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Open access Guidelines/Algorithms

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
Falls Church, Virginia, USA consensus statement is to review the present-­day Recommendation
6
Department of Surgery, Loyola diagnosis, management, and prognosis of patients who Rhabdomyolysis should be suspected in patients
University Chicago Stritch develop rhabdomyolysis. with a large burden of traumatic injury involving
School of Medicine, Maywood,
Illinois, USA muscular tissue, especially patients with crush inju-
ries involving the extremities or mangled extrem-
Correspondence to INTRODUCTION ities. Patients with vascular injuries or muscle
Dr Richard P Gonzalez; ​richard.​ The American Association for the Surgery of Trauma ischemia with subsequent reperfusion are also at
gonzalez@​lumc.​edu (AAST) Critical Care Committee develops clin- higher risk for rhabdomyolysis.
ical consensus documents for critical care-­related
Received 20 September 2021
Accepted 16 December 2021 aspects of patient care. The goal of these docu- Discussion
ments is to provide practical answers to common Rhabdomyolysis is the result of skeletal muscle
clinical questions based on the best evidence avail- breakdown with release of potentially toxic
able. They address focused topics for which the substances such as electrolytes, myoglobin, and
levels of evidence guiding care may not be strong sarcoplasmic proteins into the bloodstream.1 The
and/or practice is controversial, and are based on pathophysiology underlying all cases of rhabdomy-
expert consensus and review of the literature. This olysis is disruption of the myocyte cell membrane
issue focuses on the diagnosis and management of and leakage of cell contents into circulation.2 This
rhabdomyolysis in the critically ill surgical/trauma may result from direct myocyte injury related to
patient. trauma or from metabolic disturbances affecting
supply of ATP within the myocyte.3
METHODS Traumatic injuries are a common cause of rhab-
The topic for this document was chosen through domyolysis. One study has shown some degree of
discussion by the AAST Critical Care Committee. A biochemical evidence of rhabdomyolysis (abnormal
subgroup was formed composed of the document’s creatine kinase (CK)) among 85% of critically
authors. The subgroup formulated the clinical ques- injured patients admitted to a trauma intensive care
tions to be addressed and assigned research and unit setting, although only 10% developed renal
writing tasks. Authors were tasked with researching failure and only 5% required renal replacement
their clinical questions through literature review therapy (RRT).4 Patients with multisystem trauma,
and writing their section. Literature review was crush injuries involving the extremities or torso,
performed by the individual authors pertaining to and those with compartment syndrome of one or
their clinical questions. Recommendations, refer- more extremities are at highest risk.5 Other inde-
© Author(s) (or their ences, and content were then reviewed by the pendent risk factors for rhabdomyolysis among
employer(s)) 2022. Re-­use
permitted under CC BY-­NC. No subgroup and revised based on feedback to achieve trauma patients include age older than 55 years,
commercial re-­use. See rights consensus. The subsequent draft was distributed to Injury Severity Score greater than 16, penetrating
and permissions. Published the committee for review and comment prior to trauma with vascular injury, severe extremity injury,
by BMJ. final editing by the first and last authors. male sex, and body mass index greater than 30 kg/
To cite: Kodadek L, m2.4 6 Patients who fall with subsequent prolonged
Carmichael II SP, Seshadri A, BACKGROUND immobilization are also at higher risk for rhabdo-
et al. Trauma Surg Acute Care Rhabdomyolysis is a condition characterized by myolysis, particularly if their limbs are compressed
Open 2022;7:e000836. primary (mechanical) or secondary (metabolic) by their head or torso for a significant period of
Kodadek L, et al. Trauma Surg Acute Care Open 2022;7:e000836. doi:10.1136/tsaco-2021-000836 1
 Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on April 7, 2022 by guest. Protected by copyright.
