Toxicology – Cyanide

Core Concept

Cyanide is a rapidly acting cellular asphyxiant that prevents tissues from using oxygen despite adequate oxygen delivery. Severe poisoning can progress within minutes from headache, confusion, and dyspnea to seizures, profound lactic acidosis, cardiovascular collapse, coma, and death.

The key mechanism is:

Cyanide exposure → inhibition of mitochondrial cytochrome c oxidase → oxidative phosphorylation stops → cellular ATP failure → anaerobic metabolism → massive lactate production → cardiovascular/CNS collapse

The most important modern treatment principle is:

Suspected severe cyanide poisoning → give 100% oxygen + aggressive supportive care + hydroxocobalamin early; do not wait for a cyanide level.

Hydroxocobalamin is FDA-approved for known or suspected cyanide poisoning and can be administered immediately when clinical suspicion is high.

Forms and Sources

Important cyanide exposures include hydrogen cyanide (HCN) gas, sodium cyanide, potassium cyanide, calcium cyanide, cyanogen compounds, cyanogenic plants, nitriles, sodium nitroprusside, and combustion products from structural fires.

Hydrogen cyanide is a volatile liquid/gas that can be rapidly lethal by inhalation. Cyanide salts can generate HCN when exposed to acid, including gastric acid after ingestion.

Industrial exposures occur in mining and metal extraction, electroplating, metallurgy, jewelry manufacture, plastics and synthetic-fiber production, chemical manufacturing, fumigation, and laboratory processes.

Smoke Inhalation

Modern toxicology places particular emphasis on enclosed-space structural fires.

Combustion of nitrogen-containing synthetic materials can generate hydrogen cyanide. A fire victim may therefore have simultaneous:

thermal injury + airway injury + carbon monoxide poisoning + cyanide poisoning

Cyanide should be particularly suspected after an enclosed-space fire when the patient has altered consciousness, seizures, cardiovascular instability, severe metabolic/lactic acidosis, or cardiac arrest.

Not every smoke-inhalation victim has clinically significant cyanide poisoning, however. Empiric hydroxocobalamin use in smoke inhalation remains an area of imperfect evidence; recent systematic reviews emphasize that outcome data are largely observational and that indiscriminate administration to every smoke-exposed patient is not supported.

Cyanogenic Plants and Foods

Cyanogenic glycosides can release cyanide after enzymatic hydrolysis. Important sources include bitter cassava, apricot kernels, bitter almonds, peach and cherry pits, and certain other seeds and plants.

Proper processing of cassava substantially reduces cyanogenic compounds. Poisoning is more likely after consumption of inadequately processed bitter cassava or concentrated cyanogenic products than after ordinary consumption of fruit flesh.

Amygdalin/laetrile is particularly important because it can release cyanide and has caused serious poisoning.

Nitroprusside

Sodium nitroprusside metabolism releases cyanide. Toxicity becomes more likely with high-dose or prolonged infusions, particularly when detoxification pathways are overwhelmed.

Cyanide generated from nitroprusside is normally converted to thiocyanate, which is predominantly eliminated by the kidneys. Prolonged exposure may therefore also produce thiocyanate accumulation, especially in renal dysfunction.

Toxic Dose

There is no single clinically reliable toxic dose because toxicity depends on the cyanide compound, route, concentration, duration, gastrointestinal conditions, and speed of treatment.

Hydrogen cyanide inhalation can cause extremely rapid poisoning because pulmonary absorption is nearly immediate. The historical statement that approximately 90 ppm for 30 minutes may be lethal should not be treated as a clinical threshold.

NIOSH lists hydrogen cyanide as having a REL of 4.7 ppm (5 mg/m³) as a short-term exposure limit with skin notation; the current OSHA PEL listed by NIOSH is 10 ppm (11 mg/m³) as an 8-hour TWA with skin notation. NIOSH historically designated 50 ppm as immediately dangerous to life or health.

Reported lethal oral doses of cyanide salts vary widely, and a quoted value such as “200 mg” should therefore not be used as a reliable bedside cutoff.

Pathophysiology

Cyanide has a high affinity for the ferric iron within cytochrome c oxidase (Complex IV) of the mitochondrial electron transport chain.

