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Thread: Dr. Young - morphine into brain ventricles

  1. #1
    Senior Member alan's Avatar
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    Dr. Young - morphine into brain ventricles

    Dr. Young,

    Have you heard of treating chronic pain by injecting morphine directly into the ventricles of the brain?


    Alan

  2. #2
    Alan,

    Yes. It is used for intractable pain, particular of the upper neck and head.

    Wise.


    • Blond S, Guieu JD, Meynadier J, Le Bars D and Willer JC (1994). Intracerebroventricular morphine, analgesia, and nociceptive spinal reflexes. Lancet 343:857-8. Summary:

    • Cerda-Olmedo G, De Andres J and Moliner S (2002). Management of progressive pain in a patient with intramedullary chordoma of the spine. Clin J Pain 18:128-31. Summary: OBJECTIVES: The case here presented adequately reflects the difficulties involved in the treatment of pain in patients where the neuropathic component of pain predominates, and shows the different therapeutic steps that may be taken-from surgery and radiotherapy, to the administration of different drugs via the spinal route, to, finally, the presently little-used option of a direct intraventricular access. CONCLUSIONS: Spinal tumors are infrequent, but pose great difficulties for the management and control of the pain they cause. The utility of the spinal route as an early approach for the provision of adequate analgesia seems clear. However, it also appears to lose efficacy with time, and dose incrementing and/or the addition of drugs that enhance the analgesic action of morphine are not always effective. In such selected cases, the intraventricular route may constitute a useful alternative, allowing improved symptoms control with lower morphine doses, and the use of the system previously implanted for intrathecal spinal infusion. Multidisciplinary Pain Management Center, Department of Anesthesia, Valencia University General Hospital, Valencia, Spain. fundolor@gva.es

    • Cramond T and Stuart G (1993). Intraventricular morphine for intractable pain of advanced cancer. J Pain Symptom Manage 8:465-73. Summary: Among the most difficult pain management problems are those associated with advanced head and neck cancer, and those in which pain is midline, bilateral, or diffuse. The authors report effective control of intractable pain in 52 patients by injection of small doses of morphine via an Ommaya or a Cordis reservoir into the lateral cerebral ventricle. The technique is safe and effective. The reservoir is usually inserted under local analgesia so the method of pain relief is available to patients in whom general anesthesia would be difficult or contraindicated. The doses of morphine required to maintain analgesia remain remarkably low. Tolerance reported by other authors has not been a problem when preoperative assessment of the patient has been thorough. Maximum survival time has been 75 wk and another patient has lived 65 wk. Complications included two colonized reservoirs, one dislodged ventricular catheter, three blocked catheters, and one postoperative meningitis. For patients with diffuse midline or bilateral pain, or intractable pain associated with advanced head and neck cancer, the use of intraventricular morphine should be considered when satisfactory pain relief is not achieved with oral morphine or continuous subcutaneous infusion. Pain Relief Service, Royal Brisbane Hospital, Australia.

    • Dennis GC and DeWitty RL (1990). Long-term intraventricular infusion of morphine for intractable pain in cancer of the head and neck. Neurosurgery 26:404-7; discussion 407-8. Summary: The authors' experience with seven patients with intractable pain that was treated by continuous intraventricular infusion of morphine through an implanted Infusaid pump is reported. The pain was caused by head and neck cancer in six patients and was associated with postpolio syndrome in one. The average follow-up was 7 months. Pain was effectively managed through intraventricular administration of a combination of morphine and mild oral narcotic analgesics. Complications included one case of transient respiratory depression, one pump pocket infection, and one pump failure. The morphine dose required to maintain analgesia increased over time in all patients treated. This is a safe and effective method of pain management in patients with head and neck cancer. It is useful as well in patients who have intractable pain that cannot be managed through an intrathecal route because of a contraindication to lumbar puncture or an inaccessible subarachnoid space. Department of Surgery, College of Medicine, Howard University, Washington, District of Columbia.

