GLYCEROL AND HYPEROSMOLAR N O N K E T O T I C COMA D A V I D E. O A K L E Y , M.D.,
A N D P H I L I P P. E L L I S ,
Denver,
M.D.
Colorado
Hyperosmolar nonketotic coma (HNC), reportedly first described as a clinical entity by Frerichs 1 more than 80 years ago, has had a resurgence of interest since Sament and Schwartz 2 redescribed it in 1957. There have been only a few oblique references to HNC although ophthalmol ogists deal with many potentially suscep tible patients and employ drugs capable of precipitating or aggravating the condi tion. Hyperosmolar nonketotic coma is a serious disorder reported to have a mor tality varying between 20 and 7 0 % . 3 - 5 CASE REPORT A 29-year-old white man, an insulin-dependent diabetic for 16 years, was admitted to a private hospital with a diagnosis of neovascular glaucoma. The fasting blood glucose on admission was 357 mg/100 ml, hematocrit value was 25%, hemoglobin level was 8.8 g/100 ml, and the white blood cell count was 10,400/mm 3 ; urinalysis showed glucose 4 + , negative ketones, and 4 + protein. The intraocular pressure was 80 mm Hg. The patient was treated with 120 ml of oral glycerol, 50% solution every 12 hours, and 250 mg of oral acetazolamide (Diamox) every six hours for 24 hours. The intraocular pressure decreased to 15 mm Hg and the patient was discharged. During the next 24 hours the patient developed increasing lethargy, anorexia, nausea, and vomiting. He was admitted to a second hospital. At this time he was noted to be lethargic, tachypneic, but well oriented. The blood pressure was 170/80, pulse rate was 80 beats per minute, there were 35 to 40 respirations per minute, and temperature was 37.5° C. Further physical examination was considered within normal limits. Laboratory values were as follows: sodium, 125 mEq/liter; potassium, 6.7 mEq/liter; bicarbonate, 3 mEq/liter; chloride, 95 mEq/liter; blood urea nitrogen, 129 mg/100 ml; creatinine, 9.5 mg/100 ml; blood glucose, 1,129 mg/100 ml; hematocrit value, 29%; hemoglobin lev el, 10.2 g/100 ml; white blood cell count, 20,500 mm 3 ; total proteins, 6.2 g/100 ml; albumin, 2.5 g/100
From the Division of Ophthalmology, University of Colorado Medical Center, Denver, Colorado. Reprint requests to Philip P. Ellis, M.D., Division of Ophthalmology, University of Colorado Medical Center, 4200 E. 9th Ave., Denver, C O 80220.
ml; undiluted serum acetone, 4 + (trace at 1/16 dilution); and blood p H 6.98. Urinalysis showed a specific gravity of 1.020, 3 + protein, 4 + glucose, moderate ketones, and a p H of 6.0. Blood, urine, and sputum cultures were negative. Cerebrospinal fluid glucose level was 532 mg/100 ml. The serum osmolality was 366 mOsm/kg. The electrocardiogram (ECG) showed left ventricular hypertrophy. Stools contained occult blood. No nasogastric aspirate was obtained. The patient was treated with 8.3 liters of intrave nous hypotonie saline and 200 ml of albumin and 2 units of packed red blood cells. He also was treated with a total of 600 units of regular insulin in divided doses over several hours and 6 ampules of bicarbon ate; his blood glucose level and blood p H returned to normal levels. During the acute phase, the patient became hypotensive once; additionally, he had an episode of furosemide response oliguria and a mild transient iatrogenic alkalosis. The patient recovered from the ketoacidosis but continued to evidence chronic renal failure. DISCUSSION
Hyperosmolar nonketotic coma and ketoacidosis represent two facets of im paired carbohydrate metabolism. Our pa tient had significant acidosis and ketonemia in the face of an obvious fluid deficit and hyperosmolarity, either of which constitutes a medical emergency. In addition, the patient had evidence of renal failure, apart from prerenal azotemia secondary to dehydration, and was anemic due to uremia or gastrointestinal blood loss associated with ketoacidosis, or both. Such associated chronic and in tercurrent acute diseases are characteris tic of the patients susceptible to hyper osmolar nonketotic coma. 3 - 5 Hyperosmolar nonketotic coma may be too specific a term. First, the term nonke totic is relative, and usually means little, if any, ketonemia. Second, most patients with H N C display altered mental status, lethargy, and confusion rather than total unresponsiveness', clearly a dire sign. It usually occurs in older patients with chronic disease, of which 85% are diseas-
