|Year : 2008 | Volume
| Issue : 6 | Page : 800
Effect of Intravenous Magnesium Sulfate and Fentanyl Citrate on Circulatory Changes During Anaesthesia and Surgery: A Clinical Study
Dilip Kothari1, Amrita Mehrotra2, Bhanu Choudhary3, Alok Mehra4
1 Associate Professor, Department of Anaesthesiology, G.R. Medical College and J.A. Group of Hospitals, Gwalior (M.P.), India
2 Professor & Head, Department of Anaesthesiology, G.R. Medical College and J.A. Group of Hospitals, Gwalior (M.P.), India
3 Professor, Department of Anaesthesiology, G.R. Medical College and J.A. Group of Hospitals, Gwalior (M.P.), India
4 Jr. Consultant, Department of Paediatric Cardiac Anaesthesia, Appolo Hospital, New Delhi, India
|Date of Acceptance||18-Oct-2008|
|Date of Web Publication||19-Mar-2010|
2-A, J.A. Hospital Campus, Lashkar, Gwalior, Pin-474009
Source of Support: None, Conflict of Interest: None
The study was conducted to compare the effects of magnesium sulfate and fentanyl citrate on circulatory variables during anaesthesia and surgery. Sixty patients (ASA-I& II) of either sex, between the age of 25-45 years were given either magnesium sulfate (Group M, n=30) 20mg.kg -1 5 min before induction, 10 mg.kg -1 5 min before skin incision and 10 mg.kg -1 every 30 min interval or fentanyl citrate (Group F, n=30) 1.25 mcg.kg -1 , 0.5 mcg.kg -1 and 0.5 mcg.kg -1 at similar time intervals. Balanced general anaesthesia was maintained with O2:N2O + halothane 0.2% and relaxants throughout the study period with controlled ventilation. Changes in pulse rate (PR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded at various time intervals. A clinically significant rise in pulse rate (+11.3%) was recorded in Group M after initial injection. Statistically insignificant rise in all haemodynamic variables from baseline values were recorded immediately after intubation in both the groups, after which they returned and maintained, nearer to baseline values. No sympatho-somatic responses like tearing, sweating, eye movement etc. were observed during the course of study. In conclusion, the clinical results suggest that magnesium sulfate could be a safe and cheaper alternative analgesic to fentanyl citrate during general anaesthesia.
Keywords: Magnesium sulfate, Fentanyl, Anaesthesia
|How to cite this article:|
Kothari D, Mehrotra A, Choudhary B, Mehra A. Effect of Intravenous Magnesium Sulfate and Fentanyl Citrate on Circulatory Changes During Anaesthesia and Surgery: A Clinical Study. Indian J Anaesth 2008;52:800
|How to cite this URL:|
Kothari D, Mehrotra A, Choudhary B, Mehra A. Effect of Intravenous Magnesium Sulfate and Fentanyl Citrate on Circulatory Changes During Anaesthesia and Surgery: A Clinical Study. Indian J Anaesth [serial online] 2008 [cited 2020 Sep 25];52:800. Available from: http://www.ijaweb.org/text.asp?2008/52/6/800/60691
| Introduction|| |
Magnesium sulfate has been used as anticonvulsant and antiarrhythmic agent in the past , . Recently, magnesium has been shown to have antinociceptive effect in animal and human models of chronic pain ,, mainly due to its antagonist effect on NMDA receptors  and calcium ion channels  . It also inhibits the catecholamine release from adrenergic nerve terminals and adrenal medulla . For these reasons several authors have used magnesium sulfate to attenuate the pressor response to endotracheal intubation and perioperative analgesia ,. Fentanyl, a widely used narcotic analgesic produces effective analgesia and attenuation of the cardiovascular  , hormonal and metabolic responses to stress but has the disadvantage of prolonged respiratory depression  . In addition cumbersome narcotic laws in India make it difficult to procure in small hospitals. Hence, based on available literature we decided to compare the effects of magnesium sulfate, a cheap, readily available and widely used drug in obstetric practice with fentanyl, an established anaesthetic adjuvant on haemodynamic parameters during anaesthesia and surgery.
| Methods|| |
After approval from our hospital ethical committee and written informed consent, 60 patients (ASA grade-I& II) of either sex and between the age of 25-45 years posted for various abdominal surgical procedures lasting up to 90 minutes under general anaesthesia were divided into two small,fixed and equal size groups (n=30 each group) by simple random sampling or unrestricted sampling (lottery method)  according to drugs used as below:[Additional file 1]
Any patients with extremes of age, major organ dysfunction, A-V block, hypertension, and on medication like Ca ++ channel blockers, hypnotic, or narcotic analgesics were not included in this study.
All the patients received a uniform premedication by glycopyrrolate 0.2mg I.M., 30 min before the start of anaesthesia. Upon arrival in operating room, baseline pulse rate (PR), blood pressure both systolic (SBP) and diastolic (DBP) were measured. Mean arterial pressure (MAP) was calculated by
, formula later on.
