Publication date: Available online 25 March 2020
Source: Clinical Therapeutics
Author(s): Shuyan Liu, Peng Zhao, Yunfeng Cui, Chang Lu, Mingxin Ji, Wenhua Liu, Wei Jiang, Zhuo Zhu, Qianchuang Sun
Key words
adverse effect
bupivacaine
dexmedetomidine
meta-analysis
spinal anesthesia
Introduction
Spinal anesthesia is widely used in various operations because it provides adequate analgesia, muscular relaxation with simple operation, and rapid onset of action.1 However, use of local anesthetics alone has a short duration and is inadequate for visceral pain.2,3 Various intrathecal adjuvants, such as morphine, fentanyl, ketamine, midazolam, and clonidine, are used to improve the quality and duration of analgesia.4 Dexmedetomidine (DEX), a selective and potent α2-receptor agonist, has been used intrathecally for its antinociceptive benefits.5,6 A number of systematic reviews and meta-analyses have confirmed the efficacy of DEX for prolonging the duration of perineural nerve blocks.7, 8, 9 More specifically, perineural DEX enhances sensory, motor, and analgesic block characteristics.7, 8, 9 Furthermore, some meta-analyses have found that intravenous DEX can prolong the duration of spinal anesthesia, improve postoperative analgesia, and decrease the incidence of adverse effects.10, 11, 12 However, to our knowledge, no meta-analyses have been published on the effect of DEX as an intrathecal adjuvant. Therefore, we conducted a meta-analysis to evaluate the effectiveness of DEX as a local anesthetic adjuvant in spinal anesthesia.
Methods
The present meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations (Supplementary Table I).13 The protocol has been registered in the PROSPERO international database under number CRD42019145410.
Literature Search
Two of us (Q.C.S. and S.Y.L.) independently searched PubMed, EMBASE, Web of Science, and the Cochrane Library for articles published up to April 2019. The search was restricted to articles in the English language. The search terms were dexmedetomidine, DEX, intrathecal, and bupivacaine. To identify any other potentially relevant trials, we manually searched for the references of the identified articles and review studies.
Eligibility Criteria
Published articles of randomized controlled trials (RCTs) that compared the effects of intrathecal DEX (DEX group) with a placebo (control [CTRL] group) were sought. Inclusion criteria were as follows: (1) the study was a RCT; (2) spinal blocks were performed; (3) intrathecal DEX combined with bupivacaine versus bupivacaine alone; (4) the dose of DEX was 5 μg; (5) English language; (6) adult (≥18 years old); and (7) lower limb operations or lower abdominal operations. Exclusion criteria were as follows: (1) study design other than an RCT; (2) DEX was administered via intravenous route or if no spinal blocks were performed; (3) the dose of DEX was not 5 μg; (4) there was no CTRL group or the local anesthetic was not bupivacaine; and (5) did not report the effect of DEX on at least 1 of the following: sensory block onset, motor block onset, sensory block duration, motor block duration, and/or duration of analgesia.
Study Selection and Data Extraction
Two of us (Q.C.S. and S.Y.L.) separately evaluated the trials for inclusion according to the eligibility criteria. Disagreements about study selection were resolved by group discussion and consensus. The following data were extracted from each included study: the name of the first author, country, publication year, number of participants, type of surgery performed, and intervention details. We also extracted data regarding the durations of sensory and motor block, the onset times of sensory and motor block, time to first analgesic request, and dexmedetomidine-related adverse effects (ie, postoperative nausea and vomiting [PONV], hypotension, bradycardia, and shivering).
Assessment of Study Quality and Bias
Two of us (Q.C.S. and S.Y.L.) independently assessed the risk of bias in the included studies. The following factors were assessed according to the Cochrane risk of bias tool for each study14: (1) random sequence generation; (2) allocation concealment; (3) blinding of participants and personnel; (4) blinding of outcome assessors; (5) incomplete outcome data; (6) selective outcome reporting; and (7) other bias. Each of these factors was judged as low risk, high risk, or unclear risk.
For the assessment of publication bias, both the Begg rank correlation and the Egger linear regression tests were performed.15
Statistical Analysis
All statistical analyses were performed in Stata software, version 15.0 (Stata Corp, College Station, Texas) and Review Manager, version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Risk ratios (RRs) with 95% CIs were calculated for dichotomous data, and weighted mean differences (WMDs) with 95% CIs were calculated for continuous variables. Heterogeneity was measured by I2, with I2 > 50% indicating significant heterogeneity.16 If I2 ≤ 50%, the fixed-effects model was used; if I2 > 50%, a random-effects model was used, and the heterogeneity was assessed. Because of obvious heterogeneity, a random-effect model was chosen to analyze the continuous outcomes.17 The fixed-effect model was used to analyze the dichotomous outcomes.
