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Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
Rhabdomyolysis: an American Association for the
Surgery of Trauma Critical Care Committee Clinical
Consensus Document
Lisa Kodadek,1 Samuel P Carmichael II ,2 Anupamaa Seshadri,3 Abhijit Pathak,4
Jason Hoth,2 Rachel Appelbaum,2 Christopher P Michetti ,5 Richard P Gonzalez6
1
Department of Surgery, Yale ABSTRACT skeletal muscle injury, resulting in cell death and
University School of Medicine, Rhabdomyolysis is a clinical condition characterized by release of potentially toxic substances into circu-
New Haven, Connecticut, USA
2
Department of Surgery, Wake destruction of skeletal muscle with release of intracellular lation. Management often centers on prevention
Forest University School of contents into the bloodstream. Intracellular contents or treatment of the primary complication of the
Medicine, Winston-Salem, North released include electrolytes, enzymes, and myoglobin, condition, acute kidney injury (AKI). Here we
Carolina, USA resulting in systemic complications. Muscle necrosis is briefly review the causes, diagnosis, management,
3
Surgery, Beth Israel Deaconess and outcomes of rhabdomyolysis.
the common factor for traumatic and non-traumatic
Medical Center, Boston,
Massachusetts, USA rhabdomyolysis. The systemic impact of rhabdomyolysis
4
Department of Surgery, Temple ranges from asymptomatic elevations in bloodstream In what patient populations should
University School of Medicine, muscle enzymes to life-threatening acute kidney injury rhabdomyolysis be suspected?
Philadelphia, Pennsylvania, USA and electrolyte abnormalities. The purpose of this clinical
5
Surgery, Inova Fairfax Hospital, Trauma patients
Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
time, leading to muscle hypoxia.3 Conditions leading to skeletal in next section) into the circulation.12 Resultant organ dysfunc-
muscle ischemia, such as direct compression or compartment tion may include renal (AKI), cardiac (arrhythmia), and coag-
syndrome, may lead to irreversible damage to the muscle; much ulopathy. Despite this cluster of findings, there is no formally
of the injury may actually occur with reperfusion, in addition held definition for rhabdomyolysis and clinical presentations
to injury sustained during the period of ischemia.7 Trauma is may vary greatly. Commonly implicated muscle groups are the
a common cause of rhabdomyolysis, but less than 20% of all extremities and the lower back. Superficial pressure ulceration
cases of rhabdomyolysis are thought to be related to direct or blistering may suggest the diagnosis, but is not a reliable
injury; metabolic or medical causes of rhabdomyolysis are more finding. At the extremes of pathology, compartment syndromes
common.8 of affected muscle groups lead to increased morbidity and poten-
tial need for decompression.13
Metabolic etiologies
Recommendation What laboratory findings aid in the diagnosis of
Rhabdomyolysis should be suspected in any patient with a rhabdomyolysis?
medical condition causing increased metabolic demands on Recommendation
myocytes in excess of the available supply of ATP. This may result The most commonly implicated variables include elevated
from extreme exertional demands on skeletal muscle from exer- serum concentrations of CK (>5× the upper limit of normal
cise, exogenous agents such as drugs or toxins, genetic defects or or >1000 IU/L), myoglobin, lactate dehydrogenase (LDH),
myopathies affecting the muscle cell, and infections. potassium, creatinine, and aspartate aminotransferase (AST).
Elevated urine myoglobin provides additional evidence. A low
Discussion threshold of suspicion in the proper clinical context is warranted
Any process that impairs ATP production by skeletal muscle and to initiate appropriate therapy. A strategy for disease monitoring
any state where skeletal muscle energy requirements exceed the with serial CK measurement should be additionally undertaken.