469
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AMERICAN JOURNAL OF OPHTHALMOLOGY
es of the renal or cardiovascular systems. However, it may occur in children and in insulin-dependent diabetics. The most commonly affected patients are the elder ly with unsuspected or mild diabetes con trolled with oral agents or diet alone. Often a precipitating factor can be impli cated such as myocardial insufficiency, acute pancreatitis, pneumonia, sepsis, in fluenza, inaccessibility to proper fluids, neglect, surgical procedures, ingestion of hypertonic solutions containing glucose, the use of osmotic diuretics, or the use of drugs such as thiazides, diphenylhydantoin, or corticosteroids. 3 - 8 The unifying feature appears to be sus tained osmotic diuresis with resultant de hydration. This osmotic diuresis may be due to exogenous carbohydrate load or endogenous glucose production follow ing excess secretion of cortisol, catecholamines, or glucagon. In addition, agents such as mannitol and potentially isosorbide, which augment the obligatory diu resis of an endogenous carbohydrate load, aggravate the resultant dehydration. To our knowledge, however, isosorbide has not yet been implicated as a precipitating agent in the development of hyperosmolar coma. The more abrupt and rapid ly progressive the dehydration, the more likely it is to cause coma. 3 - 5 The effect of sustained hyperosmolality causing intracellular dehydration, particularly of the brain, is the primary cause of death. 3 - 5 The osmotic diuresis leads to the loss of salt and water from the extracellular space. However, the net fluid and electro lyte transfer to extracellular space and to serum and urine occurs at the expense of intracellular volume with subsequent cel lular dehydration. Diabetics who receive or produce small amounts of insulin may avoid ketosis but still develop hyperglycemia that slowly leads to dehydration. Such patients are particularly susceptible to the effects of decreased fluid intake or induced diuresis. 3 - 8
APRIL, 1976
Clinically, the patients display increas ing polyuria and polydipsia with increas ing lethargy over three days to three weeks, with stupor progressing to coma. Focal motor seizures may be present to gether with symptoms suggestive of an acute cerebral vascular accident. The blood glucose level is usually above 900 mg/100 ml, serum osmolality is above 340 mOsm/kg, and the blood urea nitrogen level is above 80 mg/100 ml. Mild meta bolic acidosis is usually present and there is dehydration that may require 5 to 15 liters of rapid intravenous fluid replace ment. Therapy is directed toward correc tion of the severe fluid deficit and reduc tion of the blood glucose and serum osmolality, as well as careful observation of electrolytes and maintenance of ade quate urine flow.3-5 Large amounts of glycerol have been used in animals and man without produc ing significant toxicity. Its primary use in man has been in the treatment of cerebral edema, particularly when there is associ ated renal failure where urea or mannitol are unsafe, and in ophthalmologic condi tions where dehydration of the vitreous body is desirable. 9 - 1 1 Glycerol is an osmotic diuretic which, when given orally or intravenously, caus es hyperosmolarity of the blood and later of urine, resulting in the withdrawal of water from the extracellular and eventual ly the intracellular compartments. It is almost totally metabolized by the liver without the necessity of insulin. 1 2 , 1 3 In the insulin-deficient organism, two thirds of administered glycerol is converted to glucose and metabolized to C 0 2 and H 2 0 via the Kreb's cycle. 12 · 13 The remaining one third is converted to glucose and released into the circulation. It spares fatty acids and protein utilization in dia betics by providing a source of glucose without insulin; it has been substituted isocalorically for other carbohydrates in the diet; and it decreases glycosuria, keto-
