Labor Epidural Fever and Chorioamnionitis
Michael A. Fro¨lich, MD, MS Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama
Epidural analgesia has emerged as the gold standard of pain relief for women in labor. It provides the most effective form of analgesia, with minimal transfer of drugs to the fetus. This method has withstood a very exhaustive exploration of intended and unintended effects over time,1 but episodically cautionary and, at times, profoundly critical remarks have resurfaced. Some obstetricians felt that epidural analgesia might cause detrimental changes in labor patterns, whereas some suggested an adverse effect on the cesarean section rate, a possible increased incidence of postpartum back pain and interference with breastfeeding. Many problems are attributed to the technique without appropriate scientific assessment.2 The most recent cause of concern to pregnant women, however, is the notion that epidural analgesia could cause fever3 and, as a consequence, neonatal encephalopathy.4,5 In this review, background on the topic of maternal fever and a discussion of the artifactual association of fever and the use of epidural analgesia for labor will be discussed. ’
Fever
Fever can be described as an elevation of the central thermoregulatory set point, largely achieved by disinhibiting thermogenesis. This definition is the result of over 100 years of research, during which the molecules mediating the fever response have been identified. Some were discovered only recently by groups investigating not exclusively fever but temperature homeostasis in general. Fever alone rarely revealed the nature of a pathology conclusively. The investigation into the mechanism causing fever led to the description of pyrogens, substances that can induce fever. One of the best studied exogenous REPRINTS: MICHAEL A. FRO¨LICH, MD, MS, DEPARTMENT OF ANESTHESIOLOGY, UNIVERSITY OF ALABAMA AT BIRMINGHAM, 619 19TH STREET SOUTH, JEFFERSON TOWER SUITE 868C, BIRMIGHAM, AL 35249. E-MAIL: [email protected]. INTERNATIONAL ANESTHESIOLOGY CLINICS Volume 52, Number 3, 101–109 r 2014, Lippincott Williams & Wilkins
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pyrogens utilized in the study of fever is the bacterial lysate from gramnegative bacteria.6 The key pyrogenic component of the lysate was determined in fractionation experiments to be the bacterial cell wall component lipopolysaccharide (Fig. 1). In addition to this exogenous pyrogen, several endogenous pyrogens, including interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), corticotropinreleasing hormone and others were discovered. It was shown that the antipyretic action of aspirin is because of its ability to inhibit cyclooxygenase, the rate-limiting enzyme in prostaglandin H2 and PGE2 synthesis, thus displaying antipyretic properties that are independent of the type of exogenous pyrogen causing the fever response.7,8 These findings contributed to the designation of PGE2 as the ultimate endogenous pyrogen.9 How PGE2 changes the “hypothalamic set point,” thus triggering the fever response, is yet to be determined and needs to be investigated at the cellular and molecular level. When we evaluate the effects of fever, it should be noted that there is no evidence that children with fever, as opposed to hyperthermia, are at increased risk of adverse outcomes such as brain damage.10–14 Fever is a common and normal physiological response that results in an increase in the hypothalamic “set point” in response to endogenous and exogenous pyrogens.11,13 A primary goal of treating the febrile child should be to improve the child’s overall comfort. These observations are important in the face of recent publications to suggest that maternal fever could affect neonatal brain function.4,5 ’
Chorioamnionitis
In the setting of chorioamnionitis, for which maternal fever is a hallmark symptom, there seems to be evidence to suggest that the neonate maybe adversely affected. A meta-analysis published in 2000 evaluated the relationship between chorioamnionitis and cerebral palsy. The authors reported that clinical chorioamnionitis was significantly associated with cerebral palsy.15 These findings were confirmed in a more recent meta-analysis that focused more on the infectious etiology and the molecular diagnosis of this infection.16 The authors postulate that the infectious microorganisms or their products may gain access to the fetus and trigger a systemic fetal inflammatory response. In Figure 1. Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide found in the membrane of gram-negative bacteria, which act as endotoxins and pyrogens, and elicit strong immune response in animals. LPS are comprised of the O-antigen or O-polysaccharide, the core oligosaccharide, and the lipid A. Copyright r 2000, 2001, 2002 Free Software Foundation Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301. Everyone is permitted to copy and distribute verbatim copies of this license document, but changing it is not allowed. Version 1.2, November 2002. www.anesthesiaclinics.com
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Figure 2. Routes of infection. Chorioamnionitis is an acute inflammation of the membranes and chorion of the placenta, typically due to ascending polymicrobial bacterial infection in the setting of rupture of the membranes. The pathogenesis of chorioamnionitis is marked by the passage of infectious organisms to the chorioamnion or umbilical cord of the placenta.
