Cerebral oximetry-guided anaesthesia and postoperative delirium in elderly patients undergoing off-pump coronary artery bypass grafting: a randomized controlled trial

Abstract

Introduction

While cerebral oximetry monitoring has been reported to reduce neurological dysfunction and hospital stay after cardiac surgery, its effect on postoperative delirium (POD) during off-pump coronary artery bypass grafting (CABG) remains underexplored. This study examines whether using cerebral oximetry to guide anaesthesia can reduce POD in patients aged ≥ 65 years undergoing off-pump CABG.

Methods

This single-center, randomized trial enrolled 200 patients scheduled for off-pump CABG. Participants were randomly assigned (1:1) to either the intervention or control group using sealed envelopes prior to anaesthesia. In the intervention group, cerebral oxygen saturation was continuously monitored by cerebral oximetry. A desaturation event (a drop > 20% from baseline or an absolute regional cerebral oxygen saturation < 55% at either probe) triggered predefined intervention strategies. In the control group, cerebral oximetry data were blinded to clinicians, and patients received standard anaesthetic care. The primary outcome was the incidence of POD during the first 7 days after surgery. Secondary outcomes included the incidence of postoperative acute kidney injury and myocardial infarction, mechanical ventilation duration, intensive care unit (ICU) and hospital stay, and in-hospital mortality.

Results

A total of 200 patients were randomized and included in the final analysis. Delirium occurred in 14 patients (14.0%) in the intervention group versus 24 (24.0%) in the control group within the first 7 postoperative days (P = 0.104). Subgroup analysis showed a significantly lower incidence of delirium in older patients ( > 70 years) in the intervention group compared to the controls [5/47 (10.6%) vs. 11/31 (35.5%); P = 0.011], suggesting a possible interaction between cerebral oximetry-guided anaesthesia and advanced age. ICU and hospital stays were also markedly shorter in the intervention group.

Conclusion

Cerebral oximetry-guided anaesthesia did not significantly reduce POD in patients aged ≥ 65 years undergoing off-pump CABG; exploratory analyses suggested a numeric reduction in those > 70 years. However, this observation requires prospective validation in a larger, adequately powered trial.

Trial registration

ChiCTR2300068537 (Chinese Clinical Trial Registry), registered 22/02/2023.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12877-026-07054-0.

Introduction

The acceleration of population aging and the prevalence of unhealthy lifestyles have significantly contributed to the rising incidence and mortality rates of cardiovascular diseases. Currently, there are approximately 330 million patients with cardiovascular diseases in China, among whom 12.34 million suffer from coronary heart disease [1]. Postoperative delirium (POD) is a significant and clinically relevant neuropsychiatric complication in elderly patients undergoing cardiovascular surgery, with reported rates varying from 20% to 50% [2–5]. POD is an early indicator of cognitive decline [6]. It is associated with cognitive impairment, increased mortality, and higher medical costs, which impose serious burdens on families and healthcare systems [7, 8].

Accumulating evidence has clarified the pathophysiology, clinical manifestations, and prevention of POD. Several isolated reports suggested that nonpharmacologic therapies, surgical techniques, minimization of triggering events and medications and improving postoperative pain management may reduce POD but lack precise effectiveness [9–11]. Glumac et al. reported that preoperative corticosteroid mitigated the inflammatory response and lowered the incidence of postoperative cognitive dysfunction, implicating surgery-induced systemic inflammation as a contributor to postoperative neurological injury [12]. Although the causes of POD are multifactorial, decreased intraoperative cerebral perfusion and oxygenation represent a key, modifiable pathophysiological mechanism [13–15]. Elderly patients undergoing off-pump coronary artery bypass grafting (CABG) are at higher risk of experiencing significant hemodynamic fluctuations, especially during vascular graft anastomosis, which may lead to sustained hypotension and tissue hypoperfusion.

