sign in sign up
<<
Home , Oxygen toxicity

CARBON MONOXIDE

DANA BARTLETT, BSN, MSN, MA, CSPI

Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU and ER experience and over 20 years of as a control center information specialist. Dana has published numerous CE and journal articles, written NCLEX material, written textbook chapters, and done editing and reviewing for publishers such as Elsevire, Lippincott, and Thieme. He has written widely on the subject of and was recently named a contributing editor, toxicology section, for Critical Care Nurse journal. He is currently employed at the Connecticut Poison Control Center and is actively involved in lecturing and mentoring nurses, emergency medical residents and pharmacy students.

ABSTRACT

Known as the silent killer, carbon monoxide poisoning in individuals can present in various ways and the medical literature continues to contain areas of uncertainty and controversy. Symptoms of carbon monoxide poisoning tend to be nonspecific in mild and severe cases. Delayed neuropsychiatric effects can occur, which are considered a serious complication. Diagnosis of carbon monoxide poisoning is based upon the patient history and physical examination as well as an elevated carboxyhemoglobin level. The etiology, clinical presentation and treatment are discussed, including those for children and special cases such as during pregnancy.

1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Policy Statement

This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 3 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity.

Statement of Learning Need

Carbon monoxide poisoning is a common and potentially fatal event with nonspecific clinical findings. Clinicians knowledgeable in the identification and treatment of carbon monoxide poisoning can help to initiate neuroprotective interventions and improve patient outcomes.

Course Purpose

This course will help clinicians identify carbon monoxide exposures and the standard treatments for carbon monoxide poisoning.

2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Dana Bartlett, RN, MA, MSN, CSPI, William S. Cook, PhD, Douglas Lawrence, MA, Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

3 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. Carbon monoxide (CO) is a gas that is

a. colorless. b. smells similar to car exhaust. c. taste similar to ammonia. d. All of the above

2. Carbon monoxide (CO) can be produced by

a. toluene b. methylene chloride c. cyanide d. cadmium

3. One of the basic ways carbon monoxide (CO) causes harm is

a. it decreases production of . b. it produces abnormal hemoglobin. c. it causes . d. it causes pulmonary or coronary vasoconstriction.

4. Carbon monoxide (CO) can cause

a. pulmonary capillary vasoconstriction. b. production of methemoglobin. c. . d. direct cellular .

5. Two organs particularly vulnerable to CO poisoning are

a. the brain and the heart. b. the kidneys and the pancreas. c. the gland and the small bowel. d. the and the .

4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Introduction

Carbon monoxide is sometimes called the silent killer, and aptly so. It is a gas that is produced by incomplete combustion of carbon- containing material, it is colorless, odorless, and tasteless, and carbon monoxide (CO) can be lethal. Despite large-scale public education and prevention programs, CO exposure is still a serious public health problem. The pathophysiology, clinical effects, and the best methods for treating CO poisoning have been intensively studied, but there are still areas of uncertainty and controversy.

Epidemiology Of Carbon Monoxide Poisoning

Carbon monoxide poisoning is still very common, and is a leading cause of morbidity and mortality in the United States.1 Each year a minimum of 50,000 people who have been exposed to CO present to hospital emergency rooms and the estimated number of visits because of CO poisoning is much higher;2,3 in 2014 there were 1319 deaths caused by CO;4 and, large-scale CO caused by environmental factors are relatively common.5,6 Exposures to CO can happen at any time of the year but are more common in the winter. If are very cold and/or there is a power outage, people may attempt to heat their homes in unsafe ways. In late October of 2011 in Connecticut, a heavy snowstorm caused widespread power outages, and ambient temperatures at the time were unusually low. Emergency rooms in the state were inundated with cases of carbon monoxide poisoning caused by indoor use of gasoline generators and charcoal burning grills.6

5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Carbon monoxide is produced when carbon-containing materials such as coal, oil, tobacco, or wood are burned. Common sources of CO exposures that can cause poisoning are automobile exhaust fumes, fumes from any gasoline powered engine, natural gas, and wood fires. It is important to remember that CO happen because of the production of CO that occurs when the source material is burned and when these combustion fumes are not properly ventilated.

Two other exogenous sources of carbon monoxide are methylene chloride and methylene iodide. Methylene chloride is a chemical that is a common component of commercially available paint strippers. Inhaled methylene chloride vapors or methylene chloride that is ingested or dermally absorbed is converted in vivo to CO. Because it is stored in fat tissues and the metabolizing enzymes are quickly saturated, peak CO levels produced by methylene chloride , ingestion, or dermal absorption are seen 8 hours or longer after exposure.7 Methylene iodide is used by jewelers to examine gems and, like methylene chloride, it is converted in vivo to CO.8 Carbon monoxide poisoning caused by either of these is very uncommon; there has only been thirteen reported cases of methylene iodide poisoning.9,10

Carbon monoxide is also an endogenous compound. It is produced by the breakdown of hemoglobin, peroxidation, and the of xenobiotics (substances foreign to the body), and it functions as an intrinsic signaling molecule that influences functioning proximally and distally.11,12 The normal level of carbon monoxide in the blood, which is carboxyhemoglobin (COHb) is 0.1%-1.0%, although it may be higher (carboxyhemoglobin levels are discussed later in this course).

6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Although the concept is in the experimental stages, in vitro and animal research suggests that carbon monoxide may have therapeutic value.13,14

Carbon Monoxide Poisoning: Pathophysiology

The mechanism by which CO was traditionally thought to cause poisoning was by its binding to hemoglobin. This is certainly one of the ways that CO causes harm, as will be discussed in detail later in this section. But research has shown that CO poisoning is much more complex and there are multiple, dynamic pathologic processes involved in CO poisoning. As Tomaszewski wrote: “CO toxicity cannot be attributed solely to COHb-mediated hypoxia. Neither the clinical effects nor the phenomena of delayed neurologic deficits can be completely predicted by the extent of binding between hemoglobin and CO.”1

The pathophysiologic mechanisms of CO poisoning are briefly reviewed below.1,2,15-21 Some of these are well outlined and their role in CO poisoning is known while others are more theoretical in nature, and many are interdependent but they are discussed separately for ease of understanding.

Hemoglobin Binding and Transfer Effects

Carbon monoxide binds avidly to hemoglobin. It has an affinity for hemoglobin that is 200-250 times greater than that of oxygen. When CO displaces oxygen from hemoglobin and CO occupies the binding sites for oxygen on hemoglobin, this results in CO and hemoglobin combining to form carboxyhemoglobin (COHb). Carboxyhemoglobin

7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com does not bind with oxygen, so most of the hemoglobin is rendered functionally useless.

The oxyhemoglobin dissociation curve indicates how saturated hemoglobin is at any level of oxygen tension of the blood. (Oxygen tension refers to the partial of oxygen, which said another way, is the pressure of oxygen in a mixture of gases). The oxyhemoglobin dissociation curve also indicates how tightly hemoglobin holds on to oxygen and how easily it releases oxygen for transfer to the tissues. Saturated hemoglobin levels are plotted on a vertical axis, and the prevailing oxygen tension on a horizontal axis to create the oxyhemoglobin dissociation curve. Carbon monoxide shifts the oxyhemoglobin dissociation curve to the left so for any level of less oxygen will be transferred to the tissues. This happens for two reasons. First, carbon monoxide increases the affinity hemoglobin has for oxygen and this prevents the release of oxygen. Second, because there is very little oxygen bound to hemoglobin, the difference between the oxygen level in tissues and the oxygen level of hemoglobin is greatly decreased. This difference is usually a strong driving for the transfer of oxygen from hemoglobin to the tissues, but it is significantly diminished by the presence of CO. In CO poisoning the oxyhemoglobin dissociation curve shifts to the left and less oxygen reaches the tissues.

Myoglobin is an oxygen-transporting and storage pigment that is found inside cells. Carbon monoxide binds to myoglobin, particularly in the myocardium, thus preventing oxygen utilization.

8 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Cellular Effects

Carbon monoxide binds with mitochondrial cytochrome oxidase. Mitochondrial cytochrome oxidase is an important enzyme that is needed for proper functioning of the electron transport chain in cellular that produces the bulk of the adenosine triphosphate (ATP) needed by the body.

High levels of initiate the formation of free radicals. The tissue damage that is caused by poor stimulates an inflammatory response and free formation. The result is a reperfusion injury, caused by the return of oxygen in the blood, which can affect the brain and other parts of the central .

Carbon monoxide poisoning causes . Lipid peroxidation refers to damage caused by free radicals to the that are an integral part of cell membranes. This process is thought to be one of the causes of the neurological effects of CO poisoning.

There is evidence that the induced by free radicals causes neutrophils to adhere to cerebral microvasculature. The result is an inflammatory process that may be the cause of the acute and delayed neurological damage that is a common feature of CO poisoning.

Apoptosis is the process of programmed cell death. Carbon monoxide poisoning is thought to accelerate the process of apoptosis.

9 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Cardiovascular Effects

Carbon monoxide is thought to at times produce a catecholamine surge and this can cause what is called myocardial stunning, which is a temporary, non-ischemic ventricular dysfunction. Carbon monoxide can also inhibit or impair fibrinolysis and increase the amount of thrombin that is formed. Thromboembolic complications caused by CO poisoning have been reported.

Carbon monoxide increases the formation of cyclic guanosine monophosphate. Cyclic guanosine is a second messenger like cyclic adenosine monophosphate (cAMP). Second messengers act to transfer the effects of hormones and other compounds that cannot pass through cell membranes. Cyclic guanosine causes the release of nitric acid from platelets and the vascular endothelium. Cyclic guanosine monophosphate and nitric oxide are potent vasodilators, blood is pooled in the vascular bed, and this decreases oxygen delivery to the tissues.

Pathologic Mechanisms And Clinical Picture Of CO Poisoning

The individual contribution of each of these pathologic mechanisms has not been completely clarified, and it is not understood exactly how and why CO produces the signs and symptoms of CO poisoning. Tissue hypoxia and decreased oxygen utilization at the cellular level are probably responsible for the immediate signs and symptoms of CO poisoning, but carboxyhemoglobin (COHb) levels that reflect tissue hypoxia do not always correlate with the severity of signs and symptoms.1,22,23 Evidence supporting this is that 1) patients do not always improve as CO is eliminated, 2) levels of COHb that are

10 nursece4less.com nursece4less.com nursece4less.com nursece4less.com considered harmless may cause cognitive impairment, and 3) animal experiments have shown that transfused blood with a high level of CO will cause a very high COHb level, but this is less toxic than lower levels of CO that are inhaled.1,22,24

Clinical Care For Patients With Carbon Monoxide Poisoning

Are you a clinician caring for a patient who has CO poisoning? This question may seem odd because the situation and the patient’s complaints quite often make it obvious that a CO exposure has occurred. For example, the patient often reports that the home heating system malfunctioned, the CO detector was alarming, and the patient has common signs and symptoms of CO poisoning. But the clinician needs to remember that CO is called the silent killer. It is colorless, odorless and tasteless, and some exposures to CO can be easily overlooked.

