1. Approach to Alcohol Ingestions Catherine Mobley Preissig, MD Pediatric Critical Care Medicine April 25, 2007

2. “A couple of suggestions for the lecture. Our group really likes stories. So telling the story about the guy that went blind with methanol in the 50’s would be good, finding out trivia like which alcohols give you erectile dysfunction or make you glow in the dark would go a long way…” “A couple of suggestions for the lecture. Our group really likes stories. So telling the story about the guy that went blind with methanol in the 50’s would be good, finding out trivia like which alcohols give you erectile dysfunction or make you glow in the dark would go a long way…” KP KP

3. For Kalpesh: Causes of ED Ethanol Ethanol High blood pressure High blood pressure High cholesterol High cholesterol Heart disease Heart disease Diabetes Diabetes Spinal injury/ surgery Spinal injury/ surgery Stress Stress Smoking Smoking Certain drugs (Ca-channel blockers, etc) Certain drugs (Ca-channel blockers, etc)

4. Epidemiology Pediatric poisonings: 4 million cases/yr Pediatric poisonings: 4 million cases/yr 300,000 lead to hospitalization 300,000 lead to hospitalization 30,000 lead to death 30,000 lead to death 1 million in children < 6 yo 1 million in children < 6 yo 2003 TESS database: 84,000 were toxic alcohol exposures 2003 TESS database: 84,000 were toxic alcohol exposures

5. Volatile alcohols Ethanol Ethanol Methanol Methanol Isopropanol Isopropanol Ethylene glycol Ethylene glycol

6. What do they have in common? Readily found in household products Readily found in household products Rapidly absorbed from GI tract Rapidly absorbed from GI tract –Signs of intoxication within 30 minutes! All taste pretty good! All taste pretty good!

7. Life-threatening symptoms caused by toxic breakdown products Life-threatening symptoms caused by toxic breakdown products Broken down by alchohol dehydrogenase Broken down by alchohol dehydrogenase Have many symptoms in common Have many symptoms in common –Very wide-ranging

8. When to suspect alcohol ingestions???

9. In any ingestion work-up!!!

10. Specifically… CNS depression CNS depression Nausea/ vomiting Nausea/ vomiting Seizures Seizures Coma Coma

11. Hypotension, shock Hypotension, shock Hypoglycemia Hypoglycemia High anion gap High anion gap High osmolal gap!!! High osmolal gap!!!

12. Anion gap review- yep you know it! Na – (Cl + HCO3) Na – (Cl + HCO3) Should be 8-16 Should be 8-16 MUDPILES MUDPILES

13. Methanol Methanol Uremia Uremia DKA DKA Pb Pb Iron, Inhalants, Isoniazid, Ibuprofen Iron, Inhalants, Isoniazid, Ibuprofen Lactic acidosis Lactic acidosis Ethylene glycol, Ethanol Ethylene glycol, Ethanol Salicylates, Solvents Salicylates, Solvents

14. Osmolal gap review Measured osmolality – calculated osmolality Measured osmolality – calculated osmolality

15. Normal osmolality is 275-295 Normal osmolality is 275-295 Gap should be <10 Gap should be <10 If it’s higher, then something else is there! If it’s higher, then something else is there!

16. Measured osmolality?? Measured osmolality?? That’s what the lab gives you!!

17. Calculated osmolality?? Calculated osmolality?? 2xNa + Glucose/18 + BUN/2.8

18. For Example…. Lab reports serum osm = 315 Lab reports serum osm = 315 You calculate based on Na, Gluc, BUN and get 280 You calculate based on Na, Gluc, BUN and get 280 Gap is 315-280 = 35 Gap is 315-280 = 35 Something else is contributing!! Something else is contributing!! –And you need to find it!!

19. Specific alcohols Preparations Preparations Clinical presentation Clinical presentation Work-up Work-up Treatment Treatment Disposition Disposition

20. Ethanol (yeh, the good stuff) Ethanol (yeh, the good stuff)

21. Other preparations Mouthwash preparations Mouthwash preparations –20 oz can lead to death in toddler Perfumes Perfumes Medicinal products Medicinal products

23. Clinical presentation Hypoglycemia Hypoglycemia Hypomagnesemia Hypomagnesemia AMS/ Seizures AMS/ Seizures Ataxia Ataxia Hypothermia Hypothermia Loss of airway reflexes Loss of airway reflexes

24. Work-up In addition to tox screen and ETOH levels... In addition to tox screen and ETOH levels... Follow elecs, Mg, phos, LFTs, glucose Follow elecs, Mg, phos, LFTs, glucose Calculate AG (high) Calculate AG (high) Calculate osm gap (high) Calculate osm gap (high) Consider CT head if AMS in excess of ETOH level Consider CT head if AMS in excess of ETOH level

