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INCISION OF SMALL VESSELS
425 be identified as a berry aneurysm set deep in the adrenal gland. This was excised and was found to be 12 mm in length and 10 mm in width. The patient made an uneventful recovery, but his blood-pressure remained high at 220/140 mm Hg. Histologically the wall of the aneurysm showed loss of the internal elastic lamina, but the muscular media appeared preserved although alternated. There was no evidence of atheroma nor dissection. Adrenal biopsy was normal. General Hospital, Steelhouse Lane, Birmingham B4 6NH.
MARTYN WATERWORTH
SEVERE RENAL DYSFUNCTION AFTER
TOBRAMYCIN/CEPHALOTHIN THERAPY SIR,-Gentamicin and cephalothin are valuable antibiotics which are occasionally nephrotoxic when used alone.’A number of reports have suggested that combined therapy with gentamicin and cephalothin may be particularly nephrotoxic,’-’ especially if high doses of cephalothin are used. Renal failure following simultaneous administration of these agents may be delayed until several days after the drugs have been discontinued.4 Tobramycin, a newer aminoglycoside antibiotic, has attracted interest because of its apparently greater effectiveness against Pseudomonas species.6 Klastersky et al.’7 reported raised serum-creatinine in 10 out of 48 patients treated with tobramycin and cephalothin, although underlying renal disease was present in 3 of these patients. We have recently encountered two cases in which tobramycin/cephalothin therapy was followed by severe renal dysfunction. Case 1.-A 40-year-old woman with acute myeloblastic ieuksemia was treated with a combination of cytosine arabinoside, adriamycin, vincristine, and prednisolone. Before treatment, blood-urea was 3.0 mmol/1 and serum-creatinine was 82 (imoJ/l. Three separate courses of intravenous tobramycin (4 mg/kg/day) and carbenicillin (300 mg/kg/day) were given for three episodes of fever which occurred during induction therapy, in accordance with the current practice of instituting antibiotic therapy in febrile neutropenic patients even in the absence of bacteriological confirmation. A fourth episode of fever was treated with intravenous tobramycin (4 mg/kg/day) and cephalothin (200 mg/kg/day). The antibiotics were given for 11 days, but after a week on therapy blood-urea had risen from 2.8 to 11 mmol/1 and creatinine clearance was noted to be low (26 ml/min). At this time plasma-tobramycin levels (taken from the opposite arm to that used for the injection) were 38 jig/mi 1 hour after rapid injection and 4 tg/ml 8 hours after injection, confirming abnormal accumulation of the drug. After withdrawal of antibiotic therapy creatinine clearance remained low, reaching a nadir of 17 ml/min. 8 weeks later it was still reduced (44 ml/min). Audiometry showed no abnormality. When the patient received tobramycin/carbenicillin for a further episode of infection, renal excretion of the drug was found to be normal, despite the reduced creatinine clearance (44 mt/min). On this occasion, plasma-tobramycin (after 1-33 mg/kg was given intravenously) were 5.66 g/ml (1hour), 3.66 ng/ml (4 hours), and 1.8f-lglml (6 hours). Case 2.-A 65-year-old woman with acute myeloblastic leukxmia and pulmonary tuberculosis was treated on two occasions with intravenous tobramycin (6 mg/kg/day) and cephalothin (250 mg/kg/day) for presumed bacterial infections. She was also receiving antituberculous therapy with 1
Wilfert, J N., Burke, J. P., Bloomer, H. A., Smith, C.B. J. infect. Dis. 1971, 124, suppl p. 148. 2 Burton, J. R., Lichtenstein, N., Colvin, R. B., Hyslop, N. E. J. Am. med. Ass 1974, 229, 679 3 Schultze, R G., Winters, R. E., Kauffman, H. J. infect. Dis. 1971, 124, suppl. p 145 4 Kleinknecht, D., Ganeval, D., Droz, D. Lancet, 1973, i, 1129. 5 Noone, P., Parsons, T. M. C., Pattison, J. R., Slack, R. C. B., GarfieldDavies, D., Hughes, K. Br. med. J. 1974, i, 477. 6 Waterworth, P. M. J. clin. Path. 1972, 25, 979. 7 Klastersky, J., Hensgens, C., Debusscher, L. Antimicrob. Ag. Chemother. 1975. 7, 640.
