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Open Access Journal of Urology & Nephrology Research Article 8 min read

Impact of the Agents Treated for Metabolic Syndrome on Surgical Complications

Sheng-Lung Hsu*, Chiu-Lan Chen, Kuo-Sheng Liu and Jin-Chang Hsieh
* Corresponding author
ISSN: 2578-4676  10.23880/oajun-16000162  Received: April 12, 2019  Published: May 03, 2019
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Keywords
Medication Metabolic Syndrome Odds Ratio Risk Factor Surgical Complication
Abstract

Background: The impact of metabolic syndrome (MS) on different surgical operations has gained significant attention recently. However, to date, it is unclear whether the medications used to treat MS can have an effect on surgical complications. Objectives: In this study, we aimed to investigate the effects of therapeutic agents used for the treatment of metabolic syndrome on surgical complications. Methods: We performed a retrospective case-control study based on chart reviews of 2624 surgical patients at our hospital in 2016. Data regarding surgical complications obtained from the hospital records were analyzed using binary logistic regression. The independent variables were angiotensin-converting-enzyme inhibitor, angiotensin receptor blocker (ARB), dihydropyridine calcium-channel blockers (DCCB), diuretics, potassium-sparing diuretics, nondihydropyridine calcium-channel blockers (NDCCB), dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonists (GLP1 agonists), nonselective beta-blockers, selective beta-blockers, peripheral vasodilators, alpha-glucosidase inhibitors, insulin, metformin, sulfonylureas, thiazolidinediones, bile acid sequestrants, fibrates, and statins. The dependent variable was surgical complications. Among the surgical patients included in the study, 328 (12.5%) had a history of metabolic syndrome. Results: In diseases with the same severity score [≥ ASA 3(American Society of Anesthesiologists)], diuretics, NDCCB, DCCB, insulin, GLP1 agonists, and selective beta-blockers had a significant influence in univariate logistic regression. However, multivariate logistic regression using control variables showed that only diuretic use was statistically significant (odds ratio 1.968, 95% confidence interval 1.141–3.394, p = 0.015). Conclusion: Several medications used for the treatment of metabolic syndrome pose a risk for surgical complications, although only diuretics showed a significant association.

Sheng-Lung Hsu1,2*, Chiu-Lan Chen2, Kuo-Sheng Liu2 and Jin-Chang

Hsieh3

Research, Taiwan

complications.

syndrome on surgical complications.

history of metabolic syndrome.

significant (odds ratio 1.968, 95% confidence interval 1.141–3.394, p = 0.015).

Conclusion: Several medications used for the treatment of metabolic syndrome pose a risk for surgical complications, although only diuretics showed a significant association.

Keywords: Medication; Metabolic Syndrome; Odds Ratio; Risk Factor; Surgical Complication Abbreviations: MS: Metabolic Syndrome, ARB: Angiotensin Receptor Blocker, ASA: American Society of Anesthesiologists, ICD: International Classification of Diseases, WC: Waist Circumference, BMI: Body Mass Index, WHO: World Health Organization, ACEi: Angiotensin-Converting-Enzyme inhibitor, DCCB: Dihydropyridine Calcium-Channel Blockers, NDCCB: Non- Dihydropyridine Calcium-Channel Blockers, DPP4i: Dipeptidyl Peptidase-4 inhibitor, GLP1 Agonists: Glucagon-Like Peptide-1 Receptor Agonists, OR: Odds Ratio, CI: Confidence Interval, SSIs: Surgical Site Infections.

Introduction

Although surgical complications are common in the daily practice of surgeons, they are considered serious issues related to surgery [1], which exacerbate the suffering of patients and lead to lengthy hospital stays and higher medical expenses. In recent years, the impact of metabolic syndrome on different surgical operations has gained significant attention [2, 3, 4, 5, 6, 7]. Several risk factors that could affect convalescence, including age, gender, disease history, physical status of the patient, anesthesia, blood loss, and wound condition, have been reported.

