INTRODUCTION — The hyperventilation syndrome describes a condition in which an inappropriate increase in minute ventilation beyond metabolic needs (ie, in excess of what is necessary for CO2 production, which leads to a respiratory alkalosis) is associated with a wide range of symptoms without a clear organic precipitant. As with other medical "syndromes," there is controversy about the etiology, diagnosis, and treatment of this condition. While it is generally accepted that hyperventilation episodes (or "attacks") are frequently related to or associated with concomitant panic disorder, other precipitants may also be important.
This topic will discuss the pathophysiology, clinical presentation, diagnosis, and treatment of patients presenting with hyperventilation syndrome. Detailed discussions of associated disorders are presented separately. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis" and "Management of panic disorder with or without agoraphobia in adults" and "Psychotherapy for panic disorder with or without agoraphobia in adults" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Acute stress disorder in adults: Epidemiology, clinical features, assessment, and diagnosis" and "Approach to the adult with dyspnea in the emergency department".)
Tachypnea — Increased respiratory rate >20 breaths per minute. The PaCO2 cannot be predicted by tachypnea alone since PaCO2 reflects the relationship between CO2 production and alveolar ventilation (PaCO2 = VCO2/VA). Minute ventilation is determined by the product of respiratory rate multiplied by tidal volume, and alveolar volume is the difference between tidal volume and dead space. Thus, for any given respiratory rate, calculation of alveolar ventilation requires knowledge of respiratory rate and alveolar volume. Further, for any given minute ventilation, the size of the breaths will determine the PaCO2 since larger breaths have a smaller dead space/tidal volume ratio.
Hyperpnea — Increase in the depth and rate of respiration leading to an increase in the minute volume of ventilation consistent with an increase in metabolism as reflected by CO2 production. Thus, the PaCO2 is normal in a patient with hyperpnea (an example of hyperpnea is the increase in ventilation that occurs during moderate exercise in concert with increased metabolic activity and systemic production of carbon dioxide).
Hyperventilation — Alveolar hyperventilation is present when alveolar ventilation is increased out of proportion to carbon dioxide production and the arterial tension of carbon dioxide (PaCO2) decreases below the normal range (<36 mmHg, or <4.8 kPa). At the bedside, however, it is difficult to accurately gauge minute ventilation, and it is impossible to assess alveolar ventilation. The term “hyperventilation” is commonly used to characterize any patient who clinically appears to have increased total ventilation. In this chapter, we will use the term “hyperventilation” in this common clinical sense, but we will reemphasize the distinction between the physiological definition (alveolar ventilation out of proportion to CO2 production, which requires an arterial blood gas for confirmation) and the common bedside impression.
Hyperventilation syndrome — Hyperventilation syndrome is a disorder with no widely accepted diagnostic criteria , but is most commonly characterized by respiratory symptoms (uncomfortable or difficult breathing), hyperventilation, and a general sense of distress or anxiety. Many questions have been raised about the term "hyperventilation syndrome" . Some authors suggest that the term should be avoided, as it implies that hyperventilation is the primary cause of and trigger for a patient's symptoms . Others cite that "hyperventilation syndrome" may at best describe multiple pathophysiologic processes rather than a unique, discrete clinical entity . Nonetheless, "hyperventilation syndrome" is a term in wide use clinically and is descriptive of a common objective finding, ie, excess ventilation. There is likely great overlap between hyperventilation syndrome and "sighing syndrome," which has similar characteristics .
PREVALENCE AND EPIDEMIOLOGY — The prevalence of hyperventilation syndrome is difficult to assess accurately, as estimates are based upon small sample sizes, varying diagnostic criteria, and its association with psychological symptoms. There is substantial overlap between hyperventilation syndrome, panic disorder, and anxiety disorder (figure 1). The prevalence of hyperventilation syndrome has been reported to range from 25 to 83 percent in patients with an anxiety disorder [1,6-8]. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis".)
Limited data suggest that hyperventilation syndrome occurs more commonly in women than in men [3,9,10]. In an emergency department cohort study of 616 patients clinically diagnosed with hyperventilation, 55 percent of patients were female, the median age was 36.5 years (range 16 to 85), and 30 percent had had a prior episode .
●Psychopathology – An association between hyperventilation syndrome and psychological pathologies (such as panic disorder) is clear, but whether the psychological condition is primary or secondary is often unclear. Both respiratory and somatic symptoms are common in patients with psychological distress. In a small study, patients with idiopathic hyperventilation syndrome had higher depression and anxiety scores than control subjects . Specifically, "disproportionate breathlessness" is associated with depression, anxiety, bereavement, resentment, and uncertainty about the seriousness of one's illness . In addition, patients with anxiety disorder may react to sensations from the chest wall (eg, intercostal muscle tension) by hyperventilating . Patients with anxiety may also complain of respiratory symptoms that can best be termed "sighing dyspnea," in which patients feel as if they are not getting enough air or oxygen or “as if I can’t fill my lungs with air.” Some describe a vague sub-xiphoid pressure sensation. This is described as "periodic deep sighing" in one review and as "frequent sighing and irregular breathing patterns, sometimes overlapping with hyperventilation" .
The diagnosis of panic disorder or other neuroses contributing to a patient's respiratory symptoms may be indicated by rapid shallow breathing, irregular respiratory patterns, sighing, and paroxysms of hyperventilation. These symptoms and the concomitant anxiety may be due to hyperventilation itself.
●Regulatory systems – Abnormalities in ventilatory control are important in symptom development in some patients with hyperventilation syndrome. The reticular activating system in the brainstem, which regulates breathing patterns when individuals are awake, may be overactive in hyperventilation syndrome. Under normal conditions, healthy individuals demonstrate regular breathing with no voluntary effort. When asked to voluntarily increase minute ventilation, patients with hyperventilation syndrome may experience symptoms associated with hyperventilation syndrome. As an example, hyperventilation symptoms can be induced in such patients when they are instructed to breathe through a mouthpiece, while normal control subjects can do this, usually with an increase in ventilation, with no clinical symptoms . The inability of patients with hyperventilation syndrome to breathe comfortably through a mouthpiece may indicate an overactive reticular activating system.
