Hyperventilation syndrome BY AHMAD YOUNES PROFESSOR OF THORACIC

Hyperventilation syndrome BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINE Mansoura faculty of medicine

Hyperventilation syndrome • Hyperventilation syndrome (HVS) represents a relatively common emergency department (ED) presentation that is readily recognized by most clinicians. • The underlying patho-physiology has not been clearly elucidated. • HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in hemodynamic and chemical changes that produce characteristic dysphoric symptoms. • Inducing a drop in Pa. CO 2 through voluntary hyperventilation reproduces these symptoms. • Many patients with HVS do not manifest low Pa. CO 2 during attacks.

Hyperventilation syndrome • 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. • Some patients may be physiologically at risk for the development of psychogenic dyspnea. • Symptoms of HVS and panic disorder overlap considerably, though the 2 conditions remain distinct. • Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as a symptom, whereas only 25% of patients with HVS manifest panic disorder.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, classifies the anxiety disorders into the following categories: • • • Anxiety due to a general medical condition Substance induced anxiety disorder Generalized anxiety disorder Panic disorder Acute stress disorder Posttraumatic stress disorder (PTSD) Adjustment disorder with anxious features Obsessive compulsive disorder (OCD) Social phobia Specific phobia and agoraphobia

Hyperpnea or hyperventilation • Hyperpnea or hyperpnoea is increased depth of breathing when required to meet metabolic demand of body tissues, such as during or following exercise, or when the body lacks oxygen (hypoxia), for instance in high altitude or as a result of anemia. • Tachypnea differs from hyperpnea in that tachypnea is rapid shallow breaths, while hyperpnea is deep breaths. • In hyperpnoea, the increased breathing rate is desirable as it meets the metabolic needs of the body. • In hyperventilation, the rate of ventilation is inappropriate for the body's needs (except in respiratory acidosis, when CO 2 needs to be breathed off). The resulting decrease in CO 2 concentration results in the typical symptoms of light-headedness, tingling in peripheries, visual disturbances etc. In hyperpnoea, there are generally no such symptoms.

Panic Disorder • Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks, the frequency of which can vary from several attacks per day to only a few attacks per year. • Panic attacks can occur in other anxiety disorders but occur without discernible predictable precipitant in panic disorder • To make the diagnosis of panic disorder, panic attacks cannot directly or physiologically result from substance use, medical conditions, or another psychiatric disorders

Panic attacks are a period of intense fear in which 4 of 13 defined symptoms develop abruptly and peak rapidly less than 10 minutes from symptom onset. • • • • Palpitations Sweating Trembling or shaking Sense of shortness of breath or smothering Feeling of choking Chest pain or discomfort Nausea or abdominal distress Feeling dizzy, unsteady, light-headed, or faint Derealization or depersonalization (feeling detached from oneself) Fear of losing control or going crazy Fear of dying Numbness or tingling sensations Chills or hot flashes

Collectively, phobic disorders (social phobia, specific phobia, and agoraphobia) are the most common forms of psychiatric illness, surpassing the rates of mood disorders and substance abuse • Agoraphobia is defined as anxiety toward places or situations in which escape may be difficult or embarrassing • Most cases of agoraphobia develop as a complication of panic disorders. • A person previously experiences a panic attack in a specific situation or environment and this triggers a vicious circle. • They begin to worry so much about having a panic attack again that they feel the symptoms of panic attack returning when they are in a similar situation or environment. This then causes the person to avoid that particular situation or environment.

Conversion disorder, factitious disorder, and malingering • Conversion disorder, factitious disorder, and malingering have one major characteristic in common: they represent conditions that are not ‘real’. • Properly diagnosing your patient with one of these psychiatric ailments will allow you to create appropriate plans of care for your patients.

1. Conversion Disorder: is a psychiatric condition that results in a neurological complaint or symptom, without any underlying neurological cause. • Patient’s may experience seizures (i. e. ‘pseudoseizures’), weakness, non-responsiveness, numbness, and even vision loss. • The symptoms are not intentional, yet upon further investigation no biological explanation for the symptoms can be found. • The name “conversion disorder” formerly known as "hysteria", comes from Sigmund Freud who stated that stress can cause a psychiatric ailment to ‘convert’ to a medical problem. • It is thought that symptoms arise in response to stressful situations affecting a patient's mental health.

