Programmed Intermittent Epidural Bolus for Labor Analgesia During First Stage of Labor: A Biased-Coin Up-and-Down Sequential Allocation Trial to Determine the Optimum Interval Time Between Boluses of a Fixed Volume of 10 mL of Bupivacaine 0.0625% With Fentanyl 2 μg/mL

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Most studies that have compared programmed intermittent epidural bolus (PIEB) with continuous epidural infusion regimens have included patient-controlled epidural analgesia and/or manual bolus as rescue analgesia for breakthrough pain. Consequently, the optimal time interval between PIEB is yet to be determined. We designed a study to establish the optimal time interval between PIEB of 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL to produce effective analgesia in 90% of women during first stage of labor without breakthrough pain.


We conducted a double-blind sequential allocation trial with a biased-coin up-down design to obtain the effective interval 90% for the PIEB regimen. We included American Society of Anesthesiologists physical status 2–3 nulliparous women at term undergoing spontaneous or induced labor requesting epidural analgesia. An ultrasound-assisted epidural catheter placement was performed at L2/3 or L3/4. A test dose of 3 mL of bupivacaine 0.125% plus fentanyl 3.3 μg/mL was followed by a loading dose of 12 mL of the same solution. PIEB was then started in women whose pain scores achieved Verbal Numerical Rating Score ≤1/10 within 20 minutes after the end of the loading dose. In all subjects, the programmed bolus dose was fixed at 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL. The first bolus was delivered 1 hour after the loading dose. The PIEB interval was set at 60 minutes for the first patient and at varying time intervals (60, 50, 40, and 30 minutes; groups 60, 50, 40 and 30, respectively) for the subsequent patients, according to a biased-coin design. The primary outcome was effective analgesia, defined as no requirement for a patient-controlled epidural analgesia or a manual bolus for 6 hours after the initiation of the epidural analgesia or until the patient presented with full cervical dilatation, whichever event occurred first. Pain scores, sensory block levels to ice, degree of motor block, and blood pressure were assessed hourly.


We studied 40 women. The estimated effective interval 90% was 42.6 minutes (95% confidence interval 38.9–46.4) using the truncated Dixon and Mood method and 36.8 minutes (95% confidence interval 31.0–49.0) using the Isotonic Regression analysis. Almost 70% of the patients in group 30 presented with sensory block above T6, compared with 44%, 22%, and 11% in groups 40, 50, and 60, respectively. Only patients in group 30 presented with motor blockade. The incidence of hypotension was low in all groups with no treatment required.


The optimal time interval between PIEB of 10 mL of bupivacaine 0.0625% with fentanyl 2 μg/mL is approximately 40 minutes. Further studies to determine the efficacy of this regimen throughout the entire duration of labor are warranted.

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