Effect of Magnesium Sulphate on Intra Operative Anesthetic Requirements and Post Operative Analgesia in Plastic Surgery Patients

Keywords

Magnesium Sulphate; Analgesia; VAS, Plastic Surgery.

Introduction

The management of postoperative pain is one of the most challenging issue for anesthesiologists. There have been landmark advances in the clinical pharmacology still the moderate andsevere postoperative pain is reported in 80% and 31–37% of patients, respectively. [1-3]

The pathophysiology of surgical pain is mediated by inflammation of damaged tissues or direct injury to nerve cells. The optimal management of postoperative pain is the key factor for early ambulation after surgery, patient satisfaction and reducing length of hospital stay therefore the cost of treatment.

The various factors associated with post-operative pain may be grouped as; patient-related and surgery-related. The factors like previous pain experiences, social, cultural and psychological status, as well as genetic and sexual factors are major patient-related factors. However, surgical factors include the type of anaesthesia and surgical technique including ability to diagnose and avoid nerve damage if possible.[4]

The plastic surgical procedures are usually associated with moderate to severe pain which makes intra-operative and postoperative analgesia a major concern. The use of opioid analgesics can manage the intra operative pain but the associated side effects are troublesome postoperatively.

In addition to the other issues, sub optimal management of postoperative pain is also associated with impaired wound healing and rehabilitation, delayed gastrointestinal motility, pulmonary complication, higher risk of thromboembolism due to immobilization, and myocardial ischemia.[5-9]

Magnesium sulphatehas been in use as a general anaesthetic. Recent literature has suggested that it bears potentiating effects on peri-operative analgesia by acting as an antagonist to N-methyl- D-aspartate (NMDA) receptors10and muscle relaxation. Thus its anaesthetic and analgesic-sparing effect may enable anaesthesiologists to reduce the use of anaesthetics during surgery and the use of analgesics after surgery.

Magnesium has also a central nervous system (CNS) depressantand itsanaesthetic effects result from cerebral hypoxia after progressive respiratory and cardiac depression. It was suggested that if respiratory support is maintained, patients showed no CNS depression even at very high serum concentrations of magnesium. [11]

The primary objective of the study is to evaluate the effect of preoperative systemic magnesium sulphate on intra-operative vecuronium isoflurane and fentanyl consumption and post-op analgesia .A secondary objective was to examine possible side effects and toxicity associated with the administration of preoperative magnesium.

Methods

The study protocol was approved by institute ethical committee and sample size was decided arbitrarily taking into consideration the time period of the study and average number of patients undergoing plastic surgery. After obtaining informed consent a double blinded randomized control trial was conducted on60 ASA I-II patients of both sex aged between 20-60 year, in the Department of Anaesthesiology, Sir Sunderlal Hospital and Trauma centre, Institute of Medical Sciences, Banaras Hindu University. Patients were randomly assigned to 2 equal groups using sealed envelope method.

Group M- magnesium group (n=30) patients were given intravenous 50 mg/kg of magnesium sulphate in 100 ml of Normal Saline over 20 min immediately before induction and then 10 mg/ kg/hr by continuous iv infusion till the end of surgery. Group S- Saline group (n=30) were given the same volume of isotonic saline over same duration.The patients allergic to magnesium sulphate or any other study drugs, with major renal, hepatic or cardiovascular dysfunction, atrioventricular block, neuromuscular disorder such as Myasthenia gravis, Eaton lambert syndrome, neurological disorder, asthma or chronic obstructive pulmonary disease, obesity (BMI>40), pregnancy, opioid or analgesic abuse, Patient taking chronic treatment of calcium channel blocker, magnesium or anticoagulant were excluded.

Oral Tab. Alprazolam 0.25mg, Tab. Ranitidine 150mg was given the evening and in the morning 2 hours before surgery. In the operating room, under aseptic precautions, a 18-gauge peripheralvenouscannula was established on the dorsum of non-dominant or non- operating hand. Pulse oximeter, electro cardiogram, noninvasive arterial blood pressure and BIS electrode were connected to the patients. All patients under the study were preloaded with 500 ml Lactated Ringer solution over 30 minute.

