European Journal of Cardiovascular Medicine

Postoperative recovery following major abdominal surgeries presents a critical phase in patient care, where pain control, hemodynamic stability, and early mobilization significantly influence clinical outcomes. Traditionally, opioids have been a mainstay of intraoperative and postoperative analgesia due to their potent analgesic effects.^1,2 However, their use is increasingly scrutinized owing to a growing body of evidence highlighting a range of adverse effects, including respiratory depression, postoperative nausea and vomiting (PONV), ileus, sedation, opioid-induced hyperalgesia, and potential for dependence.^3,4

The global opioid crisis has further intensified efforts to explore alternative analgesic strategies that reduce or eliminate the use of opioids without compromising patient comfort or surgical outcomes. This evolving approach has led to the development and clinical implementation of opioid-free anesthesia (OFA)—a multimodal analgesic technique that leverages non-opioid pharmacologic agents and regional anesthesia to achieve adequate pain control while mitigating opioid-related side effects.^5,6

OFA typically employs agents such as ketamine, lidocaine, dexmedetomidine, magnesium sulfate, and non-steroidal anti-inflammatory drugs (NSAIDs), either alone or in combination. These agents act on various pain pathways, aiming to provide balanced anesthesia and promote enhanced recovery after surgery (ERAS).^7,8  Several studies have demonstrated that OFA may be associated with improved postoperative outcomes, including reduced incidence of PONV, shorter duration of postoperative ileus, early ambulation, and shorter hospital stays. However, data remain limited and often heterogeneous, particularly in the context of major abdominal surgeries where the nociceptive stimulus is significant and the need for effective analgesia is paramount.^9-11

In India, and particularly in tertiary care settings such as the Career Institute of Medical Sciences and Hospital, Lucknow, the shift toward opioid-sparing or opioid-free anesthetic techniques is still in its early phases. Regional experiences and evidence are essential to validate the feasibility, safety, and efficacy of OFA protocols within local clinical practices and patient populations. Given the unique demographic, clinical, and resource considerations in this region, evaluating the impact of OFA on postoperative recovery could have significant implications for perioperative care standards.

This study aims to investigate the effect of opioid-free anesthesia on postoperative recovery in patients undergoing major abdominal surgeries, with a focus on parameters such as postoperative pain scores, time to first mobilization, incidence of PONV, duration of hospital stay, and overall patient satisfaction. By providing context-specific evidence, the study endeavors to contribute to the growing discourse on optimizing perioperative care through opioid-free approaches in surgical anesthesia.

Study Design and Setting

This prospective, comparative, observational study was conducted in the Department of Anesthesiology at the Career Institute of Medical Sciences and Hospital, Lucknow, over a period of 6 months. The study was approved by the Institutional Ethics Committee (IEC), and informed written consent was obtained from all participants prior to enrollment.

Sample Size and Study Population

A total of 80 adult patients undergoing elective major abdominal surgeries under general anesthesia were enrolled and randomly allocated into two equal groups (n=40 per group):

• Group A (OFA Group): Patients who received opioid-free anesthesia.
• Group B (OA Group): Patients who received conventional opioid-based anesthesia.

The sample size was determined based on previous studies that observed significant differences in postoperative pain scores and recovery parameters between OFA and OA groups, with a power of 80% and alpha error of 5%.

Inclusion Criteria

• Adult patients aged 18 to 65 years.
• American Society of Anesthesiologists (ASA) physical status I–III.
• Scheduled for elective major abdominal surgeries (e.g., bowel resections, hepato-pancreato-biliary procedures, exploratory laparotomy).
• Ability to provide informed consent.

Exclusion Criteria

• Emergency surgeries.
• Chronic opioid use or substance abuse.
• Known allergies to study medications.
• Pregnant or lactating women.
• Severe hepatic, renal, or cardiac impairment.
• Psychiatric illness or inability to communicate pain effectively.

Preoperative Evaluation

All participants underwent thorough pre-anesthetic assessment including detailed history, physical examination, and baseline investigations. Standard fasting guidelines were followed. No premedication was administered on the morning of surgery other than prescribed routine medications.