Subgroup analysis and sensitivity analysis were performed on factors that may have contributed to the heterogeneity. Subgroup analyses were performed for outcome measures, according to surgery types (cesarean surgery or noncesarean surgery) and 0.5% bupivacaine dosage (3 mL or <3 mL). Sensitivity analysis was performed by removing each study individually and changing effects model of the statistical method to evaluate the influence of a single study on the overall estimate.18
Results
Literature Search
Figure 1 shows a summary of the study selection process. We identified 514 studies through database searching. After excluding duplicate references and reviewing titles and abstracts, we selected 67 studies for full-text evaluation. Of these, 42 trials did not meet the inclusion criteria. Reasons for exclusion included the following: (1) the study was not randomized (n = 1), (2) the dose of DEX was not 5 μg (n = 16), (3) there was no control group (n = 20), (4) DEX was not given by the intrathecal route (n = 2), (5) the local anesthetic was not bupivacaine (n = 2), or (6) the study was not spinal anesthesia (n = 1). In the end, a total of 25 studies that consisted of 1478 patients were included.19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43
Figure 1. Flowchart summarizing the literature search. DEX = dexmedetomidine; RCT = randomized controlled trial.
Trial Characteristics and Study Quality
Table I gives details of all the studies included in the meta-analysis. All studies used bupivacaine as the local anesthetic with a 5-μg dose of DEX. Two authors (Q.C.S. and S.Y.L.) independently evaluated the quality of the RCTs. None of the 25 studies had a high risk of bias. Most trials had a low risk of bias, as well as several elements representing an unclear risk of bias. Risk assessment details are presented in Figure 2.
Table I. Characteristics of included studies.
| Study | Year | Country | Number of patients | Type of surgery | Treatment | ||
|---|---|---|---|---|---|---|---|
| DEX | CTRL | DEX group | CTRL group | ||||
| Samantaray et al19 | 2015 | India | 20 | 20 | Endourologic procedures | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Rahimzadeh et al20 | 2018 | Iran | 30 | 30 | Lower limb operations | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| He et al21 | 2017 | China | 30 | 30 | Cesarean delivery | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Salem et al22 | 2015 | Egypt | 26 | 26 | Lumbar spine fusion | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Qi et al23 | 2016 | China | 39 | 39 | Cesarean deliveries | 0.5% bupivacaine 2 mL + DEX 5 μg | 0.5% bupivacaine 2 mL |
| Safari et al24 | 2016 | Iran | 28 | 28 | Lower abdomen or lower extremities operations | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Patro et al25 | 2016 | India | 30 | 30 | Infraumbilical operations | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Naaz et al26 | 2016 | India | 20 | 20 | Lower abdominal operations | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Bi et al27 | 2017 | China | 20 | 20 | Cesarean surgery | 0.5% bupivacaine 2 mL + DEX 5 μg | 0.5% bupivacaine 2 mL |
| Nasseri et al28 | 2017 | Iran | 25 | 25 | Cesarean surgery | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Nethra et al29 | 2015 | India | 20 | 20 | Perianal operations | 0.5% bupivacaine 1.2 mL + DEX 5 μg | 0.5% bupivacaine 1.2 mL |
| Shukla et al30 | 2016 | India | 40 | 40 | Vaginal hysterectomies | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Gautam et al31 | 2017 | Nepal | 36 | 35 | Inguinal hernia repair or vaginal hysterectomy | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Gautam et al32 | 2018 | Nepal | 23 | 25 | Uncomplicated perianal surgery | 0.5% bupivacaine 1 mL + DEX 5 μg | 0.5% bupivacaine 1 mL |
| Solanki et al33 | 2013 | India | 30 | 30 | Lower limb surgery | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Kumar et al34 | 2016 | India | 50 | 50 | Lower abdominal surgery | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Sarma et al35 | 2015 | India | 50 | 50 | Lower limb surgeries | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Mahendru et al36 | 2013 | India | 30 | 30 | Lower limb surgery | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Prakash et al37 | 2015 | India | 30 | 30 | Lower abdominal operations | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Rao et al38 | 2015 | India | 30 | 30 | Infraumbilical operations | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Kaur et al39 | 2017 | India | 20 | 20 | Transurethral resection of prostrate | 0.5% bupivacaine 1.8 mL + DEX 5 μg | 0.5% bupivacaine 1.8 mL |
| Al-Mustafa et al40 | 2009 | Jordan | 21 | 22 | Transurethral resection of prostate | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Shaikh and Dattatri41 | 2014 | India | 30 | 30 | Urologic, gynecologic, or orthopedic procedures | 0.5% bupivacaine 3 mL + DEX 5 μg | 0.5% bupivacaine 3 mL |
| Shashikala et al42 | 2016 | India | 30 | 30 | Lower limb surgery | 0.5% bupivacaine 2.5 mL + DEX 5 μg | 0.5% bupivacaine 2.5 mL |
| Sushruth et al43 | 2018 | India | 30 | 30 | Cesarean surgery | 0.5% bupivacaine 1.8 mL + DEX 5 μg | 0.5% bupivacaine 1.8 mL |
CTRL = control; DEX = dexmedetomidine.
