Reduced Risk of Medical Morbidity and Mortality in Patients Selected for Laparoscopic Colorectal Resection in England: Title and subTitle BreakA Population-Based Study

Elective colorectal resection is associated with low mortality but significant postoperative morbidity. Studies have described combined surgical and medical morbidity rates of 35% to 40%.^{1 - 2} Significant changes in the perioperative management such as minimal access surgery, short-acting anesthetics, regional anesthesia, and optimized postoperative pain relief with continuous epidural analgesia have been shown to accelerate postoperative recovery and reduce postoperative morbidity.^{3 - 4}

The use of laparoscopic surgery for colorectal resection represents a significant and recent change in clinical practice. Randomized controlled trials have demonstrated the feasibility and safety of laparoscopic surgery in adult patients undergoing elective colorectal resection.^{5 - 6} Specifically, the UK Medical Research Council Conventional vs Laparoscopic-Assisted Surgery in Colorectal Cancer trial has shown that laparoscopic surgery for colon cancer is as effective as open surgery in terms of oncological outcome and preservation of quality of life.⁷ In addition, the latter and other studies support the feasibility of laparoscopic rectal surgery in this context.^{7 - 8}

Minimal access surgery may offer certain advantages such as faster recovery, decreased pain, and quicker return to normal activity when compared with colorectal procedures undertaken by the conventional open approach.⁹ A population-based study using data from the American College of Surgeons National Surgical Quality Improvement Program has suggested that significant reduction in short-term morbidity occurs with use of laparoscopy for colectomy.¹⁰ Faiz et al¹¹ retrospectively analyzed routinely collected data of all English National Health Service patients undergoing elective colorectal resection. They showed that patients undergoing laparoscopic surgery were at lower risk of perioperative mortality when compared with those undergoing open procedures. The same study demonstrated that the lower mortality risk of laparoscopic surgery was evident even at 1 year following operative intervention. The latter investigation did not, however, describe the causes of patient death or incidence of postoperative complications. As such, no explanation for the observed reduction in mortality among patients treated using laparoscopy was offered.

The numerous aforementioned studies have ratified the safety and demonstrated a potential perioperative benefit for laparoscopic colorectal surgery. We hypothesized that the reduced operative trauma associated with the laparoscopic approach may contribute toward the favorable short-term outcome described in various studies. It should, however, follow that this benefit should be directly accompanied by a reduction in cardiovascular, respiratory, thromboembolic, renal, and other morbidity outcomes. This study aimed to quantify from a national routinely collected English data set the incidence of major medical morbidity following elective colorectal resection. Moreover, it aimed to evaluate potential differences in medical morbidity rates arising in the short- and intermediate-term between patients operated on using laparoscopic and conventional approaches.

Data were obtained from the Hospital Episode Statistics database. Patients undergoing elective colorectal resections between April 2001 and March 2008 were included. Patients were tracked for a period of 365 days following surgery for subsequent unplanned admissions with specific problems related to cardiac, respiratory, and renal systems along with venous thromboembolism (VTE) and stroke. Preoperative comorbidity status was ascertained by recording admissions with medical concerns for a 5-year period prior to the index operation. Diagnosis codes from the International Classification of Diseases, 10th Revision (ICD-10) were used to group the complications.¹²

The Hospital Episode Statistics database comprises administrative data from all English NHS trusts. This database has been previously described in detail in various studies.^{13 - 15} A single episode is made up of diagnoses fields categorized according to the ICD-10 codes and procedure fields coded using the Office of Population Censuses and Surveys Classification of Interventions and Procedures, Version 4.4.¹⁶

Index cases were identified using the following Office of Population Censuses and Surveys Classification of Interventions and Procedures, Version 4.4 codes for major colorectal resections:

If a patient had more than 1 resection during the study period, the first resection was taken as the index resection. The indications for surgery were categorized as malignancy (C18-C21), diverticulosis (K57), inflammatory bowel disease (Crohn, K50; ulcerative colitis, K51), and other diagnoses. Age was subcategorized into younger than 55 years, 55 to 69 years, 70 to 79 years, and older than 79 years. Nonelective or unplanned admissions and patients younger than 18 years were excluded from analyses. The Office of Population Censuses and Surveys codes used to identify laparoscopic cases were Y058 and Y752. Y714 is the code for failed minimal access, which has been in use since 2006. Patients undergoing procedures using the latter code were included in the laparoscopic group.

