Regional anesthesia or patient-controlled analgesia and compartment syndrome in orthopedic surgical procedures: a systematic review

Introduction

Acute compartment syndrome (CS), a true medical emergency, is a rare, yet serious complication of certain injuries and operations.^1,2 It is a condition in which increased pressure within a confined, nonelastic space compromises the circulation and thus the function of the tissues within that space.³ Early recognition and treatment with an emergent fasciotomy is crucial, as the risk of complications such as muscle necrosis,^4,5 neurological deficits,^3,5,6 delayed fracture union,⁷ Volkmann ischemic contraction,⁸ myoglobinuria,^8–10 renal failure,^8–12 and potentially death^10,11,13 increases as time of tissue anoxia elapses.^14–17 The diagnosis of CS is clinical and requires a high index of suspicion.^6,18,19 Classical symptoms of CS include pain,^13,20–25 pallor,^25,26 paresthesias,^20,24,25,27 pulselessness,²⁴ and paralysis.^23,24 Of these cardinal signs and symptoms, pain is believed to be one of the first clinical indicators of an impending CS.^11,24,28,29 Specifically, when a patient experiences pain that is progressive, not relieved by narcotics, out of proportion to examination, and with passive motion, the clinician should be attuned to the possibility of CS.^13,21,24 Regional analgesia or regional anesthesia (RA) is often used to alleviate pain in patients who have had limb injuries or interventions.^1,30,31 RA has long been the accepted practice for providing postoperative pain control in elective orthopedic procedures, particularly total joint arthroplasties, despite the risk of CS.^32,33 There are several benefits to using RA in these patients, such as better pain control,^1,34 saving time and costs due to shorter hospital stays and fewer nursing interventions,³² and sparing patients the adverse effects of systemic opioids³² and general anesthesia.¹ However, some argue that RA masks the ischemic pain associated with CS^32,35–37 and therefore delays the diagnosis, putting the patient at greater risk for complications.^3,38

Patient-controlled analgesia (PCA) is a widely accepted technique for orthopedic postoperative pain management,^38–40 despite the risk of CS development. The main advantage of this technique is that patients control their own dosing.^40,41 PCA provides better matching of patient need with analgesia and avoids opioid overdose and side effects.⁴¹ However, it has also been argued that PCA may mask the symptoms of CS and potentially delay the diagnosis.^38–40

Some physicians dispute the use of RA in orthopedic injuries, believing that this modality poses a greater risk than PCA for masking the signs/symptoms of CS.²⁴ Given this controversy, we decided to conduct a systematic review of the literature to compare the two pain control modalities (RA and PCA). Specifically, we set out to compare their contribution to a delayed diagnosis of CS in traumatic and elective orthopedic cases.

In our initial search, we identified 19 relevant review articles published between 1999 and 2014,^{19,23,24,27,31,42–55} with three of these being case reports that included literature reviews.^43,47,51 However, none followed the currently accepted rigorous guidelines for conducting systematic reviews of the literature, including teams of reviewers or an iterative abstraction process.^56–59 In addition, none answered our primary question as to whether RA or PCA contributes to a delayed diagnosis of CS in traumatic and elective orthopedic cases. Thus, we proceeded with a systematic review of the literature.

Methods

Literature search

We conducted a thorough and systematic review of English language literature published on the use of RA or PCA in orthopedic cases involving extremity surgeries and that include CS, between January 1, 1980, and November 2014 using CINAHL, PubMed, and Scopus.

For the searches, we chose relevant controlled vocabulary and keywords to capture the concepts of RA or PCA “and” CS (complete details of the search strategy are available upon request from the authors, or in Table 1). The search strategy identified 471 unique articles (478 total, with seven duplicates).

Table 1 Literature search methods and results for a systematic review of RA or PCA and CS Notes: aThe Scopus search conducted on April 28, 2014, was with the “Document Search” (basic search) function; this function truncates long strings of search terms. Thus, we reran the search on May 27, 2014, with the “Advanced Search” function, so that there would be no truncation of search terms. After de-duplicating the 1,002 results, there were 475 unique articles. Database conventions: *, truncation; “”, phrase searching; [MeSH], medical subject heading; AND, OR, NOT, Boolean operators. In Scopus, there is no capability to restrict the age of the study participants. In PubMed, the author did not use truncation (via the * symbol), because the use of truncation turns off automatic mapping to MeSH terms. Abbreviations: CS, compartment syndrome; IV, intravenous; NLM, National Library of Medicine; PCA, patient-controlled analgesia; RA, regional anesthesia.

