or 2 level of consciousness;4'6'7'9 none of the patients described, though completely alert initially, would have been discharged in view of their history and physical signs (nausea, vomiting, headache and ataxia) and possibly the detection of large amounts of drugs in the gastric aspirate, a finding not mentioned in the reports. Two other patients12'13 were comatose on presentation; although delayed and prolonged absorption of the drug may have affected their subsequent clinical course, it would not have affected the decision regarding their admission. Our paper on emergency toxicology was an attempt to rationalize the toxicology laboratory investigation of cases of acute drug overdose; we did not address ourselves to the clinical management of these cases. We used the word "discharge" to mean disposal from the emergency room; the direction of such discharge, whether to a psychiatric ward, to the patient's home or elsewhere, was not specified. It may be that the interpretation of the word "discharge" has created some legitimate concerns. Finally, our conclusions were based on data obtained at the Ottawa Civic Hospital. Since the epidemiologic features and the drugs used in overdose may vary from one region to another, we intended our proposals to form a basis on which to formulate local policies and only in relation to laboratory investigation. A. QIRBI, MD, FRCP[C] Director, clinical chemistry Camp Hill Hospital Halifax, NS
References. 1. MATTHEW H: Acute poisoning: some myths and misconceptions. Br Med J 1: 519, 1971 2. KESSEL N: Self-poisoning - Part I. Br Med 1 2: 1265, 1965 3. PROUDFOOT AT, BROWN SS: Acidemia and salicylate poisoning in adults. Ibid, p 547 4. Paracetamol hepatotoxicity (E). Lancet 2:
Pneumococcal infection within a family unit To the editor: I report the unusual occurrence of presumed pneumococcal infection within a family unit. On May 26, 1977 a 19-year-old Indian woman was delivered at term of a healthy female infant. Two days post partum the mother experienced a sore throat, hectic fever and pleuritic chest pain. The leukocyte count was 32.4 x 109/L. Throat and blood cultures were negative; she was unable to produce sputum for investigation. Chest radiograph revealed consolidation of the right upper lobe. She responded well to therapy with penicillin. At this time a colleague informed me that he had treated my patient's common-law husband for left upperlobe pneumonia 3 weeks previously; the organism had not been identified. At 2 weeks of age the infant was admitted to hospital with fever, vomiting and diarrhea, oral candidiasis and mild swelling of the left wrist (which the mother believed was traumatic in origin). A radiograph of the wrist disclosed only soft tissue swelling. Over the next several days the swelling became more extensive, erythematous and fluctuant. Incision and drainage yielded a profuse purulent discharge from which Diplococcus pneumaniae was cultured. The infant improved rapidly after treatment with penicillin and parenteral fluids. The only possible site of entry of the organism was the erupting lower central incisors, which, with surrounding gingival inflammation, had been present since birth. M. CUMMING, MD Wrinch Memorial Hospital Hazelton, 3.C
1189, 1975 5. BENNETT IL, CARY FH, M5TcHELL GL, et al: Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323
The use of phenformin and metformin
6. MATELL G, THORSTRAND C: A case of fatal nialamid poisoning. Acta Med Scand 181:
To the editor: In April 1977 we submitted to the health protection branch of Health and Welfare Canada a report and recommendations on the use of the antidiabetic drugs phenformin and metformin, the substance of which follows. Phenformin, an antidiabetic drug of the biguanide type, has been in clinical use for about 20 years. It has been recommended for use in patients with maturity-onset diabetes mellitus who cannot be effectively managed by diet and exercise, cannot be given insulin, or are unresponsive to sulfonylureas. Phenformin does not have a hypoglycemic effect in healthy individuals and is of no value in patients with insulindependent diabetes. The long-term benefit of phenformin therapy has not been
cases. Medicine (Baltimore) 32: 431, 1953
7. 8. 9. 10. 11.
