Comparison of Bupivacaine Plus Magnesium Sulfate and Ropivacaine Plus Magnesium Sulfate Infiltration for Postoperative Analgesia in Patients Undergoing Lumbar Laminectomy: A Randomized Double-blinded Study.

AIM: The objective of this study was to assess and compare the analgesic duration of local infiltration of bupivacaine plus magnesium sulfate and ropivacaine plus magnesium sulfate for postoperative analgesia in patients undergoing lumbar laminectomy. STUDY
DESIGN: A randomized, prospective, double-blinded single hospital, comparative study.
METHODS: Sixty adult patients of the American Society of Anesthesiologists physical Status I and II were randomly allocated into two Groups BM and RM, comprising 30 and 31 patients. Postlumbar laminectomy, the study drug was locally infiltrated into the paravertebral muscles on either side before skin closure. Group BM was given 20 ml of 0.25% bupivacaine combined with 500 mg of magnesium sulfate (constituted with normal saline [NS]), and Group RM was given 20 ml of 0.25% ropivacaine combined with 500 mg of magnesium sulfate (constituted with NS). Postoperative visual analog scale pain score was assessed hourly for the first 24 h postoperatively. Duration of postoperative analgesia, rescue analgesia consumption and side effects were also recorded. STATISTICAL ANALYSIS: Comparison of data between the groups was done with SPSS 21.0© using independent t-test, Chi-square test, and Mann-Whitney U-test accordingly. P<0.05 was considered statistically significant.
RESULTS: Time to first analgesic consumption was significantly longer in Group BM (7.3 ± 0.46 h) compared to Group RM (6.6 ± 0.69 h) (P < 0.05). The consumption of nalbuphine rescue analgesic was significantly higher in Group RM (15.33 ± 5.07 mg) compared to Group BM (12 ± 4.07 mg) (P < 0.05).
CONCLUSION: Wound infiltration with bupivacaine and magnesium sulfate compared to ropivacaine and magnesium sulfate provided longer duration of postoperative analgesia and significantly reduced postoperative opioid consumption in patients undergoing lumbar laminectomy.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Lumbar laminectomy is a common neurosurgical and orthopedic procedure. Lumbar laminectomy patients suffer from intense postoperative pain which is usually intense in the initial 12 h after surgery, being maximum at rest, and exacerbated by movement.[1] Postoperative excitibility of the dorsal horn neurons is due to tissue injury which mediates this surgical pain.[2] Postoperative pain relief is known to reduce patient morbidity and mortality, ensures early mobilization, and increases patient satisfaction.[3] Multimodal pain control therapy is now advocated.[4] Numerous clinical studies have reported wound infiltration with local anesthetics as safe and effective for postoperative analgesia following lumbar laminectomy under general anesthesia.[567] The addition of various adjuvants such as clonidine, magnesium, and dexmedetomidine to local anesthetics for infiltration has shown promising results.[7] Magnesium sulfate, an N-methyl-D-aspartate (NMDA) receptor antagonist, is now being extensively used in the perioperative period to effectively reduce the anesthetic and analgesic requirements and even shown to reduce postlumbar laminectomy surgical pain.[789]

So far, there are no clinical studies comparing the efficacy of magnesium sulfate when combined with local anesthetic agents, such as bupivacaine and ropivacaine for lumbar spine surgical site infiltration. The objective of this study was to assess and compare the effectiveness and safety of local infiltration of bupivacaine combined with magnesium sulfate and ropivacaine combined with magnesium sulfate for postoperative analgesia in patients undergoing lumbar laminectomy.

METHODS

After Institutional Ethical Approval, this randomized, prospective, double-blinded single hospital study was performed jointly under the Department of Anaesthesiology and Critical Care and Department of Neurosurgery, Gauhati Medical College; from March 2016 to June 2016. Totally, 85 patients were enrolled for this study scheduled to undergo lumbar laminectomy, 19 patients did not meet the inclusion criteria, and 5 patients refused to participate in the study [Figure 1].

Figure 1

Consort flow diagram.

Written informed consent was obtained from the remaining 61 patients belonging to physical status American Society of Anesthesiologists (ASA) Classes I and II, aged 18–65 years with a body mass index (BMI) <30. Patients with known allergy to study drugs, known seizure disorder, severe systemic disease, psychiatric illness, and coagulopathy on regular opioid medications were excluded from the study group. All patients were made familiar with the visual analog pain scale (VAS) during the preanesthetic evaluation, where 0 represented no pain and 10 as the worst imaginable pain. Preoperative VAS scores were obtained from all patients by asking the average intensity of pain during the preanesthetic checkup. Based on computer-generated tables, the patients were randomized into two groups, Group BM (n = 30) and Group RM (n = 31). The study drugs were prepared by an anesthesia resident not taking part in the study. Both the surgeon as well as the anesthesist participating in the procedure were blinded to the study drugs.

