|Year : 2018 | Volume
| Issue : 4 | Page : 327-332
Magnesium sulfate, dexmedetomidine, and lignocaine in attenuating hypertension during laparoscopic cholecystectomy: a comparative study
Ismail M.A Ahmed, Hesham S Abdelraouf
Department of Anesthesiology, Faculty of Medicine, Al Azhar University, Cairo, Egypt
|Date of Submission||11-Apr-2018|
|Date of Acceptance||15-Jan-2019|
|Date of Web Publication||23-Apr-2019|
Hesham S Abdelraouf
Department of Anesthesia, Faculty of Medicine, Al Azhar University, Cairo, 11651
Source of Support: None, Conflict of Interest: None
Background Pneumoperitoneum during laparoscopic surgery is associated with significant hemodynamic changes represented by increasing heart rate, vascular resistance, and blood pressure. This study aimed to compare the safety of each of magnesium sulfate, dexmedetomidine, and lignocaine on hemodynamic responses during pneumoperitoneum.
Patients and methods In all, 120 patients were enrolled in the study. They were electively planned for laparoscopic cholecystectomy. Their ages were in the range of 21–60 years. Men were 38.3% and women 61.67%. American Society of Anesthesiologists I: 74.17% and II: 25.83%. The patients were randomly allocated into four groups: each of 30 patients. Group M administered magnesium sulfate preoperatively as loading followed by infusion 50 mg/kg/h, group D received dexmedetomidine preoperatively as loading followed by infusion 0.5 µg/kg/h, group L was given lignocaine preoperatively as loading followed by infusion 1 mg/kg/h, and group C received normal saline.
Results A significant difference was noticed as regards heart rate changes and mean arterial blood pressure increase between the groups of magnesium sulfate, dexmedetomidine, lignocaine, and the control group at the time of drug administration, after intubation, throughout pneumoperitoneum at 5 min intervals, postpneumoperitoneum, and in the postoperative period after 10 min (P<0.001).
Conclusion Magnesium sulfate and dexmedetomidine infusions have comparable effects. Lignocaine was less effective in the attenuation of the hypertensive response of pneumoperitoneum and reducing the dose requirements of opioids during laparoscopic cholecystectomy.
Keywords: dexmedetomidine, laparoscopic surgery, lignocaine, magnesium sulfate, pneumoperitoneum
|How to cite this article:|
Ahmed IM, Abdelraouf HS. Magnesium sulfate, dexmedetomidine, and lignocaine in attenuating hypertension during laparoscopic cholecystectomy: a comparative study. Al-Azhar Assiut Med J 2018;16:327-32
|How to cite this URL:|
Ahmed IM, Abdelraouf HS. Magnesium sulfate, dexmedetomidine, and lignocaine in attenuating hypertension during laparoscopic cholecystectomy: a comparative study. Al-Azhar Assiut Med J [serial online] 2018 [cited 2019 Jul 21];16:327-32. Available from: http://www.azmj.eg.net/text.asp?2018/16/4/327/256753
| Introduction|| |
Laparoscopic cholecystectomy (LC) procedure offers several benefits including rapid recovery and better cosmetic appearance ,. However LC heralds some cardiovascular complications; probably induced by patient positioning variations, cardiorespiratory status, and neurohormonal response of CO2-induced pneumoperitoneum ; they include an increase in vascular resistance, heart rate (HR) changes, arterial blood pressure alterations, and cardiac collapse ,. Some drugs are frequently administered to avoid circulatory response to pneumoperitoneum as vasodilators , alpha-2 adrenergic agonists , beta-blocking agents , and opioids . Magnesium blocks catecholamines and vasopressin release, and acts directly on blood vessel , attenuating the vasopressor response induced by intubation . Dexmedetomidine; an alpha-2 adrenergic agonist, suppresses the pneumoperitoneum-induced hemodynamic response by inhibiting norepinephrine release . Local anesthetics act on intracellular Na+ channels producing analgesic and anti-inflammatory effect .
