1 / 83

Cyanide and Methemoglobinemia

Cyanide and Methemoglobinemia. Presented by: Dr. Aric Storck Preceptor: Dr. Ingrid Vicas Core Rounds February 20, 2003. Cyanide. Cyanide. Anion (CN - ) solid and gaseous forms Important component of many industrial reactions mining - recover silver and gold from ores

sandra_john
Télécharger la présentation

Cyanide and Methemoglobinemia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cyanide and Methemoglobinemia Presented by: Dr. Aric Storck Preceptor: Dr. Ingrid Vicas Core Rounds February 20, 2003

  2. Cyanide

  3. Cyanide • Anion (CN-) • solid and gaseous forms • Important component of many industrial reactions • mining - recover silver and gold from ores • photographic - recovery of silver • plastic manufacturing • Naturally occurs in many plant products • Tobacco, apricot pits

  4. Cyanide pollution • 1997 - 4,513,410 cyanide released by top 100 polluters in USA • Bhopal, 1984 • worst industrial poisoning in history • 25,000 kg methyl isocyanate and combustion products released into atmosphere • 1,800 - 5,000 deaths • 200,000 injuries

  5. Man carries his wife past the Union Carbide factory in Bhopal, India. Fumes from the factory killed her the previous day Source: Greenpeace

  6. Skulls from victims of the Union Carbide disaster in the Hamidia Hospital in Bhopal, India. Source: Greenpeace

  7. Cyanide … a potential disaster • 500,000 hazardous materials shipments / day in the USA • Average 12,115 hazardous material accidents per year (1990-1996) • Large potential for significant industrial accident involving cyanide

  8. Cyanide and terrorism • 1984 - 7 Chicago area residents killed after ingesting cyanide-laced Tylenol • Cyanide gas precursors (cyanide salt + acid) found in Tokyo subway bathrooms following sarin gas attacks • Cyanide believed to be involved in World Trade Center bombing (incinerated in attack)

  9. Cyanide and Fires • Cyanide is a combustion product of • plastic • rugs • silks • furniture • construction materials

  10. Cyanide and Fires • Significant correlation between CO levels and CN- levels in fire victims • estimated 35% of fire victims have toxic levels of cyanide Source: Sauer S, Keim M. Hydroxocobalamin: Improved public health readiness for cyanide disasters. Ann Emerg Med. June 2001; 37:635-641.

  11. Cyanide - Pathophysiology • CN- has high affinity for metals • Complexes with metallic cations at catalytic sites of several enzymes • Binds ferric (3+) iron of mitochondrial cytochrome oxidase (cytochrome a-a3) • cytochrome a-a3 – mediates transfer of electrons to molecular oxygen (final step in oxidative phosphorylation)

  12. Oxidative Phosphorylation Source: Ford’s Clinical Toxicology

  13. Blockade of oxidative phosphorylation • Tissue anoxia • Anaerobic metabolism • Lactic acidosis

  14. Cyanide - Pathophysiology • Other metabolic effects • Less relevant (...because you die of anoxia first) • Interferes with lipid metabolism • Interferes with glycogen metabolism

  15. Cyanide - Poisoning • Rapid absorption • Respiratory tract • Mucous membranes • Slow absorption • Skin • GI tract

  16. Cyanide Poisoning - Inhalation • Hydrogen cyanide • Combustion of nitrogen containing polymers (vinyl, polyurethane, silk) • Immediate onset of symptoms • 50 ppm • Symptoms after several hours • Anxiety, SOB, palpitations, headache • 100 ppm • Death after 30 minutes • 270 ppm • Immediate coma, asystole, death

  17. Cyanide – Ingested Salts • Symptoms within minutes • Caustic – oral burns • Smell of bitter almonds • 50 mg – has been reported to cause death • LD50 – 140-250 mg (untreated adult)

  18. Ingestion – Cyanide producing compounds • Compounds require metabolic activation to produce cyanide • Organic nitriles • Cyanogenic glycosides • eg: amygdalin – found in bitter almonds, apricot pits • Hydrolyzed to CN in small bowel • Not toxic if taken intravenously • Acetonitrile (solvent in artificial nail remover) • Oxidized by hepatic enzymes • Delayed onset of symptoms (up to 24 hours)

  19. Cyanide - Dermal Exposure • LD50 = 100 mg/kg

  20. Cyanide & Nitroprusside • Deterioration in aqueous solutions releases cyanide • Hydroxycobalamin and thiosulfate co-infusions used in critical care settings

  21. Chronic Cyanide Poisoning • Clinical relevance controversial • Cassava – contains linamarin (cyanogenic) • Common food in many countries • Some evidence that B12 deficiency, goiter, demyelinating diseases may be related

  22. Cyanide - Detoxification • Naturally occurs in small quantities • tobacco • cassava • Small amounts routinely cleared from body

  23. Cyanide - Detoxification • Cyanide + thiosulfate = thiocyanate • Enzymatically • Rhodanase • Beta-mercaptopyruvate-cyanide sulfur transferase • Nonenzymatically • Sulfane-albumin complex combines with cyanide

  24. Cyanide - Elimination • Thiocyanate • Relatively non-toxic • Renal elimination (half life 2.5 days)

  25. Cyanide – Clinical Presentation • Physiologic manifestations of hypoxia • Metabolic acidosis • Bradycardia • Dyspnea • CNS disturbances • Normal pulse oximetry

  26. Cyanide – Clinical Presentation • CNS • Headaches • Drowsiness • Dizziness • Seizures • Coma

  27. Cyanide – Clinical Presentation • Pulmonary • Dyspnea • Tachypnea • Apnea

  28. Cyanide Poisoning - DDX • Ingestion with altered LOC and acidosis • sodium azide • salicylates • iron • Beta-adrenergic antagonists • cocaine • isoniazid • toxic alcohols

