Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 8  |  Issue : 2  |  Page : 153-159

Effect of intraperitoneal magnesium sulfate on hemodynamic changes and its analgesic and antiemetic effect in laparoscopic cholecystectomy


1 Department of Anesthesiology, Intensive Care, and Pain Management, Ain Shams University, Cairo, Egypt
2 Department of Anesthesiology and Intensive Care, October 6 University, Cairo, Egypt
3 Department of Surgery, October 6 University, Cairo, Egypt

Date of Submission27-May-2014
Date of Acceptance16-Aug-2014
Date of Web Publication8-May-2015

Correspondence Address:
Rania M Ali
Department of Anesthesiology, Intensive Care, and Pain Management, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.156661

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  Abstract 

Background
Laparoscopic cholecystectomy is now a routinely performed procedure that has replaced conventional open cholecystectomy. Magnesium sulfate (MgSO 4 ) has been used in the management of postoperative pain through different routes. This prospective randomized, double-blind study aimed to assess the effect of MgSO 4 on hemodynamic response and its analgesic and antiemetic effects in patients undergoing laparoscopic cholecystectomy.
Patients and methods
Sixty adult patients scheduled for elective cholecystectomy under general anesthesia were randomly allocated into two groups: group M and group C. Patients in group M received 20 ml of MgSO4 10% instilled intraperitoneally after pneumoperitoneum was created before any dissection, whereas group C patients received the same volume of 0.9% sodium chloride.
Results
Hemodynamic parameters were significantly higher in group C compared with group M at 10, 20, and 30 min after pneumoperitoneum, and at the time of extubation. Recovery characteristics in terms of extubation time (9.70 ± 1.12 vs. 6.77 ± 0.73), emergence time (19.83 ± 1.44 vs. 15.93 ± 1.60), and time to reach full Aldrete score (43.03 ± 8 vs. 21.4 ± 4.7) were significantly longer in group M compared with group C. Mean pain scores (visual analog scale) were significantly lower in group M compared with group C during the first 6 postoperative hours, and the time to first analgesic requirement was longer in group M (9.2 ± 3 h) compared with group C (2.4 ± 1.3 h). Postoperative nausea was significantly higher in group C (63.3%) compared with group M (36.6%). There was no incidence of vomiting in group M compared with 13.3% in group C.
Conclusion
Intraperitoneal instillation of MgSO 4 attenuated the hemodynamic stress response to pneumoperitoneum, as well as reduced postoperative pain, nausea, and vomiting in patients undergoing laparoscopic cholecystectomy.

Keywords: intraperitoneal, laparoscopic cholecystectomy, magnesium sulfate


How to cite this article:
Ali RM, Rabie AH, Elshalakany NA, El Gindy TM. Effect of intraperitoneal magnesium sulfate on hemodynamic changes and its analgesic and antiemetic effect in laparoscopic cholecystectomy. Ain-Shams J Anaesthesiol 2015;8:153-9

How to cite this URL:
Ali RM, Rabie AH, Elshalakany NA, El Gindy TM. Effect of intraperitoneal magnesium sulfate on hemodynamic changes and its analgesic and antiemetic effect in laparoscopic cholecystectomy. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2021 Apr 20];8:153-9. Available from: http://www.asja.eg.net/text.asp?2015/8/2/153/156661


  Introduction Top


Laparoscopic cholecystectomy is considered the procedure of choice for symptomatic cholelithiasis. However, it is not completely safe in the elderly and in patients with comorbidities. Alterations in hemodynamics during laparoscopy and creation of pneumoperitoneum can be potentially hazardous. Pneumoperitoneum for laparoscopic surgery increases arterial pressure, heart rate, and systemic vascular resistance [1] .

Although the intensity of postoperative pain is low after laparoscopic surgeries, patients still experience postoperative pain and postoperative nausea and vomiting, which become significant complications as they reduce the patient's satisfaction and increase costs. Acute pain after laparoscopic cholecystectomy has three different components: incisional pain (somatic pain), visceral pain (deep intra-abdominal pain), and shoulder pain (presumably referred visceral pain) [2] . Postoperative nausea and vomiting is a commonly observed phenomenon after laparoscopic procedures. Its incidence increases depending on the anesthetic techniques used.

