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Peripheral Neuropathy Associated with Ethambutol
Peripheral Neuropathy Associated with Ethambutol To the Editor: The report by Nair et al (Chest 1980; 77:98-99) serves to remind that ethambutol can cause optic neuritis and, occasionally, peripheral neuropathy. The dosage. prescribed for their patient of 20 mg/kg/day is only slightly higher than the usual dose of 15 mg/kg/day. Since the drug is cleared by the kidneys, ·we are surprised that no mention is made of her renal function. Abnormal renal function is suggested, however, by their data which indicated the failure of serum ethambutol levels to halve in value as they normally do between three and seven hours after a single oral dose. I The importance of adjusting the dose of ethambutol in renal insufliciency has been emphasized.2,a In fact, Bobrowitz,~ whose study of ethambutol toxicity in !23 patients found no cases of retrobulbar neuritis, speci&cally excluded patients with a BUN over 30 mgS. In treating over 1,000 patients with ethambutol, one of us ( M.O.L.) has seen only a single case of retrobulbar neuritis: a patient with chronic uremia who, nevertheless, received a dose over 20 mg/kg/day. Ethambutol remains a drug remarkably free of side effects when used in approptlole doses in the absence of renal insufBciency. The need to detennine serQm creatinine or BUN and to adjust the ethambutol dose when abnormal must be re-emphasized inasmuch as neither the authors of this article nor the editors of highly reputable current texts'·• appear to recognize its importance. ¥. Aelony, M.D., F.C.C.P.
Medical Director, Pulmonary Function LabMatory and Re87Jirtltorfl Therapy, Southem California Permanente Medical
Matthew 0. Loeb, M.D., F.C.C.P. Pro/BBBOf' of Medicine and Director, Tuberculosia Control, Lo8 Angele.r Countv, Rancho Los Amig08 HOSf'Jital, Downey, California
REFERENCES 1 Goodman LS, Gilman A. Pharmacological basis of therapeutics (5th ed). New York: McMillan, 1975:1207-08 2 Bennett WM, et al. Guidelines for drug therapy in renal failure. Ann Intem Med 1977; 86:745-73 3 Farer LS. What the practicing physician must know and can do about tuberculosis. Cl Notes Resp Dis 1978; 16:4 4 Bobrowitz ID. Ethambutol-isoniazid versus streptomycinethambutol isoniazid in original treatment of cavitary tuberculosis. Am Rev Respir Dis 1974; 109:548-53 5 Beeson PB, McDermott W, Wingaarden JB. Cecil's textbook of medicine (5th ed). Philadelphia: W. B. Saunders, 1979 6 Isselbacher KJ, et aL Harrison's principles of internal medicine (9th ed). New York: McGraw-Hill, 1980 To the Editor:
We appreciate the comments by Drs. Aelony and Locks pertaining to our report, "Ethambutol Induced Peripheral Neuropathy and Optic Neuritis" in Chest. As emphasized by Drs. Aelony and Locks, it is very important to adjust the dose of ethambutol based on renal function. In this context we
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COMMUNICATIONS TO THE EDITOR
would like to point out that our patient had repeated estimations of BUN, serum creatiDine and creatinine c1eanmce prior to the initiation of antituberculosis therapy and also at intervals during the course of treatment. The pretreatment serum creatinine was 0.8 mg/dl and the creatinine clearance was 97 mVmin. The BUN was 9 mg/dl at the beginning of therapy. Two months after the initiation of ethambutol the serum creatinine was 0.7 mg/dl and the creatinine clearance was 85 mVmin. Subsequent studies of renal function have also been entirely normal. The serum level of ethambutol is determined by a microbiologic assay and the levels obtained in this patient were in the lowest range of detection by this method. The usual range of serum ethambutol levels varies between 3 and 12 ,.g!ml, when measured three hours after administration of therapeutic doses of the drug. The fact that this patient's serum ethambutol level was below the lowest therapeutic value, even at a time when peak concentrations of the drug are expected in the serum, is another point against drug toxicity from impaired renal function. The absence of significant drop in the drug level at seven hours after administration of the dose merely reflects the inherent limitation of the microbiologic assay rather than impaired renal function. S. V. Nair, M.D. Pro/e880r of Medlclfle, Department of Intemal Medicine, Pulmonary Division, University of NebraJka Medical Center, Omaha Assistant
Measurement of Shunt in Respiratory Failure To the EditOf':
The observations of Shapiro et al (Chest 1980; 77: 138-41) confirm a clinically important theoretical concept, namely: an increase in measured "shunt" in patients when calculated during 100 percent oxygen breathing compared to that when breathing a lower concentration of oxygen. However, several issues need to be addressed before concluding that "clinical measurements of shunting" be measured at maintenance Flo2 or at some other arbitrary lower Flo2 than 1.0. Measured "shunt" at an Flo2 of less than 1.0 might be more properly termed calculated venous admixture.I This would reflect the contributions of both low but finite ventilation-perfusion units, which do not behave as true right-to-left shunt, and true shunt units. In particular, the response to increasing Flo2 in a lung with ventilation-perfusion mismatching is to show a decrease in the actual venous admixture by a variable amount. Even in the adult respiratory distress syndrome, the contribution of poorly-ventilated but perfused lung units may be seen in addition to the generally accepted true right-to-left shunts.z,a The observations of Shapiro et al, that patients breathing an Flo 2 in the range of 0.3-0.8 demonstrate increased "shunt" at Flo2 of 1.0 suggests the incidence of ventilation-perfusion mismatching in this series. Absorption atelectasis in, poorly-ventilated but perfused areas probably explains the rise in "shunt," and this would not occur if only true right-to-left shunt were present. It would be of interest to know if their patients' "shunts" decreased at intermediate Flo2 values between the initial maintenance values and an Flo2 of 1.0. The measurement of venous admixture and equating it with "shunt" may be misleading in the clinical setting. First, in evaluating an individual patient, lower "shunts.. may be calculated as an increasing Flo 2 is administered. In view of
