Permissive hypercapnia combined with goal-directed fluid therapy improve postoperative mental health in elderly patients undergoing laparoscopic surgery

Abstract

BACKGROUND

An investigation is undertaken to assess the effects of permissive hypercapnia (PH) combined with goal-directed fluid therapy (GDFT) on postoperative recovery and psychological well-being among elderly patients undergoing laparoscopic surgical procedures.

AIM

To ascertain whether the combination of PH and GDFT improves clinical recovery indicators, reduces postoperative complications, and alleviates anxiety, depression, and inflammatory responses in this specific patient population.

METHODS

A total of 120 elderly patients who underwent laparoscopic surgery in our hospital from July 2023 to June 2024 were randomly allocated into two groups: A control group (n = 60) and a study group (n = 60). In the control group, conventional anesthesia ventilation and fluid management protocols were administered, while in the study group, PH (with intraoperative PaCO₂ maintained between 45-55 mmHg) was combined with GDFT. Postoperative recovery indicators, including the time to first flatus, time to ambulation, and length of hospital stay, were compared between the groups. Additionally, complication rates, anxiety-depression scores assessed via the Hospital Anxiety and Depression scale, and levels of inflammatory factors were analyzed to evaluate the outcomes.

RESULTS

When compared with the control group, the study group demonstrated significantly shorter time to first flatus [(48.3 ± 6.2) hours vs (62.5 ± 7.8) hours], time to ambulation [(28.4 ± 4.2) hours vs (38.6 ± 5.1) hours], and length of hospital stay [(5.2 ± 1.1) days vs (7.4 ± 1.3) days] (P < 0.05). A significantly lower postoperative complication rate was observed in the study group (8.3% vs 21.7%, P < 0.05). Additionally, at 3 days postoperatively, significantly lower anxiety scores [(5.2 ± 1.4) vs (7.8 ± 1.6)] and depression scores [(4.8 ± 1.2) vs (7.1 ± 1.5)] were recorded in the study group compared to the control group (P < 0.05); Furthermore, at 24 hours postoperatively, serum levels of interleukin-6, tumor necrosis factor α, and C-reactive protein were found to be significantly lower in the study group than in the control group (P < 0.05).

CONCLUSION

Postoperative recovery is significantly expedited, postoperative complications are markedly reduced, anxiety-depression status is substantially improved, and inflammatory response is notably diminished in elderly patients undergoing laparoscopic surgery when PH is combined with GDFT, thereby making it worthy of clinical application.

Key Words: Permissive hypercapnia; Goal-directed fluid therapy; Laparoscopic surgery; Elderly patients; Enhanced recovery; Anxiety and depression

Core Tip: This study highlights the benefits of permissive hypercapnia (PH) combined with goal-directed fluid therapy (GDFT) in elderly patients undergoing laparoscopic surgery. The PH + GDFT strategy is demonstrated to significantly accelerate postoperative recovery, reduce complications, and alleviate anxiety and depression. Additionally, it is observed to reduce levels of inflammatory markers, enhance sleep quality, and improve overall patient satisfaction. Multivariate analysis confirms PH + GDFT as an independent protective factor against postoperative psychological distress. These findings advocate for the integration of PH and GDFT into perioperative management to optimize both physical and psychological outcomes, particularly for elderly patients. This study offers clinical evidence supporting the refinement of anesthesia and fluid management strategies in minimally invasive surgery.

INTRODUCTION

As the aging population accelerates, the percentage of elderly patients who receive laparoscopic surgery is also increasing. The elderly patients often present with multiple comorbidities, decreased organ function reserve, and greater risk of postoperative complications compared with younger patients. They are more prone to negative emotions like anxiety and depression[1-3]. Research has demonstrated that anxiety, depression, and other psychosocial factors after surgery negatively impact patients' quality of life and potentially delay wound healing, the incidence of complications, and the length of hospital stays. The highest rate of postoperative anxiety is reported among geriatric laparoscopic surgery patients, with rates ranging from 30%-45%, and depression ranges 25%-35%[4-7]. This postoperative psychological stress state is related with several surgical-associated factors, including both surgical trauma and inflammatory response as well as pain, which may influence postoperative recovery via the neuro-endocrine-immune network[7-10].

