FOCUSON:MILITARYANAESTHESIAANDCRITICALCARE (PART 2)

The toxicology and treatment of injuries fromchemicalwarfare agentsBernard Riley

Consultant in Adult Intensive Care,University Hospital,NottinghamNG7 2UH,UK

Summary The range of chemical substances used in chemical warfare is describedtogetherwith a brief historicaloverviewoftheir use.Theirphysico-chemical propertiesare described along with the types of injury they produce.The signs and symptoms ofeach agent are listedwith particular emphasis onthose likely to require critical care.Allthedatapresentedareinthepublicdomain, freelyavailableinthereferencedpapers andbooksandwhiletheymaynotreflectcurrentmilitarydoctrine,theyaimtorepresentthecurrent state of bestclinicalpractice.�c 2003 Elsevier Ltd.Allrights reserved.

KEYWORDSchemical warfare agents;classif|cation; toxicology;clinical signs; treatment

INTRODUCTIONThe f|rst description of a chemical weapon of war isprobably that of ‘Greek Fire’, an inflammable mixture ofpitch, oil and sulphur used as a primitive f|rebomblaunched by catapult.The use of plant chemical extractsto poison individuals is widely documented throughoutthe Middle Ages and Renaissance but it was not untilthe expansion of industrial chemistry in the late19th cen-tury thatmass production anddeploymenton thebattle-f|eld became a possibility.The First Hague Convention of1899 setout to commit the contractingpowers to an ob-ligation to abstain from the use of artillery projectilesdesigned solely for the distribution of ‘asphyxiating ordeleterious gases’. The use of chemical weapons on amassive scale duringWorldWar I (WWI) demonstratedthe fragility of such agreements. The birth of modernchemical warfare was ushered in by the German gas at-tack with chlorine on themorning of the 22nd April1915on theWestern Front.This new era of warfare was de-scribed-as a‘higher form of killing’ by Professor FritzHa-ber1 and gave rise to the concept, which persists to thisday that chemical weapons (CW) are ‘weapons of massdestruction’. A closer analysis of the facts shows thatduring World War I CW caused only 1.32% of the totalof just under 7 million battlef|eld deaths caused by allweapons systems.

Nonetheless, the nature and persistence of theinjuries provoked an abhorrence which lead to further

attempts to ban their use. Despite this they continuedto be used by several governments during colonial warsto a varying degree. Memories of their effects inWorldWar I ensured that Civil Defence preparations in theUK prior to the outbreak of World War II included theissue of a personal respirator to everyman, woman andchild in the country. Both the Germans and Alliesmanu-factured and stockpiled vast amounts of chemical muni-tions but none were ever used in action.The reason forthe failure of the otherwisemercilessNazi regime to useits unique armoury of nerve agents (NA) remains amys-tery. During the Cold war both the East and the Westspent enormous sums on the developmentof both offen-sive anddefensiveCW.TheUKdiscontinuedNAproduc-tion at Nancekuke in Cornwall in 1956 but productioncontinued in both the USA and the USSR formany yearsthereafter.While defoliants and irritant chemicals wereundoubtedly used by the USA during theVietnamWar,the use of other CW was limited to the probable use ofMustard compounds by Egypt in theYemen during themid-1960s. The only major use of CW since WWI oc-curred during the Iran--IraqWar in the1980s.

When deployed against military forces, the effective-ness of CW lies not in their ability to kill, but in theirability to inflict large numbers of casualties that requiretreatment by a complex evacuation andmedical supportsystem which in turn requires numerous personnel andresources.The nature of the injury they produce is oftenincapacitating rather than lethal but the threat of theirlethality often demoralizes or preoccupies soldiers outof all proportion to their effects.The need to adopt de-fensive measures such as special protective clothing,

Correspondence to: BR. Tel.: +44-115-924-9924; fax: +44-115-970-9910; E-mail: willoid.riley@virgin.net.

Current Anaesthesia & Critical Care (2003) 14,149--154�c 2003 Elsevier Ltd. All rights reserved.doi:10.1016/S0953-7112(03)00035-8

boots, gloves and respirators, degrades the ability of in-dividual soldiers to f|ght with conventional weapons andequipment.During the Gulf War the use of CW by Iraqwas a threat takenvery seriously and the author hasper-sonal experience of the physical strain of functioning inindividual protective clothing in a desert environment(Fig.1).There is no evidence of which I am aware thatCoa-lition Forces were deliberately exposed to CW agentsduring the Gulf War although some exposure during thedestruction of CWmunitions dumps is a possibility.

