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Cochrane Database of Systematic Reviews Protocol - Intervention

The use of ultrasound guidance for perioperative neuraxial and peripheral nerve blocks in children

Authors' declarations of interest

Version published: 15 December 2014 Version history

https://doi.org/10.1002/14651858.CD011436

This is not the most recent version

view the current version 27 February 2019
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

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.

Background

In 2005, in the United States alone, approximately 647,000 children were discharged from a short stay hospital after having undergone a surgical procedure (DeFrances 2007). Anaesthesiologists are implicated in these procedures at various steps of the process, amongst which anaesthesia for the procedure itself and treatment of postoperative pain are of the uttermost importance. Although the vast majority of surgeries performed in children are executed under general anaesthesia, serious concerns have been raised about the safety of inhalational agents on the developing brain of a child (Chiao 2014). As such, regional anaesthesia has been identified as a possible favourable replacement to general anaesthesia for specific surgeries (Nemergut 2014). Furthermore, in 2000 the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) suggested that pain be considered as the fifth vital sign and that under‐treatment of pain would constitute abrogation of a fundamental human right (White 2007). Following this statement, an increase in the use of opioids for treatment of acute postoperative pain was observed as well as an increase in their side effects (White 2007). 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 (Hohmeister 2010). These brain changes are frequently referred to as neuroplasticity. Young children are often unable to understand what is happening to them, and this may increase their distress leading to an increase in their inability to communicate as to what exactly is making them uncomfortable. Thus, their care provider is placed in a situation where he or she may either under‐ or over‐treat postoperative pain. In one study performed in children, clinically significant adverse events (that is, those requiring an intervention) occurred in 22% and 24% of patients with patient controlled analgesia (PCA) administered by trained relatives or nurses and by self administered PCA, respectively (Voepel‐Lewis 2008). Opioid‐based regimens may therefore be a suboptimal way of treating postoperative pain in children.

Description of the condition

Regional blockade interrupts pain transmission to the brain and may be used for the surgery itself as a replacement for general anaesthesia (regional anaesthesia), or to treat postoperative pain (regional analgesia). In adults, regional analgesic techniques decrease postoperative opioid consumption (Guay 2006), thus making them a potentially interesting alternative or adjunct to opioid‐based regimens to treat postoperative pain in children. Regional blockade techniques can be classified as central neuraxial blocks (spinal, epidural, combined spinal and epidural, or caudal) or peripheral nerve blocks. The use of regional blockade in children is considered reasonably safe nowadays (Long 2014; Polaner 2012). For a total of 14,917 regional blocks, performed on 13,725 patients from 1 April 2007 through to 31 March 2010, there were no deaths or complications with sequelae lasting more than three months (95% CI 0 to 2 per 10,000 blocks). For neuraxial blocks, there were 183 adverse events, an incidence of 3% (95% CI 26 to 35 per 1000). The most common adverse event (104, or 2% of the total and 57% of all events) was the inability to place the block, or block failure. Ninety‐three per cent of the neuraxial blocks were placed without imaging techniques. Inability to place the block or a failed block was also the most common adverse event for upper extremity blocks and accounted for 0.6% of the adverse events after lower limb blocks (Polaner 2012).

Description of the intervention

Ultrasound refers to an oscillating sound pressure wave at a frequency above the upper limit of the human ear (approximately 20 kHz). In nature, bats use ultrasound as a guide for night flights. Ultrasounds emitted by the animal are reflected when they hit an obstacle. Applying the same principle, devices have been developed where ultrasound is used to create two (2‐D) or even three dimensional (3‐D) pictures (Feinglass 2007). Ultrasound has now been used for regional blockade for almost three decades. Amongst the pioneers of the use of ultrasound for regional blockade one could cite P La Grange (La Grange 1978), RL Ting (Ting 1989), T‐J Wu (Wu 1993) and S Kapral (Kapral 1994). The probe emitting and receiving the ultrasound is placed over the area of the body containing the location where the local anaesthetic will be injected. After appropriate visualization of the target, the needle may be advanced in‐plane (parallel to the beam), which allows visualization of the needle during its entire trajectory, or out‐of‐plane (perpendicular to the beam). The local anaesthetic is then injected under visualization with ultrasound. For neuraxial blocks, ultrasound can be used in real‐time to see the advancement of the needle within the epidural space or within the intrathecal canal (Niazi 2014), but most often only as a pre‐puncture guide to identify the exact vertebral level, to find an appropriate interverbal space sufficient to allow the passage of the needle, to determine the depth at which the needle should be advanced to place its tip at the chosen location and to visualize the spread of the local anaesthetic. For peripheral nerve blocks, ultrasound allows visualization of the target nerves, advancement of the needle (in‐plane technique) and the spread of the local anaesthetic.