Open access
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 tion is identified (typically at 24–72 hours), discontinued once
levels of intracellular calcium; unregulated increases in intracel- the CK is reliably downtrending.
lular calcium lead to activation of calcium-­dependent enzymes
with eventual breakdown of the muscle cell.1 Exertional causes
of rhabdomyolysis may include extreme and prolonged exercise Discussion
or seizure activity such as status epilepticus.9 Most commonly, Traumatic or non-­traumatic injury to the skeletal muscle cellular
drugs and toxins lead to rhabdomyolysis. Alcohol abuse or membrane leads to an influx of calcium into the cytoplasm,
dependence may actually be the most common risk factor for disrupting cellular homeostasis and leading to cell death. Injury
rhabdomyolysis; ethanol has direct adverse effects on muscle may be exacerbated by the generation of reactive oxygen species
tissue metabolism and cellular integrity including inhibition of after restoration of blood flood to the affected tissue (reper-
active transport pumps.3 8 Other illicit substances such as cocaine, fusion injury). The resulting effect is the accumulation of CK,
heroin, and phencyclidine may also be implicated in cases of myoglobin, LDH, and potassium in the circulation.2 In a recent
rhabdomyolysis. Lipid-­lowering agents, especially statins, are a systematic review, the laboratory definition of rhabdomyolysis
common cause of rhabdomyolysis, particularly in patients with varied to include an elevated CK level >5× the upper limit of
concomitant renal or liver insufficiency.10 Infections such as normal or >1000 IU/L, with the CK-­MM subtype being the most
influenza, Epstein-­Barr virus, Streptococcus pyogenes, or Staph- reflective of skeletal muscle injury.1 2 CK values may become
ylococcus aureus may rarely lead to rhabdomyolysis.1 Genetic elevated within 12 hours of injury, peak at 24 to 72 hours, and
diseases including disorders of glycolysis or glycogenolysis, return to normal in roughly 5 days, depending on the degree of
lipid metabolism defects, or mitochondrial disorders are rare injury and appropriate therapy.
causes of rhabdomyolysis.1 Finally, rhabdomyolysis may be seen Myoglobin becomes elevated in the circulation once intrinsic
in patients with extreme alterations in body temperature due binding proteins are overwhelmed. Given a shorter half-­ life
to conditions such as malignant hyperthermia, heat stroke, or (1–3 hours) versus CK, myoglobin may elevate and resolve
neuroleptic malignant syndrome.11 Metabolic etiology for rhab- prior to CK depreciating its clinical utility. Myoglobin may also
domyolysis is very broad and a number of different risk factors be evident in the urine and, although the sensitivity has been
may need to be considered in this population. reported up to 100%, the specificity varies widely from 15% to
88%.5 Although a causal relationship may exist between rhabdo-
CLINICAL MANIFESTATIONS myolysis and elevations in hepatic aminotransferases (AST, ALT:
alanine transaminase), this is of unclear value as both enzymes
What clinical findings are expected with rhabdomyolysis?
exist within skeletal muscle and may become elevated as a result
Recommendation
of primary muscle injury.7 8 14 15
Rhabdomyolysis presentation may vary from asymptomatic to
commonly implicated clinical features, including acute muscle
weakness, pain/tenderness, and swelling (dolor, tumor) of the MANAGEMENT
affected extremity or body region.12 Darkened (tea-­ colored) What is the optimal crystalloid type, rate of administration,
urine may be an additional common finding. A low threshold of and urine output goals to prevent AKI in rhabdomyolysis?
clinical suspicion in the proper laboratory and historical context Recommendation
is warranted to initiate appropriate therapy. Either lactated Ringer’s solution or saline (0.9% or 0.45%) is an
acceptable fluid for resuscitation in rhabdomyolysis. A starting
Discussion rate of 400 mL/hour can be initiated, with goal-­directed therapy
Rhabdomyolysis is a clinical syndrome consequent to skeletal of urine output of 1 mL/kg/hour to 3 mL/kg/hour, and up to
muscle cell death with release of intracellular contents (described 300 cc/hour.
