Regional versus local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis
J Vasc Access 2017; 18(3): 177 - 184
Article Type: REVIEW
AuthorsAmmar Ismail, Abdelrahman Ibrahim Abushouk, Amira H. Bekhet, Osama Abunar, Omar Hassan, Ahmed A. Khamis, Mohamed Al-sayed, Ahmed Elgebaly
There is a consensus in the literature that regional anesthesia (RA) improves local hemodynamic parameters in comparison to local anesthesia (LA) during arteriovenous fistula (AVF) surgical construction. However, the effects of both techniques on fistula patency and failure rates are still controversial. The aim of this meta-analysis is to synthesize evidence from published randomized trials and observational studies regarding the safety and efficacy of RA versus LA in AVF surgical construction. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central retrieved six randomized trials (462 patients) and one retrospective study (408 patients). Pooling data using RevMan software (version 5.3) showed that RA was superior to LA in terms of primary fistula patency rate (RR = 1.22, 95% CI [1.08, 1.37], p = 0.0010); however, both types were comparable in terms of primary fistula failure rate (RR = 0.81, 95% CI [0.47, 1.40], p = 0.46). In comparison to LA, RA was associated with improved hemodynamic parameters including fistula blood flow (MD = 25.08, 95% CI [19.40, 30.76], p<0.00001), brachial artery diameter (SMD = 2.63, 95% CI [2.17, 3.08], p<0.00001), and outflow venous diameter (SMD = 0.93, 95% CI [0.30, 1.75], p = 0.004). Postoperative complications were comparable between both groups (OR = 0.23, 95% CI [0.05, 0.97], p = 0.05). In conclusion, RA was associated with higher primary patency rates of AVF and improved local blood flow in comparison to LA; however, both procedures were comparable in terms of primary failure rates and postoperative complications. Larger well-designed trials with longer follow-up periods should compare both techniques in terms of long-term patency rates and safety outcomes.
- • Accepted on 28/12/2016
- • Available online on 05/05/2017
- • Published in print on 15/05/2017
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A functional vascular access should guarantee a blood flow rate of more than 200 mL/min without causing an excessive shunt or vascular steal syndrome (1, 2). Arteriovenous fistulae (AVF) have become the standard vascular access for hemodialysis in patients with end-stage renal disease (ESRD) (3). In comparison to tunneled central venous catheters, they have a six-times reduced risk of systemic sepsis (4) and a lower risk of cardiovascular mortality (5). Arteriovenous fistulae are classified according to their anatomical site into radiocephalic, proximal radial artery inflow fistula, brachiocephalic, and brachiobasilic fistulae. The most functioning type with the least complication rate is the radiocephalic fistula (RCAVF), introduced in 1962 by Cimino and Brescia (6, 7). However, early fistula failure is an unfortunate incident that occurs in about one-third (24% to 35%) of AVFs, especially RCAVF, due to the small size of distal vessels at the wrist or radial artery spasm that occurs in response to increased sympathetic tone during and after the procedure (8). Several risk factors have been associated with the risk of early failure including: age above 65 years, female sex, smoking, diabetes, hypertension, adverse preoperative arterial and venous parameters, and low postoperative blood flow through the fistula (6, 9).
Anesthesia during AVF creation can directly affect the blood flow in the fistula (10). Local anesthesia (LA) is the most applicable and low-cost procedure, but it may cause serious complications such as vasospasm and local tissue irritation (11, 12). It is usually combined with sedation (monitored anesthesia care); however, it is hard to be maintained for long operative durations and may require multiple injections (1). Regional anesthesia (RA) or brachial plexus block (BPB) uses targeted injection of a local anesthetic to provide complete sensory, motor, and sympathetic block without systemic negative effects. Moreover, the sympatholytic effect of RA increases arterial blood flow and venous diameter during the operation and in the early post-operative period, preventing early thrombosis and associated fistula failure (13). However, there are associated risks with this technique including infection, neuropathy, pneumothorax, and intravascular injection (11, 14). Although these limitations are avoided in general anesthesia (GA), it can produce significant cardiorespiratory complications in ESRD patients who usually have multiple comorbidities (15, 16). Therefore, most of AVF creation procedures are currently performed under local or regional anesthesia (17).
There is a consensus in the literature that RA improves local hemodynamic parameters in comparison to LA. However, the effects of both techniques on fistula patency and failure rates are highly controversial. Some observational (cohort) studies (18, 19) and randomized controlled trials (20, 21) reported that RA can positively influence immediate AVF patency and failure rates; however, other randomized trials showed no significant benefit of RA in this regard (22, 23). Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized trials (11, 16, 17, 20, 22-23-24) and observational studies (12, 25) regarding the safety and efficacy of local and regional anesthesia in surgical creation of arteriovenous fistula.
