Laparoscopy, also known as minimally invasive or keyhole surgery, involves the insertion of a fibre optic instrument through the abdominal wall to observe internal organs or perform surgical procedures. Initially introduced in 1970, laparoscopy has seen significant advancements, enabling even major surgeries to be performed through this technique^1.

This surgical approach has gained popularity in recent years due to its ability to achieve therapeutic goals while minimizing traumatic and metabolic stress. The benefits of laparoscopic surgery include reduced tissue trauma, smaller incisions, lower risks of wound complications, decreased postoperative pain, fewer complications, shorter hospital stays, quicker recovery times, and cost savings.²

To create adequate surgical exposure and maintain operative freedom during laparoscopy, pneumoperitoneum is established by insufflating the abdomen with carbondioxide (CO2)³. This insufflation can lead to various physiological changes. An emerging body of research addresses the hemodynamic, respiratory, immunological, and stress responses related to pneumoperitoneum^3.

The physiological changes during laparoscopy include those caused by patient positioning to facilitate surgical access, the pressure effects of gas in a closed cavity, and the systemic effects of absorbed or embolized CO2⁴. Cardiovascular changes typically observed are an increase in mean arterial pressure without significant changes in heart rate, a 10% to 30% decrease in cardiac output, and an increase in systemic vascular resistance⁵.These vasopressor responses are due to hypercarbia-induced release of catecholamines and vasopressin.

Pharmacological agents such as nitroglycerine, β-blockers, and opioids can attenuate the hemodynamic changes associated with pneumoperitoneum to provide hemodynamic stability, though they have their own disadvantages. Clonidine, a selective α-2 adrenergic receptor agonist, has shown promise in reducing hemodynamic responses during laparoscopic surgery by decreasing heart rate, blood pressure, systemic vascular resistance, and cardiac output.

Magnesium, on the other hand, inhibits catecholamine release from adrenergic nerve terminals and the adrenal gland and induces vasodilation by acting directly on blood vessels. In high doses, magnesium also mitigates vasopressin-mediated vasoconstriction⁵.

This prospective, randomized, double-blind study was designed to compare the efficacy of intravenously administered Clonidine and Magnesium Sulphate in managing hemodynamic stress responses during laparoscopic surgeries⁵.

AIM OF THE STUDY

The primary objective of this study was to compare the effects of intravenously administered Clonidine and magnesium sulphate on hemodynamic responses during laparoscopic surgeries, specifically focusing on:

1. Heart rate
2. Systolic blood pressure
3. Diastolic blood pressure
4. Mean arterial pressure
5. Level of sedation upon recovery
6. Adverse effects

This randomized, double-blind, prospective study was carried out at the Department of Anaesthesiology, Kurnool Medical College, from February 2023 to January 2024. Institutional ethical committee approval was obtained, and informed consent was secured from participants. The study included 60 patients, aged 18-65 years, with ASA physical status I and II, scheduled for elective laparoscopic surgeries involving CO2 pneumoperitoneum. Participants were randomly divided into two groups: Group C (Clonidine group) and Group M (Magnesium group).

Statistical Analysis

Data were analysed using One-Way ANOVA for comparing different parameters and the Chi-square test for categorical data. Statistical significance was set at a p-value of less than 0.05.

Inclusion Criteria

1. ASA I and II
2. Age range: 18-65 years
3. Patients giving informed written consent
4. Patients scheduled to undergo laparoscopic surgeries

Exclusion Criteria

1. Patient refusal for procedure
2. Patients belonging to ASA 3 & 4
3. Patients with severe cardiac disease [NYHA 3& 4], renal, endocrine disorders and morbid obesity.
4. Patients on calcium channel
5. Patients with hypermagnesemia

Pre-anaesthetic Evaluation

Patients fasted for 6 hours before surgery. Premedication included intravenous ondansetron 0.08mg/kg and intravenous glycopyrrolate (0.004 mg/kg), administered one hour before the surgery in the preoperative area.

In the Operating Room

Patients were taken to the operating room and upon arrival, they were monitored for heart rate, non-invasive blood pressure (NIBP), oxygen saturation (SpO2), and electrocardiogram (ECG), and baseline vital

Signs were recorded. Analgesia was achieved with intravenous fentanyl 2 µg/kg. Following a 3-minute pre-oxygenation with 100% oxygen,

Induction was performed using propofol 2-2.5mg/kg and succinylcholine chloride 1-2 mg/kg, followed by intubation with an appropriately sized endotracheal tube. Anend-tidal CO2 (ETCO2) monitor was then connected.

Procedure

After intubation but before the creation of pneumoperitoneum, the test drugs contained in prefilled syringes were administered

• Group C: Clonidine1.0μg/kgin50 ml normal saline over15
• Group M: Magnesium Sulphate 30mg/kgin50 ml normal saline over 15 minutes.