All titles were reviewed by two teams of trained reviewers for possible inclusion (EBSD and BNH; LJ and AHM). Prior to beginning the review, both reviewers agreed to err on the side of inclusion. If either reviewer selected a reference, the full text was ordered for further review. Using this strategy, 179 articles were obtained for further review. The percent agreement on initial independent selection of articles for further review was 86%. Interrater reliability using Cohen’s kappa was κ=0.67, P<0.001. The reference sections of all included articles were checked for additional potentially relevant articles, with six being identified (Figure 1).

Figure 1 The process used during a systematic review of the literature to select articles (review, case reports, and research) on RA or PCA and CS. Abbreviations: CS, compartment syndrome; PCA, patient-controlled analgesia; RA, regional anesthesia.

Inclusion and exclusion criteria

Articles meeting the following criteria were eligible for review: English language; published between January 1, 1980, and November 2014; focused on RA or PCA used after an orthopedic surgical procedure that also included CS in an extremity; patients aged 13 years or older; and all types of research studies and case reports. Exclusion criteria included pediatric cases aged 0–12 years of age; CS not in an extremity (ie, gluteal and abdominal) or resulting from the lithotomy position; orthopedic surgeries not involving the extremities; and letters, editorials, or commentaries.

Research studies and case reports

Teams of two independent researchers (LJ, AHM, BNH, and LEN) checked all articles for initial relevance and assigned each article to one or more categories: research study or case report. Then, a subgroup of the research team (EBSD, LAR, LJ, and AHM) met to review all included articles to determine the final inclusion and accuracy of category assignment.

Abstraction process

Trained reviewers used an iterative process to develop an abstraction form designed to confirm the final eligibility for full review, assess article characteristics, and extract data relevant to the study question. This iterative process started with two initial forms, one for case reports and one for research articles. Both forms were used by multiple reviewers (BNH, AHM, LJ, and LEN) to independently abstract data from the articles. The reviewers then met with their mentor for this study (LAR) to discuss the abstraction forms, to decide whether the form should be revised, and receive guidance related to any abstraction questions. More relevant forms were then created for abstraction. This iterative process continued until the team was confident that the abstraction forms had fields for all potentially relevant information and the team no longer had questions about abstraction of these articles.

Results

We identified 477 articles in our search and deemed 34 of them relevant to our study: 28 case reports (23 RA case reports and five PCA case reports) and six research articles (three surveys and three research studies; Figure 1).

Research studies

We identified six relevant research studies (three survey and three research studies) published between 1989 and 2012.^11,60–64 Of six research studies, three (50%) authors concluded that the use of either RA or PCA does mask the symptoms of CS,^11,60,61 one (16.7%) concluded that RA does not mask the symptoms of CS,⁶² and two (33.3%) were unclear or did not provide relevant conclusions.^63,64

Three (50%) were survey studies conducted in the UK.^11,61,62 Davis et al¹¹ conducted a mail-in survey of the practices of 146 consultant and 97 non-consultant grade anesthetists. The majority, 81% and 91%, respectively, replied that they use RA in all lower extremity fractions and 17% and 9%, respectively, had personally witnessed CS masked by the RA. The authors raised concerns over these regional practices, some of which were reported to be in settings without adequate compartment pressure monitoring, though no specifics about the regional techniques, medications, or cases were discussed in the survey. Thonse et al⁶¹ administered questionnaires with seven clinical vignettes describing patients undergoing surgery of an extremity (elective and trauma) to 190 orthopedic surgery and anesthetist trainees. Subjects were not aware that the study was focused on the risk of delayed diagnosis of CS. A total of 114 (60%) responded, 56 of which were orthopedic surgeons and 58 anesthesiologists. They found statistically significant differences between the two groups, with anesthetists preferring local and regional nerve blocks in patients known to have a high risk of CS. In 2009, Pennington et al⁶² conducted a telephone survey of middle-grade physicians in 171 acute care hospitals providing trauma care. Questions focused on departmental protocols and respondent experience with femoral nerve blocks for lower limb fractures. They achieved a 100% response rate and concluded that femoral nerve block is an underutilized, effective mode of analgesia following femoral fractures. Respondents reported a low incidence of CS, but urged vigilance in monitoring patients with high-energy injuries.

