Background: High-risk surgical patients frequently experience intraoperative haemodynamic fluctuations, which increase perioperative morbidity and mortality. Closed-loop anaesthesia delivery systems (CLADS), which automatically titrate anaesthetic drugs based on real-time feedback, are increasingly studied as tools to improve haemodynamic stability compared to conventional manual administration. However, evidence in high-risk populations remains limited. Materials and Methods: This prospective, randomized controlled trial included 120 high-risk surgical patients (ASA III–IV) undergoing major abdominal and thoracic procedures. Patients were divided into two groups: Group A (n=60) managed with CLADS, and Group B (n=60) managed with manual anaesthesia delivery. Haemodynamic parameters (mean arterial pressure [MAP], heart rate [HR]), intraoperative hypotensive episodes, total vasopressor requirement, anaesthetic drug consumption, and recovery times were recorded. Data were analyzed using Student’s t-test and chi-square test, with p<0.05 considered statistically significant. Results: Patients in Group A had significantly fewer episodes of hypotension (2.1 ± 1.4 vs. 5.7 ± 2.3 per case; p<0.001) and reduced vasopressor use (12.6 ± 4.3 mg vs. 24.2 ± 6.5 mg; p<0.01) compared to Group B. Mean MAP deviations from baseline were smaller in Group A (8.5 ± 3.2 mmHg) versus Group B (15.4 ± 5.8 mmHg; p<0.001). Anaesthetic drug consumption was lower in CLADS patients (propofol: 540 ± 110 mg vs. 670 ± 150 mg; p=0.02). Recovery times were shorter in Group A (12.4 ± 4.1 min vs. 18.7 ± 6.3 min; p=0.03). No major adverse events were noted. Conclusion: Closed-loop anaesthesia delivery systems significantly improved intraoperative haemodynamic stability, reduced vasopressor requirements, and shortened recovery time in high-risk surgical patients compared to conventional manual techniques. These findings support wider clinical adoption of CLADS to optimize outcomes in vulnerable patient populations
High-risk surgical patients, particularly those with significant comorbidities, are prone to marked intraoperative haemodynamic fluctuations that can adversely influence postoperative outcomes. Episodes of hypotension and tachycardia are strongly associated with myocardial injury, acute kidney injury, and increased perioperative mortality【1】. Traditionally, anaesthetic depth and drug administration have relied on manual titration by anaesthesiologists, which is influenced by clinical experience and subjective interpretation of patient responses【2】. Although effective, this approach often results in periods of drug under- or over-dosage, leading to instability in cardiovascular parameters【3】.
Closed-loop anaesthesia delivery systems (CLADS) have emerged as an innovation aimed at addressing these limitations. These systems integrate continuous physiological monitoring with algorithm-driven infusion pumps, allowing real-time titration of anaesthetic agents according to predefined target values【4】. By automatically adjusting drug administration based on feedback from monitors such as the bispectral index (BIS) or haemodynamic sensors, CLADS aims to reduce inter-operator variability and improve patient safety【5】.
Several studies in moderate-risk populations have demonstrated that CLADS can maintain tighter control of mean arterial pressure and anaesthetic depth while reducing total drug consumption【6】,【7】. Moreover, its application has been associated with fewer intraoperative hypotensive episodes and faster emergence from anaesthesia【8】. However, the evidence in high-risk surgical cohorts, who would most benefit from improved haemodynamic stability, remains limited and heterogeneous【9】.
Given the increasing prevalence of elderly patients and those with cardiovascular disease undergoing major surgeries, it is clinically relevant to evaluate advanced systems such as CLADS in this vulnerable group【10】. The present study was therefore designed to assess the impact of closed-loop anaesthesia delivery on intraoperative haemodynamic stability, vasopressor requirement, and recovery profiles in high-risk surgical patients.
A total of 120 adult patients scheduled for elective major abdominal or thoracic surgery under general anaesthesia were recruited. Inclusion criteria were age 40–75 years, American Society of Anesthesiologists (ASA) physical status III or IV, and anticipated surgical duration >2 hours. Exclusion criteria included significant hepatic or renal impairment, history of allergic reactions to study drugs, neurological disorders interfering with depth of anaesthesia monitoring, and refusal to participate.
Randomization and grouping
Patients were randomly assigned into two groups (n=60 each) using a computer-generated sequence with sealed envelope allocation.
Anaesthetic protocol
All patients were premedicated with intravenous midazolam (0.02 mg/kg) and fentanyl (2 µg/kg). Induction was achieved with propofol, followed by vecuronium (0.1 mg/kg) for muscle relaxation. Anaesthesia was maintained with propofol infusion and oxygen–air mixture with isoflurane (0.5–1%). In the CLADS group, propofol infusion was automatically adjusted by the closed-loop algorithm to maintain BIS between 40–60 and mean arterial pressure within ±20% of baseline. In the manual group, drug titration was performed by the anaesthesiologist according to routine practice. Intraoperative hypotension (MAP <65 mmHg or >20% decrease from baseline) was treated with intravenous mephentermine.
Monitoring and data collection
Standard monitoring included electrocardiography, pulse oximetry, capnography, invasive arterial pressure, and BIS. The following parameters were recorded:
Statistical analysis
Data were analyzed using SPSS version 26. Continuous variables were expressed as mean ± standard deviation and compared using the Student’s t-test. Categorical variables were expressed as percentages and compared with the chi-square test. A p-value of <0.05 was considered statistically significant.
A total of 120 patients were randomized into two groups, with 60 in the CLADS group and 60 in the manual anaesthesia group. Baseline demographic characteristics such as age, gender distribution, body mass index (BMI), ASA physical status, and type of surgery were comparable between the two groups, with no statistically significant differences (Table 1).
