Stephen W. Borron, MD, MS

South Texas Poison Center

University of Texas Health Science Center at San Antonio

San Antonio, Texas, USA

Cyanide continues to be considered a rare poisoning, in spite of growing evidence to the contrary

This talk will review some underappreciated sources of cyanide poisoning, ways of detecting cyanide, and provide an update on antidotal therapy through a review of recent literature

Terrorism involving cyanide is a significant risk Availability

1.84 billion of HCN produced worldwide each year Incidents of concern:

2002: Ten tons of NaCN stolen in Mexico. Only 1/5 recovered

2002: Joseph Konopka (“Dr. Chaos”) indicted for possession of chemical weapons including KCN and NaCN in Chicago

2004: South Korea reports that North Korea had imported 175 tons of NaCN in 2003

Keim 2006 Prehosp Disast Med 21(2):s56-s60

2003: In May 2003 a cyanide bomb was found in the possession of white supremacists in Texas

2003: Two letters reportedly containing CN were sent to a New Zealand newspaper

2003: An Algerian terrorist was arrested in London with cyanide and “recipes” for creating chemical weapons

2006: Another arrest in London for “cyanide-laced bomb”

2007: A methamphetamine drug lab bust revealed the presence of a cyanide bomb in California

The potential for cyanide poisoning from smoke inhalation was identified by Wetherell in 1966

Smoke inhalation continues to be referred to as “carbon monoxide poisoning” even in respected, peer-reviewed literature

This misnomer results in ignorance of the risk of cyanide and perhaps under-treatment

Review of coroner’s reports in 178 fire deaths

146 died at scene, 32 in hospital Bloods obtained at autopsy and from stored

hospital samples No detail provided regarding sampling delays

Whole blood CN measured in 137/178 cases COHb obtained in 154/178 cases

Yeoh 2004 Clin Toxicol 42;855-863

Group (n=178)

COHb % Blood cyanide mg/L

Whole group 29% (n=154)

1.0 (n = 137)

Subgroup in whom CN detected

1.65 (n=86 or 63% of total)

Subgroup with potentially lethal blood CN

>3.0 (n=11 or 6% of total)

All mortal fire victims included No requirement for

closed space fire 32 deaths (18%) from

self-immolation Authors speculate

differences from Baud 1991 on basis of different building materials

Yeoh 2004 Clin Toxicol 42;855-863

Study by F.J. Baud in Paris with Paris Fire Brigade

69 victims of smoke inhalation with: Confined space fire Soot in the mouth or nose Altered mental status (LOC, confusion, slowness

of ideation) Blood samples drawn on scene for cyanide

and carbon monoxide

020406080100120140

52

96

8

123

4527 32 18 30 24

CN (µmol/L) vs COHb (%) in Smoke Inhalation Victims

CN CO

Borron 2007 Ann Emerg Med 49:794-801

Brown 2007 J Burn Care Res 28;533-536

76 y/o female found under a bed in a fire Unresponsive, GCS=3, irregular ECG rhythm pH 7.11, pCO2 39, pO2 491, AG 19, Glu 145 COHb 35% 8% after HBO, but still GCS=7 Persistent fluctuation of SBP from 230s to

80s EEG showed status epilepticus w/o motor sz Is this CO poisoning?

Brown 2007 J Burn Care Res 28;533-536

Chou 2000 Pediatr Emerg Care 16;151-155

Comparison of variables in 150 children with CO poisoning alone versus CO with smoke inhalation

