Journal of Clinical Anesthesia 74 (2021) 110375

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Journal of Clinical Anesthesia

journal homepage: www.elsevier.com/locate/jclinane

Original Contribution

Immediate preoperative hyperglycemia correlates with complications in

non-cardiac surgical cases
Sarah M. Dougherty a, 1, Julie Schommer b, 1, Jorge L. Salinas c, Barbara Zilles d,
Mary Belding-Schmitt a, W. Kirke Rogers e, Amal Shibli-Rahhal b, Brian T. O'Neill b, f, g, *
a
Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
b
Divison of Endocrinology, Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
c
Division of Infectious Disease, Department of Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
d
Program of Hospital Epidemiology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
e
Department of Anesthesiology, University of Minnesota, Minneapolis, MN 55455, USA
f
Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, University of Iowa, Iowa City, IA 52242, USA
g
Veterans Affairs Health Care System, Iowa City, IA 52242, USA

A R T I C L E I N F O A B S T R A C T

Keywords: Study objective: Assess for a relationship between immediate preoperative glucose concentrations and post­
Hyperglycemia: complications operative complications.
DM control: glycosylated Hgb Design: Retrospective cohort study.
Perioperative insulin: effects
Setting: Single large, tertiary care academic medical center.
Outpatient surgery contraindications
Patients: A five-year registry of all patients at our hospital who had a glucose concentration (plasma, serum, or
Postoperative cardiac event: risk factors
Perioperative risk of MI venous/capillary/arterial whole blood) measured up to 6 h prior to a non-emergent surgery.
Interventions: The glucose registry was cross-referenced with a database from the American College of Surgeons National
Surgical Quality Improvement Program (ACS NSQIP). We applied an outcomes review to the subset of patients for whom
we had data from both registries (n = 1774).
Measurements: Preoperative glucose concentration in the full population as well as the subgroups of patients with or
without diabetes were correlated with adverse postsurgical outcomes using 1) univariable analysis and 2) full
multivariable analysis correcting for 27 clinical factors available from the ACS NSQIP database. Logistic regression
analysis was performed using glucose level either as a continuous variable or as a categorical variable according to
the following classifications: mild (≥140 mg/dL; ≥7.8 mmol/L), moderate (≥180 mg/dL; ≥10 mmol/L), or severe
(≥250 mg/dL; ≥13.9 mmol/L) hyperglycemia. A third analysis was performed correcting for 7 clinically important
factors (age, BMI, predicted duration of procedure, sex, CKD stage, hypoalbuminemia, and diabetic status) iden­
tified by anesthesiologists and surgeons as immediately available and important for decision making.
Main results: Univariable analysis of all patients and the subgroups of patients without diabetes or with diabetes
showed that immediate preoperative mild or moderate hyperglycemia correlates with postoperative complica­
tions. Statistical significance was lost in most groups using full multivariable analysis, but not when correcting
for the 7 factors available immediately preoperatively. However, for all patients with diabetes, moderate hy­
perglycemia (≥180 mg/dL; ≥10 mmol/L) continued to significantly correlate with complications even in the full
multivariable analysis [odds ratio (OR) 1.79; 95% Confidence Intervals (CI) 1.10, 2.92], and with readmission/
reoperation within 30 days [OR 1.93; 95% CI 1.18, 3.13].
Conclusions: Preoperative hyperglycemia within 6 h of surgery is a marker of adverse postoperative outcomes.
Among patients with diabetes in our study, a preoperative glucose level ≥ 180 mg/dL (≥10 mmol/L) inde­
pendently correlates with risk of postoperative complications and readmission/reoperation. These results should
encourage future work to determine whether addressing immediate preoperative hyperglycemia can improve
complication rates, or simply serves as a marker of higher risk.

* Corresponding author at: University of Iowa, 169 Newton Road, Iowa City, IA 52242, USA.
E-mail address: [email protected] (B.T. O'Neill).
1
Authors contributed equally.

https://doi.org/10.1016/j.jclinane.2021.110375
Received 11 February 2021; Received in revised form 7 May 2021; Accepted 11 May 2021
Available online 16 June 2021
0952-8180/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