VOL. 81, NO. 4
GLYCEROL USAGE
sis, and insulin requirements in those few patients in whom it has been used. 1 4 However, as desirable as some of these effects appear to be, it is the dehydrating effect of glycerol for which it is most frequently used and it is this effect which is potentially most dangerous in patients susceptible to hyperosmolar coma. D'Alena and Ferguson 1 5 in 1966 report ed two cases of confusion and disorienta tion following the use of osmotic diuret ics in elderly patients suffering from acute glaucoma. Both were initially thought to have suffered an acute cerebral vascular accident. In both cases there was an associated water deficit. Osmotic diu resis was thought to play a responsible role. In the first case, it was presumed that there was relative cerebrovascular ische mia secondary to cardiovascular overload in a patient with marginal cardiac status. In the second case, where oral glycerol was employed, the medical problem was assumed to be secondary to electrolyte imbalance and hypovolemia. Hyperos molar coma may be suspected in these cases, particularly the second, on the basis of available clinical and laboratory data. The second patient was an elderly diabetic who displayed confusion pro gressing to a semicomatose state associat ed with an induced water deficit and elevated blood glucose level. In the same article the authors 1 5 report ed a personal communication with Bietti concerning coma after administration of oral glycerol in two diabetic patients. Bietti suggested that insulin be given simultaneously with glycerol to such pa tients. This recommendation is based on the assumption that glycerol contributes significantly to serum glucose levels. Pre vious investigators, however, have shown that in insulin-deficient animals only one third of administered glycerol, after up take by the liver, returns again to serum as glucose. When administered orally to dia betic and nondiabetic patients, glycerol
471
increases the blood glucose level slightly in diabetics and minimally in nondiabetics. 1 2 - 1 7 In addition, glycerol, when substituted isocalorically for glucose, may reduce the blood glucose level by uncertain means and cause hypoglycemia in diabetics receiving their usual insulin dosages. 1 4 More importantly, the basic deficit is not hyperglycemia per se, but dehydra tion secondary to chronic hyperglycemia. This is compounded by induced diuresis or fluid deprivation and it is the loss of fluid that must be avoided or promptly corrected when discovered. Insulin thera py may have a selected role in the treat ment of HNC once it has developed. However, many patients with HNC are reported to be unusually sensitive to insu lin and caution must be exercised with the use of this drug. 3 - 5 Again, the primary goal of therapy is the reversal of dehydra tion employing hypotonie solutions, such as half-normal saline, to correct the fluid deficit. 3-5 The principal role of the ophthalmolo gist, then, is not to treat HNC but to prevent it and recognize the disorder and the susceptible patient population: the frail, adult-onset elderly diabetic with se vere intercurrent acute or chronic disease that may predispose to fluid deprivation or its chronic loss. Of equal importance is the prior knowledge of the patient's meta bolic status and blood chemistry values. Any evidence of hemoconcentration such as elevated electrolytes, hematocrit, serum osmolality, blood glucose, and blood urea nitrogen levels out of propor tion to serum creatinine should alert the physician to the dehydrated state and possible significant fluid deficit. Hypertonic solutions such as glycerol, isosorbide, mannitol, and urea should be avoided when possible in suspected pa tients, and adequate fluid intake should be maintained in those patients in whom hypertonic therapy is unavoidable.
