Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia

BACKGROUND: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid. METHODS: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. RESULTS: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold. CONCLUSIONS: These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.     

Differences in Systemic Opioid Use Do Not Explain Increased Fever Incidence in Parturients Receiving Epidural Analgesia

Background: It has been hypothesized that an increased incidence of fever in patients receiving epidural analgesia might result not from epidural per se, but rather from the antipyretic effect of opioids preferentially administered to women in the no-epidural group. If this were the case, then one would expect the incidence of fever in parturients who did not receive systemic opioids to be independent of whether they received epidural analgesia.

Methods: Using a cohort study design, the authors evaluated the records of 1,233 nulliparous patients whose labor analgesia was managed with (1) no medication (N = 170); (2) 10 mg intravenous systemic nalbuphine plus 10 mg intramuscular every 3 to 4 h as required (N = 327); (3) epidural analgesia with continuous infusion of 0.125% bupivacaine with 2 [mu]g/ml fentanyl (N = 278); or (4) patients who received both systemic nalbuphine and epidural analgesia (N = 458). Fever was diagnosed if the maximum temperature during labor exceeded 100.4[degrees]F (38[degrees]C).

Results: The incidence of fever did not differ according to nalbuphine administration for women not receiving epidural analgesia (1% no nalbuphine, 0.3% with nalbuphine, P = 0.27) or for women receiving epidural analgesia (17% no nalbuphine, 17% with nalbuphine, P = 1.0). However, the incidence of fever differed significantly between patients who received no analgesia as compared to those who received epidural analgesia alone (1%vs. 17%, P = 10-6). Controlling for confounding did not alter these associations.     

Comparison of Three Solutions of Ropivacaine/Fentanyl for Postoperative Patient-controlled Epidural Analgesia

Background: Ropivacaine, 0.2%, is a new local anesthetic approved for epidural analgesia. The addition of 4 [micro sign]g/ml fentanyl improves analgesia from epidural ropivacaine. Use of a lower concentration of ropivacaine-fentanyl may further improve analgesia or decrease side effects.

Methods: Thirty patients undergoing lower abdominal surgery were randomized in a double-blinded manner to receive one of three solutions: 0.2% ropivacaine-4 [micro sign]g fentanyl, 0.1% ropivacaine-2 [micro sign]g fentanyl, or 0.05% ropivacaine-1 [micro sign]g fentanyl for patient-controlled epidural analgesia after standardized combined epidural and general anesthesia. Patient-controlled epidural analgesia settings and adjustments for the three solutions were standardized to deliver equivalent drug doses. Pain scores (rest, cough, and ambulation), side effects (nausea, pruritus, sedation, motor block, hypotension, and orthostasis), and patient-controlled epidural analgesia consumption were measured for 48 h.

Results: All three solutions produced equivalent analgesia. Motor block was significantly more common (30 vs. 0%) and more intense with the 0.2% ropivacaine-4 [micro sign]g fentanyl solution. Other side effects were equivalent between solutions and mild in severity. A significantly smaller volume of 0.2% ropivacaine-4 [micro sign]g fentanyl solution was used, whereas the 0.1% ropivacaine-2 [micro sign]g fentanyl group used a significantly greater amount of ropivacaine and fentanyl.     

Epidural Analgesia during Labor and Maternal Fever

Background: In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor.

Methods: Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature >or= to 38.0 [degree sign]C) versus those without was performed using Student t test and Fisher exact to determine statistical significance (P < 0.05).

Results: Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression.     

Postoperative Analgesia after Radical Retropubic Prostatectomy: A Double-blind Comparison between Low Thoracic Epidural and Patient-controlled Intravenous Analgesia

Background: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.

Methods: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 [mu]g/ml fentanyl, and 2 [mu]g/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.

Results: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.     

The effects of remifentanil or acetaminophen with epidural ropivacaine on body temperature during labor