Anesthetic Technique

Group A (Opioid-Free Anesthesia - OFA):

• Induction: IV administration of ketamine (0.5 mg/kg), lidocaine (1.5 mg/kg), dexmedetomidine (0.5 mcg/kg over 10 min), and propofol (2 mg/kg). Rocuronium (0.6 mg/kg) was used to facilitate intubation.
• Maintenance: Sevoflurane with air-oxygen mixture, IV infusions of dexmedetomidine (0.2–0.7 mcg/kg/hr) and lidocaine (1–2 mg/kg/hr). Ketamine boluses (0.25 mg/kg) were repeated as needed.
• Analgesia adjuncts: Paracetamol 1g IV every 6 hours, and magnesium sulfate 30 mg/kg (loading), followed by 10 mg/kg/hr.

Group B (Opioid-Based Anesthesia - OA):

• Induction: IV fentanyl (2 mcg/kg), propofol (2 mg/kg), and rocuronium (0.6 mg/kg).
• Maintenance: Sevoflurane in oxygen-air mixture, with repeat boluses of fentanyl (0.5–1 mcg/kg every 30–45 minutes) as required.
• Analgesia: IV paracetamol and additional opioids for breakthrough pain.

Standard intraoperative monitoring included ECG, non-invasive blood pressure, pulse oximetry, end-tidal CO₂, temperature, and BIS monitoring to maintain adequate depth of anesthesia.

Postoperative Care and Monitoring

Postoperatively, all patients were monitored in the PACU and then transferred to the surgical ward. Pain was assessed using the Visual Analog Scale (VAS) at 2, 6, 12, and 24 hours. Tramadol (1 mg/kg IV) was used as rescue analgesia if VAS >4.

Outcome Measures

Primary Outcome:

• Postoperative pain scores (VAS) at 2, 6, 12, and 24 hours.

Secondary Outcomes:

• Incidence of postoperative nausea and vomiting (PONV).
• Time to first mobilization (in hours).
• Time to return of bowel function (passage of flatus/stool).
• Length of hospital stay (in days).
• Total rescue analgesic requirement.
• Patient satisfaction (1–5 scale).

Statistical Analysis

Data were compiled using Microsoft Excel and analyzed with SPSS version 25. Quantitative variables were presented as mean ± standard deviation (SD) and analyzed using unpaired Student’s t-test. Categorical variables were expressed as percentages and compared using the Chi-square or Fisher’s exact test. A p-value <0.05 was considered statistically significant

The baseline demographic and clinical characteristics of patients in both groups were comparable, ensuring that differences in outcomes could be attributed to the anesthetic approach rather than patient-related confounders. As presented in Table 1, the mean age was 45.2 ± 12.3 years in the OFA group and 46.8 ± 11.9 years in the OA group (p = 0.54), while the gender distribution was nearly equal with 22 males and 18 females in the OFA group versus 20 males and 20 females in the OA group (p = 0.83). BMI was similar between groups (24.5 ± 3.8 vs. 25.1 ± 4.0; p = 0.47). ASA physical status also showed no significant difference (I/II/III: 12/20/8 in OFA vs. 10/22/8 in OA; p = 0.92). The types of surgeries performed—bowel resections, hepato-pancreato-biliary procedures, and exploratory laparotomies—were evenly distributed (p = 0.78). Additionally, comorbid conditions such as hypertension (10 vs. 12; p = 0.80), diabetes mellitus (8 vs. 7; p = 0.78), and others (5 vs. 6; p = 0.75) were balanced across groups, establishing a uniform baseline.

Table 1: Demographic and Baseline Characteristics of Study Participants

Intraoperative anesthetic management details, summarized in Table 2, confirm adherence to the respective protocols for both groups. The duration of surgery was similar between groups (OFA: 142.5 ± 35.6 min vs. OA: 138.9 ± 34.2 min; p = 0.62), and the use of propofol was consistent (140.8 ± 30.2 mg in OFA vs. 138.4 ± 29.8 mg in OA; p = 0.78). The OFA group received a combination of ketamine (35.2 ± 8.4 mg), lidocaine (105.6 ± 20.1 mg), and dexmedetomidine (35.0 ± 7.2 mcg) for induction, while the OA group received fentanyl (140.5 ± 25.3 mcg). Maintenance in the OFA group included dexmedetomidine and lidocaine infusions (0.45 ± 0.15 mcg/kg/hr and 1.5 ± 0.4 mg/kg/hr, respectively), while the OA group required additional fentanyl boluses totaling 75.2 ± 20.1 mcg. Sevoflurane consumption was comparable (1.1 ± 0.2 MAC in OFA vs. 1.0 ± 0.2 in OA; p = 0.12), and both groups received similar volumes of fluids (2200 ± 450 mL in OFA vs. 2150 ± 430 mL in OA; p = 0.67) and experienced similar blood loss (320 ± 110 mL vs. 310 ± 105 mL; p = 0.74), indicating no significant variation in surgical or anesthetic demands.