Normally:

O₂ → final electron acceptor → oxidative phosphorylation → ATP

With cyanide:

Cytochrome oxidase inhibited → O₂ cannot be effectively utilized → oxidative phosphorylation stops → ATP depletion → anaerobic glycolysis → lactate accumulation

This produces histotoxic hypoxia: oxygen may reach the tissues, but cells cannot use it normally.

The brain and heart are particularly vulnerable because of their high metabolic requirements.

Venous Hyperoxia

Because tissues cannot adequately extract oxygen, venous blood may remain unusually oxygenated. This explains the classic description of unusually bright venous blood or reduced arterial–venous oxygen difference.

However, this finding is neither sufficiently sensitive nor specific to diagnose cyanide poisoning and should not delay treatment.

Clinical Features

Cyanide poisoning is primarily a neurologic, cardiovascular, and metabolic catastrophe.

Early manifestations may include headache, dizziness, anxiety, agitation, confusion, nausea, vomiting, dyspnea, tachypnea, tachycardia, and hypertension.

As toxicity progresses:

agitation/confusion → seizures → coma → hypotension → bradycardia → apnea → cardiovascular collapse

Large inhalational exposures can produce this sequence within minutes. CDC describes rapid development of respiratory abnormalities, altered mental status, seizures, loss of consciousness, blood-pressure abnormalities, coma, and death after substantial exposure.

Cardiovascular Toxicity

Early sympathetic activation can produce tachycardia and hypertension.

Severe cellular hypoxia then produces myocardial dysfunction, dysrhythmias, hypotension, bradycardia, and ultimately cardiovascular collapse.

Profound hypotension after a credible cyanide exposure is therefore a major indication for immediate antidotal therapy.

Neurologic Toxicity

Early neurologic manifestations include headache, dizziness, restlessness, anxiety, and confusion.

Severe poisoning causes altered consciousness, generalized seizures, coma, and respiratory arrest.

Patients who survive profound poisoning may develop hypoxic-ischemic brain injury or delayed neurologic syndromes including movement disorders and parkinsonian features.

Respiratory Findings

Tachypnea is common initially because of metabolic acidosis and CNS stimulation.

Severe poisoning may progress to central respiratory depression, apnea, and respiratory arrest.

Smoke inhalation may simultaneously produce upper-airway thermal injury, bronchospasm, chemical pneumonitis, and pulmonary edema, so respiratory failure in a fire victim is frequently multifactorial.

Gastrointestinal Findings

Ingested cyanide salts commonly produce nausea, vomiting, abdominal pain, and rapidly developing systemic toxicity.

Onset may be slower than with inhaled hydrogen cyanide, but substantial salt ingestion remains a medical emergency.

Certain cyanogenic glycosides and nitriles can produce more delayed toxicity because cyanide must first be liberated metabolically.

Skin Exposure

Hydrogen cyanide and some cyanide compounds can be absorbed through skin, particularly when liquid contamination is present.

Contaminated clothing should therefore be removed promptly and exposed skin irrigated thoroughly.

Some cyanide salts can additionally cause local irritation or chemical injury.

“Bitter Almond” Odor

The classic bitter-almond odor associated with cyanide is unreliable.

Many people cannot genetically perceive the odor, concentrations may be insufficient to smell, and deliberately smelling a suspected cyanide source is dangerous.

Therefore:

Absence of a bitter-almond odor does not exclude cyanide poisoning.

Cyanosis

Cyanosis is not a reliable early finding. Because the primary problem is failure of cellular oxygen utilization rather than failure of oxygen delivery, severe poisoning may occur without prominent cyanosis.

Diagnosis

Cyanide poisoning is primarily a clinical diagnosis.

The combination of:

credible exposure + neurologic deterioration + cardiovascular instability + severe unexplained lactic acidosis

should trigger immediate consideration of cyanide.

Treatment should never be delayed while waiting for confirmatory testing when severe poisoning is clinically suspected. Both hydroxocobalamin and nitrite/thiosulfate labeling emphasize prompt antidotal treatment when suspicion is high.

Serum Lactate

Lactate is one of the most useful rapidly available laboratory clues.

Cyanide-induced inhibition of oxidative phosphorylation causes dramatic anaerobic lactate production. A markedly elevated lactate following an appropriate exposure strongly supports the diagnosis.

In smoke-inhalation literature, an arterial lactate >8 mmol/L increases concern for cyanide exposure, while approximately ≥10 mmol/L has historically been used as a stronger indicator of significant cyanide toxicity.