The largest single CW attack, killing around 5000people, followed an Iraqi NA attack on the Kurdish civi-lian population of Halabja.This attack illustrates the onesingle characteristic of chemical warfare agents that al-lows them to be considered asweapons ofmass destruc-tion.Namely, that success,measuredin terms of lethality,is most likely when they are deployed against a defence-less population. It is this together with the relative sim-plicity of their manufacture that makes them anattractive weapon for those engaged in the promotionof mass murder by terrorism. The release of a homemade NA, in this case Sarin, by the Japanese religiouscult, Aum Shinrikyo (SupremeTruth), on theTokyo Un-derground in1995 demonstrated the feasibilityof such at-tacks.2 The panic and illness that followed demonstratedthe comparative unpreparedness of the civilian medicaland emergency services. Mass casualties were avoidednot as a consequence of the medical response, but be-cause of the ineff|ciency of the device used to deploy re-latively impure Sarin.This article aims to provide a basicunderstanding of the nature of CWmost likely to be en-countered and the treatment regimes for the effectsthey produce.

CLASSIFICATIONOFCWAGENTSIn the past themilitary classif|ed CWagents on the basisof a simplif|edmechanism of action (Table1) and thismay

still be used as a guide to the recognition of the rangesymptoms produced.

GENERALCONSIDERATIONSREGARDINGTREATMENTOFCWCASUALTIES

1. Protect yourselfFall personnel must be equippedwith appropriate personal protection andbe familiarwithworking in such equipment.

2. Any incident involving CW agents in civilian practicewill need tobenotif|ed toyour local Fire Servicewhowill have a Chemical Incident Plan covering acciden-tal releases of hazardousmaterials (HAZMAT Plan).3

3. Casualties must be decontaminated thoroughly in adesignated area with its own ventilation system,water supply and drainage prior to admission to thehospitals normal resuscitation area. Very few UKhospitals have such decontamination areas and por-table, inflatable decontamination suites have beenproduced.

4. Remember casualties’ clothing andwoundsmay tendto‘off-gas’during the earlyphase anddiscardedcloth-ing should be regarded as dangerous.

5. The earlier casualties are decontaminated and trea-ted the greater the likelihood of survival.

6. Once decontaminated the casualties shouldbe handed over from the ‘dirty’ to the ‘clean’ area.PersonnelmustNOTcross fromonezone to the other.

7. Casualties may be mildly or severely affected; anexperienced Doctor may need to be allocated tothe decontamination area to take life or deathTriagedecisions. This person should not return to theclean areawithout complete decontamination.

8. Early identif|cation of the CW agent responsible isvital to ensure appropriate treatment. Fire ServiceFigure1 Full individualprotective equipment.

Table1 Classif|cation of CWagents

Militaryclassif|cation

Type of agent

Damagingagents(blister)

Sulphur and Nitrogenmustards

Lethal agents(nerve)

Nerve gases e.g.Sarin,Tabun,Vagents

Lethal agents(choking)

Lungdamagingagents e.g.chlorine andphosgene

Lethal agents(blood)

Cyanide compounds

In addition to the above Riot Control Agents such as CS gasmaybe includedunder theheading of sensoryirritants.

150 CURRENTANAESTHESIA & CRITICALCARE

andMilitary expertise in this area should be identif|edin the hospital Major Incident Plan.

9. Plans must be in place to deal with the ‘worriedwell’ who will often be far more numerous than thevictims.

10.Staff must be educated in dealing with Chemical inci-dents and regular reviews of practice undertaken.

TOXICOLOGYOF INDIVIDUALAGENTS

Sulphur andnitrogenmustards4

The f|rst vesicant (blister producing) agent, Sulphurmus-tard, was used at Ypres in July 1917 by the Germans inWWI was known as ‘Mustard Gas’ owing to its charac-teristic smell of mustard and garlic. Its physico-chemicalproperties are shown inTable 2. It is not a gas but an oily,yellowish liquid which slowly vaporizes at room tem-perature. The nitrogen mustards have broadly similarproperties andwill not be discussed in detail.