Occult CO exposures, poisonings in which CO was not initially identified as the cause of the patient’s complaints and which prompt a patient to seek medical attention, are relatively common; and, CO poisoning frequently produces a clinical picture that is vague and nonspecific. Carbon monoxide poisoning can be mistaken for , encephalitis, , influenza, migraine headache, or other pathologies. Aside from knowing the common signs and symptoms of CO poisoning, the health team must also know and be aware of circumstances and situations that are likely to cause exposure to CO.

11 nursece4less.com nursece4less.com nursece4less.com nursece4less.com If CO poisoning is suspected, the clinician evaluating the patient should ask the following questions.

• Where were you when you began to feel sick? If you were at home was the heating system on? If these signs and symptoms have occurred before, do they only happen when you are at home? Do they improve when you are out of the house? Does the patient have a functioning CO detector?

• Who do you live with? Has anyone else been sick? If yes, what are their symptoms? If everyone in the house is ill, did his or her symptoms begin at the same time? (If the patient is living with other people but no one else is sick, CO exposure is unlikely).

• Has your heating system, water heater, etc., and the exhaust systems and chimneys in your house been checked recently?

• Do you live in a single-family home or a multi-resident building? Research has shown that CO can diffuse through walls so the absence of a CO producing source in someone’s personal living space does not rule out the possibility of a CO exposure.

• Do you have CO detectors and, if is so, was there an alarm sounding?

• Do you get sick when you are driving your car? Do your symptoms improve after you leave the car? Has your car’s exhaust system been inspected recently?

12 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • Do the symptoms happen while you are at work? If so, what does the patient do and what is happening at work when he/she gets sick? Does the patient work inside? If yes, are there obvious sources of CO? For example, is he/she a mechanic working in a poorly ventilated garage, or working inside a building where gas- powered or gasoline-powered machinery is operating?

• Has the patient been stripping furniture in an unventilated area?

• If there is more than one patient and everyone has essentially the same signs and symptoms, determine if all the patients got sick at the same time (indicating possible CO poisoning) or did the illness start with one person and seem to spread to the others; if it was the latter, the issue may be an infectious illness.

Signs And Symptoms Of Carbon Monoxide Poisoning

Carbon monoxide poisoning can be difficult to detect because the If there is no obvious or known exposure to CO, a mild symptoms may be mild and they are CO exposure can be nonspecific. Also, the number and overlooked or misdiagnosed. intensity of the signs and symptoms of CO poisoning is not always related to the COHB level (COHb levels are discussed in detail in a later section).1,22,23 Patients with low levels may be sicker than patients with high levels.

However, despite the complexity of CO poisoning and the nonspecific nature of the signs and symptoms, the clinical presentation of CO poisoning is easily understood by remembering these three points. The

13 nursece4less.com nursece4less.com nursece4less.com nursece4less.com basic underpinnings of CO poisoning are: 1) Decreased oxygen delivery, 2) Decreased oxygen utilization, and 3) Direct toxic injuries to vulnerable tissues. Keeping these three things in mind, it is relatively simple to understand how CO poisoning presents and why certain populations are vulnerable.

Because CO impairs oxygen delivery and utilization, organs that are very metabolically active such as the brain and the heart are most affected by CO.1 The heart and the brain are also susceptible to direct cellular poisoning as CO has toxic mechanisms that affect those organs. The elderly, children (possibly), people with anemia, cardiovascular disease, or pulmonary disease, and people who smoke have a higher risk of developing serious CO poisoning than do healthy individuals or those who are neither very young nor very old.

CO Symptom Severity

The severity of CO poisoning depends on patient risk factors and on the circumstances of the exposure, but essentially the higher the CO level and the longer the time of exposure then the sicker the patient is likely to be.

The clinical picture of CO poisoning can be usefully divided into mild, moderate, and severe. There can be considerable overlap in the signs and symptoms of the presentation, and it is helpful to think of CO poisoning as a continuum of signs and symptoms, caused by tissue hypoxia and direct cellular toxicity that affect vulnerable organs.

Patients with mild CO may have confusion, dizziness, fatigue, headache, , and tachycardia. Patients with moderate CO

14 nursece4less.com nursece4less.com nursece4less.com nursece4less.com poisoning may have ataxia, chest pain, dyspnea, syncope, and tachycardia. And, patients with severe CO poisoning may have arrhythmias, coma, hypotension, metabolic acidosis, and .

As mentioned previously, the heart is particularly vulnerable to damage from CO because it is so metabolically active and has a very high need for oxygen. The heart is also affected by mechanisms of injury that cause direct cellular damage. Cardiovascular signs and symptoms, from mild to serious, are very common after CO exposure. Patients often have palpitations and tachycardia and may develop angina, arrhythmias, cardiogenic , cardiomyopathy, heart failure, nonspecific ST segment and T wave changes, pulmonary edema, and ST-segment and non-ST-segment myocardial infarction.1,16,18,19,25-33

Myocardial injury is relatively common after CO poisoning.33,34 ST- segment MI is a rare consequence of CO poisoning,16,25,35 and myocardial infarction can occur in patients who do not have coronary artery disease.16 Also, myocardial injury caused by CO poisoning has been associated with an increased risk of short-term (but not long- term) mortality.23,25,29

Neurologic signs and symptoms are a prominent part of the clinical picture of CO poisoning. Hypoxia increases intracranial pressure and can cause cerebral edema, and these effects, along with direct cellular toxicity, is partially the cause of the neurologic signs and symptoms of CO poisoning. Ataxia, dizziness, drowsiness, fatigue, headache, and other neurologic signs and symptoms are common after CO poisoning. More serious effects such as coma, cortical blindness, seizures, and syncope can occur after a moderate to severe exposure to CO.1,2,36

15 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Other neurologic effects such as hearing loss,37,38 peripheral neuropathy,37 amnesia,39 cataracts,40 chorea,41 tics,42 and monoparesis,43 have been reported.

Perhaps the most studied and most concerning of the neurologic effects of CO poisoning is a phenomenon called delayed neuropsychiatric sequelae (DNS). Some patients who have suffered CO poisoning will develop neurological deficits after a symptom-free period. Because of the seriousness of this problem and because the risk of neurological sequelae is one of the primary reasons for the use of hyperbaric oxygen (HBO) therapy to treat patients who have been poisoned with CO, DNS will be discussed separately.

Delayed Neuropsychiatric Sequelae

A neurological condition known as delayed neuropsychiatric sequelae (DNS) is among the most serious complications of CO poisoning. These neurological complications occur after a period of normal consciousness and although complete recovery from DNS is possible, permanent, severe affective disorders, cognitive, and autonomic and motor impairments can also happen.

Incidence of DNS

Delayed neuropsychiatric sequelae appear to be relatively common, but the exact incidence of this complication is not known. Researchers have reported incidences of 2.75%, 14.4%, 16.5%, 30%, 40%, and 47%,45-50 and abnormal electroencephalograms (EEGs) have been reported in 58% of patients who were diagnosed as having DNS.51 Different evaluation criteria, diagnostic criteria, and patient populations could explain why the reported incidence of DNS varies so

16 nursece4less.com nursece4less.com nursece4less.com nursece4less.com widely. Hampson (2015) estimated that each year approximately 6600 people exposed to CO develop long-term cognitive sequlae.51

Onset of DNS

The onset of DNS has been reported to be from two days to eight months after exposure.1,44

Loss of Consciousness and DNS

There is no correlation between COHb levels and the development of DNS. Patients who are comatose after a CO exposure may, or may not develop DNS, and patients who have not lost consciousness may develop serious neurological problems.36,53

DNS Risk Factors

Some factors that seem to be consistently associated with an increased risk of developing DNS are age > 36 years and a duration of exposure > 24 hours.54 Other researchers noted an association between a duration of exposure > 6 hours, seizures, a Glasgow Coma Score < 9, leukocytosis, and elevated CK, or a systolic blood pressure < 90 mm Hg and DNS.47 A recent (2014) study found that predictors for the development of delayed encephalopathy were 1) abnormal computed tomography (CT) scan findings that indicated hypoxic encephalopathy, 2) high creatine kinase, 3) high creatine-kinase MB, 4) high lactate dehydrogenase, and 5) low Global Assessment Scale score.47

17 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Signs and Symptoms of DNS

The signs and symptoms of neuropsychiatric sequelae can be divided into affective, cognitive, and autonomic and motor impairments. Affective impairments that have been reported include , depression, irritability, mood swings, and psychosis. Cognitive effects that have been reported include deficits in attention, , memory, and speech, and dementia. Autonomic and motor impairments that have been reported include chorea, dystonia, incontinence, myoclonus, and parkinsonism signs such as bradykinesia, mask face rigidity, and shuffling gait.1,15,57-59

Recovery from DNS

Recovery from DNS does occur,55,56 and the rate of recovery is quite variable, from 56% to 97%.1

The Toxic Dose 0f Carbon Monoxide

The toxic dose of carbon monoxide depends on patient characteristics of age, medical history, metabolic rate, and ; and, the environmental factors of CO concentration in the air and the duration of exposure. The concentration of CO in the inspired air and the duration of exposure are the factors that are most predictive of the seriousness of the exposure. The higher the concentration of CO and the longer the duration of the exposure, the higher the COHb level will be and the greater the risk for harm.

The Occupational Safety and Health Administration (OSHA) standard is that workers cannot be exposed in an eight-hour working day to an average of more than 50 parts per million (ppm) of CO. Most Carbon

18 nursece4less.com nursece4less.com nursece4less.com nursece4less.com monoxide detectors installed in private residences are usually calibrated to alarm if the CO concentration in the air averages 70 ppm for an hour or longer. Most people will begin to experience symptoms, such as, dizziness and headache when the CO level is 100 ppm, and a CO level of 5000 ppm is usually lethal within five minutes. Blood levels of CO do not correlate well with symptoms, but higher levels are more likely to cause signs and symptoms, and COHb levels 50% and higher have been associated with coma, seizures, and death.60

Carboxyhemoglobin Level

The carboxyhemoglobin (COHb) level is a vital piece of information that is needed to assess a patient who has or is suspected to have CO poisoning. In order to use the COHb for assessment the clinician must know: 1) If the patient smokes and, if so, how much, 2) Medical problems and clinical conditions that can affect COHb level, 3) How the COHb level was measured, 4) When the COHb level was measured in relation to the time the patient was last exposed, and 5) What treatment for CO poisoning the patient has received.

