Ultrasound guidance versus anatomical landmarks for neuraxial anaesthesia in adults

Objectives

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

To assess the clinical efficacy and safety of ultrasound guidance compared with anatomical landmarks for neuraxial anaesthesia in adults.

Background

Description of the condition

Misapplication of regional anaesthesia can have severe consequences such as neurological complications, infection, and unnecessary pain. Neuraxial anaesthesia, which normally indicates spinal, epidural, or combined spinal and epidural anaesthesia, is a common technique for regional anaesthesia. It is mainly applied to anaesthesia for surgery or during labour. In neuraxial anaesthesia, the operator inserts the needle through the patient's back and advances the needle to the target space, such as the subarachnoid space, to inject the drug or to place the catheter. Conventional neuraxial anaesthesia is performed by using anatomical landmarks, such as the Tuffier's line (the horizontal line connecting the superior iliac crests). The Tuffier’s line generally denotes the L4 or the L4/5 intervertebral space, or an imaginary line between the lower edges of the scapulae correlating with the T7 interspace (Li 2020). However, neuraxial anaesthesia is sometimes difficult to perform. The first‐pass success rate of neuraxial anaesthesia with anatomical landmarks is reported to be approximately only 60% to 70% (De Filho 2002; Parra 2017).

Neuraxial anaesthesia is considered to be successful when the needle reaches the correct position and an adequate anaesthetic effect is obtained. Neuraxial anaesthesia can be difficult to administer successfully for several reasons. First, it is difficult to determine the point of needle insertion in people with poorly palpable landmarks and positioning challenges (e.g. obese people, pregnant women, and elderly people). Second, the operator may also miscount the target intervertebral space. It is reported that proper identification of the actual vertebral level by palpation is only about 30% (Broadbent 2000; Furness 2002). Third, the needle may not accurately reach the epidural or subarachnoid space because the anatomical position imagined by palpation can deviate from the actual position. Such inaccuracy can result in multiple needle passes and longer procedures that can lead to dissatisfaction for the person undergoing the procedure. Multiple needle passes and attempts may lead to back pain, postdural puncture headache, paralysis, and spinal haematoma, which may cause permanent neurological impairment (Perlas 2016). Spinal haematoma is rare, but once it occurs, partial recovery is reported at 28% and no recovery at 25% (Bos 2018). It is important to succeed with as few punctures as possible. Increasing successful neuraxial anaesthesia can help to reduce complications and increase patient satisfaction. Neuraxial anaesthesia by ultrasound guidance may be a useful way to increase success rates.

Description of the intervention

Bogin first reported the use of ultrasound for lumbar puncture in 1971 (Bogin 1971). Cork subsequently introduced the use of ultrasound for epidural anaesthesia in 1980 (Cork 1980). By using ultrasound, we can obtain helpful information about performing neuraxial anaesthesia, including the identity of a given intervertebral level, the depth of the epidural space, and the location of the midline and interspinous/interlaminar spaces. The main views for ultrasound techniques are the paramedian and midline views of the spine. The paramedian view is used to count upward from the sacrum and to identify the target intervertebral space. The midline transverse view is then used to show points between the spinous processes, such as the transverse process, dura, subarachnoid space, vertebrae, etc. We can measure the distance from the skin to the dura and the angle of insertion of the needle with this view (Grau 2001).

Two ultrasound guided techniques are usually used in neuraxial anaesthesia. The first is a preprocedural technique. In this technique, the operator estimates the point of needle insertion and the depth of the target, then marks the insertion point. In this case, ultrasound is used before the needle is inserted. Markings may move to the wrong place before the needle is inserted, and the procedure is still done under the blind technique at the time of the puncture. Another method uses a newer real‐time technique (Grau 2002; Karmakar 2009). It is not widespread because there are technical challenges that include obtaining alignment, adequate needle visualisation, ultrasound beam, or target area (Chin 2018), and the requirement for operator training. However, this technique may increase the reliability and safety of the procedure because anaesthetists can guide the movement of the needle under ultrasound and observe the injection of the drug.