Sulphur mustard is poorly miscible with water and ifprotected fromwind andrain,maypersist on thegroundfor sometime.Other chemicals may be added to make itmore viscous thereby enhancing its ability to resist hy-drolysis and to prolong the duration of ground contami-nation. Its vapour canpass through ordinaryclothing andin the liquid formwill quickly penetrate ordinary surgicalgloves. Suitable protection such as the standard Britishchemical protection suit, respirator and butyl rubbergloves should bewornwhen decontaminating casualties.Mustard gas caused around120 000 British casualties bythe end of WW I but had a low lethality of around 2%. Itwas rapidly adopted by the British who readily appre-ciated its value as an incapacitating agent producing a pat-tern of wounding that made all but the mildest exposureresult in the need for medical treatment and prolongedhospitalization. It is an alkylating agent that binds withguanine residues in DNA so that the alkylated guanineforms base pairs with thymine rather than cytosineleading to inaccurate protein synthesis and excision of thedamaged codons by ADP ribose DNA polymerase.Howthis biochemical effect produces blistering is not known.

Clinical effects of sulphurmustard

Within 20min to an hour the casualty experiences nau-sea and retching with a gradual onset of occular symp-toms so that after about 6h the eyes become grosslyinflammed and burn intensely. Lachcrymation, blephar-ospasm, rhinorhhoea and severe photophobia develop.The skin blisters develop over the next 24h, most com-monly in the warm, moist flexural areas, particularlyaround the genitals and perineum. Over the next 24hpulmonary symptoms develop and sloughed oropharyn-geal and trachealmucosamaybe coughedup.Temporary

‘blindness’ due to intense blepharospasm may occur.Thereafter recurrent blistering and pigmentation occursand the blisters gradually heal over around 6--8 weekswith gradual desquamation of hyperpigmented areaswhich looks like viteligo.Corneal damagemay occur par-ticularly with secondary infection.

Treatment of sulphurmustard casualties 5

After casualties have been decontaminated (adsorptionof liquid mustard by fullers’ earth is the f|rst step, re-moval of contaminated clothing the second) treatmentis symptomatic and aimed at prevention of secondary in-fection.

Blisters break easily and should be aspirated, the fluiddoes not contain active mustard and may be routinelydiscarded. Silver sulphadiazine cream should be usedrather than prophylactic antibiotics. Sterile dry dres-sings are painful to remove and treatment by exposureis acceptable. Analgesia is generally required although inmost superf|cial skin lesions itching is more commonwith the eye lesions beingmost painful.

All casualties with eye injury in civilian practice shouldhave an ophthalmic opinion. Most of the eye pain is re-lated to blepharospasm and regularmydriatic drops suchas hyoscine may be used. Severe pain may be treatedbriefly with amethocaine topically but the frequent sal-inewashouts required to ensure adequate decontamina-tionmakes this diff|cult.Thehead shouldbepositioned toensure that the saline irrigation does not run over theface as in the early stage this could lead to further injury.Chloramphenicol drops should be used to minimize in-fection and petroleum jelly around the lid margins maydecrease sticking of the lids. Eye drops of potassium as-corbate alternating with sodium citrate are recom-mended. If the eyes are open then bright light should beavoided or dark glasses used to help diminish discomfortfromphotophobia.Blindnessrarelyoccursunless cornealscarring or disruption occurs.

Table 2 Physico-chemical properties of Sulphur mus-tard

Property Sulphurmustard

FormulaCH2 -CH2 -Cl

S CH2 -CH2 -Cl

Meltingpoint 141CBoilingpoint 2171CSpecif|c gravity 1.27Vapourpressure at 251C 0.1121mmHg

THE TOXICOLOGYANDTREATMENTOF INJURIES 151

Respiratory function shouldbemonitoredbymeans ofrespiratory rate and pulse oximetry with arterial bloodgas analysis if there is clinical evidence of respiratory fail-ure. Oxygen therapy may be diff|cult to provide if theface has blistered as the pressure of themask may causeskin sloughing. Severe poisoning may cause a chemicalpneumonitis resulting in type 2 respiratory failure whichmay require intubation and ventilation.No guidelines areavailable but it would seem sensible to use a lung protec-tive ventilatory strategy together with recruitmentmanoeuvres.

The majority of casualties will recover (over 6 weeksto 6 months) although some will require skin or cornealgrafts. The majority of those who died in WW I did sofrom septic pulmonary complications. Bonemarrow de-pression may lead to neutropenia and mustards areknown to be carcinogenic.

