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Ann Thorac Surg 2001;72:272-274
© 2001 The Society of Thoracic Surgeons

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Case report

Nitric oxide for the treatment of postpneumonectomy pulmonary edema

Accepted for publication June 27, 2000.

Address reprint requests to Dr Goldstein, Department of Cardiothoracic Surgery, Newark Beth Israel Medical Center, 201 Lyons Ave, Newark, NJ 07112
e-mail: dgoldstein{at}sbhcs.com

	Abstract

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Inhaled nitric oxide, a selective pulmonary vasodilator, has been used to improve arterial oxygenation in adult respiratory distress syndrome. To our knowledge, it has not been successfully used to treat this syndrome after major lung resection. We used nitric oxide to treat postpneumonectomy pulmonary edema with immediate and sustained improvement in oxygenation. The patient was successfully weaned from nitric oxide and extubated after 3 days of supportive therapy.

	Introduction

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Noncardiogenic pulmonary edema is a rare but lethal complication of major lung resection. Although first reported by Gibbon and Gibbon in 1942 [1] the importance of the syndrome was not fully appreciated until 40 years later when numerous reports began appearing in the literature [2–3]. The incidence is low (4.5%) and is more common after right pneumonectomy [3]. The clinical presentation is manifested by respiratory distress occurring hours to days after surgery, a process which probably begins intraoperatively but may have a gradual clinical presentation. Radiographic findings include diffuse interstitial infiltration or frank alveolar edema. The pathophysiology remains poorly understood but likely results from the interaction of factors that increase permeability and filtration pressure, and decrease lymphatic drainage from the affected lung [4]. The syndrome is reported to have a nearly 100% mortality despite aggressive therapy [5]. Treatment has traditionally consisted of fluid restriction, diuretics, and ventilatory support to maintain adequate oxygenation, including the use of continuous positive pressure ventilation [6]. Nitric oxide (NO), formerly known as endothelium-derived relaxing factor, is a highly diffusable vasodilator which stimulates soluble guanylyl cyclase, which catalyzes the formation of cyclic guanosine monophosphate (GMP) and relaxes vascular smooth muscle. The use of NO in the treatment of postpneumonectomy pulmonary edema has been reported once before [7]. However, in that case, as the underlying disease process progressed, the patient became hemodynamically dependent on nitric oxide and ultimately succumbed to a myocardial infarct on the 24th postoperative day. We report what we believe to be the first successful use of NO in postpneumonectomy pulmonary edema.

A 69-year-old man presented to our institution for an elective right radical pneumonectomy for squamous cell carcinoma. His past medical history was significant for a 40 pack-year history of tobacco use, hypertension, chronic obstructive pulmonary disease, gout, and hypercholesterolemia. In the months preceding his admission, the patient had complained of progressive dyspnea. Cardiac evaluation was unremarkable. Chest x-ray film was notable for a 6-cm right-lower-lobe mass and extensive mediastinal and right-sided hilar adenopathy. His preoperative metastatic workup was negative. Mediastinoscopy as a prior procedure was negative. Preoperative pulmonary function tests were in the normal range: forced vital capacity (FVC) 3.4L (87% predicted), forced expiratory volume in 1 second (FEV₁) 2.84L (109% predicted), FEV₁/FVC = 84%.

The patient underwent right intrapleural pneumonectomy and mediastinal lymph node dissection, and his trachea was extubated in the operating room. His immediate postoperative course was notable for elevations in creatinine phosphokinase and troponin to a peak of 2,199 IU/L (100% MM) and 3.2 ng/mL, respectively, without associated symptoms of myocardial ischemia or electrocardiographic changes. His 1st postoperative day was unremarkable. The 2nd postoperative day was notable for the new onset of atrial flutter with 2:1 block and a ventricular response rate in the 150s despite perioperative digitalization. An arterial blood gas revealed a PaO₂ of 85 mm Hg, PaCO₂ of 48 mm Hg and pH of 7.38 on 5 L/min oxygen by nasal cannula. On the 3rd postoperative day, the patient was still in atrial flutter and was placed on oral diltiazem and heparin. At this point, the chest x-ray film started to demonstrate increasing pulmonary vascular congestion of the left lung and a smooth air-fluid level in the right-sided pleural space.

During the early morning of the 4th postoperative day, the patient developed acute respiratory distress with tachypnea, dyspnea, and low oxygen saturation. Arterial blood gases revealed severe intrapulmonary shunting, with a PaO₂ of 78 mm Hg on 100% oxygen by face mask. There was also a noticeable lack of ventilatory compensation, with PaCO₂ 48 mm Hg and pH 7.42 in the setting of hypoxemia. The patient was afebrile and normotensive, although still in atrial flutter. His cumulative fluid balance was -1217 mL. A bedside transthoracic echocardiogram demonstrated hyperdynamic left ventricular function, normal estimated ejection fraction, and pulmonary hypertension with mild right ventricular dilatation and otherwise normal right ventricular function. On postoperative day 5, the patient was lethargic and unable to speak in full sentences. He was noted to have paradoxical respirations. The chest x-ray film showed diffuse interstitial infiltrates and increasing pulmonary vascular congestion. On 100% oxygen by face mask, the PaO₂ was 67 mmHg, PaCO₂ was 48 mm Hg, and pH 7.42. The patient was reintubated; ventilation parameters included intermittent mandatory ventilation at a rate of 20 breaths/min, positive end-expiratory pressure 7, FIO₂ 0.8, and tidal volume 550 mL. Cardioversion of his atrial arrhythmia was briefly successful, but he quickly reverted to atrial flutter. Bronchoscopy via the endotracheal tube revealed that the right main bronchial stump was intact and the left bronchi had minimal thick, nonpurulent secretions. A pulmonary artery catheter was placed without difficulty. The initial pulmonary artery pressure was 48/22 mm Hg with a pulmonary artery occlusion pressure of 8 mm Hg. The chest x-ray film (Fig 1) showed diffuse infiltrates and frank intraalveolar edema involving the entire left lung.

