Abstract
Introduction:
The relationship between preoperative hyperglycemia and complications after surgery is not well defined. We compared the relationship of preoperative versus postoperative hyperglycemia on clinical outcomes and assessed if preoperative hyperglycemia was a predictor for postoperative hyperglycemia in patients undergoing elective colorectal surgery.
Methods:
We performed a retrospective review of an institutional database for patients undergoing elective colorectal resection between July 2015 and June 2017. Data regarding patient characteristics, history of diabetes, preoperative and postoperative hyperglycemic events, and postoperative complications were collected. Bivariate and multivariate logistic analyses were used to assess relationships.
Results:
With 755 surgical operations, preoperative hyperglycemia >180 mg/dL was not significantly associated with adverse outcomes in an adjusted model. Only postoperative hyperglycemia >180 mg/dL was significantly associated with complications, including acute kidney injury (OR 2.58, p<0.001), anastomotic leak (OR 2.64, p=0.01), arrhythmia (OR 2.40, p=0.009), and sepsis (OR 3.86, p<0.001). Preoperative hyperglycemia remained a significant predictor of postoperative hyperglycemia (OR 4.91, p<0.001).
Conclusions:
Postoperative hyperglycemia was more significantly associated with adverse clinical outcomes after elective colorectal surgery than was preoperative hyperglycemia. However, preoperative hyperglycemia was associated with postoperative hyperglycemia, suggesting that improved glycemic management preoperatively may help reduce hyperglycemic events after surgery.
Introduction
Hyperglycemia has emerged as a modifiable mediator of adverse events after surgery. Potential mechanisms for these outcomes include the vascular, inflammatory, and hemodynamic derangements that occur as a result of persistently elevated glucose levels, all of which can contribute to the risk of morbidity and mortality after surgery.1 Retrospective studies spanning multiple surgical specialties, including general surgery,2 colorectal surgery,3 cardiac surgery,4 vascular surgery,5 and orthopedic surgery,6 have continued to strengthen the link between hyperglycemia and complications after surgery. Specifically, in general surgery patients, the oft-cited study by Kwon et al. utilized the Surgical Care and Outcomes Assessment Program (SCOAP) from Washington state and concluded that postoperative hyperglycemia in general surgery patients was significantly associated with infection, operative interventions, and death.2 Similarly, Kiran et al. linked postoperative hyperglycemia to both infectious and noninfectious complications in patients undergoing colorectal surgery.3
Following these landmark studies, the vast majority of studies have continued to focus on the link between postoperative hyperglycemia and morbidity and mortality after surgery. However, the role that preoperative hyperglycemia may have on these same clinical outcomes has not been as thoroughly evaluated, particularly in patients undergoing elective colorectal surgery. Understanding drivers of adverse outcomes in this cohort of patients is especially important, as these patients oftentimes present with elevated inflammatory conditions and are potentially more susceptible to worse outcomes after undergoing complex resections and anastomoses. Additionally, a better understanding of the relationship between preoperative hyperglycemia to the development of postoperative hyperglycemia may offer surgeons the opportunity to intervene and optimize glycemic control in the preoperative phase to improve outcomes. The objective of this study was to assess the clinical significance of preoperative hyperglycemia on patient outcomes after elective colorectal surgery by comparing the relationship of preoperative versus postoperative hyperglycemia with morbidity after surgery and by assessing whether preoperative hyperglycemia was a potential predictor of postoperative hyperglycemia in this population of patients.
Methods
Study Design and Patient Population:
We conducted a retrospective cohort study on patients undergoing elective colorectal surgery at Northwestern Memorial Hospital from July 2015 to June 2017. Data were abstracted and de-identified from a query of the institutional electronic medical record for patients undergoing colon or rectal resection, with or without anastomosis. Operations included for study were standard and extended right and left colectomy, sigmoid resection, low anterior resection, abdominoperineal resection, total proctocolectomy, total abdominal colectomy, and subtotal colectomy. Open, laparoscopic, open converted to laparoscopic, and laparoscopic-assisted cases were included. We excluded patients less than 18 years old, cases coded as emergent, or performed via a transanal approach or isolated pelvic resection, as has been established previously.3 These surgeries were excluded due to differences in patient type, physiological response and perioperative management when compared to an elective transperitoneal colorectal resection. The data abstraction was part of an ongoing quality improvement project at our institution and deemed Institutional Review Board (IRB) exempt. The majority of operations were performed by three colorectal-fellowship trained surgeons on a dedicated colorectal surgery service at our institution.
