Ultrasound-guided erector spinae plane block for postoperative analgesia: a meta-analysis of randomized controlled trials

Background Ultrasound-guided Erector Spinae Plane Block (ESPB) has been increasingly applied in patients for postoperative analgesia. Its effectiveness remain uncertain. This meta-analysis aimed to determine the clinical efficacy of ultrasound-guided ESPB in adults undergoing general anesthesia (GA) surgeries. Methods A systematic databases search was conducted in PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing ESPB with control or placebo. Primary outcome was iv. opioid consumption 24 h after surgery. Standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. Results A total of 12 RCTs consisting of 590 patients were included. Ultrasound-guided ESPB showed a reduction of intravenous opioid consumption 24 h after surgery (SMD = − 2.18; 95% confidence interval (CI) -2.76 to − 1.61,p < 0.00001). Considerable heterogeneity was observed (87%). It further reduced the number of patients who required postoperative analgesia (RR = 0.41,95% CI 0.25 to 0.66,p = 0,0002) and prolonged time to first rescue analgesia (SMD = 4.56,95% CI 1.89 to 7.22, p = 0.0008). Conclusions Ultrasound-guided ESPB provides effective postoperative analgesic in adults undergoing GA surgeries.


Background
Ultrasound-guided Erector Spinae Plane Block (ESPB) is a novel regional anesthesia technique that local anesthetic (LA) injection is performed into the fascial plane situated between the transverse process of the vertebra and the erector spinae muscles it is considered a relatively safe simple technique to perform [1,2]. Followed by first description by Forero et al. [1] in 2016, it has been demonstrated successfully to provide analgesia in thoracic and thoracoabdominal surgeries [3,4] However, the use of ultrasound-guided ESPB remained controversial. Recently, several randomized controlled trials (RCTs) [5][6][7] on this topic have been published, but the determine conclusions cannot be established owing to the modest sample size of these RCTs. We therefore conducted a metaanalysis to examine the efficacy of ultrasound-guided ESPB among adults undergoing general anesthesia (GA) surgery. Our primary outcome was intravenous opioid consumption 24 h after surgery. Secondly outcomes included pain scores, number of patients who need rescue analgesia, time to first rescue analgesic and postoperative nausea or vomiting (PONV).

Literature search and selection criteria
This systematic review and meta-analysis of RCTs was reported abiding by the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement [8] and it was conducted base on the statement of the Cochrane Handbook for Systematic Reviews of Interventions [9]. No formal protocol was registered for this meta-analysis.
PubMed, EMBASE, and the Cochrane Library were searched from inception to August 2019 with no language restriction. The search terms used were: ('erector spinae plan block' OR 'erector spinae block' OR 'erector spinae plan blocks' OR 'erector spinae blocks'). The bibliographies of included trials were also manually searched for any eligible trials missed by the electronic search. This process was conducted iteratively until no extra reference could be verified.
Two of us independently performed the preliminary data search, after removing duplicate references, the titles and abstracts were screening for the eligible trials. We included all RCTs in adults who were undergoing GA surgery with the intervention of ultrasound-guided ESPB Trials were excluded for the following criteria: animal or cadaveric studies; reviews; did not report opioid consumption or pain scores as an outcome; Any discrepancies were resolved by discussion with coauthors.
Data extraction and quality assessment Data collection was performed by two authors (JH and JCL). The following information was collected from each eligible trial: first author, publication year, patient number, patient characteristics, American Society of Anesthesiologists (ASA) physical status, surgical procedure, ESPB group (position, dosage and concentration), control group (placebo or no invention). Extracted data were entered into a predefined standardized Excel (Microsoft 6 Corporation, USA) file.. For continuous data, we calculated mean and SD, if not provided, median and interquartile range were seen as means and standard deviation (SD) approximately as follows: the median was considered equal to the mean, and the SD was calculated as the interquartile range divided by 1.35 [10]. Any uncertainty arose were figured out though a consensus achieved.
Two authors (JH and JCL) evaluated the methodological quality of the trials according to the Cochrane risk-of-bias tool [11]. Each item was categorized as having a 'low', 'unclear', or 'high' risk of bias. Any uncertainty arose were resolve by discussion between two researches until a consensus was achieved.

Statistical analysis
The relative risks (RRs) and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. A random effects model was selected to acquire the most conservative effects estimate. An I 2 statistic of 25-50% were defined as low heterogeneity, an I 2 statistic of 50-75% were described as moderate heterogeneity, and those with an I 2 statistic of > 75% were considered as high heterogeneity [12], The heterogeneity was substantial when an I 2 value was over 50%. Subgroup analysis was conducted based on additional analgesia (patient-controlled analgesia device (PCA) versus not PCA). Publication bias was evaluated using funnel plots. Statistical analyses were calculated using the Review Manager Version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration).