This study was conducted in a strict accordance to the guidelines of the Cochrane handbook of systematic reviews and meta-analysis, and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines (26, 27).
Literature search strategy
A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted during September 2016. For a sensitive search strategy, we used the MeSH database and the following search query: “(arteriovenous fistula OR AVF OR dialysis OR dialysis access) AND (end-stage renal disease OR ESRD OR chronic kidney disease OR CKD) AND (regional anesthesia OR brachial plexus block OR BPB)”. No restrictions by publication period were applied. We manually scanned the reference list of retrieved articles for relevant records. Moreover, we searched the clinical trial registry (clinicaltrials.gov) to identify ongoing and unpublished trials.
Eligibility criteria and study selection
We included all randomized controlled trials or observational studies that compared the safety and efficacy of regional versus local anesthesia in ESRD patients who underwent AVF surgical construction. We excluded non-English articles, reviews, case reports, and non-human trials. Eligibility screening was conducted in two steps, each by two independent reviewers (with an expertise in anesthesiology and vascular surgery): title and abstract screening for matching the inclusion criteria and full text screening for eligibility to meta-analysis. A consensus was obtained upon the opinion of a third reviewer.
Two authors extracted the data independently and conflicts were resolved upon the opinion of a third reviewer. The extracted data included the following: baseline characteristics of enrolled patients, study design, risk of bias assessment domains, and main safety and efficacy outcomes.
The primary clinical outcomes included: (i) primary fistula patency rate [which was defined as the interval from placement of AVF until the need of additional interventions to keep the fistula streaming (28)] and (ii) primary fistula failure rate [which was defined as an AVF that was unsuccessful in starting dialysis or that underwent thrombosis, infection, or ischemia before a successful cannulation]. Secondary clinical outcomes included the duration of surgery and the frequency of needing an additional intraoperative analgesia.
Hemodynamic outcomes included: (i) fistula blood flow rate at 2 to 3 hours after surgery (mL/min), (ii) immediate postoperative change of brachial artery diameter (mm), (iii) immediate postoperative change of brachial artery blood flow rate (mL/min), and (iv) immediate postoperative change of the outflow vein diameter. Safety outcomes included the incidence of all anesthetic and postoperative complications, thrombosis, and infection among both groups.
Risk of bias assessment
To assess the risk of bias within included studies, we used the Cochrane risk of bias (ROB) assessment tool, clearly described in the Cochrane Handbook of Systematic Reviews of Interventions 5.1.0 (26). This tool is designed to detect six types of bias: selection bias, performance bias (blinding of patients and personnel), detection bias (blinding of outcome assessors), attrition bias (incomplete outcome reporting), reporting bias (selective outcome reporting), and other potential sources of bias. The authors’ judgment is classified as ‘Low risk’, ‘High risk’ or ‘Unclear risk’ of bias. We used the Newcastle Ottawa scale for assessing the risk of bias in included observational studies (29). Each included observational study was assessed based on reporting three essential domains: a) selection of the study subjects, b) comparability of groups on demographic characteristics and important potential confounders, and c) ascertainment of the prespecified outcome (exposure/treatment).
We could not assess the risk of publication bias across included studies using funnel plot-based methods because they are not reliable for less than 10 pooled studies according to Egger and colleagues (30, 31).
Extracted dichotomous data were pooled as odds ratios (OR) or risk ratios (RR), using the Mantel Haenzel (M-H) method, while continuous data were pooled as a mean difference (MD) or a standardized mean difference (SMD), using the Inverse Variance (I-V) method. We used RevMan (version 5.3 for Windows) to conduct the statistical analysis. To assess for heterogeneity, we used the Chi-square and I-square statistical tests. If a significant heterogeneity was found, the analysis was performed under the random effects model; otherwise, the fixed effect model was used.
Literature database search retrieved 126 citations that were abstracted to 97 after removal of duplicates using Endnote X7. Of these records, 81 were excluded during abstract screening and the full text articles of the remaining 16 records were retrieved for further inspection. Finally, seven reports of six randomized trials that enrolled a total of 462 participants and one retrospective study that reported data of 408 participants were included for the final analysis (11, 12, 16, 17, 20, 22-23-24-25) (
Flow diagram of literature search and screening process.
