CLINICAL TOXICOLOGY 9(1), pp. 53-60 (1976)
“Bicarbonate Resistant” Metabolic Acidosis in Association with Ethylene Glycol Intoxication*
MICHAEL F. MICHELIS, M.D.; BRIAN MITCHELL, M.D.; and BERNARD B. DAVIS, M.D. Department of Medicine University of Pittsburgh School of Medicine and Veterans Administration Hospital Pittsburgh, Pennsylvania
INTRODUCTION The s e r io u s consequences of ethylene glycol ingestion have been well documented previously [ 1-31. The condition still rem ai ns a noteworthy problem since a t least 40 to 60 deaths are thought to occur annually from accidental ingestion or from i t s use as a substitute for beverage alcohol [4]. Recent r epo rt s of successful treatment resulting from ear l y institution of hemodialysis, alcohol infusion, and alkalinizing agents have been encouraging [5-7]. Ingestion of a fatal dose in the human adult (believed to be 100 m l ) dictates e a r l y detection and rapid treatment [4], E ar l y manifestations of toxicity *Reprint requests: Michael F. Michelis, M.D., Chief Nephrology, Department of Medicine, Lenox Hill Hospital, 100 E. 77 St., New York, New York 10021. 53 Copyright @ 1976 hy Marcel Dekker, Inc. All Rights Reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming. and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
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54
MICHELIS, MITCHELL, AND DAVIS
are coma, convulsions, tachypnea, tachycardia, and hypothermia. Diagnostic measures heretofore have relied on the identification of the toxin in "antifreeze" containers o r gastric washings, o r the chance determination of the presence of ethylene glycol during routine blood toxicology screening. In the following case, a comatose patient with profound "bicarbona t e resistant" metabolic acidosis and calcium oxalate crystals in the urinary sediment was found to be a victim of ethylene glycol intoxication. This report details the e a r l y findings that should suggest this diagnosis and reviews current concepts of diagnosis and therapy. CASE REPORT A 56-year-old man was admitted to the emergency room a t this hospital on March 24, 1974. He had a history of alcoholic hepatitis and alcoholic neuropathy and had received treatment with sedatives and diuretics. Two hours before admission he was found unconscious. No history was obtainable regarding recent illness o r recent ingestion of medications o r alcohol. Physical examination revealed blood pressure, 115/80 mm Hg; pulse rate, 100 beats per minute; and temperature, 94.5"F rectally. The breath was negative for characteristic odors; funduscopic examination was normal; bibasilar r a l e s and a summation gallop were noted; the urinary bladder was palpable above the umbilicus; there was no evidence of g r o s s trauma. He was deeply comatose with absent deep tendon reflexes, 3-mm reactive pupils, absent corneal and gag reflexes, plantar flexion of the great toes to Babinski testing, and no response to painful stimuli. Initial laboratory investigation disclosed the following values: a r t e r i a l blood pH 6.9; carbon dioxide p r e s s u r e 15 mm Hg; oxygen p r e s s u r e 124 mm Hg; s e r u m electrolytes: sodium 140 meq/liter, potassium 5.3 meq/liter, chloride 106 meq/liter, and bicarbonate 6 meq/liter. Blood glucose value was 90 mg/100 ml; blood u r e a nitrogen 9 mg/100 ml; hematocrit 38%; white blood cell count 20,000/ cu mm with 80% polymorphonuclear neutrophils, 10% band neutrophils, 5% lymphocytes, and 4% monocytes. Results of urinalysis revealed: pH 5.0; specific gravity 1.009; t r a c e of acetone; 3-4 W B C per highpower field (HPF); 20-25 red blood cells/HPF; many calcium oxalate crystals; few uric acid crystals; ferric chloride test for salicylate was negative. Urine culture showed no growth. Lumbar puncture, skull films, and brain scan were within normal limits. Gastric aspiration was unproductive, Endotracheal intubation was performed. Dexamethasone was
ETHYLENE GLYCOL INTOXICATION
55
