Platypnea-orthodeoxia: report of two cases and review of the literature.

Abstract: We describe two unusual cases of platypnea. The first patient had chronic obstructive pulmonary disease, but platypnea did not respond to chronic obstructive pulmonary disease therapy. He was found to have multiple pulmonary emboli, and symptoms rapidly improved on anticoagulation therapy. The second patient had Parkinson disease and developed severe platypnea, an association that has not been previously described. She had significant postural hypotension and responded to therapy with fludrocortisone.

Key Words: orthodeoxia, Parkinson disease, platypnea, pulmonary embolism

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The term dyspnea implies an unpleasant sensation of shortness of breath that is out of proportion to the ventilatory needs expected for a given level of work. Orthopnea refers to dyspnea in the supine position that is relieved by assuming an upright posture and is typically seen in left ventricular failure. Trepopnea is dyspnea that occurs when the patient is in the right or left lateral decubitus position. Dyspnea is commonly seen in association with the diseases of pulmonary and cardiovascular systems. Dyspnea in the upright position that is relieved by resuming the supine posture is called platypnea, from platys, meaning recumbent, and pnoe, meaning breath. It may be associated with a decrease in arterial oxygen saturation when the patient changes from the supine to the upright position, called orthodeoxia, from orthos, meaning upright, and deoxia, meaning desaturation. The condition was first described by Altman and Robin in 1969 (1) and since then has been reported in patients with right-to-left intracardiac shunts, (2) intrapulmonary shunts, (3) liver diseases, (4) and after pulmonary resection. (5) We report two unusual cases of platypnea and a review of the literature on this topic.

Discussion

Platypnea-orthodeoxia is a rare syndrome that is caused by a diverse set of cardiac, pulmonary, and hepatic diseases. The predominant symptom, dyspnea induced by upright posture, can be debilitating and difficult to discern without thorough evaluation of the patient's pattern of dyspnea. The cause revolves mostly around an intracardiac right-to-left shunt or intrapulmonary shunts. Table 1 shows the common clinical conditions associated with platypnea-orthodeoxia.

Cardiac Causes

The most common cause of platypnea-orthodeoxia is an intracardiac right-to-left shunt, often present as patent foramen ovale (PFO). (6-8) Less commonly, a true atrial septal defect or an atrial septal aneurysm may be present. (9-11) The condition becomes manifest as a consequence of anatomic changes after surgery (pneumonectomy (5,8,12,13) or lobectomy (8)) or development of kyphoscoliosis, (14) aortic aneurysm, (15,16) or aortic elongation. (17) Other conditions reported to produce platypnea in the presence of PFO include pericardial effusion, (18) constrictive pericarditis, (19,20) eosinophilic endomyocardial disease, (21) idiopathic hemidiaphragm paralysis, (22) compression of right heart by a large hydatid cyst of liver, (23) and blunt chest wall trauma. (24) Typically, patients have normal pulmonary artery pressures. (14, 15)

There is a high prevalence of PFO in the general population; autopsy studies indicate an incidence of 27%, with 6% having a large defect (0.6-1.0 cm). (25) Considering the high frequency of PFO and of pulmonary resection surgery carried out these days, it might be possible that this kind of complication is occurring more frequently but is not being recognized because of lack of awareness. This right-to-left shunt seems to occur more frequently after a right-sided pneumonectomy. There is a relatively symptom-free interval of a few months between the operation and the onset of symptoms. Clinical manifestations that ensue are posture dependent (becoming worse in the upright position, eg, platypnea) and volume dependent (the shunt becoming worse in a dehydrated state). (26) Cardiac catheterization studies reveal arterial desaturation in the upright position associated with increased right-to-left intracardiac shunting. The absence of a pressure gradient between the left and right atrium in either the supine or sitting position indicates that the orthodeoxia results from an increase in streaming of blood from the inferior vena cava to the left atrium caused by mechanical distortion of the interatrial septum. (27) Pneumonectomy can also affect atrial emptying by changing the relationship of right and left ventricular compliance, with the right ventricle becoming less compliant (ie, stiffer) than the left. (11) Cheng (28) proposed that an anatomic component in the form of interatrial communication must coexist with a functional component that produces deformity in the atrial septum and results in redirection of shunt flow on the assumption of an erect posture. Cyanosis without pulmonary arterial hypertension in the adult should alert the physician to the possibility of an unrecognized atrial right-to-left shunt.

