Epidural steroids, epidural morphine and epidural steroids combined with morphine in the treatment of post-laminectomy syndrome

Epidural morphine injection followed by a steroid has been reported to be effective for the post-laminectomy pain ('failed back') syndrome. This double-blind, parallel study was undertaken to evaluate that mode of therapy. Twenty-two patients who had undergone at least one prior laminectomy, who were still symptomatic, were randomized to receive 50 mg of lidocaine epidurally with: (a) 75 mg triamcinolone diacetate (TR); or (b) 8 mg of preservative-free morphine (MP); or (c) both (TR and MP), at 1 month intervals for 3 consecutive months. The spinal interspace identified with the patients' pain complaint was the site of injection. For each treatment, patients were admitted to the Clinical Research Center for 24 h and their condition continuously monitored with a pulse oximeter and apnea monitor. Five to 7 patients in each group had pain relief for less than 1 month. No patient given morphine had pain relief for more than 1 month. Life-threatening ventilatory depression occurred in the group given triamcinolone and morphine. The use of morphine alone or combined with slow release triamcinolone does not appear to be appropriate for the treatment of the post-laminectomy pain syndrome.     

CSF and plasma morphine concentrations in cancer patients during chronic epidural morphine therapy and its relation to pain relief

Seventeen patients with advanced cancer pain, treated with chronic epidural morphine, were studied. Minimum plasma and CSF morphine concentrations (Css_min) were determined at pharmacokinetic steady state. A linear relationship was found between epidural morphine dose and concentrations obtained in plasma (r = 0.92) as well as CSF (r = 0.90). The line for best fit was much steeper for CSF than for plasma. The CSF/plasma concentration gradient of morphine at Css_min was 132 ± 31 (mean ± S.E.M.). Large interindividual variations of morphine concentrations in CSF were found. It is suggested that the variations are due to substantial differences in transdural morphine diffusion between individuals. No correlation was found between pain relief, evaluated with a visual analog scale, and CSF morphine concentrations at pharmacokinetic steady state, when calculated in 9 patients. Mean duration of treatment was 104 days (range 14–366) and the daily dose was increased from 18 ± 2 to 87 ± 31 mg/day (mean ± S.E.M.). A total of 39 epidural catheters were inserted in 14 patients. The catheters were patent for 2–223 days with a mean of 38 days. When re-examined later during treatment, 2 out of 8 patients demonstrated decreased CSF morphine concentrations in spite of increased doses given. One patient with extremely high dose demand is reported on separately and data supporting the concept of a combined spinal and systemic brain morphine effect in such cases are presented. Side effects were not a major problem but the possibility of infectious complications should be considered during chronic epidural morphine therapy.     

Complications and side effects associated with epidural bupivacaine/morphine analgesia

Postoperative analgesia is a responsibility that physicians should fulfil in every patient. It is not only an act of kindness, but also an improved clinical outcome may be derived from this service when epidural techniques are used. However, complications and side effects may occur with postoperative epidural analgesia. Thus, there have been concerns among some clinicians regarding the use of local anaesthetics and opioids for epidural analgesia in the surgical wards where monitoring of patients is not as strict as it is in critical care or step down units. A review of the literature reflects a low incidence of side effects and complications in the surgical wards where the nursing staff have been trained in the early recognition of potential complications and the treatment of side effects. Many issues remain to be addressed via further research efforts. However, we believe that the current knowledge on potential complications and side effects of postoperative epidural analgesia and their treatment, allow for the safe epidural delivery of combinations of local anaesthetics and opioids in a wide range of postoperative patients. We also present the protocols that we currently use in our Acute Pain Treatment Service for the management of these complications and side effects.     

Cephalad migration of morphine in CSF following lumbar epidural administration in patients with cancer pain

This study examines the cephalad migration of morphine in CSF following lumbar epidural administration in cancer patients with pain. Fourteen cancer patients were administered 10 mg of morphine in 10 ml of normal saline via an epidural catheter inserted in the lumbar region (usually L2.3) and attached to a subcutaneously implanted portal for drug administration. There was a rapid vascular uptake of morphine from the epidural space with a mean (+/- S.D.) peak blood concentration of 110 +/- 32 ng/ml (range 76-182 ng/ml and the mean time associated with this peak blood concentration was 5.1 +/- 2.3 min (range 2-10 min). A cervical CSF sample was obtained from the C7-T1 interspace in each patient at one of the following times from the completion of the epidural morphine dose: 10, 30, 60, 120, 180, 240 or 360 min. There was a delay of at least 60 min before morphine was detected in significant concentrations (approximately 300 ng/ml) in the cervical CSF samples and peak CSF concentrations occurred after approximately 3 h. The results of this study are compatable with the hypothesis that the delayed onset of respiratory depression sometimes observed following epidural morphine in opioid naive patients results from significant amounts of morphine reaching the respiratory centre in the brain-stem as a consequence of passive CSF flow in a rostral direction from the lumbar region.     

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 post-mortem 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.     

Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats.

Epidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co-administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl- or morphine-induced antinociception in an acute pain model in rats.In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2h after treatment.Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine-induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.     

Epidural administration of morphine for control of cancer pain: long-term efficacy and complications

The long-term analgesic effects and the complications of epidural narcotic analgesia (ENA) were investigated in 40 cancer patients in whom systemic narcotic therapy failed to relieve pain or caused unacceptable side effects. In 32 patients, an externally fixated polyamide epidural catheter was used ("external group"), and in 8 patients, a polyurethane epidural catheter was tunneled and connected to a subcutaneous access port ("internal group"). The average duration of catheter treatment was 80.9 days (range 9-533 days). Twenty-five patients were treated as outpatients, and 15 remained hospitalized. Initially, all patients had significant or complete pain relief from 10 mg morphine/day, but the daily epidural morphine requirement showed a threefold increase during the first 3 weeks. During ENA, other methods of pain relief (radiotherapy, chemotherapy, surgery, epidural administration of local anesthetics, and nerve blocks) were necessary in 14 patients. Pharmacological side effects were of minor importance, with transient pruritus being the main subjective complaint. In the "external" group, 31 catheter replacements were necessary, mostly due to backflow of injected morphine outside the catheter. In two patients of the internal group, neurological complications occurred, but these disappeared spontaneously after removal of the system. They were presumably due to epidural fibrosis with compression of the spinal cord. Further technical improvements are necessary for the easier use and higher safety of the catheter technique.     

Epidural steroid injections in the treatment of symptomatic lumbar spinal stenosis associated with epidural lipomatosis

Epidural lipomatosis has been implicated as a cause or contributor of symptomatic lumbar spinal stenosis. Although epidural steroid injections have been very successful for symptomatic treatment of spinal stenosis; their role in treatment of symptomatic stenosis secondary to epidural lipomatosis is unclear. A review literature (MEDLINE, PubMed) found no reports justifying the use of steroids. We present two patients with lumbar epidural lipomatosis causing or contributing to symptomatic spinal stenosis. Both patients presented with unilateral lower limb radicular symptoms unrelieved with conservative measures such as medications and physical therapy. They were treated with a single transforaminal epidural steroid injection at the symptomatic level. Both had 80-85% pain relief. These reports suggest a beneficial role of epidural steroid injections for patients with symptomatic lumbar spinal stenosis caused by or contributing to epidural lipomatosis.     

布托啡诺与吗啡用于患者自控硬膜外术后镇痛的比较

目的:比较布托啡诺与吗啡在硬膜外术后镇痛的效果及不良反应。方法:选取80例择期硬膜外麻醉下行下肢手术患者,分成2组,分别予布托啡诺复合布比卡因(B组)和吗啡复合布比卡因(M组)硬膜外术后镇痛,记录术后4、8、24h视觉模拟评分(VAS评分)、呕吐、尿潴留及瘙痒发生率以及满意率。结果:2组患者术后的镇痛效果均满意,VAS评分<3分。呕吐发生率B组为7.5%,M组为22.5%,B组发生率较M组低。尿潴留发生率B组为7.5%,M组为55.0%,B组要低于M组。满意率B组为90.0%,M组为72.5%,B组的满意率要高。结论:布托啡诺复合布比卡因较吗啡复合布比卡因更适合于作为硬膜外术后镇痛配方。     

Evaluation of the factors affecting the efficacy and safety of postoperative epidural analgesia using morphine

Subjective and objective methods were used to assess pain in 390 surgical patients. The quality and duration of postoperative epidural analgesia (EA) with morphine was studied with regard to the analgesic concentration and volume of the solution, segment of its administration into the epidural space and its storage period. It has been shown that the degree of an antinociceptive effect does not depend on the segment of opiate administration into the epidural space, whereas the duration of analgesia increases when EA is performed into spinal segments innervating the source of pain. The effect of the first morphine dose was more durable with the increase in the analgesic concentration and decrease in the volume of the solution. Parallel enhancement of respiratory depression effect was observed. The incidence of side effects became greater towards the end of the storage period. Possible mechanisms of changes observed in EA pharmacodynamics are reviewed in terms of increased efficacy and safety of the procedure.     

Epidural and intrathecal morphine in intensive care units

Analgesia and sedation for patients in intensive care units (ICU) who require mechanical ventilation are most commonly provided by intermittent i.v. injections of opiates and benzodiazepines. However, the technique has a number of disadvantages. Also, in many case these drugs are inadequate, even in large doses, and muscle relaxants may be necessary for patient respirator coordination. The analgesic effect of epidural and intrathecal morphine was studied in 24 ICU patients requiring controlled ventilation. In spite of large doses of phenoperidine, diazepam and a number of other analgesics and sedatives, all patients were restless, agitated and coordinated poorly with the respirator. Through an indwelling epidural catheter morphine (4 mg) was injected intermittently as required in 11 patients and as a continuous infusion (20–40 mg/day) in five patients. In eight patients morphine (2–4 mg) was injected intrathecally as a single injection. Both epidural and intrathecal morphine gave potent analgesia and good patient respirator coordination. The duration of analgesia was shortest after intermittent injections of epidural morphine and longest after intrathecal morphine. However, continuous infusion of morphine in the epidural catheter appears to be the most practical method. In patients with multiple trauma and in patients where frequent assessment of the level of consciousness is important this technique is superior to parenteral analgesic sedative combinations. Intrathecal morphine may be indicated in patients in a compromised position. The daily analgesic requirement can be reduced by about 10–100 times by the use of epidural and intrathecal morphine respectively.     

