1. A 23 Year Old Woman who Presents with New Onset SE Brandon Wills, DO, MS Fellow, Clinical Toxicology Toxikon Consortium of Cook County Clinical Instructor in Emergency Medicine University of Illinois at Chicago

2. Brandon Wills, DO, MS Case Presentation 23 year-old female presents to the ED with generalized seizures x 3 Pt. found by family member initially somnolent

3. Brandon Wills, DO, MS Past Medical History & Social History No details available (initially)

4. Brandon Wills, DO, MS Physical Exam VS: AF; 90/50; 116; 24; 97% on NRM Pt. having repeated brief generalized seizures with intermittent recovery HEENT- pupils 5mm, reactive CV- Tachy, no M/G/R Lungs- CTAB Skin- Warm, pink, dry

5. Your Differential Diagnosis?

6. Brandon Wills, DO, MS Differential Diagnosis Neurologic Infectious etiologies Metabolic Endocrine Toxicologic

7. Brandon Wills, DO, MS ED Course What would be your initial management?

8. Brandon Wills, DO, MS ED Course What would be your initial management? IV, O2, Monitor IV ativan Bedside glucose Send laboratory studies CT head?

9. Brandon Wills, DO, MS ED Course Pt. given several doses of IV ativan without improvement Pt. was then intubated, sedated with propofol

10. Brandon Wills, DO, MS Lab Results EKG: Sinus tach, narrow complex HCO3- 10 Anion gap- 25 ABG- 6.99/28/172/7 WBC- 25.4 Chemistry = wnl Utox- nl ASA/APAP- negative LFT’s- nl

11. Brandon Wills, DO, MS ED Course We Want More History No history of seizure disorder No history of trauma Family members arrive with an empty bottle of INH

12. Brandon Wills, DO, MS What would be your next step in this patient ’ s management? ED Course

13. Brandon Wills, DO, MS Isonicontinic Acid Hydrazide INH Structurally similar to Pyridoxine (B6) NAD Nicotinic acid (Niacin)

14. Brandon Wills, DO, MS Isonicontinic Acid Hydrazide INH Pyridoxine (Vitamin B6) INH Nicotinic Acid (Niacin)

15. Brandon Wills, DO, MS Isonicontinic Acid Hydrazide INH Gyromitra speciesRocket fuel Structurally Similar Toxins Monomethylhydrazine

16. Brandon Wills, DO, MS Hydrazine Epidemiology 1 INH 426- Exposures 58-Minor 70-Moderate 80-Major 1-Deaths Gyromitra Species 44-Exposures 13- Minor 10- Moderate 0-Major 0-Deaths 1. AAPCC 2001 TESS Data

17. Brandon Wills, DO, MS Pathophysiology

18. INH Toxicokinetics Therapeutic dose:5-15 mg/kg Toxic dose:>20 mg/kg significant toxicity >40 mg/kg Peak [ ]:2 hours Elimination T1/2:70-180 minutes

19. Brandon Wills, DO, MS Clinical Manifestations Triad: 1. Refractory seizures 2. Severe metabolic acidosis 3. Coma

20. Brandon Wills, DO, MS Clinical Manifestations Early: May mimic anticholinergic toxidrome (N/V, tachycardia, ataxia, mydriasis, CNS dep.) Late: Seizures, acidosis Chronic: Hepatotoxicity

21. Brandon Wills, DO, MS Lab Studies Chemistries Lactate EKG Hepatic enzymes +/- INH levels

22. Brandon Wills, DO, MS Treatment of Toxicity 1.A,B,C’s 2.Initial resuscitation and supportive care 3.Decontamination - Lavage? - Whole bowel irrigation? - Activated charcoal? 4.Enhanced elimination 5.Antidotes

23. Brandon Wills, DO, MS Treatment of Toxicity 1. A,B,C’s

24. Brandon Wills, DO, MS Treatment of Toxicity 2. Initial resuscitation and supportive care IV Fluids Benzodiazepines +/- Sodium bicarb

25. Brandon Wills, DO, MS Treatment of Toxicity 3. Decontamination - Lavage? - Whole bowel irrigation? - Activated charcoal?

26. Brandon Wills, DO, MS Treatment of Toxicity 4. Enhanced elimination Hemodialysis?

27. Brandon Wills, DO, MS Treatment of Toxicity 5. Antidotes Pyridoxine (B6)

28. Brandon Wills, DO, MS Case Course Toxikon is a Medical Toxicology Consortium Including Cook County Hospital, The University of Illinois Hospital, and Rush Presbyterian St. Luke's Medical Center The Toxikon Consortium

29. Brandon Wills, DO, MS Case Course Recommended IV pyridoxine Pharmacy unable to mobilize B6 Contacted Rush antidote depot for courier Pt. given 5g IV

30. Brandon Wills, DO, MS Case Course Seizure activity terminated Repeat ABG: 7.31/34/503/17 Pt. extubated the following day Transferred to psych facility on hospital day 3

31. Brandon Wills, DO, MS Teaching Points Consider INH toxicity with patients presenting with refractory seizures

32. Brandon Wills, DO, MS Teaching Points Remember to treat the patient, not the poison (A,B,C’s)

33. Brandon Wills, DO, MS Teaching Points Gyromitra species are another source of hydrazine

34. Brandon Wills, DO, MS Teaching Points What is the antidote for INH-induced seizures? Pyridoxine (B6) Dosing- gram (INH ingested):gram (B6) Unknown ingestions, start with 5 grams IV IV pyridoxine supplies are often limited PO B6 may be crushed and given NG

35. Questions???