Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Early fluid resuscitation in patients with rhabdomyolysis

Nature Reviews Nephrology volume 7, pages 416–422 (2011)Cite this article

Subjects

Abstract

Extensive rhabdomyolysis is often lethal unless treated immediately. Early mortality arises from hypovolemic shock, hyperkalemia, acidosis and myoglobinuric acute kidney injury (AKI). Many individuals with rhabdomyolysis could be saved, and myoglobinuric AKI prevented, by early vigorous fluid resuscitation with ≥12 l daily intravenous infusion of alkaline solution started at the scene of injury. This regimen stabilizes the circulation and mobilizes edema fluids sequestered in the injured muscles into the circulation, corrects hyperkalemia and acidosis, and protects against the nephrotoxic effects of myoglobinemia and hyperuricosuria. This regime results in a large positive fluid balance, which is well tolerated in young, carefully monitored individuals. In patients with rhabdomyolysis caused by muscle crush syndrome, mortality has been reduced from nearly 100% to <20% over the past 70 years through utilization of this intervention. This Perspectives discusses the lifesaving and limb-saving potential of early vigorous fluid resuscitation in patients with extensive traumatic and nontraumatic rhabdomyolysis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Suggested protocol for early vigorous fluid resuscitation in patients with rhabdomyolysis.

Similar content being viewed by others

References

  1. Vanholder, R., Sever, M. S., Erek, E. & Lameire, N. Rhabdomyolysis. J. Am. Soc. Nephrol. 11, 1553–1561 (2000).

    CAS  PubMed  Google Scholar 

  2. Bosch, X., Poch, E. & Grau, J. M. Rhabdomyolysis and acute kidney injury. N. Engl. J. Med. 361, 62–72 (2009).

    Article  CAS  Google Scholar 

  3. Malinoski, D. J., Slater, M. S. & Mullins, R. J. Crush injury and rhabdomyolysis. Crit. Care Clin. 20, 171–192 (2004).

    Article  Google Scholar 

  4. Slater, M. S. & Mullins, R. J. Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: a review. J. Am. Coll. Surg. 186, 693–716 (1998).

    Article  CAS  Google Scholar 

  5. Schrier, R. W. Early intervention in acute kidney injury. Nat. Rev. Nephrol. 6, 56–59 (2010).

    Article  CAS  Google Scholar 

  6. Schrier, R. W. Fluid administration in critically ill patients with acute kidney injury. Clin. J. Am. Soc. Nephrol. 5, 733–739 (2010).

    Article  Google Scholar 

  7. Bouchard, J. & Mehta, R. L. Fluid accumulation and acute kidney injury: consequence or cause. Curr. Opin. Crit. Care 15, 509–513 (2009).

    Article  Google Scholar 

  8. Benedetto, U. et al. Acute kidney injury after coronary artery bypass grafting: does rhabdomyolysis play a role? J. Thorac. Cardiovasc. Surg. 140, 464–470 (2010).

    Article  Google Scholar 

  9. Solez, K. et al. International dialysis aid in earthquakes and other disasters. Kidney Int. 44, 479–483 (1993).

    Article  CAS  Google Scholar 

  10. Hatamizadeh, P. et al. Epidemiologic aspects of the Bam earthquake in Iran: the nephrologic perspective. Am. J. Kidney Dis. 47, 428–438 (2006).

    Article  Google Scholar 

  11. Vanholder, R., Stuard, S., Bonomini, M. & Sever, M. S. Renal disaster relief in Europe: the experience at L'Aquila, Italy, in April 2009. Nephrol. Dial. Transplant. 24, 3251–3255 (2009).

    Article  Google Scholar 

  12. Vanholder, R. et al. Earthquakes and crush syndrome casualties: lessons learned from the Kashmir disaster. Kidney Int. 7, 17–23 (2007).

