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A Systematic Review of Postoperative Pain Outcome Measurements Utilised in Regional Anesthesia Randomized Controlled Trials.

1. Introduction

Regional anesthesia is a rapidly growing subspecialty, with a widening spectrum of applications and uses. Despite growth in this area of research, there have been few published regional anesthesia systematic reviews, meta-analyses, Cochrane reviews, or National Institute for Health and Care Excellence (NICE) guidelines exploring pain outcomes. This maybe due to the heterogeneity of outcome variables chosen in regional anesthesia studies, making it difficult to combine and analyse data.

The Cochrane Collaboration, which aims to give the "clinical bottom line" through its reviews, has 39 reviews, which mention regional anesthesia. These reviews commonly cite the outcomes chosen as "incomplete," "poor quality," and "heterogeneous," which impeded the authors' ability to draw meaningful conclusions [1-4]. Additionally, there are four NICE guidelines centered on regional anesthesia [5-8], and of these, only one deals specifically with the use of regional anesthesia to manage surgical or postoperative pain [5].

Identification of outcomes utilised can subsequently help to create a definitive list of core outcomes, which may guide future researchers when designing studies. This systematic review aimed to explore outcomes utilised in regional anesthesia randomized controlled trials (RCTs) to measure postoperative pain.

2. Methods

We have adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards in this article [9].

We performed a literature search using three search engines (Medline, Embase, and CINAHL). These databases were searched for RCTs published between 2005 and 2017. The search strategy included manual searching of citations for further relevant articles. The search was initially performed in mid December 2016 and repeated on January 5th 2017. An example of the exact search terms used for each database is included in Appendix A. The review was limited to published English language RCTs exploring regional anesthesia, with a primary outcome of postoperative pain. Articles were included if published between 2005 and 2017, in one of the top 20 impact factor journals (Appendix B, Table 4). Since it was felt that the assessment of pain within the adult population is significantly different to the pediatric and obstetric populations, this review was limited only to adult studies (participants aged 18 years and over).

The selected studies were analysed by two of the authors (E. Pushpanathan and T. Setty). Each study was read and the following data were extracted and tabulated: authors, year of publication, postoperative pain outcome measures utilised, times of postoperative pain assessment, nerve block studied, and personnel collecting the data. The two primary outcomes explored in this systematic review were the type of pain outcome measured and the time of measurement.

The quality of studies included in this systematic review was evaluated using the Cochrane Collaboration's tool for assessing risk of bias [10]. Areas of methodological quality assessed included concealment of allocation, random sequence generation, blinding of the assessors and participants, and accounting for all subjects. Overall quality was graded as low (low risk of bias), high (high risk of bias), or unclear risk of bias for each domain entry [10]. The quality of each study was also assessed using the Jadad score, which examines withdrawals, blinding, and randomization of a study [11], although studies were not excluded on the basis of this assessment. At least two individuals extracted the study data independently utilizing a standardised review protocol and recorded the information on a data spreadsheet. Differences were resolved by reexamination of the original manuscripts and by discussion. The data were then entered into a Microsoft Excel for Mac 2016 spreadsheet (Microsoft Corporation, Redmond, WA) by one of the authors (E. Pushpanathan) and checked by a second investigator (T. Setty).

3. Results

The search identified 407 articles. One author screened the titles and abstracts of these articles, and 308 were excluded. Two authors reviewed the full text of the remaining 99 articles. Of those excluded, 20 were duplicates and 18 were not RCTs. Of the remaining excluded articles, 5 were pediatric studies, 2 were obstetric, 3 were systematic reviews or meta-analyses, 2 were foreign language, 7 did not have postoperative pain as a primary outcome, and 11 were abbreviated studies in supplements so lacked sufficient detail. The results of the literature search are summarised in Figure 1. Thirty-one articles met the inclusion criteria and were included in this systematic review [12-42]. A detailed description of the pain outcomes utilised and timings of measurements in the included studies is provided in Table 1. Table 2 summarises the number of studies utilizing each pain outcome identified from included studies. Median Jadad score of included studies was 3 (range 2-5). The majority of studies demonstrated a low risk of bias in the 7 domains. A summary of risk of bias assessment is provided in Figure 2.

3.1. Postoperative Pain Measurement Tool. Fifteen different outcome measures in total were used in the 31 included studies to assess postoperative pain. The outcome measures utilised in the included studies are summarised in Table 2. The majority of studies (27/31) utilised two or more pain outcomes. The most commonly used outcome measures were numerical grading of pain/numerical reporting scale (NRS) out of 10 (16 studies) [12, 17, 20-24, 27-29, 32-35, 38, 40], opioid consumption (16 studies), and visual analogue scale 10 cm (VAS; 12 studies) [13-16, 25, 26, 31, 36, 37, 39, 41, 42]. Other than reporting total opioid consumption, analgesia usage was also measured with the following outcomes: nonopioid analgesic requirement [14, 16, 32, 33, 36], total supplementary analgesic requirement [34, 35], and cumulative opioid consumption [26, 37]. Other pain outcome measures utilised included: time to first episode of pain [22, 33] and first analgesia or opioid request [18, 28-30, 35-37]. If a study did not use a scoring system to rate pain, the need for analgesia was utilised instead as an outcome measure. There was an evident understanding amongst the selected studies that pain may be worse on movement with separate pain scores (NRS or VAS) taken on activity in 10 of the included studies (Table 2). In the studies that utilised a scoring system to measure pain, there were two groups; those that reported scores at individual time points [12, 14-16, 19, 21, 23-26, 28, 29, 31, 32, 34-37, 39-42] and studies that recorded the worst (or maximum) pain score during the study period [17, 20, 22, 27, 33]. Average pain scores were reported in only one study [38].

