Abstract
Background:
In peripheral nerve blocks, magnesium sulfate is an excellent adjuvant to local anesthetics. The use of magnesium sulfate as an adjuvant in wound infiltration for postoperative analgesia needs to be investigated.
Aims:
This study was conducted to evaluate the analgesic efficacy of magnesium sulfate as an adjuvant when added to bupivacaine in wound infiltration technique in perianal surgeries.
Settings and Design:
This was a prospective, randomized, double-blind study.
Materials and Methods:
Sixty patients undergoing perianal surgeries were randomly divided into two groups, Group M and Group C. Following perianal surgery, Group M patients received a local wound infiltration of injection magnesium sulfate 750 mg (1.5 mL of injection 50% magnesium sulfate) added to 0.5% bupivacaine 13.5 mL making a total volume of 15 mL, whereas Group C patients received a local wound infiltration of injection 0.5% bupivacaine 13.5 mL and 1.5 mL normal saline. Postoperative vitals and pain scores were assessed.
Statistical Analysis Used:
Student's t-test for normally distributed continuous data, Mann–Whitney U-test for ordinal data, and Chi-square test or Fisher's exact test, whichever is appropriate for categorical data, were used.
Results:
The magnesium sulfate group had a lower postoperative pain score, a longer duration of postoperative analgesia, and a lesser number of rescue analgesic doses in the first 24 h.
Conclusion:
We conclude that magnesium sulfate is an effective adjuvant to bupivacaine for wound infiltration in terms of postoperative analgesia quality and duration following perianal surgeries.
Keywords: Magnesium sulfate, perianal surgery, postoperative analgesia, wound infiltration
INTRODUCTION
Hemorrhoids, anal fissures, and fistulas are all common benign anorectal diseases that have a big impact on people's lives.[1] After perianal surgeries, two types of pain have been identified, namely rest pain and defecation pain. The majority of patients experience rest pain, which happens without any effort of straining or defecation. It is usually the most intense in the first 24 h after perianal surgeries and then gradually fades on the 2nd postoperative day. Defecation pain occurs during or after defecation as a result of fecal waste irritating the anal wound mixed with internal anal sphincter spasm. On the 2nd or 3rd postoperative day, patients generally feel defecation pain, which is the second peak of anal discomfort after the first peak (rest pain) has subsided.[2]
Although opioids are the most commonly used pain relievers after surgery, they have common side effects which include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical issues that can lead to improper pain management. The most common side effects of opioid use are constipation (which occurs frequently) and nausea.[3]
Nonsteroidal anti-inflammatory Drugs (NSAIDs) are another alternative to opioids, although they have several side effects, including impaired hemostasis, renal failure, and gastrointestinal bleeding.[4]
Local wound infiltration is an appealing technique because it is effective and has few limitations.[5] The restriction is that analgesia will last until the effects of local anesthetic (LA) activity wear off. As a result, several adjuvants such as buprenorphine, fentanyl, magnesium, dexamethasone, midazolam, neostigmine, and other drugs were utilized to extend the duration of analgesia after nerve blocks and wound infiltration techniques.[6] Magnesium is one of the agents that has been utilized to extend the duration of the effect of LA skin infiltration.[7] There is sparse information about the analgesic efficacy of magnesium sulfate as an adjuvant in perianal wound infiltration with the LA solution. Hence, a study was conducted to evaluate the postoperative analgesic effects of the addition of magnesium sulfate to local analgesic solution in perianal wound infiltration.
MATERIALS AND METHODS
Following approval from the institutional ethical committee, registration at the Clinical Trials Registry was done (CTRI/2021/05/033570, dated May 12, 2021). American Society of Anesthesiologists physical status (ASA PS) classes I-II patients aged 18–50 years of both genders with normal body mass index (BMI) undergoing perianal surgeries such as fissure in ano, fistula in ano, and hemorrhoidectomy were chosen for the study after providing written informed consent. A prospective, placebo-controlled, parallel-group, double-blinded, randomized clinical trial research was done. Pregnant women, patients with bleeding and clotting disorders, patients allergic to LA agents, inadequate spinal blockade, complicated surgeries, severe cardiac, respiratory, renal disease, and neuromuscular diseases were all excluded from the study.
