Toxigenic and Metabolic Causes of Ketosis and Ketoacidotic Syndromes

Critical Care Clinics

Volumn 28, Issue 4, 2012, Pages 601-631

  Cartwright, Martina M ^a   Hajja, Waddah ^b   Al Khatib, Sofian ^b   Hazeghazam, Maryam ^b   Sreedhar, Dharmashree ^b   Li, Rebecca Na ^c   Wong McKinstry, Edna ^d   Carlson, Richard W ^b,e,f  

^a UNIVERSITY OF ARIZONA   (United States)

^b MARICOPA MEDICAL CENTER   (United States)

^c Sutter Pacific Medical Foundation   (United States)

^d UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^e UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^f MAYO CLINIC   (United States)

Author keywords

Acidosis management; Alcohol ingestion; Alcoholic ketoacidosis; Diabetic ketoacidosis; Ketoacidosis; Ketoacidotic syndromes; Ketosis; Toxic ingestions

Indexed keywords

ACETONE; ACTIVATED CARBON; ARIPIPRAZOLE; ATYPICAL ANTIPSYCHOTIC AGENT; BICARBONATE; CLOZAPINE; ETHYLENE GLYCOL; GLUCOSE; ILLICIT DRUG; IRON; ISONIAZID; KETONE; OLANZAPINE; PARALDEHYDE; PROPYLENE GLYCOL; QUETIAPINE; RISPERIDONE; SALICYLIC ACID; ZIPRASIDONE;

ALCOHOL METABOLISM; ALCOHOLIC KETOACIDOSIS; ANION GAP; BICARBONATE BLOOD LEVEL; BLOOD PH; BRAIN DISEASE; DECARBOXYLATION; DIABETIC KETOACIDOSIS; DIETARY INTAKE; DIFFERENTIAL DIAGNOSIS; DISEASE SEVERITY; DRUG OVERDOSE; DRUG TOLERANCE; DRUG USE; FATTY ACID OXIDATION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; GLYCEMIC CONTROL; GLYCOGENOLYSIS; HUMAN; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA; HYPOVOLEMIA; IRON OVERLOAD; KETOACIDOSIS; KETOGENESIS; KIDNEY FAILURE; LACTIC ACIDOSIS; LIPOLYSIS; METABOLIC ACIDOSIS; METHANOL POISONING; MORTALITY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN DEGRADATION; REVIEW; STOMACH LAVAGE; TREATMENT DURATION; TREATMENT OUTCOME; UREMIA;

ACID-BASE EQUILIBRIUM; ALCOHOLISM; CRITICAL CARE; DIABETIC KETOACIDOSIS; DRUG OVERDOSE; HUMANS; KETOGENIC DIET; KETONES; KETOSIS; METABOLISM, INBORN ERRORS; NUTRITION DISORDERS; POISONING;

EID: 84866516466     PISSN: 07490704     EISSN: 15578232     Source Type: Journal    
DOI: 10.1016/j.ccc.2012.07.001     Document Type: Review

References (167)