There were three (50%) studies conducted in the US.^60,63,64 One (33.3%) was a retrospective review conducted prior to 2000.⁶⁰ Iaquinto et al⁶⁰ reviewed 63 patients with surgical repair of a tibial fracture. These patients received postoperative epidural analgesia with local anesthetics. None of these patients developed CS.

There were two (66.7%) prospective studies.^63,64 Weller et al⁶³ conducted the only prospective randomized study comparing epidural to patient-controlled intravenous morphine following joint replacement (total hip and knee replacement) surgery. Half (15/30) received epidural morphine and the other half (15/30) received patient-controlled intravenous morphine. They followed patients for 24 hours, during which none of the patients developed CS. This prospective study focused on the pain control and side effects of the two delivery methods of morphine but has limited relevancy to our question as there were no cases of CS discovered. In addition, the postoperative follow-up focused on intravenous and epidural morphine use with the only local anesthetic used for short-term surgical anesthesia and not postoperative analgesia. Ganesh et al⁶⁴ prospectively followed 217 pediatric patients, 167 of whom were children aged ≥13 years and had continuous peripheral nerve blockade after orthopedic procedures. Again, none of these patients developed CS.

Case reports

We identified 28 case report articles published between 1986 and 2013: 23 RA articles, with 29 cases and five PCA articles, with eight cases (Tables 2 and 3). Of 23 RA articles, 13 (56.5%) authors (representing 19 cases) concluded that RA masked the symptoms of CS,^{32,34–36,65–74} delaying the diagnosis. However, of these 19 cases, eleven (57.8%) presented with “pain” (± other symptoms).^{32,35,65,67–70,74} In addition, while eight (42.1%) cases did not report pain, they did present with other classic symptoms of CS, such as paresthesia, altered sensation, swelling and edema, tense and shiny skin, loss of movement, or foot drop (Table 2).^{36,66,71–73}

Table 2 Case reports identified in a systematic review of the literature on RA and CS (23 articles, with 29 cases), 1980 to November 2014 Abbreviations: BMI, body mass index; CPK, creatine phosphokinase; CS, compartment syndrome; IV, intravenous; RA, regional anesthesia; TKA, total knee arthroplasty; h, hour.

Table 3 Case reports identified in a systematic review of the literature on PCA and CS (five articles, with eight cases), 1980 to November 2014 Abbreviations: BP, blood pressure; CS, compartment syndrome; IV, intravenous; PCA, patient-controlled analgesia.

In the remaining ten RA articles described with all available details in Table 2, eight (80%) authors (representing eight cases) concluded that RA did not mask the symptoms of CS,^{3,33,47,51,75–78} while two (20%) authors (representing two cases) provided unclear conclusions on this question.^20,79 Eight of the 23 RA articles (34.8%) were published between 2010 and 2013.^{3,33,47,51,67,75,77,79} The majority of these more current articles (six of eight; 75%) did not conclude that RA masks symptoms of CS (Table 2).^{3,33,47,51,75,77}

Of the five articles that describe the use of PCA, representing eight total cases detailed in Table 3, three (60%) of these authors (six cases) concluded that PCA does mask CS.^38–40 The other two authors (two cases) were unclear on this issue (Table 3).^80,81

Overall, of the 28 combined (RA and PCA) case report articles (representing 37 cases), 22 cases (59.5%) presented with pain (± other symptoms).^{3,32,33,35,38,47,51,65,67–70,74–76,78,79,80,81} In the remaining 15 cases (40.5%), patients did not present with pain but did present with other classic signs/symptoms of CS (Tables 2 and 3).^{20,36,39,40,66,71–73,77}

