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Table of Content - Volume 5 Issue 3 -March 2018




 

Comparative study of intrathecal dexmedetomidine and intrathecal magnesium sulphate used as adjuvants with hyperbaric bupivacaine in lower abdominal and lower limb surgeries

 

Divya Dhananjayan1*, Amrutha Sadasivan K2

 

1Assistant Professor, 2Jr. Resident, Department of Anesthesiology, Academy of Medical Sciences, Pariyaram, Kannur, Kerala, INDIA.

Email: divyadh26@gmail.com

 

Abstract               Background: Subarachnoid block is the most commonly used regional anesthetic technique for lower abdominal and lower limb surgeries. Intrathecal adjuvants have gained popularity with the aim of prolonging the duration and quality of block, better success rate and faster recovery. The purpose of the study was to evaluate the onset and duration of sensory and motor blocks well as perioperative analgesia of dexmedetomidine and magnesium sulphate when given intrathecally with 0.5% hyperbaric bupivacaine for spinal anesthesia. Materials and Methods: A randomized controlled trial in which 90 patients satisfying inclusion criteria were randomly allocated to 3 groups of 30 each (A,B,C ) by lot method. Group A received intrathecally 15mg hyperbaric bupivacaineand 0.1 ml (10mcg) dexmedetomidine while Group B received 15 mg hyperbaric bupivacaine and 0.1 ml (50 mg) magnesium sulphate and Group C received 15 mg hyperbaric bupivacaine plus 0.1ml saline (control). Onset time of sensory and motor block, regression time for sensory and motor block, duration of analgesia, hemodynamic changes and side effects were recorded. The data obtained were statistically analysed. The level of significance used was p<0.05. Results and Discussion: The onset of sensory and motor block was rapid in Group A ( 2.0+/-0.4 and 3.5+/-0.6 min) as compared to both Group B (6.0+/-0.6 and 7.4+/-0.6 min) and Group C (3.9+/-0.4 and 5.1+/-0.5 min). The onset of sensory and motor block was significantly prolonged in Group B when compared to Group A and Group C. Also, duration of sensory and motor block was significantly prolonged in Group A (335.3 +/- 18.3 and 293 +/-13.4 min) than patients in Group B (274.8+/- 13.2 and 232.3+/- 11.5 min ), which was greater than control Group C ( 178.0+/-16.6 and 134.8+/- 15.6 min ). Duration of analgesia was prolonged in Group A (214.7 +/-9.6 min ) and Group B ( 194.7+/-13.1 min ) when compared to Group C ( 150.5 +/-15.1 min). Statistical analysis of data obtained, showed a significant difference between the three groups regarding onset and duration of sensory and motor blockade and duration of analgesia. There were no significant differences in patient characteristics between the groups. It was found that onset of anaesthesia was rapid and of prolonged duration in th dexmedetomidine group (A ). In the magnesium sulphate group (B), although onset of block was delayed, the duration of analgesia was significantly prolonged as compared to control group (C), but to a lesser degree than the dexmedetomidine group (A).T he groups were similar with respect to hemodynamic parameters and there were no significant side effects seen in either of these groups. Conclusion: Intrathecal dexmedetomidine seems to be a good alternative to intrathecal magnesium sulphate as it produces rapid onset and prolonged duration of sensory and motor blockade and longer duration of analgesia without significant hemodynamic variations and side effects. Intrathecal magnesium sulphate also prolongs duration of spinal analgesia but to a lesser degree than intrathecal dexmdetomidine and has a delayed onset. Further studies are required to substantiate whether larger doses of intrathecal magnesium sulphate can produce greater potentiation of analgesia and decrease opioid requirements in patients.

Key Words: Bupivacaine, dexmedetomidine, magnesium sulphate, intrathecal.

