Analgesic effectiveness of quadratus lumborum block for patients after abdominal surgery: a systematic review and meta-analysis

Background: A series of studies have reported that quadratus lumborum block (QLB) can have a great postoperative analgesia for lower abdominal surgery. However, a meta-analysis of the analgesic effect of QLB in patients undergoing lower abdominal surgery has not been published. Methods We searched the databases of Pubmed, Embase, Cochrane Library, and Web of Science (updated to October 15, 2019). We cumulative opioid consumption at 6, 12, 24 and 48h after surgery; pain score (rest and dynamic) at 6, 12, 24 and 48h after surgery; occurrence of common opioid-related complications at 24h after surgery . Opioid consumption as the main outcome. Results Thirteen randomized controlled trials (RCTs) including 751 patients were analysed. Compared with control group, QLB group can effectively reduce 24 and 48h cumulative opioid consumption 10.1mg (95%CI: -13,-7.2; p<0.00001) and 16.22mg (95%CI: -19.39,13.03; p<0.00001) in patients with cesarean section, but can reduce effectively cumulative opioid consumption in patients undergoing laparoscopic surgery at 6, 12 and 24h. Posterior QLB group and transmuscular QLB group reduced 24h cumulative opioid consumption 4.03mg ( 95%CI: -7.89, -0.19; p=0.04) and 12.44mg ( 95%CI: -20.2, -4.68; p=0.002), respectively. QLB group reduced rest visual analogue scale (VAS) score at 12 , 24 and 48 h ,however, the effective reduction of rest VAS score in patients undergoing cesarean section only occurs at 24h after surgery. Conclusion QLB seems to provide better analgesia for patients undergoing laparoscopic surgery than patients undergoing cesarean section. Transmuscular QLB appears to have reduced postoperative opioid consumption compared to posterior QLB. More future RCTs are needed to support our conclusions.


Background
Postoperative acute pain occurs in more than 80% of operation patients, and approximately 75% of operation patients experience the moderate or higher pain [1,2].
Evidence shows that less than half of operation patients claim that postoperative pain is effectively relieved. Inadequate negative control of pain affects the quality of life, function and function recovery, risk of postoperative complications, and risk of long-term postoperative pain [3]. Proper postoperative analgesia can reduce pain, encourage patients to cough and get out of bed, reduce the occurrence of lower extremity thrombosis and pulmonary complications and improve postoperative satisfaction [4][5][6]. Postoperative analgesia using traditional opioids often causes constipation, nausea, vomiting and other adverse reactions, thus limiting its clinical application. Regional analgesia techniques combined with intravenous self-controlled analgesia can effectively reduce the dosage and adverse effects of opioids, which is conducive to rapid recovery after surgery [4].
The quadratus lumborum block (QLB) was first proposed by Blanco [7] in 2007, which is suitable for perioperative analgesia in abdominal, hip and lower extremity surgery.
However, a meta-analysis of the QLB has not been published. The purpose of this article is to report on the improvement in the analgesic effect of the QLB compared to placebo and control groups in patients undergoing lower abdominal surgery. Subgroup analyses were intended to be used to find differences in the approach of different QLB and between patients with different surgical procedures. Provide guidance for anesthesiologists to 4 choose postoperative analgesia.

Methods
The work has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines.

Eligibility criteria
We included randomized controlled trials (RCTs) that measured the postoperative analgesia of QLB in patients undergoing lower abdominal surgery. There were no restrictions on the language of the full text. In order to ensure that the outcome indicators would not be interfered by too many factors, the trials we included must compared QLB group with control group with sham block or without block.

