Volume 13 Issue 1

Table of Content - Volume 13 Issue 1 -January 2020

Effects on nondepolarizing muscle relaxant by different doses of magnesium sulphate to conduct relaxant anaesthesia

Moona Abdul Kadiru¹, Keerthi Premchandran^2*, Ravi Kumar³

¹Assistant Professor, ³Professor, Department of Anaesthesia, MMCH, Modakkallur, Calicut, Kerala, INDIA.

²Junior Consultant Anaesthesia, District Hospital Kannur, Kannur, Kerala, INDIA.

Email: kpremchandran@rocketmail.com

Abstract Background and Objectives: Magnesium sulphate is used during anaesthesia for its antihypertensive/ antiarrhythmic properties and attenuating the response to endotrachial intubation and as an anticonvulsant for women with eclampsia. At the motor nerve terminal, MgSO4 inhibits acetylcholine release. Thus, it enhances the effect of neuromuscular blocking agents. The current study determines the effect of magnesium sulphate pre-treatment on the onset, duration and recovery from non-depolarizing muscle relaxation during relaxant anaesthesia. Method: 105 patients satisfying the inclusion criteria were divided into three groups(groups A,B and C) of 35 each based on lot method. Magnesium sulphate (60mg/kg IV) was given fifteen minutes before induction in group A, magnesium sulphate (40mg/kg IV) was given fifteen minutes before induction in group B and the third group was taken as the control group C. Patients were preoxygenated and induced with 2mg/kg of propofol followed by 0.1mg/kg vecuronium. The onset, duration and recovery relating vecuronium was monitored using a peripheral nerve stimulator using train-of-four stimulus and response assessed visually. Results: There was no significant differences in patient charecteristics between the three groups. The results showed a significant difference between the three groups on the onset, duration and recovery from nondepolarizing muscle relaxants. Magnesium sulphate 60mg/kg IV(group A) is the most effective dose in acceleration of the neuromuscular blockade when compared to group B and group C. Conclusion: Monitoring of neuromuscular function and reduction in dose of vecuronium is required when using these two drugs in combination.

Key Words: Magnesium sulphate; pretreatment; nondepolarizing muscle relaxant

INTRODUCTION

Magnesium sulphate is a drug with diverse clinical applications. Magnesium homeostasis is very important for normal body functioning. Its physiological role is due to its calcium channel blocking properties at smooth muscle, skeletal muscle and conduction system levels. The analgesic properties are due to n-methyl daspartate receptor blocking action. It is beneficial in acute myocardial infarction, prevention of heart rhythm disturbances, preeclampsia and eclampsia, tetanus and acute asthma. Magnesium sulphate pretreatment potentiates the neuromuscular block induced by nondepolarizing muscle relaxants. High concentrations inhibit calcium channels at presynaptic nerve terminals. It has an inhibitory effect on postjunctional potentials and decreases muscle fiber membrane excitability. Hence in patients receiving magnesium sulphate the dose of nondepolarizing neuromuscular blocker can be reduced and could be titrated with the help of a peripheral nerve stimulator to ensure adequate recovery of neuromuscular function at the end of surgery. This characteristic of magnesium sulphate was utilized in the present study to determine the effects of magnesium sulphate on the onset, duration and recovery from nondepolarizing neuromuscular blockade in relaxant anaesthesia.

MATERIALS AND METHODS

Present study is a randomized controlled clinical study conducted on 105 patients of ASA I and II physical status satisfying the inclusion and exclusion criteria were selected and divided into three groups of 35 each based on lot method.

Inclusion criteria: Adult ASA I and II physical status of either sex. Age between 18 -55 years. Weight – 40 to 65 kg. Those who gave the consent. Cardiovascular System disease. Central Nervous System disease. Endocrine Anomalies. Metabolic Disease. Electrolyte Abnormalities. Age group 18 - 55 years. Patient refusal. Use of vasopressors. Pregnant patients

Statistical analysis –Descriptive statistics such as percentage, mean and standard deviation were used to describe the variables used in the study. One way ANOVA statistics was used to compare quantitative variables among the three different groups and chi square statistics used to compare categorical variables among the groups. Comparison of ordinal variables used in the study such as onset, duration and recovery from non depolarizing neuromuscular blockade among the groups were carried out using Scheffe Multiple Comparisons a Post Hoc test. SPSS 17.0 version was used to analyse data.