The prevalence of metabolic syndrome has been steadily increasing in Taiwan in recent years [8]. Metabolic syndrome can result in vascular thromboembolism of the tissue [9], which could lead to interruption of blood supply to wounds. However, there has been little research on the relationship between medications prescribed for metabolic syndrome and surgical complications except one case-control study about ARB. We aimed to investigate the effects of therapeutic agents used for the treatment of metabolic syndrome on surgical complications and to identify the agents that have a significant effect on surgical complications.

Material & Methods

This study is a correlational, case-control study using data from retrospective chart review. The main outcome of all subjects who received drugs for the treatment of metabolic syndrome was compared to patients without metabolic syndrome. The study was approved and monitored by the International Review Board of the XXXXX medical center and the requirement for informed consent waived. In total, 2624 surgical patients in our regional hospital between January 2016 and December 2016 with a mean age of 57.7 years (SD = 18.85) were included in our study after removing repetitive surgical data. The surgical complications were identified by the hospital surveillance system as follows: [International Classification of Diseases (ICD)-9 codes 457.0, 519.00- 519.09, 536.40-536.49, 564.2, 569.60-569.69, 674.12, 674.14, 674.32, 674.34, 996.00-996.09, 996.1, 996.2, 996.4, 996.51-996.59, 996.60-996.63, 996.66-996.69, 996.71-996.79, 996.80-996.89, 996.90-996.99, 997.00- 997.99, 998.0,998.1, 998.2, 998.3, 998.4, 998.51, 998.59, 998.6, 998.7, 998.81-998.9, 998.9]. All the above codes correlated with surgical complication in different body systems. As waist circumference (WC) is not measured routinely in our clinical practice, we chose body mass index (BMI) as a parameter indicating overall obesity. We modified the definition of metabolic syndrome after referring to the criteria of the Health Promotion Administration, Ministry of Health and Welfare (Table 1) [10] and the World Health Organization (WHO) [11, 12].

  • Any three of the following:
  • Use of anti-dyslipidemic medication
  • Use of anti-hypertensive medication or history of hypertension
  • Use of anti-diabetic medication or history of diabetic mellitus
  • BMI > 30
  • Men with HDL < 40 mg/dL, women with HDL < 50 mg/dL

Table 1: Criteria for diagnosis of metabolic syndrome.

Statistical Methods

All statistical analyses were performed with SPSS 24.0 (IBM Corporation, Armonk, NY, USA). The data were analyzed by binary logistic regression. The independent variables were angiotensin-converting-enzyme inhibitor (ACEi), ARB, dihydropyridine calcium-channel blockers (DCCB), diuretics, potassium-sparing (K+-sparing) diuretics, non-dihydropyridine calcium-channel blockers (NDCCB), dipeptidyl peptidase-4 inhibitor (DPP4i,), glucagon-like peptide-1 receptor agonists (GLP1 agonists), nonselective beta-blockers, selective beta-blockers, peripheral vasodilators, alpha-glucosidase inhibitors, insulin, metformin, sulfonylureas, thiazolidinediones, bile acid sequestrants, fibrates, and statins. The dependent variable was surgical complication. We also selected several significant variables including hypertension, diabetes mellitus, dyslipidemia, age, gender, BMI, and ASA (American Society of Anesthesiologists) as control variables to perform multivariate logistic regression.

Results

Three hundred and twenty-eight (12.5%) patients had a history of metabolic syndrome. All subjects with metabolic syndrome (odds ratio (OR) = 2.698, 95% confidence interval (CI) 1.695–4.296; p < 0.001) or any disease of metabolic syndrome had larger odds for surgical complications (p < 0.05). The elderly surgical patients had more complications than the younger patients. According to the ASA physical status classification, patients with severe disease (≥ ASA3) had more surgical complications (p < 0.001). Table 2 shows the relationship between agents used for the treatment of metabolic syndrome and surgical complications in all patients. In patients with metabolic syndrome, the agents showing a correlation with surgical complications were diuretics, NDCCB, insulin, and GLP1 agonists (Table 3). In patients with severe diseases (≥ ASA3), the agents showing a correlation with surgical complications were diuretics, NDCCB, DCCB, selective beta-blockers, insulin, and GLP1 agonists (Table 4). In multivariate logistic regression using control variables, only diuretics showed statistical significance (OR = 1.968, 95% CI 1.141–3.394; p = 0.015) (Table 5).

