Printer Friendly

Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress syndrome in primary lung cancer patients.

Pulmonary resection remains the best curative option for patients with localised non small cell lung carcinoma (1). Despite advances in surgical technique, anaesthesia and perioperative care, the morbidity and mortality rates for lung resection remain significant (2). The majority of postoperative complications after lung resection are cardiopulmonary in nature; however, pulmonary complications are the main cause of postoperative death (3-6). Although the causes of postoperative respiratory failure vary and include pneumonia, aspiration, atelectasis and pulmonary emboli, the most dreaded pulmonary complication after lung resection is acute lung injury/acute respiratory distress syndrome (ALI/ARDS) (7).

Pneumonectomy, surgical removal of an entire lung, is associated with higher rates of postoperative respiratory failure and death, compared with lesser resections (2). The reported rates of respiratory failure following pneumonectomy for lung cancer differ widely among centres and range from 3.8 to 17.6% (3-6,8-10). Several factors predicting post-pneumonectomy ALI/ARDS have been identified, including excessive perioperative fluid administration (5,9), previous treatment with radiotherapy (9), duration of operation (11), right-sided pneumonectomy (12) and high intraoperative airway pressure ([]) (10). The pathogenesis of post-pneumonectomy ALI/ARDS is not fully understood, but intraoperative factors such as tidal volume ([V.sub.T]) and airway pressure may contribute to the lung injury seen in this syndrome (13,14). Recently, Fernandez-Perez reported that a large intraoperative [V.sub.T] is associated with postoperative respiratory failure (8). Since this analysis was based on the single largest [V.sub.T] recorded during the operation (8), it could not evaluate the cumulative effect of exposure to potentially harmful ventilator settings during the operation. In addition, since they did not specify when this tidal volume was measured, [V.sub.T] may represent the [V.sub.T] measured during two-lung ventilation (TLV) as well as one-lung ventilation (OLV) (15).

This study investigated the incidence and outcome of patients with post-pneumonectomy ALI/ARDS in primary lung cancer patients and analysed risk factors for post-pneumonectomy ALI/ARDS, focusing on the intraoperative [V.sub.T] and [] during both OLV and TLV


The medical records of 146 consecutive patients who underwent pneumonectomy for primary lung cancer between May 2001 and April 2006 at Samsung Medical Center in Seoul, South Korea, were reviewed retrospectively. Internal Review Board approval was obtained for the chart review and informed consent was waived due to the retrospective nature of the study. The following clinical data were abstracted from the medical records: age, gender, height, actual body weight, predicted body weight (PBW) (16), body mass index, presence of recent weight loss (>10%), smoking history, comorbidities (chronic obstructive pulmonary disease, hypertension, coronary artery disease, diabetes and congestive heart failure), preoperative pulmonary function tests, clinical stage and the presence of neoadjuvant treatment (radiotherapy or chemotherapy). Perioperatively, side of operation, duration of anaesthesia, postoperative mechanical ventilation at the intensive care unit and amount of fluid intake during the first 24 postoperative hours were abstracted. [V.sub.T] during OLV and TLV was computed using the mean value of all tidal volumes recorded which were divided by PBW during OLV and TLV, respectively. [] during OLV and TLV were calculated in a similar manner. The clinical data including tidal volume and peak airway pressure on OLV and TLV were available for all patients.

Post-pneumonectomy ALI/ARDS was defined as the presence of: 1) severe oxygenation failure (ALI, [P.sub.a][O.sub.2]/ Fi[O.sub.2] <300 mmHg; ARDS, [P.sub.a][O.sub.2]/Fi[O.sub.2] <200 mmHg); 2) diffuse pulmonary infiltrates on chest radiography and 3) the absence of signs of left heart failure with either a) the continuation of mechanical ventilation for longer than 48 hours after surgery or b) the reinstitution of mechanical ventilation within the first postoperative week. Patients requiring mechanical ventilation for any complication other than respiratory origin were excluded.

