BioFACTS: biomarkers of rhabdomyolysis in the diagnosis of acute compartment syndrome - protocol for a prospective multinational, multicentre study involving patients with tibial fractures

Abraham Nilsson, Thomas Ibounig, Johan Lyth, Björn Alkner, Ferdinand von Walden, Lotta Fornander, Lasse Rämö, Andrew Schmidt, Jörg Schilcher, Abraham Nilsson, Thomas Ibounig, Johan Lyth, Björn Alkner, Ferdinand von Walden, Lotta Fornander, Lasse Rämö, Andrew Schmidt, Jörg Schilcher

Abstract

Introduction: The ischaemic pain of acute compartment syndrome (ACS) can be difficult to discriminate from the pain linked to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is based on clinical findings and performed at a low level of suspicion. Biomarkers of muscle cell damage may help to identify and monitor patients at risk, similar to current routines for patients with acute myocardial infarction. This study will test the hypothesis that biomarkers of muscle cell damage can predict ACS in patients with tibial fractures.

Methods and analysis: Patients aged 15-65 years who have suffered a tibial fracture will be included. Plasma (P)-myoglobin and P-creatine phosphokinase will be analysed at 6-hourly intervals after admission to the hospital (for 48 hours) and-if applicable-after surgical fixation or fasciotomy (for 24 hours). In addition, if ACS is suspected at any other point in time, blood samples will be collected at 6-hourly intervals. An independent expert panel will assess the study data and will classify those patients who had undergone fasciotomy into those with ACS and those without ACS. All primary comparisons will be performed between fracture patients with and without ACS. The area under the receiver operator characteristics curves will be used to identify the success of the biomarkers in discriminating between fracture patients who develop ACS and those who do not. Logistic regression analyses will be used to assess the discriminative abilities of the biomarkers to predict ACS corrected for prespecified covariates.

Ethics and dissemination: The study has been approved by the Regional Ethical Review Boards in Linköping (2017/514-31) and Helsinki/Uusimaa (HUS/2500/2000). The BioFACTS study will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology recommendations.

Trial registration number: NCT04674592.

Keywords: Adult orthopaedics; Musculoskeletal disorders; ORTHOPAEDIC & TRAUMA SURGERY.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Flow chart of patient recruitment. ACS, acute compartment syndrome; GFR, glomerular filtration rate; P-CK, plasma-creatine phosphokinase.