Nerve agents (NAs)6

Nerve gases were f|rst developed by Schrader in Ger-many between1936 and1944 as a result of research intoorganophosphorus insecticides (Table 3). Tabun (GA-Fethyl N, N-dimethyl-phosphoramidocyanidate) wasthe f|rst to be synthesized followed by Sarin (GBFiso-propylmethylphosphorofluoridate) and Soman(GDF1,2,2, trimethylpropylmethyl-phosphonofluori-date). After WW II a series of even more toxic agentse.g. VX (O-ethyl-S-2-di-isopropylamino-ethyl-methyl-phosphonthiolate) were developed. The original nerveagent,Tabun, like all theNAs is producedbyester or ami-dation of phosphonic acid. After Schrader realized its ex-treme lethality as an insecticide it was tested on dogsandprimates.Theyrapidly lost allmuscular control, vom-ited, defaecated, twitched uncontrollably and developedpinpoint pupils before developing grand mal convulsionsand then died. Accidents during manufacture showedthat humans died in an identical manner. Its potential asa weapon of war was enhanced by it being virtuallyodourless, colourless and was lethal by either inhalationor penetration through the skin.Their f|rst documenteduse in combat was during the Iran--Iraq war at Basra byIraqi forces usingTabun.

Mechanism ofaction

They are all long-acting organophosphorous inhibitors ofacetylcholinesterase (AChE) which act by alkyl phos-

phorylation of a hydroxyl group at the esteratic site ofthe enzyme.7, 8 This results in the enzyme being unableto hydrolyse acetylcholinewith theresult that its central,muscarinic and nicotinic effects continue unabated.The long-term effects of NAs on AChE and ACh arenot known although there is evidence from organopho-sphate poisoning that polyneuropathy may occur whichis suggestive of some sort of permanent damage.9

Clinical features 10

The pattern of onset and precise clinical effects vary de-pending on the NA itself, the dose, the mode of expo-sure, e.g. percutaneous, ocular, inhalational, etc. thepresence or absence of protective clothing, and thedura-tion of exposure. To some extent the symptoms reflectthe % inhibition of AChE.Muscarinic effects includemio-sis, ciliarybody spasm, salivation, bronchorhhoea, crying,sweating, bradycardia, vomiting, diarrhoea and faecaland urinary incontinence. The predominant nicotinic ef-fects are aremuscular fasciculation, weakness and f|nally,paralysis.Centralnervous systemeffects range fromirrit-ability, fatigue, giddiness and ataxia through lethargy, am-nesia, convulsions, coma and respiratory depressionleading to apnoea.These features should last for at least24--48h in peoplewho survive to reachmedical aid.

Treatment

The general principles described earlier are vitally im-portant as very small quantities of NA that are missedon decontamination arepotentially lethal.11Fullers’ earthand dilute bleach solutions (0.5% sodium hypochlorite)are the bestmeans of decontamination. Effective decon-taminationmay be assessed using commercially availablechemical agent monitors that ‘sniff’ for NA vapour off-gassing from the victim’s clothing, skin or wounds. Vic-tims who present with respiratory arrest have virtually100% of their AChE inactivated but if ventilatory sup-port is initiated it is theoretically possible that theymaysurvive.Drug therapy should consist of cholinolytics, re-activators of AChE and anticonvulsants. Even if the ear-liest signs of NA poisoning are present, miosis,headache, lacrimation and bronchospasm, then intrave-nous atropine in 2mg increments should be given imme-diately as progression of symptoms may be very rapid.The dose shouldbe titrated to achievepupilary dilatationand apulserate of above 80 perminute.12 Toomuch atro-pine will cause urinary retention, tachydysrhythmias,and drying of bronchial secretions.