2. Factitious Disorder (Munchausen Syndrome ) • Factitious Disorder (a Somatoform Disorder): is a condition where patients intentionally fake disease, or intentionally cause disease in order to play the ‘patient role’. • The main distinction between this and conversion disorder is the intentional nature of factitious disorder. • Often referred to a factitious disorder is characterized by patients frequently feigning illness to obtain attention, sympathy, or other emotional feedback. • They achieve this goal through exaggerating symptoms, deliberately faking symptoms, or even intentionally creating real symptoms.

Münchausen syndrome by proxy • Münchausen syndrome by proxy (MSb. P or MBP) is a term that is used to describe a behavior pattern in which a caregiver deliberately exaggerates, fabricates, and/or induces physical, psychological, behavioral, and/or mental health problems in those who are in their care. • With deception at its core, this behavior is an elusive, potentially lethal, and frequently misunderstood form of child abuse or medical neglect that has been difficult to define, detect and confirm.

3. Malingering • Malingering is the intentional faking or creating of illness in order to obtain secondary gain (e. g. workers compensation, disability payments, avoiding work or jail time, pain medication, etc. ). • Malingering is NOT a psychiatric illness; this is the first major distinction from the other two disorders. • Malingering is an intentional abuse of the medical system to obtain personal benefit. • Malingerers abuse the system to obtain secondary gain while patients with factitious disorder attempt only to obtain emotional, or primary gain. In simpler terms, the end goal of a malingerer usually involves monetary value, while the goals of patients with factitious disorder have no such value

QUICK REVIEW • Conversion Disorder: Unintentional, due to emotional stressors, no ‘gain’ to the patient • Factitious Disorder (Munchausen): Intentional, primary or ‘emotional’ gain • Malingering: Intentional, secondary and often monetary gain.

Pathophysiology of HVS • 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 over-breathing by the patient. • 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. • Certain stressors provoke an exaggerated respiratory response, including emotional distress, sodium lactate, caffeine, isoproterenol, cholecystokinin, and Co 2.

Pathophysiology • 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. • 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,

Pathophysiology • Patients with HVS tend to breathe by using the upper thorax rather than the diaphragm, and this results in chronic over-inflation 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.

Pathophysiology • 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). • 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.

Etiology • 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 hyper-expanded 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.

Etiology • 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.

Epidemiology • As many as 10% of patients in a general internal medicine practice are reported to have HVS as their primary diagnosis. • 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-tomale ratio may be as high as 7: 1.

Prognosis • 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. • 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.

Prognosis • A leftward shift in the oxyhemoglobin dissociation curve and vasospasm related to low Pa. CO 2 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 false diagnoses. • Patients with HVS often undergo unnecessary testing and suffer from the complications of these interventions (eg, angiography, thrombolytics, or nasal reconstruction). • Withholding such therapy may be difficult in a patient with crushing chest pain and dyspnea. the chronicity of the condition often causes different physicians to repeat these unnecessary investigations.

Patient Education • Patients should receive : 1 - Clear explanation of the underlying pathophysiology and 2 - should be instructed in the technique of deflation of the upper chest followed by controlled diaphragmatic breathing.

Complications • The complications encountered in patients with this syndrome are related mainly to the invasive procedures and investigations (eg, angiography) that are used in the workup of HVS. • Complications may also occur as a result of symptoms produced indirectly by hyperventilation (eg, injuries sustained in a fall during a syncopale episode attributable to hyperventilation).

Screening for OSA prior to surgery • Pulse oximetry as a single metric of sleep apnea lacks the sensitivity and specificity of PSG and multi-channel home sleep testing. • If the goal is only to cipher out those with an AHI of 15 or 20 or more, pulse oximetry can be considered. • Centers for Medicare and Medicaid Services, 2009 reported that the final decision supporting equally effective testing utilizing PSG and home sleep tests, as measured by outcomes and patient compliance . • While patients with mild OSA may not require preoperative PAP therapy, patients with moderate and severe OSA who have been on PAP therapy should continue treatment in the preoperative pe riod. • Patients who have been noncompliant with instructions for CPAP use prior to surgery and are in need of CPAP post surgery, pose the highest risk of potential complications.