How the intervention might work

As opposed to adults, in children regional anaesthetic techniques are usually performed with the child under either deep sedation or general anaesthesia. Fortunately, this does not seem to increase the risk of complications associated with regional anaesthesia (Taenzer 2014). However, as the patient cannot express any paraesthesia related discomfort (potential needle placement inside a neural structure), visualization may be even more desirable in this age group. Regional blockade may be performed by landmarks, neurostimulation, or with the use of ultrasound. Ultrasound allows adequate visualization of nerves and other structures relevant to the performance of both neuraxial and peripheral nerve blocks, particularly in children where relevant structures are relatively superficial. Failed block is the most common problem in paediatric regional anaesthesia when neuraxial blocks are performed without an imaging technique (Polaner 2012), and inadvertent vascular punctures occur in 2% (95% CI 12 to 21 per 1000) of the children undergoing neuraxial blocks. Ultrasound may decrease inadvertent vascular puncture (Walker 2009). Thus ultrasound guidance for regional anaesthesia in children may improve the success rate and decrease the complication rate.

Why it is important to do this review

The use of ultrasound has become popular for regional anaesthesia over the last two 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 neurological damage (Neal 2008). In adults, a Cochrane review determined that ultrasound guidance appeared to reduce the incidence of vascular puncture or haematoma formation but provided a similar success rate (Walker 2009). The cost of an ultrasound machine varies but most machines used in the clinical practice of regional anaesthesia cost approximately USD 40,000 or more (Liu 2010). Thus, the use of ultrasound is substantially more expensive than other tools such as those used for neurostimulation where most devices can be acquired for approximately USD 1000 or less (Liu 2010). A comprehensive review of the paediatric literature published in 2010 concluded that more outcome‐based, prospective, randomized controlled trials were required to prove the benefits of ultrasound when compared with conventional methods in children (Tsui 2010).

Objectives

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

Criteria for considering studies for this review

Types of studies

We will include all parallel randomized controlled trials (RCTs) that evaluate the effect of ultrasound guidance to perform a regional blockade technique in children and include any of our selected outcomes. We will exclude observational studies, quasi‐randomized trials, cross‐over trials and cluster‐randomized trials. We will not exclude any study based on language of publication or publication status.

Types of participants

We will include studies performed in children (≤ 18 years of age) undergoing any type of surgical procedure (open or laparoscopic) for which a neuraxial (spinal, epidural, caudal or combined spinal and epidural) or a peripheral nerve block (any peripheral nerve block including fascia (fascia iliaca, transversus abdominis plane, rectus sheath blocks) or perivascular blocks), either for surgical anaesthesia (alone or in combination with general anaesthesia) or for postoperative analgesia, was performed with ultrasound guidance. We will exclude studies where regional blockade was used to treat chronic pain.

Types of interventions

We will include studies where ultrasound guidance was used to perform the technique in real time (in‐plane or out‐of‐plane), to help as pre‐scanning before the procedure or to evaluate the spread of the local anaesthetic and readjust or complement the block. For the control groups, any other technique used to perform the block including landmarks, loss of resistance (air or fluid), click, paraesthesia, neurostimulation, transarterial or infiltration will be accepted. We will not discard any study based on the specific technique used as the comparator.

Types of outcome measures

We will evaluate the difference between the treatment group and the control group on the following outcomes.

Primary outcomes

  1. Success rate (author's definition)

  2. Pain scores in the post‐anaesthesia care unit (PACU)

  3. Block duration (author's definition)

Secondary outcomes

  1. Time to perform the procedure

  2. Number of needle passes

  3. Minor complications (bloody puncture)

  4. Major complications: local anaesthetic toxicity, signs of systemic toxicity (including seizures or cardiac arrests); infection; neurological injury (transient or lasting > one month)

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (most recent issue), Scopus (from inception to date), MEDLINE (OvidSP) (from 1946 to date) and EMBASE (OvidSP) (from 1982 to date). We will adapt our MEDLINE search strategy, provided in Appendix 1, for searching in the other electronic databases.

Searching other resources

We will look at http://www.clinicaltrials.gov, http://isrctn.org,http://www.umin.ac.jp/ctr/index.htm, http:/ /www.anzctr.org.au/, http://www.trialregister.nl/ and https:// udract.ema.europa.eu/ for trials in progress. We will also screen the reference lists of all studies that are retained and of the recent meta‐analysis or reviews related to the topic. Conference proceedings of anaesthesiology societies for the two preceding years, published in four major anaesthesiology journals, will also be screened: British Journal of Anaesthesiology,European Journal of Anaesthesiology,Anesthesiology, and Regional Anesthesia and Pain Medicine.

