Drug induced Metabolic & Electrolytes Problem

1. Drug induced Metabolic & Electrolytes Problem YC Chan

2. Why is it important? • Common problems in AED practice • Within our ability to manage • Pitfalls in “drug induced” • Recognition • Management

3. Metabolic Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis Electrolytes Sodium Potassium Calcium Magnesium Simple Stuffs - You all know this !

4. Electrolytes • Too much or too little • Absolute changes Vs Shift between compartments • Symptoms • Absolute value • Rapidity of the change

5. Electrolytes Problem in Poisoning • Expected • Therapeutic effect • Common side effect • Uncommon but well recognized side effect • Unexpected • Case reports • ? Association ? Causation

6. Electrolytes Problem in poisoning Na, K, Ca, Mg • Common • ↓ Na, ↓ K, ↑ K • Less common • ↓ Ca, ↓ Mg • Rare • ↑ Na, ↑ Ca, ↑ Mg

7. Hyponatremia

8. Pitfalls • Known psychiatric history on treatment, change of medications recently, worsening of psychiatric symptoms, admitting to PYNEH • After party, confused, triage +ve MDMA, admitting to observation ward • Known epilepsy, breakthrough seizure, admitting to observation ward • Known DM on OHA, hypoglycemic attack presented with convulsion, given valium and D50, waiting medical bed

9. Madhusoodanan. Hyponatremia associated with psychotropic medications Adv Drug React Toxicol Rev 2002: 21 (1-2): 17-29

10. Psychiatric drugs - hyponatremia • SSRI • Incidence • <1% - 39% • Wilkinson TJ. Br J Clin Pharmacol. 1999;47:211-217 • Strachan J. Aust N Z J Psychiatry. 1998;32:295-298 • Fabian TJ. Arch Intern Med. 2004;164:327-332 • Kirby D. Int J Geriatr Psychiatry 2002;17:231-7 • Likely in the first 2-3 weeks • Mean/Median 9 days (range 1-14 days) • Fabian TJ. Arch Intern Med. 2004;164:327-33 • Mean 18 days, Median 13 days (range 4-64 days) • Kirby D. Int J Geriatr Psychiatry 2002;17:231-7 • Severity • 4-14 mmol/l drops from baseline • Fabian TJ. Arch Intern Med. 2004;164:327-33

11. Psychiatric drugs - hyponatremia • TCA

12. Psychiatric drugs - hyponatremia • Antipsychotic • Typical and Atypical

13. Summary • Psychiatric drugs is associated with SIADH & hyponatremia • Causal for SSRI, ? TCA and antipsychotic • Risks include: • Age (>65) • Female gender • Use of other medications • Prior history • Early phase on medication • < 3/52

14. MDMA induced hyponatremia • 4 fatalities in literatures • All women and all died from cerebellar tonsillar herniation • Budisavljevic MN. Am J Med Sci. 2003 Aug;326(2):89-93 • As low as 101mmol/l reported • Holmes SB. Postgrad Med J. 1999 Jan;75(879):32-3 • Commonly in next morning

15. Anticonvulsants - hyponatremia • Problem Seizure • Carbamazepine • Oxcarbazepine • VPA Miyaoka T. Int Clin Psychopharmacol. 2001 Jan;16(1):59-61

16. OHA - hyponatremia • Chlorpropamide • Well recognized • 2.1% to 15.3% Hirokawa CA Ann Pharmacotherapy. 1992 Oct;26(10):1243-4 Sloan RW. J Farm Pract. 1983; 16: 937-42 • Tolbutamide • Glipizide • Only few case reports

17. Bottom-line • Any altered mental status/convulsion • Always • Glucose • Electrolytes • CT if focal neurology • Before diagnosis

18. Management of SIADH • Fluid restriction • NOT Normal Saline • Hypertonic Sodium • Convulsion (hard) • Mental status (soft) • Dose • Aim at 1-2mmol/l per hour in first few hours • Not more than 8-10mmol/l in 1st 24 hours • Generally, 1ml/kg of hypertonic saline over 1st hour in ED

19. Potassium • Renal • GI • Shift Bradberry. Clinical Toxicology 1995:33(4); 295-310

20. Hyperkalemia • Primary • Absolute increase • K, K-sparing diuretic, ACE I • Shift • Cardiac glycosides, Beta blocker, HF • Secondary • Cellular damage • Rhabdomyolysis • ARF • Acidemia

21. Hyperkalemia • Remove the offending agent • Treatment options for hyperkalemia • Resonium • Dextrose/Insulin • β agonist (puff) • Calcium • NaHCO3