    • Esposito S and Delitala A (1991). Transoval administration of opiates into trigeminal cistern for cancer pain. Preliminary report. Neurochirurgia (Stuttg) 34:116-8. Summary: A new method for administration of opiates into the ventriculo-cisternal system for intractable pain due to cancer is presented. Five patients suffering from such pain underwent the permanent implantation of a subcutaneous reservoir connected to a thin catheter inserted into the trigeminal cistern. The indications are those of the intraventricular way. Percutaneous trigeminal opiates administration (PTO) proved to be a valid and simple alternative method to intrathecal and intraventricular morphine. Divisione di Neurochirurgia, G. M. Lancisi, Ospedale San Camillo, Roma, Italia.

    • Houdek M, Opavsky J and Ostrizek J (1990). Intracerebroventricular application of morphine in the treatment of intractable malignant pain. Acta Univ Palacki Olomuc Fac Med 128:101-6. Summary: The authors' own experience with the application of morphine into the lateral cerebral ventricles of patients with intractable pain of tumorous origin is reported. The Salmon-Rickham reservoir implanted under the skin with a ventricular catheter inserted into the right lateral ventricle of the brain, allows easy and repeated application of small doses of the opiate (opioid) analgesic. This approach brings the pain relieving effect that make this method beneficial to patients suffering from chronic malignant pain in the preterminal stages of the disease. Medical Faculty, Palacky University, Olomouc, Czechoslovakia.

    • Karavelis A, Foroglou G, Selviaridis P and Fountzilas G (1996). Intraventricular administration of morphine for control of intractable cancer pain in 90 patients. Neurosurgery 39:57-61; discussion 61-2. Summary: OBJECTIVE: To quantitate the relief of intractable cancer pain by the use of intraventricular morphine administration. METHODS: Intraventricular morphine administration was performed through an Ommaya reservoir. An initial dose of 0.25 mg of morphine sulfate per 24 hours was administered to all of the patients. This dose was progressively increased in 0.25-mg increments until optimal analgesia was attained. RESULTS: Sixty men and 30 women with a median age of 58 years (range, 23-80 yr) entered the study. The median duration of pain was 6 months (range, 0.5-120 mo). A daily morphine dose of up to 1 mg was adequate to achieve an analgesic effect in 77% of the patients. Only nine patients (10%) achieved < 50% pain relief. Using a multiple regression analysis, only the morphine dosage was found to be an independent prognostic factor. The most frequent side effect [22%) was nausea/vomiting. Also, there were two patients with opioid intolerance and two with intracerebral hematomas. Three reservoirs failed. CONCLUSION: Intraventricular morphine administration is a useful method for palliation of intractable cancer pain. Department of Neurosurgery, AHEPA Hospital, Aristotle University of Thessaloniki, Macedonia, Greece.

    • Kronenberg MF, Laimer I, Rifici C, Saltuari L, Bramanti P, Moriggl U, Norer B and Kofler A (1998). Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus. Pain 75:383-7. Summary: We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed. Department of Neurology, University Hospital Innsbruck, Austria.

    • Lajat Y, Menegalli-Boggelli D, Bensignor Le Henaff M and Resche F (1992). [Intracerebral morphine therapy in cancer patients]. Cah Anesthesiol 40:477-83. Summary: An overview of recent studies concerning opioids and their pharmacokinetics is presented. In the light of these findings it is shown that intracerebral administration may be justified. The authors experience with 63 cases is detailed: all cancer patients in the final stage. Initial dosage by the intraventricular route was 500 to 700 microgram-day but in one case twice daily injections of 1.200 microgram were needed. The dosage needed doubled over the observation period of 2 to 3 months. The mean length of survival was 75 days. Among complications nausea and vomiting were observed in 15 to 35% of the cases, sweating and pruritus in 15%, urinary retention in 15 to 20%. In some cases euphoria, motor excitement and hallucinations occurred. Chronic constipation was present in all cases. Two cases of meningitis were successfully treated by antibiotics. Pain relief was judged excellent or good in 75% of the cases. In 20% other analgesics had to be added to the treatment. In 5% the method failed. Centre d'Evaluation et de Traitement de la Douleur, Hopital G. et R. Laennec, Nantes.

