Correlation and Influencing Factors of Preoperative Anxiety, Postoperative Pain, and Delirium in Elderly Patients Undergoing Gastrointestinal Cancer Surgery

Abstract

Background: The correlation and influencing factors of preoperative anxiety, postoperative pain, and delirium in elderly patients undergoing gastrointestinal cancer surgery were explored with the Beck Anxiety Inventory (BAI) scale, 10-point Visual Analogue Scale (VAS), and Confusion Assessment Method Chinese Reversion (CAM-CR) scale.

Methods: Patients aged 65 years or above were enrolled from the First Affiliated Hospital of Guangxi Medical University, from September 2019 to October 2020. A total of 120 elderly patients who underwent gastrointestinal cancer surgery under general anesthesia were collected. Perioperative anxiety, pain, and delirium were assessed with the BAI scale, VAS scale, and CAM-CR scale. The correlation and influencing factors of preoperative high anxiety, postoperative high pain, and postoperative delirium were analyzed.

Results: The incidences of high anxiety on one day before surgery (day-0) and on the postoperative day (pod) 1, 3, and 7 (pod-1, pod-3, pod-7) were 19.2%, 5.8%, 9.2%, and 0.0%, respectively. The incidences of high pain on the day-0, pod-1, pod-3, pod-7 were 0.0%, 41.7%, 15.0%, 4.2%, respectively. The incidences of delirium on the day-0, pod-1, pod-3, pod-7 were 0.0%, 24.2%, 4.2%, 0.0%, respectively. There was a positive correlation between preoperative high anxiety and postoperative high pain (P<0.001, r=0.410), and there was a positive correlation between preoperative high anxiety and postoperative delirium (P=0.005, r=0.281), and there was a positive correlation between postoperative high pain and postoperative delirium (P=0.017, r=0.236). The results from multiple linear regression analysis had shown that types of cancer and surgical approaches had an impact on preoperative high anxiety (P=0.006 and P=0.021 ); preoperative high anxiety had a positive influence on postoperative high pain (P＜0.001); age and preoperative high anxiety had a positive impact on postoperative delirium (P＜0.001 and P=0.010).

Conclusions: Elderly patients receiving gastrointestinal cancer surgery had high incidences of high anxiety before surgery, high pain, and delirium on postoperative day 1. Preoperative high anxiety was positively correlation with postoperative high pain and postoperative delirium; postoperative high pain was positively correlation with postoperative delirium. Types of cancer and surgical approaches were as influencing factors of preoperative high anxiety; preoperative high anxiety was an influencing factor of postoperative high pain; and age and preoperative high anxiety were influencing factors of postoperative delirium.

Trial registration

ChiCTR2000032008, 17/04/2020, Title: “Effects of different analgesic methods on postoperative recovery of elderly patients with digestive tract tumor”. Website: https://www.chictr.ogr.cn.

Background

Preoperative anxiety is a typical emotional issue among surgical patients. Studies have shown that preoperative anxiety affects patients on both a physiological and a psychological level¹.Surgery and anesthesia are the main factors of preoperative anxiety. The incidence of preoperative anxiety in Chinese adults is 16.9%, and female gender, highly invasive surgery were identified as risk factors for high preoperative anxiety². Preoperative anxiety plays an important role in modulating postoperative pain^3–6. Literature and research is based on the theory of a linear rather than curvilinear relationship between anxiety and pain, meaning that with increased anxiety there is an increase in pain⁷. Earlier psychological intervention for patients with preoperative anxiety that could reduce postoperative pain severity⁸. However, Kain et al pointed out that there was not positive correlation between anxiety and pain, probably due to a correlation between pain and anxiety may not be applicable to patients undergoing major surgery from a study by Kalkman et al⁹ also had come to a similar conclusion, that was preoperative pain was the best predictor of severe pain early in the postoperative period, not preoperative anxiety¹⁰.

Further, It is also unclear whether preoperative anxiety or postoperative pain contributed to postoperative delirium. Previous researches had shown that there was no association between preoperative anxiety and postoperative delirium in aged patients undergoing cardiac surgery and hip fracture patients^11–13. Nevertheless, a prospective observational cohort study had shown that preoperative anxiety was a predictor of postoperative delirium in cancer patients conducted by Saho Wada et al¹⁴.