Pulmonary Causes

Altman and Robin (1) described the first case of platypneaorthodeoxia and explained the mechanism in patients with chronic pulmonary disorders on the basis of changes in alveolar perfusion gradients. In the normal lung, blood flow is greater at the bases compared with the apical regions because of the effects of gravity, whereas the alveolar pressure remains constant throughout the lung. In various lung diseases, alveolar pressures become substantially elevated as a result of alterations of ventilatory mechanics (diffuse Zone I phenomenon). It is proposed that the assumption of an upright posture would increase this tendency, especially in the apical portions of the lung, because of a drop in pulmonary artery pressure, leading to pulmonary capillary compression. The combination of these two phenomena could lead to the cessation of blood flow, resulting in a respiratory dead space. The increased dead space causes dyspnea and hyperventilation, which augments air trapping, which further increases the alveolar pressure, initiating a vicious cycle.

Platypnea may occur in COPD patients who experience severe dyspnea and a decreased Pa[O.sub.2] in the sitting position, largely improved in the supine position. By using an isotopic method, it was shown that this phenomenon was the result of a deleterious effect of the sitting position on regional ventilation-perfusion matching. (29) It was suggested that hypoxic vascular pulmonary constriction may have been deficient in these patients, and a dramatically better ventilation-perfusion matching of the lung was achieved after treatment with almitrine bismesylate, a drug that could potentiate hypoxic pulmonary vasoconstrictive reflexes. Platypnea without orthodeoxia occurred in a COPD patient during subacute ileus, which rapidly resolved after resolution of the ileus. Impaired abdominal muscle contraction in the upright position secondary to the ileus was thought to be responsible for the development of platypnea. (30)

The cause of platypnea and orthodeoxia in our first patient with COPD was found to be multiple pulmonary emboli in the absence of an intracardiac shunt. Symptoms did not respond to COPD therapy but improved rapidly with anticoagulation therapy. There has been one previous report of multiple pulmonary emboli causing platypnea after right hemicolectomy but in a patient with right-to-left interatrial shunt. When lung ventilation-perfusion scanning was performed in a postpneumonectomy patient suspected of having pulmonary embolism, it showed no evidence of pulmonary embolism, but did show a systemic uptake of the isotope, suggesting a right-to-left shunt that was confirmed by contrast echocardiography. (31)

Tumors of the upper airway (eg, laryngeal carcinoma) may produce platypnea because of positional compression or occlusion of airways or vascular structures. (32) Platypnea has been reported in a patient with postradiation bronchitis leading to severe bronchial stenosis that was transiently relieved, initially by dilation and later by stent placement. (33)

Platypnea-orthodeoxia may develop during an episode of adult respiratory distress syndrome in a previously healthy individual. It has been described in a patient with necrotizing pneumonia with numerous pneumatoceles. (34) The abnormalities improved spontaneously with improvement of the underlying parenchymal lung disease.

Platypnea-orthodeoxia was noted during the weaning of a patient with severe organophosphorus poisoning needing prolonged mechanical ventilation. Interestingly, the patient's orthodeoxia was alleviated on continuous positive airway pressure treatment. (35) The condition has also been described in association with cryptogenic fibrosing alveolitis. (36)

Hepatic Causes

It is estimated that 15 to 45% of patients with cirrhosis of the liver are hypoxemic without apparent lung or heart disease. (37) The hepatopulmonary syndrome (HPS) is a triad of liver disease, increased alveolar-arterial oxygen gradient, and intrapulmonary vascular dilatations. In a study of 138 Indian patients, HPS was present in 17.5% of patients with cirrhosis, 13.3% of patients with noncirrhotic portal fibrosis, and 10% with extrahepatic portal vein obstruction. (38) HPS may be a transient manifestation of acute hepatitis A in the absence of fulminant liver failure. (39) Rodriguez-Roisin et al (40) have developed a set of four diagnostic criteria for the hepatopulmonary syndrome:

1. Presence of chronic hepatic disease (alcoholic, postnecrotic, or primary biliary cirrhosis or active chronic hepatitis). Severe liver dysfunction may not be mandatory.

