For patients with carcinoma of the lung, surgery - in most instances - is the only potentially curative treatment. However, the surgical procedure and the postoperative recovery period are often associated with serious, even fatal complications. Mortality and morbidity have only slightly decreased during the past decades, possibly because of the relation of carcinoma of the lung to smoking habits, chronic pulmonary disease, and generalized atherosclerosis. Pneumonectomy is associated with a higher risk of postoperative morbidity than most other surgical procedures .
Risk has been associated with the presence of chronic pulmonary disease, reduced ejection fraction or other indicators of reduced left ventricular function, other coexisting medical conditions and age [2-5]. Elevated body mass index (BMI) has been shown to be predictive of pulmonary complications in general surgery. Other potential risk factors include the extent of surgery and anaesthesia, the surgical technique, and perioperative fluid therapy.
The identification of important risk factors is necessary when preparing patient information material and for the potential prevention of postoperative complications. We performed the present study to identify important risk factors for postoperative complications and death.
One-hundred-and-thirty-six patients who underwent pneumonectomy during a consecutive period of 4 yr at Bispebjerg University Hospital constituted the study group. Twenty-nine patients were later omitted from the study analysis due to insufficient data collection in the postoperative period. One-hundred-and-seven patients thus remained in the study.
A special record sheet was designed for the study. The record included: (a) patient history and pre-operative findings, (b) surgical and anaesthesia data, (c) data from the recovery period and postoperative period until discharge from hospital, or until death. One observer, who did not participate in the care of the patients, collected all the data. All patients received general anaesthesia in combination with a segmental thoracic epidural block. General anaesthesia was induced with thiopental and fentanyl and maintained with inhalation anaesthetics.
The patients received volume expansion during anaesthesia to maintain circulation with isotonic saline 5 mL kg−1 h−1. Additionally, human albumin 5%, whole blood, or blood components were given if necessary, according to the department's guidelines. The crystalloids and colloids given during anaesthesia and the total blood loss and urine output were measured. Fluid balance was defined as (crystalloids + colloids) - (blood loss + urine output).
Definitions and classifications
Complications were defined as the appearance of untoward reactions requiring interventions beyond standard procedures, events related to the original surgical procedure until the time of discharge from hospital, re-operation or death in the hospital. The selected perioperative parameters and characteristics of patients are given in Table 1.
Postoperative severe dysrhythmias
The following severe dysrhythmias were noted: supra- and ventricular tachydysrhythmia, atrioventricular and bundle branch block.
Postoperative pulmonary complications
Prolonged respiratory insufficiency requiring treatment with bronchodilators, continuous positive airway pressure (CPAP), re-intubation, and/or mechanical ventilation for more than 24 h postoperatively (patients scheduled preoperatively for postoperative mechanical ventilation were not included), atelectasis-formation, pneumonia (chest radiograph and/or positive culture of pathogens).
Mortality associated with anaesthesia and surgery was defined as death during or following anaesthesia and surgery within 30 days (in-hospital mortality).
The data were coded and checked for missing or inconsistent values. A two-stage process was used to determine potential risk factors for postoperative complications and mortality: (a) Test of the perioperative risk variables (Tables 1 and 2) one at a time by testing for independence in two-way tables (χ2-test); (b) Multiple logistic regression analysis was used to separate the influence of the different risk factors, the postoperative complications, and mortality being the dependent variables.
One-hundred-and-seven patients underwent pneumonectomy, 28 women and 79 men, mean age 64.4 (±8.9) yr (range 42-78 yr). The total incidence of postoperative complications was 29% (31 patients) and 11 (10.3%) died within 30 days of surgery. Ten patients (9.3%) developed one or more cardiovascular complications, 24 (22.4%) patients developed severe dysrhythmias, and 19 (17.8%) developed pulmonary complications. Seventeen (15.9%) were re-operated upon and 10 (9.3%) patients were re-admitted to the intensive care unit.
Perioperative risk factors
Excess fluid balance >4000 mL was the single most important risk factor for the development of postoperative pulmonary complications (P < 0.05), for the development of any postoperative complications (P < 0.001), and for in-hospital mortality (P < 0.05) (Table 2). The mean intraoperative fluid balance was 2672 mL (range 0-6400 mL), and the mean blood loss was 961 mL (range 150-9000 mL). Blood loss exceeding 1000 mL increased the risk of excess fluid balance > 4000 mL (P < 0.05), but was not in itself a risk factor for postoperative complications. Body mass index exceeding 25 kg m−2 was a significant variable for the development of postoperative dysrhythmias (P < 0.05), but did not increase the incidence of pulmonary complications or in-hospital mortality. A history of cardiovascular disease was a risk factor for postoperative pulmonary (P < 0.001) and total complications (P < 0.05), but was not associated with increased mortality. Age, gender, duration of anaesthesia, site of pneumonectomy or preoperative reduced lung function (forced expiratory volume in one second (FEV1)) did not significantly influence postoperative complications and death. The presence of postoperative cardiovascular and pulmonary complications increased mortality from 7.2% to 40.0% (P < 0.001), and from 2.3% to 47.4% respectively (P < 0.001) compared to the rest of the study population in the univariate analysis.
