Abstract:
BACKGROUND:mu-Opioids administered spinally produce a potent, dose-dependent analgesic response in preclinical and clinical investigations. Side-effect profile of these compounds may be altered as a function of pharmacokinetics. The effects of intrathecal and intraperitoneal remifentanil, an esterase-metabolized mu opioid, alfentanil, and morphine were compared. METHODS:Intrathecal and intraperitoneal remifentanil, alfentanil, and morphine were examined in rats tested for hind-paw thermal withdrawal latency. The antinociceptive response was assessed and in parallel a scoring of four different parameters summarized as a supraspinal index to assess supraspinal side-effect profiles after the several drugs were delivered by the different routes. RESULTS:All opioids produced a dose-dependent analgesic response after intrathecal administration. The ordering of potency (intrathecal ED50 in micrograms) was remifentanil (0.7) > morphine (12.0) > alfentanil (16.3) > GR90291, principal remifentanil metabolite (> 810 micrograms). Time until onset of analgesia after intrathecal or intraperitoneal delivery was morphine > remifentanil = alfentanil. When matched for analgesic effect, the relative duration of action was morphine > alfentanil > remifentanil. The supraspinal index showed a dose-dependent increase for all agents. All intraperitoneal drugs showed dose-dependent increases in antinociception with potency (intraperitoneal ED50 in micrograms) of remifentanil (4.3) > alfentanil (24.4) > morphine (262). Calculation of intrathecal or intraperitoneal ratios for supraspinal side effects/analgesia (supraspinal index ED50/analgesia ED50) revealed remifentanil to be greatest when intrathecally administered: remifentanil (4 intrathecal: 1.4 intraperitoneal); alfentanil (0.7 intrathecal: 1.5 intraperitoneal); and morphine (1 intrathecal: 5.6 intraperitoneal). CONCLUSIONS:These observations indicate that remifentanil has a powerful spinal opioid action. Consistent with its lipid-solubility, it has an early onset like alfentanil but displays a shorter duration of action after bolus delivery. Despite lipid solubility, remifentanil has a significant spinal therapeutic ratio. These observations likely reflect the rapid inactivation of systemically redistributed agent by plasma esterases.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Buerkle H,Yaksh TLdoi
10.1097/00000542-199601000-00012subject
Has Abstractpub_date
1996-01-01 00:00:00pages
94-102issue
1eissn
0003-3022issn
1528-1175journal_volume
84pub_type
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