2. Absence of intrinsic cardiopulmonary disease, with normal chest radiograph or with nodular basal shadowing.

3. Pulmonary gas exchange abnormalities. An increased alveolar-arterial oxygen gradient ([greater than or equal to]20 mm Hg) with or without hypoxemia.

4. The extrapulmonary appearance of IV radiolabeled microspheres or a positive contrast-enhanced echocardiogram, suggesting intrapulmonary vascular abnormalities.

Although these four criteria appear straightforward, there may be other features that are not always present, namely:

1. Low transfer factor (diffusing capacity).

2. Shortness of breath, with or without platypnea and orthodeoxia.

3. Increased cardiac output and reduced pulmonary vascular pressures.

4. Small (or no) increase in pulmonary vascular resistance when the patient is breathing low oxygen mixtures.

The hypoxemia in HPS patients has several causes: diffuse shunts caused by precapillary and capillary intrapulmonary vascular dilatations, impaired hypoxic vasoconstriction, impaired matching of ventilation to perfusion, pleural effusions, and diaphragmatic dysfunction. (41) The presence of a hyperdynamic circulation and low pulmonary resistance results in the rapid transit of blood through the lungs and potentiates the transit of deoxygenated blood to the systemic circulation. Because of gravity, shifting of blood to the dilated precapillary beds of the lung bases results in an increased hypoxemic dyspnea when the patient is in the upright position.

Miscellaneous Causes

Our second case is unique and reports association of platypnea with Parkinson disease. Fox et al (42) reported a case of a middle-aged patient with profound orthostatic hypotension, diagnosed as a case of autonomic failure that showed marked improvement with fludrocortisone and a fluid challenge. The patient's symptoms were shown to be the result of an orthostatic increase in ventilation-perfusion mismatching and to be corrected with fluid challenge. Another case of platypnea had been described in a patient with diabetic autonomic neuropathy. (43)

Investigations

The diagnosis of platypnea requires a high degree of suspicion. It should be considered in the differential diagnosis of dyspnea and refractory hypoxemia. The initial assessment should consist of demonstration of platypnea followed by measurements of [O.sub.2] saturation and arterial blood gas analysis in the supine and upright positions. Orthostatic desaturation should prompt further investigations aimed at delineating cardiac, pulmonary, and hepatic causes. In the past, detection of a right-to-left shunt was performed by a 100% oxygen inhalation test, and right heart catheterization was needed for diagnosis and quantification of shunt. Nowadays, a definitive diagnosis can be readily established by echocardiography in conjunction with the use of contrast-enhanced echocardiography and postural maneuvers. (44) The shunt can be localized at the atrial level and directly visualized and semiquantitated. (7) Echocardiographic study may allow visualization of other cardiac abnormalities that could be present in conjunction with the atrial defect. (15) The most sensitive test for the noninvasive diagnosis of a right-to-left shunt is peripheral contrast tilt-table transesophageal echocardiography, (7,45) which should be performed with the patient both supine and as erect as possible. Rarely, a shunt may be seen only on Valsalva maneuvers. Mackenzie et al (46) reported a case in which IV metaraminol was successfully used to delineate an interatrial shunt not demonstrated by repeated transthoracic echocardiography.