2 Kodadek L, et al. Trauma Surg Acute Care Open 2022;7:e000836. doi:10.1136/tsaco-2021-000836
 Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on April 7, 2022 by guest. Protected by copyright.
Open access

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-
vant outcome in the study. There have been no other random- tration and/or mannitol to prevent AKI in rhabdomyolysis.26–28
ized controlled trials comparing lactated Ringer’s solution and Randomized controlled studies are lacking and the literature is
normal saline or 0.45% saline and therefore no clear recommen- composed mainly of retrospective studies or small case series.
dation as to which fluid type is better. It does appear that use of Many of these studies also lack a therapeutic endpoint such as
either type of fluid is safe in the treatment of rhabdomyolysis, so measurement of urinary pH, and furthermore most of the studies
although this area certainly requires further study, at this time couple mannitol use along with sodium bicarbonate.18 One of
the type of fluid used for management of rhabdomyolysis may the larger studies from Brown et al4 reviewed 382 patients with
be at the discretion of the treating physician. rhabdomyolysis, composed of a subset of 1771 patients with
The rate of administration of intravenous fluids in rhabdo- CK >5000 U/L; 154 (40%) received bicarbonate and mannitol
myolysis should be targeted to the patient as there is significant and 228 (60%) did not receive either bicarbonate or mannitol.
risk of volume overload should an excessive amount of fluid be There was no difference between groups in the rate of AKI or
given without goal-­directed therapy. A starting rate of 400 cc/ the need for RRT.4 Similarly, Homsi et al,29 in a study of 24
hour with a range of 200 cc/hour to 1000 cc/hour is considered patients, retrospectively compared saline versus a combination
reasonable but should be titrated to urine output, ensuring the of saline/mannitol/bicarbonate resuscitation for rhabdomyolysis
patient is receiving adequate resuscitation without suffering (CK >500 IU/L) and found no difference in the incidence of
from fluid creep.1 19 renal failure between groups.29 Nielsen et al30 retrospectively
Urine output is the traditional method by which one can deter- evaluated normal saline with mannitol and bicarbonate versus
mine the adequacy of resuscitation in rhabdomyolysis. The most normal saline alone in patients with traumatic rhabdomyolysis.
commonly cited urine output goals for intravenous fluid rehy- They used a predefined protocol at their institution for patients
dration are 1 mL/kg/hour to 3 mL/kg/hour, and up to 300 mL/ with rhabdomyolysis with CK >10 000 U/L. Only 46 of 56
hour.1–4 18 20–22 However, should the patient remain anuric despite patients who would have qualified for the protocol had received
escalating rates of intravenous fluid administration, the need for it. When comparing these 46 with the 10 patients who did not
RRT may be necessary as ongoing aggressive fluid resuscita- receive the protocol, they recognized a significant decrease in
tion without renal clearance could lead to significant and life-­ the development of AKI in those patients receiving the protocol
threatening volume overload. (26%) versus those who did not (70%).30 The question as to
which particular component of the protocol was beneficial and
the impact of a standardized approach was not answered in this
Are diuretics and/or bicarbonate administration beneficial?
study. Furthermore this study also highlights the fact that the
Recommendation
majority of the studies are fairly small and underpowered to
Clinical studies evaluating the efficacy of sodium bicarbonate
demonstrate a clear benefit. A recent comprehensive review of
and/or diuretic use (mannitol, loop diuretics) for prevention of
the role of bicarbonate and mannitol in rhabdomyolysis demon-
rhabdomyolysis-­induced AKI are limited by a lack of appropriate
strates that aggressive early-­volume therapy with normal saline
control groups, standardized definitions, retrospective design,
should be the primary management and that bicarbonate and
and low statistical power. Given these significant limitations, the
mannitol utilization should be discouraged.26
use of sodium bicarbonate or diuretics for prevention of AKI in
The clinical evidence supporting the use of loop diuretics in
rhabdomyolysis is not recommended.
