In 2005, in the United States alone, approximately 647,000 children were discharged from a short-stay hospital after having undergone a surgical procedure.1 Anesthesiologists are implicated in these procedures at various steps of the process, among which anesthesia for the procedure itself and treatment of postoperative pain are of the utmost importance. Postoperative pain relief is of particular importance in children. Pain experienced early in life may induce organic brain changes that can make these children susceptible to an exaggerated brain response when experiencing pain later in life.2 These brain changes are frequently referred to as neuroplasticity.
In one study performed in children, clinically significant adverse events (ie, those requiring an intervention) occurred in 22% and 24% of patients with IV patient-controlled analgesia administered by trained relatives or nurses and by self-administered patient-controlled analgesia, respectively.3 Opioid-based regimens may therefore be a suboptimal way of treating postoperative pain in children. The use of regional blockade in children is considered reasonably safe today.4,5
Ultrasound has now been used for regional blockade for almost 3 decades. Among the pioneers of the use of ultrasound for regional blockade, one could cite la Grange et al,6 Ting et al,7 Wu et al,8 and Kapral et al.9
Failed block is the most common problem in pediatric regional anesthesia when neuraxial blocks are performed without an imaging technique, and inadvertent vascular punctures occur in 2% (95% confidence interval [CI], 12–21 per 1000) of the children undergoing neuraxial blocks.5 Ultrasound may decrease inadvertent vascular puncture.10 Thus, ultrasound guidance for regional anesthesia in children may improve the success rate and decrease the complication rate.
The use of ultrasound guidance has become popular for regional anesthesia over the last 2 decades. However, it is actually not recognized by all experts as an essential tool. Indeed, many authorities think that there is no actual evidence that ultrasound guidance would decrease the occurrence of important complications such as neurologic damage.11 In adults, a Cochrane review determined that ultrasound guidance appeared to reduce the incidence of vascular puncture or hematoma formation but provided a similar success rate.10 The cost of an ultrasound machine varies, but most machines used in the clinical practice of regional anesthesia cost approximately 40,000 US dollars (USD) or more.12 Thus, the use of ultrasound guidance is substantially more expensive than other tools such as those used for nerve stimulation where most devices can be acquired for approximately USD 1000 or less.12 A comprehensive review of the pediatric literature published in 2010 concluded that more outcome-based, prospective, randomized controlled trials were required to prove the benefits of ultrasound guidance when compared with conventional methods in children.13
Objectives of the present review and meta-analysis were to determine whether the use of ultrasound guidance offers any clinical advantage in the performance of neuraxial or peripheral nerve blocks in children in terms of increasing the success rate or decreasing the rate of complications.
METHODS
A protocol was published before undertaking the review.14 We included all parallel randomized controlled trials that evaluated the effect of ultrasound guidance to perform a regional blockade technique in children and included any of our selected outcomes. We did not exclude any study based on language of publication or publication status. We included studies performed in children (≤18 years of age) undergoing any type of surgical procedure for which a neuraxial or a peripheral nerve block either for surgical anesthesia (alone or in combination with general anesthesia) or for postoperative analgesia was performed under ultrasound guidance. For the control groups, any other technique used to perform the block was accepted.
We evaluated the difference between the treatment group and the control group on the following outcomes:
Primary Outcomes
- Success rate (author’s definition)
- Pain scores in the postanesthesia care unit (PACU)
- Block duration (author’s definition)
Secondary Outcomes
- Time to perform the procedure
- Number of needle passes
- Minor complications (bloody puncture)
- Major complications: local anesthetic toxicity (including seizures or cardiac arrests); infection; neurologic injury (transient or lasting >1 month)
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3 2015, MEDLINE (OvidSP) (from 1946 to March 2015), EMBASE (OvidSP) (from 1982 to March 2015), and Scopus (from inception to January 27, 2015) (Supplemental Digital Content, https://links.lww.com/AA/B435). We also looked for trials in progress on various websites in January 2015.
We also screened the reference lists of all studies retained and of the recent meta-analysis or reviews related to the topic. We screened conference proceedings of anesthesiology societies for 2012, 2013, and 2014.
