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Opioid analgesia in uraemic patients
In this context, Bhutani’s proposed treatment schedules might not be applicable to the developed world. The concern with the high prevalence of primary dapsone resistance prompted the inclusion of clofazimine in WHO’s multibacillary leprosy regimen. However, since clinically relevant primary dapsone resistance has not been detected in the USA’ and the skin discolouration resulting from clofazimine is cosmetically unacceptable to many lighter skinned patients, many US clinicians2-’ find dapsone an acceptable companion to rifampicin in the multibacillary
regimen. WHO’s decision to advocate monthly rifampicin therapy is based on both its extraordinary bactericidal activity and the prohibitive cost of daily rifampicin for developing nations. Additionally, Pattyn’s analysis5 showed that equivalent amounts of rifampicin given daily result in a lower relapse rate than intermittent administration. Thus the daily rifampicin dosing advocated by Gelber and other US clinicians2-4 seems fair. Moreover, the National Leprosy Eradication Programme in India incorporates a daily dosing of rifampicin from day 1 to 14 in the proposed WHO multibacillary regimen, in view of the highly potent bactericidal action of rifampicin as well as the fact that the multiplication time of leprosy bacilli is around 14 days. With financial and therapeutic considerations in the western world, we wonder if the grand round authors would agree to such modifications to the WHO treatment regimens for the western populations? *S S Vasireddi, J
Chowdappa, H S Choudhury
Department of Medicine, Catholic Medical Center of Brooklyn and Queens, Inc, New York, NY 11432, USA
1 Gelber RH, Rea TH, Murray LP, Siu P, Tsang M, Byrd SR. Primary dapsone-resistant Hansen’s disease in California—experience with over 100 mycobacterium leprae isolates. Arch Dermatol 1990; 126: 1584-86. 2 Gelber RH. Leprosy (Hansen’s disease). In: Rakel RE, ed. Conn’s current therapy. Philadelphia, Pa: WB Saunders, 1992: 76-80. 3 Gelber RH. Leprosy (Hansen’s disease). In: Berkow R, ed. The Merck Manual, 16th ed. Rahway, NJ: Merck Research Laboratories, 1992: 146-50. 4 Gelber RH. Leprosy (Hansen’s disease). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases, 4th ed. New York, NY: Churchill Livingstone, 1994. 5 Pattyn SF. Search for effective short-course regimens for the treatment of leprosy. Int J Lepr 1993; 61: 76-81.
licensed for subcutaneous administration, we have not found skin irritation from the subcutaneous infusion, nor has there been any apparent respiratory depression. In choosing a starting dose we discussed the problem with our anaesthetic colleagues and have assumed alfentanil to be 10 times more potent than diamorphine given subcutaneously. The doses we eventually used fell very much towards the lower end of the range of alfentanil used in intensive-care settings.2 Morphine and diamorphine are eminently suitable for intermittent subcutaneous injection because they can be given every 4 h. In patients requiring a subcutaneous infusion, there is an argument for using rapid-acting drugs with short half-lives and we suggest that the use of alfentanil and midazolam may add flexibility to a regimen in a well-
supervised setting. *S R Kirkham, Rosamund Pugh Poole
Hospital National Health Service Trust, Poole BH15 2JB, UK
Gorman DJ. Opioid analgesics in the management of pain in patients with cancer: an update. Palliat Med 1991; 5: 277-94. Bodenham A, Park GR. Alfentanil infusions in patients requiring intensive care. Clinical Pharmacokinet 1988; 15: 216-26. O’Dea J, Hopkinson RB. Alfentanil-midazolam infusion. Care Critic Ill
1 2 3
1987; 3: 20-21.