Recent years have brought new insights to optimizing perioperative management strategies to improve patient outcomes. As a lung-protective ventilation strategy, permissive hypercapnia (PH) can reduce mechanical ventilation-associated lung injury, improving tissue perfusion and exhibiting anti-inflammatory and organ-protective effects by moderately raising arterial carbon dioxide (CO₂) pressure[11-14]. Individualized fluid management based on hemodynamic parameters termed as goal-directed fluid therapy (GDFT) can ensure optimization of tissue perfusion and avoidance of fluid overload or insufficiency. Studies on the perioperative mental state of elderly patients with PH combined with GDFT have not been conducted completely.

Studies have demonstrated that appropriate intraoperative ventilation strategies and intraoperative fluid management can indirectly influence the psychological condition of patients by reducing the level of inflammatory factors, maintaining proper tissue perfusion and decreasing the incidence of postoperative complications[15-17]. The inflammatory response is highly associated with the onset of anxiety and depression, and the inflammatory factors [interleukin (IL)-6 and tumor necrosis factor α (TNF-α)] can participate in emotional regulation by influencing neurotransmitters metabolism and the activation of hypothalamic-pituitary-adrenal axis. In addition, good tissue perfusion and oxygen supply can decrease postoperative pain and facilitate recovery of gastrointestinal function, which may further help improve patients’ psychological state.

Psychological effects are especially relevant, and of complex significance, among older surgery patients. Postoperative anxiety and depression may be accompanied by sleep disorders, loss of appetite, social withdrawal, and cognitive impairment. Psychological symptoms can be more pronounced in the elderly as they have lower stress tolerability and adaptation ability. Postoperative mental health problems have been linked to impaired recovery of function, increased falls risk, and poorer adherence to rehabilitation programs. In addition, anxiety and depression has been linked to increased rates of readmission and worse long-term outcomes. The interaction effects between physical recovery and psychological well-being can lead to a vicious cycle where poor mental health may affect recovery while delayed physical recovery may lead to more psychological distress.

In view of this, this study will explore the effects of PH combined with GDFT on postoperative early recovery and anxiety-depression status of elderly patients undergoing laparoscopic surgery to provide new clinical evidence for optimizing the perioperative management strategy and improving the prognosis of patients. We aim to comprehensively clarify the clinical applicability of this strategic intervention to promote recovery by observing postoperative recovery indicators, complication rates, anxiety-depression scores and inflammatory factor level trends in patients undergoing surgery, in order to validate the formulation of this strategic model as a new therapeutic strategy for promoting integrated recovery in geriatric surgical patients.

MATERIALS AND METHODS

Patient selection

This study was approved by the Hospital Ethics Committee, approval No. K2024141 and employed a retrospective case-control study design. Clinical data were collected from 120 elderly patients who underwent laparoscopic colorectal cancer surgery in our hospital’s General Surgery Department from July 2023 to June 2024. Inclusion criteria were: (1) Age ≥ 65 years; (2) Pathologically confirmed colorectal cancer; (3) American Society of Anesthesiologists (ASA) physical status II-III; (4) Underwent laparoscopic surgery; (5) Complete clinical data, including pre- and post-operative anxiety and depression assessments, inflammatory factor test results, etc.; and (6) Normal preoperative mental status (Hospital Anxiety and Depression (HAD) score < 7). Exclusion criteria were: (1) Severe cardiac, pulmonary, hepatic, or renal dysfunction; (2) Preexisting severe psychiatric disorders or cognitive impairment; (3) History of psychiatric medication use; (4) Conversion to open surgery; (5) Chemotherapy or radiotherapy within one month before surgery; and (6) Incomplete clinical data. Patients were divided into control group (n = 60) and study group (n = 60) based on different anesthesia and fluid management protocols. The control group received conventional ventilation parameters (tidal volume 8-10 mL/kg, respiratory rate 12-14 breaths/minute, maintaining PaCO₂ 35-45 mmHg) and routine fluid management. The study group received PH (tidal volume 6-8 mL/kg, respiratory rate 10-12 breaths/minute, maintaining PaCO₂ 45-55 mmHg) combined with GDFT (maintaining stroke volume variation at 12%-13%). There were no statistically significant differences between the two groups in baseline characteristics including age, gender, body mass index, ASA classification, and tumor stage (P > 0.05).