Two authors screened the list of all titles and abstracts identified by the search above and independently extracted the data. We resolved discrepancies by discussion, and the help of the third author was never required. We contacted authors to obtain additional information when required. Data were analyzed with RevMan 5.3 (Review Manager version 5.3, Copenhagen, Denmark) and Comprehensive Meta Analysis version 2.2.044 (http://www.Meta-Analysis.com) in an intention-to-treat analysis as much as feasible. We assessed the quality of the retained studies with the Cochrane Collaboration tool on generation of the allocation sequence of the interventions, concealment of allocation, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data (attrition bias), selective reporting (reporting bias), and other risk of bias: any other reason that may have influenced the results.
We gave results as risk difference (RD) and the 95% CI for dichotomous data (success rate and minor complications) and mean difference or standardized mean difference (SMD) and 95% CI for continuous data (pain scores, block duration, and time to perform the procedure). For SMD, we considered 0.2 a small effect, 0.5 a medium effect, and 0.8 a large effect.15 When there was an effect, a number needed to treat for an additional beneficial outcome or number needed to treat for an additional harmful outcome was calculated from the odds ratio. When there was no effect, we calculated the information size to make sure that there were enough participants included in the retained studies to justify a conclusion on the absence of effect.16
Statistical heterogeneity was quantified by the I2 statistic. Publication bias was examined with a funnel plot followed by Duval and Tweedie trim and fill technique for each outcome.
Fixed-effects models (I2 <25%) or random-effects models (I2 statistic ≥25%) were used.17 Heterogeneity (I2 ≥25%) was explored by the Egger regression intercept, visual inspection of the forest plots, subgroupings, or meta-regressions. Factors that were considered in the heterogeneity exploration were type of block (neuraxial versus peripheral nerve block), type of comparator (nerve stimulator versus other), age and type of guidance (prescanning versus real-time [in or out of plane]), and combined methods (ultrasound plus nerve stimulator compared with other modalities versus ultrasound alone compared with other modalities). We used the principles of the GRADE system18 to assess the quality of the body of evidence.
RESULTS
We retained 20 studies19–38 (Figure 1), including 1241 participants: 624, where the block was performed with ultrasound, and 617, without, for this review. The mean age of the participants varied from 0.9 to 9 years. The following surgeries were performed: circumcision,21,29 umbilical hernia repair,19,22,23 inguinal hernia repair,24,28,33,35,36 inguinal hernia/orchidopexy,37 low urologic/perineal surgery,25 open pyeloplasty,26 major abdominal or thoracic surgery,38 Nuss procedure for pectus excavatum, and34 upper20,27,31 or lower limb surgery.30,32 The following blocks were performed: brachial plexus block,20,27,31 sciatic and femoral nerve blocks,30,32 ilioinguinal/iliohypogastric nerve blocks,28,36,37 penile nerve block,21,29 rectus sheath block,19,22,23 transversus abdominis plane blocks,24,26,33 thoracic epidural,34 thoracic or lumbar epidural,38 and caudal blocks.25,35 Ultrasound guidance was used in real time with an in-plane,20–23,26,29,31–33 out-of-plane27,28,30,35–38 or unspecified technique,19,24 or as prescanning.25,34 Ultrasound guidance was compared with infiltration,19,22–24,26 landmarks,21,25,28,29,33–38 or nerve stimulator.20,27,30
;)
Figure 1.: Flow chart. Selection of studies.
The source of funding was from a governmental organization,22,28 a charitable organization,19 institutional department,21,29,32,34,35 or unspecified.20,23–27,30,31,33,34,36 Two studies declared help from the industry (equipment loan37,38).
Figure 2.: Risk of bias graph. Green color indicates the percentage of studies rated at low risk of bias for each specific item. Red color indicates the percentage of studies rated at high risk of bias and yellow means that the information contained in the report was insufficient to allow us to rate the study.
The risk of bias of the retained studies can be found in Figure 2. The study by Kendigelen et al24 was available as an abstract only.
Primary Outcomes
1. Success Rate (Author’s Definition)
Table 1.: Summary of Findings
Figure 3.: Forest plot for success rate (displayed as risk difference for decreased failure rate). CI indicates confidence interval; M-H, Mantel-Haenszel.
Figure 4.: Meta-regression for success rate. Occurrence of a failed peripheral nerve block for ultrasound guidance versus no ultrasound (log risk ratio of failure versus age in years). The superiority of ultrasound guidance was greater in younger children; P = 0.003.
