1. CYANIDE

2. CYANIDE TOXICITY INGESTION 60- 90 mg Hydrogen Cyanide (HCN)
LETHAL DOSES
mg Hydrogen Cyanide (HCN)
200 mg Potassium Cyanide (KCN)

3. CYANIDE TOXICITY INHALATION Concentration (mg.m-3) Effect
300 immediately lethal
200 lethal after 10 minutes
150 lethal after 30 minutes
lethal after minutes
minutes to 1 hour without effect
light symptoms after several hours

4. CYANIDE
METABOLISM

5. CYANIDE

6. CYANIDE PLANTS Almonds Cassava Wild Cherries
250 mg CN/100g plant tissue
Cassava
Wild Cherries
104 mg CN/ 100 g plant tissue
mg CN/ 100 g plant material

7. CYANIDE
PLANTS
AMYGDALIN

8. CYANIDE
“DRUGS”
AMYGDALIN

9. CYANIDE INDUSTRY ELECTROPLATING HARDENING METALS GOLD EXTRACTION
LABORATORIES

10. CYANIDE
FIRE
CYANIDE/CARBON MONOXIDE

11. CYANIDE
RODENTICIDE/FUMIGANT
FERATOX/CYANIDE PASTE

12. CYANIDE
RODENTICIDE/FUMIGANT
ZYCLON B

13. CYANIDE
RODENTICIDE/FUMIGANT
ZYCLON B

14. CYANIDE
CHEMICAL WEAPON

15. CYANIDE
SUICIDE

16. CYANIDE TOXIC MECHANISM Heme group of mitochondrial cytochrome
The final stage in respiration is catalyzed by cytochrom c oxidase, a complex hemoprotein containing two chemically different heme groups known as a and a3. Heme a oxidizes cyt c and heme a3 reduces moleculer oxygen to water. The heme a and a3 of the cytochrome c oxidase are at equilibrium having the same Eo' value +2.9V. It is the H2O-O2 couple that has a high enough Eo' (+0.82V) to provide the energy for the cytochrom c oxidase to serve as the third coupling site of oxidative phosphorylation. This final step and large change in free energy upon reduction of molecular oxygen to water serves as the major driving force for the electron transport chain and thus coupling to ATP synthesis via a proton gradient and makes the electron flux from the flavoproteins to cytochrom c oxidase essentially irreversible.
Cytochrome oxidase catalyzes a cyclic reaction in which the electrons extracted from metabolites are finally transferred to molecular oxygen in the presence of 4 protons to form 2 molecules of H2O. This is a carefully controlled mechanism because the intermediate oxygen radicals are highly reactive and damaging to the cell. Oxygen is tightly bound to an iron-copper containing coenzyme.

17. CYANIDE TOXIC MECHANISM “HISTIOTOXIC ANOXIA”
The first historically, and most commonly, recognised mechanism of cyanide pathophysiology is its effect on the final step of oxidative phosphorylation in the cytochrome oxidase system. Cyanide is attracted to the ferric ion, and as such binds avidly to the cytochrome (cytochrome a-a3) complex. This intra-mitochondrial enzyme is an essential catalyst for the use of oxygen to reoxidise reduced cytochrome a3. Its inhibition essentially halts electron transport and intra-cellular respiration. The inability to use cellular oxygen triggers chemoreceptors to stimulate the respiratory center, leading to uncontrollable gasping and hyperpnoea in those suffering from the early effects of cyanide.
“HISTIOTOXIC ANOXIA”

18. CYANIDE
TOXIC MECHANISM
VASOSPASM

19. CYANIDE SIGNS AND SYMPTOMS Mild Toxicity Nausea Dizziness Drowsiness
Moderate Toxicity
Loss of consciousness for a short period
Convulsion
Vomiting
Cyanosis
Severe Toxicity
Deep coma
Dilated non-reactive pupils
Deteriorating cardio-respiratory function

20. CYANIDE INVESTIGATIONS History Occupation, access to cyanide Smell
Bitter almonds
ECG
Sinus tachycardia/bradycardia
Ischaemic changes
Pulse oximetry
Normal

21. CYANIDE INVESTIGATIONS ABG Metabolic acidosis, normal oxygen
Anion gap (Na+ – [Cl - + HCO3-])
Elevated
Serum lactate
Blood cyanide level
Elevated – difficult to rapidly determine

22. CYANIDE MANAGEMENT HAZARD ASSESSMENT ABC’s TOXICOKINETICS ABSORPTION
DISTRIBUTION
METABOLISM
ELIMINATION
TOXICODYNAMICS
SUPPORTIVE CARE

23. CYANIDE MANAGEMENT HAZARD ASSESSMENT Cyanide is hazardous by:
Ingestion
Respiratory exposure
Dermal exposure

24. CYANIDE MANAGEMENT ABC’s Avoid: mouth to mouth, or
mouth to nose artificial ventilation

25. CYANIDE MANAGEMENT DECONTAMINATION (absorption) Nasogastric aspiration
Activated charcoal
Gastric lavage
Emesis

26. Enhanced cyanide metabolism
MANAGEMENT
ANTIDOTES (distribution/metabolism)
Enhanced cyanide metabolism
Cyanide ion binding

27. Enhanced cyanide metabolism
ANTIDOTES
Enhanced cyanide metabolism
Enhancement of body’s natural mechanisms for dealing with cyanide:
  i. oxygen
  ii. Sodium thiosulphate

28. Enhanced cyanide metabolism
ANTIDOTES
Enhanced cyanide metabolism

29. CYANIDE ANTIDOTES Cyanide ion binding Cobalt containing drugs
Methaemoglobin forming drugs

30. CYANIDE ANTIDOTES Cyanide ion binding Cobalt containing drugs:
Cyanide ions will bind to cobalt which can be supplied in the form of either;
i. Hydroxocobalamin, or
ii. Dicobalt edetate.