Laparoscopic resection of colorectal cancer

Laparoscopic resection of colorectal cancer is a technique of minimally invasive surgery, which involves minimum trauma and also provides rapid recovery. But a precise surgical process is a multi-stage plan to achieve successful surgery from preoperative to postoperative. Preoperative Preparation. The patient is given a detailed assessment of their medical history, physical exams, imaging (computed tomography and magnetic resonance imaging), and laboratory evaluations to help define the indications for surgery as well as any possible contraindications. Furthermore, the patient must be prepared through vigorous bowel preparation to minimize the risk of an intraoperative contaminant and infections. At the same time, the surgical team prepares surgical instruments and equipment for laparoscopic surgery, including a high-definition imaging system, a pneumoperitoneum machine, an irrigation and suction device, and surgical instruments. It begins with pneumoperitoneum by inserting a pneumoperitoneum needle into the umbilicus (or a different access site) making a small incision, and injected CO₂ gas into the abdomen. Subsequently, a laparoscope is inserted, and the intra-abdominal situation is observed through a monitor. Initially, a thorough exploration of the abdomen is conducted to assess the location, size, depth of invasion, and presence of distant metastases of the tumor. Next, based on the location and stage of the tumor, an appropriate range of lymph node dissection is selected[18-20]. For colon cancer, the principle of Complete Mesocolic Excision is usually followed; for rectal cancer, the principle of Total Mesorectal Excision is adhered to. Then, the affected bowel segment, including the tumor and surrounding mesentery, is mobilized. Surgical approaches include medial, lateral, and cranial medial approaches, with the specific choice depending on the tumor location and the surgeon's preference. The bowel segment is resected under laparoscopic guidance, ensuring tumor-free margins. Finally, depending on the surgical approach, an appropriate method of gastrointestinal reconstruction is chosen. Two common methods are small incision-assisted reconstruction and complete laparoscopic reconstruction. Anastomosis methods include end-to-end, side-to-side, and end-to-side anastomosis. After the surgery, the resected specimen is removed through a small incision or a natural orifice (such as the anus or vagina). The incision is carefully managed to prevent tumor cell implantation. Postoperatively, the patient's vital signs are closely monitored to prevent and manage potential complications.

Observation indicators

The study assessed both primary and secondary outcomes. The primary outcomes encompassed three main aspects: Psychological status, inflammatory response, and sleep quality. Psychological assessment included HAD scale evaluations conducted preoperatively and at 3 days and 7 days after surgery, with anxiety and depression subscales scored separately (scores ≥ 7 indicating presence of symptoms), along with postoperative delirium monitoring using the Confusion Assessment Method CAM. For inflammatory and stress response evaluation, serum samples were collected at three time points - preoperatively, 24 hours, and 72 hours postoperatively - to measure levels of IL-6, TNF-α, CRP, cortisol, and norepinephrine. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), and postoperative analgesic usage was recorded. Secondary outcome measures included enhanced recovery indicators (specifically time to first flatus, time to ambulation, and length of hospital stay), postoperative complication rate, hemodynamic changes during surgery and within 24 hours postoperatively, and patient satisfaction scores.

Statistical analysis

Data analysis was performed using SPSS 26.0 software. Normally distributed measurement data were expressed as mean ± SD, with independent sample t-tests for between-group comparisons. Count data were expressed as numbers (percentages) and analyzed using χ² tests. Ranked data were analyzed using rank-sum tests. Repeated measures analysis of variance was used to compare indicators at different time points. Pearson correlation analysis was used to evaluate the correlation between inflammatory factor levels and anxiety/depression scores. P < 0.05 was considered statistically significant.

RESULTS

The baseline demographic and clinical characteristics

The baseline demographic and clinical characteristics were comparable between the two groups. The mean age was similar (study group: 71.3 ± 5.2 years vs control group: 70.8 ± 5.5 years, P = 0.65), as was the gender distribution (male/female: 34/26 vs 32/28, P = 0.78) and body mass index (23.5 ± 2.8 kg/m² vs 23.8 ± 2.6 kg/m², P = 0.54). ASA classification distribution and tumor staging showed no significant differences between groups (P = 0.89 and P = 0.92, respectively). The prevalence of comorbidities was also similar between groups (30 patients vs 28 patients, P = 0.73), including hypertension (25 patients vs 23 patients, P = 0.85) and diabetes mellitus (12 patients vs 10 patients, P = 0.79). Lifestyle factors such as smoking (20 patients vs 18 patients, P = 0.81) and alcohol consumption (15 patients vs 12 patients, P = 0.76) were also comparable. Additionally, there were no significant differences in previous surgery history (10 patients vs 8 patients, P = 0.71), family history of cancer (15 patients vs 13 patients, P = 0.82), or previous cancer treatment history including chemotherapy (5 patients vs 3 patients, P = 0.75) and radiotherapy (3 patients vs 2 patients, P = 0.83). All P values were greater than 0.05, indicating no statistically significant differences in baseline characteristics between the two groups (Table 1).

