A total of 166 unique citations were identified by our initial search strategy after duplicate articles were removed. The full-text versions of 22 potentially eligible citations were retrieved after exclusion of 144 impertinent studies based on title and abstract screening. Of these studies, 9 were excluded for the following reasons: incorrect intervention (QLB combined with other blocks, n = 3), and irrelevant comparator (TAP or local anesthetic infiltration, n = 6). Finally, a total of 13 randomized controlled trials9-20,26 were included in this meta-analysis. The flow diagram of study selection is shown in Fig 1.
Description of included studies
The characteristics of included studies in this review are presented in table 1. The 13 randomized controlled trials involved a total of 1269 patients, of which 632 received QLB, and 637 received systemic analgesia alone (i.e., no block or sham block, as Control). The CS was conducted under spinal anesthesia with bupivacaine in 10 studies9-12,15,18-20. Of these studies, fentanyl 10-20μg, morphine 0.1 mg and sufentanil 2.5-4ug was respectively added to the bupivacaine solution in 5 studies9,11,12,19,20, 2 studies19,20 and 2 studies10,26. The combined spinal and epidural analgesia was performed in two studies and general anesthesia was adopted in only one studies for CS. The posterior QLB was conducted in 7 studies, the lateral QLB was performed in 3 studies and the transmuscular QLB was adopted in 2 studies. The QLB was performed following the completion of the CS in all studies. Sham block with equal volume of 0.9% saline was performed in 6 studies and no block was performed in the other studies as control. An included study by Tamura et al. had four groups (two active and two controls) and the individual values for each group were reported separately. Therefore, we labelled these two comparison arms as (a) and (b) for a better reader comprehension.
Risk of bias Assessment
The risk of bias assessment of the included studies is presented in figure 2. All of the included studies provided satisfactory description of random sequence generation (low risk of selection bias). Eight studies did not provide sufficient information about allocation concealment (unclear risk of selection bias). Moreover, eight studies did not explicitly state the blinding process of participants and personnel (unclear risk of performance bias). Six studies did not explicitly state the blinding process of outcome assessment (unclear risk of detection bias). All of the included studies reported the complete outcome data (low risk of attrition bias) and unclear risk of other bias were found in all studies included.
Cumulative 24-h intravenous morphine equivalent consumption
Eight studies (490 participants; QLB: 246, Control: 244) that reported cumulative 24-h intravenous morphine equivalent consumption provided sufficient data for statistical pooling. Overall, QLB significantly reduced the cumulative 24-h intravenous morphine equivalent consumption compared with Control (MD, -11.51 mg; 95% CI -17.05 to -5.96, I2=82%; P<0.01) (Fig 3A).
Subgroup analysis in the settings of transmuscular QLB and lateral QLB showed statistically significant effect of QLB in reducing the cumulative 24-h intravenous morphine equivalent consumption compared with Control (Transmuscular QLB VS. Control: MD, -17.70 mg; 95% CI, -32.78 to--2.63, I2=89%, P<0.05; Lateral QLB VS. Control: MD, -10.41 mg; 95% CI, -13.36 to -7.45, I2=19%, P<0.01). However, sub-group analysis in the settings of posterior QLB showed no statistically significant effect of QLB in reducing the cumulative 24-h intravenous morphine equivalent consumption (MD, -5.80 mg; 95% CI -15.07 to 3.47, I2=61%; P=0.22) (Fig 3A).
300 participants (QLB: 151, Control: 149) and 404 participants (QLB: 202, Control: 202) were respectively included in sensitivity analysis of excluding studies that were published in Chinese and studies with morphine in spinal anesthesia. The sensitivity analyses supported the conclusion that QLB significantly reduced the increase cumulative 24-h intravenous morphine equivalent consumption (MD, -6.81mg; 95% CI -11.46 to- 2.17, I2=1%; P<0.01; MD, -13.28mg, 95% CI -18.97 to -7.58, I2=80%; P<0.01, respectively) (Table S1).
TSA results showed that a diversity-adjusted required information size (RIS) of 2542 patients was calculated and a cumulative Z-value curve that crossed both the traditional boundary and the trial sequential monitoring boundaries (TSMB), indicating that the result of the meta-analysis is stable and no further studies is needed (Figure 3B).
Cumulative 48-h intravenous morphine equivalent consumption
Seven studies (835 participants; QLB: 418, Control: 417) that reported cumulative 48-h intravenous morphine equivalent consumption were available for statistical pooling. Overall, QLB significantly reduced the cumulative 48-h intravenous morphine equivalent consumption compared with Control (MD, -15.87 mg; 95% CI -26.36 to -5.38, I2=94%; P<0.01) (Fig 4A).
