Hyperventilation syndrome (HVS) represents a relatively common emergency department (ED) presentation that is readily recognized by most clinicians. However, the underlying pathophysiology has not been clearly elucidated.
As typically defined, HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms. Inducing a decrease in arterial partial pressure of carbon dioxide (PaCO2) through voluntary hyperventilation reproduces these symptoms.
However, this model has been challenged by the observation that many patients with HVS do not manifest a low PaCO2 during attacks. In some cases, patients with this syndrome have demonstrated altered respiratory physiology that is manifested as a slower return of the PaCO2 to baseline after voluntary hyperventilation to a defined level of PaCO2.
Current thinking suggests that a better term for this syndrome might be behavioral breathlessness or psychogenic dyspnea, with hyperventilation seen as a consequence rather than a cause of the condition. It is also recognized that some patients may be physiologically at risk for the development of psychogenic dyspnea.
Symptoms of HVS and panic disorder overlap considerably, though the two conditions remain distinct. Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as a symptom, whereas 25% of patients with HVS manifest panic disorder.
Diagnosis and management
Upon a first attack of acute HVS, the diagnosis depends on recognizing the typical constellation of signs and symptoms and ruling out the serious conditions that can cause the presenting symptoms.
A low pulse oximetry reading in a patient who is hyperventilating should never be attributed to HVS. These patients should always be evaluated for other causes of hyperventilation.
Arterial blood gas (ABG) measurement is indicated if any doubt exists as to the patient’s underlying respiratory status. In chronic HVS, ABG sampling confirms a compensated respiratory alkalosis in a majority of cases.
Electrocardiographic changes are common and may include the following:
ST depression or elevation
Prolonged QT interval
T-wave inversion
Sinus tachycardia
Noninvasive measurements of gas exchange during orthostatic testing are useful in the diagnosis of HVS.[1]
Once life-threatening conditions are eliminated, simple reassurance and an explanation of how hyperventilation produces the patient’s symptoms are usually sufficient to terminate the episode of HVS. Provoking the symptoms by having the patient voluntarily hyperventilate for 3-4 minutes often convinces the patient of the diagnosis, but it is time-consuming and may be ineffective.
Diaphragmatic breathing slows the respiratory rate, gives patients a distracting maneuver to perform when attacks occur, and provides patients with a sense of self-control during episodes of hyperventilation. This technique has been shown to be very effective in a high proportion of patients with HVS.
Several medications, including benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), have been employed to reduce the frequency and severity of episodes of hyperventilation.
Stress reduction therapy, administration of beta blockers, and breathing retraining have all proved effective in reducing the intensity and the frequency of episodes of hyperventilation. If the diagnosis of HVS has been established, the patient should be referred to an appropriate therapist to implement these techniques over the long term.
HVS occurs in acute and chronic forms. Acute HVS accounts for only 1% of cases but is more easily diagnosed. Chronic HVS can present with a myriad of respiratory, cardiac, neurologic, or gastrointestinal (GI) symptoms without any clinically apparent overbreathing by the patient. Hypocapnia can be maintained without any overt change in the minute ventilation if the patient exhibits frequent sighs interspersed with normal respirations.
Because of the subtlety of hyperventilation, many patients with chronic HVS are admitted and undergo extensive and expensive testing in an attempt to discover organic causes of their complaints.
The underlying mechanism by which some patients develop hyperventilation is unknown. One theory suggests that certain stressors provoke an exaggerated respiratory response. Several such stressors have been identified, including emotional distress, sodium lactate, caffeine, isoproterenol, cholecystokinin, and carbon dioxide.
Predisposition to HVS may also be rooted in childhood. Patients with HVS were shown to be more likely to have had overprotective parents when they were children. A sudden stressful situation later in life can then incite the first episode of HVS.[2]
Infusion of lactate provokes symptoms of panic in 80% of patients with panic disorder but in only 10% of controls. Approximately one half of the lactate responders develop acute hyperventilation as part of the panic reaction. Lactate levels are higher and remain elevated longer in patients with panic disorder than in controls, suggesting that abnormal metabolism of lactate is involved in the pathogenesis, although the exact abnormality has not been characterized. Whether the same abnormality is operant in pure HVS is unknown.