Intraperitoneal administration of some drugs can be effective for pain relief after laparoscopic surgery. Intraperitoneal instillation of local anesthetics and opioids is gaining popularity for better pain relief [3] . Absorption from a large peritoneal surface may be the mechanism of analgesia [4] . Magnesium inhibits calcium entry into the cell through a noncompetitive blockade of the N-methyl-d-aspartate (NMDA) receptor [3] . Magnesium is also a physiological calcium antagonist at different voltage-gated channels [5] . Administration of magnesium sulfate (MgSO 4 ) through different routes has been used in anesthetic practice for decreasing perioperative pain. MgSO 4 also has been used to attenuate the adverse hemodynamic changes associated with pneumoperitoneum and improve the quality of recovery [6] .

As intraperitoneal instillation of MgSO 4 might attenuate the hemodynamic stress response to pneumoperitoneum and improve the patient's satisfaction by decreasing postoperative complications, this study aimed to assess the effect of early instillation of MgSO 4 before any dissection on hemodynamic response and its analgesic and antiemetic effects in patients undergoing laparoscopic cholecystectomy.


  Patients and methods Top


The study was approved by the ethics committee of October 6 University education hospital, and all patients gave their written informed consent. Sixty patients with ASA physical status I-II (aged 18-40 years) scheduled to undergo elective cholecystectomy under general anesthesia were included in this prospective, randomized, placebo-controlled, and double-blinded study. Criteria for exclusion were presence of psychiatric disease, morbid obesity, heart block, renal impairment, and severe chronic disease.

Patients were randomly allocated into two groups, comprising 30 patients each, using a computer-generated randomization list: group M and group C. Patients in group M received 20 ml of MgSO 4 10% instilled intraperitoneally by the surgeon after pneumoperitoneum was created before any dissection, and patients in group C received the same volume of 0.9% sodium chloride. Neither opiates nor local anesthetics were added to the study solution. The solutions were prepared by the coordinator of the study, and the anesthetist in charge of the patients during the operation was unaware of the study drug.

Before operation, the patients were instructed to use a 10 cm visual analog scale (VAS) (endpoints labeled 'no pain' and 'worst possible pain'). Incisional pain was defined as superficial pain in the abdominal wall, or wound pain. Intra-abdominal pain was defined as deep, dull, and difficult to localize pain inside the abdomen, or resembling biliary colic. Shoulder pain was defined as pain in the shoulder.

A standard anesthetic technique was followed for all patients. No premedication was given. On arrival at the operating room, routine intraoperative monitoring (ECG, noninvasive blood pressure, pulse oximetry, and capnography) was established. General anesthesia was induced with intravenous fentanyl (1-2 μg/kg) and propofol (2.0 mg/kg). Orotracheal intubation was facilitated with atracurium (0.5 mg/kg). Patients were maintained with 50% O 2 in air, 0.5-1 vol% isoflurane, and 0.1 mg/kg atracurium for maintenance of muscle relaxation. Muscle relaxation was maintained at a train-of-four count of 1 throughout surgery using a peripheral nerve stimulator. Minute ventilation was adjusted to keep end-tidal PCO 2 at 35-45 mmHg.

After anesthesia induction, pneumoperitoneum was created by insufflation of CO 2 to maintain intra-abdominal pressure between 12 and 15 mmHg throughout the surgical procedure. The surgeon then instilled 20 ml of the study solution intraperitoneally before any dissection. At the end of the surgery, residual neuromuscular blockade was reversed with neostigmine 0.05 mg/kg and atropine 0.01 mg/kg intravenously after return of protective reflexes. After completion of the surgical procedure patients were transferred to the postanesthetic care unit (PACU). After achieving an Aldrete score of 9 or higher, patients were discharged from the PACU to an intermediate care unit for 24 h. The following measures were assessed and recorded:

