A Randomized Trial of the Effects of Antibiotic Prophylaxis on Epidural-Related Fever in Labor
Sharma SK, Rogers BB, Alexander JM, McIntire DD, Leveno KJ
Anesth Analg. 2014;118:604-610
This is a double-blind study of 400 healthy nulliparous women requesting epidural analgesia at Parkland Hospital at the University of Texas Southwestern Medical Center. The participants were randomly assigned to receive either cefoxitin 2 g or placebo right before an epidural catheter was placed for labor analgesia (median duration, approximately 6 hours). This trial found that 38% of women administered cefoxitin developed fever, defined as a maternal temperature of greater than 38°C, which did not differ statistically from the 40% incidence of fever in the placebo group.
Neutrophilic infiltration of the placenta and membranes was found in approximately 50% of both study groups. Although fever developed significantly more often in women with placental neutrophilic inflammation than in those without this condition, no difference was detected in placental neutrophilic inflammation between the antibiotic group and the placebo group. The investigators also found no differences in any neonatal outcomes, and sepsis was not diagnosed in any infant. The conclusion of the study is that infection is unlikely to be the cause of fever during labor epidural analgesia.
Many women having babies ask for, and receive, very effective pain relief with local anesthetics delivered through a catheter placed in the epidural space. It has been reported in many studies over the past 2 decades that these patients have a 2-4 times higher incidence of fever than similar patients not receiving epidural analgesia. It is worth mentioning that perhaps owing to the method of temperature assessment, the incidence of intrapartum fever of 38%-40% in the current study was a bit higher than the 10%-30% range in nulliparas receiving epidural analgesia reported in other studies.
The mechanism underlying epidural-related fever is unknown. It could be related to thermoregulatory effects of administering local anesthetic into the epidural space. However, this likely possibility has been ruled out by other studies, because vasodilation in the lower extremities from the sympathectomy of the epidural block would be expected to lower core body temperature, not raise it.
Another possible explanation for the association between epidural analgesia and fever is that intravenous opioids given in higher doses to laboring women who don’t receive epidural analgesia are somehow reducing maternal temperature, but there is little or no evidence to support that hypothesis.
Sharma and colleagues provide evidence that fever during labor epidural analgesia is associated with placental inflammation, but fever and placental inflammation were not reduced with antibiotic prophylaxis. The results of this randomized blinded study also go against another potential explanation — that epidural fever is a consequence of selection bias of epidural analgesia in women with dysfunctional prolonged labors who are at subsequent risk for infectious chorioamnionitis. As a result, the data presented in this study support a noninfectious inflammatory etiology as the most likely cause of epidural fever.
More research is required to elucidate how epidural analgesia might increase inflammation. Avoiding intrapartum fever matters, because it can result in neonatal sepsis evaluations and antibiotic treatment, and the parental anxiety that accompanies a sepsis evaluation if it is unneeded.