Evidence and Recommendation Framework

This clinician-facing guideline synthesizes the 2025 American Heart Association (AHA) cyanide-poisoning recommendations, current US antidote prescribing information, the 2026 Clinical Toxicology Recommendations Collaborative guidance on activated charcoal, primary human studies informing lactate interpretation, and selected public-health, occupational, and expert-consensus sources. [1-9]

A current non-US Cyanokit Summary of Product Characteristics is used only to provide pediatric administration details that are not specified in US labeling; this does not change the US-label statement that pediatric safety and effectiveness have not been established. [10]

This is an evidence synthesis rather than a de novo GRADE guideline. Source recommendations are not independently regraded. When AHA recommendations are cited, their original Class of Recommendation (COR) and Level of Evidence (LOE) are retained where they materially affect interpretation.

• COR 1: intervention should be administered.

• COR 2a: intervention is reasonable.

• COR 2b: intervention may be reasonable.

• LOE C-LD: limited human data.

• LOE C-EO: expert opinion. [1]

Activated-charcoal recommendations use a separate Clinical Toxicology Recommendations Collaborative grading system: grade 1 indicates a strong recommendation, grade 2 a weak recommendation, and D denotes very low-quality evidence. These grades are not AHA COR/LOE categories. [7]

Source Currency and Update Triggers

Evidence sources for this version were targeted and verified through September 20, 2026; this was not a systematic literature search. The ATSDR Hydrogen Cyanide Medical Management Guideline [6] is retained only as an archived historical source and is no longer updated. For operational emergency-response details, this guideline preferentially uses the active CDC/NIOSH Hydrogen Cyanide Emergency Response Card [8]. The six cyanide-specific activated-charcoal recommendations were checked against the open-access full text of reference [7], including the cyanide evidence-to-decision rationale and the single-dose, additional-dose, and multiple-dose activated-charcoal recommendations.

This guideline should be re-reviewed after major AHA or Clinical Toxicology recommendations, US antidote-labeling changes, or substantive CDC/NIOSH updates.

Exposure Context and Sources

Fire Smoke

Combustion of nitrogen-containing materials can release hydrogen cyanide. Enclosed-space fire victims may simultaneously have:

• cyanide toxicity;

• carbon monoxide poisoning;

• thermal injury;

• airway injury;

• trauma;

• other combustion-product exposures.

Not every smoke-inhalation patient has clinically important cyanide poisoning. The exposure context and physiologic findings must be integrated rather than treating smoke exposure alone as diagnostic. [2,5]

Cyanogenic Plants and Foods

Cyanogenic glycosides occur naturally in selected seeds, kernels, roots, and plant materials. Toxic potential varies according to species, plant part, processing, disruption, enzymatic conversion, gastrointestinal release, and the amount actually absorbed.

Do not mechanically convert pharmaceutical or cyanide-salt thresholds into a plant-item count.

For the narrower cherry-pit exposure question, see Cherry Pit Poisoning: Cyanide Risk, Symptoms, and What to Do.

Mechanism of Toxicity

Cyanide binds to the ferric component of mitochondrial cytochrome c oxidase, impairing the terminal step of oxidative phosphorylation.

Oxygen may reach tissues normally, but cellular oxygen utilization is impaired. The resulting sequence is:

Cytochrome c oxidase inhibition → impaired oxidative phosphorylation → reduced ATP generation → anaerobic metabolism → lactate accumulation → cellular energy failure

The brain and myocardium are particularly vulnerable because of their high metabolic requirements. Severe poisoning can rapidly produce coma, seizures, cardiovascular instability, respiratory arrest, and death. [2,8]

This is histotoxic hypoxia.

Dose and Risk Assessment

There is no single universal ingested-dose or exposure threshold that reliably predicts severe cyanide toxicity across all sources, routes, formulations, plant materials, exposure durations, and patients.