Drawback of the study- The peripheral nerve stimulator used in our hospital cannot measure T1 amplitude or TOF ratio or recovery index. Hence the twitch response of the left hypothenar muscle to nerve stimulation was used for dosing of vecuronium. Intubation was done when there was no response to stimulation. Supplemental doses of vecuronium were given when there were 2-3 twitches. Reversal was given when the twitch response was 3-4.

OBSERVATIONS AND STATISTICAL ANALYSIS

The study was conducted on 105 patients who met the inclusion criteria. They were divided into 3 groups of 35 each based on lot method.

Group A :- IV 60mg/kg Mgso4 in 100ml NS

Group B :- IV 40mg/kg Mgso4 in 100ml NS

Group C :- IV 100ml NS as control

The results were analysed and are as follows

Table 1: Comparison of sex based on group

Sex	Group A		Group B		Group C		Chi Square	p
	Count	Percent	Count	Percent	Count	Percent

Male	12	34.3	9	25.7	13	37.1	1.13	0.568
Female	23	65.7	26	74.3	22	62.9

Table 2: Comparison of age based on group

Age	Group A	Group B	Group C		Group A	Group B	Group C
Age	Count	Percent	Count		Percent	Count	Percent
<=30	20	57.1	13		37.1	14	40.0
31 – 40	8	22.9	10		28.6	11	31.4
>40	7	20.0	12		34.3	10	28.6
Mean ± SD	32.3 ± 8.3			36.6 ± 11.3		35.1 ± 11

F = 1.6, p = 0.206

Table 3: Comparison of weight based on group

Group	Mean	SD	N	t	p
Group A	55.9	6.9	35
Group B	58.7	5.3	35	1.45	0.241
Group C	57.3	8.2	35

Table 4: Comparison of pulse rate based on group

Group	Mean	SD	N	F	p	Scheffe Multiple Comparisons
						Pair	F`	p
Group A	78.3	3.2	35			A andB	0.4	0.667
Group B	79.1	3.8	35	9.73**	0.000	A and C	5.4**	0.006
Group C	75.4	4.0	35			B and C	8.8**	0.000

**: - Significant at 0.01 level

Table 5: Comparison of systolic blood pressure based on group

Group	Mean	SD	N	F	p
Group A	113.6	13.3	35	0.98	0.377
Group B	116.3	12.9	35
Group C	118.3	16.0	35

Table 6: Comparison of diastolic blood pressure based on group

Group	Mean	SD	N	F	p
Group A	75.1	5.1	35	0.5	0.609
Group B	76.0	5.0	35
Group C	76.3	4.9	35

Table 7: Comparison of ASA based on group

ASA	Group A		Group A				Chi Square	p
ASA	Count	Percent	Count	Percent	Count	Percent	Chi Square	p
I	34	97.1	24	68.6	32	91.4	13.07^**	0.001
II	1	2.9	11	31.4	3	8.6	13.07^**	0.001

**: - Significant at 0.01 level

Table 8: Comparison of onset of neuromuscular blockade based on group

Group	Mean	SD	N	F	p	Scheffe Multiple Comparisons
						Pair	F`	p
Group A	128.8	10.5	35			A and B	16.9**	0.000
Group B	138.8	5.1	35	325.07**	0.000	A and C	297.8**	0.000
Group C	170.7	4.3	35			B and C	173**	0.000

**: - Significant at 0.01 level

Table 9: Comparison of clinical duration of action based on group

Group	Mean	SD	N	F	p	Scheffe Multiple Comparisons
						Pair	F`	p
Group A	47.6	6.0	35			A and B	22.2**	0.000
Group B	39.8	4.3	35	25.71**	0.000	A and C	15.9**	0.000
Group C	41.0	4.3	35			B and C	0.5	0.598

