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Peri-operative risk factors for acute lung injury after elective oesophagectomy

2001; Elsevier BV; Volume: 86; Issue: 5 Linguagem: Inglês

10.1093/bja/86.5.633

1471-6771

S. Tandon, Anna Batchelor, R. Bullock, A. Gascoigne, Martin Griffin, Nick Hayes, Jeremy Hing, Ian Shaw, I. Warnell, Simon Baudouin,

Respiratory Support and Mechanisms

Acute lung injury after oesophagectomy is well recognized but the risk factors associated with its development are poorly defined. We analysed retrospectively the effect of a number of pre-, peri- and post-operative risk factors on the development of lung injury in 168 patients after elective oesophagectomy performed at a single centre. The acute respiratory distress syndrome (ARDS) developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in patients developing ARDS was 50% compared with 3.5% in the remainder. Features associated with the development of ARDS included a low pre-operative body mass index, a history of cigarette smoking, the experience of the surgeon, the duration of both the operation and of one-lung ventilation, and the occurrence of a post-operative anastomotic leak. Peri-operative cardiorespiratory instability (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements and the need for inotropic support) was also associated with ARDS. Acute lung injury after elective oesophagectomy is associated with intraoperative cardiorespiratory instability. Acute lung injury after oesophagectomy is well recognized but the risk factors associated with its development are poorly defined. We analysed retrospectively the effect of a number of pre-, peri- and post-operative risk factors on the development of lung injury in 168 patients after elective oesophagectomy performed at a single centre. The acute respiratory distress syndrome (ARDS) developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in patients developing ARDS was 50% compared with 3.5% in the remainder. Features associated with the development of ARDS included a low pre-operative body mass index, a history of cigarette smoking, the experience of the surgeon, the duration of both the operation and of one-lung ventilation, and the occurrence of a post-operative anastomotic leak. Peri-operative cardiorespiratory instability (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements and the need for inotropic support) was also associated with ARDS. Acute lung injury after elective oesophagectomy is associated with intraoperative cardiorespiratory instability. A recent confidential enquiry into post-operative mortality and morbidity highlighted the large contribution that respiratory complications make to poor outcome after elective oesophageal surgery.1Sherry K Management of patients undergoing oesophagectomy.in: Gray AJG Hoile RW Ingram GS Sherry K The Report of the National Confidential Enquiry Into Peri-Operative Deaths 1996/1997. National CEPOD, London1998: 57-61Google Scholar One specific pulmonary disorder, the acute respiratory distress syndrome (ARDS) is associated with oesophagectomy and occurs in 10–20% of cases.2Millikan KW Silverstein J Hart V Blair K Bines S Roberts J et al.A 15-year review of esophagectomy for carcinoma of the esophagus and cardia.Arch Surg. 1995; 130: 617-624Crossref PubMed Scopus (114) Google Scholar 3Wyncoll DLA Evans TW Acute respiratory distress syndrome.Lancet. 1999; 354: 497-501Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar Diffuse damage to the alveolar epithelial/endothelial interface of the lung increases vascular permeability and impairs pulmonary gas exchange by alveolar flooding and infiltration with acute inflammatory cells. Mortality of ARDS exceeds 50%.4Baudouin S Improved survival in ARDS: chance, technology or experience?.Thorax. 