1. Introduction Institutional Review Board (IRB), and the requirement for written
informed consent was waived by the IRB. This is a retrospective cohort
Sustained or intermittent perioperative hyperglycemia (blood study using the UIHC electronic health record (EHR, EPIC Systems,
glucose concentration > 140 mg/dL; 7.8 mmol/L) is estimated to occur Verona, WI) and our local American College of Surgeons' National Sur­
in 20–40% of non-cardiac surgery patients [1,2]. Such hyperglycemia gical Quality Improvement Program (ACS NSQIP) database. The UIHC
has been suggested to be a modifiable, independent predictor of post­ EHR contains complete demographic, clinical, laboratory, and medica­
surgical complications in patients both with and without diabetes. tion data for all patients seen at UIHC – including time-stamped glucose
Indeed, intensive insulin therapy and tight glycemic control in the concentrations from whole blood (venous, capillary and arterial),
postoperative period are, in some studies, associated with beneficial plasma, or serum. It also includes data from surgery, such as the time of
outcomes such as a decrease in postoperative infections [3–7]. induction of anesthesia, time of incision, and end of surgery. The local
Although there seems to be a correlation between poor outcomes and ACS NSQIP database is maintained by a dedicated Surgical Clinical
sustained hyperglycemia throughout the perioperative period, the pre­ Reviewer (SCR) nurse who audits all relevant patient charts every 30
dictive effect of immediate preoperative blood glucose levels on out­ days and enters patient-specific preoperative, intraoperative, and post-
comes remains poorly studied. In fact, only a limited number of studies operative outcome variables for a variety of surgical case types [17].
have attempted to specifically estimate the risk of preoperative hyper­ The local ACS NSQIP database, like its national counterpart, does not
glycemia on postoperative outcomes, and several include glucose values include peri-operative glucose values. Thus we had to query the UIHC
obtained well over 24 h prior to surgery. A large retrospective study with EHR to identify patients who had a plasma, serum, or whole blood
>61,000 individuals indicated that preoperative hyperglycemia (up to 1 (including capillary) glucose concentration obtained within 6 h of in­
month prior to surgery) strongly correlated with postoperative duction of anesthesia for their surgery. The NSQIP database does,
morbidity, but not after correction for preoperative comorbidities [8]. however, include complication rates from all vascular and general sur­
However, 1-year mortality remained significantly correlated with pre­ gery procedures as well as total hip arthroplasty, total knee arthroplasty
operative hyperglycemia in patients without diabetes, even after and hip fracture repairs, and a sampling of other general surgical pro­
correction for comorbidities. Two other studies indicated that post­ cedures performed at UIHC.
operative infections are highly correlated with preoperative hypergly­
cemia or both pre-and postoperative hyperglycemia, even after
correction for comorbidities [4,9]. However, other studies did not find a 2.2. Patients
correlation between preoperative glucose and surgical site infections
after correction for comorbid conditions [10]. Therefore, target serum Using the UIHC EHR, we identified all patients admitted for a non-
glucose levels and an optimal glucose management protocol during the cardiac surgical procedure between January 2015 and January 2020.
immediate preoperative and perioperative periods are subjects of The EHR was then queried to identify patients who had a plasma, serum,
debate. For example, the Center for Disease Control (CDC) Guidelines for or whole blood glucose concentration obtained within 6 h of their sur­
Prevention of Surgical Site infection recommend implementing “peri­ gery. This patient list was then cross-matched with our local ACS NSQIP
operative glycemic control and [using] blood glucose target levels less database, and only patients who had both a glucose level recorded on
than 200 mg/dL (11.1 mmol/L) in patients with and without diabetes” the EHR within 6 h prior to the start of anesthesia, and who were
[11]; whereas the Society for Ambulatory Anesthesia (SAMBA), the included in the ACS NSQIP database, were selected for the study.
Endocrine Society, the Joint British Diabetes Society, and the Society of Emergent surgeries were excluded. If an individual patient underwent
Thoracic Surgeons (STS) Practice Guidelines recommend maintaining multiple surgeries within 30 days, only the first surgery was used for
intraoperative blood glucose levels ≤180 mg/dL (≤10 mmol/L) analysis. If a patient had multiple glucose levels recorded within the 6 h
[5,12–14]; and the Society of Critical Care Medicine (SCCM) advises that preceding surgery, the highest glucose level was used for analysis. When
insulin treatment be triggered at blood glucose levels ≥150 mg/dL possible, any missing data was filled in by individual EHR chart review.
(>8.3 mmol/L) with a goal to maintain blood glucose below that level
[15]. No guidelines give a clear threshold value of blood glucose at
which postponement of elective surgery should be considered in the 2.3. Data elements
absence of severe dehydration, diabetic ketoacidosis, or hyperosmolar
non-ketotic states [13], in part because the threshold at which increased Relevant demographic and clinical information in the ACS NSQIP
risk based on immediate preoperative glucose is not known. Some expert database includes, but is not limited to, patient age, sex, race, Body Mass
authors have nonetheless strongly recommended that a threshold value Index (BMI), surgical specialty, elective status of the surgery, inpatient/
of glucose >250 mg/dL (>13.9 mmol/L) warrants postponement of outpatient status, whether or not the surgery required anesthesia, and
elective surgery [16] – without providing a clear justification for this American Society of Anesthesiologists (ASA) Physical Status classifica­
particular threshold value. tion. We analyzed only ASA Class I through IV patients, defined as fol­
We therefore undertook a study to evaluate whether immediate hy­ lows – ASA I: healthy patient with no systemic disease; ASA II: mild
perglycemia (within 6 h prior to the start of anesthesia) before elective systemic disease without substantive functional limitations; ASA III:
surgical procedures was associated with postoperative complications. severe systemic disease with substantive functional limitations; ASA IV:
We also attempted to identify threshold values of hyperglycemia that severe systemic disease that is a constant threat to life. There were no
may inform clinical decision-making and future clinical practice patients in our cohort with ASA of >IV, as these represent moribund
guidelines. We hypothesized that a finding of moderate to severe hy­ patients who are receiving emergent surgery and are not expected to
perglycemia immediately prior to elective surgery – regardless of why a survive without the operation, or brain-dead patients undergoing organ
serum glucose level was checked, and regardless of whether or not at­ donation. Full demographic and clinical information are summarized in
tempts were made to correct the hyperglycemia – would be associated Table 1 and under "Statistical analyses" listed below.
with an increased risk of adverse patient outcomes. Lasty, patients were excluded if they did not have laboratory values
for serum creatinine and albumin performed within 4 weeks of surgery
2. Methods (See Flow chart 1). Hypoalbuminemia was defined in our study as an
albumin level < 3.5 mg/dL. Chronic Kidney disease (CKD) stage was
2.1. Study design and data sources calculated by determining eGFR via the CKD-epi Creatinine equation
(https://www.mdcalc.
The study was approved by the University of Iowa Healthcare (UIHC) com/ckd-epi-equations-glomerular-filtration-rate-gfr#evidence).

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S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

Table 1
Summary of preoperative patient characteristics. Values are presented as median (IQR) or percentages as appropriate. (*-p < 0.05 vs. No diabetes; #-p < 0.05 vs. DM -
Ins. It is important to note that patient groups were not directly compared to each other in subsequent outcome analyses. Multivariable regression analyses adjusted for
baseline variables within each group.)
Factor All Patients (n = 1774) No Diabetes (n = 782) Diabetes DM - Ins DM + Ins
(n = 992) (n = 577) (n = 415)

Glucose (mg/dL) 117 (48) 103 (27) 136 (57)* 129 (44) 147 (71)#
Age 64 (17) 63 (22) 65 (15)* 64 (16) 65 (14)
BMI 31.8 (12.6) 27.8 (9.8) 34.9 (11.6)* 35.7 (11.3) 34.1 (12.0)#
Female gender 57.2% 57.0% 57.3% 58.4% 55.7%
Race
Caucasian 91.7% 90.9% 92.2% 93.4% 90.6%
African American 4.2% 4.6% 3.9% 3.1% 5.1%
Hispanic 2.5% 2.6% 2.4% 2.1% 2.9%
Asian 0.85% 0.89% 0.81% 0.69% 0.96%
Other 0.79% 1.02% 0.65% 0.69% 0.48%
Proportion with Hemoglobin A1C available 36.6% 11% 57%* 55% 59%