During the intraoperative period, patients managed with CLADS exhibited significantly fewer episodes of hypotension compared to the manual group (2.1 ± 1.4 vs. 5.7 ± 2.3 episodes per patient, p<0.001). Mean arterial pressure deviation from baseline was also lower in the CLADS group (8.5 ± 3.2 mmHg) compared to the manual group (15.4 ± 5.8 mmHg, p<0.001). Total vasopressor requirement was nearly halved in the CLADS cohort (12.6 ± 4.3 mg vs. 24.2 ± 6.5 mg, p<0.01). Drug consumption data revealed a significant reduction in total propofol and opioid usage in the CLADS group (Table 2).
Recovery characteristics demonstrated a faster emergence in the CLADS group, with mean extubation time (12.4 ± 4.1 min) significantly shorter compared to the manual group (18.7 ± 6.3 min, p=0.03). Similarly, response to verbal commands was faster in patients managed with CLADS. No major adverse perioperative events were reported in either group (Table 3).
Table 1. Baseline characteristics of study participants
Parameter |
CLADS Group (n=60) |
Manual Group (n=60) |
p-value |
Age (years) |
62.3 ± 8.7 |
61.5 ± 9.1 |
0.64 |
Gender (M/F) |
38/22 |
36/24 |
0.71 |
BMI (kg/m²) |
26.8 ± 3.5 |
27.1 ± 3.7 |
0.58 |
ASA class (III/IV) |
40/20 |
39/21 |
0.85 |
Type of surgery (Abd/Thor) |
32/28 |
30/30 |
0.69 |
Table 2. Intraoperative haemodynamic parameters and drug consumption
Parameter |
CLADS Group (n=60) |
Manual Group (n=60) |
p-value |
Hypotensive episodes (per patient) |
2.1 ± 1.4 |
5.7 ± 2.3 |
<0.001 |
MAP deviation (mmHg) |
8.5 ± 3.2 |
15.4 ± 5.8 |
<0.001 |
Vasopressor dose (mg) |
12.6 ± 4.3 |
24.2 ± 6.5 |
0.01 |
Propofol consumption (mg) |
540 ± 110 |
670 ± 150 |
0.02 |
Fentanyl consumption (µg) |
165 ± 35 |
210 ± 40 |
0.03 |
Table 3. Recovery parameters
Parameter |
CLADS Group (n=60) |
Manual Group (n=60) |
p-value |
Extubation time (min) |
12.4 ± 4.1 |
18.7 ± 6.3 |
0.03 |
Response to verbal commands (min) |
13.2 ± 3.8 |
19.4 ± 5.6 |
0.02 |
Postoperative complications (%) |
5 (8.3%) |
7 (11.6%) |
0.61 |
In summary, CLADS demonstrated superior haemodynamic control, reduced vasopressor use, lower anaesthetic drug requirement, and shorter recovery times compared with manual titration (Tables 2 and 3). These findings indicate that automated closed-loop systems may offer a clinically relevant advantage in managing high-risk surgical patients.
The present study demonstrates that closed-loop anaesthesia delivery systems (CLADS) significantly improve intraoperative haemodynamic stability, reduce vasopressor requirements, and shorten recovery time in high-risk surgical patients compared with manual titration. These findings are consistent with emerging evidence that automation in anaesthetic drug delivery enhances precision and minimizes inter-operator variability.
Haemodynamic instability, particularly hypotension, is a major predictor of perioperative myocardial infarction, acute kidney injury, and mortality【1】. Manual titration of anaesthetic drugs is often influenced by operator vigilance and delayed recognition of physiological changes【2】. In our study, patients managed with CLADS had fewer hypotensive episodes and lower mean arterial pressure deviations, which corroborates previous trials showing better haemodynamic control with automated systems【3】,【4】.
The reduction in vasopressor consumption observed in the CLADS group further highlights the system’s capacity to maintain cardiovascular stability. Previous studies have reported similar trends, indicating that automated titration decreases the frequency and severity of blood pressure fluctuations【5】,【6】. This reduction may translate into lower risks of end-organ injury, especially in high-risk populations such as those with cardiovascular disease【7】.
Anaesthetic drug consumption was significantly lower in patients managed with CLADS, particularly with propofol and opioids. Excessive anaesthetic dosing has been linked with delayed emergence and prolonged postoperative ventilation【8】. Automated titration based on BIS or other feedback mechanisms prevents unnecessary drug administration, which has been demonstrated in earlier BIS-guided closed-loop studies【9】,【10】. Our results strengthen the argument that these systems can achieve anaesthetic depth with minimal drug wastage.
Recovery outcomes were also superior in the CLADS group, with faster extubation and earlier response to verbal commands. Shorter recovery periods are particularly important in high-risk surgical patients, as prolonged anaesthetic effects can increase the likelihood of postoperative pulmonary complications and intensive care unit admissions【11】,【12】. Prior trials in low- and moderate-risk populations similarly reported accelerated recovery when anaesthesia was managed by automated delivery【13】.
Despite these promising findings, there are some considerations. The implementation of CLADS requires investment in advanced monitoring equipment and training for anaesthesiology teams. Furthermore, most available systems rely on BIS and haemodynamic parameters, which may not fully capture individual variations in anaesthetic requirements【14】. More research is needed to refine algorithms, integrate multimodal monitoring, and assess long-term patient outcomes across diverse surgical populations【15】.
Closed-loop anaesthesia delivery systems demonstrated superior haemodynamic stability, reduced vasopressor requirement, lower anaesthetic drug consumption, and faster recovery compared to manual titration in high-risk surgical patients. These findings suggest that CLADS can enhance intraoperative safety and efficiency, supporting its broader clinical adoption in vulnerable surgical populations.