1998; 53: 237-238Crossref PubMed Scopus (8) Google Scholar The development of ARDS is associated with systemic inflammatory conditions such as septic shock, major trauma, massive blood transfusion and pancreatitis.5Pittet JF Mackersie RC Martin TR Matthay MA Biological markers of acute lung injury: prognostic and pathogenetic significance.Am J Respir Crit Care Med. 1997; 155: 1187-1205Crossref PubMed Scopus (488) Google Scholar Systemic release of circulating inflammatory mediators and the activation of leukocytes may contribute to the lung injury. The cause of ARDS after oesophagectomy is unknown but the release of inflammatory mediators and gut-related endotoxins may contribute.6Katsuta T Saito T Shigemitsu Y Kinoshita T Shiraishi N Kitano S Relation between tumour necrosis factor alpha and interleukin 1beta producing capacity of peripheral monocytes and pulmonary complications following oesophagectomy.Br J Surg. 1998; 85: 548-553Crossref PubMed Scopus (41) Google Scholar In addition, the period of one-lung anaesthesia required during oesophagectomy may also be important. Collapse and subsequent re-expansion of the non-dependent lung may produce lung injury by an ischaemic/reperfusion mechanism,7Jordan MC Mitchell JA Quinlin GJ Goldstraw P Evans TW The pathogenesis of lung injury following pulmonary resection.Eur Respir J. 2000; 15: 790-799Crossref PubMed Scopus (183) Google Scholar and overventilation of the dependent lung could also produce injury by micro-barotrauma.8Dos Santos CC Slutsky AS Invited review: mechanisms of ventilator-induced lung injury: a perspective.J Appl Physiol. 2000; 89: 1645-1655Crossref PubMed Scopus (393) Google Scholar Recent reports of preoptimization in high-risk surgical patients suggest another mechanism of lung injury. Preoptimization techniques are used to increase cardiac output deliberately and produce so-called supranormal levels before, during and after surgery.9Boyd O Grounds RM Bennett ED A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.J Am Med Assoc. 1993; 270: 2699-2707Crossref PubMed Scopus (798) Google Scholar A number of studies have reported decreased mortality and morbidity (including respiratory) after preoptimization.10Boyd O Street M Is perioperative intensive care therapy useful in patients with limited cardiovascular reserve?.Curr Opin Crit Care. 1999; 5: 393-399Crossref Scopus (5) Google Scholar The corollary of these observations would be the finding that morbidity and mortality are increased in non-preoptimized patients who demonstrate cardiorespiratory instability in the peri-operative period. We therefore studied retrospectively the operative course of a large group of patients who underwent elective oesophagectomy at a single centre. We examined a number of measures of peri-operative cardiorespiratory instability and performed single and multi-variable analysis on the association between these and the development of ARDS, respiratory morbidity and mortality after elective oesophageal surgery. One hundred and ninety-three patients were operated on for oesophageal cancer at Newcastle General Hospital and the Royal Victoria Infirmary between January 1, 1996 and December 31, 1999. Of these, five underwent trans-hiatal oesophagectomy, two underwent emergency subtotal oesophagectomy and 17 were found to be inoperable. One hundred and sixty-nine patients underwent conventional two-phase oesophagectomy, consisting of subtotal oesophageal resection with right thoracotomy, oesophagogastrostomy and radical two-field lymph node dissection. We analysed retrospectively 168 patients who underwent elective two-phase resection (the notes of one patient could not be obtained). Two patients developed severe intraoperative haemodynamic compromise that necessitated abandonment of the resection. Data were collected from patient case notes, from our prospectively compiled oesophagectomy database and from the anaesthetic charts. Missing values were recorded as such. Data were divided into pre-operative, peri-operative and post-operative data. The pre-operative data included age, sex, smoking history, history of ischaemic heart disease, body mass index (BMI) (kg m–2), arterial blood gases on air, simple spirometry (forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) as percentage predicted and FEV1/FVC ratio), haemoglobin concentration, liver function (serum bilirubin, albumin, aspartate transaminase), renal function (blood urea and creatinine) and the stage of tumour (TNM classification: stage I, IIA, IIB, III and IV). The stage of tumour was recorded from the post-operative histology. Intraoperative data included duration of surgery (from skin incision to closure), duration of one-lung ventilation (OLV), a calculated measure of the degree