Hemoglobin A1C

6.7% (1.5) 6.0% (1.0) 6.8% (1.5)* 6.5% (1.4) 7.2% (1.8)#
Duration of Procedure (min) 152 (135) 157 (140) 146 (133) 146 (122) 148 (147)
General Anesthesia 81% 92% 73% 69% 77%
ASA Physical Status
I 1.2% 2.8% 0%* 0% 0%
II 27.9% 35.4% 22.1%* 28.2% 13.3%#
III 63.9% 54.7% 71.1%* 68.5% 74.7%#
IV 7.0% 7.0% 7.0% 3.3% 12.0%#
V and VI 0% 0% 0% 0% 0%
CKD Stage
1 34.7% 37.3% 32.6%* 35.7% 28.2%#
2 31.7% 32.9% 30.7% 34.3% 25.8%#
3 26.2% 23.4% 28.4%* 25.3% 32.8%#
4 4.7% 3.8% 5.3% 3.5% 8.0%#
5 2.8% 2.6% 2.9% 1.2% 5.3%#
Albumin < 3.5 19.7% 27.9% 13.3%* 9.0% 19.3%#
Smoker 15.4% 19.6% 12.2%* 10.7% 14.2%
COPD 6.3% 8.0% 4.8%* 4.3% 5.5%
Hypertension 67.1% 47.1% 83.0%* 83.2% 82.7%
CHF 1.4% 1.3% 1.4% 0.17% 3.1%#
ARF 0.23% 0.38% 0.1% 0% 0.24%
Ascites 1.5% 2.2% 0.9%* 0.35% 1.7%#
Cancer 8.8% 10.9% 7.2%* 7.1% 7.2%
Immunosuppressants 9.0% 12.3% 6.4%* 3.5% 10.4%#
Bleeding disorder 6.3% 6.5% 6.1% 4.3% 8.7%#
Transfused (pre-op) 1.4% 2.2% 0.7%* 0.3% 1.2%
SIRS/sepsis/septic shock 8.6% 13.8% 4.5%* 3.5% 6.0%

DM - Ins, Diabetes not treated with insulin; DM + Ins, Insulin-treated diabetes; see Methods for other abbreviations and ASA categories.

2.3.1. Preoperative glucose and diabetes status 2.3.2. Definitions of hyperglycemia and post-operative complications
Patients were classified as having diabetes or not according to ACS Glycemic levels were divided into four categories, based on the ADA
NSQIP Guidelines: either a documented history of diabetes needed to guidelines for glycemic targets in hospitalized patients [18]. In the most
appear on the medical record preoperatively, or the patient needed to recent guidelines, hyperglycemia in the hospital is defined as >140 mg/
have a documented use of oral hypoglycemic medication or insulin dL and recommended optimal glycemic targets are <180 mg/dL, but can
preoperatively. Patients with diabetes were subcategorized as not in­ range from <140 mg/dL in cardiac surgical patients to <250 mg/dL in
sulin dependent (DM - Ins) or insulin dependent (DM + Ins), although specialized cases (such as with severe comorbidities and when frequent
we were unable to further determine whether patients had Type 1 or glucose monitoring is challenging). These targets are mostly consistent
Type 2 diabetes. with many other guidelines and expert opinion [11,12,14,15,20,21].
Hemoglobin A1C (HbA1C) percentage is not needed as a diagnostic Glycemic levels were categorized as normal (≤140 mg/dL; ≤7.8 mmol/
criterion according the ACS NSQIP Guidelines and thus not routinely L), mild hyperglycemia (141-180 mg/dL; 7.8-10 mmol/L), moderate
obtained for patients in the database. Therefore only a minority of pa­ hyperglycemia (181-250 mg/dL; 10–13.9 mmol/L), and severe hyper­
tients in our combined dataset had HbA1C percentage values docu­ glycemia (>250 mg/dL; >13.9 mmol/L). We also conducted a Receiver
mented within 6 weeks of their surgical procedure (see Table 1). Operating Characteristics (ROC) analysis of pre-operative glucose as a
However, since HbA1C percentage is recognized by the American Dia­ predictor of overall post-operative complications. The analysis yielded
betes Association (ADA) as the major tool for assessing long-term gly­ an Area Under the Curve (AUC) of 0.6. The optimal cut-off glucose found
cemic control, and has been demonstrated to have strong predictive through this analysis was 141 mg/dL (7.8 mmol/L), which was consis­
value for diabetes complications [18] and potentially surgical outcomes tent the lowest cut-off chosen based on published literature.
[19–21], we did extract it from the EHR and included it in our analyses A post-operative complication was defined according to ACS NSQIP
whenever possible. criteria, and included any of the following: surgical site infection (SSI –
this includes superficial SSI, Deep SSI, Organ space SSI and wound
disruption), pneumonia, Clostridioides difficile infection, sepsis, septic

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S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

Flow chart 1. Flow chart for inclusion of patients into the retrospective cohort study.

shock, deep vein thrombosis, pulmonary embolism, myocardial infarc­ DM - Ins or DM + Ins), race (Asian, Black, Hispanic, White, Other),
tion, cerebrovascular accident, progressive renal insufficiency, acute inpatient (87%) or outpatient (13%) status after procedure, elective
renal failure, urinary tract infection, unplanned intubation, ventilator surgery where the patient is brought from home for a non-urgent/
dependency for 48 h, and cardiopulmonary resuscitation. See Table 2 for non-emergent procedure (yes 72%/no 28%), type of anesthesia
numbers of complications in each group. (general/other), ASA physical status (I to VI), functional status (in­
dependent 97%/partially dependent 2%/totally dependent 1%),
smoking status within 1 year (yes/no), dyspnea (none 91%/dyspnea
2.4. Statistical analyses upon moderate exertion 8%/dyspnea at rest 1%), COPD (present/
absent), ventilator dependency >48 h prior to procedure (yes 0.3%/
Statistical analyses were conducted using SAS for Windows, version no 99.7%), ascites within 30 days of surgery (present/absent), hy­
9.3 (SAS Institute Inc., Cary, NC, USA). All continuous variables were pertension requiring medication (present/absent), new or acute
subjected to Shapiro Wilk's test of normality, and variables not found to exacerbation of congestive heart failure (CHF) within 30 days of
be normally distributed were reported as median (Interquartile Range; surgery (present/absent), disseminated cancer (present/absent),
IQR). We began by examining patient characteristics and evaluating the bleeding disorder (present/absent), open wound (present/absent),
glucose distribution within the patient groups. We then performed 4 immunosuppressant use for chronic condition (present/absent), 10%
different logistic regression analyses for the following reasons: loss of body weight in 7 months prior to surgery (present 4%/absent
96%), transfused within 72 h of surgery (present/absent), and sys­
1- A univariable simple analysis to evaluate the effect of preoperative temic inflammatory response syndrome (SIRS)/sepsis/septic shock
glucose on postoperative complications, and to identify whether any within 48 h of surgery (present/absent). The full multivariable an­
relationship existed. alyses were repeated for the following three outcomes: 1) composite
2- Full multivariable: analyses using the variables available in the infections (Superficial SSI, Deep SSI, Organ space SSI, Wound
NSQIP databases aligned with the patient's glucose for comparison: disruption, Pneumonia, Clostridioides difficile infection, Sepsis, Septic
age (years), BMI (kg/m2), duration of procedure (minutes), sex shock, Urinary Tract Infection (UTI)); 2) readmission or reoperation
(Female/Male), CKD stage (1 to 5), hypoalbuminemia (present/ab­ within 30 days; 3) death within 30 days.
sent), diabetic status (no diabetes or diabetes, and subcategorized as