The present study aimed at comparing the safety of each of magnesium sulfate, dexmedetomidine, and lignocaine on hemodynamic responses during pneumoperitoneum.
| Patients and methods|| |
This prospective, randomized, placebo-controlled study was conducted after approval from the ethics committee at the Anesthesia Department and after obtaining informed consent from the patients. One hundred and twenty patients were scheduled for elective LC under general anesthesia in Al Azhar University Hospitals from March to August 2016. They were 38.3% men and 61.67% women, American Society of Anesthesiology (ASA) physical status I: 74.17% and II: 25.83%.
Patients were randomized using sealed envelopes, allocated into four groups each of 30 patients, depending on the drug given.
Group M received magnesium sulfate: 50 mg/kg/h.
Group D received dexmedetomidine: 0.5 mg/kg/h.
Group L received lignocaine: 1 mg/kg/h.
Group C received normal saline.
Adult patients aged 21–60 years.
The exclusion criteria included the following: morbid obesity (BMI>45 kg/m2), difficult intubation, allergy to study medications, and concomitant diseases such as hypertension whether controlled under antihypertensive therapy or not, renal or hepatic insufficiency, cardiopulmonary problems, and acute cholecystitis.
On operating room entry, the patients were monitored using pulse oximetry, five-lead surface ECG electrodes, and blood pressure cuff. The patients were preoxygenated using a face mask with 100% O2 for 3 min. Anesthesia was induced using fentanyl 2 µg/kg and propofol 1–2 mg/kg followed by cisatracurium 0.1 mg/kg. Orotracheal intubation using Macintosh laryngoscope was done. All drugs were prepared via a blind technique, in identical syringes and infused with an infusion pump (perfusion compact, B Braun). Ten minutes before surgery, all patients were premedicated with midazolam 0.01 mg/kg. Continuous infusion using 50 ml syringe throughout pneumoperitoneum and the drugs were given as follows: Group M received magnesium sulfate 50 mg/kg/20 ml normal saline over 10 min, group D administered dexmedetomidine 1 µg/kg/20 ml normal saline over 10 min, group L received lignocaine 1 mg/kg/20 ml normal saline over 10 min, and group C was given 20 ml of saline infusion over 10 min.
Maintenance of anesthesia was achieved using oxygen, sevoflurane, and intermittent boluses of cisatracurium (0.01 mg/kg). CO2 pneumoperitoneum was established and maintained to a pressure of 14 mmHg throughout the laparoscopic surgery using an automatic insufflation unit. Ventilation was adjusted and an end-tidal carbon dioxide value was maintained between 35 and 40 mmHg. Drug infusion was stopped with the release of pneumoperitoneum and neostigmine (40 µg/kg) and atropine (1–2 µg/kg) was used to reverse the residual neuromuscular blockade.
Hemodynamic monitoring and recording
Baseline data including HR and mean arterial blood pressure (MAP) changes were noninvasively monitored and recorded preoperatively, after the investigated drug administration, after induction, after intubation, during pneumoperitoneum at 5 min intervals, postpneumoperitoneum (PP) and in the postoperative period after 10 min.
Adverse effects and their management
Bradycardia, hypotension, and hypertension were measured and recorded as hemodynamic fluctuations in the studied groups. In the case of hemodynamic fluctuations, the following medications were administered: intravenous bolus dose of 0.6 mg injection atropine for bradycardia (HR<60 beats/min), excess infusion of intravenous fluids and/or intravenous bolus of ephedrine sulfate for hypotension (MAP<20% of the baseline), and intravenous bolus dose of nitroglycerine infusion for hypertension (MAP>20% of the baseline).