In addition, elevated levels of carbon dioxide have been demonstrated to induce panic symptoms in a majority of patients with panic disorder. Those patients who panicked with increased carbon dioxide levels had significantly greater baseline respiratory variability, which is also found in patients with HVS. This similarity further suggests a connection between the two disorders.[3]
The explanation of HVS lies partially in the mechanics of breathing. Normal tidal volume is approximately 500 mL per inspiration or 7 mL/kg of body mass. The elastic recoil of the chest wall resists hyperinflation of the lungs beyond that level, and inspiratory volumes beyond this level are perceived as effort or dyspnea.
Patients with HVS tend to breathe by using the upper thorax rather than the diaphragm, and this results in chronic overinflation of the lungs. When stress induces a need to take a deep breath, the deep breathing is perceived as dyspnea. The sensation of dyspnea creates anxiety, which encourages more deep breathing, and a vicious circle is created.
Another theory is that patients with panic disorder have a lower threshold for the fight-or-flight response. In susceptible patients, even minor stresses can trigger the syndrome, which then tends to manifest with primarily psychiatric complaints (eg, fear of death, impending doom, or claustrophobia). In contrast, it is believed that HVS patients tend to focus on somatic complaints related to the physiologic changes produced by hyperventilation. Initiating stimuli and abnormal stress responses may be identical but are expressed differently in each group.
The cause of HVS is unknown, but some persons who are affected appear to have an abnormal respiratory response to stress, sodium, lactate, and other chemical and emotional triggers, which results in excess minute ventilation and hypocarbia.
In most patients, the mechanics of breathing are disordered in a characteristic way. When stressed, these patients rely on thoracic breathing rather than diaphragmatic breathing, resulting in a hyperexpanded chest and high residual lung volume. Because of the high residual volume, they are then unable to take a normal tidal volume with the next breath and consequently experience dyspnea.
Proprioceptors in the lung and chest wall signal the brain with a “suffocation alarm” that triggers release of excitatory neurotransmitters that are responsible for many of the symptoms such as palpitations, tremor, anxiety, and diaphoresis.
The incidence of HVS is higher in first-degree relatives than in the general population, but no clear genetic factors have been identified.
A study by D’Alba et al evaluating the prevalence of HVS in adolescents found that the rate of HVS symptoms in adolescents with asthma was 10 times higher than that in adolescents without asthma (25% vs 2.5%, respectively). The study also found that in the adolescent population scrutinized, HVS was more prevalent in females than in males (with the odds ratio [OR] for the syndrome in females being 3.2). In addition, asthma status was seen to significantly influence the probability of HVS occurrence, with the ORs for HVS in adolescents with lifetime asthma, current episodic asthma, and current active asthma calculated as 11.2, 8.9, and 41.5, respectively.[4]
As many as 10% of patients in a general internal medicine practice are reported to have HVS as their primary diagnosis, though equivalent data are not available for ED presentations. It is thought that up to 6% of the general population exhibits aspects of HVS.
The peak incidence is between the ages of 15 and 55 years, but cases have been reported in all age groups except infants. HVS has a strong female preponderance: the female-to-male ratio may be as high as 7:1.
Patients with chronic HVS experience multiple exacerbations throughout their lives. Children who experience acute HVS often continue this pattern into adulthood. Many patients have associated disorders (eg, agoraphobia) that may dominate the clinical picture. Management of these underlying disorders affects the course of hyperventilation.
Patients who are treated with breathing retraining, stress reduction therapy, and various medications (eg, benzodiazepines or selective serotonin reuptake inhibitors [SSRIs]) experience significant reductions in the frequency and the severity of exacerbations.
Death attributable to HVS is extremely rare. A leftward shift in the oxyhemoglobin dissociation curve and vasospasm related to low PaCO2 could cause myocardial ischemia in patients with coronary artery disease (CAD) and hyperventilation syndrome.
