Carbon monoxide (CO) is the major cause of death from poisoning in the UK (Turner et al, 1999). Based on Centers for Disease Control and Prevention (CDC) data from 2004-2006, children younger than 5 years had the highest rate estimated rate of CO-related emergency room visits amongst all age groups (CDC, 2008). It is important for the prehospital specialist to remember certain situations may lend themselves to a greater risk of CO poisoning. Historical clues include a history of enclosed spaces, especially during colder months when the use of heating is more likely.
Numbers of cases sublethal exposure to CO in the UK are traditionally quoted as 200 per year, but up 250 000 gas appliances are condemned annually. Therefore, as many as 25 000 people every year may be exposed to the effects of CO within the home. It is believed that an overwhelming majority of cases go unrecognized as patients are often misdiagnosed and as a result, remain untreated (Walker and Hay, 1999).
An accurate quantification of the incidence of CO poisoning is difficult because non-lethal exposures are more common than lethal exposures, and the former often go undetected, especially in children (Chesney, 2002). Common sources of CO include house fires, wood-burning stoves, motor vehicle exhausts, and the hepatic conversion of methylene chloride—a paint stripper which can be inhaled, ingested or dermally absorbed. Most deaths are associated with exposure to motor vehicle exhaust fumes, with smoke inhalation from fires the second leading cause (Chesney, 2002).
Children are at greater risk of the deleterious effects of CO poisoning because they have higher basal metabolic and respiratory rates, rendering them more susceptible to CO intoxication (Chesney, 2002).
Pathophysiology
The mechanism of CO's toxic effects is multifactorial and has been reviewed comprehensively by Chesney (2002). CO is inhaled and is rapidly absorbed across the pulmonary endothelium into the bloodstream. It is reported to have 250 times more affinity for CO, compared to oxygen (Coburn and Forman, 1987). Once CO is bound, it greatly diminishes the capability of haemoglobin to oxygenate tissues. This can lead to cellular hypoxia. Impaired oxygen results in increased respiratory rate and consequently more CO absorption.
Compared to haemoglobin, CO binds with even greater affinity to myoglobin in skeletal and cardiac muscle (Nelson and Hoffman, 2005). This may result in impaired cardiac contractility and/ or rhabdomyolysis (Sokal and Kralkowska, 1985). Interestingly, patients with cognitive impairment have been reported to have negligible levels of COHb, making it likely that CO exhibits its toxic effects through mechanisms independent of hypoxia (Ball et al, 1951). Lending support for this theory is that clinical effects of CO poisoning cannot be completely predicted by the extent of binding between haemoglobin and CO (Coburn and Mayers, 1971).
‘The non-specific nature of the presenting features and combined with more common, alternate explanations for the patient's condition, make misdiagnosis a frequent occurrence.’
Myoglobin has an affinity for CO that is approximately 60 times greater than that of oxygen (Coburn and Mayers, 1971). As a presumed result of binding of non-hemoglobin molecules such as myoglobin, healthy volunteers and especially people with preexisting heart disease, can develop life-threatening dysrhythmias and ischemic changes even with low-level exposures (Allred et al, 1989).
Several studies suggest that CO causes hypotension due to a combination of myocardial depression and vasodilation which is an essential component of CNS injury (Allred et al, 1989; Tomaszewski, 2006). Hypotension may be represented clinically by syncope or loss of consciousness and portends a worse clinical outcome (Choi, 1983).
Maternal CO exposure during pregnancy poses increased concerns for the foetus as CO readily crosses the placenta (Sokal and Kralkowska, 1985; Tomaszewski, 2006). Decreased absorption and elimination of CO make the foetus is particularly susceptible to its toxic effects. In-vitro studies have demonstrated that foetal haemoglobin has a lower affinity for CO (Ginsberg and Myers, 1976). Of primary concern is the precipitous fall in foetal arterial oxygen content with maternal exposure to CO (Tomaszewski, 2006). This can result in foetal demise (Gasman et al, 1990).