25. –Levels 100-150mg/dl = intoxication –50mg/dl symptoms in toddlers

26. Treatment ABCs ABCs Supportive care Supportive care Glucose Glucose Thiamine Thiamine Correct dehydration/ Elec disturbances Correct dehydration/ Elec disturbances Narcan/ Flumazenil controversial Narcan/ Flumazenil controversial Folate, Mg in chronics- Folate, Mg in chronics- –adult world revisited

27. Benzos for seizures Benzos for seizures Keep em warm Keep em warm No place for gastric lavage or charcoal No place for gastric lavage or charcoal

28. Disposition Average observation for uncomplicated toxicity = 5 hours Average observation for uncomplicated toxicity = 5 hours Can delay identification of traumatic injury- be careful Can delay identification of traumatic injury- be careful Can be discharged when ambulatory Can be discharged when ambulatory Rarely needs ICU Rarely needs ICU Defer to admission for social reasons Defer to admission for social reasons

29. Isopropanol Isopropanol

30. Preparations Rubbing alcohol (70-90% concentration) Rubbing alcohol (70-90% concentration) Industrial solvents Industrial solvents Paints/ Paint thinners Paints/ Paint thinners Inks Inks Hair tonics Hair tonics

31. Beware of: Beware of: –Parents sponge-bathing febrile child with rubbing alcohol –Inhalation exposure –Overzealous application to umbilical stump

32. Clinical presentation Fruity odor Fruity odor CNS depression predominates CNS depression predominates Seizures/ Absent reflexes Seizures/ Absent reflexes Acetone is culprit- 2.7x more depression than ETOH Acetone is culprit- 2.7x more depression than ETOH Hypoventilation Hypoventilation

33. Hypotension Hypotension Noncardiogenic pulmonary edema Noncardiogenic pulmonary edema Gastritis Gastritis GI hemorrhage GI hemorrhage Hemorrhagic tracheobronchitis Hemorrhagic tracheobronchitis

34. Work-up Tox screen and ACETONE levels... Tox screen and ACETONE levels... Isopropanol levels unhelpful Isopropanol levels unhelpful Follow elecs, LFTs, glucose Follow elecs, LFTs, glucose Calculate AG- It will be normal Calculate AG- It will be normal Calculate osm gap (high) Calculate osm gap (high) Urine ketones Urine ketones

35. Treatment ABCs ABCs Fluids Fluids Keep em warm Keep em warm Dextrose Dextrose Supportive- similar to ETOH intox Supportive- similar to ETOH intox Rarely need HD- but can if not improving Rarely need HD- but can if not improving Lavage and charcoal not helpful Lavage and charcoal not helpful

36. Disposition Depends on depth of CNS depression Depends on depth of CNS depression Observe mild intox for 3-4 hrs Observe mild intox for 3-4 hrs Can be discharged to appropriate place when ambulatory Can be discharged to appropriate place when ambulatory Everyone else should be hospitalized 12-24 hrs Everyone else should be hospitalized 12-24 hrs PICU if unstable or GI complication PICU if unstable or GI complication

37. Methanol Methanol

38. Preparations Windshield washer fluid Windshield washer fluid Carburetor cleaners Carburetor cleaners Antifreeze Antifreeze Sterno Sterno Paints and varnishes Paints and varnishes Fuel octane boosters Fuel octane boosters Industrial solvents Industrial solvents

40. Formate causes toxic effects Formate causes toxic effects Responsible for increased AG Responsible for increased AG Formaldehyde rapidly metabolized Formaldehyde rapidly metabolized Formate inhibits cytochrome aa 3  anaerobic metabolism Formate inhibits cytochrome aa 3  anaerobic metabolism

41. Clinical presentation CNS disturbance CNS disturbance Electrolyte disturbances Electrolyte disturbances Hypoxic changes to cerebrum and distal optic nerve vasculature  Hypoxic changes to cerebrum and distal optic nerve vasculature  Optic disk hyperemia and blindness Optic disk hyperemia and blindness

42. Ethylene glycol Ethylene glycol

44. Preparations Radiator antifreeze Radiator antifreeze Hydraulic brake fluid Hydraulic brake fluid Condensers/ heat exchangers Condensers/ heat exchangers Foam stabilizers Foam stabilizers Solvents Solvents De-icing solutions De-icing solutions Paints Paints Lacquers Lacquers Cosmetics Cosmetics

45. Glycolate causes high AG, but isn’t toxic Glycolate causes high AG, but isn’t toxic Glycolaldehyde and glyoxylate more toxic Glycolaldehyde and glyoxylate more toxic Glyoxylate Oxalate- tissue deposition Glyoxylate Oxalate- tissue deposition

46. Clinical presentation CNS- cerebral edema, loss of Purkinje cells CNS- cerebral edema, loss of Purkinje cells Lung- edema, interstitial pneumonitis, hemorrhagic bronchopneumonia Lung- edema, interstitial pneumonitis, hemorrhagic bronchopneumonia Kidney- interstitial deposition, proximal and distal tubular dilitation Kidney- interstitial deposition, proximal and distal tubular dilitation Other- liver, heart... Other- liver, heart...