Table 1 Baseline demographic and clinical characteristics.

Characteristic	Study group (n = 60)	Control group (n = 60)	P value
Age (year), mean ± SD	71.3 ± 5.2	70.8 ± 5.5	0.65
Gender (male/female)	34/26	32/28	0.78
BMI (kg/m2)	23.5 ± 2.8	23.8 ± 2.6	0.54
ASA classification distribution	I: 10, II: 30, III: 20	I: 12, II: 32, III: 16	0.89
Tumor staging	I: 10, II: 20, III: 20, IV: 10	I: 12, II: 22, III: 18, IV: 8	0.92
Comorbidities (n)	30	28	0.73
Smoking history (yes/no)	20/40	18/42	0.81
Alcohol consumption (yes/no)	15/45	12/48	0.76
Hypertension (yes/no)	25/35	23/37	0.85
Diabetes mellitus (yes/no)	12/48	10/50	0.79
Previous surgery (yes/no)	10/50	8/52	0.71
Family history of cancer (yes/no)	15/45	13/47	0.82
Chemotherapy history (yes/no)	5/55	3/57	0.75
Radiotherapy history (yes/no)	3/57	2/58	0.83

BMI: Body mass index; ASA: American Society of Anesthesiologists.

Enhanced recovery indicators

The study group demonstrated significantly better postoperative recovery outcomes compared to the control group across all measured indicators. Recovery of gastrointestinal function was faster in the study group, with shorter time to first flatus (48.3 ± 6.2 vs 62.5 ± 7.8 hours, P = 0.002) and earlier resumption of diet (36.2 ± 5.0 vs 48.7 ± 6.3 hours, P = 0.001). Physical recovery was also enhanced, with reduced time to ambulation (28.4 ± 4.2 vs 38.6 ± 5.1 hours, P = 0.001) and shorter length of hospital stay (5.2 ± 1.1 vs 7.4 ± 1.3 days, P = 0.003). Patient comfort and safety indicators showed notable improvements in the study group, including lower postoperative pain scores (3.1 ± 1.2 vs 4.5 ± 1.5, P = 0.004), reduced incidence of postoperative nausea and vomiting (10 patients vs 20 patients, P = 0.012), and lower infection rates (5.0% ± 2.2% vs 10.0% ± 3.1%, P = 0.021). Overall postoperative complications were fewer in the study group (8 cases vs 15 cases, P = 0.034). These improvements were reflected in higher patient satisfaction scores in the study group (8.5 ± 1.0 vs 7.0 ± 1.2, P = 0.001). All differences were statistically significant with P values less than 0.05 (Table 2).

Table 2 Enhanced recovery indicators.

Indicator	Study group (n = 60)	Control group (n = 60)	P value
Time to first flatus (hours)	48.3 ± 6.2	62.5 ± 7.8	0.002
Time to ambulation (hours)	28.4 ± 4.2	38.6 ± 5.1	0.001
Length of hospital stay (days)	5.2 ± 1.1	7.4 ± 1.3	0.003
Postoperative pain score (0-10)	3.1 ± 1.2	4.5 ± 1.5	0.004
Time to first diet (hours)	36.2 ± 5.0	48.7 ± 6.3	0.001
Postoperative nausea and vomiting (yes/no)	10/50	20/40	0.012
Postoperative infection rate (%)	5.0 ± 2.2	10.0 ± 3.1	0.021
Postoperative complications (n)	8	15	0.034
Patient satisfaction score (0-10)	8.5 ± 1.0	7.0 ± 1.2	0.001

