Efficacy of low dose magnesium sulphate on attenuation of hemodynamic responses to tracheal intubation and carboperitoneum during laparoscopic cholecystectomy- a randomized, double-blind, placebo controlled study

SUMMARY OF THESIS

Name of Speciality                      :                       Anaesthesiology

Name of System of body          :                       Cardiovascular system

Title of Thesis                               :                       Efficacy of low dose intravenous magnesium sulphate on attenuation of hemodynamic responses to carboperitoneum during laparoscopic cholecystectomy.

Year of submission                     :                       2015

Name of candidate                     :                       Dr. Ramesh Subedi

Name of Supervisor                   :                       Dr. Swaran Bhalla

Name of Hospital                        :                       Jaipur Golden Hospital

OBJECTIVES OF THE STUDY

1)         To study the effect of single bolus of low dose (30mg/kg) intravenous magnesium sulphate on intra-operative hemodynamic parameters during laparoscopic cholecystectomy and to compare it with the control group.

2)          To observe the number of interventions, if any required, for episodes of intra-operative hypertension (MAP> 30% of baseline values) or tachycardia (HR>30% of baseline HR) in both the groups.

3)           To observe any unwanted side effects in the intra- and postoperative period such as hypotension (MAP<30% of baseline values) and bradycardia (HR<60/min)

4)           To study the effect of same dose of intravenous magnesium sulphate on incidence of post-operative nausea, vomiting and shivering as compared to the control group.

      

MATERIALS AND METHODS

STUDY AREA

The present study, “Efficacy of low dose intravenous magnesium sulphate on attenuation of hemodynamic responses to carboperitoneum during laparoscopic cholecystectomy†was carried out in the Department of Anaesthesiology of Jaipur Golden Hospital, Rohini Sector-3, New Delhi-110085.

STUDY POPULATION

The study was conducted on patients of both sexes in the age group between 20-60 years and scheduled for elective laparoscopic cholecystectomy under general anaesthesia.

SAMPLE SIZE AND SAMPLE TECHNIQUE

With the reference of available peer study,it was calculated that a sample size of 48 patients (24 in each group) was sufficient to detect a clinically relevant 15% difference in arterial pressure between the study and control  groups after administration of  the study drug. This was done using a two-tailed test with power of 80% and a two sided significance level of  5% (α=0.05, β=0.20). To ensure a power of study more than the desired 80% even in case of less than expected difference observed, we rounded up the calculated number to 60 (30 in each group).

The study was conducted on 60 patients, divided randomly into 2 groups of 30 each.

Group A- Magnesium group (n=30) received intravenous magnesium sulphate 30 mg/kg body weight in 100 mL of normal saline infused over 10 minutes, preoperatively.

Group B- Control group (n=30) received 100 mL of normal saline without magnesium sulphate infused over 10 minutes, preoperatively

The patients were assigned to the two groups using the computer generated random sequence of 1 and 2 (where 1=Magnesium and 2=Control) which was generated on MSExcel software.

DATA COLLECTION TECHNIQUE AND TOOLS

Data was collected peri-operatively by measurement of the parameters consisting of heart rate (HR), surface electrocardiography (ECG), non-invasive blood pressure (NIBP) and arterial oxygen saturation by pulse oximeter (SpO2).Monitoring was carried out using a multiparametermonitor (Datex-OhmedaCardiocap, S5) and measurements were carried outas per the study proforma attached.

STATISTICAL METHODS

 The quantitative data were expressed in terms of mean ± sd and compared between groups using unpaired t-test and within groups across follow-ups using paired t-test.  The qualitative data are expressed as frequencies/percentages and compared between groups using Chi-square or Fisher’s exact test as appropriate.  A p-value <0.05 was considered statistically significant. Statistical Package for Social Sciences (SPSS) version 15.0 software was used for analysis.

