Randomized trial of epidural versus intravenous analgesia during labor
Objective
To compare the effects of epidural analgesia with intravenous (IV) analgesia on the outcome of labor.
Methods
Thirteen hundred thirty women with uncomplicated term pregnancies and in spontaneous labor were randomized to be offered epidural bupivacaine-fentanyl or IV meperidine analgesia during labor.
Results
Comparison of the allocation groups by intent to treat revealed a significant association between epidural allocation and operative delivery for dystocia. However, only 65% of each randomization group accepted the allocated treatment. Four hundred thirty-seven women accepted and received meperidine as allocated, and they were compared with 432 women accepting epidural allocation. Significant associations resulted between epidural administration and prolongation of labor, increased rate of oxytocin administration, chorioamnionitis, low forceps, and cesarean delivery. Because of the high rate of noncompliance with treatment allocation, a multifactorial regression analysis was performed on the entire cohort, and a twofold relative risk of cesarean delivery persisted in association with epidural treatment. The impact of epidural treatment on cesarean delivery was significant for both nulliparous and parous women (risk ratios 2.55 and 3.81, respectively). Epidural analgesia provided significantly better pain relief in labor than did parenteral meperidine.
Conclusion
Although labor epidural analgesia is superior to meperidine for pain relief, labor is prolonged, uterine infection is increased, and the number of operative deliveries are increased. A two to fourfold increased risk of cesarean delivery is associated with epidural treatment in both nulliparous and parous women.
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Cited by (301)
Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment
2024, American Journal of Obstetrics and GynecologyClinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.
Maternal fever in labor: etiologies, consequences, and clinical management
2023, American Journal of Obstetrics and GynecologyIntrapartum fever is common and presents diagnostic and treatment dilemmas for the clinician. True maternal sepsis is rare; only an estimated 1.4% of women with clinical chorioamnionitis at term develop severe sepsis. However, the combination of inflammation and hyperthermia adversely impacts uterine contractility and, in turn, increases the risk for cesarean delivery and postpartum hemorrhage by 2- to 3-fold. For the neonate, the rates of encephalopathy or the need for therapeutic hypothermia have been reported to be higher with a maternal fever >39°C when compared with a temperature of 38°C to 39°C (1.1 vs 4.4%; P<.01). In a large cohort study, the combination of intrapartum fever and fetal acidosis was particularly detrimental. This suggests that intrapartum fever may lower the threshold for fetal hypoxic brain injury. Because fetal hypoxia is often difficult to predict or prevent, every effort should be made to reduce the risk for intrapartum fever. The duration of exposure to epidural analgesia and the length of labor in unmedicated women remain significant risk factors for intrapartum fever. Therefore, paying careful attention to maintaining labor progress can potentially reduce the rates of intrapartum fever and the risk for cesarean delivery if fever does occur. A recent, double-blind randomized trial of nulliparas at >36 weeks’ gestation demonstrated that a high-dose oxytocin regimen (6×6 mU/min) when compared with a low-dose oxytocin regimen (2×2 mU/min) led to clinically meaningful reductions in the rate of intrapartum fever (10.4% vs 15.6%; risk rate, 0.67; 95% confidence interval, 0.48–0.92). When fever does occur, antibiotic treatment should be initiated promptly; acetaminophen may not be effective in reducing the maternal temperature. There is no evidence that reducing the duration of fetal exposure to intrapartum fever prevents known adverse neonatal outcomes. Therefore, intrapartum fever is not an indication for cesarean delivery to interrupt labor with the purpose of improving neonatal outcome. Finally, clinicians should be ready for the increased risk for postpartum hemorrhage and have uterotonic agents on hand at delivery to prevent delays in treatment.
Modern labor epidural analgesia: implications for labor outcomes and maternal-fetal health
2023, American Journal of Obstetrics and GynecologyEpidural analgesia is an important means of pain control during labor throughout the world. Over its historic development, it has been implicated in several undesirable outcomes, including prolongation of labor and increased need for operative delivery. These effects have emerged in some retrospective and observational studies, but such methods of investigation are highly prone to bias and are particularly ill-suited for the study of labor analgesia. In high-quality studies, including Cochrane reviews and meta-analyses, epidural analgesia has been suggested to extend the first stage of labor by 30 minutes and the second stage by 15 minutes, when compared with alternative forms of analgesia. Although this may be a reproducible effect, it may be argued that it is clinically negligible.
With respect to mode of delivery, similar high-quality studies have consistently shown no increased risk of cesarean delivery associated with epidural analgesia. Some forms of epidural analgesia were associated with higher risk of assisted vaginal delivery, but the use of newer modalities has been shown to abolish this effect. Specific advancements have centered on reducing total anesthetic consumption, given that local anesthetic-induced motor block is theorized to interfere with maternal expulsive efforts in the second stage of labor. These measures include the use of low-concentration local anesthetic solutions equivalent to ≤0.1% bupivacaine, shown in meta-analyses to lead to no higher risk of assisted vaginal delivery relative to nonepidural analgesia. Additional advancements in the maintenance of analgesia include programmed intermittent epidural bolus and patient-controlled epidural analgesia, the combination of which has been shown to reduce the risk of assisted vaginal delivery, also likely mediated by reduction in local anesthetic dose. These techniques have gained popularity in the past two decades, such that studies published since 2005 show no higher risk of assisted vaginal delivery with epidural than with opioid analgesia (as reported in a Cochrane review).
