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Postpneumonectomy pulmonary edema (PPE) is a rarely reported form of acute lung injury which occurs in up to 4% of all pneumonectomies. The details of two well-documented cases of PPE are described with special emphasis paid to the preoperative lung functions. Both eases illustrated a striking disparity between preserved spirometric lung function and advanced emphysema as detected by quantitative CT emphysema scores and single-breath diffusion of carbon monoxide measurements. Though retrospective in nature, these results suggest a restricted capillary volume plays a critical role in the development of PPE.

(CHEST 1998; 114:928-931)

Key words: acute lung injury; adult respiratory distress syndrome; computed tomography; postpneumonectomy pulmonary edema; pulmonary artery; pulmonary artery occlusion pressure; single-breath diffusion of carbon monoxide

Abbreviations: Dsb=single-breath diffusion of carbon monoxide; PA=pulmonary artery; PAOP=PA wedge pressure; PAP=PA pressure; PPE=postpneumonectomy pulmonary edema; Vc=capillary volume

Postpneumonectomy pulmonary edema (PPE) is a form of acute lung injury which follows resectional lung surgery. Though it has been well-described in the thoracic surgery medical literature, its pathogenesis remains unclear.[1-3] Some authors attribute it to an increase in pulmonary capillary hydrostatic pressure which results from the combined effects of lung resection and a positive perioperative fluid balance.[1,3] Others believe that an increase in pulmonary capillary permeability is the primary mechanism.[2] This report contains two well-documented cases of PPE. In both cases, a striking disparity was noted between normal spirometric lung function and advanced emphysema as detected by quantitative CT emphysema scores and, in one of the cases, by single-breath diffusion of carbon monoxide (Dsb) measurements as well. A possible explanation of these findings based on the concept of critical reductions in pulmonary capillary volume (Vc) is proposed.

METHODS

Criteria for the diagnosis of PPE were similar to those of Turnage and Lunn.[2] At presentation 2 to 5 days following lung resection, all patients were in acute hypoxemic respiratory failure. Chest x-ray films demonstrated unilateral infiltrates which progressed from an interstitial to an alveolar pattern. In each case, left ventricular dysfunction (or volume overload) was ruled out by serial cardiac enzymes, pulmonary artery (PA) catheter measurements, and transthoracic or transesophageal echocardiography. At the time of presentation, there was no prevailing clinical or laboratory evidence to suggest pneumonia, sepsis, or aspiration.

Preoperative spirometric functions and Dsb measurements were performed on a rolling-seal spirometer (Collins GS modular PFT) utilizing standard techniques suggested by the American Thoracic Society.[4] All Dsb measurements were corrected for measured hemoglobin and for carbon monoxide back-diffusion by standard methods? Alveolar volume was obtained during the Dsb by helium dilution and then used to correct Dsb for total surface area available for diffusion (Dsb/alveolar volume). All measurements are expressed in absolute values and as percent predicted based on predicted norms.[4,6]

All CT scans were obtained at 1-cm intervals from apex to diaphragm at full inspiration using 10-mm collimation. Scans were viewed using appropriate window levels by three different radiologists who were unaware of the clinical history or diagnosis. Each radiologist was asked to quantify the degree of emphysema utilizing a visual scale described by Goddard and associates.[7] In this method, each lung slice is visually assessed for areas of low attenuation and vascular disruption. A score of zero represented no abnormality; 1 represented abnormalities involving up to 25% of the lung field; 2, between 25 and 50%; 3, between 50 and 75%; and 4, for near-total involvement. The scores were averaged and expressed as a percentage of the maximum CT score (number of slices x 4) and are shown in Table 1. For this study, a score of 0 to 25 was considered "mild"; a score of 25 to 50 was considered "moderate"; and any score over 50 was thought to be "severe."

REPORT OF CASES

CASE 1

A 61-year-old white man with an 80 pack-year history of smoking presented with a persistent cough. An x-ray film of the chest showed an infiltrate of the lower lobe of the left lung with volume loss. A CT scan displayed a left perihilar mass in addition to the postobstructive pneumonia of the lower lobe of the left lung. Also noted were changes consistent with advanced emphysema (Fig 1). Bronchoscopy biopsy specimens were positive for squamous cell carcinoma involving the proximal left lower lobe bronchus. Preoperative pulmonary function testing showed an FVC of 4.09 L (96%), an [FEV.sub.1] of 3.30 L/s (110%), an [FEV.sub.1]/FVC ratio of 81%, and MMEF of 3.02 L/s (103%). Dsb measurements were not obtained. With the patient breathing room air, blood gas determinations revealed a pH of 7.46, a [PCO.sub.2] of 32 mm Hg, and a Pa[O.sub.2] of 57 mm Hg.