How the intervention might work

Ultrasound provides beneficial imaging that allows the operator to visualise the local anatomy of interest and the size of important structures, and helps to determine the depth and direction of needle insertion. Targets can be identified and patient positioning adjusted while performing a scan for insertion. In addition to the operator, another anaesthetist can review the images. In children, it is indicated that ultrasound guidance leads to improved success of neuraxial anaesthesia (Guay 2019). Ultrasound guidance may also increase success rates and prevent complications in adults, especially in those who have difficulty with neuraxial anaesthesia. Other useful imaging tools for epidural anaesthesia are fluoroscopy and CT guidance (Kim 2012Parra 2017), but these require the use of radiation. Radiation can cause injuries to the skin and underlying tissues. In contrast, ultrasound is minimally invasive for the person undergoing the procedure.

Why it is important to do this review

The efficacy of ultrasound has been established for peripheral nerve blocks (Lewis 2015), and its use is recognised as standard practice. On the other hand, ultrasound guidance has not been used routinely in performing neuraxial anaesthesia for surgery or labour. Previous systematic reviews and meta‐analyses suggest that ultrasound guidance can reduce the risk of neuraxial anaesthesia technical failure (Perlas 2016; Shaikh 2013; Sidiropoulou 2021). However, those reviews only included the lumbar region and included diagnostic lumbar puncture, a non‐anaesthetic neuraxial procedure. Another systematic review and meta‐analysis was published in 2020, but it only summarised studies in obstetrics (Jiang 2020). Hence, the efficacy and safety of ultrasound guidance for neuraxial anaesthesia have not been sufficiently established. Additionally, some issues were not addressed in those reviews. First, it is unclear whether ultrasound improves patient‐reported outcomes such as patient satisfaction. More recent randomised controlled trials have reported those outcomes (Li 2019; Park 2019), but they were published after the previous reviews. Second, efficacy for all types of patients is undetermined. For example, some studies reported no advantage of ultrasound in anatomically‐easier patients, such as those who are not obese or who have easily palpable spines (Arzola 2015; Turkstra 2017). Third, to date, there is no synthesised evidence on real‐time techniques. Randomised controlled trials focused on the real‐time technique have recently been published (Chong 2017; Elsharkawy 2017), but they reported conflicting results. Thus, a methodologically rigorous meta‐analysis is needed to evaluate people for whom ultrasound guided neuraxial anaesthesia is beneficial, and to report outcomes of interest to people undergoing the procedure.

Introducing the ultrasound guidance technique is difficult in some countries, such as low‐resource countries, because the cost for purchasing an ultrasound machine is approximately USD 25,000 or more (Wynd 2009). If the use of ultrasound for neuraxial anaesthesia is shown to improve outcomes, policymakers can consider funding ultrasound machines to encourage ultrasound guided neuraxial anaesthesia. For healthcare providers, evaluation of efficacy and safety can help prioritise education and clinical resources for neuraxial anaesthesia.

Objectives

To assess the clinical efficacy and safety of ultrasound guidance compared with anatomical landmarks for neuraxial anaesthesia in adults.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs), including cluster‐RCTs. We will include studies reported in full text, those published as abstracts only, and unpublished data. We will not consider cross‐over trials and quasi‐RCTs (studies in which participants are allocated based on alternation, use of alternate medical records, date of birth, or other predictable methods).

Types of participants

We will include all adult participants (≥ 18 years) who require neuraxial anaesthesia (spinal, epidural, or combined spinal and epidural) for surgical anaesthesia (alone or in combination with general anaesthesia) or labour. Epidural anaesthesia involves any kind of region, including thoracic and lumbar. We will exclude studies reporting data from children (< 18 years) because their anatomy may differ from adults and the effect of ultrasound guidance may be different for them. We will also exclude studies in which neuraxial anaesthesia was used to treat chronic pain, because the target population and the procedure itself may be different from surgical anaesthesia. If we identify studies that include only a subset of eligible participants, we will extract the relevant data from that subset. We will contact the researcher to request data when stratified results are not provided. We will exclude studies if more than 30% of participants are ineligible, or if data for the eligible subset are not available.