PURPOSE: Epidural analgesia is associated with hyperthermia during labor and presumably causes it, although no convincing mechanism has been postulated. It seems likely that fever associated with pyrogenic factors related to labor is suppressed by opioids, whereas it is expressed normally in patients given epidural analgesia. We examined this hypothesis and the possible etiology of temperature elevation in labor. METHODS: In this prospective, randomized, controlled study, we assessed 201 parturients during spontaneous labor. Analgesia was randomly provided with one of four treatment groups: (1) epidural ropivacaine alone, (2) IV remifentanil alone, (3) epidural ropivacaine plus IV remifentanil, and (4) epidural ropivacaine plus IV acetaminophen. At randomization, patients were normothermic. Intrapartum hyperthermia (>or=38 degrees C) was correlated to the analgesic technique. RESULTS: The maximum increase in oral temperature was greatest in the ropivacaine group (0.7 +/- 0.6 degrees C) and least in the remifentanil group (0.3 +/- 0.4 degrees C; P = 0.013). The percentage of patients who became hyperthermic (>or=38 degrees C) during the first 6 h of labor was greatest in the ropivacaine group (14%) and least in the remifentanil-alone group (2%), but the difference was not statistically significant. The maximum forearm-finger gradients were lower (less vasoconstriction) in the remifentanil group when compared to the gradients in patients with epidural analgesia (1.4 +/- 1.8 vs 3.0 +/- 1.7, respectively; P < 0.001). CONCLUSION: Our results are consistent with the theory that low-dose opioids inhibit fever in patients not given epidural analgesia. However, in view of the negative results, the hypothesis of epidural-induced hyperthermia may be questionable.     

Epidural Fentanyl Produces Labor Analgesia by a Spinal Mechanism

Background: The purpose of this study was to determine if epidural fentanyl produces analgesia in laboring patients by a primary spinal or supraspinal action.

Methods: Fifty-four parturients were randomized to receive epidural 0.125% bupivacaine plus one of three treatments: epidural saline-intravenous saline, epidural fentanyl (20 [micro sign]g/h)-intravenous saline, or epidural saline-intravenous fentanyl (20 [micro sign]g/h). The study treatments were administered by continuous infusion, whereas epidural bupivacaine use was patient controlled.

Results: Epidural bupivacaine use was significantly reduced by epidural (11.5 +/- 4.6 ml/h) but not by intravenous fentanyl (15.9 +/- 4.5 ml/h) compared with saline control (16 +/- 5.9 ml/h). Analgesia characteristics and side effects were similar among groups.     

Labor Analgesia and Cesarean Delivery: An Individual Patient Meta-analysis of Nulliparous Women

Background: The authors performed an individual patient meta-analysis of 2,703 nulliparous women who were randomized to either epidural analgesia or intravenous opioids for pain relief during labor from five trials conducted at their hospital. The primary purpose in this meta-analysis was to evaluate the effects of epidural analgesia during labor on the rate of cesarean delivery.

Methods: Between November 1, 1993, and November 3, 2000, 2,703 nulliparous women (2,188 healthy parturients and 515 women with pregnancy-induced hypertension) in spontaneous labor at term were randomized to receive either epidural analgesia or intravenous opioid analgesia in the five studies. Epidural analgesia was initiated with either epidural bupivacaine or intrathecal sufentanil and was maintained with a low-dose (0.0625% or 0.125%) mixture of bupivacaine with fentanyl. Intravenous opioid analgesia was initiated with 50 mg meperidine and 25 mg promethazine hydrochloride and was maintained with intravenous boluses of meperidine as needed.

Results: A total of 1,339 nulliparous women were randomized to receive epidural analgesia, and 1,364 women were randomized to receive intravenous meperidine analgesia. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 10.5% [140 of 1,339]vs. intravenous meperidine analgesia, 10.3% [141 of 1,364]; adjusted odds ratio, 1.04; 95% confidence interval, 0.81-1.34; P = 0.920). Significantly more women randomized to epidural analgesia had forceps deliveries compared to meperidine analgesia (13% [172 of 1,339]vs. 7% [101 of 1,364]; adjusted odds ratio, 1.86; 95% confidence interval, 1.43-2.40; P < 0.001). Epidural women had longer first and second stages of labor. Women who received epidural analgesia reported lower pain scores during labor and delivery compared to women who received intravenous meperidine analgesia.     

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

Background: The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg [middle dot] kg-1 [middle dot] min-1 glucose) and amino acids (0.02 ml [middle dot] kg-1 [middle dot] min-1 Travasol(TM) 10%, equivalent to approximately 2.9 g [middle dot] kg-1 [middle dot] day-1).

Methods: Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by l-[1-13C]leucine and [6,6-2H2]glucose.

Results: Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 [mu]mol [middle dot] kg-1 [middle dot] h-1) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 [mu]mol [middle dot] kg-1 [middle dot] h-1;P = 0.054).     

Effect of Epidural Analgesia with Ambulation on Labor Duration

Background: Ambulatory epidural analgesia (AEA) is a popular choice for labor analgesia because ambulation reportedly increases maternal comfort, increases the intensity of uterine contractions, avoids inferior vena cava compression, facilitates fetal head descent, and relaxes the pelvic musculature, all of which can shorten labor. However, the preponderance of evidence suggests that ambulation during labor is not associated with these benefits. The purpose of this study is to determine whether ambulation with AEA decreases labor duration from the time of epidural insertion to complete cervical dilatation.