 

 

 

INTRODUCTION

Central neuraxial blocks with local anaesthetics are popular techniques of regional anaesthesia and is widely used for lower abdominal surgery. Of which subarachnoid block is still the first choice because of its rapid onset, superior blockade, less failure rates, low risk of infection as from catheter insitu, and cost effectiveness with minimal drug toxicity1. Bupivacaine has been used since 1963 and is now the most popular and widely used local anaesthetics2. Subarachnoid block provided by bupivacaine alone may be too short for planned surgery. With the aim of prolonging the duration of spinal anaesthesia, addition of different agents to local anaesthetic drug have been used. This study is designed to investigate and compare the effects of Dexmedetomidine and Magnesium sulphate as adjuvants on the onset and duration of sensory and motor blockade induced by intrathecal administration of hyperbaric bupivacaine and its associated adverse effects. The efficacy of intrathecal magnesium sulphate as an adjuvant with bupivacaine in prolonging the duration of spinal anaesthesia and in decreasing postoperative analgesic requirements was shown by many studies5,6,7,8 conducted previously. The usefulness of dexmedetomidine as an intrathecal adjuvant was shown by many other studies1,9,12,13. Magnesium sulphate is a cheaper drug as compared to dexmedetomidine. So at the end of our study if magnesium sulphate is found to be equally effective as dexmedetomidine as an intrathecal adjuvant, considering the majority of population in our country, magnesium sulphate may be chosen as a good alternative for dexmedetomidine in spinal anaesthesia due to cost effectiveness. Dexmedetomidine is a highly selective, potent á2 adrenergic agonist. It has sedative, anxiolytic, analgesic and sympatholytic effects3. Analgesic effect is through stimulation of á2 receptors in dorsal horn, thus directly suppressing pain transmission by reducing the release of pronociceptive transmitters, substance P and glutamate and hyperpolarisation of interneuron. Prolongation of sensory blockade is by prolonged hyperpolarisation of unmyelinated C fibres (sensory). Motor block prolongation by á2 agonists may result from binding these agonist to motor neurons in the spinal cord. Intrathecal á2 receptor agonist have been found to have antinociceptive action for both somatic and visceral pain.1 Magnesium sulphate has evolved as a drug with diverse clinical application. The effects of magnesium sulphate are primarily based on regulation of calcium influx into cell, a natural physiological calcium antagonism. Analgesic properties are due to N-Methyl D-aspartate receptor blocking action1. Noxious stimulation leads to the release of glutamate and aspartate neurotransmitters, which bind to NMDA receptors. Activation of these receptors lead to calcium entry into the cell and initiate a series of central sensitisation and long term potentiation in the spinal cord. NMDA receptor signalling may be important in determining duration of acute pain. Magnesium blocks calcium influx and non-competitively antagonises NMDA receptor channels in CNS. Such NMDA antagonism can prevent induction of central sensitisation from peripheral nociceptive stimulation1,4.

MATERIAL AND METHODS

Present study is a randomized controlled clinical study conducted in Dept. of Anaesthesia, Academy of Medical Sciences, Pariyaram, Kannur during the period from March 2015 to February 2016 after obtaining approval of Institutional Ethical Committee. 90 patients of ASA I and II physical status satisfying the inclusion and exclusion criteria were selected and divided into three groups of 30 each based on lot method.

Inclusion Criteria

  • Adult ASA I and II physical status of either sex
  • Age between 18 -65 years
  • Informed written consent
  • Patients undergoing elective lower abdominal and lower limb surgeries.

Exclusion Criteria

  • History of spinal deformities, spine surgery and pre-existing neurological disease.
  • History of bleeding diathesis and patient on anticoagulant therapy.
  • History of allergy to drugs including local anaesthetics.
  • Patient of ASA (American Society of Anaesthesiologists) grade ІІІ and above.
  • Age below 18 yrs and above 65 yrs.
  • Patients having liver, cardiac and renal disease
  • Infection at site of injection.
  • Pregnancy.
  • Mentally retarded/psychiatrically ill patients.
  • Patients on β blockers, calcium channel blockers.
  • Patient refusal to regional blockade

Informed Written Consent was obtained from each participant. Preoperative thorough Clinical assessment was done soon after admission to hospital.

Pre-Operative Investigations: Blood routine, random blood glucose, blood urea, serum creatinine and serum electrolytes (as required), electrocardiogram and Chest X ray (if required).

Pre-Medication: All patients were kept nil per oral for 8 hrs with premedication of tab. Ranitidine 150 mg and tab Metoclopramide 10 mg, preoperative night and at 6 am on the day of surgery. Tab Alprazolam 0.25 mg

was given night before surgery.

Details of The Study: Patients were randomly allocated into three groups of 30 each using lot method.