Types of interventions

We will include studies comparing ultrasound guidance with anatomical landmarks when performing neuraxial anaesthesia. Ultrasound guidance includes both preprocedural and real‐time techniques. We will include the use of any anatomical landmarks that can be identified without tools (e.g. Tuffier’s line) as a comparison. We will exclude the use of CT, fluoroscopy, or any other identification tools. We will include studies regardless of the level of training of operators, the number of operators (one or two), concentration of local anaesthetics used, ultrasound manufacturer, or ultrasound machine generation. We will exclude studies on lumbar puncture, which is usually performed in the emergency department, because participant characteristics and the situation of performing the procedure are expected to be different from those of neuraxial anaesthesia for surgery or labour. We will also exclude any other non‐anaesthetic neuraxial procedures.

Types of outcome measures

Primary outcomes

1. Number of attempts until pass success or procedure termination

2. Procedure time

3. Participant satisfaction during the procedure

The definition of the number of attempts may vary between studies. For example, it is defined as any forward needle advancement following a backward movement in order to redirect the needle in some studies (e.g. Arzola 2015), or as the number of insertions through the skin in other studies (Sahin 2014). We will define 'the number of attempts' as stated by the study authors. 

Procedure time may be reported as preparation time, needling time, or both. We will adopt the following priorities because needling time is considered to be most relevant for participants: 1) needling time, 2) total procedure time defined as preparation time plus needling time, and 3) preparation time.

Participant satisfaction can be usually reported using a scale such as a verbal rating scale (Ansari 2014). We will apply no restrictions regarding the scales. Even if it was reported as a dichotomous outcome, we will extract the data.

Secondary outcomes

1. Proportion of procedures that have first‐pass success

2. Proportion of procedures that have technical failure of neuraxial anaesthesia

3. Pain during the procedure

4. Any adverse events reported by each included study as adverse events (e.g. back pain, postdural puncture headache, radiculopathy, spinal haematoma, lasting neurological injury, and life‐threatening events)

We will define 'first‐pass success' as stated by the study authors.

We will define the 'technical failure of neuraxial anaesthesia' as any of the following situations regardless of 'pass success': 1) conversion to general anaesthesia, 2) discontinuation of the techniques, 3) the intended anaesthetic effect was not achieved (e.g. additional analgesia required).

We will handle 'pain during the procedure' in the same way as participant satisfaction. 

Search methods for identification of studies

Electronic searches

We aim to identify all relevant RCTs and cluster‐RCTs, regardless of language or publication status (published, unpublished, in press, or in progress) according to the Cochrane Handbook of Systematic Reviews of Interventions (Lefebvre 2021).

We will search the following databases for relevant trials:

• the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library

• MEDLINE (Ovid SP, 1946 to present)

• Embase (Ovid SP, 1974 to present)

• Web of Science (1945 to present)

The search strategy for MEDLINE, including a search for systematic reviews, can be found in Appendix 1.

We will also conduct a search of ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (WHO ICTPR) Search Portal (apps.who.int/trialsearch) for ongoing or unpublished trials.

Searching other resources

We will check the citations of included studies and systematic reviews for additional potentially relevant studies. We will also scan conference abstracts of the society related to the topic. If necessary, we will contact trial authors for additional information. Furthermore, we will contact field specialists and search medical ultrasound companies' websites (e.g. Canon, Fujifilm, GE Healthcare, Mindray, Mobissom, Philips, Samsung, Siemens) to enquire about relevant ongoing or unpublished studies.