Data collection and analysis

Selection of studies

We will screen the list of all titles and abstracts identified by the search above. We will retrieve and independently read any potential articles to determine their eligibility. We will resolve discrepancies by discussion. We will list the reasons for exclusions in the table ’Characteristics of excluded studies’.

Data extraction and management

We will select the studies, extract data (assessment of risk of bias in included studies; types of outcome measures; assessment of heterogeneity) and enter the data in our data extraction sheet. We will first enter the site where the study was performed and date of data collection (to facilitate exclusion of duplicate publication) then whether the study was kept for the review or the reason for rejection. After agreement, data and moderators for heterogeneity exploration will be entered in Comprehensive Meta‐analysis by one author (JG). Also, after agreement, evaluation of the risk of bias will be entered in RevMan by the same author (JG). We will resolve any disagreement by discussion. We will contact authors to obtain additional information when required. Data for analysis will then be transferred in RevMan into the format required to include the maximal numbers of studies (events and total number of patients for each group; mean, standard deviations and number of patients included in each group; or generic inverse variance if necessary). When possible, we will entered the data in an intention‐to‐treat (ITT) analysis.

Assessment of risk of bias in included studies

We will assess the quality of the retained studies with the Cochrane Collaboration tool in RevMan 5.3 (Higgins 2011). We will resolve any disagreements by discussion. A trial will be considered as having a low risk of bias if all of the following criteria were assessed as adequate, and at risk of bias if one or more of the criteria was assessed as inadequate. We will assess the risk of bias based on the information presented in the reports, with no assumptions made.

  1. Generation of the allocation sequence of the interventions: randomization will be considered adequate if it was generated by a computer or random number table algorithm. We will judge other processes, such as tossing of a coin, adequate if the whole sequence was generated prior to the start of the trial. We will consider the trial as quasi‐randomized if a non‐random system, such as dates, names or identification numbers, was used.

  2. Concealment of allocation: we will considered concealment adequate if the process that was used prevented patient recruiters, investigators and participants from knowing the intervention allocation of the next participant to be enrolled in the study. We will consider concealment inadequate if the allocation method allowed the patient recruiters, investigators or participants to know the treatment allocation of the next participant to be enrolled in the study.

  3. Blinding of participants and personnel: we will consider blinding adequate if the participant and the personnel taking care of the patient were each blinded to the intervention. We will consider blinding inadequate if the participants or the personnel were not each blinded to the intervention.

  4. Blinding of outcome assessment: we will consider blinding adequate if the outcome assessor was blinded to the intervention. We will consider blinding inadequate if the outcome assessor was not blinded to the intervention.

  5. Incomplete outcome data (attrition bias): we will consider the trial adequate if all dropouts or withdrawals were accounted for, the number of dropouts is small (< 20%) and similar for both interventions, and the reasons for the dropping out of the patients sounds reasonable. We will consider the trial inadequate for this specific item if the reasons for dropping out of the patient were not stated or do not sound reasonable, the number is high (20%), or differs greatly between the groups.

  6. Selective reporting (reporting bias): we will consider the trial at low risk of bias if all the measurements stated in the methods section are included in the results, and at high risk if only a part of the results mentioned in the methods section are given in the results section. Per protocol results (not intention to treat (ITT)) will be considered as selective reporting.

  7. Any other risk of bias: any other reason that may have influence the results. An apparent conflict of interest will be considered as a risk of bias.

Measures of treatment effect

We will give results as risk ratio (RR) and the 95% confidence interval (95% CI) for dichotomous data (success rate, minor and major complications) and mean difference (MD) and 95% CI for continuous data (pain scores, block duration, time to perform the procedure) as much as is feasible. If some of the continuous data are given on different scales (pain scores), or when results are provided with P values (number of attempts or needle passes) we will produce the results as standardized mean difference (SMD) and 95% CI. For SMD, we will consider 0.2 a small effect, 0.5 a medium effect and 0.8 a large effect (Pace 2011). When there is an effect, a number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) will be calculated from the odds ratio. We will give results for dichotomous data as the RR as the odds ratio is not easily understood by clinicians (Deeks 2002; McColl 1998). We will use odds ratio for calculation of the NNTB and NNTH (http://www.nntonline.net/visualrx/) as this value is less likely to be affected by the side (benefit or harm) on which data are entered (Cates 2002; Deeks 2002). When there is no effect, we will calculate the information size in order to make sure that there were enough participants included in the retained studies to justify a conclusion on the absence of effect (Pogue 1998) (http://www.stat.ubc.ca/˜rollin/stats/ssize/b2.html). A difference of 15% (increase or decrease) will be considered as the minimal clinically relevant difference.