All patients were premedicated with inj. Midazolam 30 mcg/kg intravenously anesthesia was Induced with 1% of inj. Propofol 2 mg/kg. Inj. Vecuronium 0.1 mg/kg was given after conformation of adequate mask ventilation. After mask ventilation for 3 minute a appropriate size endotracheal tube was placed and its position wasconformed. All patients were maintained with 50% oxygen in nitrous oxide, isoflurane andvecuronium. Peri-operative analgesia was maintained with 1 mcg/kg of fentanyl which was given just after inj. Midazolam. Depth of anaesthesia was measured using BIS and was maintained between 40-60 with the help of isoflurane. Vecuronium was administered at its maintenance bolus dose of 0.01mg/kg. The measurements of HR, SBP, DBP, MAP, Oxygen saturation(SpO2) were measured at post induction and intervals of 1, 5, 10, 15, 20, 25, 30, 45, 1 hr, 1 hr 15 min,1 hr 30 min, 2 hr and at the end of surgery. The magnesium sulphate and anaesthetic agents were discontinued at skin closure, and inj. Ondansetron 0.1 mg/kg and paracetamol 1gm were administered. At the end of surgery, neuro-muscular block was reversed by neostigmine 0.05 mg/kgandglycopyrrolate 0.01 mg kg. After termination of anaesthesia, all patients were transferred to the recovery room and assed for any sign of hypermagnesemia and other adverse event and side effects were noted and managed accordingly.

The following data were recorded in recovery room and ward:

1. Pain was evaluated using a 0-10 cm visual analogue scale (VAS, starting from 0= no pain, to 10= worst pain imaginable). The VAS score was recorded at emergence from anaesthesia and at 30 min, 1 h, 2 h, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr after the surgery.

2. The dosage and timing of rescue analgesia (ketorolac 30mg Intramuscular) was recorded at 30 min, 1 h, 2 h, 3hr, 4hr, 5hr, 6hr, 7hr, 8hr after operation.

3. Episodes of shivering, vomiting or any other significant side effect were monitored and recorded till 8th hr. Statistical analysis was performed using SPSS version 16.0 software. For comparison; paired student unpaired t test and chi square test, as appropriate. A P-value below 0.05 was considered significant.

Results

In the present study, a total 60 patients were enrolled. Two study groups were made each consisting 30 patients. Table 1 shows Patient Characteristics and Duration of Surgery in the two Groups. The mean age and duration of surgery was respectively 33.43 ± 12.979 years and 80.9(±23.8) in group S as compared to 34.57 ± 11.334 years and 76.13(±18.57) in group M showed no statistically significance difference. Other parameter like sex, weight and ASA was also comparable.

Heart Rate, Systolic Blood Pressure, Diastolic Blood Pressure and Mean Arterial Pressure at various time intervals in two Groups has been shown in Table 2. Mean HR values of both the groups were comparable and not significant (p>0.05) except the HR value at 90 minute, which was significantly lower in Group M (p<0.05). Mean SBP values of both the groups were comparable and not significant (p>0.05) except the SBP value at 5 minute, 10 minute, 60 minute, and at the end of surgery; which was significantly lower in Group M (p<0.05). Mean DBP values of both the groups were comparable and not significant (p>0.05).Mean MAP values of both the groups were comparable and not significant (p>0.05) except the MAP value at 60 minute and at the end of surgery; which was significantly lower in Group M (p<0.05). Mean vecuronium consumption was significantly lower in Group M (p<0.05) and mean fentanyl consumption was comparable but statistically not significant.

As shown in Table 3, Mean VAS score of both group are comparable and statistically not significant (p>0.05) except VAS score at 1hr and 4hr, which were significantly lower in Group M.Table 4 shows the need for rescue analgesia in the two groups and it can been seen to be less in group M as compared to group S. The incidence of shivering and vomiting in two groups are shown in Table 5. None of the patients in group M had shivering and vomiting as compare to group S.