Assessment of Parameters

Hemodynamic parameters (systolic, diastolic, and mean arterial pressure, heart rate, and SpO2) were recorded at the following intervals:

1. Baseline (prior to induction)
2. Endo infusion (P0)
3. 5 minutes post-pneumoperitoneum (P5)
4. 10 minutes post-pneumoperitoneum (P10)
5. 20 minutespost-pneumoperitoneum (P20)
6. 30 minutespost-pneumoperitoneum (P30)
7. 40 minutes post-pneumoperitoneum (P40)

Intraoperative adverse events such as bradycardia and hypotension were monitored.

Intravenous neostigmine (0.05 mg/kg) and glycopyrrolate (0.02 mg/kg) was used for Neuromuscular blockade reversal. Patients were extubated after adequate recovery.

Adverse Effects

Post-extubation, patients were observed for nausea, vomiting, sedation and shivering assessed using the Modified Ramsay Sedation Score.

Sixty ASA I and II patients, of either sex, aged between 18 and 65, were enrolled in this prospective double blinded randomized controlled trial while undergoing elective laparoscopic procedures under general anaesthesia. The purpose of the study was to evaluate the benefits and drawbacks of using Magnesium Sulphate and Clonidine intravenously to reduce the hemodynamic response during laparoscopic procedures.

Table:1 Demographic Characteristics of study population age

Age wise distribution of study groups

For Groups C and M, the age range covered the range of 18 to 65 years. The mean age's P Value did not exhibit statistical significance.

Table: 2 WEIGHTS

Comparison of groups on basis of mean body weight.

Group C's weight distribution fell between 40 and 78 kg, whereas Group M's weight fell between 42 and 78 kg. For mean weight, the P Value was not statistically significant.

Table: 3 ASA STATUS

Comparison of groups on basis of ASA status

There was no discernible statistically significant variation in the groups' ASA status

Table: 4 Duration of the surgery

Comparison of groups on basis of the surgery

Group M had a mean surgery time of 52.87 while group C had a mean surgery duration of 53.1. P is statistically not significant at 0.865.

Table: 5 Heart rate

Comparison of groups on basis of heart rate

At no point during the trial did the heart rate status of the groups differ in a way that was statistically significant.

Table: 6 Systolic blood pressure

Comparison of groups on basis of mean Systolic blood pressure

Between the groups, there was no statistically significant decrease in systolic blood pressure.

Table: 7 Diastolic BP

Between the groups, there was no statistically significant decrease in diastolic blood pressure.

Table: 8 Mean Arterial Pressure

Table: 9 Modified Ramsay sedation score

There was a statistically significant difference between the two groups' Modified Ramsay sedation scores. At the time of extubation, Clonidine was shown to have far less sedation than Magnesium.

Table: 10: Adverse effects

Now days, a growing number of elective operations are being treated with laparoscopic surgery. Despite the use of open procedures, patients and surgeons alike prefer laparoscopy due to its benefits. Therefore, improved intraoperative hemodynamic management is required for these kinds of procedures.

Recently, a number of pharmacological drugs have been investigated for their ability to lessen the hemodynamic variations after laparoscopy. The majority of research has contrasted the effects of intravenous magnesium or Clonidine with the control. There is limited research comparing intravenous Clonidine and magnesium for the purpose of attenuating the hemodynamic reactions of laparoscopy. In order to examine the impact of intravenous clonidine and magnesium on hemodynamic response in patients undergoing laparoscopic procedures, we have scheduled a prospective, randomised, double blinded trial at Kurnool Medical College, Kurnool, Andhra Pradesh.

Patient characteristics across groups

Age, weight, ASA status, and the length of the surgery were among the demographic traits that were comparable between the two groups and did not show any statistically significant differences. The average age of the Magnesium group was 43.10±11.51 years, while the Clonidine groups was 40.23±10.76 years. The average weight for the groups receiving Clonidine and magnesium was 60.42 ± 12.22 kg and 59.10 ± 13.21 kg, respectively. The patients were similar in both groups and belonged to either ASA1 or ASA 2.The average amount of time spent during surgery was 52.87±4.64 minutes for the Magnesium group and 53.10 ± 5.88 minutes for the Clonidine group.

Dosage of the drug

The medication's dosage Group C received 1.0µg/kg of Clonidine in 50ml of normal saline, while Group M received 30mg/kg of magnesium sulphate in 50 ml of normal saline.Before pneumoperitoneum, the test drug solution was administered gradually over a 15-minute interval.

