intoxicación aguda por cianuro con una actualización del tratamiento

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doi: 10.4037/ccn2011799 2011;31:72-82Crit Care Nurse Jillian HamelA Review of Acute Cyanide Poisoning With a Treatment Update

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Knowledge of the pathophysiol-ogy of acute cyanide poisoning andits antidotes in combination withthe ability to tailor management of apatient’s care to this unique situa-tion will be critical to the patient’srecovery. In this article, I discuss thepathophysiology of acute cyanidepoisoning and detail the benefitsand challenges of the antidotes cur-rently available.

Life-threatening cyanide poison-ing is treatable when quickly recog-nized and immediately counteredwith an antidote. A delay in admin-istration of an antidote can be dev-astating, allowing time for hypoxicbrain injury, cardiovascular com-promise, and death within minutesto hours.1 Ideally, an antidoteshould be administered at the sceneimmediately after the patient isremoved from the source ofcyanide.1 Unfortunately, no tests forrapid confirmation of cyanide poi-soning exist, so treatment must bebased on a presumptive diagnosis.Because treatment of personsexposed to cyanide is most oftenaway from a hospital and providedby medical personnel with limitedresources and time, the idealcyanide antidote would be quickly

Jillian Hamel, MS, ACNP-BC, CCNS, CCRN

A Review of AcuteCyanide PoisoningWith a Treatment Update

Toxicology

Although initially awake when emer-gency technicians were called to thescene, the patient became unrespon-sive and pulseless en route. After 2rounds of cardiopulmonary resuscita-tion and injections of epinephrine andatropine, the patient has regained apulse. At the hospital, the emergencydepartment team administers hydrox-ocobalamin and a sedative, intubatesthe patient, and transfers him to theICU. The complex process of manag-ing a patient with acute cyanide poi-soning begins as the critical carenurse notes the patient has cool, grayskin; blood pressure 100/50 mm Hg;heart rate 128/min; and oxygensaturation 98% on 100% fraction ofinspired oxygen.

Apatient who has occupa-tional access to cyanidearrives in the intensivecare unit (ICU) afteringesting the compound

in an apparent suicide attempt.

Cyanide causes intracellular hypoxia by reversibly binding to mitochondrialcytochrome oxidase a3. Signs and symptoms of cyanide poisoning usually occur lessthan 1 minute after inhalation and within a few minutes after ingestion. Early mani-festations include anxiety, headache, giddiness, inability to focus the eyes, and mydri-asis. As hypoxia progresses, progressively lower levels of consciousness, seizures, andcoma can occur. Skin may look normal or slightly ashen, and arterial oxygen satura-tion may be normal. Early respiratory signs include transient rapid and deep respira-tions. As poisoning progresses, hemodynamic status may become unstable. The keytreatment is early administration of 1 of the 2 antidotes currently available in theUnited States: the well-known cyanide antidote kit and hydroxocobalamin. Hydrox-ocobalamin detoxifies cyanide by binding with it to form the renally excreted, non-toxic cyanocobalamin. Because it binds with cyanide without formingmethemoglobin,hydroxocobalamin can be used to treat patients without compromising the oxygen-carrying capacity of hemoglobin. (Critical Care Nurse. 2011;31[1]:72-82)

©2011 American Association of Critical-Care Nurses doi: 10.4037/ccn2011799

This article has been designated for CE credit.A closed-book, multiple-choice examinationfollows this article, which tests your knowl-edge of the following objectives:

1. Understand the pathophysiology of acutecyanide poisoning

2. Recognize the importance of immediateantidote administration in the setting ofacute cyanide poisoning

3. Differentiate the 2 available acute cyanidepoisoning antidotes

CEContinuing Education

72 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org


http://ccn.aacnjournals.org


effective and have little to notreatment-limiting adverse effects.2

Cyanide is traditionally knownas a poison and has been used inmass homicides, in suicides, and asa weapon of war. A fruit-flavoreddrink (Kool-Aid) laced with potas-sium cyanide was the causative agentin the mass suicide of the membersof the People’s Temple in Jonestown,Guyana, in 1978.3 During WorldWar II, the Nazis used cyanide as anagent of genocide in gas chambers.4

Unintentional exposures to cyanideare also possible, as in smoke inhala-tion in fires in enclosed spaces or inoccupations in which cyanide is usedin industrial processes.5

Cyanide’s molecular structureconsists of a cyano group (a carbontriple-bonded to nitrogen) in combi-nation with other elements such aspotassium or hydrogen. Cyanide canbe a salt, a liquid or a gas. Once itenters the bloodstream, cyaniderapidly reacts with metals such asferric ions, binding to and haltingcritical enzymatic cascades, leadingto central nervous system and car-diovascular impairment.5

The annual report of theNational Poison Data System of theAmerican Association of PoisonControl Centers documented 247reported cases of chemical expo-sures to cyanide in the United Statesin 2007; of the 247, 5 were fatal.6

The number of reported cases is rel-atively small because poisonings in

adults, occupa-tional expo-sures, andfatalities aretypically under-reported to theNational PoisonData System.Nevertheless,the small num-ber does notdiminish thedevastatingeffect of acutecyanide poison-ing, the rapidprogression ofthe poisoning, and the need forquick recognition and intervention.Health care providers must be alertfor suspected poisoning and provideprompt administration of empiricantidotal therapy for successfultreatment.