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Table 1:

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Table 1. Patient Characteristics and Duration of Surgery in Two Groups.

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Table 2:

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Table 2. Heart Rate, Systolic Blood Pressure, Diastolic Blood Pressure and Mean Arterial Pressure at various time intervals in Two Groups.

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Table 3:

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Table 3. Mean Visual Analogue Scale(VAS) Score of Group S and Group M at different time intervals starting at 30 minute after the completion of surgery.

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Table 4:

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Table 4. Mean number of rescue analgesic of Group S and Group M patients at different time intervals starting at 1hr after surgery.

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Table 5:

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Table 5. Postoperative complication.

Discussion

Post operative pain control is a major area of concern for anaesthesiologists. In this study we found that with Isoflurane based balanced general anaesthesia, magnesium sulphate produced similar intraoperative conditions and haemodynamics parameter during the surgery as control.

Magnesium is known to induce hypotension, directly by vasodilation and indirectly by sympathetic blockade and inhibition of catecholamine release. In contrary to some studies [12-14] in our study we did not find any episodes of hypotension or bradycardia that warrant the use of vasopressor or atropine. That can be explain by preloading, was done with 500 ml of lactated Ringer’s solution. The heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the mean arterial pressure (MAP) were on the lower side but with statistically insignificant difference in magnesium group. We observed more stable hemodynamic during laryngoscopy and tracheal intubation (LTI) in magnesium group.

Our study demonstrates significant reduction in the consumption of isoflurane and vecuroniumin magnesium group. In comparison to previous animal study shows, increase in magnesium dose was associated with reduction of Halothane MAC in rats,[18] sevoflurane,[15] and desflurane,[16] to our knowledge this is the first study between the interaction of isoflurane and magnesium in human subject.

In accordance to other studies magnesium sulphate in patients undergoing general anesthesia resulted in decrease in the requirement for nondepolarizing muscle relaxants [17, 18] with no delay the recovery from general anaesthesia.[20, 21] Our study shows that in magnesium group mean vecuronium requirement was lower (6.466 ± 1.077mg vs7.37 ± 1.77 mg ). As a calcium channel blocker, magnesium decreases acetylcholine release at the presynaptic nerve terminals and diminishes the excitability of muscle fibre thus reduces the amplitude of endplate potential, resulting in the potentiation of neuromuscular blockade by nondepolarizing muscle relaxants.[19] However, our study demonstrated that magnesium sulphate has more advantages during the postoperative periods associated with better recovery profiles.

We observed decreased incidence of postoperative shiveringso decreases discomfort and oxygen consumption, this finding was also confirmed by other studies.[15, 21, 22] Wadhwa et al also demonstrated the effect of magnesium in reducing hypothalamic shivering threshold from 36.6OC to 36.3OC.[23]

Intraoperative use of magnesium sulphate is associated with decreased incidence of vomiting in postoperative period, also found in a study by Ryu JH et al [15] which could be due to lesser consumption of volatile anesthetic rather than any antiemetic property of magnesium. Nevertheless, because nausea and vomiting are one of the common complications encountered in post operative period and is distressing to the patient and the family member. The study shows that intraoperative use of intravenous magnesium sulphate bolus followed by infusion reduces postoperative pain and analgesic consumption without any notable complication. All patients were pain free at extubation probably because of additional analgesic effect of paracetamol at this period. Pain assessment after plastic surgery shows pain score ranging from 10 to 60 mm on VAS scale.VAS score at 1hr and 4hr were significantly lower in Group M.

Adequate bolus and infusion doses of magnesium sulphate are important for effective analgesia. Pre and intraoperative administration of magnesium sulphate in gynecology patients receiving total intravenous anaesthesia reduced rocuronium requirement and improved the quality of postoperative analgesia without any significant side-effects.[21] Accordingly, in the present study, we administered a 50 mg/kg bolus and a maintenance dose of 10 mg/kg/h.