Methods: In this prospective, randomized study, 160 nulliparous women with AEA were randomly assigned to one of two groups: AEA with ambulation and AEA without ambulation. AEA blocks were initiated with 15-20 ml ropivacaine (0.07%) plus 100 [mu]g fentanyl, followed by a continuous infusion of 0.07% ropivacaine plus 2 [mu]g/ml fentanyl at 15-20 ml/h. Maternal measured variables included ambulation time, time from epidural insertion to complete dilatation, stage II duration, pain Visual Analogue Scale scores, and mode of delivery. APGAR scores were recorded at 1 and 5 min. Results are expressed as mean +/- SD or median and analyzed using the t test, chi-square, or the Mann-Whitney test at P <= 0.05.

Results: The ambulatory group walked 25.0 +/- 23.3 min, sat upright 40.3 +/- 29.7 min, or both. Time from epidural insertion to complete dilatation was 240.9 +/- 146.1 min in the ambulatory group and 211.9 +/- 133.9 min in the nonambulatory group (P = 0.206).     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Equivalent Analgesia and Side Effects during Epidural and Pharmacokinetically Tailored Intravenous Infusion with Matching Plasma Alfentanil Concentration

Background: Recently, several clinical studies comparing intravenous and epidural infusions of fentanyl and its derivatives suggested that epidural infusions act primarily by systemic absorption to produce supraspinal analgesia. To evaluate this hypothesis, the authors used pharmacokinetically tailored intravenous infusions to produce matching plasma alfentanil concentrations during epidural and intravenous administration. The analgesia and side effects achieved with each mode of administration were compared.

Methods: Twelve volunteers participated in this placebo-controlled crossover study. The pain model was cutaneous electric stimulation of the finger and toe. The test battery included subjective rating of pain intensity; end-tidal carbon dioxide level; pupil size; ratings of alertness, nausea, and pruritus; and a plasma alfentanil assay. On one test day, the participants received epidural alfentanil (400 [micro sign]g bolus + a 400 [micro sign]g/h infusion for 2 h) and an intravenous saline infusion. The test battery was administered at regular intervals. On another test day, the participants received epidural saline and a computer-controlled intravenous infusion of alfentanil. The testing protocol was repeated as on the first test day. On the day the placebo was administered, the participants received epidural and intravenous saline infusions. The order of the placebo day was randomized.

Results: Plasma alfentanil concentration-time profiles were identical during epidural and intravenous infusions. A nearly equivalent analgesic response was observed with epidural and intravenous alfentanil at the upper and lower extremities. There were no differences in side effects for epidural and intravenous administration.     

Differences in systemic opioid use do not explain increased fever incidence in parturients receiving epidural analgesia

BACKGROUND: It has been hypothesized that an increased incidence of fever in patients receiving epidural analgesia might result not from epidural per se, but rather from the antipyretic effect of opioids preferentially administered to women in the no-epidural group. If this were the case, then one would expect the incidence of fever in parturients who did not receive systemic opioids to be independent of whether they received epidural analgesia. METHODS: Using a cohort study design, the authors evaluated the records of 1,233 nulliparous patients whose labor analgesia was managed with (1) no medication (N = 170); (2) 10 mg intravenous systemic nalbuphine plus 10 mg intramuscular every 3 to 4 h as required (N = 327); (3) epidural analgesia with continuous infusion of 0.125% bupivacaine with 2 microg/ml fentanyl (N = 278); or (4) patients who received both systemic nalbuphine and epidural analgesia (N = 458). Fever was diagnosed if the maximum temperature during labor exceeded 100.4 degrees F (38 degrees C). RESULTS: The incidence of fever did not differ according to nalbuphine administration for women not receiving epidural analgesia (1% no nalbuphine, 0.3% with nalbuphine, P = 0.27) or for women receiving epidural analgesia (17% no nalbuphine, 17% with nalbuphine, P = 1.0). However, the incidence of fever differed significantly between patients who received no analgesia as compared to those who received epidural analgesia alone (1% vs. 17%, P = 10(-6)). Controlling for confounding did not alter these associations. CONCLUSIONS: Our findings suggest that an antipyretic effect of nalbuphine in patients who do not receive an epidural does not explain the greater incidence of fever observed in women who receive epidural analgesia for labor.     

Cesarean Delivery: A Randomized Trial of Epidural Analgesia versus Intravenous Meperidine Analgesia during Labor in Nulliparous Women

Background: Controversy concerning increased cesarean births as a result of epidural analgesia for relief of labor pain has been attributed, in large part, to difficulties interpreting published studies because of design flaws. In this study, the authors compared epidural analgesia to intravenous meperidine analgesia using patient-controlled devices during labor to evaluate the effects of labor epidural analgesia, primarily on the rate of cesarean deliveries while minimizing limitations attributable to study design.