Increased sensitivity to carbon dioxide (CO2) or a hypersensitive fear network (the hippocampus, medial prefrontal cortex, amygdala and its brainstem projections) have also been proposed as mechanisms for the hyperventilation syndrome and its association with psychological symptoms . An activated hypersensitive fear network may result in an increased central respiratory drive, both as a manifestation of a "fight or flight" response and as a means to reduce arterial tension of CO2 (PaCO2) levels and thereby decrease direct stimulation of the fear network. Sighing dyspnea may result from decreased sensitivity of alveolar stretch receptors that monitor inflation of the lung; typically, large tidal volume alleviates the dyspnea associated with disorders of the respiratory system characterized by increased airway resistance or decreased respiratory system compliance . The multiple, repetitive, large-volume sighing breaths may reflect an overly sensitive deflation reflex, triggered by a different set of stretch receptors, or failure to achieve normal relief from large tidal volume.
●Neurologic symptoms – The mechanism by which hyperventilation causes symptoms such as bilaterally symmetrical paresthesias, headache, lightheadedness, and tetany is not well established. One hypothesis is that these symptoms may be due to local vasoconstriction and/or cerebral vasoconstriction. Cerebral blood flow decreases in a linear fashion with decreasing PaCO2: a decrease of 1 mmHg of PaCO2 is associated with a 2 percent decrease in cerebral blood flow . Thus, a reduction in cerebral blood flow in the setting of hyperventilation, hypocapnia, and respiratory alkalosis may explain the neurologic symptoms associated with the hyperventilation syndrome such as paresthesias, headache, lightheadedness, and tetany . If true, these symptoms should rapidly respond to normalization of PaCO2 levels.
Another proposed mechanism is that acute changes in ionized serum calcium levels, triggered by respiratory alkalosis and the consequent binding of calcium to albumin, could result in paresthesias and/or tetany. There is no evidence (nor would it be anticipated) that hyperventilation results in changes in total serum calcium levels [14,15,19]. Hypophosphatemia has been noted in hyperventilating patients, however, and may contribute to tetany [3,15].
Vestibular and balance disorders may play an etiologic role for some patients with hyperventilation syndrome, accounting for symptoms of lightheadedness. Specifically, the distress associated with postural symptoms in the setting of vestibular pathology may also trigger hyperventilation. Furthermore, the vestibular system affects the activity of respiratory muscles in response to changes in body position. In patients with vestibular pathology, such responses may be exaggerated and result in inappropriate increases in ventilation [20,21].
●Pulmonary symptoms – An imbalance between sensory signals (from pulmonary and chest wall stretch receptors) and motor signals (from the motor cortex), called efferent-afferent dissociation, may be the cause of perceived dyspnea in hyperventilation syndrome; the greater the imbalance, the greater the severity of dyspnea [22,23]. The sensation of dyspnea may then precipitate a voluntary increase in minute ventilation.
Pulmonary symptoms in some patients diagnosed with hyperventilation syndrome may be due to unrecognized pulmonary pathology. Intermittent, mild, clinically unrecognized airway obstruction due to asthma may account for some cases of hyperventilation syndrome [24,25]. The difficulty in accurately diagnosing asthma, especially mild cases, contributes to delayed recognition of this diagnosis. (See "Asthma in adolescents and adults: Evaluation and diagnosis".)
●Functional laryngeal pathology – Laryngeal air leak due to vocal fold dysfunction is a possible mechanism by which unilateral recurrent laryngeal nerve (RLN) palsy may contribute to the development of hyperventilation syndrome [13,26]. As an example, in a study including 10 patients experiencing permanent unilateral RLN palsy and dyspnea following thyroidectomy (for benign disease), eight were diagnosed with hyperventilation syndrome .
The extent to which vocal fold pathology contributes to hyperventilation syndrome is unclear, however, and further research into the relationship between neurologic, psychiatric, and structural causes of hyperventilation syndrome is needed. (See "Exercise-induced laryngeal obstruction", section on 'Clinical presentation'.)
●Other – In one small case series at a single center including 147 patients with persistent dyspnea three months after COVID-19 infection, six were ultimately diagnosed with hyperventilation syndrome . A combination of the Nijmegen score , hyperventilation challenge, and cardiopulmonary exercise testing were used to establish the diagnosis (see 'Ancillary diagnostic testing' below). The etiology by which COVID-19 may be associated with hyperventilation syndrome is unclear.
CLINICAL PRESENTATION — While the presentation of hyperventilation syndrome can vary significantly among individuals, the typical pattern is that of intermittent episodes of spontaneously resolving hyperventilation unassociated with or out of proportion to cardiopulmonary pathology. The cardinal feature of hyperventilation syndrome is a transient increase in minute ventilation, out of proportion to metabolic needs, that lasts several minutes to an hour and resolves spontaneously . While the underlying process is hyperventilation, patients report a variety of somatic and nonsomatic complaints simultaneous to the increased respiration.
Although there are rare case reports of post-hyperventilation apnea that have been associated with severe hypoxemia and even death [30,31], episodes of hyperventilation generally resolve without complications.
Somatic symptoms — Somatic complaints associated with hyperventilation syndrome may include :
●Dyspnea (60 percent)
●Dizziness or lightheadedness (13 to 50 percent) [10,24]
●Chest pain or tightness (43 percent)
●Paresthesias (35 to 60 percent) [10,24]
●Palpitations (13 percent)
●Carpopedal spasm (9 percent)
In one series, a minority of patients (17 percent) were aware that they were hyperventilating . Importantly, patients with hyperventilation syndrome are only intermittently symptomatic, and symptoms typically occur with unpredictable frequency.
Respiratory sensations associated with an acute episode may include dyspnea, air hunger, the sensation of an inability to inhale a complete breath, and/or a feeling of unsatisfying breathing (ie, a sensation that tidal volumes are too small despite each breath's volume being quite large). Patients experiencing an episode of hyperventilation syndrome typically will have a breathing pattern characterized by relatively slow, very deep breaths, sometimes punctuated by deep sighs. Patients with sighing dyspnea, which overlaps with hyperventilation, typically complain of "shortness of breath," "I can't get enough air or oxygen," or "I can't fill my lungs with air," often with some vague chest discomfort and often with an anxiety component. The sighs are typically not perceived by the patients who may instead report difficulty taking a deep breath .