Figure 2. Evaluation of risk of bias for each included study.
Sensory Block Duration
Twenty studies reported the effect of DEX on sensory block duration. DEX was superior to saline for this outcome. DEX prolonged the duration of sensory block by an estimate of 134.42 min (95% CI, 109.71–159.13; P < 0.001; I2 = 99.3%) compared with saline (Figure 3). However, the heterogeneity was significant among pooled studies (I2 = 99.3%). Additional subgroup analyses of surgery types and bupivacaine dosage (Supplemental Figures 1 and 2) as well as sensitivity analyses did not affect the pooled results (Figure 4). The Begg funnel plot (P = 0.65) and the Egger test (P = 0.84) found no evidence of publication bias (Figure 5). The details of P values and test statistics are given in Supplemental Table II.
Figure 3. Forest plot depicting sensory block duration. WMD = weighted mean difference.
Figure 4. Sensitivity analysis of the included studies.
Figure 5. Begg funnel plot analysis of the included trials. WMD = weighted mean difference.
Motor Block Duration
The effect of DEX on motor block duration was reported in 22 studies. DEX prolonged the duration of motor block by an estimate of 114.27 min (95% CI, 93.18–135.35 min; P < 0.001; I2 = 98.6%) compared with saline (Figure 6). Additional subgroup analyses of surgery types and bupivacaine dosage as well as sensitivity analyses did not affect the pooled results. The Begg funnel plot (P = 0.96) and the Egger test (P = 0.35) found no evidence of publication bias.
Figure 6. Forest plot depicting motor block duration. WMD = weighted mean difference.
Sensory Block Onset
Sensory block onset was reported in 17 studies. DEX hastened sensory block onset by an estimate of −0.80 min (95% CI, −1.21 to −0.40 min; P < 0.001; I2 = 96.9%) compared with saline (Figure 7). Additional subgroup analyses of surgery types and bupivacaine dosage as well as sensitivity analyses did not affect the pooled results. The Begg funnel plot (P = 0.65) and the Egger test (P = 0.20) found no evidence of publication bias.
Figure 7. Forest plot depicting sensory block onset. WMD = weighted mean difference.
Motor Block Onset
Motor block onset was evaluated in 14 studies. DEX hastened motor block onset by an estimate of −1.03 min (95% CI, −1.51 to −0.56 min; P < 0.001; I2 = 93.6%) compared with saline (Figure 8). Additional subgroup analyses of surgery types and bupivacaine dosage as well as sensitivity analyses did not affect the pooled results. The Begg funnel plot (P = 0.38) and the Egger test (P = 0.22) found no evidence of publication bias.
Figure 8. Forest plot depicting motor block onset. WMD = weighted mean difference.
Analgesia Duration
The duration of the analgesia was reported in 16 studies, which was defined as time to first analgesic requirement after surgery. DEX prolonged the duration of analgesia by an estimate of 216.90 min (95% CI, 178.90–254.90 min; P < 0.001; I2 = 99.0%) compared with saline (Figure 9). Additional subgroup analyses of surgery types and bupivacaine dosage as well as sensitivity analyses did not affect the pooled results. The Begg funnel plot (P = 0.096) and Egger test (P = 0.10) found no evidence of publication bias.
Figure 9. Forest plot depicting duration of analgesia. WMD = weighted mean difference.