The data were collected, tabulated, and statistics were carried out using the computerized Statistical Package for the Social Sciences for Windows (SPSS Inc., Chicago, Illionis, USA) version 20. Data were expressed as mean±SD or number of patients and percentage as appropriate. Categorical variables such as sex, ASA status, and surgical type were compared using the χ2 test while one-way analysis of variance was used to detect differences among numerical variables in the treatment groups with respect to parametric variables, followed by post-hoc analysis (Tukey’s test) for intergroup comparisons. Meanwhile, the intragroup follow-up comparisons were performed using a paired t test. A P value less than 0.05 was considered as significant.
| Results|| |
The study was conducted on 120 patients; they were randomly divided into four groups of 30 patients each. The demographic data (age, sex, and BMI), ASA status, and surgery duration were comparable between the studied groups (P>0.05) ([Table 1]).
Apart from the preoperative period, there were statistically significant differences as regards changes in the HR between the three studied groups (magnesiums sulfate, dexmedetomidine, and lignocaine) and the control group throughout the study (P<0.001). No statistically significant difference in HR changes was observed between magnesium sulfate, dexmedetomidine during the study (P>0.05) ([Table 2] and [Figure 1]).
|Figure 1 Line chart shows the heart rate at various time intervals among the four groups. Data presented as mean±SD: (a) comparison with the control group (C), (b) difference between magnesium and lignocaine groups, (c) difference between dexmedetomidine and lignocaine groups. *Significant at a P value of less than or equal to 0.05.|
Click here to view
Regarding MAP changes, statistically significant differences were observed between the three studied groups (magnesium sulfate, dexmedetomidine, and lignocaine) and control group all over the study (P<0.001) except at the preoperative period (P>0.05). The differences in MAP changes between each of magnesium, dexmedetomidine, and lignocaine during the study were statistically significant (P<0.001) except at the preoperative period (P>0.05). However, there was no statistically significant difference in MAP changes between magnesium sulfate and dexmedetomidine throughout the study (P>0.05) ([Table 3] and [Figure 2]).
|Table 3 Changes in the mean arterial blood pressure among the four study groups|
Click here to view
|Figure 2 Line chart shows mean arterial pressure (MAP) at various time intervals in the four groups. Data presented as mean±SD: (a) comparison with the control group (C), (b) difference between magnesium and lignocaine groups, (c) difference between dexmedetomidine and lignocaine groups. *Significant at a P value of less than or equal to 0.05.|
Click here to view
Bradycardia was observed in six (24%) patients in the dexmedetomidine group and two (8%) patients of the magnesium sulfate group; they were treated with atropine sulfate 0.6 mg intravenous. Hypotension was observed in five (20%) patients receiving dexmedetomidine; it responded to the administration of ephedrine sulfate 6 mg intravenously; 10 (40%) patients of the control group developed hypertensive response throughout pneumoperitoneum, managed with nitroglycerine infusion. No side effects were observed in group L ([Table 4]).
| Discussion|| |
In the present study, the effects of magnesium sulfate, dexmedetomidine, and lignocaine on the hemodynamic responses were studied in patients undergoing LC. The HR and MAP changes were found to be greater in both the lignocaine and control groups than the dexmedetomidine and magnesium sulfate groups after drug administration, after induction, after intubation, throughout pneumoperitoneum at 10 min intervals, PP and in the postoperative period after 10 min with highly significant difference. This is important because it has been reported that persistent intraoperative hypertension of more than or equal to 20 mmHg was associated with a higher incidence of cardiac ischemia, myocardial infarction, and death ,.
Our results coincide with those of Jee et al.  who studied 32 patients undergoing LC to investigate the effect of magnesium sulfate 50 mg/kg over 2–3 min on hemodynamic stress responses induced by pneumoperitoneum and they found that HR increase, and systolic and diastolic arterial pressures were lower in the magnesium group at 10, 20, and 30 min PP than those in the control group (P<0.05), and they explained their findings by that hypertension attenuation was seemingly linked to inhibiting the release of catecholamines and/or vasopressin, and magnesium sulfate was known to have a relaxing effect on vascular smooth muscles ; moreover, in support to our results, Kalra and colleagues recruited 120 patients undergoing elective LC and they reported that administration of magnesium sulfate or clonidine was associated with attenuation of hemodynamic response to pneumoperitoneum, and concluded that each of magnesium sulfate 50 mg/kg and clonidine 1 μg/kg could maintain stability of the hemodynamic response; however, another study stated that clonidine 1.5 μg/kg could blunt the hemodynamic fluctuations during pneumoperitoneum more efficiently .