Traditional anaesthetic monitoring parameters such as blood pressure and heart rate may not accurately reflect cerebral oxygenation status. Regional cerebral oxygen saturation (rSO₂) monitoring, based on near-infrared spectroscopy (NIRS), provides real-time assessment of cerebral oxygen supply/demand imbalance and allows for timely interventions to optimize cerebral perfusion [16]. Cerebral desaturation was associated with intraoperative electroencephalographic (EEG) burst suppression during cardiac surgery, most significantly during cardiopulmonary bypass (CPB). Increased intraoperative burst suppression is associated with postoperative delirium [17]. NIRS is increasingly used for goal-directed optimization of treatment regimens to improve the prognosis of neurological function [18–20]. In a retrospective study of 1439 patients who underwent off-pump CABG, Lim et al. demonstrated that a decrease in intraoperative rSO₂ was associated with an increased risk of POD, and revealed that the cut-off value of rSO₂ for predicting POD in patients younger than 68 years was 55% [21]. Recently, a randomized controlled study of off-pump CABG patients aged ≥ 60 years has proved that guiding perioperative care using cerebral and somatic tissue oxygen saturation, combined with real-time hemodynamic monitoring had no clear evidence that this approach reduced the incidence of a composite of 30-day postoperative complications [2].

To our knowledge, conclusive evidence of a successful preventive method has yet to be found. We hypothesized management guided by rSO₂ monitoring to prevent desaturation would reduce the incidence of POD compared with standard care. This study is to investigate whether anaesthesia guided by rSO₂ monitoring decreases POD in elderly patients undergoing off-pump CABG.

Materials and methods

Ethical approval

This was a single-centre, randomized, controlled trial conducted at a tertiary academic medical centre. This study was approved by the institutional ethics committee (No. 2022 − 1824) and its protocol was prospectively registered with the Chinese Clinical Trial Registry (ChiCTR2300068537) on 22 February 2023, and published in BMJ Open [22]. All procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants prior to enrollment.

Participants

From 10 July 2023 to 11 October 2024, we enrolled 200 consecutive patients aged ≥ 65 years who were scheduled for off-pump CABG. Major exclusion criteria were as follows: patients with a previous history of cardiac surgery; patients requiring emergency surgery or combined surgery such as simultaneous CABG mixed percutaneous coronary intervention; patients with history of schizophrenia, Parkinson’s disease, epilepsy, myasthenia gravis, or severe dementia; patients who were uncooperative due to linguistic difficulties and other reasons; and patients with history of brain trauma or neurosurgery, left ventricular ejection fraction < 30%, severe liver dysfunction (Child-Pugh grade C), renal failure (requiring kidney replacement therapy), or severe carotid artery stenosis.

Randomization and blinding

Eligible participants were randomly assigned (1:1) to the intervention or control group. An independent statistician generated the computer-derived randomization sequence and placed the allocations in sequentially numbered, opaque, sealed envelopes, ensuring prospective allocation concealment. Patients, surgeons, and ICU physicians were blinded to group allocation. The anesthesiologist, who was unblinded, was resoponsible for protocol implementation and data collection. Postoperative delirium was assessed for the first 7 postoperative days by two independent follow-up staff who had been well trained and remained blinded to group allocation.

Anaesthesia and monitoring protocol

Baseline rSO₂ value was obtained for the first 2 min while patients inhaled room air before anaesthetic induction. All participants received general anaesthesia and were continuously monitored by bilateral NIRS sensors (Invos 5100 C, Cerebral/Somatic oximeter; Medtronic^®) during the operation. The anaesthetic depth was maintained at a bispectral index of 40–60 using a disposable BIS sensor (Covidien, CO, USA) positioned on the forehead. The criteria for intervention was defined as a drop of more than 20% from baseline value or rSO₂ less than 55% for >60 consecutive seconds at either probe during the procedure. In the occurrence of intraoperative cerebral desaturation in the intervention group, clinical intervention strategies were implemented according to the intervention protocol Table (in Table 1) [23]. In the control group, cerebral oximetry data were hidden from the perioperative team and captured by the machine during surgery. The perioperative hemodynamic stability was maintained by adjusting anaesthetic depth and administering vasoactive drugs to achieve a mean arterial pressure (MAP) of 60 to 100 mmHg, in accordance with the standard anesthesia protocol. After surgery, the patients were transferred to the intensive care unit (ICU) for clinical care. All patients were provided with a patient-controlled intravenous analgesia (PCIA) pump (background infusion rate 2 mL / h, bolus 2 mL, and lockout time 10 min) containing 100 µg sufentanil, 20 mg dezocine and 5 mg tropisetron.