1. Mokhlesi B., Leikin J., Murray P., et al. Adult toxicology in critical care: part II: specific poisonings. Chest 2003, 123(3):897-922.
2. Goldberg P.A., Inzucchi S.E. Critical issues in endocrinology. Clin Chest Med 2003, 24(4):583-606.
3. Lieberman M., Marks A.D., Smith C.M. Oxidation of fatty acids and ketone bodies. Marks' basic medical biochemistry 2009, 421-442. Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia. 3rd edition. M. Lieberman, A.D. Marks (Eds.).
4. Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 1999, 15(6):412-426.
5. Mitchell G.A., Kassovska-Bratinova S., Boukaftane Y., et al. Medical aspects of ketone body metabolism. Clin Invest Med 1995, 18(3):193-216.
6. Bohan J.S. Chemical measurements in ketoacidosis. Arch Intern Med 1999, 27(17):2089.
7. Fukao T., Lopaschuk G.D., Mitchell G.A. Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry. Prostaglandins Leukot Essent Fatty Acids 2004, 70(3):245-251.
8. Carmant L. Assessing ketosis: approaches and pitfalls. Epilepsia 2008, 49(Suppl 8):20-22.
9. Khan A.S., Talbot J.A., Tieszen K.L., et al. Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance. Diabet Med 2004, 21(7):782-785.
10. Hendy G.W., Schwab T., Soliz T. Urine ketone dip test as a screen for ketonemia in diabetic ketoacidosis and ketosis in the emergency department. Ann Emerg Med 1997, 29(6):735-738.
11. Csako G., Elin R.J. Unrecognized false positive ketones from drugs containing free sulfhydryl groups. JAMA 1990, 269(13):1634. [letter].
12. Taboulet P., Haas L., Porcher R., et al. Urinary acetoacetate or capillary beta-hydroxybutyrate for the diagnosis of ketoacidosis in the emergency department setting. Eur J Emerg Med 2004, 11(5):251-258.
13. Porter W.H., Yao H.H., Karounos D.G. Laboratory and clinical evaluation of assays for beta hydroxybutyrate. Am J Clin Pathol 1997, 107(13):353-358.
14. Fulop M., Murthy V., Michilli A., et al. Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med 1999, 159(4):381-384.
15. Timmons J.A., Meyer P., Maturen A., et al. Use of beta-hydroxybutyric acid levels in the emergency department. Am J Ther 1998, 5(3):159-163.
16. Zur M., Moccio R.J., Nichols J.H. Evaluation of the [beta]-hydroxybutyrate ketone test on the STAT-Site M analyzer. Point of Care 2008, 7(2):60-63.
17. Palmer J.P. Alcoholic ketoacidosis: clinical and laboratory presentation, pathophysiology and treatment. Clin Endocrinol Metab 1983, 12(2):381-389.
18. Banerji M.A., Chaiken R.L., Huey H., et al. GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetes. Diabetes 1994, 43(6):741-745.
19. Expert panel on the diagnosis, classification of diabetes mellitus Diagnosis and classification of diabetes mellitus. Diabetes Care 2004, 27(Suppl 1):S5-S10.
20. Westphal S.A. The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnosed diabetic adults. Am J Med 1996, 101(1):19-24.
21. Efstathiou S.P., Tsiakou A.G., Tsioulos D.I., et al. A mortality prediction model in diabetic ketoacidosis. Clin Endocrinol 2002, 57(5):595-601.
22. Kitabchi A.E., Umpierrez G.E., Murphy M.B., et al. Management of hyperglycemic crises in patient with diabetes. Diabetes Care 2001, 24(1):131-153.
23. Kitabchi A.E., Umpierrez G.E., Murphy M.B. Diabetic ketoacidosis and hyperglycemic hyperosmolar site. International textbook of diabetes mellitus 2004, 1101-1120. John Wiley & Sons, Chichester (United Kingdom). 3rd edition. R.A. DeFronzo, E. Ferrannini, H. Keen (Eds.).
24. Kitabchi A.E., Rose B.D. Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults 2007, UptoDate, Waltham (MA), Available at:, Accessed January 20, 2012. http://www.uptodate.com/contents/treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults.
25. Fleckman A.M. Diabetic ketoacidosis. Endocrinol Metab Clin North Am 1993, 22(2):181-207.