Unlike patients with pulmonary vascular disease, who typically complain of dyspnea that develops or worsens with exertion, patients with hyperventilation syndrome typically report dyspnea at rest and the need to sigh frequently.
Although symmetric, bilateral paresthesias are the most common peripheral neurologic symptom in hyperventilation syndrome, carpopedal spasm was described in the original clinical reports of hyperventilation attacks and is still considered a feature of the syndrome . Its presence may depend on the severity of hyperventilation, to the extent that carpopedal syndrome may be triggered by alkalosis-induced metabolic changes or cerebral vasoconstriction associated with hypocapnia. (See 'Pathophysiology' above.)
Additionally, patients with hyperventilation syndrome who develop symptoms with voluntary hyperventilation or exercise typically experience delayed resolution of respiratory symptoms after exercise compared with normal subjects. Furthermore, the intensity of exertion may not correlate with the degree of dyspnea experienced by patients with hyperventilation syndrome; relatively minimal exertion may result in significant dyspnea .
Psychological symptoms — Episodes of acute hyperventilation are associated with anxiety and other psychological symptoms. Patients with hyperventilation may report [10,24]:
●Sense of impending doom and panic
●Anxiety and fear
In a small series that used a formal interview instrument (Clinical Interview Schedule) to assess psychologic symptoms, 17 of 23 patients (78 percent) exceeded the threshold for anxiety or panic . In many patients, these symptoms reflect a primary psychological pathology that is the cause of hyperventilation. In other patients, anxiety and somatoform symptoms are a result of hyperventilation and the accompanying metabolic changes that cause systemic disturbance. In one emergency department series of 616 patients with hyperventilation, fear was present in over 95 percent . Furthermore, a sensation of being "afraid" was more prevalent in patients with hyperventilation syndrome and panic disorder than in patients with dyspnea due to pulmonary disease (without panic disorder or psychiatric contributions to dyspnea) . It is likely that both mechanisms are evident in many patients with primary anxiety. (See 'Pathophysiology' above and "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical Manifestations' and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Clinical features and course'.)
Patients may report precipitating events such as a defined psychological or physical stressor. However, episodes may occur randomly, without an obvious precipitant. One case series evaluated psychological and emotional events in the three years prior to presentation in 31 patients with a clinical diagnosis of hyperventilation syndrome . Many of these patients described events or feelings of bereavement, uncertainty about the seriousness of their symptoms, or resentment towards the medical profession because the cause of their symptoms was unexplained and the feeling that their symptoms were minimized.
Physical examination — The typical physical examination findings in a patient with hyperventilation syndrome include tachycardia, tachypnea, and deep breathing and may include diaphoresis and carpopedal spasm. The cardiopulmonary examination should otherwise be normal, unless the patient has hyperventilation superimposed on asthma or chronic obstructive pulmonary disease (COPD).
Sighing dyspnea is a related form of dysfunctional breathing that is characterized by deep sighs (more than three times normal tidal volume) [32,36]. Sighing frequency may be variable, but in one study sighs occurred 4 to 15 times/15 minutes, compared with 0 to 3 times/15 minutes in normal subjects .
DIFFERENTIAL DIAGNOSIS — Multiple serious and potentially life-threatening medical conditions may present with symptoms that are common in patients with hyperventilation syndrome. These conditions need to be considered early in the evaluation of a patient who presents with dyspnea and appears to be hyperventilating. The differential diagnosis is broad (table 1); the following are some of the processes that can be misinterpreted as hyperventilation syndrome during the early evaluation of patients presenting with hyperventilation . It is important to note, however, that the following differential diagnoses primarily represents causes of acute hyperventilation, which is a clinical and pathophysiologically distinct process from the recurrent, episodic hyperventilation that defines hyperventilation syndrome. In addition, these conditions are typically not associated with true hyperventilation (ie, acute respiratory alkalosis with normal alveolar-arterial oxygen difference) as opposed to an increase in total ventilation to compensate for gas exchange abnormalities, increased metabolic activity, or metabolic acidosis.
●Metabolic acidosis – Disorders that cause metabolic acidosis can lead to compensatory respiratory alkalosis (achieved by hyperventilation). Examples include diabetic, alcoholic, or starvation ketoacidosis; severe kidney dysfunction; toxic ingestions or exposures (especially those that lead to abnormalities in cellular respiration); and lactic acidosis of any cause (table 2). Kussmaul breathing, which is relatively deep and slow, is characteristic of both hyperventilation syndrome and the respiratory response to metabolic acidosis. One should note, however, that most of the conditions associated with an increased anion gap, with the exception of chronic kidney failure, are acute in nature and would not be associated with chronic hyperventilation. A general approach to metabolic acidosis is provided separately. (See "Approach to the adult with metabolic acidosis".)
Clinical suspicion of metabolic acidosis is confirmed by arterial or mixed venous blood gas analysis. Laboratory evaluation to determine the cause of metabolic acidosis generally includes serum electrolytes and calculation of the anion gap, but may require additional testing in complicated patients (eg, plasma osmolality, urinalysis, urine and/or serum ketones, and blood and urine toxicology screens). (See "Approach to the adult with metabolic acidosis".)
The various disorders causing metabolic acidosis are discussed separately:
•Diabetic ketoacidosis (see "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis")
•Alcoholic and starvation ketoacidosis (see "Fasting ketosis and alcoholic ketoacidosis")
•Salicylate, methanol, and ethylene glycol poisoning (see "Salicylate (aspirin) poisoning: Clinical manifestations and evaluation" and "Methanol and ethylene glycol poisoning: Pharmacology, clinical manifestations, and diagnosis")
•Chronic kidney failure (see "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults")
●Other endocrine and metabolic disorders – Patients with hyperthyroidism can develop dyspnea due to increased oxygen consumption, increased carbon dioxide (CO2) production, respiratory muscle weakness, tachycardia, cardiomyopathy, or tracheal obstruction from a large goiter. Anxiety, palpitations, and diaphoresis can also be presenting symptoms. (See "Overview of the clinical manifestations of hyperthyroidism in adults".)
