Anesth Analg 2008; 106:1548-1552
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31816a67a8
ANALGESIA
Intraarticular Injection of Magnesium Sulphate and/or Bupivacaine for Postoperative Analgesia After Arthroscopic Knee Surgery
Noha M. Elsharnouby*,
Hala E. Eid*,
Nahla F. Abou Elezz , and
Ashraf N. Moharram
From the Departments of *Anesthesiology and Intensive Care, Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain-shams University, and Department of Orthopedic and Traumatology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Address correspondence and reprint requests to Noha M. Elsharnouby, 8 Moktar El Masry Street, El-Golf Land Heliopolise, Cairo, Egypt. Address e-mail to nmelsharnouby{at}hotmail.com.
Abstract
BACKGROUND: Intraarticular bupivacaine is often used for prevention of pain after arthroscopic knee surgery. Intraarticular magnesium, a N-methyl-d-aspartate receptor blocker, would be of particular interest in either producing postoperative analgesia or enhancing the analgesic effect of intraarticular bupivacaine. We designed this study to determine whether intraarticular magnesium sulfate or bupivacaine results in a decrease in visual analog scale (VAS) score followed by a decrease in analgesic requirement and whether their combination would provide more reduction in VAS, and subsequently less analgesic requirement, than either drug alone.
METHODS: One-hundred and eight patients undergoing arthroscopic meniscectomy were randomized blindly into one of four parallel groups. The saline placebo group (group S) received 20 mL of isotonic saline, and the magnesium group (group M) received 20 mL of isotonic saline containing 1 g magnesium sulfate. The bupivacaine group (group B) received 0.25% (20 mL) bupivacaine, whereas the magnesium with bupivacaine group (group MB) received bupivacaine 0.25% and 1 g of magnesium sulfate in 20 mL. The postoperative analgesia was assessed using VAS recorded after surgery at 1, 2, 4, 6, 8, 12, and 24 h. Patients were evaluated at rest and with movement.
RESULTS: Group MB had a significantly reduced VAS both at rest and on movement, a significantly increased time to first postoperative analgesic request, as well as significantly reduced total analgesic requirement than other groups.
CONCLUSION: Magnesium combined with bupivacaine produces a reduction in postoperative pain when given intraarticularly in comparison to either bupivacaine or magnesium alone, or to saline placebo.
Arthroscopic knee procedures are commonly performed in the outpatient setting. Unrelieved postoperative pain may delay discharge and prolong hospital stay. Intraarticular local anesthetics are often used for prevention of pain after arthroscopic knee surgery.1,2 However, the mean duration of analgesia provided by local anesthetics is short, and patients may need opioid analgesia, possibly delaying their discharge. To overcome this, various drugs such as opioids, nonsteroidal antiinflammatory drugs, clonidine, neostigmine, and ketamine have been used with variable effects.3–5
Recent evidence suggests that N-methyl-d-aspartate (NMDA) receptors located in the peripheral somatic and visceral pain pathways play an important role in noceiception.6 NMDA receptors have been found in joints as demonstrated in a rat model in a study conducted by Yu et al.7
The effect of magnesium sulfate as a NMDA receptor antagonist intraarticularly in reducing pain sensation, or as an adjunct to local intraarticular anesthetic, is not known. This randomized, prospective, double-blind study investigated whether magnesium sulfate or bupivacaine results in a decrease in visual analog scale scores (VAS) followed by a reduction in analgesic requirement, and whether their combination would provide more reduction in VAS, and subsequently less analgesic requirement, than either drug alone.
METHODS
The protocol was approved by our IRB and patients gave informed written consent. One-hundred and twenty-five patients with ASA I and II undergoing arthroscopic meniscectomy were assessed for randomization. Seventeen patients were excluded: 10 patients refused to participate in the study, 5 patients had insufficient baseline pain recording, and 2 patients underwent simple diagnostic procedures. Therefore, 108 patients were included in this randomized prospective study. Exclusion criteria included patients undergoing simple diagnostic procedures, biopsy or simple washout, as well as patients younger than 18-yr-old and patients already taking opioid analgesics, tramadol, or nonsteroidal antiinflammatory drugs.
