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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 6  |  Page : 1234-1238

Neopterin and mini-mental state examination scores, two independent risk factors for postoperative delirium in elderly patients with open abdominal surgery


Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

Date of Web Publication28-Nov-2018

Correspondence Address:
Dezhen Lv
No. 305 East Zhongshan Road, Nanjing, Jiangsu Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.192764

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 > Abstract 


Background: Postoperative delirium is described as one of the most common complications for elderly patients with unknown pathophysiological pathways. In this present study, we analyzed the clinical and biochemical parameters in elderly patients with or without a delirium after open abdominal surgery to investigate the possible predicative factors for a delirium.
Materials and Methods: Patients aged ≥60 years scheduled to undergo elective gastrointestinal tumor resection via laparotomy from July 2012 to June 2015 were enrolled in this study. Demographic and clinical data, characteristics of the surgical and anesthetic procedure, biochemical parameters were compared between patients with or without a delirium. Multivariate logistic regression testing was used for the evaluation of independent risk factors for postoperative delirium.
Results: Overall, 112 participants were enrolled in this study, 49 of which were diagnosed with postoperative delirium. Patients with a delirium had an older age (P = 0.013) and a lower Mini-Mental State Examination (MMSE) score (P < 0.01) compared with those patients who had no delirium. The duration of surgery and anesthesia, the levels of neopterin, C-reactive protein, interleukin-6, insulin-like growth factor-1 in patients with a delirium were significantly higher than those without a delirium (P < 0.05). Independent risk factors in the logistic regression for postoperative delirium were the levels of neopterin and MMSE scores.
Conclusions: Our present study suggested the potential roles of neopterin and MMSE scores in the pathophysiology and prediction of delirium in elderly patients after open abdominal surgery.

Keywords: Delirium, Mini-Mental State Examination score, neopterin, open abdominal surgery, risk factors


How to cite this article:
Miao S, Shen P, Zhang Q, Wang H, Shen J, Wang G, Lv D. Neopterin and mini-mental state examination scores, two independent risk factors for postoperative delirium in elderly patients with open abdominal surgery. J Can Res Ther 2018;14:1234-8

How to cite this URL:
Miao S, Shen P, Zhang Q, Wang H, Shen J, Wang G, Lv D. Neopterin and mini-mental state examination scores, two independent risk factors for postoperative delirium in elderly patients with open abdominal surgery. J Can Res Ther [serial online] 2018 [cited 2020 Apr 9];14:1234-8. Available from: http://www.cancerjournal.net/text.asp?2018/14/6/1234/192764




 > Introduction Top


Postoperative delirium, an acute neuropsychiatric syndrome characterized by cognitive functions, is described as one of the most common complications for elderly patients.[1] Delirium is associated with adverse outcomes including postoperative cognitive dysfunction,[2] decreased quality of life, increased costs, poorer recovery, greater mortality, and morbidity.[3] Several studies have established the possible clinical risk factors for delirium; however, the pathophysiological pathways for delirium still remain unclear.[4] The possible involved pathogenesis may concludes the process of aging, oxidative stress, immune activation, disturbances of cerebral neurotransmitters oxidative stress.[5] Cytokines, neopterin, and reactive oxygen species can be detected in the plasma, urine, or cerebrospinal fluid of patients with delirium associated with the activation of the immune system in response to tissue damage, hypoxia, atherosclerosis, and infection.[6],[7] Neopterin is considered as a marker of cellular oxidative stress and immune activation.[8] High levels of neopterin are associated with some cerebral disorders and poor prognosis in ischemic heart disease; however, few studies have revealed the role of neopterin in delirium.[9] Mini-Mental State Examination (MMSE) is a significant tool for the measurement of cognitive function, and the state of preoperative cognitive function strongly predicts the incidence of postoperative delirium.[10] MMSE has also been proved to be associated with postoperative delirium.[11] In this present study, we analyzed the levels of neopterin and MMSE scores in elderly patients with or without a delirium after open abdominal surgery to investigate possible predicative factors for delirium.


