HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Schnader, J. Articles by Scharf, S. M. Search for Related Content PubMed PubMed Citation Articles by Schnader, J. Articles by Scharf, S. M.

Clinical Conference On Management Dilemmas^*

Obstructive Sleep Apnea And Respiratory Failure

^* From the Department of Medicine (Drs. Schnader and Reddy), Wright State University School of Medicine, Dayton VA Medical Center, Dayton, OH; Department of Medicine (Dr. Heffner), Medical University of South Carolina, Charleston, SC; and the Pulmonary and Critical Care Division (Scharf), Long Island Jewish Medical Center, the Long Island Campus for the Albert Einstein College of Medicine, Long Island, NY.

Correspondence to: Dr. Jeff Schnader, MD, CM, FCCP, Chief, Division of Pulmonary & Critical Care Medicine, Wright State University School of Medicine, Dayton VA Medical Center (111), 4100 West Third Street, Dayton, OH 45428; e-mail: jeff.schnader{at}med.va.gov

Key Words: adrenal cortical hyperplasia • cardiopulmonary interactions • Cushing’s syndrome • Interventricular interactions • obstructive sleep apnea • respiratory failure • sudden death

	Introduction

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

 
Pulmonary clinicians are often faced with management problems for which there are no answers at hand, either because there is no literature that definitely gives answers, because there are conflicting data in the literature, or because the circumstances surrounding the clinical cases are unusual enough to prevent the application of existing scientific knowledge. When faced with these problems, clinicians are forced to make decisions based on logical extensions of their scientific knowledge into uncharted clinical waters. They are forced to make judgments based on the conviction of their speculations and on prior experiences.

This case conference addresses difficult management problems without singularly correct decisions; its object is not necessarily to seek consensus. Defining the exact issues, formulating rationales for decision making, and committing to the decisions themselves are all equally important in this presentation. This is a real case in which the decisions were made by the "Treating Pulmonologist" or "Treating Intensivist" without input from the other participants. The "Responses of Pulmonary Experts" are given only with the knowledge of the case presentation up to the moment at which each expert gives his or her decision and without the knowledge of any of the other opinions rendered. The last "Commentary" opinions are given only with the knowledge of the "Case Presentation" and the remarks of the "Treating Pulmonologist (or Intensivist)" but without the knowledge of any of the other opinions rendered. Although the "Commentary" opinions are the last in the sequence of this presentation, they are not necessarily offered as definitive solutions to the problems posed in the case. The reader is the ultimate arbiter in this presentation of decision-making alternatives.

	Case Presentation

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

 
A 76-year-old African American was admitted to hospital with increasing dyspnea for 2 weeks. He had had a myocardial infarction 20 years earlier, diabetes mellitus for 9 years, hypertension for 12 years, WPW syndrome with procainamide therapy for 4 years, chronic renal failure with nephrotic syndrome and a baseline creatinine of 2.5 mg/dL, obesity (weight chronically > 300 lbs at height 5 feet 9 inches), congestive heart failure (thought due to diastolic dysfunction with a MUGA scan 1 year earlier revealing right and left ventricular ejection fractions of 49 and 74%, respectively), and obstructive sleep apnea (OSA) on continuous positive airway pressure (CPAP) of 14 cm H₂O (sleep study results are shown in Tables 1 and 2 ). The presenting dyspnea was progressive, relieved with rest, and associated with progressive edema of both legs. The patient had trouble using his CPAP mask saying it made him more dyspneic. There were no fevers, chills, or recent weight gain. He had cough with yellow sputum for 6 months. He had smoked two packs per day for 40 years but had quit 3 years earlier. He had drunk alcohol heavily for many years but had quit 15 years earlier. Baseline pulmonary function testing 2.5 years earlier revealed that the FEV₁/FVC was 79% (same as predicted); FEV₁, 1.70 L (62%); FVC, 2.17 L (63%). The slow vital capacity, total lung capacity, residual volume and carbon monoxide diffusing capacity of the lung (DLCO) were 78, 82, 89, and 52% of predicted, respectively. Medications at admission included procainamide, amlodipine, furosemide, captopril, aspirin, and neutral protamine hagedorn insulin.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 1.. Chest radiograph on hospital admission revealing cardiomegaly.