This outcome was available for 14 studies20,21,25,27–32,34–38 (939 participants). The definition used by authors for failed blocks was based on hemodynamic variations to surgical stimulus. Data are presented as “decreased failure rate.” Ultrasound guidance decreased the failure rate RD −0.11 (95% CI, −0.17 to −0.05; I2 64%) (Figure 3). Egger regression intercept showed the possibility of a small-study effect (P = 0.02; 2-sided test). Duval and Tweedie trim and fill analysis showed no evidence of publication bias. This effect differed from one subgroup to another (Figure 3; I2 = 67% for heterogeneity between subgroups). For peripheral nerve blocks, the effect was inversely proportional to the age of the participant; younger children benefited most from ultrasound guidance (P = 0.003; Figure 4). If a failure rate of 25% is assumed, the number needed for additional beneficial outcome for peripheral nerve blocks would be 6 (95% CI, 5–8). The optimal information size for a large trial for a 25% decrease in failure rate would be 1724 (862 per group) (α 0.05; β 0.2; 1-sided test). We rated the level of evidence as high (Table 1).
2. Pain Scores in the PACU
Figure 5.: Forest plot for pain in the postanesthesia care unit at 1 hour after surgery. The difference between ultrasound guidance and no ultrasound guidance although statistically significant may not be clinically relevant (equivalent to 0.2 on a scale from 0 to 10). CI, confidence interval.
Pain scores at 1 hour in PACU were available for 8 studies19,21,23,26,30,32,37,38 (414 participants). We did not find differences for pain scores at 1 hour in PACU (SMD −0.20; 95% CI, −0.52 to 0.13; I2 = 62%) when all studies were included (Figure 5). Upon exclusion of 1 study26 in which a transversus abdominis plane block was used for open pyeloplasty, ultrasound guidance would decrease pain scores in the PACU at 1 hour (SMD −0.29; 95% CI, −0.54 to −0.04; I2 = 31%). Egger regression intercept showed no evidence of a small-study effect, and Duval and Tweedie trim and fill analysis showed no evidence of publication bias. When the study at lowest risk of bias among the studies for which pain scores were available as means and SDs32 (SD in the control group 0.9) is considered, the mean reduction in pain at 1 hour in PACU found in our meta-analysis would be equivalent to 0.2 on the Children’s and Infants’ Postoperative Pain Scale (0 = no pain and 10 = maximal pain39). On the basis of the study by Gurnaney et al23 (mean value 4.35; SD 3.1 for the control group), 238 (119 per group) would be required for a large trial, eliminating a difference of 1 on a score from 0 to 10 (α 0.05; β 0.2; 1-sided test). We rated the level of evidence for this outcome as high (Table 1).
3. Block Duration (Author’s Definition)
Figure 6.: Forest plot for block duration. The difference between ultrasound guidance and other modalities was equivalent to 62 minutes. CI indicates confidence interval.
Figure 7.: Meta-regression for block duration. Meta-regression: time to request for the first analgesic versus age. Younger children are those in whom the effect of ultrasound guidance is larger (P = 0.04).
This outcome was available for 8 studies (358 participants).21–23,26,27,30,32,33 Ultrasound guidance increased block duration (SMD 1.21; 95% CI, 0.76–1.65; I2 = 73%; Figure 6). Egger regression intercept showed no statistically significant evidence of a small-study effect. Duval and Tweedie trim and fill analysis showed that 1 study might be missing to the right of mean for an adjusted point of estimate (1.31; 95% CI, 0.87–1.75; random-effects model). This effect was inversely proportional to age (P = 0.04); younger children benefited most from ultrasound guidance (Figure 7). The mean prolongation of the block found in our meta-analysis is equivalent to 62 minutes. On the basis of the study by Ponde et al32 (mean time and SD before request of the first analgesic in the control group 457 ± 51 minutes), 8 participants (4 per group) would be required in a simple trial to eliminate a 25% difference (α 0.05; β 0.2; 2-sided test). We rated the level of evidence for this outcome as high (Table 1).
Secondary Outcomes
1. Time to Perform the Procedure
Figure 8.: Forest plot for time to perform the procedure. The difference found was equivalent to 94 seconds for an out-of-plane technique and 2.4 minutes when ultrasound guidance was used as prescanning before a neuraxial block. CI, confidence interval.