COHb Level and Smoking

Tobacco combustion produces CO and smokers have higher COHb levels than nonsmokers. Smokers typically have COHb levels of 6%- 10%61-63 and higher levels have been reported.63,64 Each pack of cigarettes smoked per day will raise the COHb level approximately 2.6%,65 and in moderate and heavy smokers a single cigarette will significantly increase the COHb level for six hours or longer.66 A COHb level of > 3% in a non-smoker or > 10% in a smoker is strongly suggestive of a CO exposure.15

19 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Medical Problems and Clinical Conditions and COHb Level

Hemolytic anemia, sickle cell disease, an elevated serum bilirubin level with hemolysis, malaria, and trauma can cause an elevated COHb level.67-72 An elevated COHb level has been reported in a patient who was mechanically ventilated and receiving nitric oxide therapy.73 The accuracy of COHb levels can be affected if the COHb level is < 2%-3%, if the blood specimen is lipemic, if the patient has received methylene blue, or in the presence of fetal hemoglobin.74

The patient’s medical conditions and age need to be considered as well when interpreting COHb levels. A patient who has anemia, cardiovascular disease, or pulmonary disease will be vulnerable to decreased oxygen delivery and utilization. Children and infants may be particularly vulnerable to CO poisoning because of their higher metabolic rate; because they cannot accurately – or cannot at all – tell someone how they feel; and, because of the presence of fetal hemoglobin.75

Fetal hemoglobin is a form of hemoglobin that has a greater affinity for oxygen than adult hemoglobin. At birth infants have a fetal hemoglobin concentration of approximately 70%; this ratio is rapidly reversed by three to six months of age, and at one year fetal hemoglobin is essentially gone.74,76 Certain methods of measuring COHb will also measure fetal hemoglobin as COHb. The higher the level of fetal hemoglobin the greater the degree of interference and in the presence of fetal hemoglobin, false COHb levels as high as 7% to 8% have been reported.1,76

20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Measurement Techniques and COHb Levels

Carboxyhemoglobin levels are measured with a co-oximeter, which is a device that can measure the amount of hemoglobin that is saturated with CO. Either arterial or venous blood can be used to measure COHb.1, 23 Older bedside pulse oximeters were not able to distinguish between hemoglobin saturated with oxygen and COHb.1 Bedside pulse co-oximeters have shown some promise as a screening device but their accuracy at specific levels and in certain clinical conditions has been questioned.1,44,77-79 A recent 2017 literature review by a subcommittee of the American College of Emergency Physicians (ACEP) recommended against using bedside pulse co-oximeters for diagnosing CO poisoning.80

Carbon Monoxide Absorption and Elimination

Carbon monoxide is rapidly absorbed. Elimination depends on several factors but increasing the of oxygen increases the rate of dissociation of COHb so the more supplemental oxygen that is delivered, the faster COHb will be eliminated. The half-life of COHb when someone is room air is approximately 4-6 hours, and it is approximately 60 minutes when 100% oxygen is applied. The half- life of COHb is reduced to approximately 20 minutes if someone is treated with hyperbaric oxygen.1,2,36,44 When a clinician is interpreting COHb levels, he/she must consider how long the patient has been away from the source of CO, and how long and how much oxygen the patient had received.

Carboxyhemoglobin levels are needed to confirm the presence of CO poisoning. Carboxyhemoglobin levels are also used to determine what

21 nursece4less.com nursece4less.com nursece4less.com nursece4less.com treatment the patient needs and to some degree the COHb level may predict the level of severity of CO poisoning. However, there is universal agreement that COHb levels are unreliable for predicting the severity of any particular case of CO poisoning and should not be depended upon to do so.1,15,22

Levels of 47% have been reported in patients who have minimal symptoms, and levels of 10% have been noted in patients who were comatose.81 Also, the level of COHb that is used to determine what treatment the patient needs - specifically whether or not the patient should receive hyperbaric - is not clear or universally agreed upon.

Treatment Of Carbon Monoxide Poisoning

Treating a case of CO poisoning begins by removing the patient from the source, assessing the patient’s airway, breathing, and circulation (ABCs), and assessing the patient’s cardiac and neurological status. Following removal from the source and after a rapid assessment of the ABCs, oxygen at 100% via a facemask should be applied; if the patient is comatose, he or she should be endotracheally intubated.44 If the patient has chronic obstructive pulmonary disease and retains , high of oxygen should be used with caution.81 Arrhythmias, hypotension, and seizures would be treated with basic, supportive care.

Sometime during the initial assessment, the circumstances of the exposure should be determined, i.e., how the exposure occurred, the duration of the exposure, when the patient(s) were removed from the source, and when oxygen was applied. If the fire department

22 nursece4less.com nursece4less.com nursece4less.com nursece4less.com responded to the scene, the clinician should find out if the ambient air concentration of CO was measured and, if so, the level of measure.

A COHb level should be done and if there is any risk for myocardial ischemia or damage, the patient should be placed on continuous electrocardiogram (ECG) , a 12-lead ECG should be done, and creatine-kinase (CK) MB and troponin levels should be obtained. If the patient has lost consciousness, has an altered level of consciousness, had a , or was hypotensive, or is at risk for acidosis, laboratory tests of an arterial blood gas (ABG), serum lactate level, serum electrolytes, BUN, creatinine, and serum creatinine kinase (CK) should be measured. Computed tomography scanning or magnetic resonance imaging (MRI) scanning of the head should be performed if the patient has neurological deficits or lost consciousness. If the CO exposure resulted from intent to cause self-harm, the clinician should request laboratory testing of acetaminophen, ethanol, and salicylate levels.

Assessment Plan for a CO Exposure

Remove the patient from the source Apply supplemental oxygen via a face mask at 100%. Document when this was started Assess the ABCs Determine the circumstances of the exposure. Measure a COHb level Risk for or evidence of myocardial ischemia/damage: Continuous ECG monitoring, 12-lead ECG, CK-MB, troponin level Acidosis, altered consciousness, hypotension or seizure: ABG, serum lactate level, serum electrolytes, BUN, creatinine, and CK should be measured CO poisoning caused by self-harm: Measure acetaminophen, ethanol, and salicylate levels

23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Patients who were asymptomatic on arrival or had mild to moderate poisoning should receive supplemental oxygen until symptoms have resolved, and they can be discharged when it is certain that myocardial and neurological injuries did not occur and the COHb level has returned to normal. In most cases, four to six hours of oxygen therapy is sufficient.

It can not be overemphasized that the clinician evaluating a patient with possible CO poisoning should be very careful to document when the patient was last exposed to CO, when and at what percent/flow oxygen therapy was started, and when the COHb level was obtained. These facts will be very important in terms of assessing the severity of the case, the patient’s response to therapy, and the possible need for more aggressive treatment. Prior to discharge, the clinician should make sure that the patient knows how and why the poisoning occurred and to make sure the patient is returning to a safe environment.

Health clinicians understand how CO is produced but the patient may not. The patient may return home and continue to use a malfunctioning heating system or neglect to purchase a CO detector. A short review about safe home heating practices is a helpful preventive measure. In addition, before the patient is discharged, consideration should be given to perform a Mini Mental Status Exam (MMSE) and if needed an arrangement for a follow- up neurologic examination. The Mini The Mini Mental Status exam is performed to screen for Mental Status Exam is a 30-question cognitive impairment, such as to patient orientation to time and exam that is used to detect cognitive place, attentiveness, memory, speech and the ability to follow impairments, and it is widely used commands. because it is quick and simple to do.

24 nursece4less.com nursece4less.com nursece4less.com nursece4less.com If cognitive deficits are detected using the MMSE then more sophisticated neurologic testing should be done. If the patient does not respond to norm-baric oxygen (oxygen delivered at normal ), if the patient has serious complications, or if the patient is considered to have a serious exposure, two issues must be considered: 1) the patient may be suffering from cyanide exposure or methemoglobinemia (the latter is very uncommon); or, 2) the patient may need hyperbaric oxygen (HBO) therapy. Cyanide can be produced as a byproduct of combustion that occurs during house fires ( complicating a CO exposure will be discussed in a later section).

Patients who have suffered a serious CO poisoning should be admitted to intensive care. There are no universally agreed upon criteria for what constitutes a serious CO poisoning but most clinicians would consider an exposure to be serious if any of indicators in the Table below is present.

Indicators of Serious CO Exposure

Arrhythmias Cardiac ischemia COHb > 25 Fetal distress Loss of consciousness Metabolic acidosis Persistent depressed level of consciousness Pregnancy and a COHb level of >15% Seizure

25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Patients for whom any of these indicators of CO poisoning apply should be admitted and a toxicologist, a poison control center, or a specialist should be consulted.

Hyperbaric Oxygen Therapy

Patients who have serious CO poisoning are potential candidates for hyperbaric oxygen (HBO) therapy. Hyperbaric oxygen therapy delivers 100% oxygen at atmospheric that are 2 to 3 times above normal. The dissolved concentration of blood oxygen concentration is typically 0.3 mL/dL, but when HBO at three times normal atmospheric pressure (3 ATM) is administered the dissolved blood oxygen concentration is increased to 6 mL/dL. The increased plasma concentration of oxygen is beneficial, and HBO also increases the dissociation of CO from hemoglobin, increases the dissociation of CO from cytochrome oxidase, and decreases free radical production and leukocyte-mediated inflammation.2,83-85

Hyperbaric oxygen is routinely used for patients with serious CO poisoning or patients who do not respond to normo-baric oxygen therapy, and most often to prevent the development and/or reduce the severity of DNS. However, important basic issues about its use have not been clarified or resolved.

Effectiveness of Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy has many beneficial physiological effects and given the pathological processes of CO poisoning, it seems logical that HBO would be an effective treatment for CO poisoning, particularly for preventing DNS. There is evidence that supports it use

26 nursece4less.com nursece4less.com nursece4less.com nursece4less.com for this 86,87 and there are many HBO advocates. However, there is no unequivocal proof that HBO can prevent DNS or reduce its severity. There is research and literature reviews that have determined that HBO is not an effective treatment;88 and, the American College of Emergency Physicians (ACEP) concluded that “It remains unclear whether HBO2 therapy is superior to normo-baric oxygen therapy for improving long-term neurocognitive outcomes.”80

Patient Selection for Hyperbaric Oxygen Therapy

There are no universally accepted criteria for selecting patients who would benefit from HBO therapy,89,90 and developing these criteria has been problematic for several reasons. First, there is no agreed upon definition of what constitutes a serious CO poisoning. Second, the level of CO that defines a serious CO poisoning – and that would prompt the use of HBO therapy – is not known and varies with each case. Third, there is no reliable way to predict which patients with CO poisoning are at risk for developing delayed neuropsychiatric sequelae. However, HBO therapy is frequently used for cases of CO poisoning and the recommendations for HBO do not vary significantly from source to source. Examples are provided in the Tables below.

Undersea and Hyperbaric Medicine Society Recommendations for HBO Therapy91

Loss of consciousness, even a transient loss Abnormal neurologic findings COHb level is ≥ 25% Pregnant patients There is a significant metabolic acidosis.

27 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Recommendations for HBO therapy cited by Maloney81

Carboxyhemoglobin >25% Confusion/altered mental status Coma Evidence of acute myocardial ischemia Focal neurologic deficit Pregnancy with carboxyhemoglobin level >15% Seizure Syncope

Recommendations for HBO Therapy by Clardy, et al.44

COHb > 25% Evidence of ongoing end-organ ischemia such as metabolic acidosis or myocardial ischemia Loss of consciousness Pregnancy and a COHb > 20% or signs of fetal distress

Duration and End-point Number of HBO Therapy Sessions

There are no standard protocols for how often someone should receive HBO therapy, when it should be discontinued and the duration of an HBO therapy session. Hyperbaric oxygen therapy is thought to be most effective when it is started within six hours of CO exposure,44 and Clardy, et al. noted that: “Benefit for patients treated more than 12 hours after their CO exposure is unproven.”44 However, there are multiple accounts in the literature that document the benefits of HBO therapy when it is administered days, months, and years after the initial CO exposure,92-95 and it appears that HBO treatment will use several treatments and have different endpoints for therapy.