Table 1.

Clinical intervention strategies to improve intraoperative cerebral desaturation

	Clinical intervention strategies
1	Verify the probe position
2	Increase blood pressure to within 20% of baseline
3	Enhance the fraction of inspired oxygen (FiO2)
4	Adjust respiratory parameters to increase end-tidal CO2 levels within normal ranges (35 to 45 mmHg)
5	Optimization of the fluid volume therapy (hemoglobin levels < 9 g/dL will warrant consideration of a red blood cell transfusion)
6	Improving ventricular function in the presence of low cardiac output
7	Eliminating hypothermia (35 to 37 °C)

Postoperative outcomes

The primary outcome was the incidence of POD during the first 7 days after surgery. Delirium screening was performed once on postoperative day 1 and twice daily (morning 08:00–12:00 and evening 18:00–20:00) from postoperative days 2–7. All assessments were carried out by an independent follow-up team blinded to group assignment; the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU) were applied [24–26]. Secondary outcomes included the incidence of postoperative acute kidney injury (AKI) and myocardial infarction (MI) during hospitalization, as well as ICU and hospital length of stay. AKI was defined according to the KDIGO criteria [27], and MI was defined based on the Fourth Universal Definition of Myocardial Infarction [28].

Statistical analysis

Given a 20–30% baseline incidence of POD in elderly patients undergoing off-pump CABG [29], comprehensive evidence indicates that cerebral oximetry-guided anesthesia can halve this risk [30]. Sample size was determined to be 200 (100 per group), accounting for a 5% dropout rate, to achieve 80% power at a 5% significance level using PASS 11.0 (NCSS, Utah, United States). Statistical analyses were conducted using SPSS^® Statistics for Windows, version 26 (IBM, Inc., New York, U.S.A.). The data with a normal distribution were expressed as mean with standard deviation (SD), and compared by independent-samples t tests. The data of non-normally distribution were presented as median (range) and analyzed using the Mann-Whitney U-tests. Categorical data were described as numbers or percentages, and analyzed using chi-square test or Fisher’s exact test. Baseline characteristics in each group were assessed with absolute standardized differences (ASD), defined as the absolute difference in means or proportions divided by the pooled SD. Postoperative outcomes were expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). All statistical analyses followed the intent-to-treat principle, which was defined as analyzing patients within the groups to which they were primarily assigned, excluding those without any follow-up records or with canceled procedures. Additionally, a sensitivity analysis (per-protocol population) was conducted after excluding 7 patients whose surgical strategies were changed. Post-hoc exploratory subgroup analyses were performed to detect potential effect-measure modification by age, sex, body-mass index (BMI), and pre-existing diabetes. Multivariable logistic regression was used to estimate the independent and interactive effects of these variables on the association between cerebral oxygen-guided anaesthesia and postoperative delirium. Odds ratios (OR) with 95% CIs were reported. Kaplan-Meier survival analysis was applied for the time to event results. Two-tailed P value of < 0.05 was considered statistically significant.

Results

Participants

Patient screening, enrollment, and follow-up data were presented in Fig. 1. 276 patients for eligibility, 22 patients refused to participate, 54 patients did not meet the inclusion criteria, and 200 were randomized in a 1:1 ratio to the intervention group or the control group. During surgery, 7 patients (3.5%) underwent conversion from off-pump CABG to on-pump CABG due to intraoperative temporary surgical considerations. Finally, the primary outcome analysis was performed on 100 patients in control group and 100 patients in intervention group. Their mean age was 70.2 ± 4.6 years (range, 65 to 86 years) and 70.5% were male. The operation time and CPB time did not significantly differ between the 3 patients (3%) in the intervention group and the 4 patients (4%) in the control group. As detailed in Table 2, the baseline demographics, clinical history, and preoperative medications were comparable between groups (P > 0.05).

Fig. 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram

Table 2.