Sixty patients were divided into two groups, Group M and Group C, at random, using the computer-generated table. Premedication was not given to any of the patients. Surgery was performed under spinal anesthesia in both the groups. In all patients, a subarachnoid block was performed in the L3–L4 space with a 26G Quincke's spinal needle with 2 mL of 0.5% bupivacaine heavy. In the operating room, patients were monitored with an electrocardiogram, noninvasive arterial blood pressure, and pulse oximetry. At the end of the surgery, local wound infiltration was performed. Group M patients received a local wound infiltration of injection magnesium sulfate 750 mg (1.5 mL of injection 50% magnesium sulfate) added to 0.5% bupivacaine 13.5 mL making a total volume of 15 mL, whereas Group C patients received a local wound infiltration of injection 0.5% bupivacaine 13.5 mL and 1.5 mL normal saline. The wound infiltration was done by various surgeons, and they were not aware of the group. Concealment of allocation was done by prefilled coded syringes.
There were no intraoperative complications in either group of patients. After the surgery is over, the patients were transferred to the recovery room and vital parameters were recorded. The length of the surgery and the duration of the spinal blockade were recorded. Mean arterial pressure (MAP), pulse rate, and respiratory rate were measured every 30 min for the first 2 h and then at 6, 12, and 24 h intervals. Hypotension was defined as a drop in systolic arterial blood pressure of more than 20% from baseline and was treated with 5 mg bolus doses of intravenous (i.v). ephedrine. Bradycardia was defined as a heart rate of <50 beats per minute and was treated with a 0.01 mg.kg−1 bolus atropine dose. Respiratory depression was defined as a respiratory rate of 10 or lower, and anesthesiologists will be alerted.
At 2, 4, 8, 12, and 24 h after surgery, the visual analog scale (VAS) was evaluated at rest and during movement (sitting from lying down position). Tramadol 50 mg i.v. was administered slowly over 2–3 min to any patient who complained of pain or reported a VAS of more than 4. If pain was not relieved after 30 min and patients continued to complain of pain, additional tramadol 50 mg i.v. doses were given, and this dose could be repeated every 30 min up to a total dose of 250 mg in 6 h and a maximum of 400 mg of tramadol over 24 h. The time of the first rescue analgesic administration, as well as the total analgesic requirement in the first 24 h, was recorded. Under the supervision of the co-investigator, the staff nurse recorded postoperative side effects such as sedation, respiratory depression, hypotension, urinary retention, nausea, and vomiting. For nausea and vomiting, ondansetron 4 mg i.v. was administered slowly.
Statistical analysis
SSPS version 17.0 software was used for statistical analysis (SPSS, Inc., Chicago, IL, USA). The normally distributed continuous data were described as mean and standard deviation, nonnormally distributed continuous data and ordinal data were described as range and median, and categorical data were described as frequency and percentage. The Student's t-test for normally distributed continuous data, Mann–Whitney U-test for ordinal data, and Chi-square test or Fisher's exact test, whichever is appropriate for categorical data, were used. P < 0.05 was considered statistically significant.
RESULTS
No statistically significant difference was observed between the groups concerning ASA PS class, gender, surgical diagnoses, age, weight, height, and BMI. The groups were comparable in regard to the duration of surgery and duration of spinal analgesia [Table 1].
Table 1.
Patients’ characteristics and clinical data
| Variable | Group M (n=30) | Group C (n=30) |
|---|---|---|
| ASA I/II (n) | 22/8 | 23/7 |
| Gender (male/female) | 14/16 | 16/14 |
| Surgery - fissure/hemorrhoids/fistula | 15/11/4 | 14/12/4 |
| Age (years) | 39.83±8.61 | 38.53±9.26 |
| Weight (kg) | 71.76±5.26 | 73.7±11.31 |
| Height (m) | 1.61±0.07 | 1.62±0.06 |
| BMI (m2.kg−1) | 27.48±1.85 | 26.05±2.01 |
| Duration of surgery (min) | 23±8.26 | 23.66±2.01 |
| Duration of spinal analgesia (min) | 135.3±10.41 | 130.33±12.72 |
Ratio or interval data are expressed as mean±SD and ASA I or II and gender are expressed as numbers. ASA=American Society of Anesthesiologists, SD=Standard deviation, BMI=Body mass index
There was no statistically significant difference between the groups in MAP, pulse rate, and respiratory rate in all measurement intervals (P > 0.05).
