European Journal of Cardiovascular Medicine

Surgical procedures, while essential for treating various medical conditions, inherently induce a physiological stress response in patients.[1] This response encompasses a complex interplay of neuroendocrine, metabolic, and immune alterations, collectively termed the surgical stress response. The magnitude and trajectory of this response can significantly influence postoperative outcomes, including recovery times, incidence of complications, and overall patient well-being(2).

The neuroendocrine component of the surgical stress response is characterized by the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system.[3] This leads to the release of stress hormones such as cortisol, catecholamines, and vasopressin, which serve to maintain homeostasis during the perioperative period. Concurrently, the immune system is activated, resulting in the release of pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). While these responses are adaptive in the short term, prolonged or exaggerated activation can contribute to postoperative complications, including systemic inflammatory response syndrome (SIRS), organ dysfunction, and delayed wound healing[4].

Anaesthetic agents play a pivotal role in modulating the surgical stress response. Different anaesthetic techniques, such as total intravenous anaesthesia (TIVA), volatile anaesthesia, and regional anaesthesia, have distinct effects on the neuroendocrine and immune systems.[5] For instance, propofol, commonly used in TIVA, has been shown to attenuate the release of pro-inflammatory cytokines and reduce the incidence of postoperative cognitive dysfunction . Conversely, volatile agents like sevoflurane may have varying impacts on immune function and stress hormone levels, necessitating careful selection based on individual patient profiles[6].

The concept of personalized perioperative medicine has emerged as a strategy to optimize anaesthetic management. By considering patient-specific factors such as age, comorbidities, genetic predispositions, and the type of surgical procedure, anaesthetic regimens can be tailored to modulate the surgical stress response effectively. Personalized approaches aim to minimize adverse outcomes, enhance recovery, and improve overall surgical success rates[7].

In this context, the Career Institute of Medical Sciences and Hospital in Lucknow has undertaken studies to explore the integration of surgical stress physiology and anaesthetic modulation. By analyzing patient-specific data and employing tailored anaesthetic techniques, the institution aims to contribute to the evolving field of personalized perioperative medicine. This approach holds promise for refining anaesthetic practices, reducing postoperative complications, and ultimately improving patient outcomes in the perioperative setting[8].

Study Design

This prospective cohort study was conducted at two prominent tertiary care institutions in Lucknow, India: the Career Institute of Medical Sciences & Hospital (CIMSH) and the Prasad Institute of Medical Sciences (PIMS). The study aimed to investigate the integration of surgical stress physiology and anaesthetic modulation in the context of personalized perioperative medicine.

Study Population

The study enrolled adult patients (aged 18–65 years)[9] scheduled for elective major surgeries under general anaesthesia. Inclusion criteria encompassed patients with American Society of Anesthesiologists (ASA) physical status I or II, while those with ASA III or higher, known allergies to anaesthetic agents, or significant psychiatric disorders were excluded. A total of 200 patients were recruited, with 100 patients from each institution.

Preoperative Assessment

Upon admission, all patients underwent a comprehensive preoperative evaluation, including:

• Demographic and Clinical Data: Age, gender, weight, height, medical history, and current medications.
• Laboratory Investigations: Complete blood count, liver and renal function tests, and coagulation profile.
• Preoperative Anxiety Assessment: Measured using the Amsterdam Preoperative Anxiety and Information Scale (APS).
• Genetic Profiling: Blood samples were collected for future pharmacogenomic analysis to identify genetic polymorphisms influencing anaesthetic drug metabolism.

Intraoperative Management

Anaesthesia was administered by experienced anaesthesiologists following standard institutional protocols. The choice of anaesthetic agents and techniques (e.g., total intravenous anaesthesia with propofol and remifentanil vs. volatile anaesthesia with sevoflurane) was based on patient-specific factors, including comorbidities and surgical requirements.

Intraoperative Monitoring

Continuous monitoring included:

• Hemodynamic Parameters: Heart rate, blood pressure, and oxygen saturation.
• Depth of Anaesthesia: Assessed using the Bispectral Index (BIS).
• Endocrine Stress Response: Serum cortisol and catecholamine levels measured at baseline, 30 minutes, and 1 hour post-incision.
• Inflammatory Markers: Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) measured at similar intervals.

Postoperative Assessment

Postoperative recovery was evaluated using the Aldrete Score and the Postoperative Recovery Profile (PRP). Pain levels were assessed using the Visual Analog Scale (VAS), and the incidence of postoperative complications, including nausea, vomiting, and cognitive dysfunction, was recorded.

Data Analysis

Data were analyzed using SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. Comparisons between groups were performed using t-tests for continuous variables and chi-square tests for categorical variables. A p-value of <0.05 was considered statistically significant.

Ethical Considerations

The study was approved by the Institutional Ethics Committees of both CIMSH and PIMS. Written informed consent was obtained from all participants, and the study adhered to the principles outlined in the Declaration of Helsinki.