Etiology ofCyanide Poisoning

Cyanide has many natural,industrial, and even householdsources (Table 1). Smoke inhalationfrom structural fires is the mostcommon cause of cyanide poisoningin Western countries.7 Materialssuch as wool, silk, and syntheticpolymers contain carbon and nitro-gen and may produce cyanide gaswhen exposed to high temperaturesduring thermal breakdown.8-10

Although carbon monoxide is

traditionally associated with mor-bidity and mortality from smokeinhalation, prospective studies5,11 inwhich cyanide concentrations aftersmoke exposure were measuredindicated that cyanide poisoning cancontribute independently andmarkedly to illness and death.

Cyanide is used in industrialprocesses that require electroplatingand the polishing of metals. Cyanidesalts such as mercury cyanide, cop-per cyanide, gold cyanide, and silvercyanide produce hydrogen cyanidegas when combined with acids, cre-ating the opportunity for industrialaccidents or purposeful harmfulexposures.8,9 Cyanide is also foundin insecticides used for some com-mercial mass fumigations.8

Iatrogenic sources of cyanideinclude administration of the intra-venous antihypertensive sodiumnitroprusside. Nitroprusside canbe cyanogenic; it is 44% cyanide bymolar weight. Cyanide groups arereleased from the nitroprussidemolecule nonenzymatically. In theliver, the enzyme rhodanese thencatalyzes the conversion of cyanide

When this article was written, Jillian Hamel was a nurse practitioner in cardiology at theUniversity of Maryland Medical Center in Baltimore.

Author

Corresponding author: Jillian Hamel, MS, ACNP-BC, CCNS, CCRN, Division of Cardiology, University of MarylandMedical Center, 22 S. Greene Street, Baltimore, MD 21201 (e-mail: [email protected]).

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656.Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].

Table 1 Potential sources of cyanide exposurea

Industrial sourcesInsecticidesPhotographic solutionsMetal polishing materialsJewelry cleanersAcetonitrileElectroplating materialsSynthetic products such as rayon, nylon, polyurethane foam,insulation, and adhesive resins

Natural sourcesSeeds and fruit pits of Prunus species (eg, apple seeds andcherry and apricot pits)

Environmental sourcesSmoke inhalation in closed-space fires

Iatrogenic sourcesSodium nitroprusside infusion

a Based on data from Borron,7 Schnepp,8 and Shepherd and Velez.9

www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 73




to thiocyanate, which is normallyexcreted through the kidneys. Poi-soning may be due to a defect incyanide metabolism or to an accu-mulation of thiocyanate during anadministration period of severaldays or more.4,12 Particularly inpatients with impaired renal func-tion, cyanide poisoning may occurbecause the patients are unable toexcrete thiocyanate at a sufficientrate.4 Careful screening of renalfunction may aid in avoiding poison-ing in patients who require sodiumnitroprusside infusions. Serial moni-toring can reveal elevations in theserum level of cyanhemoglobin orcyanmethemoglobin. Levels greaterthan 10 mg/dL confirm thiocyanatepoisoning and are an indication tostop therapy.12

Nitriles are a form of cyanidefound in solvents and glue removers.Acetonitrile and propionitrile arethe most commonly encounterednitriles. Metabolized to cyanide inthe liver, acetonitrile is the activeingredient in artificial nail removersand has been linked to cases ofcyanide poisoning.8,11

Although not a common cause ofpoisoning, natural sources can pro-duce cyanide poisoning when takenin large quantities or when they arepackaged as alternative medicines,such as Laetrile. Cyanide occurs nat-urally in amygdalin, a cyanogenicglucoside. Amygdalin occurs in lowconcentrations in the seeds and fruitpits (eg, apple seeds, cherry pits,bitter almonds, and apricot pits) ofPrunus species.

Pathophysiology of AcuteCyanide Poisoning

Cyanide is highly lethal becauseit diffuses into tissues and binds to

target sites within seconds.9 Intra-venous and inhaled exposures pro-duce more rapid onset of signs andsymptoms than does oral ingestionbecause the first 2 routes provide fastdiffusion and direct distribution totarget organs via the bloodstream.13

Oral or transdermal ingestion mayproduce a delay in signs and symp-toms as concentrations increase inthe bloodstream.5

The primary mechanism ofcyanide excretion is formation of thio-cyanate within the liver. Rhodanesecatalyzes the conversion of cyanide tothiocyanate, and thiocyanate is thenexcreted via the kidneys9 (Figure 1).This mechanism is overwhelmed byhigh doses of cyanide in acute poi-soning or in patients with decreasedkidney function.13

The toxicity of cyanide is largelyattributed to the cessation of aero-bic cell metabolism. Cyanide causesintracellular hypoxia by reversiblybinding to the cytochrome oxidasea3 within the mitochondria. Cyto-chrome oxidase a3 is necessary for

the reduction of oxygen to water inthe fourth complex of oxidative phos-phorylation. Binding of cyanide tothe ferric ion in cytochrome oxidasea3 inhibits the terminal enzyme inthe respiratory chain and haltselectron transport and oxidativephosphorylation5 (Figure 2). Thisdownward cascade is fatal if notreversed. Oxidative phosphorylationis essential to the synthesis of adeno-sine triphosphate (ATP) and thecontinuation of cellular respiration.

Figure 1 Metabolism of cyanide: theenzyme rhodanese catalyzes conver-sion of cyanide to the nontoxic thio-cyanate in the liver, and the thiocyanateis then excreted via the kidneys.