 > Materials and Methods Top


Patients

This study was approved by the Medical Institutional Ethics Committee. Patients aged ≥60 years scheduled to undergo elective gastrointestinal tumor resection via laparotomy from July 2012 to June 2015 were enrolled in this study. Patients diagnosed with Parkinson's disease,  Lewy body dementia More Details, neuroleptic malignant syndrome, or tardive dyskinesia were eliminated from the study. Patients with on-going treatment with antipsychotics or other psychiatric medications, patients with insufficient understanding of language, and a MMSE score <:10 were also excluded. Before entering the study, all participants included in this study received oral and written information and were required to provide written informed consent. The Medical Ethics Committee of Hospital approved the study.

Demographic and clinical data (including the age, gender, education, body mass index [BMI]) were collected at admission. The Charlson Comorbidity Index was used for the assessment of severity of comorbidities.[12] The MMSE score was also completed to assess the cognitive function before the surgery. The characteristics of surgical and anesthetic procedure were also recorded including the American Society of Anesthesiologists (ASA) physical status, duration of surgery, duration of anesthesia, estimated blood loss, duration of hospital stay, drugs, and anesthetic schemes.

Methods

Biochemical measurements

Nonfasting blood was collected in the morning on the day before surgery in a 8-ml tube containing ethylene diamine tetra-acetic acid (EDTA) as well as in a 10-ml serum-separating tube, stored at room temperature. To avoid the loss of neopterin, the tubes were protected from light.[13] The collected blood sample was centrifuged for 20 min (2650 g, 20°C) within 3 h. Then, the obtained serum and plasma were stored at −80°C before the detection. As described previously, the plasma levels of neopterin were measured by high-performance liquid chromatography after acid oxidation.[14] The levels of inflammatory cytokines including C-reactive protein (CRP), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) were detected by enzyme-linked immunosorbent assays. The measurement was performed according to the manufacturers' guidelines (R&D Systems, Minneapolis, MN, USA) by the same technician who was blinded to this study.

Assessment of delirium

The nursing or medical staff in our research group observed all the participants included daily under the instruction of a psychiatrist and delirium experts until discharge. The observers were all blinded to the study design. In order to avoid the research bias, assessment for delirium twice a day (morning and night) was required from the first to the seventh postoperative day. The diagnosis of delirium was according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).[15]

Statistical analysis

We used SPSS 19.0 (SPSS Inc., Chicago, IL, USA) for statistical analysis in this study with data presented as number (n) and percentage (%), or mean ± standard error of the mean Chi-square test and Mann–Whitney U-test are used for the statistical analysis. The risk factors for postoperative delirium were evaluated by multivariate logistic regression testing. All statistical tests were bilateral probability and P < 0.05 was accepted as statistically significant.


 > Results Top


Baselines

One hundred eighty-eight patients met the inclusion criteria for this study during the period of inclusion. And 76 patients were excluded due to various reasons (50 refused to provide informed consent, 20 refused to cooperate, and 6 with other reasons). The baseline characteristics of the 112 participants included in this study were presented in [Table 1]. Of the 112 participants, 49 patients were diagnosed with a delirium according to the DSM-IV. The results showed that the gender, education, BMI, and Charlson comorbidity index in patients with or without a delirium were with no statistically significant difference. Besides, patients with a delirium had an elder age (P = 0.013) and a lower MMSE score (P < 0.01) compared with those patients who had no delirium.
Table 1: Baseline characteristics of the patients with or without delirium

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Characteristics of the surgical and anesthetic procedure

[Table 2] presents the characteristics of surgical and anesthetic procedure (including ASA physical status, duration of surgery, duration of anesthesia, estimated blood loss, duration of hospital stay, drugs, and anesthetic) of the patients in two groups. The duration of surgery and anesthesia in patients with a delirium were statistically significant higher than those without a delirium (P < 0.05).
Table 2: Characteristics of the surgical and anesthetic procedure

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Biochemical parameters

Biochemical parameters including neopterin, CRP, IL-6, IGF-1, GFR, creatinine, and urea were presented in [Table 3]. The results showed that the levels of neopterin, CRP, IL-6, and IGF-1 in patients with a delirium were significantly higher than those without a delirium (P < 0.05).
Table 3: Biochemical parameters of patients with or without delirium

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Factors associated with postoperative delirium by using a multivariate logistical regression analysis

As shown in [Table 4], multiple logistic regression analysis was used to analyze the risk factors and that was correlated with the development of postoperative delirium. Independent risk factors in the logistic regression for postoperative delirium were the levels of neopterin and MMSE scores.
Table 4: Multivariate logistic regression analysis for delirium

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 > Discussion Top


This present study examined the biochemical parameters and clinical characteristics for the potential predicative factors for delirium after open abdominal surgery. Patients with a delirium had an older age and lower MMSE score in comparison with those patients without a delirium [Table 1]. The factors including the age and preoperative cognitive functioning were associated with risk of delirium, and this was quite in agreement with other studies.[16] As shown in [Table 2], patients with a delirium had generally a longer duration of surgery and anesthesia than those. The duration of surgery and anesthesia might also be associated factors for the development of postoperative delirium.