If an intracardiac shunt cannot be detected, the possibility of true intrapulmonary shunts within the lung bases should be considered. (18) The presence of intrapulmonary vascular dilatations (eg, in HPS) can be confirmed using one of three imaging modalities: contrast-enhanced echocardiography, [.sup.99m]Tc-labeled macroaggregated albumin scanning, and pulmonary arteriography. (47) Contrast-enhanced echocardiography is the method of choice for demonstrating pulmonary vascular abnormalities. Perfusion scan with macroaggregated albumin labeled with [.sup.99m]Tc shows uptake over thyroid, kidneys, liver, and spleen, suggesting an abnormal passage through the pulmonary vascular bed. (48) Angiography is best reserved for patients with poor response to therapy and defines whether vascular dilatations are of the diffuse "spongy" type or, less commonly, discrete arteriovenous communications amenable to embolization.

Treatment

The treatment of platypnea-orthodeoxia syndrome depends on the cause. Definitive treatment of the underlying cause, when possible, leads to rapid improvement of symptoms. In some patients, the symptoms are related to loss of volume, and the administration of fluids can bring about symptomatic relief. (2,42)

The treatment of choice for an intracardiac shunt is surgical closure of the defect. (10,12,14) Surgical closure of an intracardiac shunt is also recommended in patients at risk of developing stroke caused by paradoxical embolism and in divers at risk of developing decompression sickness. (25) The closure of an intracardiac shunt can now be performed less invasively by transcatheter techniques. (28,49,50) Various devices have been used, including the transcatheter clamshell device, (51) Amplatzer device (Amplatzer septal occluder/ Amplatzer PFO occluder) (AGA Medical Corporation, Golden Valley, MN), (50) and transcatheter button device implantation for closure of the PFO/atrial septal defect. (49)

No medical treatment has demonstrated its efficacy in improving platypnea in HPS. Pharmacologic treatment with almitrine bismesylate, somatostatin analog, indomethacin, and treatment with plasmapheresis have been disappointing. (52) Standard therapy with spironolactone can worsen the condition, and there was no additional benefit of propranolol in the reduction of the shunt fraction. (41) The medical therapy consists of oxygen supplement and low-dose diuretics in patients with edema. Prolonged treatment with oral norfloxacin resolved the symptoms of HPS in a patient with hepatitis C cirrhosis who developed brain abscess caused by Streptococcus intermedius. (53) It was hypothesized that the patient's pulmonary vascular disease was attributable, in large part, to chronically elevated levels of nitric oxide (a potent vasodilator thought to be generated by endotoxin absorbed from the gut), and treatment with oral norfloxacin reduced endotoxemia and concomitant nitric oxide production.

Approximately 80% of patients with the hepatopulmonary syndrome eventually have improved oxygenation after liver transplantation, thereby making worsening hypoxemia the primary indication for transplantation in many instances. Nevertheless, severe hypoxemia carries a perioperative mortality of 30%, and reliable predictors of successful outcome after transplantation remain to be determined. (47) The placing of an intrahepatic portal systemic shunt can be proposed for patients waiting for transplant or patients not requiring liver transplant. (54) Coil embolotherapy was successful in a patient with large pulmonary arteriovenous shunts who underwent orthotopic liver transplantation for autoimmune hepatitis, but her symptoms failed to improve postoperatively. (55)

Treatment of the underlying pulmonary condition leads to improved ventilation-perfusion matching, with resolution of platypnea-orthodeoxia. In a patient with acute respiratory distress syndrome caused by an invasive fungal infection and a patent foramen ovale, it was noted that blood gas values improved dramatically as the patient was turned to the prone position. Doppler sonography with bubble study confirmed a massive right-to-left shunt in the supine position, which instantaneously decreased in the prone position. (56)

Conclusion

Platypnea is a rare syndrome that can occur in a variety of clinical settings. Right-to-left intracardiac or intrapulmonary shunts are usually present and can be demonstrated by contrast-enhanced echocardiography. Careful consideration of the cause in each particular case must be undertaken to provide the appropriate treatment for the given patient. The treatment of choice for intracardiac shunt is surgical closure. Definitive treatment of other underlying causes leads to rapid improvement of symptoms.

