Mr. C, a 29-year-old office manager, lives alone in a 90-year-old house that he's renovating in the evenings. One chilly fall morning, he fails to report to work and doesn't answer repeated phone calls to his home. A coworker goes to Mr. C's house and discovers him in bed, confused, lethargic, and covered in vomit.
The coworker drives Mr. C to the ED four blocks away. Upon arrival, Mr. C has a Glasgow Coma Scale score of 10. He opens his eyes only to painful stimuli, is unable to obey simple commands but localizes to painful stimuli and attempts to remove the source, and is able to speak but only in words and phrases that don't make sense. His cough and gag reflexes are intact. The nurse administers 100% supplemental oxygen by non-rebreather face mask. The coworker informs the nurse that Mr. C was out the night before celebrating a friend's birthday and was last seen at about 2 a.m. acting normally. Mr. C is placed on a cardiac monitor, peripheral venous access is obtained and blood specimens are sent to the lab, and a stat 12-lead ECG is obtained. The ED nurse educates the coworker about the importance of calling 911 instead of transporting Mr. C to the hospital himself.
The ECG shows sinus tachycardia with a heart rate of 117 and no ectopy or ST-T wave changes. Mr. C's BP is 98/61 and his SpO2 on supplemental oxygen by pulse oximetry is within normal limits. He's afebrile with a respiratory rate of 24. His complete blood cell (CBC) count and basic metabolic panel are normal, and he has a negative blood ethanol and toxicology screen. A computed tomography scan of the head doesn't reveal any acute abnormalities.
After 2 hours in the ED, Mr. C is awake and alert, with no recollection of why he was brought to the hospital. He states that he remembers going out last evening and coming home, taking a shower, and going to bed. The next thing he remembers is waking up in the ED. Mr. C is discharged home with a diagnosis of altered mental status. Follow-up appointments with his healthcare provider and a neurologist are arranged.
What was missed?
Do you think the ED staff appropriately investigated the reason for Mr. C's altered mental status? Or should more have been done to assess this patient and protect him from further harm?
This article explores these questions because Mr. C's history and clinical manifestation are part of a typical presentation of acute carbon monoxide (CO) toxicity. Even experienced healthcare professionals may miss signs and symptoms of this potentially fatal disorder. During winter, the risk of CO toxicity from malfunctioning heaters and inadequate ventilation increases.
A byproduct of the incomplete burning of carbon-containing materials, CO is a colorless, odorless, and tasteless gas. However, it can cause severe organ damage in minutes, making it the third most common cause of death by toxicity in the United States.1
In the United States, CO toxicity is responsible for about 2,700 deaths and an estimated 50,000 ED visits, although the real number is likely higher because the signs and symptoms of CO toxicity mimic many other disorders.2,3
Data from the CDC on total ED visits in the United States in 2006 indicate that at least 11,000 cases of CO toxicity are undiagnosed every year. Increased public awareness and the use of CO detectors in homes have decreased accidental exposures, but CO toxicity remains a serious health concern.3
Although most people know that CO toxicity can result from smoke inhalation during a structure fire, it can also develop from many other causes. Potential sources include gas and fuel oil heating systems in homes and buildings; gas-fired hot water heaters; coal, wood, or wood pellet stoves; engine exhaust; charcoal and gas grills; and factories with smokestack emissions. People participating in water sports can be exposed to CO in boat engine exhaust.
How CO affects the body
The human body produces minute amounts of CO from the natural breakdown of heme, resulting in a normal carboxyhemoglobin (COHb) level of up to 2% in nonsmokers.4 Smokers and those who frequently inhale engine exhaust, such as truck drivers, may have a level between 5% and 13%, which is normal for them and doesn't cause acute signs and symptoms.4 It isn't fully understood why smokers with elevated levels of COHb don't exhibit signs and symptoms, whereas nonsmokers with the same level do.5
Each hemoglobin molecule is a tetramer with four available oxygen-binding sites (see The ties that bind). However, CO's affinity for hemoglobin is about 300 times greater than that of oxygen. CO binds rapidly with hemoglobin (forming COHb) and prevents hemoglobin from binding with oxygen.1 The result: hypoxemia and the potential for hypoxic injury.
CO toxicity also causes a left shift of the oxyhemoglobin dissociation curve, making it more difficult for the limited amounts of oxygen bound to hemoglobin (oxyhemoglobin) to be released to tissues for use in cellular metabolism. The combination of reduced oxyhemoglobin levels and increased affinity of hemoglobin for oxygen creates a chemical anemia.6
Chemical anemia can be even more damaging than anemia that occurs from blood loss. During hemorrhage, oxygen delivery is reduced solely by bleeding, which depletes the amount of oxygen-carrying hemoglobin in the bloodstream. During chemical anemia, not only does oxygen delivery to tissues decrease, but delivery of CO to the tissues also continues. This creates a metabolic catastrophe due to oxygen deprivation combined with the interaction of CO and various cellular components.6 (See Cellular damage: An inside job.)