Clinical features
The clinical presentation of CO poisoning is nonspecific and highly variable in both adults and children. The non-specific nature of the presenting features and combined with more common, alternate explanations for the patient's condition make misdiagnosis a frequent occurrence. The most common misdiagnosis is influenza (Barret et al, 1985), followed by others such as food poisoning (Barret et al, 1985), gastroenteritis (Gasman et al, 1990), and even colic (Crocker and Walker, 1985). Headache is the most common presenting symptom (Barret et al, 1985). Myocardial infarction, life-threatening dysrhythmias, and cardiac arrest are also frequently described (Klasner et al, 1998). In fact, acute mortality from CO usually results from ventricular dysrhythmias (Klasner et al, 1998).
Due to higher respiratory and basal metabolic rates, children often manifest the deleterious effects of CO intoxication before adults (Tomaszewski, 2006). In children, symptoms can be seen at COHb levels less than 10% (Rudge, 1993).
Children often present with similar symptoms as adults, namely nausea, headache, or lethargy (Klasner et al, 1998) but may present with only an isolated seizure or vomiting (Herman, 1998). Infants may demonstrate nonspecific signs such as fussiness and poor feeding as a sole manifestation (Piatt, et al, 1990).
Not surprisingly, symptoms are seen most prominently in organs with high oxygen uptake such as the CNS and myocardium. The central nervous system is the organ most sensitive to CO poisoning. Exposed patients may experience headache, dizziness, or cerebellar dysfunction at COHb levels as low as 15-20%. With longer exposures, syncope, seizures, or coma can result (Satran et al, 2005).
Features of CNS impairment are important to recognize as these patients are at risk of delayed neurologic sequelae. Acute myocardial injury is common in CO poisoning and contributes significantly to mortality (Henry et al, 2006). In healthy young adults, mortality is approximately 25% among those who have sustained acute myocardial injury, more than twice that of CO poisoned patients without myocardial injury (Burney et al, 1982).
Rhabdomyolysis can result from hypoxemic injury to striated and cardiac muscle and can lead to acute renal failure (ARF). The often described cherry red skin discoloration on mucosal surfaces is usually seen only after excessive exposure (Tomaszewski, 2006). Another classic but uncommon phenomenon is the development of cutaneous bullae following severe exposures (Myers et al, 1985).
Metabolic changes are thought to more accurately reflect the toxic effects of CO over that of the COHb level. Mild cases of CO poisoning may be accompanied by respiratory alkalosis as a compensatory response to reduced oxygen-carrying capacity and delivery (Mathieu, 1985). Longer exposures with decreased levels of consciousness result in metabolic (lactic) acidosis from tissue hypoxia (Sokal and Kralkowska, 1985).
‘It is important that prompt recognition and treatment of CO poisoning is effected to prevent ongoing hypoxic tissue injury’
The most serious complication of CO poisoning is persistent or delayed neurologic sequelae (DNS), which occur in up to 50% of patients with symptomatic acute poisonings (Baum, 2008). Prominent features include dementia, amnesia, psychosis, parkinsonism, paralysis, chorea, cortical blindness, apraxia and agnosias, peripheral neuropathy, and incontinence (Ginsberg, 1985).
Neurologic deterioration can emerge 2-40 days after the initial poisoning episode (Choi, 1983). The effect appears to be transient, lasting from 1-3 years (Choi, 1983; Nelson and Hoffman, 2005). The risk of DNS correlates poorly with the level of COHb, although most cases of this phenomenon have been described among patients who suffer a loss of consciousness in the acute phase (Choi, 1983). Children also develop behavioural and educational difficulties after severe poisoning but have a lower incidence of DNS (Ginsberg, 1985). Older patients (age>30 years) appear to be much more susceptible to developing delayed sequelae (Choi, 1983; Baum, 2008). Spontaneous improvement is usually seen in 33 to 75% of cases over the subsequent year (Choi, 1983).
In summary, it is important to understand CO effects on multiple organ systems, including but not limited to, the cardiac and neurologic systems. As the symptoms can be non-specific, it is commonly mistaken for viral illnesses such as influenza. A high index of suspicion is necessary. Some paramedics have devices which alert the provider on scene to increased CO levels which can be carried on the equipment bag. Specialized saturation probes also exist that can detect substances such as CO and methaemoglobin.