Assess:

• exact source or chemical;

• hydrogen cyanide gas versus cyanide salt versus smoke versus plant or other source;

• route: inhalation, ingestion, dermal, ocular, or mixed;

• time and duration of exposure;

• maximum plausible amount when relevant;

• enclosed-space exposure;

• intentional versus accidental exposure;

• coexposures, especially carbon monoxide;

• prehospital collapse, syncope, seizure, apnea, or cardiac arrest;

• evolving mental status, blood pressure, perfusion, acid-base status, and lactate;

• treatment already administered.

Do not use a theoretical lethal-dose calculation alone to determine antidote use or disposition.

The cyanide dose thresholds used in the activated-charcoal recommendations are decontamination thresholds, not validated toxicity or antidote thresholds. [7]

Clinical Presentation and Severity

Mild or Early Toxicity

Possible findings include:

• headache;

• dizziness;

• anxiety or agitation;

• nausea or vomiting;

• weakness;

• dyspnea;

• chest tightness;

• tachypnea or hyperpnea;

• tachycardia;

• early hypertension;

• confusion.

These findings are nonspecific.

Severe or Life-Threatening Toxicity

Features of severe poisoning include:

• marked altered mental status;

• seizures;

• coma;

• respiratory depression or apnea;

• severe metabolic or lactic acidosis;

• hypotension or shock;

• significant dysrhythmia;

• cardiovascular collapse;

• cardiac arrest. [1,2,8]

Lactate as a Diagnostic and Severity Clue

Smoke Inhalation

Cyanide toxicity should move higher on the differential when an enclosed-space fire is accompanied by:

• altered mental status or coma;

• unexplained hypotension;

• cardiovascular collapse or cardiac arrest;

• severe lactic acidosis;

• soot involving the face, mouth, nose, or airway. [2,5,9]

In the classic fire-victim study, plasma lactate >10 mmol/L was a sensitive marker for significant cyanide exposure in patients without severe burns. This historical value is supportive evidence, not a treatment threshold. [5]

However, lactate is not cyanide-specific. Severe burns, shock, seizures, catecholamines, carbon monoxide, and other forms of tissue hypoperfusion can also increase lactate.

Non-Fire Cyanide Poisoning

In an 11-patient retrospective study of acute cyanide poisoning excluding fire victims, plasma lactate ≥8 mmol/L was 94% sensitive and 70% specific for a blood cyanide concentration ≥1 mg/L; specificity improved in patients not receiving catecholamines. [4]

Critical Distinction: Lactate Supports the Diagnosis; It Does Not Define Treatment

The non-fire 8 mmol/L value and the >10 mmol/L value from the classic fire-victim study are supportive historical clues, not validated universal antidote, ICU, or disposition thresholds.

Do not require a historical lactate cutoff before giving hydroxocobalamin to a patient with an otherwise convincing life-threatening cyanide syndrome.

A patient with a credible exposure and rapidly evolving life-threatening findings should be treated clinically even if lactate is unavailable or below a historical cutoff.

Focused History

Determine as quickly as possible:

• exact exposure source;

• hydrogen cyanide versus cyanide salt versus smoke versus plant;

• route of exposure;

• time and duration;

• maximum plausible amount when relevant;

• enclosed-space fire exposure;

• soot in the mouth, nose, or airway;

• occupational setting and chemical identity;

• coexposure to carbon monoxide;

• intentional versus accidental exposure;

• co-ingestants;

• prehospital collapse, seizure, syncope, apnea, or cardiac arrest;

• treatment already given.

For workplace events, obtain the Safety Data Sheet or chemical identifier when available, but do not delay resuscitation to retrieve documentation.

Evaluation and Monitoring

Immediate Bedside Assessment

Prioritize:

• airway patency;

• respiratory effort;

• oxygenation;

• circulation and tissue perfusion;

• mental status;

• continuous ECG;

• frequent blood-pressure assessment;

• bedside glucose;

• temperature where relevant.

Laboratory Evaluation

For clinically significant poisoning, obtain and serially reassess as appropriate:

• venous or arterial blood gas;

• lactate;

• electrolytes and bicarbonate;

• anion gap;

• glucose;

• creatinine/BUN;

• hepatic studies;

• CBC;

• carboxyhemoglobin in smoke exposure;

• methemoglobin when nitrites have been used or dyshemoglobinemia is suspected;

• CK when prolonged seizures, collapse, or muscle injury occur.