Data collection and analysis

Selection of studies

We will use the search strategy described above to obtain titles and abstracts of the studies. Two review authors (YM, SY) will independently screen titles and abstracts of the results of the search to identify potentially relevant studies. We will obtain the full text of these studies, if necessary, to determine which studies meet eligibility. We will resolve conflicts by discussion. If we are unable to reach a consensus, we will consult the third review author (NW). We will record the selection process in sufficient detail to complete a PRISMA flow diagram and characteristics of excluded studies table (Liberati 2009).

Data extraction and management

We will develop a standardised data collection form for study characteristics and outcome data, and pilot test it on at least one study included in the review, resolving any disagreements by discussion. 

• Methods: study design, total duration of study, number of study centres and country, study setting, and date of study.

• Participants: number randomised, number lost to follow‐up/withdrawn, number analysed, mean age, age range, gender, body mass index (BMI), difficulty of palpating landmarks, type of surgery or procedure, inclusion criteria, and exclusion criteria.

• Interventions: intervention and comparison characteristics, intervertebral level, route of approach (i.e. median or paramedian), experience of the operators, types of needle, the types of probe for ultrasound, the manufacturer or generation of ultrasound machines used, concomitant medications, and excluded medications.

• Outcomes: primary and secondary outcomes specified and collected, and time points reported.

• Notes: funding for trial, and notable conflicts of interest of trial authors.

Three review authors (YM, SY, DR) will independently extract the data using standard data extraction forms. Studies reported in journals in languages other than English will be translated prior to assessment. Where multiple publications of a single study exist, we will group the reports together and extract the most likely correct data from multiple reports for analysis. We will resolve conflicts on data extraction by discussion. If we are unable to reach a consensus, we will consult the fourth review author (NW). If additional information is needed, one review author (YM) will contact the corresponding author of the relevant studies. After we have completed data extraction, one review author (YM) will transfer the data into RevMan Web (RevMan Web 2021), and another review author (IN) will check the data.

Assessment of risk of bias in included studies

Three review authors (YM, SY, DR) will independently assess the risk of bias for each included study using version 2 of the Cochrane risk of bias tool for randomised trials (RoB 2) (Higgins 2021a). We will assess the risk bias for the effect of assignment to the intervention (intention‐to‐treat effect; ITT) for all seven outcomes. We will use the RoB 2 Excel tool to manage the assessment of bias (available from: www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2). We will resolve conflicts by discussion. If we are unable to reach a consensus, we will consult the fourth review author (NW). We will assess the following five domains by answering signalling questions to judge the risk of:

• bias arising from the randomisation process;

• bias due to deviations from intended interventions;

• bias due to missing outcome data;

• bias in measurement of the outcome; and

• bias in selection of the reported result.

We will assess all domains of each outcome across different studies.  We will summarise the overall risk of bias for each result (outcome) as described in Higgins 2021a. If we include cluster‐RCTs, we will use the RoB2 tool for cluster‐RCTs and assess an additional domain specific to this study design (bias arising from the timing of identification and recruitment of participants) (Higgins 2021b).

We will define the overall risk of bias as follows.

• Low risk of bias: all the above domains are at low risk of bias.

• Some concerns: one or more the above domains are rated as 'some concerns', but are not at high risk of bias for any domain.

• High risk of bias: one or more the above domains are at high risk of bias or multiple domains are rated as 'some concerns' in a way that substantially lowers confidence in the result.

Measures of treatment effect

We will analyse dichotomous data as risk ratios (RR) with 95% confidence interval (CI); continuous data as mean difference (MD) for continuous data using the same scale and standardised mean difference (SMD) for continuous data using different scales, with 95% CI. We will use SMD for the outcome ‘pain’ or ‘participant satisfaction’ and express it in the units of the measurement instruments mostly used by the included studies (e.g. Visual Analogue Scale (VAS)). We interpret the results of SMD as follows: 0.2 indicates a small effect, 0.5 indicates a medium effect, and 0.8 indicates a large effect (Cohen 1988). If each trial reported continuous data as median and interquartile range (IQR), we will convert median to mean and estimate the standard deviation (SD) as IQR/1.35 (Higgins 2021c). When the data are skewed, we will use a formula for imputing a missing mean value based on the lower quartile, median, and upper quartile summary statistics proposed by Wan and colleagues, which has been reported to work well in analysing skewed outcomes (Wan 2014).