administered intravenously and glycerol was given via nasogastric tube. The patient had several grand ma1 s e i z u r e s which were treated with intravenous diazepam. Sodium bicarbonate and fluids were given parenterally to correct the severe metabolic acidosis. Subsequent laboratory investigation revealed: s e r u m bicarbonate eight hours after admission and after 356.8 meq of sodium bicarbonate was 10 meq/liter; toxicology screen for s e r u m salicylate and s e r u m methanol were negative; venous lactic acid was 13 meq/liter. Ethylene glycol intoxication had been considered due to the presence of calcium oxalate c r y s t a l s in the urinary sediment and the persistent metabolic acidosis. Serum ethylene glycol obtained shortly after admission and measured by g a s chromatography was 425 mg/100 ml, the highest reported level within the decade in Allegheny County (personal communication from Charles L. Winek, Ph.D., Toxicologist, Allegheny County, Pennsylvania). Specific therapy was begun with intravenous 5% ethyl alcohol with 5% dextrose administered a t a rate of 100 cc/hr and hemodialysis. After three hours of dialysis the patient remained comatose; however, bicarbonate therapy was no longer required. Following ten hours of hemodialysis therapy, the level of ethylene glycol in the s e r u m was no longer measurable. On the third hospital day, the patient developed pulmonary congestion and bronchopneumonia. Antibiotics and diuretics were given. On the fifth hospital day, the patient developed oliguric renal failure; maintenance fluids and additional diuretics were administered. Progressive pulmonary edema with bilateral pleural effusions resulted in progressive hypoxia and hypercarbia requiring tracheostomy and positive p r e s s u r e breathing with 70% oxygen. The patient was given additional dialysis therapy, but died on the twenty-ninth hospital day. Throughout the hospital course, there was no significant change in the patient's neurologic status. Autopsy revealed severe bilateral bronchopneumonia and right c e r e b r a l encephalomalacia. Microscopic examination of the kidneys showed extensive tubular cell degeneration and disruption associated with a moderate degree of mononuclear interstitial infiltrate. Extensive oxalate crystalization could be demonstrated in the tubules by light microscopy (Fig. 1). This was particularly evident with the u s e of polarizing lenses (Fig. 2). DISCUSSION The clinical manifestations of ethylene glycol intoxication are related to e a r l y central nervous and pulmonary system depression with the subsequent development of oliguric acute renal failure if
56
MICHELE, MITCHELL, AND DAVIS
FIG, 1. Extensive tubular destruction and disruption are present on kidney section. Widespread deposition of oxalate is also apparent but not as easily visible as in Fig. 2. (Hematoxylin and eosin; original magnification, X350.) the patient survives [8]. The agents responsible are believed to be ethylene glycol itself and its metabolic derivatives, oxalic acid and calcium oxalate [ 1, 81. Therapy with alcohol infusion is thought to competitively inhibit the metabolism of ethylene glycol to oxalic acid, while hemodialysis will remove ethylene glycol from the circulation as well as manage renal insufficiency [5, 61. Profound metabolic acidosis is an invariant early manifestation of ethylene glycol intoxication, and it is currently thought to result, in part, from the production of oxalic acid o r i t s acid intermediates [ 1, 91. Vigorous alkalinization and hemodialysis have been required to correct the acidosis [ 71. T his nonhyperchloremic metabolic acidosis, secondary to the organic anionic derivatives of ethylene glycol, is also in part due to significant lactic acidosis. Friedman h a s noted that on a molal bas is insufficient oxalic acid is produce to account entirely f or the profound acidosis seen [ 11. Although an elevated
ETHYLENE GLYCOL INTOXICATION
57
FIG. 2. Same section as in Fig. 1, as it appeared with the use of polarizing lenses. The c r y s t a l s are now much m o r e easily identifiable. (Hematoxylin and eosin; original magnification, x350.) lactic acid level is also seen with heavy ethanol ingestion, it may reflect a diffuse tissue lesion and direct toxic effect when accompanying ethylene glycol intoxication. Urinalysis in these patients has shown albuminuria, microhematuria, and the presence of the characteristic c r y s t a l s of calcium oxalate in the urinary sediment (Fig. 3) [ 11. The calcium oxalate c r y s t a l s are believed to precipitate secondary to supersaturation of the urine due to the overproduction of oxalic acid, r a t h e r than changes in urinary pH [ l o , 111. The case herein described illustrates that the e a r l y findings of "bicarbonate resistant" metabolic acidosis and calcium oxalate c r y s t a l s in the urine in a comatose patient are highly suggestive of ethylene glycol toxicity. These findings do not substitute for direct determination of blood ethylene glycol levels, but provide a rapid and convenient means of identifying possible cases of intoxication in the emergency room.
