Intraspinal Morphine Research Articles

Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain : Neurosurgery, 18 (1986) 740–747

Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain : Neurosurgery, 18 (1986) 740–747

Intraspinal morphine for cancer pain.

From a survey of the recent literature on chronic intraspinal morphine administration for cancer pain concerning 412 cases, the present authors observe that: 1. data regarding follow-up on pain relief and complications are lacking; 2. continuous administration by closed systems shows more efficacy in long-term pain relief; 3. tolerance, although not reported by all authors, is present and becomes remarkable in prolonged administration; 4. serious side-effects are less frequent with the epidural administration technique. These data are confirmed by the present authors' clinical experience of 22 patients treated with epidural morphine administration and 53 patients treated with intrathecal morphine. The widespread use of these methods is limited not only by technical complications but also by the existence of certain types of pain which do not respond to morphine and which may develop, as part of the evolution of the neoplastic disease, even during treatment with intraspinal morphine.

A Clinical Study on Pruritus Due to Intrathecal Morphine

Herein is a review of eigthy six surgical cases from March to August, 1986 which recieved tetracaine hydrochloride spinal anesthesia. In an attempt to relieve postoperative pain, 0.5 mg morphine sulfate was administrated into the lumbar subarachnoid space. Pruritus, a side effect of intraspinal morphine, was explored in detail. The results were as follows : 1) The incidence of pruritus was 67.4%, 65.5% in man and 71.0% in woman. 2) The time of onset of pruritus was between 30 and 120 minutes with an average of 79.1 minutes. 3) Pruritus primary occurred on the face(87.9%), especially on the nasal, perinasal and periocular areas. Other sites included the scalp, neck, chest, abdomen, shoulder, hip, thigh, flank, and whole body. 4) The severity of pruritus was classified as mild and moderate, but 4 cases(6.9%) were regarded as severe and were treated with naloxone. 5) The duration of pruritus was from 15 minutes to 19 hours with an average of 4.7 hours. 6) There was no significant difference in the prevention of pruritus between the group recieving diphenhydramine and the one which received normal saline.

Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain

Administration of intraspinal morphine sulfate for the treatment of intractable cancer pain

Morphine Concentration in Brain and Spinal Cord after Subarachnoid Injection in Baboons

Tritium-labeled morphine was injected into the lumbar (L4-5) subarachnoid space of three baboons. The animals were sacrificed 3, 6, and 24 hr thereafter. Morphine concentrations were measured at five predetermined positions within the spinal cord, medulla oblongata, and frontal lobes of the brain by scintillation-count assay. The results revealed that morphine ascends in the subarachnoid space and is absorbed into the spinal cord and medulla oblongata in a time-dependent fashion. Ventilation was most depressed and maximal concentrations of morphine were detected in the medulla six hours after injection. Delayed respiratory depression, occasionally reported after intraspinal morphine injection, may therefore be caused as a result of the affinity of morphine for binding sites, possibly opiate receptors, situated within the vital respiratory and cardiovascular neuronal complexes of the medulla.

Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study

Seven patients with chronic intractable pain due to cancer were given chronic intraspinal narcotic administration (CINA) and subsequently underwent postmortem examination. All deaths were unrelated to CINA. Two of these patients were found to have clinically unsuspected posterior column degeneration. Both patients had had epidural catheters placed and one had received prior radiotherapy to ports which included parts of the spinal cord. In retrospect, it is impossible to ascertain whether the degeneration occurred before or after infusion of morphine began. Review of the potential causes for posterior column degeneration suggests that neuropathy associated with malignant disease is more likely the cause of the degeneration rather than intraspinal infusion of morphine. However, continued vigilance at autopsy is recommended. In addition, utilizing a new method for measuring cerebrospinal fluid (CSF) concentrations of morphine via high-pressure liquid chromatography, CSF morphine levels at steady state were measured in 5 patients. These levels were much lower than peak levels previously reported following bolus intraspinal administration. The ability of these measurements to contribute to knowledge of efficacy, toxicity. lumbar-cisternal concentration gradients and differentiation of tolerance from drug delivery problems is discussed.