Statistical analysis

Data are presented as medians and interquartile ranges (25th and 75th percentiles) for continuous variables and as number (percentages) for categorical variables. Data were compared using the Mann-Whitney test for continuous variables and chi-square or Fisher's exact test for categorical variables. A multiple logistic regression analysis was used to identify independent risk factors associated with post-pneumonectomy ALI/ARDS. The development of post-pneumonectomy ALI/ARDS was the dependent variable and all clinical parameters were the independent variables in the forward stepwise multiple logistic regression model. Adjusted odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated. Data were analysed using SPSS 13.0 (SPSS Inc, Chicago, IL, USA).


Over the five-year study period, a total of 146 patients had undergone elective pneumonectomy for primary lung cancer. All patients were transferred to the intensive care unit for postoperative care; 120 (82%) patients were extubated in the operating room and the remaining 26 (18%) patients were mechanically ventilated for a median time of 20 (interquartile range, five to 40) hours postoperatively.

In all, 18 (12%) patients met the definition for post-pneumonectomy ALI/ARDS. All 18 patients were re-entubated for mechanical ventilation within a median of 3.5 (three to five) days after surgery. Patients who developed post-pneumonectomy ALI/ ARDS had a longer hospital stay (26 [18 to 75] vs. 8 [7 to 11] days; P <0.001) and higher in-hospital mortality (12 [67%] vs. 0 [0%]; P <0.001) than those who did not.

The clinical characteristics of patients who did and did not develop post-pneumonectomy ALI/ARDS are presented in Table 1. There were no significant differences in age, gender, height, body weight, body mass index, the presence of weight loss, comorbidities, smoking history, preoperative pulmonary function test and clinical stage, the presence of neoadjuvant treatment, side of pneumonectomy, duration of operation, postoperative ventilation or the amount of perioperative fluid infusion. However, patients who developed post-pneumonectomy ALI/ARDS were ventilated with a larger [V.sub.T] and higher [] during OLV than those who did not (V T, 8.2 [7.5 to 9.0] vs. 7.7 [6.9 to 8.2] ml/kg PBW, P=0.016; [], 28.9 [27.6 to 30.0] vs. 27.2 [25.6 to 28.5] cm[H.sub.2]O, P=0.001) (Figure 1). [V.sub.T] during TLV was also larger in the patients who developed ALI/ARDS (8.8 [7.9 to 9.8] vs. 8.2 [7.3 to 8.9] ml/kg PBW P=0.014), while [] during TLV did not differ between patients who did and did not develop ALI/ARDS (21.8 [21.0 to 23.0] vs. 22.0 [20.2 to 23.7] cm[H.sub.2]O, P=0.950) (Table 1). In addition, the largest [V.sub.T] recorded during the operation did not differ between patients who did and did not develop ALI/ARDS (9.3 [8.0 to 10.3] vs. 8.9 [8.0 to 9.81, P=0.326).


In the multiple logistic regression analysis, post-pneumonectomy ALI/ARDS was independently associated with a larger [V.sub.T] (OR 3.37 per 1 ml/kg PBW increase; 95% CI, 1.65 to 6.86) and higher [] (OR 2.32 per 1 cm[H.sub.2]O increase; 95% CI 1.46 to 3.67) during the period of OLV (Table 2).


In this study of patients who underwent pneumonectomy for primary lung cancer, we observed that a large [V.sub.T] and high [] during OLV were independently associated with the development of post-pneumonectomy ALI/ARDS. In addition, patients who developed post-pneumonectomy ALI/ ARDS had a longer hospital stay and greater mortality.

The occurrence of lung injury following lung resection, especially after pneumonectomy, has long been recognised and the term post-pneumonectomy pulmonary oedema was first used to describe this syndrome in 1984 (17). However, since the clinical and radiologic characteristics of post-pneumonectomy pulmonary oedema are identical to those of ALI/ ARDS (18-20), post-pneumonectomy ALI/ARDS is now more commonly used to describe this syndrome (3-6).