Other endocrine conditions that can mimic some features of hyperventilation syndrome include pregnancy, pheochromocytoma, hypoglycemia, and hypocalcemia. (See "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes", section on 'Physiologic dyspnea of pregnancy' and "Clinical presentation and diagnosis of pheochromocytoma", section on 'Clinical presentation' and "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, causes, and diagnosis", section on 'Clinical manifestations' and "Clinical manifestations of hypocalcemia", section on 'Acute manifestations'.)
●Acute coronary syndrome – Patients with atypical presentations of acute coronary syndrome may present with dyspnea, palpitations, dizziness, or diaphoresis without discrete retrosternal chest pressure. An electrocardiogram (ECG) and measurement of cardiac biomarkers (eg, serum troponin) may be indicated depending on the patient's age and risk factors for coronary disease. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
●Heart failure – Patients with previously undiagnosed heart failure can present with dyspnea, tachypnea, tachycardia, and diaphoresis; hyperventilation may be present if stimulation of pulmonary vascular receptors due to elevated pulmonary capillary pressure leads to increased central controller activity out of proportion to the ventilation/perfusion mismatch. Clues to the presence of heart failure include orthopnea, paroxysmal nocturnal dyspnea, an irregularly irregular rhythm, peripheral edema, a history of cardiac disease, crackles on chest exam, and increased jugular venous distension. Diagnostic assessment usually includes an ECG, a serum brain natriuretic peptide (BNP; or N-terminal pro-BNP [NT-pro-BNP]) level, cardiac biomarkers, a chest radiograph, and, depending on the results to these tests, an echocardiogram. (See "Heart failure: Clinical manifestations and diagnosis in adults".)
●Pulmonary embolism – It may be appropriate to exclude pulmonary embolism (PE) in some patients presenting with apparent hyperventilation. This is done by a combination of assessment of risk factors for PE, examination for evidence of hemodynamic compromise (eg, tachycardia >100/minute), pulse oximetry, and D-dimer in appropriate patients. The majority of patients with PE have a widened alveolar-arterial oxygen gradient, in contrast to patients with hyperventilation syndrome in whom gas exchange is generally normal. The hyperventilation associated with PE is likely due to stimulation of pulmonary and vascular receptors that increase the central drive to breathe. The decision to obtain computed tomography (CT) pulmonary angiography is based on the likelihood of PE according to probability scores or overall clinical suspicion. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Hemodynamically stable patients'.)
●Pneumothorax – Spontaneous pneumothorax can present with any combination of dyspnea, tachycardia (palpitations), and chest pain. Depending on the size of the pneumothorax, physical findings of decreased chest excursion on the affected side, diminished breath sounds, and hyperresonance to percussion may be absent. Pulse oximetry may show decreased oxygen saturation, although oxygen saturation may be normal in a patient with otherwise normal lungs. A chest radiograph, or thoracic ultrasound by a trained clinician, is needed to exclude the diagnosis. (See "Pneumothorax in adults: Epidemiology and etiology" and "Treatment of secondary spontaneous pneumothorax in adults".)
●Airway diseases – Exacerbations of asthma, paradoxical vocal fold motion (PVFM), chronic obstructive pulmonary disease (COPD), and upper airway obstruction can present with dyspnea, tachypnea, and other features common to hyperventilation syndrome. Asthma is a common comorbid disease among patients with hyperventilation syndrome, and such patients are often unable to differentiate the two causes of "dyspnea."
The presence of wheezing favors a diagnosis of asthma but must be differentiated from PVFM. The latter is more often an inspiratory phenomenon, associated with audible stridor, and the oxygen saturation will usually be normal. Patients with PVFM can "pant" during an episode, whereas asthmatic patients cannot. Fiberoptic laryngoscopy during an acute PVFM attack is diagnostic, the key finding being that the vocal cords come together during inspiration, especially posteriorly, rather than move apart from the midline. Measuring peak expiratory flow or forced expiratory volume in one second can help in the assessment of asthma exacerbations but are dependent on patient effort and technique. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Inducible laryngeal obstruction (paradoxical vocal fold motion)".)
Exacerbations of COPD can be associated with anxiety and hyperventilation. Generally, other features, such as cough, sputum production, and >20 pack-year smoking history, provide clues to the diagnosis. It is also important to remember that tachypnea or hyperventilation from any cause in the setting of airflow obstruction (eg, COPD) may lead to dynamic hyperinflation and associated physiological changes that will cause or worsen dyspnea. (See "Chronic obstructive pulmonary disease: Diagnosis and staging".)
Various causes of central and upper airway obstruction can present with dyspnea, sometimes occurring acutely. Lack of response to bronchodilators, monophonic wheeze, and inspiratory stridor are clues to upper airway obstruction, but their absence does not exclude this diagnosis. In addition, such patients may have arterial blood gas evidence of respiratory acidosis without an increased alveolar-to-arterial gradient. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure".)
●Infection and sepsis – Patients with sepsis can present with diaphoresis, tachypnea, and tachycardia and a metabolic acidosis before other symptoms and signs of infection are apparent. Patients with cirrhosis may have impaired metabolism of lactic acid, such that infections such as spontaneous bacterial peritonitis can present with increased ventilation in response to metabolic acidosis. Identification of symptoms and signs suggesting infection (eg, fever) or specific to an infectious source (eg, productive cough, abdominal pain, urinary symptoms) and knowledge of underlying disorders can help lead to the correct diagnosis. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Spontaneous bacterial peritonitis in adults: Clinical manifestations".)
●Central nervous system disorders – Patients will frequently hyperventilate after a grand mal seizure, particularly if metabolic acidosis developed during the seizure. If the seizure was not witnessed, patients could present with hyperventilation, although this would almost always be associated with decreased mental status. Patients with partial seizures can also present with attacks that suggest panic attacks and which can be associated with hyperventilation . Finally, brainstem pathology, usually tumors or inflammation in the pons, can be associated with central hyperventilation syndrome.