Group A: Received intrathecally 15mg hyperbaric bupivacaine plus 0.1ml (10 μg) dexmedetomidine.

Group B: Received intathecally 15mg hyperbaric bupivacaine plus 0.1ml (50mg) magnesium sulphate.

Group C: Received intrathecally 15 mg hyperbaric bupivacaine plus 0.1ml saline as control.

Preparation: The anaesthesia machine was checked. All necessary drugs was drawn in syringes, labelled and was kept ready before the patient was brought to operation theatre. ECG leads was connected. Non-invasive blood pressure monitoring was done and pulse oximeter probe was connected. Baseline heart rate, blood pressure, oxygen saturation was recorded.

Technique: With the patient in lateral position, sub arachnoid block was performed at the level of L3-L4 interspinous  space through midline approach using a 25 G Quincke spinal needle. Drug was given intrathecally after ensuring clear CSF flow, either dexmedetomidine or magnesium sulphate or normal saline along with hyperbaric bupivacaine depending on the group allocated. Patient was positioned supine after spinal block. Monitoring of heart rate, blood pressure, oxygen saturation and ECG was done at 3 min interval till the end of surgery. The variables that were assessed were onset of sensory blockade (time to reach T10 dermatome sensory blockade), duration of sensory blockade (time for regression of sensory level to S1 dermatome), onset of motor blockade (time to reach modified Bromage 3 scale), duration of motor blockade (time for regression of motor block to Bromage scale 0) and onset of breakthrough pain. Postoperative pain was assessed by Visual Analogue Scale (VAS) in which 0 corresponds to no pain at all and 10 corresponds to worst pain imaginable. Duration of analgesia is the time taken from the administration of the drug to the time when the patient complains of pain more than 5 in the VAS Scale. Break through pain was managed with Injection Diclofenac Sodium 1.5-2 mg/kg and time noted and the study ends here. Intraoperative side effects expected were hypotension (decrease in blood pressure >25% from baseline) and bradycardia (decrease in heart rate >25% from baseline).

Statistical Analysis: Descriptive statistical tools( mean, standard deviation, frequency and percentage) were used and inferential statistical tool like ANOVA was used to test for significance between the groups. Value of p<0.05 was considered as significant. SPSS 17.0 version was used to analyse the data.

OBSERVATION AND RESULTS

The study was conducted on 90 patients who met the inclusion criteria. They were divided into 3 groups of 30 each based on lot method.

Group A: Intrathecal hyperbaric bupivacaine 15mg with 0.1ml dexmedetomidine (10μg).

Group B: Intrathecal hyperbaric bupivacaine 15mg with 0.1ml magnesium sulphate (50mg).

Group C: Intrathecal hyperbaric bupivacaine 15mg with 0.1ml saline.

The results were analysed and are as follows:

Table 1: Comparison of age based on group

Age ( Yrs)

Group A

Group B

Group C

20 - 39

36.7%

43.3%

30%

40 - 59

53.3%

46.7%

60%

>=60

10%

10%

10%

Mean ± SD Group A 42.2 ± 10.7, Group B 42.4 ± 10.5, Group C 45.4 ± 10.3 F= 0.88, p = 0.419. The mean age of patients in group A, B and C were comparable with p=0.419 which is not statistically significant.

 

Table 2: Comparison of sex based on group

Sex

Group A

Group B

Group C

P

Male

33.3%

26.7%

30%

0.853

Female

66.7%

73.3%

70%

 

In this study females were predominant in all the three groups compared to males with a p value 0.853, hence not statistically significant.

 

Table 3: Comparison of weight based on group

Group

Mean

Sd

N

F

P

A

55.8

6.2

30

0.19

0.826

B

56.4

6.9

30

 

 

C

55.4

6.3

30

 

 

The mean weight in group A was 55.8 kg, Group B was 56.4kg and Group C was 55.4kg which was

 comparable with p=0.826, hence not statistically significant.

 

Table 4: Comparison of ASA based on group

ASA

Group A

Group B

Group C

X2

P

ASA I

83.3%

83.3%

83.3%

0

1

ASA II

16.7%

16.7%

16.7%

 

 

75 out of 90 patients studied belonged to ASA physical status I and the remaining 15 patients belong to ASA physical status II. The difference between these groups with regard to ASA physical status is not significant (p=1.000).