CyanideRhodanese

Thiocyanate

Excreted viathe kidneys

Figure 2 Effect of cyanide on cellular respiration: cyanide reversibly binds to theferric ion in cytochrome oxidase a3 within the mitochondria, effectively haltingcellular respiration by blocking the reduction of oxygen to water.

Abbreviation: ATP, adenosine triphosphate.

2 H++ 1⁄2O2→ H2O(Necessary for ATP generation)

Ferric ion(Fe3+)

Cyanide

Cytochromeoxidase a3

Mitochondrion

Anaerobic metabolismLactic acidosis





As supplies of ATP become depleted,mitochondria cannot extract or usethe oxygen they are exposed to. As aresult, metabolism shifts to glycoly-sis through anaerobic metabolism,an inefficient mechanism for energyneeds, and produces lactate. Pro-duction of lactate results in a high-anion-gap metabolic acidosis.5,9 Pooroxygen extraction associated withcessation of aerobic cellular respira-tion also leads to an accumulationof oxygen in the venous supply. Inthis situation, the problem is notdelivery of oxygen but extractionand utilization of oxygen at the cel-lular level. The increased oxygena-tion of venous blood also explainsthe presence of elevated venous levelof oxygen indicated by blood gasanalysis and a reduced arteriove-nous oxygen saturation difference(<10 mm Hg).13 Some cyanide alsobinds to the ferric form of hemoglo-bin (a transient physiological formof methemoglobin), which accountsfor normally 1% to 2% of all hemoglo-bin. Binding of cyanide to the ferricform makes this type of hemoglobinincapable of transporting oxygen.5

Clinical ManifestationsThe clinical manifestations of

cyanide poisoning are largely areflection of intracellular hypoxia(Table 2). The onset of signs andsymptoms is usually less than 1minute after inhalation and withina few minutes after ingestion.5 Earlyneurological manifestations includeanxiety, headache, and giddiness.Patients may be unable to focus theireyes, and mydriasis may developbecause of hypoxia. As hypoxia pro-gresses, patients may experienceprogressively lower levels of con-sciousness, seizures, and coma.4,13

In acute cyanide poisoning, theskin may have a normal or a slightlyashen appearance despite tissuehypoxia, and arterial oxygen satura-tion may also be normal. Early res-piratory signs of cyanide poisoninginclude transient rapid and deeprespirations.4,5 This respiratorychange reflects stimulation ofperipheral and central chemorecep-tors within the brain stem in anattempt to overcome tissue hypoxia.

Cyanide has a profound hypoxiceffect on the cardiovascular system.Patients may initially have palpita-tions, diaphoresis, dizziness, orflushing. They may have an initialincrease in cardiac output andblood pressure associated with cat-echolamine release. Vasodilatation,

hypotension, and a decrease in theinotropic ability of the heart ensue,with shunting of blood to the brainand heart.4 Cyanide depresses thesinoatrial node, causes an increasein arrhythmias, and decreases theforce of contraction of the heart.4

As poisoning progresses, patients’hemodynamic status may becomeunstable, with ventricular arrhyth-mias, bradycardia, heart block, car-diac arrest, and death.4

Serum concentrations of cyanidegreater than 0.5 mg/L are typicallyassociated with acute cyanide poi-soning.7 Unfortunately this findingis not helpful in the initial diagnosisand management of acute poisoningbecause of cyanide’s rapid action andlethality. Furthermore, measurement

Table 2 Clinical manifestations of cyanide’s toxic effecta

System

Central nervous

Respiratory

Cardiovascular

Manifestations

Early (due to hypoxia)AnxietyHeadacheGiddinessDizzinessConfusionMydriasisBright retinal veins (elevated venous PO2)

LateDecreased consciousnessSeizuresParalysisComa

EarlyHyperventilation and tachypnea (due to hypoxic stimulationof peripheral and central chemoreceptors)

LateAbsence of cyanosis (caused by an increase in oxygencontent in venous blood)

HypoventilationApnea (cells cannot take up oxygen)

EarlyTachycardia

LateHypotensionSupraventricular tachycardiaAtrioventricular blocksVentricular fibrillationAsystole

a Based on data from DesLauriers et al,4 Hall et al,5 and Nelson.13





of serum cyanide levels may requireseveral days, depending on the labo-ratory facility.5 Serum cyanide con-centrations also do not correlatewith specific degrees of severity.Borron7 addressed this issue byexamining serial lactate levels as analternative way to assess the severityof cyanide poisoning. He reportedthat serum lactate levels greaterthan 8 mmol/L are associated withacute poisoning and may aid indetermining the need for repeatedantidotal therapy. However, lacticacidosis is not specific to cyanidepoisoning, and future research isstill needed to find a rapid test toaid in diagnosis of this poisoning.