Table 2: Intraoperative Anesthetic Details

Postoperative pain scores, detailed in Table 3, were consistently lower in the OFA group across all time points, reflecting better analgesic efficacy. At 2 hours post-surgery, the OFA group reported a mean VAS score of 2.8 ± 1.1 compared to 3.5 ± 1.3 in the OA group (p = 0.02). This trend continued at 6 hours (3.0 ± 1.2 vs. 3.8 ± 1.4; p = 0.01), 12 hours (2.5 ± 1.0 vs. 3.2 ± 1.2; p = 0.03), and 24 hours (2.0 ± 0.9 vs. 2.6 ± 1.0; p = 0.04). These differences were statistically significant, demonstrating that the opioid-free protocol provided superior postoperative analgesia throughout the critical recovery period.

Table 3: Postoperative Pain Scores (Visual Analog Scale, VAS)

As shown in Table 4, secondary recovery outcomes also favored the OFA group. The incidence of postoperative nausea and vomiting (PONV) was significantly lower in OFA (6 patients, 15%) compared to OA (14 patients, 35%) (p = 0.04). The mean time to first mobilization was faster in the OFA group (18.5 ± 4.2 hours vs. 24.8 ± 5.6 hours; p < 0.01), as was the return of bowel function (36.2 ± 8.5 hours vs. 48.7 ± 10.2 hours; p < 0.01). Patients in the OFA group also had a shorter hospital stay (5.2 ± 1.3 days vs. 6.5 ± 1.7 days; p < 0.01) and required significantly less rescue analgesia (mean tramadol dosage: 50.5 ± 20.1 mg vs. 80.3 ± 25.4 mg; p < 0.01). Importantly, patient satisfaction scores were higher in the OFA group, averaging 4.3 ± 0.6 compared to 3.8 ± 0.7 in the OA group (p = 0.01), suggesting an overall better recovery experience.

Table 4: Secondary Postoperative Recovery Outcomes

Finally, Table 5 compares the incidence of adverse events between the two groups. Although not statistically significant, the trend indicated fewer opioid-related complications in the OFA group. Respiratory depression occurred only in the OA group (2 patients; 5%), while none was reported in OFA (p = 0.49). Hypotension (SBP <90 mmHg) was seen in 4 patients (10%) in OFA and 3 (7.5%) in OA (p = 0.69), and bradycardia was slightly more frequent in the OFA group (5 patients, 12.5%) than OA (2 patients, 5%; p = 0.43). Postoperative confusion or delirium occurred in 1 patient (2.5%) in the OFA group and 3 patients (7.5%) in the OA group (p = 0.61), while a single allergic reaction was reported in the OA group only (p = 1.00). These findings suggest that opioid-free anesthesia did not increase the risk of adverse events and may, in fact, reduce opioid-associated complications.

Table 5: Adverse Events and Complications

This study evaluated the impact of opioid-free anesthesia (OFA) on postoperative recovery in patients undergoing major abdominal surgeries. The findings demonstrated that OFA was associated with significantly improved postoperative outcomes in terms of pain control, recovery parameters, and patient satisfaction, while maintaining a favorable safety profile. These results are consistent with the growing body of literature supporting OFA as a viable alternative to traditional opioid-based anesthesia (OA), particularly in the context of enhanced recovery after surgery (ERAS) protocols.

The demographic and baseline clinical characteristics of the two groups were comparable, confirming that the patient cohorts were evenly matched. There were no statistically significant differences in age, gender, BMI, ASA status, comorbidities, or types of surgical procedures performed. This homogeneity reinforces the internal validity of our results, allowing us to attribute postoperative differences more confidently to the anesthetic approach rather than patient-related confounding factors.