28 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Hyperbaric Oxygen Therapy Sessions

An HBO therapy session (which is often called a dive) is done in an HBO chamber. These can be small mono-place (holding a single person) chambers or a multi-place sealed room that can accommodate one or more patients, a , monitoring equipment, and (occasionally) a nurse. The mono-place chamber is filled with 100% oxygen, which is compressed to the desired atmospheric pressure. In the multi-place chamber, the patient breathes 100% oxygen from an outside source and the ambient air in the chamber is compressed.

Most large cities have a hyperbaric oxygen treatment center, but the referring health facility may be far away from the HBO treatment center. Deciding who is stable enough to be transferred and when he/she should be transferred should be considered very carefully.

Patients who have been intubated may need sedation and occasionally neuromuscular paralysis during hyperbaric oxygen treatment. The cuff of the endotracheal tube should be deflated and refilled with sterile saline before the patient enters the chamber; the high atmospheric pressure can collapse the cuff if it is filled with air. The patient’s pulmonary status and blood pressure must be monitored carefully when he/she is in the chamber. can increase the risk of seizures, so the PACO2 should be maintained at a normal level.

Hyperbaric oxygen therapy can lower the blood pressure so blood pressure should be checked frequently, especially if the patient has cardiovascular disease or is receiving an intravenous vasopressor. The duration of most dives is about 2 hours. Some patients will be prescribed several sessions over the course of several days.

29 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Side Effects/Adverse Outcomes of HBO Therapy

Most side effects of HBO therapy are mild and temporary. Middle ear such as bleeding, pain, and perforation of the eardrum is the most common side effect of HBO therapy96,97 with a reported incidence as high as 10.3% - 35.8%.98,99 Factors that increase the risk of middle ear barotrauma during HBO therapy are age (very young and very old), the use of sedation during the HBO session, history of ear, nose and throat (ENT) radiation, history of cardiovascular disease, endotracheal intubation and , inflammatory processes in the nasopharynx, and anticoagulant use.96,99 Barotrauma to the and air embolization are rare adverse effects.100,101

Seizures are possible, but they do not cause residual damage. The incidence of seizures during hyperbaric oxygen therapy is very low, typically < 1%.102-104 The presence of anxiety, fever, , prior seizure, traumatic brain injury (TBI) and high HBO pressure may increase the risk of seizure occurrence during HBO therapy.102-104 The only absolute contraindication to using HBO is pneumothorax. Relative contraindications include asymptomatic pulmonary blebs or bullae seen on chest X-ray, claustrophobia, obstructive lung disease, recent ear or thoracic surgery, uncontrolled fever, or upper respiratory or sinus infections.

Pediatric Carbon Monoxide Poisoning

Children have a higher metabolic rate and a developing nervous system, so it seems intuitive that they would be more susceptible to the effects of CO poisoning at lower levels of CO. effects of CO poisoning such as lethargy and syncope are more

30 nursece4less.com nursece4less.com nursece4less.com nursece4less.com common in children than in adults,105 but DNS is less common for children; the reported incidence of this complication has been 3% - 17%,44 but a more recent study in 2016 found a 33.3% incidence of DNS in pediatric CO poisonings.106 Permanent neurologic sequelae can occur in children, as well.106

Significant cardiac damage in pediatric patients with CO poisoning can occur.107 A 2010 study found that 16 of 107 pediatric patients with CO poisoning had cardiac biomarkers indicating myocardial damage, and evidence of ventricular wall abnormalities, and low ejection fraction,108 which were findings that were mirrored in a later study in 2016.109

If HBO therapy is necessary for a child who has CO poisoning, there are specific issues to keep in mind.44

• If the child is < five years old, has otitis media, and cannot equalize middle ear pressure, a myringotomy should be performed. • Children may need a parent to accompany them in the HBO chamber. • When HBO is administered to an infant, the infant should be kept warm; hypothermia is a risk for this age group. • Certain congenital abnormalities can complicate HBO therapy. A chest X-ray should be done to be sure the child does not have lobar emphysema; this could cause a pneumothorax during HBO therapy. • Children who have unpalliated ductal dependent cardiac lesions should be treated very cautiously because HBO therapy can cause duct closure. These patients may not be suitable candidates for HBO; and a pediatric cardiologist should be consulted.

31 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Carbon Monoxide Poisoning And The Pregnant Patient

Carbon monoxide can be very dangerous to a fetus because even a relatively small decrease in maternal oxygen saturation can cause a sharp drop in fetal oxygen saturation. In addition, fetal hemoglobin has a higher affinity for binding to CO than maternal hemoglobin and fetal elimination of COHb is much slower than the maternal elimination rate.44,110

There is little published information about CO poisoning in pregnant women. Friedman, et al. reviewed the medical literature from 1970 to 2010 and located 19 articles,110 and the largest cases series was by Koren, et al. in 1991, examining CO poisoning in 32 patients.111 Koren, et al. found that mild to moderate CO poisoning did not cause physical or neurobehavioral damage but that in five cases of significant maternal exposure there were two fetal deaths and one case of cerebral palsy.111 Fetal morbidities associated with maternal CO poisoning include flexia, cardiomegaly, hypotonia, hypoxic ischemic encephalopathy, limb malformations, microcephaly, persistent seizures, preterm delivery, and death.110 Fetal death and fetal injury can also occur even if the mother is relatively asymptomatic and the COHb level is low.112,113

The recommendations for treating the pregnant patient who has CO poisoning are essentially the same as for any other patient, but there are several important differences. A medical toxicologist or a hyperbaric medicine physician should be consulted in all such cases. Administration of 100% oxygen may need to be continued for much longer than it would normally be needed because of the COHb-fetal hemoglobin binding and the higher fetal COHb levels. Additionally, as

32 nursece4less.com nursece4less.com nursece4less.com nursece4less.com pregnancy is an indication for the use of HBO therapy in cases of CO poisoning, early notification of the local HBO treatment facility would be prudent. There is very little information on the effects of HBO therapy of the fetus but it appears to be safe.44

Patient Non-Response To Oxygen Treatment

There are several reasons why a patient who has been poisoned with CO does not respond to treatment, but perhaps the most common reason may be cyanide poisoning. Cyanide is a highly toxic gas that results from the incomplete combustion of -containing material, and cyanide gas exposure is thought to be common during fires and smoke inhalation.2,114

Cyanide is a chemical asphyxiant, and it interferes with aerobic production of ATP by binding to cytochrome oxidase and preventing the use of oxygen by the electron transport chain. Since situations such as house fires very often cause CO poisoning, the patient is at great risk for hypoxic injury and there may be a synergistic effect between CO and cyanide that increases their respective toxicity.

Determining if a patient who has CO poisoning also has been poisoned by cyanide is not simple. Cyanide poisoning should be suspected if the patient:114 • with CO poisoning caused by a fire does not respond to oxygen therapy as expected. • was involved in an enclosed space during a fire. • has an altered level of consciousness. • has an elevated plasma lactate level.

33 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • has hypotension that cannot be explained by the CO poisoning or by another pathologic mechanism.

Cyanide poisoning will not respond to oxygen therapy; the pathologic mechanism of cyanide poisoning and CO poisoning are distinctly different. Patients with cyanide poisoning must be given the cyanide antidote kit or hydroxocobalamin (an injectable form of vitamin B-12).

Patients with combined CO and cyanide poisoning may also benefit from hyperbaric oxygen therapy but there is no evidence that it is effective for cyanide poisoning. Some toxicologists and emergency department physicians feel that hydroxocobalamin should be given empirically to most fire victims; these patients should be evaluated on a case-by-case basis for the use of this antidotal therapy.

Are Ambient Levels Of Carbon Monoxide Harmful?

Carbon monoxide is a by-product of the combustion of fossil fuels and the combustion of carbon-containing material for fuel and it is a common air pollutant. The ambient levels of CO in urban areas have been found to range from 2-40 ppm, but in areas of heavy automobile traffic the ambient level can reach an average of 500 ppm.115 Second- hand smoke can also be a significant source of ambient CO,116,117 and there is also strong evidence that chronic exposure to ambient CO as part of air pollution increases cardiovascular morbidity and mortality.118 The studies that have examined the health effects of chronic exposure to CO as an air pollutant are in part confounded by the presence of other air pollutants and varying study group populations, and the exact contribution of ambient CO to cardiovascular morbidity and mortality has not yet been determined.

34 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Follow-Up After CO Poisoning

People who have had CO poisoning should be followed closely after discharge. Survivors of CO poisoning appear to have a significantly higher rate of death than the general population. One study found the increase in deaths in this population to be twice what would be expected.119

The onset of delayed neuropsychiatric sequelae can occur weeks after an exposure to CO, so the patient and the clinician who is providing follow-up care must be aware of this. If these complications do occur, there are no treatments that have been evaluated with clinical trials. Symptomatic and supportive care should be provided, and this can include (when appropriate) occupational therapy, physical therapy, and speech therapy. Cognitive symptoms from DNS have been treated with donepezil (a drug used for the treatment of mild to moderate dementia), but this is an unlabeled use of the drug, very little experience using donepezil for this purpose exists, and the results have been equivocal.120-122

Stimulant drugs such as dextroamphetamine, methylphenidate, and modafanil might be helpful to treat attention and memory deficits, but there is no clinical experience with them yet. Anticholinergics, aripiprazole, bromocriptine, levodopa, and levothyroxine have been used for Parkinsonism caused by CO but there is very little clinical experience with this approach.123-126

35 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Summary

Carbon monoxide is a dangerous gas that is produced by the incomplete combustion of fossil fuels such as gasoline and kerosene, and by the combustion of carbon-containing materials like coal and wood. Carbon monoxide is also produced endogenously and by burning of tobacco. The normal COHb level for a nonsmoker is usually ≤ 1% and for a smoker it is 6% to 10%. Poisoning with CO occurs when the gas is inhaled, and CO causes harm by two basic mechanisms: 1) Preferentially binding hemoglobin, thus causing tissue hypoxia; and, 2) Direct cellular toxic mechanisms. The result of these two basic pathologic mechanisms is decreased oxygen delivery and disruption of cellular metabolism.

The signs and symptoms of CO poisoning are vague and nonspecific, but CO is the most toxic to the organs that are the most metabolically active and have high oxygen demands, so the brain and the heart are particularly vulnerable to CO. Cardiac and neurologic signs and symptoms predominate in cases of CO poisoning. These can be mild and self-limiting or quite serious. Most patients will complain of headache, dizziness, and palpitations, but coma, myocardial infarction, permanent neurological deficits, seizures and death are possible. A particularly concerning effect of CO poisoning is delayed neuropsychiatric sequelae (DNS). Some patients who have suffered CO poisoning will have an asymptomatic period of days to weeks and then will develop debilitating affective, cognitive, and autonomic/motor deficits.

