Impact of dexmedetomidine preconditioning on analgesic and postoperative recovery in elderly patients undergoing laparoscopic cholecystectomy

Abstract

BACKGROUND

Elderly patients undergoing laparoscopic cholecystectomy (LC) are at increased risk for postoperative complications.

AIM

To investigate the impact of dexmedetomidine (DEX) preconditioning on postoperative analgesia and recovery in elderly patients undergoing LC.

METHODS

A retrospective analysis was conducted involving elderly patients (aged ≥ 60 years), who underwent LC between May 2023 and April 2024. Patients were categorized into two groups based on DEX administration protocols: (1) DEX preconditioning anesthesia (DEX-PA) group; and (2) DEX conventional anesthesia group. Postoperative assessments included pain (Visual Analog Scale), sedation (Ramsay Sedation Scale), oxidative stress and inflammation at 6 hours, recovery from anesthesia, gastrointestinal function recovery, cognitive scores (mini-mental state examination), and incidence of adverse events.

RESULTS

Among 182 patients (DEX-PA = 87, DEX conventional anesthesia = 95), the DEX-PA group showed significantly lower Visual Analog Scale scores (6 hours: 3.86 ± 1.23 vs 4.46 ± 1.38, P = 0.002), reduced oxidative stress (malondialdehyde: 3.17 ± 0.56 μmol/L vs 3.39 ± 0.61 μmol/L, P = 0.013) and inflammation (C-reactive protein: 5.24 ± 1.35 mg/L vs 5.77 ± 1.62 mg/L, P = 0.018), shorter awakening times (14.87 ± 2.67 minutes vs 15.75 ± 2.82 minutes, P = 0.032), shorter stays in the post-anesthesia care unit (58.24 ± 10.85 minutes vs 62.38 ± 12.47 minutes, P = 0.018), accelerated gastrointestinal recovery (time to first defecation: 36.82 ± 7.63 hours vs 39.95 ± 8.24 hours, P = 0.009), better cognitive performance at 6 hours (25.53 ± 1.87 vs 24.72 ± 2.15, P = 0.008), and fewer adverse events (agitation: 4.60% vs 14.74%, P = 0.022).

CONCLUSION

DEX preconditioning prior to anesthesia induction significantly enhances postoperative analgesia, reduces oxidative stress and inflammatory responses, accelerates gastrointestinal and cognitive recovery, and decreases adverse events in elderly patients undergoing LC.

Key Words: Dexmedetomidine; Preconditioning anesthesia; Laparoscopic cholecystectomy; Elderly patients; Postoperative pain; Recovery

Core Tip: This study demonstrates that administering a loading dose of dexmedetomidine (DEX) as a pre-treatment strategy before anesthesia induction offers notable benefits for elderly patients undergoing laparoscopic cholecystectomy. Compared to the routine use of DEX solely during surgery, pre-treatment with DEX enhanced postoperative analgesia, reduced oxidative stress and inflammation, accelerated recovery of gastrointestinal and cognitive functions, and lowered the incidence of agitation without increasing intraoperative hemodynamic risks. These findings highlight the critical importance of the timing of DEX administration and suggest a promising optimized anesthesia approach to promote recovery in elderly surgical patients.

INTRODUCTION

Gallstones and gallbladder polyps are common biliary diseases, particularly prevalent among older adults[1]. Gallstones develop as solid particles from cholesterol, bilirubin, or a mixture of both within the gallbladder, leading to symptoms such as biliary colic, acute cholecystitis, pancreatitis, or cholangitis[2]. This condition arises due to bile supersaturation with cholesterol, which promotes crystal formation[3]. Although gallbladder polyps are often asymptomatic, they require monitoring or removal due to their potential for malignant transformation[4]. For symptomatic patients, laparoscopic cholecystectomy (LC) remains the definitive treatment and the gold standard surgical approach[5]. Despite its minimally invasive nature, LC can still induce significant surgical stress, inflammation, and pain, especially in elderly patients, who often exhibit reduced physiological reserves, heightened pain sensitivity, altered drug metabolism, increased risk of postoperative cognitive dysfunction (POCD), and prolonged recovery times[6,7]. Therefore, optimizing perioperative management, particularly anesthesia and analgesia, is crucial to alleviate these challenges and facilitate faster recovery in this growing patient population[8]. This study aims to evaluate whether dexmedetomidine (DEX) pre-treatment offers benefits superior to conventional anesthesia (CA) in improving pain control, reducing surgical stress, and accelerating postoperative recovery in elderly patients undergoing LC.