22. Hyperkalemia Reflects the toxicity Prognostic indicator K > 5 mmol/l – DigiFab No other explainable cause for hyperkalemia Calcium in treating hyperkalemia Controversial Cardiac Glycosides Bismuth C. Clin Toxicol 1973;6:153-162

23. Calcium + Digoxin ? synergism

26. My bottom line • Avoid Ca in digitalis poisoning • Clinical + ECG

27. ACE I induced hyperkalemia • 10% of patient in 1st year of ACE I treatment • K > 6mmol/l • Risk – age >70, Renal impaired, CCF Reardon LC Arch Intern Med 1998;158:26-32 • 10-38% of hyperkalemic patients in hospital is secondary to ACE I Palmer BF N Engl J Med 2004;351:585-92

28. Hypokalemia • Primary • Absolute loss • Diuretic, RTA – Toluene • Cathartics • Shift • Beta agonist, Methylxanthines • OHA/insulin/glucose • Chloroquine, HCQ, Barium • Secondary • Alkalemia

29. Bradberry SM. Disturbances of Potassium Homestasis in Poisoning.Clinical Toxicology 1995; 33(4): 295-310

30. Replacement of Potassium • Yes or No • Weakness, ECG abnormalities • Beware in the “shift” group • Risk of hyperkalemia • IV or Oral • IV preferred Sigue G. Arch Intern Med. 2000 Feb 28;160(4):548-51

31. Hypocalcemia • Acute poisoning • HF • Ethylene glycol • Therapeutic Drugs • Anticonvulsants (VPA, Phenytoin, Phenobarbital) • Aminoglycosides • Bisphosphonates • Fleet enema (Na phosphate, esp in kid and infant)

32. Hypomagnesium • Rarely life threatening • Hand in hand with hypokalemia • Ethanol • Diuretic

33. Long QTc • Long list of drugs • www.qtdrugs.org • Correct hypo K, Ca and Mg

34. Hypernatremia • Simply “salts” • Tablet salt • Na 234 mmol/l SurvivedKupiec TC. J Anal Toxicol. 2004 Sep;28(6):526-8 • Na 255 mmol/l Died Ofran Y.J Intern Med. 2004 Dec;256(6):525-8 • Soy sauce • Na 176 mmo/l Survived Sakai Y. Chudoku Kenkyu. 2004 Jan;17(1):61-3 • DI • Lithium • Others rare

35. A few more • Hypercalcaemia • Cholecalciferol, Vitamin A, Milk alkali syndrome • Hypermagnesemia • Mg containing antacids or cathartics Med J Aust 2005; 182 (7): 350-351

36. Metabolic Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis Electrolytes Sodium Potassium Calcium Magnesium Simple Stuffs - You all know this !

37. Principle Toxin induced respiratory problem • Directly stimulate or depress respiratory centre • Alter chemoreceptor response to PaCO2 or pH • Affect respiratory muscles • Secondary to metabolic changes

38. Respiratory Acidosis • Hypoventilation • Rate Vs Tidal volume • Oxygenation = Ventilation • Two mechanisms • CNS e.g. opioids • Non-CNS e.g. NMB • Management • Supportive (BVM) • Antidotes

39. Respiratory Alkalosis • Direct • Aspirin (Protective) • Methylxanthines • Sympathemimetics • Secondary • Metabolic acidosis • Management • Usually not necessary but may be harmful

40. Metabolic acidosis • Challenging problem • MUDPILES • KULT • Ketones • Uremia • Lactate • Toxic alcohol

41. Lactate • Source of lactate • Endogenous • Impaired aerobic respiration • Primary (Cyanide) or • Secondary (Hypoxia, Hypotension) • Exogenous • Propylene glycol • Intestine Bacteria • Unit to unit for anion gap

42. Ketones (Ketoacids) • Aspirin • DKA/AKA/SKA • Ketosis without acidosis • Isopropyl alcohol - Acetone • Ketoacids • β-Hydroxybutyrate • Acetoacetate

43. Uremia • Need Cr ~ 400 • Urea NOT related to the anion gap metabolic acidosis • Failure to deal with “acid” renally • Unmeasured anion • Phosphate • Sulphate

44. Toxic Alcohol • Methanol • Formic acid • Ethylene Glycol • Glycolic acid • Toxic alcohol “Hint” • Symptoms and Signs • High Osmol Gap • Urine Fluorescence • Crystaluria

45. An approach • Any obvious “lactate” production causes • Urine ketones/Bedside glucose/Alcohol hx • RFT • Lactate • Toxic alcohol “hints” + send level (TRL)

46. Metabolic alkalosis • Least likely metabolic problem • Base administration • Bicarbonate

47. Management of Metabolic problems in poisoning • Pyramid again • Treatment • Assisted ventilation • Sedative • Sodium bicarbonate

48. Thank You