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Postoperative Tight Glycemic Control Wang et al. BMC Endocrine Disorders (2018) 18:42 https://doi.org/10.1186/s12902-018-0268-9 RESEARCHARTICLE Open Access Postoperative tight glycemic control significantly reduces postoperative infection rates in patients undergoing surgery: a meta-analysis Yuan-yuan Wang1, Shuang-fei Hu2, Hui-min Ying1, Long Chen2, Hui-li Li1, Fang Tian1 and Zhen-feng Zhou2* Abstract Background: The benefit results of postoperative tight glycemic control (TGC) were controversial and there was a lack of well-powered studies that support current guideline recommendations. Methods: The EMBASE, MEDLINE, and the Cochrane Library databases were searched utilizing the key words “Blood Glucose”, “insulin” and “Postoperative Period” to retrieve all randomized controlled trials evaluating the benefits of postoperative TGC as compared to conventional glycemic control (CGC) in patients undergoing surgery. Results: Fifteen studies involving 5053 patients were identified. As compared to CGC group, there were lower risks of total postoperative infection (9.4% vs. 15.8%; RR 0.586, 95% CI 0.504 to 0.680, p < 0.001) and wound infection (4. 6% vs. 7.2%; RR 0.620, 95% CI 0.422 to 0.910, p = 0.015) in TGC group. TGC also showed a lower risk of postoperative short-term mortality (3.8% vs. 5.4%; RR 0.692, 95% CI 0.527 to 0.909, p = 0.008), but sensitivity analyses showed that the result was mainly influenced by one study. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia (22.3% vs. 11.0%; RR 3.145, 95% CI 1.928 to 5.131, p < 0.001) and severe hypoglycemia (2.8% vs. 0.7%; RR 3.821, 95% CI 1.796 to 8.127, p < 0.001) as compared to CGC group. TGC showed less length of ICU stay (SMD, − 0.428 days; 95% CI, − 0.833 to − 0.022 days; p = 0.039). However, TGC showed a neutral effect on neurological dysfunction (1.1% vs. 2.4%; RR 0.499, 95% CI 0.219 to 1.137, p = 0.098), acute renal failure (3.3% vs. 5.4%, RR 0.610, 95% CI 0.359 to 1.038, p = 0.068), duration of mechanical ventilation (p = 0.201) and length of hospitalization (p = 0.082). Conclusions: TGC immediately after surgery significantly reduces total postoperative infection rates and short-term mortality. However, it might limit conclusion regarding the efficacy of TGC for short-term mortality in sensitivity analyses. The patients in the TGC group experienced a significant higher rate of postoperative hypoglycemia. This study may suggest that TGC should be administrated under close glucose monitoring in patients undergoing surgery, especially in those with high postoperative infection risk. Keywords: Tight glycemic control, Postoperative, Infection * Correspondence: [email protected] 2Department of Anesthesiology, Zhejiang Provincial People’s Hospital (People’s Hospital of Hangzhou Medicine College), Hangzhou 315000, China Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. BMC Endocrine Disorders (2018) 18:42 Page 2 of 12 Background infection or mortality. Two authors (Long CHEN and Tight glycemic control (TGC) was found to decrease the Fang TIAN) evaluated all records according to the above mortality and morbidity in critically ill patients [1] and it eligibility criteria (Table 1). We abstracted the year of has therefore been recommended as the standard treat- publication, sample size, type of surgery, population type ment for the duration of the perioperative intensive care (adult or infant), patient age, gender, history of diabetes, unit (ICU) throughout the world. However, subsequent baseline BG (blood glucose level), time of TGC interven- trials have failed to confirm the benefits of this recom- tion (only during the post-operative or intra-operative mendation [2, 3]. plus post-operative), target BG and trigger BG for inter- Perioperative hyperglycemia is reported in approxi- vention, any insulin infusion protocol, and reported clin- mately 20–40% of patients after general surgery [4] and ical outcomes. almost 80% of patients undergoing cardiac surgery [5]. Several studies in cardiac surgery and general surgery Outcomes definition and quality assessment have shown a clear association between perioperative The primary endpoint for the current review was any hyperglycemia and adverse clinical outcomes including postoperative infection including wound infection, pneu- delayed wound healing, surgical site infections, and pro- monia, urinary tract infection and sepsis. Secondary effi- longed hospital stay [4, 6]. However, the optimal glucose cacy outcomes were the duration of mechanical target during the post-operative period is widely contro- ventilation, length of ICU stay, length of hospital stay versial. No significant difference was found between (LOS) and other adverse events