Literature search
We searched the databases of Pubmed, Embase, Cochrane Library and Web of Science (updated to October 15, 2019

Data collection and presentation
The characteristics and results data of the included trials were extracted independently by two authors(Chao Xu and He Zhu), and the work of quality assessment was also completed 5 independently by two authors(Chao Xu and He Zhu) using the Cochrane risk bias tool and Review Manager 5.3 software (Cochrane, London, UK) according to the Cochrane handbook [32]. If the two authors disagree about the quality of the article, it will be decided by the third author(Tianyu Liu) to join the discussion.
To assess the effect of QLB on postoperative analgesia in patients after abdominal surgery, we extracted the following data: cumulative opioid consumption (transformed to morphine equivalent) [33,34] at 6, 12, 24 and 48h after surgery; time interval from the end of the surgery to the first use of additional analgesic; the number of patients who used additional analgesic after surgery; pain score (rest and dynamic) at 6, 12, 24 and 48h after surgery; nausea and vomiting, itching, sedation, muscle weakness, and postoperative patient satisfaction at 24h after surgery; We contacted the author to ask about the results and got some responses to complete the meta-analysis [16,18].

Meta-analysis
Two authors collaborated on data processing using the Review Manager 5.3 software (Cochrane, London, UK) for data synthesis. Considering the heterogeneity among different trials, we chose random effect modeling for the synthesis of dichotomous and continuous data. The synthesized dichotomous variables were represented by the odds ratios (OR) and their 95% confidence intervals (CI). The synthesized continuous variables were represented by the mean differences and their 95% CIs. The findings were considered statistically significant when the 95% CI of the OR excluded 1 and the 95% CI of the mean difference excluded 0.
The heterogeneity between trials was determined using an I 2 test [35,36]. If the I 2 value was less than 25%, low heterogeneity was considered to exist; If I 2 value was greater than 25% and less than 50%, moderate heterogeneity was considered to exist; and if I 2 value 6 was greater than 50%, high heterogeneity was considered to exist. If there was high heterogeneity (I 2 value 50%), a sensitivity analysis was performed to determine the source of heterogeneity. If the included variables were excluded one by one and the I 2 value was still greater than 50%, the result was considered to be reliable. If the characteristics of the included trials varied widely, subgroup analysis was performed to reduce heterogeneity.

Study selection
The two authors(Chao Xu and He Zhu) retrieved a total of 843 articles, 32 of which were Additional file 1 presents the outcomes of included articles, Additional file 2 presents the results of the meta-analysis and Fig. 2 presents the results of quality assessment completed by two authors; the characteristics of the included articles were presented in Additional file 3. Sensitivity analysis was performed on all data synthesis, and no trials were found to reduce I 2 to 50%. Since less than 10 articles were included, the Begg's test was not performed.

Interval opioid consumption
We synthesized the total consumption of opioids at 12h, 24h and 48h after surgery to quantitatively evaluate whether QLB could reduce the need for opioids in patients after surgery. Cumulative opioid consumption was transformed to intravenous morphine Compared with control group, QLB group can effectively reduce 6, 12 and 24h cumulative opioid consumption, but the data are highly heterogeneous (I 2 =92%, 93% and 93%,respectively), after the subgroup analysis, we found: QLB group can effectively The cumulative morphine consumption in the laparoscopic subgroup at 12h and in the cesarean section subgroup at 24 and 48h showed low heterogeneity (I 2 =41%, 18% and 0%,respectively). The rest of the morphine consumption data showed high heterogeneity, 8 and the sensitivity analysis still could not effectively reduce the I 2 value.
Two articles [14,16] used NRS scores to measure the degree of nausea and vomiting. We synthesized the incidence of nausea and vomiting 24 hours after surgery. There was no significant difference in the incidence of nausea and vomiting between the QLB group and the control group.
Few observations were reported about the incidence of itching and sedation[10, 18,22], therefore statistical synthesis was not performed. Only one article[10] observed the incidence of itching and sedation (one case of itching and one case of sedation), and it was not possible to determine whether a significant difference exists between the QLB group and the control group.

Additionalanalgesic
Three articles [14,18,29] reported the time interval to the first additional analgesic ,and 5 articles [14,18,23,26,28] reported the numbers of patients who used additional analgesic. No statistical differences were found after subgroup analysis (Additional file 2).
Four articles[10, 18,26,31] reported the incidence of pruritus within 24 hours after surgery, and no statistical differences were found after analysis (Additional file 2 and
Zhu et al [28] reported that the recovery quality of patients in the QLB group was significantly higher than that of the control group. No statistical difference was found in the other two articles[23, 31].

