Introduction
Colon cancer is a common malignancy. Patients have adverse symptoms such as abdominal distension and bloody stools in the early stage of the disease, and peritoneal effusion and other more serious symptoms gradually emerge as the disease deteriorates, seriously threatening patients’ lives [1]. Currently, surgery is the preferred therapy for colon cancer. Laparoscopic colectomy is a typical minimally invasive surgery. However, both surgery and anesthesia, as potent stressors for elderly patients, induce severe stress responses, increase the activity of platelets and restrain the immune function. Meanwhile, it causes more intense postoperative pain than other types of laparoscopic surgery. Severe pain not only further aggravates the stress response but also decreases the immunity, thus affecting the prognosis. Therefore, it is of great clinical value to improve the effectiveness and safety of analgesia for elderly patients undergoing laparoscopic colectomy [2–4].
Traditional anesthetic drugs, such as midazolam, exert analgesic effects by acting on the gamma-aminobutyric acid system, but they suppress the immune function. Nevertheless, anesthetic drugs have a more serious impact on the central nervous system of elderly patients, with a higher risk of postoperative delirium [5–9]. Delirium is a common clinical syndrome of acute temporary disturbance of neurological function, manifested as consciousness and cognitive dysfunction [10]. The central depressant effects (anti-anxiety and sedation) of dexmedetomidine are achieved through acting on the subcortical locus coeruleus rather than the cerebral cortex, which substantially reduces the incidence rate of postoperative delirium in elderly patients undergoing laparoscopic colectomy [11].
Transversus abdominis plane block (TAPB), which is essentially a regional block, refers to ultrasound-guided injection of local anesthetic drugs into the plane between the internal oblique fascia and the transversus abdominis fascia to block the anterior sensory nerves of the abdominal wall, which can achieve good anesthetic and analgesic effects [12]. TAPB combined with low-dose dexmedetomidine (an α2 adrenergic receptor agonist) can inhibit sympathetic nerves without a greater impact on the hemodynamic indicators, protect the nervous system, reduce the number of apoptotic brain cells, lower the incidence rate of postoperative delirium, and improve surgical safety [13].
Aim
In this study, the effect of TAPB combined with low-dose dexmedetomidine on elderly patients undergoing laparoscopic colectomy was assessed.
Material and methods
General data
This study has been approved by the ethics committee of our hospital (approval No. JPH202103002), and written informed consent has been obtained from all patients. Sixty-two elderly patients undergoing laparoscopic colectomy from March 2021 to March 2022 were randomly selected and equally divided into Group A and Group B by a randomized double-blind method.
Methods
All patients were fasted for 8 h preoperatively and given 250 ml of glucose 2 h before the operation. After the patient entered the operating room, venous access was established, and vital signs (including heart rate (HR), pulse, and blood pressure) were monitored. Then laparoscopic colectomy was performed under general intravenous anesthesia.
Methods for Group A
Low-dose dexmedetomidine was used for Group A. Specifically, dexmedetomidine (Yangtze River Pharmaceutical Group Co., Ltd., NMPA H20183219, batch No.: 20041231) was pumped at a loading dose of 1 μg/kg for 15 min during anesthesia induction. During the operation, dexmedetomidine was continuously pumped at 0.2–0.7 μg kg–1·h–1 until 30 min before the end of the operation. During general anesthesia induction, the patient was given high-flow oxygen for 3 min, and then atracurium (0.1–0.15 mg/kg) + propofol (2.0–2.5 mg/kg) + sufentanil (0.2–0.5 μg/kg). After tracheal intubation, mechanical ventilation was performed with a respiratory rate (RR) of 10–14 times/min and a tidal volume of 8 ml/kg. During the operation, propofol (4–8 mg/kg) and sufentanil (0.15–0.3 μg/kg) were continuously pumped every hour, and atracurium was administered intermittently until the end of the operation.