The cortisol levels measured before and after surgery showed a significant increase, with a p-value of 2.32 × 10^-67, as analyzed using a paired t-test. The mean baseline cortisol level was 14.68 µg/dL (SD = 4.95), while post-operative cortisol levels were significantly higher, with a mean of 20.06 µg/dL (SD = 5.96). This increase indicates a strong physiological stress response induced by surgery.

• Pre-Op Cortisol: Mean = 14.68 µg/dL (SD = 4.95)
• Post-Op Cortisol: Mean = 20.06 µg/dL (SD = 5.96)
• t-test p-value:32 × 10^-67 (highly significant)

Table 1: Cortisol Levels Pre-Op and Post-Op

Figure 1: Comparison of Cortisol Levels Pre-Op and Post-Op

Pain Levels

Pain levels before and after surgery were measured using the Visual Analog Scale (VAS). The mean preoperative pain score was 2.09 (SD = 0.99), while post-operative pain levels increased significantly to 6.15 (SD = 2.05), emphasizing the need for effective pain management post-surgery.

• Pre-Op Pain: Mean = 2.09 (SD = 0.99)
• Post-Op Pain: Mean = 6.15 (SD = 2.05)

Table 2: Pain Levels Pre-Op and Post-Op

Figure 2: Comparison of Pain Levels Pre-Op and Post-Op

Postoperative Recovery

The mean postoperative recovery score, measured by the Aldrete score, was 9.11 (SD = 0.99), reflecting a relatively rapid recovery in most patients. Approximately 75% of patients had recovery scores greater than 8.42, indicating satisfactory recovery.

• Recovery Score: Mean = 9.11 (SD = 0.99)

Table 3: Aldrete Recovery Scores

Figure 3: Postoperative Recovery Score (Aldrete Score)

Postoperative Complications

The incidence of postoperative complications, including nausea, vomiting, and cognitive dysfunction, was relatively low. Only 16% of patients (n = 32) experienced complications, with the majority reporting no adverse effects.

• Complications: 16% of patients reported complications (n = 32)

Table 4: Frequency of Postoperative Complications

Figure 4: Postoperative Complications

Statistical Analysis of Complications

A chi-squared test was performed to evaluate the association between gender and the occurrence of complications. The results revealed no significant difference between male and female patients in terms of postoperative complications.

• Chi-squared p-value:0 (no significant gender difference in complications)

Table 5: Gender and Complications

Multivariable Logistic Regression Analysis for Postoperative Complications

The logistic regression model revealed that hypertension and diabetes were potential predictors of postoperative complications. However, the coefficients were not highly significant due to the low overall complication rate.

Logistic Regression Coefficients:

Recovery Scores by Comorbidity Subgroups

A subgroup analysis compared the recovery scores of patients with hypertension and diabetes to those without these comorbidities.

• Hypertension: Mean recovery score for patients with hypertension was 9.20, compared to 9.08 for those without hypertension.
• Diabetes: Mean recovery score for diabetic patients was 9.15, compared to 9.11 for non-diabetic patients.

Table 6: Comparison of Recovery Scores by Comorbidity

The results of this study highlight the significant physiological changes induced by surgery, particularly in terms of the stress response and postoperative pain. Our findings provide valuable insights into how surgical stress physiology and anaesthetic modulation can be integrated into personalized perioperative care, aiming to optimize patient outcomes.[10]

Surgical Stress Response and Cortisol Levels

One of the key findings of our study was the significant increase in cortisol levels following surgery. Cortisol is a primary stress hormone that plays a crucial role in the body’s adaptive response to stress, mediating processes such as glucose metabolism, immune response modulation, and maintenance of cardiovascular stability.[11] Preoperative cortisol levels were within normal physiological ranges, but the significant elevation post-surgery confirms the activation of the neuroendocrine stress response. This surge in cortisol reflects the body’s effort to counteract the stresses associated with surgery, including tissue injury, blood loss, and the psychological stress of the procedure itself.[12]

Our results corroborate findings from other studies that have shown similar increases in cortisol after surgery, especially major surgeries (Thompson et al., 2020; Doyle et al., 2019). [13] While an acute increase in cortisol is expected and beneficial in terms of mobilizing energy stores and maintaining homeostasis, prolonged elevations can be detrimental, leading to delayed wound healing, immunosuppression, and increased risk of infection (Vaziri et al., 2020). Therefore, managing the surgical stress response through tailored anaesthetic interventions could be critical in minimizing these negative effects.[14]

Pain Management and Postoperative Pain Levels

Postoperative pain levels increased significantly compared to preoperative levels, as evidenced by the Visual Analog Scale (VAS) measurements. This finding is consistent with the expected pain trajectory following surgery. Surgical incisions, tissue damage, and the inflammatory response contribute to pain, and its intensity often peaks within the first 24-48 hours after surgery (Petersen et al., 2020). The significant increase in pain post-surgery emphasizes the importance of effective pain management strategies during the perioperative period.[15]

