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BLEEDING PROBLEMS WITH CARBENICILLIN
599 that this would bond anything. Again, the rubbers failed to hold. It then became obvious that there was a continuing inexorable process of liquefactive necrosis. I was reluctant to cut the ends off the rubbers because my stethoscope is one of those scientific ones in which the length is the appropriate one for the internal diameter. However, eventually I had to sacrifice some rubber, only to find that the process of liquefaction continued even though I ceased using the phisohex. In the long run, I had to get completely new rubbers. Princess Alexandra Hospital, Woolloongabba, Queensland 4102, K. J. MURPHY. Australia.
BLEEDING PROBLEMS WITH CARBENICILLIN SIR,-We have seen striking prolongation of the onestage prothrombin-time associated with the recommended dosage of carbenicillin. man developed acute right-flank pain late in and was admitted to a hospital near his home. A right renal calculus was noted and the blood-urea-nitrogen (B.u.N.) was 25 mg. per 100 ml. Because of anuria, bilateral retrograde catheterisations and pyelograms were performed which did not reveal any obstruction. Mannitol and frusemide did not increase his urinary output. With rapidly increasing azotxmia he was transferred to this hospital. Pseudomonas was isolated from his urine and his sputum. Serum-creatinine on admission was 8 mg. per 100 ml. and B.u.N. 80 mg. per ml. Since the pseudomonas bacteriuria was resistant to all agents except the aminoglycoside antibiotics, the patient was started on intravenous carbenicillin 2 g. 8-hourly and was given one intramuscular dose of gentamicin 80 mg. Extracorporeal hsmodialysis was initiated with an arteriovenous shunt. An arteriogram revealed no evidence of renal arterial or venous occlusion. On April 20, he had minimal haemoptysis and the prothrombintime was prolonged to 22-4 seconds (control 13 seconds). Initially, systemic heparinisation was used, but this was changed to regional heparinisation after prolongation of the one-stage prothrombin-time was noted. Over the next four days, the prothrombin-time became progressively longer (27 seconds on April 23 and 38 seconds on April 24). During this same period the fibrinogen, activated partial thromboplastin-time, fibrin split products, and platelet-count were all within normal limits. The patient received 10 mg. intramuscular phytomenadione on April 24. Carbenicillin was discontinued on April 23. The prothrombin-time had returned to normal by April 26. On April 24, when his prothrombin-time was 38 seconds (control 13 seconds), melasna and a drop in blood-pressure were noted, the haemoglobin being 4 g. per 100 ml. He received a total of 8 units of blood between April 24 and April 26. Over the next few weeks, the patient’s azotxmia gradually lessened and a diuretic phase was entered. The upper gastrointestinal bleeding did not recur and radiography revealed a duodenal ulcer. The cause of his acute renal failure was not clearly delineated. A renal biopsy was not performed because of his advanced age and adequate recovery.
A
77-year-old
April, 1972,
Many factors may cause prolongation of the prothrombintime-e.g., severe hepatic parenchymal disease, obstructive jaundice, malabsorption syndrome, altered intestinal microflora following antibiotic therapy, and inadequate dietary intake-but none of these applied in this case. Disseminated intravascular coagulation seemed unlikely in view of the normal activated partial thromboplastin-time, platelet-count, fibrinogen, and fibrin split products. In addition, schistocytosis was absent. Systemic heparinisation used for hsemodialysis can prolong the prothrombin-time, but not to the extent seen in this case. When the prolongation of the prothrombin-time was observed regional heparinisation was employed, and subsequent prothrombintimes were obtained before hxmodialysis. Coagulation abnormalities and hxmorrhagic problems can occur with carbenicillin dosages of 24 g. or above in
renal failure. The manufacturer’s recommended saJ a day. The case presented hei at this dosage, the prothrombir time can be seriously prolonged and that frequent coaguk tion studies are necessary. acute
dose in anuria is 4-6 g. demonstrates that, even
Department of Medicine, Abington Memorial Hospital,
Abington, Pennsylvania, U.S.A.
MELVIN YUDIS WILLIAM H. MAHOOD ROBERT MAXWELL.
TYPHOID FEVER SiR,—I read your leader (Aug. 26, p. 415) and there are some points I should like to outline. We have reviewed 75 cases of typhoid fever admitted to this unit from 1959 to 1969, and in a third of these patients there was no history of a recent trip abroad; so an affirmative to " have you been out of the country ? " may not be forthcoming from every patient. Typhoid carriers (1 in 100,000 in England and Wales),! immigrants, and food imported from endemic areas should also be considered as likely sources of infection, in spite of excellent public-health controls in this country. Coppetts Wood Hospital, Muswell Hill, London N10 1JN.
