A PRELIMINARY REPORT ON THE POSTOPERATIVE RESPIRATORY EFFECTS FOLLOWING A SINGLE EPIDURAL DOSE OF SUSTAINED-RELEASE ECAPSULATED MORPHINE (C0401)*:

S232 INTRODUCTION: DepoFoam[trade mark sign] drug delivery technology (DepoTech Corp.) consists of lipid based, spherical, multivesicular particles used to encapsulate water-soluble, water-stable compounds. A sustained-release encapsulated morphine (C0401) was recently developed for epidural administration to provide prolonged postoperative analgesia [1]. A dose-escalating phase I study in healthy volunteers demonstrated significant respiratory depression in some subjects at a 40 mg dose. In this phase II open-label study, 2 cohorts of 5 patients each are to receive 20 or 30 mg of epidural C0401 in ascending fashion. This study investigated the respiratory effects of lower C0401 doses as part of the safety and efficacy evaluation of this drug. METHODS: To date 4 patients, scheduled for total hip arthroplasty under regional anesthesia, consented for this IRB approved study. A 20 mg dose of C0401 was injected in the lumbar epidural space over 15 seconds. The epidural catheter was removed and the interspace, 1 level caudad from the epidural placement, was identified and bupivacaine injected intrathecally for surgical anesthesia. Postoperatively, selected respiratory variables were continuously monitored: nasal capnometry for end tidal PCO2 (PET CO2), respiratory rate (RR), and pulse oximetry (SpO2) on room air FIO2. All measurements were recorded after a 5 min observation period and confirmation of a plateau waveform for PET CO2 measurement. PCA fentanyl and acetaminophen with codeine were available for additional analgesia. RESULTS: Patients' mean (+/- SD) age, height and weight were 46 +/- 10 years, 170 +/- 6.6, cm and 71 +/- 13 kg respectively. Mean RR and PET CO2 are presented in the figure. The lowest RR and SpO2 values recorded were 8 breaths/min and 94% respectively. Those occurred postoperatively within the first 8 hr post C0401 dose. DISCUSSION: In this small patient sample 20 mg of C0401 did not cause any adverse respiratory events. PET CO2 and RR remained in acceptably safe ranges. PET CO2 increases were most notable between 5 and 8 hr postoperatively. Respiratory rate did not show a similar trend which may be explained by a decreased tidal volume. The lower RR and SpO2 values were transient and SpO2 could be maintained at 98-100% with low flow nasal oxygen administration.