addition, the maternal release of exotoxins and endotoxins stimulates leukocyte migration and the production and release of inflammatory cytokines, including TNF-a, IL-1, IL-6, IL-8, and granulocyte colonystimulating factors.17,18 The concern surrounding neonatal effects of maternal fever was augmented by reports from Impey et al4,5 who found a significant association between maternal fever and neonatal encephalopathy. As maternal fever is the hallmark of chorioamnionitis, the observed association in these large cohorts is not astonishing. Perhaps more surprising is the narrow interpretation of Impey et al5 to suggest that maternal fever is the cause of neonatal brain damage rather than exploring the effects of the underlying maternal condition, in most cases chorioamnionitis, on the fetus. Fortunately, these claims have not resulted in unnecessary neonatal sepsis work-ups as the neonatal evaluation for sepsis and/or meningitis is typically based on neonatal symptoms such as lethargy, trouble feeding, or hepatosplenomegaly rather than maternal symptoms alone.19 Clinically, maternal fever is almost synonymous with chorioamnionitis, an acute inflammation of the membranes of the chorion of the placenta, typically due to ascending polymicrobial bacterial infection in the setting of rupture of membranes (Fig. 2). Although low-grade fever (< 1011F) is occasionally recorded in otherwise asymptomatic patients, temperature >100.41F persisting >1 hour warrants further evaluation. www.anesthesiaclinics.com
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Clinical signs associated with clinical chorioamnionitis include fever, uterine fundal tenderness, maternal tachycardia (> 100/min), fetal tachycardia (> 160/min), and purulent or foul amniotic fluid.20–22 The clinical diagnosis can be supported by maternal leukocytosis, and high levels of C-reactive protein and IL-6. The role of chorioamnionitis in the pathogenesis of neonatal complications is increasingly accepted.23 Several other conditions should be considered in the differential diagnosis of chorioamnionitis. Extrauterine infections can cause fever and abdominal pain, during or in the absence of labor, including urinary tract infection (pyelonephritis), influenza, appendicitis, and pneumonia. Noninfectious conditions associated with abdominal pain (usually in the absence of fever) include thrombophlebitis, round ligament pain, colitis, connective tissue disorders, and placental abruption.
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Epidural Analgesia and Fever
With the increasing use of neuraxial anesthesia in obstetrics, a large proportion of women with ensuing or fully established chorioamnionitis will have epidural analgesia for labor. Therefore, fever in the setting of epidural anesthesia, particularly among nulliparous women with prolonged labor (so-called epidural fever), is often encountered. When compared with women who receive parenteral forms of analgesia, a larger proportion of women with epidural analgesia tend to have fever because the 2 conditions share other major risk factors, such as low parity, prolonged labor, and frequent pelvic examinations.24 Despite the likely artificial association of epidural analgesia and maternal fever, a few investigators continued to publish statements that would have the casual reader think that there is a causal relationship when, in fact, firm evidence to support such a claim is nonexistent. For example, in a recent study, Goetzl et al25 recruited term pregnant women who had epidural analgesia and noted that some women developed fever. In their discussion, they then stated that “temperature rose dramatically after initiation of epidural analgesia,” suggesting that fever was attributable to the epidural technique without pointing out that all women had this type of analgesia and that any of the known causes of fever such as chorioamnionitis would be a far more likely etiology. Similarly, Greenwell et al26 concluded that “Among low-risk women receiving epidural analgesia, intrapartum maternal temperature >99.51F was associated with adverse neonatal outcomes,” without highlighting that prolonged labor was a highly significant (P < 0.0001) predictor that offered a much more plausible explanation of the observed association. As Segal27 noted in a recent review article, studies that make mention of maternal temperature while investigating effects of labor analgesia can be categorized as observational28–32 and www.anesthesiaclinics.com