The oxime, pralidoxime, methanesulphonate, shouldbe given in conjunction with atropine to antagonize thenicotinic effects of NA poisoning. NA binds to AChE toform irreversible covalent bonds, a process knownas ‘ageing’. Ageing occurs at different rates depend-ing on the NA concerned. Ageing takes 2min forSoman, 5h for Sarin, 13h for Tabun and up to 48h for

Table 3 Physico-chemicalproperties of nerve agents

Agent Tabun Sarin Soman VX

MW 162 140 182 267VPat 201C 0.036 2.10 0.27 0.044LD50mg/kg IV 0.08 0.01 0.025 0.007

152 CURRENTANAESTHESIA & CRITICALCARE

VX. If pralidoxime is given early enough then itmay reac-tivate AChE by de-phosphorylating the esteratic site ofthe enzyme. A total of 15--30mg/kg should be given byslow IV injection over 20min in conjunction with atro-pine.The dosemay be repeated after 4h.13

Convulsions may be treated acutely with bolus dosesof benzodiazepines but victims may require continuoussedation, intubation for airway protection and ventila-tion inwhich case continuous infusionsmay be used.

In military environments where exposure NA is con-sidered a tactical possibility then ‘Nerve Agent Pyridos-tigmine Pre-treatment’ (NAPP) tablets may be takenprophylactically.14 Pyridostigmine (30mg) is taken every8h with the view of the pyridostigmine binding to some(about 30%) of the body’s AChE as a carbamate makingsuch enzymes inaccessible to covalent binding by NAs.The AChE/carbamate complex splits spontaneously un-less the NAPP treatment continues thereby liberatingthe normal enzyme, which should decrease the intensityof the cholinergic effects of NAs. Such pre-treatment istheoretically advantageous where the NA threat in-volvesrapidly ageing agents such as Soman.Whendealingwith casualties needing anaesthesia and muscle relaxa-tion who have taken NAPP tablets, the anaesthetistshould be aware that they are more sensitive to suxa-methoniumbutmoreresistant to non-depolarizingmus-cle relaxants.

Lung damaging agents

Phosgene15

Although chlorine was the f|rst lung damaging, choking,gas used during WWI, phosgene was by far the mostlethal causing 85% of deaths resulting from gaseous CWexposure. Phosgene (COCl2 ) is a by-product ofmany in-dustrial chemical processes. It is easily stored and dis-persed but is of short persistence. Modern respiratorsprovide effective protection and to be effective it mustbe inhaled. It would probably cause greater casualtynumbers if used against an unprotected population. It isnot readily detected by commercially available monitorsbut has a characteristic odour of new mown hay whichmaybe detected at concentrations as low as1.5ppm. It isheavier than air and inWWIwas noted to collect in cel-lars, Dug-outs and the bottom of trenches.

Mechanism of action. The mechanism of action isunclear, it was initially thought was that phosgenedissolved in water in the respiratory tract and formedhydrochloric acid producing a direct chemical injuryalthough it seems more likely that carbonyl free radicalformation ismore likely.

Clinical effects and treatment.16 Exposure to a lethaldose may not immediately produce symptoms for

several hours following exposure and gross pulmonaryoedema is produced after a latent period whichmay lastfrom 30min to 24h.Dyspnoea, cough and cyanosis thendevelops followed by copious loss of pulmonary oedemafluid of over a litre per hour. Exercise during the latentperiod was reported to exacerbate symptoms and bedrest is recommended for anyone suspected of havingbeen exposed. Thereafter the treatment is supportivewith oxygen therapy. There is no evidence base forsteroid use in human practice but it has beenrecommended. Intubation, ventilation with a lungprotective strategy and PEEP would seem to be sensiblein theory but there is no evidence for its use in humans.

Blood agents

Only hydrogen cyanide was used inWWI but was rela-tively ineffective as its low density means the gas rapidlyrises and disperses. Its use as a terrorist weapon rests inits eff|cacy if deployed in enclosed spaces. Its notorietyrests on its use in Nazi extermination camps in WWII.It is relatively unstable and decomposes rapidly to be-come ineffective. It is a readily available by product ofmany chemical processes but its appeal to terroristsmaybe diminishedby its insatability on storage.The clas-sical smell of bitter almonds is detectable at sub-lethallevels. Such is its rapidity of action that victims who sur-vive to reachmedical aidwill havebeen subjected to sub-lethal doses. Estimates of toxicity to humans suggestthat mild symptoms of dizziness and nausea may occurat exposures of 50--60mg/m3 for up to an hour but thatexposures of over100mg/m3 for only 30min are likely tobe lethal.Tissue hypoxia occurs as the result of cessationof cytochrome oxidase activity caused by the binging oftrivalent iron atomswith the enzyme to cyanide.The re-sulting tissue hypoxia causes confusion, dizziness, airhunger, grandmal convulsions, coma and respiratory ar-rest. If victims survive to reach hospital they have a pro-found metabolic acidosis and high lactate levels witha low arterio-venous oxygen difference owing to lowtissue oxygen uptake. Pulse oximetry is normal. Thetreatment involves the rapid administration ofantidotes including sodium thiosulphate (150mg/kg IVover 10min), which converts cyanide to thiocyanatewhich does not block cytochrome electron transfer. Itshould be given along with sodium nitrite (300mg IVover 10min) which converts haemoglobin to methae-moglobin which binds to any remaining cyanide. Othercyanide chelating agents include hydroxycobalamin anddicobalt edetate.17

