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Regional Anesthesia: Research Report

The Effect of Intraoperative Blood Glucose Management on Postoperative Blood Glucose Levels in Noncardiac Surgery Patients

Nair, Bala G. PhD; Horibe, Mayumi MD; Neradilek, Moni B. MS; Newman, Shu-Fang MS; Peterson, Gene N. MD, PhD

Author Information
doi: 10.1213/ANE.0000000000001100

Uncontrolled perioperative hyperglycemia has been associated with an increased risk of postoperative morbidity and mortality.1–10 Although an optimal target glucose range remains unknown, there is general consensus that adequate glycemic control, without hypoglycemia and excessive hyperglycemia, results in better surgical outcome.11–18 Thus far, studies on perioperative glucose management have primarily focused on the postoperative phase.1,3,7,8,10 These studies have shown positive association between postoperative hyperglycemia and poor surgical outcome in both cardiac and surgery patients. However, studies specifically focused on intraoperative glycemic management and patient outcome have been limited to cardiac surgery patients.4,5,9 In cardiac surgery patients, intraoperative hyperglycemia and large glycemic variability have been shown to have a positive association with postoperative complications. For the above reasons, intraoperative glucose management is given close attention during cardiac surgery with the goal to minimize hyperglycemia in the intraoperative and postoperative periods. However, thus far, the association between intraoperative glucose level and surgical outcome in surgery patients remains poorly understood. Even less understood is the effect of intraoperative glucose management on postoperative glucose levels in these patients. Because postoperative hyperglycemia has been associated with postsurgical complications even in surgery patients,3,6–8,16,17 an obvious question that arises is whether adequate intraoperative glucose control could lead to better postoperative glucose levels, which in turn could lead to better postoperative outcomes. Specifically, would adequate intraoperative glucose management provide a good starting point for postoperative glucose management resulting in better postoperative glycemic levels?

In this study, we explored the association between intraoperative glycemic levels and corresponding postoperative glycemic levels. In addition, we explored whether better intraoperative glycemic control leads to better postoperative glycemic levels.


Study Setting

We performed a retrospective cohort study of surgery patients who required intraoperative glucose management at our medical center. Our institution is an academic medical center that performs approximately 17,000 adult surgical procedures every year. Anesthesia providers practicing at our institution include attending anesthesiologists, residents, and Certified Registered Nurse Anesthetists. Our institution uses a standardized protocol of glycemic management that recommends an intraoperative glucose target 100 to 140 mg/dL (Appendix 1). The study was approved by our IRB.

Inclusion and Exclusion Criteria

Adult surgery patients (18 years or older) who had glucose management recommended by our institutional glucose management protocol during the years 2011 to 2013 were considered. Diabetic patients and nondiabetic patients who had at least 1 intraoperative blood glucose measurement higher than 140 mg/dL were included. Because the goal of the study was to determine the association between intraoperative and postoperative glucose levels, only cases that had intraoperative glucose and subsequent postoperative glucose measured were considered for analysis. In addition, very short duration cases (<1 hour) for which glucose management is normally not performed by anesthesia providers were excluded.

Data Sources

Intraoperative anesthesia care at our institution is documented through an anesthesia information management system (AIMS). The AIMS automatically acquires and documents blood glucose measurements performed by both central laboratory and point-of-care glucose meters. Patient characteristics, such as diabetes status, medication history, and postoperative glucose results, are documented in a hospital information management system and archived in a data warehouse called AMALGA (Microsoft Inc., Redmond, WA). Both intraoperative and postoperative glucose management and patient- and surgery-specific data were retrospectively extracted from the AIMS and AMALGA databases. Data were extracted for the entire period of the study.

Being a retrospective study based on electronic medical record data, we chose to use all available data for this study. Because the sample size was expected to be quite large and more than adequate for this study, we did not perform a sample size calculation a priori.

Study Outcomes

Figure 1:
Visual representation of the main analyses steps.