DEX is a highly selective α2-adrenergic receptor agonist that has garnered significant interest in anesthesiology due to its unique pharmacological properties[9]. It offers dose-dependent sedation, analgesia, anti-anxiety effects, and sympathetic relaxation without causing significant respiratory depression. Beyond these direct effects, preclinical and some clinical evidence suggest that DEX may offer organ-protective benefits by modulating inflammatory cascades, reducing oxidative stress, and inhibiting neuroendocrine stress responses triggered by surgery and anesthesia[10]. Activation of α2-adrenergic receptors in the central nervous system and peripheral tissues is associated with reduced release of pro-inflammatory cytokines and catecholamines, potentially mitigating systemic inflammatory response syndrome associated with major surgeries[11]. Furthermore, its neuroprotective potential may be linked to decreased excitotoxicity and inhibition of inflammatory signaling within the central nervous system, mechanisms closely tied to the prevention of POCD in elderly patients[12]. While DEX is commonly used as an adjunct during anesthesia maintenance, administering it as a pre-treatment prior to surgical injury represents a strategic approach aimed at actively regulating these stress and inflammation pathways from the outset[13].

Therefore, this retrospective study aims to investigate the specific effects of administering DEX as a pre-treatment prior to anesthesia induction on pain relief, postoperative recovery parameters, and the incidence of adverse events in elderly patients undergoing elective LC. By introducing this innovative anesthesia approach, we aim to offer a promising alternative for patients undergoing cholecystectomy that may considerably improve clinical outcomes. These findings could contribute to refining perioperative protocols, enhancing pain management, accelerating recovery, reducing complications, and ultimately improving postoperative care quality for elderly surgical patients.

MATERIALS AND METHODS

Selection of participants and criteria

This retrospective study included 182 elderly patients who underwent LC at the First People's Hospital of Linping District Hangzhou City, between May 2023 and April 2024. Inclusion Criteria: (1) Definitive diagnosis of gallstones[14] or gallbladder polyps[15] confirmed by abdominal ultrasound; (2) Age ≥ 60 years, regardless of gender; (3) American Society of Anesthesiologists (ASA)[16] classification I or II; and (4) Complete medical records without missing data. Exclusion Criteria: (1) Use of anesthetic sedatives or analgesics within three months prior to surgery; (2) History of abdominal surgery or presence of severe abdominal infection; (3) Neurological dysfunction or severe mental disorders; and (4) Respiratory diseases or severe cardiac, hepatic, or renal dysfunction.

Based on the DEX administration protocols, the 182 eligible patients were divided into two groups: (1) The DEX-CA group; and (2) The DEX preconditioning anesthesia (DEX-PA) group. Patients in the DEX-CA group (n = 95) received the standard LC anesthesia protocol, whereas those in the DEX-PA group (n = 87) received anesthesia in addition to the CA protocol.

Ethical statement

All procedures in this study complied with the ethical guidelines set by the First People's Hospital of Linping District Hangzhou City, as well as national ethics committee for human research, and were conducted in accordance with the Declaration of Helsinki. Furthermore, the study received approval from the Ethics Committee of the First People's Hospital of Linping District Hangzhou City. Considering that the data utilized in this study comprised anonymized patient information and posed no potential risk or impact on patient care, the ethics committee waived the requirement for informed consent for this retrospective study.

Treatment procedure

Preoperative preparation: Both groups of patients fasted for 8 hours and abstained from drinking for 4 hours prior to surgery. Upon entering the operating room, intravenous access was immediately established, followed by radial artery puncture and catheterization. Vital signs, including mean arterial pressure, electrocardiogram, heart rate, and oxygen saturation, were continuously monitored using a multi-parameter monitor (Infinity^® Gamma XL, Dräger, Germany) to maintain stable circulatory and respiratory function during anesthesia.

Preconditioning anesthesia: Ten minutes prior to anesthesia induction, patients in the DEX-PA group received an intravenous injection of DEX hydrochloride at a dose of 0.5 μg/kg. Patients in the DEX-CA group did not receive any pre-treatment medications during this stage.