Study Variables and Statistical Analysis:
Basic patient demographics, clinical history, and operative details were abstracted from the electronic medical record. Data abstracted included age, sex, race, body mass index (BMI) closest to admission, American Society of Anesthesiologist (ASA) classification, indication and type of operation performed, and patient disposition. Indications were classified as for benign or malignant neoplasm, inflammatory bowel disease, or other indication (e.g., diverticulitis or prolapse).
Diagnosis of diabetes was determined based on whether the patient had the diagnosis documented in his/her chart at the time of preoperative screening. Hyperglycemia was defined as a blood glucose value >180 mg/dL, due to established glycemic targets recommended by multiple organizations, including the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists.7,8 A preoperative hyperglycemic event was then defined as a blood glucose value >180 mg/dL within 90 days prior to the surgery date. A postoperative hyperglycemic event was defined as blood glucose level >180 mg/dL during a patient’s initial postoperative stay, for up to 90 days, drawn from a point-of-care glucometer check or blood chemistry value.
Complications after surgery were extrapolated from the electronic medical record based on laboratory values and diagnosis codes up to 90 days after surgery. Degree of postoperative kidney injury was stratified based on thresholds from the Acute Kidney Injury Network (AKIN) classification, with a 1.5x increase over baseline creatinine corresponding to Stage 1 acute kidney injury, and 2.0x increase over baseline creatinine corresponding to Stage 2 acute kidney injury.9 Baseline creatinine was defined as a patient’s last known preoperative creatinine. Other studied clinical outcomes included anastomotic leak, arrhythmia, urinary tract infection (UTI), and sepsis. Patients were deemed to have an anastomotic leak if the diagnosis appeared in their chart. Each individual diagnosis of anastomotic leak was determined based on a combination of clinical, biochemical, radiographic, or intraoperative findings. Association of hyperglycemia, either preoperatively or postoperatively, to these complications was first assessed using standard bivariate analysis. Multivariate logistic regression was then utilized to obtain odds ratios adjusted for established clinical risk factors, including patient’s age, ASA classification, sex, and diagnosis of diabetes.
We then sought to assess potential predictors for postoperative hyperglycemia in our cohort of patients. In addition to preoperative blood glucose, other clinical covariates were chosen based on their potential to be indicators for hyperglycemia or diabetes screening in the preoperative phase. Clinical covariates included age, sex, BMI, diagnosis of diabetes and race. Predictors were coded as binary or categorical variables. Preoperative blood glucose was assessed at two thresholds: mild preoperative hyperglycemia >125 mg/dL or high preoperative hyperglycemia >180 mg/dL. A threshold of 125 mg/dL was chosen based on prior study thresholds for defining and examining mild hyperglycemia in surgical patients.3,10 Age was categorized as <45 years or ≥45 years old based on recommendations from the American Diabetes Association for initiating screening for type 2 diabetes on patients 45 years or older.11 BMI was categorized as <35 kg/m2 or ≥35 kg/m2. Race was categorized based on patient self-reporting into White or Caucasian, Black or African American, Other, or declined to answer or unknown. White or Caucasian was used as the baseline group for comparison. These clinical variables were analyzed independently to assess association with postoperative hyperglycemia using univariate logistic regression. Significantly associated variables in univariate logistic analysis were then added into a multivariate logistic regression model to determine adjusted odds ratios for association with postoperative hyperglycemia. P value <0.05 was deemed statistically significant for all analyses. Data analysis was generated using STATA (v15.1, StataCorp LLC., College Station, TX) and SAS software (v.9.4, SAS Institute Inc., Cary, NC).
