a febrile mother had documented evidence of infection on surveillance blood cultures.

Fig. 1
Fig. 1
Image Tools
Table 1
Table 1
Image Tools

We subsequently reexamined mean maternal tympanic temperature over time stratified by ultimate intrapartum fever status (Fig. 2). We restricted our analysis to the first 4 hours after epidural analgesia to pinpoint thermoregulatory changes rather than acquired infection. In the 77 women (77.8%) who remained afebrile, epidural analgesia was not associated with any temperature increase during the 4 hours after catheter placement (P=.26). In contrast, in the subset of 22 women who subsequently became febrile, mean maternal temperature rose dramatically after initiation of epidural analgesia. This increase was significant as early as 1 hour after catheter placement (P<.05). Over the 4-hour interval, the rise in mean maternal tympanic temperature was 1.3ºF (0.33ºF per hour). In comparison to the unstratified temperature curve, the magnitude of the standard error bars indicates less variability within each subgroup.

Fig. 2
Fig. 2
Image Tools
Back to Top | Article Outline

DISCUSSION

To our knowledge, this study represents the largest prospective cohort with hourly evaluation of maternal temperature after epidural analgesia (MEDLINE search January 1966 to November 2006; keywords: “hyperthermia,” “temperature,” “fever,” “epidural analgesia,” “labor”). When the cohort is examined as a whole, our results closely resemble the findings of Camann et al (1.3ºF versus 1.1ºF over 8 hours).6 However, the larger size of our cohort allowed us to present a stratified analysis that reveals a bimodal temperature response among nulliparous patients receiving epidural analgesia. The majority of women do not demonstrate an increase in mean tympanic temperature after epidural analgesia. In contrast, a minority subset of women demonstrates a brisk temperature response of higher magnitude than has been previously reported (0.33ºF per hour). Our findings do not support the current theory of a universal perturbation in maternal thermoregulation after epidural analgesia. Hyperthermia appears to be an abnormal response that occurs only in a relatively small subset of women at term. Our recent randomized controlled trial demonstrating that prophylactic maternal methylprednisolone (100 mg intravenously every 4 hours) reduced the rate of intrapartum fever after epidural analgesia by more than 90% also suggests an inflammatory, rather than a thermoregulatory, etiology.7

Of equal interest, those women who respond to epidural analgesia with hyperthermia do so immediately. A significant increase in maternal temperature was observed just 1 hour after epidural placement. This early onset of maternal temperature response precedes the accumulation of other maternal exposures to known risk factors for chorioamnionitis (eg, vaginal exams, prolonged membrane rupture). This rapid temperature rise suggests that factors which mediate alterations in maternal temperature response are already present in early labor and that identification of women at risk of subsequent fever may be possible. Although the two subsets of women receiving epidural analgesia appear clinically similar, they may have subclinical alterations in serum or cerebral spinal fluid markers, including altered levels of pro- or anti-inflammatory cytokines. Of note, women with the tumour necrosis factor (TNF) α Δ308 polymorphism, which increases levels of this pro-inflammatory cytokine, have an increased risk of intrapartum fever (24.4%) compared with controls with a relative risk of 3.3 (95% confidence interval 1.3–7.1).8 Currently, our group is actively investigating underlying maternal inflammatory balance to develop a strategy for early identification of women at high risk for subsequent intrapartum fever.

Early identification is critical if intervention to prevent fetal exposure to intrauterine hyperthermia and inflammation is found to be beneficial. Recent reports of neonatal hypothermia to treat hypoxic encephalopathy have refocused clinical attention on the interrelationship between fetal and neonatal brain temperature and the extent of brain injury after a hypoxic insult.9,10 Fetal hyperthermia at term (potentially in combination with intrauterine inflammation) is associated with a more than 4-fold increased risk of neonatal encephalopathy,11 and a 4- to 9-fold increased risk of cerebral palsy.12,13 Most recently, data has linked fetal cytokine polymorphisms, including heterozygous carriage of the Δ308 polymorphism of TNF α, to an increased risk of cerebral palsy in term infants.14 The fetal contribution to maternal temperature response is not known, but is an active area of research. Alternatively, fetal cytokine polymorphisms may reflect inherited maternal polymorphisms.

Back to Top | Article Outline

REFERENCES

1. Fusi L, Steer PJ, Maresh MJ, Beard RW, et al. Maternal pyrexia associated with the use of epidural analgesia in labour. Lancet 1989;1:1250–2.