Vitamin D SiR-The review by Fraser (Jan 14, p 104) on vitamin D is informative and provides a concise overview of this important vitamin. Fraser includes a reference to our work,’ but the message he conveys is the opposite of that in the article to which the statement was referenced. The implication that vitamin D deficiency is "readily corrected and prevented by treatment with 10 Ilg of vitamin D orally each day" was the main subject of our report and there is indication, as noted in that article, that many elderly individuals who get no contribution to their vitamin D status from sunlight may indeed require more than 10 Ilg (400 IU) per day. The exact amount that is needed in such elderly individuals is unclear, but on the basis of our studies and those of others,’ it seems to be somewhere between 20 g and 40 Ilg orally each day. F Michael Gloth III Department of Medicine, Union Memorial Hospital, Baltimore, Maryland 21218, USA
Opioid analgesia
in uraemic
patients
SIR-Morphine and diamorphine (where available) are the commonly used opioid analgesics in palliative care. We have become increasingly concerned about the use of these drugs in renal failure, particularly in the last few days of life, and suspect that a substantial proportion of terminal agitation is caused by the accumulation of active morphine metabolites in patients with impaired renal function.’ We have started to use the short-acting opioid alfentanil in uraemic patients within the last few days of life. Alfentanil most
chosen because it has a short elimination half-life, of about 87-104 minutes;2 because it is eliminated virtually entirely by conversion in the liver to inactive metabolites;’ because it is potent and is available in the UK in a concentrated formulation (Rapifen Intensive Care 5 mg/mL); and because there is some evidence that it is stable when mixed with midazolam.3 Our experience is presently limited to 4 patients all of whom became increasingly agitated on a continuous subcutaneous infusion of diamorphine and were known to have impaired renal function. In all 4 cases, agitation settled rapidly on changing to alfentanil. Although alfentanil is not
1
2
3
4
Gloth FM,Tobin JD, Sherman SS, Hollis BW. Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatr Soc 1991; 39: 137-41. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327: 1637-42. McKenna M, Freaney R, Keating D, Muldowney FP. The prevalence and management of vitamin D deficiency in an acute geriatric unit. Irish Med J 1981; 74: 336-38. Honkanen R, Alhava E, Parviainen M, Talasniemi S, Mönkkönen R. The necessity and safety of calcium vitamin D in the elderly. J Am Geriatr Soc 1990; 38: 862-66.
was
SIR-I
interested to read Fraser’s comprehensive and review of vitamin D in your series on fat-soluble convincing vitamins. However, as a general practitioner (GP) I am now confused and have the following questions. First, should we continue to advise breastfeeding mothers and their babies to take vitamin D supplements as recommended in government publications?’2 This advice seems to have been practised only very halfheartedly according to my GP and healthvisitor contacts, but we are reminded to implement this in another report that appeared only one week before Fraser’s review.’ Second, should we stop advising vitamin was
1185
regimen. WHO’s decision to advocate monthly rifampicin therapy is based on both its extraordinary bactericidal activity and the prohibitive cost of daily rifampicin for developing nations. Additionally, Pattyn’s analysis5 showed that equivalent amounts of rifampicin given daily result in a lower relapse rate than intermittent administration. Thus the daily rifampicin dosing advocated by Gelber and other US clinicians2-4 seems fair. Moreover, the National Leprosy Eradication Programme in India incorporates a daily dosing of rifampicin from day 1 to 14 in the proposed WHO multibacillary regimen, in view of the highly potent bactericidal action of rifampicin as well as the fact that the multiplication time of leprosy bacilli is around 14 days. With financial and therapeutic considerations in the western world, we wonder if the grand round authors would agree to such modifications to the WHO treatment regimens for the western populations? *S S Vasireddi, J
Chowdappa, H S Choudhury
Department of Medicine, Catholic Medical Center of Brooklyn and Queens, Inc, New York, NY 11432, USA
1 Gelber RH, Rea TH, Murray LP, Siu P, Tsang M, Byrd SR. Primary dapsone-resistant Hansen’s disease in California—experience with over 100 mycobacterium leprae isolates. Arch Dermatol 1990; 126: 1584-86. 2 Gelber RH. Leprosy (Hansen’s disease). In: Rakel RE, ed. Conn’s current therapy. Philadelphia, Pa: WB Saunders, 1992: 76-80. 3 Gelber RH. Leprosy (Hansen’s disease). In: Berkow R, ed. The Merck Manual, 16th ed. Rahway, NJ: Merck Research Laboratories, 1992: 146-50. 4 Gelber RH. Leprosy (Hansen’s disease). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and practice of infectious diseases, 4th ed. New York, NY: Churchill Livingstone, 1994. 5 Pattyn SF. Search for effective short-course regimens for the treatment of leprosy. Int J Lepr 1993; 61: 76-81.