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randomized controlled trials.33–37 The common thread among those studies is that although there is a higher proportion of mothers who have Z1 temperature reading >100.41F in the epidural group, patients receiving epidural analgesia also tend to have longer labor, one of the known risk factors for chorioamnionitis. The observed association is therefore likely noncausal. It is not surprising that epidural analgesia is associated with intrapartum fever only in the presence of placental inflammation as noted by Dashe et al.38 From a physiological point of view, Bromage39 pointed out that epidural analgesia affects a variety of human thermoregulatory mechanisms by its blockade of the sympathetic nervous system. As, in his view, the majority of these changes result in heat retention, he believed that “there is a tendency for heat retention to occur in warm surroundings.” Contrary to this idea by Bromage is the observation by Holdcroft et al40 who showed that, in surgical patients, sympathetic blockade caused by epidural anesthesia results in hypothermia from the redistribution of heat from the core to the periphery, and thus a net heat loss to the environment. Because maternal temperature recordings were a secondary observation in most studies, we recently designed a prospective cohort study in women scheduled for induced labor, specifically designed to evaluate several possible factors that could affect maternal temperature.41 We measured hourly temperatures from the time of admission to the labor floor until delivery and recorded length of labor, length of membrane rupture, parity, body mass index, white
Figure 3. Temperature course during labor. Boxplots of temperatures from 86 women scheduled for elective labor induction. This graph depicts the summary information of temperatures. Individual temperature slopes (not depicted) show mixed (positive and negative) trends. Linear and cubic fit lines are also displayed. www.anesthesiaclinics.com
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blood cell count, group B streptococcus status, oxytocin dose, and labor intensity using Montevideo units (a method of quantifying uterine activity during labor based on intrauterine pressure measurements). We carefully excluded women with infections and medications that might alter maternal temperature. The goal of our study was 3-fold: to evaluate whether, on average, maternal temperature increased during labor, whether this observation was uniformly observed in all women, and to identify intrapartum risk factors for maternal fever. We observed that almost an equal number of women showed a slight temperature decrease as women who showed a temperature increase. On average, however, we found a clinically insignificant temperature rise of 0.31F/ 10 h (Fig. 3). One of the most important findings was that the placement of the epidural catheter did not alter the temperature trend in laboring women. In other words, any temperature increase observed was present before the epidural catheter was placed. As noted by others, we identified a longer time from rupture of membranes to delivery and increased maternal body mass index as risk factors for maternal fever. ’
Summary and Clinical Implications
Maternal temperature varies during labor. On average, there is a small but clinically insignificant rise in temperature and this positive trend in maternal temperature is more frequently observed in women receiving epidural analgesia. The latter group of women requesting neuraxial pain relief are also more likely to have longer labor, more frequent pelvic examinations and chorioamnionitis, and an observed temperature trend, positive or negative, is not changed when epidural analgesia is started. The scientific evidence does not support a claim that epidural analgesia affects maternal fever, a classic symptom of chorioamnionitis that, if unrecognized or untreated, can pose a serious threat to the mother and baby.
The author has no conflicts of interest to disclose.
’
References
1. Leighton BL, Halpern SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systematic review. Am J Obstet Gynecol. 2002;186(suppl Nature): S69–S77. 2. Halpern SH, Leighton BL. Misconceptions about neuraxial analgesia. Anesthesiol Clin North America. 2003;21:59–70. 3. Goetzl L. Epidural analgesia and maternal fever: a clinical and research update. Curr Opin Anesthesiol. 2012;25:292–299. www.anesthesiaclinics.com