Recognizing CO toxicity
Some patients who present to the ED with CO toxicity are readily identified based on history, such as those found in a closed garage with a car engine running or victims of house fires. However, most patients present with a less obvious history or subtler signs and symptoms; as a result, healthcare providers may not initially suspect CO toxicity.
The wide range of signs and symptoms associated with CO toxicity include headache, dizziness, nausea, dyspnea, chest pain, and seizures, depending on the level of COHb. Levels over 70 are associated with cardiopulmonary arrest.3 These nonspecific signs and symptoms can also indicate thousands of other disease processes, so obtaining a detailed history is essential for early diagnosis and treatment. Ask patients (or someone accompanying them) the following questions; if the answers are yes, suspect CO toxicity.
* Do your symptoms occur only in the house? Do they disappear or decrease when you leave home and reappear when you return?
* Is anyone else in your household complaining of similar symptoms? Did everyone's symptoms appear about the same time?
* Are you using any fuel-burning appliances in the home?
* Has anyone inspected your appliances lately? Are you certain they're working properly?
* Do you smoke? Smokers normally have a higher COHb level than nonsmokers, often as much as 13%.4
* Do you have an occupation that puts you at risk for exposure to harmful levels of CO? People with occupational risks include welders, garage mechanics, and toll booth or tunnel attendants.
Obtain an arterial blood specimen to determine the patient's COHb level, which is normally 2% or less in nonsmokers. Keep in mind, however, that this test may produce false negatives and may not correspond to clinical signs and symptoms. In addition, as already noted, smokers and others chronically exposed to CO may have levels as high as 13% without apparent signs and symptoms.
Additionally, patients will need to have a CBC, cardiac biomarkers, basic chemistries, COHb, ethanol, and toxicology screens. Monitoring of renal function including urine output is important, as CO toxicity may cause rhabdomyolysis, resulting in renal failure.
As you monitor the patient's clinical status, remember that you can't rely on standard pulse oximetry to estimate SaO2. Values will be misleading because the light-emitting diode sensor can't distinguish between hemoglobin saturated with CO and hemoglobin saturated with oxygen. Multiwavelength co-oximeters are available that can rapidly differentiate COHb from oxyhemoglobin.7
Co-oximeters obtain a noninvasive COHb level within seconds, helping to guide early therapy.
The hallmark treatment for patients with CO toxicity is prompt removal from the source of CO exposure and 100% oxygen therapy. CO has a half-life of 4 to 5 hours without treatment.4 Administering 15 L/minute of oxygen by non-rebreather face mask cuts the half-life of CO to 90 minutes.3 High-flow oxygen is continued until the patient's neurologic status has returned to baseline and the COHb level is normal.
CO dissipates from the blood with oxygen administration, but it remains bound to tissues for longer.4 Although somewhat controversial, hyperbaric oxygen therapy is believed to help move CO from the tissue back into the circulatory system. After returning to the lungs, CO is removed from the body via exhalation.4 The use of a hyperbaric oxygen chamber decreases the half-life of CO to 30 minutes, but no evidence-based COHb level has been determined as an indication to begin hyperbaric oxygen treatment.3
Prompt use of hyperbaric oxygen therapy, generally within 2 to 6 hours of exposure, has been shown to decrease the incidence of delayed neuropsychiatric symptoms.2 Availability is the main problem with this therapy—most facilities don't have a hyperbaric chamber on site, requiring a delay to transport the patient to another hospital for therapy.3 Other potential drawbacks of hyperbaric oxygen therapy include anxiety from being in an enclosed environment, middle ear barotrauma, and seizures.4
Various criteria are generally accepted for determining which patients will undergo hyperbaric oxygen therapy, including loss of consciousness, seizures, myocardial damage, continued neurologic symptoms despite high-flow oxygen for at least 4 hours, metabolic acidosis, and hypotension.1,3 However, using hyperbaric oxygen therapy for hemodynamically unstable patients may not be indicated because performing resuscitation while the patient is enclosed in the chamber is difficult.