In the current study, the recorded beneficial effect of administered dexmedetomidine (an α-2 adrenergic agonist) coincides with Tripathi et al. , who conducted a prospective, randomized, controlled study on 90 adults planned for LC, and they stated that the alpha-2 adrenergic receptor agonist group (clonidine 2 µg/kg intravenous over 30 min as loading) has shown promising results for attenuation of hemodynamic response associated with laparoscopic surgery during intubation, pneumoperitoneum, and extubation as compared with the control group (P<0.001). Moreover, Yu et al. , reported that oral clonidine 150 µg administered as premedication was beneficial for hemodynamic stability maintenance throughout pneumoperitoneum, when routinely used in laparoscopic surgeries. On the other hand, some authors observed the significant incidence of bradycardia and hypotension when they used intravenous clonidine 3 µg/kg over a period of 15 min before induction and 2 µg/kg/min by continuous intraoperative infusion . This can be explained by the difference in the doses administered.
In accordance to our results, dexmedetomidine was investigated by Srivastava et al.  and they found that it was more efficient than esmolol in maintaining the hemodynamic response stability to pneumoperitoneum during the LC procedure.
On the other hand, Gulabani et al.  examined 90 consecutive adults, and they reached the conclusion that dexmedetomidine 1 µg/kg adequately diminishes the hemodynamic response to laryngoscopy and endotracheal intubation by more than 0.5 µg/kg of the same drug combined with lignocaine 1.5 mg/kg. In our study, we used the lower dose of dexmedetomidine of only 0.5 µg/kg, and the dose has produced the desirable effects of attenuating the hemodynamic response without excess side effects.
Koppert et al.  studied the perioperative local anesthetic lidocaine infusion effects in patients submitted to major abdominal surgeries starting with a loading dose of intravenous 1.5 mg/kg lidocaine over 30 min, and infusion was continued for 1 h after the termination of surgery; however, the authors found no intergroup difference as compared with the control group in sedation scores. This can be compared with our results.
In our study, reversible bradycardia and hypotension were recorded in the dexmedetomidine group in 24 and 20% of the studied patients, respectively. Interestingly, none of them required nitroglycerine infusion, while 10 (40%) patients in the control group developed hypertensive response and received nitroglycerin infusion. This can be compared with a previous study  as they reported that intravenous clonidine 2 µg/kg, 30 min administered before induction was safe and promising in preventing the hemodynamic fluctuation response during LC, whereas 14 patients in the control group developed hypertensive response and received nitroglycerin.
| Conclusion|| |
We report dexmedetomidine and magnesium sulfate to attenuate the hemodynamic stress responses more than lignocaine during LC (P<0.001). The dose requirements of intraoperative fentanyl could be reduced in the dexmedetomidine and magnesium sulfate groups.
The authors are thankful to the nurses, the anesthesia residents, and physicians for their cooperation.
Place of the study: Al Azhar University Hospitals.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gerges FJ, Kanazi GE, Jabbour-Khoury SI. Anaesthesia for laparoscopy: a review. J Clin Anesth 2006; 18:67–78.
Leonard IE, Cunningham AJ. Anaesthetic consideration for laparoscopic cholecystectomy. Best Pract Res Clin Anaesthesiol 2002; 16:1–20.
Larsen JF, Svendsen FM, Pedersen V. Randomized clinical trial of the effect of pneumoperitoneum on cardiac function and hemodynamics during laparoscopic cholecystectomy. Br J Surg 2004; 91:848–854.