Anesthesia induction: Both groups of patients received intravenous anesthesia induction with midazolam (0.03 mg/kg), propofol (2 mg/kg), sufentanil (0.4 μg/kg), and cisatracurium besylate (0.2 mg/kg). These agents were administered sequentially via intravenous injection. Three minutes after drug administration, endotracheal intubation was performed, followed by mechanical ventilation. Ventilation parameters were set as follows: (1) Oxygen flow rate of 2 L/minute; (2) Tidal volume of 7 mL/kg; (3) Fraction of inspired oxygen at 60%; (4) Respiratory rate of 12 breaths/minute; (5) Inspiratory-to-expiratory ratio of 1:1.5; and (6) End-tidal carbon dioxide concentration maintained between 35 mmHg and 40 mmHg to ensure stable intraoperative respiratory function.

Anesthesia maintenance: Both groups received maintenance anesthesia via intravenous infusion of propofol at a rate of 4-6 mg/kg/hour, remifentanil at 0.3-0.5 μg/kg/minute, and DEX hydrochloride at 0.5 μg/kg/hour. During surgery, cisatracurium besylate was intermittently administered intravenously at 0.1 mg/kg as needed for muscle relaxation. Anesthesia depth was adjusted using bispectral index monitoring, with bispectral index value maintained between 40 and 60. All anesthesia agents were immediately discontinued upon completion of the surgery.

LC procedure: Patients were positioned supine with the head elevated approximately 15°-20° and tilted 10°-15° to the left. The abdominal skin was routinely disinfected, from the nipple line superiorly, to the pubic symphysis inferiorly, and laterally to the midaxillary lines, and sterile drapes were applied. A 10 mm incision was made at the lower edge of the umbilicus, through which a Veress needle was inserted to establish pneumoperitoneum, maintaining pressure between 12 mmHg and 14 mmHg. A 10 mm trocar was then introduced at the same site to serve as the observation port. After exploring the abdominal cavity, two additional 5 mm trocars were placed: One in the subxiphoid region and another 2 cm below the right midclavicular line at the costal margin, serving as operation ports.

Adhesions around the gallbladder were carefully dissected to expose Calot’s triangle. Once the anatomical relationships were clearly identified, the cystic duct and artery were clipped and transected. Electrocautery was used to dissect and completely remove the gallbladder. After achieving hemostasis, the gallbladder specimen was retrieved through the umbilical trocar. Residual carbon dioxide was released, all trocars were removed, and the incisions were sutured. Throughout the procedure, anesthesiologists continuously monitored vital signs and adjusted the depth of anesthesia in real time to maintain stable patient conditions.

Postoperative management: At the end of surgery, patients received an intravenous injection of tropisetron (5 mg) and parecoxib sodium (40 mg). Once the patients regained spontaneous breathing and were fully awake, the endotracheal tube was removed, and they were transferred to the anesthesia care unit for further observation.

Evaluation contents

Analgesic and sedative effect: Pain and sedation levels in both patient groups were assessed at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively using the visual analog scale and the Ramsay sedation scale. The Visual Analog Scale scores range from 0 to 10, with higher scores indicating more severe pain. The intraclass correlation coefficient for test-retest reliability of this scale ranges from 0.97 to 0.99[17]. The Ramsay scores range from 1 to 6, with higher scores indicating deeper sedation. The Cronbach’s alpha for this scale is 0.83[18].

Postoperative recovery status: (1) Oxidative stress and stress response markers: Blood samples (3 mL) were collected from both patient groups preoperatively and 6 hours postoperatively. The samples were centrifuged at 3000 rpm for 10 minutes, and the supernatant was retained for analysis. Enzyme-linked immunosorbent assay was used to measure levels of malondialdehyde (MDA), superoxide dismutase (SOD), cortisol (Cor), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Total antioxidant capacity (TAC) was determined using a micro-method; (2) Recovery of anesthesia and gastrointestinal function. The following parameters were recorded: Time to awakening (from discontinuation of anesthesia to the patient’s response to verbal stimuli), time to extubating (from discontinuation of anesthesia to removal of the endotracheal tube), duration of stay in the anesthesia care unit, time to recovery of bowel sounds (first audible bowel sounds postoperatively), time to first exhaust, and time to first defecation; (3) Cognitive function recovery: Cognitive function was assessed using the mini-mental state examination (MMSE) at preoperative, 6-hour, 12-hour, 24-hour, and 48-hour postoperative intervals. The MMSE has a maximum score of 30 points, with higher scores indicating better cognitive function. The Cronbach’s alpha for this scale is 0.61[19]; and (4) Adverse reaction: Intraoperative and postoperative adverse reactions were observed and compared between the two patient groups. Intraoperative complications, including hypotension and bradycardia, were closely monitored. Postoperative adverse reactions, such as nausea and vomiting, bradycardia, hypotension, and agitation, were also assessed.