Certain patients are disabled psychologically by their symptoms, and many patients carry misdiagnoses. Patients with HVS often undergo diagnostic testing and may have complications from related interventions (eg, angiography, thrombolytics, or nasal reconstruction).[5] Withholding such therapy may be difficult in a patient with crushing chest pain and dyspnea.
One study reported a series of 45 patients with chest pain who had normal coronary arteries on angiography. These patients ultimately were diagnosed as having HVS. Over a 3.5-year average follow-up period, 67% of the patients had made subsequent ED visits for chest pain, and 40% of the patients had been readmitted to rule out myocardial infarction (MI).
Clearly, HVS not only causes severe and genuine discomfort for the patient but also accounts for considerable medical expense through the process of excluding more serious disorders. That patients with HVS appear ill tends to prompt further esoteric testing, which is inevitably nondiagnostic. The chronicity of the condition often causes different physicians to repeat these diagnostic investigations.
Patients should receive a clear explanation of the underlying pathophysiology and should be instructed in the technique of deflation of the upper chest followed by controlled diaphragmatic breathing.
For patient education resources, see the Anxiety Center, as well as Anxiety, Panic Attacks, and Hyperventilation.
Patients with acute hyperventilation syndrome (HVS) may present with agitation and anxiety. Most commonly, the history is one of sudden onset of dyspnea, chest pain, or neurologic symptoms (eg, dizziness, weakness, paresthesias, or near-syncope) after a stressful event. Patients with chronic HVS present with similar symptoms, including recurrent chest pain, dyspnea, and neurologic deficits, and usually have had many similar presentations in the past.
Acute hyperventilation
Patients often present dramatically, with agitation, hyperpnea and tachypnea, chest pain, dyspnea, wheezing, dizziness, palpitations, tetanic cramps (eg, carpopedal spasm), paresthesias, generalized weakness, and syncope. The patient often complains of a sense of suffocation. An emotionally stressful precipitating event can often be identified.
Cardiac symptoms
The chest pain associated with HVS usually has atypical features, but on occasion, it may closely resemble typical angina. It tends to last hours rather than minutes, and is often relieved rather than provoked by exercise. It is usually unrelieved by nitroglycerin.
The diagnosis of HVS should be considered in young patients without cardiac risk factors who present with chest pain, particularly if the pain is associated with paresthesias and carpopedal spasm. However, this diagnosis should be reached cautiously, because many other potentially lethal conditions can also cause young patients to present with chest pain (eg, pulmonary embolism [PE] and spontaneous pneumothorax).
Electrocardiographic (ECG) changes are common in patients with HVS. Abnormalities may include prolonged QT interval, ST depression or elevation, and T-wave inversion.
In patients with subcritical coronary artery stenosis, the vasospasm induced by hypocarbia may be sufficient to provoke myocardial injury.
The incidence of HVS is high among patients with mitral valve prolapse (MVP), and the chest pain associated with MVP may be due to hyperventilation.
Prinzmetal angina (ie, coronary artery vasospasm) is triggered by HVS, but the chest pain associated with this syndrome normally would be expected to respond to nitrates or calcium channel blockers.
Central nervous system symptoms
Central nervous system (CNS) symptoms occur because hypocapnia causes cerebral artery vasoconstriction and reduced cerebral blood flow (CBF). CBF decreases by 2% for every 1 mm Hg decrease in the arterial partial pressure of carbon dioxide (PaCO2).
The symptoms of dizziness, weakness, confusion, and agitation are common. Patients may report feelings of depersonalization and may experience visual hallucinations. Syncope or seizure may be provoked by hyperventilation.[6] Paresthesias occur more commonly in the upper extremity and are usually bilateral. Perioral numbness is very common.
Gastrointestinal symptoms
Gastrointestinal (GI) symptoms (eg, bloating, belching, flatus, or epigastric pressure) may result from aerophagia.
Metabolic changes
Acute metabolic changes result from intracellular shifts and increased protein binding of various electrolytes during respiratory alkalosis.