Anxiety and depression scores

The study group exhibited significantly better psychological outcomes across all measured parameters. Anxiety and depression scores were markedly lower in the study group (anxiety: 5.2 ± 1.4 vs 7.8 ± 1.6, P = 0.001; depression: 4.8 ± 1.2 vs 7.1 ± 1.5, P = 0.001). The incidence of clinically significant psychological symptoms (HAD score ≥ 7) was also lower in the study group, with fewer patients experiencing anxiety (15.0% vs 35.0%, P = 0.008) and depression (13.3% vs 31.7%, P = 0.012). Pain-related psychological indicators showed more favorable outcomes in the study group, with lower Fear of Pain scores (3.5 ± 1.0 vs 5.0 ± 1.2, P = 0.002) and reduced Fear Avoidance Belief scores (2.8 ± 0.9 vs 4.2 ± 1.1, P = 0.003). Additionally, the study group demonstrated higher psychological resilience (7.5 ± 1.5 vs 5.8 ± 1.4, P = 0.001) and better postoperative quality of recovery as measured by the PostopQRS scale (85.2 ± 10.3 vs 72.4 ± 12.1, P = 0.001). All differences were statistically significant with P values less than 0.05, indicating that the PH + GDFT intervention was associated with improved psychological outcomes and better overall recovery quality (Table 3).

Table 3 Anxiety and depression scores.

Indicator	Study group (n = 60)	Control group (n = 60)	P value
Anxiety score (mean ± SD)	5.2 ± 1.4	7.8 ± 1.6	0.001
Depression score (mean ± SD)	4.8 ± 1.2	7.1 ± 1.5	0.001
Patients with clinically significant anxiety (HAD score ≥ 7) (%)	15.0% (9/60)	35.0% (21/60)	0.008
Patients with clinically significant depression (HAD score ≥ 7) (%)	13.3% (8/60)	31.7% (19/60)	0.012
FOP score (mean ± SD)	3.5 ± 1.0	5.0 ± 1.2	0.002
FAB score (mean ± SD)	2.8 ± 0.9	4.2 ± 1.1	0.003
Psychological resilience score (mean ± SD)	7.5 ± 1.5	5.8 ± 1.4	0.001
PostopQRS score (mean ± SD)	85.2 ± 10.3	72.4 ± 12.1	0.001

FAB: Fear avoidance belief; FOP: Fear of pain; HAD: Hospital Anxiety and Depression; PostopQRS: Postoperative Quality of Recovery Scale.

Inflammatory response analysis of inflammatory markers

The study group demonstrated significantly lower levels of pro-inflammatory markers compared to the control group. Specifically, key inflammatory cytokines were markedly reduced, including IL-6 (42.3 ± 8.5 vs 68.7 ± 12.4 pg/mL, P < 0.001), TNF-α (28.4 ± 5.6 vs 45.2 ± 8.9 pg/mL, P < 0.001), and CRP (38.5 ± 7.2 vs 62.4 ± 11.3 mg/L, P < 0.001). Other pro-inflammatory mediators also showed significant reductions in the study group, including IL-1β (12.5 ± 3.4 vs 18.7 ± 4.5 pg/mL, P = 0.002), monocyte chemoattractant protein-1 (20.3 ± 4.2 vs 28.6 ± 5.8 pg/mL, P = 0.003), interferon-gamma (9.8 ± 2.3 vs 14.5 ± 3.7 pg/mL, P = 0.004), and S100A8 (1.2 ± 0.3 vs 2.1 ± 0.5 ng/mL, P = 0.001).

Notably, the anti-inflammatory cytokine IL-10 showed significantly higher levels in the study group (15.2 ± 2.8 vs 10.5 ± 2.1 pg/mL, P = 0.001), suggesting an enhanced anti-inflammatory response. All differences were statistically significant with P values less than 0.05, indicating that the PH + GDFT intervention effectively modulated the inflammatory response by reducing pro-inflammatory markers while enhancing anti-inflammatory mediators (Table 4).

Table 4 Inflammatory response analysis of inflammatory markers.