This outcome was available for 6 studies20,25,29,34,35,38 (362 participants). We found no differences between treatment groups when all studies were included in the analysis (SMD −0.77; 95% CI, −1.57 to 0.02; I2 = 93%), and Egger regression intercept showed no significant evidence of a small-study effect. Duval and Tweedie trim and fill analysis showed the possibility of publication bias for an adjusted point of estimate of SMD −1.10 (95% CI, −2.04 to −0.17). Ultrasound guidance decreased the time required to perform the block only when used as an out-of-plane technique (SMD −0.68; 95% CI, −0.96 to −0.40; I2 = 0%) or as prescanning before a neuraxial block (SMD −1.97; 95% CI, −2.41 to −1.54; I2 = 0%) (Figure 8). A significant difference was noted among the 3 subgroups (I2 = 93%). This difference between ultrasound guidance versus no ultrasound guidance was equivalent to 94 seconds for an out-of-plane technique and 2.4 minutes when ultrasound guidance was used as prescanning before a neuraxial block was performed. Based on the study by Liu et al25 (mean time and SD of the control group 3.2 ± 1.2 minutes), 46 participants (23 per group) would have been required to eliminate a 1-minute difference (α 0.05; β 0.2; 2-sided test). We rated the quality of prescanning before a neuraxial block as high (Table 1).
2. Number of Needle Passes
Figure 9.: Forest plot for number of needle passes. This difference was equivalent to a mean of 0.6 less needle pass per participant. CI, confidence interval.
This outcome was available for only 2 studies25,34 (122 participants). Ultrasound guidance reduced the number of needle passes (SMD −0.90; 95% CI, −1.27 to −0.52; I2 = 0%) (Figure 9). This difference was equivalent to a mean of 0.6 fewer needle passes per participant. On the basis of the study by Liu et al25 (mean 1.6 and SD 0.6), a trial would have to include 12 participants (6 per group) to eliminate a difference of 1 needle pass (α 0.05; β 0.2; 2-sided test). We rated the quality of prescanning before a neuraxial block as high (Table 1).
3. Minor Complications (Bloody Puncture)
Figure 10.: Forest plot for minor complications (bloody punctures). CI indicates confidence interval; M-H, Mantel-Haenszel.
This outcome was available for 6 studies27,28,30,35,37,38 (490 participants). Ultrasound did not decrease the incidence of bloody punctures (RD −0.02; 95% CI, −0.06 to 0.02; I2 = 53%; Figure 10). Egger regression intercept showed no evidence of a small-study effect, and Duval and Tweedie trim and fill analysis showed the possibility of publication bias for an adjusted point of estimate (RD −0.04; 95% CI −0.04 to 0.01) (random-effects model). Only 2 trials studied the effect of ultrasound for neuraxial blocks35,38 and showed a moderate amount of heterogeneity (RD −0.07; 95% CI, −0.19 to 0.04; I2 = 68%). Given a basal rate of 13.5% for bloody puncture during neuraxial block in children, the optimal information size for a large trial for a 25% decrease would be 2226 (1113 per group). We rated the level of evidence as low (Table 1).
4. Major Complications
There were no major complications reported in any of the included studies.