The incidence of post-pneumonectomy ALI/ ARDS seen in this study is within the reported range, which varies from 4 to 18% (3-6,8-10). The reported differences probably reflect different definitions of post-pneumonectomy ALI/ARDS or study populations. In addition, the in-hospital mortality rate of post-pneumonectomy ALI/ARDS was similar to reported rates (3,4).

Post-pneumonectomy ALI/ARDS usually manifests clinically as respiratory distress and hypoxaemia within 72 hours of surgery, but may manifest as late as seven days after lung resection (18-20). Interestingly, the time frame of ALI/ARDS in this syndrome is very similar to other aetiologies of ALI/ ARDS, which also develop within one week of an inciting event (21). Although the precise mechanism of post-pneumonectomy ALI/ARDS is not known, some perioperative event(s) or factor(s) probably initiates the inflammatory process leading to lung injury. One possible culprit might be the method of mechanical ventilation during surgery.

During pneumonectomy, the patient has to rely on one lung for adequate gas exchange. During this period, the ventilated lung may be exposed to excessive [V.sub.T], which may cause over-distension. This over-distension of the lung units can induce an inflammatory response and may contribute to the development of lung injury (13,14). Alveolar over-distension associated with a large [V.sub.T] may lead to alveolar stretch injury and the development of permeability pulmonary oedema (22,23). These adverse effects of mechanical ventilation are well described in patients with ALI/ARDS (24). In addition, Gajic reported that initial ventilator settings with a large [V.sub.T] are associated with the subsequent development of ALI in mechanically ventilated patients without pre-existing lung injury (16,25). This finding is supported by experimental evidence that mechanical ventilation with a large [V.sub.T] leads to ventilator-induced lung injury (13,14). Several studies suggest that a large [V.sub.T] during OLV also leads to ventilator-induced lung injury. A recent experimental study of an isolated rabbit lung model reported that OLV with a large [V.sub.T] led to lung injury and this could be minimised by setting the [V.sub.T] to avoid lung over-distension (26). Schilling studied 32 patients who underwent lung resection and found that the levels of inflammatory markers in bronchoalveolar lavage fluid were higher after OLV with a [V.sub.T] of 10 ml/kg vs. 5 ml/kg (27). In addition, a recently published randomised clinical trial has shown that a protective ventilatory strategy during OLV decreases the proinflammatory response, improves lung function and results in earlier extubation (28). These studies support our finding that a large [V.sub.T] during OLV was significantly associated with an increased risk of post-pneumonectomy ALI/ARDS.

There are some suggestions that a high intraoperative [] leads to lung injury. Van der Werff found that peak inspiratory pressures exceeding 40 cm[H.sub.2]O were associated with the development of post-pneumonectomy pulmonary oedema (10). Licker found that a barotrauma index that considered both the duration of OLV and increased inspiratory pressure was associated with the development of postoperative acute lung injury (5). In agreement with these studies, we found that a high [] during OLV was also associated with an increased risk of post-pneumonectomy ALI/ARDS. However, it is possible that a high [] during OLV in our patients represents more severe underlying lung disease, with decreased compliance or increased resistance of the lung tissue, rather than being an independent risk factor for lung injury. However, there were no differences in the preoperative pulmonary function tests, including the forced expiratory volume in one second and forced vital capacity between patients who did and did not develop ALI/ARDS.

There are several limitations to this study. Given its retrospective nature, there is always the possibility of selection bias over- or underestimating the significance of our findings. Our study is from a single institution, which limits the generalisability of our findings to other populations. In addition, other important parameters, such as the plateau pressure during anaesthesia, could not be determined because of incomplete data in the medical records.

In conclusion, a large [V.sub.T] and high [] during OLV were associated with an increased risk of post-pneumonectomy ALI/ARDS and patients who developed ALI/ARDS had longer hospital stays and greater mortality.


(1.) Deslauriers J. Current surgical treatment of nonsmall cell lung cancer 2001. Eur Respir J Suppl 2002; 35:61s-70s.