Methods: Four hundred fifty-nine nulliparous women in spontaneous labor at term were randomly assigned to receive either epidural analgesia or intravenous meperidine analgesia. Epidural analgesia was initiated with 0.25% bupivacaine and was maintained with 0.0625% bupivacaine and fentanyl 2 [mu]g/ml at 6 ml/h with 5-ml bolus doses every 15 min as needed using a patient-controlled pump. Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump. A written procedural manual that prescribed the intrapartum obstetric management was followed for each woman randomized in the study.

Results: A total of 226 women were randomized to receive epidural analgesia, and 233 women were randomized to receive intravenous meperidine analgesia. Protocol violations occurred in 8% (38 of 459) of women. There was no difference in the rate of cesarean deliveries between the two analgesia groups (epidural analgesia, 7% [16 of 226; 95% confidence interval, 4-11%]vs. intravenous meperidine analgesia, 9% [20 of 233; 95% confidence interval, 5-13%];P = 0.61). Significantly more women randomized to epidural analgesia had forceps deliveries compared with those randomized to meperidine analgesia (12% [26 of 226]vs. 3% [7 of 233];P < 0.001). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received intravenous meperidine analgesia.     

Cesarean Delivery: A Randomized Trial of Epidural versus Patient-controlled Meperidine Analgesia during Labor

Background: Reports indicate that the administration of epidural analgesia for pain relief during labor interferes with labor and increases cesarean deliveries. However, only a few controlled trials have assessed the effect of epidural analgesia on the incidence of cesarean delivery. The authors' primary purpose in this randomized study was to evaluate the effects of epidural analgesia on the rate of cesarean deliveries by providing a suitable alternative: patient-controlled intravenous analgesia.

Methods: Seven hundred fifteen women of mixed parity in spontaneous labor at full term were randomly assigned to receive either epidural analgesia or patient-controlled intravenous meperidine analgesia. Epidural analgesia was maintained with a continuous epidural infusion of 0.125% bupivacaine with 2 micro gram/ml fentanyl. Patient-controlled analgesia was maintained with 10-15 mg meperidine given every 10 min as needed using a patient-controlled pump. Procedures recorded in a manual that prescribed the intrapartum management were followed for each woman randomized in the study.

Results: A total of 358 women were randomized to receive epidural analgesia, and 243 (68%) of these women complied with the epidural analgesia protocol. Similarly, 357 women were randomized to receive patient-controlled intravenous meperidine analgesia, and 259 (73%) of these women complied with the patient-controlled intravenous analgesia protocol. Only five women who were randomized and received patient-controlled intravenous meperidine analgesia according to the protocol crossed over to epidural analgesia due to inadequate pain relief. There was no difference in the rate of cesarean deliveries between the two analgesia groups using intention-to-treat analysis based on the original randomization (epidural analgesia, 4% [95% CI: 1.9-6.2%] compared with patient-controlled intravenous analgesia, 5% [95% CI: 2.6-7.2%]). Similar results were observed for the analysis of the protocol-compliant groups (epidural analgesia, 5% [95% CI: 2.6-8.5%] compared with patient-controlled intravenous analgesia, 6% [95% CI: 3-8.9%]). Women who received epidural analgesia reported lower pain scores during labor and delivery compared with women who received patient-controlled intravenous analgesia.     

Epidural Ropivacaine versus Epidural Morphine and the Catabolic Response to Colonic Surgery: Stable Isotope Kinetic Studies in the Fasted State and during Infusion of Glucose

Background: The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose.

Methods: Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg [middle dot] kg-1 [middle dot] min-1 glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by l-[1-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured.

Results: Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused.     

Continuous Epidural Blockade Arrests the Postoperative Decrease in Muscle Protein Fractional Synthetic Rate in Surgical Patients

Background: Epidural anesthesia with local anesthetics is associated with postoperative attenuation of nitrogen loss. The protein-sparing effect could be the result of either a decreased protein breakdown or increased protein synthesis. Although the role of epidural local anesthetics in effectively limiting the increase in postoperative protein breakdown is established at the whole-body level, it is necessary to determine whether the muscle protein fractional synthetic rate is directly modulated when nociceptive stimuli are blocked.