Treating CO poisoning begins with understanding the circumstances and situations in which CO poisoning likely occurs. These may not

36 nursece4less.com nursece4less.com nursece4less.com nursece4less.com always be obvious or reported by the patient, and studies have shown that occult CO poisonings, poisonings in which CO was not initially identified as the cause of the patient’s complaints, are relatively common.127 Treatment of confirmed cases of CO poisoning always begins with assessment and stabilization of the ABCs, administration of 100% oxygen, and continuous cardiac monitoring.

Diagnostic and laboratory tests should include a COHb level, creatine kinase MB and troponin levels, and a 12-lead ECG. Other tests that may be needed will depend on the patient’s condition, and have been discussed. A thorough assessment of the patient’s neurological and cardiovascular status should be done. The COHb level is a vital part of the assessment, but COHb levels do not accurately predict the seriousness of the exposure or correlate well with signs and symptoms.

Patients should receive supplemental oxygen at 100% via face mask and be observed for at least four to six hours, and most patients can be discharged from the hospital emergency department when the COHb level has returned to normal and signs and symptoms have resolved. A Mini Mental Status Exam should be performed before the patient leaves the emergency department. In addition, the health team should make sure that the patient understands how CO poisoning happens and (if he/she is returning home) that there are functioning CO detectors at the residence. A follow-up appointment for a neurologic exam should be arranged. If the patient has had serious signs or symptoms of CO poisoning, admission to the hospital is advised and HBO therapy may be indicated.

37 nursece4less.com nursece4less.com nursece4less.com nursece4less.com There are no universally accepted criteria for when to use HBO and for whom, but commonly cited indications for HBO raised in this course involving serious CO exposure should prompt the treating clinician to consult with a hyperbaric medicine specialist, a poison control center, or a toxicologist. Hyperbaric oxygen therapy is primarily used to prevent the development of DNS. However, despite many years of clinical experience and much study, the clinical benefits of HBO therapy for the prevention of DNS are still unproven.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation.

Completing the study questions is optional and is NOT a course requirement.

38 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. Carbon monoxide (CO) is a gas that is

a. colorless. b. smells similar to car exhaust. c. taste similar to ammonia. d. All of the above

2. Carbon monoxide (CO) can be produced by

a. toluene b. methylene chloride c. cyanide d. cadmium

3. One of the basic ways carbon monoxide (CO) causes harm is

a. it decreases production of hemoglobin. b. it produces abnormal hemoglobin. c. it causes tissue hypoxia. d. it causes pulmonary or coronary vasoconstriction.

4. Carbon monoxide (CO) can cause

a. pulmonary capillary vasoconstriction. b. production of methemoglobin. c. hemolysis. d. direct cellular toxicity.

5. Two organs particularly vulnerable to carbon monoxide (CO) poisoning are

a. the brain and the heart. b. the kidneys and the pancreas. c. the thyroid gland and the small bowel. d. the lungs and the liver.

6. True or False: Carboxyhemoglobin (COHb) level is a good predictor of the seriousness of the carbon monoxide (CO) exposure.

a. True b. False

39 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7. The primary treatment for carbon monoxide (CO) poisoning in a patient who is conscious is

a. hydroxocobalamin. b. 100% oxygen via a facemask. c. endotracheal intubation. d. methylene blue.

8. Patients who have had carbon monoxide (CO) poisoning are at risk for

a. delayed neuropsychiatric sequelae. b. increased risk of developing metabolic syndrome. c. delayed onset of liver damage. d. increased risk of developing Alzheimer’s.

9. True or False: Tobacco combustion produces CO and smokers have higher COHb levels than non-smokers.

a. True b. False

10. According to Clardy, et al., which of the following are indications for the use of HBO?

a. Age < 5 years or COHb level > 10% b. Pregnancy and a COHb >20% or signs of fetal distress c. Age > 55 years and headache d. Female gender and metabolic acidosis

11. Which of the following are indications for the use of HBO?

a. The development of delayed myocardial ischemia b. The development of shock to the liver c. The development of rhabdomyolysis d. The development of delayed neuropsychiatric sequelae

40 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12. The ambient levels of carbon monoxide (CO) in urban areas have been found to range from 2-40 ppm, but in areas of heavy automobile traffic the ambient level can reach an average of

a. 500 ppm. b. 50 ppm. c. 100 ppm. d. 250 ppm.

13. Because of large-scale public education and prevention programs, carbon monoxide poisoning has become uncommon in the United States.

a. True b. False

14. Peak carbon monoxide (CO) levels produced by methylene chloride inhalation, ingestion, or dermal absorption are seen

a. immediately after exposure. b. within minutes of exposure. c. only if inhaled. d. 8 hours or longer after exposure.

15. Oxyhemoglobin dissociation indicates the level of hemoglobin saturation at any level

a. of lipid peroxidation. b. of oxygen tension of the blood. c. of cerebral microvasculature. d. above toxic levels.

16. The difference between the oxygen level in body tissue and the oxygen level of hemoglobin

a. helps drive the transfer of O2 from hemoglobin to tissue. b. slows the transfer of O2 from hemoglobin to tissue. c. is the primary cause of cellular toxicity. d. increases the risk of developing metabolic syndrome.

41 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17. In carbon monoxide (CO) poisoning the oxyhemoglobin dissociation curve shifts to the

a. right and less oxygen reaches the tissues. b. left and more oxygen reaches the tissues. c. left and less oxygen reaches the tissues. d. right and more oxygen reaches the tissues.

18. True or False: In vitro and animal research suggests that carbon monoxide may have therapeutic value.

a. True b. False

19. ______is an oxygen-transporting and storage pigment that is found inside cells.

a. Hydroxocobalamin b. Hemoglobin c. Myoglobin d. Methemoglobin

20. There is evidence that the oxidative stress induced by ______causes neutrophils to adhere to cerebral microvasculature.

a. oxygen tension b. apoptosis c. catecholamine surge d. free radicals

21. A patient presents with metabolic acidosis, which is a symptom of

a. moderate CO poisoning. b. severe CO poisoning. c. cyanide poisoning not CO poisoning. d. methemoglobinemia

42 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22. Which of the following conditions is symptomatic of moderate CO poisoning?

a. metabolic acidosis b. seizures c. hypotension d. syncope

23. True or False: Levels of COHb that are considered harmless may cause cognitive impairment.

a. True b. False

24. Symptoms of delayed neuropsychiatric sequelae (DNS) - potential effect of CO poisoning - include affective and cognitive impairment and the onset of DNS has been reported to be

a. within 8 hours of exposure. b. more than a year after exposure. c. from two days to eight months after exposure. d. from 48-72 hours after exposure.

25. The most common side effect of HBO therapy is

a. lethargy. b. syncope. c. seizures. d. middle ear barotrauma.

43 nursece4less.com nursece4less.com nursece4less.com nursece4less.com CORRECT ANSWERS:

1. Carbon monoxide (CO) is a gas that is

a. colorless.

“Carbon monoxide (CO) is sometimes called the silent killer, and aptly so. It is a gas that is produced by incomplete combustion of carbon-containing material, it is colorless, odorless, and tasteless, and CO can be lethal.”

2. Carbon monoxide (CO) can be produced by

b. methylene chloride

“Inhaled methylene chloride vapors or methylene chloride that is ingested or dermally absorbed is converted in vivo to CO. Because it is stored in fat tissues and the metabolizing enzymes are quickly saturated, peak CO levels produced by methylene chloride inhalation, ingestion, or dermal absorption are seen 8 hours or longer after exposure. Methylene iodide is used by jewelers to examine gems and, like methylene chloride, it is converted in vivo to CO.”

3. One of the basic ways carbon monoxide (CO) causes harm is

c. it causes tissue hypoxia.

“Poisoning with CO occurs when the gas is inhaled, and CO causes harm by two basic mechanisms: 1) Preferentially binding hemoglobin, thus causing tissue hypoxia; and, 2) Direct cellular toxic mechanisms.”

4. Carbon monoxide (CO) can cause

d. direct cellular toxicity.

“Neurologic signs and symptoms are a prominent part of the clinical picture of CO poisoning. Hypoxia increases intracranial pressure and can cause cerebral edema, and these effects, along with direct cellular toxicity, is partially the cause of the neurologic signs and symptoms of CO poisoning.”

44 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5. Two organs particularly vulnerable to carbon monoxide (CO) poisoning are

a. the brain and the heart.

“The signs and symptoms of CO poisoning are vague and non- specific, but CO is the most toxic to the organs that are the most metabolically active and have high oxygen demands, so the brain and the heart are the particularly vulnerable to CO.”

6. True or False: Carboxyhemoglobin (COHb) level is a good predictor of the seriousness of the carbon monoxide (CO) exposure.

b. False

“Carboxyhemoglobin levels are also used to determine what treatment the patient needs and to some degree the COHb level may predict the level of severity of CO poisoning. However, there is universal agreement that COHb levels are unreliable for predicting the severity of any particular case of CO poisoning and should not be depended upon to do so.”

7. The primary treatment for carbon monoxide (CO) poisoning in a patient who is conscious is

b. 100% oxygen via a facemask.

“Following removal from the source and after a rapid assessment of the ABCs, oxygen at 100% via a facemask should be applied; if the patient is comatose, he or she should be endotracheally intubated. If the patient has chronic obstructive pulmonary disease and retains carbon dioxide, high concentrations of oxygen should be used with caution. Arrhythmias, hypotension, and seizures would be treated with basic, supportive care.”

8. Patients who have had carbon monoxide (CO) poisoning are at risk for

a. delayed neuropsychiatric sequelae.

“One potential effect of CO poisoning is delayed neuropsychiatric sequelae (DNS).”

45 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9. True or False: Tobacco combustion produces CO and smokers have higher COHb levels than non-smokers.

a. True

“Tobacco combustion produces CO and smokers have higher COHb levels than non-smokers.”

10. According to Clardy, et al., which of the following are indications for the use of HBO?

b. Pregnancy and a COHb >20% or signs of fetal distress

“Recommendations for HBO Therapy by Clardy et al.,… Pregnancy and a COHb >20% or signs of fetal distress.”

11. Which of the following are indications for the use of HBO?

d. The development of delayed neuropsychiatric sequelae

“Hyperbaric oxygen is routinely used for patients with serious CO poisoning or patients who do not respond to normo-baric oxygen therapy and most often, to prevent the development and/or reduce the severity of DNS. However, important, basic issues about its use have not been clarified or resolved.”

12. The ambient levels of carbon monoxide (CO) in urban areas have been found to range from 2-40 ppm, but in areas of heavy automobile traffic the ambient level can reach an average of

a. 500 ppm.

“The ambient levels of CO in urban areas have been found to range from 2-40 ppm, but in areas of heavy automobile traffic the ambient level can reach an average of 500 ppm.”

