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Analgesia with epidural nimodipine
Letters to the Editor
Analgesia with epidural nimodipine SIR-A strong relation between calcium and the action of opioids on the central nervous system has been suggested. In animals, calcium-channel antagonists have facilitatory and/or modulatory effects on the behavioural and physiological 1 consequences of endogenous p and 8 opioid activity.’ Intravenous nimodipine enhanced fentanyl analgesia2 although others doubted this synergistic effect.3 No reports on epidural administration of nimodipine for pain management exist. We report 2 patients with bone metastases producing intractable somatic pain that could not be controlled by the second-step regimen of the WHO three-step analgesic ladder. After informed consent, our patients agreed to participate in a double-blind patient-controlled trial that consisted of 6 randomised sequential intravenous and epidural schemes, each lasting 1 day, starting every morning (0800 h, baseline). Both patients were given nimodipine (10 mg per 50 mL ampoule, polyethylene glycol 400 and ethanol solvent), administered intravenously alone, in combination with low-dose (3 mg) and high-dose (10 mg) epidural morphine, or epidurally as sole agent (table). Pain assessment by a visual analogue score (VAS), haemodynamics, and possible adverse effects were recorded at 20,40,60,90, and 120 min, and then every hour. On request of the patient, or with a VAS score above the baseline pain score, the sequential scheme was terminated and the patient received intravenous meperidine until 0200 h the next
morning, given by patient-controlled analgesia. Patient 1 was a 68-year-old man with somatic pain due to terminal lung cancer. The most prolonged analgesic effect was observed after 10 mg morphine epidurally as well as after the combination of 3 mg epidural morphine combined with continuous intravenous nimodipine. Epidural nimodipine alone produced an intense but short-lasting VAS reduction. The patient reported a burning sensation during the epidural bolus of nimodipine, which lasted only a few minutes. Throughout the study, mean arterial pressure never fell below 65 mm Hg and no therapeutic intervention was necessary at any time. Heart rate and Sp02 were unaffected during all trial days.
Patient 2 was a 37-year-old woman with somatic pain due to end-stage breast cancer. Epidural nimodipine alone produced intense analgesia, but of shorter duration than that in patient 1. Patient 2 also described a burning sensation after epidural
nimodipine. Not enough information is available on the possible analgesic’ effect of calcium-channel antagonists in man. Our findings suggest that nimodipine has some analgesic properties that seem to be more profound after epidural than after intravenous administration. Furthermore, intravenous nimodipine enhanced the analgesic effect of epidural morphine. However, because plasma concentrations of the study drugs were not determined, carryover effects cannot be excluded. Although the role of calcium in nociception has to be determined, the cited laboratory and clinical data and our findings suggest that nimodipine may prove valuable in the treatment of cancer pain when epidural morphine is used. However, the role of the nimodipine solvent in the analgesic effect attributed to epidural nimodipine cannot be excluded. The toxicity of nimodipine and its solvent has been extensively evaluated and seems to be low even after intrathecal4 or intracisternal administration.5 In conclusion, our cases suggest that nimodipine may have potential as an adjuvant to morphine in the treatment of cancer pain. Properly designed controlled trials are needed to identify the effectiveness of nimodipine after different doses and routes of administration. Kriton S Filos, Leonidas C Vassilios Tassoudis
Goudas, Ourania Patroni,
Department of Anaesthesiology and Critical Care Medicine, School of Medicine, University of Patras, Patras, Greece 26500
Kavaliers M. Stimulatory influences of calcium channel antagonists on stress-induced opioid analgesia and locomotor activity. Brain Res 1987; 408: 403-07. 2 von Bormann B, Boldt J, Sturm G, et al. Calciumantagonisten in der Anaesthesie: additive analgesie durch Nimodipin waehrend cardiochirugischer Eingriffe. Anaesthesist 1985; 34: 429-34. 3 Lehmann KA, Kriegel R, Ueki M. Zur klinischen Bedeutung von Arzneimittelinteraktionen zwischen Opiaten und Kalziumantagonisten. Anaesthesist 1989; 38: 110-15. 4 Lewis PJ, Weir BKA, Nosko MG, Tanabe T, Grace MG. Intrathecal nimodipine therapy in a primate model of chronic cerebral vasospasm. Neurosurgery 1988; 22: 492-500. 5 Ljunggren B, Brandt L, Saveland H, et al. Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 1984; 61: 864-73. 1
Topical morphine for peripheral pain
’Minutes of pain relief at under 50% of baseline.
