12 years: 25-50 mg/d hs or bid/tid; increase gradually to 100 mg/d Contraindications Documented hypersensitivity; avoid use in patients with urinary retention or glaucoma, and during the acute recovery phase following MI Interactions TCAs may enhance the effects of anticholinergic medications. Barbiturates may lower the serum levels of TCAs. Charcoal can prevent TCA absorption, thereby reducing their effectiveness or toxicity. Cimetidine can increase TCA levels in patients taking cimetidine. Ranitidine may be an alternative. It can increase blood pressure to dangerous levels and can cause a hypertensive crisis in patients receiving concurrent TCAs. Avoid coadministration. TCAs may increase the half-life or bioavailability of dicumarol, possibly resulting in increased anticoagulation effects. Disulfiram and TCA coadministration may result in acute organic brain syndrome. The bioavailability of the antidepressant may be increased. TCAs may antagonize the antihypertensive action of guanethidine by inhibiting uptake into adrenergic neurons. Avoid this combination when possible. Haloperidol may increase serum concentrations of TCAs. Levodopa absorption may be delayed and its bioavailabilitydecreased by TCAs. Hypertensive episodes have also occurred. MAOIs should not be given with or immediately following TCAs. Such combinations can produce seizures, sweating, coma, hyperexcitability, hyperthermia, tachycardia, tachypnea, headache, mydriasis, flushing, confusion, hypotension, disseminated intravascular coagulation, and death. At least 7-10 days should pass between MAOI discontinuation and TCA institution. Oral contraceptives inhibit the hepatic _meta_bolism of TCAs and may increase their plasma levels. Phenothiazines may increase serum TCA levels by inhibiting hepatic _meta_bolism. Smoking may increase the _meta_bolic biotransformation of TCAs. Pregnancy C - Safety for use during pregnancy has not been established.   Precautions Perform _base_line and periodic leukocyte and differential counts and LFTs. Discontinue therapy if neutropenia is evident. Prior to initiating large doses of TCAs and at appropriate intervals thereafter, monitor ECG. Monitor patients with cardiovascular disease. Elderly patients and patients with cardiac disease or a history of cardiac disease can develop cardiac abnormalities with TCAs. TCAs may increase the hazards of electroconvulsive therapy. FOLLOW-UP Further Inpatient Care: Inpatient care is not indicated, but many patients with chronic HVS are admitted because their symptomatology resembles many serious organic problems and because a simple way to confirm the diagnosis in the ED is not available. Further Outpatient Care: Patients should be referred to a consultant psychiatrist, psychologist, or family physician with expertise and interest in managing HVS. Some physiotherapists and respiratory therapists have extensive experience in retraining patients in proper breathing techniques and should be consulted (if available). In/Out Patient Meds: Several medications, including benzodiazepines, tricyclic antidepressants, and beta-blockers, are effective in reducing the frequency and the severity of hyperventilation; however, these agents require prolonged use and are best managed by a consultant on an ongoing outpatient basis, rather than sporadic pre_script_ions following an ED visit. Complications: Complications are related mainly to invasive procedures and investigations (eg, angiography) or to symptoms produced indirectly by hyperventilation (eg, injuries sustained in a fall during a syncopal episode due to hyperventilation). Prognosis: Patients with chronic HVS experience multiple exacerbations throughout their lives. Children who experience acute hyperventilation often will continue this pattern into adulthood. Many patients have associated disorders (eg, agoraphobia) that may predominate the clinical picture. Management of these underlying disorders will affect the course of hyperventilation. Patients who are treated with breathing retraining, stress reduction therapy, and various medications (eg, beta blockers, benzodiazepines, tricyclics) experience significant reductions in the frequency and the severity of exacerbations. Patient Education: Patients should have the underlying pathophysiology explained in layman's terms and be instructed in the technique of deflating the upper chest followed by controlled diaphragmatic breathing. MISCELLANEOUS Medical/Legal Pitfalls: Hyperventilation can be a symptom of serious underlying pathology, including pulmonary embolism, asthma and other respiratory disorders. Particular care must be exercised when considering a diagnosis of HVS in an elderly person or in those with existent co-morbid disease. TEST QUESTIONS CME Question 1: Which of the following is most accurate with regard to acute hyperventilation syndrome? A: Characteristic ABG findings of respiratory alkalosis are essential to make the diagnosis. B: Having the patient rebreathe into a paper bag is a safe and effective method of relieving symptoms. C: Hypocalcemia produced by hyperventilation commonly results in torsades des pointes. D: It is less common than chronic hyperventilation syndrome. E: Unilateral paresthesias do not occur with hyperventilation and suggest a focal CNS lesion. The correct answer is D: Acute hyperventilation syndrome is estimated to account for only 1% of the cases. The diagnosis is clinical, and an ABG is not required to make the diagnosis, although it may be helpful in confusing cases. Hypocalcemia occurs, but torsades has not been reported in association with acute hyperventilation syndrome. Unilateral paresthesias occur in up to 10% of cases of HVS and are usually left-sided. CME Question 2: All of the following statements are correct EXCEPT: A: Benzodiazepines are effective in controlling symptoms of HVS, and they should be prescribed routinely. B: It is associated with obsessive-compulsive disorder, agoraphobia, and panic disorder. C: Once established, respiratory alkalosis can be maintained with occasional sighing respirations. D: Patients with chronic hyperventilation syndrome have abnormal mechanics of breathing, using the upper thorax rather than the diaphragm. E: Tricyclic antidepressants are effective in decreasing the frequency and the severity of episodes of hyperventilation. The correct answer is A: Benzodiazepines may be necessary in a minority of severe cases but are not prescribed routinely in the ED. Pearl Question 1 (T/F): Hypoxia is the most serious entities to be considered in the differential diagnosis of hyperventilation? The correct answer is True: 1. Hypoxia: asthma/COPD, CHF, acute MI, pulmonary embolus, pneumothorax, pleural effusion, and pneumoniaOthers are:2. _meta_bolic acidosis: (MUDPILES) especially DKA, salicylate toxicity, alcohols, and shock Pearl Question 2 (T/F): ST elevation or depression may be associated with acute hyperventilation syndrome. The correct answer is True: Others are T wave inversion and prolonged QT interval. Pearl Question 3 (T/F): Myocardial or cerebral ischemia (shift of HbO2 dissociation curve, vasospasm may be provoked by hyperventilation? The correct answer is True: Others are seizure and syncope. Pearl Question 4 (T/F): The typical ABG findings in patients with chronic hyperventilation syndrome are chronic compensated respiratory alkalosis. The correct answer is True: Chronic compensated respiratory alkalosis: normal or minimally elevated pH, low pCO2, and low HCO3 BIBLIOGRAPHY Blau JN, Wiles CM, Solomon FS: Unilateral somatic symptoms due to hyperventilation. 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