A randomized controlled trial using patient-controlled epidural analgesia with 0.25% versus 0.0625% bupivacaine in nulliparous labor: effect on analgesia requirement and maternal satisfaction.

BACKGROUND: The effect of epidural local anesthetic concentration on analgesic action is still the subject of debate. This study compared the effect of a four-fold change in concentration of bupivacaine for epidural analgesia in labor. METHODS: Nulliparous women in early active labor were recruited. All women received analgesic drugs via a lumbar epidural catheter, and all received fentanyl 1 microg/kg with the epidural induction dose and no further opioids throughout the study. Patients were randomized to receive either a 5-mL bolus followed by a 5-mL/h infusion of concentrated (0.25%) bupivacaine or a 20-mL bolus followed by a 20-mL/h infusion of dilute (0.0625%) bupivacaine. Patient-controlled epidural analgesia of the study solution was then used to assess additional analgesia requirements. Analgesic requirement, maternal satisfaction and obstetric outcome were compared. RESULTS: For subjects receiving 0.25% bupivacaine, the median total dose of drug administered was greater (117 vs. 90 mg, P=0.0008), and the mean maternal satisfaction score was less (82 vs. 93, P=0.04) than with the 0.0625% solution. CONCLUSIONS: Larger volumes of more dilute solutions may result in dose sparing and provide more effective labor analgesia. This study supports the continued trend towards dilute local anesthetic mixtures for labor epidural analgesia.

Antepartum continuous epidural ropivacaine therapy reduces uterine artery vascular resistance in pre-eclampsia: a randomized, dose-ranging, placebo-controlled study.

BACKGROUND: No therapy is currently available to improve the reduced uteroplacental blood flow (UPBF) that characterizes pre-eclampsia. We hypothesized that sympathectomy induced by epidural local anaesthesia reduces uterine vascular resistance (which is inversely correlated with UPBF) in pre-eclampsia. METHODS: Ten pregnant women between 24 and 32 weeks of gestation with pre-eclampsia and uterine artery flow abnormalities were randomized to antepartum continuous epidural therapy (ACET) or control. ACET was initiated by a 5 day dose-ranging trial (ACET-1) of 0.04, 0.06, 0.08, and 0.1% ropivacaine and saline placebo, each at 10 ml h(-1) for 24 h. Doses were randomized and double-blind. Doppler ultrasound indices of vascular resistance were assessed at baseline and after each 24 h dosing period in both uterine arteries. Subsequently, these ACET patients were administered 0.1% ropivacaine until delivery (ACET-2), with one additional randomized double-blind placebo day. RESULTS: Five patients were randomized to ACET. In each patient, one uterine artery exhibited a dose-dependent reduction in vascular resistance (P=0.035), a response that returned to baseline following placebo (P<0.001). The contralateral uterine artery exhibited either increased vascular resistance or no change. In all cases, the uterine artery that responded to ACET had higher baseline resistance than its pair (P=0.043). Baseline right-left difference in resistance between paired uterine arteries was greatly diminished following ACET. Although ACET patients had a mean (sd) duration to delivery of 19 (9) days compared with control 2 (1) days (P=0.008), this should be interpreted with caution because of demographic differences between groups. CONCLUSIONS: ACET reduces uterine artery resistance in pre-eclampsia <32 weeks. Uteroplacental re-distribution is a novel observation and warrants further investigation.

Reduction in pulmonary fibrosis in vivo by halofuginone.

Pulmonary fibrosis is a disorder causing a high mortality rate for which therapeutic options are limited. Therefore, the effect of halofuginone, a novel inhibitor of collagen type I synthesis, on bleomycin-induced pulmonary fibrosis was studied in rats. Pulmonary fibrosis was induced by intraperitoneal injections of bleomycin for seven consecutive days, and halofuginone was administered intraperitoneally every second day during the entire experimental period of 42 d. Collagen determination in the lungs and the examination of histologic sections showed that halofuginone significantly reduced fibrosis relative to the untreated control rats. We conclude that halofuginone is a potent in vivo inhibitor of bleomycin-induced pulmonary fibrosis, and that it may potentially be used as a novel therapeutic agent for the treatment of this dysfunction.