The first study outcome determined the association between the mean intraoperative and the postoperative glucose levels. Specifically, the mean intraoperative glucose levels were compared against the first postoperative glucose levels within 60 minutes of leaving the operating room and the mean glucose levels within the first 12 and 24 hours of postoperative admission. A second study outcome determined the association between intraoperative glucose levels exceeding 2 thresholds (140 and 180 mg/dL) and the occurrence of postoperative hyperglycemia. The hyperglycemia threshold for the study was chosen as ≥180 mg/dL, a commonly recommended limit of severe hyperglycemia below which perioperative glucose levels should be maintained.12,14,19 Postoperative hyperglycemia within the first 12 and 24 hours of the postoperative period was considered for this analysis. A third study outcome compared mean postoperative glucose levels, as well as occurrence of postoperative hyperglycemia (>180 mg/dL) and hypoglycemia (<60 mg/dL), for 2 scenarios, one in which the intraoperative insulin was started at a glucose threshold of 140 mg/dL (our institutional threshold for initiating insulin infusion) to avoid hyperglycemia and the other in which intraoperative insulin was started but hyperglycemia was not avoided. For the third study, outcome-only surgical procedures ≥2 hours in duration and those with a glucose measurement frequency >1 measurement every 2 hours during both intraoperative and postoperative periods were considered. The main analysis steps are shown in Figure 1. We also conducted a secondary analysis to determine the postoperative glucose levels in diabetic patients who did not have glycemic management initiated during the intraoperative phase.

Statistical Analysis

Descriptive statistics for the patient and procedure characteristics are presented as mean ± SD for continuous variables and as percentages for categorical variables. Linear regression was used to evaluate the effect of intraoperative glucose control variables (mean glucose levels and insulin initiation status) on continuous postoperative variables (first glucose measurement, mean glucose level within the first 12 hours, and mean glucose level within the first 24 hours). The regression models calculated adjusted effects. The adjusted effects controlled for covariates selected by a forward stepwise variable selection technique (P < 0.05 for entry). The candidate covariates used in the selection included diabetes status, American Society of Anesthesiologists patient acuity score, age, procedure duration, intraoperative steroid use, and body mass index (BMI). After the main effects for covariates were selected into the model, 2-way interactions were selected by the forward stepwise procedure (P < 0.05 for entry). To control for the false-positive error rate for the 3 continuous outcomes, the P values and confidence intervals (CIs) were adjusted by the Bonferroni correction. As sensitivity analysis, we also controlled for the number of glucose measurements in the final multivariate model.

The association between intraoperative and postoperative hyperglycemia (glucose level > 180 mg/dL) was tested by the χ2 test and logistic regression. The adjusted effects were calculated for logistic regression models (covariates for adjustment were selected by forward stepwise regression, P < 0.05 for entry; 2-way interactions were selected as well).

Normal Q-Q plots of the linear regression residuals were used to verify the validity of the CIs and P values for the coefficients. In addition, variable plots and component residual plots for the linear and logistic regression models were used to assess linearity in the effects of continuous predictors. We did not find any compelling evidence for nonlinear effects in any of the models.

All calculations were performed in R, version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). A P value <0.05 was used to define statistical significance. All tests were 2-sided.


Table 1:
Patient and Surgery Characteristics of Cases Included in the Study
Table 2:
Intraoperative and Postoperative Characteristics of Blood Glucose Measurements

A total of 2440 general surgery patients met the criteria for intraoperative glucose management per our institutional glucose management protocol during the study period (2011–2013). These patients were either diabetic or had an intraoperative glucose level >140 mg/dL. The patient and procedural characteristics of these cases are shown in Table 1. The blood glucose level characteristics during intraoperative and postoperative periods are shown in Table 2.