rifampicin and isoniazid. After the first course of tobramycin/ cephalothin, lasting 8 days, there was no evidence of renal dysfunction. At the end of the second course, renal function was still normal, with blood-urea 7-2 mmol/1 and plasma-creatinine 102 p.mol/1. However, 6 days later an unexplained rise in blood-urea was noted. On successive days, blood-ureas were 34, 37, 38, 39, 44, and 50 mol/1. Creatinine clearance was 1-4 ml/min. Throughout this time she was producing 370-800 ml urine/day. There was no response to intravenous frusemide and mannitol, and she died 2 weeks after the onset of renal failure. Although other causes for the renal failure in these two patients cannot entirely be excluded, it seems likely that the antibiotic therapy was indeed nephrotoxic. We have given combined tobramycin and carbenicillin therapy on over 30 occasions and have not seen convincing evidence of nephrotoxicity in a single case. Although tobramycin may be less nephrotoxic than gentamicin,8 there seems to be a strong case for discouraging the use of any aminoglycoside antibiotic in combination with high doses of cephalothin.
J. S. TOBIAS J. MICHAEL WHITEHOUSE
St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE.
P. F. M. WRIGLEY
INCISION OF SMALL VESSELS
SiR,—The development of microvascular surgical techniques has allowed significant advances in cardiac surgery, plastic surgery, and neurosurgery and in the creation of arteriovenous nstulx for dialysis. Your readers may find the technique depicted in the accompanying figure useful for accurate incision
Incision
technique
(A) Needle inserted into vessel (B) Making the incision.
and scimitar blade in position.
of small vessels. A small (23 or 25 gauge) needle, bent, is inserted into the vessel with the bevel facing anteriorly. A curved (scimitar) blade is inserted into the bevel of the needle, and the simultaneous withdrawal of needle and blade produces a clean linear incision in the vessel. Albert Einstein College of Medicine, Bronx, N.Y. 10461, U.S.A.
Mary’s Hospital and McGill University, Montreal, Canada.
RONALD M. BECKER
St.
8. Valdivieso, M., Horikoshi, 1974, 268, 149.
MOHAMMED S. CHUGHTAI
N., Rodriguez, V., B G.
P.
Am. J.
med Sci.
MARTYN WATERWORTH
SEVERE RENAL DYSFUNCTION AFTER
TOBRAMYCIN/CEPHALOTHIN THERAPY SIR,-Gentamicin and cephalothin are valuable antibiotics which are occasionally nephrotoxic when used alone.’A number of reports have suggested that combined therapy with gentamicin and cephalothin may be particularly nephrotoxic,’-’ especially if high doses of cephalothin are used. Renal failure following simultaneous administration of these agents may be delayed until several days after the drugs have been discontinued.4 Tobramycin, a newer aminoglycoside antibiotic, has attracted interest because of its apparently greater effectiveness against Pseudomonas species.6 Klastersky et al.’7 reported raised serum-creatinine in 10 out of 48 patients treated with tobramycin and cephalothin, although underlying renal disease was present in 3 of these patients. We have recently encountered two cases in which tobramycin/cephalothin therapy was followed by severe renal dysfunction. Case 1.-A 40-year-old woman with acute myeloblastic ieuksemia was treated with a combination of cytosine arabinoside, adriamycin, vincristine, and prednisolone. Before treatment, blood-urea was 3.0 mmol/1 and serum-creatinine was 82 (imoJ/l. Three separate courses of intravenous tobramycin (4 mg/kg/day) and carbenicillin (300 mg/kg/day) were given for three episodes of fever which occurred during induction therapy, in accordance with the current practice of instituting antibiotic therapy in febrile neutropenic patients even in the absence of bacteriological confirmation. A fourth episode of fever was treated with intravenous tobramycin (4 mg/kg/day) and cephalothin (200 mg/kg/day). The antibiotics were given for 11 days, but after a week on therapy blood-urea