 

Table 5: Comparison of pulse rate between groups

Group

Mean

Sd

N

F P

A

75.3

6.2

30

 

B

76.1

6.6

30

0.33                 0.719

C

76.5

5.5

30

 

Mean pulse rate was comparable in all the three groups, hence not statistically significant (P = 0.719).

Table 6: Comparison of systolic blood pressure between the groups

Group

Mean

Sd

N

F

P

A

119.7

10.3

30

 

 

B

118.3

11.2

30

0.15

0.864

C

118.3

11.5

30

 

 

 

Table 7: Comparison of diastolic blood pressure between the groups

GROUP

MEAN

SD

N

F

P

A

73.7

5.6

30

 

 

B

74

6.7

30

0.33

0.720

C

72.7

7.4

30

 

 

Both systolic and diastolic BP were comparable in all the three groups, hence not statistically significant.

 

Table 8: Comparison of onset of sensory blockade between the groups

Group

Mean

Sd

N

F

P

A

2

0.4

30

 

 

B

6

0.6

30

466.32

0.000

C

3.9

0.4

30

 

 

Mean onset of sensory blockade in group A was 2 minutes compared to group B (6 minutes) and group C (3.9 minutes) which is found to be statistically significant.

 

Table 9: Comparison of onset of motor blockade between the groups

Group

Mean

Sd

N

F

P

A

3.5

0.6

30

 

 

B

7.4

0.6

30

373

0.000

C

5.1

0.5

30

 

 

Onset of motor blockade was faster in group A (3.5 minutes) compared to group B (7.4 minutes) and group C (5.1 minutes), which is found to be statistically significant.

Table 10: Comparison of duration of sensory blockade between the groups

Group

Mean

Sd

N

F

 

A

335.3

18.3

30

 

 

B

274.8

13.2

30

720.98

0.000

C

178

16.6

30

 

 

Mean duration of sensory blockade was more in Group A (335.3 minutes) compared to Group B (274.8 minutes) and Group C (178 minutes),which is found to be statistically significant..

 

Table 11: Comparison of duration of motor blockade between groups

Group

Mean

Sd

N

F

P

A

293.0

13.4

30

 

 

B

232.3

11.5

30

1031.97

0.000

C

134.8

15.6

30

 

 

The duration of motor blockade in Group A (293 minutes) was more as compared to group B (232.3 minutes) and group C (134.8 minutes), hence statistically significant.

 

Table 12: Comparison of duration of analgesia between groups

Group

Mean

Sd

N

F

P

A

214.7

9.6

30

 

 

B

194.7

13.1

30

196.61

0.000

C

150.5

15.1

30

 

 

Duration of analgesia of group A (214.7 minutes) was more as compared to group B (194.7 minutes) which is greater compared to group C (150.5 minutes), and the result is found to be statistically significant.

 

Table 13: Comparison of complications between groups

Complication

GROUP A (%)

GROUP B (%)

GROUP C (%)

X2

P

Nil

60

56.7

33.3

 

 

Hypotension

20

26.7

33.3

 

 

Bradycardia

10

0

10

8.93

0.538

Hypotension andBradycardia

3.3

6.7

6.7

 

 

Shivering

6.7

6.7

13.3

 

 

Nausea

0.0

33

3.3

 

 

18 patients in group A, 17 patients in group B and 10 patients in group C were not having any complications. Hypotension was observed in 6 patients (20%) of group A, 8 patients of group B (26.7%) and 10 patients of group C (33.3%). Bradycardia was seen in 3 patients of group A and C (10%). Hypotension + bradycardia was seen in only 1 patient in group A and 2 patients in group B and C (6.7%). Shivering was seen in 2 patients of both A and B (6.7%),and 4 patients of group C(13.3%). Nausea was seen in only 1 patient of both B and C (3.3%).