Methods for Group B
Group B received TAPB + low-dose dexmedetomidine (same as above). Anesthesia induction was performed by intravenous injection of sufentanil (0.2–0.5 μg/kg), atracurium (0.1 mg/kg) and propofol (1.5 mg/kg). After tracheal intubation, the puncture site of the transversus abdominis plane was located under the guidance of ultrasound, clearly displaying the external oblique, internal oblique and transversus abdominis muscles. A puncture needle was inserted between the internal oblique and transversus abdominis muscles. When no blood return was seen with the needle slowly withdrawn, 2% ropivacaine (20 ml) was injected on each side. After the drug fully diffused to the transversus abdominis plane, the contralateral transversus abdominis plane was blocked in the same way. During the operation, propofol (4–8 mg/kg) and sufentanil (0.1–0.2 μg/kg) were continuously pumped every hour and discontinued 10 min before the end of suture. Rocuronium bromide (0.2 mg/kg) was intravenously injected when needed to maintain muscle relaxation. After the operation, a patient-controlled intravenous analgesia pump (200 μg of sufentanil + 200 ml of normal saline) was used.
Measurement of hemodynamic indicators
Hemodynamic indicators (mean arterial pressure (MAP), HR, pulse oxygen saturation (SpO2), and RR) were recorded and compared at different time points (before anesthesia (T0), at extubation (T1), 8 h after the operation (T2), 24 h after the operation (T3), and 48 h after the operation (T4)) [14].
Observation of postoperative delirium [15]
The incidence rate, duration and clinical manifestations (dysphoria, disorientation, gibberish, obnubilation, sleep disorder, and auditory hallucinations) of postoperative delirium were evaluated.
Detection of stress response indicators [16]
Stress response indicators (adrenocorticotropic hormone (ACTH), cortisol (Cor), and angiotensin II (Ang-II)) were recorded and compared at different time points (before anesthesia induction, after anesthesia induction, at extubation, and 1 h after extubation).
Observation of adverse reactions [17]
The adverse reactions during anesthesia recovery (tachycardia, bucking, and restlessness) and after the operation (bradycardia, hypotension, and hypoxemia) were recorded, and the incidence rate was calculated.
Assessment of Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) scores [18]
The pain at rest and activity were evaluated using VAS at different time points (6 h, 1 day, 2 days and 3 days after the operation). The total score was 10 points, and a higher score meant severer pain. Additionally, the sleep quality was evaluated using the PSQI at different time points (6 h, 1 day, 2 days and 3 days after the operation). The total score was 21 points, and a higher score corresponded to a poorer sleep quality.
Measurement of laboratory indicators [19]
Before anesthesia and 24 h after the operation, 3 ml of peripheral blood was collected, added to a test tube containing anticoagulant and centrifuged at 3000 rpm for 15 min, after which the supernatant was taken. The levels of cluster of differentiation 4+ (CD4+), CD8+, CD4+/CD8+ ratio and NK cells in serum were measured by flow cytometry. The level of free Cor was measured by chemiluminescence assay.
Detection of blood oxygen metabolism indicators [20]
Partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and pH were detected and compared.
Statistical analysis
SPSS 21.0 software was used for statistical analysis. The normally distributed measurement data were described by mean ± standard deviation (x ± s), and compared by the paired t-test within the same group and by the independent-samples t-test between two groups. The count data were described by frequency (n) and percentage (%), and analyzed by the χ2 test or Fisher’s exact probability test. P < 0.05 was considered statistically significant.
Results
General data
The general data were comparable between the two groups (p > 0.05) (Table I).
Table I
General data (n (%), (x ± s))
Hemodynamic indicators
MAP and HR had no statistically significant differences between the two groups at T0 and T1 (p > 0.05), but they were higher in Group B ((85.14 ±8.92)/(86.92 ±9.31)/(85.31 ±8.64) mm Hg, (71.42 ±5.84)/(69.48 ±6.54)/(67.62 ±8.62) beats/min) than those in Group A at T2, T3, and T4 (p < 0.05). SpO2 had no statistically significant difference between the two groups at T0, T1, T2, T3, and T4 (p > 0.05). There was no statistically significant difference in the RR between the two groups at T0 (p > 0.05), but Group B had a lower RR ((18.14 ±1.85)/(16.92 ±1.83)/(16.62 ±1.95)/(16.25 ±1.94) times/min) than Group A at T1, T2, T3, and T4 (p < 0.05) (Table II).