Postoperative medical morbidity was classified according to the presence of relevant ICD-10 codes (eTable). In analyzing complications according to an organ system, presence of any 1 complication pertaining to that system was considered. The presence of any of the earlier-mentioned diagnosis codes (acute and chronic) in admissions up to 5 years preceding the resection was termed as preoperative comorbidity. The presence of any of the acute codes postoperatively was termed as a morbidity or medical complication. For subsequent admissions, only the primary diagnosis code was used to identify medical morbidity. Thirty-day in-hospital mortality and 365-day in-and-out-of-hospital mortality were considered in our analysis. Three-hundred-sixty-five–day mortality was only available and analyzed for patients discharged before March 31, 2006. Length of stay was taken as the duration (in days) spent in the hospital during the primary admission. Median lengths of stay (± the interquartile range [IQR]) are described. Reintervention was defined as any return to the operating theater on the index admission or on a subsequent admission within 28 days of the initial resection. This was either for laparotomy, intra-abdominal abscess drainage (image-guided or open approach), stoma, or wound complications requiring reoperation.

Statistical analyses were carried out using SPSS version 18.0 (IBM SPSS). Categorical variables were investigated using the χ² test. For tests of significance, P values <.05 were considered significant. Medians and IQRs have been presented for nonnormal variables. Multiple regression analyses were carried out to identify predictors of postoperative medical morbidity with these covariates: age, sex, diagnosis, type of resection, surgical approach (ie, laparoscopic or open surgery), preoperative comorbidity, and reintervention or return to the operating theater within 28 days. Subgroup analyses were performed using the χ² test and Mann-Whitney U test for categorical and continuous variables, respectively.

A total of 212 248 colonic and rectal resections were carried out between April 1, 2001, and March 31, 2008; 138 735 (65.4%) resections were elective or planned and 73 513 (34.6%) were nonelective. Of the elective resections, 92.9% (128 840) were open procedures and 7.1% (9895) were laparoscopic. In the analysis, laparoscopic surgery converted to open surgery was included in the laparoscopic group. The percentage of laparoscopic procedures performed each year increased significantly between 2001-2002 (0.8%) and 2007-2008 (19.6%). The frequencies of colorectal resections performed are described in Table 1. Detailed analyses were performed only for elective resections.

The characteristics of patients undergoing elective colorectal resection between the study dates are described in Table 2. The median patient age was 69 years (IQR, 59-77 years) and there were slightly more men (52.9%; n = 73 379) within the study population. Overall, 70.1% (n = 97 303) of resections were assigned a diagnostic code for colorectal malignancy and just over half of all resections were colonic procedures (53.1%; n = 73 724). Preoperative comorbidity was summarized according to organ system. The most frequently occurring comorbidities were those assigned cardiac, respiratory, and diabetic codes (Table 2).

Overall, 30-day in-hospital mortality was 3.3% (n = 4515 of 138 735). Thirty-day mortality following open colorectal surgery was 3.4% (n = 4351) and 1.7% (n = 164) after a laparoscopic procedure (P < .001). Overall, mortality within 365 days of the index procedure was 11.9% (n = 8958 of 75 101). Mortality at 1 year was higher among patients undergoing conventional surgery (12.1%; n = 8875 of 73 540) vs laparoscopic surgery (5.3%; n = 83 of 1561) (P < .001). Multiple logistic regression models for 30-day and 365-day mortality were developed with case-mix adjustment for surgical approach, age, sex, diagnosis, type of resection, and reintervention (Table 3). Laparoscopic surgery was identified as strongly associated with reduced mortality when compared with traditional surgery and corrected for other covariates (odds ratio [OR] 0.46; 95% confidence interval [CI], 0.39-0.53; P < .001 for 30-day mortality and OR, 0.43; 95% CI, 0.34-0.54; P < .001 for 365-day mortality). Other statistically significant determinants of mortality were advanced patient age (P < .001) and male sex (P < .001). The risk of death within 30 days of surgery was doubled in the presence of preoperative renal failure (P < .001) and previous stroke (P < .001).

Overall, the median length of stay for patients treated with conventional surgery was 12 days (IQR, 9-17 days) and for those who underwent laparoscopy, 7 days (IQR, 5-11 days). The median length of stay for patients who had no medical complication during their index admission was 11 days (IQR, 8-15 days) while that for patients with at least 1 medical complication postoperatively was 15 days (IQR, 11-25 days).