[Figure 1 ILLUSTRATION OMITTED]

Following resection of the lower lobe of the left lung, 'a completion pneumonectomy was performed due to a positive tumor margin. During the first 24 h, the patient had a net positive fluid balance of 4,500 mL. Thereafter, fluid balance was maintained with intermittent doses of intravenously administered furosemide. On postoperative day 2, crackles were heard in the base of the right lung, but the chest x-ray film showed no new infiltrates. On postoperative day 5, the patient was noted to be dyspneic with a resting tachycardia and a pulse oximetry saturation of only 60% while receiving nasal cannula oxygen at a rate of 4 L/min. A cardiac examination revealed prominent neck veins, a right ventricular S4, and a murmur consistent with tricuspid regurgitation. Following a "low" probability ventilation-perfusion scan, the patient was transferred to the ICU. A chest x-ray film showed a new interstitial infiltrate developing in the right lower lung field along with left-sided postoperative changes (Fig 2). He was intubated and mechanically ventilated with an [FIO.sub.2] of 80%. A PA catheter was inserted and revealed the presence of mild PA hypertension with a PA systolic/PA diastolic pressure of 44/15 mm Hg and a mean PA pressure (PAP) of 25 mm Hg. The PA wedge pressure (PAOP) was 4 mm Hg, the central venous pressure was 4 mm Hg, the cardiac output was 4.6 L/min, and the calculated systemic vascular resistance and pulmonary vascular resistance were 1,530 and 365 dyne [multiplied by] s/[cm.sup.5], respectively. On the next day, a transesophageal echocardiogram disclosed normal left ventricular function along with right atrial and right ventricular enlargement. Cardiac enzyme levels were not indicative of acute injury. Though all tracheal aspirates and blood cultures were negative for bacterial pathogens, empiric treatment with intravenously administered antibiotics (ceftriaxone disodium and aztreonam) was begun. Two days later, the infiltrates had become more alveolar and spread to involve the entire right lung field. By postoperative day 14, the patient's PAP was 84/20 mm Hg with a calculated pulmonary vascular resistance of nearly 900 dyne [multiplied by] s/ [cm.sup.5]. He was transferred to a referral hospital for consideration of nitric oxide therapy but died shortly after transfer. No autopsy was obtained.

[Figure 2 ILLUSTRATION OMITTED]

CASE 2.

A 69-year-old Asian man with a 100 pack-year history of smoking and a long-standing seizure disorder was admitted to the hospital for evaluation of hemoptysis. A chest x-ray film showed a lobulated 4 x 7-cra mass of the upper lobe of the right lung. A CT scan of the chest confirmed the findings just mentioned and additionally revealed a small 1 x 1-cm nodule of the lower lobe of the right lung. No mediastinal adenopathy was detected. Lung windows disclosed changes consistent with advanced emphysema (Fig 3). Pulmonary function testing showed an FVC of 2.70 L (83%), an [FEV.sub.1] of 2.44 L/s (110%), an [FEV.sub.1]/FVC ratio of 90%, an MMEF of 2.56 L/s (102%), a Dsb of 8.74 mL/min/mm Hg (36%), and a ratio of carbon monoxide diffusing capacity to alveolar volume of 1.99 L/min/mm Hg (45%). Arterial blood gases revealed a pH of 7.40, a Pa[O.sub.2] of 67 mm Hg, and a [PCO.sub.2] of 46 mm Hg. The patient underwent a right-sided thoracotomy. Intraoperatively, the small nodule of the lower lobe of the right lung was found to be malignant, and a right-sided pneumonectomy was performed. During the first 24-h period, the patient received a positive fluid balance of 1 L. Thereafter, fluid balance was maintained with intravenously administered furosemide. Two days postoperatively, the patient developed a grand mal seizure followed by persistent hypotension. A PA catheter was inserted revealing a right atrial pressure of 11 mm Hg, a PAP of 47/17 mm Hg with a mean of 26 mm Hg, a cardiac output of 4.35 L/min and a calculated systemic vascular resistance of 1,177 dyne-s/[cm.sup.5]. PAOP measurements were not obtained since partial occlusion of the remaining left PA led to systemic hypotension, a reported complication following pneumonectomy.[3,8] A transthoracic echocardiogram disclosed normal left ventricular function, and serial cardiac enzyme values did not indicate acute cardiac injury. A chest x-ray film showed postoperative changes consistent with a right pneumonectomy and a developing interstitial infiltrate involving the left lung field. Although blood pressure initially stabilized when the patient was receiving low-dose (2 [micro]g/kg/min) dopamine, oxygenation continued to worsen such that while breathing 60% oxygen via a face mask, the pH was 7.43, the [PCO.sub.2] was 44 mm Hg, and the Pa[O.sub.2] was 55 mm Hg. The patient was electively intubated and placed on an [FIO.sub.2] of 100%. At the time of direct laryngoscopy, there was no evidence of aspiration. Positive end-expiratory pressure was adjusted between 5 and 12 cm [H.sub.2]O because higher levels caused systemic hypotension. Gentamicin was added to intravenously administered sterile ceflazolin sodium (Ancef) as empiric treatment for nosocomial pneumonia. One day later, homogeneous alveolar infiltrates filled the left lung field. The balance of the hospital course was characterized by persistent hypoxemia despite [FIO.sub.2] greater than 80%, intermittent hypotension, decreased cardiac output despite the addition of inotropic agents (dobutamine), and markedly elevated PAPs which failed to respond to either dinoprostone (prostaglandin Es) or intravenously administered epinephrine. After remaining hypoxemic for 8 h despite an [FIO.sub.2] of 100%, the patient developed persistent hypotension and later died during the 4th hospital day.