26. Umpierrez G.E., Khajavi M., Kitabchi A.E. Review: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Am J Med Sci 1996, 311(5):225-233.
27. Umpierrez G.E., Murphy M.B., Kitabchi A.E. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Diabetes Spectrum 2002, 15(1):28-36.
28. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity Consensus development conference on antipsychotic drugs and obesity and diabetes. J Clin Psychiatry 2004, 65(2):267-272.
29. Jin H., Meyer J.M., Jeste D.V. Atypical antipsychotics and glucose dysregulation: a systematic review. Schizophr Res 2004, 71(2-3):195-212.
30. Ucok A., Gaebel W. Side effects of atypical antipsychotics: a brief overview. World Psychiatry 2008, 7(1):58-62.
31. Henderson D.C., Cagliero E., Gray C., et al. Clozapine, diabetes mellitus, weight gain and lipid abnormalities: a five year naturalistic study. Am J Psychiatry 2000, 157(6):975-981.
32. Jin H., Meyer M., Jeste D.V. Phenomenology of and risk factors for new onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases. Ann Clin Psychiatry 2002, 14(1):59-64.
33. Koller E.A., Doraiswamy P.M. Olanzapine associated diabetes mellitus. Pharmacotherapy 2002, 22(7):841-852.
34. Koller E., Schneider B., Bennett K., et al. Clozapine associated diabetes. Am J Med 2001, 111(9):716-723.
35. Koller E., Cross J.T., Doraiswamy P.M., et al. Risperidone associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy 2003, 23(6):735-744.
36. Kibby K.J., Roberts A.M., Nicholson G.C. Diabetic ketoacidosis and elevated serum lipase in the setting of aripiprazole therapy. Diabetes Care 2010, 33(7):e96.
37. Lee P., Greenfield J.R., Campbell L.V. "Mind the gap" when managing ketoacidosis in type I diabetes. Diabetes Care 2008, 31(7):e58.
38. Umpierrez G., Freire A.X. Abdominal pain in patients with hyperglycemic crises. J Crit Care 2002, 17(1):63-67.
39. Warner E.A., Greene G.S., Buchsbaum M.S., et al. Diabetic ketoacidosis associated with cocaine abuse. Arch Intern Med 1998, 158(16):1799-1802.
40. Sreedhar D., Hazeghazam M.H., Li R.N., et al. Serum bicarbonate vs closure of anion gap (AG) in diabetic ketoacidosis (DKA). Crit Care Med 2008, 36(2 Suppl 12):A69.
41. Hazeghazam M.H., Sreedhar D., Li N.R., et al. The importance of correcting anion gap for albumin and evaluation of hyperchloremia in the management of diabetic ketoacidosis. J Diabetes Sci Technol 2010, 4(2):456/A21. [abstract A21], Abstracts of International Hospital Diabetes Meeting, October 8-9, 2010. Available at:, Accessed April 5, 2012. http://www.journalofdst.org/March2011/PDF/Abstract/VOL-5-2-MTG2-IHDM2010-ABSTRACTS.pdf.
42. Mendelsen J.H., Teoh S.K., Mello N.K., et al. Acute effects of cocaine on plasma adrenocorticotropic hormone, luteinizing hormone and prolactin levels in cocaine-dependent men. J Pharmacol Exp Ther 1992, 263(2):505-509.
43. Beesch C.M., Negus B.H., Keffer J.H., et al. Effects of cocaine on cortisol secretions in humans. Am J Med Sci 1995, 310(2):61-64.
44. Gerich J.E., Karam J.H., Fosham P.H. Stimulation of glucagon secretion by epinephrine in man. J Clin Endocrinol Metab 1973, 37(3):479-481.
45. Keller U., Gerber P.P., Stauffacher W. Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans. Am J Physiol 1984, 247(6 Pt 1):E732-E739.
46. Byard R.W., Riches K.J., Kostakis C., et al. Diabetic ketoacidosis-a possible complicating factor in deaths associated with drug overdose: two case reports. Med Sci Law 2006, 46(1):81-84.
47. Gama M.P., de Souza B.V., Ossowski A.C., et al. Diabetic ketoacidosis complicated by the use of ecstasy: a case report. J Med Case Rep 2010, 4(1):240-243.
48. Seymor H.R., Gilmand D., Quin J.D. Severe ketoacidosis complicated by ecstasy and prolonged exercise. Diabet Med 1996, 13(10):908-909.