CHEST, 78: 6, DECEMBER, 1980
Medical Director, Pulmonary Function LabMatory and Re87Jirtltorfl Therapy, Southem California Permanente Medical
Matthew 0. Loeb, M.D., F.C.C.P. Pro/BBBOf' of Medicine and Director, Tuberculosia Control, Lo8 Angele.r Countv, Rancho Los Amig08 HOSf'Jital, Downey, California
REFERENCES 1 Goodman LS, Gilman A. Pharmacological basis of therapeutics (5th ed). New York: McMillan, 1975:1207-08 2 Bennett WM, et al. Guidelines for drug therapy in renal failure. Ann Intem Med 1977; 86:745-73 3 Farer LS. What the practicing physician must know and can do about tuberculosis. Cl Notes Resp Dis 1978; 16:4 4 Bobrowitz ID. Ethambutol-isoniazid versus streptomycinethambutol isoniazid in original treatment of cavitary tuberculosis. Am Rev Respir Dis 1974; 109:548-53 5 Beeson PB, McDermott W, Wingaarden JB. Cecil's textbook of medicine (5th ed). Philadelphia: W. B. Saunders, 1979 6 Isselbacher KJ, et aL Harrison's principles of internal medicine (9th ed). New York: McGraw-Hill, 1980 To the Editor:
We appreciate the comments by Drs. Aelony and Locks pertaining to our report, "Ethambutol Induced Peripheral Neuropathy and Optic Neuritis" in Chest. As emphasized by Drs. Aelony and Locks, it is very important to adjust the dose of ethambutol based on renal function. In this context we
-
COMMUNICATIONS TO THE EDITOR
would like to point out that our patient had repeated estimations of BUN, serum creatiDine and creatinine c1eanmce prior to the initiation of antituberculosis therapy and also at intervals during the course of treatment. The pretreatment serum creatinine was 0.8 mg/dl and the creatinine clearance was 97 mVmin. The BUN was 9 mg/dl at the beginning of therapy. Two months after the initiation of ethambutol the serum creatinine was 0.7 mg/dl and the creatinine clearance was 85 mVmin. Subsequent studies of renal function have also been entirely normal. The serum level of ethambutol is determined by a microbiologic assay and the levels obtained in this patient were in the lowest range of detection by this method. The usual range of serum ethambutol levels varies between 3 and 12 ,.g!ml, when measured three hours after administration of therapeutic doses of the drug. The fact that this patient's serum ethambutol level was below the lowest therapeutic value, even at a time when peak concentrations of the drug are expected in the serum, is another point against drug toxicity from impaired renal function. The absence of significant drop in the drug level at seven hours after administration of the dose merely reflects the inherent limitation of the microbiologic assay rather than impaired renal function. S. V. Nair, M.D. Pro/e880r of Medlclfle, Department of Intemal Medicine, Pulmonary Division, University of NebraJka Medical Center, Omaha Assistant
Measurement of Shunt in Respiratory Failure To the EditOf':
The observations of Shapiro et al (Chest 1980; 77: 138-41) confirm a clinically important theoretical concept, namely: an increase in measured "shunt" in patients when calculated during 100 percent oxygen breathing compared to that when breathing a lower concentration of oxygen. However, several issues need to be addressed before concluding that "clinical measurements of shunting" be measured at maintenance Flo2 or at some other arbitrary lower Flo2 than 1.0. Measured "shunt" at an Flo2 of less than 1.0 might be more properly termed calculated venous admixture.I This would reflect the contributions of both low but finite ventilation-perfusion units, which do not behave as true right-to-left shunt, and true shunt units. In particular, the response to increasing Flo2 in a lung with ventilation-perfusion mismatching is to show a decrease in the actual venous admixture by a variable amount. Even in the adult respiratory distress syndrome, the contribution of poorly-ventilated but perfused lung units may be seen in addition to the generally accepted true right-to-left shunts.z,a The observations of Shapiro et al, that patients breathing an Flo 2 in the range of 0.3-0.8 demonstrate increased "shunt" at Flo2 of 1.0 suggests the incidence of ventilation-perfusion mismatching in this series. Absorption atelectasis in, poorly-ventilated but perfused areas probably explains the rise in "shunt," and this would not occur if only true right-to-left shunt were present. It would be of interest to know if their patients' "shunts" decreased at intermediate Flo2 values between the initial maintenance values and an Flo2 of 1.0. The measurement of venous admixture and equating it with "shunt" may be misleading in the clinical setting. First, in evaluating an individual patient, lower "shunts.. may be calculated as an increasing Flo 2 is administered. In view of
CHEST, 78: 6, DECEMBER, 1980