Measure n CO pure n CO + smoke P

Mean COHb 85 23.5 ± 11.53 59 27.6 ± 16.25 0.07

Death 81 0% 53 20.3% <0.001

Initial GCS 17 14.7 18 6.7 <0.001

Depressed MS in ED 83 13.6% 57 76.3% <0.001

Initial pH 43 7.4 44 7.2 <0.001

Respiratory Arrest 80 0% 54 68.5% <0.001

Cardiac Arrest 80 0% 54 25.9% <0.001

Median time to ED 27 40 min 10 25 min 0.04

Median time to HBO 69 70 min 47 50 min 0.23

Myers, 1989114 cases of CO ±

smoke inhalation COHb

○ 1.3 to 62% Acidotic○ 1.9 to 56% Alkalotic○ 1 to 58% Normal pH

pH range○ 6.8 to 7.9

Lebby, 198946 cases of pure

CO poisoningCOHb

○ 10-63.9% ○ (mean 21.8 ±

10.2%)pH range

○ 7.37 to 7.54 ○ Mean 7.43 ± 0.04

Myers 1989 Crit Care Med 17;139-142Lebby 1989 Vet Human Toxicol 31;138-140

Baud, unpublished review of 142 cases of pure CN poisoning: 26% had seizures

Benaissa, published review of 146 cases of pure CO poisoning: 0% had seizures

Choi, published review of 188 cases of pure* CO poisoning: 2.1% had seizures

Choi 1998 J Korean Neurol Assoc 16;500-505

Benaissa, 2003 Intensive Care Med 29:1372–1375

Baud, 2007 Manuscript in Preparation

* Source of CO not stated, but not from structure fires

Baum et al tested vehicles for HCN production for environmental impact

Reports that older vehicles produced HCN orders of magnitude above current

“Severe residential garage” scenario poses potential toxicity risk at today’s emissions levels

Warm vehicles emitted up to 60 mcg/min of HCN

Source Timemin

Concentration (mcg/m-3)

Residential garage, typical

0.5 0.32

Residential garage, severe

180 192

Parking garage, typical

4.5 0.15

Parking garage, severe

25 3

Reference value (CEPA)

60 340

ERPG-1 60 1820

Baum 2007 Environ Sci Technol 41;857-862

Rabbits given intravenous NaCN, total dose of 6 mg

Broadband diffuse optical spectroscopy (DOS) used to non-invasively monitor physiological changes

Oxygen saturation ↑ 10%, Oxidized cytox ↓

Lee 2007 Physiol Meas 28;1057-1066

Cyanide tends to cause symmetrical lesions in the globi palladi and putamina. The hippocampal gyri are usually spared.

Lesions in the substantia nigra, subthalamic nucleus and cerebellum are also reported

Associated extrapyramidal signs are common

Hemorrhagic lesions are common (generally more common than in CO poisoning)

MRI is generally superior to CT

Lesions may be reversible

Hantson 2006 Toxicol Rev 25;87-98

KCN ordered on the internet, given to a ‘friend’ vying for a girl’s affection

Patient apneic, GCS=3, hypotensive, zero A-V 02 sat difference, lactate 20 mmol/l

Received antidote at 4h Total 1.8 g sodium nitrite 75g sodium thiosulfate Continuous infusions of both

Iatrogenic methemoglobinia 35%

Death: organs donatedPeddy 2006 Pediatr Crit Care Med

39 y/o male with dyspnea, drowsiness, upper respiratory irritation after transporting barrels of MIC

Desaturated to 67% in ED requiring intubation

Report from scene that CN released as well

Given 450 mg DMAP, bicarbonate and sodium thiosulfate for metabolic acidosis with lactate of 1.8 mmol/l

Iatrogenic methemoglobin 86.7% requiring toluidine

Hypotension, hemolysis, MOF ensued, Survived!

Kerger 2005 Resuscitation 66;231-235

Hydroxocobalamin Enters the CNS Rapidly, irreversibly

binds cyanide Efficacy demonstrated

in GLP animal study Safety demonstrated in

clinical trials and healthy volunteer study

Sodium thiosulfate Limited entry into CNS,

mitochondria Enzyme-dependent for

function No clinical trials Efficacy in humans

based on case reports and mixed animal reviews

Hall 2007 Ann Emerg Med 49;806-813Uhl 2006 Clin Toxicol 44;17-28

Borron 2006 Clin Toxicol 44;1-11

Survey of hospitals in British Columbia following recommendations to hospitals in 2003 re: stocking

70-90% of hospitals had “adequate stocking” of cyanide antidotes

Adequate stocking for the cyanide antidote kit was 1 kit

Primary barrier to obtain antidotes: cost of $10,000 to obtain the minimum list

Wiens 2006 Can J Emerg Med 8;409-416

Cyanide poisoning continues to be under-recognized, particularly in the setting of smoke inhalation

It likewise poses a risk as an agent of suicide, homicide, or terror

Diagnosis is often difficult and therapy can be dangerous

Stocking of antidotes is insufficient to deal with multiple casualties