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S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

Table 2 continuous variable and as a categorical variable first to assess for the
Summary of raw numbers of postoperative complications. These included: general presence of an association with postsurgical complications. If an
surgical site infections (SSI), wound disruption, pneumonia, Clostridioides diffi­ association was detected, the analyses were repeated using serum
cile (C. diff) infection, sepsis, septic shock, deep vein thrombosis (DVT) pulmo­ glucose at the pre-specified cutoffs listed in “Definitions of hyperglyce­
nary embolism (PE), myocardial infarction (MI), cerebrovascular accident mia and post-operative complications” above. The purpose of the latter
(CVA) progressive renal insufficiency, acute renal failure (ARF), urinary tract
analyses was to try to define a practical glucose cut-off that could be
infection (UTI), unplanned intubation, ventilator dependency for 48 h and
used in the design of future interventional studies.
cardiopulmonary resuscitation (CPR). (*-p < 0.05 vs. No diabetes; #-p < 0.05 vs.
DM - Ins. Patient groups were not directly compared to each other in any of the Using size effect estimates from existing literature [8,9] and
subsequent outcome analyses). G*Power software [22], a post-hoc power analysis for the full multi­
variable logistic regression was performed (n = 1774). The analysis
Postoperative All No Diabetes DM - DM +
complications Patients (n Diabetes (n = Ins Ins (n
yielded an estimated power of 0.86 for effect of hyperglycemia (defined
= 1774) (n = 782) 992) (n = = 415) both as a glucose of >140 mg/dL and > 180 mg/dL) on the composite
577) post-operative complication end point.
Superficial SSI 44 25 19 9 10
Deep SSI 10 3 7 3 4 3. Results
Organ space SSI 45 23 22 17 5
Wound disruption 7 2 5 3 2
3.1. Demographics and serum glucose concentrations
Pneumonia 25 14 11 6 5
C. diff infection 20 10 10 4 6
Sepsis 34 12 22 11 11 Patient demographics and pre-surgical characteristics are presented
Septic shock 15 6 9 4 5 in Table 1. While the different patient groups demonstrated statistically
UTI 32 10 22 9 13 significant differences in some of their baseline clinical characteristics
________________________
Composite 232 105 127 66 61
and post-surgical outcomes, it is important to note that these patient
infections groups were not directly compared to each other in any of the subse­
DVT 23 15 8* 4 4 quent outcome analyses, and that the multivariable regression analyses
PE 15 8 7 5 2 adjusted for baseline variables within each group. We were able to
MI 13 4 9 2 7#
identify 3394 patients who both had a glucose value measured in the 6-h
CVA 8 2 6 3 3
Progressive renal 16 6 10 4 6 pre-surgical time frame and who were included in the ACS NSQIP
insufficiency database at the University of Iowa from January 2015 to January 2020.
ARF 13 4 9 4 5 Prior to a recent quality improvement project and policy change at our
Unplanned 34 15 19 7 12 hospital, immediate pre-operative glucose testing was not protocolized
intubation
Ventilator 22 11 11 5 6
(levels could be checked at the discretion of anesthesiology, surgery, or
dependency pre-op nursing providers, and usually were drawn if the patient was
CPR 9 2 7 2 5 known to have diabetes or there was other reason to suspect dysglyce­
________________________ mia). 489 emergent surgical cases were then excluded from this study,
Total complications 385 172 213 102 111
and 1131 patients did not have a serum creatinine or albumin measured
Reoperation/ 234 96 138 73 65
Readmission within 4 weeks of the procedure, resulting in a final study population of
Death 33 16 17 5 12 1774 patients (see Flow chart 1).
The median age of the patient population was 64 years, and was
slightly higher in patients with diabetes compared to patients without
3- Limited multivariable: This analysis used a limited number of pre­ diabetes (Table 1). The median BMI was 31.8, with patients with dia­
dictor variables that were generated by a literature search and a betes having a higher BMI than patients without diabetes (34.9 versus
survey of local surgeons and anesthesiologists to identify simple and 27.8, respectively). DM + Ins patients were more likely to have CKD
easily accessible preoperative variables that were felt to be most stage 4–5 compared to DM - Ins (13.3% vs 4.7%, respectively). ASA
relevant when determining the likelihood of perioperative compli­ physical status was also highest in the DM + Ins group. Lastly, HbA1C
cations. The variables in this analysis were: age (years), BMI (kg/ measured within 1 month of surgery was only available in 11% of pa­
m2), duration of procedure (minutes), sex (Female/Male), CKD stage tients without diabetes and in 57% of patients with diabetes, but the vast
(1 to 5), hypoalbuminemia (present/absent), and diabetic status (no majority showed well-controlled diabetes with a median HbA1C of 7.2%
diabetes, DM - Ins, or DM + Ins). These variables were chosen and set even in the DM + Ins subgroup (Table 1). But, patients with reasonably
prior to analysis to avoid bias. controlled HbA1C levels did not always arrive with a well-controlled
4- Full multivariable with HbA1C within 1 month: analyses using the preoperative glucose. Among patients with a HbA1C ≤8.0% within 1
variables listed for the full multivariable in addition to HbA1C. We month of surgery, 10.4% had a glucose >180 mg/dL immediately prior
chose to conduct this analysis separately because only 649 patients to surgery. In addition, 49 of the 99 patients who had an HbA1C that was
had a HbA1C measurement within 1 month of surgery. We thought >8.0% had a glucose level < 180 mg/dL immediately prior to surgery.
the additional data afforded by analyzing a model with HbA1C Of the 1774 patients, most (n = 1254, 71%) had a pre-operative
percentages would be useful even if less statistically powerful than glucose less than 140 mg/dL (7.8 mmol/L) prior to surgery (Fig. 1A).
the evaluation of the larger dataset which did not include these Of the 520 patients with a pre-operative glucose greater than 140 mg/dL
values. (7.8 mmol/L), 450 (87%) had a preoperative-diagnosis of diabetes. The
median preoperative serum glucose concentration for purportedly non-
We also conducted subgroup analyses on patients without diabetes diabetic patients was 103 mg/dL compared to 136 mg/dL for patients
and patients with diabetes, further subcategorized as not on insulin (DM with known diabetes. Patients treated with insulin also showed higher
- Ins) or on insulin (DM + Ins). For these analyses, we used the variables median glucose levels: for DM - Ins it was 129 mg/dL, and for DM + Ins
listed for the full multivariable analysis without “diabetes status” since 147 mg/dL (Table 1). Of the 782 patients without diabetes, over 90%
the subgroups were defined based on this variable. This represented a had a preoperative glucose concentration less than 140 mg/dL(7.8
different attempt to stratify patients with diabetes in the absence of mmol/L), whereas among the group with diabetes, 81% had a preop­
adequate HbA1C values. erative serum glucose concentration of less than 180 mg/dL (10 mmol/
For each of the analyses listed above, serum glucose was studied as a L) (Fig. 1B). Severe hyperglycemia (serum glucose greater than 250 mg/

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S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

Fig. 1. Glycemia in the patient population and glycemic categories in subgroups. (A) Number of patients with glucose levels separated into glycemic categories
in No diabetes, DM - Ins, and DM + Ins subgroups. (B) Percent of patients in defined glycemic categories within each subgroup. (DM - Ins – patients with diabetes
treated with medications other than insulin; DM + Ins – patients with diabetes treated with insulin).