49. Hartung T.K., Schofield E., Short A.I., et al. Hyponatremic states following 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") ingestion. QJM 2002, 95(7):431-437.
50. Tibaldi J.M., Lorber D.L., Nerenberg A. Diabetic ketoacidosis and insulin resistance with subcutaneous terbutaline infusion: a case report. Am J Obstet Gynecol 1990, 163(2):509-510.
51. Mori S., Ebihara K. A sudden onset of diabetic ketoacidosis and acute pancreatitis after introduction of mizoribine therapy in a patient with rheumatoid arthritis. Mod Rheumatol 2008, 18(6):634-638.
52. Case C.C., Maldonado M. Diabetic ketoacidosis associated with Metabolife: a report of two cases. Diabetes Obes Metab 2002, 4(6):402-406.
53. Astrup A., Toubro S., Cannon S., et al. Thermogenic, metabolic, and cardiovascular effects of a sympathomimetic agent, ephedrine: a double-blind placebo-controlled study. Curr Ther Res 1990, 48(6):1087-1100.
54. Haller C.A., Benowitz N.L. Adverse cardiovascular and central nervous system effects associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000, 343(25):1833-1838.
55. United States General Accounting Office Dietary supplements containing ephedra. health risks and FDA's oversight 2003, US General Accountability Office, Washington, DC, Available at:, Accessed April 4, 2012. http://www.gao.gov/assets/120/110228.pdf.
56. Gwen O.E., Caprio S., Reichard G.A., et al. Ketosis of starvation: a revisit and new perspectives. Clin Endocrinol Metab 1983, 12(2):359-379.
57. Hoffer L.J. Metabolic consequences of starvation. Modern nutrition in health and disease 1999, 645-655. Lippincott Williams & Wilkins, Baltimore (MD). 9th edition. M.E. Shils, J.A. Olson, M. Shike (Eds.).
58. Mahoney C.A. Extreme gestational starvation ketoacidosis: case report and review of pathophysiology. Am J Kidney Dis 1992, 20(3):276-280.
59. Toth H., Greenbaum L. Severe acidosis caused by starvation and stress. Am J Kidney Dis 2003, 42(5):16-19.
60. Burbos N., Shiner A.M., Morris E. Severe metabolic acidosis as a consequence of acute starvation in pregnancy. Arch Gynecol Obstet 2009, 279(3):399-400.
61. Miaskiewicz S., Levey G.S., Owen O. Severe metabolic ketoacidosis induced by starvation and exercise. Am J Med Sci 1989, 297(3):178-180.
62. Owen D., Little S., Leach R., et al. A patient with an unusual aetiology of a severe ketoacidosis. Intensive Care Med 2008, 34(5):971-972.
63. Bartels P.D., Kristensen L.O., Heding L.G., et al. Development of ketonemia in fasting patients with hyperthyroidism. Acta Med Scand 1979, 205(Suppl 624):43-47.
64. Wood E.T., Kinlaw W.B. Nondiabetic ketoacidosis caused by severe hyperthyroidism. Medscape. 2004, Available at:, Accessed September 20, 2011. http://www.medscape.com/viewarticle/488880.
65. Cartwright M.M. Eating disorder emergencies: understanding the complexities of the hospitalized eating disordered patient. Crit Care Nurs Clin North Am 2004, 16(4):515-530.
66. Causso C., Arrieta F., Hernández J., et al. Severe ketoacidosis secondary to starvation in a frutarian patient. Nutr Hosp 2010, 25(6):1049-1052.
67. Freeman J.M., Kossoff E.H. Ketosis and the ketogenic diet, 2010: advances in treating epilepsy and other disorders. Adv Pediatr 2010, 57(1):315-329.
68. Sondike S.B., Copperman N., Jacobson M.S. Effects of a low carbohydrate diet on weight loss and cardiovascular risk factors in overweight adolescents. J Pediatr 2003, 142(3):253-258.
69. Westman E.C., Yancy W.S., Edman J.S., et al. Effect of 6-month adherence to a very low carbohydrate program. Am J Med 2002, 113(1):30-36.
70. Yancy W.S., Olsen M.K., Guyton J.R., et al. A low carbohydrate ketogenic diet versus a low fat diet to treat obesity and hyperlipidemia. Ann Intern Med 2004, 140(10):769-777.