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4. Impey L, Greenwood C, MacQuillan K, et al. Fever in labour and neonatal encephalopathy: a prospective cohort study. BJOG. 2001;108:594–597. 5. Impey LW, Greenwood CE, Black RS, et al. The relationship between intrapartum maternal fever and neonatal acidosis as risk factors for neonatal encephalopathy. Am J Obstet Gynecol. 2008;198:49.e1–49.e6. 6. Blatteis CM, Hunter WS, Busija DW, et al. Thermoregulatory and acute-phase responses to endotoxin of full-term-pregnant rabbits. J Appl Physiol. 1986;60: 1578–1583. 7. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirinlike drugs. Nat New Biol. 1971;231:232–235. 8. Vane JR, Botting RM. Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997;26(suppl 1):2–10. 9. Oka T. Prostaglandin E2 as a mediator of fever: the role of prostaglandin E (EP) receptors. Front Biosci. 2004;9:3046–3057. 10. Steering Committee on Quality Improvement and Management SoFSAAoP. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008;121:1281–1286. 11. Bouchama A, Knochel JP. Heat stroke. N Engl J Med. 2002;346:1978–1988. 12. El-Radhi AS. Why is the evidence not affecting the practice of fever management? Arch Dis Child. 2008;93:918–920. 13. Kohl KS, Marcy SM, Blum M, et al. Fever after immunization: current concepts and improved future scientific understanding. Clin Infect Dis. 2004;39:389–394. 14. Schmitt BD. Fever in childhood. Pediatrics. 1984;74(pt 2):929–936. 15. Wu YW, Colford JM Jr. Chorioamnionitis as a risk factor for cerebral palsy: a metaanalysis. JAMA. 2000;284:1417–1424. 16. Shatrov JG, Birch SC, Lam LT, et al. Chorioamnionitis and cerebral palsy: a metaanalysis. Obstet Gynecol. 2010;116(pt 1):387–392. 17. Garland SM, Ni Chuileannain F, Satzke C, et al. Mechanisms, organisms and markers of infection in pregnancy. J Reprod Immunol. 2002;57:169–183. 18. Terzidou V. Preterm labour. Biochemical and endocrinological preparation for parturition. Best Pract Res Clin Obstet Gynaecol. 2007;21:729–756. 19. Escobar GJ. The neonatal “sepsis work-up”: personal reflections on the development of an evidence-based approach toward newborn infections in a managed care organization. Pediatrics. 1999;103(suppl E):360–373. 20. Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intraamniotic infection. Am J Obstet Gynecol. 1991;164(pt 1):1317–1326. 21. Newton ER. Chorioamnionitis and intraamniotic infection. Clin Obstet Gynecol. 1993;36:795–808. 22. Riggs JW, JD Blanco. Pathophysiology diagnosis, and management of intraamniotic infection. Seminars in perinatology. 1998;22:251–259. 23. Cassell GH, Waites KB, Watson HL, et al. Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns. Clin Microbiol Rev. 1993;6: 69–87. 24. Apantaku O, Mulik V. Maternal intra-partum fever. J Obstet Gynaecol. 2007;27:12–15. 25. Goetzl L, Rivers J, Zighelboim I, et al. Intrapartum epidural analgesia and maternal temperature regulation. Obstet Gynecol. 2007;109:687–690. 26. Greenwell EA, Wyshak G, Ringer SA, et al. Intrapartum temperature elevation, epidural use, and adverse outcome in term infants. Pediatrics. 2012;129:e447–e454. 27. Segal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111:1467–1475. 28. Herbst A, Wolner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol. 1995;86:790–794. 29. Kaul B, Vallejo M, Ramanathan S, et al. Epidural labor analgesia and neonatal sepsis evaluation rate: a quality improvement study. Anesth Analg. 2001;93:986–990. www.anesthesiaclinics.com
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30. Lieberman E, Lang JM, Frigoletto F Jr, et al. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics. 1997;99:415–419. 31. Ploeckinger B, Ulm MR, Chalubinski K, et al. Epidural anaesthesia in labour: influence on surgical delivery rates, intrapartum fever and blood loss. Gynecol Obstet Invest. 1995;39:24–27. 32. Vinson DC, Thomas R, Kiser T. Association between epidural analgesia during labor and fever. J Fam Pract. 1993;36:617–622. 33. Hocquelet C, Cormier P, Leng JJ, et al. Hyperthermia during labor. Role of peridural analgesia. Rev Fr Gynecol Obstet. 1989;84:737–741. 34. Lucas MJ, Sharma SK, McIntire DD, et al. A randomized trial of labor analgesia in women with pregnancy-induced hypertension. Am J Obstet Gynecol. 2001;185: 970–975. 35. Ramin SM, Gambling DR, Lucas MJ, et al. Randomized trial of epidural versus intravenous analgesia during labor. Obstet Gynecol. 1995;86:783–789. 36. Sharma SK, Alexander JM, Messick G, et al. Cesarean delivery: a randomized trial of epidural analgesia versus intravenous meperidine analgesia during labor in nulliparous women. Anesthesiology. 2002;96:546–551. 37. Sharma SK, Sidawi JE, Ramin SM, et al. Cesarean delivery: a randomized trial of epidural versus patient-controlled meperidine analgesia during labor. Anesthesiology. 1997;87:487–494. 38. Dashe JS, Rogers BB, McIntire DD, et al. Epidural analgesia and intrapartum fever: placental findings. Obstet Gynecol. 1999;93:341–344. 39. Bromage PR. Spinal Epidural Analgesia. Baltimore: Lippincott Williams & Wilkins; 1954. 40. Holdcroft A, Hall GM, Cooper GM. Redistribution of body heat during anaesthesia. A comparison of halothane, fentanyl and epidural anaesthesia. Anaesthesia. 1979; 34:758–764. 41. Frolich MA, Esame A, Zhang K, et al. What factors affect intrapartum maternal temperature? A prospective cohort study: maternal intrapartum temperature. Anesthesiology. 2012;117:302–308.