Postoperative analgesia
The results of the statistical synthesis show that the QLB can effectively reduce the cumulative opioid consumption within 24 hours after surgery, even the pain score of 48h after surgery. The blocking range of the QLB may explain this result; a cadaver study [37] showed that the QLB can stably block the T12-L3 nerve roots, and another cadaver study [38] claimed that the coloring agent of the QLB can reach the thoracic sympathetic trunk, which can effectively reduce visceral pain.
Interestingly, for patients underwent laparoscopic surgery, statistically significant analgesic effect began to appear from 6h after operation; for patients with cesarean section, the analgesic effect often showed statistical difference from 24h after operation.
Compared with the control group, the QLB group had a lower reduction in dynamic pain 11 score than the rest pain score. There is no statistical difference in time to the first additional analgesic and numbers of patients who used additional analgesic. These seem to indicate that the postoperative analgesic effect of QLB is more pronounced when the pain is relatively mild.
QLB showed limited analgesic efficacy in patients undergoing cesarean section within 12 hours of surgery. However it's undeniable that QLB reduced the cumulative consumption of opioids , rest pain scores and dynamic pain scores in patients underwent cesarean section at 24h postoperatively, and the heterogeneity of these data was low, indicating that QLB can provide good analgesia for parturients. All QLB were performed at the end of cesarean section, which would not affect the operation. Blanco et al [8] have shown that QLB has a better postoperative analgesia after cesarean section than TAPB. QLB may be a good choice for parturients who are prone to postoperative pain.

PONV
The occurrence of nausea and vomiting after lower abdominal surgery is one of the most common side effects, mainly related to the traction of the intestine and the application of postoperative opioids. As a part of postoperative analgesia, QLB may have the potential to reduce the use of opioids. Although the cumulative opioid consumption in each subgroup decreased significantly within 24 h after surgery, only the transmuscular QLB group [28, 12 29] had statistically preventive effects on PONV and showed low heterogeneity. This may be related to the more reduction on postoperative opioid consumption of transmuscular QLB compared to posterior QLB (Additional file 2 and Fig. 3). Because few articles were included, this conclusion is restrictive. In the future, more research is needed to study the effect of transmuscular on the incidence of postoperative nausea and vomiting.

Complications of QLB
Because there is no great vessel and loose connective tissue around the optimal point of injection, this reduces the possibility of tissue damage, and complications of local hematoma and abdominal organ damage have not been reported. However, because local anesthetics can spread to the lumbar plexus, there is a potential risk of quadriceps weakness and accidental falls [40,41]. SaM et al [42] reported that after 30-40 minutes of QLB in two patients, severe hypotension and tachycardia occurred, possibly due to the spread of local anesthetic to the paravertebral space and epidural space, leading to sympathetic blockade.

Limitations
Our meta-analysis had some limitations. First, the number of articles included was small, 13 and the amount of data that could be synthesized was limited. Because the articles obtained during the search were limited, only the amount of literature for the lower abdominal surgery[10, 14,16,18,[23][24][25][26][27][28][29][30][31] was met and no analysis of upper abdomen [19,43], hip[44-47] and lower limb surgery was performed. Some outcomes could not be analyzed because of insufficient documentation. The incidence of postoperative opioidrelated complications was too small, which may mask the significant difference between the QLB group and the control group. Furthermore, prospective studies of patients with long-term follow-up were not retrieved, making it impossible to judge the impact of the QLB on long-term prognosis in patients. Finally, the heterogeneity within the literature is large and cannot be eliminated by subgroup analysis and sensitivity analysis, which affects the reliability of the results.

Conclusion
QLB showed effective postoperative analgesia at 6-24h after laparoscopic surgery and 24-48h after cesarean section. Transmuscular QLB appears to have more reduction on postoperative opioid consumption compared to posterior QLB. Transmuscular QLB had statistically preventive effects on PONV. In future, more RCTs are needed to support our conclusions.

Ethics approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

5.
Abdallah    The results of quality assessment of the included articles.
25 Figure 3 Cumulative opioid consumption 24 hours after surgery.

Figure 4
Rest pain score at 24 hours after surgery. Visual analogue scale (VAS) score at rest 24 hours after surgery. Numerical rating scale (NRS) score at rest 24 hours after surgery.