Additional testing should follow the clinical context.

Cyanide Concentration

A pretreatment cyanide sample may be collected if doing so does not delay therapy.

Do not wait for the result.

Current CYANOKIT labeling states that blood cyanide measurement is not required for management and that sampling after hydroxocobalamin may be inaccurate. [2]

If laboratory confirmation is desired for occupational, forensic, or public-health purposes, collect the sample before hydroxocobalamin when feasible without delaying treatment.

Diagnostic and Management Traps

Bitter-Almond Odor Is Not Reliable

The odor may be absent, and not everyone can detect it. [8]

Cherry-Red Skin Is Not Required

Do not use its absence to exclude cyanide poisoning.

Normal Pulse Oximetry Does Not Exclude Cyanide Toxicity

Cyanide primarily prevents cellular oxygen utilization rather than oxygen entry into blood. A normal pulse-oximeter value should not deter treatment when cyanide poisoning is clinically suspected.

Smoke Exposure Alone Does Not Diagnose Cyanide Poisoning

Integrate exposure context with neurologic findings, hemodynamics, soot, acid-base status, lactate, and competing causes of shock or altered mental status. [2,5]

A Cyanide Level Is Not a Prerequisite for Treatment

A rapidly actionable cyanide concentration is usually unavailable. Waiting for laboratory confirmation can dangerously delay antidotal therapy. [1,2]

Historical Lactate Cutoffs Are Not Treatment Thresholds

Do not convert the historical 8 mmol/L or >10 mmol/L values into a rule that delays antidote treatment in a convincing life-threatening syndrome. [4,5]

Management Overview

Life-threatening cyanide poisoning should be treated with parallel rather than rigidly sequential interventions.

AHA 2025 Antidote Strategy

Severe Cyanide Poisoning Decision Pathway

1. Suspected Clinically Significant Cyanide Exposure

→ Remove the patient from ongoing exposure while protecting rescuers
→ Give high-concentration oxygen
→ Continuous ECG and frequent blood pressure
→ Assess mental status, ventilation, circulation, and tissue perfusion
→ Obtain lactate and blood gas when clinically significant poisoning is suspected
→ Evaluate for carbon monoxide coexposure after smoke inhalation
→ Obtain a pretreatment cyanide sample only if immediately feasible and without delaying therapy

When the exposure history and clinical findings strongly suggest systemic cyanide poisoning, administer hydroxocobalamin promptly. Hypotension, cardiovascular collapse, laboratory confirmation, or a specified lactate concentration need not be present. Exposure alone does not establish an antidote indication. [2]

2. Life-Threatening Syndrome Present

Life-threatening findings include altered mental status, seizures, severe acidosis, shock, apnea, cardiovascular collapse, or cardiac arrest.

Begin appropriate measures concurrently:

• airway and ventilation support;

• high-concentration oxygen;

• circulatory resuscitation;

• seizure treatment;

• standard cardiac-arrest care when indicated;

• hydroxocobalamin without waiting for cyanide confirmation or a lactate threshold. [1,2]

3. Select the Antidote According to Clinical Context

Hydroxocobalamin available

→ Hydroxocobalamin is the preferred first-line antidote for life-threatening cyanide poisoning.

Hydroxocobalamin unavailable and no important concurrent CO poisoning

→ Sodium nitrite + sodium thiosulfate. [1,3]

Hydroxocobalamin unavailable + concurrent CO poisoning likely

→ Sodium thiosulfate alone is reasonable under AHA guidance. Avoid reflexive sodium-nitrite administration because additional methemoglobinemia can worsen oxygen-carrying capacity. [1]

Persistent severe toxicity after hydroxocobalamin

→ Reassess severity and response; repeat hydroxocobalamin may be appropriate according to the labeled regimen and clinical response. [2]

4. Reassess the Whole Clinical Trajectory

Reassess:

• mental status;

• respiratory effort;

• blood pressure and tissue perfusion;

• cardiac rhythm;

• acid-base status;

• lactate trajectory;

• recurrent or persistent toxicity;

• need for repeat antidote;

• complications of smoke inhalation or other co-exposures;

• need for ICU-level care and specialist-directed therapy.