The presence of any single (or multiple) postoperative complication(s) was classified as medical “morbidity.” Frequencies of specific medical complications following elective colorectal resection are shown in Table 4. The overall 30-day morbidity rate was 14.6%. Morbidity occurred within 30 days in 14.8% of open cases and 12.4% of laparoscopic cases (P < .001). Medical morbidity occurring within 365 days of surgery was also lower among patients treated using the laparoscopic approach (15.8% for the open group and 13.6% for the laparoscopic group; P < .001). Medical complications were classified per organ system involvement as cardiac, respiratory, VTE (deep vein thrombosis [DVT] and pulmonary embolism), renal failure, and cerebrovascular (ischemic stroke).

Unadjusted analyses revealed that cardiac, respiratory, VTE, stroke, and renal complications arose less frequently in patients undergoing laparoscopic procedures (Table 4). Specific medical complications such as myocardial infarction, congestive cardiac failure, respiratory failure, pneumonia, DVT, and pulmonary embolism were coded more frequently in patients undergoing conventional surgery. The laparoscopic approach was associated with reduced postoperative morbidity following risk adjustment for age, sex, diagnosis, resection, and comorbidity (Table 5 and Table 6). Patients selected for laparoscopic surgery were at lower risk of cardiac (OR, 0.79; P < .001), respiratory (OR, 0.78; P < .001), VTE (OR, 0.55; P = .001), stroke (OR, 0.46; P = .008), and renal (OR, 0.72; P = .001) morbidity at 30 days following surgery. At 1 year, the same cohort demonstrated a lower risk of cardiac (OR, 0.68; P = .001), respiratory (OR, 0.75; P = .03), and VTE (OR, 0.41; P = .049) complications as compared with the open group. The risk of developing postoperative medical complications was higher in the presence of preoperative comorbidity (Table 7) and where postoperative reintervention occurred. Patients with previous thromboembolic complications demonstrated a significantly elevated risk of developing DVT or pulmonary embolism up to 1 year following surgery (OR, 9.79; 95% CI, 7.06-13.56; P < .001). The presence of a preoperative diagnosis of diabetes mellitus predisposed to postoperative cardiac complications (OR, 1.14) and renal failure (OR, 1.71) (P < .001).

We tested for an interaction between surgical approach and age with patients younger than 55 years and undergoing open surgery as the reference group. This showed that patients aged 55 to 80 years and undergoing laparoscopic surgery had a lower risk of mortality (P < .001). Only elderly patients older than 80 years showed a higher risk of death when compared with those younger than 55 years (OR, 1.26; 95% CI, 1.00-1.59; P = .049). Similar analysis for comorbidity and surgical approach demonstrated that patients with preoperative comorbidity who underwent laparoscopic surgery had a 44% lower risk of mortality when compared with those in the open group but with no comorbidity (OR, 0.56; 95% CI, 0.44-0.79; P < .001).

Elective colorectal surgery is associated with significant postoperative medical and surgical morbidity.^{1 - 2 ,17 - 18} The current study has quantified from a routinely collected English national database the medical complications occurring following elective colorectal resection. This study has demonstrated that the incidence of medical morbidity is substantial in these patients not only in the immediate postoperative period but thereafter also. In recent years, laparoscopic surgery has become a viable alternative to the conventional approach to elective colorectal resection. This national observational study has demonstrated lower mortality and medical morbidity risk in patients selected for the laparoscopic approach to colorectal resection.

Cardiac events such as myocardial infarction, angina, and congestive heart failure have been found to occur in approximately 5% of patients undergoing noncardiac surgery and in about 30% of patients classified as high-risk surgical candidates.¹⁹ General anesthesia is associated with respiratory effects including reduced vital capacity, decreased respiratory rate, and inefficient breathing resulting in a decrease in lung expansion and gas exchange.²⁰ The physiological impact of the pneumoperitoneum incurred at the time of laparoscopy includes an increase in cardiac afterload with an associated decrease in venous return.^{21 - 22} Our findings suggest, however, that such intraoperative physiological changes do not translate into increased postoperative complications. Case series and small trials are usually not adequately powered to identify differences in rarely occurring events.²³