Acute secondary hypocalcemia can result in carpopedal spasm, muscle twitching, a prolonged QT interval, and positive Chvostek and Trousseau signs. Hypokalemia tends to be less pronounced than hypocalcemia but can produce generalized weakness. Acute secondary hypophosphatemia is common and may contribute to paresthesias and generalized weakness.
Chronic hyperventilation
The diagnosis of chronic HVS is much more difficult than that of acute HVS because hyperventilation is usually not clinically apparent. Often, these patients have already undergone extensive medical investigations and have been assigned several misleading diagnoses.
Two thirds of patients with chronic HVS have a persistently slightly low PaCO2 with compensatory renal excretion of bicarbonate, resulting in a near-normal pH level. These patients tend to have prominent CNS symptoms. In addition, they typically present with dyspnea and chest pain.
The respiratory alkalosis can be maintained with occasional deep sighing respirations, which are observed often in patients with chronic HVS.
When faced with an additional stress that provokes hyperventilation, the physiologic acid-base reserve is less, and these patients become symptomatic more readily than patients without HVS.
Other symptoms
Dry mouth occurs with mouth breathing and anxiety. Many of these patients suffer from obsessive-compulsive disorders, experience sexual and marital difficulties, and have poor adaptations to stress.
Patients with chronic HVS may have symptoms that mimic those of virtually any serious organic disorder, but they usually have atypical features of these diseases.
In acute HVS, obvious tachypnea and hyperpnea are present. Although chest wall tenderness is common in patients with HVS, it is not a helpful finding, because chest wall tenderness is also found in pneumonia, pneumothorax, pulmonary embolism, coronary artery syndromes, and a wide variety of other serious and benign thoracoabdominal diseases.
Carpopedal spasm occurs when acute hypocarbia causes reduced ionized calcium and phosphate levels, resulting in involuntary contraction of the feet or (more commonly) the hands (see the image below). Chvostek or Trousseau signs may be positive because of hyperventilation-induced hypocalcemia. Wheezing may be heard because of bronchospasm from hypocarbia.
View Image
Trousseau sign.
Tremor, mydriasis, pallor, tachycardia, and other manifestations of anxiety can occur. Evidence of depersonalization or hallucination may be noted.
Chronic hyperventilation syndrome
In chronic HVS, hyperventilation is usually not readily apparent. Frequent sighing respirations (2-3 breaths/min) and frequent yawning are noted. Chest wall tenderness, numbness, and tingling may be present. Characteristically, patients have multiple complaints without much supporting physical evidence of disease.
The complications encountered in patients with this syndrome are related mainly to the invasive procedures and investigations (eg, angiography) that are employed to rule out other diseases (see Workup).
However, complications may also occur as a result of symptoms produced indirectly by hyperventilation (eg, injuries sustained in a fall during a syncopal episode attributable to hyperventilation).
Upon a first attack of acute hyperventilation syndrome (HVS), the diagnosis depends on recognizing the typical constellation of signs and symptoms and ruling out the serious conditions that can cause the presenting symptoms.
Acute coronary syndrome (ACS) and pulmonary embolism (PE) are two of the most common serious entities that may present similarly to HVS. Usually, clinical assessment is sufficient to rule out these entities. Depending on that assessment, more specific testing is sometimes warranted.
A standard workup for atypical chest pain, including pulse oximetry, chest radiography, and electrocardiography (ECG), may still be warranted depending on the clinical picture.
Patients with a history of HVS who have undergone an appropriate workup at some earlier time may not need any further laboratory evaluation in the setting of a recurrence. Recognition of the typical constellation of dyspnea, agitation, dizziness, atypical chest pain, tachypnea and hyperpnea, paresthesias, and carpopedal spasm in a young, otherwise healthy patient with an adequate prior evaluation is often sufficient to establish the diagnosis.
A low pulse oximetry reading in a patient who is hyperventilating should never be attributed to HVS. These patients should always be evaluated for other causes of hyperventilation. A normal pulse oximetry reading is not helpful, because a severe defect in gas exchange can be masked by hyperventilation. A fraction of patients with chronic PE will have compensated chronic hyperventilation that may mimic primary chronic hyperventilation.