These are decision-support thresholds, not absolute diagnostic cutoffs. Lactate can also rise from burns, seizures, shock, carbon monoxide poisoning, catecholamines, trauma, or cardiac arrest.

Thus:

High lactate + compatible exposure + neurologic/cardiovascular collapse is much more important than lactate alone.

Acid–Base Findings

Severe poisoning typically causes a high-anion-gap metabolic acidosis with elevated lactate.

Obtain blood gas, electrolytes, bicarbonate, lactate, glucose, and renal function in significantly symptomatic patients.

Profound acidosis supports severe cellular poisoning but is not specific for cyanide.

Cyanide Concentrations

Whole-blood cyanide concentrations can confirm exposure but are usually not useful for acute treatment decisions because results are often unavailable quickly enough.

Cyanide is also unstable in biologic specimens, making proper collection and handling important. Published reviews note that cyanide measurements may require hours while critically poisoned patients can die within minutes.

Therefore:

Never wait for a cyanide concentration before treating a critically ill patient.

The old tables correlating individual cyanide concentrations with tachycardia, obtundation, coma, or death are too rigid for modern bedside use.

Additional Investigations

Obtain continuous ECG monitoring in significant poisoning. Troponin may be useful when myocardial injury is suspected.

In smoke-inhalation patients, measure carboxyhemoglobin by co-oximetry because concomitant carbon monoxide poisoning is common.

Other testing should be guided by the circumstances and may include CBC, renal and liver function, CK, toxicology testing, chest imaging, and evaluation for trauma or burns.

An intentional ingestion should prompt testing for relevant occult coingestants such as acetaminophen according to standard overdose practice.

Differential Diagnosis

The most important toxicologic mimics include carbon monoxide, hydrogen sulfide, methemoglobinemia, sodium azide, toxic alcohols, salicylates, iron, isoniazid, and other cellular or chemical asphyxiants.

Nontoxicologic causes include sepsis, cardiogenic shock, status epilepticus, severe hypoxemia, diabetic or alcoholic ketoacidosis, mesenteric ischemia, and other causes of profound lactic acidosis.

In an enclosed-space fire, cyanide and carbon monoxide should not be considered mutually exclusive:

CO poisoning + cyanide poisoning can coexist.

Immediate Treatment

Management begins simultaneously with diagnosis.

Remove the patient from exposure while protecting rescuers. Give 100% oxygen immediately, establish airway and ventilatory support as required, obtain IV/IO access, treat seizures, support circulation, correct life-threatening metabolic disturbances, and administer an antidote promptly when severe cyanide poisoning is suspected.

FDA labeling specifically emphasizes that antidote administration must occur together with airway, ventilation, circulatory support, oxygen, and seizure management.

Oxygen

Give 100% oxygen, even if pulse oximetry appears normal.

Cyanide prevents normal oxygen utilization rather than necessarily lowering arterial oxygen content. Supplemental oxygen therefore does not correct the fundamental biochemical lesion, but it maximizes available oxygen and is particularly important because pulmonary injury and carbon monoxide poisoning may coexist.

Pulse oximetry cannot rule out either cyanide or carbon monoxide poisoning.

Airway and Ventilation

Early intubation is appropriate for progressive coma, recurrent seizures, inadequate ventilation, severe hypoxemia, respiratory failure, or anticipated airway edema after smoke inhalation.

Mechanical ventilation should use a high inspired oxygen concentration initially.

Seizures

Treat seizures promptly with benzodiazepines.

Persistent seizures can dramatically increase lactate production and oxygen demand and should be treated aggressively using standard status-epilepticus escalation if necessary.

Hypotension and Shock

Give appropriate isotonic crystalloid while avoiding unnecessary volume overload.

Persistent shock should be treated with a titratable vasopressor. Norepinephrine is generally the preferred first-line vasopressor for undifferentiated distributive or vasoplegic shock rather than the historical dopamine-first strategy.

Severe cyanide-induced shock may improve rapidly after effective antidotal therapy.

The Trendelenburg position is obsolete as a treatment for shock.

Antidote – Hydroxocobalamin

Hydroxocobalamin is the preferred modern antidote for most suspected severe cyanide poisoning.

Hydroxocobalamin binds cyanide to form cyanocobalamin, which is substantially less toxic and eliminated in the urine.