    Article  Google Scholar 

  13. Barbera, J. A. & Cadoux, C. G. Search, rescue, and evacuation. Crit. Care Clin. 7, 321–337 (1991).

    Article  CAS  Google Scholar 

  14. Ashkenazi, I. et al. Prehospital management of earthquake casualties buried under rubble. Prehosp. Disaster Med. 20, 122–133 (2005).

    Article  Google Scholar 

  15. Agu, O. & Ackroyd, J. S. Crush syndrome after isolated abdominal crush injury in flood water. J. Trauma 53, 378–379 (2002).

    Article  Google Scholar 

  16. Heppenstall, R. B., Scott, R., Sapega, A., Park, Y. S. & Chance, B. A comparative study of the tolerance of skeletal muscle to ischemia. Tourniquet application compared with acute compartment syndrome. J. Bone Joint Surg. Am. 68, 820–828 (1986).

    Article  CAS  Google Scholar 

  17. Mubarak, J. S. Compartment syndromes and Volkmann's contracture. 207–226 (W. B. Saunders, Philadelphia, 1981).

    Google Scholar 

  18. Better, O. S. History of the crush syndrome: from the earthquakes of Messina, Sicily 1909 to Spitak, Armenia 1988. Am. J. Nephrol. 17, 392–394 (1997).

    Article  CAS  Google Scholar 

  19. Freedman, B. J. Dr. Edward Wilson of the Antarctic. Proc. R. Soc. Med. 47, 183–189 (1954).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Better, O. S., Rubinstein, I. & Reis, D. N. Muscle crush compartment syndrome: fulminant local edema with threatening systemic effects. Kidney Int. 63, 1155–1157 (2003).

    Article  Google Scholar 

  21. Reis, N. D. & Better, O. S. Mechanical muscle-crush injury and acute muscle-crush compartment syndrome: with special reference to earthquake casualties. J. Bone Joint Surg. Br. 87, 450–453 (2005).

    Article  CAS  Google Scholar 

  22. Bywaters, E. G. & Beal, D. Crush injuries with impairment of renal function. BMJ 1, 427–432 (1941).

    Article  CAS  Google Scholar 

  23. Bywaters, E. G. 50 years on: the crush syndrome. BMJ 301, 1412–1415 (1990).

    Article  CAS  Google Scholar 

  24. Better, O. S., Rubinstein, I., Winaver, J. M. & Knochel, J. P. Mannitol therapy revisited (1940–1997). Kidney Int. 52, 886–894 (1997).

    Article  CAS  Google Scholar 

  25. Bywaters, E. G. L. & Knochel, J. P. Comments in Milestones Nephrology, Crush injuries with impairment of renal function (reprinted). J. Am. Soc. Nephrol. 9, 322–332 (1998).

    CAS  PubMed  Google Scholar 

  26. Sever, M. S., Vanholder, R. & Lameire, N. Management of crush-related injuries after disasters. N. Engl. J. Med. 354, 1052–1063 (2006).

    Article  CAS  Google Scholar 

  27. Sever, M. S. The crush syndrome. 146–163 (Karger, Basel, 2005).

    Google Scholar 

  28. Hwang, S. J., Shu, K. H., Lain, J. D. & Yang, W. C. Renal replacement therapy at the time of the Taiwan Chi-Chi earthquake. Nephrol. Dial. Transplant. 16 (Suppl. 5), 78–82 (2001).

    Article  Google Scholar 

  29. Gunal, A. I. et al. Early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes. J. Am. Soc. Nephrol. 15, 1862–1867 (2004).

    Article  Google Scholar 

  30. Williams, M. E. & Epstein, F. H. in The Regulation of Potassium Balance Ch. 1 (eds Seldin, D. W. & Giebisch, G.) 3–20 (Raven, New York, 1989).

    Google Scholar 

  31. Knochel, J. P. Rhabdomyolysis and myoglobinuria. Semin. Nephrol. 1, 75–86 (1981).

    CAS  Google Scholar 

  32. Better, O. S. & Stein, J. H. Early management of shock and prophylaxis of acute renal failure in traumatic rhabdomyolysis. N. Engl. J. Med. 322, 825–829 (1990).