  29. Cyanide Poisoning - DDX • Inhalational Exposures • hydrogen sulfide • carbon monoxide • simple asphyxiants

  30. Cyanide – Clinical Presentation • Cardiovascular Effects • Hypertension • Tachycardia • Hypotension • Bradycardia • Asystole • Cardiac collapse

  31. Laboratory Investigation • Electrolytes • Elevated anion gap (lactic acidosis) • ABG • Metabolic acidosis (lactic acidosis) • Normal PO2 • SaO2 • Normal

  32. Laboratory Investigation • AVO2 • Decreased (decreased tissue oxygen utilization) • Cyanide levels • Not rapid enough for clinical utility • Serum cyanide level • Toxic = >0.5mg/L • Fatal = >3.0 mg/L • Erythrocyte cyanide level • Normal = <1.9 uM/L (50ug/L) • Fatal = > 40 uM/L (1mg/L)

  33. Laboratory Investigation • Serum lactate – elevated • ECG • Sinus bradycardia • Sinus tachycardia

  34. Cyanide Poisoning - Sequellae • Directly related to severity of exposure and delay in treatment • long term sequellae are those of hypoxia • cerebral hypoxia / encephalopathy (common)

  35. Cyanide - Treatment • Monitors • IV access • Administer 100% O2 • Gastric lavage • Indicated in very recent ingestion • Activated charcoal (1g/kg)

  36. Cyanide Antidote Kit Manufacturer: Taylor Pharmaceuticals Cost: $317 USD

  37. Cyanide Antidote Kit • Contents • Amyl nitrite 0.3 ml x 12 • Inhaled while IV access established • Not necessary if immediate IV access • Can be given in pre-hospital setting • Sodium nitrite 300mg/10cc x 2 • Sodium thiosulfate 12.5g/50cc x2 • syringes, needles, tourniquet, stomach tube, instructions

  38. Cyanide Antidote Kit • Instructions • Crush and inhale one ampoule (0.3ml) of amyl nitrite q15-30 seconds until iv access achieved • Rapid infusion sodium nitrite 300mg • Infuse sodium thiosulfate 12.5g over 10 minutes • Repeat sodium nitrite and thiosulfate infusion at half dose prn x 1 • Caution • Sodium nitrite infusion limited by hypotension

  39. Cyanide Antidote Kit - Mechanism • Nitrites • Therapeutic induction of methemoglobinemia NO2 + Hb = MHb • Methemoglobin binds strongly to CN- and removes it from tissues CN- + MHB = cyanomethemoglobin • cyanomethemoglobin relatively non-toxic

  40. Sodium Thiosulfate • donates sulfur molecule to rhodanese (enzyme which catalyzes formation of thiocyanate) Na2S2O3 + HCN + O = HSCN • Synergistic effect • Oxygen • Synergy of 100% O2 with nitrites/thiosulfate

  41. CAK - Children • 0.33 mL/kg of 3% NaNO2 • Adjust dose if anemic • Hb 70 – 0.19mL/kg • Hb 100 – 0.27mL/kg • Hb 120 – 0.33mL/kg • Hb 140 – 0.39mL/kg • 1.65 mL/kg of 25% Na2S2O3

  42. Cyanide Antidote Kit • Effectiveness • able to detoxify 20 lethal ingested doses in dogs • effective even after respiratory arrest as long as no cardiac arrest • Complications • Hypotension • Related to vasodilatory effects of nitrites • Methemoglobinemia • Death reported in asymptomatic cyanide poisonings (NB: only use CAK if symptomatic poisoning)

  43. Cyanide Antidote Kit • Limitations • MHb production prevents its use in unconfirmed cases • not practical for smoke inhalation victims (bad idea to induce MHb when already high level of carboxyhemoglobin) • many hospitals poorly supplied • 81% of Tennessee hospitals unable to treat two 70 kg patients

  44. Cyanide – other antidotes • Hyperbaric Oxygen • No therapeutic effect • Useful if concomitant CO inhalation • Dicobalt edetate • Widely used in UK • Effective antidote with significant toxicity (esp. when cyanide not present)

  45. DMAP (4-dimethylaminophenol) • Produces very rapid methemoglobinemia • Used widely in Germany • No more effective than sodium nitrite • Less hypotension than sodium nitrite • Linked with renal failure in animal models

  46. Hydroxycobalamin (vitamin B12a) • Widely used in France • Very effective and non-toxic • precursor of B12 (cyanocobalamin) • ideal choice for vegan victims of cyanide poisoning • Recognized by FDA for cyanide poisoning • Used in ICU settings to mitigate nitroprusside toxicity

  47. Reduces cyanide to cyanocobalamin B12a + CN- = B12 • 5g B12a will treat patients with up to 40 umol/L • Low concentrations available in US mean very large quantities required

  48. Hydroxycobalamin (vitamin B12a) • When combined with sodium thiosulfate end product is thiocyanate Na2S2O3 + B12 = HSCN + B12a • Recycling of hydroxycobalamin • Renally cleared • Synergistic effect of thiosulfate and B12a

  49. Hydroxycobalamin (vitamin B12a) • Advantages vs CAK • less toxic • does not produce MHb (thus appropriate for smoke inhalation victims) • may be administered out of hospital • cheaper

  50. Hydroxycobalamin (vitamin B12a) • Available in Europe as Cyanokit • 2.5 and 5.0 g doses • very concentrated (5g/100 ml) • in USA hydroxycobalamin available in 1mg/mL (5L infusion required for 5g dose) • No pharmaceutical company willing to sponsor FDA approval and development in North America

More Related