Do not postpone established antidotal therapy while pursuing low-yield confirmatory testing or nonstandard therapies.

For broader ICU management principles, see Comprehensive Guide to Managing Poisoning in the Intensive Care Unit: Best Practices and Protocols.

Initial Stabilization

Prioritize airway, breathing, and circulation while initiating cyanide-specific treatment.

Airway and Breathing

Provide high-concentration oxygen immediately.

Secure the airway and provide mechanical ventilation when there is:

• apnea or inadequate ventilation;

• profound altered mental status;

• inability to protect the airway;

• severe respiratory failure.

A normal pulse-oximeter value should not deter treatment when cyanide poisoning is clinically suspected.

Circulation

Establish IV or IO access in critically ill patients.

Treat shock with appropriate resuscitation, including careful fluid administration and vasoactive support when indicated.

Hydroxocobalamin should be given concurrently rather than waiting for conventional shock treatment to fail. [1,2]

Seizures

Treat seizures promptly with standard resuscitation and critical-care anticonvulsant therapy. Persistent seizures increase metabolic demand and can contribute to lactic acidosis.

Cardiac Arrest

Provide high-quality CPR, ventilation, high-concentration oxygen, and standard advanced life support.

Administer cyanide antidotal therapy when poisoning is known or strongly suspected. The 2025 AHA cyanide recommendations specifically apply to life-threatening toxicity including cardiac arrest. [1]

Decontamination and Responder Safety

Inhalation Exposure

Remove the patient from the contaminated environment using appropriately protected responders.

Patients exposed only to hydrogen cyanide gas who are no longer in the contaminated atmosphere generally do not require skin decontamination unless liquid contamination or significant eye irritation is present. [6]

Liquid or Dermal Contamination

Contaminated clothing or skin may expose healthcare workers.

Remove contaminated clothing while flushing exposed skin and hair with water, then wash with mild soap and rinse thoroughly. Bag contaminated clothing and belongings appropriately. [8]

Eye Exposure

Irrigate exposed eyes promptly with water or saline while continuing other critical care.

Ingestion

Do not induce vomiting.

Gastric contents and vomitus from significant cyanide ingestion may create a secondary-exposure hazard and should be handled with appropriate precautions. [8]

Activated Charcoal

Cyanide absorption is rapid, so any potential benefit from activated charcoal is highly time-dependent and secondary to resuscitation and antidotal treatment.

The 2026 Clinical Toxicology Recommendations Collaborative provides the following cyanide-specific recommendations: [7]

These are charcoal-management thresholds, not validated toxicity, antidote, or disposition thresholds. The evidence is very low-quality and largely experimental. [7]

Full-text source verification completed September 20, 2026: all six cyanide-specific activated-charcoal recommendations in the table above were checked against the published open-access full article, cyanide section, and match the source thresholds and recommendation grades. In reference [7], additional-dose activated charcoal means a further decontamination dose intended to limit ongoing gastrointestinal absorption; multiple-dose activated charcoal refers to repeated dosing for enhanced elimination. [7]

Do not administer activated charcoal to a patient with an unprotected airway. In selected ingestions, consider charcoal only after assessing airway safety, aspiration risk, and expected benefit; it must not delay hydroxocobalamin, resuscitation, or other indicated antidotal therapy. Do not routinely intubate solely to administer activated charcoal. When intubation is otherwise required, charcoal may be considered after airway protection. In selected patients at substantial risk of life-threatening poisoning, intubation to facilitate decontamination may be reasonable after an individualized risk-benefit assessment, particularly when other treatments are unavailable. In cyanide poisoning, this must not delay resuscitation or indicated antidotal therapy. [7]

These recommendations apply to cyanide ingestion and should not be mechanically transferred to inhalation exposures or poorly quantified cyanogenic plant exposures.