included the following: TGC and conventional glycemic control (CGC) when (1) short-term mortality (30-day mortality or hospital evaluating the variety of complications [5, 7, 8]. However, mortality). Any postoperative mortality including the fol- another study. [9] including cardiac surgery patients re- lowing outcomes: 30-day mortality, hospital mortality, ported a reduction of postoperative complications in TGC 6-month mortality and 1-year mortality; (2) neurological group. dysfunction including delirium, seizures and stroke; (3) Given the conflicting results and the lack of acute renal failure that required postoperative CRRT well-powered studies that support current guideline rec- (continuous renal replacement therapy); and (4) ommendations, the present study employed meta-analysis hypoglycemia, which was defined as a BG < 70 mg/dL, to evaluate the current evidence and analyze the associ- and the reported severe hypoglycemia (BG < 40 mg/dL). ation between the strategies of postoperative glycemic control and outcomes in patients undergoing elective Quality of the included studies surgery. The quality assessment of studies was independently performed by two investigators (Long CHEN and Fang Methods TIAN) and the Jadad scale was used to assess the meth- This meta-analysis was performed according to odological quality of individual studies [11]. These evalu- meta-analyses (PRISMA) format guidelines [10]. ative criteria included the generation of allocation sequence (2 points), allocation concealment (2 points), Search strategy investigator blindness (2 points), description of with- EMBASE, MEDLINE, and the Cochrane Library were drawals and drop-outs (1 points), and the efficacy of searched electronically by two investigators (Long CHEN randomization (2 points) (Additional file 2). The dis- and Fang TIAN) for relevant studies, and the following crepancies were resolved by a third author. key words were used: “Blood Glucose”“insulin” and “Postoperative Period”. The searches were last updated Data synthesis and analysis in 16th April 2018. Search strategies are available in Add- The statistical analysis was performed using STATA (Ver- itional file 1. Two investigators (Long CHEN and Fang sion 12.0). Dichotomous data were expressed as the risk ra- TIAN) independently screened the titles and abstracts to tio (relative risk [RR]) with 95% confidence interval (CI). exclude irrelevant articles. Then, they reviewed the Data were pooled using a random-effects model (M-H het- full-text articles to ensure all relevant articles had been in- erogeneity). Statistical heterogeneity was tested by the I2 cluded. A third author resolved any controversies. statistic and the χ2 test and heterogeneity was considered to be significant when values I2 > 50% and p ≤ 0.05. Sub- Study selection and data extraction group analyses and meta-regression analyses were applied We only included randomized controlled trials (RCTs) to detect the potential sources of heterogeneity. Sensitivity with surgery patients who had received postoperative analysis was performed to assess the stability of the results. TGC. Specific eligibility criteria were as follows: (a) pub- Publication bias was evaluated by Egger’sandBegg’stest, lished in English; (b) treatment with postoperative TGC; butitwasnotperformedasthenumberofincludedstudies and (c) the study documented any endpoints including was less than10 [12]. All reported p values were two-tailed Table 1 Main characteristics of the included trials Wang First author Type of surgery Patient type Sample Time of Insulin infusion Mean age Male (%) BMI(mean ± SD) et al. BMC Endocrine Disorders intervention protocol (mean ± SD, year) TGC/CGC TGC CGC TGC CGC TGC CGC Van Den et al. (2001) various surgeries adult 1548(765/ postoperative Yes 63.4 ± 13.6 62.2 ± 13.9 71 71 26.2 ± 4.4 25.8 ± 4.7 783) Salah M et al. (2013) cardiac surgery adult 100(50/ Intra + post Yes 46.0 ± 9.0 49.0 ± 8.0 60 70 28.0 ± 0.8 26.0 ± 2.0 50) operative Konstantinos et al. cardiac surgery adult 212(105/ postoperative Yes 64.9 ± 11.5 66.9 ± 11.1 66 68 27.8 ± 4.4 28.0 ± 3.9 (2013) 107) Amisha et al. (2017) liver adult 164(82/ postoperative Yes 58.1 ± 8.0 56.9 ± 7.6 65 65 30.3 ± 6.0 30.0 ± 6.6 (2018)18:42 transplantation 82) Rehong Zheng et al. cardiac surgery adult 100(50/ Intra + post Yes 43.3 ± 11.7 44.0 ± 11.5 48 46 (2010) 50) operative Raquel Pei Chen Chan cardiac surgery adult 108(54/ Intra + post Yes 57.0 ± 12.0 58 ± 12 43 56 24.0 ± 3.4 26.0 ± 4.9 et al. (2009) 55) operative Shou-gen Cao et al. elective radical adult 248(125/ postoperative Yes 58.5 ± 8.1 59.9 ± 7.6 67 64 20.8 ± 2.1 21.2 ± 2.1 (2011) gastrectomy with 123) D2 lymphadenectomy Shou-gen Cao et al.
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