    • Langlade A, Serrie A, Sandouk P, Thurel C and Cunin G (1991). Levels of morphine and metabolites in CSF during respiratory depression after intraventricular morphine injection. Pain 44:175-8. Summary: 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. Departement d'Anesthesie Reanimation, Hopital Lariboisiere, Paris,France.

    • Lazorthes YR, Sallerin BA and Verdie JC (1995). Intracerebroventricular administration of morphine for control of irreducible cancer pain. Neurosurgery 37:422-8; discussion 428-9. Summary: Intracerebroventricular morphine analgesic for the treatment of cancer pain was administered, using implanted access ports, in 82 patients from 1984 to January 1994. All of the patients who were selected for treatment were no longer responsive and had developed drug side effects to oral or parenteral opiates in varying doses (60-400 mg/d). The mean follow-up was 66 days (range, 12-443 d) for this series of 82 patients. The effective control of pain was achieved in nearly all of the patients, with only two failures. During the treatment, the daily morphine doses were moderately increased. The initial doses of morphine were a mean of 0.30 mg (range, 0.10-2 mg), and the final doses were a mean of 2.5 mg (range, 0.10-60 mg). The results show that the ratio of the terminal dose to the initial dose increased more rapidly for patients who had a follow-up of over 60 days. However, the increase seems to have been because of the progress of the disease rather than because of drug tolerance. Department of Neurosurgery, Faculty of Pharmaceutical Sciences, Paul Sabatier University, Toulouse, France.

    • Lee TL, Kumar A and Baratham G (1990). Intraventricular morphine for intractable craniofacial pain. Singapore Med J 31:273-6. Summary: This case management report on a patient with advanced craniofacial neoplasm discusses the successful treatment of chronic pain by the cortical intraventricular narcotic administration. A previously treated patient with surgery and radiotherapy for carcinoma of the palate developed severe intractable pain despite high dose oral morphine therapy. Investigations revealed that neoplasm had reoccurred with extensive infiltration. Intraventricular morphine therapy was discussed and accepted by the patient and family. A ventricular shunt with an Ommaya reservoir was inserted under local anaesthesia. Preservative-free morphine sulphate in increasing doses of 0.25 to 1 mg was administered, once daily, which kept the patient in a pain-free state. The treatment was initiated in the hospital and continued at home till the demise of the patient on the 9th week. The home care was provided by the nurses of Home Nursing Foundation and Singapore Cancer Society under physician supervision. There were no complications which had been reported in the literature, observed in the management of this patient. Department of Anaesthesia, National University Hospital, Singapore.

    • Leong MS, Calabrese JF and Heit G (2001). Intraventricular administration of morphine and clonidine. Anesthesiology 94:1141-3. Summary: Department of Anesthesiology, Stanford University School of Medicine, California, USA. msleong@stanford.edu

    • Opavsky J and Houdek M (1990). [Administration of morphine into the cerebral ventricles in chronic intractable pain]. Cesk Neurol Neurochir 53:264-8. Summary: The study evaluated the effect of intraventricular morphine administration on chronic pain associated with malignant diseases in five subjects. To facilitate repeated application of the analgesic a reservoir was fixed subcutaneously on the calvaria with the catheter tip place in the lateral ventricle. The described approach made it possible to reduce substantially the dosage and to protract the action of morphine, as compared with intramuscular administration. No serious complications developed when the described mode of application was used. Because of the technically unpretentious procedure, the simple administration into the reservoir and the significant analgetic effect this method can be used in patients with malignant pain even in advanced stages of the disease. Katedra farmakologie LF UP, Olomouc.

    • Reeve WG and Todd JG (1990). Intraventricular diamorphine via an Ommaya shunt for intractable cancer pain. Br J Anaesth 65:544-7. Summary: We describe two patients in whom diamorphine was administered into the intraventricular space via an Ommaya reservoir, producing excellent pain relief. The use of this technique for long term administration of analgesia is reviewed. Division of Anaesthesia, Western Infirmary, Glasgow.