Patients with surgicalPatients without surgical
Odds ratio (95% CI)
Drugscomplications (n =97)complications (n =2527)p value
(n%)(n%)
ACEi5 (5.2)57 (2.3)2.355 (0.922–6.014)0.073
ARB24 (24.7)397 (15.7)1.764 (1.099–2.832)0.019
DCCB44 (45.4)441 (17.5)3.927 (2.599–5.933)<0.001
Diuretics40 (41.2)463 (18.3)3.128 (2.062–4.475)<0.001
K+-sparing diuretics7 (7.2)84 (3.3)2.262 (1.017–5.030)0.045
NDCCB15 (15.5)118 (4.7)3.734 (2.090–6.674)<0.001
Nonselective beta-blockers8 (8.2)91 (3.6)2.406 (1.133–5.110)0.022
Peripheral vasodilators7 (7.2)118 (4.7)1.588 (0.720–3.502)0.252
Selective beta-blockers34 (35.1)328 (13.0)3.618 (2.347–5.578)<0.001
Alpha-glucosidase inhibitors5 (5.2)61 (2.4)2.197 (0.862–5.597)0.099
DPP4i17 (17.5)182 (7.2)2.738 (1.588–4.721)<0.001
Insulin36 (37.1)285 (11.3)4.643 (3.020–7.137)<0.001
GLP1 agonists19 (19.6)70 (2.8)8.550 (4.909–14.892)<0.001
Metformin16 (16.5)206 (8.2)2.226 (1.278–3.876)0.005
Sulfonylureas7 (7.2)129 (5.1)1.446 (0.657–3.183)0.36
Thiazolidinediones3 (3.1)26 (1.0)3.070 (0.913–10.323)0.07
Bile acid sequestrants2 (2.1)24 (0.9)2.196 (0.511–9.426)0.29
Fibrates5 (5.2)19 (0.8)7.174 (2.621–19.635)<0.001
Statin (high intensity)10 (10.3)169 (6.7)1.604 (0.818–3.143]0.169
Statin (low intensity)1 (1.0)31 (1.2)0.839 (0.113–6.208)0.863
Statin (moderate intensity)4 (4.1)61 (2.4)1.739 (0.619–4.883)0.294
Patients with surgicalPatients without surgical
Odds ratio (95% CI)
Drugscomplications (n =26)complications (n =302)p value
(n%)(n%)
ACEi3 (11.5)23 (7.6)1.582 (0.442–5.668)0.481
ARB12 (46.2)167 (55.3)0.693 (0.310–1.548)0.371
DCCB11 (42.3)122 (40.4)1.082 (0.481–2.435)0.849
Diuretics16 (61.5)118 (39.1)2.495 (1.095–5.683)0.03
K+-sparing diuretics3 (11.5)25 (8.3)1.445 (0.406–5.151)0.57
NDCCB7 (26.9)35 (11.6)2.811 (1.103–7.162)0.03
Nonselective beta-blockers2 (7.7)18 (6.0)1.315 (0.288–6.006)0.724
Peripheral vasodilators4 (15.4)42 (13.9)1.126 (0.369–3.429)0.835
Selective beta-blockers7 (26.9)96 (31.8)0.791 (0.321–1.944)0.609
Alpha glucosidase inhibitors4 (15.4)46 (15.2)1.012 (0.333–3.072)0.983
DPP4i11 (42.3)137 (45.4)0.883 (0.393–1.986)0.764
Insulin20 (76.9)145 (48.0)3.609 (1.410–9.238)0.007
GLP1 agonists9 (34.6)38 (12.6)3.678 (1.531–8.837)0.004
Metformin11 (42.3)138 (45.7)0.871 (0.388–1.960)0.739
Sulfonylureas4 (15.4)90 (29.8)0.428 (0.143–1.278)0.129
Thiazolidinediones1 (3.8)21 (7.0)0.535 (0.069–4.147)0.55
Bile acid sequestrants1 (3.8)13 (4.3)0.889 (0.112–7.079)0.912
Fibrates3 (11.5)15 (5.0)2.496 (0.673–9.252)0.171
Statin (high intensity)7 (26.9)118 (39.1)0.574 (0.234–1.409)0.226
Statin (low intensity)1 (3.8)15 (5.0)0.765 (0.097–6.035)0.8
Statin (moderate intensity)3 (11.5)41 (13.6)0.830 (0.239–2.891)0.77