Results
Patient Demographics and Incidence of Hyperglycemia:
After exclusion criteria were applied, 755 patients were included from within the study period. The study population was 50% male (n=378) and 50% female (n=377), with a median age of 57 years (IQR: 45-67). Mean BMI was 27.1 ± 6.6 kg/m2 and 17% (n=127) of patients carried a diagnosis of diabetes. Distribution of operations performed included 32% (n=242) right or extended right colectomies; 23% (n=174) left, extended left or sigmoid colectomies; 24% (n=181) low anterior (LAR) or abdominoperineal resections (APR); and 21% (n=158) subtotal or total colectomies. A laparoscopic or laparoscopic-assisted approach was utilized in 41% (n=310) of cases. Conversely, an open or laparoscopic converted to open approach was utilized in 59% (n=445) of operations. Indications for surgery were 43% (n=325) for benign or malignant neoplasm; 21% (n=158) for inflammatory bowel disease; and 36% (n=272) for diverticulitis or other indication. A total of 33% (n=252) of patients had mild preoperative hyperglycemia with a blood glucose value >125 mg/dL, and 11% (n=85) of patients had high preoperative hyperglycemia with a blood glucose value >180 mg/dL. Postoperative hyperglycemia >180 mg/dL occurred in 23% (n=175) of patients. The overall incidence of specific complications was 11% (n=81) for 1.5x increase over baseline creatinine, 4% (n=32) for 2.0x increase over baseline creatinine, 5% (n=35) for anastomotic leak, 6% (n=44) for arrhythmia, 5% (n=41) for UTI and 4% (n=32) for sepsis. A summary of the study cohort is provided in Table 1.
Table 1:
Cohort Characteristics
| Total Patients | 755 |
| Age, median (IQR) | 57 (45-67) |
| Sex, no. (%) | |
| Male | 378 (50%) |
| Female | 377 (50%) |
| Diagnosis of Diabetes, no. (%) | 127 (17%) |
| BMI (kg/m2), mean (SD) | 27.1 (6.6) |
| Race, no. (%) | |
| White | 573 (77%) |
| Black | 81 (11 %) |
| Other | 64 (9%) |
| Declined to Answer / Unknown | 37 (5%) |
| ASA Classification, no. (%) | |
| I – II | 430 (57%) |
| III – IV | 325 (43%) |
| Indication for Operation, no. (%) | |
| Neoplasm | 325 (43%) |
| Inflammatory Bowel Disease | 158 (21%) |
| Diverticulitis / Other | 272 (36%) |
| Resection Type, no. (%) | |
| Right / Extended Right | 242 (32%) |
| Left / Extended Left / Sigmoid | 174 (23%) |
| LAR/APR | 181 (24%) |
| Subtotal / Total Colectomy | 158 (21%) |
| Surgical Approach, no. (%) | |
| Laparoscopic or Laparoscopic-Assisted | 310 (41%) |
| Open or Converted to Open | 445 (59%) |
| Complications, no. (%) | |
| 1.5x Baseline SCr | 81 (11 %) |
| 2.0x Baseline SCr | 32 (4%) |
| Anastomotic Leak | 35 (5%) |
| Arrhythmia | 44 (6%) |
| UTI | 41 (5%) |
| Sepsis | 32 (4%) |
| Blood Glucose Value, no. (%) | |
| Preoperative Blood Glucose >125 mg/dL | 252 (33%) |
| Preoperative Hyperglycemia >180 mg/dL | 85 (11 %) |
| Postoperative Hyperglycemia >180 mg/dL | 175 (23%) |
| HbA1c within 3 months, no. (% of values) | |
| <6.5% | 55 (58%) |
| 6.5-7.9% | 25 (26%) |
| >8.0% | 15 (16%) |
IQR indicates interquartile range; BMI, body mass index; SD, standard deviation; ASA, American Society of Anesthesiologists; SCr, serum creatinine; UTI, urinary tract infection; HbA1c, hemoglobin A1c
Association of Preoperative Hyperglycemia with Adverse Outcomes:
Preoperative hyperglycemia >180 mg/dL was independently associated with postoperative complications. On unadjusted bivariate analysis, preoperative hyperglycemia >180 mg/dL was independently associated with a 1.5x increase in baseline creatinine (Odds Ratio [OR]: 2.16, 95% Confidence Interval [CI] 1.18-3.94, p=0.01) and with a 2.0x increase in baseline creatinine (OR 3.33, 95% CI: 1.49-7.46, p=0.003). Preoperative hyperglycemia was also independently associated with arrhythmia (OR 2.87, 95% CI 1.39-5.92, p=0.004) and UTI (OR: 2.36, 95% CI: 1.09-5.13, p=0.03). Preoperative hyperglycemia was not significantly associated with anastomotic leak (OR 1.33, 95% CI 0.50-3.54, p=0.6) or with sepsis (OR 2.32, 95% CI 0.97-5.53, p=0.06). After adjustment for age, ASA classification, sex, and diagnosis of diabetes, preoperative hyperglycemia was no longer significantly associated with increased odds for postoperative complications (Table 2).