Pregnant women present a unique situation because fetal hemoglobin has a higher affinity for CO than maternal hemoglobin, and high-flow oxygen can't be delivered directly to a fetus. Pregnant patients with CO levels greater than 15% should receive hyperbaric oxygenation in an attempt to help clear fetal CO.6 CO easily moves into the placenta and fetal circulation, so fetal COHb levels may be as much as 15% higher than those recorded in the maternal circulation. The half-life of fetal CO can also be up to five times longer than in the mother.8
Delayed neurologic impairment
Neurologic complications of CO toxicity aren't well understood and can be difficult to anticipate. Delayed onset of neurologic signs and symptoms occurs in 10% to 30% of patients with CO toxicity.6 Patients may present with a normal neurologic exam but begin to exhibit signs and symptoms from 2 to 21 days after the initial toxicity.1 Signs and symptoms of delayed neurologic impairment include:
* loss of memory
* difficulty with concentration
Nearly 10% of patients with toxic levels of CO experience parkinsonian features such as bradykinesia and cogwheel rigidity.4 Drugs used to treat Parkinson disease, such as levodopa and anticholinergic medications, aren't effective in reducing the parkinsonian effects from delayed neuropsychiatric syndrome, a condition seen in some patients after CO toxicity. This syndrome is characterized by delays in cognitive abilities and thought processes.9 Most patients with neurologic complications recover fully.1
Although predicting which patients will experience neurologic complications from CO toxicity is impossible, a tool has been designed to screen for those patients suffering neurologic impairment. The Carbon Monoxide Neuropsychological Screening Battery consists of six individual tests to measure neuropsychometric abilities and assess for cognitive dysfunction.4 For accuracy, the patient must be breathing room air during testing because supplemental oxygen can cause false-negative results. Consequently, testing can't be performed in the initial resuscitation period because the need for supplemental oxygen administration takes precedence.6
Teach patients and their families to recognize neurologic signs and symptoms and promptly report them to their healthcare provider.
Teach patients to avoid problems
Advise patients to install CO detectors in their homes to reduce the risk of CO toxicity; recommend installing one detector outside each sleeping area.10 Remind them to change the batteries twice a year in battery-operated models (for example, when resetting the clocks in the spring and fall). Hardwired CO alarms should have a battery backup so they'll still function if the power fails.10
Although many preventive steps may seem common sense, you still need to educate your patients and families on ways to prevent CO exposure in their homes. The inappropriate use of gasoline-powered generators is a common source of toxicity—even units placed outside of the residence may be near windows or air-conditioning units that let fumes enter the house. Remind patients of the dangers of having a running automobile in a closed garage, using gas-powered ovens and dryers for heating purposes, and using old, faulty furnaces, as these all can lead to CO exposure. Advise them that charcoal grills should be used outdoors only, in a well-ventilated area and away from windows, doors, and air conditioners.10
Clearing the air
Two days later, Mr. C returns to the ED via ambulance. He's asymptomatic and tells you he had placed a CO alarm in his house last night as part of his reconstruction. He was woken up in the middle of the night to the alarm going off. Firefighters arrived at his house after he called 911; they found him standing outside. The ambulance crew reports that firefighters found CO levels inside the house at three times the normal level, with the highest concentration around a 60-year-old oil furnace in the basement.
Be alert for possible CO toxicity when assessing all your patients, but especially those with vague, flulike symptoms. Without a proper diagnosis, a patient exposed to CO may unknowingly return to the same dangerous environment and become poisoned again—with possibly fatal results. Make checking for CO toxicity part of routine patient assessment so you don't miss this invisible killer.
The ties that bind
Once oxygen has diffused into the pulmonary capillary, it moves rapidly into the red blood cells and reversibly binds to hemoglobin to form HbO2. The hemoglobin molecule contains four heme units, each capable of attaching an oxygen molecule. Hemoglobin is 100% saturated when all four units are occupied and is usually 97% saturated in the systemic arterial blood. The capacity of the blood to carry oxygen depends on both hemoglobin levels and the lungs' ability to oxygenate the hemoglobin.
Cellular damage: An inside job
As CO is taken up by cells in the body, it binds with the cytochromes of the mitochondria. This binding prevents electrons from moving through the sequence of cytochromes, which in turn stops the production of adenosine triphosphate (ATP). Because ATP can't be produced, metabolism moves from aerobic to anaerobic, producing lactic acid. With continued anaerobic metabolism, cellular death occurs, continuing a vicious cycle that ultimately progresses to organ failure if not reversed.9
CO also binds with cardiac myoglobin, causing hypoxia in cardiac tissue that may lead to cardiac ischemia.4 Research indicates that 37% of patients with moderate-to-severe CO toxicity develop ECG abnormalities and/or elevation of serum cardiac biomarkers.9 CO bound to myoglobin also reduces myocardial contractility and decreases cardiac output.11
After ischemic damage to the cardiac muscle, white blood cells (WBCs) adhere to the walls of coronary arteries. When oxygenated blood returns to the ischemic myocardium, free radicals released from the attached WBCs enhance lipid peroxidation in the cells, leading to more tissue destruction. This process has also been linked to reperfusion injury.11 Nitric acid production from CO inhalation increases free radical formation and leads to systemic vasodilation, resulting in decreased myocardial blood flow because of decreased venous return, further increasing the risk of a sudden cardiac event.9
Another potential complication of CO toxicity is renal failure from renal tissue hypoxia. Skeletal muscle cell hypoxia can progress to rhabdomyolysis, compounding renal failure.4
© 2013 Lippincott Williams & Wilkins, Inc.