How does cyanide poisoning from inhalation compare clinically and forensically to other chemical asphyxiants like carbon monoxide?
Executive summary
Cyanide and carbon monoxide (CO) inhalation both produce chemical asphyxia but through distinct molecular targets: CO binds hemoglobin, impairing oxygen delivery, while cyanide disables cellular respiration by inhibiting cytochrome c oxidase in mitochondria [1] [2]. Clinically they can appear similar—confused sensorium, collapse, bright red venous blood—but differences in onset, specific signs (seizures, pupillary changes), laboratory patterns (high venous O2 and lactate in cyanide; elevated carboxyhemoglobin in CO) and forensic detectability guide diagnosis and postmortem interpretation [2] [3] [4].
1. Mechanisms: two routes to the same end of metabolic arrest
Carbon monoxide exerts toxicity by binding to hemoglobin to form carboxyhemoglobin, reducing oxygen-carrying capacity and shifting oxygen-hemoglobin dissociation, whereas cyanide is a highly reactive molecule that binds iron and copper in cytochrome c oxidase, halting mitochondrial electron transport and cellular aerobic respiration—both therefore disrupt oxygen utilization but at different biological levels [1] [2].
2. Clinical picture: overlapping presentations but key distinguishing features
Both poisonings produce nonspecific symptoms—headache, confusion, collapse—and in smoke inhalation both may coexist, making clinical distinction difficult [5] [6]. Cyanide classically causes rapid central nervous system and cardiovascular dysfunction and more commonly produces seizures and pupillary dilation, while CO is notorious for headaches, nausea, and delayed neurologic sequelae; the presence of seizures and marked cardiovascular collapse should heighten suspicion for cyanide [7] [3] [8].
3. Laboratory and bedside clues: what points toward cyanide versus CO
A central venous oxygen saturation greater than 90% and bright red venous blood reflect failure of peripheral oxygen utilization and are suggestive of cyanide toxicity, although this finding can also appear with CO and hydrogen sulfide exposures, so it is not pathognomonic [2]. In cyanide, profound metabolic acidosis with very high lactate (e.g., lactate >8 mmol/L has high sensitivity in small series) supports the diagnosis, whereas CO is identified by elevated carboxyhemoglobin measured by co-oximetry [3] [9].
4. Treatment implications: antidotes, oxygen, and controversies
Oxygen therapy—including hyperbaric oxygen in select cases—remains the cornerstone for CO poisoning, while cyanide requires specific antidotes such as hydroxocobalamin; other historical antidotes (nitrites, thiosulfate) have limitations and risks, particularly when exposures to multiple agents are possible, which complicates empiric therapy [10] [7] [9]. Published animal and clinical literature supports early hydroxocobalamin for suspected cyanide in smoke inhalation, but timing and diagnostic uncertainty remain controversial in some settings [10] [6].
5. Forensic detection and interpretation: measuring exposure after death
Forensic workup in fire victims routinely measures carboxyhemoglobin and cyanide because both gases are products of combustion and may coexist; quantifying levels helps reconstruct survival time and cause of death, but interpretation is complex—CO is more frequently implicated in fire deaths, yet cyanide can be primary in some cases and postmortem artifacts or treatment (e.g., nitrite antidotes) can confound cyanide assays [11] [12] [9]. Cherry‑red lividity is a classic autopsy clue for CO but not definitive; toxicological assays and correlation with scene evidence (materials burned that generate HCN) are essential [4] [11].
6. Combined exposures and synergistic danger in fires
Multiple studies and reviews emphasize that in enclosed fires victims are often exposed to both CO and cyanide, and their effects can be additive or synergistic—CO impairs oxygen delivery while cyanide prevents utilization—so combined exposure increases lethality and complicates both clinical management and forensic attribution [10] [5] [11]. Forensic series report varied prevalence: some found toxic CO more common than cyanide, while others documented substantial cyanide exposure rates, which underscores the case‑by‑case nature of attribution [12] [13].
7. Bottom line for clinicians and forensic investigators
Clinically, suspect cyanide when inhalation victims show rapid neurologic collapse, seizures, bright red venous blood, very high lactate and high venous O2 saturations; confirm CO with co‑oximetry for carboxyhemoglobin and treat accordingly—oxygen for CO, hydroxocobalamin for cyanide—while recognizing that simultaneous exposures are common in fires and may require parallel strategies and careful postmortem toxicology to apportion causality [2] [3] [9] [11].