European Journal of Cardiovascular Medicine

Laparoscopic cholecystectomy is among the most frequently performed surgeries today, offering benefits such as a shorter hospital stay, minimal incisions, reduced postoperative pain, and quicker recovery. Despite these advantages, it still triggers a stress response due to surgical and anesthetic stimuli.^[1]

Modern anesthetic practices aim to suppress sympathetic discharge and maintain perioperative hemodynamic stability. Various pharmacologic agents-opioids, beta-blockers, and centrally acting sympatholytics-have been employed to attenuate this stress response. Among these, alpha-2 adrenergic agonists are notable for their anxiolytic, sedative, sympatholytic, and analgesic-sparing properties.^[1]

Inadequately controlled postoperative pain can lead to significant physiological and psychological morbidity, delayed recovery, prolonged hospitalization, and even the development of chronic pain.^[2] Effective pain control improves patient satisfaction and recovery. Preemptive analgesia has been proposed to reduce overall analgesic needs and enhance pain outcomes.^[3]

Dexmedetomidine, a selective alpha-2 agonist, has eight times greater affinity for alpha-2 receptors compared to clonidine. Its intravenous use has been shown to reduce serum catecholamine levels by up to 90%, thereby blunting the hemodynamic stress responses to laryngoscopy, intubation, pneumoperitoneum, and extubation. It also provides sedation without respiratory depression and lowers postoperative analgesic requirements.^[1] Approved by the FDA in 1999 for short-term sedation and analgesia in ICU settings, dexmedetomidine acts via alpha-2A, 2B, and 2C receptors, mediating hypotension, bradycardia, sedation, and analgesia through central and spinal pathways.

This study aims to compare the effects of two maintenance infusion doses-0.2 mcg/kg/hr and 0.4 mcg/kg/hr-of dexmedetomidine in patients undergoing laparoscopic cholecystectomy, focusing on perioperative hemodynamic response and 24-hour postoperative analgesic requirements.

Aims and Objectives

This study aims to compare the perioperative hemodynamic responses, specifically mean arterial pressure and heart rate, between two groups of patients undergoing laparoscopic cholecystectomy who receive different maintenance infusion doses of dexmedetomidine (0.2 mcg/kg/hr and 0.4 mcg/kg/hr). Additionally, the study aims to evaluate the timing of the first requirement for postoperative analgesia and the total analgesic consumption within the first 24 hours after surgery.

Study Design

This prospective observational study was conducted in the Department of Anesthesiology at Government Medical College, Thrissur, over a period of one year from January 2020 to December 2020. The study population comprised patients undergoing elective laparoscopic cholecystectomy at the institution, with the objective of evaluating perioperative hemodynamic responses and postoperative analgesic requirements associated with two different doses of dexmedetomidine infusion.

Inclusion and Exclusion Criteria

The study included patients aged between 18 and 60 years of both genders, classified as ASA (American Society of Anesthesiologists) physical status I or II, who were scheduled to undergo elective laparoscopic cholecystectomy at Government Medical College, Thrissur. Patients who were unwilling to undergo surgery were excluded from the study.

Sample Size Calculation

d=|x1—x2|

Power (beta) = 80%  Alpha error = 5% mean BP after extubation was highest between two groups in the study done by Manne et al., in 2014 on low dose dexmeditomedine in patients undergoing laparoscopic cholecystectomy.^[1]

X1 = 106.35, X2 = 98.30, σ1 = 12.45, σ2 = 6.82

Sample size = 25 each in both groups.

Data Collection Tools

Data were collected using a self-designed proforma to document patient demographics, pre-anesthetic evaluation, intraoperative hemodynamic parameters, and postoperative analgesic requirements. Monitoring equipment included multiparameter monitors, pulse oximeters, ECGs, and a cuff pressure monitor, used as required throughout the perioperative period.

Data Collection Procedure

After obtaining informed written consent and ethical clearance, patients were divided into two groups based on the dexmedetomidine infusion dose (0.2 mcg/kg/hr for Group 1 and 0.4 mcg/kg/hr for Group 2). Standard preoperative medications and fasting guidelines were followed. Dexmedetomidine infusion was prepared and administered by a senior anesthesia provider, and patients were monitored using standard protocols. Baseline and perioperative hemodynamic parameters (pulse rate, mean arterial pressure, and oxygen saturation) were recorded at defined intervals, along with intraoperative observations for bradycardia, tachycardia, hypotension, or hypertension. Anesthesia was induced and maintained using standard drugs and techniques. Time to extubation was noted. Postoperatively, patients were monitored for pain using the VAS, and the time to first rescue analgesia (tramadol) and total 24-hour analgesic requirement were recorded.

Statistical Analysis

Data were entered using Microsoft Excel and analyzed with SPSS software version 16. Continuous variables such as age, height, and weight were summarized using mean and SD (Standard Deviation), while categorical variables like gender and ASA physical status were expressed as proportions and compared between the two groups. Hemodynamic parameters, including SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), MAP (Mean Arterial Pressure), and HR (Heart Rate) were recorded at various predefined intraoperative time points. These parameters, along with the timing and dose of rescue analgesia, were summarized as mean ± SD. Comparisons between the two groups were made using independent (unpaired) t-tests. A p-value of less than 0.05 was considered statistically significant.

Table 1 summarizes the baseline demographic and physical parameters of the participants. Both groups were statistically comparable in terms of age, gender distribution, ASA classification, weight, and height.