Delirium, a severe disorder of attention and cognition, is a common postoperative complication among elderly adults, with an incidence of 15–25% after major elective operation¹⁵. More commonly delirium is multifactorial in older persons. Delirium is often caused by multiple factors, such as dementia, depression, older age. There is no any convincing evidence to support that postoperative pain could lead to delirium. But high levels of postoperative pain and using high opioid doses increased risk for postoperative delirium¹⁶, and proper postoperative pain management could lower the incidence of postoperative delirium¹⁷.

In this study, with the aim of finding out the correlation and influencing factors of preoperative anxiety, postoperative pain, and delirium in elderly patients undergoing gastrointestinal Cancer Surgery, scale scores of anxiety, pain, delirium on one day before surgery and on several days after surgery were collected. The primary outcome of this study was the correlation between preoperative high (moderate to severe) anxiety, postoperative high (moderate to severe) pain, and postoperative delirium.

Methods

Study Population

This was a single-centered, prospective, and observational study approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (identifier: NO.2019 (KY-E-115)) and registered at www.chictr.org.cn (ChiCTR2000032008). Patients with gastrointestinal cancer were asked to join our clinical trial before surgery, and all the patients participating in the study signed the informed consent forms. Inclusion criteria were as follows: (1) age not less than 65 years old, (2) American Society of Anesthesiologist physical status class I-III, (3) gastrointestinal cancer surgery under general anesthesia, (4) hospital stay at least senven days after surgery, (5) ability to sign informed consent forms and to read and write, (6) a preoperative Mini-Mental State Examination (MMSE) score of 15 or higher. Exclusion criteria were: patients, with mental illness or history of opioid and alcohol abuse, communication impairment, serious postoperative complications, or American Society of Anesthesiologist physical status class not less than IV, or those transferred to the intensive care unit (ICU) after surgery.

Study Design

A total of 120 patients who underwent elective radical surgery for gastric cancer or colorectal cancer with general anesthesia were recruited. Anesthesia and postoperative analgesia method could be chosen based on the patient's current situation and the anesthesiologist's preference. All patients received general anesthesia, including total intravenous anesthesia or combined intravenous and inhalation anesthesia. Patients were either administered a single bilateral transversus abdominis plane block (TAP) with 0.25% ropivacaine, volume 40 ml before surgery, or received patient-controlled intravenous analgesia (PCIA) pump, or received TAP combined with PCIA (TAP-PCIA ) or received patient-controlled epidural analgesia (PCEA) pump, or received oral analgesics in the ward without any analgesic pump.

Follow-up, Retention, And Scales Evaluation

In this study, the level of anxiety and pain, and occurrence of delirium were assessed on one day before surgery (day-0) and on the postoperative day (pod) 1, 3, and 7 (pod-1, pod-3, pod-7) with Beck Anxiety Inventory (BAI) scale, 10-point Visual Analogue Scale (VAS), and Confusion Assessment Method Chinese Reversion (CAM-CR) scale, respectively.

The BAI¹⁸ scale consisted of 21 items, each describing a common symptom of anxiety. The respondent was asked to rate how much he or she has been bothered by each symptom a 4-point scale ranging from 0 (Not at all) to 3 (Severely—I could barely stand it). The items were summed to obtain a total score that could range from 0 to 63 (0 = absent, 8–15 = mild, 16–25 = moderate, greater or equal to 26 = severe). Patients were diagnosed with high (moderate to severe) anxiety when BAI score ≥ 16.

The VAS score score was converted to a numerical value between 0 and 10 and to a verbal scale (0 = absent, 1–3 = mild, 4–6 = moderate, 7–9 = intense and 10 = unbearable)¹⁹. Patients were believed to experience high (moderate to severe) pain when VAS score༞3 on any day of day-0, pod-1, pod-3 and pod-7.