71. Agnew B. Rethinking Atkins. New research suggests that the famous low-carb diet may be safe-at least in the short term. Diabetes Forecast 2004, 57(4):64-66. 68-70.
72. Rollo I. Understanding the implications of adopting the Atkins' diet. Nurs Times 2003, 99(43):20-21.
73. Furth S.L., Casey J.C., Pyzik P.L., et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol 2000, 15(1-2):125-128.
74. Wheless J. The history of the ketogenic diet. Epilepsia 2008, 49(8):3S-5S.
75. Kossoff E.H. More fat and fewer seizures: dietary therapies for epilepsy. Lancet Neurol 2004, 3(7):415-420.
76. Mady M.A., Kossoff E.H., McGregor A.L., et al. The ketogenic diet: adolescents can do it too. Epilepsia 2003, 44(6):847-851.
77. Gasior M., Rogawski M.A., Hartman A.L. Neuroprotective and disease modifying effects of the ketogenic diet. Behav Pharmacol 2006, 17(5-6):431-439.
78. Henderson S.T. Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics 2008, 5(3):470-480.
79. Dillon E.S., Dyer W.W., Smelo L.S. Ketone acidosis in non-diabetic adults. Med Clin North Am 1940, 24:1813-1822.
80. Halperin M.L., Hammeke M., Josse R.G., et al. Metabolic acidosis in the alcoholic: a pathophysiologic approach. Metabolism 1983, 32(3):308-315.
81. McGuire L.C., Cruickshank A.M., Munro P.T. Alcoholic ketoacidosis. Emerg Med J 2006, 23(6):417-420.
82. Shull P.D., Rapoport J. Life-threatening reversible acidosis caused by alcohol abuse. Nat Rev Nephrol 2010, 6(9):555-559.
83. Umpierrez G.E., DiGirolamo M., Tulvin J.A., et al. Differences in metabolic and hormonal milieu in diabetic and alcohol induced ketoacidosis. J Crit Care 2000, 15(2):52-59.
84. Wrenn K.D., Slovis C.M., Minion G.E., et al. The syndrome of alcoholic ketoacidosis. Am J Med 1991, 91(2):119-128.
85. Cooperman M.T., Davidoff F., Spark R., et al. Clinical studies of alcoholic ketoacidosis. Diabetes 1974, 23(5):433-439.
86. Levy L.J., Duga J., Girgis M., et al. Ketoacidosis in association with alcoholism in nondiabetic subjects. Ann Intern Med 1973, 78(2):213-219.
87. Cuevas-Korensky C.E., Kruse J.A., Carlson R.W. Characteristic findings in patients with alcoholic ketoacidosis. Chest 1991, 100(Suppl 2):81S.
88. Weissman C. The metabolic response to stress: an overview and update. Anesthesiology 1990, 73(2):308-327.
89. Kraut J.A., Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis and management. Clin J Am Soc Nephrol 2008, 3(1):208-225.
90. Reuler J.B., Poorman J. Anion and osmolal gaps in a patient with alcoholism. West J Med 1993, 158(2):191-194.
91. Elisaf M., Merkouropoulos M., Tsianos E.V., et al. Acid-base and electrolyte abnormalities in alcoholic patients. Miner Electrolyte Metab 1994, 20(5):274-281.
92. Kamel K.S., Gowrishankar M., Gougoux A., et al. Metabolic acidosis in the alcoholic: an emphasis on intracellular events. Endocrinologist 1995, 5(4):278-285.
93. Thomasen J.L., Simonsen K.W., Felby S., et al. A prospective toxicology analysis in alcoholics. Forensic Sci Int 1997, 90(1-2):33-40.
94. Yanagawa Y., Sakamoto T., Okada Y. Six cases of sudden cardiac arrest in alcoholic ketoacidosis. Intern Med 2008, 47(2):113-117.
95. Brinkman B., Fechner B., Karger B., et al. Ketoacidosis and lactic acidosis-frequent causes of death in alcoholics. Int J Legal Med 1998, 111(3):115-119.
96. Kadiš P., Balažic J., Ferlan-Marolt V. Alcoholic ketoacidosis: a cause of sudden death in chronic alcoholics. Forensic Sci Int 1999, 103:S53-S59.
97. Pounder D.J., Stevenson R.J., Taylor K.K. Alcoholic ketoacidosis at autopsy. J Forensic Sci 1998, 43(4):812-816.
98. Thomsen J., Felby S., Theilade P., et al. Alcoholic ketoacidosis as a cause of death in forensic cases. Forensic Sci Int 1995, 75(2-3):163-170.
99. Yalamanchili S., Rempe S., Puri N., et al. Profound, reversible myopathy with severe hypophosphatemia in a patient with diabetic ketoacidosis. Resid Staff Physician 2005, 51(6):35-38.