46 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13. Because of large-scale public education and prevention programs, carbon monoxide poisoning has become uncommon in the United States.

b. False

“Despite large-scale public education and prevention programs, CO exposure is still a serious public health problem. The pathophysiology, clinical effects, and the best methods for treating CO poisoning have been intensively studied, but there are still areas of uncertainty and controversy. Carbon monoxide poisoning is still very common. Carbon monoxide poisoning is a leading cause of morbidity and mortality in the United States.”

14. Peak carbon monoxide (CO) levels produced by methylene chloride inhalation, ingestion, or dermal absorption are seen

d. 8 hours or longer after exposure.

“Because it is stored in fat tissues and the metabolizing enzymes are quickly saturated, peak CO levels produced by methylene chloride inhalation, ingestion, or dermal absorption are seen 8 hours or longer after an exposure.”

15. Oxyhemoglobin dissociation indicates the level of hemoglobin saturation at any level of

b. oxygen tension of the blood.

“The oxyhemoglobin dissociation indicates how saturated hemoglobin is at any level of oxygen tension of the blood. It also indicates how tightly hemoglobin holds on to oxygen and how easily it releases oxygen for transfer to the tissues.”

16. The difference between the oxygen level in body tissue and the oxygen level of hemoglobin

a. helps drive the transfer of O2 from hemoglobin to tissue.

“… because there is very little oxygen bound to hemoglobin, the difference between the oxygen level in tissues and the oxygen level of hemoglobin is greatly decreased. This

47 nursece4less.com nursece4less.com nursece4less.com nursece4less.com difference is usually a strong driving force for the transfer of oxygen from hemoglobin to the tissues, but it is significantly diminished by the presence of CO.”

17. In carbon monoxide (CO) poisoning the oxyhemoglobin dissociation curve shifts to the

c. left and less oxygen reaches the tissues.

“In CO poisoning the oxyhemoglobin dissociation curve shifts to the left and less oxygen reaches the tissues.”

18. True or False: In vitro and animal research suggests that carbon monoxide may have therapeutic value.

a. True

“Although the concept is in the experimental stages, in vitro and animal research suggests that carbon monoxide may have therapeutic value.”

19. ______is an oxygen-transporting and storage pigment that is found inside cells.

c. Myoglobin

“Myoglobin is an oxygen-transporting and storage pigment that is found inside cells. Carbon monoxide binds to myoglobin - particularly in the myocardium - thus preventing oxygen utilization.”

20. There is evidence that the oxidative stress induced by ______causes neutrophils to adhere to cerebral microvasculature.

d. free radicals

“Carbon monoxide poisoning causes lipid peroxidation. Lipid peroxidation refers to damage caused by free radicals to the lipids that are an integral part of cell membranes. This process is thought to be one of the causes of the neurological effects of CO poisoning. There is evidence that the oxidative stress induced by free radicals causes neutrophils to adhere to cerebral microvasculature.”

48 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21. A patient presents with metabolic acidosis, which is a symptom of

b. severe CO poisoning.

“Patients with severe CO poisoning may have arrhythmias, coma, hypotension, metabolic acidosis, and seizures.”

22. Which of the following conditions is symptomatic of moderate CO poisoning?

d. syncope

“Patients with mild CO may have confusion, dizziness, fatigue, headache, nausea, and tachycardia…. Patients with moderate CO poisoning may have ataxia, chest pain, dyspnea, syncope, and tachycardia…. Patients with severe CO poisoning may have arrhythmias, coma, hypotension, metabolic acidosis, and seizures.”

23. True or False: Levels of COHb that are considered harmless may cause cognitive impairment.

a. True

“Evidence supporting this is that patients do not always improve as CO is eliminated; levels of COHb that are considered harmless may cause cognitive impairment; and, animal experiments have shown that transfused blood with a high level of CO will cause a very high COHb level, but this is less toxic than lower levels of CO that are inhaled.”

24. Symptoms of delayed neuropsychiatric sequelae (DNS) - potential effect of CO poisoning - include affective and cognitive impairment and the onset of DNS has been reported to be

c. from two days to eight months after exposure.

“One potential effect of CO poisoning is delayed neuropsychiatric sequelae (DNS). Symptoms include affective and cognitive impairment. The onset of DNS has been reported to be from two days to eight months after exposure. …. Delayed neuropsychiatric sequelae appear to be relatively

49 nursece4less.com nursece4less.com nursece4less.com nursece4less.com common, but the exact incidence of this complication is not known…. The onset of DNS has been reported to be from two days to eight months after exposure.”

25. The most common side effect of HBO therapy is

d. middle ear barotrauma.

“Most side effects of HBO therapy are mild and temporary. Middle ear barotrauma such as bleeding, pain, and perforation of the eardrum is the most common side effect of HBO therapy.”

References Section

The References below include published works and in-text citations of published works that are intended as helpful material for your further reading.

1. Tomaszewski C. (2014). Carbon monoxide. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbuam NE, eds. Goldfrank’s Toxicologic Emergencies, 10th ed. New York, NY: McGraw-Hill; 2014: 1581-1593. 2. Rose JJ, Wang L, Xu Q, McTiernan CF, Shiva S, Tejero J, Gladwin MT. (2016). Carbon monoxide poisoning: Pathogenesis, management and future directions of therapy. Am J Respir Crit Care Med. 2016 Oct 18. [Epub ahead of print] 3. Iqbal, S., et al. (2007). Hospital burden of unintentional carbon monoxide poisoning in the United States, 2007. Am J Emerg Med. 2012;30(5):657-664. 4. Hampson NB. (2016). U.S. mortality due to carbon monoxide poisoning, 1999-2014. Accidental and intentional deaths. Ann Am Thorac Soc. 2016;13(10):1768-1774. 5. Chen BC, Shawn LK, Conors NJ, et al. (2013). Carbon monoxide exposures in New York City following Hurricane Sandy in 2012. Clin Toxicol (Phila). 2013;51(9):879-885. 6. Johnson-Arbor K, Quental AS, Li D. (2014). A comparison of carbon monoxide exposures after snowstorms and power outages. Am J Prev Med. 2014;46(5):481-486.

50 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7. Cabrera VJ, Farmakiotis D, Aggarwal V. (2011). Methylene chloride intoxication treated with hyperbaric oxygen therapy. Am J Med. 2011;124(5):e3-e4. 8. Weimerskirch PJ, Burkhart KK, Bono MJ, Finch AB, Montes JE. (1990). Methylene iodide poisoning. Ann Emerg Med. 1990;19(10):1171-1176. 9. Schwartz MD, Obamwonyi AO, Thomas JD, Moorhead JF, Morgan BW. (2005). Acute methyl iodide exposure with delayed neuropsychiatric sequelae: report of a case. Am J Ind Med. 2005;47(6):550-556. 10. Mackenzie Ross S. (2016). Delayed cognitive and psychiatric symptoms following methyl iodide and manganese poisoning: Potential for misdiagnosis. Cortex. 2016;74:427-39. 11. Ji X, Damera K, Zheng Y, Yu B, Otterbein LE, Wang B. (2016). Toward carbon monoxide-based therapeutics: Critical drug delivery and developability issues. J Pharm Sci. 2016;105(2):406-416. 12. Wegiel, B., et al. (2013). The social network of carbon monoxide in medicine. Trends Mol Med. 2013;19(1):3-11. 13. Nakahira K, Choi AM. (2015). Carbon monoxide in the treatment of . Am J Physiol Lung Cell Mol Physiol. 2015 Dec 15;309(12):L1387-93. doi: 10.1152/ajplung.00311.2015. Epub 2015 Oct 23. 14. Ryter SW, Choi AM. (2013). Carbon monoxide: present and future indications for a medical gas. Korean J Intern Med. 2013;28(2):123-140 15. Guzman JA. (2012). Carbon monoxide poisoning. Crit Care Clin. 2012;28(4):537-548. 16. Dziewierz A Ciszowski K, Gawlikowski T, et al. (2013). Primary angioplasty with patient with ST-segment elevation myocardial infarction in the setting of intentional carbon monoxide poisoning. J Emerg Med. 2013;45(6):831-834. 17. Hampson NB, Piantadosi CA, Thom SR. Weaver LK. (2012). Practice recommendations in the diagnosis, management, and prevention of carbon monoxide poisoning. Am J Resp Critl Care Med. 2012;186(11):1095-1101. 18. Jung YS, Lee JS, Min YG, et al. (2014). Carbon monoxide- induced cardiomyopathy. Circulation Journal. 2014;78(6):1437- 1444. 19. Teodoro T, Geraldes R, Pinho E, Melo T. (2013). Symptomatic internal carotid artery thrombosis in acute carbon monoxide poisoning. Am J Emerg Med. 2013; 32(6):684.e5-e6.

51 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20. Ryoo SM, Sohn CH, Kim HJ, Kwak MK, Oh BJ, Lim KS. (2013). Intracardiac thrombus formation induced by carbon monoxide poisoning. Hum Expl Toxicol. 2013;32(11):1193-1196. 21. Gawlikowski T, Gomolka E, Piekoszewski W, Jawień W, Undas A. (2013). Acute CO poisoning is associated with impaired fibrinolysis and increased thrombin formation. Basic Clin Pharmacol Toxicol. 2013;112(5):352-356. 22. Hampson NB, Dunn SL. (2012). Symptoms of carbon monoxide poisoning do not correlate with the initial carboxyhemoglobin level. Undersea Hyperb Med. 2012;39(2):657-665. 23. Hampson NB. (2016). Myth busting in carbon monoxide poisoning. Am J Emerg Med. 2016;34(2):295-297. 24. Goldbaum LR, Orellano T, Dergal E. (1976). Mechanism of the toxic action of carbon monoxide. Ann Clin Lab Sci. 1976;6(4):372-376. 25. Sward DG, Sethuraman KN, Wong JS, Rosenthal RE. (2016). Carbon monoxide and ST-elevation myocardial infarction: case reports. Undersea Hyperb Med. 2016;43(1):63-69. 26. Salih SB, Alenezi H, Alghamdi A. (2013). A case of first degree AV block in carbon monoxide poisoning patient. J Saudi Heart Assoc. 2013;25:255-259. 27. Cetin M, Ornek E, Murat SN, Cetin ZG, Oksuz F, Gokcen E. (2011). A case of carbon monoxide poisoning presenting with supraventricular tachycardia. Intern Med. 2011;50:2607-2609. 28. Garg J, Krishnamoorthy P, Palaniswamy C, et al. (2014). Cardiovascular abnormalities in carbon monoxide poisoning. Am J Ther. 2014; Feb 10. [Epub ahead of print] 29. Lee FY, Chen WK, Lin CL, Kao CH. (2015). Carbon monoxide poisoning and subsequent cardiovascular disease risk: a nationwide population-based cohort study. Medicine (Baltimore). 2015 Mar;94(10):e624. doi: 10.1097/MD.0000000000000624. 30. Chung WS, Lin CL, Kao CH. (2015). Carbon monoxide poisoning and risk of deep vein thrombosis and pulmonary embolism: a nationwide retrospective cohort study. J Epidemiol Community Health. 2015;69(6):557-562. 31. Lee JH, Kim HS, Park JH, et al. (2016). Incidence and clinical course of left ventricular systolic dysfunction in patients with carbon monoxide poisoning. Korean Circ J. 2016;46(5):665-671. 32. Teerapuncharoen K, Sharma NS, Barker AB, Wille KM, Diaz- Guzman E. (2015). Successful treatment of severe carbon monoxide poisoning and refractory shock using extracorporeal membrane oxygenation. Respir Care. 2015;60(9):e155-160. 33. Unlu M, Ozturk C, Demirkol S, et al. (2016). Thrombolytic therapy in a patient with inferolateral myocardial infarction after