Study identification and characteristics
A total of 675 studies were obtained by the literature search. One further citations were found by hand searching. 212 records were excluded for duplicate studies and a further 448 records removed by screening titles and abstracts. 16 full text publications remained were scrutinized for conclusive identified. 4 of them were excluded because 2 did not report data of interest [13,14], one was currently ongoing study [15],one was review article [16].Finally,12 RCT [5-7, 17-25] satisfied our inclusion criteria. A flowchart of the literature search is shown in (Fig. 1). All RCTs included in this meta-analysis were published between 2018 and 2019, with a total of 490. The main characteristics of the 12 RCTs included are presented in Table 1.

Quality assessment and publication bias
Four trials at a low risk of bias, and 8 trials at an unclear risk of bias. The randomisation procedure was adequately generated in 11 trials [5-7, 17-20, 22-25].
Since we subjectively judge the outcome measurement was little prone to be changed by lacking of blinding, all RCTs included were classified as low risk of bias at blinding of outcome assessments. Assessment of risk-ofbias summary of all RCTs are presented in (Fig. 4). There was no evidence of publication bias by inspection of the funnel plot (Fig. 5).

Main finding
The main finding of this meta-analysis is that ultrasound-guided ESPB significantly reduced opioid consumption 24 h after surgery. It further reduced pain scores and patients who need rescue analgesia, besides, it prolonged the time to first request of rescue analgesia. Despite of the high heterogeneity, the main finding was consistent in subgroup analyses.

Possible mechanisms for findings
Ultrasound-guided ESPB is a peri-paravertebral regional anesthesia technique which is supposed to block the dorsal and ventral rami of the thoracic and abdominal spinal nerves [1], and thereby to block the anterior, posterior, and lateral thoracic and abdominal walls. However, the mechanisms of action and spread of LA are not fully elucidated. Several potential mechanisms have been posited. One of the suggested mechanisms of ultrasound-guided ESPB is paravertebral spread of LA, LA infiltration was observed from injection site to three vertebral levels cranially and four levels caudally [26]. Based on this mechanism, Coşarcan SK et al. [27] reported a modification ESPB and got good pain relief in various surgeries. However, the mechanism of paravertebral spread of LA remained debated in several cadaveric studies [28][29][30]. Another potential mechanism is epidural spread of LA. Schwartzmann A et al. [31], Tulgar S, et al. [32] and Altıparmak B, et al. [33] found  [34,35].

Implications for clinical researches
Our findings demonstrated that ultrasound-guided ESPB was associated with a reduction of opioid consumption, which further proved the effectiveness of ESPB.
However, ultrasound-guided ESPB has only been utilized in clinical setting for about 3 years, several important issues have not been resolved yet. First, the optimal concentration, volume and type of LA in ESPB is not well established. Although 20 and 30 ml of 0.25% bupivacaine or 0.5% ropivacaine were recommended [36], concentrations of 0.25-0.5% bupivacaine 10-20 ml were used in ultrasound-guided ESPB among all 12 RCTs included in this meta-analysis. Is bupivacaine more preferred than ropivacaine? why? We tried to make a judgment but stop by the insufficient evidence.  [40][41][42].

Strengths and limitations
Our meta-analysis has several strengths. As far as we know, this is the first meta-analysis to evaluate the efficacy of ultrasound-guided ESPB in adults undergoing GA surgery. Besides, we performed this meta-analysis in compliance with the Cochrane Handbook and the PRISMA statement. Several notable limitations should be considered when interpreting the results. Firstly, the trials included have a modest sample size which could magnify the treatment effect. Secondly, the substantial heterogeneity was observed, one major factor result in heterogeneity is the diversity of surgery types (breast, lumbar spine, hip, abdominal etc). Parietal pain is more prominent in breast and lumbar spine, while visceral pain is the main component of postoperative pain following abdominal surgeries. The use of different types of opioid and supplementary analgesics such as paracetamol [23,24] may also add an extra heterogeneity. Furthermore, owing to all patients were under GA surgeries, sensory blocking could not be evaluated adequately to exclude potential block failures of ESPB. Last, although we conducted a comprehensive literature search, it is hard to rule out the possibility of missing studies.

Conclusion
In summary, ESPB block provides an effective analgesic in adults. However, the results should be interpreted cautiously since insufficient evidence, although accumulating. Further large-scale RCTs are required to support our results.