Although carbon monoxide (CO) is universally recognized as a toxic gas, it continues to cause tens of thousands of unintentional, non-fire-related exposures in the US every year. True, it is odorless, colorless, and tasteless, so its presence is not easily detected without a special air monitor. However, many people are at risk simply because they do not know the common situations in which CO can form, collect, and poison them. This is important because accidental CO poisoning results in approximately 500 deaths a year, and intentional self-poisoning causes another 500 deaths. A significant number who need medical treatment after exposure show neurologic sequelae that can last for weeks to months and sometimes longer. It is never a bad time to brush up on how to recognize CO poisoning and treat it.
SOURCES
Carbon monoxide forms during incomplete combustion of any carbon-containing substance in the presence of oxygen. If the combustion of the fuel molecule is complete, carbon dioxide (CO2) is formed instead of carbon monoxide (CO).
Of course, house fires are notorious for producing CO as well as cyanide, both potent asphyxiant toxins. Other common, non-fire sources of CO include camp stoves and lanterns, charcoal grills, gasoline-powered equipment (e.g., generators and power washers), internal combustion engines in cars, trucks and boats, and natural gas furnaces, water heaters, ranges, and ovens. Winter, with its snow, ice, and power outages, brings the risk of CO poisoning to its peak as people turn to unsafe options to heat their homes. In fact, most cases occur in homes with faulty furnaces during the colder months.
It is also helpful to appreciate that carbon monoxide poisoning can occur from a high air concentration over a short period of time and also from a low air concentration over a longer period of time.
PATHOPHYSIOLOGY
Carbon monoxide is readily absorbed after inhalation, having ideal solubility to cross cell membranes. The toxic mechanism most familiar to health care practitioners is the displacement of oxygen from its binding sites on hemoglobin due to the 200-250 times higher affinity of hemoglobin for CO over oxygen. There is a lesser percentage binding of oxygen, and so less oxyhemoglobin arrives at the tissues. Furthermore, the presence of carboxyhemoglobin shifts the oxygen-hemoglobin dissociation curve to the left so that even if oxygen is delivered, it is less likely to unload in the tissues. This naturally gives the impression that tissue hypoxia is solely responsible for the adverse effects of CO, and the faster that oxygenation is restored, the better the patient’s chances of avoiding tissue injury.
However, it turns out that the activity of CO in the body is far more complex. CO also binds to mitochondrial cytochrome oxidase where it interferes with cellular energy production. It generates reactive oxygen molecules that induce damaging lipid peroxidation of membrane lipids in a self-perpetuating chain reaction. The accumulated cell damage, also known as oxidative stress, incites reactive inflammation. The brain, being an organ with a vast membrane-lipid content, can suffer heavily from cell damage due to lipid peroxidation and the resulting neuroinflammation. Therefore, there are more pathologic problems than tissue hypoxia that severe CO poisoning can bring.
To be fair, the role of CO extends to a much deeper level than what is seen in poisoning. It actually has beneficial actions in the body. Carbon monoxide has been identified as a gasotransmitter, which is an endogenous signaling molecule. It enables vasodilation, increased tissue perfusion, and cell protection during ischemia. When delivered by a CO-releasing molecular carrier, it shows multifaceted therapeutic properties, including anti-inflammatory, immune modulation, and apoptosis management. It has potential roles in organ transplantation and cancer therapy. CO is indeed a mixed bag.
CLINICAL MANIFESTATIONS OF CARBON MONOXIDE POISONING
Early symptoms in acute exposure to CO are quite non-specific and include pounding headache, nausea, and dizziness. In the absence of a suspicious exposure scenario, the patient may be misdiagnosed as having a viral syndrome or some other self-limiting minor illness. CO-exposed patients may also complain of decreased exercise tolerance, chest pain, and shortness of breath and may have EKG or biochemical evidence of myocardial ischemia or cardiomyopathy/impaired cardiac function. This directs the workup along a cardiopulmonary route. Sometimes, the patient presents because of a fall that was precipitated by a significant CO exposure, and ED attention is directed to injury assessment and the common reasons for a fall. In severe CO exposure, the patient may present obtunded or comatose, which initiates a multi-pronged workup including intracerebral events. Carbon monoxide poisoning should have at least some consideration on the differential diagnosis for common, non-specific complaints of any severity.
LABORATORY DIAGNOSIS
The most useful diagnostic test is the carboxyhemoglobin (COHb) level in the blood obtained in the lab by co-oximetry analysis of an arterial, capillary, or venous sample. It is reported as a percentage of total hemoglobin. However, other etiologies for elevated COHb levels must be kept in mind. Normal ranges for nonsmokers are typically 0-3%, with people who smoke one pack per day having a COHb of 6% to 10%, depending on when the last cigarette was smoked. Water pipe/hookah smoking can raise COHb levels to 30%. Infants can have falsely higher COHb levels due to the interference of fetal hemoglobin with analyzer equipment. Patients with hemolytic anemia can have higher levels of COHb because CO is a natural byproduct that results from the breakdown of protoporphyrin to bilirubin.