Hydroxocobalamin

The 2025 AHA guideline states that hydroxocobalamin should be administered for life-threatening cyanide poisoning. For adults, this is COR 1, LOE C-LD; for children, COR 1, LOE C-EO. [1]

Hydroxocobalamin binds cyanide to form cyanocobalamin, which is then excreted in urine. [2]

AHA / CYANOKIT Dosing

The second adult dose may be infused over approximately 15 minutes to 2 hours depending on the patient's condition. [2]

The US CYANOKIT label states that pediatric safety and effectiveness have not been formally established, but reports non-US use of 70 mg/kg. [2]

For operational pediatric administration, the current non-US SmPC specifies an initial 70 mg/kg IV dose (maximum 5 g) infused over 15 minutes. If a second dose is required according to severity and response, the same 70 mg/kg dose (maximum 5 g) may be repeated; the second infusion may run over 15 minutes to 2 hours. The non-US maximum total pediatric dose is 140 mg/kg, not exceeding 10 g. These administration details do not upgrade the AHA pediatric evidence level and do not alter the US-label statement that pediatric safety and effectiveness have not been established. [10]

Because pediatric human evidence remains limited, independently verify weight and dose and involve poison-center or medical-toxicology expertise early.

Practical Administration

Current CYANOKIT contains 5 g hydroxocobalamin and is reconstituted to 200 mL.

The manufacturer's preferred diluent is 0.9% sodium chloride. Lactated Ringer's or D5W may be used when normal saline is not readily available. [2]

Hydroxocobalamin requires a separate IV line from incompatible medications.

Local Medication-Use Implementation

This guideline is clinical guidance and is not a medication order set, prescribing protocol, or substitute for institution-specific medication-use policy. Before institutional bedside adoption, local pharmacy/medication-safety and medical toxicology or poison-center leadership should verify the stocked antidote formulation and vial size, reconstitution and diluent, IV/IO access and infusion equipment, dedicated-line and compatibility requirements, pediatric weight-based calculation and independent double-check procedures, repeat-dose criteria and maxima, NITHIODOTE concentrations and administration rates, required monitoring, and antidote availability. A locally approved order set or medication protocol should operationalize these details. If an institutionally approved medication protocol differs, the local protocol governs.

Hydroxocobalamin Adverse Effects and Monitoring

Expected or recognized effects include:

• dark red discoloration of skin;

• chromaturia;

• transient hypertension;

• rash;

• nausea;

• infusion-site reactions;

• renal injury;

• calcium oxalate crystals in urine; [1,2]

• hypersensitivity reactions, including anaphylaxis; [2]

• potential photosensitivity; avoid intense direct sunlight while skin discoloration persists. [2]

Monitor blood pressure during treatment.

Current US labeling advises monitoring renal function for 7 days following CYANOKIT because postmarketing acute renal failure, acute tubular necrosis, renal impairment, and calcium oxalate crystalluria have been reported. [2]

These potential adverse effects should not delay treatment of credible life-threatening cyanide poisoning.

Laboratory Interference

Hydroxocobalamin's intense red color can interfere with laboratory and clinical methods. Affected results vary by analyzer and may include:

• creatinine;

• bilirubin;

• glucose;

• phosphate;

• AST/ALT;

• coagulation studies;

• urinalysis parameters;

• selected co-oximetry measurements. [2]

Interference after 5 g may persist for hours to days depending on the assay; higher doses may prolong interference.

Tell the laboratory that hydroxocobalamin has been administered.

Interpret unexpected laboratory results in collaboration with the laboratory and toxicology team.

Hemodialysis Blood-Leak Detector Interference

Hydroxocobalamin may cause some hemodialysis machines to falsely detect a “blood leak” because of red discoloration of plasma. [2]

If renal replacement therapy becomes necessary for a conventional critical-care indication, communicate prior hydroxocobalamin administration to nephrology and the dialysis team before therapy begins.