ManagementInitial management of patients

with acute cyanide poisoning requiresrapid assessment and identificationof the most likely route of exposure

to determine proper decontamina-tion (Table 3). Patients with sus-pected inhalation exposure shouldfirst undergo decontamination bybeing evacuated from the contami-nated area and having affectedclothing removed.5,9,14 For patientswith oral ingestion who have vom-ited or spilled liquid on their skinor clothing, care must be taken byhealth care providers to avoid sec-ondary contamination. Providersshould use personal protectiveequipment per the hospital stan-dard. During decontamination, theprotective steps may include usingface masks, eye shields, and doublegloving, with frequent replacementof gloves or the use of butyl rubbergloves, which have a breakthroughtime of 1 to 4 hours.7,14 Emesis shouldnot be induced in patients with sus-pected ingestion. Activated charcoalmay be administered if the patient

is alert, the time is within 1 hour ofthe suspected oral ingestion, andadministration is not otherwisecontraindicated. Although it maynot be effective in countering acutecyanide poisoning because of thehigh potency of cyanide, the rapidonset of poisoning, and the smallsize of cyanide molecules, activatedcharcoal may be useful in patientswho may have ingested another poi-son in addition to cyanide.9

Because cyanide causes a decreasein oxygen utilization, the adminis-tration of 100% oxygen by nonre-breather mask or endotracheal tubeis indicated in acute poisoning.10

Although 100% oxygen will not cor-rect the problem, it may enhancethe effectiveness of antidotal therapyby competing with cyanide for thecytochrome oxidase binding sites.10

After decontamination and life-support measures are started, the

Table 3 Management of patients with acute cyanide poisoninga

Supportive care

Admit to an intensive careunit for cardiac monitor-ing, respiratory and car-diovascular support

Perform routine laboratorytesting, including arterialblood gas analysis, serumlactate levels, completeblood cell counts, serumglucose level, a serumcyanide level (confirma-tory), and electrolytelevels

Monitor and treat dysrhyth-mias

Monitor for and treatadverse effects of antidotaltherapy

Antidotal therapy

Administer thecyanide antidotekit or hydroxo-cobalamin oncean airway hasbeen secured

Basic LifeSupport/Advanced

Cardiac Life Support(ACLS)

Establish ABCs (airway,breathing, circulation)

Establish intravenousaccess

Start cardiac monitoringStart ACLS if respiratoryor cardiovascular com-promise evident

a Based on data from Koschel.14b Protection of responders from contamination is essential with the use of personal protective equipment such as face masks, eye shields, and frequent doublegloving or the use of butyl rubber gloves.

Decontamination

Smoke inhalationRemove from source into fresh airRemove contaminated clothing

Dermal exposurebRemove wet clothingWash skin with soap and water or water aloneIrrigate exposed eyes with water or salineRemove contact lenses

IngestionDo not induce emesisActivated charcoal may be administered if the victimis alert and the ingestion occurred within 1 hour

Isolate emesis (it may emit hydrogen cyanide)





key to treatment of cyanide poison-ing is early administration of anantidote.2 The decision to adminis-ter the antidote must often be madeempirically, without full knowledgeof the patient’s underlying healthstatus or complicating factors. Theavailable antidotes are discussed indetail in the following section.

Additional supportive careincludes controlling seizures withanticonvulsants, cardiac monitor-ing to evaluate and treat dysrhyth-mias and conduction defects, andblood pressure support with fluidsand vasopressors. Care should betaken when administering intra-venous fluids, because noncardio-genic pulmonary edema can developin patients with cyanide poisoning.Hyperbaric oxygenmay have a role intherapy, but its use remains contro-versial and is not standard practice.

Routine laboratory studiesinclude arterial blood gas analysis,measurement of serum lactate lev-els, a complete blood cell count,measurement of serum glucose andelectrolyte levels, and determina-tion of the serum cyanide level for

confirmation. Common laboratoryfindings in cyanide poisoning includemetabolic acidosis, plasma lactatelevel greater than 8 mmol/L, andreduced arteriovenous oxygen satu-ration difference (<10 mm Hg).

AntidotesCurrently, 2 antidotes for acute

cyanide poisoning are available inthe United States: the cyanide anti-dote kit, which has been in use inthe United States for decades, andhydroxocobalamin, which wasapproved by the Food and DrugAdministration in December 2006.Approval of hydroxocobalamin issignificant; because of its low inci-dence of adverse events, it is a poten-tially acceptable choice in prehospitalsettings.1,8,9 Hydroxocobalamin alsoappears to be safer than the cyanideantidote kit in patients who havepreexisting hypotension, inhaledthe poison in smoke in a closed space,or are pregnant. An understandingof both available antidotes and theirrespective benefits, contraindications,side effects, and monitoring require-ments is essential to the proper care

and management of patients withacute cyanide poisoning.

Cyanide Antidote KitThe cyanide antidote kit has been

used for decades in the United Statesfor acute cyanide poisoning on thebasis of the animal studies and clini-cal reports of Chen and Rose in themid-twentieth century.9,15 Death ratesin the United States associated withcyanide poisoning have decreasedsince the 1930s, most likely becauseof the use of the cyanide antidotekit.10 This kit consists of 3 medica-tions given together for their syner-gistic effect: amyl nitrite, sodiumnitrite, and sodium thiosulfate. Amylnitrite is administered via inhalationover 15 to 30 seconds while intra-venous access is established. Sodiumnitrite is then administered intra-venously over 3 to 5 minutes, andthen intravenous sodium thiosulfateover 30 minutes (Table 4).

