The purpose of this article is to review the literature on the side effects of intrathecal and epidural opioids. English-language articles were identified through a MEDLINE search and through review of the bibliographies of identified articles. With the increasing utilization of intrathecal and epidural opioids in humans during the 1980s, a wide variety of clinically relevant side effects have been reported. The four classic side effects are pruritus, nausea and vomiting, urinary retention, and respiratory depression. Numerous other side effects have also been described. Most side effects are dose-dependent and may be more common if the opioid is administered intrathecally. Side effects are less common in patients chronically exposed to either intrathecal, epidural, or systemic opioids. Some side effects are mediated via interaction with specific opioid receptors while others are not. It is concluded that the introduction of intrathecal and epidural opioids marks one of the most important breakthroughs in pain management in the last two decades. However, a wide variety of clinically relevant non-nociceptive side effects may occur. All physicians utilizing intrathecal and epidural opioids must be aware of these side effects, for while most are minor, others are potentially lethal.

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Side effects of intrathecal and epidural opioids.

A study was performed to evaluate the clinical and histopathologic characteristics of a distinctive degenerative lesion within the central nervous system (CNS) of children with acute lymphocytic leukemia (ALL). Of the 231 patients in this study, 13 were found to have specific degenerative changes in telencephalic white matter. Morphologically, the principal changes consisted of diffuse reactive astrocytosis and multiple, noninflammatory necrotic foci, often containing varying amounts of mineralized cellular debris. Clinical features common to all patients with this leukoencephalopathy were: 1) cranial irradiation of 2000 rads or more and 2) methotrexate administered systemically after irradiation. Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL. Age at time of irradiation, bacterial infections, nutrition, and CNS leukemia were not causally related to the development of this disease. This study suggests that chemotherapeutic agents may diffuse through the blood-brain barrier following CNS irradiation of 2000 rads or more.

The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy

THE INTEMPERATE use of alcoholic beverages is a serious problem for American society. In 1985 an estimated 10.6 million Americans were alcohol dependent, and 7.3 million more experienced some negative consequence of alcohol abuse such as arrest, accident, or impairment of health or job performance.1Alcohol is involved in 35% to 50% of marital violence cases and 10% of occupational injuries. In 1984 at least 18 500 traffic deaths (approximately 40% ) were alcohol related. The National Institute on Alcohol Abuse and Alcoholism estimated that alcoholrelated problems cost our society $117 billion in 1983. The impact on health includes increased morbidity from cirrhosis, gastrointestinal hemorrhage, trauma, cancer, and infection. Factors that contribute to the high incidence of infection among alcoholics include dulled mental function, breakdown of local protective barriers, aspiration, exposure, and malnutrition. Both malnutrition and cirrhosis of the liver are known to adversely affect the body's immune response, and so

Alcohol and Immune Defense

THE incidence of neurologic disorders has been steadily increasing in several neoplastic diseases as recent advances in therapy have lengthened patient survival.1 2 3 The neurologic complications of cancer most frequently result from metastasis to the nervous system or compression of neural structures by extraneural tumor. In addition, an interesting group of nonmetastatic neuromuscular disorders has recently been described,4 , 5 and the broad concept of "carcinomatous neuromyopathy" is frequently invoked to explain obscure neurologic symptoms in patients with cancer.6 However, it is also important to realize that neurologic dysfunction may be iatrogenic — i.e., caused by the treatment of cancer. Radiation myelitis and . . .

Neurotoxicity of Commonly Used Antineoplastic Agents

This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitt's lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuro-pathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swellings both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197502%2935%3A2%3C291%3A%3AAID-CNCR2820350202%3E3.0.CO%3B2-V

Disseminated necrotizing leukoencephalopathy: A complication of treated central nervous system leukemia and lymphoma

A case report and review of the literature of paraplegia following intrathecal chemotherapy with methotrexate and cytosine arabinoside is presented. Autopsy identified damage to the spinal nerve roots within the subarachnoid space, which accounted for the neurologic deficit. The only substances common to both chemotherapeutic agents were their preservatives, methylhydroxybenzoate and benzyl alcohol, which were used, in the diluent. Prolonged exposure to these preservatives is known to cause severe neurotoxicity. Though the specific agent responsible for paraplegia following intrathecal chemotherapy is unknown, there is evidence to suggest that the preservatives rather than the therapeutic agents themselves are responsible.

Paraplegia following intrathecal chemotherapy.

Alcoholism, infection and altered host defenses: a review of clinical and experimental observations.

Whole sera and serum fractions from 24 patients with Felty's syndrome, 42 patients with systemic lupus erythematosus (SLE), and 48 patients with rheumatoid arthritis (RA), as well as 30 patients with miscellaneous acute and chronic disease states, were studied for their effect on numbers of mouse bone marrow colonies grown on soft agar in the presence of human colony stimulating factor. Significant early retardation of mouse bone marrow colony counts was recorded in 87.5 percent of Felty's sera, 43 percent of SLE sera, and 12.5 percent of sera from patients with uncomplicated RA. Forty percent of 30 other control patients with acute or chronic inflammatory diseases also showed this activity. No diminution was noted with any of 40 normal control sera. Degree of marrow colony retardation could be directly correlated to amounts of test serum added. No single serum fraction isolated by ion exchange chromatography, gel filtration, or electrophoresis was identified as solely responsible for marrow growth retardation; however lipoprotein fractions including chylomicrons, LDL and HDL showed inhibiting activity in various sera.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780180405

Retardation of colony growth of in vitro bone marrow culture using sera from patients with felty' syndrome, disseminated lupus erythematosus (sle), rheumatoid arthritis, and other disease states

Fredrica E. Smith

Papers

Paraplegia following intrathecal chemotherapy.

Alcoholism, infection and altered host defenses: a review of clinical and experimental observations.

Retardation of colony growth of in vitro bone marrow culture using sera from patients with felty' syndrome, disseminated lupus erythematosus (sle), rheumatoid arthritis, and other disease states