472
AMERICAN JOURNAL OF OPHTHALMOLOGY SUMMARY
Hyperosmolar nonketotic coma oc curred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonie saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma. REFERENCES 1. Frerichs, cited by Solvesteen, P., Vestergaard, O., and Hansen, E. L.: Diabetic coma without ketoacidosis. Acta Med. Scand. 184:83, 1968. 2. Sament, S., and Schwartz, M. B.: Severe diabet ic stupor without ketosis. S. Afr. Med. J. 31:893, 1957. 3. Arieff, A., and Carroll, H. J.: Nonketotic hyper osmolar coma with hyperglycemia. Medicine 51:73, 1972. 4. Gerich, J. E., Martin, M. M., Recant, L., and Ullmann, T. D.: Clinical and metabolic characteris tics of hyperosmolar coma. Diabetes 20:228, 1971. 5. Danowski, T. S.: Nonketotic coma and diabetes mellitus. Med. Clin. North Am. 55:913, 1971. 6. Aviram, A., Pfau, A., and Czaczkes, J. W.: Hyperosmolality with hypernatremia caused by in appropriate administration of mannitol. Am. J. Med. 42:648, 1967. 7. Goldberg, E. M., and Shafeek, S.: Hyperos molar nonketotic coma following administration of
APRIL, 1976
Dilantin (diphenylhydantoin). Diabetes 18:107, 1969. 8. Spenney, J. G., Eure, C. A., and Kreisberg, R. A.: Hyperglycémie hyperosmolar nonketoacidotic diabetes. A complication of steroid and immunosuppressive therapy. Diabetes 18:107,1969. 9. .Tourtellotte, W. W., Reinglass, J. L., and Newkirk, T. A.: Cerebral dehydration action of glycerol. 1. Historical aspects with emphasis on toxicity and intravenous administration. Clin. Pharmacol. Ther. 13:159, 1972. 10. Meyer, J. S., Charney, J. Z., Rivera, V. M., and Mathew, N. T.: Treatment with glycerol of cerebral edema due to acute cerebral·infarction. Lancet 2: 993, 1971. 11. Sollam, A. W.: Dangers of glycerol therapy for acute glaucoma after a partial gastrectomy. Br. J. Ophthalmol. 56:506, 1972. 12. Doerschuk, A. P.: Some studies on the metab olism of glycerol-l-C u . J. Biol. Chem. 193:39,1951. 13. Deuel, H. J.: The Lipids. New York, Interscience Publishers, 1957, vol. 3, pp. 43-48. 14. Freund, G.: The metabolic effects of glycerol administered to diabetic patients. Arch. Intern. Med. 121:123, 1968. 15. D'Alena, P., and Ferguson, W.: Adverse ef fects after glycerol orally and mannitol parenterally. Arch. Ophthalmol. 75:201, 1966. 16. Wishnofsky, M., Kane, A. P., Spitz, W. C , Michalover, S., and Byron, C. S.: Influence of glycerol on glycemia in normal and diabetic indi viduals. J. Lab. Clin. Med. 26:526, 1940. 17. Greene, H. L., Stifel, F. B., and Herman, R. H.: Ketotic hypoglycemia due to hepatic fructose-l-6-diphosphatase deficiency. Am. J. Dis. Child. 124:415, 1972.
A N D P H I L I P P. E L L I S ,
Denver,
M.D.
Colorado
Hyperosmolar nonketotic coma (HNC), reportedly first described as a clinical entity by Frerichs 1 more than 80 years ago, has had a resurgence of interest since Sament and Schwartz 2 redescribed it in 1957. There have been only a few oblique references to HNC although ophthalmol ogists deal with many potentially suscep tible patients and employ drugs capable of precipitating or aggravating the condi tion. Hyperosmolar nonketotic coma is a serious disorder reported to have a mor tality varying between 20 and 7 0 % . 3 - 5 CASE REPORT A 29-year-old white man, an insulin-dependent diabetic for 16 years, was admitted to a private hospital with a diagnosis of neovascular glaucoma. The fasting blood glucose on admission was 357 mg/100 ml, hematocrit value was 25%, hemoglobin level was 8.8 g/100 ml, and the white blood cell count was 10,400/mm 3 ; urinalysis showed glucose 4 + , negative ketones, and 4 + protein. The intraocular pressure was 80 mm Hg. The patient was treated with 120 ml of oral glycerol, 50% solution every 12 hours, and 250 mg of oral acetazolamide (Diamox) every six hours for 24 hours. The intraocular pressure decreased to 15 mm Hg and the patient was discharged. During the next 24 hours the patient developed increasing lethargy, anorexia, nausea, and vomiting. He was admitted to a second hospital. At this time he was noted to be lethargic, tachypneic, but well oriented. The blood pressure was 170/80, pulse rate was 80 beats per minute, there were 35 to 40 respirations per minute, and temperature was 37.5° C. Further physical examination was considered within normal limits. Laboratory values were as follows: sodium, 125 mEq/liter; potassium, 6.7 mEq/liter; bicarbonate, 3 mEq/liter; chloride, 95 mEq/liter; blood urea nitrogen, 129 mg/100 ml; creatinine, 9.5 mg/100 ml; blood glucose, 1,129 mg/100 ml; hematocrit value, 29%; hemoglobin lev el, 10.2 g/100 ml; white blood cell count, 20,500 mm 3 ; total proteins, 6.2 g/100 ml; albumin, 2.5 g/100
From the Division of Ophthalmology, University of Colorado Medical Center, Denver, Colorado. Reprint requests to Philip P. Ellis, M.D., Division of Ophthalmology, University of Colorado Medical Center, 4200 E. 9th Ave., Denver, C O 80220.