Unit of analysis issues

We will include only parallel group trials. If a study contains more than two groups, we will fuse two groups (by using the appropriate formula for adding the standard deviations when required) when we think that they are equivalent according to the criteria of our protocol (taking our factors for heterogeneity exploration into account) or separate them and split the control group in half if we think that they are different.

Dealing with missing data

We will contact the authors for apparent missing data. We will not consider medians as equivalent to means. Instead, we will use the P value and the number of patients included in each group to calculate the effect size. We will not used imputed results. Data will be entered as ITT data as much as is feasible. If not, the study will be quoted as at high risk of bias for selective reporting and then the data will be entered on a per protocol basis.

Assessment of heterogeneity

We will consider clinical heterogeneity before pooling results and examine statistical heterogeneity before carrying out any meta‐analysis. Statistical heterogeneity will be quantified by the I2 statistic with data entered in the way (benefit or harm) yielding the lowest amount. The amount will be qualified as low (< 25%), moderate (50%) or high (75%) depending on the value obtained for the I2 statistic (Higgins 2003).

Assessment of reporting biases

Publication bias will be examined with the classical fail‐safe number (< 10 studies) or a funnel plot followed by Duval and Tweedie’s trim and fill technique for each outcome (≥ 10 studies). Publication bias is the risk of bias introduced by the possibility that medical journals published studies favouring one treatment more often than studies favouring the other. The classical fail‐safe number is the number of missing negative studies required to reduce the P value of a statistically significant finding to 0.05 (not statistically significant). A low number means that the conclusions could easily be reversed with new negative studies. When there is no publication bias and no small‐study effect, if a graph is constructed with either the standard error or the precision (1/standard error) on the y‐axis and the logarithm of the odds ratio on the x‐axis then studies should be equally distributed on both sides of a vertical line passing through the effect size found (log odds ratio). The entire graph should have the shape of a reversed funnel. Duval and Tweedie’s trim and fill analysis corrects the asymmetry by removing the extremely small studies from the positive side (re‐computing the effect size at each iteration until the funnel plot is symmetric around the new effect size). The algorithm then adds the original studies back into the analysis and imputes a mirror image for each. The latter step does not modify the ’new effect size’ but corrects the variance which was falsely reduced by the first step. The Duval and Tweedie’s trim and fill analysis gives an estimate of what would be the effect size (odds ratio, risk ratio etc) if there was no publication bias.

Data synthesis

We will analyse the data with RevMan 5.3 and Comprehensive Meta‐Analysis Version 2.2.044 (www.Meta‐Analysis.com) with fixed‐effect models for comparisons with a low level of heterogeneity as assessed by the I2 statistic (I2 statistic < 25%) or random‐effects models for comparisons containing a moderate or high amount of heterogeneity (I2 statistic ≥ 25%) (Higgins 2003). Fixed‐effect and random‐effects models give the same results in the absence of statistical heterogeneity (I2 = 0%). When there is statistical heterogeneity random‐effects models will usually widen the CI, thus decreasing the chance of finding an effect when there is none. They may, however, increase the weight of smaller studies. We will present the characteristics of included and excluded studies in tables. We will present the risk of bias assessment in a risk of bias graph. We will present results for each comparison as forests plots when appropriate. For comparisons with less than two studies available, or that still include a moderate or high level of heterogeneity after heterogeneity exploration, we may provide the results as a narrative review.

Subgroup analysis and investigation of heterogeneity

Any amount of heterogeneity will be explored but we will focus more specifically on comparisons with significant heterogeneity (I2 ≥ 25%) (Higgins 2003) and explore the heterogeneity by the Egger’s regression intercept (to assess the possibility of a small study effect (Rucker 2011), visual inspection of the forest plots with studies placed in order according to a specific moderator, subgroupings (categorical moderators) or meta‐regressions (continuous moderators). Factors that will be considered in the heterogeneity exploration are: type of block (neuraxial versus peripheral nerve block), type of comparator (neurostimulation versus other), age and type of guidance (pre‐scanning versus real‐time (in or out of plane)), and combined methods (ultrasound plus neurostimulation compared to other modalities versus ultrasound alone compared to other modalities).

Sensitivity analysis

A sensitivity analysis (based mainly on the risk of bias assessment: allocation concealment and blinding of the assessor) may also be used if judged appropriate.

Summary of findings

We will use the principles of the GRADE system (Guyatt 2008) to assess the quality of the body of evidence associated with specific outcomes (success rate; pain scores in PACU; block duration; time to perform the procedure; number of needle passes; minor complications; and major complications) in our review and construct a summary of findings (SoF) table using the GRADE software (http://tech.cochrane.org/revman/gradepro). The GRADE approach appraises the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The quality of a body of evidence takes into consideration within study risk of bias (methodologic quality), the directness of the evidence, heterogeneity of the data, precision of effect estimates and risk of publication bias.