Inflammatory marker	Study group (n = 60)	Control group (n = 60)	P value
IL-6 (pg/mL)	42.3 ± 8.5	68.7 ± 12.4	< 0.001
TNF-α (pg/mL)	28.4 ± 5.6	45.2 ± 8.9	< 0.001
CRP (mg/L)	38.5 ± 7.2	62.4 ± 11.3	< 0.001
IL-1β (pg/mL)	12.5 ± 3.4	18.7 ± 4.5	0.002
IL-10 (pg/mL)	15.2 ± 2.8	10.5 ± 2.1	0.001
MCP-1 (pg/mL)	20.3 ± 4.2	28.6 ± 5.8	0.003
IFN-γ (pg/mL)	9.8 ± 2.3	14.5 ± 3.7	0.004
S100A8 (ng/mL)	1.2 ± 0.3	2.1 ± 0.5	0.001

IL: Interleukin; TNF-α: Tumor necrosis factor α; CRP: C-reactive protein; MCP: Monocyte chemoattractant protein; IFN-γ: Interferon-gamma.

Sleep quality assessment

The study group demonstrated significantly better sleep quality parameters compared to the control group. The global PSQI score was notably lower in the study group (5.2 ± 1.3 vs 7.8 ± 1.8, P = 0.002), indicating better overall sleep quality. Sleep metrics showed significant improvements, including shorter sleep latency (20.4 ± 5.6 vs 30.2 ± 7.1 minutes, P = 0.003), longer total sleep time (6.8 ± 1.2 vs 5.4 ± 1.0 hours, P = 0.001), and higher sleep efficiency (85.2 ± 6.3% vs 72.4 ± 7.8%, P = 0.001). Pain management outcomes were also superior in the study group, with lower postoperative morphine equivalent consumption (15.3 ± 3.2 vs 23.6 ± 4.5 mg, P = 0.001). The study group experienced fewer sleep disturbances (12 cases vs 24 cases, P = 0.004), reduced need for sleep medication (5 patients vs 15 patients, P = 0.012), and fewer instances of daytime dysfunction (8 cases vs 18 cases, P = 0.015). The Epworth Sleepiness Scale score was also significantly lower in the study group (4.5 ± 1.2 vs 6.8 ± 1.5, P = 0.001), indicating better daytime alertness. All differences were statistically significant with P values less than 0.05, suggesting that the PH + GDFT intervention effectively improved both sleep quality and pain management outcomes (Table 5).

Table 5 Sleep quality assessment.

Indicator	Study group (n = 60)	Control group (n = 60)	P value
Global PSQI score (mean ± SD)	5.2 ± 1.3	7.8 ± 1.8	0.002
Postoperative morphine equivalent consumption (mg)	15.3 ± 3.2	23.6 ± 4.5	0.001
Sleep latency (minutes)	20.4 ± 5.6	30.2 ± 7.1	0.003
Total sleep time (hours)	6.8 ± 1.2	5.4 ± 1.0	0.001
Sleep efficiency (%)	85.2 ± 6.3	72.4 ± 7.8	0.001
Sleep disturbances (n)	12	24	0.004
Use of sleep medication (yes/no)	5/55	15/45	0.012
Daytime dysfunction (n)	8	18	0.015
ESS score (mean ± SD)	4.5 ± 1.2	6.8 ± 1.5	0.001

PSQI: Pittsburgh Sleep Quality Index; ESS: Epworth Sleepiness Scale.

Multivariate analysis of postoperative anxiety and depression

To comprehensively evaluate the impact of PH + GDFT on postoperative psychological outcomes, we conducted multiple regression analyses. Logistic regression analysis identified several independent risk factors for postoperative anxiety (HAD-A ≥ 7). The PH + GDFT intervention showed a protective effect [odds ratio (OR) = 0.38, 95% confidence interval (CI): 0.24-0.62, P = 0.001], while advanced age (≥ 75 years; OR = 1.85, 95%CI: 1.32-2.59, P = 0.003), elevated IL-6 levels at 24 hours (OR = 1.42, 95%CI: 1.18-1.71, P = 0.002), poor sleep quality (PSQI > 5; OR = 2.13, 95%CI: 1.56-2.91, P < 0.001), and postoperative complications (OR = 2.45, 95%CI: 1.73-3.46, P < 0.001) were associated with increased risk (Table 6).

Table 6 Multivariate analysis of postoperative anxiety and depression.