Outcomes and complications of continuous intraspinal narcotic analgesia for cancer pain control.

Preliminary reports of continuous intraspinal morphine analgesia have been enthusiastic regarding the resultant cancer pain control. Reports of continuous intraspinal infusion have not documented the duration of useful analgesia, need for concomitant analgesic therapies, or complication rates. Thus, the overall outcomes and complications of six chronic intrathecal and eight epidural morphine infusions were analyzed in the first 14 cancer pain patients implanted with continuous intraspinal morphine infusion reservoirs at this clinic. A five-point scale was used to assess the analgesic therapy required to maintain pain control during three consecutive intervals of intraspinal morphine infusion (zero to two months, two to six months, after six months). Comparison with pre-implant narcotic requirements revealed equal or reduced narcotic use for up to six months of therapy, with a definite trend toward escalation of intraspinal narcotics, systemic analgesia, and adjunctive procedures after two months. This occurred most likely due to narcotic tolerance and disease progression. Failure of pain control was the rule with continuous intraspinal morphine after six months. Three patients ultimately required neurolytic blocks. No clear difference was found in pain control requirements between epidural and intrathecal morphine infusion. No infection or respiratory depression occurred as a direct result of the intraspinal morphine implanted system.

Behavioral effects of morphine, levorphanol, dextrorphan and naloxone in the frog Rana pipiens

Systemic morphine induces explosive motor behavior and generalized muscular rigidity in frogs. Naloxone does not reverse either of these effects of morphine but at high doses causes muscular flaccidity and unresponsiveness to stimulation. Intraspinal morphine induces rigidity, but not explosive motor behavior, and this action is blocked by naloxone. Behavioral effects are seen rarely after intraspinal levorphanol (rigidity) and never after intraspinal dextrorphan or naloxone. In contrast to systemic morphine and naloxone, systemic levorphanol and dextrorphan are lethal to frogs at high doses.

Relief of Continuous Chronic Pain by Intraspinal Narcotics Infusion Via an Implanted Reservoir

Ten patients with intractable pain (five cancer and five nonmalignant) were treated with continuous intraspinal morphine delivered by an implanted continuous infusion system. Both patient groups were evaluated and compared using an identical battery of psychometric examinations administered before and 12 weeks after therapy. The cancer-pain group reported significant reduction in pain on serial visual pain analogue scales at 12 weeks compared with no change in the nonmalignant-pain group reports despite a much lower baseline report in the cancer group. Both groups of patients reduced their oral narcotic requirement significantly during continuous intraspinal morphine infusion. While the cancer patients took more oral narcotic at baseline, at 12 weeks no difference existed in oral intake between the two groups. Both groups required significant serial increases in infused morphine, indicating that spinal opiate receptor tolerance occurs. The results of this study confirm the sustained analgesic efficacy reported earlier in cancer-related pain syndromes, thus supporting further cautious expansion of this therapy within the cancer-related pain population. In contrast, a poor response was seen in the nonmalignant-pain group, consistent with the unsatisfactory responses to many potentially analgetic approaches to chronic nonmalignant pain. We are thus discouraged from further use of this therapy in the patient with chronic nonmalignant pain.

Intraspinal Narcotic Tolerance: Preliminary Experience with Continuous Bupivicaine HCL Infusion via Implanted Infusion Device

Spinal opiate receptor tolerance is the major limitation of continuous intraspinal narcotic analgesia delivered by implanted reservoir pump. Six intractable pain patients receiving continuous epidural morphine were given trials of low dose bupivicaine HCL in order to assess the effects on implanted reservoir function, analgesia, and safety. Daily infusion of 2.6-18.8 mg bupivicaine HCL had no consistent effect on flow rates. Subjectively, three patients had at least partial relief of pain while their intraspinal morphine doses were weaned. No sympathectomy was appreciated at these doses. The future of continuous intraspinal analgesia might require further advances in implantable infusion pump technology to allow manipulation of both daily infusion doses and multiple intraspinal analgesics. Further study is needed to assess the safety and effectiveness of higher continuous intraspinal bupivicaine doses for chronic pain relief.