Labor epidural analgesia has implications for maternal and fetal health perinatally. It is known to result in transient maternal hypotension (particularly with initiation), which may progress to the level of necessitating fluid or vasopressor therapy. This is not clearly associated with any adverse outcomes. There is also a consistently higher incidence of fever in parturients receiving neuraxial anesthesia, likely of noninfectious origin, which has similarly not been associated with adverse neonatal outcomes. Finally, neonates of parturients who receive epidural analgesia have been shown to have no worse Apgar scores and more favorable acid-base status than their counterparts. These observations should serve to reassure providers that modern labor analgesia, as currently understood, is not consistently associated with any significant adverse outcomes for the parturient or fetus.
In this review, we describe variations of modern labor epidural analgesia, conduct an in-depth review of current literature on its use, and explore the most up-to-date evidence on its implications for the progression and outcomes of labor, including the pertinent maternal and fetal side effects.
Epidural-related maternal fever: incidence, pathophysiology, outcomes, and management
2023, American Journal of Obstetrics and GynecologyEpidural-related maternal fever affects 15% to 25% of patients who receive a labor epidural. Two meta-analyses demonstrated that epidural-related maternal fever is a clinical phenomenon, which is unlikely to be caused by selection bias. All commonly used neuraxial techniques, local anesthetics with or without opioids, and maintenance regimens are associated with epidural-related maternal fever, however, the impact of each component is unknown. Two major theories surrounding epidural-related maternal fever development have been proposed. First, labor epidural analgesia may lead to the development of hyperthermia through a sterile (noninfectious) inflammatory process. This process may involve reduced activation of caspase-1 (a protease involved in cell apoptosis and activation of proinflammatory pathways) secondary to bupivacaine, which impairs the release of the antipyrogenic cytokine, interleukin-1-receptor antagonist, from circulating leucocytes. Detailed mechanistic processes of epidural-related maternal fever remain to be determined. Second, thermoregulatory mechanisms secondary to neuraxial blockade have been proposed, which may also contribute to epidural-related maternal fever development. Currently, there is no prophylactic strategy that can safely prevent epidural-related maternal fever from occurring nor can it easily be distinguished clinically from other causes of intrapartum fever, such as chorioamnionitis. Because intrapartum fever (of any etiology) is associated with adverse outcomes for both the mother and baby, it is important that all parturients who develop intrapartum fever are investigated and treated appropriately, irrespective of labor epidural utilization. Institution of treatment with appropriate antimicrobial therapy is recommended if an infectious cause of fever is suspected. There is currently insufficient evidence to warrant a change in recommendations regarding provision of labor epidural analgesia and the benefits of good quality labor analgesia must continue to be reiterated to expectant mothers.
Interventions for the prevention or treatment of epidural-related maternal fever: a systematic review and meta-analysis
2022, British Journal of AnaesthesiaEpidural-related maternal fever in women in labour has consequences for the mother and neonate. There has been no systematic review of preventive strategies.
RCTs evaluating methods of preventing or treating epidural-related maternal fever in women in active labour were eligible. We searched MEDLINE, EMBASE, CINAHL, Web of Science, CENTRAL, and grey literature sources were searched from inception to April 2021. Two review authors independently undertook study selection. Data extraction and quality assessment was performed by a single author and checked by a second. The Cochrane Risk of Bias 2 tool was used. Meta-analyses for the primary outcome, incidence of intrapartum fever, were performed using the DerSimonian and Laird random effects model to produce summary risk ratios (RRs) with 95% confidence intervals (95% CIs).
Forty-two records, representing 34 studies, were included. Methods of reduced dose epidural reduced the incidence of intrapartum fever, but this was not statistically significant when six trials at high risk of bias were removed (seven trials; 857 participants; RR=0.83; 95% CI, 0.41–1.67). Alternative methods of analgesia and high-dose prophylactic systemic steroids reduced the risk of intrapartum fever compared with epidural analgesia. Prophylactic paracetamol was not effective.
There is no clear evidence to support the use of any individual preventative or therapeutic intervention for epidural-related maternal fever. Further research should focus on understanding the mechanism of fever development to enable RCTs of potential interventions to reduce the incidence of intrapartum fever development and the subsequent disease burden felt by the neonate.
Pulse perfusion index for predicting intrapartum fever during epidural analgesia
2022, Journal of Clinical AnesthesiaTo assess whether pulse perfusion index (PI) values could be employed to predict intrapartum fever and to provide a cut-off PI value for predicting intrapartum fever occurrence.
We conducted a single-center, prospective, observational study.
Delivery room at the Department of Obstetrics, Affiliated Hospital of Jiangsu University.
117 parturients who intended to have a vaginal delivery.
Each parturient received epidural analgesia.
We checked each parturient's tympanic temperature before analgesia (T0), at 1 h (T1) and 2 h (T2) after analgesia, immediately at the end of the second (T3) and third (T4) stages of labor, and at 1 h postpartum (T5). A temperature of ≥38°C was defined as fever. PI, measured on the right second toe, was recorded before analgesia (PI0) and at 10 min (PI10), 20 min (PI20), and 30 min (PI30) after analgesia. The PI change rate was calculated as the incremental change in PI30 from PI0, divided by the PI0. Receiver operating characteristic (ROC) curves were used to verify the utility of the PI30 and PI change rate values for predicting intrapartum fever.
We found that peak temperature (TP) occurred at the end of the second or the third stage of labor. Within 30 min after analgesia, the PI showed a significant increase over time and there was a linear correlation between PI30 and TP values (P < 0.001, r = 0.544). The PI10, PI20, PI30 and PI change rate in febrile parturients were higher than those in afebrile parturients (P < 0.001). The area under the ROC (AUROC) for PI30 was 0.818 (P < 0.001) with a cut-off of 9.30. The AUROC of the PI change rate was 0.738 (P < 0.001) with a cut-off of 3.45.
PI30 and PI change rate values could be used to predict intrapartum fever in parturients after epidural analgesia.