Table II
Hemodynamic indicators (x ± s), n = 31)
Incidence of postoperative delirium
The incidence rate of postoperative delirium in Group B (3.23%) was lower than that in Group A (22.58%) (χ2 = 5.166, p = 0.023), and the duration of delirium in Group B ((0.76 ±0.31) days) was shorter than that in Group A ((2.05 ±0.68) days) (t = 9.610, p < 0.001) (Table III).
Table III
Incidence of postoperative delirium (x ± s, n)
Stress response indicators
Compared with those before anesthesia induction, the levels of ACTH, Cor and Ang-II were improved in both groups after anesthesia induction, at extubation, and 1 h after extubation. The levels of ACTH, Cor and Ang-II had no statistically significant differences between the two groups before anesthesia induction (p > 0.05), but they were lower in Group B (ACTH: (11.56 ±3.38)/(8.16 ±2.91)/(6.42 ±2.34) pmol/l, Cor: (231.35 ±30.86)/(212.35 ±23.16)/(208.03 ±13.27) nmol/l, and Ang-II: (51.56 ±5.62)/(46.26 ±5.27)/(43.21 ±4.45) pg/ml) than those in Group A after anesthesia induction, at extubation, and 1 h after extubation (p < 0.05) (Table IV).
Table IV
Stress response indicators (x ± s, n = 31)
Incidence rate of adverse reactions
The incidence rates of adverse reactions during anesthesia recovery and after the operation in Group B (9.68% and 6.45%) were lower than those in Group A (12.90% and 9.68%) (χ2 = 0.161 and 0.217, p = 0.688 and 0.640) (Table V).
Table V
Incidence rate of adverse reactions [n (%)]
VAS and PSQI scores
The resting and active VAS scores and PSQI scores were lower in Group B ((0.68 ±0.23)/(0.41 ±0.38)/0/0 points, (2.38 ±0.56)/(2.13 ±0.37)/(1.59 ±0.46)/(0.67 ±0.28) points, and (14.62±1.37)/(12.87±0.84)/(6.26±0.57)/(4.58±0.21) points) than those in Group A at 6 h, 1 day, 2 days and 3 days after the operation (p < 0.05) (Table VI).
Table VI
VAS and PSQI scores (x ± s, point)
Laboratory indicators
The two groups had no statistically significant differences in the levels of CD4+, CD8+ and free Cor, CD4+/CD8+ ratio and NK cell level before anesthesia (p > 0.05), but at 24 h after the operation, the level of CD4+, CD4+/CD8+ ratio and NK cell level were higher in Group B ((45.67 ±6.14)%, (1.57 ±0.24), and (20.38 ±4.21)%) than those in Group A (p < 0.05), and the levels of CD8+ and free Cor were lower in Group B ((28.26 ±1.21)% and (456.56 ±91.16) nmol/l) than those in Group A (p < 0.05) (Table VII).
Table VII
Laboratory indicators (x ± s)
Blood oxygen metabolism indicators
Group B had higher PaO2 ((45.52 ±11.14) mm Hg) and pH value (7.42 ±0.06) (p < 0.05) and a lower PaCO2 ((4.05 ±0.32) mm Hg) than Group A (p < 0.05) (Table VIII).