Joris JL, Hamoir EE, Hartstein GM, Meurisse MR, Hubert BM, Charlier CJ et al.
Hemodynamic changes and catecholamine release during laparoscopic adrenalectomy for pheochromocytoma. Anesth Analg 1999; 88:16–21.
Joris JL, Chiche JD, Canivet JL, Jacquet NJ, Legros JJ, Lamy ML. Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine. J Am Coll Cardiol 1998; 32:1389–1396.
Koivusalo AM, Scheinin M, Tikkanen I, Yli-Suomu T, Ristkari S, Laakso J et al.
Effects of esmolol on haemodynamic response to CO2 pneumoperitoneum for laparoscopic surgery. Acta Anaesthesiol Scand 1998; 42:510–517.
Lentschener C, Axler O, Fernandez H, Megarbane B, Billard V, Fouqueray B et al.
Haemodynamic changes and vasopressin release are not consistently associated with carbon dioxide pneumoperitoneum in humans. Acta Anaesthesiol Scand 2001; 45:527–535.
Herroeder S, Schӧnherr ME, De Hert SG, Hollmann MW. Magnesium − essentials for anesthesiologists. Anesthesiology 2011; 114:971–993.
Do SH. Magnesium: a versatile drug for anesthesiologists. Korean J Anesthesiol 2013; 65:4–8.
Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and perioperative fentanyl. Br J Anaesth 1992; 68:126–131.
Market E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg 2008; 95:1331–1338.
Charlson ME, MacKenzie CR, Gold JP, Ales KL, Tompkins M, Fairclough GP et al.
The preoperative and intraoperative hemodynamic predictors of postoperative myocardial infarction or ischemia in patients undergoing noncardiac surgery. Ann Surg 1989; 210:637–648.
Jee D, Lee D, Yun S, Lee C. Magnesium sulphate attenuates arterial pressure increase during laparoscopic cholecystectomy. Br J Anaesth 2009; 103:484–489.
Delhumeau A, Granary JC, Cottineau C, Bukowski JG, Corbeau JJ, Moreau X. Comparison of vascular effects of magnesium sulfate and nicardipine during extracorporeal circulation. Ann Fr Anesth Reanim 1995; 14:149–153.
Kalra NK, Verma A, Agarwal A, Pandey HD. Comparative study of intravenously administered clonidine and magnesium sulfate on hemodynamic responses during laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol 2011; 27:344–348.
] [Full text]
Tripathi DC, Shah KS, Dubey SR, Doshi SM, Raval PV. Hemodynamic stress response during laparoscopic cholecystectomy: effect of two different doses of intravenous clonidine premedication. J Anaesthesiol Clin Pharmacol 2011; 27:475–480.
Yu HP, Hseu SS, Yien HW, Teng YH, Chan KH. Oral clonidine premedication preserves heart rate variability for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Scand 2003; 47:185–190.
Altan A, Turgut N, Yildiz F, Turkmen A, Ustun H. Effect of magnesium sulphate and clonidine on propofol consumption, haemodynamics and postoperative recovery. Br J Anaesth 2005; 94:438–441.
Srivastava VK, Nagle V, Agrawal S, Kumar D, Verma A, Kedia S. Comparative evaluation of dexmedetomidine and esmolol on hemodynamic responses during laparoscopic cholecystectomy. J Clin Diag Res 2015; 9:UC01–UC05.
Gulabani M, Gurha P, Dass P, Kulshreshtha N. Comparative analysis of the efficacy of lignocaine 1.5 mg/kg and two different doses of dexmedetomidine (0.5 μg/kg and 1 μg/kg) in attenuating the hemodynamic pressure response to laryngoscopy and intubation. Anesth Essays Res 2015; 9:5–14.
Koppert W, Weigand M, Neumann F, Sittl R, Schuettler J, Schmelz M et al.
Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg 2004; 98:1050–1055.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]