In the study, CAM Chinese reversion (CAM-CR) scale was used to screen delirium. CAM-CR scale²⁰ as a revision of CAM scale, which was tailor-made for assessment and diagnosis of delirium in elderly Chinese patients. The sensitivity and specificity of CAM-CR were 0.90 and 0.94, respectively. There were 11 fundamental CAM items in the CAM-CR scale. The criteria for each item was separated into categories based on the severity of patients’ symptoms: 1 = absent, 2 = mild, 3 = moderate, 4 = severe. The items were summed to obtain a total score that could range from 11 to 44. CAM-CR score ≤ 19 suggested that the patient did not have delirium; CAM-CR score of 20–22 suggested that the patient was suspicious for delirium; CAM-CR score༞22 suggested the patient was diagnosed delirium. Patient was diagnosed with delirium on any day of day-0, pod-1, pod-3 and pod-7.

All scales were operated by trained anaesthesiologist through face-to-face assessment during hospital stay. In order to promote follow-up and retention, all scale assessments were conducted in a quiet environment and wrer assessed by the same attending anaesthesiologist. Meanwhile, baseline demographics, such as sex, age, occupation, types of cancers, ASA physical status, duration of anesthesia, duration of surgery, and duration in the postanesthesia care unit (PACU), were collected.

Result

Of 120 patients screened for eligibility and had finished followed-up on the day-0, pod-1, and pod-3. Of 4 patients refuse BAI scale assessment, and of 6 patients refuse CAM-CR scale assessment on the pod-7. The baseline demographics of study population were as follows (Table 1).

Comparison of the BAI, VAS, and CAM-CR scores on the day-0, pod-1, pod-3, and pod-7. (Table 2 and Table 3)

The BAI scores were significantly lower on pod-7 [7 (4 to 8)] than on day-0 [10 (8 to 13)], pod-1 [9 (8 to 10)], and pod-3 [8 (7 to 10)] (unadjusted P < 0.001, P < 0.001, P = 0.001, respectively; adjusted P < 0.001, P < 0.001, P = 0.005 ). The BAI scores were lower on pod-1 and pod-3 than on day-0. (unadjusted P = 0.004 and P < 0.001; adjusted P = 0.239 and P < 0.001 ). The BAI scores were lower on pod-1 than on pod-3 ((unadjusted P = 0.001, adjusted P = 0.006). (Table 2). The incidences of high anxiety (BAI score ≥ 16) occurred on day-0, pod-1, pod-3, and pod-7 were 19.2%, 5.8%, 9.2%, and 0.0%, respectively (Table 3).

The VAS scale shown that the patient's pain scores gradually decreased over time. The pain VAS scores were signifcantly higher on pod-1 [3 (2 to 4)], pod-3 [2 (2 to 3)], and pod-7 [2 (1 to 2)] than on day-0 [0 (0 to 0)] (unadjusted P < 0.001, P < 0.001, P < 0.001, respectively; adjusted P < 0.001, P < 0.001, P < 0.001, respectively ). The pain VAS scores were signifcantly higher on pod-1 than on pod-3 and pod-7 (unadjusted P = 0.001 and P < 0.001; adjusted P = 0.006 and P < 0.001). The pain VAS scores were signifcantly higher on pod-3 than on pod-7 (unadjusted P = 0.001; adjusted P = 0.004 ) (Table 2). The incidences of high pain (VAS score༞3) occurred on day-0, pod-1, pod-3, and pod-7 were 0.0%, 41.7%, 15.0%, and 4.2%, respectively (Table 3).

The CAM-CR scores were significantly higher on pod-1 [17 (16 to 20)], pod-3 [17 (15 to 19)], and pod-7 [16 (15 to 18)] than on day-0 [15 (14 to 16)] (unadjusted P < 0.001, P < 0.001, P < 0.001, respectively; adjusted P < 0.001, P < 0.001, P < 0.001, respectively). The CAM-CR scores were higher on pod-1 than on pod-3 and pod-7 (unadjusted P = 0.026 and P < 0.001; adjusted P = 0.157 and P < 0.001). The CAM-CR scores were significantly higher on pod-3 than pod-7 (unadjusted P = 0.002 and adjusted P = 0.014 ) (Table 2). The incidences of delirium (CAM-CR score༞22) occurred on day-0, pod-1, pod-3, and pod-7 were 0.0%, 24.2%, 4.2%, and 0.0%, respectively (Table 3).