had risen from 2.8 to 11 mmol/1 and creatinine clearance was noted to be low (26 ml/min). At this time plasma-tobramycin levels (taken from the opposite arm to that used for the injection) were 38 jig/mi 1 hour after rapid injection and 4 tg/ml 8 hours after injection, confirming abnormal accumulation of the drug. After withdrawal of antibiotic therapy creatinine clearance remained low, reaching a nadir of 17 ml/min. 8 weeks later it was still reduced (44 ml/min). Audiometry showed no abnormality. When the patient received tobramycin/carbenicillin for a further episode of infection, renal excretion of the drug was found to be normal, despite the reduced creatinine clearance (44 mt/min). On this occasion, plasma-tobramycin (after 1-33 mg/kg was given intravenously) were 5.66 g/ml (1hour), 3.66 ng/ml (4 hours), and 1.8f-lglml (6 hours). Case 2.-A 65-year-old woman with acute myeloblastic leukxmia and pulmonary tuberculosis was treated on two occasions with intravenous tobramycin (6 mg/kg/day) and cephalothin (250 mg/kg/day) for presumed bacterial infections. She was also receiving antituberculous therapy with 1
Wilfert, J N., Burke, J. P., Bloomer, H. A., Smith, C.B. J. infect. Dis. 1971, 124, suppl p. 148. 2 Burton, J. R., Lichtenstein, N., Colvin, R. B., Hyslop, N. E. J. Am. med. Ass 1974, 229, 679 3 Schultze, R G., Winters, R. E., Kauffman, H. J. infect. Dis. 1971, 124, suppl. p 145 4 Kleinknecht, D., Ganeval, D., Droz, D. Lancet, 1973, i, 1129. 5 Noone, P., Parsons, T. M. C., Pattison, J. R., Slack, R. C. B., GarfieldDavies, D., Hughes, K. Br. med. J. 1974, i, 477. 6 Waterworth, P. M. J. clin. Path. 1972, 25, 979. 7 Klastersky, J., Hensgens, C., Debusscher, L. Antimicrob. Ag. Chemother. 1975. 7, 640.
rifampicin and isoniazid. After the first course of tobramycin/ cephalothin, lasting 8 days, there was no evidence of renal dysfunction. At the end of the second course, renal function was still normal, with blood-urea 7-2 mmol/1 and plasma-creatinine 102 p.mol/1. However, 6 days later an unexplained rise in blood-urea was noted. On successive days, blood-ureas were 34, 37, 38, 39, 44, and 50 mol/1. Creatinine clearance was 1-4 ml/min. Throughout this time she was producing 370-800 ml urine/day. There was no response to intravenous frusemide and mannitol, and she died 2 weeks after the onset of renal failure. Although other causes for the renal failure in these two patients cannot entirely be excluded, it seems likely that the antibiotic therapy was indeed nephrotoxic. We have given combined tobramycin and carbenicillin therapy on over 30 occasions and have not seen convincing evidence of nephrotoxicity in a single case. Although tobramycin may be less nephrotoxic than gentamicin,8 there seems to be a strong case for discouraging the use of any aminoglycoside antibiotic in combination with high doses of cephalothin.
J. S. TOBIAS J. MICHAEL WHITEHOUSE
St. Bartholomew’s Hospital, West Smithfield, London EC1A 7BE.
P. F. M. WRIGLEY
INCISION OF SMALL VESSELS
SiR,—The development of microvascular surgical techniques has allowed significant advances in cardiac surgery, plastic surgery, and neurosurgery and in the creation of arteriovenous nstulx for dialysis. Your readers may find the technique depicted in the accompanying figure useful for accurate incision
Incision
technique
(A) Needle inserted into vessel (B) Making the incision.
and scimitar blade in position.
of small vessels. A small (23 or 25 gauge) needle, bent, is inserted into the vessel with the bevel facing anteriorly. A curved (scimitar) blade is inserted into the bevel of the needle, and the simultaneous withdrawal of needle and blade produces a clean linear incision in the vessel. Albert Einstein College of Medicine, Bronx, N.Y. 10461, U.S.A.
Mary’s Hospital and McGill University, Montreal, Canada.
RONALD M. BECKER
St.
8. Valdivieso, M., Horikoshi, 1974, 268, 149.
MOHAMMED S. CHUGHTAI
N., Rodriguez, V., B G.
P.
Am. J.
med Sci.