All randomized trials were of a low risk in terms of attrition bias (incomplete outcome data) and reporting bias (selective outcome reporting). Blinding of the patients was not possible in all included studies, owing to the nature of the procedure. Two randomized trials achieved acceptable random sequence generation and allocation concealment, while only one study blindly assessed their intended primary outcomes (
Risk of bias summary for included randomized trials.
Primary clinical outcomes
Primary patency rate “intervention-free access survival”
Pooled analysis of three trials including 246 patients (20, 22, 23) showed that RA was associated with higher primary patency rates, compared to LA (RR = 1.22, 95% CI [1.08, 1.37], p = 0.0010); (
Forest plots of (
Primary fistula failure rate
Pooled analysis of two trials (22, 23) and one retrospective study (25) including 528 patients showed no significant difference between RA and LA in terms of primary fistula failure rate (RR = 0.81, 95% CI [0.47, 1.40], p = 0.46); (
Secondary clinical outcomes
Operative time (min)
Pooled analysis of two trials (17, 20) including 229 patients showed no significant difference between RA and LA in terms of operative time (MD = -33.94 min, 95% CI [-99.11, 31.23], p = 0.31); (
Forest plots of (
Need for an additional intraoperative pain killer
Pooled analysis of two trials (17, 20) including 229 patients showed no significant difference between RA and LA in terms of the need for an additional intraoperative analgesia (RR = 0.52, 95% CI [0.14, 1.98], p = 0.34); (
Blood flow of the fistula (mL/min)
Pooled analysis of two trials (16, 22) including 78 patients showed that fistula blood flow was significantly more voluminous in the RA group, compared to the LA group (MD = 25.08, 95% CI [19.40, 30.76], p<0.00001); (
Forest plots of (
Immediate change of brachial artery diameter (mm)
Pooled analysis of two trials (16, 20) including 142 patients showed a significant immediate increase of brachial artery diameter in the RA group, compared to the LA group (SMD = 2.63, 95% CI [2.17, 3.08], p<0.00001); (
Immediate change of brachial artery blood flow (mL/min)
Pooled analysis of two trials (16, 20) including 138 patients showed a significant immediate increase of brachial artery blood flow in the RA group, compared to the LA group (SMD = 1.34, 95% CI [0.97, 1.72], p<0.00001); (
Immediate change of outflow vein diameter
Pooled analysis of three trials (11, 20, 23) including 224 patients showed that fistula blood flow was significantly more voluminous in the RA group, compared to the LA group (SMD = 0.93, 95% CI [0.30, 1.75], p = 0.004); (
All postoperative and anesthetic complications
Pooled analysis of three trials (11, 20, 22) including 226 patients showed no significant difference between RA and LA groups in terms of the incidence of postoperative and anesthetic complications (OR = 0.23, 95% CI [0.05, 0.97], p = 0.05); (
Forest plots of (
Pooled analysis of two trials (11, 22) including 226 patients showed no significant difference between RA and LA groups in terms of the incidence of thrombosis (OR = 0.21, 95% CI [0.03, 1.27], p = 0.09); (
Pooled studies were homogenous (p = 0.39, I2 = 0%).
Vascular access infection
Pooled analysis of one trial (22) and one retrospective study (25) including 468 patients showed no significant difference between RA and LA groups in terms of the incidence of vascular access infection (OR = 0.68, 95% CI [0.23, 2.02], p = 0.49); (
Our meta-analysis provides class I evidence that RA improves local hemodynamic parameters and primary patency rates of AVF, in comparison to LA; however, no significant difference was found between both groups in terms of primary fistula failure rate or the incidence of postoperative and anesthetic complications. A large randomized clinical trial by Aitken et al was the first to report improved mid-term patency rates (at 3 months after surgery) in the RA group; however, this finding was not translated into higher functional patency rates (20). Two included studies compared both anesthetic techniques in terms of pulsatility index (PI) and pulsatility index ratio. PI is calculated by dividing the difference between maximum and minimum velocities of arterial flow by the mean maximum velocity and the PI ratio (the ratio between the Pl at 10 minutes after the block and the Pl before the block) and its value represents the degree of the sympatholytic effect of the block (13). Both studies showed that the PI and PI ratio were significantly higher in the RA group than the LA group (p<0.05) (11, 23).
