The intrathecal application of an opioid presents a more direct way to administer the opioid close to its site of action, the substantia gelatinosa at the dorsal column
of the spinal cord. Aside from the lack of diffusion through the dura mater, the usual migration of the opioid within the cerebrospinal fluid and the unspecific binding of the opioid to epidural fat tissue as well as the vascular reabsorption through the venous plexus within the epidural space is avoided . From such consideration it can be concluded that the activity of intrathecal use of opioids is far better foreseeable, is more intense, and results in a longer duration of action. This for instance has been demonstrated for sufentanil and morphine given in obstetric anesthesia during the first stage of labor where the analgesic dose was 10 ^g and 1 mg respectively, resulting in a duration of action lasting 1-2 h (Figure III-80). Such low doses are incapable to induce sufficient analgesia when using the epidural or the intravenous route .
Several studies however have documented that the highly lipophilic opioids (e.g. sufentanil, fentanyl, alfentanil, butorphanol, pethidine) demonstrate little dose reduction when comparing the intravenous with the intrathecal mode of application . When comparing the intrathecal with the epidural mode, clearly there is an advantage for the intrathecal route, and in order to achieve similar cerebrospinal concentrations, the epidural dose has to be increased 5fold . For morphine and fentanyl there are similar dose differences, whereby morphine 0.3 mg or fentanyl 25 ^g in combination with bupivacaine results in a good analgesic level during labor pain. In spite of such encouraging results, and contrary to the peridural use of opioids, there are only few controlled studies. In order to give general recommendations and definitively outline the putative advantage of an intrathecal use of opioids, additional studies are needed. Since the known side effects, as
Figure III-80. Visual analogue scale (VAS) in patients using different routes and dosages of sufentanil for treatment of labor pain (*p < 0.01)
they are observed after epidural application (i.e., respiratory depression, pruritis) very likely appear shortly following application . In case of an inadvertent respiratory depression, low-dose naloxone is the agent of choice to reverse this side effect without significantly affecting the analgesic level .
In summary the followed advantages of intrathecal versus peridural application of an opioid are obvious:
1. Lower systemic reabsorption.
2. Lower non-specific absorption via peridural fat tissue.
3. Lower dosages, resulting in a reduced incidence in side effects.
4. Pronounced selection of the analgesic level .
However, there are several considerations why presently, contrary to intrathecal use, the epidural route is still considered to have a major advantage [230, 253]:
1. The necessary catheter technology is not fully developed.
2. Lipophilic opioids necessarily do not result in a longer duration of action than the hydrophilic morphine.
3. There is a higher potential risk in incidence of side effects, especially of respiratory depression.
4. The question of a possible neurotoxicity of agents has not been answered adequately.
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