and duration of hypotension during the procedure (the hypotension index; see below), a calculated measure of the degree and duration of oxygen desaturation during OLV (the hypoxaemia index; see below), inotrope requirement (both bolus and infusion), estimated blood loss (ml) and blood transfusion (units), crystalloid infusion (litres), colloid infusion (litres) and the use of epidural analgesia. The experience and grade of the surgeon and anaesthetist were also recorded. All operations were performed by a consultant surgeon. The surgeon and anaesthetist were classified as experienced if they had more than 5 yr of consultant experience in the management of oesophagectomies.11Sutton DN Wayman J Griffin SM Learning curve for oesophageal cancer surgery.Br J Surg. 1998; 85: 1399-1402Crossref PubMed Scopus (101) Google Scholar Post-operative data included post-operative blood transfusion, post-operative inotrope use and the occurrence of post-operative anastomotic leak. Information on the occurrence of specific post-operative complications was collected. Acute lung injury (ALI) and ARDS were defined according to the American European Consensus Conference on ARDS criteria.12Bernard GR Artigas A Brigham KL Carlet J Falke K Hudson L et al.The American–European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination.Am J Respir Crit Care Med. 1994; 149: 818-824Crossref PubMed Scopus (4857) Google Scholar ALI was defined as PaO2/FiO2 less than 40 kPa and ARDS as PaO2/FiO2 less than 27 kPa. Additional criteria included the presence of bilateral infiltrations on plain chest radiograph, and a pulmonary artery occlusion pressure of less than 18 mm Hg if measured or no clinical evidence of left atrial hypertension. We also defined a group of patients with post-operative respiratory failure on the basis of having ALI and the continuing need for invasive ventilatory support [not CPAP (continuous positive airway pressure) alone] more than 48 h after oesophagectomy. Specific respiratory complications included persistent pleural effusions, prolonged (>7 days) pneumothoraces and hydropneumothoraces, empyema, chylothoraces, pneumonia (fever, purulent sputum, new pulmonary infiltrate and organisms identified), pulmonary emboli, laryngeal oedema and the development of fistulae. In-hospital deaths during the admission for oesophagectomy were also recorded. All of the patients in this study were anaesthetized by one of three consultant anaesthetists. When appropriate, premedication was prescribed and patients received their normal medication pre-operatively. Anaesthesia was induced i.v. and maintained with a combination of systemic opiates, neuromuscular paralysis and a volatile anaesthetic agent. Subtotal oesophagectomy is a two-phase procedure, the first phase being a laparotomy conducted in the supine position and the second phase involving a right-sided thoracotomy in the left lateral position. Surgical access in the latter stage necessitates the collapse of the non-dependent lung. To facilitate a period of one-lung anaesthesia, intubation was performed using a left-sided double-lumen Robertshaw endobronchial tube. After intubation, the correct position of the double lumen tube was confirmed by fibre-optic bronchoscopy and patients were ventilated with an Engstrom MIE Carden Ventilator (Engstrom MIE, Exeter, Devon, UK). Initial ventilation settings were adjusted to achieve a tidal volume of 8–10 ml kg–1, a respiratory rate of 10–12 b.p.m., an inspiratory:expiratory (I:E) ratio of 1:2 and an end-tidal carbon dioxide tension of 4–5 kPa. Before the second part of the operation the patient was placed on an FiO2 of 100%, placed in the left lateral decubitus position and OLV was commenced. Ventilator settings were adjusted to maintain tidal volume and end-tidal carbon dioxide at pre-OLV levels. Peak airway pressures invariably increased because of the high resistance of the single lumen within the double-lumen tube, and no changes in ventilation were made on the basis of increased airway pressure alone. Tube displacement or malposition was always excluded by fibre-optic inspection during any period of ventilatory difficulty. Full monitoring was established, including invasive measurement of systemic blood pressure, central venous pressure, urine