**: - Significant at 0.01 level

Table 10: Comparison of neuromuscular recovery based on group

Group	Mean	SD	N	F	p	Scheffe Multiple Comparisons
						Pair	F`	p
Group A	17.1	2.1	35			A andB	101**	0.000
Group B	11.7	1.3	35	345.34**	0.000	A and C	344.6**	0.000
Group C	7.1	1.3	35			B and C	72.5**	0.000

**: - Significant at 0.01 level

Table 8.11: Distribution of Side effects based on group

	Group A		Group B		Group C
SE	Count	Percent	Count	Percent	Count	Percent
No	35	100.0	35	100.0	35	100.0
Yes	0	0.0	0	0.0	0	0.0

DISCUSSION

Magnesium sulphate(MgSO4) is increasingly used as an adjuvant to general anesthesia, mainly for haemodynamic control and nociception modulation. MgSO4 may enhance the action of non-depolarizing neuromuscular blockers by reducing end plate sensitivity and decreasing muscle fiber excitability. The increasing interest in therapeutic uses of MgSO4 in anaesthesia and intensive care unit mandate an independent study for its neuromuscular effect and its possible interaction with non-depolarizing muscle relaxants. The present study was a randomized controlled clinical study. 105 patients satisfying the inclusion criteria were divided into 3 groups of 35 each based on lot method. The purpose of the study was to compare the efficacy of two different premedication regime of magnesium sulphate that is 60mg/kg versus 40mg/kg magnesium sulphate on the speed of onset, duration and recovery from neuromuscular blockade during relaxant anaesthesia. . Two different doses of magnesium sulphate were chosen for study because individual studies relating to their efficacy in accelerating the speed of onset of non depolarizing neuromuscular blockade , prolongation of neuromuscular blockade and recovery were performed earlier but both were not compared. In Group A 60mg/kg of magnesium sulphate in 100ml normal saline was given as premedication fifteen minutes before induction, in Group B 40mg/kg of magnesium sulphate in 100ml normal saline was given as premedication fifteen minutes before induction and Group C was the control group and received 100ml normal saline fifteen minutes before induction. The neuromuscular monitoring was done using a peripheral nerve stimulator which was set to deliver a train of four stimuli and the response assessed visually. There were no significant differences in patient characteristics between the three groups. Among 105 patients studied, mean age in Group A, Group B, Group C were 32.3 ± 8.3, 36.6 ± 11.3 and 35.1 ± 11respectively and a p value of 0.206 (p>0.05) which shows that there were not much significant differences between the 3 groups in relation to age which could have affected the study. Comparision of sex and weight among the 105 patients revealed a p value of 0.568 (p>0.05) and 0.241 (p>0.05) respectively which shows that the sex and weight of the participants has not influenced the study. Comparison of pulse rate between Group A and Group B (p=0.667) has not influenced the study. Neither the systolic blood pressure SBP(p=0.337) nor the diastolic blood pressure DBP(p=0.609) of the patients had impact on the study. Comparing the ASA status between the three groups showed a significant difference between the three groups ( p = 0.001 ). So the ASA status of the patients are statistically significant in the outcome of the study.Comparison on the speed of onset of nondepolarizing neuromuscular blockade between the three groups showed a significant difference between the three groups ( p=0.000 ). The onset of nondepolarizing neuromuscular blockade was fastest in Group A ( p = 0.000 ) with mean onset time of 128.8 seconds. The mean onset time in Group B is 138.8 seconds. The onset of blockade was slowest in Group C ( p = 0.000 ) with a mean onset time of 170.7 seconds. Comparison of clinical duration of nondepolarizing neuromuscular blockade showed a significant difference between the three groups ( p = 0.000 ). The duration of neuromuscular blockade was prolonged in Group A when compared to Group B ( p = 0.000 ) and Group C ( p = 0.000 ).The mean duration of blockade was for 47.6 minutes in Group A. But there was no significant difference between Group B and Group C ( p = 0.598) on the duration of neuromuscular blockade and the mean duration being 39.8 and 41 minutes respectively. Comparison of clinical sign of neuromuscular recovery between the three groups showed a significant difference among them ( p = 0.000 ). Group A took the longest time when compared to Group B ( p = 0.000 ) and Group C ( p = 0.000 ). The mean onset time of recovery from non depolarizing muscle relaxant after reversal is 17.1 minutes in Group A, 11.7 minutes in Group B, 7.1 minutes in Group C. There were no side effects in all the three groups like bradycardia , hypotension and arrhythmias. Thus from the results obtained Group A and Group B receiving 60mg/kg and 40mg/kg magnesium sulphate respectively as premedication had faster onset of neuromuscular blockade when compared to control group with vecuronium as the nondepolarizing muscle relaxant. Magnesium sulphate also prolonged the duration of neuromuscular blockade. The results are supported by similar studies done by Fuchs-Buder et al in 19961 where he concluded that pre-treatment with MgS04 before vecuronium accelerated the onset time, and prolonged the clinical duration of neuromuscular block. The study conducted by Kaussman et al in 1997² to determine the effects of prior administration of MgSO4 60 mg/kg intravenous, on the onset and duration of rocuronium induced neuromuscular block also supports our results. The other studies which are of our favour are the study of Lamp et al in 19933, and Azer et al in 2002⁴, where speed of onset of atracurium was increased markedly, when patients were pre-treated with MgSO4. Shortest onset time and longest duration of neuromuscular blockade was seen with 60mg/kg magnesium sulphate premedication. This dose of MgSO4 used in the current study was considered safe by Tramer et al in 1996⁵. The longest time for neuromuscular recovery was seen in Group A premedicated with 60mg/kg magnesium sulphate. This is in accordance with the study done by Fuchs-Buder et al in 1999⁶ who investigated the dose-effect relationship of neostigmine, in antagonizing vecuronium induced neuromuscular block, with and without MgSO4 pre-treatment. The study shows that when MgSO4 was used with vecuronium, the dose of vecuronium required was less for the same duration of surgery. Adequate neuromuscular blockade monitoring is mandatory in patients pre-treated with MgSO4. No adverse effects were reported by any of the participants.