References

    1. Schmidt AH. Continuous compartment pressure monitoring-better than clinical assessment? J Bone Joint Surg Am 2013;95:e52. 10.2106/JBJS.M.00029
    1. Schmidt AH. Acute compartment syndrome. Injury 2017;48 Suppl 1:S22–5. 10.1016/j.injury.2017.04.024
    1. Matsen FA, Krugmire RB. Compartmental syndromes. Surg Gynecol Obstet 1978;147:943–9.
    1. Park S, Ahn J, Gee AO, et al. . Compartment syndrome in tibial fractures. J Orthop Trauma 2009;23:514–8. 10.1097/BOT.0b013e3181a2815a
    1. Dover M, Memon AR, Marafi H, et al. . Factors associated with persistent sequelae after fasciotomy for acute compartment syndrome. J Orthop Surg 2012;20:312–5. 10.1177/230949901202000309
    1. Schmidt AH. The impact of compartment syndrome on hospital length of stay and charges among adult patients admitted with a fracture of the tibia. J Orthop Trauma 2011;25:355–7. 10.1097/BOT.0b013e3181f18ad8
    1. Lollo L, Grabinsky A. Clinical and functional outcomes of acute lower extremity compartment syndrome at a major trauma Hospital. Int J Crit Illn Inj Sci 2016;6:133–42. 10.4103/2229-5151.190648
    1. Shuler FD, Dietz MJ. Physicians' ability to manually detect isolated elevations in leg intracompartmental pressure. J Bone Joint Surg Am 2010;92:361–7. 10.2106/JBJS.I.00411
    1. Heckman MM, Whitesides TE, Grewe SR, et al. . Compartment pressure in association with closed tibial fractures. The relationship between tissue pressure, compartment, and the distance from the site of the fracture. J Bone Joint Surg Am 1994;76:1285–92. 10.2106/00004623-199409000-00002
    1. McQueen MM, Court-Brown CM. Compartment monitoring in tibial fractures. The pressure threshold for decompression. J Bone Joint Surg Br 1996;78:99–104.
    1. Prayson MJ, Chen JL, Hampers D, et al. . Baseline compartment pressure measurements in isolated lower extremity fractures without clinical compartment syndrome. J Trauma 2006;60:1037–40. 10.1097/01.ta.0000215444.05928.2f
    1. Schmidt AH, Di J, Zipunnikov V, et al. . Perfusion pressure lacks diagnostic specificity for the diagnosis of acute compartment syndrome. J Orthop Trauma 2020;34:287–93. 10.1097/BOT.0000000000001719
    1. Shuler MS, Reisman WM, Kinsey TL, et al. . Correlation between muscle oxygenation and compartment pressures in acute compartment syndrome of the leg. J Bone Joint Surg Am 2010;92:863–70. 10.2106/JBJS.I.00816
    1. Shuler MS, Reisman WM, Cole AL, et al. . Near-infrared spectroscopy in acute compartment syndrome: case report. Injury 2011;42:1506–8. 10.1016/j.injury.2011.03.022
    1. Schmidt AH, Bosse MJ, Obremskey WT, et al. . Continuous near-infrared spectroscopy demonstrates limitations in monitoring the development of acute compartment syndrome in patients with leg injuries. J Bone Joint Surg Am 2018;100:1645–52. 10.2106/JBJS.17.01495
    1. Etheridge A, Lee I, Hood L, et al. . Extracellular microRNA: a new source of biomarkers. Mutat Res 2011;717:85–90. 10.1016/j.mrfmmm.2011.03.004
    1. O'Toole RV, Whitney A, Merchant N, et al. . Variation in diagnosis of compartment syndrome by surgeons treating tibial shaft fractures. J Trauma 2009;67:735–41. 10.1097/TA.0b013e3181a74613
    1. Shadgan B, Menon M, O'Brien PJ, et al. . Diagnostic techniques in acute compartment syndrome of the leg. J Orthop Trauma 2008;22:581–7. 10.1097/BOT.0b013e318183136d
    1. Valdez C, Schroeder E, Amdur R, et al. . Serum creatine kinase levels are associated with extremity compartment syndrome. J Trauma Acute Care Surg 2013;74:441–7. 10.1097/TA.0b013e31827a0a36
    1. Hefler-Frischmuth K, Lafleur J, Brunnmayr-Petkin G, et al. . Compartment syndrome after gynecologic laparoscopy: systematic review of the literature and establishment of normal values for postoperative serum creatine kinase and myoglobin levels. Arch Gynecol Obstet 2017;296:285–93. 10.1007/s00404-017-4440-7
    1. Nilsson A, Alkner B, Wetterlöv P, et al. . Low compartment pressure and myoglobin levels in tibial fractures with suspected acute compartment syndrome. BMC Musculoskelet Disord 2019;20:15. 10.1186/s12891-018-2394-y
    1. Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: pathophysiology and diagnosis. Eur J Intern Med 2007;18:90–100. 10.1016/j.ejim.2006.09.020
    1. Siracusa J, Koulmann N, Bourdon S, et al. . Circulating miRNAs as biomarkers of acute muscle damage in rats. Am J Pathol 2016;186:1313–27. 10.1016/j.ajpath.2016.01.007
    1. Dubowitz V A, Sewry C, Oldfors A. Muscle biopsy: a practical approach: expert consul. Elsevier Health Sciences, 2013: 8–10.
    1. Hällgren R, Karlsson FA, Roxin LE, et al. . Myoglobin turnover-influence of renal and extrarenal factors. J Lab Clin Med 1978;91:246–54.
    1. Mandrekar JN. Receiver operating characteristic curve in diagnostic test assessment. J Thorac Oncol 2010;5:1315–6. 10.1097/JTO.0b013e3181ec173d
    1. Collins GS, Reitsma JB, Altman DG, et al. . Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. J Clin Epidemiol 2015;68:112–21. 10.1016/j.jclinepi.2014.11.010

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