MICHELIS, MITCHELL, AND DAVIS
FIG. 3. The characteristic geometric shape of calcium oxalate crystals as they appear in the urine. Recently, it h a s been recognized that early measurement of serum osmolality can be a useful diagnostic aid in c a s e s of suspected intoxications [ 121. Unfortunately, such a determination was not made initially on this patient although the history of ethanol abuse should have suggested the need f o r this measurement. The usefulness of this determination results from the fact that the significant increase in s e r u m osmolality produced by certain alcohols, especially ethyl alcohol which can increase s e r u m osmolality by as much as 100 mOsm/kg HzO above normal, may be of major diagnostic import [ 12, 131. Ethyl alcohol intoxication, however, is not uniformly associated with a decrease in s e r u m pH so that when an elevated serum osmolality is associated with systemic acidosis, ingestion of methanol, which tends to cause a rise in s e r u m osmolality of 20-30 mOsm/kg HzO a t lethal s e r u m levels, should also be considered [ 121. The change in s e r u m osmolality associated with ethylene glycol ingestion is of still l e s s e r magnitude a t toxic s e r u m levels [ 121, Therefore, the presence of severe and protracted metabolic acidosis, which can occur with either methanol o r ethylene glycol
ETHYLENE GLYCOL INTOXICATION
59
intoxication, and relatively unaltered s e r u m osmolality (unless extremely high blood levels of the toxin are present) should a l e r t one to the possibility of ethylene glycol toxicity. This suspicion can gain further support if oxalate c r y s t a l s are noted to be present on urine analysis. Therapy with intravenous ethanol may be quickly instituted along with the administration of alkali and preparation for dialysis while m o r e exact laboratory confirmation by blood examination is performed. The post mortem examination performed on this patient revealed extensive renal damage consistent with the observed development of oliguric renal failure during the latter part of the patient's hospital course. Hemodialysis initially quickly cleared the patient's blood of ethylene glycol, and alcohol infusion was employed to block conversion to oxalic acid, which also affects the kidney adversely. Since further dialysis therapy was required a s renal failure l a t e r supervened, the untoward effects of the ingestion were not prevented. Undoubtedly the unusually large size of the ingestion contributed to the outcome in this particular patient. E a r l y institution of therapy h a s resulted in a favorable outcome for other such patients, however [ T I . The importance of early recognition cannot be overemphasized. SUMMARY A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well a s changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of e a r l y diagnosis and therapy is stressed. REFERENCES [ l ] E. A. Friedman, J. B. Greenberg, J. P. Merrill, and G. J. Dammin, Consequences of ethylene glycol poisoning, Am. J. Med., 32, 891 (1962). ~[2] G. E. Schreiner and J. F. Maher, Toxic nephropathy, Am. J. Med., 38, 409 (1965). ~(31 L. B. Seeff, E. D. Hendler, A. 0. Hosten, and R. J. Shalhoub,
