Postoperative surgical and medical complications are common following emergency laparotomy, and perioperative cardiovascular events are the leading cause of morbidity and mortality after non-cardiac surgery.1,2 Patient age, male sex, and chronic medical conditions such as ischemic heart disease, peripheral vascular disease, diabetes, and renal insufficiency are independent preoperative predictors of myocardial injury after non-cardiac surgery.3 The surgical stress response associated with surgery and anesthesia is characterized by activation of the sympathetic nervous system with a rise in catecholamines, systemic inflammation, and immune dysfunction, all of which may trigger cardiovascular complications.2,4 Systemic inflammation, which is the main defining characteristics of the surgical stress response, has also been suggested as an essential promoter of acute coronary syndrome and cardiac arrhythmia.5–8 Similarly, the importance of the inflammatory response as an enabling characteristic of cancer has become increasingly recognized in recent years.9 On tumor level, necrosis and tumor products cause the release of pro-inflammatory cytokines such as IL-6, IL-1, TNF-α and interferons.10 We hypothesized that systemic inflammation, based on present malignant disease, increased the risk of postoperative cardiovascular events in patients undergoing emergency abdominal surgery.
The objective of this study was to determine the relationship between malignancy and postoperative cardiovascular complications. Secondarily, we aimed to identify other potential risk factors for cardiovascular complications after emergency laparotomy.
We conducted a retrospective cohort study at the general surgery department at Zealand University Hospital, Denmark. All patients with emergency admission to the emergency department and scheduled for any emergency gastrointestinal surgical procedure from January 2010 to October 2016 were included in the cohort. We only included adults ≥ 18 years undergoing emergency laparotomy. A detailed description of the data collection can be found elsewhere.11 Briefly, data extraction was obtained from electronic medical journals covering the time from admission to 30 days after surgery. We extracted pre-, per- and postoperative variables including age, weight, height, tobacco use, alcohol consumption, comorbidities, malignancy status, prescription medicine, oncological treatment within eight weeks prior to surgery, information on the surgical procedure, postoperative complications, and 30-day mortality. WHO Performance Status was defined as the patient’s level of function and capacity for self-care, according to ECOG/WHO classification.12 ASA score was graded according to the American Society of Anesthesiologists physical status classification system. Body mass index (BMI) was defined as kg/m2. Alcohol consumption was classified according to the recommendations provided by the Danish Health Authority, where weekly use is recommended not to exceed seven units for women and 14 units for men. Comorbidities were registered if being medically treated at the time of admission or if prior treatment was described in the admission journal.
We constructed a composite malignancy variable consisting of any diagnosis of active malignancy at admission or any ICD-10 codes with a diagnosis of cancer (ICD-10 C0-97) or any perioperative finding of malignancy. Patients with a diagnosis of non-melanoma skin cancer were not included in the malignancy group. All patients undergoing laparoscopic procedures were excluded. Any laparoscopic procedure converted to laparotomy was classified as laparotomy. Postoperative complications were graded according to the Clavien-Dindo Classification of Surgical Complications.13,14 Complications were defined as any deviation from the ordinary postoperative course and ranked 1–5 according to the severity and treatment required. Complications ranked 3–5 were severe adverse cardiovascular events composed of either organ dysfunction, the requirement of surgery or percutaneous coronary intervention, intermediate or intensive care, or death. The primary outcome was cardiovascular complication Clavien-Dindo grade 3–5.
Data were presented as frequencies and percentages for categorical variables and mean with standard deviation (SD) for continuous variables. To identify risk factors for cardiovascular complications graded 3–5 on the Clavien-Dindo score, we performed a multivariate logistic regression analysis on all complete cases with the predefined clinically relevant variables: age in ten-year increments, sex, WHO performance status ≥ 2, ASA score ≥ III, current smoking, weekly alcohol consumption above the threshold recommended by the Danish Health Authority, comorbidity in the form of malignancy, diabetes, cerebrovascular disease, hypertension, ischemic heart disease, chronic nephropathy, the use of statins, immune modulation therapy, and anticoagulation therapy. Odds ratios (OR) with 95% confidence intervals (CI) were given and considered statistically significant if p < 0.05. We assessed multicollinearity with variance inflation factor analysis. A factor higher than 1.5 was subjected to further analysis. The goodness of fit was estimated with McFadden’s R2 test. Analyses were performed using the statistical software RStudio (ver. 3.5.1), including the packages tidyverse, tableone, icd, and sjPlot. The study was approved by the Region of Zealand on behalf of the Danish Data Protection Agency (approval number REG-028-2019). Informed consent was not required, according to Danish law. All reporting was done in accordance with the STROBE statement.15