The use of RA for trauma and orthopedic surgery remains controversial.^{24,47,49–51,55} Of the reviewed articles, seven authors recommend that postoperative RA be used cautiously^65,75 or with a lower dose of local anesthetic^{31,42,50,54,62} in patients who are at risk for the development of a CS, and five believe that nerve block should not be used when there is a possibility of a CS.^{35,38,44,63,66} In addition, two authors support establishing a protocol or guidelines for the use of inpatient nerve blocks.^62,64

Discussion

We conducted a systematic review of the literature on the use of either RA or PCA in orthopedic surgical cases of the extremities. Our goal was to objectively describe the current state of evidence relevant to RA and/or PCA and the development of CS. We identified 34 articles (28 case reports, three surveys, and three research studies). Of these, 19 (55.9%) concluded that RA or PCA does mask symptoms of CS,^{1,32,35,36,38–40,60,61,65–74} nine (26.5%) concluded that RA or PCA does not mask symptoms,^{3,33,47,51,62,75–78} and six (17.6%) were unclear.^{20,63,64,79,81,82}

However, 25 articles (73.5%) were published between 1986 and 2009. One could argue that these earlier articles do not accurately reflect current practice. When looking only at eight case report articles published after 2009, the abovementioned percentages markedly change, with one (12.5%) concluding that RA or PCA does mask symptoms of CS,⁶⁷ six (75%) concluding that RA or PCA does not mask symptoms,^{3,33,47,51,62,75,77} and one (12.5%) was unclear.⁷⁹ The change in attribution in more recent publications may be due to advances in ultrasound-guided nerve blocks, making these procedures more desirable as they are often quicker and less technically challenging.^83,84 Ultrasound-guided techniques often result in a decreased volume of local anesthetic required to achieve a successful regional block.^85,86 In addition, the risk of misdiagnosing CS may be reduced by using continuous RA techniques, with decreased local anesthetic concentrations and using newer local anesthetics drugs.^27,33,87 Some authors have noted that ischemic pain is different from nociceptive pain, temperature discrimination, or neuropathic pain, and ischemic pain should not be masked when using RA, even with complete sensory and motor blockade.⁵¹

Only two (5.9%) of the 34 identified articles were relevant prospective research studies, and neither of these reported any cases of CS.^63,64 Despite this finding, there are possible design issues with these studies. Both had small sample sizes, which leaves open the possibility that they were underpowered to identify a difference. CS incidence has been shown to be 3.1 per 100,000, which makes CS a relatively rare event.^3,16 A larger sample size would be required to ensure that a negative study is adequately powered. Most importantly, neither project was specifically designed to look at CS as an end point, but instead reported the lack of any CS cases as a secondary outcome. Thus, these articles were discovered with our literature search despite their only marginal relevance to our question of whether certain anesthesia techniques delay the diagnosis of CS.

On the other hand, a large prospective pediatric study does exist that supports RA.⁸² This article was excluded from our systematic review based on our age criterion (≥13 years). But its conclusions are relevant, given the paucity of evidence in adult studies. Llewellyn and Moriarty⁸² conducted a large prospective audit of pediatric patients with more than 10,000 epidurals, concluding that “[t]he occurrence of compartment syndrome does not appear to be masked by the presence of working [epidural infusion analgesia].”

It is evident from our systematic review that there is no clear evidence to support the use of one modality of analgesia over the other with regard to a lessened risk of developing CS. Of the cases that we deemed relevant to our study, the authors only suggested that a given modality either did or did not put the patient at greater risk of developing CS without giving objective means for drawing their conclusions. Still others did not draw a clear conclusion, and some debated whether better monitoring could have prevented the development of CS (Tables 2 and 3).