t10 mL, #10 mL/h. Table : Analgesic effects of nimodipine and/or morphine
SiR-Stein and colleagues (Aug 7, p 321) document the presence of opioid peptides in inflamed synovial tissue and provide support for the notion of peripheral opioid analgesia. Joshi (Aug 7, p 320; and ref 1) and Stein and associates have shown that intra-articular morphine after knee arthroscopy provides pain relief and call for further clinical studies to clarify the issues raised by this experimental work. As a result of these preliminary findings, we attempted to find out whether topical morphine sulphate applied over the back of patients with severe, chronic back pain provides pain relief. 1047
Analgesia with epidural nimodipine SIR-A strong relation between calcium and the action of opioids on the central nervous system has been suggested. In animals, calcium-channel antagonists have facilitatory and/or modulatory effects on the behavioural and physiological 1 consequences of endogenous p and 8 opioid activity.’ Intravenous nimodipine enhanced fentanyl analgesia2 although others doubted this synergistic effect.3 No reports on epidural administration of nimodipine for pain management exist. We report 2 patients with bone metastases producing intractable somatic pain that could not be controlled by the second-step regimen of the WHO three-step analgesic ladder. After informed consent, our patients agreed to participate in a double-blind patient-controlled trial that consisted of 6 randomised sequential intravenous and epidural schemes, each lasting 1 day, starting every morning (0800 h, baseline). Both patients were given nimodipine (10 mg per 50 mL ampoule, polyethylene glycol 400 and ethanol solvent), administered intravenously alone, in combination with low-dose (3 mg) and high-dose (10 mg) epidural morphine, or epidurally as sole agent (table). Pain assessment by a visual analogue score (VAS), haemodynamics, and possible adverse effects were recorded at 20,40,60,90, and 120 min, and then every hour. On request of the patient, or with a VAS score above the baseline pain score, the sequential scheme was terminated and the patient received intravenous meperidine until 0200 h the next
morning, given by patient-controlled analgesia. Patient 1 was a 68-year-old man with somatic pain due to terminal lung cancer. The most prolonged analgesic effect was observed after 10 mg morphine epidurally as well as after the combination of 3 mg epidural morphine combined with continuous intravenous nimodipine. Epidural nimodipine alone produced an intense but short-lasting VAS reduction. The patient reported a burning sensation during the epidural bolus of nimodipine, which lasted only a few minutes. Throughout the study, mean arterial pressure never fell below 65 mm Hg and no therapeutic intervention was necessary at any time. Heart rate and Sp02 were unaffected during all trial days.
Patient 2 was a 37-year-old woman with somatic pain due to end-stage breast cancer. Epidural nimodipine alone produced intense analgesia, but of shorter duration than that in patient 1. Patient 2 also described a burning sensation after epidural
nimodipine. Not enough information is available on the possible analgesic’ effect of calcium-channel antagonists in man. Our findings suggest that nimodipine has some analgesic properties that seem to be more profound after epidural than after intravenous administration. Furthermore, intravenous nimodipine enhanced the analgesic effect of epidural morphine. However, because plasma concentrations of the study drugs were not determined, carryover effects cannot be excluded. Although the role of calcium in nociception has to be determined, the cited laboratory and clinical data and our findings suggest that nimodipine may prove valuable in the treatment of cancer pain when epidural morphine is used. However, the role of the nimodipine solvent in the analgesic effect attributed to epidural nimodipine cannot be excluded. The toxicity of nimodipine and its solvent has been extensively evaluated and seems to be low even after intrathecal4 or intracisternal administration.5 In conclusion, our cases suggest that nimodipine may have potential as an adjuvant to morphine in the treatment of cancer pain. Properly designed controlled trials are needed to identify the effectiveness of nimodipine after different doses and routes of administration. Kriton S Filos, Leonidas C Vassilios Tassoudis
Goudas, Ourania Patroni,
Department of Anaesthesiology and Critical Care Medicine, School of Medicine, University of Patras, Patras, Greece 26500
Kavaliers M. Stimulatory influences of calcium channel antagonists on stress-induced opioid analgesia and locomotor activity. Brain Res 1987; 408: 403-07. 2 von Bormann B, Boldt J, Sturm G, et al. Calciumantagonisten in der Anaesthesie: additive analgesie durch Nimodipin waehrend cardiochirugischer Eingriffe. Anaesthesist 1985; 34: 429-34. 3 Lehmann KA, Kriegel R, Ueki M. Zur klinischen Bedeutung von Arzneimittelinteraktionen zwischen Opiaten und Kalziumantagonisten. Anaesthesist 1989; 38: 110-15. 4 Lewis PJ, Weir BKA, Nosko MG, Tanabe T, Grace MG. Intrathecal nimodipine therapy in a primate model of chronic cerebral vasospasm. Neurosurgery 1988; 22: 492-500. 5 Ljunggren B, Brandt L, Saveland H, et al. Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 1984; 61: 864-73. 1
Topical morphine for peripheral pain
’Minutes of pain relief at under 50% of baseline.
t10 mL, #10 mL/h. Table : Analgesic effects of nimodipine and/or morphine
SiR-Stein and colleagues (Aug 7, p 321) document the presence of opioid peptides in inflamed synovial tissue and provide support for the notion of peripheral opioid analgesia. Joshi (Aug 7, p 320; and ref 1) and Stein and associates have shown that intra-articular morphine after knee arthroscopy provides pain relief and call for further clinical studies to clarify the issues raised by this experimental work. As a result of these preliminary findings, we attempted to find out whether topical morphine sulphate applied over the back of patients with severe, chronic back pain provides pain relief. 1047