On hospital day 10, the patient would not leave his CPAP mask in place. By hospital day 12, he was again obtunded, difficult to arouse, and unable to follow simple commands. It took four hospital employees to get him into bed. He complained of "not feeling good." Heart rate was 95 beats/min; respiratory rate 28 breaths/min; BP, 108/51 mm Hg. Arterial blood gas analysis on FIO₂ of 0.28 were pH of 7.32; PCO₂, 59 mm Hg; PO₂, 49 mm Hg; HCO₃, 32 mmol/L; O₂ saturation, 80%. He was diuresed over the next 40 h with measured fluid intake and output of 1891 mL and 4150 mL, respectively. A repeat arterial blood gas analysis on FIO₂ of 0.32 revealed pH 7.28; PCO₂, 66 mm Hg; PO₂, 49 mm Hg; HCO₃, 33 mmol/L; O₂ saturation, 77%; BP was 160/66 mm Hg; heart rate 91 beats/min. His BUN and creatinine had increased to 93 mg/dL and 4.1 mg/dL, respectively. A nephrologist felt that procainamide-induced nephritis was unlikely and that prerenal azotemia superimposed on deteriorating diabetic nephropathy was present. Antinuclear antibody was positive at 1:320 (homogenous pattern), but antidouble stranded DNA was negative. As he was continually obtunded and unarousable, he was intubated and mechanically ventilated on hospital day 13. Chest radiograph showed pulmonary congestion (see Fig. 2 ). Initially his mental status improved, but later he became obtunded, hypoxemic, and ventilator-dependent. He was wheezing on the ventilator, and it was unclear if the wheezing was from the upper airway, the lung, or both. Although management had not changed dramatically, by day 18 he was again somewhat better and exubated himself. Because of the wheezing, he was placed on solumedrol 30 mg IV every 12 hours. Results of arterial blood gas analysis on a CPAP of 12 cmH₂O, with oxygen flowing at 8 L/min via nasal mask, were pH 7.34; PCO₂, 50 mm Hg; PO₂, 62 mm Hg; HCO₃, 28 mmol/L; O₂ saturation, 90%. He became lethargic again and was noted to have upper airway obstruction, but he remained off the ventilator. On hospital day 20, arterial blood gas analysis on FIO₂ 0.40 was pH 7.33; PCO₂, 60 mm Hg; PO₂, 75 mm Hg; O₂ saturation, 93.4%.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 2.. Chest radiograph on hospital day 13 showing a rotated film with pulmonary vascular congestion and edema with cardiomegaly and possible pleural effusion. An endotracheal tube is in place.

	Response of the Pulmonary Expert

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

Patients with Pickwickian syndrome are at risk for developing acute exacerbations of ventilatory failure, which present as a critical care syndrome with altered mental status, acute respiratory failure, and cor pulmonale.⁴ I suspect that this patient presented with increasing dyspnea and daytime hypersomnolence due to worsening OHS, which progressed to acute respiratory failure during his hospitalization. I agree with the initiation of CPAP therapy, which can promote awake eucapnia in many patients with OHS. Up until day 10, CPAP was effective in improving his gas exchange and reversing his obtundation. Unfortunately, some patients with OHS cannot tolerate CPAP; this patient frequently removed his mask, which was associated with worsening mental status and acute respiratory failure on hospital day 4.

In the first several days of his hospitalization, I would have considered that this patient had a life-threatening condition that required urgent relief of his upper airway obstruction. Because CPAP therapy failed in both the in-patient and out-patient settings, I would have performed a tracheotomy. I would not need a repeat sleep study to demonstrate the need for a tracheotomy considering the results of his previous study and the seriousness of his subsequent clinical course. Because of the technical challenges presented by the patient’s cervical adiposity, I would consult a surgeon with experience in performing tracheotomies for patients with OHS, who have increased risk of infection and appliance instability.⁵

In the absence of a tracheotomy, I am concerned about the sole reliance on respiratory stimulants and diuretics to reverse this patient’s OHS-related critical care syndrome, especially considering his underlying chronic azotemia and the need to maintain adequate renal perfusion. Acetazolamide, which was started on transfer to the ICU, is of unproven benefit as a respiratory stimulant in OHS, and it could combine with his acute hypercapnia to worsen acidemia. Few data support the use of theophylline as a respiratory stimulant in this clinical setting.