output, core temperature, and the usual airway and ventilation measurements. Measures were taken to maintain normothermia. Manipulation of the non-ventilated lung to maintain systemic oxygenation included insufflation of 100% oxygen (2–3 litre min–1) and the application of 5–10 cm H2O CPAP. After surgery and before transfer to the intensive care unit, the patient was reintubated with an endonasal or endotracheal tube. Sedation was maintained with i.v. propofol and opiate. Early extubation was encouraged once the patient was regarded as cardiorespiratory-stable, normothermic and comfortable and if blood loss from the chest drains was less than 50 ml h–1. When early extubation was not possible, the patient was ventilated overnight. After extubation, the patient remained in the intensive care unit until he or she could safely be transferred to a high dependency unit (HDU). Post-operative analgesia was provided by a thoracic epidural infusion of 0.125% bupivacaine containing diamorphine 40 µg ml–1, and adjusted in accordance with the patient’s needs. To pharmacokineticists, the area under the concentration–time curve is an important measure of exposure to a drug or metabolite. When using estimates of exposure, determination of the area under the concentration–time curve (AUC) is customarily carried out using the trapezoidal method.13Gagnon RC Peterson JJ Estimation of confidence intervals for area under the curve from destructively obtained pharmacokinetic data.J Pharmacokinet Biopharm. 1998; 26: 87-102Crossref PubMed Google Scholar We used the analogy of hypotension or hypoxaemia as a metabolic toxin to which the patient was exposed to during the surgery. The measure of the exposure could then be determined by estimating the AUC. Oxygen saturation recorded during OLV was plotted on a fixed linear scale of 0–100% against time for each patient and the AUC was calculated using the trapezoidal rule. The area was standardized for time by dividing the area by the OLV duration. A plot of mean arterial pressure (MAP) against time was made and the total AUC was calculated using a MAP of less than 70 mm Hg as the cut-off value. The hypotension index was then calculated by dividing the total AUC by the total duration of surgery. Data were analysed using SPSS for Windows 8.1 (SPSS Inc., Chicago, IL, USA) under the Windows 95 operating system. Patients with data missing for a given variable were not included in univariant analysis for that variable. Initial univariant analysis, using the independent Student t-test for discrete variables and the χ2 test for categorical variables, was used to compare patient outcomes (mortality, ARDS and respiratory failure) against individual pre-, peri- and post-operative variables. Multiple logistic regression analysis, using a forward conditional strategy, was then used to examine the importance and interaction of variables with respect to the outcome. ARDS occurred in 14.5% of all patients who underwent oesophagectomy for oesophageal cancer between January 1996 and December 1999. Intensive therapy unit (ITU) and hospital stays were prolonged in this group compared with patients who did not develop ARDS [mean (sd) ITU stay 16 (16) vs 1 (1) day; mean hospital stay 36 (34) vs 15 (8) days]. Mortality in the group with ARDS was 50% compared with 3.5% in the group without ARDS. ARDS-associated mortality accounted for 71% of total post-operative mortality. Post-operative respiratory failure occurred in 23.8% of all patients, and this group had a mean (sd) ITU stay of 17 (25) days. Mortality in this group was 37%. Specific respiratory complications occurred in 44% of all patients, including persistent pleural effusions (15%), prolonged pneumothoraces (4.1%) and hydropneumothoraces (1.8%), empyema (2.4%), chylothorax (2.4%), pneumonia (17.8%), pulmonary emboli (1.8%) and laryngeal oedema (n=1). Variables associated with the development of ARDS are shown in Table 1. Pre-operative factors included a low pre-operative BMI and a history of cigarette smoking. Peri-operative instability was associated with ARDS, as indicated by the need for fluids and blood products during operation, the use of inotropes and peri-operative hypoxaemia and hypotension. Longer duration of procedure and length of time of OLV