Subgroup analysis in the settings of both posterior QLB and lateral QLB showed statistically significant effect of QLB in reducing the cumulative 48-h intravenous morphine equivalent consumption compared with Control [Posterior QLB VS. Control: MD, -17.04 mg; 95% CI, -29.79 to -4.28, I2=96%, P<0.01; Lateral QLB VS. Control: MD, -9.90 mg; 95% CI, -16.62 to -3.17, I2=0%, P<0.01] (Fig 4A).
749 participants (QLB: 374, Control: 375) were included in sensitivity analysis of excluding studies without morphine in spinal anesthesia and the result of the sensitivity analysis showed significant reduction of cumulative 48-h intravenous morphine equivalent consumption (MD, -19.23mg; 95% CI, -30.49 to -7.97, I2=95%, P <0.01). However, the sensitivity analysis of excluding studies that were published in Chinese did not suggested QLB significantly reduced the cumulative 48-h intravenous morphine equivalent consumption (QLB: 127, Control: 125, MD, -18.8 mg; 95% CI -47.5 to 9.9, I2=95%; P=0.2) (Table S1).
TSA results showed that a diversity-adjusted RIS of 1625 patients was calculated and a cumulative Z-value curve that crossed both the traditional boundary and the TSMB, suggesting that the result of the meta-analysis is stable and no further studies is needed (Fig 4B).
Postoperative Pain score at rest
Comparing QLB with Control for postoperative pain scores at rest, the number of participants included at each time point was 887 (QLB:439, Control: 448), 438(QLB:218, Control: 220), 1003 (QLB:502, Control: 501), 1147 (QLB:570, Control: 577), 539 (QLB:468, Control: 467) at 2, 6, 12, 24 and 48h, respectively. Compared with Control, QLB improved pain control at 2, 6, 12, 24 and 48h postoperatively, by a mean difference [99% CI] equivalent to -0.65 [-1.13, -0.17] (P < 0.01, I2= 99%), -0.97 [-1.55, -0.39] (P < 0.01, I2= 87%), -0.95 [-1.18, -0.71] (P < 0.01, I2= 83%), -0.65 [-0.88, -0.43] (P < 0.01, I2= 86%), -0.29 [-0.45, -0.13] (P < 0.01, I2= 78%), respectively. The overall effect of meta-analysis showed that QLB significantly reduced postoperative pain scores at rest between compared with Control (MD= -0.66, 95% CI -0.84 to -0.49, P < 0.01, I2= 98%) (Fig 5).
Postoperative Pain score during movement
Comparing QLB with Control for postoperative pain scores at movement, the number of participants included at each time point was 709 (QLB:351, Control: 358), 388 (QLB:193, Control: 195), 825 (QLB:414, Control: 411), 971 (QLB:484, Control: 487), 757 (QLB:380, Control: 377) at 2, 6, 12, 24 and 48h, respectively. Compared with Control, QLB improved pain control at 6, 12, 24 and 48h postoperatively, by a mean difference [99% CI] equivalent to -0.68 [-1.33, -0.03] (P < 0.05, I2= 61%), -1.38 [-2.05, -0.72] (P < 0.01, I2= 98%),-0.73 [-1.45, -0.01] (P < 0.01, I2= 94%), -0.89 [-1.54, -0.25] (P < 0.01, I2= 96%), respectively. However, QLB did not showed significant effect in reducing pain score during movement at 2h postoperatively (MD= -0.58, 95% CI -1.28 to 0.12, P=0.1, I2= 97%). The overall effect of meta-analysis showed that QLB significantly reduced postoperative pain scores during movement compared with control (MD= -0.87, 95% CI -1.17 to -0.58, P < 0.01, I2= 99%) (Fig 6).
Time to First Analgesic Request
For QLB versus Control, the time to first analgesic request was reported in five studies (709 patients; QLB: 353, Control: 356). Compared with Control, patients receiving QLB had a longer time to first analgesic request, by 8.37h [0.19, 16.54] (P < 0.05, I2 = 100%) (Fig S1).
Incidence of postoperative PONV
Nine studies (965 participants; QLB:484, Control:481) reported the incidence of postoperative PONV. The result of meta-analysis showed that QLB significantly reduced the incidence of PONV compared with Control (RR = 0.51, 95% CI 0.32 to 0.80, P<0.01, I2 = 43%) (Fig S2).
Quality of evidence
For each included outcome, quality of the evidence synthesized using the GRADE approach was shown in table 2. Overall, most quality of the evidence of the included outcomes were moderate and low.