The median VAS scores at rest and on the movement of both the groups are given in Table 2 and shown in Figure 1 which shows the median value of both the groups over 24 h. Group M had lower VAS scores than Group C at 4 and 8 h intervals and was found to be statistically significant (P < 0.05). There were no statistically significant differences in VAS scores among the groups at 12 h (P > 0.05), but the variation range was narrow in the study group and wide in the control group. The study group had lower VAS scores at 24 h interval when compared to the control group. This difference was statistically significant (P < 0.05).
Table 2.
Visual Analog Scale score at rest and on movement
| Time (h) | Median (range) |
|||||
|---|---|---|---|---|---|---|
| VAS score on rest |
VAS score on movement |
|||||
| Group M (n=30) | Group C (n=30) | P | Group M (n=30) | Group C (n=30) | P | |
| 2 | 0 | 0 | - | 0 | 0 | - |
| 4 | 1 (0-1) | 2 (1-3) | <0.05 | 2 (1-3) | 3 (3-5) | <0.05 |
| 8 | 2 (2-5) | 3 (1-5) | <0.05 | 3 (2-5) | 3 (1-5) | <0.05 |
| 12 | 3 (1-5) | 3 (2-5) | >0.05 | 3 (2-5) | 4 (2-5) | >0.05 |
| 24 | 2 (2-4) | 3 (2-5) | <0.05 | 3 (2-5) | 4 (2-5) | <0.05 |
VAS=Visual Analog Scale
Figure 1.
Visual Analog Scale score at rest
The need for rescue analgesic for the first time was at 452 ± 52.97 min in Group M and 289.66 ± 54.05 min in Group C [Table 3]. Thus, the need for the first dose of rescue analgesia was earlier in Group C as compared to Group M, and the difference was statistically significant (P < 0.05). Group M had a longer duration of postoperative analgesia when compared with Group C (P < 0.05).
Table 3.
First analgesic request time and total consumption of tramadol
| Variable | Group M (n=30) | Group C (n=30) | P |
|---|---|---|---|
| Time for first analgesic request (min) | 452±52.97 | 289.66±54.05 | <0.001 |
| Total tramadol consumption in 24 h (mg) | 181.66±54.9 | 298.33±57.95 | <0.001 |
Data are expressed as mean±SD. SD=Standard deviation
The 24 h analgesic requirement in Group M was lower 181.66 ± 54.9 mg when compared with Group C with 298.33 ± 57.95 mg [Table 3], and the difference was statistically significant (P < 0.05).
The incidence of adverse events is shown in Table 4. None of the patients developed sedation, urinary retention, hypotension respiratory depression, nausea, and vomiting. Group C had fewer incidences of nausea and vomiting than Group M, but this difference was not statistically significant (P > 0.05).
Table 4.
Incidence of adverse events
| Adverse event | Group M (n=30) | Group C (n=30) | P |
|---|---|---|---|
| Sedation | 2 | 3 | >0.05 |
| Urine retention | 1 | 1 | >0.05 |
| Hypotension | 1 | 1 | >0.05 |
| Respiratory depression | 0 | 0 | >0.05 |
| Nausea and vomiting | 1 | 3 | >0.05 |
DISCUSSION
Perianal surgeries play an important role in surgical practice and it requires a deep plane of anesthesia because this zone gets multiple nerve supplies and is reflexogenic. The goal is accomplished by regional anesthesia, localized blocks alone or in combination with monitored anesthetic care, and deep general anesthesia, which is often administered using muscle relaxants and tracheal intubation.[8] Modern general anesthetics are an excellent choice for daycare surgeries because they provide smooth, easily adjustable anesthesia with rapid recovery. Spinal anesthesia, caudal blockade, posterior perineal blocks, and LA are popular regional anesthesia techniques in practice for perianal surgeries.[9] The current tendency in regional anesthesia is to use a lower dosage of a LA to provide the specific segmental block. In addition, adjuvants are added to provide longer postoperative pain relief. The postoperative phase may be worsened by certain factors, namely extreme pain, urinary retention due to shared nerve supply, and surgical hemorrhage.[10] Management of postsurgical pain is an important element of perioperative anesthetic care, according to Garimella and Cellini,[11] because acute postsurgical pain influences surgical results. Postoperative pain is a primary cause of prolonged hospitalization and patient unhappiness, necessitating the anesthesiologist's provision of adequate postoperative analgesia that expedites patient recovery and facilitates mobilization.