were also significant. Post-operatively, the need for emergency re-exploration for bleeding was associated with ARDS. The experience of the consultant surgeon, but not the consultant anaesthetist, was also associated with the development of ARDS (P=0.005). Risk factors for the development of acute lung injury and for overall mortality were identical to those for ARDS.Table 1Results of univariable analysis of pre-, peri- and post-operative factors associated with the development of ARDS after oesophagectomy. Data are mean (se) and 95% confidence interval (CI) or percentages. P<0.05 was considered significantVariableNumber of patientsMean (se; CI) or percentagePNon-ARDS groupARDS groupCurrent or ex-smoker14762%92%<0.004BMI (kg m–2)14624.9 (0.4; 24.1–25.7)21.8 (3.7; 14.5–29.1)<0.002OLV duration (min)164120 (3; 114–126)136 (7; 122–150)<0.02Hypoxaemia index1643.3 (0.2; 2.9–3.7)5.7 (0.7; 4.3–7.1)<0.0001Hypotension index1648.6 (0.8; 7.0–10.2)17.4 (2.6; 12.3–22.5)<0.0001Ephedrine (mg)1644.0 (0.6; 2.8–5.2)8.8 (1.8; 5.2–12.4)<0.005Inotrope infusion1640.7%20.8%<0.0001Fluids infused (litres)1644.4 (0.1; 4.2–4.6)5.0 (0.3; 4.4–5.6)<0.027Colloids (litres)1641.5 (0.1; 1.3–1.7)2.0 (0.2; 1.6–2.4)<0.002Post-operative1671.0 (0.2; 0.6–1.4)5.3 (1.5; 2.3–8.3)<0.0001transfusions (units)Total peri-operative1671.6 (0.2; 1.2–2.0)6.3 (1.6; 3.1–9.5)<0.0001transfusions (units)Emergency1684.9%20.8%<0.016re-explorationPost-operative leak1688.3%41.6%<0.0001 Open table in a new tab Multiple logistic regression analysis was used to determine the relative contributions of the variables to the development of ARDS (Table 2). In a forward conditional model, analysing the complete data on 146 patients, six factors were found to be significant. A low BMI and a past or current history of smoking were the only pre-operative factors of significance. Peri-operative instability, as indicated by hypoxaemia during OLV, hypotension and the need for fluids all increased the risk of post-operative ARDS. The factor with the highest odds ratio for the development of ARDS was the development of post-operative anastomotic breakdown.Table 2Results of forward conditional multiple logistic regression analysis on 146 patients with complete data using factors found to be significant in the univariant analysis of ARDS. Data are given for each significant factorFactorOdds ratio95% CI (lower)95% CI (upper)PBMI0.580.410.820.004Smoker9.951.0792.70.04Hypoxaemia index1.761.262.470.001Hypotension index1.081.011.160.04Fluids2.981.167.670.04Leak22.523.16160.360.002 Open table in a new tab The recent Confidential Enquiry into Peri-Operative Deaths (CEPOP) recorded ‘respiratory problems as being a major cause of morbidity and mortality after elective oesophageal surgery’.1Sherry K Management of patients undergoing oesophagectomy.in: Gray AJG Hoile RW Ingram GS Sherry K The Report of the National Confidential Enquiry Into Peri-Operative Deaths 1996/1997. National CEPOD, London1998: 57-61Google Scholar This conclusion is supported by many published reports and a systematic review.6Katsuta T Saito T Shigemitsu Y Kinoshita T Shiraishi N Kitano S Relation between tumour necrosis factor alpha and interleukin 1beta producing capacity of peripheral monocytes and pulmonary complications following oesophagectomy.Br J Surg. 1998; 85: 548-553Crossref PubMed Scopus (41) Google Scholar 14Bartels H Stein HJ Siewert JR Preoperative risk analysis and postoperative mortality of oesophagectomy for resectable oesophageal cancer.Br J Surg. 1998; 85: 840-844Crossref PubMed Scopus (250) Google Scholar, 15Kusano C Baba M Takao S Sane S Shimada M Shirao K et al.Oxygen delivery as a factor in the development of fatal postoperative complications after oesophagectomy.Br J Surg. 1997; 84: 252-257Crossref PubMed Scopus (61) Google Scholar, 16Nagawa H Kobori O Muto T Prediction of pulmonary complications after transthoracic oesophagectomy.Br J Surg. 1994; 81: 860-862Crossref PubMed Scopus (85) Google Scholar, 17Rocker GM Wiseman MS Pearson D Shale DJ Neutrophil degranulation and increased pulmonary capillary permeability following oesophagectomy: a model of early lung injury in man.Br J Surg. 1988; 75: 883-886Crossref PubMed Scopus (25) Google Scholar, 18Schilling MK Gassmann N Sigurdsson GH Regli B Stoupis C Furrer M et al.Role of thromboxane and leukotriene B4 in patients with acute respiratory distress syndrome after oesophagectomy.Br J Anaesth. 