available ATP may lead to rhabdomyolysis.3 With ATP deple- Interval CK values should be followed until a peak concentra-
tion, active transport pumps are no longer able to maintain low
Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
Discussion development of myoglobin-induced renal toxicity are hypovo-
Although early-volume resuscitation in rhabdomyolysis is well lemia and aciduria.23 Ferrihemate, which is a breakdown product
accepted as a mainstay of promoting renal tubule flow, diluting of myoglobin, in the presence of a low pH can generate free
nephrotoxins such as myoglobin, and supplying adequate renal radicals which can lead to direct renal cell injury. Furthermore,
perfusion to prevent AKI, the best type of crystalloid for this heme proteins can potentiate renal vasoconstriction, which may
purpose remains controversial.1 16–18 The two most commonly have been initiated by hypovolemia and can activate the cyto-
cited fluids used for this resuscitation are lactated Ringer’s solu- kine cascade.23–25 Pigmented casts, which are the hallmark of
tion and saline (0.9% or 0.45%). Saline is promoted due to its rhabdomyolysis-associated AKI, have been suggested to arise as
lack of potassium; in rhabdomyolysis, crush injury can lead to a result of an interaction between the Tamm-Horsfall protein
hyperkalemia and there is a theoretic concern for worsening and myoglobin in an acidic environment. Other mechanisms
this issue by using a potassium-containing fluid for resuscita- that have been suggested propose that the precipitation of heme
tion. Conversely, receiving large amounts of resuscitation with protein and its ability to generate free radicals at a low pH with
normal saline can lead to metabolic acidosis, which can be resultant toxicity to the tubules is what may give way to cast
counterproductive if urine alkalinization is desired.16 The only formation.23 24 Ultimately, AKI is the result of the combination of
randomized controlled trial comparing these crystalloid fluid vasoconstriction, oxidant injury, and tubular obstruction, which
types evaluated patients with doxylamine-induced rhabdomy- leads to decreased glomerular filtration.
olysis.19 Of note, in this study, urine pH was a targeted end goal, For the aforementioned reasons, it has been suggested that
with a goal pH >6.5. In patients who received lactated Ringer’s alkalinization of the urine may minimize renal injury in rhab-
solution, urine and serum pH were significantly higher after 12 domyolysis and may ameliorate or prevent AKI. Furthermore,
hours of aggressive resuscitation with significantly less need for mannitol, an osmotic diuretic, is a potentially attractive thera-
bicarbonate administration to achieve goal urine pH, and there peutic option in this setting, given its capacity for renal vaso-
was no difference between groups in serum potassium level. dilation, free radical scavenging, and potential for reduction of
However, there was also no difference in median time to serum muscle compartment pressures.1 26 There is no strong clinical
CK less than 200 IU/L, which arguably is the most clinically rele- evidence supporting the use of sodium bicarbonate adminis-
Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
vasoconstriction, acidify urine, and promote aggregation of muscle and mild secondary hyperparathyroidism secondary to
the Tamm- Horsfall protein within the tubular lumen. Taken AKI.1 2 40 41
together, the pathophysiologic consequences of loop diuretics Hypermagnesemia seen with rhabdomyolysis is infrequent but
may potentiate precipitation of myoglobin and worsen the distal when it occurs is typically in association with AKI and should be
tubular obstruction.35 36 Additionally, hypokalemia due to loop treated accordingly with hemodialysis.1
diuretic use has been reported to result in hypokalemic myop-
athy and rhabdomyolysis.37 What is the role of RRT in rhabdomyolysis?
Recommendation
What electrolyte abnormalities should be expected and what There is no role for RRT (either continuous (CRRT) or intermit-
are the optimal methods for management? tent) in rhabdomyolysis to prevent AKI. The utilization of RRT
Recommendation in patients with rhabdomyolysis should be based on traditional
Hyperkalemia, hyperphosphatemia, and hypocalcemia are indications for AKI and the degree of renal impairment.
electrolyte abnormalities most commonly encountered when In patients with rhabdomyolysis who develop AKI and need
treating rhabdomyolysis. Correcting biochemical equilibrium RRT, either CRRT or intermittent RRT should be used based
and electrolytes during rhabdomyolysis should proceed metic- on the degree of renal impairment and the clinical status of the
ulously to avoid complications from treatment. Hyperkalemia patient. There are no recommendations regarding RRT modal-
is the electrolyte abnormality that requires timely correction to ities (filtration vs. diffusion), filter type (low vs. high cut-off
reduce risk of cardiac arrhythmia. membranes), or high-flow versus low-flow dialysis.
Discussion Discussion
Since AKI in rhabdomyolysis is associated with myoglobinuria,
In rhabdomyolysis, electrolyte abnormalities occur as a result
it has been proposed that extracorporeal removal of myoglobin
of cellular component release associated with induced AKI.
may be an effective preventative strategy.1 42 Despite case reports
Electrolyte abnormalities that occur due to rhabdomyolysis
Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
an accumulation of electrolyte imbalances, edema, and toxic prognostication.3 A score greater than or equal to 6 is predictive
cellular components. Morbidity can present early or late, of a need for high-volume fluid resuscitation, RRT, and death.
