CO binds to the heme moieties in hemoglobin (at the same site that binds O₂) to produce carboxyhemoglobin (COHb). The affinity of CO for binding to Hb is 200–300 times greater than the affinity of O₂ (1,2).

Progressive increases in COHb are accompanied by proportional decreases in arterial O₂ content: if severe enough, this can result in inadequate tissue oxygenation and impaired aerobic energy production (1,2,3).

In addition to the deleterious effects of COHb on tissue oxygenation, CO poisoning can promote cell injury via: (a) inhibition of cytochrome oxidase (which further impairs the oxidative production of ATP), (b) generation
of peroxynitrite (a potent oxidant capable of widespread cell injury), and (c) enhanced lipid peroxidation by neutrophils (which damages cell and mitochondrial membranes) (1,2,4).

There is no combination of symptoms that confirms or excludes a diagnosis of CO poisoning; COHb levels do not correlate with clinical manifestations of CO poisoning (1,4).

Headache (usually frontal) and dizziness are the earliest and most common complaints in CO poisoning (reported in 85% and 90% of patients, respectively) (1).

Progressive exposure to CO can produce ataxia, confusion, delirium, generalized seizures, and coma (1).

Cardiac effects of CO poisoning include elevated biomarkers with normal coronary angiography, and transient LV systolic dysfunction (5).

Advanced cases of CO poisoning can be accompanied by rhabdomyolysis, lactic acidosis, and acute respiratory distress syndrome (ARDS) (1).

The “cherry red” skin color in classic descriptions of CO poisoning (because COHb is a brighter shade of red than hemoglobin) is a rare finding (4).

Delayed neurological sequelae are possible (within about one year), usually consisting of cognitive deficits (ranging from mild confusion to severe dementia) and parkinsonism (1,4,6). These occur most frequently following prolonged (24 hrs) exposure to CO, and in patients with loss of consciousness or COHb levels above 25% (4).

Pulse oximetry is NOT reliable for the detection of COHb. Pulse oximeters use two wavelengths of light to measure oxygenated and deoxygenated Hb in blood. Light absorbance at one of the wavelengths (660 nm) is very similar for oxygenated Hb and COHb, so COHb is measured as oxygenated Hb by pulse oximeters, and this results in spuriously high readings for O₂ saturation (4).

The measurement of COHb requires an 8-wavelength co-oximeter, which measures the relative abundance of all 4 forms of Hb in blood.

COHb levels are negligible (<1%) in healthy nonsmokers, but smokers have COHb levels of 3–5% or even higher (4). The threshold for elevated COHb levels is 3–4% for nonsmokers, and 10% for smokers (4).

The principal treatment for CO poisoning is inhalation of 100% oxygen. The elimination half-life of COHb is 320 minutes while breathing room air, and 74 minutes while breathing 100% oxygen (1,4), so only a few hours of breathing 100% oxygen is needed to return COHb levels to normal (<3%).

In patients with severe neurologic manifestations, hyperbaric oxygen has been used (with variable results) to reduce the risk and severity of delayed neurologic sequelae (1,7).

Cyanide ions have a high affinity for metalloproteins, most notably the oxidized iron (Fe³⁺) in cytochrome oxidase, the last enzyme system in the electron-transport chain within mitochondria (where the electrons collected during ATP production are used to reduce O₂ to H₂O).

CN-induced inhibition of cytochrome oxidase halts the process of oxidative metabolism in mitochondria, which halts the uptake of pyruvate into mitochondria and results in excess production of lactic acid. The accumulation of lactate in plasma produces a progressive metabolic (lactic) acidosis, which is one of the hallmarks of CN poisoning.

Early signs of CN poisoning include agitation, tachycardia, and tachypnea. Progressive CN accumulation eventually results in loss of consciousness, bradycardia, hypotension, and cardiac arrest.

Plasma lactate levels are typically elevated (>10 mmol/L), and venous blood may appear “arterialized” because of the marked decrease in tissue O₂ utilization.

Cyanide poisoning should be strongly suspected if a smoke inhalation victim exhibits a severe metabolic acidosis (pH <7.2) or a markedly elevated lactate level. The time to onset of symptoms after smoke inhalation is rapid, and progression to cardiac arrest can occur in less than 5 minutes (8).

Cyanide poisoning is a clinical diagnosis. Whole blood cyanide levels, while useful for purposes of documentation, are typically not readily available. Cyanide antidotes must be administered rapidly and empirically if poisoning is suspected. Diagnosis can be challenging because many of the clinical features of cyanide poisoning are indistinguishable from CO poisoning.

As a general rule of thumb, severe metabolic (lactic) acidosis
and hemodynamic instability are the clinical features that distinguish CN from CO poisoning in victims of smoke inhalation (8,9).