Sodium Nitrite and Sodium Thiosulfate

When hydroxocobalamin is unavailable, the 2025 AHA guideline states that sodium nitrite plus sodium thiosulfate should be administered for life-threatening cyanide poisoning. For adults, this is COR 1, LOE C-LD; for children, COR 1, LOE C-EO. [1]

NITHIODOTE Dosing

If signs of cyanide poisoning recur, current NITHIODOTE labeling permits repeating one-half of the original dose of both agents. [3]

Monitor blood pressure during sodium-nitrite administration. Reduce the infusion rate if significant hypotension develops. Do not administer additional nitrite merely to achieve a methemoglobin target; discontinue sodium nitrite if methemoglobin exceeds 30%. [3]

Administer sodium thiosulfate by slow IV injection immediately after sodium nitrite. [3]

Why Sodium Nitrite Requires Caution

Sodium nitrite oxidizes hemoglobin to methemoglobin. Methemoglobin binds cyanide, but it also reduces functional oxygen-carrying capacity.

This is particularly important in:

• carbon monoxide poisoning;

• severe smoke inhalation;

• anemia;

• infants;

• patients with compromised oxygen delivery.

The NITHIODOTE label recommends reducing sodium-nitrite dosing proportionally in known anemia and warns that infants younger than 6 months may be particularly vulnerable to severe methemoglobinemia. [3]

For a detailed discussion of methemoglobin physiology, see Acquired Methemoglobinemia: Causes, Diagnosis, and Treatment.

Monitoring After NITHIODOTE

Current NITHIODOTE labeling recommends monitoring patients for at least 24–48 hours after administration for adequacy of oxygenation and perfusion and for recurrent signs or symptoms of cyanide toxicity. When feasible, obtain hemoglobin/hematocrit when treatment is initiated. [3]

Because sodium nitrite can produce methemoglobinemia, standard pulse oximetry and calculated oxygen saturation derived from measured PaO₂ may be unreliable in that setting. Monitor methemoglobin when possible and interpret oxygenation together with the clinical picture and co-oximetry. [3]

Combined Carbon Monoxide and Cyanide Poisoning

Enclosed-space fire victims can have both carbon monoxide and cyanide toxicity.

The mechanisms compound impaired oxygen delivery:

• carbon monoxide reduces effective oxygen transport;

• cyanide prevents cellular oxygen utilization.

Preferred Antidote

When life-threatening cyanide toxicity is suspected, hydroxocobalamin is preferred because it does not rely on intentionally generating methemoglobin. [1]

If Hydroxocobalamin Is Unavailable

The 2025 AHA guideline states that sodium thiosulfate alone is reasonable in adults and children with concurrent carbon monoxide and cyanide poisoning when hydroxocobalamin is unavailable (COR 2a, LOE C-EO). [1]

Avoid reflexive sodium-nitrite administration in this setting because additional methemoglobin can worsen oxygen-carrying capacity.

Additional Evaluation

Obtain carboxyhemoglobin by co-oximetry when available, ideally before hydroxocobalamin if this can be accomplished without delaying therapy.

Give high-concentration oxygen.

Manage carbon monoxide poisoning according to its own severity and treatment criteria. Hyperbaric oxygen is not a substitute for cyanide antidotal therapy.

Adjunctive and Nonstandard Therapies

Hydroxocobalamin Plus Sodium Thiosulfate

The AHA guideline states that adding sodium thiosulfate to hydroxocobalamin may be reasonable in adults and children (COR 2b, LOE C-EO), but supporting human comparative evidence is limited. [1]

This should be considered a specialist-directed adjunct rather than mandatory routine combination therapy.

If both are used:

Do not administer hydroxocobalamin simultaneously through the same IV line as sodium nitrite or sodium thiosulfate because these agents are chemically incompatible. [2,3]

Methylene Blue

Methylene blue is not included as a cyanide antidote in current AHA recommendations and should not be incorporated into the routine cyanide-treatment algorithm. [1]

Current 2025 AHA cyanide recommendations center on:

• hydroxocobalamin;

• sodium nitrite plus sodium thiosulfate when hydroxocobalamin is unavailable;

• sodium thiosulfate alone in selected combined CO/cyanide poisoning when hydroxocobalamin is unavailable. [1]

If clinically important methemoglobinemia develops in a complex poisoning case, its management should be individualized with medical-toxicology guidance rather than assuming methylene blue is treating the cyanide itself.

