Search Results and Selected Articles
The initial literature search retrieved 72 citations, among which 17 were excluded due to duplication. After screening the titles and abstracts, 36 citations were excluded based on the inclusion criteria, while eight studies were subsequently excluded after reading the full-text. Eventually, 11 RCTs [26-36] met the inclusion criteria and were qualified for this meta-analysis (Fig. 1).
The characteristics of the included trials are presented in Table 1. These 11 studies were published between 2006 and 2018, and a total of 677 patients were included, with individual sample sizes ranging from 18 to 51. Five studies compared IA Mg versus saline or bupivacaine alone [26, 28, 30, 31, 34], five studies compared IA Mg plus bupivacaine versus bupivacaine [27, 29, 32, 33, 36], while one study contained these two kinds of comparisons [35], and both were included.
Table 1
Characteristics of the included 11 randomized controlled trials
Mg = magnesium sulfate; B = bupivacaine; LB = levobupivacaine; ACL = anterior cruciate ligament; Un = unknown; FNB = femoral nerve block; VAS = visual analogue scale score; NRS = numeric rating scale; AC = analgesic consumption; AD = analgesic consumption duration; SE = side effects
Study Quality and GRADE of Evidence
Figure 2 illustrates the risk of bias assessment. Among the 11 included studies, two [28, 29] did not describe their random sequence generation (high risk of selection bias) and four [26, 29, 32, 33] did not design a clear allocation concealment plan (unclear or high risk of selection bias). All trials adopted the double-blind method, except one [31], which adopted a single-blind method (high risk of performance bias). The GRADE level of evidence for each RCT is shown in Table 2, and the quality was mostly high or moderate.
Table 2
The GRADE evidence quality for each outcome
(1) GRADE working group grades of evidence:
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: Any estimate of effect is very uncertain.
(2) Explanations:
a Study limitation: included trials are quasi design.
b Inconsistency of results: large heterogeneity.
c Indirectness of evidence: large differences between the interventions in different trials.
d Imprecision: small sample size and wide 95%CI.
e Reporting bias: positive values showing benefits of the studied intervention.
Outcomes of the Meta-analysis
VAS Scores at Rest
Nine studies, including ten trials, evaluated the effects of IA Mg on pain relief at rest. The combined results demonstrated significantly lower pain scores at postoperative 2 h (MD = −0.74, 95% CI: −0.84–−0.64; p = 0.51; I2 = 0%), 4 h (MD = −0.24, 95% CI: −0.37–−0.11; p = 0.11; I2 = 45%), 12 h (MD = −0.53, 95% CI: −0.64–−0.41; p = 0.10; I2 = 47%), and 24 h (MD = −0.33, 95% CI: −0.42–−0.24; p = 0.20; I2 = 30%) in patients who received IA Mg alone or IA Mg plus local bupivacaine compared with placebo or bupivacaine alone after arthroscopic knee surgery (Table 2, Figure 3). The heterogeneity test showed that the heterogeneity was acceptable, hence a fixed-effects model was used, and further sensitivity analysis was not performed.
VAS Scores with Movement
Seven trials evaluated the effects of IA Mg on pain intensity with movement. Similarly, the pain scores with movement were also lower in patients who received IA Mg administration alone or plus local bupivacaine compared with the controls at postoperative 2 h (MD = −0.46, 95% CI: −0.64–−0.27; p = 0.14; I2 = 39%), 4 h (MD = −0.85, 95% CI: −1.40–−0.30; p < 0.0001; I2 = 95%), 12 h (MD = −0.83, 95% CI: −1.17–−0.48; p = 0.004; I2 = 71%), and 24 h (MD = −0.58, 95% CI: −0.79–−0.36; p = 0.05; I2 = 45%) (Table 2, Figure 4). Regarding the pain scores at postoperative 4 h, sensitivity analysis demonstrated that removal of the study Kemalettin et al. [31] significantly changed the results (MD = −0.51, 95% CI: −0.62–−0.39; p = 0.45; I2 = 0%). In this RCT, postoperative analgesia was maintained by IV tramadol during the first 4 h after surgery. Meanwhile, sensitivity analyses after excluding one trial at a time still showed a substantial heterogeneity in the pain outcomes at postoperative 12 h.
Postoperative Opioid Consumption
Eight eligible trials assessed the effect of IA Mg on postoperative opioid consumption (IV morphine equivalent). Within postoperative 24 h, opioid consumption was significantly decreased in patients who received IA Mg alone or in combination with bupivacaine compared with the control group (MD = −4.23, 95% CI: −4.64–−3.82; p = 0.21; I2 = 27%) (Table 2, Figure 5). No statistical heterogeneity was observed, and a fixed-effects model was used.
Time to First Analgesic Request (Min)
Eleven trials evaluated the effects of IA Mg on the time to first analgesic request after surgery. The administration of IA Mg alone or with bupivacaine resulted in a statistically significant prolonging of the time to analgesic requirement compared with control (MD = 329.99, 95% CI: 228.73–431.24; P < 0.00001; I2 = 99%) (Table 2, Figure 6). The heterogeneity was considerable; however, further sensitivity analysis did not change the heterogeneity when any of the studies were removed.
Safety Analysis
Only three included RCTs reported adverse reactions. In the study by Abdulatif et al. [28], postoperative shivering was observed in 12 and 10 patients in the IA Mg administration (n = 28) and control (n = 27) groups, respectively. In the RCT conducted by Radwan et al. [30], one patient in both the IA Mg (n = 20) and placebo (n = 20) groups developed knee effusion. In the study conducted by Suhrita et al. [32], two patients developed hypotension and bradycardia in the IA Mg group (n = 30), while no side effects were observed in the placebo group (n = 30). There was no statistically significant difference between the comparable groups in each RCT.