Furthermore, the results also showed that the mean preoperative plasma levels of neopterin, CRP, IL-6, and IGF-1 were significantly elevated in elderly patients with a delirium, which is in agreement with previous studies.[17] Neopterin was reported to reflect the oxidative stress and cell-mediated immune activation by previous studies.[18] The results suggested that inflammatory state and oxidative stress play important roles in the induction of postoperative delirium. The renal function was also evaluated between the patients with or without a delirium, and no statistically significant differences were found. The detected values of neopterin were probably not influenced by the effect of renal function. The elevated serum CRP and IL-6 levels in patients with a delirium suggested a higher inflammatory state and an activated immune system. Our findings were in line with the results reported by previous researches.[19] As shown in our results, the serum IGF-1 levels were significantly reduced when with a delirium. Since IGF-1 has been proved to be a neuroprotective cytokine, it could pass the blood-brain barrier.[20] The reduced IGF-1 levels might suggest a loss of brain reserve.[21] An increased vulnerability of the brain reserve, a disturbed activation of the immune system and oxidative stress might contribute to the development of a delirium.

All these possible risk factors for delirium including age, MMSE score, duration of surgery and anesthesia, biochemical parameters as mentioned above were then analyzed by multiple logistic regression. The results suggested that preoperative levels of neopterin and MMSE score were independent associated factors for the development of postoperative delirium. The cognitive function before the surgery (evaluated by MMSE score), were significantly associated with the incidence of postoperative delirium in geriatric patients with open abdominal surgery under general anesthesia. Our findings are consistent with from the results of previous studies, demonstrating that lower preoperative state of cognitive function was associated with higher incidence of postoperative delirium.[22] Some researchers have even suggested MMSE scores as the prediction of postoperative delirium in patients undergoing cardiac surgery.[23]

Whether neopterin plays a direct role in the development of delirium or that it interacts with other factors still remains unclear. Neopterin in cerebrospinal fluid was found to be significantly elevated in various diseases with neurological complications.[24] Neopterin was reported to derive from infiltrating macrophages and monocytes in the brain, and it could not be produced by astrocytes, microglia, and neurons.[25] Neopterin was able to induce apoptosis in astrocytes and neurons through its derivative 7,8-dihydroneopterin. The induction of apoptosis in the brain was probably an important mechanism for the association between neopterin and delirium. Interferon-gamma could evaluate the production of neopterin by stimulating the enzyme guanosine triphosphate cyclohydrolase-I in macrophages.[18] The impact of neopterin on the metabolism of amino acids in the brain might be another correlated explanation for the induction of a delirium.[26],[27] We hypothesized that maybe the neuronal injury induced by elevated biochemical parameters (neopterin, IL-6, CRP, and IGF-1) involved in the pathogenesis of a delirium.[28] Previous studies suggested that serum level of S100B, as an important marker of cerebral damage, is proved to be elevated in patients with a delirium, which is in agreement with our hypothesis.[29],[30] Moreover, few studies have revealed the correlation between neopterin and MMSE scores. It has been reported that the increase of neopterin was significantly associated with the decrease in the MMSE scores, along with the clinical progression of Alzheimer's disease (AD).[31] However, other findings suggested that neopterin levels were within the normal range in AD patients and were not altered with increased pro-inflammatory cytokines or MMSE scores.[32]


 > Conclusions Top


Our present study might suggest the potential roles of neopterin and MMSE scores in the pathophysiology and prediction of delirium in elderly patients after open abdominal surgery. However, the involved pathways by which neopterin and MMSE scores are associated with a delirium still remain unclear. To investigate whether neopterin could be an effective biomarker for delirium, further and more large-scale studies were required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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