Methods: Twelve otherwise healthy patients scheduled for elective colorectal surgery, who were receiving a constant intake of nitrogen (0.1 g [center dot] kg sup -1 [center dot] day sup -1) and calories (20 kcal [center dot] kg sup -1 [center dot] day sup -1) before and after surgery, were randomly assigned to receive either general anesthesia (with thiopentone, vecuronium, fentanyl, or enflurane; control group, n = 6) or epidural anesthesia (T3-S5 sensory block with 0.75% bupivacaine) and general anesthesia (epidural group, n = 6). In the control group, postoperative analgesia was achieved with papaveretum given subcutaneously, whereas a continuous epidural bupivacaine infusion (T8-L5 sensory block) was maintained for 48 h in the epidural group. The postabsorptive muscle protein fractional synthetic rate was determined using a 6-h continuous infusion of13 C-labeled leucine (1 mg [center dot] kg sup -1 [center dot] h sup -1), and the13 C enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured.

Results: Plateau13 C enrichment of plasma alpha-ketoisocaproate (taken to represent the intracellular leucine precursor pool enrichment for protein synthesis) was achieved during the 6-h infusion (mean coefficient of variation was 2.8%). Muscle protein synthesis at 48 h after operation compared with preoperative levels decreased significantly in the control group (P = 0.03). In contrast, it increased by 25% in the epidural group. Although this was not significantly (P = 0.15) different from preoperative levels, it was significantly greater than in the control patients.     

Effect of Intravenous versus Epidural Fentanyl on the Minimum Local Analgesic Concentration of Epidural Bupivacaine in Labor

Background: The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration (EC50) in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine.

Methods: In this double-blind, randomized, prospective study, 84 parturients at <= 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups. After lumbar epidural catheter placement, 20 ml bupivacaine (n = 44) or bupivacaine with 3 [mu]g/ml (60 [mu]g) fentanyl (n = 40) was administered. The plain bupivacaine group then received 60 [mu]g intravenous fentanyl. The bupivacaine-fentanyl group received intravenous saline. The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up-down sequential allocation. Analgesic efficacy was assessed using 100-mm visual analog pain scores, with <= 10 mm within 30 min defined as effective.

Results: The MLAC of bupivacaine-intravenous fentanyl was 0.064% wt/vol (95% confidence interval, 0.049-0.080), and the MLAC of bupivacaine-epidural fentanyl was 0.034% wt/vol (95% confidence interval, 0.017-0.050). Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 (95% confidence interval, 1.09-3.67) compared with intravenous fentanyl. The epidural fentanyl group demonstrated significantly higher dermatomal spread (P = 0.0064) and increased pruritus (P = 0.01).     

Epidural analgesia during labor and maternal fever.

BACKGROUND: In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor. METHODS: Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature > or = 38.0 degrees C) versus those without was performed using Student t test and Fisher exact test to determine statistical significance (P < 0.05). RESULTS: Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression. CONCLUSIONS: Epidural analgesia is associated with maternal fever. However, nulliparity and dysfunctional labor are also significant cofactors in the fever attributed to epidural analgesia.     

Epidural infusions for labor analgesia: A comparison of 0.2% ropivacaine, 0.1% ropivacaine,and 0.1% ropivacaine with fentanyl

Background and Objectives: Epidural infusion of 0.2% ropivacaine is recommended by the manufacturer for labor analgesia, but lower concentrations may be effective. The objective of this study was to compare 0.1% ropivacaine with 0.2% ropivacaine and to examine the effect of addition of fentanyl. Methods: In a randomized double-blind study, 58 nulliparous laboring parturients had epidural analgesia established with 0.2% ropivacaine and were then randomized to receive one of the following epidural infusions at 10 mL/h: 0.2% ropivacaine (group R2, n = 19), 0.1% ropivacaine (group R1, n = 19), or 0.1% ropivacaine with 2 [mu ]g/mL fentanyl (group RF, n = 20). Supplementary analgesia was provided on request with 5-mL boluses of 0.2% ropivacaine. Results: All solutions provided effective analgesia during early labor, with all groups requiring similar numbers of supplementary top-ups. Visual analog pain scores in groups R2 and RF were equivalent and lower than in group R1 (P = .006). Hypotension was more frequent in group RF compared with groups R2 and R1 (P = .014). Patient and midwife satisfaction and obstetric and neonatal outcomes were similar among groups. Maternal venous plasma concentrations of ropivacaine were greater in group R2 compared with groups R1 and RF (P = .008), but umbilical venous concentrations were similar. Conclusions: We conclude that epidural infusion of 0.1% ropivacaine alone at 10 mL/h provided adequate analgesia in the first stage of labor, and that the addition of 2 [mu ]g/mL fentanyl to that concentration improved analgesia to a quality similar to 0.2% ropivacaine alone. Reg Anesth Pain Med 2002;27:31-36.