DEX-Related Adverse Effects
The incidence of PONV was reported in 17 trials, but no differences were found between the 2 groups, with an estimate of 0.87 (95% CI, 0.62–1.24; P = 0.45; I2 = 1.9%) (Table II). The incidences of bradycardia and hypotension were described in 17 studies. Pooled analysis found that intrathecal DEX increased the risk of bradycardia (1.59-fold increase; 95% CI, 1.07-fold–2.37-fold; P = 0.022; I2 = 0) and hypotension (1.40-fold increase; 95% CI, 1.04-fold–1.89-fold; P = 0.026; I2 = 26.8%) (Table II). Data from 14 studies of 851 participants indicated that the addition of DEX significantly reduced the incidence of shivering by 61% (RR = 0.39; 95% CI, 0.27–0.55; P < 0.001; I2 = 0) (Table II).
Table II. Incidences of adverse events.
| Adverse Event | No. of Studies (Patients) | No. in DEX Group/Total No. (%) | No. in CTRL Group/Total No. (%) | RR (95% CI) | P | I2 Test, % |
|---|---|---|---|---|---|---|
| PONV | 17 (1038) | 46/519 (8.86) | 53/519 (10.21) | 0.87 (0.62–1.24) | 0.45 | 1.9 |
| Bradycardia | 17 (1078) | 54/539 (10.02) | 33/539 (6.12) | 1.59 (1.07–2.37) | 0.022 | 0 |
| Hypotension | 17 (1058) | 120/529 (22.68) | 81/529 (15.31) | 1.40 (1.04–1.89) | 0.026 | 26.8 |
| Shivering | 14 (851) | 33/426 (7.74) | 89/425 (20.94) | 0.39 (0.27–0.55) | <0.001 | 0 |
DEX = dexmedetomidine; CTRL = control; PONV = postoperative nausea and vomiting; RR = risk ratio.
Discussion
Our meta-analysis indicated that 5 μg of DEX administered intrathecally prolonged the durations of sensory and motor block when administered to patients undergoing spinal anesthesia. Intrathecal DEX also hastened the onsets of both sensory and motor blockade and delayed the time to first analgesic request. However, the onsets of sensory and motor block lacked clinical significance. In addition, spinal administration of DEX could effectively prevent perioperative shivering but did not increase the incidence of PONV. However, these effects were associated with an increased risk of transient bradycardia and hypotension.
Many drugs have been used intrathecally as an adjuvant to local anesthetic to prolong intraoperative and postoperative analgesia in recent years.44,45 DEX is a highly selective α2-adrenergic receptor agonist and can provide good sedation, high-quality analgesia, and stable hemodynamic conditions with minimal adverse effects.46 Studies have reported that the use of intrathecal DEX as an adjuvant to hyperbaric bupivacaine is associated with longer duration of analgesia and faster onset time.19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 The pooled results from our meta-analysis indicated that DEX treatment prolonged the duration of sensory block, the duration of motor block, and the duration of analgesia by 134.42 min, 114.27 min, and 216.90 min, respectively. The mechanism of DEX for increasing the duration of block may be attributable to the depression of C-fiber transmitter release and the hyperpolarization of neuronal cation currents.47 Moreover, intrathecal DEX hastened the onsets of sensory block and motor block by 0.80 min and 1.03 min, respectively. Although the onsets of sensory and motor block were statistically significant, the results were clinically insignificant. Casati et al48 found that a faster onset of sensory block did not reduce the preparation time for surgery.
Some studies found that DEX could effectively reduce the incidence of shivering in spinal anesthesia.21,23,28 The present meta-analysis found that spinal administration of DEX could prevent shivering after surgery. Our results are consistent with another recent meta-analysis that evaluated the effects of intrathecal DEX on shivering in cesarean section.49 The antishivering effect of intrathecal DEX may be explained by its peripheral and central α2-adrenergic receptor agonist effect. DEX administration suppresses the spontaneous firing rate of neurons in the spinal cord and decreases the central thermosensitivity in the hypothalamus.50,51 DEX was able to reduce vasoconstriction and increase the shivering threshold.50,52 In addition, some evidence suggests that DEX exerts its antishivering effects by attenuating the hyperadrenergic response to perioperative stress.53,54
This meta-analysis is subjected to several limitations worthy of consideration. First, the included trials were generally small and of variable methodologic quality. Second, no standardized assessment of dependent variables, such as sensory block duration (eg, time to S1 regression,20,22,23,30,31,33, 34, 35,37, 38, 39, 40, 41, 42, 43 time to 4 dermatomes,24 time to below S1 dermatome level,29 and time to 2 segments regression36), motor block duration, and analgesia duration may also potentially limit the generalizability of our findings. Third, our analysis was unable to draw conclusions regarding important outcomes, such as chronic pain, patient satisfaction, long-term safety profiles, and potential for neurotoxicity associated with intrathecal use of DEX. Fourth, the range of doses of local anesthetics used for spinal anesthesia as well as the different types of operations may also affect the reliable translation of our results into clinical practice. Fifth, publication bias may also potentially limit the generalizability of our results because most of the included studies were conducted in developing countries. Additional studies conducted in different countries are still needed to confirm our findings.