[Figure 3 ILLUSTRATION OMITTED]

Postmortem examination disclosed normal myocardium with no evidence of myocardial infarction or significant coronary artery disease. The left lung showed diffuse hemorrhagic interstitial and intra-alveolar edema along with panacinar emphysema. Pulmonary capillary congestion was a predominant finding. Additionally, two small marrow emboli were noted along with one area of neutrophilic infiltration and necrosis. These findings, however, were not considered the proximate cause of death. Numerous antemortem cultures of' blood, urine, and sputum were negative for all bacterial pathogens. Postmortem lung cultures were not done. Incidentally found was a small cerebral arteriovenous malformation of the left frontal lobe which showed evidence of remote hemorrhage.

DISCUSSION

PPE is a poorly understood form of acute lung injury which followed resectional lung surgery.[1,3] In an autopsy review by Turnage and Lunn,[5] ARDS as demonstrated histologically in 15 or 17 PPE patients. This finding is nonspecific, however, and does not indicate a particular inciting cause or trigger unique to pneumonectomy patients. Other investigators believe volume overload contributes to the development of PPE.[3] The present study does not support this theory. Though patient 1 in this series did have a positive fluid balance during the 1st postoperative day, he did not present clinically or radiographically until 4 days later. Hemodynamic measurements, cardiac enzyme levels, echocardiography, and, in case 2, postmortem examination all failed to demonstrate any evidence of volume overload or left ventricular failure.

For over 50 years, investigators have hypothesized that PPE results from critical reductions in pulmonary (Vc).[9] Because of a large unused pulmonary vascular reserve, lung resection is normally tolerated without an increase in mean PAP. Once this reserve is depleted, further resection would lead to increased blood flow to the remaining lung and an increase in PAP if pulmonary vascular resistance remains unchanged. Given a normal PAOP, the pulmonary capillary hydrostatic pressure (Pc) will rise as shown in equation 1:

(1) (Pc = PAOP + 0.4 [PAP mean - PAOP])

Such an increase will lead to distention of the remaining capillary bed and move the mean capillary pressure point toward the venous end.3 The net effect of increasing pulmonary capillary hydrostatic pressure and capillary surface area is an increase in fluid flux and hydrostatic edema if other compensatory mechanisms, such as the lympathic pump, are overwhelmed. In support of this concept, Zeldin and colleagues[3] convincingly demonstrated PPE in 6 of 13 dogs following right-sided pneumonectomy and 1 of 2 volume infusions. According to their hemodynamic calculations, blood flow to the remaining lung increased five- to six-fold as a result of both volume loading and pneumonectomy. Staub[10] suggested such an increased blood flow and flow velocity may physically injure capillary endothelium, allowing protein-rich fluid to enter the interstitium and the alveolar space.

The two cases reported in this communication indirectly support the role of critical reductions in Vc in the pathogenesis of PPE. Despite normal spirometry, each patient had advanced emphysema as determined by CT emphysema scores (Table 1). Using the visual CT scoring method of Goddard and associates,[7] all three radiologists scored each patient as having moderately advanced emphysema. Patient 2 in this series had a significantly reduced Dsb which, in the absence of other causes, is also consistent with emphysema.[11] One may suspect that both these measurements reflect advanced emphysema with corresponding reductions in Vc.