Effect of Mean Intraoperative Glucose Levels on Postoperative Glucose Levels

Scatter plots comparing intraoperative and postoperative glucose levels are shown in Figure 2. Specifically, mean intraoperative glucose levels are compared with the first 1-hour postoperative glucose level and the mean postoperative glucose levels during the first 12 and 24 hours of postoperative care. Trend lines (in purple color) show an increase in postoperative glucose levels with an increase in mean intraoperative glucose levels. Both univariate (unadjusted) and multivariate (adjusted) regression models consistently showed a positive slope for the trend line. The univariate model showed that an increase in mean intraoperative glucose level by 10 mg/dL was associated with an increase in postoperative glucose levels by 4.7 mg/dL (CI, 4.1–5.3; P < 0.001) for the first postoperative glucose, 2.6 mg/dL (CI, 2.1–3.1; P < 0.001) for the mean 12-hour postoperative glucose, and 2.4 mg/dL (CI, 2.0–2.9; P < 0.001) for the mean 24-hour postoperative glucose. All estimated effects of intraoperative glucose changed very little (<1%) in our sensitivity analysis that controlled for the number of glucose measurements.

Figure 2:
The postoperative glucose levels (first 1-h value, first 12-h mean and first 24-h mean) plotted against the mean intraoperative glucose levels. The trend lines showing the association are shown in purple. The unadjusted slopes of the trend lines depicting the change in postoperative glucose for a change in mean intraoperative glucose level of 10 mg/dL are also presented. Confidence intervals and P value were adjusted for the 3 multiple comparisons using the Bonferroni correction.
Table 3:
Multivariate Linear Regression Models for Postoperative Glucose Levels

Table 3 shows the multivariate models for postoperative glucose levels. Specifically, regression coefficients (β) for the effects of the patient- and procedure-specific variables and their interactions along with the CIs and P value are presented. The model includes several 2-way interactions, indicating that certain pairwise combinations of variables are associated with the postoperative glucose levels. Notably, we found several variables that interacted with intraoperative glucose levels. Specifically, the effect of intraoperative glucose level on all 3 postoperative glucose level parameters was stronger for patients with larger BMI (BMI-intraoperative glucose interaction). The effect of intraoperative glucose level on the 12-hour and 24-hour postoperative mean was also stronger for patients with diabetes mellitus. Intraoperative steroid use had a significant positive effect on the first postoperative (β = 13.4; P < 0.001), 12-hour mean (β = 13.5; P < 0.001), and 24-hour mean (β = 10.2; P < 0.001) glucose levels. Larger BMI had a positive effect on all 3 postoperative glucose variables although the interactions in the models suggest that the effect depended on other characteristics. Specifically, for all 3 postoperative glucose parameters, the positive effect of BMI effect was stronger in procedures with higher intraoperative glucose. The BMI effect was also stronger in older patients (positive BMI-age interaction) in the model for the 24-hour mean postoperative levels. Diabetes status, however, had a positive effect only on the 12-hour and 24-hour glucose levels without affecting the first postoperative glucose level. The effect of diabetes also depended on (interacted with) other variables. The diabetes effect was more pronounced among procedures with higher intraoperative glucose levels and, in the case of 12-hour postoperative glucose levels, also among younger patients. Increasing age had a positive effect on the 12-hour and 24-hour postoperative glucose levels although the effect of age on the 12-hour glucose levels was significantly larger (P = 0.01) among nondiabetic patients (β = 3.3 per 10 years) than diabetic patients (β = 0.5 per 10 years). Sensitivity analysis that adjusted for the number of glucose measurements in the models in Table 3 revealed very little difference in the covariate effects (change in β < 5%) from the original models (Supplemental Digital Content 1, Supplemental Appendix,

Association Between Intraoperative Glucose Levels and Postoperative Hyperglycemia

Table 4 presents multivariate models that describe the association of intraoperative glucose levels and patient and procedure characteristics with postoperative hyperglycemia (>180 mg/dL). Intraoperative glucose level >140 mg/dL was associated with an increased probability of postoperative hyperglycemia in the first 12 hours and the first 24 hours, but the effect was smaller for longer surgeries (Fig. 3). A similar effect was found for intraoperative glucose level >180 mg/dL.

Table 4:
Multivariate Logistic Regression Models for Postoperative Hyperglycemia
Figure 3:
Effects of intraoperative glucose (GLU) levels on postoperative hyperglycemia conditional on procedure duration. Dotted line is odds ratio (OR) = 1.0 (no effect of intraoperative glucose on postoperative hyperglycemia).