52 nursece4less.com nursece4less.com nursece4less.com nursece4less.com carbon monoxide poisoning. Hum Exp Toxicol. 2016;35(1):101- 105. 34. Satran D, Henry CR, Adkinson C, et al. (2005). Cardiovascular manifestations of moderate to severe carbon monoxide poisoning. J Am Coll Cardiol.2005; 45(9):1513-1516. 35. Onal O, Celik D, Aslanlar E, Avci A, Bengi Celik J. (2016). Myocardial infarction in a young patient after acute exposure to carbon monoxide. Anesth Pain Med. 2016 Feb 13;6(3):e33154. doi: 10.5812/aapm.33154. 36. Olson KR. (2012). Carbon monoxide. In: Olson KR, Anderson IB, Benowitz NL, et al, eds. Poisoning & Drug Overdose. 6th ed. New York, NY: Lange Medical Books/McGraw-Hill;2012. 37. Weaver LK. (2014). Hyperbaric oxygen therapy for carbon monoxide poisoning. Undersea Hyperb Med. 2014;41(4):339- 354. 38. Mehrparvar AH, Davari MH, Mollasadeghi A, et al. (2013). Hearing loss due to carbon monoxide poisoning. Case Rep Otolaryngol. 2013;2013:940187. doi: 10.1155/2013/940187. 39. Mahmoud O, Mestour M, Loualidi M. (2009). Carbon monoxide intoxication and anterograde amnesia. Encéphale. 2009; 35:281-285. 40. Kasbekar S, Gonzalez-Martin JA. (2011). Chronic carbon monoxide poisoning resulting in bilateral cataracts and a cystic globus pallidus lesion. BMJ Case Rep. 2011 Jul 15;2011. pii: bcr0320113985. doi: 10.1136/bcr.03.2011.3985. 41. Ubaidulhaq M, Lee YA, Jiang H. (2016). Chorea as the neurological symptom of delayed encephalopathy after carbon monoxide intoxication in a child. Neurohospitalist. 2016 Jul;6(3):130-131. 42. Alioglu Z, Boz C, Sari A, Aynaci M. (2004). Transient tic disorder following carbon monoxide poisoning. Journal of Neuroradiology. 2004;31:231-233. 43. Tajima Y, Satoh C, Yaguchi H, Mito Y. (2014). Neurological picture. Pure motor monoparesis of the leg after carbon monoxide intoxication. J Neurol Neurosurg Psychiatry. 2014;85(11):1286-1287. 44. Clardy PF, Manaker S, Perry H. (2017). Carbon monoxide poisoning. UpToDate, February 2, 2017. https://www.uptodate.com/contents/carbon-monoxide- poisoning?source=search_result&search=carbon%20monoxide% 20poisoning&selectedTitle=1~73#H8. 45. Choi IS. (2002). Parkinsonism after carbon monoxide poisoning. Eur Neurol. 2002;48(1):30–33.

53 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 46. Duenas-Laita A, Ruiz-Mambrilla, GM, Gandia F, et al. (2001). Epidemiology of acute carbon monoxide poisoning in a Spanish region. J Toxicol-Clinl Toxicol. 2001;39(1):53-57. 47. Kudo K, Otsuka K, Yagi J, et al. (2014). Predictors for delayed encephalopathy following acute carbon monoxide poisoning. BMC Emerg Med. 2014 Jan 31; 14:3. doi: 10.1186/1471-227X-14-3. 48. Ernst A, Zibrak JD. (1998). Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603-1608. 49. Pepe G, Castelli M, Nazerian P, et al. (2011). Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the emergency department. A retrospective study. Scand J Trauma Resusc Emerg Med. 2011 Mar 17;19:16. doi: 10.1186/1757-7241-19-16. 50. Kao LW, Nañaga KA. (2006). Toxicity associated with carbon monoxide poisoning. Clin Lab Med. 2006;26(1):99-125. 51. Quinn DK, McGahee SM, Politte LC, et al. (2009). Complications of carbon monoxide poisoning. Prim Care Companion J Clin Psychiatry. 2009;11(2):74-79. 52. Hampson NB. (2015). Cost of accidental carbon monoxide poisoning: A preventable expense. Prev Med Rep. 2015 Dec 3;3:21-4. doi: 10.1016/j.pmedr.2015.11.010. eCollection 2016. 53. Min SK. (1986). A brain syndrome associated with delayed neuropsychiatric sequelae following acute carbon monoxide poisoning. Acta Psychiat Scand. 1986;73(1):80-86. 54. Weaver LK, Valentine KJ, Hopkins RO. (2007). Carbon monoxide poisoning: risk factors for cognitive sequelae and the role of hyperbaric oxygen. Am J Resp Crit Care Med. 2007;176(5):491- 497. 55. Song IU, Cho HJ, Kim YD, Chung SW. (2011). Improvement of cognitive impairment following delayed CO encephalopathy. Can J Neurol Sci. 2011;38(6):934-935. 56. Seino K, Hayashida A, Iseki K. (2013). Case of carbon monoxide poisoning with delayed encephalopathy assessed by magnetic resonance imaging. Chudoku Kenkyu. [Article in Japanese].2013;26(1):54-60. 57. Kao HW, Cho NY, Hsueh CJ, et al. (2012). Delayed Parkinsonism after CO exposure: Evaluation of the substantia nigra with inversion-recovery MR imaging. Radiology. 2012;265(1):215- 221. 58. Kuroda H, Fujihara K, Takahashi S, Shinozawa Y, Itoyama Y. (2012). A case of delayed encephalopathy after carbon monoxide poisoning longitudinally monitored by tensor monitoring. AJNR Am J Neuroradiol. 2012;33(4): E52-E54.

54 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 59. Kudo K, Sanjo K, Koizumi N, et al. (2012). Two patients with delayed neuropsychiatric sequelae caused by exposure to carbon monoxide under the same conditions. Prim Care Companion CNS Disord. 2012;14(3). pii: PCC.11l01316. doi: 10.4088/PCC.11l01316. Epub 2012 May 24. 60. Micromedix. ® Poisindex. (2016). Carbon Monoxide. http://www.micromedexsolutions.com.online.uchc.edu/microme dex2/librarian. 61. Hart CL, Smith GD, Hole DJ, Hawthorne VM. (2006). Carboxyhaemoglobin concentration, smoking habit, and mortality in 25 years in the Renfrew/Paisley prospective cohort study. Heart. 2006;92(3):321-324. 62. García Arroyo I, Fernández Testa A, Ochoa Sangrador C, et al. (2003). [Article in Spanish]. Subclinical carbon monoxide poisoning in our health area. Rev Clin Esp. 2003;203(8):378- 381. 63. Ernst A, Zibrak JD. (1998). Carbon monoxide poisoning. N Engl J Med. 1998;339(22):1603-1608. 64. Sen S, Peltz C, Beard J, Zeno B. (2010). Recurrent carbon monoxide poisoning from cigarette smoking. Am J Med Sci. 2010;340(5):427-428. 65. Aker J. (1987). Carboxyhemoglobin levels in banked blood: a comparison of cigarette smokers and non-smokers. AANA. 1987;55(5):421-426. 66. Sokolova-Djokić L, Milosević S, Skrbić R, Salabat R, Voronov G, Igić R. (2011). Pulse carboxyhemoglobin-oximetry and cigarette smoking. J BUON. 2011;16(1):170-173. 67. Hampson NB. (2007). Carboxyhemoglobin elevation due to hemolytic anemia. J Emerg Med. 2007;33(1):17-19. 68. Sears DA, Udden MM, Thomas LJ. (2001). Carboxyhemoglobin levels in patients with sickle-cell anemia: relationship to hemolytic and vasoocclusive severity. Am J Med Sci. 2001;322(6):345-348. 69. Lozar-Krivec J, Bratanic B, Paro-Panjan D. (2016). The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization. J Matern Fetal Neonatal Med. 2016;29(3):452-6. 70. Serita R, Morisaki H, Satoh T, et al. (2002). Carboxyhemoglobin and postsurgical hyperbilirubinemia in patients undergoing esophagectomy. J Anesth. 2002;16(3):251-254. 71. Yeo, TW, Lampah DA, Kenangalem E, Tjitra E, Price RN, Anstey NM. (2013). Increased carboxyhemoglobin in adult falciparum malaria is associated with disease severity and mortality. J Infect Dis. 2013;208(5):813-817.

55 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 72. Moncure M, Brathwaite CE, Samaha E, Marburger R, Ross SE. (1999). Carboxyhemoglobin elevation in trauma victims. J Trauma. 1999;46(3):424-427. 73. Ruisi P, Ruisi M. (2011). Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and . South Med J. 2011;104(1):46-48 74. Mehrotra S, Edmonds M, Lim RK. (2011). False elevation of carboxyhemoglobin: a case report. Pediatr Emerg Care. 2011;27(2):138-140 75. Macnow TE, Waltzman ML. (2016). Carbon monoxide poisoning in children: Diagnosis and management in the emergency department. Pediatr Emerg Med Pract. 2016;13(9):1-24. 76. Perrone J, Hoffman RS. (1996). Falsely elevated carboxyhemoglobin levels secondary to fetal hemoglobin. [Letter to the editor]. Acad Emerg Med. 1996;3(3):287-9. 77. Hess DR. (2016). Pulse oximetry: Beyond SpO2. Respir Care. 2016;61(12):1671-1680. 78. Harlan N, Weaver LK, Deru K. (2016). Inaccurate pulse CO- oximetry of carboxyhemoglobin due to digital clubbing: case report. Undersea Hyperb Med. 2016;43(1):59-61 79. Feiner JR, Rollins MD, Sall JW, Eilers H, Au P, Bickler PE. (2013). Accuracy of carboxyhemoglobin detection by pulse CO-oximetry during hypoxemia. Anesth Analog. 2013;117(4):847-858. 80. Wolf SJ, Maloney GE, Shih RD, Shy BD, Brown MD. (2017). American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Carbon Monoxide Poisoning: Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute carbon monoxide poisoning. Ann Emerg Med. 2017;69(1):98-107. 81. Maloney G. (2017). Carbon Monoxide. In: Tintinalli JE, Stapczynski JS, Ma OJ, Yealy DM, Meckler GD, Cline DM, eds. Tintinalli’s : A Comprehensive Study Guide, 8th ed. New York, NY; McGraw-Hill: 2016, on-line ed. www.UCHC.edu. 82. Lane TR, Williamson WJ, Brostoff JM. (2008). Carbon monoxide poisoning in a patient with carbon dioxide retention: a therapeutic challenge. Cases J. 2008;1(1):102. 83. Mechem CC, Manaker S. (2016). Hyperbaric oxygen therapy. UpToDate, June 6, 2016 http://www.uptodate.com/contents/hyperbaric-oxygen-therapy.