Diagnosis
Despite the inconsistent and non-specific clinical presentation, it is important that prompt recognition and treatment of CO poisoning is effected to prevent ongoing hypoxic tissue injury. In general, all members of the same dwelling should have similar symptoms with some degree of temporal synchrony that abate, once they are removed from the source of exposure. Fire victims should be suspected as having CO as well as concomitant cyanide intoxication which can further impair tissue oxygenation (Gasman et al, 1990).
The most useful and feasible method of confirming CO exposure is a carboxyhaemoglobin (COHb) level. It is rapid, convenient, and relatively accurate (Mehotra et al, 2011). The normal COHb value among non-smokers is less than 1.5% (Coburn, 1970; Russell, 1973). COHb levels as high as 5% can be seen normally in individuals with hemolytic anemias. Falsely elevated COHb levels can also be seen in neonates (Copel et al, 1982; Caravati et al, 1988; Mehotra et al, 2011).
With regard to pregnant patients, maternal COHb levels do not accurately reflect those experienced by the foetus (Koren et al, 1991). Foetal demise has been reported in pregnancies with low maternal levels of COHb (Vreman et al, 1988). In contrast, there are multiple reports that demonstrate that exposed pregnant women without loss of consciousness and a normal mental status have normal deliveries of infants without developmental concerns (Vreman et al, 1988; Myers and Britten, 1989). Therefore, clinicians should focus on maternal symptoms of CO intoxication rather than value of COHb as an indicator of the degree of foetal intoxication.
It is important to recognize that once removed from the source, the patient's COHb levels will fall rapidly. The presenting COHb level is a weak predictors of peak CO levels (Caravati et al, 1988). Furthermore, COHb levels do not necessarily correlate with symptoms, nor are they predictive of outcome (Mathieu et al, 1985; Tomaszewski, 2006; CDC, 2008) or delayed neurologic sequelae (Myers and Britten, 1989). The wide variation in clinical manifestations with identical COHb levels precludes the use of COHb levels as a basis for treatment decisions (Myers, 1984). Nomograms have not been validated (Gasman et al, 1990).
Blood gas analysis will confirm the presence of a metabolic acidosis and may serve as a more reliable index of severity than COHb (Gasman et al, 1990). Unfortunately, arterial pH does not correlate well with either initial neurologic examination or the COHb level, making it a poor criterion upon which to base decisions on whether or not hyperbaric oxygen (HBO) therapy is indicated (Bozeman et al, 1997).
Routine pulse oximetry is often falsely reassuring as standard pulse oximeters cannot distinguish between oxyhemoglobin and carboxyhemoglobin (Bozeman et al, 1997). In addition, arterial oxygen tension (PaO2) is often normal.
Continuous cardiac monitoring and a 12-lead electrocardiogram (ECG) are essential for identifying ischaemia or dysrhythmias in severe exposures (Gasman et al, 1990). Nonspecific elevations in troponin (Chamberland et al, 2004) and creatine phosphokinase (Shapiro et al, 1989) have been reported (Horowitz et al, 1987).
In patients who have a loss of consciousness following CO exposure, changes on cranial CT can be seen within 12 hours of exposure (Ikeda et al, 1978; Jones et al, 1994) and often portend a poor outcome (Miura et al, 1985). MRI appears to be superior (Horowitz et al, 1987) but findings have not been found to correlate with either COHb level or cognitive sequelae (Parkinson et al, 2002). In general, neuroimaging modalities are usually reserved for patients who show poor response to therapy or have an equivocal diagnosis.
Management
Since no method for predicting bad outcomes is completely reliable, CO poisoning should be treated aggressively with oxygen and perhaps hyperbaric oxygen therapy. The first step in management of suspected CO poisoning is removal of the patient from the offending source, providing 100% supplemental oxygen, and ensuring that there are no urgent airway, breathing, or circulatory issues. The patient should be placed on continuous electrocardiographic monitoring. All efforts should be made to minimize oxygen consumption with bed rest and avoiding agitating the patient. An intravenous line should be placed to provide parental fluids and possibly inotropes should circulatory support be required.
Hypoglycaemia has been described in animal studies and therefore a rapid bedside glucose check should routinely be performed (Piantadosi, 1991). Urine output must be followed closely to identify early signs of rhabdomyolysis. Patients who exhibit ongoing neurologic abnormalities despite a decreasing COHb level should be investigated for the presence of anoxic neurologic injury either CT or urgent MRI.