Table 2 reveals no statistically significant differences in baseline haemodynamic parameters between the two groups, confirming physiological comparability before intervention.

Table 3 illustrates equal duration of surgery in both groups. However, Group 2 showed a significantly higher incidence of bradycardia and hypotension post-infusion, indicating greater haemodynamic depression.

Table 4 tracks intraoperative heart rate trends. Group 2 consistently maintained lower heart rates up to 60 minutes of pneumoperitoneum, supporting the hypothesis of better sympathetic control.

Table 5 highlights MAP trends across intraoperative phases. Group 2 maintained significantly lower MAP throughout, which aligns with their higher incidence of hypotension.

Table 6 reveals that Group 2 required rescue analgesia much later and in a significantly lower dose, indicating better postoperative pain control.

Table 7 aggregates adverse event occurrences. Group 2 was more prone to bradycardia and hypotension, suggesting a need for vigilant intraoperative monitoring when using the same regimen.

Laparoscopic cholecystectomy has become the preferred surgical technique for treating gallstone disease, replacing the open approach due to its advantages, such as faster recovery, reduced postoperative pain, earlier return of bowel function, shorter hospital stay, and better cosmetic outcomes. However, despite its minimally invasive nature, it is still associated with significant postoperative pain-visceral, somatic, and shoulder pain due to diaphragmatic irritation. Visceral pain, most prominent in the first 24 hours postoperatively, is typically short-lived and unaffected by movement but aggravated by coughing. Shoulder pain, likely due to phrenic nerve irritation, can persist for up to three days.

Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that provides sedation, anxiolysis, analgesia, and sympatholysis through action on α2A, α2B, and α2C receptors located in the brain and spinal cord. Activation of α2A receptors in the brainstem vasomotor center results in inhibition of norepinephrine release, leading to hypotension and bradycardia. Sedation is mediated via α2A and α2C receptors in the locus ceruleus, while analgesia results from suppression of substance P release in the spinal cord through α2A and α2C receptor activation.

Previous studies have highlighted the effectiveness of dexmedetomidine in controlling perioperative hemodynamic responses. Hall et al. demonstrated its dose-dependent sedative effects along with minimal respiratory depression.^[4] Bakhamees et al. observed that dexmedetomidine reduced anesthetic and opioid requirements while maintaining stable heart rate and MAP in morbidly obese patients undergoing laparoscopic bariatric surgery.^[5] Bhattacharjee et al. also reported superior intraoperative and postoperative hemodynamic control in patients undergoing laparoscopic cholecystectomy with dexmedetomidine.^[6]

Shamim et al. compared different dexmedetomidine dosing strategies and found improved hemodynamic stability in both loading and maintenance infusion groups.^[7] Similarly, Masoori Tahir et al. found better suppression of the hemodynamic stress response using a higher maintenance dose of 0.6 µg/kg/hr in laparoscopic cholecystectomy.^[8] In contrast, Shefali Gautam et al. found that both 0.5 and 0.7 µg/kg/hr doses were equally effective in hypertensive patients.^[9] Vora et al. demonstrated stable hemodynamics and stress attenuation during intubation and extubation with a loading dose followed by maintenance infusion.^[10]

Dexmedetomidine can be administered with or without a loading dose, and infusion rates ranging from 0.1 to 10 µg/kg/hr have been studied. High-dose infusions are associated with increased cardiovascular side effects. A biphasic blood pressure response is often seen with a bolus dose-initial hypertension due to α2B receptor stimulation followed by hypotension-especially in young, healthy individuals.^[1]

In our study, we compared maintenance doses of 0.2 µg/kg/hr and 0.4 µg/kg/hr without administering a loading dose. Both groups exhibited stable intraoperative hemodynamics, with no significant episodes of hypertension or tachycardia. However, in the 0.4 µg/kg/hr group (Group 2), hypotension was observed in 18 patients, occurring 15 minutes after starting the infusion and shortly after induction. These episodes were managed effectively with intravenous fluids. Bradycardia was noted in 8 patients in the same group, reflecting the known sympatholytic action of dexmedetomidine.

Postoperative analgesia was significantly better in the higher-dose group. Venn et al. reported that dexmedetomidine reduces the need for rescue analgesia for up to 24 hours postoperatively.^[11] Manne et al. also observed delayed onset of first rescue analgesia and reduced total analgesic requirement within 24 hours.^[1] In our study, the mean time to first rescue analgesia was longer in Group 2 (236 minutes) compared to Group 1 (136 minutes), and the total dose of tramadol required in 24 hours was lower in Group 2, supporting the analgesia-sparing effect of higher-dose dexmedetomidine.

These findings align with existing literature and reinforce the efficacy of dexmedetomidine, particularly at 0.4 µg/kg/hr, in providing better hemodynamic control and reducing postoperative analgesic needs in laparoscopic cholecystectomy patients.

A low-dose infusion of dexmedetomidine at 0.4 mcg/kg/hr without a bolus has proven to be an effective adjuvant for attenuating the hemodynamic stress response during critical perioperative events such as intubation, pneumoperitoneum, and extubation in patients undergoing laparoscopic cholecystectomy. This dosage not only contributes to intraoperative hemodynamic stability but also reduces the requirement for anesthetic agents, particularly opioids. Furthermore, it provides effective postoperative analgesia with minimal adverse effects, making it a safe and valuable component of balanced anesthesia in laparoscopic procedures.

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