Immediately after admission, patients were instructed to use a 10-point linear VAS and were asked to record his or her level of perceived pain intensity on the scale from 0 to 10, with the zero representing no pain and the 10 representing the worst pain possible preoperatively. Patients were monitored using standard monitoring (pulse oximetry, electrocardiogram, noninvasive arterial blood pressure monitoring, and capnography). No premedication was given and surgery was done under general anesthesia using IV fentanyl 2 µg/kg, propofol 2 mg/kg, and maintenance of anesthesia using 70% N2O: 30% O2 and the inhaled anesthetic sevoflurane 1 MAC. No other analgesic was given intraoperatively. Patients breathed spontaneously using a laryngeal mask. Before surgical incision, a pneumatic tourniquet was inflated to 300 mm Hg and the surgeon performed arthroscopic meniscectomy. Patients were randomized using a computer-generated randomization list into one of four groups. [placebo saline group (group S) n = 27, magnesium group (group M) n = 27, bupivacaine group (group B) n = 27, and magnesium with bupivacaine group (group MB) n = 27]. Each patient received 20 mL of isotonic saline alone or containing the drug injected intraarticularly using the arthroscope 10 min before release of the tourniquet. Both the anesthesiologist in charge and the surgeon were unaware of the study medication.
Group M received 20 mL of isotonic saline containing 1 g magnesium sulfate. Group B received 0.25% (20 mL) bupivacaine; group MB received 0.25% bupivacaine and 1 g of magnesium sulfate in 20 mL saline, whereas group S received 20 mL of saline. Magnesium sulfate for intraarticular injection is an off-label drug and in this study 10% magnesium sulfate was used for IV, pH 5.5–7.0, and did not contain any bacteriostatic agent or preservative. Bondok and EL-Hady8 conducted a study of the analgesic effect of intraarticular magnesium sulfate compared with saline intraarticularly. Magnesium sulfate was also investigated in an in vitro animal study by Egerbacher et al.9 regarding its effect on articular cartilage.
Patients' age, sex, body weight, and tourniquet time were recorded. Postoperative analgesia was assessed by a blinded observer using VAS. VAS was recorded after surgery at 1, 2, 4, 6, 8, 12, and 24 h. Patients were evaluated at rest and with movement (active knee flexion). Postoperative analgesia was provided using IV ketorolac 30 mg per dose that could be repeated every 6 h if needed (when the VAS score was 5 or more) with a maximum daily dose of 120 mg. The duration of effective analgesia was recorded as the time from completion of surgery until the first analgesic dose was required. The total analgesic doses required during the first 24 h postoperatively were also recorded.
Data were analyzed using computer statistical software system SPSS® version 11 (Statistical Packages for the Social Sciences, Chicago, IL). Data were presented as mean and sd. Demographic data and tourniquet time were analyzed by using analysis of variance for numerical data and 2 tests for categorical data. Time to first analgesic requirement, pain scores, and amount of postoperative analgesics were analyzed by using the Kruskal-Wallis test, a Bonferroni adjustment was made for multiple comparisons. The sample size was calculated using the pain score as the primary variable. Based on a previous study8 assuming a sd of 1 cm, we calculated a group size of 27 patients would be sufficient to detect a difference of 1 cm on the VAS at an  threshold of 0.05 with power of analysis 95%.
RESULTS
One-hundred and eight patients ASA physical status I and II (10 females) underwent knee arthroscopic meniscectomy performed by the same surgeon. The groups were comparable with respect to age [ages ranged from 18 to 62 yr (mean age group 41 ± 11)], weight range (between 56 and 110 kg, mean 81 ± 12), sex distribution, and tourniquet time (Table 1).
Preoperatively, there was no significant difference in the pain scores among the groups at rest (P = 0.286) and on movement (P = 0.111). Pain scores were significantly different among the groups both at rest and on movement at 1, 2, 4, 6, 8, 12, and 24 h postoperatively.
At 1, 2, 4, 6, 8, 12, and 24 h, pain scores were significantly lower in group MB (at rest P < 0.0001and on movement P < 0.0001), and group B (at rest P < 0.005, and on movement P < 0.05) compared with either group M or group S. Pain scores were significantly lower in group MB compared with those in group B at rest and on movement respectively at 1 h (P = 0.033 and 0.004), 2 h (P = 0.015 and 0.006), 4 h (P = 0.023 and P = 0.007), 6 h (P = 0.015 and P = 0.003), and at 8 h (P = 0.024 and 0.037), whereas there was no significant difference in pain scores at 12 h (at rest P = 0.790, and on movement P = 0.428), and 24 h (at rest P = 0.288, and on movement P = 0.118). Pain scores were significantly reduced in group M compared with group S only at 1 h (P < 0.0001) postoperatively (Fig. 1 and 2).
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Figure 1. Visual analog scale score (VAS) (mean) at rest in the four groups preoperatively and at 1, 2, 4, 6, 8 12, and 24 h postoperatively. *P < 0.0001 more significant than group S. P < 0.005 more significant than group M and group S. ±P < 0.05 more significant than the other three groups. Group MB = magnesium and bupivacaine; group B = bupivacaine; group M = magnesium; group S = saline/placebo.