this setting is sparse and composed primarily of case reports.31–34
As such, it cannot be interpreted with any confidence. Although
Discussion loop diuretics have been shown to reduce metabolic demand
The precise mechanism of AKI in rhabdomyolysis is controver- and oxygen consumption by the proximal tubular cells, they
sial and likely multifactorial. The two important factors in the have also been shown to worsen renal afferent arteriole
Kodadek L, et al. Trauma Surg Acute Care Open 2022;7:e000836. doi:10.1136/tsaco-2021-000836 3
 Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on April 7, 2022 by guest. Protected by copyright.
Open access
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
using plasmapheresis,43 it has not been shown to have an effect on
are hyperkalemia, hyperphosphatemia, hypocalcemia, and
outcome or myoglobin clearance.44 Furthermore, there is insuf-
hypomagnesemia.
AKI in rhabdomyolysis is often associated with excessive ficient evidence to recommend RRT in the prevention of AKI in
potassium levels and correlates with the volume of muscle rhabdomyolysis.38 45 Indeed, a Cochrane review evaluated CRRT
destruction. Baseline levels of potassium and all pertinent elec- for rhabdomyolysis. It sought to assess the efficacy of CRRT in
trolytes should be evaluated when the possibility of rhabdo- myoglobin reversal, the influence of CRRT on mortality and
myolysis development is present. Hyperkalemia that occurs in kidney-­related outcomes, and to evaluate the safety of CRRT for
rhabdomyolysis-­induced AKI occurs early in the course of the treatment in patients with rhabdomyolysis.39 46–48 There was no
disease process and should be monitored closely. Potassium significant difference in mortality compared with conventional
levels should be serially evaluated. Patients with high potassium therapy. The review concluded that overall the studies had poor
levels (>6 mmol/L) should have cardiac monitoring. ECG should quality and there was insufficient evidence to determine any
be obtained and assessed for manifestations of severe hyperka- benefits of CRRT over conventional therapy for rhabdomyolysis
lemia (QRS widening, small p waves, and severe arrhythmias). and prevention of AKI in rhabdomyolysis.
Hypocalcemia aggravates the electrical effects of hyperkalemia There have been several studies investigating myoglobin
and should be aggressively treated with calcium chloride or clearance using different dialysis modalities, filters, and flow
calcium gluconate in this scenario. Elevated potassium levels types. The RRT techniques in these studies were initiated
should be treated with insulin and glucose infusions. Consider based on traditional indications for AKI and sought to deter-
administration of a β-2 adrenergic agent such as albuterol via mine if any of these different modalities, filter, and flow types
aerosol inhalation. Lastly, consider potassium removal via cation facilitate myoglobin clearance and hence affect kidney-­related
exchange resin or dialysis as indicated.1 2 38 39 outcomes. Since myoglobin has a molecular weight of 17 KDa
and is thought to be poorly cleared by diffusion (dialysis), inves-
Similar to hyperkalemia, hyperphosphatemia occurs as a result
tigators have studied whether the technique of RRT (continuous
of phosphate release from damaged muscle cells. High levels
vs. intermittent), hemodiafiltration versus hemofiltration, use of
of phosphate may be problematic because phosphate binds to
special high cut-­off membrane filters (which enhance clearance
calcium and this complex deposits in the soft tissues. Addition-
of larger molecules), as well as high-­flow versus low-­flow dial-
ally, by inhibiting 1α-hydroxylase, hyperphosphatemia inhibits
ysis improve overall or kidney-­related outcomes.49–53 The overall
calcitriol formation and thus limits formation of the active form
of vitamin D. Treatment of hyperphosphatemia should be done studies are small in number and seem to lack sufficient evidence
with caution since treatment involves administration of a calcium to make any recommendations.