Estimated risk of complications and mortality
Multivariate analysis identified the following variables independently associated with the occurrence of postoperative complications and mortality (Tables 3, 4):
• Prediction of postoperative dysrhythmias: BMI > 25 kg m−2
• Prediction of postoperative pulmonary complications: History of cardiac disease and excess fluid balance > 4000 mL during anaesthesia
• Prediction of in-hospital mortality: Excess fluid balance > 4000 mL during anaesthesia, postoperative pulmonary complications.
This study shows that pneumonectomy in patients with neoplastic disease is associated with a high risk of morbidity and mortality after operation. The two most important risk factors for postoperative complications in the present study were a positive fluid balance in excess of 4000 mL and a history of cardiac disease. The most important risk factors of in-hospital mortality were a positive fluid balance in excess of 4000 mL and the development of postoperative pulmonary complications. Intraoperative blood loss exceeding 1000 mL increased the risk of excess fluid balance, but was not an independent risk factor of any complications in itself in the multivariate analysis.
Perioperative blood loss and infusions of excess fluid in the perioperative period have previously been suspected to influence postoperative morbidity rates , but the risk-predictive value of these factors is questionable, since it might only reflect the severity of some underlying medical or surgical condition or the extent of surgery. We therefore used logistic regression analysis to evaluate these risk factors in relation to morbidity and mortality. Consequently, the conclusions from this part of the study are that a positive fluid balance > 4000 mL during anaesthesia is independently associated with the occurrence of postoperative complications and death. The pathophysiological background relating fluid overload to mortality is generally poorly described, and it has not been the focus of this study. A plausible explanation would be generation of interstitial oedema, impeding the transcapillary exchange of oxygen and nutritional components, as well as the presence of pulmonary congestion impeding oxygen uptake.
The in-hospital mortality rate was 10.3%, which is in agreement with the mortality range of 5-27% reported in other series [5-9]. The overall rate of postoperative complications was 29% in this series, whereas others have found rates from 19-58% [10,11].
The most frequent complication was cardiac dysrhythmia (22.4%). The risk of dysrhythmias was associated with an increased BMI (> 25 kg m−2) and age > 70 yr; there was no correlation with a history of cardiac or pulmonary disease. The incidence of dysrhythmia matches other findings of 19-22% [5,12]. Krowka and colleagues found a mortality rate of 25% in patients with postoperative dysrhythmias. We could not demonstrate any correlation between severe dysrhythmias and the site of pneumonectomy, unlike others [13-15]. Nevertheless, cardiac dysrhythmias did not affect mortality rate.
Nineteen patients (17.8%) developed postoperative pulmonary complications. This figure is low compared to other series. Patel and colleagues found an incidence of 49%, others of 39% [3,5]. The risk factors for postoperative pulmonary complications in the present study were intraoperative fluid balance exceeding 4000 mL and a history of cardiac disease. Whether this finding can be explained by pulmonary congestion caused by overload remains unclear, but has previously been suggested [16-18].
The site of pneumonectomy did not affect the incidence of complications, an observation supported in other studies . However, some authors found an increased risk associated with right pneumonectomy . Seventeen patients (15.9%) were re-admitted to the intensive care unit because of serious complications, mainly of pulmonary origin (71%).
Postoperative cardiovascular complications other than dysrhythmias were seen in 9.3% of patients, but were not associated with any other of the risk factors examined in the present series. In the univariate analysis we found increased mortality rates in patients who developed postoperative cardiovascular complications. This is supported by the findings of some observers , while others did not find the presence of concomitant cardiovascular disease to influence mortality after thoracic surgery [3,7].
One-third of the patients in this study were > 70 yr old. Old age disposed only to the development of postoperative cardiac dysrhythmias. Mortality was not influenced by age. Didolkar and colleagues suggested an increased risk in the elderly , but others have found a low operative mortality among older patients [5,20].
We found that excess fluid balance was the most important predictor for morbidity and mortality after pneumonectomy. From these data, we cannot tell whether it was the fluid overload itself or some underlying factor(s). Care should be taken when using retrospective, epidemiological, descriptive data to describe cause and effect relationships. In order to explore the possibility of reducing post-operative complications, new randomized controlled studies need to be conducted. The focus could be restrictive fluid regimens, using artificial colloids instead of crystalloids for blood component therapy, or an extended use of vasopressors for blood pressure control during anaesthesia.
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