In the present investigation, patients undergoing laparoscopic surgery demonstrated a lower incidence of acute myocardial infarction, congestive cardiac failure, pneumonia, and acute respiratory failure. An explanation for these findings might be accounted for by the reduced surgical stress inflicted by laparoscopic surgery when compared with traditional care. Minimal access surgery for colorectal resection is associated with reduced postoperative pain, earlier mobilization, and earlier return of bowel function.^{24 - 25} However, these benefits are dually associated with enhanced-recovery protocols also. In the United Kingdom, many enthusiasts for laparoscopy are also proponents of enhanced recovery. In our study, an excess of patients receiving enhanced-recovery care in the laparoscopic group could potentially have contributed, to some extent, to the reduced morbidity identified in this group. Conversely, it has to be acknowledged that laparoscopy represents a major component of enhanced-recovery protocols and may mediate an accelerated recovery through an attenuated surgical stress response.^{26 - 28}

The current study has identified important findings regarding VTE risk and colorectal surgery. Patients selected to undergo a laparoscopic approach were at nearly half the risk of developing VTE at 30 days when compared with those undergoing open surgery. Routine inpatient data (as relate to our findings) are unlikely to identify a significant proportion of cases of DVT that are treated on an outpatient basis if occurring beyond discharge. On analysis of DVT cases on the index admission, however, a statistically significant increase in the incidence of DVT following open surgery was still identified. This may in part be explained by a higher number of patients with a history of VTE in the open group. Risk adjustment including preoperative comorbidity demonstrated a 10-fold risk in developing VTE within 30 days of surgery among patients with a history of VTE. Certainly, laparoscopy is associated with early ambulation, which may limit postoperative venous stasis. Conversely, prospective randomized studies comparing laparoscopic surgery with the open approach have reported longer operations in the laparoscopic group,^{29 - 30} potentially predisposing toward intraoperative venous stasis. As stated previously, a confounding factor such as greater use of thoracic epidural analgesia in laparoscopic surgery, which cannot be substantiated from this study but is an intervention associated with reduced thromboembolic events, might account for this finding. Last, the surgical stress response is a recognized procoagulant state. The reduced stress response following laparoscopic surgery may therefore explain the study findings. To this extent, the reduced tissue trauma associated with less intraoperative blood loss and lower transfusion requirements appear to be more important determinants of outcome.^{31 - 32}

The benefits of laparoscopic surgery are not limited to the younger population. Studies have suggested that it is safe and beneficial among high-risk groups such as morbidly obese patients and those with high American Society of Anesthesiologists grades.^{33 - 35} Studies have also ratified its safety in elderly cohorts.^{32 ,36} This has prompted an increase in the use of minimally invasive techniques in elderly patients. Age-related reduction in physiological reserves and presence of comorbidities make elderly patients susceptible to complications. From the covariate interaction analyses in our study, it is possible to suggest that laparoscopy is safe and possibly advantageous among elderly patients and those with associated comorbidity.

The current study analyzed routinely collected data. Such data are collected by nonclinicians, albeit trained coders, which questions the reliability. However, the accuracy of UK hospital administrative data was found to approximate 84% and 97% for diagnostic and operation codes, respectively, in a systematic review of coding accuracy.³⁷ The strengths of these routinely collected data sets are that they capture all patients and thereby negate the potential reporting bias inherent in any carefully selected series of patients. However, this study is not immune to selection bias regarding the surgical approach, and evidence from randomized controlled trials with carefully constrained inclusion criteria is essential to draw firm conclusions. Obesity is a known predictor of postoperative morbidity following colectomy.^{38 - 39} Although some recent studies have shown laparoscopic colectomy to be feasible in obese patients with comparable outcomes with nonobese patients, many surgeons remain hesitant to offer a minimally invasive approach to this patient group.^{40 - 42} Hospital Episode Statistics data do not include patient body mass index and hence cannot account for this potential difference in patient selection. Similarly, a history of abdominal surgery cannot be ascertained from administrative data sources such as Hospital Episode Statistics and may lead to unaccounted for bias between patients selected for the conventional and laparoscopic approach. Nevertheless, the large numbers of patients involved in such population-based series mean that rarely occurring events can be detected in sufficient volume to permit comparative analyses. One further limitation that we recognize is that morbidity occurring outside of the hospital, ie, managed on an outpatient basis, was not included in our data. Thus, this study underestimates total complications occurring following surgery. Severe complications are, however, likely to require readmission and therefore be included. For these reasons, as well as the exclusion of surgical morbidity, we accept that total actual postoperative morbidity is likely to be higher than our recorded figures.

Using a national database, this study has quantified the medical morbidity arising following elective colorectal resection. Patients selected for the laparoscopic approach in this large population-based observational study were at reduced risk of mortality as well as cardiorespiratory and possibly venous thromboembolic complications in the short- and intermediate-term.