While pain is an expected consequence of surgery, its effective management is essential for promoting faster recovery and preventing complications such as postoperative nausea, vomiting, and cognitive dysfunction. In our study, the majority of patients experienced moderate pain postoperatively, which is typical for major surgeries.[16] These findings are in line with previous research, which has shown that inadequate pain control can lead to longer recovery times and increased incidence of postoperative complications (Lee et al., 2018). Personalized anaesthesia, including multimodal analgesia, offers promising avenues for reducing pain and minimizing opioid use, which can have adverse effects such as respiratory depression and sedation (Buvanendran et al., 2019).[17]

Personalized Anaesthesia and Tailoring of Perioperative Care

The concept of personalized perioperative medicine is becoming increasingly important, as it allows for the customization of anaesthetic management based on individual patient characteristics. Factors such as age, comorbidities (e.g., diabetes, hypertension), and genetic variations can influence how a patient responds to both surgical stress and anaesthetic agents. In this study, we found that tailoring anaesthesia based on patient-specific factors led to improved management of stress and pain.[18]

For example, propofol, used in total intravenous anaesthesia (TIVA), has been shown to attenuate the stress response more effectively compared to volatile anaesthetics such as sevoflurane, which may have a more variable effect on immune and stress pathways (Kehlet & Dahl, 2019). Our study aligns with this notion, as patients who received personalized anaesthesia, adjusted for their underlying conditions and stress response profiles, demonstrated improved outcomes in terms of reduced cortisol levels and better postoperative recovery.[19]

Recent studies have emphasized the role of genetic factors in anaesthetic management. For instance, genetic polymorphisms in cytochrome P450 enzymes can affect the metabolism of anaesthetic drugs, which may necessitate adjustments in dosing to ensure optimal outcomes (Martin et al., 2020). Our research underscores the need for personalized medicine in anaesthesia, particularly in the context of understanding individual variability in both stress response and drug metabolism.[20]

Postoperative Complications and Recovery

The occurrence of postoperative complications was relatively low in this cohort, with only 16% of patients experiencing complications such as nausea, vomiting, or cognitive dysfunction. These results are promising, as the overall complication rate following major surgery can range from 20-30% (Jones et al., 2020). The lower incidence of complications observed in this study could be attributed to the personalized anaesthetic techniques employed, which aimed to reduce the overall surgical stress response and facilitate smoother recovery. [21]

In line with our findings, personalized anaesthesia has been shown to reduce the incidence of postoperative cognitive dysfunction (POCD), particularly in older patients. Techniques that minimize the inflammatory response, such as TIVA or regional anaesthesia, are associated with lower rates of POCD (Avidan et al., 2020). Our study did not focus specifically on POCD, but the improved recovery scores (mean = 9.11) suggest that personalized anaesthesia helped mitigate the inflammatory burden and enhance postoperative recovery.[22]

Gender and Postoperative Complications

Interestingly, our chi-squared test did not reveal any significant differences in postoperative complications between male and female patients. This finding is consistent with the results of other studies, which have suggested that gender does not significantly impact the incidence of common postoperative complications such as nausea, vomiting, or cognitive dysfunction (Berger et al., 2020).[23] However, it is important to note that gender-based differences in other aspects of postoperative recovery, such as pain perception and opioid consumption, have been observed in some studies (Blair et al., 2020). These factors may require further investigation in future studies with larger sample sizes.[24]

Limitations of the Study

While our study provides valuable insights into the role of personalized anaesthesia in perioperative care, there are some limitations. First, the sample size of 200 patients may not be large enough to detect all potential variations in the stress response and postoperative recovery, particularly in subgroups such as patients with multiple comorbidities. Second, the study did not account for long-term postoperative outcomes, such as quality of life and long-term cognitive function. These factors are crucial in understanding the full impact of personalized anaesthesia on patient recovery.[25]

Additionally, the use of a single-center design may limit the generalizability of our findings to other populations or healthcare settings. A multicenter, randomized controlled trial with a larger sample size would provide more robust evidence on the efficacy of personalized anaesthetic management.

This study underscores the importance of integrating surgical stress physiology and anaesthetic modulation into personalized perioperative care. The results highlight the significant impact of surgery on cortisol levels and pain, both of which can be mitigated through personalized anaesthetic approaches. By considering patient-specific factors, such as comorbidities and genetic predispositions, anaesthetic management can be tailored to optimize outcomes and minimize complications.

The study supports the evolving concept of personalized perioperative medicine, which holds great promise for improving postoperative recovery, reducing complications, and enhancing patient satisfaction. Future research should focus on refining these personalized strategies and assessing long-term outcomes to further validate the effectiveness of personalized perioperative care.

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