www.anesthesiaclinics.com
Michael A. Fro¨lich, MD, MS Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama
Epidural analgesia has emerged as the gold standard of pain relief for women in labor. It provides the most effective form of analgesia, with minimal transfer of drugs to the fetus. This method has withstood a very exhaustive exploration of intended and unintended effects over time,1 but episodically cautionary and, at times, profoundly critical remarks have resurfaced. Some obstetricians felt that epidural analgesia might cause detrimental changes in labor patterns, whereas some suggested an adverse effect on the cesarean section rate, a possible increased incidence of postpartum back pain and interference with breastfeeding. Many problems are attributed to the technique without appropriate scientific assessment.2 The most recent cause of concern to pregnant women, however, is the notion that epidural analgesia could cause fever3 and, as a consequence, neonatal encephalopathy.4,5 In this review, background on the topic of maternal fever and a discussion of the artifactual association of fever and the use of epidural analgesia for labor will be discussed. ’
Fever
Fever can be described as an elevation of the central thermoregulatory set point, largely achieved by disinhibiting thermogenesis. This definition is the result of over 100 years of research, during which the molecules mediating the fever response have been identified. Some were discovered only recently by groups investigating not exclusively fever but temperature homeostasis in general. Fever alone rarely revealed the nature of a pathology conclusively. The investigation into the mechanism causing fever led to the description of pyrogens, substances that can induce fever. One of the best studied exogenous REPRINTS: MICHAEL A. FRO¨LICH, MD, MS, DEPARTMENT OF ANESTHESIOLOGY, UNIVERSITY OF ALABAMA AT BIRMINGHAM, 619 19TH STREET SOUTH, JEFFERSON TOWER SUITE 868C, BIRMIGHAM, AL 35249. E-MAIL: [email protected]. INTERNATIONAL ANESTHESIOLOGY CLINICS Volume 52, Number 3, 101–109 r 2014, Lippincott Williams & Wilkins
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pyrogens utilized in the study of fever is the bacterial lysate from gramnegative bacteria.6 The key pyrogenic component of the lysate was determined in fractionation experiments to be the bacterial cell wall component lipopolysaccharide (Fig. 1). In addition to this exogenous pyrogen, several endogenous pyrogens, including interleukin-1 (IL-1), tumor necrosis factor (TNF), prostaglandin E2 (PGE2), corticotropinreleasing hormone and others were discovered. It was shown that the antipyretic action of aspirin is because of its ability to inhibit cyclooxygenase, the rate-limiting enzyme in prostaglandin H2 and PGE2 synthesis, thus displaying antipyretic properties that are independent of the type of exogenous pyrogen causing the fever response.7,8 These findings contributed to the designation of PGE2 as the ultimate endogenous pyrogen.9 How PGE2 changes the “hypothalamic set point,” thus triggering the fever response, is yet to be determined and needs to be investigated at the cellular and molecular level. When we evaluate the effects of fever, it should be noted that there is no evidence that children with fever, as opposed to hyperthermia, are at increased risk of adverse outcomes such as brain damage.10–14 Fever is a common and normal physiological response that results in an increase in the hypothalamic “set point” in response to endogenous and exogenous pyrogens.11,13 A primary goal of treating the febrile child should be to improve the child’s overall comfort. These observations are important in the face of recent publications to suggest that maternal fever could affect neonatal brain function.4,5 ’
Chorioamnionitis
In the setting of chorioamnionitis, for which maternal fever is a hallmark symptom, there seems to be evidence to suggest that the neonate maybe adversely affected. A meta-analysis published in 2000 evaluated the relationship between chorioamnionitis and cerebral palsy. The authors reported that clinical chorioamnionitis was significantly associated with cerebral palsy.15 These findings were confirmed in a more recent meta-analysis that focused more on the infectious etiology and the molecular diagnosis of this infection.16 The authors postulate that the infectious microorganisms or their products may gain access to the fetus and trigger a systemic fetal inflammatory response. In Figure 1. Lipopolysaccharides (LPS), also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide found in the membrane of gram-negative bacteria, which act as endotoxins and pyrogens, and elicit strong immune response in animals. LPS are comprised of the O-antigen or O-polysaccharide, the core oligosaccharide, and the lipid A. Copyright r 2000, 2001, 2002 Free Software Foundation Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301. Everyone is permitted to copy and distribute verbatim copies of this license document, but changing it is not allowed. Version 1.2, November 2002. www.anesthesiaclinics.com
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Figure 2. Routes of infection. Chorioamnionitis is an acute inflammation of the membranes and chorion of the placenta, typically due to ascending polymicrobial bacterial infection in the setting of rupture of the membranes. The pathogenesis of chorioamnionitis is marked by the passage of infectious organisms to the chorioamnion or umbilical cord of the placenta.