79, 1967 ACHONG MR, FERNANDEZ PG, McLaoo PJ: Fatal self-poisoning with lithium carbonate. Can Med Assoc J 112: 868, 1975 JENSEN H, LADEFOGED J: Delayed absorption of lithium intoxication: a case history. Eur J Gun Pharmacol 8: 285, 1975 FaRousot'. RK, Boumos AR: Death following self-poisoning with aspirin. JAMA 213: 1186, 1970 MATTHEW H, MACKINTOSH TF, TOMPSETT SL, et al: Gastric aspiration and lavage in acute poisoning. Br Med 1 1: 1333 1966 WIDDoI' B: Discussion, in Th'e Poisoned Patient: The Role of the Laboratory, CIBA Foundation
Symposium
26,
Oxford,
Assoc
Sci PubI, 1974, p 225 meprobamate poisoning: a fatal case following a lucid interval. JAMA 207: 361, 1969 13. SCHWARTZ HS: Acute meprobamate poisoning with gastrotomy and removal of a drug12. JaN15 EH, PAYNE RJ, GOLDBAUM LR: Acute
containing mass. N Engi I Med 295: 1177,
1976
14. SHARMAN JR, CRETNEY MJ, ScoTT RD, et al: Drug overdoses: is one stomach washing
enough? NZ Med 1 81: 195, 1975 15. SAINSBURY P: Suicide, in Psychiatric Dis-
orders 3, ROTH M, SCOT PRICE J (eds), sect 30 of Medicine, London, Eng, Med Educ (Int), 1972-74, p 1772
established. The short-term benefits are limited to its mild hypoglycemic action and improvement of weight reduction in some obese diabetic patients. A serious metabolic complication associated with phenformin therapy is lactic acidosis, which has a reported mortality of between 40 and 50%. In the United States the estimated number of patients taking phenformin is 500000, based on sales and assuming that the average dose is 100 mg daily. About 400 cases of lactic acidosis have been reported to journals, the Food and Drug Administration and pharmaceutical firms. Thus the incidence is suggested to be about 1 in 1200 but could be much higher because of incomplete reporting. The mechanisms by which phenformin can cause lactic acidosis are unknown. While plasma concentrations of phenformin seem to be greater in older patients, the development of lactic acidosis is apparently not necessarily correlated with the plasma concentration of the drug. In Canada, of the approximately 130 000 patients who take antidiabetic drugs orally, an estimated 18 000 use phenformin. However, the use of phenformin is decreasing. For example, phenformin therapy has not been instituted in new patients in 3 years at the diabetic clinic of the Montreal General Hospital. Metformin, which is closely related to phenformin chemically, has been used since 1959 in European countries. Among an estimated 600 000 patients receiving metformin therapy 18 cases of lactic acidosis have been reported. In Canada metformin is not so widely used; an estimated 2000 patients take metformin (1500 in Quebec) and no case of lactic acidosis has been reported. We considered the benefit! risk ratio for phenformin therapy to be unacceptably low because of the high incidence of associated lactic acidosis, with its high mortality. Although the data are incomplete, it appears that the incidence of lactic acidosis associated with metformin therapy is less than that with phenformin therapy, and we therefore considered the benefit/risk ratio for metformin to be acceptable. We concluded that patients presently taking phenformin can be adequately managed by other forms of therapy, and that nonavailability of phenformin would not present a hardship to patients with diabetes mellitus. There is only limited justification, and no absolute need, for the use of biguanides in the treatment of diabetes mellitus. However, there is still a need for a safe drug capable of producing a predictable hypoglycemic effect in obese diabetic patients without increasing the plasma insulin concentration.
CMA JOURNAL/SEPTEMBER 3, 1977/VOL. 117 429
References. 1. MATTHEW H: Acute poisoning: some myths and misconceptions. Br Med J 1: 519, 1971 2. KESSEL N: Self-poisoning - Part I. Br Med 1 2: 1265, 1965 3. PROUDFOOT AT, BROWN SS: Acidemia and salicylate poisoning in adults. Ibid, p 547 4. Paracetamol hepatotoxicity (E). Lancet 2:
Pneumococcal infection within a family unit To the editor: I report the unusual occurrence of presumed pneumococcal infection within a family unit. On May 26, 1977 a 19-year-old Indian woman was delivered at term of a healthy female infant. Two days post partum the mother experienced a sore throat, hectic fever and pleuritic chest pain. The leukocyte count was 32.4 x 109/L. Throat and blood cultures were negative; she was unable to produce sputum for investigation. Chest radiograph revealed consolidation of the right upper lobe. She responded well to therapy with penicillin. At this time a colleague informed me that he had treated my patient's common-law husband for left upperlobe pneumonia 3 weeks previously; the organism had not been identified. At 2 weeks of age the infant was admitted to hospital with fever, vomiting and diarrhea, oral candidiasis and mild swelling of the left wrist (which the mother believed was traumatic in origin). A radiograph of the wrist disclosed only soft tissue swelling. Over the next several days the swelling became more extensive, erythematous and fluctuant. Incision and drainage yielded a profuse purulent discharge from which Diplococcus pneumaniae was cultured. The infant improved rapidly after treatment with penicillin and parenteral fluids. The only possible site of entry of the organism was the erupting lower central incisors, which, with surrounding gingival inflammation, had been present since birth. M. CUMMING, MD Wrinch Memorial Hospital Hazelton, 3.C
1189, 1975 5. BENNETT IL, CARY FH, M5TcHELL GL, et al: Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323
The use of phenformin and metformin
6. MATELL G, THORSTRAND C: A case of fatal nialamid poisoning. Acta Med Scand 181:
To the editor: In April 1977 we submitted to the health protection branch of Health and Welfare Canada a report and recommendations on the use of the antidiabetic drugs phenformin and metformin, the substance of which follows. Phenformin, an antidiabetic drug of the biguanide type, has been in clinical use for about 20 years. It has been recommended for use in patients with maturity-onset diabetes mellitus who cannot be effectively managed by diet and exercise, cannot be given insulin, or are unresponsive to sulfonylureas. Phenformin does not have a hypoglycemic effect in healthy individuals and is of no value in patients with insulindependent diabetes. The long-term benefit of phenformin therapy has not been
cases. Medicine (Baltimore) 32: 431, 1953
7. 8. 9. 10. 11.