Its major advantage is that it does not intentionally induce methemoglobinemia, making it especially attractive when carbon monoxide poisoning or smoke-induced hypoxemia may coexist.

CYANOKIT is FDA-approved for known or suspected cyanide poisoning.

Hydroxocobalamin Dose

For adults:

Hydroxocobalamin 5 g IV over 15 minutes

If severe toxicity persists or recurs, a second 5-g IV dose may be given, for a maximum total dose of 10 g according to current U.S. labeling. The second dose may be infused over approximately 15 minutes to 2 hours depending on clinical severity.

Pediatric hydroxocobalamin dosing is generally 70 mg/kg IV, maximum 5 g for the initial dose, with repeat dosing considered in severe poisoning according to toxicology protocols and specialist guidance.

Antidotal treatment should not be delayed for laboratory confirmation.

Hydroxocobalamin Adverse Effects

Hydroxocobalamin commonly causes dramatic but usually benign red discoloration of the skin and urine (chromaturia).

Other effects include transient hypertension, nausea, headache, rash, infusion reactions, and occasional hypersensitivity.

Current labeling also warns of acute kidney injury and urinary calcium oxalate crystals, and recommends renal-function monitoring after treatment.

Recent observational literature has raised concern about an association between hydroxocobalamin and AKI in smoke-inhalation patients, although causality is difficult to establish because these patients are often critically ill.

Laboratory Interference After Hydroxocobalamin

The intense red coloration of hydroxocobalamin can interfere with colorimetric laboratory assays and some bedside or dialysis equipment.

The laboratory should therefore be informed immediately that hydroxocobalamin has been administered.

This interference can affect interpretation of several chemistry, hematology, and co-oximetry measurements depending on the analyzer.

Hemodialysis After Hydroxocobalamin

The red pigment can trigger false blood-leak alarms on some hemodialysis machines, potentially complicating renal replacement therapy.

This is clinically important in severely ill fire victims who develop AKI.

Sodium Nitrite and Sodium Thiosulfate

The traditional cyanide antidote kit used:

Sodium nitrite → methemoglobin formation → cyanide binding

followed by:

Sodium thiosulfate → sulfur donor → conversion of cyanide to thiocyanate

The combination remains FDA-approved as NITHIODOTE for serious or life-threatening acute cyanide poisoning.

However, it is no longer the preferred empiric strategy for many smoke-inhalation patients when hydroxocobalamin is available.

Why Sodium Nitrite Can Be Dangerous

Sodium nitrite deliberately oxidizes hemoglobin to methemoglobin, which binds cyanide.

The problem is that methemoglobin cannot carry oxygen normally.

In an enclosed-space fire victim who may already have:

carbon monoxide → reduced functional hemoglobin

plus

smoke/airway injury → impaired oxygenation

creating additional methemoglobinemia can further compromise oxygen delivery.

Sodium nitrite can also cause hypotension, which is particularly undesirable in cyanide-induced cardiovascular collapse. Current NITHIODOTE labeling specifically warns about hypotension and methemoglobin formation.

Therefore:

Avoid routine nitrite administration in smoke-inhalation patients when significant CO poisoning or impaired oxygen delivery is possible and hydroxocobalamin is available.

NITHIODOTE Dosing

If the nitrite/thiosulfate regimen is selected for serious confirmed or strongly suspected cyanide poisoning, current U.S. labeling recommends in adults:

Sodium nitrite 300 mg IV — supplied as 10 mL — administered slowly, followed immediately by sodium thiosulfate 12.5 g IV — supplied as 50 mL.

For children, sodium nitrite is 6 mg/kg IV, maximum 300 mg, followed by sodium thiosulfate 250 mg/kg IV, maximum 12.5 g. If toxicity recurs, one-half of the original doses may be repeated.

Blood pressure must be monitored during nitrite administration.

Hydroxocobalamin Plus Thiosulfate

Sodium thiosulfate has historically been used as an adjunct because it enhances conversion of cyanide to thiocyanate.

However, modern management usually prioritizes hydroxocobalamin when rapid empiric therapy is needed.

If hydroxocobalamin and nitrite/thiosulfate products are used in the same patient, compatibility matters: current product labeling states that NITHIODOTE components are chemically incompatible with hydroxocobalamin and should not be administered through the same IV line.