Table 2:
Association of Preoperative Hyperglycemia >180 mg/dL with Adverse Outcomes
| Unadjusted | Adjusted* | |||||
|---|---|---|---|---|---|---|
| Complication | OR | 95% CI | P | OR | 95% CI | P |
| Stage 1 Acute Kidney Injury (1.5x Baseline SCr) | 2.16 | (1.18 - 3.94) | 0.01 | 1.61 | (0.85 - 3.07) | 0.1 |
| Stage 2 Acute Kidney Injury (2.0x Baseline SCr) | 3.33 | (1.49 - 7.46) | 0.003 | 2.45 | (0.92 - 5.47) | 0.07 |
| Anastomotic Leak | 1.33 | (0.50 - 3.54) | 0.6 | 1.70 | (0.61 - 4.69) | 0.3 |
| Arrhythmia | 2.87 | (1.39 - 5.92) | 0.004 | 1.60 | (0.73 - 3.52) | 0.2 |
| UTI | 2.36 | (1.09 - 5.13) | 0.03 | 2.33 | (1.00 - 5.38) | 0.05 |
| Sepsis | 2.32 | (0.97 - 5.53) | 0.06 | 2.00 | (0.80 - 5.01) | 0.1 |
Clinical covariates included in adjusted model: age, ASA classification, sex, diagnosis of diabetes
Association of Postoperative Hyperglycemia with Adverse Outcomes:
Postoperative hyperglycemia >180 mg/dL after elective colorectal surgery was more significantly associated with adverse outcomes than was preoperative hyperglycemia. Patients with postoperative hyperglycemia >180 mg/dL had a significantly higher incidence of studied complications than patients with blood glucose ≤180 mg/dL (Figure 1). On unadjusted bivariate analysis, postoperative hyperglycemia >180 mg/dL was significantly associated with increased odds for postoperative complications, including a 1.5x increase in baseline creatinine (OR 2.58, 95% CI 1.59-4.16, p<0.001), a 2.0x increase in baseline creatinine (OR 4.05, 95% CI 1.98-8.30, p<0.001), arrhythmia (OR 4.03, 95% CI 2.17-7.47, p<0.001), UTI (OR 2.23, 95% CI 1.16-4.29, p=0.02) and sepsis (OR 4.05, 95% CI 1.98-8.30, p<0.001). Postoperative hyperglycemia was independently associated with increased odds for anastomotic leak at the threshold for statistical significance (OR 2.03, 95% CI 1.00-4.13, p=0.05). After adjustment for patient’s age, ASA classification, sex, and diagnosis of diabetes, postoperative hyperglycemia >180 mg/dL remained significantly associated with a 1.5x increase in baseline creatinine (OR 2.16, 95% CI 1.31-3.57, p=0.003), a 2.0x increase in baseline creatinine (OR 3.38, 95% CI 1.57-7.25, p=0.002), anastomotic leak (OR 2.64, 95% CI 1.25-5.65, p=0.01), arrhythmia (OR 2.40, 95% CI 1.25-4.63, p=0.009), and sepsis (OR 3.86, 95% CI 1.82-8.22, p<0.001). In the adjusted model, postoperative hyperglycemia >180 mg/dL was associated with UTI at the threshold for significance (OR 2.01, 95% CI 1.01-4.00, p=0.05) (Table 3).