licensed for subcutaneous administration, we have not found skin irritation from the subcutaneous infusion, nor has there been any apparent respiratory depression. In choosing a starting dose we discussed the problem with our anaesthetic colleagues and have assumed alfentanil to be 10 times more potent than diamorphine given subcutaneously. The doses we eventually used fell very much towards the lower end of the range of alfentanil used in intensive-care settings.2 Morphine and diamorphine are eminently suitable for intermittent subcutaneous injection because they can be given every 4 h. In patients requiring a subcutaneous infusion, there is an argument for using rapid-acting drugs with short half-lives and we suggest that the use of alfentanil and midazolam may add flexibility to a regimen in a well-
supervised setting. *S R Kirkham, Rosamund Pugh Poole
Hospital National Health Service Trust, Poole BH15 2JB, UK
Gorman DJ. Opioid analgesics in the management of pain in patients with cancer: an update. Palliat Med 1991; 5: 277-94. Bodenham A, Park GR. Alfentanil infusions in patients requiring intensive care. Clinical Pharmacokinet 1988; 15: 216-26. O’Dea J, Hopkinson RB. Alfentanil-midazolam infusion. Care Critic Ill
1 2 3
1987; 3: 20-21.
Vitamin D SiR-The review by Fraser (Jan 14, p 104) on vitamin D is informative and provides a concise overview of this important vitamin. Fraser includes a reference to our work,’ but the message he conveys is the opposite of that in the article to which the statement was referenced. The implication that vitamin D deficiency is "readily corrected and prevented by treatment with 10 Ilg of vitamin D orally each day" was the main subject of our report and there is indication, as noted in that article, that many elderly individuals who get no contribution to their vitamin D status from sunlight may indeed require more than 10 Ilg (400 IU) per day. The exact amount that is needed in such elderly individuals is unclear, but on the basis of our studies and those of others,’ it seems to be somewhere between 20 g and 40 Ilg orally each day. F Michael Gloth III Department of Medicine, Union Memorial Hospital, Baltimore, Maryland 21218, USA
Opioid analgesia
in uraemic
patients
SIR-Morphine and diamorphine (where available) are the commonly used opioid analgesics in palliative care. We have become increasingly concerned about the use of these drugs in renal failure, particularly in the last few days of life, and suspect that a substantial proportion of terminal agitation is caused by the accumulation of active morphine metabolites in patients with impaired renal function.’ We have started to use the short-acting opioid alfentanil in uraemic patients within the last few days of life. Alfentanil most
chosen because it has a short elimination half-life, of about 87-104 minutes;2 because it is eliminated virtually entirely by conversion in the liver to inactive metabolites;’ because it is potent and is available in the UK in a concentrated formulation (Rapifen Intensive Care 5 mg/mL); and because there is some evidence that it is stable when mixed with midazolam.3 Our experience is presently limited to 4 patients all of whom became increasingly agitated on a continuous subcutaneous infusion of diamorphine and were known to have impaired renal function. In all 4 cases, agitation settled rapidly on changing to alfentanil. Although alfentanil is not
1
2
3
4
Gloth FM,Tobin JD, Sherman SS, Hollis BW. Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatr Soc 1991; 39: 137-41. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992; 327: 1637-42. McKenna M, Freaney R, Keating D, Muldowney FP. The prevalence and management of vitamin D deficiency in an acute geriatric unit. Irish Med J 1981; 74: 336-38. Honkanen R, Alhava E, Parviainen M, Talasniemi S, Mönkkönen R. The necessity and safety of calcium vitamin D in the elderly. J Am Geriatr Soc 1990; 38: 862-66.
was
SIR-I
interested to read Fraser’s comprehensive and review of vitamin D in your series on fat-soluble convincing vitamins. However, as a general practitioner (GP) I am now confused and have the following questions. First, should we continue to advise breastfeeding mothers and their babies to take vitamin D supplements as recommended in government publications?’2 This advice seems to have been practised only very halfheartedly according to my GP and healthvisitor contacts, but we are reminded to implement this in another report that appeared only one week before Fraser’s review.’ Second, should we stop advising vitamin was
1185