Fig. 2. Immediate preoperative hyperglycemia correlates with increased risk of postoperative complications. Odds ratios from logistic regression analysis
correlating glucose level drawn within 6 h of anesthesia as a continuous variable (A) or correlating glucose within specified categories (B) to postoperative com­
plications. ***p < 0.001.

dL [13.9 mmol/L]) was noted in 57 (3.2%) patients, including 7 (0.9%)

purportedly nondiabetic patients, 11 (1.9%) DM - Ins, and 39 (9.4%)
Table 3 DM + Ins.
Odds ratios for complications correlated to Glucose as a Categorical Variable
(glucose levels were binned into 4 categories: normal, mild, moderate, or severe
according to Methods section 2.3.2). Results presented as point estimate (con­ 3.2. Analyses of glucose as a continuous variable and within glycemic
fidence interval). *-p < 0.05, **-p < 0.01, ***-p < 0.001, ND - Not detectable categories
with OR < 0.001.
Analysis All No Diabetes DM - Ins DM+Ins Composite post-operative infections (SSI, pneumonia, Clostridioides
(n=1774) Diabetes (n=992) (n=577) (n=415) difficile, UTI, sepsis, and septic shock) were the most common compli­
(n=782)
cation in our cohort (Table 2). But, given the low number of individual
Univariable 1.41 *** 1.42 1.46 *** 1.48 * 1.35 * complications, analyses were performed with all complications com­
(1.19, (0.93, (1.19, (1.06, (1.04, bined. Univariable analyses of the entire cohort (n = 1774) revealed a
1.66) 2.16) 1.78) 2.06) 1.76)
Limited 1.32 ** 1.38 1.33 ** 1.15 1.38 *
positive correlation between glucose and postoperative complications,
Multivariable (1.09, (0.90, (1.08, (0.79, (1.05, both with glucose as a continuous variable (Fig. 2A) and when classified
1.60) 2.11) 1.65) 1.66) 1.83) into normal, mild, moderate, and severe glycemic categories (Fig. 2B).
Full 1.18 1.07 1.23 1.06 1.21 However, this correlation was lost with the full multivariable analysis
Multivariable (0.96, (0.65, (0.98, (0.71, (0.88,
whether HbA1C was included or not (Fig. 2). Interestingly, the associ­
1.44) 1.75) 1.55) 1.59) 1.66)
p=0.07 ation between glucose within glycemic categories remained significant
Full 1.25 ND 1.27 1.93 1.13 when correcting for the subjectively chosen risk criteria of age, sex, BMI,
Multivariable (0.87, (0.86, (0.71, (0.68, diabetic status, low albumin, CKD stage, and duration of surgery
with HbA1C 1.81) 1.87) 5.26) 1.89) (Table 3, limited multivariable analysis), indicating that these factors
(n=649)
alone do not account for the increased risk in our patient population.

6
S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

Fig. 3. Moderate (>180 mg/dL; >10 mmol/L) preoperative hyperglycemia correlates with postoperative complications in patients with diabetes. Odds
ratios from logistic regression analysis using glycemic cutoffs of mild ≥140 mg/dL (≥7.8 mmol/L)(A), moderate ≥180 mg/dL (≥10 mmol/L)(B), or severe ≥250 mg/
dL (≥13.9 mmol/L)(C) in all patients, non-diabetic patients and patients with Diabetes using full multivariable analysis. *p < 0.05.

Table 3 shows the results for the subgroup analyses using glycemic 0.73–3.87) groups lost significance indicating that patients on non-
categories. In individuals without diabetes, neither the full multivari­ insulin therapy and those treated with insulin both contribute to the
able nor limited multivariable analyses showed a correlation between increased risk.
glycemic category and postoperative complications. By contrast, in in­ In an effort to determine if the increased complication risk was
dividuals with diabetes, the limited multivariable analyses showed a restricted to infections or extended also to risk of reoperation/read­
significant association between hyperglycemia and complications, but mission or death within 30 days, we performed a secondary analysis
this correlation was lost with correction for all 27 factors in the full using these outcomes. Full multivariable logistic regression analysis
multivariable analysis. When individuals with diabetes were further (excluding HbA1C) was performed using the prespecified glycemic
subdivided into DM - Ins (n = 577) and DM + Ins (n = 415), the full cutoffs. Composite infections (Superficial SSI, Deep SSI, Organ space SSI,
multivariable analyses did not show correlations. Wound disruption, Pneumonia, Clostridioides difficile infection, Sepsis,
Septic shock, UTI) showed no correlation with mild or severe glycemia,
although moderate hyperglycemia in patients with diabetes tended to
3.3. Analysis using individual glycemic categories
increase correlation (Table 4). Moderate hyperglycemia (≥180 mg/dL)
was significantly correlated with readmission or reoperation within 30
Given that our univariable analyses indicated a correlation between
days in all patients and in just those patients with diabetes (Table 4).
glycemic category and postoperative complications, we sought to deter­
There were few deaths in our population and neither mild, moderate,
mine whether a specific glucose cut-off (140, 180 or 250 mg/dL) best
nor severe hyperglycemia correlated with death within 30 days. These
predicted post-operative complications in each of our individual sub­
data demonstrate that immediate preoperative hyperglycemia is an in­
groups. Shown in Fig. 3 are the results of these full multivariable logistic
dicator of higher risk for postoperative complications that can be used
regression analyses using the previously described glycemic cutoffs.
with other important preoperative clinical data. Furthermore, in our
In all patients, as well as patients with/without diabetes, a glucose
cohort, moderate hyperglycemia remains an independent risk factor for
concentration ≥ 140 mg/dL (≥7.8 mmol/L) showed no significant risk
patients with diabetes when glucose levels are above ≥180 mg/dL (10
of postoperative complications when correcting for the 27 clinical fac­
mmol/L).
tors in the full multivariable analysis (Fig. 3A). Similarly, if a glucose
cutoff of ≥250 mg/dL (≥13.9 mmol/L) was used, there was no increased
3.4. Anesthesia type, CKD stage, duration of surgery and sepsis contribute
risk in the full cohort or subgroups (Fig. 3C). However, correlations
to increased risk of complications
between preoperative moderate hyperglycemia (≥180 mg/dL, ≥10
mmol/L) and postoperative complications were most striking in patients
Other factors found to be significantly related to postoperative
with diabetes. Even using the full multivariable analysis, patients with
complications using the full multivariable analysis included Anesthesia
diabetes with a preoperative glucose level ≥ 180 mg/dL (≥10 mmol/L)
type with odds ratio (OR) of 2.17 (CI 1.12, 4.19), CKD stage with OR of
showed a significant 1.79 (95% CI 1.10–2.92) odds ratio of having a
1.24 (CI 1.03, 1.50), Duration of Surgery with OR of 1.004 (CI 1.003,
postoperative complication (Fig. 3B). In subgroup analyses, the odds
1.006), and Sepsis with OR of 2.81 (CI 1.73, 4.57).
ratio of postoperative complications with moderate hyperglycemia in
the DM - Ins (OR 2.00, CI 0.94–4.25) and DM + Ins (OR 1.68, CI