Figure 1:
Unadjusted incidence rates of postoperative complications in patients with postoperative hyperglycemia >180 mg/dL versus patients with blood glucose ≤ 180 mg/dL (*p<0.001 / † p <0.05)
Table 3:
Association of Postoperative Hyperglycemia >180 mg/dL with Adverse Outcomes
| Unadjusted | Adjusted* | |||||
|---|---|---|---|---|---|---|
| Complication | OR | 95% CI | P | OR | 95% CI | P |
| Stage 1 Acute Kidney Injury (1.5x Baseline SCr) | 2.58 | (1.59 - 4.16) | <0.001 | 2.16 | (1.31 - 3.57) | 0.003 |
| Stage 2 Acute Kidney Injury (2.0x Baseline SCr) | 4.05 | (1.98 - 8.30) | <0.001 | 3.38 | (1.57 - 7.24) | 0.002 |
| Anastomotic Leak | 2.03 | (1.00 - 4.13) | 0.05 | 2.64 | (1.25 - 5.65) | 0.01 |
| Arrhythmia | 4.03 | (2.17 - 7.47) | <0.001 | 2.40 | (1.25 - 4.63) | 0.009 |
| UTI | 2.23 | (1.16 - 4.29) | 0.02 | 2.01 | (1.01 - 4.00) | 0.05 |
| Sepsis | 4.05 | (1.98 - 8.30) | <0.001 | 3.86 | (1.82 - 8.22) | <0.001 |
Clinical covariates included in adjusted model: age, ASA classification, sex, diagnosis of diabetes
Clinical Predictors of Postoperative Hyperglycemia:
Both mild preoperative hyperglycemia >125 mg/dL (OR 5.95, 95% CI 4.10-8.64, p<0.001) and high preoperative hyperglycemia >180 mg/dL (OR 13.95, 95% CI 8.04-24.21, p<0.001) were independently associated with postoperative hyperglycemia >180 mg/dL. Other significant independent clinical covariates with an association to postoperative hyperglycemia included diagnosis of diabetes (OR 18.57, 95% CI 11.61-29.70, p<0.001), age ≥45 years old (OR 2.34, 95% CI 1.44-3.80, p=0.001), ASA classification III / IV (OR 3.44, 95% CI 2.38-4.97, p<0.001) and BMI ≥35 kg/m2 (OR 2.09, 95% CI 1.34-3.28, p=0.001). Sex and race were not independently associated with increased odds for postoperative hyperglycemia in our study population. After adjustment for significant covariates in a multivariate regression model, mild preoperative hyperglycemia >125 mg/dL (OR 3.28, 95% CI 2.12-5.07, p<0.001) and high preoperative hyperglycemia >180 mg/dL (OR 4.91, 95% CI 2.55-9.42, p<0.001) remained significantly associated with postoperative hyperglycemia. In the multivariate logistic regression model incorporating high preoperative hyperglycemia >180 mg/dL, other significant clinical covariates associated with postoperative hyperglycemia included diagnosis of diabetes (OR 10.73, 95% CI 6.39-18.01, p<0.001) and ASA III / IV (OR 1.97, 95% CI 1.25-3.09, p=0.003) (Table 4).
Table 4:
Predictors of Postoperative Hyperglycemia >180 mg/dL
| Unadjusted | Adjusted† | |||||
|---|---|---|---|---|---|---|
| Variable | OR | 95% CI | P | OR | 95% CI | P |
| Mild Preoperative Hyperglycemia | ||||||
| ≤125 mg/dL | * | * | ||||
| >125 mg/dL | 5.95 | (4.10 - 8.64) | <0.001 | 3.28 | (2.12 - 5.07) | <0.001 |
| High Preoperative Hyperglycemia | ||||||
| ≤180mg/dL | * | * | ||||
| >180 mg/dL | 13.95 | (8.04 - 24.21) | <0.001 | 4.91 | (2.55 - 9.42) | <0.001 |
| Diabetes | ||||||
| No | * | * | ||||
| Yes | 18.57 | (11.61 - 29.70) | <0.001 | 10.73 | (6.39 - 18.01) | <0.001 |
| Age | ||||||
| <45 years old | * | * | ||||
| ≥45 years old | 2.34 | (1.44 - 3.80) | 0.001 | 1.32 | (0.74 - 2.34) | 0.35 |
| Sex | ||||||
| Male | * | |||||
| Female | 0.93 | (0.66 - 1.31) | 0.67 | |||
| ASA classification | ||||||
| I – II | * | * | ||||
| III - IV | 3.44 | (2.38 - 4.97) | <0.001 | 1.97 | (1.25 - 3.09) | 0.003 |
| BMI | ||||||
| <35 mg/kg2 | * | * | ||||
| ≥35 mg/kg2 | 2.09 | (1.34 - 3.28) | 0.001 | 0.90 | (0.49 - 1.64) | 0.73 |
| Race | ||||||
| White or Caucasian | * | |||||
| Black or African American | 1.60 | (0.96 - 2.70) | 0.07 | |||
| Other | 1.76 | (0.86 - 3.59) | 0.12 | |||
| Declined to Answer / Unknown | 0.93 | (0.45 - 1.91) | 0.84 | |||
Reference category
Significant independent clinical covariates included in adjusted model: diabetes, age, ASA classification, BMI
Discussion
In a population of patients undergoing elective colorectal surgery, postoperative hyperglycemia was more strongly associated with adverse clinical outcomes than was preoperative hyperglycemia. In this patient population, preoperative hyperglycemia >180 mg/dL was not significantly associated with a decline in renal function, anastomotic leak, arrhythmia, UTI, or sepsis after adjustment for confounding clinical variables. In contrast, postoperative hyperglycemia >180 mg/dL was significantly associated with these studied complications, conveying a 2- to nearly 4-fold increased odds for morbidity after colorectal surgery. Demonstrating the clinical significance of preoperative glucose control, patients with preoperative hyperglycemia were more likely to be hyperglycemic postoperatively, with preoperative hyperglycemia >180 mg/dL conveying approximately a 5-fold increased odds for postoperative hyperglycemia after adjustment for clinical covariates.