Although diuretic therapy may assist in managing the edematous manifestations of cor pulmonale in hemodynamically stable patients with OHS, I would not pursue an aggressive diuresis to improve this patient’s course in the absence of a tracheotomy. He has left ventricular diastolic dysfunction as shown by his MUGA study. Patients with diastolic dysfunction have small, poorly compliant left ventricular chambers that do not tolerate excessive preload reduction.⁶ I assume that he has ischemic heart disease on the basis of his previous myocardial infarction and on the observation that myocardial ischemia is a frequent accompaniment of diastolic dysfunction. Consequently, combined diuretic therapy with acetazolamide, metolazone, and furosemide, as was ordered on this patient’s transfer to the ICU, may decrease ventricular filling, produce a subaortic outflow obstruction, promote myocardial ischemia, and aggravate his hemodynamic and renal status.⁷ Over–diuresis of patients with cor pulmonale may limit right ventricular function and further decrease left ventricular preload, which can have catastrophic consequences for patients with left ventricular diastolic dysfunction. Decreased cerebral perfusion due to decreased cardiac output can produce confusion and obtundation, which may explain this patient’s lethargy on day 20 despite the return of his arterial blood gas results to baseline values.

Because of the patient’s WPW syndrome, the clinicians were limited to using ß-blockers or calcium channel blockers for managing this patient’s left ventricular failure due to diastolic dysfunction. Restarting the patient’s angiotensin converting enzyme inhibitor would have been warranted when his hypertension returned after the tenth hospital stay, before he became volume depleted. The use of angiotensin converting enzyme inhibitors in diastolic dysfunction is controversial, but careful titration may result in improved compliance of the left ventricle and enhanced myocardial performance.

What features of this patient’s clinical course warrant additional consideration to be certain we are not missing a new problem that might be obscured by his underlying OHS and diastolic dysfunction? His lethargy on day 20 after correction of acidosis is explainable by a stroke or myxedema, but cerebral hypoperfusion due to overdiuresis in the setting of diastolic dysfunction appears to be a sufficient explanation. Positive pressure ventilation in the setting of over-diuresis may have decreased ventricular preload and further impaired cerebral and renal perfusion. The patient may have developed upper airway injury as a consequence of intubation, which could explain his wheezing after extubation. Although I would attribute his wheezing to congestive heart failure and a low functional residual capacity due to obtundation and obesity, it seems prudent to inspect his larynx during performance of a tracheotomy. The patient’s unusual-appearing chest radiograph was interpreted as showing cardiomegaly. No results of a cardiac echo are provided, however, to confirm enlargement of the cardiac chambers or thickening of cardiac walls to a sufficient degree to explain the enlarged right cardiac silhouette. I would like to see additional radiographs to exclude a mediastinal mass, intrathoracic stomach, or megaesophagus, which can produce upper airway obstruction and wheezing. Finally, this patient is at high risk for pulmonary thromboembolic events, which represent a common and lethal (30% in-hospital mortality) complication of OHS-related critical care syndrome.

If I had been consulted on hospital day 20, I would have seen a lethargic but hemodynamically stable patient with worsening azotemia. I would not delay the tracheotomy any longer. I would have supported his airway with intubation in preparation for the tracheotomy, discontinued aggressive diuresis, and attempted to achieve normal blood volume to improve his renal function.

	Comments by the Treating Pulmonologist

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

 
Dr. Jeff Schnader, Dayton, OH
Based on prior testing and in view of his altered mental status, worsening disease correlating with CPAP intolerance, severe hypersomnolence, witnessed upper airway obstructions, and pedal edema, severe OSA was strongly suspected. The upper airway obstruction appeared responsible for both his respiratory failure and biventricular heart failure. Such severe, repetitive obstruction inevitably results in significant alveolar hypoventilation and hypoxia, which then leads to hypoxic pulmonary vasoconstriction.⁸ The implication is that chronic restrictive pulmonary hypertensive vascular remodeling results with medial hypertrophy akin to chronic mountain sickness.^{8 9 10 11} Clinically, this patient shared the altered mental status, hypersomnolence, and heart failure also seen in chronic mountain sickness patients. Polycythemia may occur in both conditions and, through a viscosity effect, may further increase the pulmonary hypertension. However, polycythemia did not occur in this patient.