    • Sandouk P, Serrie A, Scherrmann JM, Langlade A and Bourre JM (1991). Presence of morphine metabolites in human cerebrospinal fluid after intracerebroventricular administration of morphine. Eur J Drug Metab Pharmacokinet Spec No 3:166-71. Summary: After intracerebroventricular administration of morphine in four cancer patients, cerebrospinal fluid (CSF) was analyzed by two morphine radioimmunoassays (RIA), liquid chromatography (LC) and radioreceptor assay (RRA) to evaluate the presence of morphine metabolites. Immunoreactive morphine-like substances were detected by differential RIA's. The maximum concentrations of these compounds were achieved 3 hours after drug administration. These concentrations, according to the specificity of the antiserum, represent a mixture of several metabolites in which only morphine 3-glucuronide(M 3-G) and morphine 6-glucuronide (M 6-G) were identified by LC, and M 6-G by LC-RRA. These results confirm that brain is able to metabolize morphine to inactive (M 3-G) or more potent (M 6-G) derivatives. INSERM U.26, Laboratoire de Neurotoxicologie, Hopital Fernand Widal, Paris, France.

    • Sandouk P, Serrie A, Urtizberea M, Debray M, Got P and Scherrmann JM (1991). Morphine pharmacokinetics and pain assessment after intracerebroventricular administration in patients with terminal cancer. Clin Pharmacol Ther 49:442-8. Summary: Morphine pharmacokinetics and pain relief were evaluated after intracerebroventricular administration of morphine (0.4 +/- 0.11 mg) in seven patients with cancer suffering from intractable pain. Ventricular cerebrospinal fluid (CSF), lumbar CSF, and plasma morphine concentrations were analyzed by a specific morphine radioimmunoassay. A two-compartment model was sufficient to describe the kinetics of morphine in ventricular CSF. Morphine diffuses to the lumbar level, and the mean maximum concentration was 192 +/- 105 ng/ml at 4.5 +/- 1.3 hours. Ventricular and lumbar CSF morphine kinetics showed a similar decline during the elimination phase, with terminal half-lives of 3.8 +/- 0.6 hours and 4.2 +/- 1.6 hours, respectively. Pain relief was evaluated by a visual analog scale: the test showed a rapid onset of analgesia (less than 10 minutes). Analgesic effectiveness reached a maximum between 6 and 10 hours. The relationship between pharmacologic effect and morphine concentrations in ventricular CSF resulted in an anticlockwise hysteresis curve. The presence of morphine in lumbar CSF suggested an additive spinal action of morphine, which probably plays a role in the duration of analgesia. INSERM U 26, Hopital Fernand Widal, Paris, France.

    • Smith KA and Frank E (1991). Stereotaxic placement of a ventricular catheter and reservoir for the administration of morphine sulfate. Axone 13:12-5. Summary: Patients with intractable pain due to cancer present a unique challenge to both medical and nursing personnel. This case study illustrates a unique home hospice managed pain control regime that has been implemented for a terminal cancer patient with intractable pain. A ventricular catheter attached to a reservoir was stereotaxically implanted for the administration of preservative-free morphine sulfate. The presentation will include the history of intraspinal morphine, the surgical placement of the ventricular access devise, and the procedure for intraventricular morphine administration. Also, the preoperative nursing assessment and patient family education will be discussed. Education of hospice nurses in the technique of injection, postoperative pain assessment, monitoring of side effects and discharge planning will conclude the presentation.

  3. #3
    Senior Member alan's Avatar
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    My neck and head are about the only parts that don't hurt!


    Alan

  4. #4
    Many studies have suggested the morphine is less or ineffective for treatment of chronic pain. This has been attributed to down-regulation of central opioid receptors in central pain.

    Usually, very high doses of morphine (up to 5 mg/kg) are required to ameliorate neuropathic pain. Systemic morphine just cannot achieve such high doses without unacceptable side effects. This is one of the reasons why direct administration of morphine intrathecally or intraventricularly may be more effective in controlling central pain after spinal cord injury (Kim, et al, 2003).

    The ineffectiveness of morphine for treating neuropathic pain may be related to changes in neurotransmitter levels and neurotransmitter receptors in the central nervous system after spinal cord injury or deafferentation. Thus, one of the goals of treating neuropathic pain is to alter these neurotransmitter levels with drugs such as amitryptaline (Elavil) and also clonidine (see Motsch & Kamler, 1997 below) which can be also be administered topically. A new approach has been the use of benzodiazepine blockers (Holtman, et al. 2003) to prevent tolerance development.