Demographic and baseline characteristics of the study patients

Variables	Intervention group (n = 100 )	Control group (n = 100 )	ASD
Baseline demographics
Age (y)	70.7 ± 4.7	69.8 ± 4.4	0.21
Male (%)	77(77.0)	64(64.0)	0.29
Body Mass Index (kg.m2)	25.2 ± 3.1	26.1 ± 3.1	0.27
Clinical history
Diabetes (%)	41( 41.0)	29( 29.0)	0.25
Hyperlipidemia (%)	65(65.0)	61(61.0)	0.08
Hypertension (%)	87(87.0)	82(82.0)	0.14
Cerebrovascular disease (%)	9 (9.0)	17(17.0)	0.24
Previous myocardial infarction (%)	29(29.0)	39(39.0)	0.21
Peripheral vascular disease (%)	18(18.0)	16(16.0)	0.05
Medication
Aspirin (%)	42(42.0)	47(47.0)	0.10
Beta-blockers (%)	60(60.0)	53(53.0)	0.14
Education level
Primary school or below (%)	38(38.0)	45(45.0)	0.14
Middle school or above (%)	62(62.0)	55(55.0)	0.14
Left ventricular ejection fraction (%)	58.4 ± 7.4	58.5 ± 7.3	0.01
Preoperative lab parameters
Platelets (109/L)	208.4 ± 54.9	219.7 ± 90.2	0.14
Hemoglobin (g/L)	138.3 ± 15.0	136.5 ± 15.8	0.11
Creatinine (mmol/L)	72.0 ± 19.1	70.3 ± 20.4	0.08
Blood urea nitrogen (mmol/L)	6.8 ± 1.9	6.7 ± 2.2	0.07
Troponin I ( ng/mL)*	0.006 (0.001 ,0.316 )	0.007 (0.001 ,0.223 )	0.001

ASD  Absolute standardized differences, Data are expressed as means ± SDs or n (%), *data are expressed as medians (range)

Perioperative course and cerebral oximetry parameters

In the intervention group, intraoperative cerebral desaturation (rSO₂ < 80% of baseline or rSO₂ less than 55%) occurred in 44 patients (44%); the intervention algorithm prompted stepwise rescue manoeuvres; the frequency and type of these therapeutic adjustments were detailed in Supplemental Table 1. Therapeutic measures restored cerebral oxygenation in 93.2% (41/44) of desaturation episodes, and no patient required protocol withdrawal due to surgical or haemodynamic instability. Norepinephrine was required in 70% (70/100) of the intervention group versus 51% (51/100) of the control group (P = 0.009). There was no significant difference in dopamine use between the two groups: 45% and 37% respectively (P = 0.314) in Table 3. The control group exhibited a markedly prolonged intraoperative cerebral oximetry desaturation burden compared with the intervention group (P < 0.001), and significantly lower minimum rSO₂ values bilaterally ( P < 0.001) in Table 3.

Table 3.

Perioperative variables and cerebral oximetry parameters

Variables	Intervention group (n = 100 )	Control group (n = 100 )	P
Operation time (min)	213.2 ± 43.0	214.2 ± 49.8	0.860
Norepinephrine administration (%)	70(70.0)	51(51.0)	0.009
Vasopressor support (dopamine) (%)	45(45.0)	37(37.0)	0.314
Cerebral Parameters
Baseline rSO2 (right)	66.9 ± 3.3	66.3 ± 3.1	0.180
Baseline rSO2 (left)	66.8 ± 3.9	66.5 ± 3.5	0.515
Minimum rSO2 (right)	59.1 ± 4.6	55.3 ± 5.0	< 0.001
Minimum rSO2 (left)	59.6 ± 4.6	55.7 ± 5.1	< 0.001
Cerebral oximetry desaturation (%)	44 (44.0)	58 (58.0)	0.07
Duration of cerebral oximetry desaturation (min)*	2 (1,10)	8 (1,25)	< 0.001
Postoperative sedative use
Dexmedetomidine administration	26 (26.0)	35 (35.0)	0.219

rSO2  Regional cerebral oxygen saturation, Data are expressed as means ± SDs or n (%), *data are expressed as medians (range)