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Figure 2. Visual analog scale score (VAS) (mean) on movement in the four groups preoperatively and at 1, 2, 4, 6, 8 12, and 24 h postoperatively. *P < 0.0001 more significant than group S. P < 0.05 more significant than group M and group S. ±P < 0.05 more significant than the other three groups. Group MB = magnesium and bupivacaine; group B = bupivacaine; group M = magnesium; group S = saline/placebo.
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The duration of analgesia was significantly different among the groups (P < 0.0001). Group MB had a significantly longer time to first analgesic requirements than group B (P < 0.0001), group M (P < 0.0001), and group S (P < 0.0001). Group B had a significantly longer time to first analgesic requirement than either group M or group S (P < 0.0001). Group M also had significantly longer analgesic duration than group S (P = 0.001) (Fig. 3).
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Figure 3. The analgesic duration (minutes) in the four groups. The box represents the 25th to 75th percentiles, and the median is represented by the solid line. The extended bars represent the 10th to 90th percentiles. Group magnesium and bupivacaine (MB) had a significantly (±P < 0.0001) longer time to first analgesic request than group bupivacaine (B), group magnesium (M), or group saline/placebo (S). Group B had a significantly (P < 0.0001) longer time to first analgesic request than either group M or group S. Also, group M had a significantly (*P < 0.001) longer time to first analgesic request than group S.
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The 24 h consumption of ketorolac was significantly different among groups (P < 0.0001) (Table 2). Group MB consumed significantly lower doses than did group B (P < 0.0001), group M (P < 0.0001), and group S (P < 0.0001). Group B consumed significantly lower doses than did either group M (P = 0.009), or group S (P < 0.0001). There was no significant difference in analgesic consumption between group M and group S (P = 0.523). No side effects were detected from intraarticular injection of magnesium and bupivacaine during the 24 h period after surgery, as no patient experienced significant reduction in arterial blood pressure or heart rate (more than 15% from baseline), arrhythmia, flushing, central nervous system changes sedation, excitation, or respiratory depression. Values were recorded at the same time points as those for VAS.
DISCUSSION
This study revealed a significant analgesic benefit from the intraarticular administration of combined magnesium and bupivacaine for postoperative analgesia after arthroscopic knee surgery. The analgesic effect of intraarticular bupivacaine after arthroscopic knee surgery has been confirmed by various studies.10–12 This study not only confirmed this analgesic benefit, it further revealed that the addition of magnesium to bupivacaine provided even more effective analgesia. Patients in the group receiving intraarticular magnesium and bupivacaine had reduced postoperative pain scores, a longer analgesic duration, and lower 24-h analgesic use compared with the other groups receiving intraarticular bupivacaine, magnesium, or saline.
NMDA receptors have been found in joints,7 and activation of peripheral NMDA receptors contributes to human pain.13 In our study, the analgesic effect of magnesium alone was significantly less than bupivacaine alone, suggesting local anesthetic action as a mechanism for this analgesic effect.13
Although the beneficial effect of magnesium might be the result of antagonism of NMDA receptors, magnesium's inhibitory properties for calcium channels may play a role as well. The analgesia effect of magnesium may be the result of pharmacodynamics (causing a delayed uptake of bupivacaine from the joint) rather than a pharmacologic receptor effect. Calcium channel blockers have shown antinociceptive effects in animals and a morphine-enhancing effect in patients with chronic pain.14 In a study by Turan et al., magnesium used as an adjunct to lidocaine improved the quality of anesthesia and analgesia for IV regional anesthesia.15
Intraarticular bupivacaine has a long safety record of effective intraarticular use after arthroscopic knee surgery with significant reduction in postoperative analgesic consumption and increasing the time to first analgesic dose demanded,10,11 which was confirmed in our study (time to first analgesic request 287 ± 56 min). In this study, intraarticular administration of magnesium and bupivacaine resulted in a prolonged time to first analgesic request (676 ± 56 min) comparable to other adjuncts to bupivacaine used in previous studies such as clonidine16 or morphine.17
Magnesium sulfate for intraarticular injection is an off-label drug. However, an unpublished animal study was conducted on rats and then as an in vitro animal study by Egerbacher et al.9 and no side effects were encountered. Safety was not tested in our study, and further studies regarding the effect of magnesium on tissue healing and local anesthetics are recommended.
This study, though placebo-controlled, lacked an active control for systemic magnesium effect. Perhaps, IM or IV magnesium would have the same effect; thus, further studies comparing the effect of IV or IM magnesium to intraarticular injection of magnesium are also recommended.
We conclude that magnesium combined with bupivacaine produces a reduction in postoperative pain when given intraarticularly in comparison to either bupivacaine or magnesium alone, or to saline placebo.
Footnotes
Accepted for publication January 14, 2008.
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