Table 4
Odds ratio of composite infections, readmission or reoperation, or death related to mild, moderate, or severe hyperglycemia. Results presented as point estimate
(confidence interval). † − p = 0.053, **-p < 0.01.
Composite Infections Readmission or Reoperation Death

All Patients ≥140 mg/dL 1.29 (0.88, 1.89) 1.26 (0.88, 1.81) 0.79 (0.33, 1.91)
≥180 mg/dL 1.54 (0.97, 2.45) 1.80** (1.16, 2.78) 0.36 (0.09, 1.39)
≥250 mg/dL 0.97 (0.43, 2.20) 1.28 (0.62, 2.67) ND
No Diabetes ≥140 mg/dL 1.11 (0.50, 2.50) 1.17 (0.54, 2.56) 0.07 (0.00, 2.75)
≥180 mg/dL 0.67 (0.14, 3.13) 0.66 (0.14, 3.12) ND
≥250 mg/dL ND ND ND
Diabetes ≥140 mg/dL 1.34 (0.85, 2.11) 1.19 (0.77, 1.82) 1.23 (0.40, 3.84)
≥180 mg/dL 1.64† (0.99, 2.72) 1.93** (1.18, 3.13) 0.39 (0.07, 2.13)
≥250 mg/dL 1.14 (0.48, 2.69) 1.66 (0.76, 3.63) 1.75 (0.20, 15.3)

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S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

4. Discussion after correction for preoperative comorbidities. However, 1-year mor­

tality after surgery was significantly related to preoperative blood
In this retrospective analysis of patients undergoing non-emergent, glucose measured up to 1 month prior to surgery in this retrospective
non-cardiac surgery, elevated glucose levels obtained in the immedi­ study [8]. The study by Abdelmalek, et al., further showed that a ma­
ate preoperative period (up to 6 h prior to induction of anesthesia) were jority of this increased risk of postoperative complications came from
associated with an increase in postoperative complications, as defined patients without a known diagnosis of diabetes, which contradicts our
by the ACS NSQIP database. The most significant finding was that own results. There are many differences in the populations studied
glucose levels equal to or above 180 mg/dL(10 mmol/L) in patients with which may account for the different results, including but not limited to
diabetes independently correlated with increased risk of complications. lower rates of CHF, COPD, and cancer in our group of patients with
We hypothesized that hyperglycemia in the immediate pre-operative diabetes. The findings of our study are also partially contradicted by a
period would be associated with an increased risk of complications publication of 229 general and vascular surgery patients which
relative to patients who also had a glucose concentration checked but demonstrated that preoperative blood glucose levels (measured up to 24
were not hyperglycemic. Indeed, our findings do show that if glucose h before surgery) were not correlated with post-operative surgical site
concentration is evaluated (for whatever justification) in the immediate infections, whereas a preoperative HbA1C value >7% and a post­
pre-operative period, a higher value is associated with an increased risk operative capillary glucose value ≥180 mg/dL (10 mmol/L) were
of complications relative to patients who also had their glucose level associated [10]. Interestingly, in that study the odds ratio of SSI when
checked but were not found to be hyperglycemic. The fact that this as­ preoperative glucose was ≥180 mg/dL was still 1.92 (CI 0.78–4.76) in
sociation remained significant in the entire cohort when correcting for 7 elective procedures but did not reach significance, perhaps due to a
subjectively chosen factors that surgeons and anesthesiologists felt were lower sample number. Lastly, another study of patients without diabetes
relevant indicates that hyperglycemia provides some added information in the NSQIP database indicated that preoperative hyperglycemia was
about risk. However, the relationship was lost in a full multivariable correlated with an increased risk of surgical site infections [9].
analysis that included 27 patient factors used to judge severity of illness These prior studies, like our own, could not determine whether
in the ACS NSQIP database. treatment of hyperglycemia will be beneficial or detrimental. Some
To some degree, our findings suggest that fasting hyperglycemia previous studies in both surgical and non-surgical populations have
already serves as a marker of “sicker” patients who are likely to have shown that attempts at tight blood glucose control can perversely
other illnesses or end-organ dysfunction that places them at higher risk worsen outcomes (presumably by causing dangerous hypoglycemia)
of postoperative complications. We find support for such a theory in the [23,26–28]. However, other studies indicate that coordinated preoper­
multitude of studies demonstrating that HbA1C percentage levels – a ative care for diabetes by a clinical program focused on controlling
marker of long-term diabetes control – correlate with the risk of post­ glucose before and after surgery can reduce antibiotic use 24 h after
operative complications [1,19,23], although this is not a universally surgery and reduce hypoglycemia in patients with diabetes [29].
identified finding [24]. Our study could suggest that HbA1C level may Nonetheless, future research should focus on whether treating hyper­
not fully capture the risk of hyperglycemia prior to surgery. Indeed, glycemia – using insulin immediately pre-procedure to bring serum
10.4% of patients in our study with a HbA1C ≤8.0% arrived with a glucose levels below threshold values such as 140 mg/dL (7.8 mmol/L)
glucose ≥180 mg/dL immediately prior to surgery, indicating that a or 180 mg/dL (10 mmol/L) – can change the risk of postoperative
small but significant portion of patients with “good” glycemic control complications, or if preoperative hyperglycemia is simply a marker of
can arrive on the day of surgery with hyperglycemia. Furthermore, 49 of unmodifiable risk.
the 99 patients who had an HbA1C that was >8.0% actually had a Our study has many limitations, the most significant of which are
glucose level < 180 mg/dL immediately prior to surgery, making it that 1.) there was no standardized procedure for determining from
important for future studies to define whether immediate preoperative which patients a serum, plasma, or whole blood glucose concentration
glucose imparts a separate risk beyond HbA1C. Unfortunately, due to would be obtained; 2.) the vast majority of elective surgical patients at
the relatively small proportion of our population who HbA1C level our institution did not have an immediate preoperative glucose level
measured within 1 month of surgery, we cannot fully evaluate this. Prior available (n = 41,216); and 3.) we could not evaluate whether attempts
studies have suggested up to 20–30% of patients presenting for elective were made to control hyperglycemia pre-, intra-, or postoperatively. We
non-cardiac surgery have undiagnosed diabetes or pre-diabetes, and that were also unable to obtain data on other important risk factors for
such previously undiagnosed patients have higher fasting glucose levels infection or complication such as intraoperative hypothermia, specific
compared with patients with diabetes [18,25]. It may therefore be that type of procedure, history of coronary artery disease, or surgical
some of our patients classified as “no diabetes” would have been approach. We are therefore unable to determine whether or how our
recognized as belonging in the group with diabetes had a more rigorous sample subpopulation differs from all patients presenting for elective
screening regimen been performed, such as that recommended by the surgery at our institution. While we cannot use our data to make rec­
American Diabetes Association [18]. This may have also affected the ommendations as to which patients should have a glucose concentration
apparent relationship between fasting hyperglycemia and post- checked pre-operatively nor does this tell us whether treating hyper­
operative outcomes in our study. glycemia might affect patient outcomes, we do identify hyperglycemia
Guideline documents often use threshold values of glucose concen­ ≥180 mg/dL as a significant marker of risk in patients with diabetes that
tration. Logistic regression analyses in our study using individual is not accounted for by most other clinical factors.
glucose cutoffs in both the full cohort of patients and subgroups of pa­ In conclusion, our study demonstrates a clear association between
tients as separated by diabetic status clearly identified 180 mg/dL (10 hyperglycemia within 6 h of elective surgery and the risk of adverse
mmol/L) as a potential threshold for diabetic patients who have their postoperative outcomes in patients who had a glucose level measured
serum glucose level checked pre-operatively, above which the risk of for unknown reasons. In multivariable analyses, preoperative hyper­
complications increases significantly. A previously published retro­ glycemia by itself is not as predictive of adverse outcomes as other
spective review showed that in non-cardiac, non-vascular surgery pa­ factors such as CKD stage and duration of surgery, but nonetheless, our
tients, preoperative blood glucose levels >200 mg/dL (11.1 mmol/L) data show that among patients with diabetes in our study, a preoperative
were associated with a 2.1-fold increased risk in overall 30-day mor­ glucose level ≥ 180 mg/dL (≥10 mmol/L) has a very high and statisti­
tality [21]. In agreement with our results, a much larger retrospective cally independent correlation with risk of postoperative complications
analysis by Abdelmalek, et al., of >61,000 patients demonstrated that and readmission/reoperation rates. Our study and others clearly identify
preoperative hyperglycemia (measured up to 1 month prior to surgery) preoperative hyperglycemia as a marker of postoperative complications
is significantly correlated with postoperative complications – but not that needs further investigation to clarify whether a precise glycemic