DIAGNOSIS — Hyperventilation syndrome is a disorder with no widely accepted diagnostic criteria; it is a diagnosis of exclusion that is made after careful observation and evaluation of alternate explanations for the symptoms and findings and is usually reserved for patients with a pattern of recurrent episodes without other signs and symptoms of underlying cardiopulmonary disease . The combination of the patient's presentation, absence of findings to support an alternative diagnosis, and symptom resolution may be sufficient to diagnose hyperventilation syndrome in the majority of cases. However, the challenge to the clinician is that for patients presenting acutely with hyperventilation, a number of respiratory, cardiac, and metabolic, and infectious illnesses are in the differential diagnosis and must be excluded clinically or with further testing (table 1). (See 'Differential diagnosis' above.)
The overlap of cardiopulmonary conditions and emotional conditions that are associated with hyperventilation should be kept in mind. As examples, hyperventilation syndrome is well described in patients with asthma and other pulmonary diseases, and panic disorder is sometimes associated with hyperventilation.
Having excluded physiologic causes for hyperventilation, one is often left with a syndrome that may be characterized by features of a number of psychological and behavioral disorders (figure 1).
Initial evaluation — Hyperventilation syndrome may be suspected in a young (eg, <40 years old), well-appearing adult patient with rapid and/or deep respirations and a history of subacute and/or chronic symptoms, but no prior history of cardiopulmonary disease. However, to make the diagnosis of hyperventilation syndrome, alternative etiologies need to be considered and excluded. The patient history, physical examination, and screening laboratory testing should focus on these potential alternative etiologies. (See 'Differential diagnosis' above.)
The diagnostic approach to an adult patient with suspected hyperventilation syndrome depends upon the clinical suspicion for an alternate diagnosis (based on bedside assessment) and the patient's response to reassurance. For a young, otherwise healthy and well-appearing adult patient whose symptoms resolve and vital signs normalize quickly with reassurance, a diagnostic evaluation beyond a careful history, physical, and pulse oximetry may not be needed. For patients with a first episode of hyperventilation, atypical associated symptoms or signs, or slow response to reassurance, additional point-of-care testing is advisable, as outlined below.
Bedside assessment — A careful bedside assessment is appropriate for all patients with suspected hyperventilation syndrome.
●History – The history should include the frequency, severity, and duration of episodes, concomitant symptoms, precipitants, and relievers. Patients whose symptoms are not intermittent or recurrent should not be considered as having hyperventilation syndrome. The absence of reproducible exertional symptoms may be helpful in excluding chronic pulmonary disease. Key points of the history in patients presenting to the emergency department with acute dyspnea are described separately (table 3). (See "Approach to the adult with dyspnea in the emergency department", section on 'History'.)
●Physical examination – Tachycardia, tachypnea, exaggerated deep breaths, and anxiety may be present due to activation of the sympathetic nervous system, and blood pressure may be high for the same reason; bradycardia or low blood pressure suggests an alternative diagnosis. Fever and hypoxemia should not be seen with hyperventilation syndrome and alternative causes for hyperventilation must be investigated. In addition, the patient should be examined for signs of significant respiratory distress, such as the use of accessory muscles, inability to lie flat, distended jugular veins, profound diaphoresis, or altered mental status. Other physical findings that would suggest a cause other than hyperventilation include signs of dehydration, goiter, new loud murmur, S3 gallop, pericardial rub, abdominal tenderness, encephalopathy, or new peripheral edema. If any of these is present, particular care should be taken to exclude causes of dyspnea and hyperventilation due to alternative diseases. Other than findings of a breathing pattern with an inordinately large tidal volume at rest, the lung and cardiovascular examinations should be normal in patients with hyperventilation syndrome.
●Pulse oximetry – Pulse oxygen saturation (SpO2), including saturation during ambulation, should be normal, remembering that pulse oximetry may be inaccurate in carbon monoxide poisoning or methemoglobinemia (consider co-oximetry) and that hyperventilation can mask a gas transfer defect, such as in pulmonary embolism (PE) and pneumothorax (ie, normal O2 saturation due to hyperventilation with abnormal alveolar to arterial oxygen gradient calculated from arterial blood gas). Symptoms associated with SpO2 <95 percent on room air should not be attributed to hyperventilation syndrome. (See "Pulse oximetry".)
●Capnography – If capnography is available, it can be used to assess end-tidal carbon dioxide (etCO2); in hyperventilation syndrome, etCO2 would be expected to be low initially and increase towards normal as the episode resolves. However, there is no consensus regarding the threshold for the decrease in arterial tension of CO2 (PaCO2) or etCO2 that would establish a diagnosis hyperventilation syndrome . In patients with underlying lung disease, capnography may not correlate well with PaCO2. (See "Carbon dioxide monitoring (capnography)".)
●Assessment for features of a panic attack – There is no optimal screening tool for reliably diagnosing psychiatric causes of hyperventilation. However, the Multidimensional Dyspnea Profile (figure 2) is a questionnaire that has demonstrated some discriminative capacity in identifying panic disorder in patients with dyspnea, regardless of the presence of underlying pulmonary disease . Using this tool, patients with panic disorder expressed more prominent affective symptoms (eg, feeling depressed) and reported feeling “air hunger” and a sensation of “concentrating” on their breathing more frequently than those without panic disorder.
Diagnostic criteria for psychiatric disorders associated with hyperventilation, such as panic disorder and generalized anxiety, have been established. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis' and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Screening, assessment, and diagnosis'.)
Point-of-care testing — Point-of-care testing is performed as needed, based on the above evaluation.
●Fingerstick or serum glucose – Measurement of glucose is prudent to assess for hyperglycemia as a potential marker for diabetic ketoacidosis. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".)
●Basic laboratory tests – Measurement of complete blood count, blood urea nitrogen, creatinine, and electrolytes (with calculation of the anion gap). (See "Approach to the adult with metabolic acidosis", section on 'Assessment of the serum anion gap'.)
●Arterial blood gas – Measurement of arterial blood gases (ABG) is prudent if there is any concern about underlying cardiopulmonary disease or metabolic derangement; for example, to check the alveolar-arterial gradient to assess for disease (elevated gradient) versus hyperventilation (normal gradient), or to assess acid-base balance, if the serum bicarbonate is low or electrolyte measurement shows an anion gap. (See "Arterial blood gases".)