S. HAIDER.
SEVERE NON-KETOTIC HYPERGLYCÆMIC PRE-COMA IN A HYPERTENSIVE PATIENT RECEIVING DIAZOXIDE SIRi--There has been renewed interest in oral diazoxide therapy for severe hypertension resistant to conventional
drugs. We report a patient who developed non-ketotic pre-coma suddenly and rapidly ment with oral diazoxide.
hyperosmolar during treat-
A 35-year-old Nigerian had a short history of breathlessness. There was no relevant history, and he had a blood-pressure of 280/190 mm.Hg, clinical and radiological signs of pulmonary oedema, a gallop rhythm, and bilateral hypertensive retinal hxmorrhages and exudates. Full investigation revealed no cause for this hypertension, although the blood-urea level was 155 mg. per 100 ml. Fasting blood-sugar level was 86 mg. per 100 ml. Control of the hypertension proved extremely difficult. Twice during the two months after discharge he was readmitted with standing diastolic blood-pressures cf 165 and 150, while he was on a low-salt diet, methyldopa 2-5 g., propranolol 360 mg., and bendrofluazide 10 mg. daily. On the second occasion he was discharged when his blood-pressure was 190/130 lying and 140/100 standing, when he was taking methyldopa 2-5 g., bendrofluazide 10 mg., and diazoxide 100 mg. daily. The dose of diazoxide was increased at weekly intervals and urine and blood-sugar estimations were performed. One month after oral diazoxide was started and one week after the daily dose was increased to 400 mg., the urine showed 0-25% glucose and the blood-sugar level was 243 mg. per 100 ml. The bloodpressure was 190/110 lying and 180/105 standing. 3! days later he was readmitted-confused, disorientated, and violent. Urine: 2% glucose and no ketones. Blood-sugar: 1200 mg. per 100 ml.; serum sodium 149, potassium 4-2, bicarbonate 18 meq. per 1.; and calculated osmolarity 364 mosmole per kg. He was given small doses of soluble insulin and became rational 30 hours after admission. When he was discharged, he was having methyldopa 25 g., diazoxide 500 mg., frusemide 80 mg., ’ Slow-K ’ 32 meq., and tolbutamide 2 g. daily. He had been taught to test his urine for sugar once a day. Blood-pressure was 180/125 lying and 150/100 standing. Fasting blood-sugar was 86 mg. per 100 mL, blood-urea 64 mg. per 100 ml., and creatinine clearance 26 ml. per min.
Diazoxide is a very effective oral or intravenous hypotensive drug, but the major drawback restricting its use in hypertension is the production of hyperglycxmia. In 1. Public Health Laboratory Service 1961, 59, 231.
Working Party. J. Hyg. Camb.
BLEEDING PROBLEMS WITH CARBENICILLIN SIR,-We have seen striking prolongation of the onestage prothrombin-time associated with the recommended dosage of carbenicillin. man developed acute right-flank pain late in and was admitted to a hospital near his home. A right renal calculus was noted and the blood-urea-nitrogen (B.u.N.) was 25 mg. per 100 ml. Because of anuria, bilateral retrograde catheterisations and pyelograms were performed which did not reveal any obstruction. Mannitol and frusemide did not increase his urinary output. With rapidly increasing azotxmia he was transferred to this hospital. Pseudomonas was isolated from his urine and his sputum. Serum-creatinine on admission was 8 mg. per 100 ml. and B.u.N. 80 mg. per ml. Since the pseudomonas bacteriuria was resistant to all agents except the aminoglycoside antibiotics, the patient was started on intravenous carbenicillin 2 g. 8-hourly and was given one intramuscular dose of gentamicin 80 mg. Extracorporeal hsmodialysis was initiated with an arteriovenous shunt. An arteriogram revealed no evidence of renal arterial or venous occlusion. On April 20, he had minimal haemoptysis and the prothrombintime was prolonged to 22-4 seconds (control 13 seconds). Initially, systemic heparinisation was used, but this was changed to regional heparinisation after prolongation of the one-stage prothrombin-time was noted. Over the next four days, the prothrombin-time became progressively longer (27 seconds on April 23 and 38 seconds on April 24). During this same period the fibrinogen, activated partial thromboplastin-time, fibrin split products, and platelet-count were all within normal limits. The patient received 10 mg. intramuscular phytomenadione on April 24. Carbenicillin was discontinued on April 23. The prothrombin-time had returned to normal by April 26. On April 24, when his prothrombin-time was 38 seconds (control 13 seconds), melasna and a drop in blood-pressure were noted, the haemoglobin being 4 g. per 100 ml. He received a total of 8 units of blood between April 24 and April 26. Over the next few weeks, the patient’s azotxmia gradually lessened and a diuretic phase was entered. The upper gastrointestinal bleeding did not recur and radiography revealed a duodenal ulcer. The cause of his acute renal failure was not clearly delineated. A renal biopsy was not performed because of his advanced age and adequate recovery.