Statistical analysis

All statistical analyses in this research were performed using Statistical Package for the Social Sciences software (version 29.0; developed by SPSS Inc., based in Chicago, IL, United States). Continuous variables were evaluated for normality using the Shapiro-Wilk test and presented as mean ± SD. Group differences were analyzed using independent samples t-test. Categorical variables were expressed as n (%) and compared between groups using χ² test.

RESULTS

Basic data

In the comparison of demographic characteristics between the DEX-CA and DEX-PA groups, no significant differences were observed in age, body mass index, gender distribution, educational background, smoking history, drinking history, as well as the prevalence of hypertension, diabetes, coronary heart disease, hyperlipidemia, and ASA grading (all P values > 0.05; Table 1). However, a trend toward significance in disease type distribution was observed between the two groups (P = 0.091), with the DEX-CA group exhibiting a higher proportion of patients with gallstones and a lower proportion with gallbladder polyps than the DEX-PA group.

Table 1 Comparison of demographic characteristics between two groups, n (%)/mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t/χ2	P value
Age (years)	71.38 ± 5.26	71.41 ± 5.42	0.031	0.975
Gender			0.316	0.574
Male	52 (54.74)	44 (50.57)
Female	43 (45.26)	43 (49.43)
Body mass index (kg/m2)	24.37 ± 1.27	24.43 ± 1.32	0.337	0.736
Educational background			0.356	0.837
Junior high or below	38 (40.00)	32 (36.78)
High school	30 (31.58)	31 (35.63)
Tertiary and above	27 (28.42)	24 (27.59)
Smoking history	22 (23.16)	20 (22.99)	0.001	0.978
Drinking history	18 (18.95)	15 (17.24)	0.089	0.765
Complication
Hypertension	21 (22.11)	23 (26.44)	0.465	0.495
Diabetes	10 (10.53)	12 (13.79)	0.456	0.499
Coronary heart disease	11 (11.58)	14 (16.09)	0.781	0.377
Hyperlipidemia	17 (17.89)	19 (21.84)	0.445	0.505
American Society of Anesthesiologists grading			0.173	0.677
I grade	65 (68.42)	57 (65.52)
II grade	30 (31.58)	30 (34.48)
Disease type			2.854	0.091
Gallstone	81 (85.26)	81 (93.10)
Gallbladder polyps	14 (14.74)	6 (6.90)

DEX: Dexmedetomidine.

In terms of surgery features, no significant differences were observed between the DEX-CA and DEX-PA groups in operative duration, anesthesia duration, intraoperative bleeding volume, fluid replacement volume, or in the doses of anesthesia inducing drugs including midazolam, propofol, sufentanil, and atracurium (all P > 0.05; Table 2). Similarly, no significant differences were found in the doses of anesthesia maintenance drugs, such as propofol, remifentanil, and DEX, or in the frequency of atracurium administration.

Table 2 Comparison of surgery features between two groups, n (%)/mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t/χ2	P value
Operative duration (minutes)	82.86 ± 12.43	82.25 ± 12.27	0.334	0.739
Anesthesia duration (minutes)	89.62 ± 13.84	89.84 ± 13.43	0.107	0.915
Intraoperative bleeding volume (mL)	14.44 ± 1.92	14.86 ± 2.24	1.351	0.178
Fluid replacement volume (mL)	746.25 ± 48.43	758.24 ± 50.91	1.628	0.105
Dose of anesthesia inducing drugs
Midazolam (mg)	2.12 ± 0.35	2.08 ± 0.32	0.711	0.478
Propofol (mg)	135.52 ± 20.25	132.75 ± 19.83	0.932	0.353
Sufentanil (μg)	24.38 ± 3.72	23.92 ± 3.69	0.847	0.398
Atracurium (mg)	12.25 ± 1.87	12.16 ± 1.78	0.344	0.731
Dose of anesthesia maintenance drugs
Propofol (mg)	452.38 ± 67.21	443.92 ± 65.84	0.856	0.393
Remifentanil (μg)	1286.54 ± 214.36	1262.47 ± 208.92	0.766	0.445
DEX (μg)	42.18 ± 6.32	41.75 ± 6.18	0.459	0.647
Times of atracurium is added	25 (26.32)	20 (22.99)	0.270	0.603

DEX: Dexmedetomidine.