View larger version (123K): [in this window] [in a new window]   Fig 1. Postoperative day 5: The remaining lung demonstrates marked intraalveolar edema, diffuse interstitial infiltrates and pulmonary vascular congestion. The postpneumonectomy space contains an effusion. Gas in the space was gradually replaced by liquid from "weeping" lymphatics and passive transudation of fluid.

View larger version (18K): [in this window] [in a new window]   Fig 2. Postoperative changes in PaCO2 and PaO2.

	Comment

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Although impossible to exclude a cardiogenic source, it appears that the respiratory distress in this patient was noncardiogenic in origin despite a persistent dysrhythmia. The pulmonary artery pressures recorded after tracheal reintubation demonstrated only moderate pulmonary hypertension with low-to-normal left ventricle filling pressure (although we acknowledge that pulmonary artery occlusion pressures may be spurious after pneumonectomy), and echocardiogram revealed normal ventricular function. To us, this was convincing evidence that the diffuse intraalveolar infiltrate in the left lung was a primary pulmonary process. This observation is consistent with experimental observations in which canine pneumonectomy resulted in increased pulmonary artery pressure but normal pulmonary capillary wedge pressure from distension and recruitment of the pulmonary microvasculature and reduction in total pulmonary vascular resistance [8].

Positive perioperative fluid balance, although associated in some studies with postresection pulmonary edema [2], has been found to be unrelated in others. Our patient, excluding insensible losses, was in positive fluid balance in the early perioperative period, but never by more than a liter. Indeed, he was in negative fluid balance during the onset of symptoms.

Nitric oxide, a selective pulmonary vasodilator, likely decreased vascular hydrostatic pressures while not affecting colloid pressures, thus decreasing extravasation of fluid from the pulmonary vasculature and decreasing the interstitial barrier to gas exchange. In addition, NO is thought to improve oxygenation in adult respiratory distress syndrome (ARDS) by increasing perfusion of well-ventilated portions of lung, thus improving ventilation-perfusion matching. Since solumedrol was begun concurrently with the NO, the data are confounded. However, it is unlikely that steroids alone could rapidly improve oxygenation and radiographic appearance in the absence of an inflammatory component to the respiratory distress, for which there is no evidence. The patient was afebrile, and had a normal white count and nonpurulent secretions on flexible bronchoscopy.

This isolated experience suggests that NO may be an important addition in the treatment of postpneumonectomy ARDS. The low cost, insignificant side-effect profile and ease of delivery of NO coupled with the high mortality of postpneumonectomy ARDS warrants further consideration of this therapy in patients afflicted with this devastating complication.

	References

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1. Gibbon J.H., Gibbon M.H. Experimental pulmonary edema following lobectomy and plasma infusions. Surgery 1942;12:694-704.
2. Zeldin R.A., Normandin D., Landtwing D., Peters R.M. Postpneumonectomy pulmonary edema. J Thorac Cardiovasc Surg 1984;87:359-365.[Abstract]
3. Verheijen-Breemhaar L., Bogaard J.M., van der Berg B., Hilvering C. Postpneumonectomy pulmonary edema. Thorax 1988;43:323-326.[Abstract/Free Full Text]
4. Mathru M., Blakemean B., Dries D.J., Kleinman B., Kumar P. Permeability pulmonary edema following lung resection. Chest 1990;98:1216-1218.[Abstract/Free Full Text]
5. Tsukada G., Stark P. Postpneumonectomy complications. Am J Roentgenol 1997;169:1363-1370.[Free Full Text]
6. Nabers J., Hoogsteden H.C., Hilbering C. Postpneumonectomy pulmonary edema treated with continuous positive airway pressure mask. Crit Care Med 1989;17:102-103.[Medline]
7. Chiche J.D., Cenivet J.L., Demas P., Joris J., Lemy M. Inhaled nitric oxide for hemodynamic support after postpneumonectomy ARDS. Intensive Care Med 1995;21:675-678.[Medline]
8. Nakahara K., Nanjo S., Matsumara A., Kawashima Y. Effect of pulmonary blood flow on lung water and pulmonary hemodynamics in the canine lung lobe. Eur Surg Res 1990;22:136-142.[Medline]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kenneth M. Steinglass Daniel J. Goldstein Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rabkin, D. G. Articles by Goldstein, D. J. Search for Related Content PubMed PubMed Citation Articles by Rabkin, D. G. Articles by Goldstein, D. J. Related Collections Lung - other