 

DISCUSSION

Spinal anesthesia is the most commonly used regional anesthesia technique for lower abdominal and lower limb surgeries as it is easy to administer and economical. However, intrathecal adjuvants are now being administered with the aim of improving the quality of block and prolonging the postoperative analgesia. Antinociceptive effect of Magnesium seems to be relevant not only in chronic pain but also in postoperative pain. Magnesium blocks calcium influx and noncompetitively antagonises NMDA channels. NMDA receptor signalling determine the duration of acute pain. Because of their role in CNS function and their involvement in pain processing, blocking NMDA receptors promises to be useful in preventing development of prolonged pain states. This favours the use of magnesium sulphate as a neuraxial adjuvant. Dexmedetomidine, a highly selective alpha 2 adrenergic agonist is under evaluation as a neuraxial adjuvant as it provides stable hemodynamic conditions, good quality of intraoperative and prolonged postoperative analgesia with minimal side effects. The present study was conducted in Department of Anesthesiology, Academy of Medical Sciences, Pariyaram, Kannur, Kerala. It was a randomized controlled clinical study. Ninety patients satisfying the inclusion criteria were divided into three groups of thirty each based on lot method. The purpose of study was to compare efficacy of intrathecal magnesium sulphate and intrathecal dexmedetomidine as adjuvants with bupivacaine on the onset and duration of sensory blockade, onset and duration of motor blockade, duration of analgesia and adverse effects. In Group A, 0.1ml of dexmedetomidine was added to intrathecal hyperbaric bupivacaine, in Group B0.1ml of magnesium sulphate was added to intrathecal hyperbaric bupivacaine and Group C was the control group and received 0.1ml normal saline with hyperbaric bupivacaine. There were no significant differences in patient characteristics between the three groups. Among 90 patients studied, there were no significant differences between the three groups with respect to mean age, sex, weight, ASA physical status, pulse rate, systolic and diastolic blood pressure. The onset time of block, both sensory up to T10 dermatome and motor to Bromage 3 scale, was rapid in the dexmedetomidine group A (2.0 ± 0.4 and 3.5 ± 0.6 minutes) and delayed in the Mg group B (6.0 ± 0.6 and 7.4 ± 0.6 minutes) in comparison with the control group C (3.9 ± 0.4 and 5.1 ± 0.5 minutes). The difference between the groups conducted through ANOVA test was statistically significant in both sensory (F=466.32, P =0.000) and motor (F=373, P =0.000) block. The regression time of block, both sensory up to S1 dermatome and motor to bromage0 scale, was prolonged in the dexmedetomidine group A (335.3 ± 18.3 and 293 ± 13.4 minutes) and in the Magnesium group B (274.8 ± 13.2 and 232.3 ± 11.5 minutes) when compared with the control group C (178 ± 16.6 and 134.8 ± 15.6 minutes). However, the duration was longest in the dexmedetomidine group among the three groups. The difference between the groups conducted through ANOVA test was statistically significant in both sensory (F=720.98, P =0.000) and motor (F=1031.97, P =0.000) blockade. The duration of analgesia, was prolonged in the dexmedetomidine group A (214.7 ± 9.6 minutes) and in the Magnesium group B (194.7 ± 13.1 minutes) when compared with the control group C (150.5 ± 15.1 minutes. However, the duration was longest in the dexmedetomidine group among the three groups. The difference between the groups was statistically significant for duration of analgesia (F=196.61,p=0.000). In our study, 18 patients in group A, 17 patients in Group B and 10 patients in group C were not having any complications. Hypotension wasobserved in 6 patients (20%) of group A, 8 patients of group B (26.7%) and 10 patients of Group C (33.3%). Bradycardia was seen in 3 patients of group A and C (10%). Both hypotension and bradycardia was seen only in 1 patient in group A and 2 patients in Group Band C (6.7%). Shivering was seen in 2 patients of both A and B (6.7%) and 4 patients of group C (13.3%). This shows that there was no statistical significance between these three groups regarding sideffects (p=0.538). The results from the study show that the onset time to reach T10 dermatome and modified Bromage 3 block was shorter in the dexmedetomidine group (group A) as compared with control group (group C) and it was significantly prolonged in magnesium sulphate group (group B). Also, patients in group A had significantly longer duration sensory and motor block than patients in group B which was greater than in the control group C. Duration of analgesia was more in group A compared to group B, which is more  than in group C. There were no significant side effects in either of the groups. The results are supported by similar studies done by Deepika Shukla1 et al in 2011 where they concluded that onset of anesthesia was rapid and of prolonged duration in the dexmedetomidine group. However, in magnesium sulphate group, although onset of block was delayed, duration was significantly prolonged as compared with control, but to a lesser degree than dexmedetomidine group. The groups were similar with respect to hemodynamic variables and adverse effects. Similar findings were obtained in another study conducted by Sunil BV15 et al in 2013 where they compared the effects of dexmedetomidine, fentanyl and magnesium sulphate as adjuvants with hyperbaric bupivacaine for spinal anaesthesia. Kanazi9 et al in 2006 found that low dose dexmedetomidine when added to intrathecal bupivacaine prolong the duration of sensory and motor block with preserved hemodynamic stability and lack of sedation. Addition of dexm edetomidine to intrathecal bupivacaine leads to early onset of sensory and motor block with prolonged duration, hemodynamic stability and reduced demand for rescue analgesia in 24 hours. The studies in favour of these findings were done by Al Ghanam13 et al in 2007, Rajin Gupta16 et al in2011, Ashraf Amin18 et al in 2012, GA Tarbach et al in 2013 where they compared the effects of intrathecal dexmedetomidine and fentanyl as adjuvant with bupivacaine. They found that intrathecal dexmedetomidine was more advantageous than fentanyl regarding quality and duration of anesthesia and postoperative analgesia. The study shows that onset of anesthesia was rapid and prolonged in duration in the dexmedetomidine group (A). However, in the magnesium sulphate group (B) although onset of block was delayed, duration was prolonged significantly as compared with control group (C) but to a lesser duration than in dexmedetomidine group (A). Groups were similar with respect to hemodynamic variables and there were no significant side effects in either of the groups.