Analgesic and sedative effect

Significant differences in postoperative analgesia scores were observed between the DEX-CA and DEX-PA groups at several time points (Figure 1). At 6 hours postoperatively, the DEX-CA group reported higher scores than the DEX-PA group (P = 0.002). This pattern persisted at 12 hours (P = 0.003) and 24 hours (P = 0.024) postoperatively, with the DEX-CA group consistently showing higher scores. At 48 hours postoperatively, the difference remained statistically significant (P = 0.033), indicating that the higher analgesia scores in the DEX-CA group persisted even though the magnitude of the difference had decreased.

Figure 1 Comparison of postoperative analgesia scores (points) between two groups. ^aP < 0.05; ^bP < 0.01. Error bars represent standard deviation. CA: Conventional anesthesia; DEX: Dexmedetomidine; PA: Preconditioning anesthesia.

Postoperative sedation scores did not differ significantly between the DEX-CA and DEX-PA groups at any of the measured time points (Table 3). Scores were comparable between the two groups at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively (all P > 0.05).

Table 3 Comparison of postoperative sedation scores (points) between two groups, mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t value	P value
Postoperative 6 hours	4.23 ± 0.47	4.26 ± 0.35	0.440	0.660
Postoperative 12 hours	3.97 ± 0.39	4.01 ± 0.32	0.847	0.398
Postoperative 24 hours	3.52 ± 0.45	3.66 ± 0.68	1.652	0.101
Postoperative 48 hours	3.07 ± 0.26	3.14 ± 0.33	1.470	0.143

DEX: Dexmedetomidine.

Oxidative stress and stress response markers

In the comparison of oxidative stress and stress response markers between the DEX-CA and DEX-PA groups, no significant differences were observed preoperatively in levels of MDA, SOD activity, TAC, Cor, TNF-α, or CRP (all P > 0.05; Table 4). However, significant differences emerged at 6 hours postoperatively. The DEX-CA group exhibited higher MDA levels than the DEX-PA group (P = 0.013), indicating greater oxidative stress in the DEX-CA group. Conversely, SOD activity was lower in the DEX-CA group than in the DEX-PA group (P = 0.014), suggesting reduced antioxidant capacity. Similarly, TAC levels were lower in the DEX-CA group (P = 0.018), reinforcing this trend. Regarding stress response markers, Cor levels were higher in the DEX-CA group than the DEX-PA group (P = 0.032). In addition, TNF-α levels were significantly elevated in the DEX-CA group relative to the DEX-PA group (P = 0.016). Lastly, CRP levels were also higher in the DEX-CA group (P = 0.018).

Table 4 Comparison of oxidative stress and stress response markers between two groups, mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t value	P value
Oxidative stress markers
Malondialdehyde (μmol/L)
Preoperative	2.31 ± 0.43	2.23 ± 0.35	1.465	0.145
Postoperative 6 hours	3.39 ± 0.61	3.17 ± 0.56	2.520	0.013
Superoxide dismutase (U/mL)
Preoperative	73.41 ± 7.85	72.04 ± 7.62	1.193	0.234
Postoperative 6 hours	88.32 ± 8.46	91.14 ± 6.79	2.494	0.014
Total antioxidant capacity (mmol ascorbic acid Eq/L)
Preoperative	16.23 ± 2.26	16.79 ± 2.95	1.420	0.157
Postoperative 6 hours	13.59 ± 2.33	14.47 ± 2.61	2.391	0.018
Stress response markers
Cortisol (µg/dL)
Preoperative	12.62 ± 1.47	12.94 ± 1.08	1.663	0.098
Postoperative 6 hours	15.02 ± 2.35	14.32 ± 2.01	2.164	0.032
Tumor necrosis factor-alpha (pg/mL)
Preoperative	1.83 ± 0.31	1.86 ± 0.37	0.577	0.565
Postoperative 6 hours	3.47 ± 0.98	3.15 ± 0.76	2.429	0.016
C-reactive protein (mg/L)
Preoperative	1.54 ± 0.32	1.49 ± 0.43	0.874	0.384
Postoperative 6 hours	5.77 ± 1.62	5.24 ± 1.35	2.388	0.018

DEX: Dexmedetomidine.