including hyperkalemia, hepatic dysfunction, cardiac dysfunc-
tion, AKI, acute renal failure (ARF), disseminated intravascular
Discussion
coagulation (DIC), and compartment syndrome. AKI is the
Rhabdomyolysis is a syndrome characterized by deposition
most common systemic complication of rhabdomyolysis and is
of muscle protein that can be life- threatening, and identifi-
responsible for most of the morbidity and mortality associated
cation of severity biomarkers is key. CK is usually taken as a
with rhabdomyolysis.
reference to estimate prognosis; however, this is not the most
effective parameter.22 McMahon et al55 performed a retrospec-
Discussion tive cohort study to develop a risk prediction tool to identify
In rhabdomyolysis, hyperkalemia is the most significant electro- patients at greatest risk of RRT or in-hospital mortality. In total,
lyte abnormality.54 Hepatic dysfunction occurs in approximately these outcomes occurred in 19.0% of patients with rhabdomy-
25% of patients with rhabdomyolysis. Proteases released from olysis.55 The independent predictors identified were age, female
injured muscle may be implicated in hepatic inflammation. sex, cause of rhabdomyolysis, and values of initial creatinine,
Cardiac symptoms may be secondary to electrolyte abnormali- creatine phosphokinase, phosphate, calcium, and bicarbonate.
ties, such as severe hyperkalemia, and range from dysrhythmia In the validation cohort, among patients with the lowest risk
to cardiac arrest.2 score (<5), 2.3% died or needed RRT. Among patients with the
The overall mortality among inpatients with CK >5000 IU/L highest risk score (>10), 61.2% died or needed RRT.54 Rodrí-
is approximately 14%.22 ARF develops in up to 15% of patients. guez et al56 conducted a retrospective observational cohort study
Among those requiring RRT, mortality may be as high as 59%.54 to assess the risk factors for AKI and to develop a risk score for
Additionally, the release of intracellular products may activate early prediction. The variables of peak CK, hypoalbuminemia,
the clotting cascade, leading to DIC in patients with rhabdomy- metabolic acidosis, and decreased prothrombin time were inde-
olysis.22 54 This presentation is often subclinical with prolonged pendently associated with AKI. A risk score for AKI was calcu-
coagulation studies, thrombocytopenia, and elevated fibrin
Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
3 Allison RC, Bedsole DL. The other medical causes of rhabdomyolysis. Am J Med Sci
Table 2 Rhabdomyolysis consensus summary 2003;326:79–88.
Problem Recommendations/findings 4 Brown CVR, Rhee P, Chan L, Evans K, Demetriades D, Velmahos GC. Preventing
renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a
Populations at risk ► Large burden of injury involving muscle. difference? J Trauma 2004;56:1191–6.
► Vascular injury or muscle ischemia. 5 Oda J, Tanaka H, Yoshioka T, Iwai A, Yamamura H, Ishikawa K, Matsuoka T, Kuwagata
► Extreme exertional demands/toxins. Y, Hiraide A, Shimazu T, et al. Analysis of 372 patients with crush syndrome caused by
Clinical findings ► May be asymptomatic. the Hanshin-Awaji earthquake. J Trauma 1997;42:470–6.
► Acute muscle weakness. 6 Brown CVR, Rhee P, Evans K, Demetriades D, Velmahos G, Velhamos G.
► Pain/tender/swelling involved extremity. Rhabdomyolysis after penetrating trauma. Am Surg 2004;70:890–2.
7 Odeh M. The role of reperfusion-induced injury in the pathogenesis of the crush
Laboratory findings ► CK >5× upper limit of normal or >1000 IU/L. syndrome. N Engl J Med 1991;324:1417–22.
► Elevated myoglobin, LDH, K+, Cr, and AST. 8 Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine
Fluid management ► LR or NaCl (0.9 or 0.45%) initiated at 400 cc/ 1982;61:141–52.
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Med 1994;23:1301–6.
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► Up to 300 cc/hour. 2002;128:159–68.
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12 Stahl K, Rastelli E, Schoser B. A systematic review on the definition of rhabdomyolysis.
Electrolyte abnormalities ► Elevated K+ and phosphate. J Neurol 2020;267:877–82.
► Decreased calcium. 13 Cabral BMI, Edding SN, Portocarrero JP, Lerma EV. Rhabdomyolysis. Dis Mon
Renal replacement therapy ► No role for RRT in AKI prevention. 2020;66:101015.
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Complications of rhabdomyolysis ► AKI.
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Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on October 23, 2023 at Instituto Mexicano del
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