Decontamination – Inhalation

Rescuers must not enter a contaminated atmosphere without appropriate respiratory protection.

Remove the patient to fresh air and administer 100% oxygen.

A patient exposed only to cyanide gas who has no liquid or particulate contamination generally does not require extensive skin decontamination once removed from the source.

Decontamination – Dermal Exposure

Remove contaminated clothing and jewelry promptly.

Wash contaminated skin thoroughly with water and soap as appropriate while preventing secondary contamination of staff.

Liquid hydrogen cyanide and soluble cyanide compounds can be absorbed through skin, making rapid removal important.

Decontamination – Ingestion

Do not induce vomiting.

Ipecac is obsolete.

Routine gastric lavage is also not recommended because of aspiration risk, rapid cyanide absorption, and potential danger to staff from released hydrogen cyanide.

Activated charcoal may be considered after a very recent significant oral exposure when the airway is intact or protected, but it must never delay airway stabilization or antidote administration.

Because severe cyanide poisoning can progress extremely rapidly, antidote and resuscitation take priority over gastrointestinal decontamination.

Sodium Bicarbonate

Metabolic acidosis usually improves when cyanide toxicity, shock, seizures, and hypoxia are corrected.

Sodium bicarbonate is not an antidote to cyanide.

It may be used selectively for severe life-threatening acidemia according to ordinary critical-care principles, but routine administration based solely on cyanide exposure is not indicated.

Hyperbaric Oxygen

Hyperbaric oxygen is not a standard antidotal treatment for isolated cyanide poisoning.

The historical suggestion that HBO prevents delayed neurologic injury from cyanide is not supported sufficiently to justify routine use.

In smoke-inhalation patients, hyperbaric oxygen may be considered independently for significant carbon monoxide poisoning according to CO-specific indications, but transport to an HBO facility must never delay hydroxocobalamin, airway management, seizure control, or hemodynamic resuscitation.

Extracorporeal Elimination

Hemodialysis is not routinely used to remove cyanide itself because poisoning evolves too rapidly and effective antidotes are available.

Renal replacement therapy may nevertheless be required for conventional indications such as severe AKI, refractory electrolyte disturbance, or acid-base abnormalities.

Thiocyanate generated during cyanide detoxification is renally eliminated and can accumulate in renal failure, particularly during prolonged sodium nitroprusside exposure.

Smoke-Inhalation Decision Making

In an enclosed-space fire victim, empiric hydroxocobalamin is most compelling when there is a combination such as:

altered consciousness or coma + severe lactic acidosis + hypotension/cardiovascular collapse ± seizures/cardiac arrest

Soot around the mouth or nose, carbonaceous sputum, burns, and enclosed-space exposure strengthen the history but do not by themselves prove cyanide poisoning.

An unexplained lactate around 8–10 mmol/L or higher substantially increases suspicion in the correct clinical context.

Because recent evidence remains observational and heterogeneous, hydroxocobalamin should not be viewed as mandatory for every patient who merely inhaled smoke.

Cardiac Arrest

Cyanide should be considered in otherwise unexplained cardiovascular collapse or cardiac arrest immediately following a credible high-concentration exposure or enclosed-space fire.

Standard high-quality resuscitation should continue while 100% oxygen and hydroxocobalamin are administered when severe cyanide poisoning is suspected.

Successful resuscitation is possible even after profound poisoning when antidotal therapy and cardiovascular support are delivered rapidly.

Pregnancy

Pregnancy should not delay life-saving antidotal treatment.

Severe maternal cyanide poisoning threatens both mother and fetus through profound cellular hypoxia. Maternal stabilization and rapid antidotal treatment therefore take priority.

Specialist toxicology and obstetric involvement is appropriate after stabilization.

Monitoring

Severely poisoned patients require continuous ECG, blood pressure, oxygenation, respiratory, temperature, and neurologic monitoring.

Serial lactate, blood gas/pH, electrolytes, glucose, renal function, and markers of end-organ injury help determine response to treatment.

After hydroxocobalamin, monitor renal function and recognize that several laboratory measurements may be analytically distorted by the drug’s intense red pigmentation. Current labeling recommends monitoring renal function for 7 days following treatment.