In an emergency department study of hyperventilation syndrome, arterial blood gases were obtained in 244 patients; the mean pH was 7.47, mean arterial tension of oxygen (PaO2) was 97 mmHg (12.9 kPa), and mean PaCO2 was 29 mmHg (3.87 kPa) .
●Peak expiratory flow – Peak expiratory flow or portable spirometry may be helpful to reassure the patient that they are indeed able to inhale and exhale a normal volume of air, or conversely to identify airflow limitation indicative of asthma or chronic obstructive pulmonary disease (COPD). (See "Peak expiratory flow monitoring in asthma" and "Office spirometry".)
●Imaging – Chest radiography with careful attention to features of pneumothorax, PE, pneumonia, or heart failure.
●Electrocardiogram – An electrocardiogram (ECG) should be obtained in patients with chest pain not associated with chest wall tenderness and in those with risk factors for coronary ischemia.
Caution against breathing into paper bag — There are few data on the use of rebreathing into a paper bag to diagnose or treat an episode of hyperventilation and there is a potential for harm. Despite one small series in children and anecdotal reports of success with this maneuver [39,40], it has been associated with adverse outcomes in adults; particular caution is advised in those with underlying respiratory or cardiovascular disease because of the risk of acute hypoxemia resulting from the maneuver . In patients with metabolic acidosis as a cause of the hyperventilation, breathing into a paper bag may acutely worsen the acidosis by interfering with the body's attempt at respiratory compensation.
Further evaluation — Further evaluation to investigate the possibility of a pulmonary, cardiac, metabolic, or neurologic cause of the patient's symptoms should be based upon the patient's history and examination findings, and the likelihood of underlying pathology.
Other evaluations that may be indicated for certain patients include:
●Laboratory testing – Toxicology screens, electrolyte measurement, and testing for pheochromocytoma may be indicated if tachycardia, hypertension, and other findings suggestive of pheochromocytoma are prominent features of the presentation.
●Fiberoptic laryngoscopy – While not appropriate for all patients presenting with hyperventilation or concern for hyperventilation syndrome, in selected patients examination of the upper airway during an attack can help exclude processes such as paradoxical vocal fold dysfunction and laryngeal angioedema. In the case of paradoxical vocal fold dysfunction, the study may be normal when the attack is over. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Laryngoscopy' and "An overview of angioedema: Clinical features, diagnosis, and management", section on 'Angioedema in or near the airway'.)
●D-dimer and computed tomography pulmonary arteriography – Use of the D-dimer depends upon the patient's pretest probability for PE. The diagnosis of PE can be excluded in patients at low risk for PE according to a validated scoring system (eg, modified Wells criteria, PE rule-out criteria [PERC rule], or Geneva score) and a negative enzyme-linked immunosorbent assay (ELISA) D-dimer. If the clinical evaluation and D-dimer testing do not exclude the possibility of a PE, computed tomography pulmonary angiography (CTPA) is usually the next step unless contrast media is contraindicated. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Hemodynamically stable patients'.)
●Cardiac biomarkers – In cases of persistent diagnostic uncertainty in which a coronary etiology is being considered, sequential troponin measurements can help to exclude the diagnosis. The timing of repeat troponin measurements is dependent upon the patient's presentation (eg, duration of chest pain) and degree of suspicion for a cardiac etiology. This is reviewed in detail elsewhere. (See "Diagnosis of acute myocardial infarction", section on 'Timing of measurement'.)
Follow-up testing — Sometimes an episode of hyperventilation will resolve prior to a confident exclusion of intermittent processes such as asthma, paradoxical vocal fold dysfunction, upper airway obstruction, dysrhythmia, or cardiac ischemia, and further testing may be warranted.
●Pulmonary function tests – For patients in whom differentiation of hyperventilation syndrome from asthma or other pulmonary diseases cannot be confidently made at the time of their presentation, the next test is usually formal spirometry (including pre- and post-bronchodilator measurements) in a pulmonary function laboratory. If possible, testing during an episode of hyperventilation may be more likely to identify airflow limitation indicative of asthma. (See "Asthma in adolescents and adults: Evaluation and diagnosis".)
A flow-volume loop performed at the same time may identify an upper airway contribution, although vocal fold dysfunction can be intermittent, resulting in a normal flow-volume loop at the time of testing. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Pulmonary function tests'.)
If the spirometry and flow-volume loop are normal, bronchoprovocation testing (such as a methacholine challenge test) may be indicated for patients with symptoms suggestive of asthma or reactive airways disease syndrome. Patients whose hyperventilation episodes are associated with wheezing or follow environmental (dust, allergen, smoke), occupational, or other (exercise, cold air) exposures may also warrant provocation testing. Patients with wheezing, a complaint of chest tightness, or an apparent precipitant, however, are unlikely to require bronchoprovocation testing to confirm the diagnosis of asthma. Most patients with asthma and a positive bronchoprovocation challenge will describe their shortness of breath as "chest tightness" [42,43]. (See "Bronchoprovocation testing", section on 'Pharmacologic challenge'.)
●Chest imaging – In the vast majority of cases, patients with a normal chest radiograph and low suspicion for PE do not require chest computed tomography (CT) imaging. Chest CT scanning is indicated to evaluate abnormalities on chest radiography, including possible pulmonary nodules or masses, parenchymal opacities, pulmonary vascular abnormalities, or large airway abnormalities. A CT scan may be useful to assess for subtle interstitial opacities when physical examination suggests possible interstitial disease (eg, basilar crackles) and the chest radiograph is normal; approximately 10 percent of patients with interstitial lung disease present with a normal chest radiograph.
●Ambulatory electrocardiogram monitoring – Patients with palpitations may have tachycardia as part of the hyperventilation syndrome, but ambulatory ECG monitoring may be helpful if an arrhythmia is suspected.
●Cardiac stress testing – If coronary heart disease is suspected on the basis of the patient's age and risk factors, but the ECG and cardiac biomarkers obtained at the time of the episode were normal, exercise ECG or other cardiac stress test may be indicated in selected cases based on clinical judgment. (See "Selecting the optimal cardiac stress test", section on 'Indications for stress testing'.)