Primary outcomes

Delirium occurred in 14 of 100 patients (14.0%) in the intervention group and 24 of 100 (24.0%) in the control group (P = 0.104) (in Table 4). In a per-protocol analysis, we excluded the 7 patients experienced the intraoperative temporary surgical strategies, which yielded similar results for the major outcome [intervention group: 13/97 (13.4%); control group: 22/96 (22.9%); P = 0.096 in Supplemental Table 2]. By the log-rank test, time to delirium onset did not differ significantly between the groups (hazard ratio, 0.56 [95% CI, 0.29–1.09]; Log-rank P = 0.08; Supplemental Fig. 1). With the enrolled sample size (100 participants per group), and assuming a two-sided α of 0.05 and 80% statistical power, the minimal detectable absolute difference in POD incidence between groups was 15.5%. The observed absolute difference of 10% (24% vs. 14%) was smaller than the post-hoc minimal detectable effect, the possibility of a type II error remained plausible. The duration of POD did not differ significantly between the intervention and control groups [1.5 (1.0–3.0) days vs. 1.3 (1.0–6.0) days; P = 0.689]; however, onset of POD was significantly delayed in the intervention group [2.0 (1.0–4.0) days vs. 1.0 (1.0–2.5) days; P = 0.026, in Table 4]. Compared with the control group, the incidence of delirium in elderly patients (> 70 years) in the intervention group was significantly lower [11/31 (35.5%) vs. 5/47 (10.6%), P = 0.011]. In post-hoc exploratory subgroup analyses using multivariable logistic regression, a potential delirium-reducing benefit of cerebral oximetry-guided anaesthesia was observed in patients > 70 years, whereas no association was observed in those aged 65–70 years (P for interaction = 0.042 in Table 5). No significant interactions were observed on sex, BMI (≥ 25.0 kg.m²) or diabetes (dichotomy) with relative rates of postoperative delirium between the two groups (in Table 5).

Table 4.

Primary and secondary outcomes

Variables	Intervention group (n = 100)	Control group (n = 100)	OR / MD (95%CI)	P
Primary outcomes
Postoperative delirium (%)	14 (14.0)	24 (24.0)	0.58 (0.32 to 1.06)	0.104
Postoperative delirium duration (d)*	1.5 (1.0, 3.0)	1.3 (1.0, 6.0)	-0.09(-0.78 to 0.61)	0.689
Time to first postoperative delirium (d)*	2.0 (1.0, 4.0)	1.0 (1.0, 2.5)	0.63(0.14 to 1.11)	0.026
Secondary outcomes
Postoperative mechanical ventilation time (h)*	9 (5,100)	9 (5,207)	-1.50(-6.24 to 3.24)	0.984
Postoperative intensive care unit stay time (d)*	1 (1,5)	2 (1,28)	-0.69(-1.31 to -0.06)	0.023
Postoperative duration of hospital stay (d)	7.1 ± 1.7	8.3 ± 3.9	-1.22(-2.06 to -0.38)	0.005
Myocardial infarction (%)	4(4.0)	3(3.0)	1.33 (0.30 to 5.80)	1.000
Acute kidney injury	5(5.0)	10(10.0)	0.50 (0.18 to 1.41)	0.283
Grade 1 (%)	4(4.0)	6(6.0)	-	0.537
≥ Grade 2 (%)	1(1.0)	4(4.0)	-	0.369
In-hospital mortality (%)	0(0)	1(1.0)	-	0.497

MD  Mean difference, OR Odds ratio, CI  Confidence interval, Data are expressed as means ± SDs or n (%), *data are expressed as medians (range)

Table 5.

Subgroup analysis of primary outcomes

Subgroup	Intervention group	Control group	P	OR (95%CI)	P for interaction
Age (years)				0.20(0.04 to 0.95)	0.042
≥ 71.0 (n = 78 )	5/47 (10.6)	11/31 (35.5)	0.011
65–70.0 (n = 122)	9/53 (17.0)	13/69 (18.8)	0.817
Gender				2.53(0.47 to 13.57)	0.280
Male (n = 141 )	11/77 (14.3)	12/64 (18.8)	0.500
Female (n = 59 )	3/23 (13.0)	12/36 (33.3)	0.126
Body mass index (kg.m2)				0.32(0.07 to 1.57)	0.161
≥ 25.0 (n = 108 )	7/49 (14.3)	18/59 (30.5)	0.067
< 25.0 (n = 92 )	7/51 (13.7)	6/41 (14.6)	1
Diabetes				0.96(0.21 to 4.36)	0.955
Yes (n = 70 )	7/41 (17.1)	9/29 (31.0)	0.248
No (n = 130 )	7/59 (11.9)	15/71 (21.1)	0.240