The link between postoperative hyperglycemia and complications after surgery has been demonstrated previously, including with large scale, retrospective cohort studies.2,3,12 Whether preoperative hyperglycemia has a similar relationship with these surgical complications has been less well-studied, as preoperative blood glucose values are not routinely included in the databases that have been utilized in these prior studies. To begin to address this issue, Ata et al. independently abstracted preoperative blood glucose values from a review of their institutional electronic medical record. Their study concluded that in a cohort of 1,561 general surgery patients and in a subgroup analysis of 226 colorectal surgery patients, preoperative hyperglycemia was not significantly associated with surgical site infection (SSI).13 Building upon these results, we have expanded the group of colorectal surgery patients studied to 755 patients and were able to examine the potential association of preoperative hyperglycemia to additional complications other than SSI. Similarly to the results of Ata et al., we also found that preoperative hyperglycemia was not significantly associated with adverse outcomes after surgery. We did not observe a significant relationship between preoperative hyperglycemia and a decline in renal function, anastomotic leak, arrhythmia, UTI, or sepsis after adjustment for clinical covariates. The absence of increased clinical morbidity as seen by both Ata et al. and our study contrasts the results of a study performed by Davis et al., which did demonstrate a link between preoperative hyperglycemia and adverse outcomes in a cohort of neurosurgery patients.14 These conflicting findings likely allude to the major differences in baseline patient characteristics, types of operations performed, perioperative management, and clinical outcomes between neurosurgery patients and elective colorectal surgery patients.
Given the breadth of observational evidence linking postoperative hyperglycemia with adverse outcomes after surgery, the American Diabetes Association and the American Association of Clinical Endocrinologists have released a consensus statement, recommending 180 mg/dL as the upper threshold for blood glucose in both critically and noncritically ill patients.8 Therefore, identifying and quantifying patient risk factors for postoperative hyperglycemia offers the possibility of targeting interventions on these at risk patients and optimizing their blood glucose prior to surgery. In patients undergoing cardiac surgery, Garg et al. identified preoperative patient characteristics that were associated with postoperative hyperglycemia; characteristics included age, BMI, male sex, and comorbidities such as hypertension and hypercholesteremia. Notably, in their cohort of cardiac surgery patients, the authors found no significant difference in mean preoperative blood glucose values between postoperative normoglycemic and hyperglycemic patients.15 Conversely, in our cohort of colorectal surgery patients, we found that preoperative hyperglycemia was a predictor for postoperative hyperglycemia and that the degree of association increased in a dose response relationship with the severity of hyperglycemia. After adjustment for significant clinical covariates, mild preoperative hyperglycemia >125 mg/dL conveyed a 3-fold increased odds for postoperative hyperglycemia. Comparatively, high preoperative hyperglycemia >180 mg/dL was associated with nearly a 5-fold increased odds for developing hyperglycemia in the postoperative setting. Given that mild hyperglycemia is a relatively common occurrence preoperatively and is oftentimes considered unproblematic, these findings suggest that even mild preoperative hyperglycemia may have consequences and that additional glycemic optimization in the preoperative phase may be beneficial to encompass and optimize these newly at-risk individuals.