Of note, typical pulse oximetry is usually normal even if there is markedly elevated COHb because oxyhemoglobin and carboxyhemoglobin read at approximately the same wavelength. Specialized pulse co-oximeters that non-invasively read carboxyhemoglobin have been available for 20 years. According to a 2023 meta-analysis of studies evaluating accuracy, they have a relatively high false positive and false negative rate, which makes their routine use unreliable to rule in or rule out carbon monoxide poisoning. And as with other conditions affecting oxygen delivery and energy metabolism, blood pH and lactate concentrations can be helpful in indicating the severity of poisoning.
However, neither COHb level nor ancillary lab results always correlate well with the clinical signs and symptoms of poisoning. For example, symptomatic patients can have lower COHb concentrations than asymptomatic patients based on their overall medical fragility or pre-existing conditions, especially anemia, heart disease, and lung disease. Severely affected patients may have marginally elevated COHb by the time they present to the ED if a long period of time has elapsed since their exposure. This is because decline of COHb proceeds spontaneously as soon as exposure ceases.
TREATMENT – SUPPORTIVE CARE AND OXYGEN
The first goal of immediate treatment is survival of the patient, and the second is mitigation of delayed manifestations of tissue damage, primarily neuropsychiatric symptoms such as brain fog, headache, depression and anxiety, tremor, or other movement abnormalities. These can be detected in some 20-30% of patients with significant exposure but are self-limited in most cases.
Currently, in addition to supportive care, the mainstay of specific treatment is high-concentration supplemental oxygen, which accelerates the dissociation of CO from hemoglobin and its elimination through the lungs. The average half-life of COHb on room air is 5 hours and decreases to about 1 hour on 100% oxygen. The endpoint of oxygen treatment is reduction of COHb levels to <5%. The time this takes depends on the half-life and how high the COHb level was at the time the oxygen therapy was started. If the starting level is 40% COHb, it will take 3 half-lives to fall to 5% or lower, i.e., 15 hours in room air or 3 hours on 100% oxygen. Pregnant women are routinely placed on oxygen for a longer period of time to treat the fetus because fetal hemoglobin has a higher affinity for CO, and supplemental oxygen is less efficient in dislodging it.
We recommend giving high-concentration oxygen (nominally 100%) as soon as possible by non-rebreather mask. Endotracheal intubation and mechanical ventilation will be needed in some patients.
HYPERBARIC OXYGEN THERAPY IS NOT STANDARD OF CARE
There are some who believe Hyperbaric Oxygen (HBO) treatment should be given to patients with significant CO exposures. Oxygen at 3 atmospheres of pressure in a specialized chamber lowers the average half-life of COHb to 20 – 30 minutes. It also increases the total amount of dissolved oxygen in the bloodstream compared to supplemental 100% oxygen at ambient air pressure. Restoration of oxygenation to the tissues as fast as possible has intuitive appeal, but it has not yet translated into demonstrably better clinical outcomes. HBO does not solve the problems of pathologic lipid peroxidation and subsequent inflammation. Delayed neuropsychiatric effects are more likely tied to these effects than to tissue oxygenation.
The superiority of HBO over 100% normobaric oxygen in reducing the incidence of delayed effects has not been demonstrated clinically as trials have had conflicting results. A recent commentary outlines the flaws in the two studies usually referenced to show better outcomes after HBO (Juurlink DN, 2022). Interestingly, both the American Academy of Medical Toxicology and the American Academy of Clinical Toxicology declined to designate HBO as the standard of care for significant CO poisoning.
Most institutions do not have rapid access to hyperbaric facilities, and transferring a patient to a capable facility can take so long that the theoretical benefit evaporates. Similarly, favorable outcomes can be achieved with 100% oxygen by non-rebreather mask. Regardless, HBO is considered safe and can be used for serious CO poisoning when the facility is readily available.
Looking to the future, current investigational approaches to decrease incidence of delayed neurologic sequelae from CO poisoning include dexamethasone and n-acetyl cysteine. These are intended to target the oxygen radical damage and inflammatory aftermath.
CONCLUSION
Unintentional exposures to CO are easily missed or misdiagnosed. The current mainstay of treatment in carbon monoxide poisoning is good supportive care and 100% oxygen to accelerate the elimination of COHb. Hyperbaric oxygen is not considered standard of care and is not widely available for emergency therapy, but nonetheless may be considered in severe exposures.
The Missouri Poison Center is available round the clock to assist in managing carbon monoxide exposed patients. Our specially trained nurses, pharmacists, and toxicologist can provide the most up-to-date information regarding exposures and treatment. For patient specific guidance, please contact the poison center’s dedicated line for healthcare professionals at 1-888-268-4195.
This Poison Alert was developed with contributions from Dr. Kim-Long Nguyen.