    The effects of morphine are complex for one other reason. A recent study suggests that a metabolic byproduct has direct excitatory effects on brain neurons.

    Rawal, 1996 (see below) applied interesting approach, epidural morphine. A pump controlled by the patient applies the morphine to the outside of the spinal cord. There was no difference between thoracic or lumbar epidural morphine.

    Wise.

    • Motsch J and Kamler M (1997). [alpha(2)-adrenergic agonists. Use in chronic pain - a meta-analysis]. Schmerz 11:339-3344. Summary: alpha(2)-adrenergic agonists, mimicking the action of the inhibitory transmitter norepinephrine, cause antinociception due to postsynaptic inhibition of spinothalamic projection neurons, presynaptic inhibition at the central nervous system termination of primary sensory nerves, presynaptic inhibition of brainstem noradrenergic neurons and a generalized decrease in central nervous system sympathetic efferent activity. There is a mutual potentiation of antinociceptive effects of clonidine and morphine. Clonidine is used in chronic pain states for treatment of neuropathic, neuralgic and deafferentiating pain. Based on a meta-analysis of the studies published in the years 1996-1996, the therapeutic efficacy of systematically administered clonidine was evaluated in chronic pain states. Out of 403 screened published studies, only 9 fulfilled the selection criteria. Besides three case reports with successful clonidine treatment, four placebo-controlled studies could be analyzed treating the following chronic pain states: chest pain despite normal coronary angiograms; painful diabetic neuropathy; postherpetic neuralgia; hyperalgia in patients with sympathetically maintained pain and chronic low back pain. Although three studies demonstrated statistically significant improvement in pain scores, the improvement in pain relief in these cases was slight. Long-term treatment was successful in a few responders over a period of 17 months. Hyperalgesia caused by sympathetically maintained pain was relieved by topical (transdermal) application of clonidine. Based on this evaluation a grade C recommendation is derived, which relates to responders. Successful treatment is expected only in pain states with increased sympathetic nervous system activity. Therefore, in chronic pain, treatment with systemic clonidine is of no significant value. Klinik fur Anaesthesiologie, Ruprecht-Karls-Universitat Heidelberg.

    • Rawal N (1996). [The clinical use of spinal opioids, part 1]. Schmerz 10:176-89. Summary: Spinal opioids are effective analgesics for surgical and non-surgical pain. Central and systemic side effects are less frequent than with epidural local anaesthetics or parenteral opioids. This review focuses on the analgesic efficacy of spinal opioids and their combination with local anaesthetics for postoperative analgesia, including patient-controlled epidural analgesia. Intrathecal administration of opioids has some advantages over their administration by the epidural route. Several factors may influence selection of the opioid; however, in most situations morphine is the drug of choice. Thoracic epidural administration of opioids seems to have no clinically important advantages over the lumbar route in terms of quality of analgesia, adverse effects, doses required or pulmonary function. However, evidence suggesting that effective postoperative analgesia can significantly improve postoperative morbidity in patients at risk is accumulating. In such patients, combined use of epidural local anaesthetics and opioids may become the technique of choice for postoperative analgesia. However, there is no evidence that this would have any clinically relevant benefit in low-risk patients. Abteilung fur Anasthesiologie und Intensivmedizin, Orebro Medical Center Hospital, S-70185 Orebro, Schweden.

  5. #5
    Senior Member alan's Avatar
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    Even if morphine plus bupivicaine would be effective, and the side effect of urinary retention could be controlled, I can't see myself allowing the doctor to place a pump catheter at C-3, for fear of a granuloma or other catheter-related problem developing. I can't afford to lose what little function I have, and wind up on a vent. Sure, such problems are rare, but my family and bad luck go together like crabs and Old Bay seasoning.

    Meanwhile, the pains continue to increase and spread, and have now begun affecting my forearms, too (which never had pain before this year.) MRI still shows nothing new since the first post-laminectomy scan in 1987.

    Web site note - painonline.com is now up. It's a central pain site, and includes a survey for patients.


    Alan

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