The right ventricular failure and increased right ventricular end diastolic volume and pressure resulting from the increased afterload (pulmonary hypertension due to decreased pulmonary vascular cross-sectional area) is not unexpected, but left ventricular failure and documented elevation in pulmonary capillary pressures may also result.⁸ There are several potential reasons that could explain elevated pulmonary capillary pressures. These include increased myocardial stiffness from hypoxia or left ventricular hypertrophy and a ventricular interdependence effect in which either the ballooning of the right ventricle or the prolongation of right ventricular systole increases the stiffness and decreases the filling of the left ventricle. Other reasons include hypoxic constriction of pulmonary veins and increased left ventricular afterload from excessively negative intrathoracic pressure during upper airway obstructive events.^{8 12 13}

Initial treatment should include adequate oxygen delivery to alveoli in order to reverse pulmonary vasoconstriction and remodeling. This involves both oxygen administration and enough CPAP to keep the upper airway open. If the CPAP fails and the patient is acutely and severely ill, like this one, I generally move toward a method of "bypassing" the upper airway to assure adequate alveolar oxygen delivery, ie, intubation, tracheostomy or intubation followed by tracheostomy. Physiologically, with respect to the upper airway or hemodynamics, there should be no difference between endotracheal intubation or tracheostomy. Mechanical ventilation, considered a separate entity from intubation or tracheostomy, may become necessary when hypoventilation occurs. Once the upper airway obstruction is relieved and the patient is oxygenated and ventilated, the afterloads of both the right and left ventricles will be reduced, myocardial stiffness will be ameliorated, and interventricular interactions will be normalized to some extent. Left ventricular filling pressures will decrease, and cardiac output will increase and promote diuresis, which is facilitated by using diuretics (generally furosemide). Often these patients suffer from a gas exchange abnormality due to some degree of pulmonary edema, either overt or mild, and it helps to reduce right ventricular volume overload, which impedes left ventricular performance. Acetazolamide is useful as a diuretic and has the extra effect of stimulating respiration in patients with respiratory failure (as long as they are not acidemic). Theophylline is another useful respiratory stimulant.

This patient had a very stormy course. Initially, his lung fields were clear without evidence of left ventricular failure (see Fig. 1 ), and after transfer to the medical ICU on day 4, medical therapy with CPAP but without intubation resulted in reversal of his obtundation and improvement in his edema. This strategy seemed to work, and improvement persisted for four days. Thereafter, he would not leave the CPAP in place, which is not uncommon for sleep apnea patients who are improving, and this resulted in his relapse into obtundation. It was at this point that the decision to intubate was unavoidable. He was a hypoventilator and required mechanical ventilation, but even the ventilator did not seem to reverse his problems. The wheezing on the ventilator, which at times seemed to be from the upper airway, brought up the specter of a possible intratracheal obstruction of some kind, eg, a carcinoma, a fungal or other infection, etc. Thus, I elected to have the patient undergo tracheostomy and then bronchoscopy to examine the full extent of the airway, including that stretch of upper airway hidden by the current indwelling endotracheal tube.

Hospital Course
The patient underwent tracheostomy on hospital day 21. Bronchoscopy through the stoma revealed normal tracheal mucosa but an overly lengthy posterior membrane billowing into the trachea and resulting in the total obstruction of the tracheal lumen whenever the patient coughed or exhaled. Initially, the patient was managed with FIO₂ of 0.30 via tracheostomy collar while awake and CPAP of 14 cm H₂O while asleep. Over the next week, his mental status improved greatly, and his personality was found to be demanding, argumentative, and noncompliant. BUN and creatinine levels fell to 52 mg/dL and 1.9 mg/dL, respectively. But soon after, he developed respiratory acidosis and respiratory failure and required mechanical ventilation with an intermittent mechanical ventilation of 4. The chest radiograph is seen in Figure 3 . With time he gradually began to tolerate lowering of the IMV. Eventually he was able to tolerate the tracheostomy collar during the day, with IMV at night.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 3.. Chest radiograph on hospital day 25 with medial lower lung field alveolar shadows suggesting mild pulmonary edema. The patient has an indwelling tracheostomy tube.