The 2 nitrites are administeredto form methemoglobin and bindcyanide.9 Nitrites oxidize the iron inhemoglobin to form cyanmethemo-globin (Figure 3). Because cyanide

Dosing

Crushed 0.3-mL ampule inhaled for 15 seconds; may repeat 3-5 minutesuntil intravenous access established

Amyl nitrite should be discontinued once intravenous access is obtainedand sodium nitrite infusion is started

300 mg (10 mL in a 3% solution) or 10 mg/kg given intravenously for 3-5minutes (a rate of 2.5-5 mL/min) in adults

6-8 mL/m2, or 0.2 mL/kg in children, not to exceed 10 mL

1 ampule, or 12.5 g in 50 mL, given intravenously for 30 minutes in adults

The dosage for children is 7 g/m2, not to exceed 12.5 g

5 g for adults, administered intravenously for 15 minutes, repeat a halfdose if needed; 70 mg/kg in children

Table 4 The cyanide antidote kit and hydroxocobalamina

Medication

Amyl nitrite

Sodium nitrite

Sodium thiosulfate

Hydroxocobalamin

Mechanism of action

Induces methemoglobinemia viaoxidation to bind cyanide

Induces methemoglobinemia viaoxidation to bind cyanide

Combines with unbound cyanide toform renally excreted thiocyanate

Combines with unbound cyanide toform cyanocobalamin

a Based on data from Koschel.14

Hydroxocobalamin





appears to bind preferentially tothe ferric ion of methemoglobinrather than to the ferric ion of thecytochrome oxidase a3 in the mito-chondria, cyanmethemoglobin drawscyanide away from the mitochondria.This process frees the mitochondriafor electron transport and return toaerobic cellular respiration. The cellsare able to generate ATP, and theproduction of lactic acid ceases.Sodium thiosulfate is administeredin combination with the nitrites toclear cyanide by acting as a sulfhydryldonor.9 The unbound, extracellularcyanide binds with sulfur of thiosul-fate to form the renally excretedthiocyanate.9

When the cyanide antidote kit isused, critical care nurses must watchfor vasodilatation and hypotension,important adverse effects of nitrites9

(Table 5). Sodium nitrite must be

administeredslowly, over atleast 3 to 5 min-utes, with fre-quent bloodpressure moni-toring. Hypoten-sion can betreated with

intravenous fluid and vasopressors.Another important considera-

tion is the production of methemo-globin. Although this process freescells to continue aerobic metabo-lism, methemoglobinemia reducesthe level of functional circulatinghemoglobin and may exacerbateconditions in certain patients, suchas those with concurrent carbonmonoxide poisoning or those withpoor cardiopulmonary reserve, byworsening the patients’ deficit inoxygen-carrying capacity.5,9 Nitritesshould also be avoided in pregnantpatients because of the oxidativestress on fetal hemoglobin.9 Sodiumthiosulfate occasionally causes ahypersensitivity reaction andhypotension, depending on the rateof infusion. Although sodium thio-sulfate is a relatively efficaciousantidote for cyanide poisoning, its

slow onset of action is a disadvan-tage for its use as the sole medica-tion in antidotal therapy.9

HydroxocobalaminThe Food and Drug Administra-

tion approved hydroxocobalamin(Cyanokit) for the treatment ofacute cyanide poisoning in Decem-ber 2006.16,17 Each kit contains two250-mL glass vials, and each vialcontains 2.5 g of lyophilized hydrox-ocobalamin. The kit also contains 2sterile transfer spikes and 1 sterileintravenous infusion set. The man-ufacturer recommends storing thepowder form at room temperature,or approximately 25ºC (77ºF). Onceit is reconstituted, the medicationcan be kept at room temperature,but it must be used within 6 hours.An initial starting dose for adults is5 g (two 2.5-g vials) diluted in 0.9%saline and administered over 15minutes (Table 4). A second 5-gdose can be given over 15 minutesto 2 hours thereafter if deemed nec-essary for reversal of signs andsymptoms of cyanide poisoning.5,17

Hydroxocobalamin detoxifiescyanide by binding with it to formthe renally excreted, nontoxic

Figure 3 Nitrites oxidize the iron in hemoglobin to formcyanmethemoglobin.

NNiittrriitteess ++ ooxxyyhheemmoogglloobbiinn ⇒⇒ mmeetthheemmoogglloobbiinn++

ccyyaanniiddee⇓⇓

ccyyaannmmeetthheemmoogglloobbiinn

Table 5 Nursing considerations for the cyanide antidote kit and hydroxocobalamina

Antidote

Cyanide antidote kit

Hydroxocobalamin

Other considerations

Monitoring of methemoglobin levels is indi-cated and should not exceed 20%

Contraindicated in smoke-inhalation patients

Is not considered safe in pregnant patients

Is safe for smoke-inhalation patients

May be used in pregnant patients

May interfere with colorimetric testsbecause of its red color

Effect on blood pressure may be beneficialin patients in shock

Adverse effects

Potent vasodilatation from the nitrites may lead to hypotension

Methemoglobinemia may be harmful or even lethal in patientswho already have a deficiency of oxygen-rich blood, such asthose exposed to carbon monoxide

May cause transient hypertension

Most common adverse effects include reddening of the skin and urine

a Based on data from Shepherd and Velez9 and Koschel.14





cyanocobalamin (vitamin B12).Cyanocobalamin releases cyanideat a rate that is slow enough to allowthe enzyme rhodanese to detoxifythe cyanide in the liver.4 Cyanidehas a greater affinity for hydroxo-cobalamin than for the cytochromeoxidase within the mitochondriaand so frees the mitochondria forcellular respiration. This character-istic makes hydroxocobalamin aneffective antidote against cyanidepoisoning.9 Because it binds withcyanide without forming methemo-globin, hydroxocobalamin also canbe used to treat patients with cyanidepoisoning without compromisingthe oxygen-carrying capacity ofhemoglobin.5 This property is espe-cially important for patients whoalready have decreased concentra-tion of useful hemoglobin becauseof exposure to carbon monoxide orwho are pregnant.