(2.) Kiser AC, Detterbeck FC. General aspect of surgical treatment. In: Detterbeck FC, Socinski MA, Rivera MP, Rosenuran JG, eds. Diagnosis and treatment of lung cancer: An evidence-based guide for the practicing clinician, 1st ed. Philadelphia, Pennsylvania: WB. Saunders Company 2001. p. 133-147.

(3.) Kutlu CA, Williams E A, Evans T W, Pastorino U, Goldstraw P Acute lung injury and acute respiratory distress syndrome after pulmonary resection. Ann Thorac Surg 2000; 69:376-380.

(4.) Ruffini E, Parola A, Papalia E, Filosso PL, Mancuso M, Oliaro A et al. Frequency and mortality of acute lung injury and acute respiratory distress syndrome after pulmonary resection for bronchogenic carcinoma. Eur J Cardiothorac Surg 2001; 20:3036.

(5.) Licker M, de Perrot M, Spiliopoulos A, Robert J, Diaper J, Chevalley C et al. Risk factors for acute lung injury after thoracic surgery for lung cancer. Anesth Analg 2003; 97:1558-1565.

(6.) Dulu A, Pastores SM, Park B, Riedel E, Rusch V, Halpern NA. Prevalence and mortality of acute lung injury and ARDS after lung resection. Chest 2006; 130:73-78.

(7.) Roberts JR. Postoperative respiratory failure. Thorac Surg Clin 2006; 16:235-241, vi.

(8.) Fernandez-Perez ER, Keegan MT, Brown DR, Hubmayr RD, Gajic O. Intraoperative tidal volume as a risk factor for respiratory failure after pneumonectomy. Anesthesiology 2006; 105:14-18.

(9.) Parquin F, Marchal M, Mehiri S, Herve P, Lescot B. Post-pneumonectomy pulmonary edema: analysis and risk factors. Eur J Cardiothorac Surg 1996; 10:929-932.

(10.) van der Werff YD, van der Houwen HK, Heijmans PJ, Duurkens VA, Leusink HA, van Heesewijk HP et al. Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and possible risk factors. Chest 1997; 111:1278-1284.

(11.) Deslauriers J, Aucoin A, Gregoire J. Postpneumonectomy pulmonary edema. Chest Surg Clin N Am 1998; 8:611-631, ix.

(12.) Turnage WS, Lunn JJ. Postpneumonectomy pulmonary edema. A retrospective analysis of associated variables. Chest 1993; 103:1646-1650.

(13.) Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive-pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis 1985; 132:880-884.

(14.) Tsuno K, Prato P, Kolobow T Acute lung injury from mechanical ventilation at moderately high airway pressures. J Appl Physiol 1990; 69:956-961.

(15.) Slinger Peter D. Postpneumonectomy pulmonary edema: good news, bad news. Anesthesiology 2006; 105:2-5.

(16.) Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004; 32:1817-1824.

(17.) Zeldin RA, Normandin D, Landtwing D, Peters RM. Postpneumonectomy pulmonary edema. J Thorac Cardiovasc Surg 1984; 87:359-365.

(18.) Jordan S, Mitchell JA, Quintan GJ, Goldstraw P, Evans TW The pathogenesis of lung injury following pulmonary resection. Eur Respir J 2000; 15:790-799.

(19.) Beddow E, Goldstraw P The pulmonary physician in critical care * Illustrative case 8: Acute respiratory failure following lung resection. Thorax 2003; 58:820-822.

(20.) Villeneuve PJ, Sundaresan S. Complications of pulmonary resection: postpneumonectomy pulmonary edema and post-pneumonectomy syndrome. Thorac Surg Clin 2006; 16:223-234.

(21.) Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1995; 151:293-301.

(22.) Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998; 157:294-323.

(23.) International consensus conferences in intensive care medicine: Ventilator-associated Lung Injury in ARDS. This official conference report was cosponsored by the American Thoracic Society, The European Society of Intensive Care Medicine, and The Societe de Reanimation de Langue Francaise, and was approved by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 1999; 160:2118-2124.