The patient did not respond to prolonged resuscitative efforts and was pronounced dead. Autopsy showed cardiomegaly with biventricular hypertrophy, significant multifocal coronary artery disease with a prior myocardial infarction involving the interventricular septum and posterior wall of the left ventricle. Nephrosclerosis, pulmonary emphysema, and severe atherosclerosis of the aorta were seen. There was diffuse congestion and moderate edema of the lungs with intra-alveolar red blood cells. Pituitary and thyroid glands appeared normal. Bilateral adrenal hypertrophy was seen grossly, and cortical hyperplasia was noted microscopically. Blood that had been sent for antihistone antibodies came back positive.

	Commentary

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

 
Dr. Steven M. Scharf, New Hyde Park, NY
This is a case of a patient with severe OSA syndrome who developed refractory congestive heart failure and died. Although hemodynamic data were not presented, the clinical course and chest radiograph was consistent with biventricular failure. In addition, he had coronary artery disease and a myocardial infarction of indeterminate age.

OSA is a well characterized disorder in which patients develop airway obstruction at the level of the velopharynx and/or oropharynx at night. As inspiratory efforts continue, there are increasingly negative swings in intrathoracic pressure and progressive hypoxemia. Apneas are terminated by arousal. Apnea termination and airway opening is associated with loud snorting or gasping noises, frequently described as snoring so loud that it may be heard in another room. Following a few breaths the apnea-interapnea cycle repeats itself, often hundreds of times a night. Because of severe sleep fragmentation, patients are often excessively somnolent during the day. Treatment is directed to maintaining airway patency at night. Weight loss in obese patients (approximately 50% of sleep apnea patients) may bring about improvement. The most common treatment consists of administering CPAP nasally, at a level sufficient to hold the airway open and eliminate or substantially reduce the number of apneas. Because long-term compliance with CPAP treatment is often poor—only 40 to 60% of patients treated with CPAP continue to use it 2 years later—other modes of treatment have been devised. Mild to moderate cases may be treated with mandibular repositioning or dental orthotic device. Various forms of tongue and jaw advancement have been examined to open the oropharynx. Radiofrequency ablation of the soft palate and/or tongue is currently undergoing evaluation as treatment. Tracheostomy, the original treatment for sleep apnea, is currently performed only in selected cases in which treatment is considered emergent and in which nasal CPAP either fails or cannot be complied with, as was the case here.

Sleep apnea is extremely prevalent, especially in males, and it increases with increasing age.¹⁴ The association between cardiovascular disease and OSA has been well established.¹⁵ For example, some 50% of patients with sleep apnea have hypertension, and between 20 and 50% of patients with "essential" hypertension also have sleep apnea. In many of these patients obesity, a major risk factor for sleep apnea, has been identified as a confounding factor. However, it is likely that a major mechanism by which obesity leads to cardiovascular morbidity is in fact the associated sleep apnea. In one study, an apnea index (number of apneas per hour of sleep) of >5/h was associated with a greater odds for risk of myocardial infarction than many of the classic risk factors such as obesity, hypertension, or hypercholesterolemia.¹⁶

Obstruction of the upper airway during sleep results in striking neural and circulatory changes that persist even into the daytime. Among the important changes of sleep apnea that influence cardiovascular function are periodic hypoxemia, recurrent large negative inspiratory swings in intrathoracic pressure, and arousals. Periodic hypoxemia, combined with recurrent arousals, leads to periodic sympathetic stimulation, which is likely the primary mechanism for elevation of BP. Increased sympathetic tone in sleep apnea has been well documented by measurements of muscle sympathetic nerve activity and urinary catecholamines. Surges of sympathetic nerve activity (associated with apneas) are well documented, and treatment of sleep apnea is associated with decreased muscle sympathetic nerve activity.¹⁷ The associated systemic hypertension can lead to left ventricular hypertrophy and is associated with an increased incidence of other complications such as stroke and myocardial infarction. Finally, in the presence of coronary artery disease, experimental studies have demonstrated that sleep apnea with associated hypoxemia can result in the rapid development of cardiac ischemia, probably exacerbating congestive failure and increasing the risk for infarction.¹⁵ Sleep apnea may be associated with other medical conditions such as obesity, hypothyroidism, familial dysautonomia, diabetes, and connective tissue disorders such as Marfan’s syndrome. Approximately 15% of patients with COPD also suffer from sleep apnea. While this is expected on the basis of the known prevalence of sleep apnea in older adults, the simultaneous occurrence of these two disorders can have particulary disastrous consequences for nocturnal oxygenation.