3.2. Time of Measurement. Time of measurement of pain outcomes also varied with a total of 51 different time points utilised in the 31 studies (Table 1). The time points ranged from immediately following surgery [20,26,27,29, 31, 34, 37,41] to 12 months postoperatively [25]. Intervals between measurements ranged from every 5 minutes [41] to 6 months [25]. Twenty-two out of 31 of the studies (71%) only evaluated pain over the first 24 hours postoperatively [12, 14, 16, 17, 19, 20, 22-24, 26, 27, 29, 31-34, 36, 38-42].

3.3. Nerve Blocks Studied. A variety of nerve blocks were studied (16 in total), which are summarised in Table 3 and may indicate which blocks were seen as important over the study period. Six studies explored continuous infusions [12, 16, 20, 23, 29, 38] with either peripheral nerve or epidural infusions. The remaining studies evaluated single-shot peripheral nerve blocks.

3.4. Personnel Collecting Data. Twelve out of the 31 included studies (39%) used an independent or blinded assessor or independent assessment (i.e., postal survey) to assess patients' pain [12, 14, 17, 19, 22, 25-27, 33, 34, 36, 42].

3.5. Acute Pain Studies. All but two of the included studies focused on acute pain outcomes. Choi et al. assessed pain outcomes of acute and chronic pain [17] NRS at 4.5 months postoperatively and Wegener et al. [25] looked at the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and VAS at two different time points (3 months and 12 months).

4. Discussion

This systematic review demonstrates that postoperative pain in regional anesthesia RCTs is reported inconsistently. The 31 studies included in this review utilised 15 different types of postoperative pain outcomes, measured at 51 different time points. Therefore at present, there appears to be multiple analyses of different nerve blocks in different centers using different acute pain outcome measures.

Heterogeneity in pain outcomes chosen in the included studies was high. One of the difficulties in deciding which pain outcomes to study in regional anesthesia trials is that there is no reliable method of objectively measuring postoperative pain [43]. Physiological parameters, such as heart rate and skin conductance, appear to correlate poorly with pain levels [44, 45]. Instead, pain is often measured by patient-reported intensity, surrogate measures such as the use of supplemental analgesia, or measures of the impact of pain on functioning including the following: sleep, coughing, or ability to perform activities of daily living. Each of these assessment strategies has strengths and limitations, which are demonstrated in this review by the majority of studies using two or more outcome measures to assess pain.

The visual analogue scale (VAS) is a widely used tool to assess postoperative pain. It is considered by some to be more sensitive to fine changes in pain score than numerical scales and four point scales [46]. It also has been shown to demonstrate generally high usability and acceptance; however, elderly patients have been found to not engage with this tool as well as younger patients, since lengthy explanations may be necessary and inconsistent marking along the line has previously been reported [47]. The NRS is another widely used tool to measure pain. Both VAS and NRS are one-dimensional pain tools that are easy to measure and largely reproducible, and thus it may explain why these are often chosen in preference to lengthier multidimensional tools, such as the McGill Pain Questionnaire. Since NRS is a verbal tool, requiring no writing or marking (in contrast to VAS), and is simple to perform by clinical and research team members [43], it should perhaps be considered as an ideal core outcome rather than VAS in studies involving elderly age groups.

Total opioid consumption over the study period (excluding daily and cumulative opioid consumption) was another popular outcome choice, which was utilised in 12 of the 31 studies reporting postoperative pain in this review. This outcome can be interpreted in different ways. A higher total opioid consumption value over a study period is presumed to indicate a higher pain state, necessitating requirement for supplemental opioid-based analgesia. Total opioid consumption could also reflect average pain scores (either NRS or VAS), with higher scores indicating greater opioid requirement. The psychological factors involved in patients requesting additional analgesia warrant further consideration. This involves evaluation of anticipated pain outcome with and without further analgesia, and in order for the request to be made, the patient must feel the treatment of pain outweighs the potential risk of side effects from the drug. This has been shown to be a key decision-making factor when patients are in pain [48]. Total opioid consumption as an outcome may therefore result in patients with different pain states, intensities, and satisfaction levels with analgesia being inappropriately grouped together.

Regional anesthesia is gaining popularity, partly due to improvements in safety and success attributed to ultrasound-guided techniques [49]. The Sprint National Anaesthesia Project (SNAP-1) examined patient-reported outcomes related to satisfaction with anesthesia [50]. Anxiety was found to be the worst part of the perioperative experience. With regard to anesthesia, specific reasons for dissatisfaction: thirst, drowsiness, pain at the surgical site, and hoarseness, were found to be among the most troubling for patients. Regional anesthesia (as a whole) was found to be associated with a reduced burden of side effects. It is unclear what level of pain correlates to adequate patient satisfaction in this population. Nine studies included in this systematic review utilised outcomes consisting of a variant of determinant of effective block duration such as time to first pain or time to first analgesic/opioid request. This suggests that some researchers value the importance of duration of patient being pain-free or experiencing a low enough pain level not to require additional analgesia. However, it should also be noted that a prolonged, dense block may not be in the patients' best interests and may be associated with worse patient satisfaction in this population.

Adequate assessment of pain, using validated tools appropriate to the population or individual, is an essential prerequisite of successful pain management. It has been shown in many countries that inadequate pain assessment is common, with resultant failings in management of pain [51]. Although our review may prove helpful to clinicians and researchers in the future, by summarizing some of the available measures, there are still unanswered questions in this field. In order to assimilate multiple studies with meta-analysis and to derive meaningful clinical conclusions, this review highlights the need for the formulation of a minimum set of outcomes that can be used in future regional anesthesia studies. Use of such a "core set of outcomes" would allow for comparison of outcomes from studies. The COMET or (Core Outcome Measures in Effectiveness Trials) group is a United Kingdom initiative set up in 2010 in response to disjointed outcome measures in clinical research as a whole [52]. Their aim is to standardize outcomes and provide a database from which researchers can access existing outcome sets to design future trials. Specific analysis into the subset of patients undergoing regional anesthesia requires further research. The perspective of patients of the correct demographic ("key stakeholders") must be considered when deciding core outcomes for postoperative pain assessment in regional anesthesia. This would require exploration of what patients expect following regional anesthesia, including pain expectations following surgery performed with regional anesthesia.

The core outcome set for chronic pain studies may help researchers decide which outcomes to utilize in future regional anesthesia pain studies. A core outcome set of six outcomes for chronic pain was formalised in 2005 by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group [53]. This group formalised outcomes to be used for physical functioning, emotional functioning, participant rating for improvement and satisfaction, symptoms and adverse events, and participant disposition, as well as for the assessment of pain. With regards to pain, recommendations included an 11 point 0-10 scale, usage of rescue analgesics, and categorical scale if the patient was unable to use a verbal scale. This systematic review has shown that the IMMPACT recommended pain outcomes for chronic pain are also the most commonly used in the acute pain setting in regional anesthesia RCTs. The 2005 IMMPACT recommendations, which are primarily for improving clinical trial methodology of chronic pain treatments, do not seem to have made any impact on outcomes in regional anesthesia efficacy studies. This may be because the pain outcomes considered clinically important in recovery following elective surgery are different to those important in patients with chronic pain. Acute pain can be reliably assessed, both at rest (important for comfort) and during movement (important for function and risk of postoperative complications), with one-dimensional tools such as NRS or VAS. Chronic pain assessment however and its impact on physical, emotional, and social functions require multidimensional qualitative tools and health-related quality of life instruments [51]. For example, it should be noted that while VAS was found to be one of the most commonly utilised acute pain outcomes identified in this review, it was omitted as an assessment for chronic pain outcomes.

When deciding what should be a "core outcome set," one must consider if there is an implied core set or if there are outcomes that are chosen more commonly among regional anesthesia studies. Until a core outcome set for regional anesthesia pain studies has been formulated, researchers may wish to consider utilizing the most commonly used outcomes identified in this review in order to allow for comparisons between existing data in the literature. It should however be noted that this assumes that the most commonly used outcomes represent what clinicians and researchers believe to be the most important. Based on frequency of utilization, this review suggests that the core outcomes for regional studies exploring acute pain should include NRS (verbal out of 10) at rest, NRS on activity, VAS at rest, total opioid consumption over the study period, analgesic consumption, and time to first analgesic request. The most commonly utilised time points of pain outcome data measurement in the descending order of frequency were 24, 4, 6, 12, and 48 hours postoperatively.

This review does have some limitations. Restricting included RCTs to English language studies may have reduced the number of clinically useful studies analysed. Additionally, the restriction to the top 20 impact factor journals may not reflect the outcome measures utilised in the majority of regional anesthesia studies. This did however serve as a marker of study quality and peer review, which we felt was required in this review. However, there are always risks inherent in limiting groups to be studied. The year of publication of included studies is important to note, and established blocks such as femoral nerve blocks may have already been extensively studied prior to 2005. Use of ultrasound guidance may have made some small differences to pain assessment outcome choice and the debate surrounding adductor canal versus femoral nerve block may continue; however, 2005 to 2017 is a relatively short period of time for major changes in clinical practice to have occurred. We limited the search to articles published over this 12-year period as our intention was to provide the reader with information regarding regional anesthesia studies that would be most relevant to current practice. Finally, although we have attempted to locate all relevant articles by using a robust search methodology, it is possible that with a review of this size, some relevant articles may have been missed. Furthermore, since these studies explore different peripheral nerve and plexus blocks, this may make it more difficult to derive an implied core outcome set from the included group of studies. We appreciate that different surgeries have different temporal pain profiles. Some surgeries for example may peak in pain immediately after surgery, whereas others may have pain that peaks when the nerve block wears off or during days following surgery. However, despite the apparent heterogeneity among the included studies, the vast majority of the RCTs included utilised generic outcomes and only one study used a scoring system specific to the type of surgery performed (the Western Ontario and McMasters Universities Osteoarthritis Index) [25, 54].

In summary, this robust review of the postoperative pain outcomes used in regional anesthesia RCTs between 2005 and 2017 demonstrates significant heterogeneity in choice of outcomes and times of measurements utilised. These findings represent a starting point for further work into developing a core outcome set for future regional anesthesia studies.

Appendix

A: Literature Search Terms

The basic components of the search were as follows:
   Postoperative pain (ti.ab) AND regional anaesthesia
   (ti.ab) AND randomised controlled trial (ti.ab) AND top
   20 impact factor journals (j.n.) [limited to 2005-2017]


These were the search terms used in OpenAthens to formulate the final search:

(1) EMBASE, Medline, CINAHL; (((postoperative pain adj4 pain*) OR (post-operative adj4 pain*) OR postoperative-pain* OR (post* NEAR pain*) OR (postoperative adj4 analgesi*) OR (post-operative adj4 analgesi*) OR (post-operative adj4 analgesi*))) ti.ab

(2) EMBASE, Medline, CINAHAL; (((post-surgical adj4 pain*) OR ("post-surgical" adj4 pain*) OR (post-surgery adj4 pain*))) ti.ab

(3) EMBASE, Medline, CINAHL; ((("pain-relief after surgery") OR ("pain following surg") OR ("pain control after"))) ti.ab

(4) EMBASE, Medline, CINAHL; ((("post surg*" OR post-surg*) AND (pain* OR discomfort))) ti.ab

(5) EMBASE, Medline, CINAHL; (((pain* adj4 "after surg$") OR (pain* adj4 "follow* operat") OR (pain* adj4 "follow* surg*"))) ti.ab

(6) EMBASE, Medline, CINAHL; (((analgesi* adj4 "after surg*") OR (analgesi* adj4 "after operat*") OR (analgesi* adj4 "follow* operat*") OR (analgesi* adj4 "follow* surg*"))) ti.ab

(7) 1 OR 2 OR 3 OR 4 OR 5 OR 6

(8) "Anesthesia, Conduction" ti.ab

(9) "Anesthesia, Spinal" ti.ab

(10) "Analgesi, Epidural" ti.ab

(11) "Anesthesia, Epidural" ti.ab

(12) "Anesthesia, Caudal" ti.ab

(13) "Nerve Block" ti.ab

(14) "regional anesthesia" ti.ab

(15) "conduction anesthesia" ti.ab

(16) "spinal block" ti.ab

(17) "Epidural block" ti.ab

(18) "epidural anesthesia" ti.ab

(19) "plexus block" ti.ab

(20) (plexus AND block) ti.ab

(21) (bier AND block) ti.ab

(22) 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21

(23) ("randomi?ed controlled trial") OR ("randomi?ed trial") OR ("controlled trial") ti.ab

(24) EMBASE, Medline, CINAHL; ("anesthesiology" OR "pain" OR "british journal of anaesthesia" OR "pain physician"OR "anesthesia and analgesia" OR "anaesthesia" OR "regional anesthesia and pain medicine" OR "journal of neurosurgical anesthesia" OR "european journal of anaesthesia" OR "european journal of pain" OR "canadian journal of anesthesia" OR "clinical journal of pain" OR "pain practice" OR "acta anaesthesia scandinavia" OR "Minerva anesthesiology" OR "journal of clinical monitoring and computing" OR "current opinion anesthesiology" OR "journal of cardiothoracic and vascular anaesthesia" OR "BMC anesthesiology").jn

(25) 7 AND 22 AND 23 AND 24 [Limit to: Publication Year 2005-2017]

B: Top Impact Factor Journal List

These are the current impact factors of all the top international anesthesia journals as of 21st October 2015 [55] and were used as limiting functions in the literature review.

Conflicts of Interest

No study-related external funding or competing interests declared.

Authors' Contributions

All authors are responsible for data collection and data analysis and wrote the manuscript.

Received 24 March 2018; Accepted 24 June 2018; Published 29 July 2018

Please Note: Illustration(s) are not available due to copyright restrictions.

https://doi.org/10.1155/2018/9050239

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[55] M. Wang, J. P. Smith, R. Choy et al., "Impact factor list 2014," July 2018, http://www.citefactor.org/journal-impact-factorlist-2014.html.

E. Pushpanathan, (1) T. Setty, (2) B. Carvalho, (3) and P. Sultan (4)

(1) Department of Anaesthesia, Guy's and St. Thomas' NHS Foundation Trust, London, UK

(2) Department of Anaesthesia, University College Hospitals London NHS Foundation Trust, London, UK

(3) Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA

(4) Department of Anaesthesia, University College Hospitals London NHS Foundation Trust, University College London, London, UK

Correspondence should be addressed to E. Pushpanathan; ellile@yahoo.com

Academic Editor: Enrico Camporesi

Caption: FIGURE 1: Summary of literature search and included studies.

Caption: FIGURE 2: Risk of bias assessment in included studies.
TABLE 1: Summary of measurement timings of pain outcomes utilised
in included studies.

Author/year    Country       Measurement tool
               of study

Ambrosoli      Not           NRS (not stated; 0-10)
et al. [12]    stated

                             NRS at rest (0-10)

                             NRS on activity (0-10)

                             Number of occasions
                             sleep was disturbed
                             by pain

Andersen       Denmark       Worst pain during knee
et al. [13]                  movement VAS (10 cm)
                             at rest

                             Time from surgery to
                             VAS score 3
                             (not stated)

                             Sleep disturbance due
                             to pain (yes/no)

                             Total opioid
                             consumption

Bengisun       Turkey        VAS (10 cm; not stated)
et al. [39]

Bharti                       VAS (10 cm; not stated)
et al. [14]    India

                             Total analgesic
                             requirement (opiate
                             and nonopiate)

Boussofara     Tunisia       VAS (10 cm; not stated)
et al. [15]

                             Total opioid
                             consumption

Capdevilla     France        VAS (10 cm; not stated)
et al. [16]

                             Total analgesic
                             consumption (nonopiate)

Choi           Canada        NRS on activity (0-10)
et al. [17]

                             Total opioid
                             consumption

                             NRS at rest (0-10)

                             NRS on activity (0-10)

                             Worst NRS (0-10)

                             NRS (0-10; not stated)

Diakomi        Greece        Time to first IV
et al. [18]                  opioid request (hours)

                             Total opioid
                             consumption

Elkassabany    USA           Pain scores (type of
                             pain score not stated)

et al. [19]                  Pain scores (type of
                             pain score not stated)

                             Pain scores (aPS-POQ-R)

                             Total opioid
                             consumption

Fredrickson    New           NRS (not stated; 0-10)
et al. [20]    Zealand

Fritsch        Austria       NRS at rest (0-10)
et al. [21]

                             NRS on activity (0-10)

Hamdani        Switzerland   Average pain score
et al. [38]                  (NRS; 0-10)
                             (not stated)

                             Average pain score
                             (NRS; 0-10)
                             (not stated)

                             Total opioid
                             consumption

                             Total opioid
                             consumption

                             Maximum pain score
                             (NRS; 0-10)
                             (not stated)

                             Maximum pain score
                             (NRS; 0-10)
                             (not stated)

Karthikeyan    India         VAS (10 cm)
et al. [37]                  (not stated)

                             Time to first
                             analgesic request

                             Total analgesic
                             consumption (opioid
                             consumption)

Kim            Republic      VAS (10 cm; not stated)
et al. [42]    of Korea

Kulhari        Not stated    Time to first rescue
et al [36]                   analgesia

                             Total analgesic
                             consumption (opioid
                             consumption)

                             VAS (10 cm; not stated)

Moura          Brazil        NRS (not stated; 0-10)
et al. [35]

                             Total dose of
                             supplementary
                             analgesia (opioid and
                             nonopioid)

                             Time to first
                             analgesic
                             supplementation

Nagafuchi      Japan         NRS (not stated; 0-10)
et al. [34]

                             Total dose of
                             diclofenac

Salviz         USA           Time to first pain
et al. [33]

                             Analgesic consumption
                             (opioid)

                             Maximum NRS
                             (not stated; 0-10)

Sawhney        Canada        NRS on activity (0-10)
et al. [32]

                             NRS at rest and with
                             knee bending (0-10)

                             NRS on activity (0-10)

                             NRS at rest and with
                             knee bending (0-10)

                             Analgesic consumption
                             (opioid and nonopioid)
                             per day

Sato           Japan         VAS (10 cm) at rest
et al. [31]

                             Morphine consumption

Siddiqui       USA           VAS (10 cm) at rest
et al. [41]

Sindjelic      Serbia        Time to first analgesic
et al. [30]                  request

                             Total opioid
                             consumption

Schoenmakers   Netherlands   Time to first
et al. [29]                  analgesic request

                             NRS at rest (0-10)

                             NRS on activity (0-10)

Subramanyam    Canada        NRS (not stated; 0-10)
et al. [28]

                             Time to first
                             analgesic request

                             NRS at rest (0-10)

Stundner       Austria       NRS on activity (0-10)
et al. [27]

Thybo          Denmark       VAS (10 cm) during
et al. [26]                  30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Pain at rest VAS
                             (10 cm) and during
                             30[degrees] hip
                             flexion

                             Cumulative oxycodone
                             consumption

Wegener        Netherlands   WOMAC score
et al. [25]

                             VAS (10 cm)

                             Oxford knee score
                             (inc. pain)

Wegener        Netherlands   NRS at rest (0-10)
et al. [24]

                             NRS on mobilisation
                             0-10)

                             Total morphine
                             consumption

Wongyingsinn   Canada        NRS at rest (0-10)
et al. [23]

                             NRS on walking (0-10)

                             NRS on coughing (0-10)

                             NRS at rest (0-10)

Ya Deau        USA           NRS on movement (0-10)
et al. [40]

Zhai           Not stated    NRS at rest (0-10)
et al. [22]

                             Worst NRS (0-10)

                             Time of first shoulder
                             pain

Author/year    Time measured                        Nerve block

Ambrosoli      4 hours post-op                Sciatic nerve catheter
et al. [12]    Upon discharge

               24 hours
               48 hours

               24 hours
               48 hours

               24 hours
               48 hours

Andersen       On day of surgery               Saphenous nerve block
et al. [13]

               Hours

               D1 post-op
               D2 post-op
               D3 post-op

               48 hours

Bengisun       2 hours post-op
et al. [39]    4 hours post-op                  Interscalene block
               6 hours post-op
               12 hours post-op
               24 hours post-op

Bharti         Every 30 min for 2 hours      Supraclavicular brachial
et al. [14]    Every 1 hour for 6 hours            plexus block
               Every 2 hours for 12 hours
               24 hours post-op

               24 hours post-op

Boussofara     Every 15 min post-op whilst   Spinal anaesthetic block
et al. [15]    in PACU

               Whilst in PACU

Capdevilla     10 min post-op                    Interscalene and
et al. [16]    1 hour post-op                   popliteal infusions
               4 hours post-op
               12 hours post-op
               AM D1 post-op during
               physiotx
               AM D2 post-op during
               physiotx
               AM D3 post-op during
               physiotx
               AM D4 post-op during
               physiotx

               Over 72 hours

Choi           AM D2 post-op                   Femoral nerve block
et al. [17]                                  continuous versus single

               48 hours

               AM D1 post-op

               D1 post-op

               D1 post-op

               4.5 months post-op

Diakomi        No. of hours                     Fascia iliaca block
et al. [18]

               Over first 24 hours

Elkassabany    Before physiotherapy             Femoral nerve block
                                                  versus adductor
                                                    canal block

et al. [19]    After physiotherapy

               At 24 hours

               AM D1 post-op

               AM D2 post-op

Fredrickson    Emergence                      Interscalene catheters
et al. [20]    Worst in 24 hours on
               movement
               Worst in 24 hours at rest
               Worst in second 24 hours
               on movement
               Worst in second 24 hours
               at rest

Fritsch        4 hours post-op                 Interscalene brachial
et al. [21]    6 hours post-op                     plexus block
               8 hours post-op
               10 hours post-op
               12 hours post-op
               14 hours post-op

               4 hours post-op
               6 hours post-op
               8 hours post-op
               10 hours post-op
               12 hours post-op
               14 hours post-op

Hamdani        Over first 24 hours                  Continuous
et al. [38]                                        interscalene

               Over first 48 hours

               Over first 24 hours

               Over first 48 hours

               Over first 24 hours

               Over first 48 hours

Karthikeyan    Admission to PACU                Bilateral cervical
et al. [37]    2 hours post-op                     plexus block
               4 hours post-op
               6 hours post-op
               8 hours post-op 16 hours
               post-op

               24 hours post-op Min

               24 hours post-op

Kim            1 hour post-op                  Serratus-intercostal
et al. [42]    3 hours post-op                    plane block and
               6 hours post-op                 intermediate cervical
               9 hours post-op                     plexus block
               24 hours post-op                   versus control

Kulhari        After administration of         Pectoral nerve block
et al [36]     block                              versus thoracic
                                                paravertebral block

               24 hours post-op

               0 hours post-op
               0.5 hours post-op
               1 hour post-op
               2 hours post-op
               4 hours post-op
               6 hours post-op
               8 hours post-op
               12 hours post-op
               24 hours post-op

Moura          T0 (after recovering                   Femoral
et al. [35]    consciousness)                       nerve block
               1 hour post-op
               2 hours post-op

               First 2 hours

Nagafuchi      Exiting operating room              Femoral nerve
et al. [34]    3 hours post-op                  block-sciatic nerve
               12 hours post-op                block versus femoral
                                                  nerve block-LIA

               24 hours post-op

Salviz         Hours                           Interscalene brachial
et al. [33]                                        plexus block

               D1 post-op
               D2 post-op
               D3 post-op
               D4 post-op
               D5 post-op
               D6 post-op
               D7 post-op

               D1 post-op
               D2 post-op
               D3 post-op
               D4 post-op
               D5 post-op
               D6 post-op
               D7 post-op

Sawhney        D1 post-op                        Combined adductor
et al. [32]                                      canal block with
                                                  periarticular
                                               infiltration versus
                                               adductor canal nerve
                                                       block

               D1 post-op

               D2 post-op

               D2 post-op

Sato           At rest just after surgery       Sciatic and femoral
et al. [31]    6 hours after surgery             continuous versus
               AM D1 post-op                        single shot
               PM D1 post-op
               AM D2 post-op
               PM D2 post-op

               Over first 48 hours

Siddiqui       Every 5 min first hour           Lumbar plexus block
et al. [41]    4 hours post-op
               8 hours post-op
               16 hours post-op
               20 hours post-op
               24 hours post-op
               28 hours post-op
               32 hours post-op
               36 hours post-op

Sindjelic      Min                             Cervical plexus block
et al. [30]

               24 hours post-op

Schoenmakers   Min                             Popliteal continuous
et al. [29]

               Immediately post-op
               24 hours

               Immediately post-op
               24 hours

Subramanyam    30 min post-op                     Supraclavicular
et al. [28]    60 min post-op                  brachial plexus block
               90 min post-op

               Min

               Baseline before ISB
               Immediately post-op
               6 hours post-op worst pain
               8 hours post-op worst pain
               10 hours post-op worst pain
               12 hours post-op worst pain
               14 hours post-op worst pain
               AM D1 post-op worst pain

Stundner       Baseline before ISB             Interscalene brachial
et al. [27]    Immediately post-op                 plexus block
               6 hours post-op worst pain
               8 hours post-op worst pain
               10 hours post-op worst pain
               12 hours post-op worst pain
               14 hours post-op worst pain
               AM D1 post-op worst pain

Thybo          4 hours post-op (T4) at T0
et al. [26]    (pts able to move toes but
               before SAB worn off)

               T0                                Lateral cutaneous
                                                femoral nerve block

               T1 (after T0)

               T2 (after T0)

               T4 (after T0)

               T8 (after T0)

               T12 (after T0)

               T24 (after T0)

               0-24 hours post-op

Wegener        At rest at 3 months              Sciatic nerve block
et al. [25]    On mobilising at 3 months
               At rest 12 months
               On mobilising at 12 months

               At rest 3 months
               On mobilising at 3 months
               At rest 12 months

               On mobilising at 12 months

Wegener        AM D1 post-op                    Sciatic and femoral
et al. [24]    PM D1 post-op                        continuous
               AM D2 post-op                       versus single
               PM D2 post-op
               AM D3 post-op
               PM D3 post-op

               AM D1 post-op
               PM D1 post-op
               AM D2 post-op PM D2 post-op
               AM D3 post-op
               PM D3 post-op

               D0 post-op
               D1 post-op
               D2 post-op
               D3 post-op

Wongyingsinn   24 hours post-op                      Thoracic
et al. [23]    48 hours post-op                   epidural block
               72 hours post-op

               24 hours post-op
               48 hours post-op
               72 hours post-op

               24 hours post-op
               48 hours post-op
               72 hours post-op

               30 min post-op
               1 hour post-op
               2 hours post-op
               3 hour post-op
               4 hours post-op
               24 hours post-op

Ya Deau        30 min post-op                   Lumbar plexus block
et al. [40]    1 hour post-op
               2 hours post-op
               3 hour post-op
               4 hours post-op
               24 hours post-op

Zhai           Before block                    Interscalene brachial
et al. [22]    Right before discharge from         plexus block
               PACU
               4 hours after block
               8 hours after block
               24 hours after block

               24 hours after block

D0 post-op = Day 0 postoperatively; D1 post-op = Day 1 postoperatively;
D2 post-op = Day 2 postoperatively; D3 post-op = Day 3 postoperatively;
D4 post-op = Day 4 postoperatively; D5 post-op = Day 5 postoperatively;
D6 post-op = Day 6 postoperatively; D7 post-op = Day 7 postoperatively;
min- = minutes; NRS = numeric (verbal) rating scale (0 = no pain to
10 = worst imaginable pain); VAS = visual analogue scale (0 mm = no
pain to 100 mm = worst imaginable pain); APS-POQ-R = American Pain
Society Patient Outcome Questionnaire Revised; WOMAC score = Western
Ontario and McMaster Universities Osteoarthritis Index (5 pain
questions included) OA specific; Oxford Knee Score 12-item knee
questionnaire on pain; for measurement tool, "not stated" = whether
pain score recorded at rest or on movement not stated in methods.

TABLE 2: Summary of pain outcomes reported in included studies.

Pain outcome       No. of studies                  Studies
                  utilising outcome

VAS                      11           Andersen et al. [13]; Bengisun et
                                        al. [39]; Bharti et al. [14];
                                           Boussofara et al. [15];
                                           Capdevilla et al. [16];
                                       Karthikeyan et al. [37]; Kim et
                                       al. [42]; Kulhari et al. [36];
                                      Sato et al. [31]; Siddiqui et al.
                                          [41]; Wegener et al. [25]

VAS on a                  1                   Thybo et al. [26]
specified
activity

Time to VAS 3             1                 Andersen et al. [13]
cm

NRS at rest              10            Ambrosoli et al. [12]; Choi et
                                       al. [17]; Fritsch et al. [21];
                                      Sawhney et al. [32]; Schoenmakers
                                        et al. [29]; Stundner et al.
                                         [27]; Wegener et al. [24];
                                      Wongyingsinn et al. [23]; YaDeau
                                       et al. [40]; Subramanyam et al.
                                                    [28]