  1. Arterial pressure and heart rate, measured before induction (baseline), after intubation (Tin), before pneumoperitoneum (P0), every 10 min after pneumoperitoneum for 30 min (P10, P20, and P30), after extubation (Tex), and before discharge from the operating room.
  2. Surgical duration, corresponding to the time from skin incision until skin closure.
  3. Extubation time (from the end of anesthesia to extubation).
  4. Time of emergence (time to first response to a simple verbal command following discontinuation of isoflurane).
  5. Baseline plasma magnesium levels after anesthesia induction, through a blood sample. A second blood sample was taken 15 min after intraperitoneal instillation of the study solution.
  6. Modified Aldrete Score 7 evaluated in the PACU every 5 min until discharge. Patients were ready for discharge upon achieving an Aldrete score of 9 or higher. Time to achieve an Aldrete score of at least 9 corresponded to the time from arrival at the PACU until discharge to the intermediate care unit.
  7. Patient-evaluated incisional, intra-abdominal, and shoulder pain at the first, second, third, sixth, and 24th postoperative hour using VAS. When the VAS score was 4 or higher, patients were given 50 mg intramuscular pethedine.
  8. The time to first analgesic administration, number of analgesic requests in the first 24 h, and total analgesic requirement during the first postoperative 24 h.
  9. The occurrence of any adverse events, including bradypnea (respiratory rate (RR) <10 bpm), SpO2 reaching 92% or less, sedation, hypotension (mean arterial pressure (MAP) <55 mmHg), bradycardia (heart rate (HR) <60 bpm), nausea, and vomiting.
  10. Nausea was assessed at the same intervals of VAS using a scoring system (0 = none, 1 = mild, 2 = moderate, 3 = severe). Patients suffering from vomiting or who rated their nausea at level 2 or more received 4 mg intravenous ondansetron and their postoperative antiemetic needs were recorded.
  11. Sedation was also assessed at the same intervals of VAS using a four-point scale (0 = alert, 1 = quietly awake, 2 = asleep but easily aroused, and 3 = deep sleep).
Statistical analysis

Sample size calculation was done from previous study results by assuming that a reduction of 2.0 in the treated group relative to control value in VAS would be detectable using a sample size of 28 patients per group with 80% power and α level of 0.05. Thirty patients were included to replace any dropouts. Statistical analysis was carried out with SPSS for windows, version 18 (SPSS Inc., Chicago, Illinois, USA). Significance test was done with independent samples t-test, intragroup comparison was done using paired t-test and Chi-square test was performed for categorical data. Results are displayed as mean ± SD, median and interquartile range, or numbers of patients.


  Results Top


Sixty patients scheduled for elective cholecystectomy under general anesthesia were enrolled in the study and randomly allocated into two groups: group M and group C. Patients in group M received 20 ml of MgSO 4 10%, whereas patients in group C received the same volume of 0.9% sodium chloride in a double-blinded manner.

Both groups were comparable regarding demographic data as well as surgical duration ([Table 1]).
Table 1 Patient characteristics and surgical data

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Baseline serum magnesium concentrations were comparable in the two groups (P = 0.529). Postoperative serum magnesium concentrations in group M were significantly higher (2.24 ± 0.28 mg/dl) as compared with group C (1.93 ± 0.30 mg/dl) and with baseline (1.92 ± 0.32 mg/dl) (P < 0.001) ([Table 2]).
Table 2 Serum magnesium levels

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As regards hemodynamic parameters, baseline mean arterial pressure and heart rate were similar in the two groups. However, mean arterial pressure and heart rate were significantly higher in group C than in group M at 10, 20, and 30 min after pneumoperitoneum, and at the time of extubation ([Figure 1]). Compared with baseline values, mean arterial pressure was higher at 10, 20, and 30 min after pneumoperitoneum and after surgery in group C (P < 0.01).
Figure 1: Hemodynamic parameters during laparoscopic cholecystectomy. Values are expressed as mean (SD). Lines are mean and error bars are SD. * Significant P-value. (a) Heart rate, (b) mean blood pressure.