56 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 84. Lin YT, Chen SY, Lo CP, et al. (2015). Utilizing cerebral perfusion scan and diffusion-tensor MR imaging to evaluate the effect of hyperbaric oxygen therapy in carbon monoxide-induced delayed neuropsychiatric seqeulae - A case report and literature review. Acta Neurol Taiwan. 2015;24(2):57-62. 85. Thom SR. (2014). Hyperbaric oxygen. In: Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbuam NE, eds. Goldfrank’s Toxicologic Emergencies, 10th ed. New York, NY: McGraw-Hill; 2014: 1594-1601. 86. Weaver LK, Hopkins RO, Chan KJ, et al. (2002). Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347(14):1057-1067. 87. Chan MY, Au TTs, Leung KS, Yan WW. (2016). Acute carbon monoxide poisoning in a regional hospital in Hong Kong: historical cohort study. Hong Kong Med J. 2016;22(1):46-55. 88. Buckley NA, Juurlink DN, Isbister G, Bennett MH, Lavonas EJ. (2011). Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst Rev. 2011 Apr 13;(4):CD002041. doi: 10.1002/14651858.CD002041.pub3. 89. Byrne BT, Lu JJ, Valento M, Bryant SM. (2012). Variability in hyperbaric oxygen treatment for acute carbon monoxide poisoning. Undersea & Hyperbaric Medicine. 2012;39(2):627- 638. 90. Roderique JD, Josef CS, Feldman MJ, Spiess BD. (2015). A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology. 2015;334:45-58. 91. Gesell LB, ed. (2008). Hyperbaric oxygen therapy indications. 12th ed. Durham, NC; Undersea and Hyperbaric Medicine Society: 2008. 92. Spagnolo F, Costa M, Impellizzeri M, et al. (2011). Delayed hyperbaric oxygen treatment after acute carbon monoxide poisoning. J Neurol. 2011;258(8):1553-1554. 93. Stoller KP. (2007). Hyperbaric oxygen and carbon monoxide poisoning: a critical review. Neurol Res. 2007;29(2):146-155. 94. Senol MG, Yildiz S, Ersanli D, et al. (2009). Carbon monoxide- induced cortical visual loss: treatment with hyperbaric oxygen four years later. Med Princ Pract. 2009;18(1):67-69. 95. Ziser A, Shupak A, Halpern P, Gozal D, Melamed Y. (1984). Delayed hyperbaric oxygen treatment for acute carbon monoxide poisoning. Br Med J (Clin Res Ed). 1984;289(6450):960. 96. Lima MA, Farage L, Cury MC, Bahamad F Júnior. (2014). Update on middle ear barotrauma after hyperbaric oxygen therapy-

57 nursece4less.com nursece4less.com nursece4less.com nursece4less.com insights on pathophysiology. Int Arch Otorhinolaryngol. 2014;18(2):204-209. 97. Camporesi EM. (2014). Side effects of hyperbaric oxygen therapy. Undersea Hyperb Med. 2014;41(3):253-257. 98. Bessereau J, Tabah A, Genotelle N, Français A, Coulange M, Annane D. (2010). Middle-ear barotrauma after hyperbaric oxygen therapy. Undersea Hyperb Med. 2010;37(4):203-208. 99. Commons KH, Blake DF, Brown LH. (2013). A prospective analysis of independent patient risk factors for middle ear barotraumas in a multi-place hyperbaric chamber. Diving Hyperb Med. 2013;43(3):143-147. 100. Jaeger NJ, Brosious JP, Gustavson RB, et al. (2013). Pneumomediastinum following hyperbaric oxygen therapy for carbon monoxide poisoning: a case report. Undersea Hyperbar Med. 2013;40(6):521-523. 101. Buschmann DK. (2010). Arterial gas embolism during pressure tolerance testing in a hyperbaric chamber: a report of two cases. Aviat Space Environl Med. 2010;81(12):1133-1136. 102. Heyboer M 3rd, Jennings S, Grant WD, Ojevwe C, Byrne J, Wojcik SM. (2014). Seizure incidence by treatment pressure in patients undergoing hyperbaric oxygen therapy. Undersea Hyperb Med. 2014;41(5):379-385 103. Banham ND. (2011). Oxygen toxicity seizures: 20 years' experience from a single hyperbaric unit. Diving Hyperb Med. 2011;41(4):202-210. 104. Sanders RW, Katz AD, Suyama J, et al. (2012). Seizure during hyperbaric oxygen therapy for carbon monoxide toxicity: a case series and five-year experience. J Emerg Med. 2012;42(4):e-69- e72. 105. Crocker PJ, Walker JS. (1985). Pediatric carbon monoxide toxicity. J Emerg Med. 1985;3(6):443-448. 106. Chang YC, Lee HY, Huang JL, Chiu CH, Chen CL, Wu CT. (2016). Risk factors and outcome analysis in children with carbon monoxide poisoning. Pediatr Neonatol. 2016 Jul 17. pii: S1875- 9572(16)30077-8. doi: 10.1016/j.pedneo.2016.03.007. [Epub ahead of print] 107. Gandini C, Castoldi AF, Candura SM. (2001). Cardiac damage in pediatric carbon monoxide poisoning. Jf Toxicol-Clin Toxicol. 2001;39(1):45-51. 108. Teksam O, Gumus P, Bayrakci B, Erdogan I, Kale G. (2010). Acute cardiac effects of carbon monoxide poisoning in children. Eur J Emerg Med. 2010;17(4):192-196. 109. Ozyurt A, Karpuz D, Yucel A, Tosun MD, Kibar AE, Hallioglu O. (2016). Effects of acute carbon monoxide poisoning on ECG and

58 nursece4less.com nursece4less.com nursece4less.com nursece4less.com echocardiographic parameters in children. Cardiovasc Toxicol. 2016 Oct 24. [Epub ahead of print] 110. Friedman P, Guo XM, Stiller RJ, Laifer SA. (2015). Carbon monoxide exposure during pregnancy. Obstet Gynecol Surv. 2015;70(11):705-712. 111. Koren G, Sharav T, Pastuszak A, et al. (1991) A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy. Reprod Toxicol.1991;5(5):397-403. 112. Farrow JR, Davis GJ, Roy TM, McCloud LC, Nichols GR (1990). Fetal death due to nonlethal maternal carbon monoxide poisoning. J Forensic Sci. 1990;35(6):1448-1452. 113. Greingor JL, Tosi JM, Ruhlmann S, Aussedat M. (2001). Acute carbon monoxide intoxication during pregnancy. One case report and review of the literature. Emerg Med J. 2001;18(5):399-401. 114. Anseeuw K, Delvau N, Burillo-Putze G, et al. (2013). Cyanide poisoning by fire smoke inhalation: a European expert consensus. Eur J Emerg Med. 2013;20(1):2-9. 115. Reboul C, Thireau J, Meyer G. (2012). Carbon monoxide in the urban environment: an insidious foe for the heart? Respir Physiol Neurobiol. 2012;184(2):204-212. 116. Krzych-Fałta E, Modzelewska D, Samoliński B. (2015). Levels of exhaled carbon monoxide in healthy active and passive smokers. Przegl Lek. 2015;72(3):99-102. 117. Torrey CM, Moon KA, Williams DA, et al. (2015). Waterpipe cafes in Baltimore, Maryland: Carbon monoxide, particulate matter, and nicotine exposure. J Expo Sci Environ Epidemiol. 2015;25(4):405-410. 118. Tirosh E, Schnell I. (2016). The relationship between ambient carbon monoxide and heart rate variability-a systematic world review-2015. Environ Sci Pollut Res Int. 2016 Nov;23(21):21157-21164. Epub 2016 Sep 13. 119. Hampson NB, Rudd RA, Hauff NM. (2009). Increased long-term mortality among survivors of carbon monoxide poisoning. Crit Care Med. 2009;37(6):1941-1947. 120. Song IU, Cho HJ, Kim YD, Chung SW. (2011). Improvement of cognitive impairment following delayed CO encephalopathy. Can J Neurol Sci. [Letter]. 2011;38(6):934-935. 121. Wang P, Zeng T, Chi ZF. (2009). Recovery of cognitive dysfunction in a case of delayed encephalopathy of carbon monoxide poisoning after treatment with donepezil hydrochloride. Neurol India. 2009;57(4):481-482. 122. Price JD, Grimley Evans J. (2002). An N-of-1 randomized controlled trial (‘N-of-1 trial’) of donepezil in treatment of non-

59 nursece4less.com nursece4less.com nursece4less.com nursece4less.com progressive amnestic syndrome. Age Ageing. 2002;31(4):307- 309. 123. Pae CU, Kim TS, Lee C, Paik IH. (2006). Effect of aripiprazole for a patient with psychotic symptoms and parkinsonism associated with delayed-sequelae of carbon monoxide intoxication. J Neuropsychiatry Clin Neurosci. [Letter]. 2006;18(1):130-131. 124. Choi IS. (2002). Parkinsonism after carbon monoxide poisoning. Eur Neurol. 2002;48(1):30-33. 125. Tack E, de Reuck J. (1987). The use of bromocriptine in parkinsonism after carbon monoxide poisoning. Clin Neurol Neurosurg. 1987;89(4):275-279. 126. Jaeckle RS, Nasrallah HA. (1985). Major depression and carbon monoxide-induced parkinsonism: diagnosis, computerized axial tomography, and response to L-dopa. J Nerv Ment Dis. 1985;173(8):503-508. 127. Zorbalar N, Yesilaras M, Aksay E. (2014). Carbon monoxide poisoning in patients presenting to the emergency department with a headache in winter months. Emerg Med J. 2014 Oct;31(e1):e66-70. doi: 10.1136/emermed-2012-201712. Epub 2013 Oct 15.

The information presented in this course is intended solely for the use of healthcare professionals taking this course, for credit, from NurseCe4Less.com.

The information is designed to assist healthcare professionals, including nurses, in addressing issues associated with healthcare.

The information provided in this course is general in nature, and is not designed to address any specific situation. This publication in no way absolves facilities of their responsibility for the appropriate orientation of healthcare professionals.

Hospitals or other organizations using this publication as a part of their own orientation processes should review the contents of this publication to ensure accuracy and compliance before using this publication.

Hospitals and facilities that use this publication agree to defend and indemnify, and shall hold NurseCe4Less.com, including its parent(s), subsidiaries, affiliates, officers/directors, and employees from liability resulting from the use of this publication.

The contents of this publication may not be reproduced without written permission from NurseCe4Less.com.

60 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

61 nursece4less.com nursece4less.com nursece4less.com nursece4less.com