Group BM received 50 mg of bupivacaine combined with 500 mg of magnesium sulfate (1 ml) made up to 20 ml solution using normal saline (NS).

Group RM received 50 mg of ropivacaine (10 ml) combined with 500 mg of magnesium sulfate (1 ml) made up to 20 ml solution using NS.

In both Groups BM and RM, general anesthetic technique was used. In the operating room, standard ASA monitors were attached, and baseline vitals were recorded. All the patients were premedicated with injection fentanyl 2 μg/kg intravenous (IV), injection midazolam 0.05 mg/kg IV. Induction with IV propofol 2 mg/kg was done. Muscle relaxation achieved with injection rocuronium 0.9–1.2 mg/kg IV for tracheal intubation. Patients were adequately positioned and ventilated using volume-controlled mode with a tidal volume of 8 ml/kg. Intraoperative anesthesia and muscle relaxation were maintained with isoflurane 0.4%–0.8% and divided doses of injection rocuronium 0.3 mg/kg IV dose. Intraoperative analgesia was maintained with continuous infusion of fentanyl at a dosage of 1 μg/kg/h. Patients were adequately monitored intraoperatively. Fentanyl infusion was stopped 15 min before the expected time for completion of the procedure. Thirty minutes before skin closure local infiltration with the study drug was done by the surgeon into the paravertebral muscles 10 ml volume on either side. A standard 8–10 cm incision was used for lumbar laminectomy with three point infiltration on each side was done using a 3-5 cm long 22 gauge needle. After completion, patient was made supine, and neuromuscular blockade was reversed adequately. All the patients were extubated when awake and following commands. Patients who remaining sedated up to 1 h postextubation were excluded from our study group. After the operation, patients were observed in the postanesthetic care unit where VAS pain scores were assessed hourly up to a VAS score of >5[7] or up to the first 24 h postoperatively by a third anesthesia resident blinded to the study group. Duration of analgesia was deemed as the time from the completion of surgery till a vas score of >5 was noted or up to the time when the first demand for analgesic was made.[7] If VAS score of >5 was noted rescue analgesic in the form of injection nalbuphine 5 mg IV was administered over 15 min and repeated after 3 h if required. Similarly, sedation score, blood pressure, and heart rate changes were also observed on an hourly basis up to a maximum duration of 24 h. Side effects and complications were also observed and reported if any.

Statistical analysis

Data was expressed as mean and standard deviation for height, weight, duration of surgery, age, etc. Data was analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0© (SPSS Inc., Chicago, IL, USA). The data was tested for normality using Kolmogorov–Smirnov test. Comparison of continuous data between the Groups RM and BM was done using independent t-test. Nominal data in both groups was compared using Chi-square test and Mann–Whitney U-test wherever applicable. P < 0.05 was considered statistically significant.

As no previous study comparing bupivacaine and magnesium with ropivacaine and magnesium for postlumbar spine surgical pain relief, had been conducted on the Indian population we conducted this study as a pilot study to obtain baseline data for the population, hence sample size estimation was not done.

RESULTS

In both Groups BM and RM, the demographic parameters such as age, weight, BMI, sex, and duration of surgery were comparable [Table 1].

Table 1

Demographic parameters in both the groups RM and BM

A significantly higher duration of postoperative analgesia was observed in patients in Group BM (7.3 ± 0.46 h), compared to patients in Group RM (6.6 ± 0.69 h) (P = 0.0001) [Figure 2]. Nalbuphine consumption was significantly higher in Group RM (15.33 ± 5.07 mg) compared to Group BM (12 ± 4.07 mg) for the first 24 h postoperatively (P = 0.0068) [Figure 3]. Rescue analgesic was required in all of our study patients. Higher visual analog pain scores were observed among Group RM patients compared to Group BM patients at the 4th, 5th, 6th, and 8th h, respectively [Figure 4].

Figure 2

Duration of postoperative analgesia in Groups BM and RM.

Figure 3

Nalbuphine consumption in both the groups for first 24 h postoperatively.

Figure 4

Comparison of visual analog scale scores between Group BM and Group RM.

A higher number of patients were agitated and restless in Group RM at the 6th and 7th h whereas in Group BM, it was observed at the 7th and 8th h, respectively, probably due to the onset of pain [Figure 5].

Figure 5

Comparison of postoperative Ramsay sedation score in Group BM and Group RM.