Acute hyperventilation • Patients often present dramatically, with agitation, hyperpnea and tachypnea, dyspnea, wheezing, chest pain , 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. • Wheezing may be heard because of bronchospasm from hypo-carbia.

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.

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 carpo-pedal spasm. • ECG abnormalities may include prolonged QT interval, ST depression or elevation, and T-wave inversion.

Cardiac symptoms • 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 reduced cerebral blood flow (CBF). CBF decreases by 2% for every 1 mm Hg decrease in Pa. CO 2. • Symptoms of dizziness, weakness, confusion, and agitation are common. Patients may experience visual hallucinations, syncope or seizure. • Paresthesias occur more commonly in the upper extremity and are usually bilateral. Perioral numbness is very common. Gastrointestinal 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.

Chvostek’s sign is twitching of facial muscles in response to tapping over the area of the facial nerve Trousseau’s sign is carpopedal spasm that results from ischemia, such as that induced by pressure applied to the upper arm from an inflated sphygmomanometer cuff.

• Chvostek’s sign is neither sensitive nor specific for hypocalcemia, since it is absent in about one third of patients with hypocalcemia and is present in approximately 10% of persons with normal calcium levels. • Trousseau’s sign is more sensitive and specific; it is present in 94% of patients with hypocalcemia and in only 1% of persons with normal calcium levels.

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 Pa. CO 2 with compensatory renal excretion of bicarbonate, resulting in a near-normal p. H level. • These patients tend to have more prominent CNS symptoms than patients who maintain normal Pa. CO 2 during attacks. • Usually present with dyspnea and chest pain. • Frequent sighing respirations (2 -3 breaths/min) and frequent yawning are noted.

Chronic hyperventilation • 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. • 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. • Chronic HVS may have symptoms that mimic those of virtually any serious organic disorder, but they usually have atypical features of these diseases.

Differential Diagnoses : • • • Asthma Atrial Fibrillation Myocardial Infarction Diabetic Ketoacidosis Metabolic Acidosis Nasopharyngeal Stenosis Pneumothorax, Pneumomediastinum Pulmonary Embolism Respiratory Distress Syndrome, Adult Carbon monoxide poisoning Panic Disorders

Approach Considerations • 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. • Acute coronary syndrome (ACS) and pulmonary embolism (PE) are the 2 most common serious entities that may present similarly to HVS. • Clinical assessment is sufficient to rule these out. More specific testing is sometimes warranted. • A standard workup for atypical chest pain, including pulse oximetry, chest radiography, and ECG, may still be warranted depending on the clinical picture.

Approach Considerations • 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 sufficient to make the diagnosis. • A low pulse oximetry reading in a patient who is hyperventilating should never be attributed to HVS. The patient should always be evaluated for other causes of hyperventilation.

Approach Considerations • A normal pulse oximetry reading is not helpful, because a severe defect in gas exchange can easily be masked by hyperventilation. • A fraction of patients with chronic PE will have compensated chronic hyperventilation that may mimic primary chronic hyperventilation. • ABG is indicated if any doubt exists as to the patient’s underlying respiratory status; it may be helpful when HVS-induced acidosis is suspected, or when shunting or impaired pulmonary gas exchange is considered.

Approach Considerations • ABG sampling confirms a compensated respiratory alkalosis in a majority of cases. The p. H is typically near normal, with a low Pa. CO 2 and a low bicarbonate level. • ABG sampling is also useful in ruling out toxicity from carbon monoxide poisoning, which may present similarly to HVS. • Toxicology screening is indicated. • If acute PE is being considered, ELISA D-dimer assay may be helpful.

Pulse CO-oximeters • Pulse Co-oximetry measures absorption at several wavelengths to distinguish the percentage of oxygenated Hemoglobin compared to the total amount of hemoglobin (Hb), including carboxyhemoglobin (carboxy. Hb), Methemoglobin (met-Hb), oxyhemoglobin (oxy-Hb), and reduced Hb. • When a patient presents with carbon monoxide poisoning (CO), the pulse CO-oximeter will detect the levels of each hemoglobin and will report the oxyhemoglobin saturation as markedly reduced ,

Pulse CO-oximeters • Traditionally, this measurement is made from arterial blood processed in a blood gas analyzer with a COoximeter. • More recently, pulse CO-oximeters have made it possible to estimate carboxyhemoglobin with noninvasive technology similar to a Pulse oximeter. • In contrast, the use of a standard pulse oximeter is not effective in the diagnosis of CO poisoning as patients suffering from carbon monoxide poisoning may have a normal oxygen saturation reading on a pulse oximeter.