100. Bronstein A.C., Spyker D.A., Cantilena L.R., et al. 2010 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 28th annual report. Clin Toxicol 2011, 49(10):910-941.
101. Lewin G.A., Oppenheimer P.R., Wingert W.A. Coma from alcohol sponging. J Am Coll Emerg Physicians 1977, 6(4):165-167.
102. Lehman A.J., Chase H.F. The acute and chronic toxicity of isopropyl alcohol. J Lab Clin Med 1944, 29:561-567.
103. Lacouture P.G., Wason S., Abrams A., et al. Acute isopropyl alcohol intoxication: diagnosis and management. Am J Med 1983, 75(4):680-686.
104. Kulig K., Duffy J.P., Linden C.H., et al. Toxic effects of methanol, ethylene glycol and isopropyl alcohol. Top Emerg Med 1984, 6(2):14-28.
105. Fuller H.C., Hunter O.B. Isopropyl alcohol. J Lab Clin Med 1927, 12:326-349.
106. Bronstein A.C., Spyker D.A., Cantilina L.R., et al. American Association of Poison Control Centers. NPDS annual reports. Clin Toxicol 2007, 45(8):815-917.
107. Doyon S., Welsh C. Intoxication of a prison inmate with an ethyl alcohol-based hand sanitizer. N Engl J Med 2007, 356(5):529-530.
108. Thanarajasingam G., Diedrich D.A., Mueller P.S. Intentional ingestion of ethanol-based hand sanitizer by a hospitalized patient with alcoholism. Mayo Clin Proc 2007, 82(10):1288-1289.
109. Emadi A., Coberly L. Intoxication of a hospitalized patient with isopropanol based hand sanitizer. N Engl J Med 2007, 356(5):530-531.
110. Vujasinovic M., Kocar M., Kramer K., et al. Poisoning with 1-propanol and 2-propanol. Hum Exp Toxicol 2007, 26(12):975-978.
111. Jammalamadaka D., Faissi R. Ethylene glycol, methanol and isopropyl alcohol intoxication. Am J Med Sci 2010, 339(3):276-281.
112. Zaman F., Pervez A., Abreo K. Isopropyl alcohol intoxication: a diagnostic challenge. Am J Kidney Dis 2002, 40(3):E12.
113. Chan K.M., Wong E.T., Matthews W.S. Severe isopropanolemia without acetonemia or clinical manifestations of isopropanol intoxication. Clin Chem 1993, 39(9):1922-1925.
114. Hayden S.R., Kallus L., McCuskey C.F. Aldehydes, ketones, ethers and esters. Emergency toxicology 1998, 292. Lippincott-Raven, Philadelphia. 2nd edition. P. Viccellio (Ed.).
115. Gamis A.S., Wasserman G.S. Acute acetone intoxication in a pediatric patient. Pediatr Emerg Care 1988, 4(1):24-26.
116. Gitelson S., Werozberger A., Herman J.B. Coma and hyperglycemia following drinking of acetone. Diabetes 1966, 15(11):810-811.
117. Sivlott M.L. Methanol, ethylene glycol and other toxic alcohols. Other toxic alcohols. Haddad & Winchester's clinical management of poisoning and drug overdose 2007, 625. WB Saunders, Philadelphia. 4th edition. M.W. Shannon, S.W. Borron, M.J. Burns (Eds.).
118. Rainsford K.D. History and the development of the salicylates. Aspirin and related drugs 2004, 1-5. Taylor & Francis, London. K.D. Rainsford (Ed.).
119. Rodnan G.P., Benedek T.G. Early history of antirheumatic drugs. Arthritis Rheum 1970, 13(2):145-165.
120. Haas H. History of antipyretic analgesic therapy. Am J Med 1983, 75(5A):1-3.
121. Waseem M., Aslam M., Gernsheimer J. Salicylate toxicity. Medscape 2011 2011, WebMD, New York, Available at:, Accessed November 16, 2011. http://emedicine.medscape.com/article/1009987-overview.
122. Durnas C., Cusack B.J. Salicylate intoxication in the elderly. Recognition and recommendations on how to prevent it. Drugs Aging 1992, 2(1):20-34.
123. Litovitz T.L., Smikstein L., Felberg L., et al. 1996 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1997, 15(5):447-500.
124. Burke A., Smyth E., FitzGerald G.A. Analgesic-antipyretic agents; pharmacotherapy of gout. Goodman and Gillman's pharmacologic basis of therapeutics 2006, 689. McGraw-Hill, New York. 12th edition. L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds.).