Recovery of anesthesia and gastrointestinal function

Regarding recovery from anesthesia, the awakening time was significantly shorter in the DEX-PA group than the DEX-CA group (P = 0.032), indicating a more rapid return to consciousness in patients receiving DEX-PA (Table 5). However, no significant difference in extubating time was found between the two groups (P > 0.05). The duration of stay in the anesthesia care unit was also significantly shorter for the DEX-PA group (P = 0.018). For gastrointestinal function recovery, significant differences were observed in all measured parameters. Bowel sounds recovery time was shorter in the DEX-PA group (P = 0.001), as were the first exhaust time (P = 0.003) and the first defecation time (P = 0.009). These results indicate that patients in the DEX-PA group experienced a faster recovery of gastrointestinal function following surgery.

Table 5 Comparison of the recovery of anesthesia and gastrointestinal function recovery between two groups, mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t value	P value
Anesthesia recovery
Awakening time (minutes)	15.75 ± 2.82	14.87 ± 2.67	2.164	0.032
Extubating time (minutes)	17.44 ± 3.51	17.46 ± 3.63	0.039	0.969
Duration of stay in the anesthesia care unit (minutes)	62.38 ± 12.47	58.24 ± 10.85	2.377	0.018
Gastrointestinal function recovery
Bowel sounds recovery time (hours)	7.52 ± 1.85	6.73 ± 1.42	3.259	0.001
First exhaust time (hours)	20.47 ± 4.32	18.63 ± 3.75	3.052	0.003
First defecation time (hours)	39.95 ± 8.24	36.82 ± 7.63	2.653	0.009

DEX: Dexmedetomidine.

Cognitive function

Cognitive function scores showed no significant differences between the DEX-CA and DEX-PA groups preoperatively (P = 0.691; Table 6). However, significant differences were noted at 6 hours and 12 hours postoperatively. At 6 hours postoperatively, the DEX-CA group had lower scores than the DEX-PA group (P = 0.008), indicating poorer cognitive function. This difference persisted at 12 hours postoperatively (P = 0.025). However, by 24 hours postoperatively, no significant difference in cognitive function scores was observed between the two groups (P > 0.05), a trend that continued at 48 hours postoperatively (P > 0.05).

Table 6 Comparison of cognitive function scores between two groups (points), mean ± SD.

Parameter	DEX conventional anesthesia group (n = 95)	DEX preconditioning anesthesia group (n = 87)	t value	P value
Preoperative	27.35 ± 1.24	27.42 ± 1.18	0.398	0.691
Postoperative 6 hours	24.72 ± 2.15	25.53 ± 1.87	2.683	0.008
Postoperative 12 hours	25.63 ± 1.96	26.24 ± 1.65	2.254	0.025
Postoperative 24 hours	26.85 ± 1.47	26.92 ± 1.32	0.296	0.767
Postoperative 48 hours	26.93 ± 1.25	27.15 ± 1.18	1.236	0.218

DEX: Dexmedetomidine.

Adverse reaction

When comparing intraoperative complications between the DEX-CA and DEX-PA groups, no significant differences were observed. Specifically, no significant differences in the incidence of intraoperative hypotension (P = 0.576) and bradycardia (P = 0.654) were observed between the two groups (Figure 2). In comparing the incidence rates of adverse reactions postoperatively between the DEX-CA and DEX-PA groups, significant differences were noted for nausea and vomiting (P = 0.026) and agitation (P = 0.022). The DEX-CA group experienced a higher incidence of nausea and vomiting than the DEX-PA group. Similarly, the incidence of agitation was greater in the DEX-CA group than in the DEX-PA group. For other adverse reactions, no significant differences were observed in the incidence rates of bradycardia and hypotension between the two groups (all P > 0.05).

Figure 2 Comparison of adverse reaction incidence rate between two groups. A: Intraoperative adverse reaction incidence rate; B: Postoperative adverse reaction incidence rate. ^aP < 0.05. CA: Conventional anesthesia; DEX: Dexmedetomidine; NS: Not significant; PA: Preconditioning anesthesia.