Table 1--Emphysema Score as a Percentage of Maximum Possible CT Score

(*) N is too small for valid interobserver analysis.

Direct measurement of Vc requires a series of Dsb measurements to be obtained at different oxygen concentrations utilizing the method of Roughton and Forster.[12] Unfortunately, such measurements are not routinely available. Even so, it is commonly assumed that Vc is reduced in proportion to the degree of emphysema since emphysema involves destruction of alveolar walls and septa that contain pulmonary capillaries. This idea is supported by the work of Morrison and associates[13] who measured Vc and Dsb in 110 patients undergoing lung resection and found both measures were proportionately reduced and correlated (negatively) with the presence of histologic emphysema. Morrison and coworkers[13] also found a high positive correlation between CT emphysema score and pathologic emphysema, a finding that has been documented by others.[14,15]

Since Vc was not measured directly in this study, the proposed link between PPE and Vc is speculative. If possible, a larger prospective study is needed to ascertain if there is a true' relationship between measured Vc and PPE. Measuring Vc preoperatively may not be unreasonable in evaluating advanced emphysema patients with preserved spirometric function. Such patients with "nonobstructive emphysema"[16] who undergo aggressive lung resection may be at increased risk for PPE.

REFERENCES

[1] Verheijen-Breemhaar L, Boggard JM, van den Berg B, et al. Postpneumonectomy pulmonary edema. Thorax 1988; 43: 323-326

[2] Turnage WS, Lunn JJ. Postpneumonectomy pulmonary edema: a retrospective analysis of associated variables. Chest 1993; 103:1646-1650

[3] Zeldin RA, Normandin D, Landtwing D, et al. Postpneumonectomy pulmonary edema. J Thorac Cardiovasc Surg 1984; 87:359-365

[4] Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981; 123:659-664

[5] Dinikara P, Blumenthal WS, Johnston RF, et al. The effect of anemia on pulmonary diffusing capacity with derivation of a correction equation. Am Rev Respir Med 1970; 102:965-969

[6] Crapo RO, Morris AH. Standardized single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 1981; 123:185-187

[7] Goddard PR, Nicholson EM, Laszlo G, et al. Computed tomography in pulmonary emphysema. Clin Radiol 1982; 33:379-387

[8] Wittnich C, Trudel J, Zidulka A, et al. Misleading "pulmonary wedge pressure" after pneumonectomy: its importance in postoperative fluid therapy. Ann Thorac Surg 1986; 42:192-196

[9] Gibbon JH, Gibbon MH. Experimental pulmonary edema following lobectomy and plasma infusions. Surgery 1942; 12:694-704

[10] Staub NC. Pulmonary edema due to increased microvascular permeability to fluid and protein. Circ Res 1978; 43:143-151

[11] Symonds G, Ronzetti AD, Mitchell MM. The diffusing capacity in pulmonary emphysema. Am Rev Respir Dis 1974; 109:391-394

[12] Roughton FJW, Forster RE. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J Appl Physiol 1957; 11:291-302

[13] Morrison NJ, Abboud RT, Mueller NL, et al. Pulmonary capillary blood volume in emphysema. Am Rev Respir Dis 1990; 141:53-61

[14] Bergin C, Muller N, Nichols DM, et al. The diagnosis of emphysema. Am Rev Respir Dis 1986; 133:541-546

[15] Hruban RH, Meziane MA, Zerhouni EA, et al. High resolution computed tomography of inflation-fixed lungs. Am Rev Respir Dis 1987; 136:935-940

[16] Klein JS, Gamsu G, Webb RW, et al. High-resolution CT diagnosis of emphysema in symptomatic patients with normal chest radiographs and isolated low diffusing capacity. Radiology 1992; 182:817-821

LTC William E. Caras, MD, FCCP([dagger])

(*) From the Pulmonary Disease/Critical Care Service, Fitzsimons Army Medical Center, Aurora, CO.

([dagger]) Currently at Madigan Army Medical Center, Tacoma, Wash. The views expressed herein are those of the authors and do not purport to reflect the views of the US Army or the Department of Defense.

Manuscript received November 11, 1997; revision accepted February 13, 1998.

Correspondence to: William E. Caras, MD, FCCP, 2618 Thomhill Rd, Puyallup, WA 98374

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