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Interesting Case Rounds Chris McCrossin Special Thanks to Dr Vicas and Paul Tourigny.

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Presentation on theme: "Interesting Case Rounds Chris McCrossin Special Thanks to Dr Vicas and Paul Tourigny."— Presentation transcript:

1 Interesting Case Rounds Chris McCrossin Special Thanks to Dr Vicas and Paul Tourigny

2 Case 21 yo M presents to ED at 8:50 AM Drank 1 glass of antifreeze at 2am, was tired of life Vomited immediately after the ingestion Now he wants to live so he thought he should get checked out in the ED Vitals –T 37.2, HR 129, RR 18, BP 138/96 O/E –CVS, Resp, Neuro, Abdo all unremarkable

3 Case Are you worried? He tells you he vomited right away, does this change anything? What if you are a rural doc with access only to basic to labs?

4 Ethylene Glycol Pathophysiology Diagnostics Treatment modalities

5 ~ 30% excreted unchanged

6 Stages of Toxicity 1.Acute CNS Within 12 h I.Slurred Speech II.Ataxia III.Altered mental status AG, Oxalate crystalluria 2.Cardiopulmonary h I.HTN II.Tachycardia III.CHF 3.Renal Failure h I.Oliguria II.Flank Pain III.Azotemia 4.Delayed CNS 6-12 days I.Cranial neuropathies II.Motor deficits III.Cognitive deficits

7 Toxic Levels What ingested dose do you start to worry about EG toxicity? –Minimum Lethal Dose: »1-2 ml/kg (ie 70 cc in 70 kg adult = 1/3 cup) »30-60 ml can result in death or severe impairment What serum level do you worry about EG toxicity? –Not reliable, especially if late presenting; metabolites that are toxic (EG may be low in presence of high [metabolites]) –Will talk about more specifics with treatment

8 Case Labs –Na 141, K 3.6, Cl 107, CO 2 21 –EthOH 8.3 mmol/L –Ethylene Glycol 10 mmol/L –Isopropanol, methanol undetectable

9 Case What do you want to do? –More labs? –Treatment? Start ethanol drip? Start fomepazole? Start dialysis?

10 Urinalysis Crystalluria is only seen in ~ 15-50% of cases Hematuria and proteinuria are more common Helpful if you see oxalate crystals in the unknown overdose but it doesnt tell you anything if you dont see it

11 Anion Gap Na - [HCO3 + Cl] Normal 7 +/- 4 Detects toxic metabolites; expect it to be normal in the early period following ingestion

12 Anion Gap [107+21] = 13 What does this tell you? What if he had an AG of 28 and an EthOH level of 40?

13 Osmol Gap To Calculate –2 Na + Glu + BUN + [EthOH x 1.2] –Calculated - Measured –A difference > 10 suggests a gap is present Primary use is as a screening test for the presence of toxic alcohols Detects presence of parent alcohol; toxic metabolites dont contribute to the osmol gap

14 Anion Gap & Osmol Gap

15 Osmol Gap Our patient: –Calculated Osmol 2(141) (8.3) = 303 – Measured Osmol 321 –Osmol Gap 18 –Irrelevant in this case

16 Osmol Gap Limitations –Only estimates molar quantity of uncharged molecules (ie measures only the parent compound, not the toxic metabolites {glycolate, glyoxylate, and oxalate}) therefore insensitive for late presentations –Can see a gap in ketoacidosis, lactic acidosis, and chronic renal failure* –Gap is not sensitive enough to rule out small ingestions* –Cannot distinguish between the alcohols –Large quantities of Alcohol raise the gap more than expected based on its molecular weight

17 Osmol Gap Conclusion –An abnormal gap may be helpful in identifying toxic alcohol ingestion, however, a normal gap does not rule out the diagnosis, nor does an abnormal gap confirm the diagnosis.

18 Treatment Options 1.Gut Decontamination? 2.Hemodialysis 3.Bicarb 4.Cofactors 5.Ethanol 6.Fomepazole Memory Aid: 4 As: block ADH, Alkalinize, Accelerate, Adjunct

19 Treatment Gastric Lavage or Charcoal? –EG is very rapidly absorbed –Activated charcoal does not absorb significant amounts of alcohol –Gastric lavage may be beneficial only within the 1st hour after ingestion and before toxic symptoms develop

20 Treatment Cofactors –Thiamine & Pyridoxine –MOA Involved in the metabolism of glyoxylic acid to non-toxic substrates –Theoretical benefit with some indirect evidence –Cheap therefore use them

21 Treatment NaHCO3? –Rationale EG is metabolized to glycolate, glyoxalate, and oxalate. Acidemia leads to protonation of these metabolites and making them more likely to penetrate end-organ tissues (ie kidney). Tx with bicarb deprotonates metabolites making them less toxic. –However No clear evidence exists to determine how bicarb should be given.