Conclusion
This study found that 5 μg of DEX administered intrathecally could prolong the duration of sensory block, the rotation of motor block, and the time to first analgesic request as well as expedite onset of sensory motor blockade. Nonetheless, the benefits of dexmedetomidine should also be weighed against increased risk of transient bradycardia and hypotension.
Declaration of Competing Interest
The authors have indicated that they have no conflicts of interest regarding the content of this article.
Acknowledgments
We thank Wendy Feng for her linguistic assistance during the preparation of the manuscript. Dr. Sun designed the study; Drs. Liu and Sun performed the study; Drs. Zhao, Cui, Lu, Ji, Liu, Jiang, and Zhu analyzed the data; Dr Liu wrote the original manuscript; and Dr Sun revised the manuscript.
Appendix.
Supplementary Table S. I. PRISMA Checklist.
| Section/topic | # | Checklist item | Reported on page # |
|---|---|---|---|
| Title | |||
| Title | 1 | Identify the report as a systematic review, meta-analysis, or both. | 1 |
| Abstract | |||
| Structured summary | 2 | Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number. | 2, 3 |
| Introduction | |||
| Rationale | 3 | Describe the rationale for the review in the context of what is already known. | 4 |
| Objectives | 4 | Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS). | 4 |
| Methods | |||
| Protocol and registration | 5 | Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number. | N/A |
| Eligibility criteria | 6 | Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale. | 5 |
| Information sources | 7 | Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched. | 4, 5 |
| Search | 8 | Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated. | 5 |
| Study selection | 9 | State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis). | 7 |
| Data collection process | 10 | Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. | 5 |
| Data items | 11 | List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made. | 6, 7 |
| Risk of bias in individual studies | 12 | Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis. | 6 |
| Summary measures | 13 | State the principal summary measures (e.g., risk ratio, difference in means). | 6, 7 |
| Synthesis of results | 14 | Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis. | 6, 7 |
| Risk of bias across studies | 15 | Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies). | 6 |
| Additional analyses | 16 | Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified. | 7 |
| Results | |||
| Study selection | 17 | Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram. | 7 |
| Study characteristics | 18 | For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations. | 7 |
| Risk of bias within studies | 19 | Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). | 7 |
| Results of individual studies | 20 | For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. | 7, 8, 9 |
| Synthesis of results | 21 | Present results of each meta-analysis done, including confidence intervals and measures of consistency. | 7, 8, 9 |
| Risk of bias across studies | 22 | Present results of any assessment of risk of bias across studies (see Item 15). | 7 |
| Additional analysis | 23 | Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]). | 7, 8, 9 |
| Discussion | |||
| Summary of evidence | 24 | Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers). | 10, 11 |
| Limitations | 25 | Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). | 11 |
| Conclusions | 26 | Provide a general interpretation of the results in the context of other evidence, and implications for future research. | 11, 12 |
| Funding | |||
| Funding | 27 | Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review. | Acknowledgements relating to this article |
From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097.
Supplementary Table S. II. The p-values and test statistics.
| Continuous outcomes | P value | Pooling model | Test statistic (Z) |
|---|---|---|---|
| Sensory block duration | P < 0.001 | Random (I–V heterogeneity) | 10.66 |
| Motor block duration | P < 0.001 | Random (I–V heterogeneity) | 10.62 |
| Sensory block onset | P < 0.001 | Random (I–V heterogeneity) | 3.87 |
| Motor block onset | P < 0.001 | Random (I–V heterogeneity) | 4.26 |
| Anesthesia duration | P < 0.001 | Random (I–V heterogeneity) | 11.19 |
| Binary outcomes | |||
| PONV | 0.45 | Fixed, Mantel-Haenszel | 0.76 |
| Bradycardia | 0.022 | Fixed, Mantel-Haenszel | 2.28 |
| Hypotension | 0.026 | Fixed, Mantel-Haenszel | 2.22 |
| Shivering | <0.001 | Fixed, Mantel-Haenszel | 5.34 |
PONV, postoperative nausea and vomiting.
Figure S1. Subgroup analysis of sensory block duration for surgery types.
Figure S2. Subgroup analysis of sensory block duration for bupivacaine dosage.
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