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Recovery characteristics in terms of extubation time (9.70 ± 1.12 vs. 6.77 ± 0.73) and emergence time (19.83 ± 1.44 vs. 15.93 ± 1.60) were significantly longer in group M compared with group C. Also, time to reach full Aldrete score was significantly longer in group M compared with group C (43.03 ± 8 vs. 21.4 ± 4.7) ([Table 3]).
Table 3 Recovery characteristics

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Median pain scores (VAS) were significantly lower in group M when compared with group C during the first 6 postoperative hours ([Figure 2]). Regarding the pattern of pain, it was predominantly of incisional type (53.3%), followed by intra-abdominal type (33.3%), in group M. In group C, it was predominantly of intra-abdominal type (83.3%) followed by incisional type (70%). Only two patients in group M and three patients in group C complained of shoulder pain ([Table 4]).
Figure 2: Visual Analog Score (VAS) for pain during the first 24 postoperative hours. The middle line in each box represents the median, the outer margins of the box represent the interquartile range, and the whiskers
represent the minimum and maximum for each time point.


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Table 4 Type of pain during the first 24 postoperative hours

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Time to first analgesic requirement was longer in group M (9.2 ± 3 h) than in group C (2.4 ± 1.3 h). Analgesic consumption/patient was higher in group C (80 ± 24.9 mg) than in group M (50 mg), and the difference was statistically significant. Rescue analgesics for postoperative pain control were administered only once in group M, whereas rescue analgesics were administered once in 12 patients (40%) and twice in 18 patients (60%) in group C ([Table 5]).
Table 5 Analgesic profile during the first 24 postoperative hours

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There were no postoperative side effects attributable to the MgSO 4 , such as bradypnea, hypotension, or bradycardia. Postoperative nausea was significantly higher in group C (63.3%) compared with group M (36.6%). There was no incidence of vomiting in group M as compared with four patients in group C (13.3%) ([Table 6]).
Table 6 Nausea score during the first 24 postoperative hours

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Sedation scores were significantly lower in group M when compared with group C during the first 6 postoperative hours ([Figure 3]).
Figure 3: Sedation score during the fi rst 24 postoperative hours (sedation score is expressed as median (IQR). The middle line in each box represents the median, and the outer margins of the box represent
the interquartile range. IQR, interquar tile range.


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  Discussion Top


As laparoscopic cholecystectomy is usually performed as an outpatient procedure [8] , reducing the intensity of postoperative pain and nausea becomes a clinical challenge [9] .

Improved postoperative pain treatment using opioid-sparing regimens [10] may facilitate a high success rate of outpatient laparoscopic cholecystectomy, as both pain and opioids may induce nausea. Acute hemodynamic response usually occurs during the period of the pneumoperitoneum in patients undergoing laparoscopic surgical procedures. These changes are consequent to hypercarbia-induced release of catecholamines [11] , vasopressin, or both [12],[13] . In addition, the shifts in intravascular volume resulting from the trendelenburg position can lead to hemodynamic alterations during laparoscopy.

In this study, the effect of intraperitoneal instillation of MgSO 4 alone in laparoscopic cholecystectomy was evaluated as regards hemodynamics, patient sedation and recovery characteristics, postoperative pain and analgesic requirements, and postoperative nausea and vomiting. Blood magnesium level and the sedation score in the PACU were studied to conclude a safe and effective level of MgSO 4 after peritoneal instillation.

Several analgesic interventions with varying targets and mechanisms have been investigated for their influence on early pain after laparoscopic cholecystectomy. The efficacy of intraperitoneal instillation of local anesthetics, alone or in combination with other drugs, has been demonstrated in numerous studies on laparoscopic cholecystectomy, but there is no consensus regarding the dose, concentration, site, and manner of administration [14] . Intraperitoneal local anesthetics block the visceral afferent signaling, potentially modifying visceral nociception and providing analgesia. Also, absorption of local anesthetics from a large peritoneal surface may be a further mechanism of analgesia [4] . The timing of the administration of the local anesthetic during surgery is a matter of debate. Some trials [4],[15] suggested that early instillation of intraperitoneal local anesthetics provided better postoperative pain control compared with instillation at the end of surgery, but was contradicted by other trials [16],[17] .