DISCUSSION

This retrospective study demonstrated that administering DEX prior to anesthesia induction may offer greater benefits than CA alone in elderly patients undergoing LC. Findings across multiple domains of postoperative recovery suggest that early administration of DEX may help modulate the body’s response to surgical stress, contributing to more favorable recovery outcomes in this patient population.

The pain scores recorded at all postoperative time points in the DEX-PA group underscored its effective and sustained analgesic effect. This finding aligns with the established analgesic properties of DEX, mediated through central α2-adrenergic receptor activation in the locus coeruleus and spinal cord, inhibiting the release of nociceptive neurotransmitters[20]. Notably, although both groups received continuous infusion of DEX during surgery, the superior performance of the DEX-PA group was attributed to the administration of a loading dose prior to induction. The key difference lay in the timing of drug action. With a distribution half-life of approximately six minutes, DEX distributed rapidly[21]. Therefore, prior to the start of surgical stimulation, the pre-induction loading dose could rapidly achieve an effective plasma concentration and occupy central and peripheral α2-adrenergic receptors[22]. The analgesic benefits persisted immediately after surgery and continued up to 48 hours postoperatively, suggesting that PA may influence central sensitization pathways or reduce the development of secondary hyperalgesia following surgical trauma[23]. While previous studies have demonstrated that intraoperative DEX reduces opioid consumption and alleviates early postoperative pain, pre-treatment further enhanced this effect[24]. Although both groups received intraoperative DEX maintenance, the unique contribution of the PA phase was evident. Findings from other surgical settings support this observation, indicating that initiating DEX administration prior to surgical injury yields superior pain control compared with starting it intraoperatively. This benefit may stem from by preemptive inhibition of the neuroendocrine stress response and its role in amplifying pain perception[25,26].

Biochemical analysis revealed notable differences in oxidative stress and systemic inflammatory response markers. The DEX-PA group demonstrated lower levels of MDA, a marker of lipid peroxidation and oxidative damage, along with higher levels of SOD and TAC. These findings suggest that DEX pre-treatment effectively reduced oxidative stress in the early postoperative period. In addition, the DEX-PA group exhibited reduced levels of Cor, TNF-α, and CRP, indicating a dampened surgical stress and inflammation. These results align with growing clinical and preclinical evidence supporting the anti-inflammatory and antioxidant properties of DEX[27]. Previous studies have shown that elevated oxidative stress correlate with poorer postoperative outcomes, including prolonged recovery times and increased complication risks[28]. Activation of central α2-adrenergic receptors by DEX can inhibit sympathetic outflow, reducing catecholamine surges and subsequent pro-inflammatory cytokine release[29]. Moreover, DEX may directly modulate inflammatory signaling pathways, such as nuclear factor kappa B inhibition, and enhance endogenous antioxidant defenses[30]. Our findings reinforce the role of DEX in reducing inflammatory markers, highlight the effectiveness of the pre-treatment strategy in elderly patients undergoing LC.

Accelerated recovery was a notable feature of the DEX-PA group. Patients in this group experienced shorter awakening times and reduced durations in the anesthesia care unit, suggesting that the combined effects of anesthetics and neuromuscular blockers manifested more rapidly. This enhanced recovery may be attributed to more stable intraoperative hemodynamics and an optimized anesthesia process facilitated by pre-treatment, which could directly affect recovery pathways[31]. Notably, gastrointestinal function recovered more rapidly in the DEX-PA group. Shorter times to bowel sound return, first flatus, and first defecation strongly suggest that DEX pre-treatment contributed to a reduction in postoperative ileus, consistent with findings from previous research[32]. This finding is important because postoperative ileus can cause discomfort, extend hospital stays, and increase costs. Mechanistically, DEX likely improved gastrointestinal function by reducing inflammation and oxidative stress, both known to impair gut motility. DEX's anti-inflammatory effects primarily involved inhibiting nuclear factor kappa B signaling pathways and suppressing pro-inflammatory cytokines such as TNF-α and interleukin-6, thereby reducing inflammation and edema in gut tissues. In addition, its antioxidant properties effectively decrease the production of oxygen free radicals including MDA, protecting gut neurons and interstitial cells of Cajal from oxidative damage and preserving normal gut motility. The central sympatholytic action of DEX also contributes by enhancing vagal tone and suppressing catecholamine release, counteracting the inhibitory influence of sympathetic activity on gastrointestinal motility. This enhancement of vagal tone likely further promoted gut motility, whereas its opioid-sparing properties provided more effective pain relief, reducing one of the primary contributors to postoperative ileus[33].