22 Treatment NaHCO 3 –Recommendations UpToDate –1-2 meq/kg bolus with maintenance infusion for patients with pH < 7.3 Micromedex Poison Index –NaHCO3 should NOT be routinely administered prophylactially…or for the tx of mild to mod acisosis –Tx should be reserved for temporizing measure in manageing cases of severe and life-threatening acidosis prior to hemodialysis CJEM 2002 –MA should be treated aggressively with NaHCO3 to bring the serum pH back to within normal limits ( )

23 Treatment Hemodialysis –Best method to rapidly remove both parent alcohols and their toxic metabolites –May be avoidable with early administration of an ADH inhibitor

24 Treatment Hemodialysis –Indications Deteriorating vital signs Unresponsive significant MA (pH < 7.3) Renal failure, fluid, or electrolyte disturbances not responsive to the usual therapy A serum ethylene glycol concentration of greater than 8 mmol/L is traditionally an indication for dialysis »Micromedix, CJEM 2002

25 Treatment Hemodialysis –Recommendations from European Conference

26 Treatment Hemodialysis Endpoints –Serum pH is normal –Parent alcohol concentration is less than 3.2 mmol/L –Resolution of the osmolar gap

27 Treatment ADH Inhibitors –Prevents conversion of parent alcohol into its toxic metabolites –Two options: EthOH (65 x more affinity for ADH than EG) Fomepazole ( x more affinity for ADH than EthOH) –ADH inhibitors do nothing once the toxic metabolites have formed (other than prevent further parent alcohol from forming) –May prevent need for HD even in large ingestions; same is not true for Methanol »WHY?

28 Treatment ADH Inhibition: MOA N Engl J Med 1999

29 Treatment

30 Ethanol –How to give it (CJEM 2002) ADH is effectively saturated at mmol/L IV loading dose – ml/kg as 10% soln IV maintenance dose –1-2 ml/kg hourly –Draw levels hourly –Higher doses required for dialysis –Continue until EG levels are undetectable (1/2 life is increased when ADH inhibitor is given)

31 Treatment Fomepazole –How to give it (CJEM 2002) Loading dose –15 mg/kg IV (oral is effective but not available in Canada) Maintenance –10 mg/kg every 12 hours for 4 doses; then 15 mg/kg every 12 hours until EG levels are below 3.2 mmol/L* –Shortened dosing interval or infusion recommended if patient is undergoing hemodialysis –Cost $1075 per 1.5 gram vial (avg 4 vials per patient) –Restricted access to PADIS

32 Treatment How good is Fomepazole? –Anecdotal cases with ingestions between mL presenting 1-12 h post ingestion. All treated with fomepazole, no dialysis, complete recovery. –42 yo M with 1.5 L of antifreeze presented 4.5 h post ingestion, EG 51 mmol/L. Received initial loading dose of ethanol, then fomepazole. Complete recover without dialysis. »CJEM 2002

33 Treatment Ethanol –Pros Cheap Effective –Cons Notoriously difficult to titrate (easy to over/under shoot) S/E of hypoglycemia Risk of aggressive behaviour Peds require ICU Admit Need to monitor levels Need to be on an infusion (oral difficult to titrate) Fomepazole –Pros Effective No levels required Long 1/2 life Easy dosing Peds dont require ICU Safe, minimal side effects –Cons Expensive

34 Treatment When to consider Fomepazole over Ethanol? –Rural areas without adequate lab support –Pediatrics (decrease ICU admissions) –Patients prone to hypoglycemia –Liver failure

35 Back to the Case His EthOH level was only 8, not protective He doesnt have an AG He does have an osmol gap Based on what weve reviewed how do you want to treat him?

36 Case He was started on an EthOH drip and titrated to a level > 20 mmol/L and maintained on the drip until his EG level became undetectable and his Osmol gap cleared

37 Proposed Treatment Algorithm

38 Summary EG is rapidly absorbed and toxic in small amounts A low/neg EG level and osmol gap can be misleading in late presenters Expect AG to be normal in early presenters Significant metabolic acidosis suggests presence of toxic metabolites of which our only definitive therapy is dialysis ADH inhibitors are used to prevent further metabolization of the parent alcohol

39 References Scalley, RD et al. Treatment of ethylene glycol poisoning. Am Fam Phys 2002; 66(5): Megarbane, B et al. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med 2005; 31: Glaser, DS. Utility of the serum osmol gap in the diagnosis of methanol or ethylene glycol poisoning. Ann Emerg Med 1996; 27(3): Hall, T. Fomepazole in the treatment of ethylene glycol poisoning. CJEM 2002; 4(3): Micromedix Poison Index: Ethylene Glycol. Accessed June 29, Sivilotti, ML. Methanol and ethylene glycol intoxication. UpToDate Accessed June 29th, 2008 (updated Feb 14, 2008).

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