Intrathecal Magnesium Sulfate as Analgesic and Anaesthetic Adjunct to Bupivacaine in Patients Undergoing Lower Extremity Orthopaedic Surgery

Background Subarachnoid block is a popular mode of anesthesia for lower limb surgeries. Studies of Magnesium Sulfate (MgS04 ) as an adjuvant to intrathecal local anaesthetic are limited. The objective was to find out the analgesic and anaesthetic effect of intrathecal MgS04 added to bupivacaine for spinal anaesthesia in patients undergoing lower extremity orthopaedic surgery. Methods Sixty ASA I or II adult patients undergoing lower extremity orthopaedic surgery were randomly allocated in a double blinded fashion into two groups of thirty each. Group A received 3.0 ml of 0.5% hyperbaric bupivacaine with 0.15 ml of 50% MgSO4. Group B received 3.0 ml of 0.5% hyperbaric bupivacaine with 0.15 ml of NS. Onset of sensory and motor block as well as time to attain highest level of sensory block were recorded. Duration of sensory and motor block along with duration of spinal anaesthesia were also assessed. Any adverse effects were noted and treated. Results Duration of sensory and motor block along with duration of spinal anaesthesia were prolonged in patients of MgSO4 but were not statistically significant with p-value of 0.33, 0.23 and 0.68 respectively. Onset of anaesthesia, requirement of rescue analgesics, haemodynamic parameters and adverse effects were comparable between two groups. Conclusion In patients undergoing lower extremity orthopaedic surgery the addition of 75mg of MgSO4 to intrathecal bupivacaine did not prolong the duration of sensory block, spinal anaesthesia nor decreased postoperative analgesic consumption without any additional side effects.


Introduction
Pain has adverse physiologic effects that can contribute to significant morbidity and mortality. 1Adequate postoperative analgesia is very important as it is associated with less physiological derangement with quicker recovery and ambulation.
Subarachnoid block (SAB) is a popular mode of anaesthesia for lower limb surgeries.It reduces perioperative complications and provides superior analgesia compared to general anaesthesia. 2Various intrathecal adjuvants are in use with local anaesthetics (LA) to provide intraoperative and prolonged postoperative analgesia.Agents like opioids, 3 clonidine, 4 dexmedetomidine, 5 neostigmine, 6 midazolam 7 and dexamethasone 8 have been used with varying result as an adjuvant to LA but with various side effects.7][18][19][20] Even with an inadvertent intrathecal injection of 1500 mg for emergency strangulated inguinal hernia repair patient recovered back to normal on fifth day without any residual complicatons in a report by Najafi et al. 21At present there is still in need of an ideal intrathecal adjuvant which would prolong the duration of anaesthesia and analgesia.Perhaps MgSO 4 could be the one that we are looking for.This study was therefore conducted to find out the analgesic and anesthetic effect of intrathecal MgSO 4 added to LA for SAB in patients undergoing lower extremity orthopaedic surgery.One day prior surgery, each patient and their relatives were explained about the study.The patients were instructed about the assessment of pain in the postoperative period by visual analog scale (VAS) (0 no pain at all and 10 maximum pain attainable).All patients were kept NPO for eight hours and received diazepam 0.2 mg/kg not exceeding 10 mg as pre medication in the evening a day before surgery and in morning two hours before surgery.After arrival of the patient to the operating room electrocardiogram (ECG), noninvasive blood pressure (NIBP) and pulse oximeter were attached to the patient and baseline measurements of heart rate (HR) , blood pressure(BP), peripheral oxygen saturation (SpO 2 ) and respiratory rate(RR) were recorded.These were recorded five minutes before intrathecal injection and every ten minutes until the completion of surgery.Patients were preloaded with 500ml of Ringers' lactate (RL) over a period of 20 min prior to SAB.Patient in MgSo 4 group received 3.0 ml of 0.5% hyperbaric bupivacaine (15 mg) with 0.15 ml of 50% MgSO 4 (75 mg).Patient in NS group received 3.0 ml of 0.5% hyperbaric bupivacaine (15 mg) with 0.15 ml NS.Both groups received a total volume 3.15 ml & since both NS & MgSO 4 were colourless & similar looking blinding was maintained.Subarachnoid block was done with 25 Gauge Quincke's needle at L3-4 or L4-L5 interspace.

This
Anaesthetic features of SAB were defined and evaluated as follows after SAB . 14Onset of sensory blockade was defined as time taken to achieve loss of pinprick sensation to 23 G hypodermic needle tested every two minute at T10 dermatome.Time of highest dermatome level of sensory blockade was defined as the time taken for loss of pinprick sensation to 23 G hypodermic needle tested every two minutes until highest level had stabilized for four consecutive tests.Duration of sensory block was defined as time taken to regress from the highest level of loss of pinprick sensation achieved to two lower sensory dermatome level tested every 10 min after 60 min of SAB.Duration of spinal anaesthsia was defined as time taken from the time of spinal injection to the time when the patient complained of pain at surgical site or VAS > three.
Motor block was assessed based on Modified Bromage Scale. 22Onset of motor block was defined as time taken to reach a bromage scale of two tested every two minutes.Duration of motor block was defined as duration from time of injection till the patient attained complete motor recovery of lower limb i.e.Bromage scale of 0.
Adverse events were observed in the intraoperative as well as in the post anaesthetic care unit (PACU).
Hypotension was defined as a decrease in systolic blood pressure (SBP) by > 20% from baseline or < mm Inj.Phenylephreine 50 µcg IV stat.was given as intervention.Bradycardia was defined as HR < 50 bpm.Atropine 0.3 mg IV stat was given as intervention.
Nausea and vomiting was rated on a scale of 0 to three.Intraoperative haemodynamics measured every 10 min after SAB till the end of surgery were also similar between two groups at different time intervals.
Anaesthetic effects were compared between the two groups (Table 3) .There were no significant differences between the two groups.