Hydroxocobalamin has been usedoutside the United States for acutecyanide poisoning for more than 30years.5 Licensed in 1996 in France,the medication is used there forempiric prehospital and in-hospitaltreatment of acute cyanide poison-ing.18 A study19 in 2006 of the safetyand effects of hydroxocobalamin inhealthy volunteers supports empiric,prehospital administration and indi-cated few side effects. The results ofthe study cannot be directly appliedto the prehospital treatment of acutecyanide poisoning in the United

States because, unlike in the UnitedStates, first responders in France arenurses and physicians. However, thestudy did confirm that unlike thenitrites, hydroxocobalamin does notinterfere with tissue oxygenation.5,18,20

Reddening of the skin and urineare the most common drug-relatedside effects of treatment with hydrox-ocobalamin. These effects occurredin more than 60% of 136 healthyvolunteers who were given hydroxo-cobalamin in a double-blind, ran-domized, placebo-controlled study18

of the safety of the medication andpatients’ tolerance to it. The 2 maineffects are due to the color of thedrug itself and appear to resolvewithin 2 to 3 days of administrationof the drug (Table 5). Of note, hydrox-ocobalamin can also interfere withcertain colorimetric tests, such asthose for bilirubin, creatinine, mag-nesium, serum iron, serum aspartateaminotransferase, carboxyhemoglo-bin, methemoglobin, and oxyhemo-globin, but such interference hasnot been associated with any clini-cally meaningful changes.8,21

Hydroxocobalamin also doesnot compromise hemodynamic sta-bility. In the study18 of the effects ofhydroxocobalamin in healthy volun-teers, 12 volunteers (18%) had anelevation in blood pressure greaterthan 180 mm Hg systolic or greaterthan 110 mm Hg diastolic. This tran-sient increase in blood pressure isthought to be caused by the bindingof hydroxocobalamin to nitric oxideand may actually benefit patientswith acute cyanide poisoning whoare hypotensive. The increase inblood pressure has also been linkedanecdotally with improvement inpatients’ condition and does notrequire treatment.2,18

Summary of Patient ScenarioThe patient in the clinical scenario

at the beginning of this article received5 g of hydroxocobalamin reconstitutedin normal saline and administeredintravenously over 15 minutes. Duringinfusion, the patient’s blood pressuregradually increased from 100/50 mm Hgto 156/90 mm Hg, and he experiencedconcurrent reflex bradycardia (heartrate of 128/min decreased to 100/min).These changes were transient and self-limiting and did not require treatment.The patient received normal salineintravenously for hydration but didnot require vasopressor support in theresuscitation period. Because of thepositive response to antidotal therapy,a second 5-g dose of hydroxocobal-amin was not administered.

No serious adverse events were notedor attributed to the treatment with theantidote. Reddening of the skin andurine was visible on day 1 but subsidedwithout treatment by day 3. Because ofthe red color of hydroxocobalamin, col-orimetric laboratory values, such asthose for bilirubin, creatinine, and mag-nesium, were thought to have beenfalsely elevated on day 1. These labora-tory values were in the reference range byday 4, and no treatment was necessary.

The results of arterial blood gasanalysis on admission were pH 7.21,PO2 80 mm Hg, PaCO2 55 mm Hg, andbicarbonate 18 mEq/L when the frac-tion of inspired oxygen was 100%. Serialblood gas monitoring after hydroxo-cobalamin infusion indicted a gradualresolution of metabolic acidosis, andon the morning of day 3, the patientwas extubated. A neurological exami-nation at that time revealed a drowsybut oriented and responsive patient.Case management, psychiatry, andspiritual services were consulted inpreparation for transition out of the


To learn more about toxicology, read “Free andTotal Digoxin in Serum During Treatment ofAcute Digoxin Poisoning With Fab Fragments:Case Study,” by Eyer et al in the AmericanJournal of Critical Care, 2010;19:391-387.Available at www.ajcconline.org.




ICU and to ensure that adequate sup-port systems would be in place for asafe discharge home.

SummaryAlthough both the cyanide anti-

dote kit and hydroxocobalamin areconsidered acceptable for treatmentof cyanide poisoning in uncompli-cated exposures, few data are avail-able to compare the 2 in the UnitedStates.5 The type of exposure and therisk-benefit profile of each antidotemust be considered when decidingwhich antidote to administer.Although the cyanide antidote kithas been traditionally used in theUnited States, nurses may begin tosee hydroxocobalamin used as analternative, because the latter appearsto be safer than the kit in patientswho have preexisting hypotension,are pregnant, or inhaled smoke in aclosed space. Barring new evidenceto the contrary, hydroxocobalaminmost likely will become the standardof care in the treatment of acutecyanide poisoning. ICU nurses mustunderstand the current options andthe adverse effects, contraindications,and monitoring requirements ofeach antidote for proper care andmanagement of patients with acutecyanide poisoning. CCN

Financial DisclosuresNote reported.

References1. Fortin JL, Giocanti JP, Ruttimann M, Kowal-

ski JJ. Prehospital administration of hydrox-ocobalamin for smoke-inhalation associatedcyanide poisoning: 8 years of experience inthe Paris Fire Brigade. Clin Toxicol (Phila).2006;44(suppl 1):37-44.

2. Borron SW, Baud FJ, Mégarbane B, Bis-muth C. Hydroxocobalamin for severe acutecyanide poisoning by ingestion or inhala-tion. Am J Emerg Med. 2007;25(5):551-558.

