The Influence of Time of Day of Administration on Duration of Opioid Labor Analgesia

Abstract

Medications administered into the epidural or intrathecal space for labor analgesia may demonstrate variable effects dependent on time of day, and this may affect clinical research trials investigating the pharmacology of specific drugs. In this retrospective study, we evaluated the effect of time of day of administration of intrathecal fentanyl and systemic hydromorphone labor analgesia from data collected as part of a randomized clinical trial examining the influence of analgesia method on labor outcome. Six hundred ninety-two healthy parturients were randomized early in labor to receive combined spinal-epidural (intrathecal fentanyl 25 μg followed by a lidocaine and epinephrine containing epidural test dose) versus systemic (hydromorphone 1 mg IV and 1 mg IM) labor analgesia at first analgesia request. No further analgesics were administered until the patient requested additional analgesia (second analgesia request). Subjects were assigned to the daytime group (DAY) if initial analgesia (neuraxial or systemic) was administered between the hours of 07:01 and 23:00 and to the nighttime group (NIGHT) if it was administered between 23:01 and 07:00. Within each mode of analgesia study arm (neuraxial or systemic), the DAY and NIGHT groups were compared. The primary outcome variable was analgesia duration, defined as the time interval from administration of labor analgesia until the second analgesia request. Cervical dilation at first and second analgesia requests, pain score at first analgesia request, and average amount of pain between analgesia administration and second analgesia request were also compared between DAY and NIGHT groups. Rhythm analyses for duration of analgesia, cervical dilation, and pain scores were performed. There was no difference in the median duration of either neuraxial or systemic analgesia in DAY versus NIGHT subjects, and no harmonic variation was observed for analgesia duration. Rhythm analysis demonstrated a 24-h harmonic cycle for cervical dilation at first analgesia request with maximum values occurring near 17:00 and minimum values near 05:00, but the amplitude of the difference was very small. Rhythm analysis demonstrated a 24-h harmonic cycle with maximum values occurring near 22:00 and minimum values near 10:00 for the average amount of pain between analgesia administration and second analgesia request in neuraxial group patients, but amplitude was small. Time of day of administration did not seem to influence combined spinal-epidural or systemic labor analgesia duration under these study conditions.