In addition to preoperative blood glucose control, other significant predictors for postoperative hyperglycemia included age ≥45 years old, BMI ≥35 kg/m2, diagnosis of diabetes and ASA classification III / IV. The link between a patient’s preoperative characteristics with the development of hyperglycemia postoperatively suggests that the hyperglycemia that develops after surgery is likely more than just a result of the post-surgery stress response. Rather, a patient’s preoperative characteristics, such as underlying blood glucose control, may directly contribute to the pathogenesis of hyperglycemia after surgery. This relationship offers surgeons the opportunity to treat or adjust these baseline characteristics with the goal of reducing postoperative hyperglycemia and its associated complications.
Taking these results into consideration, we have initiated a quality improvement project focused on perioperative glucose management in patients undergoing elective colorectal surgery at our institution. Part of these new protocols are standardized screening guidelines, including preoperative blood glucose checks on all patients ≥45 years old or with a BMI >35 kg/m2 to assess for undiagnosed diabetes and to potentially improve glycemic control prior to surgery. On the postoperative side, the central tenet of this project is directed at creating a basal-bolus insulin therapy order set that will be initiated by the surgery team. This initiative is based on prior studies that have shown that insulin therapy can reduce the complication rates associated with hyperglycemia.2,16 Furthermore, in a randomized control trial in general surgery patients with type 2 diabetes, basal-bolus insulin therapy was more effective than sliding-scale insulin administration in regards to postoperative glycemic control, without an increase in significant hypoglycemia.17 The ADA now recommends that basal-bolus insulin therapy be the preferred method of glycemic control for patients with diabetes, including those with poor or no oral intake. For those with better nutritional intake, the ADA recommends the addition of a prandial dose of insulin.18 Predetermined basal-bolus insulin protocols such as those being developed at our institution, help to reduce the reliance on sliding scale insulin regimes and serve to educate prescribers, including surgeons and surgery residents, on the appropriate and effective dosing of basal-bolus insulin therapy postoperatviely.19 Our study, among others, emphasizes the association between postoperative hyperglycemia with worse outcomes after surgery and calls for improved glycemic management in surgical patients.
This study has notable limitations. As a retrospective study, our study was not designed to determine if hyperglycemia can directly result in the complications seen, but can only infer associations. Further investigation into the inflammatory and vascular changes directly induced by hyperglycemia and the effect these changes have on the development of adverse outcomes after surgery is warranted. We also acknowledge that there is sample bias inherent to a single institution study of this scope. However, by limiting our analysis to patients undergoing elective colorectal resection at a single institution, we reduce potential confounding effects due to differences in surgical technique and perioperative management. By defining the diagnosis of diabetes based on its appearance in the patient’s chart, we also miss any patients with undiagnosed diabetes and likely underrepresent the true incidence of diabetes in our population. In addition, we may potentially underestimate both the true incidence of preoperative hyperglycemia as well as postoperative complications if patients respectively did not have blood glucose values drawn preoperatively or were lost to follow-up after their surgeries. Finally, though we used multivariate regression models to assess for the effect of confounding variables, we acknowledge that there are likely additional significant variables that upon incorporation into our model may adjust the results seen. Future studies utilizing comprehensive databases that include preoperative, intraoperative and postoperative blood glucose values are warranted to further assess the relationship of preoperative blood glucose to postoperative hyperglycemia as well as complications after surgery.
In conclusion, in a cohort of patients undergoing elective colorectal surgery, postoperative hyperglycemia >180 mg/dL was more significantly associated with adverse outcomes after surgery than was preoperative hyperglycemia. Notably, preoperative hyperglycemia was a predictor for the development of postoperative hyperglycemia after elective colorectal surgery, with the degree of association increasing with the severity of preoperative hyperglycemia. Other significant predictors included age ≥45 years old, BMI ≥35 kg/m2, diagnosis of diabetes, and ASA classification III / IV. Overall, these findings suggest that improved preoperative glycemic control may reduce the incidence of postoperative hyperglycemic events and may lead to improved clinical outcomes after elective colorectal surgery.
Acknowledgments
Funding/Support
Work reported in this publication was partially supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number T32HL094293 in the form of partial stipend support for authors EBC and MJN. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Authors EBC and MJN were also partially supported in the form of a partial stipend by the Abbot Fund.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Conflicts of Interest/Disclosure
The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.
Presented at the 76th Annual Meeting of the Central Surgical Association, Palm Harbor, FL, March 9th, 2019.
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