(24.) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301-1308.

(25.) Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A. Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med 2005; 31:922-926.

(26.) Gama de Abreu M, Heintz M, Heller A, Szechenyi R, Albrecht DM, Koch T One-lung ventilation with high tidal volumes and zero positive end-expiratory pressure is injurious in the isolated rabbit lung model. Anesth Analg 2003; 96:220-228.

(27.) Schilling T, Kozian A, Huth C, Buhhng F, Kretzschmar M, Welte T et al. The pulmonary immune effects of mechanical ventilation in patients undergoing thoracic surgery. Anesth Analg 2005; 101:957-965.

(28.) Michelet P, D'Journo X-B, Roch A, Doddoli C, Marin V, Papazian L et al. Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study. Anesthesiology 2006; 105:911-919.

K. JEON *, J. W YOON ([dagger]), G. Y. SUH ([double dagger]), J. KIM ([section]), K. KIM ([section]), M. YANG **, H. KIM ([dagger][dagger]), O. J. KWON ([dagger][dagger]), Y. M. SHIM ([double dagger][double dagger])

Division of Pulmonary and Critical Care Medicine, Departments of Medicine, Thoracic and Cardiovascular Surgery, Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

* M.D., Fellow, Division of Pulmonary and Critical Care Medicine, Department of Medicine.

([dagger]) M.D., Fellow, Division of Pulmonary and Critical Medicine, Department of Medicine.

([double dagger]) M.D., Associate Professor, Division of Pulmonary and Critical Medicine, Department of Medicine.

([section]) M.D., Thoracic Surgeon, Professor, Department of Thoracic Surgery.

** M.D., Anaesthesiologist, Associate Professor, Department of Anaesthesiology and Pain Medicine.

([dagger][dagger]) M.D., Professor, Division of Pulmonary and Critical Medicine, Department of Medicine.

([double dagger][double dagger]) M.D., Thoracic Surgeon, Professor, Department of Thoracic Surgery.

Address for reprints: Dr Gee Young Sub, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kanguam-ku, Seoul 135-710, Republic of Korea.

Accepted for publication on September 12, 2008.
Preoperative and perioperative variables and outcomes of 146 patients
who had undergone pneumonectomy for primary lung cancer

Variables Patients with ALI/ARDS (n=18)

Age 63(59-67)
Gender, M:F 18:0
Height, cm 165.6 (160.1-174.7)
Actual body weight, kg 62.0 (51.8-66.5)
Body mass index, kg/[m.sup.2] 21.9 (18.2-24.2)
Weight loss (>10%) 6% (33%)
Comorbidity 7% (39%)
 COPD 3% (17%)
 Hypertension 2% (11%)
 Coronary artery disease 2% (11%)
 Diabetes 1% (6%)
Current smoker 18% (100%)
Preop PFTs, % predicted value
 FEV1 89(80-99)
 FEV1/FVC 71(64-76)
 FVC 87(83-101)
Stage, I:II:III 2:7:9
Neoadjuvant treatment 2 (11%)
Side of pneumonectomy, right:left 6:12
Time of anaesthesia, min 270 (240-300)
Intraoperative input, ml 1775 (1500-2400)
 Crystalloid 1325 (1000-1600)
 Colloid 500 (500-500)
Postoperative input, ml 1949 (1736-2688)
Total input, ml 3835 (3340-5003)
Postoperative ventilation in ICU 3 (17%)
[V.sub.T] during TLV, ml/kg PBW 8.8 (7.9-9.8)
[] during TLV, cm[H.sub.2]0 21.8 (21.0-23.0)
[V.sub.T] during OLV, ml/kg PBW 8.2 (7.5-9.0)
[] during OLV, cm[H.sub.2]O 28.9 (27.6-30.0)
Largest [V.sub.T], ml/kg PBW 9.3 (8.0-10.3)

Variables Patients without P value
 ALI/ARDS (n=128)