Other patient- and surgery-specific intraoperative covariates were associated with postoperative hyperglycemia. Diabetes status (odds ratio [OR] = 4.18; P < 0.001) and intraoperative steroid use (OR = 1.75; P < 0.001) were the major risk factors for postoperative hyperglycemia (within 24 hours) when intraoperative hyperglycemia was encountered. Patient age (OR = 1.17; P < 0.001) and BMI (OR = 1.12; P = 0.03) also had a positive effect on postoperative hyperglycemia. Procedure duration had a significant effect on postoperative hyperglycemia (OR = 2.73 per 1 hour; P < 0.001) in procedures with intraoperative glucose ≤180 mg/dL, but the effect was significantly smaller in procedures with intraoperative glucose >180 mg/dL (OR = 1.28 per 1 hour; P = 0.01 for the interaction between intraoperative glucose and duration).

Effect of Initiating Intraoperative Insulin Infusion

Table 5 shows the effect of intraoperative glucose management on postoperative glucose levels and postoperative hyperglycemia (>180 mg/dL) under 2 scenarios: (1) insulin initiated for a glucose level >140 mg/dL while avoiding hyperglycemia, and (2) insulin initiated for a hyperglycemia threshold of 180 mg/dL. The mean postoperative glucose levels were less when insulin was started at a glucose threshold of 140 mg/dL when compared with initiation of insulin for a hyperglycemia threshold of 180 mg/dL (153 ± 26 vs 162 ± 34 mg/dL for first 12 hours and 150 ± 25 vs 158 ± 33 mg/dL for first 24 hours). The adjusted difference in mean glucose levels (first, 12 and 24 hours) in postoperative glucose levels under the above scenarios was 9 mg/dL (95% CI, 4–13 mg/dL) and 7 mg/dL (95% CI, 3–12 mg/dL), respectively (P < 0.001). The differences were smaller among patients with small BMI and larger among patients with large BMI (BMI-intraoperative glucose level interaction; Fig. 4). Postoperative hyperglycemia was observed in fewer cases when insulin was initiated at a glucose threshold of 140 mg/dL without hyperglycemia when compared with a threshold of 180 mg/dL (50% vs 62% for first 12 hours and 59% vs 70% for first 24 hours). The adjusted OR for postoperative hyperglycemia (first 12 and 24 hours) under the above scenarios were 1.62 (95% CI, 1.18–2.21; P = 0.003) and 1.53 (95% CI, 1.10–2.13; P = 0.01), respectively.

Table 5:
Effect of Intraoperative Glucose Management on Postoperative Glucose Levels, Postoperative Hyperglycemia (at Least 1 Glucose Measurement >180 mg/dL) and Hypoglycemia (at Least 1 Glucose Measurement <60 mg/dL) Under 2 Scenarios: (1) Insulin Initiated for a Glucose Level Threshold of 140 mg/dL Avoiding Hyperglycemia and (2) Insulin Initiated for a Hyperglycemia Threshold of 180 mg/dL
Figure 4:
Effect of intraoperative glucose management on postoperative glucose levels under 2 scenarios: (1) insulin initiated for a glucose level threshold of 140 mg/dL avoiding hyperglycemia and (2) insulin initiated for a hyperglycemia threshold of 180 mg/dL, conditional on body mass index (BMI). Lines are loess smoothers for mean postoperative glucose levels conditional on BMI. Shaded area represents point wise 95% confidence interval.

Hypoglycemia (<60 mg/dL) was encountered in both the scenarios as depicted in Table 5. There was no statistically significant difference in the frequency of hypoglycemia either intraoperatively or postoperatively for the 2 scenarios. For the entire study population, intraoperative hypoglycemia was encountered in 12 patients (8 diabetic and 4 nondiabetic patients) and postoperative hypoglycemia in 29 patients (15 diabetic and 14 nondiabetic patients). Immediate postoperative hypoglycemia upon admission to a recovery area was observed in 5 patients. Postoperative hypoglycemia occurred in 23 of the 29 incidences during the first 12 hours of the postoperative phase. Severe hypoglycemia (<40 mg/dL) was observed in 2 patients intraoperatively and in 6 patients postoperatively.