CONCLUSION

The study concluded that magnesium sulphate pre-treatment, before non-depolarizing muscle relaxant, accelerated the speed of onset of neuromuscular block necessary for intubation of the trachea. Magnesium sulphate in the presence of non-depolarising muscle relaxant, intensified and prolonged the neuromuscular blockade and recovery. The most effective dose for neuromuscular blockade is 60mg/kg. So, monitoring of neuromuscular function and reduction in dose of vecuronium are required when using these two drugs in combination

REFERENCES

Fuchs-Buder T, Tassonyi E. Magnesium sulphate enhances residual neuromuscular block induced by vecuronium. Br J Anaesth 1996;76:565-6
Kussman B, Shorten G, Uppington J, Comunale ME. Administration of magnesium sulphate before recuronium: effects on speed of onset and duration of neuromuscular block. Br J Anaesth. 1997;79:122-4.
Lampl E, Dandoy M. Priming of atracurium with magnesium. Br J Anaesth 1993;70:139
Azer NFT. The effect of intraoperative magnesium sulphate infusion on the course of neuromuscular blockade of atracurium. Journal of the Egyptian Nat Cancer Inst 2002;14:137-44.
Tramer MR, Schneider J, Marti R, Rifat K. Role of MgSO4 in postoperative analgesia. Anesthesiology 1996;84:349-47
Fuchs-Buder T, Ziegenfub T. Antagonism of vecuronium induced neuromuscular block in patients pre-treated with magnesium sulphate: dose-effect relationship of neostigmine. Br J Anasth 1999;82:61-5.

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