Observation, Disposition, and Referral

There is no single universal observation interval appropriate for every cyanide exposure.

Disposition should reflect:

• route;

• exposure certainty;

• product or chemical;

• plant versus cyanide salt versus gas;

• time since exposure;

• clinical course;

• lactate and acid-base trajectory when relevant;

• delayed gastrointestinal absorption;

• coexposures;

• antidote use;

• reliability of follow-up.

ICU / Critical-Care Admission

Patients require ICU-level or equivalent monitored care when they have:

• antidote-requiring systemic toxicity;

• altered mental status;

• seizures;

• respiratory failure;

• significant metabolic or lactic acidosis;

• hypotension or shock;

• dysrhythmia;

• cardiac arrest;

• significant smoke-inhalation injury;

• multiorgan dysfunction.

Patients Receiving Hydroxocobalamin

Observe for:

• recurrent toxicity;

• hemodynamic response;

• laboratory trajectory;

• renal injury;

• assay interference;

• complications of the underlying exposure.

Patients Receiving Sodium Nitrite Plus Sodium Thiosulfate

Follow product-specific monitoring after NITHIODOTE. Current labeling recommends at least 24–48 hours of monitoring for adequate oxygenation and perfusion and for recurrent cyanide toxicity. [3]

Asymptomatic or Minimally Symptomatic Exposure

Low-risk disposition must be exposure-specific.

Do not apply a short inhalation-exposure observation strategy to:

• significant cyanide-salt ingestion;

• cyanogenic plant exposure with ongoing gastrointestinal release;

• intentional ingestion;

• uncertain amounts;

• delayed presentation;

• evolving abnormalities.

NIOSH Exposure-Specific Observation Considerations

CDC/NIOSH notes that patients who have ingested hydrogen cyanide solutions or had direct skin or eye contact should be observed in the emergency department for at least 4–6 hours for delayed symptoms. Patients with significant hydrogen cyanide inhalation exposure should be monitored for pulmonary edema, which may occur 24–72 hours after exposure. These are route- and agent-specific emergency-response recommendations, not universal discharge rules for all cyanide exposures. [8]

For cherry-pit-specific low-risk assessment, use Cherry Pit Poisoning: Cyanide Risk, Symptoms, and What to Do rather than extrapolating this systemic-management guideline into a fixed pit-count rule.

Pediatric Considerations

The 2025 AHA guideline gives a COR 1, LOE C-EO recommendation for hydroxocobalamin in children with life-threatening cyanide poisoning; pediatric evidence is limited and substantially extrapolated from adult data. [1]

Important pediatric priorities include:

• accurate current weight;

• independent verification of antidote calculations;

• rapid airway and ventilation support;

• avoidance of treatment delay;

• careful sodium-nitrite use in infants and patients with impaired oxygen delivery;

• early poison-center or medical-toxicology consultation;

• monitored care after clinically significant poisoning or antidote administration, with ICU-level care for systemic toxicity, hemodynamic or respiratory instability, significant acidosis, neurologic toxicity, or other critical illness.

Pediatric Hydroxocobalamin

Initial dose: 70 mg/kg IV/IO, maximum 5 g under AHA guidance. The current non-US Cyanokit SmPC specifies administration of the initial dose over 15 minutes. [1,10]

If a second dose is required according to severity and clinical response, the non-US SmPC specifies 70 mg/kg (maximum 5 g) again, infused over 15 minutes to 2 hours according to patient condition; maximum total pediatric dose 140 mg/kg, not exceeding 10 g. Pediatric human evidence remains limited, and weight, dose, and administration should be independently verified. [10]

Pediatric Sodium Nitrite

6 mg/kg IV, maximum 300 mg. [3]

Use particular caution in:

• infants younger than 6 months;

• anemia;

• concomitant CO poisoning;

• impaired oxygen delivery.