The study conducted by Nand Kishore Kalra et al.⁶ examined the effect of intravenous Clonidine (1μg/kg), Clonidine1.5 μg/kg, Magnesium 50mg/kg, and placebo on the reduction of hemodynamic response during laparoscopic cholecystectomy due to pneumoperitoneum. The results indicated that both Clonidine doses and magnesium significantly reduced the hemodynamic stress response in comparison to placebo. After 15 minutes after intubation, the test medication solution was injected. A statistically significant difference was observed between Clonidine1.5µg/kg and Magnesium 50mg/kg. Adverse effects such as bradycardia and hypotension were not observed in this case.

In a similar manner, Altan and Turgut et al.⁷ employed intravenous Clonidine at a doseof3μg/kgfor15 minutes prior to induction, followed by a continuous infusion of 2 μg/kg/min during the procedure. In their investigation, they found noteworthy cases of hypotension and bradycardia. In their trial, Ray et al. ⁸ employed intravenous Clonidine at a dose of 3 μg/kgfor15 minutes prior to induction, followed by a continuous infusion of 1 μg/kg/min during operation. The researchers noted notable occurrences of bradycardia and hypotension. As a result, we gave 1.0µg/kg of Clonidine instead of the recommended dose before pneumoperitoneum. We saw a 7% incidence of bradycardia in the Clonidine group patients, despite the fact that we lowered the Clonidine dosage and forwent the intraoperative infusion.

MgSO4 40 mg/kg was infused intravenously by Elsharnouby and Elsharnouby et al.⁹ 15 minutes prior to induction, and 15 mg/kg/hour was continuously infused during the procedure. When taking this dosage of MgSO4, they observed episodes of severe hypotension.

Hemodynamic Stability

Heart rate

Nand Kishore Kalra et al.⁶found that patients who took clonidine1.5µg/kg at the following intervals—30 minutes and 40 minutes after pneumoperitoneum (P <0.05) had a statistically significant lower heart rate than the magnesium 50mg/kg group. This is not the case with our research, as the heart rate did not alter statistically significantly between the magnesium 30 mg/kg and Clonidine 1.0µg/kg groups at any point of time.

The patients who received Magnesium Sulphate 30 mg/kg as a bolus followed bya10 mg/kg/hr infusion and Clonidine 3µg/kg as a bolus followed by a 2µg/kg/hr infusion did not show a statistically significant change in heart rate, according to Altan et al.⁷ During the intraoperative time, Ray et al ⁸ administered Clonidine at a dose of 3µg/kg and subsequently continuously infused 1µg/kg. They noted a substantial incidence of bradycardia and hypotension. In order to prevent bradycardia and hypotension, we lowered the Clonidine dosage to 1ug/kg after intubation and before pneumoperitoneum as 15 min infusion in 50 m NS but not as infusion during the intraoperative period. There were no discernible differences in heart rate between the groups.

Systolic Blood Pressure

Our results are in contrast with those of Nand Kishore Kalra et al.⁶, who observed a substantial decrease in systolic blood pressure in patients who received1.5 µg/kg of Clonidine at10C minutes(P< 0.05)and 30minutes (P< 0.01) following pneumoperitoneum, as compared to the magnesium 50 mg/kg group.A.CAltan et al., in contrast, did not find any significant difference in systolic blood pressure between patients treated with Magnesium Sulphate (30mg/kg bolus followed by10mg/kg/hr infusion)and those treated with Clonidine (3 µg/kg bolus followed by 2 µg/kg/hr infusion), which is consistent with the findings of our study that is not statistically

Significant differences in systolic blood pressure but with Magnesium 30 mg/kg and clonidine 1ug/kg doses.

In contrast to our findings, Deepshikha C. Tripathi et al.¹⁰ reported that patients receiving Clonidine 2 µg/kg had a significantly lower systolic blood pressure at 20 minutes post-pneumoperitoneum (P < 0.05) than the placebo group.

Diastolic Blood Pressure

We found that, individuals receiving magnesium 30mg/kg group, individuals receiving Clonidine at 1.0 µg/kg had no substantial decrease in diastolic blood pressure at any point of time after pneumoperitoneum. Altan et al. found no statistically significant variation in diastolic blood pressure between patients treated with a bolus of Clonidine 3 µg/kg followed by a 2 µg/kg/hr infusion and those who received a bolus of Magnesium Sulphate30 mg/kg followed by a 10 mg/kg/hr infusion.

Mean Arterial Pressure

When comparing theme an arterial blood pressure of the Clonidine group (3 µg/kg) to the placebo group at different times prior to and during pneumoperitoneum, R.Uma et al.found a substantial drop. This result is at odds with what we found.

Corresponding with our findings, A. Altan et al. discovered no statistically significant difference in mean arterial blood pressure between patients receiving Magnesium Sulphate and those receiving Clonidine.