60
MICHELIS, MITCHELL, AND DAVIS
Ethylene glycol poisoning. Survival after ingestion of 400 m l with 42 days of oliguria and 17 days of coma, Med. Ann. D.C., 39, 31 (1970). [41 R. H. Dreisbach, "Ethylene Glycol, Diethylene Glycol," in Handbook of Poisoning, Lange Medical Publ., Los Altos, Cal., 1974, p. 151. 151 G. E. Schreiner, J. F. Maher, J. Marc-Aurele, D. Knowland, and M. Alvo, Ethylene glycol: two indications for hemodialysis, Trans. Am. SOC.Artificial Internal Organs, 5, 81 (1959). W. E. C. Wacker, H. Haynes, R. Druyan, W.Fisher, and J. E. Coleman, Treatment of ethylene glycol poisoning with ethyl alcohol, JAMA, 194, 1231 (1965). F. Underwood and W. M. Bennett, Ethylene glycol intoxication, JAMA, _ _ 226, 1453 (1973). J. H. Knepshield, G. E. Schreiner, D. T. Lowenthal, and M. C. Gelfand, Dialysis of poisons and drugs-annual review, Trans. Am. SOC. Artificial Internal Organs, 19, 590 (1973). [91 T. Sollmann, "Oxalic Acid and Oxalates," in A Manual of Pharmacology, 6th ed., Saunders, Philadelphia, Pa., 1942, p. 941. R. M. Kark, J. R. Lawrence, V. E. Pollack, C. L. Pirani, R. C. Muehrcke, and H. Silva, "Crystals," in A P r i m e r for Urinalysis, 2nd ed., Harper and Row, New York, 1963, p. 74. J. S. King, Currents in renal stone research, Clin. Chem., 17, 971 (1971). L. Glasser, P. D. Sternglanz, J. Combie, and A. Robinson, Serum osmolality and i t s applicability to drug overdose, Am. J. Clin. Pathol., 60, 695 (1973). A. G. Robinson a a J. M. Loeb, Ethanol ingestion-commonest cause of elevated plasma osmolality, New Engl. J. Med., 284, 1253 (1971).
“Bicarbonate Resistant” Metabolic Acidosis in Association with Ethylene Glycol Intoxication*
MICHAEL F. MICHELIS, M.D.; BRIAN MITCHELL, M.D.; and BERNARD B. DAVIS, M.D. Department of Medicine University of Pittsburgh School of Medicine and Veterans Administration Hospital Pittsburgh, Pennsylvania
INTRODUCTION The s e r io u s consequences of ethylene glycol ingestion have been well documented previously [ 1-31. The condition still rem ai ns a noteworthy problem since a t least 40 to 60 deaths are thought to occur annually from accidental ingestion or from i t s use as a substitute for beverage alcohol [4]. Recent r epo rt s of successful treatment resulting from ear l y institution of hemodialysis, alcohol infusion, and alkalinizing agents have been encouraging [5-7]. Ingestion of a fatal dose in the human adult (believed to be 100 m l ) dictates e a r l y detection and rapid treatment [4], E ar l y manifestations of toxicity *Reprint requests: Michael F. Michelis, M.D., Chief Nephrology, Department of Medicine, Lenox Hill Hospital, 100 E. 77 St., New York, New York 10021. 53 Copyright @ 1976 hy Marcel Dekker, Inc. All Rights Reserved. Neither this work nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming. and recording, or by any information storage and retrieval system, without permission in writing from the publisher.
.