Some authors advocate for lower concentrations of local anesthetics in regional blockade, which might provide analgesia while improving the detection of CS.^{31,42,50,54,62} Others advocate improved monitoring.^{19,27,36,39,65,67,68,71} This could include increased involvement of the RA team in postoperative care,^31,49,76 more screening of compartment pressure^35,37,65,66 using advanced noninvasive techniques,⁵³ and increased frequency of nursing neurovascular checks.^34,48

In addition, recommendations published in 2010 by British military leadership, stated that clinicians in the field should be encouraged to use regional analgesic techniques in limb trauma.⁸⁸ This recommendation was based on a review of their historical data that found that the majority of CS cases were identified.⁸⁸

Limitations

The current study is limited by the search strategy used. Specifically, the search terms we identified may not have included every relevant term. Nonetheless, the quality of our systematic review was strengthened by the development of a study protocol at the outset, which included an explicit search strategy and clear inclusion/exclusion criteria. In addition, our search was conducted by a master’s prepared librarian who searched multiple databases, and we reviewed the reference sections of all included articles. Although our strategy minimizes the risk of missing germane articles, it does not eliminate the possibility.

The study question simply cannot be answered with case reports. Scientific inferences cannot be derived from the latter, as the conclusions inevitably contain some biases stemming from the authors and journals. For instance, all case reports that reported that RA masked CS^{32,35,36,65,66,68–74} were published in surgical journals. Interestingly, most reports that defended RA^{3,33,47,51,77} were published in anesthesiology or pain journals.

Unfortunately, the published literature on this topic identified by our review included only six research studies. In addition, three of these were surveys and the other three were heterogeneous in their methodology and populations. As a result, the evidence is weak at best. Finally, one would expect a highly concentrated RA infusion to have a greater chance of masking CS than a dilute infusion. However, due to the small number of actual research studies, we were not able to address this question.

Our exhaustive systematic review included a search that ended in November 2014. A simple PubMed search using our keywords to date of manuscript submission identified six additional articles that have been published from November 2014 until submission. One is a case report of a 4-year-old boy which would have been excluded from our search based on age.⁸⁹ Two others were case reports on adults, one with an upper extremity nerve block for distal radius fracture that did not delay the diagnosis of CS and the other a total knee arthroplasty that had an epidural for postoperative pain control that was removed after 24 hours who had CS diagnosed after 48 hours.^90,91 Pinheiro et al⁹¹ states that though the epidural described above contributed to the delayed diagnosis of CS, it was not the sole cause of the delay.

The PubMed search from November 2014 until submission date resulted in three additional articles, two review articles and one practice advisory. Gadsden and Warlick⁹² in their review article discuss the use of RA in traumatic extremity injuries and summarized that peripheral nerve blocks do not appear to contribute to a delayed diagnosis of CS while advocating for prudent use of blocks and extra vigilance when they are used. Although a pediatric review article, Muhly et al⁹³ additionally comment that there is “theoretical evidence” that peripheral regional techniques do not hide the ischemic pain symptom of CS and that blocks can be safely used in their pediatric population with appropriate attentiveness and monitoring. The practice advisory was published in September 2015 by the European Society of Regional Anaesthesia and Pain Therapy and the American Society of Regional Anesthesia and Pain Medicine regarding controversial topics in pediatric pain medicine, including RA and CS. Although another pediatric-focused article that does not fit within the scope of our systematic review, it is important to note that these societies advocate for the use of regional anesthetic techniques in pediatric orthopedic procedures and outlines six “best practice rules” for its use, which includes use of reduced concentrations of local anesthetics, reducing the volume of local anesthetics in high-risk surgeries such as those involving the tibial compartment, using caution with additives in blocks, and close follow-up by a pain service with easily accessible compartment pressure monitoring.⁹⁴

Currently, there are no clear recommendations regarding the use of RA in adult patients with orthopedic extremity procedures who are at increased risk of developing CS.^11,27,95 In addition, our search identified cases and opinions suggesting that PCA contributes to a delayed diagnosis of CS. Thus, more studies are needed. Randomized prospective trials may not be appropriate given the lack of convincing evidence and the ongoing controversy regarding the safety of RA in this at-risk population. However, the widespread use of computerized medical records today makes large-scale data mining feasible. This would allow for retrospective data analysis, reviewing all cases of CS, as well as prospective comparison of similar orthopedic practices that use different analgesic techniques.

Acknowledgment

The authors thank Amos J Wright, MLS, Voluntary Associate Professor and Director, Section on the History of Anesthesia, University of Alabama at Birmingham, for his assistance in locating and obtaining articles.

Disclosure

The authors report no conflicts of interest in this work.

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