1998; 80: 36-40Crossref PubMed Scopus (20) Google Scholar, 19Muller JM Erasmi H Stelzner M Zieren U Pichlmaier H Surgical therapy of oesophageal carcinoma.Br J Surg. 1990; 77: 845-857Crossref PubMed Scopus (878) Google Scholar The precise incidence of respiratory problems after oesophagectomy depends on definition, but MuÕller and colleagues, in their review,19Muller JM Erasmi H Stelzner M Zieren U Pichlmaier H Surgical therapy of oesophageal carcinoma.Br J Surg. 1990; 77: 845-857Crossref PubMed Scopus (878) Google Scholar reported the average incidence of postoesophagectomy respiratory failure to be 27% on the basis of a database of 83 783 patients drawn from 121 publications. The incidence of respiratory failure in our group (23.8%) was similar to that reported by MuÕller in his review series. Pulmonary complications occurred in 44% of our patients, and this group had prolonged hospital admissions and increased mortality. ARDS is a major contributor to respiratory morbidity and mortality after oesophagectomy. In one series of 157 patients,2Millikan KW Silverstein J Hart V Blair K Bines S Roberts J et al.A 15-year review of esophagectomy for carcinoma of the esophagus and cardia.Arch Surg. 1995; 130: 617-624Crossref PubMed Scopus (114) Google Scholar ARDS occurred in 17% of cases after a transthoracic approach and had a mortality of 78%. In a smaller series of 19 patients, ARDS was reported in 53%,6Katsuta T Saito T Shigemitsu Y Kinoshita T Shiraishi N Kitano S Relation between tumour necrosis factor alpha and interleukin 1beta producing capacity of peripheral monocytes and pulmonary complications following oesophagectomy.Br J Surg. 1998; 85: 548-553Crossref PubMed Scopus (41) Google Scholar and in another report ARDS occurred in 33% of 18 patients.18Schilling MK Gassmann N Sigurdsson GH Regli B Stoupis C Furrer M et al.Role of thromboxane and leukotriene B4 in patients with acute respiratory distress syndrome after oesophagectomy.Br J Anaesth. 1998; 80: 36-40Crossref PubMed Scopus (20) Google Scholar The incidence of ARDS in our series was 14.5%, which is lower than in previous reports, although mortality in this group was high at 50%. In addition, patients with ARDS accounted for 71% of the total mortality after oesophagectomy. ARDS is characterized clinically by impaired pulmonary gas exchange leading to hypoxaemia, and plain chest radiology showing diffuse alveolar infiltrates.3Wyncoll DLA Evans TW Acute respiratory distress syndrome.Lancet. 1999; 354: 497-501Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar 20Ware LB Matthay MA The acute respiratory distress syndrome.N Engl J Med. 2000; : 1334-1349Crossref PubMed Scopus (4224) Google Scholar Most patients will require some form of mechanical ventilatory support, often for a prolonged period. Despite modern intensive care, mortality remains high and most series report a survival rate of less than 50%.4Baudouin S Improved survival in ARDS: chance, technology or experience?.Thorax. 1998; 53: 237-238Crossref PubMed Scopus (8) Google Scholar The precise cause of ARDS remains uncertain. It may represent a stereotyped response to a variety of direct and indirect insults to the lung. Most cases of ARDS are preceded by a major systemic insult between 24 and 48 h before the full clinical syndrome develops. Initial descriptions of the condition concentrated on pulmonary vascular permeability disturbances. More recent research has emphasized that ARDS is an inflammatory condition of the lung and that lung injury is probably initiated and perpetuated by a number of inflammatory mediators.5Pittet JF Mackersie RC Martin TR Matthay MA Biological markers of acute lung injury: prognostic and pathogenetic significance.Am J Respir Crit Care Med. 1997; 155: 1187-1205Crossref PubMed Scopus (488) Google Scholar 21Reid PT Donnelly SC Haslett C Inflammatory predictors for the development of the adult respiratory distress syndrome.Thorax. 