Unit of analysis issues

The unit of analysis is the individual participant. If we include any cluster‐RCTs, we will consider the cluster as the unit of randomisation. We will adjust reported standard errors using the trial's intracluster correlation coefficient (ICC), using the method described in the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2021c). If we cannot obtain the ICC, we will use an approximate ICC from a similar trial.

If we find studies with multiple treatment groups, we will include all intervention groups relevant to the review. If an RCT has two intervention groups and one comparison group, we will divide the number of participants in the comparison group by the number of intervention groups to avoid double counting the participants when they are included in the same analysis.

Dealing with missing data

We will contact the original investigators or study sponsors in order to verify key study characteristics and to obtain missing numerical outcome data where possible (e.g. when a study is identified as an abstract only). Where this is not possible, and the missing data are thought to introduce serious bias, we will explore the impact of including such studies in the overall assessment of results by a sensitivity analysis.

Assessment of heterogeneity

We will visually inspect forest plots to consider the direction and magnitude of effects and the degree of overlap between confidence intervals. We will use the I² statistic to measure heterogeneity amongst the trials in each analysis but acknowledge that there is substantial uncertainty in the value of I² when there is only a small number of studies. Therefore, we will also consider the P value from the Chi² test, with a significance level of the P value set to 0.10 (Deeks 2021). If we identify substantial heterogeneity, we will investigate and report potential reasons for this by prespecified subgroup analysis. We will interpret the heterogeneity as follows.

• 0 to 40%: might not be important

• 30 to 60%: may represent moderate heterogeneity

• 50% to 90%: may represent substantial heterogeneity

• 75% to 100%: considerable heterogeneity

When I² lies in an area of overlap between two categories (e.g. between 50% and 60%), we will consider differences in participants and interventions among the trials contributing data to the analysis (Deeks 2021).

Assessment of reporting biases

If we can pool more than 10 trials, we will create and examine funnel plots to explore possible small‐study biases for the primary outcomes. We will also evaluate reporting bias by checking the protocol of the study, if we can identify one from searching trial registries.

Data synthesis

We will review the data from all eligible studies and, if possible, synthesise and analyse data using RevMan Web 2021. For dichotomous outcomes, we will use the number of participants in each trial arm and the number of events. For continuous outcomes, we will use means and standard deviations for each trial arm. We will report data narratively if it is not appropriate to combine them in a meta‐analysis. We will undertake a meta‐analysis only where this is meaningful, i.e. if the treatments, participants, and the underlying clinical question are similar enough for pooling. We will use a random‐effects model to pool data because we expect the definitions of participants and operators to vary to some extent between studies.

Subgroup analysis and investigation of heterogeneity

We plan to carry out the following subgroup analyses if we find sufficient data from the included studies.

• Difficulty of palpating landmarks, such as in obese people; pregnant women; people with scoliosis or previous spinal surgery, and elderly people: difficult versus not difficult

• Experience of operators (e.g. Residents, Fellows): experienced versus inexperienced

• Types of ultrasound guidance: preprocedural versus real‐time techniques

• Types of neuraxial anaesthesia: spinal versus lumbar epidural versus thoracic epidural

• Different definitions of the number of attempts

Because we plan to explore possible causes of substantial heterogeneity with subgroup analysis, we will use all outcomes in subgroup analyses. We will use the formal test for subgroup differences in RevMan Web 2021 and base our interpretation on this.