 

SUMMARY

This was a prospective observational study to compare the effects of intrathecal dexmedetomidine and intrathecal magnesium sulphate as adjuvants to hyperbaric bupivacaine in lower abdominal and lower limb surgeries. Of the 90 patients included in the study, 30 patients (Group A) received intrathecally 15 mg hyperbaric bupivacaine and 10 mcg (0.1 ml) dexmedetomidine, 30 patients (Group B) received intrathecally 15 mg hyperbaric bupivacaine and 50 mg (0.1 ml ) magnesium sulphate and 30 patients (Group C ) received 15mg hyperbaric bupivacaine and 0.1 ml saline as control. The objective of the study was to compare the onset and duration of sensory blockade, onset and duration of motor blockade, duration of postoperative analgesia and adverse effects if any, between these three groups. The study groups were comparable with respect to age (years), weight (kg), sex and ASA Status. There were no significant differences in hemodynamic parameters among the three groups. The onset of sensory blockade was faster in the dexmedetomidine group (onset time 2+/-0.4 min), delayed in magnesium group (6+/- 0.6 min) compared to control group (3.49+/-0.4 min). The onset of motor blockade was also faster in dexmedetomidine group (3.5 +/-0.6 min), delayed in magnesium group (7.4+/-0.6 min) in comparison with control group (5.1+/- 0.5 min). The duration of sensory blockade was prolonged in dexmedetomidine group (335.3+/-18.3 min) and magnesium group (274.8+/- 13.2 min) compared with control group (178 +/-16.6 min). The duration of motor blockade was also prolonged in the dexmedetomidine group (293 +/- 13.4 min) as compared to the magnesium group (232.3+/-11.5 min) in comparison with control Group (134.8+/-15.6 min). The duration of analgesia was prolonged in the dexmedetomidine group (214.7+/-9.6min) and magnesium group (194.7+/-13.1 min) when compared with control (150.5+/-15 min). There was no statistical difference between the three groups regarding adverse effects (p= 0.538).

 

CONCLUSION

Intrathecal supplementation of dexmedetomidine to hyperbaric bupivacaine produces rapid onset and prolonged duration of sensory and motor blockade without significant hemodynamic variations and adverse effects. Dexmedetomidine (10 mcg) as adjuvant in spinal anesthesia for surgeries of prolonged duration has minimal side effects and provides excellent quality of postoperative analgesia. Intrathecal magnesium sulphate (50 mg) also prolongs duration of spinal analgesia but less than intrathecal dexmedetomidine and also has delayed onset of both sensory and motor blockade which is undesirable. Further studies are required to determine whether larger doses of intrathecal magnesium. Sulphate can produce greater potentiation of analgesia and decrease postoperative opioid requirements in patients.