addition, the maternal release of exotoxins and endotoxins stimulates leukocyte migration and the production and release of inflammatory cytokines, including TNF-a, IL-1, IL-6, IL-8, and granulocyte colonystimulating factors.17,18 The concern surrounding neonatal effects of maternal fever was augmented by reports from Impey et al4,5 who found a significant association between maternal fever and neonatal encephalopathy. As maternal fever is the hallmark of chorioamnionitis, the observed association in these large cohorts is not astonishing. Perhaps more surprising is the narrow interpretation of Impey et al5 to suggest that maternal fever is the cause of neonatal brain damage rather than exploring the effects of the underlying maternal condition, in most cases chorioamnionitis, on the fetus. Fortunately, these claims have not resulted in unnecessary neonatal sepsis work-ups as the neonatal evaluation for sepsis and/or meningitis is typically based on neonatal symptoms such as lethargy, trouble feeding, or hepatosplenomegaly rather than maternal symptoms alone.19 Clinically, maternal fever is almost synonymous with chorioamnionitis, an acute inflammation of the membranes of the chorion of the placenta, typically due to ascending polymicrobial bacterial infection in the setting of rupture of membranes (Fig. 2). Although low-grade fever (< 1011F) is occasionally recorded in otherwise asymptomatic patients, temperature >100.41F persisting >1 hour warrants further evaluation. www.anesthesiaclinics.com
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Clinical signs associated with clinical chorioamnionitis include fever, uterine fundal tenderness, maternal tachycardia (> 100/min), fetal tachycardia (> 160/min), and purulent or foul amniotic fluid.20–22 The clinical diagnosis can be supported by maternal leukocytosis, and high levels of C-reactive protein and IL-6. The role of chorioamnionitis in the pathogenesis of neonatal complications is increasingly accepted.23 Several other conditions should be considered in the differential diagnosis of chorioamnionitis. Extrauterine infections can cause fever and abdominal pain, during or in the absence of labor, including urinary tract infection (pyelonephritis), influenza, appendicitis, and pneumonia. Noninfectious conditions associated with abdominal pain (usually in the absence of fever) include thrombophlebitis, round ligament pain, colitis, connective tissue disorders, and placental abruption.