54
MICHELIS, MITCHELL, AND DAVIS
are coma, convulsions, tachypnea, tachycardia, and hypothermia. Diagnostic measures heretofore have relied on the identification of the toxin in "antifreeze" containers o r gastric washings, o r the chance determination of the presence of ethylene glycol during routine blood toxicology screening. In the following case, a comatose patient with profound "bicarbona t e resistant" metabolic acidosis and calcium oxalate crystals in the urinary sediment was found to be a victim of ethylene glycol intoxication. This report details the e a r l y findings that should suggest this diagnosis and reviews current concepts of diagnosis and therapy. CASE REPORT A 56-year-old man was admitted to the emergency room a t this hospital on March 24, 1974. He had a history of alcoholic hepatitis and alcoholic neuropathy and had received treatment with sedatives and diuretics. Two hours before admission he was found unconscious. No history was obtainable regarding recent illness o r recent ingestion of medications o r alcohol. Physical examination revealed blood pressure, 115/80 mm Hg; pulse rate, 100 beats per minute; and temperature, 94.5"F rectally. The breath was negative for characteristic odors; funduscopic examination was normal; bibasilar r a l e s and a summation gallop were noted; the urinary bladder was palpable above the umbilicus; there was no evidence of g r o s s trauma. He was deeply comatose with absent deep tendon reflexes, 3-mm reactive pupils, absent corneal and gag reflexes, plantar flexion of the great toes to Babinski testing, and no response to painful stimuli. Initial laboratory investigation disclosed the following values: a r t e r i a l blood pH 6.9; carbon dioxide p r e s s u r e 15 mm Hg; oxygen p r e s s u r e 124 mm Hg; s e r u m electrolytes: sodium 140 meq/liter, potassium 5.3 meq/liter, chloride 106 meq/liter, and bicarbonate 6 meq/liter. Blood glucose value was 90 mg/100 ml; blood u r e a nitrogen 9 mg/100 ml; hematocrit 38%; white blood cell count 20,000/ cu mm with 80% polymorphonuclear neutrophils, 10% band neutrophils, 5% lymphocytes, and 4% monocytes. Results of urinalysis revealed: pH 5.0; specific gravity 1.009; t r a c e of acetone; 3-4 W B C per highpower field (HPF); 20-25 red blood cells/HPF; many calcium oxalate crystals; few uric acid crystals; ferric chloride test for salicylate was negative. Urine culture showed no growth. Lumbar puncture, skull films, and brain scan were within normal limits. Gastric aspiration was unproductive, Endotracheal intubation was performed. Dexamethasone was
ETHYLENE GLYCOL INTOXICATION
55
administered intravenously and glycerol was given via nasogastric tube. The patient had several grand ma1 s e i z u r e s which were treated with intravenous diazepam. Sodium bicarbonate and fluids were given parenterally to correct the severe metabolic acidosis. Subsequent laboratory investigation revealed: s e r u m bicarbonate eight hours after admission and after 356.8 meq of sodium bicarbonate was 10 meq/liter; toxicology screen for s e r u m salicylate and s e r u m methanol were negative; venous lactic acid was 13 meq/liter. Ethylene glycol intoxication had been considered due to the presence of calcium oxalate c r y s t a l s in the urinary sediment and the persistent metabolic acidosis. Serum ethylene glycol obtained shortly after admission and measured by g a s chromatography was 425 mg/100 ml, the highest reported level within the decade in Allegheny County (personal communication from Charles L. Winek, Ph.D., Toxicologist, Allegheny County, Pennsylvania). Specific therapy was begun with intravenous 5% ethyl alcohol with 5% dextrose administered a t a rate of 100 cc/hr and hemodialysis. After three hours of dialysis the patient remained comatose; however, bicarbonate therapy was no longer required. Following ten hours of hemodialysis