Postoperative Glucose Levels in Diabetic Patients Without Intraoperative Glucose Management

Postoperative blood glucose levels were determined for diabetic patients who had no glucose management initiated intraoperatively (no intraoperative glucose measurement or insulin infusion). Only a subset of diabetic patients (n = 78) did not receive intraoperative glucose management. Among these patients, for those who had short (<2 hours) and long (≥2 hours) duration surgery, the mean postoperative glucose levels were 158 ± 47 mg/dL (n = 50) and 156 ± 36 mg/dL (n = 28), respectively. In addition, for both short- and long-duration cases, hyperglycemia was encountered half the time (48% for short and 57% for long cases).


Previous studies have shown that perioperative hyperglycemia could lead to postsurgical complications in both cardiac and surgery patients.1–10 However, most studies have focused on the effect of postoperative hyperglycemia on outcome, leaving the significance of glucose management during the shorter intraoperative phase unclear.1,3,7,8,10 Institutions generally extend their postoperative glucose management protocol to cover the intraoperative phase with the belief that adequate intraoperative glucose management could improve postoperative glucose levels. However, whether intraoperative glucose management has any significant effect on postoperative glucose levels is poorly understood. To specifically answer this question, we performed the current study. The study revealed that an elevated mean intraoperative glucose level is associated with higher mean postoperative glucose levels in surgery patients. Diabetes status and intraoperative steroid use had strong positive effects consistent with the reported literature.20 Age and BMI also had a positive effect on elevated postoperative glucose levels. Intraoperative hyperglycemia (>180 mg/dL) was associated with increased odds for postoperative hyperglycemia. Increased odds for postoperative hyperglycemia were observed even when intraoperative glucose levels exceeded 140 mg/dL. Diabetes status, higher BMI, and intraoperative steroid use favored the odds for postoperative hyperglycemia.

Multivariate models showed significant interactions between patient- and procedure-specific parameters and the association between intraoperative and postoperative glucose levels. The interactions were somewhat unexpected, and this makes the relationship between intraoperative and postoperative glucose levels complicated, as well as difficult to interpret. For example, the association between intraoperative glucose level and postoperative glucose levels is modified by the BMI. Because of this interaction, the association is amplified for patients with larger BMI and diminished for patients with smaller BMI. Future studies to estimate marginal treatment effect would be needed to appropriately apply the results of this study in clinical practice.

An elevated glucose level during surgery is commonly treated by initiating insulin infusion.19,21–23 However, when to initiate insulin remains unclear.12,15,18 Fear of hypoglycemia under anesthesia and an unclear target for optimal glucose management have perhaps created a variable practice pattern among anesthesia providers when it comes to intraoperative glucose management. The glucose management protocol in our institution recommends initiation of insulin treatment when the intraoperative glucose level exceeds 140 mg/dL. The results from this study seem to justify the choice of this threshold because starting insulin at a glucose level of 140 mg/dL was associated with lower postoperative glucose levels and fewer incidents of postoperative hyperglycemia. Furthermore, starting insulin early at this threshold did not increase the incidence of hypoglycemia.

This study was limited in scope to compare just intraoperative glucose management to postoperative glucose level. We did not explore whether adequate intraoperative glucose management improves postsurgical patient outcome. In addition, the association between postoperative glucose levels and postoperative outcome was not explored because this had already been performed by others previously.1,3,7,8,10 Intraoperative and postoperative blood glucose levels are affected by a variety of patient, surgical, anesthesia, and postsurgical factors. We attempted to compensate for confounding factors by adjusting for several patient and procedural risk factors in the statistical models. Whether other factors, such as compliance to institutional glucose control protocol, that were not considered in the statistical models may have influenced the results is unknown.