chelator which can increase precipitation of calcium phosphate The utilization of RRT in patients with rhabdomyolysis should
in injured muscle. Early hyperphosphatemia typically decreases be based on traditional indications for AKI and the degree of
as phosphate is excreted in the urine.1 2 renal impairment, such as severe acid/base disturbances, electro-
lyte abnormalities, and hypervolemia, all of which are refractory
Hypocalcemia occurs early in rhabdomyolysis due to calcium
to medical management.
entry into damaged cells and calcium phosphate deposition in
necrotic muscle. Early hypocalcemia treatment in rhabdomy-
olysis should be avoided unless patients are symptomatic or OUTCOMES
severe hyperkalemia is present. Correction of hypocalcemia with What complications should be suspected by clinicians
calcium chloride or gluconate should be avoided since calcium treating rhabdomyolysis?
deposition may occur in injured muscle. During the recovery Recommendation
phase, serum calcium levels return to normal and may rebound, Clinicians should monitor for a variety of complications,
causing hypercalcemia due to release of calcium from injured ranging from an asymptomatic elevation of muscle protein to
4 Kodadek L, et al. Trauma Surg Acute Care Open 2022;7:e000836. doi:10.1136/tsaco-2021-000836
 Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on April 7, 2022 by guest. Protected by copyright.
Open access
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 lated for each patient, with an OR of 1.72 (95% CI 1.45 to
degradation studies without significant bleeding or thrombosis.54 2.04).56
Compartment syndrome may be an early or late complication, Several other retrospective studies brought forth other predic-
resulting from direct muscle injury or vigorous muscle activity. tion variables for AKI, ARF, and need for RRT. Baeza-­Trinidad
This complication occurs primarily due to limited muscle expan- et al57 found initial creatinine levels associated with progression
sion from enveloping tight fascia. A delay of more than 6 hours to AKI and mortality at 30 days. The cut-­off point of creati-
in diagnosing this complication can lead to irreversible muscle nine of 1.15 mg/dL had the best ratio of sensitivity (74.6%) and
damage or death.53 specificity (67.4%) to predict mortality.57 Chen et al58 looked
at predictive factors for ARF including dark urine, initial and
Can prediction scoring be used in rhabdomyolysis? peak serum myoglobin level, rhabdomyolysis caused by body
Recommendation temperature change, and elevated serum potassium. Risk factors
The risk of AKI, RRT, and/or in-­hospital mortality in patients for RRT initiation were peak BUN (Blood Urea Nitrogen)/creat-
with rhabdomyolysis can be estimated using admission demo- inine levels and CK level on the third day as rhabdomyolysis
graphic, clinical, and laboratory variables. Risk prediction scores developed. The initial serum myoglobin threshold associated
may not directly influence treatment; however, they may be with development of ARF is 600 ng/mL.58 In ambiguous cases,
useful in estimating prognosis and setting expectations. clinical suspicion of rhabdomyolysis is confirmed by a positive
As no single laboratory value is sufficient to predict the urine or serum test for myoglobin. There is a loose correlation
course of rhabdomyolysis, a combined index of metrics, the between CK levels and the development of ARF, with levels
McMahon Score (table 1), may be calculated at admission for higher than 16 000 IU/L more likely to be associated with renal
failure.22
The McMahon Score is a prospectively validated risk predic-
Table 1 McMahon Score
tion tool to identify patients at high risk of RRT or in-­hospital
Variable Score mortality (table 1). When calculated at admission from demo-
Age, years graphic and blood chemistry data, a score ≥6 is 86% sensitive
>50 to ≤70 1.5 and 68% specific for patients who will require RRT. In this
>70 to ≤80 2.5
setting, the authors recommend the initiation of renal protective
>80 3
therapy with a target urine output of 1 mL/kg/hour to 3 mL/kg/