Beside the discussed advantages of RA, its associated vasodilatory effect makes creating the anastomosis less challenging (13, 22). Moreover, it increases blood flow in the fistula and blood flow in the local venous circulation: either directly or indirectly through increasing venous return after arterial vasodilatation (19). Postoperatively, increasing venous blood flow is important because a slow flow in the vein activates platelets and endothelial cells, causing thrombosis, usually about 3 or 4 cm away from the anastomosis site (32). In a study by Hingorani et al, RA improved venodilatation by 19% to 42%, in comparison to tourniquet application (33).
Moreover, RA can allow changing the operative plan (from graft to fistula) and the selected site for anastomosis (from proximal to more distal) after anesthesia. In a study by Laskowski et al, the induced vasodilatation after RA enabled changing the surgical plan or anastomosis site in 30% of patients (34). In an included trial by Aitken et al, the planned anastomosis site was changed from brachiocephalic to radiocephalic in four patients because administration of RA increased the diameter of the cephalic vein at the wrist (20).
Despite the aforementioned advantages, inaccurate anesthetic injection during RA administration can increase the risk of intravascular injection and associated systemic toxicity (1). Neurological complications such as postoperative paresthesia or paralysis may occur due to intra-neural injection, direct trauma, ischemia following edema or hematoma formation, or neural toxicity from the anesthetic agent (11, 14). Moreover, the success rate of BPB is operator-dependent, and it usually takes longer time and additional resources to administer the anesthetic agent (35). The introduction of ultrasound and neurostimulation technologies in BPB increased the accuracy of needle placement, leading to a faster onset of action, lower required volume of anesthetic compounds, and a more prolonged anesthetic effect. It also reduced the incidence of related vascular and neurological complications (36-37-38).
Included studies used different approaches for BPB including supraclavicular, infraclavicular, and axillary approaches. Infraclavicular and axillary approaches are claimed to be safer than supraclavicular and interscalene approaches because the latter two approaches can cause Horner’s syndrome, breathing difficulties, or pneumothorax (39). Moreover, anesthesia through the infraclavicular approach can be performed after a single injection, while axillary block requires additional doses to block the musculocutaneous nerve (21).
Choosing the proper anesthetic drug is important because the safety of these compounds in ESRD patients depends on non-renal elimination (40). Included studies used lidocaine, bupivacaine, or ropivacaine injections for local and regional anesthesia. The risk of intravascular injection or systemic absorption causing cerebral and cardiac toxicity is more pronounced in regional anesthesia (39). Moreover, the risk of systemic absorption of these compounds is augmented by the hyperdynamic circulation in ESRD patients (41). Therefore, more caution should be employed while selecting the anesthetic compound for this technique. Although some studies have reported elevated plasma concentration of mepivacaine or a metabolite of ropivacaine (pipecoloxylidide), no cases of systemic toxicity have yet been reported (42, 43). A study by Pongraweewan et al found that adding lidocaine 2% to bupivacaine 0.5% in BPB does not increase the duration of sensory block or improve the surgeon’s and patient’s satisfaction (44). Future studies should investigate the effect of different anesthetic compounds on the outcomes of BPB.
RA improves the primary patency rate of AVF, in comparison to LA, through inducing vasodilatation and increasing fistula blood flow. No significant difference was found between both techniques in terms of primary fistula failure rate and postoperative complications. However, larger well-designed randomized trials with longer follow-up periods are needed to illustrate the safety differences between the two anesthetic techniques.
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- Ismail, Ammar [PubMed] [Google Scholar] 1, 2, 3, * Corresponding Author (Ammaryasser3240@azhar.edu.eg)
- Abushouk, Abdelrahman Ibrahim [PubMed] [Google Scholar] 2, 4
- Bekhet, Amira H. [PubMed] [Google Scholar] 3, 5
- Abunar, Osama [PubMed] [Google Scholar] 6
- Hassan, Omar [PubMed] [Google Scholar] 7
- Khamis, Ahmed A. [PubMed] [Google Scholar] 8
- Al-sayed, Mohamed [PubMed] [Google Scholar] 8
- Elgebaly, Ahmed [PubMed] [Google Scholar] 1
Faculty of Medicine, Al-Azhar University, Cairo - Egypt
NovaMed Medical Research Association, Cairo - Egypt
Medical Research Group of Egypt, Cairo - Egypt
Faculty of Medicine, Ain Shams University, Cairo - Egypt
Faculty of Physical Therapy, Cairo University, Cairo - Egypt
Faculty of Medicine, Mansoura University, Mansoura - Egypt
Faculty of Medicine, Al Azhar University, Assiut - Egypt
Faculty of Medicine, Alexandria University, Alexandria - Egypt
Ammar Ismail and Abdelrahman Ibrahim Abushouk contributed equally to this work
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