125. Krenzelok E.P., Kerr F., Proudfoot A. Salicylate toxicity. Clinical management of poisoning and drug overdose 1998, 675-687. WB Sanders, Philadelphia. 3rd edition. L.M. Haddad, M.W. Shannon, J.F. Winchester (Eds.).
126. Abramson S.B., Howard R. Aspirin: mechanism of action, major toxicities and use in rheumatic diseases 2012, UptoDate, Waltham (MA), Available at:, Accessed January 30, 2012. http://www.uptodate.com/contents/aspirin-mechanism-of-action-major-toxicities-and-use-in-rheumatic-diseases.
127. Miyahara J.T., Karler R. Effect of salicylate on oxidative phosphorylation and respiration of mitochondrial fragments. Biochem J 1965, 97(1):194-198.
128. Bartels P.D., Lund-Jacobsen H. Blood lactate and ketone body concentrations in salicylate intoxication. Hum Toxicol 1986, 5(6):363-366.
129. Gabow P.A., Anderson R.J., Potts D.E., et al. Acid-base disturbances in the salicylate poisoning in adults. Arch Intern Med 1978, 138(10):1481-1484.
130. Togo K., Suzuki Y., Yoshimaru T., et al. Aspirin and salicylates modulate IgE-mediated leukotriene secretion in mast cells through a dihydropyridine receptor-mediated Ca2+ influx. Clin Immunol 2009, 131(1):146-156.
131. Lapenna D., Ciofani G., Pierdomenico S.D., et al. Inhibitory activity of salicylic acid on lipoxygenase-dependent lipid peroxidation. Biochim Biophys Acta 2009, 1790(1):25-30.
132. Buchanan M.R., Butt R.W., Hirsh J., et al. Role of lipoxygenase metabolism in platelet function: effect of aspirin and salicylate. Prostaglandins Leukot Med 1986, 21(2):157-168.
133. Tremoli E., Maderna P., Eynard A., et al. In vitro effects of aspirin and non steroidal anti-inflammatory drugs on the formation of 12-hydroxyeicosatetraenoic acid by platelets. Prostaglandins Leukot Med 1986, 23(2-3):117-122.
134. Cerletti C. Interaction of non-steroidal anti-inflammatory drugs on platelet cyclo-oxygenase and lipoxygenase activity. Int J Tissue React 1985, 7(4):309-312.
135. Jung T.T., Hwang A.L., Miller S.K., et al. Effect of leukotriene inhibitor on cochlear blood flow in salicylate ototoxicity. Acta Otolaryngol 1995, 115(2):251-254.
136. Hormaechea E., Carlson R.W., Rogove H., et al. Hypovolemia, pulmonary edema and protein changes in severe salicylate poisoning. Am J Med 1979, 66(6):1046-1050.
137. Done A.K. Salicylate intoxication: significance of measurements of salicylate in blood in cases of acute ingestion. Pediatrics 1960, 26(5):800-807.
138. Krenzelok E.P., Kerr F., Proudfoot A.T. Salicylate toxicity. Clinical management of poisoning and drug overdose 1998, 682. WB Saunders, Philadelphia. 3rd edition. L.M. Haddad, M.W. Shannon, J.F. Winchester (Eds.).
139. Dugandzic R.M., Tierney M.G., Dickinson G.E., et al. Evaluation of the validity of the Done nomogram in the management of acute salicylate intoxication. Ann Emerg Med 1989, 18(11):1186-1190.
140. Flomenbaum N.E. Salicylates. Goldfrank's toxicologic emergencies 2006, 550-564. McGraw-Hill, New York. 8th edition. N.E. Flomenbaum, L.R. Goldfrank, R.S. Hoffman (Eds.).
141. Boyer E.W. Aspirin poisoning in adults 2011, UptoDate, Waltham (MA), Available at:, Accessed January 13, 2012. http://www.uptodate.com/contents/aspirin-poisoning-in-adults%3Fsource=search_result%26search=boyer+aspirin+poisoning+in+adults%26selectedTitle=1%7E52.
142. O'Malley G.F. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am 2007, 25(2):333-346.
143. Hoffman R.J., Nelson L.S., Hoffman R.S. Use of ferric chloride to detect salicylate-containing poisons. J Toxicol Clin Toxicol 2002, 40(5):547-549.
144. Dargan P.I., Wallace C.I., Jones A.L. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J 2002, 19(3):206-209.
145. Shannon M.W. Isoniazid. Clinical management of poisoning and drug overdose 1998, 721. WB Saunders, Philadelphia. 3rd edition. M.W. Shannon, J.F. Winchester (Eds.).