Contrary to our findings, Manjeree Mishra et al.¹¹ found substantial variations in mean arterial pressure in patients who received Clonidine (1.5 µg/kg) at many times following pneumoperitoneum. In contrast to ours tudy,

Level of Sedation

Magnesium and Clonidine both has sedative effects. We employed the modified Ramsay sedation scale at the time of extubation in our study to examine the sedative effects of magnesium and Clonidine. In the Clonidine group, we found that three patients received a score of four (10%), whereas 27 out of 30 patients obtained a score of 3. However, of the 30 patients in the Magnesium group, 18 had a score of 3 (or 60%), and the remaining 12 got a score of 4 (40%).

Magnesium has a longer-lasting sedative effect than Clonidine, which could account for the difference in sedative impact. The statistical significance is established by the p value of less than 0.003.

Additionally, Nand K et al.⁶ found that there was no statistically significant difference in the time taken by patients taking magnesium to attenuate hemodynamic stress response when it came to responding to verbal commands such opening the eyes. This is not the case with our research. To be statistically significant in 31/43 (72%) patients and>3(P<0.05) in 12/43 (28%) patients. This matches the findings of our investigation.

Adverse Effects

In our study, we looked for side effects from the laparoscopy, such as bradycardia, hypotension, post-operative nausea, vomiting, and shivering. Of the thirty patients in the Clonidine group, two experienced bradycardia episodes (7%).No other patient experienced any negative outcomes. There were no negative effects reported by any patients in the magnesium group.

For a duration of fifteen minutes, Nand K et al.⁶ administered Magnesium 50 mg kg and Clonidine 3 µg/kg intravenously. In their investigation, they found no instances of bradycardia or hypotension. This is not the case with our research. Clonidine was utilized intravenously by Altan and Turgut et al.⁷ at a dose of 3 μg/kg for 15 minutes prior to induction, and then continuously infuse data dose of 2μg /kg/ min during the surgical procedure. In their investigation, they found noteworthy cases of hypotension and bradycardia.

When it comes to reducing the hemodynamic stress responses during laparoscopic procedures, intravenous Clonidine administration 1.0 µg/kg before pneumoperitoneum is just as beneficial as intravenous Magnesium Sulphate administration 30mg/kg before pneumoperitoneum. Additionally, Clonidine causes less sedation following extubation than Magnesium.

Conflict of Interest: None

Funding Support: Nil

1. Rudiman, R. "Minimally Invasive Gastrointestinal Surgery: From Past to the Future." Annals of Medicine and Surgery (London), Elsevier, 2021.
2. Vorst, A. L., C. Kaoutzanis, and A. M. Carbonell. "Evolution and Advances in Laparoscopic Ventral and Incisional Hernia Repair." World Journal of Gastrointestinal Endoscopy, vol. 7, no. 10, 2015, pp. 826–839.
3. Alkatout, I., U. Mechler, L. Mettler, et al. "The Development of Laparoscopy—A Historical Overview." Frontiers in Surgery, vol. 8, 2021, article 799442.
4. Cao, Y., S. Zhou, and G. Wang. "A Bibliometric Analysis of Global Laparoscopy Research Trends During 1997–2011." Scientometrics, vol. 96, no. 2, 2013, pp. 635–650.
5. Lefor, A. K. "Robotic and Laparoscopic Surgery of the Pancreas: An Historical Review." BMC Biomedical Engineering, vol. 1, 2019, p. 1.
6. Altan, A., et al. "Effects of Magnesium Sulphate and Clonidine on Perioperative Haemodynamics, Propofol Consumption and Postoperative Recovery." British Journal of Anaesthesia, Apr. 2005.
7. Ray, et al. "Effects of Clonidine and Magnesium Sulphate." Indian Journal of Anaesthesia, vol. 54, no. 2, Mar.–Apr. 2010.
8. Modanlou Juibari, H., H. R. Eftekharian, and H. R. Arabion. "Intravenous Magnesium Sulphate to Deliberate Hypotension and Bleeding After Bimaxillary Orthognathic Surgery: A Randomized Double-Blind Controlled Trial." Journal of Dentistry (Shiraz), vol. 17, no. 3 Suppl, Sept. 2016, pp. 276–282. PMID: 27840841; PMCID:
9. Tripathi, D. C., T. S. Shah, S. R. Dubey, S. M. Doshi, and P. V. Raval. "Hemodynamic Stress Response During Laparoscopic Cholecystectomy: Effect of Two Different Doses of Intravenous Clonidine Premedication." Journal of Anaesthesiology Clinical Pharmacology, vol. 27, 2011, pp. 475–480.
10. Mishra, M., et al. "Comparison of Hemodynamic and Intraocular Pressure Effects of Clonidine and Nitroglycerin Infusion in Laparoscopic Cholecystectomy." Journal of the Society of Laparoendoscopic Surgeons, vol. 18, no. 3, Jul.–Sept. 2014.