ml; undiluted serum acetone, 4 + (trace at 1/16 dilution); and blood p H 6.98. Urinalysis showed a specific gravity of 1.020, 3 + protein, 4 + glucose, moderate ketones, and a p H of 6.0. Blood, urine, and sputum cultures were negative. Cerebrospinal fluid glucose level was 532 mg/100 ml. The serum osmolality was 366 mOsm/kg. The electrocardiogram (ECG) showed left ventricular hypertrophy. Stools contained occult blood. No nasogastric aspirate was obtained. The patient was treated with 8.3 liters of intrave nous hypotonie saline and 200 ml of albumin and 2 units of packed red blood cells. He also was treated with a total of 600 units of regular insulin in divided doses over several hours and 6 ampules of bicarbon ate; his blood glucose level and blood p H returned to normal levels. During the acute phase, the patient became hypotensive once; additionally, he had an episode of furosemide response oliguria and a mild transient iatrogenic alkalosis. The patient recovered from the ketoacidosis but continued to evidence chronic renal failure. DISCUSSION
Hyperosmolar nonketotic coma and ketoacidosis represent two facets of im paired carbohydrate metabolism. Our pa tient had significant acidosis and ketonemia in the face of an obvious fluid deficit and hyperosmolarity, either of which constitutes a medical emergency. In addition, the patient had evidence of renal failure, apart from prerenal azotemia secondary to dehydration, and was anemic due to uremia or gastrointestinal blood loss associated with ketoacidosis, or both. Such associated chronic and in tercurrent acute diseases are characteris tic of the patients susceptible to hyper osmolar nonketotic coma. 3 - 5 Hyperosmolar nonketotic coma may be too specific a term. First, the term nonke totic is relative, and usually means little, if any, ketonemia. Second, most patients with H N C display altered mental status, lethargy, and confusion rather than total unresponsiveness', clearly a dire sign. It usually occurs in older patients with chronic disease, of which 85% are diseas-
469
470
AMERICAN JOURNAL OF OPHTHALMOLOGY
es of the renal or cardiovascular systems. However, it may occur in children and in insulin-dependent diabetics. The most commonly affected patients are the elder ly with unsuspected or mild diabetes con trolled with oral agents or diet alone. Often a precipitating factor can be impli cated such as myocardial insufficiency, acute pancreatitis, pneumonia, sepsis, in fluenza, inaccessibility to proper fluids, neglect, surgical procedures, ingestion of hypertonic solutions containing glucose, the use of osmotic diuretics, or the use of drugs such as thiazides, diphenylhydantoin, or corticosteroids. 3 - 8 The unifying feature appears to be sus tained osmotic diuresis with resultant de hydration. This osmotic diuresis may be due to exogenous carbohydrate load or endogenous glucose production follow ing excess secretion of cortisol, catecholamines, or glucagon. In addition, agents such as mannitol and potentially isosorbide, which augment the obligatory diu resis of an endogenous carbohydrate load, aggravate the resultant dehydration. To our knowledge, however, isosorbide has not yet been implicated as a precipitating agent in the development of hyperosmolar coma. The more abrupt and rapid ly progressive the dehydration, the more likely it is to cause coma. 3 - 5 The effect of sustained hyperosmolality causing intracellular dehydration, particularly of the brain, is the primary cause of death. 3 - 5 The osmotic diuresis leads to the loss of salt and water from the extracellular space. However, the net fluid and electro lyte transfer to extracellular space and to serum and urine occurs at the expense of intracellular volume with subsequent cel lular dehydration. Diabetics who receive or produce small amounts of insulin may avoid ketosis but still develop hyperglycemia that slowly leads to dehydration. Such patients are particularly susceptible to the effects of decreased fluid intake or induced diuresis. 3 - 8
APRIL, 1976
Clinically, the patients display increas ing polyuria and polydipsia with increas ing lethargy over three days to three weeks, with stupor progressing to coma. Focal motor seizures may be present to gether with symptoms suggestive of an acute cerebral vascular accident. The blood glucose level is usually above 900 mg/100 ml, serum osmolality is above 340 mOsm/kg, and the blood urea nitrogen level is above 80 mg/100 ml. Mild meta bolic acidosis is usually present and there is dehydration that may require 5 to 15 liters of rapid intravenous fluid replace ment. Therapy is directed toward correc tion of the severe fluid deficit and reduc tion of the blood glucose and serum osmolality, as well as careful observation of electrolytes and maintenance of ade quate urine flow.3-5 Large amounts of glycerol have been used in animals and man without produc ing significant toxicity. Its primary use in man has been in the treatment of cerebral edema, particularly when there is associ ated renal failure where urea or mannitol are unsafe, and in ophthalmologic condi tions where dehydration of the vitreous body is desirable. 