    Article  CAS  Google Scholar 

  33. Better, O. S. et al. The mechanism of muscle injury in the crush syndrome: ischemic versus pressure-stretch myopathy. Miner. Electrolyte Metab. 16, 181–184 (1990).

    CAS  PubMed  Google Scholar 

  34. Carafoli, E. & Penniston, J. T. The calcium signal. Sci. Am. 253, 70–78 (1985).

    Article  CAS  Google Scholar 

  35. Rubinstein, I. et al. Involvement of nitric oxide system in experimental muscle crush injury. J. Clin. Invest. 101, 1325–1333 (1998).

    Article  CAS  Google Scholar 

  36. Manfredi, A. A. & Rovere-Querini, P. The mitochondrion—a Trojan horse that kicks off inflammation? N. Engl. J. Med. 362, 2132–2134 (2010).

    Article  CAS  Google Scholar 

  37. Clausen, T. & Everts, M. E. Regulation of the Na, K-pump in skeletal muscle. Kidney Int. 35, 1–13 (1989).

    Article  CAS  Google Scholar 

  38. Zager, R. A. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int. 49, 314–326 (1996).

    Article  CAS  Google Scholar 

  39. Bywaters, E. G. & Stead, J. K. The production of renal failure following injection of solution containing myohaemoglobin. Q. J. Exp. Physiol. 33, 53–70 (1944).

    Article  CAS  Google Scholar 

  40. Shimazu, T. et al. Fluid resuscitation and systemic complications in crush syndrome: 14 Hanshin-Awaji earthquake patients. J. Trauma 42, 641–646 (1997).

    Article  CAS  Google Scholar 

  41. Oda, J. et al. Analysis of 372 patients with crush syndrome caused by the Hanshin-Awaji earthquake. J. Trauma 42, 470–475 (1997).

    Article  CAS  Google Scholar 

  42. Sever, M. S. et al. The Marmara earthquake: admission laboratory features of patients with nephrological problems. Nephrol. Dial. Transplant. 17, 1025–1031 (2002).

    Article  Google Scholar 

  43. Vanholder, R., Sever, M. S., De Smet, M., Erek, E. & Lameire, N. Intervention of the Renal Disaster Relief Task Force in the 1999 Marmara, Turkey earthquake. Kidney Int. 59, 783–791 (2001).

    Article  CAS  Google Scholar 

  44. Eneas, J. F., Schoenfeld, P. Y. & Humphreys, M. H. The effect of infusion of mannitol-sodium bicarbonate on the clinical course of myoglobinuria. Arch. Intern. Med. 139, 801–805 (1979).

    Article  CAS  Google Scholar 

  45. Ron, D. et al. Prevention of acute renal failure in traumatic rhabdomyolysis. Arch. Intern. Med. 144, 277–280 (1984).

    Article  CAS  Google Scholar 

  46. Altintepe, L. et al. Early and intensive fluid replacement prevents acute renal failure in the crush cases associated with spontaneous collapse of an apartment in Konya. Ren. Fail. 29, 737–741 (2007).

    Article  Google Scholar 

  47. Myers, B. D. in Acute Renal Failure in the Intensive Therapy Unit. Ch. 15 (eds Bihari, D. & Nield, G.) 167–180 (Springer, London, 1990).

    Book  Google Scholar 

  48. Barry, K. G. et al. Mannitol infusion. II. The prevention of acute functional renal failure during resection of an aneurysm of the abdominal aorta. N. Engl. J. Med. 264, 967–971 (1961).

    Article  CAS  Google Scholar 

  49. van Valenberg, P. L. et al. Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation. Transplantation 44, 784–788 (1987).