OR  Odds ratio, CI  Confidence interval, Data are expressed as n (%)

Secondary outcomes

In the secondary outcomes, the mean (SD) length of postoperative hospital stay was statistically significantly longer in the control group than the intervention group [8.3 (3.9) days vs. 7.1 (1.7) days; (P = 0.005)]. Patients in the control group had longer median (range) ICU length of stay times than the intervention group [2.0 (range:1.0–28.0) days vs. 1.0 (range:1.0–5.0) days; P = 0.023]. The median (range) duration of postoperative tracheal intubation was 9.0 (range:5.0-100.0) hours in the intervention group and 9.0 (range:5.0-207.0) hours in the control group with no statistical significance. We diagnosed grade 1 or ≥ grade 2 postoperative AKI in 4 and 1 participants in the intervention group and 6 and 4 control participants, (P = 0.537, P = 0.369, respectively). MI occurred in 4 of 100 patients ( 4.0% ) in the intervention group and 3 of 100 patients ( 3.0% ) in the control group with no statistical significance. There was 1 death in the control group from bleeding before hospital discharge (in Table 4). There was no statistical difference in the other postoperative outcomes (in Supplemental Table 3).

Discussion

In this single-centre, randomized trial of 200 patients aged ≥ 65 years undergoing off-pump CABG, cerebral oximetry-guided anaesthetic management did not significantly reduce POD. Exploratory post-hoc analyses suggested a potential benefit, manifesting as a reduced incidence of POD among patients older than 70 years. The duration of ICU and hospital stay was markedly shorter in the intervention group than in the control group.

Various factors contribute to the development of POD, such as advancing age, preoperative comorbid conditions, frailty, and surgical type [31–33]. Some studies showed that cerebral oxygen saturation could be affected by adjusting physiological variables such as cardiac output, inhaled oxygen concentration, optimization of mechanical ventilation strategy, vasopressor delivery, temperature and hemoglobin concentration [15, 23, 34, 35]; NIRS-guided optimization improved systemic perfusion and protected vital organs [17, 36, 37]. In our investigation, the incidences of POD patients undergoing off-pump CABG surgery were evaluated in 200 patients of whom 38 (19.0%) were diagnosed positive. There was no difference in the incidence of POD between the intervention group and control group. A meta-analysis suggested that intraoperative intervention guided by cerebral oximetry monitoring was associated with reduced risk of POD (OR 0.28, P = 0.02; I² = 81%) in adults undergoing cardiac surgery [30]. This might be attributable to the inclusion of both off-pump and on-pump cardiac surgery populations in this meta-analysis. One study combined rSO₂ monitoring with processed electroencephalography, which complicated the explanation. Although several isolated reports suggested a positive correlation between reduced intraoperative rSO₂ values and postoperative neurological injury, the data is insufficient to draw the conclusion that improved rSO₂ could prevent neurocognitive deterioration [3, 38]. The absence of a significant reduction in POD with cerebral oximetry-guided intervention was most plausibly attributable to the lower-than-expected POD incidence in the control group (24% observed vs. 30% assumed in the sample-size calculation). This discrepancy reduced the study’s statistical power and increased the risk of a type II error. Consequently, future adequately powered trials with larger sample sizes are warranted to confirm the potential benefit of cerebral oximetry-guided anaesthesia.

POD, a common postoperative complication in hospitalized elderly patients, is an acute and fluctuating disturbance of attention, consciousness, perception, or cognition that typically emerges on postoperative day 1 and can persist for up to one week [2, 6, 39]. The shorter desaturation burden and higher bilateral minimum rSO₂ values observed in our intervention group were accompanied by a significant delay in POD onset, plausibly reflecting diminished ischaemic injury and attenuated postoperative organ dysfunction. The results of this study are consistent with a previous report that cerebral oximetry index-guided blood pressure management during CPB reduced the severity of POD after acute type-A aortic dissection repair [40].