8
S.M. Dougherty et al. Journal of Clinical Anesthesia 74 (2021) 110375

cutoff indeed increases risk and may provide potential benefit from [10] Showen A, Russell TA, Young S, Gupta S, Gibbons MM. Hyperglycemia is
associated with surgical site infections among general and vascular surgery
treatment. Our findings should prompt further studies that may help
patients. Am Surg 2017;83(10):1108–11. Epub 2018/02/03, 29391105.
inform clinical decision-making on the day of surgery for patients with [11] Berrios-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al.
hyperglycemia and may be relevant for future guideline documents. Centers for Disease Control and Prevention guideline for the prevention of surgical
site infection, 2017. JAMA Surg 2017;152(8):784–91. Epub 2017/05/04, htt
ps://doi.org/10.1001/jamasurg.2017.0904. PubMed PMID: 28467526.
Author contributions [12] Dhatariya K, Levy N, Kilvert A, Watson B, Cousins D, Flanagan D, et al. NHS
diabetes guideline for the perioperative management of the adult patient with
diabetes. Diabet Med 2012;29(4):420–33. Epub 2012/02/01, https://doi.org/1
S.M.D. and J.Sch. wrote the IRB, obtained and researched the data­ 0.1111/j.1464-5491.2012.03582.x. PubMed PMID: 22288687.
base, and wrote the manuscript. B.Z., M.B.S., and J. L. S. helped obtain [13] Joshi GP, Chung F, Vann MA, Ahmad S, Gan TJ, Goulson DT, et al. Society for
data from the electronic health record and the ACS NSQIP database. A.S. Ambulatory Anesthesia consensus statement on perioperative blood glucose
management in diabetic patients undergoing ambulatory surgery. Anesth Analg
R. helped design the study, performed all statistical analyses, and helped 2010;111(6):1378–87. Epub 2010/10/05, https://doi.org/10.1213/ANE.0b013e3
write the manuscript. W.K.R. helped design the study, obtain data, and 181f9c288. PubMed PMID: 20889933.
helped write the manuscript. B.T.O. designed the study, helped research [14] Lazar HL, McDonnell M, Chipkin SR, Furnary AP, Engelman RM, Sadhu AR, et al.
The Society of Thoracic Surgeons practice guideline series: blood glucose
data, and helped write the manuscript.
management during adult cardiac surgery. Ann Thorac Surg 2009;87(2):663–9.
Epub 2009/01/24.
Funding [15] Jacobi J, Bircher N, Krinsley J, Agus M, Braithwaite SS, Deutschman C, et al.
Guidelines for the use of an insulin infusion for the management of hyperglycemia
in critically ill patients. Crit Care Med 2012;40(12):3251–76. Epub 2012/11/21.
This work was supported in part by VA Merit Review Award Number [16] Simha V, Shah P. Perioperative glucose control in patients with diabetes
lO1 BXOO4468 (to B.T.O) and by startup funds from the Fraternal Order undergoing elective surgery. JAMA. 2019;321(4):399–400. Epub 2019/01/08.
[17] Surgeons ACo. https://www.facs.org/quality-programs/acs-nsqip/about. About
of Eagles Diabetes Research (to B.T.O.). No competing interests ACS NSQIP [internet]2020.
declared. [18] American Diabetes A. 15. Diabetes Care in the hospital: standards of medical care
in diabetes-2021. Diabetes Care 2021;44(Suppl. 1). https://doi.org/10.2337/dc21-
S015. S211-S20. Epub 2020/12/11. PubMed PMID: 33298426.
Declaration of interest [19] Gandhi GY, Nuttall GA, Abel MD, Mullany CJ, Schaff HV, O'Brien PC, et al.
Intensive intraoperative insulin therapy versus conventional glucose management
None. during cardiac surgery: a randomized trial. Ann Intern Med 2007;146(4):233–43.
Epub 2007/02/21.
[20] Mraovic B, Hipszer BR, Epstein RH, Pequignot EC, Parvizi J, Joseph JI.
References Preadmission hyperglycemia is an independent risk factor for in-hospital
symptomatic pulmonary embolism after major orthopedic surgery. J Arthroplasty
2010;25(1):64–70. Epub 2008/12/06.
[1] Duggan E, Chen Y. Glycemic management in the operating room: screening,
[21] Noordzij PG, Boersma E, Schreiner F, Kertai MD, Feringa HH, Dunkelgrun M, et al.
monitoring, oral hypoglycemics, and insulin therapy. Curr Diab Rep 2019;19(11):
Increased preoperative glucose levels are associated with perioperative mortality
134. Epub 2019/11/22.
in patients undergoing noncardiac, nonvascular surgery. Eur J Endocrinol 2007;
[2] Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C, et al. Prevalence and
156(1):137–42. Epub 2007/01/16, https://doi.org/10.1530/eje.1.02321. PubMed