    Article  CAS  Google Scholar 

  50. DeFronzo, R. A. & Bia, M. in The Kidney: Physiology and Pathophysiology Ch. 14 (eds Seldin, D. W. & Giebisch, G.) 1179–1206 (Raven, New York, 1985).

    Google Scholar 

  51. Knochel, J. P. in The Regulation of Potassium Balance Ch. 2 (eds Seldin, D. W. & Giebisch, G.) 31–55 (Raven, New York, 1989).

    Google Scholar 

  52. McKechnie, J. K., Leary, W. P. & Joubert, S. M. Some electrocardiographic and biochemical changes recorded in marathon runners. S. Afr. Med. J. 41, 722–725 (1967).

    CAS  PubMed  Google Scholar 

  53. Schaller, M. D., Fischer, A. P. & Perret, C. H. Hyperkalemia. A prognostic factor during acute severe hypothermia. JAMA 264, 1842–1845 (1990).

    Article  CAS  Google Scholar 

  54. Allister, C. Cardiac arrest after crush injury. Br. Med. J. (Clin. Res. Ed.) 287, 531–532 (1983).

    Article  CAS  Google Scholar 

  55. Hudson, J. B., Chobanian, A. V. & Relman, A. S. Hypoaldosteronism—a clinical study of a patient with an isolated adrenal mineralocorticoid deficiency, resulting in hyperkalemia and Stokes–Adams attacks. N. Engl. J. Med. 257, 529–536 (1957).

    Article  CAS  Google Scholar 

  56. Montague, B. T., Ouellette, J. R. & Buller, G. K. Retrospective review of the frequency of ECG changes in hyperkalemia. Clin. J. Am. Soc. Nephrol. 3, 324–330 (2008).

    Article  Google Scholar 

  57. Burns, K., Cone, D. C. & Portereiko, J. V. Complex extrication and crush injury. Prehosp. Emerg. Care 14, 240–244 (2010).

    Article  Google Scholar 

  58. Allon, M. Hyperkalemia in end-stage renal disease: mechanisms and management. J. Am. Soc. Nephrol. 6, 1134–1142 (1995).

    CAS  PubMed  Google Scholar 

  59. Sterns, R. H., Rojas, M., Bernstein, P. & Chennupati, S. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J. Am. Soc. Nephrol. 21, 733–735 (2010).

    Article  CAS  Google Scholar 

  60. Boutaud, O. et al. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc. Natl Acad. Sci. USA 107, 2699–2704 (2010).

    Article  CAS  Google Scholar 

  61. Nickolas, T. L., Barasch, J. & Devarajan, P. Biomarkers in acute and chronic kidney disease. Curr. Opin. Nephrol. Hypertens. 17, 127–132 (2008).

    Article  CAS  Google Scholar 

  62. Vaidya, V. S., Ferguson, M. A. & Bonventre, J. V. Biomarkers of acute kidney injury. Annu. Rev. Pharmacol. Toxicol. 48, 463–493 (2008).

    Article  CAS  Google Scholar 

  63. Devarajan, P. Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease. Scand. J. Clin. Lab. Invest. 241 (Suppl.), 89–94 (2008).

    Article  Google Scholar 

  64. Haase, M. et al. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am. J. Kidney Dis. 54, 1012–1024 (2009).

    Article  CAS  Google Scholar 

  65. Mitchell, J. H., Wildenthal, K. & Johnson, R. L. Jr The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int. 1, 375–389 (1972).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, Faculty of Medicine Technion IIT, Rambam Hospital, Haifa, 31096, Israel

    Ori S. Better & Zaid A. Abassi

Authors
  1. Ori S. Better
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zaid A. Abassi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed equally to all aspects of this article.

Corresponding author

Correspondence to Ori S. Better.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Better, O., Abassi, Z. Early fluid resuscitation in patients with rhabdomyolysis. Nat Rev Nephrol 7, 416–422 (2011). https://doi.org/10.1038/nrneph.2011.56

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2011.56

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing