Traumatic Rhabdomyolysis in Critically Ill Patients: Current Concepts and Clinical Strategies

Traumatic rhabdomyolysis is a clinical and biochemical syndrome frequently encountered in the intensive care unit, characterised by skeletal muscle necrosis and the release of intracellular components such as myoglobin, creatine kinase, and electrolytes into the bloodstream. Trauma-induced muscle injury may result from crush injuries, compartment syndrome, prolonged immobilisation, or severe burns. This review focuses on the specific pathophysiology, clinical presentation, diagnostic approach, and targeted therapeutic strategies for rhabdomyolysis of traumatic origin in critically ill patients.

Introduction

Traumatic rhabdomyolysis, also known as crush syndrome, is a common cause of morbidity in the intensive care unit (ICU), especially following high-impact trauma, prolonged compression, crush injuries, or extensive soft tissue damage (Chavez et al. 2016). This syndrome is characterised by the release of intracellular contents—most notably myoglobin and creatine kinase (CK)—into the bloodstream (Torres et al. 2015), triggering systemic inflammatory responses, metabolic disturbances, and acute kidney injury (AKI) (Cabral et al. 2020). The pathophysiological cascade is initiated by sarcolemmal disruption, which leads to intracellular calcium overload, activation of proteolytic enzymes, and widespread myocyte necrosis (Chen et al. 2021). Filtered myoglobin can precipitate in acidic urine, forming obstructive casts that contribute to tubular damage and oxidative stress (Bosch et al. 2009). Up to 10-50% of patients with severe rhabdomyolysis may develop AKI (Cervellin et al. 2018). CK levels above 5,000 U/L are strongly suggestive of significant muscle injury, with levels >50,000 U/L correlating with increased renal risk (Cervellin et al. 2018).

Trauma-related rhabdomyolysis is frequently encountered in mass casualty scenarios, vehicular collisions, natural disasters, structural collapses, and combat injuries (Karayel et al. 2023). Crush syndrome is often accompanied by haemodynamic instability and renal dysfunction. Delayed extrication, hypovolaemia, and comorbid injuries further increase the risk of poor outcomes (Chavez et al. 2016).

Pathophysiology

Traumatic myocyte injury is typically the result of prolonged compression, ischaemia-reperfusion damage, or thermal and electrical injury (Torres et al. 2015). Mechanical stress leads to disruption of cellular membranes, allowing extracellular calcium influx and activation of catabolic enzymes including calpains and phospholipases (Chen et al. 2021). This process damages mitochondria and exacerbates ATP depletion. Massive release of myoglobin, potassium, phosphate, lactate dehydrogenase (LDH), and other intracellular solutes can overwhelm the body’s clearance systems (Torres et al. 2015). In the kidney, myoglobin toxicity is mediated by three principal mechanisms: intratubular obstruction, direct cytotoxicity via free radicals in the presence of catalytic iron, and renal vasoconstriction (Bosch et al. 2009). Systemic inflammation and hepatic dysfunction may arise due to circulating heme and oxidative stress, particularly in patients with underlying liver disease. Electrolyte imbalances are frequent and include hyperkalaemia, hyperphosphataemia, early hypocalcaemia due to calcium-phosphate precipitation, and subsequent hypercalcaemia during the recovery phase (Cabral et al. 2020). Lactic acidosis and elevated anion gap metabolic acidosis are also common (Chen et al. 2021).

Clinical Presentation and Diagnosis

The clinical manifestations of traumatic rhabdomyolysis are highly variable. Myalgias are reported in up to 70% of patients, typically presenting as intense cramping pain in proximal muscle groups such as the shoulders, thighs, and calves (Gupta et al. 2021). Dark-coloured urine resembling tea or cola, a hallmark of myoglobinuria, occurs in approximately 50% of cases. Muscle weakness, particularly in the affected compartments, is observed in around 40% of patients (Chavez et al. 2016). Notably, up to 50% of individuals may lack overt muscular symptoms, underscoring the need for a high index of suspicion in trauma settings (Gupta et al. 2021). Systemic symptoms such as fever (20-30%), nausea and vomiting (25%), and profound fatigue are also common (Cabral et al. 2020). Clinical signs may reflect complications: oliguria or anuria, often signals evolving acute kidney injury; cardiac arrhythmias may result from hyperkalaemia; and muscle swelling or tense compartments may indicate evolving compartment syndrome (Chen et al. 2013).