Middle age: when you begin to exchange your emotions for symptoms.
--Irvin Cobb

Table 1. Clinical states associated with the platypneaorthodeoxia
syndrome (a)

Intracardiac right-to-left shunts (patent foramen ovale or atrial
    septal defect)
  After pulmonary resection (eg, pneumonectomy, lobectomy)
  Associated cardiac abnormality (eg, aortic aneurysm, pericardial
    effusion)
  Associated skeletal deformity (kyphoscoliosis)
Intrapulmonary right-to-left shunts
  Hepatopulmonary syndrome
Pulmonary diseases
  Chronic obstructive pulmonary disease
  Pulmonary embolism
  Upper airway tumor
  Acute respiratory distress syndrome
Miscellaneous causes
  Autonomic neuropathy

(a) ARDS, acute respiratory distress syndrome.

RELATED ARTICLE: Case Reports

Patient 1

An 80-year-old man who was an ex-smoker was admitted with a 1-month history of increasing dyspnea unaccompanied by edema, chest pain, palpitation, cough, or sputum. He was known to have chronic obstructive pulmonary disease (COPD) and ischemic heart disease. The symptoms had worsened rapidly during the week before admission and did not respond to therapy aimed at treating COPD or left ventricular dysfunction. General and systemic examination was unremarkable except for generally reduced breath sounds on chest auscultation. Chest radiography showed hyperinflated lung fields indicative of emphysema. He had normal blood counts and routine blood chemistry. Arterial blood gases on supplemental oxygen (2 L/min) revealed a pH of 7.41, a PaC[O.sub.2] of 40 mm Hg, a Pa[O.sub.2] of 81 mm Hg, and an oxygen ([O.sub.2]) saturation of 97%. Spirometry revealed mild obstructive airway disease.

The patient was initially treated with a combination of bronchodilators, corticosteroids, antibiotics, diuretics, and nitrates. Observation over the next 24 hours revealed that attempts to sit the patient from the supine position resulted in tachycardia, tachypnea, severe dyspnea, and a >4% drop in [O.sub.2] saturation. The patient was unable to tolerate upright posture for more than few minutes. There was no significant postural drop in blood pressure. An echocardiogram did not reveal atrial septal defect or right-to-left shunt. Isotope lung perfusion scanning was performed and revealed multiple perfusion defects with a high probability of pulmonary emboli. The patient was treated with IV heparin with rapid improvement in symptoms. He was discharged a week later on oral anticoagulants. He remained well 6 months after discharge, able to walk unaided for 10 to 15 minutes.

Patient 2

A 60-year-old woman was recently diagnosed as having Parkinson disease on the basis of clinical findings of unsteady gait, increased rigidity, and diminished facial expressions. She complained of progressive dyspnea that was relieved by lying flat but aggravated by sitting or standing. Lately, she had been unable to stand or walk unaided. She had received amitriptyline 30 mg daily but no anti-Parkinson drug from her family physician. She was comfortable lying flat, with a pulse rate of 86 beats/min and a blood pressure of 130/80 mm Hg. On assuming an upright posture, there was 30-mm Hg drop in systolic pressure, and within a minute she became extremely distressed with dyspnea that resolved on lying flat. Blood tests including a full blood count, serum creatinine and electrolytes, thyroid function, and short synacthen tests were all within normal ranges. She was advised to use elastic stockings during the day and sleep in a propped-up position and prescribed fludrocortisone 0.2 mg daily. This resulted in improvement of postural hypotension and dyspnea and she was able to ambulate with minimal support.

RELATED ARTICLE: Key Points

* Platypnea-orthodeoxia is a less recognized syndrome that can occur in a variety of clinical settings.

* The underlying mechanism mostly involves a right-to-left intracardiac or intrapulmonary shunt.

* Definitive treatment of the underlying cause leads to rapid improvement of symptoms.

Accepted March 6, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9707-0657

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Syed Fayyaz Hussain, MBBS, FRCP(EDIN) and Sabeen Fatima Mekan, MBBS

From the Section of Pulmonary Medicine, The Aga Khan University Hospital, Karachi, Pakistan.

Reprint requests to Syed Fayyaz Hussain, FRCP(Edin), Section of Pulmonary Medicine, The Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan. Email: [e-mail] or [e-mail]