1995; 50: 1023-1026Crossref PubMed Scopus (21) Google Scholar Rocker and colleagues17Rocker GM Wiseman MS Pearson D Shale DJ Neutrophil degranulation and increased pulmonary capillary permeability following oesophagectomy: a model of early lung injury in man.Br J Surg. 1988; 75: 883-886Crossref PubMed Scopus (25) Google Scholar reported a high frequency of subclinical lung injury after oesophagectomy. They measured lung vascular permeability, using a double radioisotope technique, in nine consecutive patients. Although none developed clinical ARDS, all the patients showed an increase in lung permeability after operation. They also noted that lung permeability was higher on the thoracotomy side than on the dependent side after operation. Both local and systemic factors may therefore be important in the aetiology of postoesophagectomy ARDS. Oesophagectomy involves a long period of OLV.22Tugrul M Camci E Karadeniz H Senturk M Pembeci K Akpir K Comparison of volume controlled with pressure controlled ventilation during one-lung anaesthesia.Br J Anaesth. 1997; 79: 306-310Crossref PubMed Scopus (157) Google Scholar To optimize surgical access, the lung on the thoracotomy side is deliberately collapsed while the contralateral lung receives all the ventilation and most of the pulmonary blood flow. This procedure could result in lung injury to both the collapsed and dependent lung. There is much experimental data showing that even moderate mechanical ventilation may produce a form of micro-barotrauma indistinguishable from ARDS.8Dos Santos CC Slutsky AS Invited review: mechanisms of ventilator-induced lung injury: a perspective.J Appl Physiol. 2000; 89: 1645-1655Crossref PubMed Scopus (393) Google Scholar In addition, a recent large multicentre study of ARDS demonstrated more mortality in patients receiving conventional high tidal volume ventilation than those receiving lower tidal volume ventilation.23Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (8791) Google Scholar Relatively high tidal volumes are often used during OLV and could result in ventilator-induced lung injury. Injury to the collapsed lung may follow lung reperfusion. Organ injury by reperfusion is well recognized, and there is good evidence for free radical-related lung injury in a number of experimental models of lung reperfusion injury.7Jordan MC Mitchell JA Quinlin GJ Goldstraw P Evans TW The pathogenesis of lung injury following pulmonary resection.Eur Respir J. 2000; 15: 790-799Crossref PubMed Scopus (183) Google Scholar Systemic factors that may also result in lung injury include peri-operative endotoxaemia. One group has reported raised circulating endotoxin levels after oesophagectomy.24Moriyama H Hirata S Kubo Y Alteration of serum levels of endotoxin, polymorphonuclear leukocyte elastase, and the molecular markers of the coagulation and fibrinolytic system in the patients with esophageal cancer and lung cancer before and following operation.Rinsho Byori Jpn J Clin Pathol. 1995; 43: 233-237PubMed Google Scholar Endotoxin is a potent cause of lung injury in experimental animals, and ARDS commonly follows septic shock.25Ghosh S Latimer RD Gray BM Harwood RJ Oduro A Endotoxin-induced organ injury.Crit Care Med. 1993; 21: S19-S24Crossref PubMed Scopus (102) Google Scholar Major surgical injury, including oesophagectomy, also releases a number of proinflammatory cytokines, which may contribute to lung injury.26Lin E Calvano SE Lowry SF Inflammatory cytokines and cell response in surgery.Surgery. 2000; 127: 117-126Abstract Full Text Full Text PDF PubMed Scopus (394) Google Scholar A number of pre-operative factors have been linked to mortality after elective oesophagectomy, including age, lung function, arterial blood gases and the presence of chronic respiratory and liver disease.14Bartels H Stein HJ Siewert JR Preoperative risk analysis and postoperative mortality of oesophagectomy for resectable oesophageal cancer.Br J Surg. 1998; 85: 840-844Crossref PubMed Scopus (250) Google Scholar 16Nagawa H Kobori O Muto T Prediction of pulmonary complications after transthoracic oesophagectomy.Br J Surg. 1994; 81: 860-862Crossref PubMed Scopus (85) Google Scholar 27Ferguson MK Martin TR Reeder LB Olak J Mortality after esophagectomy: risk factor analysis.W J Surg. 1997; 21: 599-603Crossref PubMed Scopus (144) Google Scholar Pre-operative screening procedures and case selection will affect the importance of these variables, as some centres may not operate on higher-risk