Diagnosis is based on clinical suspicion and biochemical confirmation. CK elevation above five times the upper normal limit (typically >1,000–5,000 U/L) is a key diagnostic marker (Cervellin et al. 2018). A positive urine dipstick for heme without microscopic haematuria strongly suggests myoglobinuria (Bosch et al. 2009). Laboratory workup should include renal function tests, serum electrolytes, lactate, liver enzymes, and arterial blood gases (Chen et al. 2013). Rising creatinine and potassium levels may indicate evolving AKI. Imaging with ultrasound or MRI may assist in evaluating the extent of muscle damage or detecting compartment syndrome (Flores-Ramírez et al. 2022). Differential diagnoses include soft tissue infections, necrotising fasciitis, thermal burns, and hereditary or acquired myopathies (Chatzizisis et al. 2008). Although CK and myoglobin are essential for diagnosis, their prognostic accuracy for AKI or mortality is limited. Composite scores, such as the McMahon Score, have demonstrated superior predictive value for adverse renal outcomes (Cervellin et al. 2018). A McMahon Score of ≥6 calculated at admission has shown a sensitivity of 86% and a specificity of 68% for predicting the need for renal replacement therapy (RRT) (Simpson et al. 2016). Muscle-specific microRNAs (e.g., miR-1, miR-133a) are under investigation as novel biomarkers (Chen et al. 2021).

Management

Intravenous fluids

The cornerstone of management is early and adequate intravenous fluid resuscitation. Evidence from a recent systematic review and meta-analysis suggests that administration of 3–8 litres of isotonic crystalloids per day is associated with the lowest risk of AKI and need for renal replacement therapy (Bitaraf et al. 2024). Protocols administering <3 L/day or >8 L/day were associated with worse outcomes. These findings challenge traditional practices advocating aggressive fluid administration (>10–12 L/day), such as those proposed by earlier reports, which did not show superior clinical benefits and may not be feasible in disaster settings (Ameer et al. 2024).

Although high urine output (200-300 mL/h ) has historically been targeted to prevent pigment nephropathy, current evidence supports fixed-volume resuscitation strategies guided by clinical judgment and dynamic assessments of volume status. Rather than relying solely on a fixed-volume approach, individualised fluid resuscitation tailored to parameters of volume responsiveness and tolerance may lead to improved outcomes (Sharif et al. 2025). Overzealous fluid administration should be avoided due to the risk of pulmonary oedema and abdominal compartment syndrome (Cabral et al. 2020).

Bicarbonate

The use of bicarbonate to alkalinise urine and mitigate myoglobin nephrotoxicity remains controversial. Alkaline urine may reduce myoglobin precipitation in renal tubules and attenuate oxidative damage by limiting free radical generation in acidic environments (Bosch et al. 2009). Bicarbonate therapy is often administered with the aim of maintaining urinary pH above 6.5, theoretically reducing pigment cast formation and protecting tubular integrity. However, concerns persist regarding its potential to exacerbate hypocalcaemia and promote volume overload. Despite widespread use in clinical practice, no randomised controlled trials have demonstrated a clear benefit, and systematic reviews have failed to show consistent improvements in renal outcomes (Michelsen et al. 2019). As such, bicarbonate administration should be considered on a case-by-case basis, particularly in patients with severe acidosis or oliguria, and avoided in those at risk of fluid or electrolyte imbalance.