The heart rate variation shows that peak heart rate in Group BM was observed between 6th and 7th h whereas for Group RM between 7th and 8th h, respectively, which was probably due to the onset of pain in our study patients [Figure 6]. Similarly, higher mean blood pressure in Group BM and Group RM was observed at 7th and 8th h due to the onset of pain in our study patients [Figure 7]. Postoperative urinary retention was the most common complication observed in our study patients.

Figure 6

Heart rate variation in both the Groups BM and RM.

Figure 7

Mean blood pressure variation in both the Groups BM and RM.

DISCUSSION

The results of our study show that infiltration of lumbar spine surgical area with bupivacaine and magnesium sulfate provided better postoperative pain control while lowering postoperative opioid consumption, without any added side effects compared to the use of ropivacaine and magnesium sulfate infiltration. Pain following spine surgery is mediated through the activation of nociceptors and mechanoreceptors located in the vertebrae, intervertebral disc, dura, nerve roots, facet joint capsules, muscles, ligaments, and fascial sheaths.[7] These structures are mainly innervated by the posterior rami of the spinal nerve roots linked to the autonomic nervous system. Inflammation or mechanical compression of these structures generates nociceptive impulses.[1011] The activation of these nociceptors leads to sensitization of adjacent neurons. Significant alterations occur with time as nociceptive impulses from both the peripheral as well as the central nervous systems amalgamate causing central pain sensitization, leading to exaggerated, and prolonged postoperative pain.[11] Inadequate postoperative pain control after lumbar laminectomy hampers early ambulation increasing the risk of deep vein thrombosis and contributes to the development of chronic pain.[1213] Various modalities of postoperative pain control therapy such as intravenous, intramuscular, surgical site infiltration and epidural analgesia are now being extensively used and studied.[7] Postlumbar surgery recovery and rehabilitation depends on the extent of pain relief with recent literature advocating the use of multimodal approach of postoperative pain control.[14] The use of opioids and nonsteroidal anti-inflammatory drugs for multimodal pain control carries risk of potential complications such as respiratory depression, renal injury, upper gastrointestinal bleeding.[14] The use of spinal and epidural technique for postoperative analgesia is often associated with delayed neurological recovery.[15] Local anesthetic drug infiltration used in our study was based on available literature describing its action on the pain-mediating free nerve endings and deeper tissues for the analgesic effect.[7] The use of bupivacaine, levobupivacaine and ropivacaine for surgical site infiltration is documented,[16] so we selected bupivacaine and ropivacaine for our study. 0.25% concentration of both local anesthetic was used to obtain adequate sensory blockade without any motor block and to prevent systemic toxicity by the absorption of large volumes of local anesthetic from the highly vascular vertebral and paravertebral tissues.

Magnessium sulphate, a known physiological antagonist of NMDA receptor in its inactive state.[17] NMDA receptors are not only present in the central nervous system but also in the peripheral tissues such as the skin and the muscles.[18] It has got no analgesic property of its own, but its NMDA receptor antagonistic property abolishes the central mechanism of pain transmission, modulation, sensitization and even modulates pain transmission from the peripheral tissues.[717] This unique property of magnesium sulfate promoted its use in our study patients in combination with local anesthetic. The dose of magnesium sulfate was selected as per Donadi et al.[7]

Bupivacaine and magnesium sulfate infiltration used in our study patients had significantly reduced the postoperative nalbuphine consumption compared to the use of ropivacaine and magnesium sulfate. Reduction in the amount of rescue analgesic consumption is a better predictor of analgesic efficacy compared to the total duration of analgesia.[19] Donadi et al.[7] had observed a similar mean analgesic duration of 7.8 h with reduction in postoperative tramadol consumtion using bupivacaine and magnesium sulfate in the same dosage for postoperative wound infiltration. The higher duration of analgesia observed for bupivacaine compared to ropivacaine may be attributed to its greater lipid solubility leading to greater tissue penetration.

Postoperative urinary retention was the most common complication observed in our study patients. Donadi et al.[7] had also observed urinary retention as the most common complication without any other major systemic complications. Limitations of our study include the use of equal concentration and not equianalgesic concentration of both local anesthetics which was done to prevent usage of higher doses of ropivacaine tissue infiltration within the highly vascular vertebral and paravertebral tissues preventing systemic toxicity. We would like to test the validity of our study results by large population-based trials.

CONCLUSION

The use of bupivacaine combined with magnesium sulfate when compared to the use of ropivacaine combined with magnesium sulfate for surgical site infiltration, prolonged the duration of postoperative analgesia, and reduced postoperative opioid consumption in patients undergoing lumbar laminectomy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.