patients. In our study, most pre-operative variables recorded were not associated with the development of post-operative complications. Only low BMI and a history of smoking were associated with ARDS, while peri-operative lung function and arterial blood gases did not predict the development of lung injury. The lack of association between these variables and outcome in our study could explain by our screening procedures and careful case selection. There are few reports of the relationship between intraoperative variables and the post-operative course. One study of 269 patients found that intraoperative blood loss and the need for inotropic support were associated with post-operative mortality.27Ferguson MK Martin TR Reeder LB Olak J Mortality after esophagectomy: risk factor analysis.W J Surg. 1997; 21: 599-603Crossref PubMed Scopus (144) Google Scholar We are not aware of any previous study that has examined the relationship between cardiorespiratory instability during surgery and subsequent ARDS. Factors associated with ARDS include the durations of both surgery and OLV, surgical experience, the need for blood and fluid replacement during and after operation, the need for inotropic support during surgery, and cardiorespiratory instability, indicated by hypoxaemia and hypotension. The magnitude of the surgical stress and the patient’s cardiorespiratory responses seem to be linked to the development of lung injury. These results support the hypothesis that tissue ischaemia/reperfusion injury contributes to ARDS.7Jordan MC Mitchell JA Quinlin GJ Goldstraw P Evans TW The pathogenesis of lung injury following pulmonary resection.Eur Respir J. 2000; 15: 790-799Crossref PubMed Scopus (183) Google Scholar Recurrent intraoperative episodes of hypoxaemia and hypotension cause a series of tissue ischaemia and reperfusion injuries, and thus the release of soluble, proinflammatory mediators, and activate circulatory leucocytes. Injury of the lungs and other distant organs is then the result of endothelial/epithelial cell damage caused by a soluble and cellular inflammatory response. Our results are not unexpected in view of recent reports on the pre-operative optimization of high-risk patients.9Boyd O Grounds RM Bennett ED A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk surgical patients.J Am Med Assoc. 1993; 270: 2699-2707Crossref PubMed Scopus (798) Google Scholar 10Boyd O Street M Is perioperative intensive care therapy useful in patients with limited cardiovascular reserve?.Curr Opin Crit Care. 1999; 5: 393-399Crossref Scopus (5) Google Scholar In these studies, patients undergoing major elective surgery underwent invasive cardiac monitoring before surgery. Cardiac output was then augmented into the supranormal range using a combination of fluid and inotrope therapy. At least two randomized studies have reported significantly lower mortality in surgical patients receiving this therapy.10Boyd O Street M Is perioperative intensive care therapy useful in patients with limited cardiovascular reserve?.Curr Opin Crit Care. 1999; 5: 393-399Crossref Scopus (5) Google Scholar Our finding could show the corollary of this approach. When no attempt is made to optimize cardiac output before operation, those patients who need more intraoperative fluid replacement and inotropes and have more hypotension and hypoxaemia have the worst outcome. This hypothesis is supported by a study of post-operative haemodynamics in 115 patients after oesophagectomy.15Kusano C Baba M Takao S Sane S Shimada M Shirao K et al.Oxygen delivery as a factor in the development of fatal postoperative complications after oesophagectomy.Br J Surg. 1997; 84: 252-257Crossref PubMed Scopus (61) Google Scholar The patients who required prolonged ITU ventilation and those who died had worse post-operative haemodynamics than survivors. In summary, we have found an association between various measures of intraoperative instability and the development of postoesophagectomy ARDS. These findings suggest the need for prospective studies to investigate the optimization of haemodynamics before and during major elective surgery. In addition, they suggest that the intraoperative cardiopulmonary management of high-risk surgical patients may have an important effect on outcome.