DISCUSSION
In their large prospective study, Polaner et al5 found that failed block and inadvertent vascular punctures were the 2 common problems encountered in pediatric regional anesthesia. Our meta-analysis showed that ultrasound guidance increases the success rate (or decreases the failure rate) (Figure 3 and Table 1). There was, however, some heterogeneity in the results when all studies were included. The increased success rate was most evident for peripheral nerve blocks, where the amplitude of the effect size (difference between ultrasound guidance and no ultrasound guidance) was inversely proportional to the age of the participant. Younger children being the ones who benefitted the most from ultrasound guidance (Figure 4). Ultrasound guidance also significantly prolongs block duration (longer time to first request of an analgesic) and here again the effect was more evident in the studies performed in younger participants (Figure 7). Thus, the younger the child, the more likely he/she is to benefit from ultrasound guidance. We cannot determine an exact age at which ultrasound will no longer be useful from our review. Although this is pure speculation from our part, we think that a higher effect of ultrasound guidance in younger children could be attributed to a combination of a higher difficulty of targeting smaller structures and increased visibility of shallow structures with ultrasounds in small infants. Similar findings have sometimes been reported with other techniques. For instance, percutaneous pediatric central venous catheter cannulations are more likely to fail in children with weight <3 kg,40 whereas some authors reported that ultrasound guidance resulted in a higher success rate than the other methods with comparable procedure time for smaller-body-weight (<5 kg) patients.41 Except for 1 study,27 all blocks were performed under general anesthesia. This is viewed as the standard of care in this population.42 It allows not to have pursuing a moving target in an uncooperative patient while avoiding a potentially painful procedure for the child. Fortunately, this practice does not increase the risk of complications associated with regional anesthesia.43
Pain scores at 1 hour after the surgery were reduced when ultrasound guidance was used; however, the difference was probably not clinically relevant (equivalent to −0.2 on a scale from 0 to 10). For this outcome, we excluded 1 study from the analysis.26 The amount of heterogeneity was moderate (62%) when all studies were included and low (31%) when the study by Lorenzo et al26 was excluded. Lorenzo et al26 compared transversus abdominis plane blocks (0.4 mL/kg of 0.25% bupivacaine with epinephrine) to wound infiltration for open pyeloplasty (both before surgical incision). All surgeries followed a similar muscle splitting access using the tip of the ipsilateral 12th rib as a landmark with incisions systematically <2 to 2.5 cm. Involved dermatomes were approximately T7 to T10.26 The exact location of the injection for the transversus abdominis plane block (subcostal/iliac or midaxillary/posterior area) was not prespecified. The study was stopped prematurely at the interim analysis after enrollment of one-third of the planned total recruitment on the basis that the transversus abdominis plane block was ineffective for this type of surgery. This block has received mixed degrees of enthusiasm in the literature because of its high variability in the number and in the distribution of dermatoma depending on the exact site of injection, dose, or volume used.44,45 It is, therefore, possible that the distribution of the sensory block did not cover the surgical incision in the study by Lorenzo et al.26 For this reason, we chose to exclude the study from the analysis. The failure was, in our opinion, a failure of transversus abdominis plane blockade for postoperative pain control after open pyeloplasty and should not be considered a failure of ultrasound guidance.
Time to perform the block was also reduced by ultrasound guidance when used as an out-of-plane technique or as prescanning before a neuraxial block. The mean difference was however small: equivalent to 2.4 minutes when used as prescanning. Also, ultrasound guidance accordingly reduces the number of needle passes required to perform the block (0.6 per procedure). None of the included studies reported any major complication. Because of the extremely low incidence of major complications associated with pediatric regional anesthesia, the incidence of these very rare events is best evaluated by large prospective studies.
Altogether, whether or not these differences justify the extra cost of ultrasound guidance may need to be evaluated while taking into account the resources that a specific hospital can afford for this indication.
We conclude that there is a high quality of evidence that ultrasound guidance increases success rate and increases block duration for regional blockade in children. Although we do not have enough information to state a specific age limit, there was evidence that the improved success rate and block duration were more pronounced in studies including younger children.
ACKNOWLEDGMENTS
We would like to thank Dr. Jason Hayes, David Faraoni, Harshad Gurnaney, Peter Marhofer, Stephan Kettner, Michael O’Sullivan, Vrushali Ponde, and Gildasio S. De Oliveira Jr. who provided additional information on their studies or took the time to inform us that their original data were no longer available. We are also in debt to Jiang Jia for the translation of Liu 2012 and Nan 2012. Finally, we would like to thank Rodrigo Cavallazzi (Content Editor), Jing Xie (Statistical Editor), Kevin Walker, Thomas Vaughn (Peer Reviewers), and Sheila Page (Consumer Referee) for help and editorial advice provided during preparation of this Cochrane systematic review.
DISCLOSURES
Name: Joanne Guay, MD.
Contribution: This author published the protocol, searched for studies, quantified the risk of bias, extracted the data, analyzed the data, wrote the review, and approved the manuscript before submission.
Name: Santhanam Suresh, MD.
Contribution: This author published the protocol, wrote the review, and approved the manuscript before submission.
Name: Sandra Kopp, MD.
Contribution: This author searched for studies, quantified the risk of bias, extracted the data, analyzed the data, wrote the review, and approved the manuscript before submission.
IRB: This is a Cochrane Review: ethics committee approval, informed consents, and original data collection were the responsibility of the authors of each study. Therefore, we can only attest that data are those published by the study authors or provided to us by them.
This manuscript was handled by: Richard Brull, MD, FRCPC.
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