●Cardiopulmonary exercise testing – The use of cardiopulmonary exercise testing (CPET) may have a limited role in the evaluation of patients with hyperventilation . As an example, in a retrospective analysis of CPET studies, patients with hyperventilation syndrome had a lower resting end-tidal carbon dioxide (PETCO2) than healthy controls, and no change in peak exercise PETCO2 levels or ventilatory efficiency compared with healthy controls, in whom there was an increase in both .
Evaluation of recurrent episodes — For patients with an established diagnosis of hyperventilation syndrome, repeating all of the above "initial" testing may not be necessary, particularly if the episode resolves quickly and completely.
Specialist referral — Patients who exhibit a predominance of psychiatric symptoms associated with the presentation of hyperventilation episodes may require further assessment by a psychiatrist or other mental health professional. (See "Panic disorder in adults: Epidemiology, clinical manifestations, and diagnosis" and "Psychotherapy for panic disorder with or without agoraphobia in adults" and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Generalized anxiety disorder in adults: Management" and 'Treatment' below.)
Referral to a pulmonologist is appropriate for patients with multiple medical comorbidities contributing to atypical presentations of dyspnea, when hyperventilation syndrome appears to be superimposed on an underlying lung disease (eg, COPD), when abnormalities are noted on pulmonary function testing or chest imaging, and those in whom there is difficulty in establishing a definitive diagnosis. Patients who are refractory to standard treatment may also warrant referral to a specialist. (See 'Treatment' below.)
Ancillary diagnostic testing — Certain ancillary tests may be indicated in patients whose diagnosis remains uncertain after the above evaluation. These components of an advanced diagnostic evaluation are indicated only for a minority of patients with suspected hyperventilation syndrome and should be pursued in concert with a specialist (such as a pulmonologist). Such non-routine testing may include a hyperventilation provocation test (HVPT) and investigational carbon dioxide inhalation testing [46-48].
In the HVPT, subjects are asked to hyperventilate (typically for three to five minutes) in an effort to precipitate spontaneous symptoms. A patient's symptoms are assessed after voluntary hyperventilation and compared with the symptoms experienced by the patient during spontaneous "attacks." Compared with normal subjects, minute ventilation may be elevated, and normalization of PaCO2 after voluntary hyperventilation may be delayed in patients with hyperventilation syndrome . The HVPT has several limitations, however, and its clinical utility is uncertain [2,49,50]. One study reports that in a randomized trial the HVPT was positive in 85 of 115 subjects with suspected hyperventilation (74 percent), but that 56 of the 85 also had a positive placebo test (in which CO2 levels were maintained during overbreathing) .
In another study, HVPT was compared with CPET in 59 patients with hyperventilation syndrome; HVPT more consistently reproduced symptoms of hyperventilation syndrome as compared with CPET . The impact of these results on clinical practice is uncertain; however, patients with mild hyperventilation at baseline typically normalize their PaCO2 with exercise until they exceed anaerobic threshold.
Additional testing that may be considered in the evaluation of hyperventilation syndrome includes dyspnea questionnaires such as the Nijmegen questionnaire [28,52,53]. First described in 1982, this tool assesses symptoms and complaints potentially attributable to hyperventilation . The clinical utility of the Nijmegen questionnaire is uncertain in the evaluation of patients with suspected hyperventilation syndrome, however, as the correlation between a positive Nijmegen score and confirmed hyperventilation syndrome is variable . Although the Nijmegen questionnaire is used in research and in some clinical settings, its use should be restricted to specialists and should not be part of the initial patient assessment .
TREATMENT — Our approach to the management of hyperventilation syndrome in adults is based upon our clinical experience, since high-quality data to inform definitive recommendations are lacking. When pharmacologic therapy is suggested, the recommendations are based upon indirect evidence in patients with panic disorder or generalized anxiety disorder.
●Acute management of patients who are hyperventilating should focus upon patient reassurance, an explanation of the symptoms the patient is experiencing, removal of any stressors, and initiation of breathing retraining. Breathing retraining in the acute setting attempts to focus the patient on abdominal (diaphragmatic) breathing.
While sitting or recumbent (recumbent is often easier), the patient should place one hand on their abdomen, the other on the chest, and then be asked to observe which hand moves with greater excursion. In hyperventilating patients, this will almost always be the hand on the chest. Ask the patient to adjust their breathing so that the hand on the abdomen moves with greater excursion and the hand on the chest barely moves at all. Assure the patient that this is hard to learn and will take some practice to fully master. Ask the patient to breathe in slowly over four seconds, pause for a few seconds, and then breathe out over a period of eight seconds. After 5 to 10 such breathing cycles, the patient should begin to feel a sense of calmness with a reduction in anxiety and an improvement in hyperventilation. Symptoms should ideally resolve with continuation of this breathing exercise.
●If the technique described above is not fully successful in resolving the episode, and severe symptoms persist, the patient may be given a small dose of a short-acting benzodiazepine (eg, lorazepam 0.5 to 1 mg orally or 0.5 to 1 mg intravenously, alprazolam 0.25 to 0.5 mg orally).
●Rebreathing of carbon dioxide (CO2) by breathing into a paper bag can cause significant hypoxemia with consequent complications; therefore, we do not advise using this maneuver [3,41]. If rebreathing is used, we urge continuous monitoring of the patient’s oxygen saturation and clinical status.
Treatment to prevent recurrent episodes
●A breathing retraining program should be initiated as the first step to decrease the risk of recurrent acute episodes of hyperventilation syndrome. The breathing exercise as described above should be practiced twice daily, in the morning and evening. Breathing retraining education can be provided by a respiratory therapist, a physical therapist in a pulmonary rehabilitation program, or any other qualified provider. (See 'Acute management' above.)
●Many patients will have symptoms that recur despite breathing retraining, and we refer such patients to cognitive behavioral therapy (CBT). Patients typically respond to a CBT approach more readily having already mastered the breathing retraining that is a component of CBT.