Table 2: Univariate logistic regression analysis showing the relationship between medications used to treat metabolic syndrome an

Patients with surgicalPatients without surgical
p
Drugscomplications n =63complications n =1252Odds ratio (95% CI)
value
(n%)(n%)
ACEi3 (4.8)50 (4.0)1.202 (0.364–3.965)0.763
ARB17 (27.0)293 (23.4)1.210 (0.683–2.142)0.514
DCCB28 (44.4)318 (25.4)2.350 (1.407–3.925)0.001
Diuretics30 (47.6)321 (25.6)2.637 (1.583–4.393)<0.001
K+-sparing diuretics6 (9.5)62 (5.0)2.020 (0.839–4.867)0.117
NDCCB10 (15.9)96 (7.7)2.272 (1.120–4.608)0.023
Nonselective beta blockers6 (9.5)59 (4.7)2.128 (0.882–5.136)0.093
Peripheral vasodilators3 (4.8)85 (6.8)0.686 (0.211–2.235)0.532
Selective beta-blockers20 (31.7)223 (17.8)2.146 (1.238–3.719)0.006
Alpha glucosidase inhibitors4 (6.3)51 (4.1)1.579 (0.558–4.566)0.383
DPP4i7 (11.1)132 (10.5)1.061 (0.474–2.375)0.886
Insulin22 (34.9)215 (17.2)2.588 (1.511–4.434)0.001
GLP1 agonists6 (9.5)40 (3.2)3.189 (1.299–7.831)0.011
Metformin11 (17.5)157 (12.5)1.475 (0.745–2.888)0.256
Sulfonylureas5 (7.9)102 (8.1)0.972 (0.381–2.477)0.952
Thiazolidinediones1 (1.6)22 (1.8)0.902 (0.120–6.799)0.92
Bile acid sequestrants2 (3.2)16 (1.3)2.533 (0.570–11.264)0.222
Fibrates2 (3.2)14 (1.1)2.899 (0.645–13.042)0.165
Statin (high intensity)7 (11.1)115 (9.2)1.236 (0.550–2.775)0.608
Statin (low intensity)1 (1.6)21 (1.7)0.945 (0.125–7.143)0.957
Statin (moderate intensity)3 (4.8)44 (3.5)1.373 (0.414–4.548)0.604

Table 3: Multivariate logistic regression analysis using control variables showing the relationship between medications used to t

DrugsOdds ratio95% CIp value
NDCCB1.429(0.660–3.097)0.365
DCCB1.697(0.988–2.916)0.055
ARB0.945(0.503–1.775)0.861
ACEi0.919(0.269–3.141)0.892
Diuretics1.968(1.141–3.394)0.015
K+-sparing diuretics1.461(0.587–3.636)0.415
Nonselectivebeta-blockers1.322(0.457–3.824)0.607
Peripheral vasodilators0.549(0.165–1.820)0.327
Selectivebeta-blockers1.648(0.922–2.946)0.092
Alpha-glucosidase inhibitors0.924(0.301–2.834)0.891
DPP4i0.546(0.221–1.351)0.191
Insulin1.848(0.788–4.334)0.158
GLP1 agonists1.761(0.621–4.991)0.287
Metformin1.038(0.483–2.232)0.924
Sulfonylureas0.824(0.339–2.000)0.668
Thiazolidinediones0.642(0.082–5.050)0.674
Bile acidsequestrants1.412(0.275–7.243)0.679
Fibrates2.297(0.458–11.529)0.312
Statin (high intensity)0.884(0.315–2.481)0.814
Statin (low intensity)0.707(0.089–5.598)0.742
Statin (moderate intensity)1.502(0.445–5.065)0.512

Table 4: Multivariate logistic regression analysis using control variables showing the relationship between medications used to t

Note: Control variables are hypertension, diabetes mellitus, dyslipidemia, age, gender, BMI, and ASA.