31. CYANIDE ANTIDOTES Cyanide ion binding Methaemoglobin forming drugs:
Cyanide will also bind to methaemoglobin formed after administration of:
i. Amyl nitrite;
ii. Sodium nitrite, or;
iii. 4-dimethylaminophenol
(4-DMAP)

32. CYANIDE ANTIDOTES Cyanide ion binding
Nitrite leads to oxidation of ferrous (++) haemoglobin to ferric (+++) methaemoglobin.
The basis of this treatment is methaemoglobin’s ability to bind to cyanide ions. If enough methaemoglobin is formed in the blood stream it attracts cyanide away from inhibited cytochrome oxidase, by mass action, forming cyan methaemoglobin and allowing resumption of cellular respiration. Thus the well known methaemoglobin formers amyl nitrite and sodium nitrite were tested, and found to be very effective in treatment.

33. CYANIDE
TOXIC MECHANISM
Heme group of mitochondrial cytochrome

34. CYANIDE
TOXIC MECHANISM

35. CYANIDE ANTIDOTES Cyanide ion binding
Nitrite leads to oxidation of ferrous (++) haemoglobin to ferric (+++) methaemoglobin.
The basis of this treatment is methaemoglobin’s ability to bind to cyanide ions. If enough methaemoglobin is formed in the blood stream it attracts cyanide away from inhibited cytochrome oxidase, by mass action, forming cyan methaemoglobin and allowing resumption of cellular respiration. Thus the well known methaemoglobin formers amyl nitrite and sodium nitrite were tested, and found to be very effective in treatment.

36. CYANIDE ANTIDOTES Cyanide ion binding
Nitrite leads to oxidation of ferrous (++) haemoglobin to ferric (+++) methaemoglobin.
The basis of this treatment is methaemoglobin’s ability to bind to cyanide ions. If enough methaemoglobin is formed in the blood stream it attracts cyanide away from inhibited cytochrome oxidase, by mass action, forming cyan methaemoglobin and allowing resumption of cellular respiration. Thus the well known methaemoglobin formers amyl nitrite and sodium nitrite were tested, and found to be very effective in treatment.

37. CYANIDE FIRST AID If the patient is unconscious:
Commence forced artificial ventilation with 100% oxygen using a mask and bag with a “non-return” valve (to prevent inspiration of inhaled gases)
Amyl nitrite may be administered via the ambu bag mL for adults and 0.1 mL for children
NOTE:
Amyl nitrite forms a flammable mixture when combined with oxygen. It must therefore not be used in situations where it may be ignited.

38. CYANIDE MILD POISONING
In those circumstances where an individual exposed to hydrogen cyanide by inhalation is conscious five minutes after exposure has ceased, and complains only of nausea, dizziness, drowsiness or other mild symptoms:
Oxygen
Reassurance
Bed rest

39. CYANIDE MODERATE POISONING
Those patients who have been observed to have lost consciousness for a short period, or are suffering convulsions, vomiting and/or cyanosis:

40. CYANIDE MODERATE POISONING
Oxygen 100%: but for no longer than hours
Amyl nitrite: mL for adults and 0.1 mL for children via “ambu bag” (if there is delay in administering sodium thiosulphate)

41. CYANIDE MODERATE POISONING Then
Sodium thiosulphate: 50 mL of 25% solution (12.5g) IV over 10 minutes. In children the dose is 300 to 500 mg/kg

42. CYANIDE MODERATE POISONING
Oxygen 100%: but for no longer than hours
Amyl nitrite: mL for adults and 0.1 mL for children via “ambu bag” (if there is delay in administering IV antidote)

43. CYANIDE SEVERE POISONING And either
Hydroxocobalamin: 5 g (70 mg/kg for children) by rapid IV infusion. This dose may be repeated once or twice, depending upon response, with IV infusions over 30 minutes to 2 hours
Sodium nitrite: 10 ml of 3% solution (300mg) IV for minutes. May be repeated at half initial dose
Dicobalt edetate: 20 ml of 1.5% solution (300mg) IV over 1 minute followed immediately by 50 ml of hypertonic glucose solution. May be repeated twice
Sodium nitrite should not be used in the presence of concomitant carbon monoxide poisoning, or in those with G6PD deficiency.
Dicobalt edetate should not be used if the diagnosis of cyanide intoxication is in doubt due to risk of anaphylaxis.

44. CYANIDE SEVERE POISONING Then
Sodium thiosulphate: 50 mL of 25% solution (12.5g) IV over 10 minutes. In children the dose is 300 to 500 mg/kg

45. CYANIDE