Pediatric Sodium Thiosulfate

250 mg/kg IV, maximum 12.5 g. [3]

Pregnancy

Cyanide poisoning threatens both maternal and fetal oxygen utilization.

Current CYANOKIT labeling states that although animal data identify fetal risk, hydroxocobalamin may be lifesaving and treatment should not be withheld because of pregnancy. [2]

Maternal resuscitation and timely antidotal therapy remain the priority.

Occupational and Responder Prevention

Occupational cyanide prevention depends on:

• substitution and engineering controls where feasible;

• enclosed handling systems and adequate ventilation;

• appropriate chemical-resistant PPE;

• respiratory protection for hazardous atmospheres;

• rapid-access emergency procedures;

• worker education;

• spill and decontamination planning;

• prompt availability of emergency medical response.

For emergency response to potentially unsafe hydrogen cyanide concentrations, NIOSH recommends positive-pressure self-contained breathing apparatus and appropriate chemical-protective clothing. [8]

Current US NIOSH values include:

• REL STEL: 4.7 ppm (5 mg/m³), skin notation

• IDLH: 50 ppm. [8]

These are occupational exposure limits, not clinical toxicity, antidote, or disposition thresholds.

A workplace with credible cyanide risk should have a rehearsed emergency plan, rapid EMS activation pathway, chemical identification resources, and ready access to poison-center/medical-toxicology consultation.

Prevention and Patient Advice

• Never mix cyanide-containing chemicals with acids or incompatible chemicals.

• Use industrial cyanide products only under appropriate occupational controls.

• Store cyanide salts in clearly labeled, secured containers.

• Do not consume unidentified cyanogenic plants, kernels, extracts, or homemade preparations.

• Do not induce vomiting after suspected cyanide ingestion.

• Preserve product labels, Safety Data Sheets, plant photographs, or packaging when safe to do so.

• After a meaningful exposure, seek immediate professional toxicology guidance rather than relying on odor, skin color, or theoretical dose calculations.

Key Takeaways

1. Cyanide poisoning is a rapidly evolving form of cellular asphyxia caused primarily by inhibition of mitochondrial cytochrome c oxidase.

2. Diagnosis is clinical because confirmatory cyanide testing is rarely available quickly enough to guide emergency treatment.

3. Severe lactic acidosis supports the diagnosis but must be interpreted in context; the ≥8 mmol/L non-fire value and >10 mmol/L classic smoke-inhalation value are historical diagnostic clues, not universal antidote thresholds.

4. In smoke inhalation, an enclosed-space fire plus altered mental status, cardiovascular instability, soot exposure, and markedly elevated lactate should increase concern for cyanide.

5. Hydroxocobalamin is the preferred first-line antidote for life-threatening cyanide poisoning in adults and children under 2025 AHA guidance. [1]

6. Adult hydroxocobalamin begins with 5 g IV over 15 minutes; a second 5-g dose may be used according to severity and response. [2]

7. The AHA pediatric initial dose is 70 mg/kg IV/IO, not exceeding the adult initial dose. [1]

8. When hydroxocobalamin is unavailable, sodium nitrite plus sodium thiosulfate is recommended for life-threatening poisoning. [1,3]

9. When carbon monoxide and cyanide poisoning coexist and hydroxocobalamin is unavailable, sodium thiosulfate alone is reasonable because sodium nitrite can further compromise oxygen-carrying capacity. [1]

10. Hydroxocobalamin can interfere with laboratory assays, selected co-oximetry measurements, and hemodialysis blood-leak detectors. [2]

11. Methylene blue is not a standard cyanide antidote.

12. Decontamination and activated charcoal must never delay oxygenation, resuscitation, or indicated antidotal therapy.

13. Pediatric dosing requires independent verification, especially when sodium nitrite is used.

14. Patients receiving NITHIODOTE require product-specific monitoring, including at least 24–48 hours for oxygenation, perfusion, and recurrent toxicity. [3]

15. Significant occupational and industrial exposures require simultaneous patient care, responder protection, and hazardous-material control.