Epidural abscess and meningitis after epidural corticosteroid injection

Epidural abscess with and without associated meningitis after epidural corticosteroid injections for radicular back pain is a rarely reported complication. We report the occurrence of an epidural abscess and meningitis in a 70-year-old man after 2 epidural corticosteroid injections for treatment of acute radicular lumbar back pain. At the time of diagnosis, cerebrospinal fluid cultures grew Staphylococcus aureus, and the patient was treated with intravenous antibiotics. Possible predisposing factors for the development of an epidural abscess and meningitis in this patient include a 2-year history of neutropenia and an accidental dural puncture that occurred during performance of the first epidural injection. A literature search identified 11 reported cases of epidural abscess, 2 of epidural abscess and meningitis, and 1 of meningitis attributed to epidural corticosteroid injections. Eight of the 14 reported patients were immunocompromised, and 8 (67%) of the 12 in whom cultures of blood, cerebrospinal fluid, or epidural pus were performed had results positive for S. aureus. Antibiotic prophylaxis for S. aureus should be considered for immunocompromised patients undergoing epidural corticosteroid injections.     

Epidural hematoma associated with dextran infusion

The authors describe a case of epidural hematoma in association with dextran infusion in a patient who had undergone a peripheral vascular operation with epidural analgesia. Possible mechanisms for the anticoagulant effect of dextran and guidelines for the use of anticoagulant therapy in patients undergoing epidural anesthesia are discussed.     

Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection

We report a case of respiratory depression after intracerebroventricular morphine administration of a dose inadvertently 10 times greater than the typical daily dose. At the time of the respiratory dysfunction, the concentrations of morphine and its metabolites in cerebrospinal fluid (CSF) and plasma samples were determined. On comparison of these results with previous clinical studies in which there was no respiratory depression, no relationship was found between the occurrence of respiratory depression and the concentration of morphine or its metabolites in the CSF. The occurrence and characteristics of respiratory depression may be related to the concentrations of morphine and its metabolites in bulbar tissue.     

An experience with epidural morphine in lumbar surgery patients

A chart review of the patients who received epidural morphine for lumbar surgery during the first year of implementation of the procedure was conducted. This article reviews the pharmacology and side effects of epidural morphine, describes the procedure of administering epidural morphine, discusses side effects and technical problems encountered, and presents implications for nursing practice.     

吗啡与新斯的明注入硬膜外腔术后镇痛的对照研究

目的 研究吗啡与新斯的明的镇痛作用,同时对其用于硬膜外镇痛的安全性和有效性进行评价。方法采用完全随机设计。随机选择90例拟行腰段硬膜外麻醉的病人随机分为5组,按实验分组予以不同的镇痛配方,用视觉模拟疼痛评分进行疼痛评分,记录相应指标和不良反应。结果镇痛效果从好到差依次为新斯的明1.5mg加吗啡1.5mg加氟哌啶2.5mg组（Ⅰ组）、吗啡2.0mg加氟哌啶2.5mg组（对照组）、新斯的明1.0mg加吗啡1.0mg加氟哌啶2.5mg（Ⅱ组）、新斯的明0.7mg加吗啡0.7mg加氟哌啶2.5mg组（Ⅲ组）、新斯的明0.5mg加吗啡0.5mg加氟哌啶2.5mg组（Ⅳ组）;Ⅰ组、Ⅱ组、Ⅲ组、Ⅳ组和对照组另加镇痛药使用率分别为0％、2.0％、30.0％、65.0％和6％;不良反应发生率分别为66.7％、20.0％、20.0％、5.0％和73.4％。结论 吗啡与新斯的明应用于硬膜外腔有镇痛作用,且新斯的明1.0mg、吗啡1.0mg的剂量加氟哌啶能提供相对较好的镇痛作用,不良反应发生率低。     

Paraplegia associated with epidural anesthesia

Spinal anesthesia has lost its popularity among physicians due to rare occurrences of paraplegia that have precipitated lawsuits, with staggering judgments in favor of claimants. Epidural block has now become a popular alternative because some believe it cannot cause paraplegia; however, paraplegia is as prevalent after induction of epidural anesthesia as after spinal anesthesia. Arachnoiditis has been incriminated as the causative agent when paraplegia has followed spinal anesthesia. Arachnoiditis is also a causative factor when paraplegia follows epidural block. Cord compression and anterior spinal artery syndrome have also been associated with paraplegia after epidural block though they have not been a problem with spinal block.