The Relationship between Cardiopulmonary Exercise testing (CPET), other Related Factors and Outcomes in Patients Undergoing Major Upper Gastrointestinal Surgery

INTRODUCTION

ecreasing complications and death following major surgery remains a significant challenge. Postoperative complications have an enormous influence on early recovery and hospital outcome as well as on long term survival after surgery^1,2 therefore, identification of vulnerable groups before surgery is important in order to stratify postoperative risk, future intervention studies and ensure the efficient use of resources related to health care².

   Outcome following surgery is dependent on two main factors: patient fitness and the operation itself. Postoperative complications most probably occur in a small group of high risk patients; furthermore many patients undergoing gastro-oesophageal cancer surgery have major co-morbid disease, which strongly influences their postoperative death risk^2,3.

   Oesophageal and gastric cancer are common diseases that cause great challenges to surgeons because most patients present with advanced disease and curative surgery needs considerable resources in the operating theatre and in critical care³.

   There is a simple scoring system called the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM) and this system has proved an efficient indicator of the risk of morbidity and mortality in the general surgical patients. It requires, however, information both pre-operatively and post-operatively⁴ and over-estimates post-operative mortality and morbidity for pancreaticoduodenectomy^5,6.  Other risk stratification tests such as resting spirometry, electrocardiogram and echocardiogram are designed to predict specific organ postoperative complications, mainly respiratory or cardiac^7-9.  Blood gas analysis and anthropometry has been recommended in certain conditions, for example pre-operative respiratory symptoms, major operation, prolonged duration of surgery or when obesity is a risk factor for operation^10,11. These investigations have been found to be limited predictive tools for more generalised post-operative complications^12,13. In addition, some of these investigations are often time and resource limited¹⁴.

   Recently, it has been reported that CPET offers an objective measurement of cardiopulmonary fitness that can determine the physiological capacity of the individual to meet the increases in metabolic demands that occur during trauma like major surgery^15,16. There is, however, no clear agreement on the best CPET parameter to predict post-operative outcome. Some studies demonstrated that exercise test variables (Peak VO₂ (PVO₂), anaerobic threshold) can predict post oesophagectomy cardiopulmonary complications in oesophageal cancer patients^17,18; while another study suggested that CPET was of limited value in predicting cardiopulmonary complication post oesophagectomy¹⁹. Anaerobic threshold measurement improved the prediction of post- non-cardiopulmonary surgery complications compared with questionnaire-based activity assessment of metabolic equivalent score functional capacity ¹³.

Aim of the study

There have been few comparative studies of the role of CPET in the analysis of peri-operative risk assessment in patients undergoing major upper gastrointestinal surgery and neoadjuvant chemotherapy. The aim of the present study was to examine the relationship between these pre-operative measurements and post-operative outcomes in those patients.

PATIENTS AND METHODS

243 patients were referred to the Pulmonary Function Laboratory of Glasgow Royal Infirmary between August 2008 and December 2011 who subsequently underwent surgery. A total of 193 of these patients underwent major upper gastrointestinal surgery within 60 days post CPET. Age, sex and smoking status were recorded.

   A further 19 patients underwent major upper gastrointestinal surgery more than 60 days post CPET, 17 patients underwent abdominal aortic aneurysm surgery, 13 underwent less radical upper gastrointestinal surgery (laparoscopic excision or laparotomy only) and 1 patient’s case record was not accessible to evaluate the degree of upper gastrointestinal surgery. These cases were excluded from this study.

Investigations at the pulmonary function laboratory:The diagnosed patients were referred to the pulmonary laboratory. Tests including anthropometric measurements, flow-volume curve spirometry test, blood gas analysis, transfer factor for carbon monoxide test (TLCO) and cardiopulmonary exercise tests (CPET) were performed. CPET was conducted by using an electrically braked bicycle ergometer. An electronic sphygmomanometer and 12- ECG electrodes were connected to the patient and the CPET protocol was started with 3 minutes rest.  At the end of 3 minutes, the patients were asked to start unloaded cycling for 1 minute at a constant pedaling rate of between 50-60 revolution per minute (rpm) depending on the metronomic of the bike ^20,21.  After that the work load started to increase incrementally of 10-20 watt/minute but it was modified depending on subject’s fitness, so when the patient was very frail and old, the increment rate was decreased to 5 watt/min and when the patient was young and fit, the increment rate was increased to 15 watt/min ^22-24. The patients continued pedaling until either; they reached their exhaustion level or they had any other limiting symptom that prevent them to continue more cycling ^{25, 26}. At the end point of the test, the patient entered the recovery period where they were asked to continue pedaling without load for at least 2 minutes.  ECG, heart rate, blood pressure, respiratory exchange ratio (RER) and pulse oximetry were monitored ²⁰.