A
77-year-old
April, 1972,
Many factors may cause prolongation of the prothrombintime-e.g., severe hepatic parenchymal disease, obstructive jaundice, malabsorption syndrome, altered intestinal microflora following antibiotic therapy, and inadequate dietary intake-but none of these applied in this case. Disseminated intravascular coagulation seemed unlikely in view of the normal activated partial thromboplastin-time, platelet-count, fibrinogen, and fibrin split products. In addition, schistocytosis was absent. Systemic heparinisation used for hsemodialysis can prolong the prothrombin-time, but not to the extent seen in this case. When the prolongation of the prothrombin-time was observed regional heparinisation was employed, and subsequent prothrombintimes were obtained before hxmodialysis. Coagulation abnormalities and hxmorrhagic problems can occur with carbenicillin dosages of 24 g. or above in
renal failure. The manufacturer’s recommended saJ a day. The case presented hei at this dosage, the prothrombir time can be seriously prolonged and that frequent coaguk tion studies are necessary. acute
dose in anuria is 4-6 g. demonstrates that, even
Department of Medicine, Abington Memorial Hospital,
Abington, Pennsylvania, U.S.A.
MELVIN YUDIS WILLIAM H. MAHOOD ROBERT MAXWELL.
TYPHOID FEVER SiR,—I read your leader (Aug. 26, p. 415) and there are some points I should like to outline. We have reviewed 75 cases of typhoid fever admitted to this unit from 1959 to 1969, and in a third of these patients there was no history of a recent trip abroad; so an affirmative to " have you been out of the country ? " may not be forthcoming from every patient. Typhoid carriers (1 in 100,000 in England and Wales),! immigrants, and food imported from endemic areas should also be considered as likely sources of infection, in spite of excellent public-health controls in this country. Coppetts Wood Hospital, Muswell Hill, London N10 1JN.
S. HAIDER.
SEVERE NON-KETOTIC HYPERGLYCÆMIC PRE-COMA IN A HYPERTENSIVE PATIENT RECEIVING DIAZOXIDE SIRi--There has been renewed interest in oral diazoxide therapy for severe hypertension resistant to conventional
drugs. We report a patient who developed non-ketotic pre-coma suddenly and rapidly ment with oral diazoxide.
hyperosmolar during treat-
A 35-year-old Nigerian had a short history of breathlessness. There was no relevant history, and he had a blood-pressure of 280/190 mm.Hg, clinical and radiological signs of pulmonary oedema, a gallop rhythm, and bilateral hypertensive retinal hxmorrhages and exudates. Full investigation revealed no cause for this hypertension, although the blood-urea level was 155 mg. per 100 ml. Fasting blood-sugar level was 86 mg. per 100 ml. Control of the hypertension proved extremely difficult. Twice during the two months after discharge he was readmitted with standing diastolic blood-pressures cf 165 and 150, while he was on a low-salt diet, methyldopa 2-5 g., propranolol 360 mg., and bendrofluazide 10 mg. daily. On the second occasion he was discharged when his blood-pressure was 190/130 lying and 140/100 standing, when he was taking methyldopa 2-5 g., bendrofluazide 10 mg., and diazoxide 100 mg. daily. The dose of diazoxide was increased at weekly intervals and urine and blood-sugar estimations were performed. One month after oral diazoxide was started and one week after the daily dose was increased to 400 mg., the urine showed 0-25% glucose and the blood-sugar level was 243 mg. per 100 ml. The bloodpressure was 190/110 lying and 180/105 standing. 3! days later he was readmitted-confused, disorientated, and violent. Urine: 2% glucose and no ketones. Blood-sugar: 1200 mg. per 100 ml.; serum sodium 149, potassium 4-2, bicarbonate 18 meq. per 1.; and calculated osmolarity 364 mosmole per kg. He was given small doses of soluble insulin and became rational 30 hours after admission. When he was discharged, he was having methyldopa 25 g., diazoxide 500 mg., frusemide 80 mg., ’ Slow-K ’ 32 meq., and tolbutamide 2 g. daily. He had been taught to test his urine for sugar once a day. Blood-pressure was 180/125 lying and 150/100 standing. Fasting blood-sugar was 86 mg. per 100 mL, blood-urea 64 mg. per 100 ml., and creatinine clearance 26 ml. per min.
Diazoxide is a very effective oral or intravenous hypotensive drug, but the major drawback restricting its use in hypertension is the production of hyperglycxmia. In 1. Public Health Laboratory Service 1961, 59, 231.
Working Party. J. Hyg. Camb.