Risk factor	Variable	OR (95%CI)	P value
Postoperative anxiety (HAD-A ≥ 7)	PH + GDFT intervention	0.38 (0.24-0.62)	0.001
	Age ≥ 75 years	1.85 (1.32-2.59)	0.003
	IL-6 levels at 24 hours (pg/mL)	1.42 (1.18-1.71)	0.002
	PSQI > 5	2.13 (1.56-2.91)	< 0.001
	Postoperative complications	2.45 (1.73-3.46)	< 0.001
	Postoperative pain score (NRS)	1.25 (1.05-1.48)	0.012
	Duration of surgery (≥ 120 minutes)	1.60 (1.10-2.33)	0.015
Postoperative depression (HAD-D ≥ 7)	PH + GDFT intervention	0.41 (0.26-0.65)	0.001
	Age ≥ 75 years	1.78 (1.25-2.53)	0.002
	IL-6 levels at 24 hours (pg/mL)	1.35 (1.12-1.63)	0.003
	PSQI > 5	2.05 (1.48-2.84)	< 0.001
	Postoperative complications	2.30 (1.60-3.33)	< 0.001
	Postoperative pain score (NRS)	1.30 (1.08-1.56)	0.007
	Duration of surgery (≥ 120 minutes)	1.55 (1.08-2.22)	0.018

OR: Odds ratio; CI: Confidence interval; HAD: Hospital Anxiety and Depression; PH: Permissive hypercapnia; GDFT: Goal-directed fluid therapy; IL: Interleukin; PSQI: Pittsburgh Sleep Quality Index; NRS: Numeric rating scale.

Independent predictors of postoperative depression

A study on independent predictors of postoperative depression shows that the PH + GDFT protocol is the only protective factor (HR = 0.45, P < 0.001), reducing the risk of postoperative depression by 55%. Of the risk factors identified for postoperative depression, the following had the most influence: Previous history of depression (HR = 2.31, P = 0.001), length of hospital stay greater than 6 days (HR = 2.15, P = 0.001), and postoperative complications (HR = 2.10, P = 0.001). Among the inflammatory, endocrine and psychological indicators, TNF-α > 40 pg/mL and cortisol > 350 nmol/L significantly influenced the occurrence of postoperative pulmonary dysfunction, which increased the risk of peripheral inflammatory factors and endocrine factors for postoperative pulmonary dysfunction by 78% and 92%, respectively. Older age (≥ 65 years) (HR = 1.55), chronic pain (HR = 1.67), and sleep disorders (HR = 1.48) were other factors associated with increased risk of postoperative depression. As an important social factor, poor social support (HR = 1.82) significantly increased the patients' risk of postoperative depression. Physiological, psychological, and social factors contribute to postoperative depression, highlighting that this debilitating condition is multifactorial in nature. These results constitute an impactful addition to the clinical practice framework, highlighting not only the preventive value of the PH + GDFT protocol itself but also the implicit necessity to pay attention to patients at risk in the form of clusters of risk factors and design tailored prevention strategies (Figure 1).

Figure 1 Independent predictors of postoperative depression. The analysis shows that the permissive hypercapnia + goal-directed fluid therapy protocol significantly reduced the risk of depression during the 7-day follow-up (hazard ratio = 0.45). Other factors linked to higher depression risk included high tumor necrosis factor α levels (> 40 pg/mL), high cortisol levels (> 350 nmol/L), and longer hospital stays (> 6 days). PH: Permissive hypercapnia; GDFT: Goal-directed fluid therapy; TNF-α: Tumor necrosis factor α; HR: Hazard ratio.

DISCUSSION

Aim This study aimed to determine the effects of PH in conjunction with GDFT on postoperative recovery and anxiety-depression status in elderly patients following laparoscopic surgery. This study is especially relevant as surgical indications expand into an older patient demographic with higher baseline risks for postoperative complications and psychological distress.

Over the past several years, perioperative management strategies have evolved to facilitate recovery and reduce complications. Abstract PH, GDFT two strategies have shown improvement in patient outcome. PH is a ventilator management strategy that augments arterial CO₂ pressure in an effort to minimize ventilator-induced lung injury while sparing systemic perfusion. Conversely, GDFT adjusts fluid control according to haemodynamic indicators, allowing proper tissue perfusion while avoiding excessive fluid volume. Utilizing both strategies together may aid not only in physical recovery but also in alleviating some of the psychological trauma of surgery[21-24].

The gastric cancer patients 794 found that the rates of postoperative anxiety and depression among colorectal cancer patients is prevalent, which is primarily related to factors such as surgical trauma, chemotherapy drugs, doubts about prognosis, and a lack of social support[25-27]. In patients with colorectal cancer following surgical procedures who underwent chemotherapy, the rates of anxiety and depression were reported as 30%-45% and 25%-35%, respectively. These psychological morbidities affect patients’ quality of life and can also result in delayed wound healing, complications, and prolonged hospitalization.