A non-rebreather mask delivers a fractional inspired oxygen concentration of 70-90%, whereas a positive pressure mask or an endotracheal tube is necessary to deliver oxygen concentrations closer to 100% (Burkhart and Stoller, 1998). Oxygen enhances the dissociation of COHb from haemoglobin (Roughton and Darling, 1944). The half-life of COHb decreases from 5 hours in room air to approximately 1 hour with the provision of 100% oxygen at atmospheric pressure. Hyperbaric oxygen at 2-3 atmospheres decreases the half-life to 20-30 minutes (Pace et al, 1950).
HBO therapy appears to be the treatment of choice for patients with significant CO exposures (Feldmeier, 2003). Hyperbaric therapy will raise the level of dissolved oxygen in the blood to provide basal oxygen requirements, even in the presence of dysfunctional haemoglobin (Piantadosi, 1991). The benefits of HBO likely extend to encompass a neuro-protective role (Thom, 1990). HBO has been shown to prevent ischaemic-reperfusion injury in the CNS (Tomaszewski, 2006). In the rat model, HBO prevented delayed deficits in a learning and memory (Tomaszewski et al, 1992). In humans, the data is less convincing but several studies demonstrate a reduced incidence of DNS with HBO therapy (Camporesi, 1996; Weaver et al, 2002). Given the low risk of adverse consequence of HBO therapy, it has become the standard of care for serious CO poisoning despite the lack of evidence-based guidelines governing the selection of patients (Gasman et al, 1990). The patients most likely to benefit are those most at risk for persistent or delayed neurologic sequelae, such as those presenting with cerebellar signs (Camporesi, 1996), coma (Waisman et al, 1998) or syncope (Tomaszewski, 2006).
Indications for the use of HBO have not been prospectively evaluated generally include any of the following:
HBO therapy does not seem to adversely affect the foetus but experience is limited. Indications for HBO for pregnant women are more conservative (Ginsberg et al, 1974) and include:
Early treatment with HBO is essential because patients treated beyond 6 hours have poorer outcomes in terms of DNS (Ernst and Zibrak, 1998). Patients may benefit if treated so it is not unreasonable to consider HBO within 24 hours of presentation for symptomatic acute poisoning (Gasman et al, 1990). Multiple treatments should be reserved for patients who do not fully recover after one treatment (Ilano and Raffin, 1990).
Although there is a paucity of evidence to support the use of HBO in children, these recommendations should likely be extended to children given their greater susceptibility to the toxic effects of CO. Prior to administration, a few considerations must be addressed. First, myringotomy should be performed in children with active otitis media who are younger than five years (Feldmeier, 2003). Second, infants at risk of hypothermia should be kept warm. A chest radiograph should be obtained prior to HBO therapy to rule out the presence of congenital lung abnormalities that could predispose the child to a pneumothorax. Patients with unrepaired duct dependent congenital cardiac lesions should undergo HBO with caution as oxygen may predispose closure of the ductus arteriosus (Ilano and Raffin, 1990).
Supplemental oxygen should be provided until symptoms resolve and COHb levels fall to below 5% (Ernst and Zibrak, 1998). Despite the fall in COHb, careful attention must be paid to the consequences of tissue hypoxia and oxygen therapy should be provided until symptoms resolve.
Prevention
The advent of high quality home CO detectors provides an early warning system to prevent CO exposures in the home. These devices are widely available and inexpensive. The threshold for a CO alarm to sound at most correlates to a COHb of 10%. Alarms activate earlier with increasing concentrations of CO. If the alarm sounds, occupants should immediately evacuate the dwelling and activate EMS. Until emergency personnel arrive, appliances fuelled by natural gas should be turned off and the windows and doors should be left open (Gasman et al, 1990). Source identification is critical in cases of accidental poisoning in order to minimize the risk to exposure to others. Local fire departments can assist with an assessment of CO level in the suspected environment and removal of victims (Ernst and Zibrak, 1998).
Conclusion
It is imperative that prehospital specialists are aware of CO poisoning and its management. Awareness of CO's epidemiology, and the common presentations of CO poisoning not only lead to prompt evaluation and early initiation of therapy, it can also be life-saving for the prehospital specialist.