therapy, the level of ethylene glycol in the s e r u m was no longer measurable. On the third hospital day, the patient developed pulmonary congestion and bronchopneumonia. Antibiotics and diuretics were given. On the fifth hospital day, the patient developed oliguric renal failure; maintenance fluids and additional diuretics were administered. Progressive pulmonary edema with bilateral pleural effusions resulted in progressive hypoxia and hypercarbia requiring tracheostomy and positive p r e s s u r e breathing with 70% oxygen. The patient was given additional dialysis therapy, but died on the twenty-ninth hospital day. Throughout the hospital course, there was no significant change in the patient's neurologic status. Autopsy revealed severe bilateral bronchopneumonia and right c e r e b r a l encephalomalacia. Microscopic examination of the kidneys showed extensive tubular cell degeneration and disruption associated with a moderate degree of mononuclear interstitial infiltrate. Extensive oxalate crystalization could be demonstrated in the tubules by light microscopy (Fig. 1). This was particularly evident with the u s e of polarizing lenses (Fig. 2). DISCUSSION The clinical manifestations of ethylene glycol intoxication are related to e a r l y central nervous and pulmonary system depression with the subsequent development of oliguric acute renal failure if
56
MICHELE, MITCHELL, AND DAVIS
FIG, 1. Extensive tubular destruction and disruption are present on kidney section. Widespread deposition of oxalate is also apparent but not as easily visible as in Fig. 2. (Hematoxylin and eosin; original magnification, X350.) the patient survives [8]. The agents responsible are believed to be ethylene glycol itself and its metabolic derivatives, oxalic acid and calcium oxalate [ 1, 81. Therapy with alcohol infusion is thought to competitively inhibit the metabolism of ethylene glycol to oxalic acid, while hemodialysis will remove ethylene glycol from the circulation as well as manage renal insufficiency [5, 61. Profound metabolic acidosis is an invariant early manifestation of ethylene glycol intoxication, and it is currently thought to result, in part, from the production of oxalic acid o r i t s acid intermediates [ 1, 91. Vigorous alkalinization and hemodialysis have been required to correct the acidosis [ 71. T his nonhyperchloremic metabolic acidosis, secondary to the organic anionic derivatives of ethylene glycol, is also in part due to significant lactic acidosis. Friedman h a s noted that on a molal bas is insufficient oxalic acid is produce to account entirely f or the profound acidosis seen [ 11. Although an elevated
ETHYLENE GLYCOL INTOXICATION
57
FIG. 2. Same section as in Fig. 1, as it appeared with the use of polarizing lenses. The c r y s t a l s are now much m o r e easily identifiable. (Hematoxylin and eosin; original magnification, x350.) lactic acid level is also seen with heavy ethanol ingestion, it may reflect a diffuse tissue lesion and direct toxic effect when accompanying ethylene glycol intoxication. Urinalysis in these patients has shown albuminuria, microhematuria, and the presence of the characteristic c r y s t a l s of calcium oxalate in the urinary sediment (Fig. 3) [ 11. The calcium oxalate c r y s t a l s are believed to precipitate secondary to supersaturation of the urine due to the overproduction of oxalic acid, r a t h e r than changes in urinary pH [ l o , 111. The case herein described illustrates that the e a r l y findings of "bicarbonate resistant" metabolic acidosis and calcium oxalate c r y s t a l s in the urine in a comatose patient are highly suggestive of ethylene glycol toxicity. These findings do not substitute for direct determination of blood ethylene glycol levels, but provide a rapid and convenient means of identifying possible cases of intoxication in the emergency room.