Intraoperatively, both groups had comparable surgical durations, fluid administration, and blood loss, indicating similar procedural complexity and surgical stress. However, the anesthetic regimens varied distinctly. The OFA group received a combination of ketamine, lidocaine, dexmedetomidine, and magnesium sulfate—agents that act on different nociceptive pathways and possess synergistic analgesic and anti-inflammatory properties. These drugs are known not only for their analgesic efficacy but also for reducing sympathetic responses and opioid-induced side effects. In contrast, the OA group relied on fentanyl, a potent μ-opioid receptor agonist, for intraoperative analgesia. While effective in blunting pain, opioids are associated with a range of adverse effects, including respiratory depression, nausea, vomiting, ileus, and potential for dependence—issues that OFA aims to avoid.

Pain management remains a cornerstone of postoperative recovery. In our study, patients in the OFA group consistently reported significantly lower pain scores at all assessed intervals (2, 6, 12, and 24 hours postoperatively), supporting the efficacy of OFA in achieving adequate analgesia. This aligns with previous studies suggesting that multimodal opioid-sparing strategies provide comparable or superior pain control while avoiding the drawbacks of opioids. Lower pain scores in the OFA group also translated to a reduced requirement for rescue analgesics, with significantly lower mean tramadol consumption compared to the OA group. Effective early pain control not only enhances patient comfort but also facilitates earlier mobilization and return of physiological functions, key principles of ERAS.

Our study further demonstrated that the OFA group experienced a significantly faster recovery trajectory. Patients ambulated earlier and had a quicker return of bowel function compared to those in the OA group. These findings are clinically significant, as early mobilization reduces the risk of postoperative complications such as deep vein thrombosis and pulmonary infections, while early gastrointestinal recovery is essential for nutritional optimization and hospital discharge planning. Moreover, the length of hospital stay was significantly shorter in the OFA group, reflecting a tangible healthcare benefit in terms of reduced resource utilization and cost savings. Enhanced recovery also positively impacted patient satisfaction, which was significantly higher among patients who received OFA.

Another noteworthy outcome was the reduced incidence of postoperative nausea and vomiting (PONV) in the OFA group. Opioids are known to delay gastric emptying and stimulate the chemoreceptor trigger zone, both of which contribute to PONV. By avoiding opioids, OFA minimizes these effects, resulting in a smoother recovery experience. Lower PONV incidence not only improves patient comfort but also decreases the risk of aspiration, dehydration, and electrolyte imbalance—factors that can prolong hospital stay.

In terms of safety, the incidence of adverse events was low and comparable between groups. Importantly, respiratory depression—a hallmark opioid-related complication—was observed only in the OA group. Although not statistically significant, this trend underscores the potential of OFA to reduce opioid-specific complications. Other adverse events, including hypotension, bradycardia, delirium, and allergic reactions, were infrequent and did not differ significantly between groups, indicating that the OFA protocol is both safe and well-tolerated.

The findings of our study resonate with previous research advocating for opioid-free and opioid-sparing anesthesia techniques, particularly in the context of the global opioid crisis. OFA offers a patient-centered, evidence-based alternative that aligns with the principles of ERAS by improving clinical outcomes, enhancing patient satisfaction, and potentially reducing opioid dependency.^12-14 Moreover, the adoption of OFA may be particularly relevant in resource-limited settings, where minimizing postoperative complications and shortening hospital stays are essential for optimizing healthcare delivery.^15,16

Despite its strengths, this study has certain limitations. First, it was conducted at a single tertiary care institution, which may limit the generalizability of the findings. Multicenter trials involving larger and more diverse populations are needed to validate and expand upon our results. Second, while pain scores and recovery parameters were assessed for the first 24 hours postoperatively, longer follow-up could provide additional insights into chronic pain development and long-term functional outcomes. Finally, patient blinding was not feasible due to the nature of anesthetic protocols, which may introduce subjective bias in satisfaction scoring.

In conclusion, this study provides compelling evidence that opioid-free anesthesia is an effective, safe, and advantageous approach for patients undergoing major abdominal surgeries. Compared to conventional opioid-based anesthesia, OFA resulted in lower pain scores, faster postoperative recovery, reduced opioid-related side effects, and higher patient satisfaction, without increasing the risk of adverse events. These findings support the broader implementation of OFA as part of modern, multimodal perioperative care strategies and emphasize the need for further research to refine and personalize OFA protocols in diverse surgical populations.

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