9 - 1 1 Glycerol is an osmotic diuretic which, when given orally or intravenously, caus es hyperosmolarity of the blood and later of urine, resulting in the withdrawal of water from the extracellular and eventual ly the intracellular compartments. It is almost totally metabolized by the liver without the necessity of insulin. 1 2 , 1 3 In the insulin-deficient organism, two thirds of administered glycerol is converted to glucose and metabolized to C 0 2 and H 2 0 via the Kreb's cycle. 12 · 13 The remaining one third is converted to glucose and released into the circulation. It spares fatty acids and protein utilization in dia betics by providing a source of glucose without insulin; it has been substituted isocalorically for other carbohydrates in the diet; and it decreases glycosuria, keto-
VOL. 81, NO. 4
GLYCEROL USAGE
sis, and insulin requirements in those few patients in whom it has been used. 1 4 However, as desirable as some of these effects appear to be, it is the dehydrating effect of glycerol for which it is most frequently used and it is this effect which is potentially most dangerous in patients susceptible to hyperosmolar coma. D'Alena and Ferguson 1 5 in 1966 report ed two cases of confusion and disorienta tion following the use of osmotic diuret ics in elderly patients suffering from acute glaucoma. Both were initially thought to have suffered an acute cerebral vascular accident. In both cases there was an associated water deficit. Osmotic diu resis was thought to play a responsible role. In the first case, it was presumed that there was relative cerebrovascular ische mia secondary to cardiovascular overload in a patient with marginal cardiac status. In the second case, where oral glycerol was employed, the medical problem was assumed to be secondary to electrolyte imbalance and hypovolemia. Hyperos molar coma may be suspected in these cases, particularly the second, on the basis of available clinical and laboratory data. The second patient was an elderly diabetic who displayed confusion pro gressing to a semicomatose state associat ed with an induced water deficit and elevated blood glucose level. In the same article the authors 1 5 report ed a personal communication with Bietti concerning coma after administration of oral glycerol in two diabetic patients. Bietti suggested that insulin be given simultaneously with glycerol to such pa tients. This recommendation is based on the assumption that glycerol contributes significantly to serum glucose levels. Pre vious investigators, however, have shown that in insulin-deficient animals only one third of administered glycerol, after up take by the liver, returns again to serum as glucose. When administered orally to dia betic and nondiabetic patients, glycerol
471
increases the blood glucose level slightly in diabetics and minimally in nondiabetics. 1 2 - 1 7 In addition, glycerol, when substituted isocalorically for glucose, may reduce the blood glucose level by uncertain means and cause hypoglycemia in diabetics receiving their usual insulin dosages. 1 4 More importantly, the basic deficit is not hyperglycemia per se, but dehydra tion secondary to chronic hyperglycemia. This is compounded by induced diuresis or fluid deprivation and it is the loss of fluid that must be avoided or promptly corrected when discovered. Insulin thera py may have a selected role in the treat ment of HNC once it has developed. However, many patients with HNC are reported to be unusually sensitive to insu lin and caution must be exercised with the use of this drug. 3 - 5 Again, the primary goal of therapy is the reversal of dehydra tion employing hypotonie solutions, such as half-normal saline, to correct the fluid deficit. 3-5 The principal role of the ophthalmolo gist, then, is not to treat HNC but to prevent it and recognize the disorder and the susceptible patient population: the frail, adult-onset elderly diabetic with se vere intercurrent acute or chronic disease that may predispose to fluid deprivation or its chronic loss. Of equal importance is the prior knowledge of the patient's meta bolic status and blood chemistry values. Any evidence of hemoconcentration such as elevated electrolytes, hematocrit, serum osmolality, blood glucose, and blood urea nitrogen levels out of propor tion to serum creatinine should alert the physician to the dehydrated state and possible significant fluid deficit. Hypertonic solutions such as glycerol, isosorbide, mannitol, and urea should be avoided when possible in suspected pa tients, and adequate fluid intake should be maintained in those patients in whom hypertonic therapy is unavoidable.