clinical outcome of hyperglycemia in the perioperative period in noncardiac
PMID: 17218737.
surgery. Diabetes Care 2010;33(8):1783–8. Epub 2010/05/04. doi: 10.2337/dc10-
[22] Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power
0304. PubMed PMID: 20435798; PMCID: PMC2909062.
3.1: tests for correlation and regression analyses. Behav Res Methods 2009;41(4):
[3] Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, et al. Continuous
1149–60. Epub 2009/11/10, https://doi.org/10.3758/BRM.41.4.1149. PubMed
insulin infusion reduces mortality in patients with diabetes undergoing coronary
PMID: 19897823.
artery bypass grafting. J Thorac Cardiovasc Surg 2003;125(5):1007–21. Epub
[23] Goh SN, Yeoh E, Tan KY. Impact of perioperative hypoglycaemia in subjects with
2003/05/29.
diabetes undergoing colorectal surgery. Int J Colorectal Dis 2017;32(2):209–14.
[4] Kwon S, Thompson R, Dellinger P, Yanez D, Farrohki E, Flum D. Importance of
Epub 2016/11/20, https://doi.org/10.1007/s00384-016-2680-9. PubMed PMID:
perioperative glycemic control in general surgery: a report from the Surgical Care
27864588.
and Outcomes Assessment Program. Ann Surg 2013;257(1):8–14. Epub 2012/12/
[24] van den Boom W, Schroeder RA, Manning MW, Setji TL, Fiestan GO, Dunson DB.
14. doi: 10.1097/SLA.0b013e31827b6bbc. PubMed PMID: 23235393; PMCID:
Effect of A1C and glucose on postoperative mortality in noncardiac and cardiac
PMC4208433.
surgeries. Diabetes Care 2018;41(4):782–8. Epub 2018/02/15, https://doi.org/
[5] Umpierrez G, Cardona S, Pasquel F, Jacobs S, Peng L, Unigwe M, et al. Randomized
10.2337/dc17-2232. PubMed PMID: 29440113.
controlled trial of intensive versus conservative glucose control in patients
[25] Prevalence of Both Diagnosed and Undiagnosed Diabetes. Centers for disease
undergoing coronary artery bypass graft surgery: GLUCO-CABG trial. Diabetes Care
control and prevention. National Diabetes Statistics Report. US Department of
2015;38(9):1665–72. Epub 2015/07/17. doi: 10.2337/dc15-0303. PubMed PMID:
Health and Human Services; 2020 [Online]. Available: https://www.cdc.gov/dia
26180108; PMCID: PMC4542267.
betes/data/statistics-report/diagnosed-undiagnosed-diabetes.html.2020.
[6] van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M,
[26] Luethi N, Cioccari L, Biesenbach P, Lucchetta L, Kagaya H, Morgan R, et al. Liberal
et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345(19):
glucose control in ICU patients with diabetes: a before-and-after study. Crit Care
1359–67. Epub 2002/01/17.
Med 2018;46(6):935–42. Epub 2018/03/07, https://doi.org/10.1097/CC
[7] Wang YY, Hu SF, Ying HM, Chen L, Li HL, Tian F, et al. Postoperative tight
M.0000000000003087. PubMed PMID: 29509570.
glycemic control significantly reduces postoperative infection rates in patients
[27] Marik PE. Tight glycemic control in acutely ill patients: low evidence of benefit,
undergoing surgery: a meta-analysis. BMC Endocr Disord 2018;18(1):42. Epub
high evidence of harm! Intensive Care Med 2016;42(9):1475–7. Epub 2016/05/11,
2018/06/23. doi: 10.1186/s12902-018-0268-9. PubMed PMID: 29929558;
https://doi.org/10.1007/s00134-016-4299-2. PubMed PMID: 27161084.
PMCID: PMC6013895.
[28] Investigators N-SS, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive
[8] Abdelmalak BB, Knittel J, Abdelmalak JB, Dalton JE, Christiansen E, Foss J, et al.
versus conventional glucose control in critically ill patients. N Engl J Med 2009;
Preoperative blood glucose concentrations and postoperative outcomes after
360(13):1283–97. Epub 2009/03/26, https://doi.org/10.1056/NEJMoa0810625.
elective non-cardiac surgery: an observational study. Br J Anaesth 2014;112(1):
PubMed PMID: 19318384.
79–88. Epub 2013/09/07.
[29] Garg R, Schuman B, Bader A, Hurwitz S, Turchin A, Underwood P, et al. Effect of
[9] Wang R, Panizales MT, Hudson MS, Rogers SO, Schnipper JL. Preoperative glucose
preoperative diabetes management on glycemic control and clinical outcomes after
as a screening tool in patients without diabetes. J Surg Res 2014;186(1):371–8.
elective surgery. Ann Surg 2018;267(5):858–62. Epub 2017/05/27, https://doi.
Epub 2013/10/24, https://doi.org/10.1016/j.jss.2013.09.014. PubMed PMID:
org/10.1097/SLA.0000000000002323. PubMed PMID: 28549013.
24148355.

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