Of 23 (19.2%) patients experienced preoperative high anxiety (BAI score ≥ 16). Of 57 (47.5%) patients experienced postoperative high pain (VAS score༞3). Of 31(25.8%) patients were diagnosed delirium (CAM-CR score༞22).

The correlation and influencing factors of preoperative high anxiety, postoperative high pain, and postoperative delirium and baseline data. (Table 4 and Table 5 )

The result of cross-table continuous corrected chi-square test and Pearson correlation analysis shown that preoperative high anxiety had a significant difference with age, types of cancer, methods of anesthesia and analgesia, and surgical approaches (P = 0.021, r = 0.125; P<0.001, r=-0.367; P = 0.005, r=-0.139; and P<0.001, r = 0.324, respectively) (Table 4). Through multiple linear regression analysis to analyze statistically significant variables (age, types of cancer, methods of anesthesia and analgesia, and surgical approaches) from chi-square test, types of cancer and surgical approaches were considered to be independent risk factors of preoperative high anxiety (P = 0.006 and P = 0.021) (Table 5).

Postoperative high pain had a significant difference with types of cancer, methods of anesthesia and analgesia, and preoperative high anxiety (P = 0.004, r=-0.260; P<0.001, r=-0.120; P<0.001, r = 0.410, respectively) (Table 4). Through multiple linear regression analysis to analyze statistically significant variables (types of cancer, methods of anesthesia and analgesia, and preoperative high anxiety) from chi-square test, preoperative high anxiety was considered to be an independent risk factor of postoperative high pain (P<0.001) (Table 5). It means that preoperative high anxiety had a significant positive impact on postoperative high pain.

Postoperative delirium had a significant difference with age, occupation, preoperative high anxiety and postoperative high pain (P<0.001, r = 0.566; P = 0.038, r = 0.181; P = 0.005, r = 0.281; P = 0.017, r = 0.236, respectively) (Table 4). Through multiple linear regression analysis to analyze statistically significant variables ( age, occupation, preoperative high anxiety and postoperative high pain) from chi-square test, age and preoperative high anxiety were considered to be independent risk factors of postoperative delirium (P<0.001 and P = 0.010). (Table 5).

Discussion

Most of anxiety during perioperative period occurs before surgery, especially the closer to the surgery date, the more serious the anxiety symptoms. Therefore, in order to obtain the most serious preoperative anxiety symptoms, anxiety was assessed on the day before surgery. In this study, the incidence of high anxiety before surgery was much higher than that after surgery. The cause for this difference might be the patients' lack of knowledge and fear of surgery and anesthesia. Mild anxiety reflected patient's normal psychological function and would not be harmful. However, high anxiety may induce a series of adverse effects, including the increase of anesthetic drugs^21,22, aggravating postoperative pain²³ and lowering immunity and delaying healing²⁴. The incidence rate of high anxiety was 19.2% in the study, lower than a cross-sectional study²⁵ involving 3087 adult patients(40.5%). The obvious difference may be caused by patient’s age, sample size and anxiety scales in two studies.

In the study, the patients experienced high pain mainly on the first day after operation, and the incidence rate was as high as 47.5%. There was not only a positive correlation betweent preoperative high anxietyand postoperative high pain, but also high anxiety was considered to be an independent risk factor of postoperative high pain. Previous studies had shown that preoperative anxiety had been considered as an important predictor of postoperative pain^26,27. One of the possible mechanisms of preoperative anxiety aggravating postoperative pain was that, GABA participated in the regulation of pathological pain and inhibits hyperalgesia, but anxiety could diminish presynaptic GABA release and impede the action of postsynaptic GABA receptors^28,29. This study had shown that the patients who suffered from preoperative high anxiety would experience more severe pain. The result was consistent with previously reported findings^{[2, 16, 17]}.