’
Epidural Analgesia and Fever
With the increasing use of neuraxial anesthesia in obstetrics, a large proportion of women with ensuing or fully established chorioamnionitis will have epidural analgesia for labor. Therefore, fever in the setting of epidural anesthesia, particularly among nulliparous women with prolonged labor (so-called epidural fever), is often encountered. When compared with women who receive parenteral forms of analgesia, a larger proportion of women with epidural analgesia tend to have fever because the 2 conditions share other major risk factors, such as low parity, prolonged labor, and frequent pelvic examinations.24 Despite the likely artificial association of epidural analgesia and maternal fever, a few investigators continued to publish statements that would have the casual reader think that there is a causal relationship when, in fact, firm evidence to support such a claim is nonexistent. For example, in a recent study, Goetzl et al25 recruited term pregnant women who had epidural analgesia and noted that some women developed fever. In their discussion, they then stated that “temperature rose dramatically after initiation of epidural analgesia,” suggesting that fever was attributable to the epidural technique without pointing out that all women had this type of analgesia and that any of the known causes of fever such as chorioamnionitis would be a far more likely etiology. Similarly, Greenwell et al26 concluded that “Among low-risk women receiving epidural analgesia, intrapartum maternal temperature >99.51F was associated with adverse neonatal outcomes,” without highlighting that prolonged labor was a highly significant (P < 0.0001) predictor that offered a much more plausible explanation of the observed association. As Segal27 noted in a recent review article, studies that make mention of maternal temperature while investigating effects of labor analgesia can be categorized as observational28–32 and www.anesthesiaclinics.com
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randomized controlled trials.33–37 The common thread among those studies is that although there is a higher proportion of mothers who have Z1 temperature reading >100.41F in the epidural group, patients receiving epidural analgesia also tend to have longer labor, one of the known risk factors for chorioamnionitis. The observed association is therefore likely noncausal. It is not surprising that epidural analgesia is associated with intrapartum fever only in the presence of placental inflammation as noted by Dashe et al.38 From a physiological point of view, Bromage39 pointed out that epidural analgesia affects a variety of human thermoregulatory mechanisms by its blockade of the sympathetic nervous system. As, in his view, the majority of these changes result in heat retention, he believed that “there is a tendency for heat retention to occur in warm surroundings.” Contrary to this idea by Bromage is the observation by Holdcroft et al40 who showed that, in surgical patients, sympathetic blockade caused by epidural anesthesia results in hypothermia from the redistribution of heat from the core to the periphery, and thus a net heat loss to the environment. Because maternal temperature recordings were a secondary observation in most studies, we recently designed a prospective cohort study in women scheduled for induced labor, specifically designed to evaluate several possible factors that could affect maternal temperature.41 We measured hourly temperatures from the time of admission to the labor floor until delivery and recorded length of labor, length of membrane rupture, parity, body mass index, white
Figure 3. Temperature course during labor. Boxplots of temperatures from 86 women scheduled for elective labor induction. This graph depicts the summary information of temperatures. Individual temperature slopes (not depicted) show mixed (positive and negative) trends. Linear and cubic fit lines are also displayed. www.anesthesiaclinics.com
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blood cell count, group B streptococcus status, oxytocin dose, and labor intensity using Montevideo units (a method of quantifying uterine activity during labor based on intrauterine pressure measurements). We carefully excluded women with infections and medications that might alter maternal temperature. The goal of our study was 3-fold: to evaluate whether, on average, maternal temperature increased during labor, whether this observation was uniformly observed in all women, and to identify intrapartum risk factors for maternal fever. We observed that almost an equal number of women showed a slight temperature decrease as women who showed a temperature increase. On average, however, we found a clinically insignificant temperature rise of 0.31F/ 10 h (Fig. 3). One of the most important findings was that the placement of the epidural catheter did not alter the temperature trend in laboring women. In other words, any temperature increase observed was present before the epidural catheter was placed. As noted by others, we identified a longer time from rupture of membranes to delivery and increased maternal body mass index as risk factors for maternal fever. ’
Summary and Clinical Implications
Maternal temperature varies during labor. On average, there is a small but clinically insignificant rise in temperature and this positive trend in maternal temperature is more frequently observed in women receiving epidural analgesia. The latter group of women requesting neuraxial pain relief are also more likely to have longer labor, more frequent pelvic examinations and chorioamnionitis, and an observed temperature trend, positive or negative, is not changed when epidural analgesia is started. The scientific evidence does not support a claim that epidural analgesia affects maternal fever, a classic symptom of chorioamnionitis that, if unrecognized or untreated, can pose a serious threat to the mother and baby.
The author has no conflicts of interest to disclose.
’
References
1. Leighton BL, Halpern SH. The effects of epidural analgesia on labor, maternal, and neonatal outcomes: a systematic review. Am J Obstet Gynecol. 2002;186(suppl Nature): S69–S77. 2. Halpern SH, Leighton BL. Misconceptions about neuraxial analgesia. Anesthesiol Clin North America. 2003;21:59–70. 3. Goetzl L. Epidural analgesia and maternal fever: a clinical and research update. Curr Opin Anesthesiol. 2012;25:292–299. www.anesthesiaclinics.com
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