hour, and up to 300 cc/hour.1–4 18 20–22
Female 1
Initial creatinine, mg/dL
CONCLUSION
1.4–2.2 1.5
Rhabdomyolysis is a relatively uncommon but important condi-
>2.2 3
tion seen in critically ill and injured patients. Surgical critical care
Initial calcium <7.5 mg/dL 2 providers should be familiar with the less frequently encountered
Initial CPK (Creatine Phosphokinase) >40 000 U/L 2 metabolic etiologies of rhabdomyolysis, in addition to the well-­
Origin not seizure, syncope, exercise, statins, or myositis 3 known traumatic causes. The diagnosis is made with a combina-
Initial phosphate, mg/dL tion of clinical and laboratory findings and should lead to prompt
4.0–5.4 1.5 intervention to halt any processes causing muscle damage and to
>5.4 3
prevent or treat known complications of the disease. A consensus
summary for the diagnosis and management of rhabdomyolysis
Initial bicarbonate <19 mEq/L 2
is provided in (table 2). Although traditional therapies such as
Kodadek L, et al. Trauma Surg Acute Care Open 2022;7:e000836. doi:10.1136/tsaco-2021-000836 5
 Trauma Surg Acute Care Open: first published as 10.1136/tsaco-2021-000836 on 27 January 2022. Downloaded from http://tsaco.bmj.com/ on April 7, 2022 by guest. Protected by copyright.
Open access
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Contributors All authors contributed extensively to the work presented in this 1999;65:250–5.
article and to writing of the individual sections of the article. All authors were 24 Zager RA. Studies of mechanisms and protective maneuvers in myoglobinuric acute
involved in planning and editing the article leading up to its final edition. renal injury. Lab Invest 1989;60:619–29.
Funding The authors have not declared a specific grant for this research from any 25 Huerta-­Alardín AL, Varon J, Marik PE. Bench-­to-­bedside review: rhabdomyolysis -- an
funding agency in the public, commercial or not-­for-­profit sectors. overview for clinicians. Crit Care 2005;9:158–69.
26 Somagutta MR, Pagad S, Sridharan S, Nanthakumaran S, Arnold AA, May V, Malik
Competing interests None declared. BH. Role of Bicarbonates and mannitol in rhabdomyolysis: a comprehensive review.
Patient consent for publication Not required. Cureus 2020;12:e9742.
27 Zager RA, Foerder C, Bredl C. The influence of mannitol on myoglobinuric acute renal
Ethics approval This study does not involve human participants. As this is a
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consensus document, investigational review board approval was not obtained at
1991;2:848–55.
individual institutions. Additionally, no study ethics approval was deemed necessary
28 Zager RA. Combined mannitol and deferoxamine therapy for myohemoglobinuric
as this article is a consensus statement and had no study or patient participants.
renal injury and oxidant tubular stress. mechanistic and therapeutic implications. J Clin
Provenance and peer review Commissioned; internally peer reviewed. Invest 1992;90:711–9.
Open access This is an open access article distributed in accordance with the 29 Homsi E, Barreiro MF, Orlando JM, Higa EM. Prophylaxis of acute renal failure in
Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which patients with rhabdomyolysis. Ren Fail 1997;19:283–8.
permits others to distribute, remix, adapt, build upon this work non-­commercially, 30 Nielsen JS, Sally M, Mullins RJ, Slater M, Groat T, Gao X, de la Cruz JS, Ellis MKM,
and license their derivative works on different terms, provided the original work is Schreiber M, Malinoski DJ. Bicarbonate and mannitol treatment for traumatic
properly cited, appropriate credit is given, any changes made indicated, and the use rhabdomyolysis revisited. Am J Surg 2017;213:73–9.
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sodium bicarbonate on the clinical course of myoglobinuria. Arch Intern Med
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Christopher P Michetti http://orcid.org/0000-0002-3744-0603 acute renal failure in traumatic rhabdomyolysis. Arch Intern Med 1984;144:277–80.
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