Age is a well-established risk factor for POD, with the risk rising substantially in individuals over 65 years old [41, 42]. The average age of the population was 70.2 years (ranging from 65 to 86 years). Post-hoc exploratory subgroup analysis revealed cerebral oximetry-guided management was associated with reduced incidence of POD among patients aged > 70 years, though this finding should be interpreted with caution given the risk of type I error from multiple comparisons. The age-related differences observed in our study were in accordance with the commonly acknowledged cognitive alterations associated with aging. Advanced age was characterized by progressive decline in cerebral autoregulation and cognitive reserve, which increases susceptibility to perioperative cerebral hypoxia and subsequent cognitive complications [39, 43]. Liu et al. have demonstrated that brain aging was a complex and nonlinear process, marked by abrupt functional declines at specific age milestones [44]. This decline was strongly associated with impairments in cognitive and motor functions, as well as structural abnormalities in the brain, including cortical and subcortical regions. The subgroup of patients aged > 70 years might have benefited from cerebral oximetry monitoring, which enabled more precise anesthetic adjustments to maintain optimal balance between cerebral oxygenation and ischemia, preventing oxygen supply compromise and brain dysfunction associated with ischemia-reperfusion injury. Exploring the pathogenesis and prevention of POD in elderly patients would be clinically significant for preventing neurocognitive disorders and promoting recovery.

This study is subject to several limitations. First, only elderly patients undergoing off-pump CABG at our single centre were enrolled in this trial, which may limit the generalisability of the study. Second, the single-blind design was an inherent limitation: anesthesiologists, who were responsible for patient management, could not be masked to group allocation and might have introduced performance bias through intraoperative interventions. These potential biases should be considered when interpreting the results. Third, the primary analysis was based on a relatively low incidence of POD, which may have reduced the statistical power to detect significant differences in the overall cohort. The potential for this approach to improve outcomes in high-risk patients with cognitive impairment remains to be evaluated in randomized controlled trials. Fourth, due to intraoperative hemodynamic fluctuations, this study exclusively focused on the effect of intraoperative anaesthesia guided by cerebral oximetry on POD, and did not evaluate the impact of long-term cognitive impairment. Other projects of our research group are currently conducting investigations on the related factors of long-term postoperative cognitive dysfunction. Fifth, POD was screened once on postoperative day 1 and twice daily from postoperative days 2 to 7; this schedule may have underestimated the true incidence, particularly of hypoactive or rapidly fluctuating episodes. To minimise the influence of postoperative pain, both groups received identical analgesic regimens. Finally, cerebral oximetry-guided anaesthesia did not reduce POD, and no formal cost-effectiveness analysis was performed. The modest reduction in ICU and hospital length of stay observed in the present study might suggest potential savings in direct medical costs. Future trials should incorporate a dedicated economic evaluation that includes the societal burden attributable to long-term cognitive decline.

In conclusion, cerebral oximetry-guided anaesthesia did not significantly reduce POD in patients aged ≥ 65 years undergoing off-pump CABG. The observed reduction in those > 70 years is hypothesis-generating; nevertheless, the study was underpowered and the evidence remains inconclusive. Larger, adequately powered trials are needed to determine whether intraoperative cerebral oxygen optimisation decreases POD in elderly cardiac surgical patients.

Authors’ contributions

Concept and design: LJT HBW, and SY.Drafting of the manuscript: LJT, YJ, and SY.conducted the study: LJT and JFG.Statistical analysis: JCS and HBW.Acquisition, analysis, or interpretation of data: JFG, YJ, WZ, and HYZ.Obtained funding: LJT.All authors were involved in drafting and revision of intellectual content in the manuscript and approved the final version to be published.

Funding

This work was supported by the National High-Level Hospital Clinical Research Funding (2022 GSP-QN-16).

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable requirements.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences (approval No. 2022 − 1824), and registered with the Chinese Clinical Trial Registry (ChiCTR2300068537) on 22 February 2023. Written informed consents were obtained from each patient or their legal representatives before enrolment.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.