Magnesium decreases calcium influx to the cell, and also antagonizes NMDA receptors, which have an important role in neuronal signaling and pain processing in the central nervous system. By blocking this receptor, MgSO 4 decreases postoperative pain due to blockage of both somatic and visceral pain fibers [4],[5] . MgSO 4 has been used in laparoscopic cholecystectomy as an intravenous bolus, continuous infusion [18],[19] , epidural infusion, and in the subarachnoid space [20] . In these studies MgSO 4 improved the quality of analgesia, with fewer requirements for postoperative analgesics. Also, intraperitoneal local anesthetics alone or in addition to MgSO 4 have been shown to improve postoperative pain after laparoscopic cholecystectomy [21],[22] .

MgSO 4 blocks the release of catecholamines from both adrenergic nerve terminals and the adrenal gland. Moreover, magnesium produces vasodilatation by acting directly on blood vessels, and high-dose magnesium attenuates vasopressin-stimulated vasoconstriction and normalizes sensitivity to vasopressin [23],[24] .

Our results showed that MgSO 4 improved the hemodynamic response to pneumoperitonium, surgical stimulation, and extubation. Both the heart rate and the mean arterial BP were significantly lower in group M compared with group C. This was in accordance with the results of Jee et al. [1] , who administered MgSO 4 50 mg/kg intravenously before pneumoperitoneum in patients undergoing laparoscopic cholecysyectomy and found that it effectively attenuated the effects of pneumoperitoneum. Serum magnesium concentrations of at least 2-4 mmol/l (0.8-1.6 mg/dl) are required to exert these effects [25] . In our study, a lower dose of MgSO 4 (20 mg/kg) was used to avoid oversedation and prolonged recovery time. As MgSO 4 has a half-life of 30 min with immediate onset of action after intravenous administration, the serum magnesium level was determined 15 min after intraperitoneal instillation of the study solution, and it reached up to 2.24 ± 0.28 mg/dl.

Patient recovery was longer in group M compared with group C. Both extubation time and emergence time were significantly longer in group M. This prolongation may be due to the potentiating effect of MgSO 4 on neuromuscular blockade induced by nondepolarizing neuromuscular blocking agents [26],[27],[28] . Also, sedation was significantly higher in group M when compared with group C during the first 3 h. Patients required more time to reach an Alderete score of 9 to be discharged from the PACU. This sedation may be due to the depressant effect of MgSO 4 on central nervous system and the antagonism of NMDA receptors. Our results were comparable to those of Kalra et al. [29] , who compared the effect of intravenously administered MgSO 4 and clonidine during laparoscopic cholecystectomy.

In our study, the mean pain scores (VAS) were significantly lower in group M compared with group C during the first 6 postoperative hours. On analysis of the VAS for pain, it was found to be predominantly of the incisional type in both groups (M = 53.3%; C = 83.3%), followed by the intra-abdominal type (M = 33.3%; C = 70%). Shoulder pain was minimal in both groups. Analgesic consumption per patient was higher in group C compared with group M, as rescue analgesics for postoperative pain control were administered only once in group M, whereas it was administered twice in 30% of patients in group C.

The results of several studies are in accordance with ours. Maharjan and Shrestha [22] compared intraperitoneal instillation of bupivacaine, alone and in addition to MgSO 4 . Their results showed that patients who were given intraperitoneal bupivacaine plus MgSO 4 at the end of surgery had better pain relief for a period of 2-5 h compared with patients who were given intraperitoneal bupivacaine alone.

In our study, there was a significant reduction in the incidence of nausea in group M compared with group C. There was no incidence of vomiting in group M compared with 13.3% of patients in group C. The results of Mentes et al. [19] , who used preoperative infusion of MgSO 4 (50 mg/kg) in laparoscopic cholecystectomy, were in agreement with ours, as the incidence of nausea in the magnesium group was lower than in the control group. Magnesium blocks NMDA receptors, which lie in both emetic pathways and structures associated with the final common pathway for vomiting. NMDA antagonists have the potential to be broad-spectrum antiemetics [30] ; however, there are no current data available on the direct effect of MgSO 4 on postoperative nausea and vomiting.


  Conclusion Top


Intraperitoneal instillation of MgSO 4 before any dissection attenuated the hemodynamic stress response to pneumoperitoneum, as well as reduced postoperative pain, nausea, and vomiting in patients undergoing laparoscopic cholecystectomy.


  Acknowledgements Top


Conflicts of interest

None declared.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


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