The large negative swings in intrathoracic pressure associated with apneas can also have adverse consequences. Sustained decreases in intrathoracic pressure can increase the afterload applied to the left ventricle.¹⁸ This could contribute to both systolic and diastolic dysfunction. However, recent experimental studies suggest that the neural sympathetic responses are more important contributors to increased left ventricular afterload with sleep apnea than decreased intrathoracic pressure.¹⁹ Finally, treatment of sleep apnea in patients with congestive heart failure with CPAP has been demonstrated to result in improved left ventricular function and resolution of symptoms of congestive failure.²⁰

Sleep apnea is known to be associated with cor pulmonale in only approximately 5% of patients. One possible mechanism is that recurrent hypoxemia can lead to pulmonary vasoconstriction and pulmonary vascular remodeling. However, it has been observed that waking cor pulmonale is observed primarily in patients with daytime hypoxemia as well as sleep apnea.²¹ Another possibility is that with the large negative swings in intrathoracic pressure associated with apneas there are large increases in venous return, which can themselves be associated with flow overload of the right ventricle,¹⁵ leading to hypertrophy and/or dilation of that cardiac chamber. Leftward shift of the interventricular septum could stiffen the left ventricle and contribute to increased left ventricular filling pressure.

Given the above, it is not surprising that this patient with a predisposition to cardiomyopathy based on diabetes, hypertension, and renal disease should, in the presence of sleep apnea, develop congestive heart failure. Although difficult to prove, it is not unlikely that, due to the combination of sleep apnea and coronary disease, this patient had profound ischemia while asleep. Treatment with afterload reduction and diurectics is usually undertaken along with treatment of the sleep apnea. It is ideal to study patients in the sleep lab to titrate CPAP, as was done previously in this patient. Acutely ill patients cannot be studied in the sleep lab, and treatment may need to be instituted empirically before formal studies can be undertaken. We usually begin empiric treatment with CPAP at a pressures of 7.5 to 10 cm H₂O. By monitoring and recording O₂ saturation at night, CPAP can often be empirically titrated; however, a formal sleep study should be done as soon as clinically feasible. Although treatment with CPAP may be lifesaving, many patients do not tolerate CPAP well, as was the case in this patient. In some cases CPAP training can improve compliance. Our policy is generally to go to tracheostomy rapidly in patients with heart failure who cannot tolerate CPAP well. In the outpatient setting, patients sleep with a cuffless tracheostomy tube open at night, with or without oxygen as needed, and they cap the tube during the day. However, this is not a step to be taken lightly, as was shown in this case.

Finally, although there was evidence of obstruction in the trachea due to the posterior membranous sheath, it is likely that this did not play much of a role. According to the bronchoscopic description, airway closure occurred during expiration, suggesting that the site of obstruction was intrathoracic. This is commonly seen in patients with emphysema and is not usually associated with any clinical consequences, and certainly not with the sleep apnea syndrome where obstruction of the upper airway occurs during inspiration. With respect to the adrenal findings in this case, I have not personally seen a case of Cushing’s syndrome associated with sleep apnea.

	Footnotes

Received for publication August 6, 1999. Accepted for publication August 24, 1999.