 

REFERENCES

    • Shukla D , Verma A , Agarwal A , Pandey HD ,Tyagi C . Comparative study of intrathecal dexmedetomidine with intrathecal magnesium sulphate used as adjuvants to bupivacaine . Journal of Anesthesiology Clinical Pharmacology . 2011 Oct 1 ; 27(4)- 495
    • Charles B Berde , Gary R Strichartz . Local Anesthetics . In Miller ‘s Anesthesia 8th edition . Miller , RD ed. Pages 1028-1031 . Elsevier Philadelphia , Penn.2015
    • Jaap Vayk , Elske Sitsen , Marije Reekers . Intravenous Anesthetics . In Miller’s  Anesthesia 8th edition , Miller , RD ed .Pages 854-858 . Elsevier Philadelphia , Penn 2015
    • Woolf CJ , Thompson SW . The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation ; implications for the treatment of for the treatment ofpost-injury pain hypersenesitvity states . Pain. 1991 Mar 1 ; 44930 : 293-9
    • Tramer MR , Schneider J , Marti RA , Rifat K . Role of mgnesium sulphate in postoperative analgesia . The Journal Of The American Society  Of Anesthesiologists . 1996 Feb 1 ; 84920 : 340-7
    • Kroin JS , Mc Carthy RJ , Von Roenn N , Schwab B , Tuman KJ , Ivankovich AD . Magnesium sulphate potentiates morphine antinociception at the spinal level . Anaesthesia & Analgesia . 2000 Apr 1 ; 90(4) : 913-7
    • Buvanenedran A  , Mc Carthy RJ , Kroin JS , Leong W , Perry P, Tuman KJ . Intrathecal magnesium prolongs fentanyl analgesia : a prospective randomized controlled  trial . Anesthesia & Analgesia . 2002 Sep 1 ; 95(3) : 661-6
    • Ozalevli M ,Cetin  TO , Unlugenc H ,Guler T , Isik G . The effect of adding intrathecal magnesium sulphate to bupivacain-fentanyl spinal anesthesia . Acta anesthesiologica scandinavica . 2005  Nov 1 : 49 (10) : 1514-9
    • Kanazi GE , Aouad MT , Jabbour-Khoury SI , Al Jazar MD , Alameddine MM , Al –Yaman R , Bulbul M , Baraka AS . Effect of low dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block . Acta anethesiologica Scandinavica . 2006 Feb 1 ; 50(2 ): 222-7
    • Shoeibi G, Sadegi M , Firozian A ,Tabassomi F. The additional effect of magnesium sulphate to lidocaine in spinal anesthesia for caesarean section.Int J Pharmacol.  2007 ; 3 (95): 425-7
    • Unlugenc H , Ozalevli M , Gunduz M , Gunasti S , Urunsak IF , Guler T , Isik G . Comparison of intrathecal mgnesium , fentanyl , or  placebo combined with bupivacaine 0.5% for parturients  undegoing elective caesarean delivery .Acta Anaesthesiologica Scandinavica .2009 Mar 1; 53 (3) :346-53
    • Al- Mustafa MM , Abu –Halaweb SA , Aloweidid AS , Murshidi MM , Ammari  BA , Awwad ZM , Al-Edwan GM , Ramsay MA .  Effect of dexmedetomidine added to spinal bupivacaine for urological procedures. Saudi medical journal. 2009 ; 30(3)) : 365-70
    • Ai –Ghanam  SM , Massad IM , Al-Mustafa MM , Al-Zaben KR , Qudaisat IY , Qatawneh AM ,Abu-Ali HM. Effect of adding dexmedetomidine versus fentanyl to intrathecal bupivacaine on spinal block characteristics in gynecological procedures : A doube blind controlled study . American journal of applied  sciences . 2009; 6 (5) ; 882
    • Malleswaran S , Panda N , Mathew P, Bagga R . Magnesium as an intrathecal adjuvant in mild preecclampsia . Int J Obstet Anesth . 2010 ;19 : 161-6
    • Khalili G , Janghorbani M , Sajedi P , Ahmadi G Effects of adjunct intrathecal magnesium sulphate to bupivacaine for spinal anesthesia : a randomized , double blind trial in patients undergoing lower extremity surgery .  Journal of anesthesia. 2011 Dec 1; 25(6) : 892-7.


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