 

SALIENT FINDINGS

 This is an interventional study conducted to evaluate the clinical efficacy of low dose of intravenous magnesium sulphate in attenuation of hemodynamic stress response associated with carbon dioxide pneumoperitoneum during laparoscopic cholecystectomiesand its effect on post-operative nausea, vomiting and shivering. The study included sixty patients from 20 to 60 years of age, of either gender and of ASA physical status 1 and 2 scheduled for elective laparoscopic cholecystectomy.They were randomly assigned to one of the 2 groups of thirty patients each in a double blinded manner to receive either intravenous magnesium sulphate 30 mg/kg body weight in 100 mL normal saline (group A) or 100 mL of normal saline (group B), infused over 10 minutes, prior to induction of anesthesia.

The parameters observed were peri-operative hemodynamic variables (heart rate, systolic, diastolic and mean blood pressures) and incidence of any untoward side effects, if any, during the intra- and post-operative period.

In our study, an initial increase in heart rate was observed in both the groups following the 10 minute infusion and it increased further, immediately after intubation. However, 3 minutes later, the heart rate increase in group A (magnesium group) was much less compared to that in group B (control group). Post-pneumoperitoneum, the heart rate in group A showed no significant rise from baseline values whereas in group B, the rise in mean heart rate was significant compared to baseline.

The increase in systolic blood pressure post-intubation, was significant from baseline in both groups A and B but the rise was significantly higher in group B. Again, the systolic blood pressure in group A showed no significant difference from the baseline whereas the rise in systolic blood pressure following pneumoperitoneum in group B was significantly higher compared to baseline and to group A.

The increase in diastolic blood pressure post intubation in the magnesium group was not significant compared to baseline but remained significantly higher in the control group. Following pneumoperitoneum, the diastolic blood pressure remained significantly lower in the magnesium group when compared to the control group and remained so for about 40 minutes post pneumoperitoneum.

The mean arterial pressure in the magnesium group remained comparable to the baseline at 3 minutes post intubation as well as after pneumoperitoneum. The control group showed significant increase in mean blood pressure compared to the baseline as well as to the magnesium group, following intubation and pneumoperitoneum. This trend continued till 40 minutes after pnemoperitoneum.

After exsufflation, arterial pressures were found to be comparable to baseline levels in both the magnesium and control groups.

We observed that two patients in group A developed hypotension, whereas it was not seen in any patient in group B. This was, however, a statistically insignificant finding and this hypotension was managed with intravenous ephedrine 3 mg in titrated doses. No episode of bradycardia was noted in any of the two groups in our study.

The incidence of post-operative nausea and vomiting was much higher in the control group than in the magnesium group. Also, only 3.33% of patients in group A complained of shivering whereas in group B, the incidence of shivering was 33.33% which was a statistically significant finding.

             

CONCLUSION

The following conclusions and inferences were drawn from our study:

1.      Pre-induction administration of intravenous magnesium sulphate in the dose of 30 mg/kg body weight attenuates hemodynamic stress response to laryngoscopy and endotracheal intubation but is associated with a mild increase in heart rate, which is however, clinically insignificant.

2.      The same single bolus dose of magnesium sulphate also provides significant hemodynamic stability during laparoscopic cholecystectomy.

3.      Magnesium sulphate at this dose, is not associated with significant intra-operative adverse events adverse effects like hypotension or bradycardia.

4.      Magnesium sulphate premedication has an added benefit of mitigation of post-operative complications such as nausea, vomiting and shivering.

Therefore, intravenous magnesium sulphate in the low dose of 30 mg/kg, administered prior to induction, may be effective in attenuating hemodynamic alterations secondary to laryngoscopy and intubation as well as to pneumoperitoneum created during laparoscopic cholecystectomy.

  

RECOMMENDATIONS

On the basis of our study we recommend following suggestions:

1.     Magnesium sulphate is an effective pharmacological agent for control ofhemodynamic changes during intubation and CO2 pneumoperitoneum.

2.     Magnesium sulphate is almost free from unwanted side effects in the intra-operative periodwhen used in the optimal dose.

3.      Use of low dose magnesium sulphate intra-operatively is associated with added advantage of reduced incidence of post-operative adverse events.

4.      The ready availability and good safety profile of magnesium sulphate together with the versatility of its use in anaesthesia makes it a cost effective agent for use in a set up with limited resources.

5.      Further studies are recommended for studying the recovery profile associated with this low pre-induction dose of magnesium sulphate and associating with serum magnesium levels during the peri-operative period.