472
AMERICAN JOURNAL OF OPHTHALMOLOGY SUMMARY
Hyperosmolar nonketotic coma oc curred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonie saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma. REFERENCES 1. Frerichs, cited by Solvesteen, P., Vestergaard, O., and Hansen, E. L.: Diabetic coma without ketoacidosis. Acta Med. Scand. 184:83, 1968. 2. Sament, S., and Schwartz, M. B.: Severe diabet ic stupor without ketosis. S. Afr. Med. J. 31:893, 1957. 3. Arieff, A., and Carroll, H. J.: Nonketotic hyper osmolar coma with hyperglycemia. Medicine 51:73, 1972. 4. Gerich, J. E., Martin, M. M., Recant, L., and Ullmann, T. D.: Clinical and metabolic characteris tics of hyperosmolar coma. Diabetes 20:228, 1971. 5. Danowski, T. S.: Nonketotic coma and diabetes mellitus. Med. Clin. North Am. 55:913, 1971. 6. Aviram, A., Pfau, A., and Czaczkes, J. W.: Hyperosmolality with hypernatremia caused by in appropriate administration of mannitol. Am. J. Med. 42:648, 1967. 7. Goldberg, E. M., and Shafeek, S.: Hyperos molar nonketotic coma following administration of
APRIL, 1976
Dilantin (diphenylhydantoin). Diabetes 18:107, 1969. 8. Spenney, J. G., Eure, C. A., and Kreisberg, R. A.: Hyperglycémie hyperosmolar nonketoacidotic diabetes. A complication of steroid and immunosuppressive therapy. Diabetes 18:107,1969. 9. .Tourtellotte, W. W., Reinglass, J. L., and Newkirk, T. A.: Cerebral dehydration action of glycerol. 1. Historical aspects with emphasis on toxicity and intravenous administration. Clin. Pharmacol. Ther. 13:159, 1972. 10. Meyer, J. S., Charney, J. Z., Rivera, V. M., and Mathew, N. T.: Treatment with glycerol of cerebral edema due to acute cerebral·infarction. Lancet 2: 993, 1971. 11. Sollam, A. W.: Dangers of glycerol therapy for acute glaucoma after a partial gastrectomy. Br. J. Ophthalmol. 56:506, 1972. 12. Doerschuk, A. P.: Some studies on the metab olism of glycerol-l-C u . J. Biol. Chem. 193:39,1951. 13. Deuel, H. J.: The Lipids. New York, Interscience Publishers, 1957, vol. 3, pp. 43-48. 14. Freund, G.: The metabolic effects of glycerol administered to diabetic patients. Arch. Intern. Med. 121:123, 1968. 15. D'Alena, P., and Ferguson, W.: Adverse ef fects after glycerol orally and mannitol parenterally. Arch. Ophthalmol. 75:201, 1966. 16. Wishnofsky, M., Kane, A. P., Spitz, W. C , Michalover, S., and Byron, C. S.: Influence of glycerol on glycemia in normal and diabetic indi viduals. J. Lab. Clin. Med. 26:526, 1940. 17. Greene, H. L., Stifel, F. B., and Herman, R. H.: Ketotic hypoglycemia due to hepatic fructose-l-6-diphosphatase deficiency. Am. J. Dis. Child. 124:415, 1972.