   The test was ended before the patients reached exhaustion level or when the patients signaled that they had chest pain or difficulty in breathing. The test was also stopped if there was depression or elevation of the ST segment of the ECG ≥2 mm, T wave inversion or sustained ventricular tachycardia ^{15, 27,28}.

   Anaerobic threshold determination was done using the V-slope method ^16,28,29 which was confirmed by ventilatory equivalent, end tidal partial pressure methods [Reviewed 16,28 and respiratory exchange ratio (RER) changes ³⁰.

Follow up of patients for postoperative outcomes:The prospective follow up of all patients who underwent major surgery was performed by examining the following categories:

Morbidity - defined as complications at 30 days postoperatively including medical (cardiac and pulmonary) complications and /or surgical technique (wound infection and an anastomotic leak) complications.

   Length of hospital stay (LOHS), high dependency unit (HDU) stay, intensive care unit (ICU) stay and ward stay during the in-hospital period and any readmission to them which happened within 30 days postoperatively. Length of high dependency unit stay and length of intensive care stay were merged in this study as length of high dependency care stay.

Mortality - defined as 30 day postoperatively or postoperative in-hospital mortality ³. The duration between the date of operation and the date of commencing post-operative chemotherapy when it was indicated.

Statistics:The data were presented as median and range or numbers and percentages. An appropriate comparison of patient groups was carried out using a Kruskal-Wallis test, Mann-Whitney and chi square test from SPSS software; significant was defined as P value < 0.05 (two-sided).

RESULTS

The 193 patients were categorised depending on development of post operative cardiopulmonary complications into patients with no post-operative cardiopulmonary complications and those with post operative cardiopulmonary complications. 54% of patients developed post-operative cardiopulmonary complications. Table 1.

Table 1: The relationship between clinicopathological characteristic indices and CPET parameters in patients having upper gastrointestinal surgery in the 1^st 60 days post CPET grouped into those with and without post-operative cardiopulmonary complications (n=193).

*All values given as median (range) or numbers (%).

Total patients’ numbers vary due to incomplete data.

SA = surface area; VE = ventilatory equivalent.

   There were significant associations between postoperative cardiopulmonary complications and mortality within the first month postoperatively or in-hospital mortality (p≤0.01), where patients with post-operative cardiopulmonary complications had a higher percentage of mortality compared with patients with no post-operative cardiopulmonary complications. There were significant difference between the groups with and without post operative cardiopulmonary complications in FVC % predicted (118 vs. 110, respectively; p≤0.01), anaerobic threshold % predicted maximumVO₂ (47.2 vs. 41.4, respectively; p<0.05), length of high dependency care stay (7 vs. 9, respectively; p<0.001), in length of ward stay (5 vs. 9, respectively; p<0.001) and length of hospital stay (12 vs. 19, respectively; p<0.001).  There were no significant differences between the two groups in other variables.

   The 193 patients who underwent major upper gastrointestinal surgery within 60 days post CPET were then categorised depending on development of post operative pulmonary complications into two groups; those with no post operative pulmonary complications those with post operative pulmonary complications. 44% of patients developed post-operative pulmonary complications.Table 2.

Table 2: The relationship between clinicopathological characteristic indices and CPET parameters in patients having upper gastrointestinal surgery in the 1^st 60 days post CPET grouped into those with and without post-operative pulmonary complications (n=193).

*All values given as median (range) or numbers (%). Total patients’ numbers vary due to incomplete data.

SA = surface area; VE = ventilatory equivalent.

   There were significant associations between postoperative pulmonary complications with smoking status (p≤0.05), where patients without postoperative pulmonary complications had a higher percentage of non-smokers and lower percentage of current smokers compared with those with postoperative pulmonary complications. There were significant associations between postoperative pulmonary complications and mortality within the first month postoperatively or in-hospital mortality (p<0.001), where patients with post-operative pulmonary complications had higher mortality levels compared with patients without post-operative pulmonary complications. There were significant differences between without and those with post operative pulmonary complications in FVC % predicted (118 vs. 109, respectively; p≤0.01), in anaerobic threshold % predicted maximum VO₂ (47.2 vs. 40.4, respectively; p<0.05), in length of high dependency care stay (7 vs. 10, respectively; p<0.001), in length of ward stay (5 vs. 9, respectively; p≤0.01) and in length of hospital stay (12 vs. 19, respectively; p<0.001).  There were no significant differences between the two groups in other variables.

   The 193 patients were then further categorised depending on the development of post operative anastomotic leak complications into two groups:  Those without post operative anastomotic leak and those patients with post operative anastomotic leak. 16% of patients developed post-operative anastomotic leak. Table 3.

Table 3: The relationship between clinicopathological characteristic indices, CPET parameters in 1st 60 days in patients with and without postoperative anastomotic leak in upper gastrointestinal surgery (n=193).