Arterial blood gas (ABG) measurement is indicated if any doubt exists as to the patient’s underlying respiratory status. Arterial blood gas analyses may be helpful when HVS-induced alkalosis is suspected, or when shunting or impaired pulmonary gas exchange is being considered.
In chronic HVS, ABG sampling confirms a compensated respiratory alkalosis in a majority of cases. The pH is typically near normal, with a low PaCO2 and a low measured serum bicarbonate level. ABG sampling is also useful in ruling out toxicity from carbon monoxide poisoning, methemoglobinemia, and sulfhemoglobinemia which may present similarly to HVS.[7]
Drug toxicology screening is often indicated. If acute PE is being considered, a quantitative enzyme-linked immunosorbent assay (ELISA) D-dimer assay may be helpful in young patients who are free from comorbid illnesses.
Imaging studies
Imaging studies are not indicated when the diagnosis of HVS is clear. In less obvious cases of HVS, imaging studies are typically normal. Chest radiographs may reveal hyperinflation.
Because PE can present with findings identical to those of HVS, a first-ever episode of acute HVS may warrant ventilation/perfusion scanning or computed tomography (CT) pulmonary angiography to rule out perfusion defects. Chest radiography is indicated for patients who are at high risk for cardiac or pulmonary pathology. Chest radiography is also indicated when the diagnosis is not clear.
Electrocardiography
ECG changes are common and may include the following:
ST depression or elevation
Prolonged QT interval
T-wave inversion
Sinus tachycardia
Orthostatic respiratory rate changes
In a normal individual, the respiratory rate typically increases when the person moves from a supine to a standing position. Patients with HVS have an accentuated increase in minute ventilation. End-tidal carbon dioxide is significantly lower in patients with HVS, and ventilatory equivalents for oxygen and carbon dioxide are significantly higher. Thus, noninvasive measurements of gas exchange during orthostatic testing are useful in the diagnosis of HVS.[1]
Because respiratory distress or chest pain has many potentially serious causes, the diagnosis of hyperventilation syndrome (HVS) should never be made in the field. Even when a patient with these complaints carries a prior diagnosis of HVS, he or she must still be transported to a hospital for a more complete evaluation.
Rebreathing into a paper bag is not recommended. Deaths have occurred in patients with acute myocardial infarction (MI), pneumothorax, and pulmonary embolism (PE) who were initially misdiagnosed with HVS and treated with paper bag rebreathing.[8]
Subspecialty consultation usually is not required for HVS. Patients should be treated by a psychiatrist, psychologist, or family physician with experience and interest in managing HVS. Some physiotherapists and respiratory therapists have extensive experience in retraining patients in proper breathing techniques and should be consulted. Pharmacotherapy may be helpful.
Although inpatient care is not indicated, many patients with chronic HVS are admitted because their symptoms resemble those of many serious organic problems and because there is no simple way of confirming the diagnosis in the emergency department (ED).
Patients may also be referred for treatment with acupuncture. This modality is useful in decreasing anxiety and thereby reducing the severity of the symptoms associated with HVS. Lowering patients’ anxiety levels may also reduce the frequency of symptomatic periods.[9]
ED treatment of hyperventilation syndrome is often ineffective. Rebreathing into a paper bag is no longer a recommended technique, because significant hypoxia and death have been reported.[8]
In patients who are hyperventilating for organic reasons (eg, pulmonary edema, metabolic acidosis), increasing the arterial partial pressure of carbon dioxide (PaCO2) and decreasing oxygen may be disastrous. In addition, paper bag rebreathing is often unsuccessful in reversing the symptoms of HVS, because patients have difficulty complying with the technique. Moreover, carbon dioxide itself may be a chemical trigger for anxiety in these patients.
Once life-threatening conditions are eliminated, simple reassurance and an explanation of how hyperventilation produces the patient’s symptoms are usually sufficient to terminate the episode. Provoking the symptoms by having the patient voluntarily hyperventilate for 3-4 minutes often convinces the patient of the diagnosis, but it is time-consuming and may be ineffective.