Age 61(54-66) 0.086
Gender, M:F 118:10 0.612
Height, cm 164.5 (161.2-168.9) 0.149
Actual body weight, kg 62.5 (55.3-68.0) 0.234
Body mass index, kg/[m.sup.2] 22.8 (20.7-24.9) 0.065
Weight loss (>10%) 33% (26%) 0.571
Comorbidity 43% (34%) 0.658
 COPD 6% (5%) 0.083
 Hypertension 20% (16%) 0.430
 Coronary artery disease 4% (3%) 0.160
 Diabetes 15% (12%) 0.694
Current smoker 111% (87%) 0.131
Preop PFTs, % predicted value
 FEV1 84 (70-98) 0.485
 FEV1/FVC 68 (63-75) 0.365
 FVC 90 (81-99) 0.695
Stage, I:II:III 25:29:74 0.338
Neoadjuvant treatment 25% (20%) 0.528
Side of pneumonectomy, right:left 49:79 0.685
Time of anaesthesia, min 270 (240-300) 0.641
Intraoperative input, ml 1845 (1500-2300) 0.961
 Crystalloid 1200 (900-1600) 0.527
 Colloid 500 (500-500) 0.629
Postoperative input, ml 1834 (1483-2325) 0.197
Total input, ml 3785 (3265-4340) 0.419
Postoperative ventilation in ICU 23% (18%) 0.892
[V.sub.T] during TLV, ml/kg PBW 8.2 (7.3-8.9) 0.014
[] during TLV, cm[H.sub.2]0 22.0 (20.2-23.7) 0.950
[V.sub.T] during OLV, ml/kg PBW 7.7 (6.9-8.2) 0.016
[] during OLV, cm[H.sub.2]O 27.2 (25.6-28.5) 0.001
Largest [V.sub.T], ml/kg PBW 8.9 (8.0-9.8) 0.326

FEV1=forced expiratory volume in one second, FVC=forced vital capacity,
ICU =intensive care unit, [V.sub.T] = tidal volume, TLV = two-lung
ventilation; PBW = predicted body weight, Paw = airway pressure,
OLV = one-lung ventilation, COPD=chronic obstructive pulmonary disease.

Risk factors associated with development of post pneumonectomy
ALI /ARDS by multiple logistic regression analysis

 OR 95% CI P value

[V.sub.T] during OLV 3.37 * 1.65-6.86 0.001
[] during OLV 2.32 ([dagger]) 1.46-3.67 <0.001

OR=odds ratio, CI=confidence interval, [] = airway pressure,
[V.sub.T] = tidal volume, PBW = predicted body weight, OLV = one-lung
ventilation. * Per each ml/kg predicted body weight increase.
([dagger]) Per each cm[H.sub.2] O increase.
COPYRIGHT 2009 Australian Society of Anaesthetists
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:Original Papers
Author:Jeon, K.; Yoon, J.W.; Suh, G.Y.; Kim, J.; Kim, K.; Yang, M.; Kim, H.; Kwon, O.J.; Shim, Y.M.
Publication:Anaesthesia and Intensive Care
Article Type:Report
Geographic Code:9SOUT
Date:Jan 1, 2009
Previous Article:In situ simulation-based team training for post-cardiac surgical emergency chest reopen in the intensive care unit.
Next Article:APOE genotype affects outcome in a murine model of sepsis: implications for a new treatment strategy.

Related Articles
Patients with ARDS have dysfunction 1 year after discharge. (Half of Patients Return to Work).
Acute respiratory distress syndrome.
Acute respiratory distress syndrome in a child with Kawasaki disease.
Anti-interleukin 8 autoantibody:interleukin 8 immune complexes visualized by laser confocal microscopy in injured lung: colocalization with...
Alcoholic lung disease.
Effect of recruitment and body positioning on lung volume and oxygenation in acute lung injury model.

Terms of use | Copyright © 2017 Farlex, Inc. | Feedback | For webmasters