●If persistent and severe hyperventilatory episodes continue despite CBT and breathing retraining, pharmaceutical interventions are warranted. Selective serotonin reuptake inhibitors (SSRIs) are the most appropriate first-line medications. Escitalopram, citalopram, or sertraline are the best choices. Although there are no studies of the efficacy of SSRIs for the treatment of hyperventilation syndrome, these agents are beneficial in the treatment of panic disorder and generalized anxiety disorder. (See "Management of panic disorder with or without agoraphobia in adults" and "Generalized anxiety disorder in adults: Management".)
We do not recommend benzodiazepines as first-line treatment for panic or generalized anxiety disorder, and these anxiolytics should not be prescribed for either without referral to and evaluation by a behavioral medicine consultant (See "Management of panic disorder with or without agoraphobia in adults" and "Generalized anxiety disorder in adults: Management".)
●For patients with suspected significant underlying psychiatric conditions contributing to or resulting in hyperventilation syndrome, immediate referral to a psychiatrist may be warranted, depending upon the severity of symptoms, patient preference, and availability of mental health services. (See "Generalized anxiety disorder in adults: Management" and "Management of panic disorder with or without agoraphobia in adults".)
Breathing retraining, which focuses on enhancing a patient's awareness of breathing pattern and normalization of the breathing pattern when symptoms occur, may provide significant benefit to affected patients [55-57]. High-quality evidence supporting our approach is lacking, but in our experience, breathing retraining followed, if needed, by CBT will help decrease overall anxiety and should be used to help manage and prevent hyperventilation symptoms. (See "Psychotherapy for panic disorder with or without agoraphobia in adults", section on 'Cognitive-behavioral therapy' and "Generalized anxiety disorder in adults: Cognitive-behavioral therapy and other psychotherapies", section on 'Administering CBT'.)
Although SSRIs are first-line medications for patients with symptoms refractory to breathing retraining and CBT, other medications that have been used include benzodiazepines and, less commonly, beta blockers.
Benzodiazepines are commonly prescribed for patients with hyperventilation syndrome and underlying anxiety or panic disorder. However, there are limited efficacy data. One small study demonstrated no efficacy of benzodiazepines compared with breathing retraining . Furthermore, benzodiazepines are to be reserved for use in treatment-resistant patients with panic and generalized anxiety disorders and would have limited if any use in the treatment of hyperventilation syndrome. (See "Management of panic disorder with or without agoraphobia in adults", section on 'Treatment resistance' and "Generalized anxiety disorder in adults: Management", section on 'Unresponsive to multiple agents'.)
The evidence in favor of beta blocker therapy is mixed. Some studies of beta blockers have demonstrated short-term improvement in the frequency of hyperventilation episodes . In one randomized trial over three weeks, bisoprolol 5 mg once daily led to a 75 percent decrease in the frequency of hyperventilation episodes compared with a 12.5 percent decrease with placebo . However, a retrospective study of beta blockers compared with benzodiazepines and anxiolytics demonstrated no effect of either therapy on subjective complaints, and although beta blockers were effective at raising the PCO2, there was poor correlation between subjective complaints and objective measurements of ventilation . In addition, there is no evidence that beta blockers are effective treatments for panic and limited evidence that they are weakly effective for generalized anxiety.
SUMMARY AND RECOMMENDATIONS
●Hyperventilation syndrome – Hyperventilation syndrome is characterized by intermittent episodes of transient increases in minute ventilation, with respiratory alkalosis with a normal alveolar-arterial oxygen gradient, and is associated with a wide range of symptoms without an alternative, contributory cardiorespiratory diagnosis. (See 'Introduction' above.)
●Associated symptoms – A variety of symptoms, including dyspnea, lightheadedness, paresthesias, chest pain, palpitations, diaphoresis, fear and sense of impending doom, and anxiety, have been associated with hyperventilation syndrome. (See 'Clinical presentation' above.)
●Contributors – Psychological, neurologic, and cardiopulmonary pathologies may all contribute to a patient's symptoms. There is significant overlap with psychiatric comorbidities (especially panic and anxiety disorders) (figure 1). (See 'Prevalence and epidemiology' above.)
●No specific diagnostic criteria – Hyperventilation syndrome is a disorder with no widely accepted diagnostic criteria; it is a diagnosis of exclusion that is made after careful observation and evaluation of alternate possibilities. (See 'Diagnosis' above.)
●Differential diagnosis – The differential diagnosis of acute hyperventilation includes multiple serious and potentially life-threatening medical conditions, such as metabolic acidosis, asthma, upper airway obstruction, pulmonary embolism (PE), acute coronary syndrome, and sepsis (table 1), most of which have identifiable abnormalities in gas exchange (ie, abnormal alveolar to arterial oxygen gradient) unless hyperventilation syndrome is superimposed upon coexisting cardiopulmonary disease. (See 'Differential diagnosis' above.)
●Diagnosis – The patient history (table 3), physical examination, and screening laboratory testing should focus on potential alternative etiologies for patients presenting with acute hyperventilation. The evaluation is step-wise, with results of initial history, physical examination, laboratory tests, and response to treatment guiding subsequent testing. (See 'Diagnosis' above.)
●Acute management of hyperventilation – The acute management of a hyperventilation episode due to hyperventilation syndrome should focus on patient reassurance and an initial attempt at breathing retraining. If this fails to resolve the acute episode and severe symptoms persist, a small dose of a short-acting benzodiazepine may be administered. Paper bag rebreathing carries the risk of hypoxemia and is not advised. (See 'Acute management' above.)
●Management of recurrent hyperventilation – Among patients with recurrent episodes of hyperventilation, we suggest initial treatment with breathing retraining rather than cognitive behavioral therapy (CBT) or pharmacologic therapy (Grade 2C). For those not responding to breathing retraining alone, we suggest a referral for CBT with continued breathing retraining (Grade 2C). If breathing retraining and CBT are ineffective in preventing recurrent episodes, we suggest initiating pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI) rather than a benzodiazepine or a beta blocker (Grade 2C). (See 'Treatment to prevent recurrent episodes' above.)
●Indications for referral – Referral to a pulmonologist for specialty testing is only necessary in complicated diagnostic cases, in patients with multiple comorbidities, or for patients who are refractory to standard interventions. Referral to a psychiatrist or other mental health professional may be appropriate for patients with significant underlying psychiatric contributors. (See 'Specialist referral' above.)
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