Perioperative insulin administration should be performed cautiously to prevent hypoglycemia. This is particularly true in the intraoperative setting where hypoglycemia is difficult to detect under anesthesia. In this study, although the frequency of occurrence of hypoglycemia was low, both intraoperative and postoperative hypoglycemia was still observed. Diabetes status did not predispose a patient to have hypoglycemia. There was also a greater tendency to have postoperative hypoglycemia during the first 12 hours of recovery.

Additional surgery and anesthesia-specific parameters that can affect perioperative glucose levels would need to be explored to better understand the risk factors for poor glycemic control. Examples would be the effects of the type and severity of diabetes and hemoglobin A1C level on intraoperative and postoperative glucose levels. An association between preoperative hyperglycemia and postsurgical complications has been shown in a study by Abdelmalak et al.24 In this context, it would be interesting to explore the effect of preoperative glucose levels on intraoperative and postoperative levels. Our study revealed that intraoperative steroid use is strongly associated with elevated perioperative glucose levels consistent with previous studies.20 However, withholding the use of steroids may not always be feasible because of clinical reasons such as postoperative nausea and vomiting prophylaxis and cerebral or airway edema reduction. Future studies exploring the dose-response relationship between steroid use and glucose levels may clarify the optimal use of steroids that balances its clinical need and effect on glucose levels.

In this study, we did not differentiate point-of-care and central laboratory glucose measurements in our analysis. Approximately 30% of the glucose measurements in the study came from point-of-care glucose meters. Although Rice et al.25 caution about the inaccuracies of self-monitored glucose meters in a perioperative setting, it should be noted that our institution uses an accurate point-of-care glucose meter that is approved for in-hospital use (ACCU-CHEK Inform II; Roche Diagnostics, Indianapolis, IN). Furthermore, the anesthesia providers were trained and certified to properly use these meters.

Consensus among anesthesia providers on what constitutes adequate intraoperative glucose control is poor because of a variety of reasons such as the fear of hypoglycemia during anesthesia, an unclear glucose target range for optimal patient outcome, and the varying effects of surgical stress and anesthesia management. Guidelines for intraoperative glycemic management remain nonstandard and poorly followed by anesthesia providers.12,15 Our study explored the question of whether intraoperative glycemic management affects postoperative glucose levels. The results indicate that adequate glucose management avoiding intraoperative hyperglycemia leads to better postoperative glucose levels and fewer incidences of postoperative hyperglycemia. In addition, our study highlights the importance of initiating insulin intraoperatively when the glucose level exceeds a threshold of 140 mg/dL and to administer an insulin dose targeted to avoid hyperglycemia. Early and adequate treatment of elevated intraoperative glucose levels provides a better “starting point” or lower starting glucose levels for postoperative glucose management.


Institutional Protocol for Intraoperative Glucose Management (the Target Glucose Range is 100–140 mg/dL)



Name: Bala G. Nair, PhD.

Contribution: This author is the primary investigator and the primary individual who performed the study design, conducted the study, analyzed the data, and prepared the manuscript.

Attestation: Bala G. Nair approved the final manuscript, attests to the integrity of the original data and the analysis reported in this manuscript, and is also the archival author.

Name: Mayumi Horibe, MD.

Contribution: This author is the co-investigator and helped with clinical advice, data analysis, and manuscript preparation.

Attestation: Mayumi Horibe approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Moni B. Neradilek, MS.

Contribution: This author helped with statistical study design and analysis, and assisted with manuscript preparation.

Attestation: Moni B. Neradilek approved the final manuscript and also attests to the integrity of the statistical analysis reported in this manuscript.

Name: Shu-Fang Newman, MS.

Contribution: This author helped with data extraction and processing from clinical information systems.

Attestation: Shu-Fang Newman approved the final manuscript.

Name: Gene N. Peterson, MD, PhD.

Contribution: This author is the clinical advisor for research study and assisted with manuscript preparation.

Attestation: Gene N. Peterson approved the final manuscript.

This manuscript was handled by: Sorin J. Brull, MD.


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Supplemental Digital Content

© 2016 International Anesthesia Research Society