	References

TOP Introduction Case Presentation Response of the Pulmonary... Comments by the Treating... Commentary References

 

1. Brown, LK (1998) A 23-year-old obese man with cardiopulmonary failure. Sahn, SA Heffner, JE eds. Critical Care Pearls ,131-133 Hanley & Belfus Philadelphia.
2. Juan, G, Calverly, P, Talamo, C, et al (1984) Effects of carbon dioxide on diaphragmatic function in human beings. N Engl J Med 310,874-879[Abstract]
3. Schnader, J, Juan, G, Howell, S, et al (1985) Arterial CO₂ partial pressure affects diaphragmatic function. J Appl Physiol 58,823-829[Abstract/Free Full Text]
4. Fletcher, E (1991) "Near miss" death in obstructive sleep apnea: a critical care syndrome. Crit Care Med 19,1158-1164[ISI][Medline]
5. Conway, W, Victor, L, Magilligan, D, et al (1981) Adverse effects of tracheostomy for sleep apnea. JAMA 246,347-350[Abstract]
6. Grossman, W (1991) Diastolic dysfunction in congestive heart failure. N Engl J Med 325–328,1557
7. Gaasch, WH (1994) Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 271,1276-1280[Abstract]
8. Schnader, J (1996) Increase of pulmonary artery occlusion pressure during upper airway obstruction in sleep apnea. Crit Care Med 24,354-358[Medline]
9. Monge, MC (1928) La enfermedad de los Andes, sindromes eritremicos. An Fac Med Lima 11,314
10. Grover, RF (1990) Familial pulmonary hypertension. Fishman, AP eds. The pulmonary circulation: normal and abnormal ,283-299 University of Pennsylvania Press Philadelphia, PA.
11. Newman, JH, Loyd, JE (1990) Familial pulmonary hypertension. Fishman, AP eds. The pulmonary circulation: normal and abnormal ,301-313 University of Pennsylvania Press Philadelphia.
12. Gomez, A, Mink, S (1992) Interaction between effects of hypoxia and hypercapnia on altering left ventricular relaxation and chamber stiffness in dogs. Am Rev Respir Dis 146,313-320[Medline]
13. Brower, RG (1992) Role of pulmonary hypertension in high-altitude pulmonary edema. Weir, EK Archer, SL Reeves, JT eds. The diagnosis and treatment of pulmonary hypertension ,241-255 Futura Publishing Mount Kisco, NY.
14. Young, T, Palta, M, Dempsey, J, et al (1993) The occurrence of sleep disordered breathing among middle aged adults. N Engl J Med 328,1230-1235[Abstract/Free Full Text]
15. Podszus, TE, Greenberg, H, Scharf, SM (1993) Influence of sleep state and sleep-disordered breathing on cardiovascular function. Sullivan, CE Saunders, NA eds. Sleep and breathing II ,257-310 Marcel Dekker New York, NY.
16. Hung, J, Whitford, EG, Parsons, RW, et al (1990) Association of sleep apnea with myocardial infarction. Lancet 336,261-264[CrossRef][ISI][Medline]
17. Waravdeker, N, Sinoway, L, Zwillich, C, et al (1996) Influence of treatment on muscle sympathetic nerve activity in sleep apnea. Am J Respir Crit Care Med 153,1333-1338[Abstract]
18. Scharf, SM, Brown, R, Tow, DE, et al (1979) Cardiac effects of increased lung volume and decreased pleural pressure in man. J Appl Physiol 47,257-262[Abstract/Free Full Text]
19. Chen, L, Scharf, SM (1997) Comparative hemodynamic effects of periodic obstructive and simulated central apneas in sedated pigs. J Appl Physiol 83,485-494[Abstract/Free Full Text]
20. Malone, S, Liu, P, Holloway, R, et al (1991) Obstructive sleep apnea in patients with dilated cardiomyopathy: effects of continuous positive airway pressure. Lancet 338,1480-1484[CrossRef][ISI][Medline]
21. Bradley, TD, Rutherford, R, Grossman, RF, et al (1985) Role of daytime hypoxemia in the pathogenesis of right heart failure in the obstructive sleep apnea syndrome. Am Rev Respir Dis 131,835-839[ISI][Medline]

This article has been cited by other articles:

				D Schlosshan and M W Elliott Sleep * 3: Clinical presentation and diagnosis of the obstructive sleep apnoea hypopnoea syndrome Thorax, April 1, 2004; 59(4): 347 - 352. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Schnader, J. Articles by Scharf, S. M. Search for Related Content PubMed PubMed Citation Articles by Schnader, J. Articles by Scharf, S. M.