After securing an intravenous line the study drug was injected slowly over a period of two minutes, then general anaesthesia was induced with thiopentone sodium 5 mg.kg -1 followed by succinylcholine 2 mg.kg -1 . Endotracheal intubation with appropriate size tube was done and lungs were ventilated with O 2 : N 2 O (33% : 66%) and 0.2% halothane using Bain's circuit with a fresh gas flow of 110 ml.kg -1 . min -1 . Muscle relaxation was provided by vecuronium 0.08 mg.kg -1 (loading dose) and 0.02 mg.kg -1 (incremental doses). Study drug was repeated at 5 min before skin incision and at every 30 min interval thereafter. All the patients were reversed with glycopyrrolate 0.4 mg and neostigmine 2.5 mg at the end of procedure. PR, SBP, DBP were recorded at 0 min (basal value), after study drug, immediately after intubation, at every 5 min interval for next 30 min and thereafter every 15 min till 90 min. Observation of those surgeries lasting more than ninety min (three cases) were excluded from analysis, but to complete the study three other cases were included.
In addition sympathosomatic responses were also recorded regarding the presence of lacrimation, sweating, eye movement and any somatic response like swallowing, grimacing, coughing and eye opening through out the study period. Any change in haemodynamic values (±20% of basal values) were recorded and treated accordingly eg. bradycardia by atropine or hypotension by increasing infusion rate or mephentermine 6 mg. I.V. Rise in B.P.& HR was treated by increasing the concentration of halothane. Routine monitoring by E.C.G. recording and pulse oximetry was done by Mindray MEC-509B Multiparameter Patient Monitor.
Observations recorded in both the groups of study were tabulated and statistical analysis was carried out by using "percent changes for intragroup(within group) and by using analysis of variance (ANOVA) test student unpaired test for intergroup comparison(Group M and F). Values >0.05 were considered as nonsignificant (NS) and <0.05 as significant(S).
| Results|| |
Both the groups were comparable for their demographic data [Table 1] and baseline haemodynamic variables [Table 2].
A clinically significant increase from baseline PR(+11.3%) was observed after the injection of magnesium sulfate (Group M), whereas statistically insignificant decrease(-0.94%) was observed after fentanyl citrate (Group F). Both SBP and DBP decreased continuously in two groups except for a rise of 6.95% and 4.01% in SBP and 5.96% and 4.95% in DBP in group M and F respectively immediately after intubation. All these values were statistically insignificant (P>0.05). MAP also showed similar pattern [Table 2].
None of the patients in either group showed any sympatho-somatic response like tearing, sweating, eye movements etc.
None of these patients had any residual effect of muscle relaxant because they did not require any additional doses of reversal agents nor they require any ventilatory support in post operative period.
[Table 3] shows the incidence of different problems observed in immediate post operative period. None of the patients required any active measures.
| Discussion|| |
Fentanyl plays an important role in balanced general anaesthesia by virtue of meeting all aspects of balanced anaesthesia like narcosis, analgesia and attenuation of stress responses, but apart from associated respiratory depression, chest rigidity and PONV, its procurement in India is difficult due to rigid narcotic regulation.
Although obstetricians have been using magnesium sulfate in prevention or treatment of convulsion in eclampsia, recently reports have appeared about its role as analgesic during intra and post-operative period ,,, .
In this comparative study we evaluated the circulatory changes after the injection of magnesium sulfate and fentanyl citrate during anaesthesia and surgery. Oliver et al used similar doses as adjuvant to general anaesthesia in abdominal hysterectomies. 
A clinically significant rise (+11.3%) in PR was observed after the injection of magnesium sulfate, which further stabilized near to baseline values during the course of study. Ability of magnesium sulfate to inhibit acetylcholine release from vagus nerve in intact animal has been attributed to this effect  .
As shown in [Table 2] both the drugs produced statistically insignificant (P>0.05) fall in blood pressure immediately after initial injection but later in the course of study insignificant rise was observed up to 5 minutes after intubation. No significant changes were observed during rest of the study period in both the groups. Our results are in accordance with Puri et al  who also observed increase in pulse rate after magnesium sulfate which further increased after intubation. They noted a significant fall in MAP after MgSO4 at preinduction stage with a sudden rise in postintubation period. James et al  also observed a rise in blood pressure after intubation in patient pretreated with i.v. magnesium sulfate.
The stability with magnesium sulfate could be attributed to its antagonistic activity on Ca++  and NMDA receptor  or inhibition of catecholamine release  or vasodilatory effect of the ion  or a combination of all these. Fentanyl suppresses the nociceptive stimulation or centrally decreases the sympathetic tone . MgSO4 in several studies is shown to reduce the requirement of narcotics for postoperative pain due to analgesic and co-analgesic effects. , 
In the practice of anaesthesia, any increase in haemodynamic values in ASA status I& II patients is usually considered to be due to inadequate analgesia  . Therefore we think that near stable haemodynamic variables and absence of any sympathosomatic response with both the drugs in this study should be an indication of adequate analgesia.