79, 1967 ACHONG MR, FERNANDEZ PG, McLaoo PJ: Fatal self-poisoning with lithium carbonate. Can Med Assoc J 112: 868, 1975 JENSEN H, LADEFOGED J: Delayed absorption of lithium intoxication: a case history. Eur J Gun Pharmacol 8: 285, 1975 FaRousot'. RK, Boumos AR: Death following self-poisoning with aspirin. JAMA 213: 1186, 1970 MATTHEW H, MACKINTOSH TF, TOMPSETT SL, et al: Gastric aspiration and lavage in acute poisoning. Br Med 1 1: 1333 1966 WIDDoI' B: Discussion, in Th'e Poisoned Patient: The Role of the Laboratory, CIBA Foundation
Symposium
26,
Oxford,
Assoc
Sci PubI, 1974, p 225 meprobamate poisoning: a fatal case following a lucid interval. JAMA 207: 361, 1969 13. SCHWARTZ HS: Acute meprobamate poisoning with gastrotomy and removal of a drug12. JaN15 EH, PAYNE RJ, GOLDBAUM LR: Acute
containing mass. N Engi I Med 295: 1177,
1976
14. SHARMAN JR, CRETNEY MJ, ScoTT RD, et al: Drug overdoses: is one stomach washing
enough? NZ Med 1 81: 195, 1975 15. SAINSBURY P: Suicide, in Psychiatric Dis-
orders 3, ROTH M, SCOT PRICE J (eds), sect 30 of Medicine, London, Eng, Med Educ (Int), 1972-74, p 1772
established. The short-term benefits are limited to its mild hypoglycemic action and improvement of weight reduction in some obese diabetic patients. A serious metabolic complication associated with phenformin therapy is lactic acidosis, which has a reported mortality of between 40 and 50%. In the United States the estimated number of patients taking phenformin is 500000, based on sales and assuming that the average dose is 100 mg daily. About 400 cases of lactic acidosis have been reported to journals, the Food and Drug Administration and pharmaceutical firms. Thus the incidence is suggested to be about 1 in 1200 but could be much higher because of incomplete reporting. The mechanisms by which phenformin can cause lactic acidosis are unknown. While plasma concentrations of phenformin seem to be greater in older patients, the development of lactic acidosis is apparently not necessarily correlated with the plasma concentration of the drug. In Canada, of the approximately 130 000 patients who take antidiabetic drugs orally, an estimated 18 000 use phenformin. However, the use of phenformin is decreasing. For example, phenformin therapy has not been instituted in new patients in 3 years at the diabetic clinic of the Montreal General Hospital. Metformin, which is closely related to phenformin chemically, has been used since 1959 in European countries. Among an estimated 600 000 patients receiving metformin therapy 18 cases of lactic acidosis have been reported. In Canada metformin is not so widely used; an estimated 2000 patients take metformin (1500 in Quebec) and no case of lactic acidosis has been reported. We considered the benefit! risk ratio for phenformin therapy to be unacceptably low because of the high incidence of associated lactic acidosis, with its high mortality. Although the data are incomplete, it appears that the incidence of lactic acidosis associated with metformin therapy is less than that with phenformin therapy, and we therefore considered the benefit/risk ratio for metformin to be acceptable. We concluded that patients presently taking phenformin can be adequately managed by other forms of therapy, and that nonavailability of phenformin would not present a hardship to patients with diabetes mellitus. There is only limited justification, and no absolute need, for the use of biguanides in the treatment of diabetes mellitus. However, there is still a need for a safe drug capable of producing a predictable hypoglycemic effect in obese diabetic patients without increasing the plasma insulin concentration.
CMA JOURNAL/SEPTEMBER 3, 1977/VOL. 117 429