Admission and Disposition

Any patient with significant neurologic symptoms, severe lactic acidosis, cardiovascular instability, respiratory compromise, substantial intentional ingestion, or requirement for antidotal treatment should be admitted, usually to an ICU.

Minor exposures with no symptoms and reassuring serial assessment may eventually be discharged after an exposure-specific observation period. A rigid historical 8-hour observation rule should not be applied to every cyanide exposure.

Delayed toxicity is more relevant after cyanogenic glycosides, certain nitriles, or potentially ongoing gastrointestinal absorption than after a brief low-level HCN inhalation.

Intentional exposure requires appropriate psychiatric assessment after medical stabilization.

Prognosis

Outcome is strongly dependent on dose, route, duration of exposure, and speed of resuscitation and antidotal therapy.

Massive HCN inhalation may cause death within minutes.

Patients who regain cardiovascular and neurologic function rapidly may recover completely. Patients who experience prolonged coma, seizures, severe hypotension, or cardiac arrest are at risk for hypoxic-ischemic brain injury.

Delayed neurologic sequelae have been described after severe poisoning, including cognitive impairment, movement disorders, and parkinsonism.

Important Pitfalls

The first major pitfall is waiting for a cyanide concentration. Cyanide poisoning is treated clinically; laboratory confirmation is generally too slow to guide emergency antidotal therapy.

The second is assuming normal pulse oximetry excludes poisoning. Cyanide is a cellular oxygen-utilization poison, so SpO₂ may appear reassuring despite profound mitochondrial hypoxia.

The third is relying on the smell of bitter almonds. Odor perception is unreliable and should never determine diagnosis.

The fourth is overlooking cyanide in an enclosed-space fire victim with coma, hypotension, seizures, or marked lactic acidosis.

The fifth is treating every smoke-inhalation patient automatically with hydroxocobalamin. Empiric treatment is most defensible when clinical findings suggest significant cyanide toxicity; recent evidence for indiscriminate use remains uncertain.

The sixth is using sodium nitrite indiscriminately in a smoke-inhalation victim. Nitrite-induced methemoglobinemia can further compromise oxygen delivery when carbon monoxide poisoning and pulmonary injury already coexist.

The seventh is allowing decontamination, imaging, laboratory testing, or hyperbaric transfer to delay antidotal therapy in a critically ill patient.

Finally, after hydroxocobalamin, remember the striking red skin and urine discoloration, laboratory interference, possible AKI, and interference with some hemodialysis blood-leak detectors.

High-Yield Toxicology Pearls

Cyanide = histotoxic hypoxia.

The core mechanism is:

Cyanide → cytochrome c oxidase inhibition → oxidative phosphorylation failure → ATP depletion → anaerobic metabolism → severe lactic acidosis

The classic severe syndrome is:

Rapid altered mental status/seizures + profound lactic acidosis + hypotension/cardiovascular collapse

Think particularly about cyanide after an enclosed-space structural fire, industrial exposure, cyanide-salt ingestion, cyanogenic plant ingestion, or problematic nitroprusside exposure.

A markedly elevated lactate—particularly around 8–10 mmol/L or greater in a compatible smoke-inhalation presentation—strongly increases suspicion but is not diagnostic by itself.

Blood cyanide levels can confirm exposure but are usually too slow to guide emergency treatment.

Give 100% oxygen even when SpO₂ is normal.

For severe known or suspected poisoning:

Hydroxocobalamin 5 g IV over 15 minutes

A second 5 g may be administered if severe toxicity persists or recurs, for an adult total of 10 g.

Hydroxocobalamin is particularly advantageous in smoke inhalation because it does not induce methemoglobinemia.

Expect red skin and urine, laboratory interference, transient hypertension, and possible renal injury after hydroxocobalamin.

The traditional sodium nitrite + sodium thiosulfate antidote regimen remains FDA-approved, but nitrite produces methemoglobinemia and hypotension and is therefore problematic when carbon monoxide poisoning or impaired oxygen delivery coexists.

Do not induce vomiting. Routine gastric lavage is obsolete. Activated charcoal has only a selective role after very recent oral exposure and must never delay resuscitation or antidote.

Hyperbaric oxygen is not routine treatment for isolated cyanide poisoning; in a fire victim it may be considered separately for significant concomitant carbon monoxide poisoning.

Most importantly:

If severe cyanide poisoning is clinically likely, treat first—the patient can die long before the cyanide level returns.