Aluminum Toxicity Due to Intravenous Injection of Boiled Methadone
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《新英格兰医药杂志》
To the Editor: A 42-year-old man who was in rehabilitation for intravenous substance abuse presented with a three-month history of seizures and incoordination. Other symptoms included dysarthria, a hesitant pattern of speech, myoclonic jerks, postural tremor, emotional lability, and fluctuating short-term memory. On questioning he admitted that for four years he had been concentrating his methadone preparation, which was diluted with a grape-flavored drink, by heating it in an uncoated aluminum pot. He would then reconstitute the residue for intravenous injection. His serum aluminum level was 6650 nmol per liter (reference interval, <400). The patient reported that he did not use antacids, had had no occupational exposure to aluminum, and did not use the aluminum pot for cooking.
Chelation therapy with a continuous intravenous infusion of desferrioxamine was initiated at a rate of 50 mg per hour. Chelation was interrupted on several occasions because of renal dysfunction; however, renal function improved with supportive measures and adjustment of the continuous infusion rate (Figure 1). The infusion was maintained for seven months, followed by weekly intermittent intravenous desferrioxamine for another two months, at the end of which he refused further treatment. The serum aluminum level at this time was 2390 nmol per liter (a 64 percent reduction), and he was able to speak comprehensibly, write legibly, and walk with a walker.
Figure 1. Relationship among the Patient's Creatinine Clearance Rate, Serum Aluminum Level, and Desferrioxamine Infusion Rate during the First Two Months of Hospitalization.
Increases in the infusion rate were associated with reductions in the creatinine clearance rate and serum aluminum level. When the infusion rate was lowered, both the creatinine clearance rate and the serum aluminum level rose. This relationship was demonstrated on two more occasions during the first two months of hospitalization, suggesting a causal association. The reason for this association is unclear, but it could relate to the known nephrotoxic effects of desferrioxamine or of aluminoxamine (i.e., the coordination complex formed between desferrioxamine and aluminum ions), although the latter has not been reported in humans.
Parenteral exposure to aluminum was first documented in patients undergoing hemodialysis who were exposed to dialysate derived from aluminum-treated water.1 Parenteral exposure can also occur through contaminated intravenous-feeding solutions.2 Concentrating an oral methadone solution by heating it and redissolving the residue allows the drug user to avoid injecting large volumes of fluid intravenously. We think that the citric acid in the methadone preparation reacted with the aluminum oxide of the pot, resulting in water-soluble aluminum species.3
Our patient demonstrated the characteristic encephalopathy of aluminum toxicity, first described by Alfrey et al. in 1976.4 Other manifestations include microcytic anemia, adynamic bone disease, and osteomalacia. Desferrioxamine is the only aluminum-chelating agent that is used routinely in patients undergoing dialysis. There is only one other reported case of treatment with desferrioxamine for hyperaluminemia without concurrent hemodialysis,5 probably because of the rarity of hyperaluminemia outside the setting of end-stage renal disease. On the basis of our experience with the use of desferrioxamine for iron chelation in patients with thalassemia, a protocol for aluminum chelation in a patient with preserved renal function was used with encouraging results.
We conclude that exposure to aluminum can occur through intravenous substance use. Desferrioxamine should be considered for the treatment of chronic aluminum toxicity in patients who are not undergoing hemodialysis.
Raymund L. Yong, M.D.
Daniel T. Holmes, M.D.
Gayatri M. Sreenivasan, M.D.
University of British Columbia
Vancouver, BC V5Z 4E3, Canada
raymund.yong@vch.ca
References
Ward MK, Feest TG, Ellis HA, Parkinson IS, Kerr DN. Osteomalacic dialysis osteodystrophy: evidence for a water-borne aetiological agent, probably aluminium. Lancet 1978;1:841-845.
Bishop NJ, Morley R, Day JP, Lucas A. Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Engl J Med 1997;336:1557-1561.
Poe CF, Leberman JM. The effect of acid foods on aluminum cooking utensils. Food Technol 1949;3:71-74.
Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome: possible aluminum intoxication. N Engl J Med 1976;294:184-188.
Kanwar VS, Jenkins JJ III, Mandrell BN, Furman WL. Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis. Med Pediatr Oncol 1996;27:64-67.
Chelation therapy with a continuous intravenous infusion of desferrioxamine was initiated at a rate of 50 mg per hour. Chelation was interrupted on several occasions because of renal dysfunction; however, renal function improved with supportive measures and adjustment of the continuous infusion rate (Figure 1). The infusion was maintained for seven months, followed by weekly intermittent intravenous desferrioxamine for another two months, at the end of which he refused further treatment. The serum aluminum level at this time was 2390 nmol per liter (a 64 percent reduction), and he was able to speak comprehensibly, write legibly, and walk with a walker.
Figure 1. Relationship among the Patient's Creatinine Clearance Rate, Serum Aluminum Level, and Desferrioxamine Infusion Rate during the First Two Months of Hospitalization.
Increases in the infusion rate were associated with reductions in the creatinine clearance rate and serum aluminum level. When the infusion rate was lowered, both the creatinine clearance rate and the serum aluminum level rose. This relationship was demonstrated on two more occasions during the first two months of hospitalization, suggesting a causal association. The reason for this association is unclear, but it could relate to the known nephrotoxic effects of desferrioxamine or of aluminoxamine (i.e., the coordination complex formed between desferrioxamine and aluminum ions), although the latter has not been reported in humans.
Parenteral exposure to aluminum was first documented in patients undergoing hemodialysis who were exposed to dialysate derived from aluminum-treated water.1 Parenteral exposure can also occur through contaminated intravenous-feeding solutions.2 Concentrating an oral methadone solution by heating it and redissolving the residue allows the drug user to avoid injecting large volumes of fluid intravenously. We think that the citric acid in the methadone preparation reacted with the aluminum oxide of the pot, resulting in water-soluble aluminum species.3
Our patient demonstrated the characteristic encephalopathy of aluminum toxicity, first described by Alfrey et al. in 1976.4 Other manifestations include microcytic anemia, adynamic bone disease, and osteomalacia. Desferrioxamine is the only aluminum-chelating agent that is used routinely in patients undergoing dialysis. There is only one other reported case of treatment with desferrioxamine for hyperaluminemia without concurrent hemodialysis,5 probably because of the rarity of hyperaluminemia outside the setting of end-stage renal disease. On the basis of our experience with the use of desferrioxamine for iron chelation in patients with thalassemia, a protocol for aluminum chelation in a patient with preserved renal function was used with encouraging results.
We conclude that exposure to aluminum can occur through intravenous substance use. Desferrioxamine should be considered for the treatment of chronic aluminum toxicity in patients who are not undergoing hemodialysis.
Raymund L. Yong, M.D.
Daniel T. Holmes, M.D.
Gayatri M. Sreenivasan, M.D.
University of British Columbia
Vancouver, BC V5Z 4E3, Canada
raymund.yong@vch.ca
References
Ward MK, Feest TG, Ellis HA, Parkinson IS, Kerr DN. Osteomalacic dialysis osteodystrophy: evidence for a water-borne aetiological agent, probably aluminium. Lancet 1978;1:841-845.
Bishop NJ, Morley R, Day JP, Lucas A. Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Engl J Med 1997;336:1557-1561.
Poe CF, Leberman JM. The effect of acid foods on aluminum cooking utensils. Food Technol 1949;3:71-74.
Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome: possible aluminum intoxication. N Engl J Med 1976;294:184-188.
Kanwar VS, Jenkins JJ III, Mandrell BN, Furman WL. Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis. Med Pediatr Oncol 1996;27:64-67.