CAM-CR scale²⁰which had been revised and strictly verified in Chinese was adopted to screen delirium. Although strong correlation between subjective emotional factors (pain and anxiety) and delirium was generally acknowledged³², the effect of subjective emotional factors has not been clearly studied so far. In this study, the highest incidence of delirium was the one day after operation, and preoperative high anxiety strongly predicted postoperative delirium in ederly patients receiving gastrointestinal cancer surgery. It was controversial the influence of preoperative anxiety on postoperative delirium. Some studies had shown that preoperative anxiety was a predictor of postoperative delirium ^14,33,34. However, other studies had shown that there was no association between preoperative anxiety and postoperative delirium in elderly patients ^{[11, 12, 13]}. Therefore, more studies about the the correlation between preoperative anxiety and postoperative delirium need to research.

As an acute response after surgical stimulation, postoperative pain often induced psychological, physiological, and behavioral changes such as anxiety, fear, depression, and sleep disorders in elderly patients due to the occurrence or aggravation of their underlying diseases. Several observational studies had found that preoperative pain and depression were associated with an increased risk of delirium^35,36. High levels of postoperative pain and using high opioid doses increased the risk for postoperative delirium¹⁶. however, evidence about the influence of postoperative pain on postoperative delirium was currently limited. In this study, postoperative moderate to severe pain was considered a predictor of postoperative delirium in elderly patients receiving gastrointestinal cancer surgery. Despite the lack of a recognized mechanism of action, the outcome was trustworthy and required more research.

Potential Limitations

There were several limitations in this study. First, due to the workload and patient cooperation, the evaluation time of our scale was an interval of one day, which may cause some missed diagnoses. There should be more patients with high pain and delirium. It has been reported that the incidence of delirium in the first two days after surgery is the highest. Delayed delirium can be found on the 7th day after the operation. Second, this study did not include the operation conditions (such as bleeding and fluid volume, the amount of anesthetic) and the use of analgesia pumps that may affect the incidence of postoperative pain and delirium. Third, the scale used for delirium in this study CAM-CR scale, which was revised by Chinese scholar Juan Li²⁰ based on the CAM scale in 2003. It conforms to the evaluation of Chinese adult delirium, and has high sensitivity and specificity.

Conclusions

Elderly patients undergoing gastrointestinal tumor surgery had the high incidence of high anxiety before surgery, high anxiety pain and delirium on the first postoperative day. Preoperative high anxiety was positively associated with postoperative high pain and postoperative delirium; and postoperative high pain was positively associated with postoperative delirium. Types of cancer and surgical approaches were as influencing factors of preoperative high anxiety; preoperative high anxiety was an influencing factor of postoperative high pain; and age and preoperative high anxiety were influencing factors of postoperative delirium.

Declarations

Authors’ contributions

LHL and YBX designed the study. LHL collected the data. LHL and QL revised the manuscript. YBX was responsible for clinical coordination. LHL interpreted the data. All authors have read and approved the manuscript.

Acknowledgments

The study was approved by the ethics committee of the first affiliated hospital of Guangxi Medical University (identifier: NO.2019 (KY-E-115)).

Funding

Yubo Xie was supported by Guangxi Key Research and Development Program (No.AB20159019), National Key Research and Development Program (No.2018YFC2001905), Guangxi Natural Science Foundation Key Project (No.2020GXNSFDA238025), and the Research Fund of Beijing Hongyi Medical Development Foundation (No.HY20210037-A-02). No other external funding or competing interests declared.

Contributions

Qing Liu and Yubo Xie wrote the main manuscript text. Qing Liu prepared table 1-5. Liheng Li contributed to data collection and analysis. All authors reviewed the manuscript.

Corresponding author

Correspondence to Yubo Xie.

Ethics declarations

Ethics approval and consent to participate

The study had been performed in accordance with the Declaration of Helsinki. The study protocol was conducted with the consent of the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University in China on 4 December 2019 (identifier: NO.2019 (KY-E-115)). The informed consents to participate in the study had been obtained from all participants or their legal guardian(s). The study was registered at Chinese Clinical Trial Registry (ChiCTR2000032008).

Consent for publication

Not applicable.

Data Availability statement

All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing interests

The authors declare that they have no competing interests.

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