We found that infusion of magnesium sulphate can provide a clinically important reduction in ketorolac consumption and pain severity in the first 8 hours postoperatively. In consistency with our results, Koglerobserved that intra-operative fentanyl consumption was decreased significantly in magnesium treated group compared to control group in thoracotomy procedure. However, there was no difference in pain intensity at 48 hours after surgery. [25] Albrecht E and colleagues,in a meta-analysis on twentyfive trials comparing magnesium with placebo concluded that perioperative intravenous magnesium reduces opioid consumption and pain scores, in the first 24 hour postoperatively.[26]

In contrast to our findings, Bhatia and colleagues reported no significant decrease in the amount of consumed morphine during cholecystectomy.[24] Tramer and Glynn showed that pre treatment with magnesium sulphate no effect on post operative analgesia for first 3 postoperative days.[22] However, unlike our study they did not use fentanyl for intraoperative analgesia. Intense or repeated noxious stimulation causes release of excitatory amino acidsin the dorsal horn. Activation of NMDA receptor leads to Ca2+entry into the cell that initiates a series of central sensitization causes long-term potentiation in the spinal cord in response of cells to prolonged stimuli. Central sensitization has an important role for pain perception and the persistence of postoperative pain. Magnesium acts as an antagonist at the same NMDA receptor and its associated ion channels. Therefore, magnesium could modulate postoperative pain via blockade of NMDA-receptor.

Ryu et al demonstrated the effect of intravenous magnesium sulphate in reducing intraoperative anaesthetic requirement and postoperative analgesia in gynecological patients received TIVA, as against the isoflurane based balanced general anaesthesia in our study, and found that IV magnesium sulphate improves quality of postoperative analgesia.[19] Gupta et al also reported that magnesium reduces requirements ofpropofol, rocuronium and fentanyl in spinal surgical patients.[27] It is conceivable that the intraoperative use of magnesium sulphate may mitigate remifentanilinduced hyperalgesia in patients receiving TIVA.

Explanations for these discrepancies in study outcome could be due to the differences in dose, onset of magnesium administration, the type of magnesium salt, pain scores used, choice of patient population, standard baseline pain medication and anesthesia. Besides it, there are many confounding factors, such as age, preoperative pain level and perception, and comedication that are hard to control.

Pain in plastic surgery patient can be multifactorial. Pain perception can be influenced by variety of factors such as gender, psychological, personality, genetic and ethnicity.[28, 29] In both groups of our study, pain score was moderate particularly in early hours (mean VAS of <3) this might be due to the residual effect of paracetamol 1 gm.

Limitations

We did not measure serum and cerebrospinal fluid magnesium concentration however it has been studied that most of the body magnesium is intracellular and estimation of plasma magnesium does not represent magnesium content of body tissue.[30] Performing lumber puncture could have given us further information in normal human subject. Furthermore, the study population was not large; however the sample size was based on predefined effect size and power. We did not assess patient satisfaction, therefore we cannot comment on future use of same analgesia again after similar operation. Movement-related pain during forced expiration might be more sensitive to altered sensory processing; which was not assessed in our study. However, the role of hyperalgesia in postoperative pain is not fully understood.

Conclusion

The reason for failure to provide adequate postoperative analgesia is multifactorial, for Postoperative pain management to be effective it should beproperly planned, delivered in a consistent, evidence based manner and based on patients’ assessment of their own pain whenever possible.We conclude that magnesium has anaesthetic, analgesic and muscle relaxant properties and its intraoperative use lead to significantlyreduces the drug requirements of vecuronium and isoflurane during anaesthesia and post-operative consumption of ketorolac and reduced VAS score.

The current literature of analgesic effects of magnesium is conflicting, and additional major clinical trials using well-defined dose regimens and pain scores are required to achieve more data on possible anti-nociceptive effects.

The high therapeutic index and cost-effectiveness of magnesium could makes it’s a potent adjuvant drug for anaesthesia and with appropriate use it can improve surgical outcome and patients' satisfaction.