Discussion
Intrathecal MgSO 4 when combined with opioid and LA agent is known to potentiate the analgesic effect of an opioid. 6,17,18,25Inhibition of calcium influx is presumed to augment opioid-induced analgesia.Potentiation of the analgesic effect of LA agent with intrathecal MgSO 4 has also been suggested.The addition of magnesium reduces the activation of c-fibres by inhibiting the slow excitatory postoperative-synaptic currents produced by NMDA receptor activation. 26Magnesium acting as NMDA receptor antagonist abolish calcium and sodium influx into cells leading to central sensitization and wind up attributed to peripheral nociceptive stimulation.

27,28
They abolish hypersensitization by blocking NMDA receptor activation in the dorsal horn by excitatory amino acid transmitters, notably glutamate and aspartate.

28
Various doses of intrathecal magnesium sulfate have been used ranging from 50mg to 100 mg with 50 mg being the most commonly used dose.However 50 mg of intrathecal MgSO 4 when combined with bupivacaine alone did not prolong spinal anaesthesia in a study done by Jabalameli et al. 15 We chose 75 mg as this dose was enough to prolong the duration of sensory and motor blockade without increasing the frequency of major adverse effects in comparison to 100 mg in the same study.
The anaesthetic effect was compared between two groups.The onset of sensory, motor block and time to attain highest dermatome level of sensory block were comparable in both groups.Our results were similar to Faiz et al. 6 where intrathecal MgSO 4 had no effect on the onset of sensory or motor block but contrasted to other studies. 5,7,14The authors of these studies suggested that differences in the pH and baricity of the solution containing MgSO 4 could have contributed to the delayed onset.Similarly intrathecal MgSO 4 did not prolong the duration of sensory or motor blockade as compared to NS in our study.Our findings is similar to study by Khalili et al. 14  Visual Analog Score was comparable in both the groups.The requirement of tramadol and morphine as rescue analgesics was comparable in both groups over 24 hours similar to the findings of Dayioglu et al. 25 and Buvanendran et al. 16 Use of lower dose (75 mg) of MgSO 4 could be the reason for not decreasing the requirement of rescue analgesic in our patients.In contrast Khalili et al. 14 observed the opioid sparing effect of intrathecal MgSO 4 when used in a higher dose of 100 mg.Lesser requirement of analgesic was also reported by Malleeswaran et al. 17 Fentanyl in addition to intrathecal MgSO 4 could have played a role producing opioid sparing effect leading to decrease in analgesic consumption.
Occurrence of hypotension, bradycardia and shivering were common adverse effects which were comparable between the two groups similar to a study by Unlugenc et al. 19 These events may be merely due to the effect of SAB related to bupivacaine.
There are several limitation to the study .Our study involved all types of procedure on different locations of lower limb including femur, tibia or fibula.Perhaps study involving a specific location would have better results in terms of postoperative analgesic consumption.Study with a larger dose of intrathecal magnesium or a larger sample size might have shown significant difference in analgesic and anaesthetic effect.

Conclusion
In patients undergoing lower extremity orthopaedic surgery the addition of 75mg of MgSO 4 to intrathecal bupivacaine did not prolong the duration of sensory block, spinal anaesthesia nor decreased postoperative analgesic consumption without any additional side effects.

23
It was treated by ondansetron 4 mg intravenously.Shivering was graded using a scale byTsai and Chu.24   Shivering score of one to two was treated by infusing warm IV fluids.Score of three and four was treated with ondansetron 4 mg intravenously.Pain was evaluated using VAS score in the postoperative period at every 15 min for the first hour and every 20 min in the next hour.Diclofenac 75 mg IM was given 1 hour after SAB.Second dose of diclofenac was given when patient first complained of pain and was repeated every eight hourly for 24 h.If the VAS > three or patient complained of pain at least 15 min after diclofenac administration, tramadol 100 mg IV as a rescue analgesic was administered.If the patient still complained of persistent pain or had VAS > 3 despite giving tramadol, Morphine 0.05 mg/kg IV was added as a second rescue analgesic.Morphine was added only after 10 min of tramadol administration.
MgSO 4 ) has gained popularity as an adjuvant to LA or spinal anesthesia.Studies on the use of intrathecal MgSO 4 added only to LA for spinal anaesthesia are very few in number.

Table 1
The number of rescue analgesics required in first 24 h were noted.HR, BP, RR and SpO 2 were analyzed using unpaired t-test.. Categorical values such as gender and ASA PS were analyzed using Pearson chisquare Test.Anaesthetic effects in terms of time in minutes such as onset of sensory, motor & time to attain highest level of sensory block were analyzed using Mann Statistical analysis was done accordingly.Normally distributed interval data such as demographic variables like age, height, Ideal body weight (IBW) and preoperative haemodynamics

Table 1 : Characteristics of patients between two groups
).

Table 4 : Comparison of adverse effects between two groups
but in contrary to Ulgenc et al.