2. Sharma SK, Alexander JM, Messick G, Bloom SL, McIntire DD, Wiley J, et al. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology 2002;96:546–51.

3. Philip J, Alexander JM, Sharma SK, Leveno KJ, McIntire DD, Wiley J. Epidural analgesia during labor and maternal fever. Anesthesiology 1999;90:1271–5.

4. Ramin SM, Gambling DR, Lucas MJ, Sharma SK, Sidawi JE, Leveno KJ. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol 1995;86:783–9.

5. Eltzschig HK, Lieberman ES, Camann WR. Regional anesthesia and analgesia for labor and delivery. N Engl J Med 2003;348:319–32.

6. Camann WR, Hortvet LA, Hughes N, Bader AM, Datta S. Maternal temperature regulation during extradural analgesia for labour. Br J Anaesth 1991;67:565–8.

7. Goetzl L, Zighelboim I, Badell M, Rivers J, Mastrangelo MA, Tweardy DJ, Suresh MS. Maternal corticosteroids to prevent intrauterine exposure to hyperthermia and inflammation: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol 2006;195:1031–7.

8. Simhan HN, Krohn MA, Zeevi A, Daftary A, Harger G, Caritis SN. Tumor necrosis factor-α promoter gene polymorphism -308 and chorioamnionitis. Obstet Gynecol 2003;102:162–6.

9. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomized trial. Lancet 2005;365:663–70.

10. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574–84.

11. Impey L, Greenwood C, MacQuillan K, Reynolds M, Sheil O. Fever in labour and neonatal encephalopathy: a prospective cohort study. BJOG 2001;108:594–7.

12. Wu YW, Escobar GJ, Grether JK, Croen LA, Greene JD, Newman TB. Chorioamnionitis and cerebral palsy in term and near-term infants. JAMA 2003;290:2677–84.

13. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight [published erratum appears in JAMA 1998;279:118]. JAMA 1997;278:207–11.

14. Gibson CS, MacLennan AH, Goldwater PN, Haan EA, Priest K, Dekker AG. The association between inherited cytokine polymorphisms and cerebral palsy. Am J Obstet Gynecol 2006;194:674.e1–e11.

Cited By:

This article has been cited 6 time(s).

Clinics in Perinatology
The Association Between Epidural Labor Analgesia and Maternal Fever
Arendt, KW; Segal, BS
Clinics in Perinatology, 40(3): 385-+.
10.1016/j.clp.2013.06.002
CrossRef
Pediatric Infectious Disease Journal
Approach to term neonates born after maternal intrapartum fever and unknown maternal group B Streptococcus status - Value of serum C-reactive protein and 16s rRNA gene pcr amplification
Makhoul, IR; Sprecher, H; Smolkin, T; Sawaid, R; Ben-David, S; Sujov, P; Tamir, A; Kassis, I; Blazer, S
Pediatric Infectious Disease Journal, 26(): 1064-1066.
10.1097/INT.0b013e31812f5701
CrossRef
American Journal of Obstetrics and Gynecology
When to stop pushing: effects of duration of second-stage expulsion efforts on maternal and neonatal outcomes in nulliparous women with epidural analgesia
Le Ray, C; Audibert, F; Goffinet, F; Fraser, W
American Journal of Obstetrics and Gynecology, 201(4): -.
ARTN 361.e1
CrossRef
International Journal of Obstetric Anesthesia
The incidence of maternal fever during labor is less with intermittent than with continuous epidural analgesia: a randomized controlled trial
Mantha, VRR; Vallejo, MC; Ramesh, V; Phelps, AL; Ramanathan, S
International Journal of Obstetric Anesthesia, 17(2): 123-129.
10.1016/j.ijoa.2007.07.006
CrossRef
New England Journal of Medicine
Epidural Analgesia for Labor and Delivery
Hawkins, JL
New England Journal of Medicine, 362(): 1503-1510.

Anesthesiology
Temperature Monitoring and Perioperative Thermoregulation
Sessler, DI
Anesthesiology, 109(2): 318-338.
10.1097/ALN.0b013e31817f6d76
PDF (737) | CrossRef
Back to Top | Article Outline

© 2007 The American College of Obstetricians and Gynecologists

Login

Article Tools

Images

Share