Hence, we conclude that although the action of magnesium sulfate is not superior to the actions of potent short acting opiate fentanyl, however, use of opiate has been associated with some side effects like respiratory depression, PONV etc. In circumstances, where these complications are undesirable, magnesium sulfate could be a cheap, easily available and useful alternative.
| References|| |
|1.||The Eclampsia Trial Collaborative Group. Which anticonvulsant for women with eclampsia? Evidence from Collaborative Eclampsia Trial. Lancet 1995;345:1455-63. |
|2.||Arsenian MA. Magnesium and cardiovascular disease. Prog Cardiovasc Dis 1993; 35:271-310. [PUBMED] [FULLTEXT] |
|3.||Tramer MR, Glynn C. Magnesium bier's block for treatment of chronic limb pain. Pain 2002,99,235-241. |
|4.||Feria M, Abad F, Sanchez A. Magnesium sulphate injected subcutaneously suppresses autonomy in peripherally deafferented rats. Pain 1993; 53:287-93. |
|5.||Petrenko AB, Yamakura T, Baba H and Shimoji K. the role of NMDA receptors in pain:a review. Anesth Analg 2003; 97:1108-16. |
|6.||Iseri LT, French JH. Magnesium: nature's physiological calcium blocker. Am Heart J 1984;108:188-94. [PUBMED] [FULLTEXT] |
|7.||Douglas WW, Rubin RP. The mechanism of catecholamine release from the adrenal medulla and the role of calcium in stimulus-secretion coupling. J Physiol 1963; 167: 288-310. [PUBMED] [FULLTEXT] |
|8.||MFM, Beer RE, Esser JD. Intravenous magnesium sulphate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989, 68:772-6. |
|9.||Tramer MR, Schneider J, Marti RA. Role of magnesium sulfate in postoperative analgesia. Anesthesiology 1996;84:340-7. |
|10.||Puri GD, Marudhachalam KS, Chari Pramila, Suri RK. The effect of magnesium sulphate on haemodynamics and its efficacy in attenuating the response to endotracheal intubation in patients with coronary artery disease.AnesthAnalg 1998;87:808-11. |
|11.||Klausner JM, Caspi J, Lelcuk S, Khazam A, Marin G, Hechtman HB, Rozin RR. Delayed muscular rigidity and respiratory depression following fentanyl anesthesia. Arch Surg 1988;123:66-7. [PUBMED] [FULLTEXT] |
|12.||Rao Bhaskara T Methods of Biostatistics 2nd edition, 2004, Paras Publications, Hyderabad, India:106-110. |
|13.||Koing H, Wallner T, Marhofer P, Andel H, Horauf K, Mayer N. Magnesium sulfate reduces intra- and postoperative analgesic requirements. Anesth Analg 1998; 87: 206-10. |
|14.||Oliver HG, Wilder S, Lars AN , Dorothec G, Edomer T, Kaplan RR. Sensory changes and pain after abdominal hysterectomy: A comparison of anaesthetic supplementation with fentanyl versus magnesium or ketamine. Anesth Analg 1998; 86:95-101. |
|15.||Somen GG, Baskerville EN. Effect of excess magnesium and vagal inhibition and acetylcholine sensitivity of the mammalian heart in situ and in vitro. Nature 1968;217:679-80. |
|16.||James MF, Beer RE, Esser JD. Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth Analg 1989; 68:772-6. [PUBMED] [FULLTEXT] |
|17.||Altura BM, Altura BT. Magnesium and vascular tone and reactivity. Blood Vessels 1978;15:5-16. [PUBMED] |
|18.||Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on NMDA receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain 1991; 44:293-299. |
|19.||Telci L, Esen F, Akcora D, Erden T, Canbolat AT, Akpir K. Evaluationof effects of magnesium sulfate in reducing intraoperative anaesthetic requirements. Br J Anaesth 2002; 89: 594-8. [PUBMED] [FULLTEXT] |
|20.||Chan Choi, Kyung Bong Yoon, Dae Ja Um, Chan kim, Soo Kim, Sang Gyu Lee. Intravenous magnesium sulfate administration reduces propofol infusion requirementsduring maintenance of propofol -N 2 O anaesthesia. Anesthesiology 2002;97: 1137-41. |
|21.||Laubie M, Schmitt H, Canellas J, Roquebert J, Demichel P. Centrally mediated bradycardia and hypotension induced by narcotic analgesics: dextromoramide and fentanyl. Eur J Pharmacol 1974;28:66-75. [PUBMED] [FULLTEXT] |
[Table 1], [Table 2], [Table 3]