CONCLUSIONChemical warfare agents are most effective as weaponsof mass destruction when used against unprepared

THE TOXICOLOGYANDTREATMENTOF INJURIES 153

civilian populations.The technology for their productionis considerably easier and cheaper to acquire than thatneeded to produce a thermonuclear device. No matterwhatgovernments agree to, andnomatter what treatiesare signed, terrorists, or rouge states look towards che-mical weapons as providing massive offence capabilityandknow that their ‘best’use is against non-military tar-gets. Everymajor hospital should have a Major ChemicalIncident or ‘HAZMAT’plan and in 2002, it appears that aknowledge of the effects of these agents and a plan fordealing with chemical casualties should form a compo-nent of such plans.

REFERENCES

1. Paxman J, Harris R A. Higher Form of Killing: The Secret Story of

Chemical and Biological Warfare. New York: Hill and Wang, 1982.

2. Okumura T, Suzuki K, Fukuda A, et al. The Tokyo subway sarin

attack: disaster management, Part 2: hospital response. Acad.

Emerg. Med. 1998; 5(6): 618--624.

3. Moles T M. Emergency medical services systems and HAZMAT

major incidents. Resuscitation 1999; 42: 103--116.

4. Borak J, Sidell F R. Agents of chemical warfare: sulfur mustard. Ann

EmergMed 1992; 21: 303--308.

5. Willems J L. Clinical management of mustard gas casualties. Ann

Med Milit Belg 1989; 3(Suppl): 1--61.

6. Weinbroum A A, Rudick V, Paret G, Kluger Y, Ben Abraham R.

Anaesthesia and critical care considerations in nerve agent warfare

trauma casualties. Resuscitation 2000; 47(2): 113--123.

7. Karalliedde L. Organophosphorous poisoning, anaesthesia. Anaes-

thesia 1999; 54: 1073--1088.

8. Maynard R L, Beswick F W. Organophosphorous compounds as

chemical warfare agents. In: Ballantyne B, Marrs T C. (eds.) Clinical

and Experimental Toxicology of Organophosphates and Carba-

mates. Butterworth-Heinemann, Oxford 1992; 373--385.

9. Lotti M. The pathogenesis of organophosphate polyneuropathy.

Crit. Rev. Toxicol 1991; 21(6): 465--487.

10. Maynard R L. Toxicology of chemical warfare agents. In: Ballantyne

B, Marrs T C, Syversen T. (Eds.),General and Applied Toxicology,

Vol. 3, 2nd edn. London: MacMillan 1999; 2092--2095.

11. Nozaki H, Hori S, Shinozawa Y, et al. Secondary exposusre of

medical staff to sarin vapor in the emergency room. Inten Care

Med 1995; 21(12): 1032--1035.

12. Nozaki H, Hori S, Shinozawa Y et al. Relationship between pupil

size and acetylcholinesterase activity in patients exposed to sarin

vapor. Inten Care Med 1997; 23(9): 1005--1007.

13. Dawson R M. Review of oximes available for treatment of nerve

agent poisoning. J Appl Toxicol 1994; 14: 317--331.

14. Keeler J R, Hurst C G, Dunn M A. Pyridostigmine used as a nerve

agent pretreatment under wartime conditions. JAMA 1991; 226(5):

693--695.

15. Everett E D, Overholt E L. Phosgene poisoning. JAMA 1968;

205(4): 243--245.

16. Diller W F. Medicalphosgeneproblems, their possible solution. J

Occup Med 1978; 20: 189--193.

17. Vogel S N, Sultan T R, Ten Eyck R P. Cyanide poisoning. Clin

Toxicol 1981; 18(3): 367--383.

154 CURRENTANAESTHESIA & CRITICALCARE