Discussion
TAPB is defined as ultrasound-guided injection of ropivacaine into the plane between the internal oblique fascia and the transversus abdominis fascia to block the nerves on the plane. Ultrasonically, the patient’s anatomical structure, the entry of the puncture needle and the diffusion of anesthetic drugs can be directly observed, and the dosage of anesthetic drugs can be adjusted based on the actual situation of the patient, so that a better analgesic effect can be obtained, which not only lays a foundation for the smooth implementation of surgery, but also reduces the postoperative pain and helps shorten the recovery time of patients. Moreover, TAPB combined with low-dose dexmedetomidine can better prevent postoperative delirium [21]. In this study, the incidence rate of postoperative delirium in Group B (3.23%) was lower than that in Group A (22.58%) (χ2 = 5.166, p = 0.023), and the duration of delirium in Group B ((0.76 ±0.31) days) was shorter than that in Group A ((2.05 ±0.68) days) (t = 9.610, p < 0.001), suggesting that TAPB combined with low-dose dexmedetomidine has higher safety in elderly patients undergoing laparoscopic colectomy. The reason is that dexmedetomidine can effectively improve the blood perfusion in the cerebral ischemic region, reduce the number of apoptotic neurons, and stimulate the secretion of growth factors to inhibit NO production, thereby protecting the nervous system and avoiding postoperative delirium.
The antitumor effect is achieved through the immune system, and the metastasis and recurrence rates of tumors increase in the case of immune system damage. Surgery and anesthesia are both potent stressors for elderly patients undergoing laparoscopic colectomy, which weaken the immunity to some extent [22, 23]. In elderly patients undergoing laparoscopic colectomy, cellular immunity is dominant postoperatively. T lymphocytes are the major immune effector cells, and CD4+ and CD8+ are jointly involved in the immune response. Decreases in CD4+ and CD4+/CD8+ and an increase in CD8+ suggest immunosuppression [24]. In this study, it was found that TAPB combined with low-dose dexmedetomidine caused less damage to the immune system of elderly patients undergoing laparoscopic colectomy. TAPB can effectively restrain the spinal nerve impulse transmission caused by surgical stimulation and reduce sympathetic activity, without decreasing the sensitivity of the immune system. Meanwhile, the overall dosage of anesthetic drugs is reduced, so that the secretion of stress-responsive hormones (plasma Cor, catecholamines, etc.) is suppressed and the adverse impact of oxidative stress on the immune system is relieved, thus ameliorating immunosuppression [25].
In this study, Group B had higher PaO2 ((45.52 ±11.14) mm Hg) and pH (7.42 ±0.06) (p < 0.05) and lower PaCO2 ((4.05 ±0.32) mm Hg) than Group A (p < 0.05), demonstrating that TAPB combined with low-dose dexmedetomidine can reduce surgical injury in elderly patients undergoing laparoscopic colectomy. Since surgery is bound to induce tissue damage and metabolic disorders, these outcomes can be reflected in the results of blood gas analysis, which in turn can help determine the surgical safety and recovery of patients. In detail, blood gas analysis can be used to assess the following changes. 1) pH: After surgery, the acid concentration of tissue metabolites increases, which may lead to acid-base imbalance and decrease pH. This reflects the metabolism and degree of tissue damage [26]. 2) PaCO2: After surgery, the breathing depth and rate may change, causing PaCO2 to rise or fall. An increase in PaCO2 may reflect abnormal lung function and poor ventilation, whereas a decrease in PaCO2 may indicate accelerated tissue metabolism and respiratory compensation [27]. 3) PaO2: After surgery, tissue oxygen consumption may change, leading to the reduction in PaO2. The decrease of PaO2 may reflect poor ventilation, abnormal lung function, insufficient blood flow, etc. [28]. Although general anesthesia inhibits brain functions to a certain extent, it is difficult to inhibit the activation of the sympathetic nervous system and pituitary system by surgery [29]. In contrast, through ultrasound-guided block of the transversus abdominis plane, TAPB can reduce sympathetic excitability and diaphragmatic excitability without inhibiting the respiratory system, and relieve blood acidification, thereby improving the safety of surgery.
Conclusions
TAPB combined with low-dose dexmedetomidine can achieve better anesthetic, analgesic and sedative effects, ameliorate stress responses, and enhance immunity with higher safety in elderly patients undergoing laparoscopic colectomy. Nevertheless, this study has a limitation. The PSQI score was determined only during 3 days instead of a 1-month period. Further in-depth studies are ongoing in our group.
