Analgesic nephropathy, 1972-76 To the editor: The earliest reports of an association between heavy consumption of analgesics and nephropathy in Canada were in 1961 and 1962.1.2 In 1968, 37 such patients were reported,3'4 and, in 1972, an additional 314 from a survey of Canadian nephrologists.5 About 60 new cases were reported annually for the 3 years 1969 through 1971; the prevalence was 50 per million in Toronto, where reporting was probably most complete. The analgesic taken by most of these patients was a 222 tablet with phenacetin, 160 mg; acetylsalicylic acid (ASA), 220 mg; caffeine citrate, 32 mg; and codeine phosphate, 8 mg. Phenacetin was available in this and other analgesic combinations over the counter, but sales were limited largely to pharmacies. In 1970 the phenacetin was voluntarily replaced by Charles E. Frosst & Co. in this and their related compound analgesics by an additional 220 mg of ASA. In 1973 federal legislation was passed prohibiting sale of phenacetin in combination with salicylic acid and its derivatives. Because phenacetin had been sold almost completely in combination with ASA this legislation virtually eliminated phenacetin from both prescription and over-the-counter markets. Results of a survey conducted recently to determine numbers of cases encountered in the period 1972-76 represent findings in, to date, about one half the population covered by the first survey. The 114 new cases were reported from specific nephrologists or hospitals that contributed to the first survey, and data are continuous at least from 1970 to 1976. The number of new cases reported decreased to 52 for the last 3 years (1974-76) from 89 for 1970-72 and 97 for 1971-73. This represents a decrease of roughly 40 to 50% in the period 1974-76. However, the number of patients with end-stage disease, as reflected in the number commencing dialysis, has not changed greatly, being 19 in 1974-76, compared with 21 in 1970-72. Fifty-nine new cases were diagnosed at Vancouver General Hospital from January 1972 to June 1976. These have not been included because comparable data are not available for the years before 1972. A comparison of changes in renal function for patients in the two surveys shows a slight improvement for those in the second survey. Renal function declined in 31% in the second survey, compared with 42% in the first, im-
proved in 29% in the second, compared with 25% in the first and was unchanged in 40% in the second, compared with 34% in the first. It declined particularly in those who had severe impairment of function at the time of diagnosis and in those who continued to use analgesics. In the second survey determinations of serum creatinine concentration were done in 64% of the patients for 3 or more years and in 88% for 1 or more years, compared with 45% and 82% in the first survey. All patients had follow-up data for at least 3 months. These results could be interpreted as evidence that ASA can contribute to deterioration of renal function in established analgesic nephropathy. However, at least 85% of the 114 new patients had a history of heavy phenacetin ingestion for 3 years or more, and 50% for 10 years or more; only 5% claimed they had taken no phenacetin. The first survey represents a period when the main analgesic consumed was the combination of phenacetin, ASA, caffeine and codeine; in the second survey the primary analgesic consumed was ASA, frequently combined with caffeine and codeine. Acetaminophen consumption remains light compared with that of ASA in Canada but is increasing and could become more important in the future. The effects of reduced consumption of phenacetin appear particularly after 4 to 6 years.6'7 Our recent survey was made 6 years after a major decrease in availability of phenacetin and 3 years after its virtual elimination. Prospective recording of the incidence of analgesic nephropathy for several more years will be required to determine the long-term effects of the removal of phenacetin in Canada. Patients with analgesic nephropathy will continue to present, and our index of suspicion must remain high. The importance of this disorder rests on the fact that it is a potentially preventable cause of renal disease and renal failure. Progression can frequently be arrested when the diagnosis is made.
We thank the following members of the Canadian Society of Nephrology, who contributed to the recent follow-up study: Dr. S.P. Handa, Saint John; Drs. M.D. McGoldrick and J.F. Seely, Montreal; Drs. P.A.F. Morrin and E.R. Yendt, Kingston; Drs. R.C. Charron, GA. de Veber, I.D. Elkan, S.S.A. Fenton, M.B. Goldstein, M.D. Johnson, G.W. Smith and D.A. Thompson, Toronto; Drs. A.L. Linton and P.E. Cordy, London; Drs. A.G. Shimizu and E.K.M. Smith, Hamilton; Dr. M.A. Baltzan, Saskatoon; Dr. A.A.