In this study, we determined the impact of therapeutic agents used for the treatment of metabolic syndrome on surgical complications. We found that diuretics, NDCCB, DCCB, selective beta blockers, insulin, and GLP1 agonists showed a correlation with surgical complications in patients with ASA score ≥3. Regarding the definition of metabolic syndrome, the WHO criteria for the diagnosis of metabolic syndrome are complex, because it takes into account microalbuminuria, plasma insulin level, and BMI and WC. Central obesity is a key criterion of the global consensus definition for metabolic syndrome. As our study lacked data on WC, future studies including WC criterion are warranted.

Our results demonstrated that patients with metabolic syndrome who were administered diuretics, NDCCB, DCCB, selective beta-blockers, insulin, and GLP1 agonists had more surgical complications. However, the results were equivocal, with a relatively small odds ratio when the correlation of surgical complications with each of these medications was examined. As we already know, the larger the odds ratio, the higher the statistical significance in case-control studies. To avoid bias, we also performed multivariate logistic regression using control variables, namely, hypertension, diabetes mellitus, dyslipidemia, age, results were in agreement with the above findings of the systematic review.

In 2016, ICD 9 classification, which was still used in our hospital, was revised to ICD-10; however, this did not affect our assessment. Perioperative statin therapy for metabolic syndrome has gained popularity in recent years [18, 19]. Since patients with cardiovascular operations showed a higher risk for developing surgical complications, the counteraction of statins on the detrimental effect help in combating surgical stress. In the near future, the surgical complications of metabolic syndrome, especially vascular injury, might be prevented by the available anti-diabetic medicines [20]. The urological complications (ICD9 997.5) were included in our study without exception. Urinary tract complications were no different from other systems in spite of their vast endoscopic nature. There are certain limitations to the present study. First, in subjects receiving multiple drugs or compound medicine, assessment was only performed separately for each drug. Second, this is a retrospective study with a non-experimental design and therefore, a prospective research is warranted.

Conclusion

In patients with severe diseases (≥ ASA3), the agents showing a correlation with surgical complications were diuretics, NDCCB, DCCB, selective beta blocker, insulin, and GLP1 agonists. Among them, the most prominent impact was for diuretics.

Acknowledgments

The authors thank the staff at the information technology department for their assistance.

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@article{shenglung2019,
  title   = {Impact of the Agents Treated for Metabolic Syndrome on
Surgical Complications},
  author  = {Sheng-Lung Hsu, Chiu-Lan Chen, Kuo-Sheng Liu and Jin-Chang
Hsieh},
  journal = {Open Access Journal of Urology & Nephrology},
  year    = {2019},
  volume  = {4},
  number  = {2},
  doi     = {10.23880/oajun-16000162}
}
Sheng-Lung Hsu, Chiu-Lan Chen, Kuo-Sheng Liu and Jin-Chang
Hsieh (2019). Impact of the Agents Treated for Metabolic Syndrome on
Surgical Complications. Open Access Journal of Urology & Nephrology, 4(2). https://doi.org/10.23880/oajun-16000162
TY  - JOUR
TI  - Impact of the Agents Treated for Metabolic Syndrome on
Surgical Complications
AU  - Sheng-Lung Hsu, Chiu-Lan Chen, Kuo-Sheng Liu and Jin-Chang
Hsieh
JO  - Open Access Journal of Urology & Nephrology
PY  - 2019
VL  - 4
IS  - 2
DO  - 10.23880/oajun-16000162
ER  -