Peripheral nerve blocks, which are routinely used for regional anesthetic before or after hand or arm surgery, neck or spine surgery, and other operations, have been studied with a variety of drugs. The large diversity of co-administered adjuvants to the LAs and locations of administration poses difficulty in determining the comparative benefits of nerve block adjuncts. In a few studies, tramadol, epinephrine, buprenorphine, sodium bicarbonate, dexamethasone, and clonidine appear to be useful additions.[7]
Local infiltration using a LA agent such as bupivacaine at the end of surgery is a simple and easier procedure.[12] Pettersson et al. studied the effects of wound infiltration of LAs (bupivacaine 100 mg and ropivacaine 300 mg) in inguinal hernia surgeries. They found that wound infiltration with long-acting LAs resulted in low pain levels after hernia surgery.[12] Analgesia can be provided by continuous wound infiltration of LA through a variety of techniques. It prevents pain from being transmitted from the wound's nociceptive afferents. In addition, the local inflammatory response to injury that leads to discomfort and hyperalgesia is also minimized. This may decrease the release of inflammatory mediators, the generation of free oxygen radicals, and edema formation.[13]
In this study, we compared the effects of bupivacaine and bupivacaine-magnesium sulfate infiltration into the perianal surgical site on postoperative pain. Magnesium is an N-methyl-d-aspartate (NMDA) receptor and related ion channel antagonist. It is mostly an intracellular ion and is detected in extremely modest amounts in the plasma. Magnesium is thought to perform many critical roles in nociception.[14] The degree of pain associated with many painful medical and surgical situations is inversely related to serum magnesium levels.[14] Magnesium sulfate can be used as an adjuvant to LA solutions for various types of regional anesthesia and analgesia to increase the quality and prolong the duration of the block.[15] Pastore et al. hypothesized that the mechanism of central sensitization caused by nociceptive stimulation of peripheral neurons is prevented by magnesium used as an adjuvant to analgesia, which is based on a noncompetitive antagonism toward the NMDA receptor and the blockage of calcium channels. As a result, the VAS score decreases after surgery, which is linked to magnesium's influence on the pain pathway.[16]
Kaur et al., in their study, compared the effects of the addition of magnesium sulfate and ketamine to ropivacaine in supraclavicular brachial plexus block, and found that magnesium sulfate significantly prolongs the duration of analgesia when compared to ketamine.[17] According to Hazarika et al., wound infiltration with bupivacaine and magnesium sulfate offered a longer duration of postoperative analgesia and considerably decreased postoperative opioid usage in patients following lumbar laminectomy compared to ropivacaine and magnesium sulfate.[18] Eldaba et al. discovered that continuous wound infiltration with a mixture of bupivacaine and magnesium sulfate after cesarean section provided effective analgesia and reduced postoperative patient-controlled analgesia requirements when compared to continuous wound infiltration with LA alone or placebo, with fewer opioid adverse effects.[19] Ahmed demonstrated that the addition of magnesium sulfate to LAs in pectoral nerve block reduces intra- and postoperative narcotic doses and prolongs the pain-free duration.[20]
In a study conducted by Tauzin-Fin et al., co-administration of magnesium sulfate with ropivacaine for postoperative infiltration analgesia after radical retropubic prostatectomy had lower postoperative tramadol requirements.[21] Kundra et al. conducted a randomized double-blinded trial in 60 parturients undergoing lower-segment cesarean section and encountered that subcutaneous magnesium infiltration mixed with a LA agent extends the analgesic efficacy without any significant adverse effect.[5]
In the first 24 h after surgery, bupivacaine infiltration with magnesium sulfate outperformed infiltration with only bupivacaine in terms of duration of postoperative pain relief, 24 h analgesic requirements, and defecation pain score in our study.
Limitations
However, there are several limitations to our study. Much research has been conducted on the use of magnesium sulfate in wound infiltration for postoperative analgesia in various surgical procedures. The dosage ranged from 100 mg to 750 mg, with one study using solely magnesium sulfate at a dose of 2000 mg for wound infiltration. Because there has been no previous research on the use of magnesium sulfate in wound infiltration for perianal surgeries, we chose 750 mg at arbitrary to get better results. More research may be needed to determine the optimal dosage of magnesium sulfate for perianal wound infiltration. The technique of perianal wound infiltration also needs to be standardized to avoid variations among surgeons.
CONCLUSION
Magnesium sulfate when added to bupivacaine in wound infiltration technique following perianal surgeries provided a longer duration of postoperative analgesia, lesser analgesic requirements, and a lower defecation pain score.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
The authors would like to acknowledge the Department of Anaesthesiology and critical care for their help in this research.
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