16 CMA JOURNAL/JULY 9, 19771 VOL. 117
Siddiqui, Victoria; and Dr. EC. Cameron, Vancouver. D.R. WILSON, MD, FRCP[C] Director, division of nephrology Toronto General Hospital Toronto, Ont. M.H. GAULT, MD, 1.RCP[C] Director, dialysis unit and renal laboratory General Hospital St. John's, Nfld. References 1. L.u.a. WH: Interstitial nephritis due to chronic phenacetin poisoning. Can Med AsSoc 1 85: 477, 1961 2. RAPOPORT
Renal acetin 1962 3. Koc.s Renal gesics.
A,
WHITE
LW,
RANKING
GN:
damage associated with chronic phenoverdosage. Ann intern Med 57: 970, B, IRvINE AH, Mclvaa JR, et al: papillary necrosis and abuse of analCan Med Assoc 1 98: 8, 1%8
4. GAULT MH, RUDWAL TC, ENOLES WD, et
al: Syndrome of analgesic nephropathy associated with the abuse of analgesics. Ann intern Med 68: 906, 1968 5. WILSON DR: Renal disease due to analgesics: II. Analgesic nephropathy in Canada: a retrospective study of 351 cases. Can Med Assoc 1 107: 752, 1972 6. MuRRAY RM: Analgesic nephropathy: removal of phenacetin from proprietary anal. gesics. Br Med 1 4: 131, 1972 7. NORDENFELT 0: Deaths from renal failure in abusers of phenacetin-containing drugs. Ada Med Scand 191: 11, 1972
Case of hypothermia To the editor: I recently treated a patient with severe hypothermia. The patient, a 21-year-old woman, had been found lying in 15 cm of water approximately 20 m below a bridge. It was thought that she had been pushed from the bridge about 2 hours earlier. Her rescuers reported ice forming on the water when she was found. On her arrival in the emergency department her rectal temperature was 21 0C. She was not responding to painful stimuli. Her pupils were dilated and not reacting to light. Respiratory rate was 28/mm. Pulse and blood pressure were not detectable but an electrocardiogram showed sinus bradycardia of 48 beats/mm. All procedures were difficult to perform because of muscle rigidity. Endo. tracheal intubation was not possible since her mouth could not be opened and an appropriate nasotracheal tube could not be advanced through a naris. Management in the emergency department consisted of surface rewarming, with the warming blanket applied from neck to calves posteriorly and neck to groin anteriorly. Her arms and calves were wrapped in sheets to prevent further heat loss and to minimize active rewarming of the extremities. Radiographs were not made and all other unnecessary movement was similarly restricted until rewarming had been accomplished. A long central venous line was introduced percutaneously through each antecubital fossa. Fluids were run through blood warmers into these lines and thus introduced centrally at a temperature of 370C.
proved in 29% in the second, compared with 25% in the first and was unchanged in 40% in the second, compared with 34% in the first. It declined particularly in those who had severe impairment of function at the time of diagnosis and in those who continued to use analgesics. In the second survey determinations of serum creatinine concentration were done in 64% of the patients for 3 or more years and in 88% for 1 or more years, compared with 45% and 82% in the first survey. All patients had follow-up data for at least 3 months. These results could be interpreted as evidence that ASA can contribute to deterioration of renal function in established analgesic nephropathy. However, at least 85% of the 114 new patients had a history of heavy phenacetin ingestion for 3 years or more, and 50% for 10 years or more; only 5% claimed they had taken no phenacetin. The first survey represents a period when the main analgesic consumed was the combination of phenacetin, ASA, caffeine and codeine; in the second survey the primary analgesic consumed was ASA, frequently combined with caffeine and codeine. Acetaminophen consumption remains light compared with that of ASA in Canada but is increasing and could become more important in the future. The effects of reduced consumption of phenacetin appear particularly after 4 to 6 years.6'7 Our recent survey was made 6 years after a major decrease in availability of phenacetin and 3 years after its virtual elimination. Prospective recording of the incidence of analgesic nephropathy for several more years will be required to determine the long-term effects of the removal of phenacetin in Canada. Patients with analgesic nephropathy will continue to present, and our index of suspicion must remain high. The importance of this disorder rests on the fact that it is a potentially preventable cause of renal disease and renal failure. Progression can frequently be arrested when the diagnosis is made.
