Management of Rhabdomyolysis on the ICU
Dr John Griffiths DICM MRCP FRCA MA
Focus on management of rhabdomyolysis on the ICU
Rhabdomyolysis accounts for approximately 5-10% of acute renal failure (ARF) managed on the ICU. The pathogenesis of ARF associated with rhabdomyolysis can be described in terms of pre-renal, intrinsic and post-renal factors. Common associations include major trauma, drug overdose with narcotics, vascular embolism and response to a variety of agents that induce major muscle injury (Table 1). The management of ARF associated with rhabdomyolysis is informed predominantly by retrospective data, small series, and multivariate logistic regression analysis, as no prospective randomised controlled trial has been conducted. Important aspects of management include prompt and aggressive fluid resuscitation, elimination of causative agents, correction of compartment pressures, alkalisation of urine (pH > 7.5) and ensuring adequate polyuria ( > 300mls/hr). A summary of the management principles is given Table 2.
Table 1. Common causes of rhabdomyolysis encountered on the ICU
- ‘Crush injuries’
- Prolonged immobilisation
- The elderly
- Drug overdose
- Vascular occlusion
- Prolonged surgery
- lithotomy position
- Burns and electrocution injury
Table 2. Management of rhabdomyolysis on the ICU
- Confirm diagnosis
- General management
- Exclude compartment syndrome
- Appropriate fluid resuscitation
- Only treat hypocalcaemia if patient symptomatic (risk of crystal CaPO4 precipitation)
- Consider urgent renal replacement therapy if hyperkalaemia resistant to medical management
- Acute renal failure may be prevented by:
- Prompt and appropriate fluid resuscitation (6-10 L/day crystalloid for 3-5 days)
- Forced alkaline diuresis (maintain urinary pH >6 and blood pH <7.5 with up to 500 ml/h 1.24% sodium bicarbonate)
- Fluid overload managed by:
- Furosemide and/or mannitol
- Careful monitoring and replacement of electrolyte
- If ARF established
- Continuous renal replacement therapy (dose 35 ml/kg/h)
Focus on diagnosis of rhabdomyolysis
Diagnosis of rhabdomyolysis invariably depends on serum creatinine kinase (CK) or myoglobin levels or the presence of myoglobinuria. In patients with severe rhabdomyolysis, the serum CK level predicts the development of ARF. However, the true value of CK as an accurate prognostic tool has not been determined given the wide range of CK levels found. Myoglobin plays a major role in rhabdomyolysis-induced acute renal failure. Suggested mechanisms of renal tubular injury include tubular obstruction and lipid peroxidation. The metabolism of myoglobin is poorly understood. The major routes for myoglobin elimination include both the reticuloendothelial system and renal tubule, and under normal conditions, only small amounts of myoglobin are detected in both serum and urine. Studies have demonstrated that patients treated with forced alkaline diuresis for rhabdomyolysis show faster elimination kinetics for serum myoglobin than CK. This suggests that myoglobin may be the main pathogen for ARF associated with rhabdomyolysis, and monitoring of serum myoglobin level, rather than that of CK, should be used to guide therapy.
Focus on the use of mannitol in preventing acute tubular necrosis (ATN)
The use of mannitol has been promoted in patients considered to be at high risk for ATN, such as those at risk of rhabdomyolysis and those undergoing vascular (aortic aneurysm), cardiac and renal transplantation surgery. Many of the studies indicate that mannitol increases urine flow but does not reduce the incidence of ATN. More convincing are the results obtained with the prophylactic administration of mannitol during renal transplant surgery, just before clamp release. In a randomised study comparing moderate hydration with or without mannitol administration, the incidence of post transplant ATN was significantly lower in the mannitol group both in cyclosporin and in azathioprine-treated patients. At the current time, there is little evidence to support the prophylactic use of mannitol in non-transplant surgery. Moreover, there are no randomised, controlled clinical trials of the use of mannitol in the face of rhabdomyolysis. Animal studies suggest that urinary alkalinisation with HCO3- and the administration of mannitol (after prompt and adequate volume resuscitation) may have a role in the management of patients with severe rhabdomyolysis. In the absence of complicating factors such as severe hypokalaemia and hypocalcaemia, administration of mannitol is associated with a low level of significant adverse effects.
Focus on renal replacement therapy
If rhabdomyolysis leads to the established of renal failure, renal replacement therapy (RRT) may be indicated. There are several important considerations in the face of RRT:
Daily vs alternate day intermittent haemodialysis (IHD)
Daily IHD reduces mortality without increasing haemodynamically induced morbidity in patients with ARF. This was demonstrated in a randomised controlled trial of 160 patients, comparing daily IHD with conventional (alternate-day) IHD.
Dose of haemofiltration
Evidence comes from a randomised controlled trial that randomised patients with ARF to treatment with haemofiltration at three different doses of: 20 ml/kg/h, 35 ml/kg/h and 45 ml/kg/h. Survival in the 20 ml/kg/h group was inferior to that observed in the 35 ml/kg/h and the 45 ml/kg/h groups. No survival advantage was observed between the two highest doses. Thus, the authors’ conclusion was that the optimal dose for haemofiltration is 35 ml/kg/h.
Intermittent haemodialysis (IHD) vs continuous renal replacement therapy (CRRT)
A meta-analysis of more than 600 patients found no significant difference in mortality of critically ill patients with ARF treated with IHD compared with CRRT. However, in the face of the haemodynamic instability often found on the ICU, most intensive care practitioners would favour CRRT.
Key learning points
- Rhabdomyolysis is often encountered on the ICU
- The modern day management of rhabdomyolysis does not have a large evidence base
- Serum myoglobin may be a useful marker of progression of rhabdomyolysis
- In established renal failure there is evidence is in favour of continuous renal replacement therapy at a dose of 35 ml/kg/h.
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