Diuretics

Mannitol has theoretical benefits as an osmotic diuretic and free radical scavenger, promoting diuresis through increased tubular flow and reducing intratubular cast formation (Cabral et al. 2020). It may enhance renal perfusion and decrease post-ischemic oxidative stress. However, its effectiveness remains uncertain, as highlighted by systematic and high-dose mannitol has been associated with hyperosmolar states and renal dysfunction (Michelsen et al. 2019). Its routine use is not supported by high-level evidence. In contrast, loop diuretics such as furosemide, while often used in ICU settings to manage volume overload, have no role in preventing myoglobin-induced AKI. Although they may increase urine output transiently, they do not address the primary pathophysiological mechanisms such as tubular toxicity and cast formation (Torres et al. 2015). Their use in the early phase of rhabdomyolysis may lead to intravascular volume depletion and exacerbate renal hypoperfusion. Loop diuretics should be reserved for cases with fluid overload and preserved renal perfusion once adequate resuscitation has been achieved. It may be considered in select patients with established compartment syndrome or fluid overload risk (Michelsen et al. 2019).

Renal replacement therapy

Renal replacement therapy (RRT) is indicated in the presence of life-threatening electrolyte disturbances—particularly severe hyperkalaemia unresponsive to medical management—volume overload with refractory pulmonary oedema, progressive metabolic acidosis (pH < 7.1), or overt signs of uraemia (Cabral et al. 2020). Unfortunately, neither continuous renal replacement therapy (CRRT) nor intermittent RRT has been shown to be effective in preventing acute kidney injury (AKI) in patients with rhabdomyolysis (Kodadek et al. 2022).

Continuous renal replacement therapy (CRRT) is preferred in haemodynamically unstable patients, as it allows for gradual fluid and solute removal, minimising the risk of hypotension. Standard dialysis membranes have limited efficacy in clearing myoglobin due to its molecular weight; therefore, adjunctive haemoadsorption strategies have been explored (Forni et al. 2024). Standard dialysis techniques have limited capacity to remove myoglobin due to its molecular weight (~17 kDa) (Zager 1996).

Haemoadsorption

Haemoadsorption cartridges have emerged as a potential adjunctive therapy for removing myoglobin and inflammatory cytokines. According to a 2024 international consensus, haemoadsorption may be considered in patients with myoglobin levels >10,000 ng/mL, particularly if CRRT is already initiated (Forni et al. 2024). Cartridges are typically replaced every 12 hours and discontinued once myoglobin falls below 5,000 ng/mL. Despite encouraging data from case series and retrospective studies, the overall quality of evidence remains low, and large prospective trials are needed.

Experimental treatments include anti-myoglobin monoclonal antibodies and antioxidant agents such as N-acetylcysteine, which have shown renoprotective effects in preclinical models (Chen et al. 2021). Dynamic volume assessment is critical and can be performed using passive leg raising with stroke volume monitoring, point-of-care ultrasound (POCUS), and pulse contour analysis (Monnet et al. 2022). A fluid balance to fluid intake (FB/FI) ratio >0.25 has been associated with increased in-hospital mortality (Argaiz et al. 2021).

Despite decades of clinical experience, no universally accepted guidelines exist for the management of traumatic rhabdomyolysis. Variability in fluid type, volume targets, and use of adjunctive therapies underscores the need for standardised protocols informed by robust evidence. Figure 1 illustrates the pathophysiology and various management strategies for traumatic rhabdomyolysis.

Conclusion

Traumatic rhabdomyolysis in the ICU is a time-sensitive and high-risk condition requiring prompt recognition and evidence-based management. Early isotonic fluid resuscitation remains the most effective strategy to prevent AKI (Bitaraf et al. 2024). While adjunctive therapies such as bicarbonate, mannitol, and haemoadsorption may be beneficial in selected patients, their use should be individualised until stronger data are available (Forni et al. 2024). Future research must focus on prospective validation of fluid strategies, biomarkers, and targeted interventions to improve outcomes in critically ill trauma patients (Ameer et al. 2024).

Conflict of Interest

None.