We thank the following members of the Canadian Society of Nephrology, who contributed to the recent follow-up study: Dr. S.P. Handa, Saint John; Drs. M.D. McGoldrick and J.F. Seely, Montreal; Drs. P.A.F. Morrin and E.R. Yendt, Kingston; Drs. R.C. Charron, GA. de Veber, I.D. Elkan, S.S.A. Fenton, M.B. Goldstein, M.D. Johnson, G.W. Smith and D.A. Thompson, Toronto; Drs. A.L. Linton and P.E. Cordy, London; Drs. A.G. Shimizu and E.K.M. Smith, Hamilton; Dr. M.A. Baltzan, Saskatoon; Dr. A.A.
16 CMA JOURNAL/JULY 9, 19771 VOL. 117
Siddiqui, Victoria; and Dr. EC. Cameron, Vancouver. D.R. WILSON, MD, FRCP[C] Director, division of nephrology Toronto General Hospital Toronto, Ont. M.H. GAULT, MD, 1.RCP[C] Director, dialysis unit and renal laboratory General Hospital St. John's, Nfld. References 1. L.u.a. WH: Interstitial nephritis due to chronic phenacetin poisoning. Can Med AsSoc 1 85: 477, 1961 2. RAPOPORT
Renal acetin 1962 3. Koc.s Renal gesics.
A,
WHITE
LW,
RANKING
GN:
damage associated with chronic phenoverdosage. Ann intern Med 57: 970, B, IRvINE AH, Mclvaa JR, et al: papillary necrosis and abuse of analCan Med Assoc 1 98: 8, 1%8
4. GAULT MH, RUDWAL TC, ENOLES WD, et
al: Syndrome of analgesic nephropathy associated with the abuse of analgesics. Ann intern Med 68: 906, 1968 5. WILSON DR: Renal disease due to analgesics: II. Analgesic nephropathy in Canada: a retrospective study of 351 cases. Can Med Assoc 1 107: 752, 1972 6. MuRRAY RM: Analgesic nephropathy: removal of phenacetin from proprietary anal. gesics. Br Med 1 4: 131, 1972 7. NORDENFELT 0: Deaths from renal failure in abusers of phenacetin-containing drugs. Ada Med Scand 191: 11, 1972
Case of hypothermia To the editor: I recently treated a patient with severe hypothermia. The patient, a 21-year-old woman, had been found lying in 15 cm of water approximately 20 m below a bridge. It was thought that she had been pushed from the bridge about 2 hours earlier. Her rescuers reported ice forming on the water when she was found. On her arrival in the emergency department her rectal temperature was 21 0C. She was not responding to painful stimuli. Her pupils were dilated and not reacting to light. Respiratory rate was 28/mm. Pulse and blood pressure were not detectable but an electrocardiogram showed sinus bradycardia of 48 beats/mm. All procedures were difficult to perform because of muscle rigidity. Endo. tracheal intubation was not possible since her mouth could not be opened and an appropriate nasotracheal tube could not be advanced through a naris. Management in the emergency department consisted of surface rewarming, with the warming blanket applied from neck to calves posteriorly and neck to groin anteriorly. Her arms and calves were wrapped in sheets to prevent further heat loss and to minimize active rewarming of the extremities. Radiographs were not made and all other unnecessary movement was similarly restricted until rewarming had been accomplished. A long central venous line was introduced percutaneously through each antecubital fossa. Fluids were run through blood warmers into these lines and thus introduced centrally at a temperature of 370C.