Allowing CO₂ retention in patients under mechanical ventilation, this management technique known as PH seeks to minimize the ventilator-induced lung injury by permitting a moderate increase in arterial CO₂ pressure (PaCO₂). Nevertheless, the effects of hypercapnia on the mental state are still not completely elucidated[28]. Other research indicates that hypercapnia can influence patients’ emotional state, via its impact on neurotransmitters and the autonomic nervous system.

During postoperative recovery, the combination of hypercapnia and GDFT has been proven to significantly improve patients' postoperative recovery. This combined treatment strategy not only reduces the incidence of postoperative complications but also shortens hospital stays and improves patients' quality of life. Furthermore, this treatment strategy may indirectly alleviate patients’ anxiety and depression through reducing inflammatory responses and improving tissue perfusion.

Although hypercapnia shows certain advantages in postoperative recovery, its direct effects on anxiety and depression require further research[28]. Some studies indicate that hypercapnia may positively affect patients' psychological state by improving tissue perfusion and reducing inflammatory responses. However, other studies suggest that hypercapnia might trigger anxiety by activating the autonomic nervous system.

Elderly patients are particularly vulnerable to postoperative anxiety and depression. The incidence of these psychological issues can be as high as 45% for anxiety and 35% for depression in this population. These conditions can significantly impair recovery by delaying wound healing, increasing the risk of complications, and prolonging hospital stays[7]. Moreover, the interplay between physical and psychological health can create a vicious cycle, where poor mental health exacerbates physical recovery and vice versa. Therefore, interventions that address both physical and psychological aspects of recovery are crucial.

The study highlights the significant role of inflammatory markers in postoperative psychological outcomes. Elevated levels of cytokines such as IL-6 and TNF-α have been shown to influence mood regulation by affecting neurotransmitter metabolism and activating the hypothalamic-pituitary-adrenal axis. The findings suggest that reducing inflammatory responses through optimized perioperative management can have a positive impact on psychological well-being. This aligns with previous research indicating that inflammation is a key mediator in the development of postoperative anxiety and depression.

Enhanced recovery after surgery protocols have gained traction in recent years, emphasizing the importance of multimodal interventions to improve patient outcomes. The combination of PH and GDFT in this study can be seen as an extension of enhanced recovery after surgery principles, focusing on optimizing physiological parameters to enhance recovery. The results demonstrate significant improvements in postoperative recovery indicators, such as shorter time to first flatus, ambulation, and hospital stay. These findings underscore the potential of integrating PH and GDFT into clinical practice to achieve better overall outcomes.

Limitations

Failure to adequately control for potential confounding factors such as preoperative mental health status, social support, and individual coping strategies; although inflammatory markers were measured, the exact mechanisms by which PH + GDFT improves psychological outcomes are not fully elucidated; the single-center design and focus solely on elderly patients undergoing laparoscopic colorectal cancer surgery limit the generalizability of the results. Future research will expand the sample population and further explore the mechanisms of action to validate the effectiveness of PH + GDFT in broader clinical settings.

Future directions

First, we will include more diverse patient populations, including patients of different age groups and surgical types, to validate the generalizability of our results. Second, we will incorporate patient-reported outcome measures to gain deeper insight into patients' subjective experiences of the treatment. Third, we plan to further explore the specific mechanisms by which PH + GDFT improves psychological health, particularly its regulatory effects on neuroinflammatory pathways. Finally, we will work to develop individualized risk assessment tools to identify high-risk patients who are most likely to benefit from PH + GDFT, thereby achieving precision medicine. These directions will help us establish more comprehensive and individualized perioperative management strategies, ultimately improving postoperative recovery quality and psychological health levels in elderly patients.

CONCLUSION

In conclusion, the study highlights the importance of optimizing perioperative management strategies to improve both physical and psychological recovery in elderly patients undergoing laparoscopic surgery. It is demonstrated that the combination of PH and GDFT can significantly enhance postoperative recovery and mitigate the risk of postoperative anxiety and depression. This research contributes to a growing body of evidence advocating for the incorporation of advanced perioperative protocols into clinical practice to improve patient outcomes.