146. Alvarez F.G., Guntupalli K.K. Isoniazid overdose: four case reports and a review of the literature. Intensive Care Med 1995, 21(8):641-644.
147. Romero J.A., Kuczler F.J. Isoniazid overdose: recognition and management. Am Fam Physician 1998, 57(4):749-752.
148. Temmerman W., Dhondt A., Vandewoude K. Acute isoniazid intoxication: seizures, acidosis and coma. Acta Clin Belg 1999, 54(4):211-216.
149. Cameron W.M. Isoniazid overdose. Can Med Assoc J 1978, 2(6145):127-128.
150. Kingston R.L., Saxena K. Management of acute isoniazid overdosages. Clinical Toxicology Consultant 1980, 2(2):37-44.
151. Sullivan E.A., Geoffroy P., Weisman R., et al. Isoniazid poisonings in New York City. J Emerg Med 1998, 16(1):57-59.
152. Orlowski J.P., Paganini E.P., Pippenger C.E. Treatment of a potentially lethal dose of isoniazid ingestion. Ann Emerg Med 1988, 17(1):73-76.
153. Kelso T., Toll H.W., Pinkerton D.C., et al. Death due to intentional overdose of isoniazid. A case report. J Forensic Sci 1965, 10(3):313-318.
154. Bear E.S., Hoffman P.F., Siegel S.R., et al. Suicidal ingestion of isoniazid. An uncommon cause of metabolic acidosis and seizures. Southampt Med J 1976, 69(1):31-32.
155. Pahl M.V., Vaziri N.D., Ness R., et al. Association of beta-hydroxybutyric acidosis with isoniazid intoxication. Clin Toxicol 1984, 22(2):167-176.
156. Sass J.O. Inborn errors of ketogenesis and ketone body utilization. J Inherit Metab Dis 2012, 35(1):23-28.
157. Fukao T. Succinyl-CoA: 3-keotacid CoA transferase (SCOT) deficiency. Orphanet encyclopedia 2006, Orphanet, Available at:, Accessed December 20, 2011. http://www.orpha.net/data/patho/GB/uk-scot.pdf.
158. Middleton B., Day R., Lombes A., et al. Infantile ketoacidosis associated with decreased activity of succinyl-CoA: 3-ketoacid CoA-transferase. J Inherit Metab Dis 1987, 10(Suppl 2):273s-275s.
159. Niezen-Koning K.E., Wanders R.J.A., Ruiter J.P.N., et al. Succinyl-CoA: acetoacetate transferase deficiency: identification of a new patient with a neonatal onset and review of the literature. Eur J Pediatr 1997, 156(11):870-873.
160. Fukao T., Song X.Q., Mitchell G.A., et al. Enzymes of ketone body utilization in human tissues: protein and mRNA levels of succinyl-coenzyme A (CoA): 3-ketoacid CoA transferase and mitochondrial and cytosolic acetoacetyl-CoA thiolases. Pediatr Res 1997, 42(4):498-502.
161. Fukao T., Sass J.O., Kursula P., et al. Clinical and molecular characterization of five patients with succinyl-Co A: 3-ketoacid CoA transferase (SCOT) deficiency. Biochim Biophys Acta 2011, 1812(5):619-624.
162. Mitchell G.A., Fukao T. Inborn errors of ketone body catabolism. Metabolic and molecular bases of inherited disease 2001, 2327-2356. McGraw-Hill, New York. 8th edition. C.R. Scriver, A.L. Beaudet, W.S. Sly (Eds.).
163. Sarafoglou K., Matern D., Redlinger-Grosse K., et al. Siblings with mitochondrial acetoacetyl-CoA thiolase deficiency not identified by newborn screening. Pediatrics 2011, 128(1):e246-e250.
164. Sovik O. Mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency: an inborn error of isoleucine and ketone body metabolism. J Inherit Metab Dis 1993, 16(1):46-54.
165. Thummler S., Dupont D., Acquaviva C., et al. Different clinical presentation in siblings with mitochondrial acetoacetyl-Co A thiolase deficiency and identification of two novel mutations. Tohoku J Exp Med 2010, 220(1):27-31.
166. Saudubray J.M., Specola N., Middleton B., et al. Hyperketotic states due to inherited defects of ketolysis. Enzyme 1987, 38(1):80-90.
167. Ansstas G., Robinson I., Rubinchick S., et al. Alcoholic ketoacidosis. Medscape 2011, Available at:, Accessed July 25, 2011. http://emedicine.medscape.com/article/116820-overview.