3. Thompson RL, Manders WW, Cowan RW.Postmortem findings of the victims of theJonestown tragedy. J Forensic Sci. 1987;32(2):433-443.

4. DesLauriers CA, Burda AM, Wahl M.Hydroxocobalamin as a cyanide antidote.Am J Ther. 2006;13(2):161-165.

5. Hall AH, Dart R, Bogdan G. Sodium thio-sulfate or hydroxocobalamin for the empirictreatment of cyanide poisoning? Ann EmergMed. 2007;49(6):806-813.

6. Bronstein AC, Spyker DA, Cantilena LR Jr,et al; American Association of Poison Con-trol Centers. 2007 Annual report of theAmerican Association of Poison ControlCenters’ National Poison Data SystemNPDS: 25th annual report. Clin Toxicol(Phila). 2008;46(10):927-1057.

7. Borron SW. Recognition and treatment ofacute cyanide poisoning. J Emerg Nurs. 2006;32(4 suppl):S11-S18.

8. Schnepp R. Cyanide: sources, perceptions andrisks. J Emerg Nurs. 2006;32(4 suppl):S3-S7.

9. Shepherd G, Velez L. Role of hydroxocobal-amin in acute cyanide poisoning. Ann Phar-macother. 2008;42(5):661-669.

10. Barillo DJ. Diagnosis and treatment of cyanidetoxicity. J Burn Care Res. 2009;30(1):148-152.

11. Smith D, Cairns B, Ramadan F, et al. Effectof inhalation injury, burn size, and age onmortality: a study of 1447 consecutive burnpatients. J Trauma. 1994;37:655-659.

12. Benowitz NL. Antihyptertensive agents. In:Katzung BG, ed. Basic and Clinical Pharma-cology. 10th ed. New York, NY: McGraw-HillCo Inc; 2007:173-174.

13. Nelson L. Acute cyanide toxicity: mechanismsand manifestations. J Emerg Nurs. 2006;32(4 suppl):S8-S11.

14. Koschel MJ. Management of the cyanide-poisoned patient. J Emerg Nurs. 2006;32(4suppl):S19-S26.

15. Chen KK, Rose CL. Nitrite and thiosulfatetherapy in cyanide poisoning. JAMA. 1952;149:113-115.

16. US Food and Drug Administration. FDAnews: FDA approves drug to treat cyanidepoisoning. US Food and Drug Administra-tion Web site. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108807.htm. Published December 15,2006. Updated June 18, 2009. AccessedOctober 29, 2010.

17. Cyanokit [package insert]. Columbia, MD:Meridian Medical Technologies Inc. http://www.cyanokit.com/pdf/cyanokit_pi.pdf.Accessed October 29, 2010.

18. Uhl W, Nolting A, Golor G, Rost KL, Kovar A.Safety of hydroxocobalamin in healthy vol-unteers in a randomized, placebo-controlledstudy. Clin Toxicol (Phila). 2006;44(suppl 1):17-28.

19. Dart RC. Hydroxocobalamin for acutecyanide poisoning: new data from preclini-cal and clinical studies; new results from theprehospital emergency setting. Clin Toxicol(Phila). 2006;44(suppl 1):1-3.

20. Borron SW, Baud FJ, Barriot P, Imbert M,Bismuth C. Prospective study of hydroxo-cobalamin for acute cyanide poisoning insmoke inhalation. Ann Emerg Med. 2007;49(6):794-801.

21. Lee J, Mukai D, Kreuter K, Mahon S,Tromberg B, Brenner M. Potential interfer-ence by hydroxocobalamin on cooximetryhemoglobin measurements during cyanideand smoke inhalation treatments. AnnEmerg Med. 2007;49(6):802-805.

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CCN Fast Facts CriticalCareNurseThe journal for high acuity, progressive, and critical care

A Review of Acute Cyanide Poisoning With a Treatment Update

Initial management of patients with acute cyanide poison-ing requires rapid assessment and identification of the mostlikely route of exposure to determine proper decontamination(see Table).

The key treatment is early administration of 1 of the 2 anti-dotes currently available in the United States: the well-knowncyanide antidote kit and hydroxoco balamin. Hydroxocobalamindetoxifies cyanide by binding with it to form the renally excreted,nontoxic cyanocobalamin. Because it binds with cyanide with-out forming methemoglobin, hydroxocobalamin can be usedto treat patients without compromising the oxygen-carryingcapacity of hemoglobin.

FactsCyanide causes intracellular hypoxia by reversibly binding

to mitochondrial cytochrome oxidase a3. Signs and symptomsof cyanide poisoning usually occur less than 1 minute afterinhalation and within a few minutes after ingestion. Earlymanifestations include anxiety, headache, giddiness, inabilityto focus the eyes, and mydriasis. As hypoxia progresses, pro-gressively lower levels of consciousness, seizures, and comacan occur. Skin may look normal or slightly ashen, and arterialoxygen saturation may be normal. Early respiratory signs includetransient rapid and deep respirations. As poisoning progresses,hemodynamic status may become unstable.

Hamel J. A review of acute cyanide poisoning with a treatment update. Crit Care Nurse. 2011;31(1):72-82.