Most patients with HVS tend to breathe with the upper thorax and have hyperinflated lungs throughout the respiratory cycle. Because residual lung volume is high, they are unable to achieve full tidal volume and experience dyspnea. Physically compressing the upper thorax and having patients exhale maximally decreases hyperinflation of the lungs. Instructing patients to breathe abdominally, using the diaphragm more than the chest wall, often leads to improvement in subjective dyspnea and eventually corrects many of the associated symptoms.
Diaphragmatic breathing slows the respiratory rate, gives patients a distracting maneuver to perform when attacks occur, and provides patients with a sense of self-control during episodes of hyperventilation. This technique has been shown to be very effective in a high proportion of patients with HVS.
Patients should be referred to a specialist (eg, physiotherapist, psychologist, psychiatrist, family physician, internist, respiratory therapist) who can reinforce this approach.
Several medications, including benzodiazepines and selective serotonin reuptake inhibitors (SSRIs), have been employed to reduce the frequency and severity of episodes of hyperventilation. These agents require prolonged use and are best managed by a consultant on an ongoing outpatient basis rather than through sporadic prescriptions after an ED visit.
Use of benzodiazepines for stress relief and for resetting the trigger for hyperventilation is effective, but again, patients may require prolonged treatment. Although acute chemical sedation may be effective and humane in selected severe cases, prolonged use of these medications should not be initiated in the ED.
Stress reduction therapy, administration of beta blockers, and breathing retraining have all proved effective in reducing the intensity and the frequency of episodes of hyperventilation. If the diagnosis of HVS has been established, the patient should be referred to an appropriate therapist to implement these techniques over the long term.
Benzodiazepines are effective in reducing stress that may provoke hyperventilation syndrome (HVS) and are thought to reset the central nervous system (CNS) response to a variety of “panicogens.” Selective serotonin reuptake inhibitors (SSRIs) have been reported to reduce the frequency and the severity of episodes of hyperventilation.
Clinical Context:
Lorazepam is a sedative-hypnotic of the benzodiazepine class that has a short time to onset of effect and a relatively long half-life. By enhancing the action of GABA, a major inhibitory neurotransmitter, it may depress all levels of the CNS, including the limbic area and reticular formation.
Clinical Context:
Diazepam depresses all levels of the CNS (eg, limbic and reticular formation), possibly by increasing the activity of GABA. It is considered second-line therapy for seizures.
Benzodiazepines are useful in the treatment of hyperventilation resulting from anxiety and panic attacks. By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and to facilitate inhibitory GABA neurotransmission and the actions of other inhibitory transmitters.
Clinical Context:
Paroxetine is the alternative drug of choice for HVS. It is a potent selective inhibitor of neuronal reuptake of serotonin and has a weak effect on neuronal reuptake of norepinephrine and dopamine.
Brian Kern, MD, Staff Physician, Department of Emergency Medicine, Detroit Medical Center; Clinical Assistant Professor, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Adam J Rosh, MD, Assistant Professor, Program Director, Emergency Medicine Residency, Department of Emergency Medicine, Detroit Receiving Hospital, Wayne State University School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
John J Oppenheimer, MD, Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA
Disclosure: Received research grant from: quintiles, PRA, ICON, Novartis: Adjudication<br/>Received consulting fee from AZ for consulting; Received consulting fee from Glaxo, Myelin, Meda for consulting; Received grant/research funds from Glaxo for independent contractor; Received consulting fee from Merck for consulting; Received honoraria from Annals of Allergy Asthma Immunology for none; Partner received honoraria from ABAI for none. for: Atlantic Health System.
Acknowledgements
Paul Blackburn, DO, FACOEP, FACEP Attending Physician, Department of Emergency Medicine, Maricopa Medical Center
Paul Blackburn, DO, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Medical Association, and Arizona Medical Association
Disclosure: Nothing to disclose.
Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University School of Medicine
Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Edward J Newton, MD, FACEP, FRCPC Professor of Clinical Emergency Medicine, Chairman, Department of Emergency Medicine, University of Southern California Keck School of Medicine
Edward J Newton, MD, FACEP, FRCPC is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Royal College of Physicians and Surgeons of Canada, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
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