Cognitive function assessments indicated that the DEX-PA group exhibited a brief but clear protective effect during the critical early recovery phase. Higher cognitive scores at 6 hours and 12 hours postoperatively suggested that DEX pre-treatment may provide early neuroprotection against POCD, which is particularly important for older adults. These findings are consistent with proposed neuroprotection mechanisms of DEX reported in previous studies, including reducing central inflammation, mitigating excitotoxicity, lowering cerebral metabolic rate, and improving cerebral perfusion stability[34]. The absence of these differences beyond 24 hours implied that pre-treatment primarily mitigates acute neuroinflammatory responses triggered by surgery and anesthesia, rather than preventing long-term dysfunction. The MMSE tool may have lacked the sensitivity to capture subtle or prolonged cognitive changes in this specific context. Nonetheless, our findings emphasized the effects of a pre-treatment approach during the early stages, adding nuanced insight into its potential role in mitigating immediate postoperative cognitive decline.

Safety data further supported the advantages of the DEX-PA group. Lower rates of nausea and vomiting aligned with improved pain relief and reduced opioid requirements, given that opioids are a primary trigger to postoperative nausea and vomiting[35]. In addition, reduced agitation rates indicated a smoother emergence and recovery process associated with DEX. Importantly, no notable differences in hemodynamic adverse events, such as bradycardia and hypotension, were observed between the DEX-CA and DEX-PA groups during surgery and postoperatively, which is reassuring. Although DEX is known to produce dose-dependent hemodynamic effects, the specific doses and timing used in this study, coupled with vigilant monitoring protocols, appeared to be well-tolerated in elderly patients with ASA I and II status[36,37]. This favorable safety profile, alongside the observed clinical benefits, further enhanced the potential clinical utility of this approach.

Several limitations of this study merit consideration. As a single-center retrospective analysis, the results might not generalize to broader populations or different healthcare settings. Although we conducted rigorous statistical adjustments for available baseline and surgical variables, residual confounding could not be entirely ruled out. Practices in anesthesia protocols, fluid management, surgical techniques, and postoperative care vary across institutions. Furthermore, the follow-up period was limited to 48 hours postoperatively, restricting the assessment of long-term outcomes such as sustained cognitive changes, development of chronic pain, or overall hospital stay and readmission rates. The Ramsey sedation scale did not show differences in sedation, possibly because it is not the most sensitive tool for detecting subtle sedation effects in a multimodal analgesia context. Moreover, the results of gastrointestinal recovery assessment indicated that the first passage of flatus and feces was a highly subjective indicator. This measure heavily depended on patient self-reports and the frequency of nursing records, potentially introducing measurement bias.

Future research should focus on conducting prospective, randomized, double-blind, multicenter controlled trials to address these limitations. This approach is essential for confirming the efficacy and safety of DEX pre-treatment in this population. Such studies should use more sensitive cognitive assessment tools, closely monitor opioid consumption, and extend follow-up times to observe long-term recovery and complications. Delving into potential mechanisms is also crucial. Exploring the optimal dosing regimen for pre-treatment and comparing it with other regional or multimodal analgesia strategies would provide valuable insights. Future studies could incorporate more objective indicators, such as postoperative changes in serum gastrointestinal hormone levels, to more accurately assess gastrointestinal function recovery. In addition, assessing economic impacts, particularly the cost-effectiveness associated with potentially shortened post-anesthesia care unit stays and accelerated overall recovery, would strengthen the rationale for adopting this approach in clinical practice.

CONCLUSION

In elderly patients undergoing LC, PA with DEX administered prior to induction was associated with reduced oxidative stress, attenuated systemic inflammation, and improved postoperative pain control. This approach also helped facilitated faster recovery of gastrointestinal function and cognitive performance. Compared with CA approaches, administering DEX at this critical time enhanced clinical outcomes and safety, offering a promising direction for optimizing perioperative results in this vulnerable population.