Table Management of patients with acute cyanide poisoninga

Supportive care

Admit to an intensive careunit for cardiac monitor-ing, respiratory and car-diovascular support

Perform routine laboratorytesting, including arterialblood gas analysis, serumlactate levels, completeblood cell counts, serum glucose level, a serumcyanide level (confirma-tory), and electrolyte levels

Monitor and treat dysrhyth-mias

Monitor for and treatadverse effects of antidotaltherapy

Antidotal therapy

Administer thecyanide antidotekit or hydroxo-cobalamin oncean airway hasbeen secured

Basic Life Support/Advanced

Cardiac Life Support(ACLS)

Establish ABCs (airway,breathing, circulation)

Establish intravenousaccess

Start cardiac monitoringStart ACLS if respiratoryor cardiovascular com-promise evident

a Based on data from Koschel MJ. Management of the cyanide-poisoned patient. J Emerg Nurs. 2006;32(4 suppl):S19-S26.b Protection of responders from contamination is essential with the use of personal protective equipment such as face masks, eye shields, and frequent double glov-ing or the use of butyl rubber gloves.

Decontamination

Smoke inhalationRemove from source into fresh airRemove contaminated clothing

Dermal exposurebRemove wet clothingWash skin with soap and water or water aloneIrrigate exposed eyes with water or salineRemove contact lenses

IngestionDo not induce emesisActivated charcoal may be administered if the victim is alert and the ingestion occurred within 1 hour

Isolate emesis (it may emit hydrogen cyanide)





CE Test Test ID C111: A Review of Acute Cyanide Poisoning With a Treatment UpdateLearning objectives: 1. Understand the pathophysiology of acute cyanide poisoning 2. Recognize the importance of immediate antidote administration in thesetting of acute cyanide poisoning 3. Differentiate the 2 available acute cyanide poisoning antidotes

Program evaluationYes No

Objective 1 was met � �Objective 2 was met � �Objective 3 was met � �Content was relevant to my nursing practice � �My expectations were met � �This method of CE is effectivefor this content � �The level of difficulty of this test was: � easy �medium � difficultTo complete this program, it took me hours/minutes.

Test answers:Mark only one box for your answer to each question. You may photocopy this form.

1. What is the most common source of cyanide poisoning in Western countries?a. Insecticides c. Sodium nitroprussideb. Acetonitrile d. Smoke inhalation

2. What enzyme catalyzes conversion of cyanide to nontoxic thiocyanate in the liver?a. Rhodanese c. Glutathione peroxidaseb. Catalase d. Superoxide dismutase

3. Which routes of cyanide exposure produce the most rapid onset of signs and symptoms?a. Oral and transdermalb. Intravenous and transdermalc. Inhaled and intravenousd. Oral and inhaled

4. What acid-base imbalance results from cessation of aerobic cellular metabolism in cyanide poisoning?a. Metabolic alkalosisb. Respiratory alkalosisc. Respiratory acidosisd. Metabolic acidosis

5. Cyanide causes intracellular hypoxia by reversibly binding to the cytochrome oxidase a3 within what intracellular organelle?a. Mitochondria c. Lysosomesb. Golgi complex d. Peroxisomes

6. What is a late central nervous system manifestation of cyanide’s toxic effect?a. Bright retinal veinsb. Headachec. Mydriasisd. Seizures

7. Which is correct about diagnostic testing in acute cyanide poisoning?a. Serum cyanide levels correlate well with specific degrees of poisoning severity.

b. Research is needed to find a rapid diagnostic test.c. Lactic acidosis is specific for acute cyanide poisoning.d. Serum cyanide levels greater than 0.5 mg/L are helpful in initial diagnosis.

8. What are common laboratory findings in acute cyanide poisoning?a. Plasma lactate level >8 mmol/L and arteriovenous oxygen saturation difference <10 mm Hg

b. Plasma lactate level >8 mmol/L and arteriovenous oxygen saturation difference >10 mm Hg

c. Plasma lactate level <8 mmol/L and arteriovenous oxygen saturation difference <10 mm Hg

d. Plasma lactate level <8 mmol/L and arteriovenous oxygen saturation difference >10 mm Hg

9. Which is correct about hydroxocobalamin?a. It should be refrigerated immediately after reconstitution.b. It binds with cyanide without forming methemoglobin.c. It should be used within 24 hours after reconstitution.d. It binds with cyanide to form vitamin B9.

10. What combines with unbound cyanide to form renally excretedthiocyanate?a. Amyl nitrite c. Sodium thiosulfateb. Sodium nitrate d. Hydroxocobalamin

11. What is the initial intravenous dose of hydroxocobalamin inadults?a. 2.5 mg c. 2.5 gb. 5 mg d. 5 g

12. What are the most common drug-related side effects of hydroxocobalamin?a. Yellow skin and amber urineb. Blue-gray skin and orange urine c. Red skin and red urined. Gray skin and blue-green urine

13. What is a nursing consideration for hydroxocobalamin?a. It is contraindicated in patients with smoke inhalation.b. It may cause transient hypertension.c. It requires monitoring of methemoglobin levels.d. It is not considered safe for pregnant patients.

For faster processing, takethis CE test online atwww.ccnonline.org

(“CE Articles in this issue”)or mail this entire page to:

AACN, 101 Columbia Aliso Viejo, CA 92656.

Test ID: C111 Form expires: February 1, 2013 Contact hours: 1.0 Fee: AACN members, $0; nonmembers, $10 Passing score: 10 correct (77%) Synergy CERP: Category ATest writer: Denise Hayes, RN, MSN, CRNP

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intoxicación aguda por cianuro con una actualización del tratamiento

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