NRS on activity           9            Ambrosoli et al. [12]; Choi et
                                       al. [17]; Fritsch et al. [21];
                                      Sawhney et al. [32]; Schoenmakers
                                        et al. [29]; Stundner et al.
                                         [27]; Wegener et al. [24];
                                      Wongyingsinn et al. [23]; YaDeau
                                                 et al. [40]

Maximum NRS               3            Hamdani et al. [38]; Salviz et
score                                    al. [33]; Zhai et al. [22]

Average NRS               1                  Hamdani et al. [38]

Analgesic                 7           Bharti et al. [14]; Capdevilla et
consumption                            al. [16]; Kulhari et al. [36];
                                       Moura et al. [35]; Nagafuchi et
                                        al. [34]; Salviz et al. [33];
                                             Sawhney et al. [32]

Opioid                   16            Andersen et al. [13]; Bharti et
consumption                           al. [14]; Boussofara et al. [15];
                                      Choi et al. [17]; Diakomi et al.
                                       [18]; Elkassabany et al. [19];
                                      Hamdani et al. [38]; Karthikeyan
                                      et al. [37]; Kulhari et al. [36];
                                      Moura et al. [35]; Salviz et al.
                                       [33]; Sawhney et al. [32]; Sato
                                        et al. [31]; Sindjelic et al.
                                      [30]; Thybo et al. [26]; Wegener
                                                 et al. [24]

Time to 1st               2            Salviz et al. [33]; Zhai et al.
pain                                                [22]

Time to 1st               6           Karthikeyan et al. [37]; Kulhari
analgesic                              et al. [36]; Moura et al. [35];
request                                   Schoenmakers et al. [29];
                                           Sindjelic et al. [30];
                                           Subramanyam et al. [28]

Time to 1st               1                  Diakomi et al. [18]
opioid request

Sleep                     2            Ambrosoli et al. [12]; Andersen
disturbance                                      et al. [13]

WOMAC                     1                  Wegener et al. [25]

APS-POQ-R                 1                Elkassabany et al. [19]

TABLE 3: Summary of regional techniques investigated in
included studies.

Blocks studied           Number                  Studies
                       of studies

Supraclavicular            2        Subramanyam et al. [28]; Bharti et
                                                 al. [14]

Interscalene               5         Bengisun et al. [39]; Fritsch et
                                      al. [21]; Salviz et al. [33];
                                    Stundner et al. [27]; Zhai et al.
                                                   [22]

Pectoral                   1               Kulhari et al. [36]

Serratus-intercostal       1                 Kim et al. [42]

Fascia iliaca              1               Diakomi et al. [18]

Femoral                    6         Sato et al. [31]; Wegener et al.
                                     [24]; Choi et al. [17]; Thybo et
                                     al. [26]; Nagafuchi et al. [34];
                                         Elkassabany et al. [19]

Sciatic                    4         Sato et al. [31]; Wegener et al.
                                     [25]; Wegener et al. [24]; Moura
                                               et al. [35]

Adductor                   1               Sawhney et al. [32]

Saphenous                  1               Andersen et al. [13]

Cervical plexus            2        Sindjelic et al. [30]; Karthikeyan
                                               et al. [37]

Lumbar plexus              2         YaDeau et al. [40]; Siddiqui et
                                                 al. [41]

Thoracic epidural          1             Wongyingsinn et al. [23]

Spinal                     1              Boussofara et al. [15]

Interscalene catheter      3        Hamdani et al. [38]; Capdevilla et
                                    al. [16]; Fredrickson et al. [20]

Popliteal catheter         2             Capdevilla et al. [16];
                                         Schoenmakers et al. [29]

Sciatic catheter           1              Ambrosoli et al. [12]

TABLE 4

Rank                                                         Impact
                                                             factor

1                        Anesthesiology                      5.879
2                             Pain                           5.213
3                British Journal of Anaesthesia              4.853
4                        Pain physician                      3.542
5                   Anesthesia and Analgesia                 3.472
6                          Anaesthesia                       3.382
7           Regional Anaesthesia and Pain management         3.089
8             Journal of Neurosurgical Anaesthesia            2.99
9                European Journal of Anaesthesia             2.942
10                  European Journal of Pain                 2.928
11               Canadian Journal of Anesthesia              2.527
12                  Clinical Journal of Pain                 2.527
13                        Pain Practice                      2.361
14                Acta Anaesthesia Scandinavia               2.322
15                   Minerva Anesthesiology                  2.134
16        Journal of Clinical Monitoring and Computing       1.985
17               Current Opinion Anesthesiology              1.979
18                   * Pediatric Anesthesia                   1.85
19       * International Journal of Obstetric Anesthesia     1.598
20     Journal of Cardiothoracic and Vascular Anaesthesia    1.463
21                     BMC Anesthesiology                    1.375
22               Anaesthesia and Intensive Care              1.296

* These journals cover obstetric and pediatric anesthesia; hence,
they were not used in this study (owing to the inclusion criteria of
general adult population).
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Author:Pushpanathan, E.; Setty, T.; Carvalho, B.; Sultan, P.
Publication:Anesthesiology Research and Practice
Article Type:Report
Geographic Code:4EUUK
Date:Jan 1, 2018
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