47. AMS, seizures, herniation syndromes AMS, seizures, herniation syndromes Hypertension Hypertension Pulmonary edema Pulmonary edema Acute renal failure, Ca oxalate crystalluria Acute renal failure, Ca oxalate crystalluria

48. Work-up for Ethylene glycol and Methanol Tox screen, ethylene glycol and methanol levels by gas chromatography Tox screen, ethylene glycol and methanol levels by gas chromatography Elecs, LFTs, glucose, Ca Elecs, LFTs, glucose, Ca Calculate AG (high) Calculate AG (high) Calculate osm gap (high) Calculate osm gap (high)

49. UA shows Ca oxylate crystals in ethylene glycol toxicity UA shows Ca oxylate crystals in ethylene glycol toxicity Fun with Woods lamp Fun with Woods lamp Level of 20mg/dL for either substance is toxic, even without acidosis Level of 20mg/dL for either substance is toxic, even without acidosis

50. Note on tox screens Toxic alcohol screen measures ETOH, isopropanol, and methanol Toxic alcohol screen measures ETOH, isopropanol, and methanol Must specifically request ethylene glycol Must specifically request ethylene glycol Tests measure only parent alcohols Tests measure only parent alcohols So level <20mg/dL in face of increased AG indicates toxicity So level <20mg/dL in face of increased AG indicates toxicity

51. Propylene glycol, glycerol, and beta- hydroxybutyrate cause false-positive ethylene glycol Propylene glycol, glycerol, and beta- hydroxybutyrate cause false-positive ethylene glycol

52. Treatment ABCs ABCs Monitor for increased ICP, especially in ethylene glycol Monitor for increased ICP, especially in ethylene glycol Fluids, glucose Fluids, glucose Na Bicarb only in life-threatening acidemia Na Bicarb only in life-threatening acidemia Benzos for seizures Benzos for seizures Calcium for symptomatic hypocalcemia Calcium for symptomatic hypocalcemia

53. Ethanol: Load 0.8grams/kg 100% ETOH Ethanol: Load 0.8grams/kg 100% ETOH –130mg/kg/hr gtt of 100% ETOH diluted in 10% dextrose Monitor hourly until steady state acheived Monitor hourly until steady state acheived Goal level 100-150mg/dL Goal level 100-150mg/dL

54. Alcohol dehydrogenase inhibitors Fomepizole: load with 15mg/kg Fomepizole: load with 15mg/kg –Maintainence: 10mg/kg q 12hrs x 4 doses, then 15mg/kg q 12 Treat until levels <20 and acidosis resolved Treat until levels <20 and acidosis resolved

55. Disposition Admit for unstable vital signs Admit for unstable vital signs Levels >20 Levels >20 Acidosis Acidosis Clinical manifestations of end-organ damage Clinical manifestations of end-organ damage Most require ICU management Most require ICU management

56. So which alcohol is it???

57. 3 simple rules... Anion Gap Anion Gap Ketosis Ketosis Calcium Calcium

58. Look at Anion Gap 3 of 4 have increased AG, so memorize the one that doesn’t! 3 of 4 have increased AG, so memorize the one that doesn’t!Isopropanol!! Hallmark is normal AG

59. Anion Gap KetosisHypocalcemia Ethanol Methanol IsopropylAlcohol EthlyleneGlycol

60. Look at Ketosis A little harder… 2 of 4 have it… A little harder… 2 of 4 have it… Ethanol and Isopropanol: Ketotic Methanol and Ethylene Glycol: Nonketotic

61. Anion Gap KetosisHypocalcemia Ethanol Methanol IsopropylAlcohol EthlyleneGlycol

62. One more trick… Calcium Hallmark of Ethylene Glycol: Hallmark of Ethylene Glycol:Hypocalcemia!!

63. Anion Gap KetosisHypocalcemia Ethanol Methanol IsopropylAlcohol EthlyleneGlycol

64. So… High AG, nonketotic, hypocalcemic? High AG, nonketotic, hypocalcemic?

65. Ethylene Glycol

66. Normal AG, ketotic? Normal AG, ketotic?

67. Isopropanol

68. High AG, nonketotic? High AG, nonketotic?

69. Methanol

70. I drank lots of beer? I drank lots of beer?

71. Ethanol

72. Why do we care?

73. Because treatment is different!! Methanol and Ethylene Glycol Methanol and Ethylene Glycol Fomepizole is antidote!! Fomepizole is antidote!! So recognize it quickly!!! So recognize it quickly!!!

74. ??Questions??