Sensitivity analysis

We plan to carry out the following sensitivity analyses, to test whether key methodological factors or decisions have affected the main result.

• Including only 'overall low risk of bias' results and excluding results with 'some concerns' or 'high risk of bias'

• Including only the studies that report needling time as procedure time

• Excluding studies with incomplete or imputed data, such as outcomes and ICC

Summary of findings and assessment of the certainty of the evidence

We will construct a summary of findings table using GRADEpro software (gradepro.org) (Schünemann 2021). The summary of findings table will include the relative and absolute effects and the certainty of the evidence for all seven primary and secondary outcomes: number of attempts until pass success or procedure termination, procedure time, participant satisfaction during the procedure, proportion of procedures that have first‐pass success, proportion of procedures that have technical failure of neuraxial anaesthesia, pain during the procedure, and any adverse events. Three review authors (YM, SY, DR), working independently and in duplicate, will apply GRADE criteria to evaluate the certainty of the evidence for each outcome (Guyatt 2011). We may rate down the level of certainty due to risk of bias, imprecision, inconsistency, indirectness, and publication bias. We will feed the overall RoB 2 judgement into the GRADE assessment for study limitations. We will resolve conflicts by discussion. If we are unable to reach a consensus, we will consult the fourth review author (NW). In case of credible subgroup effects based on characteristics of the population, we will present results stratified across subgroups in the summary of findings table.

Appendices

Appendix 1. MEDLINE search strategy

Database: Ovid MEDLINE(R) ALL <1946 to 16 December 2020>

Search Strategy:

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐

1 exp Anesthesia, Spinal/ (12313)

2 exp Anesthesia, Epidural/ (13655)

3 exp Analgesia, Epidural/ (8286)

4 exp spinal canal/ (7583)

5 neuraxial*.ti,ab,kf. (2844)

6 lumbar.ti,ab,kf. (110462)

7 spinal.ti,ab,kf. (281663)

8 epidural*.ti,ab,kf. (43250)

9 peridural*.ti,ab,kf. (2113)

10 extradural*.ti,ab,kf. (6909)

11 subarachnoid*.ti,ab,kf. (37360)

12 intrathecal*.ti,ab,kf. (24335)

13 (caudal adj2 an?esth*).ti,ab,kf. (715)

14 or/1‐13 (434840)

15 exp Ultrasonography/ (443282)

16 (ultrasonograph* or ultra sonograph*).ti,ab,kf. (112885)

17 (ultrasound* or ultra sound*).ti,ab,kf. (260586)

18 (ultrasonic* or ultra sonic*).ti,ab,kf. (58627)

19 echotomograph*.ti,ab,kf. (760)

20 or/15‐19 (641956)

21((randomized controlled trial or controlled clinical trial).pt. or randomi?ed.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (exp animals/ not humans.sh.) (4245743)

22 14 and 20 and 21 (2153)

Contributions of authors

YM conceived, designed, and drafted the protocol.

SY designed, and drafted the protocol.

IN, ES, and NW provided general advice and revised the protocol.

DR read and approved protocol

IN provided feedback and comments from an anesthesiology perspective.

ES provided feedback and comments from a methods' perspective.

NW provided feedback and comments from a methods' perspective.

Sources of support

Internal sources

• No sources of support provided

External sources

• No sources of support provided

Declarations of interest

Yuto Makino has none to declare.

Satoshi Yoshimura has research funds from Nagasaki Prefectural Medical Association. The conduct of this review is completely independent of the intention of this grant.

Isao Nahara has no conflict of interest directly relevant to the content of this grant.

Ethan Sahker reports unrelated grants from Kyoto University and Japan Society for the Promotion of Science. The conduct of this review is completely independent of the intention of these grants.

David Roche has no conflict of interest to declare.

Norio Watanabe has received royalties from Sogensha and Medical View for writings, and consulting fees from Advantage Risk Management. The conduct of this review is completely independent of the intention of this grant.

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