Approach Considerations • Imaging studies are not indicated when the diagnosis of HVS is clear. • Because PE can present with findings identical to those of HVS, a first-ever episode of acute HVS may warrant V/Q scanning or CT pulmonary angiography to rule out perfusion defects. • Chest radiography is indicated for patients who are at high risk for cardiac or pulmonary pathology.

Approach Considerations • ECG changes are common and may include the following: 1 - ST depression or elevation 2 - Prolonged QT interval 3 - T-wave inversion 4 - Sinus tachycardia • Rebreathing into a paper bag is not recommended in the field. 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.

Rebreathing into a paper bag 1 - Have the hyperventilating person breathe slowly into a paper bag that's held closely around his or her mouth and nose. 2 - The person should breathe like this for five to seven minutes. 3 -Talk to the individual the entire time. Try to distract him or her and make the person feel comfortable and safe. 4 - If symptoms fail to improve or the person loses consciousness, take him or her to the emergency room.

Approach Considerations • Patients should be referred to a consultant psychiatrist, psychologist with expertise in managing HVS. • Some physiotherapists and respiratory therapists have extensive experience in retraining patients in proper breathing techniques and should be consulted.

Breathing Techniques • Rebreathing into a paper bag is no longer a recommended technique, because significant hypoxia and death have been reported. • 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. • 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.

Breathing Techniques • Most patients with HVS tend to breathe with the upper thorax and have hyper-inflated 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.

What is “calm breathing”? • Calm breathing (sometimes called “diaphragmatic breathing”) is a technique that helps you slow down your breathing when feeling stressed or anxious. • Newborn babies naturally breathe this way, and singers, wind instrument players, and yoga practitioners use this type of breathing. • 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.

Why is calm breathing important? • ¨ Our breathing changes when we are feeling anxious. We tend to take short , quick, shallow breaths, or even hyperventilate; this is called “overbreathing”. • ¨ It is a good idea to learn techniques for managing “overbreathing”, because this type of breathing can actually make you feel even more anxious (e. g. , due to a racing heart, dizziness, or headaches)! • ¨ Calm breathing is a great portable tool that you can use whenever you are feeling anxious. However, it does require some practice.

How to Do It? • Calm breathing involves taking smooth, slow, and regular breaths. • Sitting upright is usually better than lying down or slouching, because it can increase the capacity of your lungs to fill with air. • It is best to 'take the weight' off your shoulders by supporting your arms on the side-arms of a chair, or on your lap.

How to Do It ? 1. Take a slow breath in through the nose, breathing into your lower belly (for about 4 seconds) 2. Hold your breath for 1 or 2 seconds 3. Exhale slowly through the mouth (for about 4 seconds) 4. Wait a few seconds before taking another breath • About 6 -8 breathing cycles per minute is often helpful to decrease anxiety, but find your own comfortable breathing rhythm. • These cycles regulate the amount of oxygen you take in so that you do not experience the fainting, tingling, and giddy sensations that are sometimes associated with overbreathing.

Helpful Hints • Make sure that you aren’t hyperventitating; it is important to pause for a few seconds after each breath. • Try to breathe from your diaphragm or abdomen. • Your shoulders and chest area should be fairly relaxed and still. If this is challenging at first, it can be helpful to first try this exercise by lying down on the floor with one hand on your heart, the other hand on your abdomen. Watch the hand on your abdomen rise as you fill your lungs with air, expanding your chest. (The hand over your heart should barely move, if at all. )

Pharmacologic Therapy • 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.

Pharmacologic Therapy • 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. • Alprazolam (xanax) is indicated for treatment of anxiety and management of panic attacks. • Lorazepam (ativan) is a sedative-hypnotic of the benzodiazepine class that has a short time to onset of effect and a relatively long half-life.

Pharmacologic Therapy • Diazepam (valium) 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. • Paroxetine (paxil) 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.