MICHELIS, MITCHELL, AND DAVIS
FIG. 3. The characteristic geometric shape of calcium oxalate crystals as they appear in the urine. Recently, it h a s been recognized that early measurement of serum osmolality can be a useful diagnostic aid in c a s e s of suspected intoxications [ 121. Unfortunately, such a determination was not made initially on this patient although the history of ethanol abuse should have suggested the need f o r this measurement. The usefulness of this determination results from the fact that the significant increase in s e r u m osmolality produced by certain alcohols, especially ethyl alcohol which can increase s e r u m osmolality by as much as 100 mOsm/kg HzO above normal, may be of major diagnostic import [ 12, 131. Ethyl alcohol intoxication, however, is not uniformly associated with a decrease in s e r u m pH so that when an elevated serum osmolality is associated with systemic acidosis, ingestion of methanol, which tends to cause a rise in s e r u m osmolality of 20-30 mOsm/kg HzO a t lethal s e r u m levels, should also be considered [ 121. The change in s e r u m osmolality associated with ethylene glycol ingestion is of still l e s s e r magnitude a t toxic s e r u m levels [ 121, Therefore, the presence of severe and protracted metabolic acidosis, which can occur with either methanol o r ethylene glycol
ETHYLENE GLYCOL INTOXICATION
59
intoxication, and relatively unaltered s e r u m osmolality (unless extremely high blood levels of the toxin are present) should a l e r t one to the possibility of ethylene glycol toxicity. This suspicion can gain further support if oxalate c r y s t a l s are noted to be present on urine analysis. Therapy with intravenous ethanol may be quickly instituted along with the administration of alkali and preparation for dialysis while m o r e exact laboratory confirmation by blood examination is performed. The post mortem examination performed on this patient revealed extensive renal damage consistent with the observed development of oliguric renal failure during the latter part of the patient's hospital course. Hemodialysis initially quickly cleared the patient's blood of ethylene glycol, and alcohol infusion was employed to block conversion to oxalic acid, which also affects the kidney adversely. Since further dialysis therapy was required a s renal failure l a t e r supervened, the untoward effects of the ingestion were not prevented. Undoubtedly the unusually large size of the ingestion contributed to the outcome in this particular patient. E a r l y institution of therapy h a s resulted in a favorable outcome for other such patients, however [ T I . The importance of early recognition cannot be overemphasized. SUMMARY A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well a s changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of e a r l y diagnosis and therapy is stressed. REFERENCES [ l ] E. A. Friedman, J. B. Greenberg, J. P. Merrill, and G. J. Dammin, Consequences of ethylene glycol poisoning, Am. J. Med., 32, 891 (1962). ~[2] G. E. Schreiner and J. F. Maher, Toxic nephropathy, Am. J. Med., 38, 409 (1965). ~(31 L. B. Seeff, E. D. Hendler, A. 0. Hosten, and R. J. Shalhoub,
60
MICHELIS, MITCHELL, AND DAVIS
Ethylene glycol poisoning. Survival after ingestion of 400 m l with 42 days of oliguria and 17 days of coma, Med. Ann. D.C., 39, 31 (1970). [41 R. H. Dreisbach, "Ethylene Glycol, Diethylene Glycol," in Handbook of Poisoning, Lange Medical Publ., Los Altos, Cal., 1974, p. 151. 151 G. E. Schreiner, J. F. Maher, J. Marc-Aurele, D. Knowland, and M. Alvo, Ethylene glycol: two indications for hemodialysis, Trans. Am. SOC.Artificial Internal Organs, 5, 81 (1959). W. E. C. Wacker, H. Haynes, R. Druyan, W.Fisher, and J. E. Coleman, Treatment of ethylene glycol poisoning with ethyl alcohol, JAMA, 194, 1231 (1965). F. Underwood and W. M. Bennett, Ethylene glycol intoxication, JAMA, _ _ 226, 1453 (1973). J. H. Knepshield, G. E. Schreiner, D. T. Lowenthal, and M. C. Gelfand, Dialysis of poisons and drugs-annual review, Trans. Am. SOC. Artificial Internal Organs, 19, 590 (1973). [91 T. Sollmann, "Oxalic Acid and Oxalates," in A Manual of Pharmacology, 6th ed., Saunders, Philadelphia, Pa., 1942, p. 941. R. M. Kark, J. R. Lawrence, V. E. Pollack, C. L. Pirani, R. C. Muehrcke, and H. Silva, "Crystals," in A P r i m e r for Urinalysis, 2nd ed., Harper and Row, New York, 1963, p. 74. J. S. King, Currents in renal stone research, Clin. Chem., 17, 971 (1971). L. Glasser, P. D. Sternglanz, J. Combie, and A. Robinson, Serum osmolality and i t s applicability to drug overdose, Am. J. Clin. Pathol., 60, 695 (1973). A. G. Robinson a a J. M. Loeb, Ethanol ingestion-commonest cause of elevated plasma osmolality, New Engl. J. Med., 284, 1253 (1971).
