Rhabdomyolysis is a medical condition caused by the breakdown of skeletal muscle with leakage of intracellular contents into the circulation (Khan, 2009). It can range in severity from a benign asymptomatic illness to a life-threatening condition with a broad range of severe complications including acute renal failure (ARF) (Huerta-Alardin et al, 2005).
The causes of rhabdomyolysis are diverse, but as this article will outline, a number are relevant to the pre-hospital practitioner and for this reason the authors will go on to recommend that those practicing in the pre-hospital environment should have a basic understanding of this condition.
This is not meant as a definitive guide to rhabdomyolysis, many of which have already been produced (Khan, 2009), but more as an introduction for those pre-hospital clinicians not currently familiar with the condition.
As well as considering what rhabdomyolysis is the authors will discuss the implications for pre-hospital practice, before going on to make future recommendations for the inclusion of this condition as a frequent differential, especially in those at-risk patient groups.
What is rhabdomyolysis?
Rhabdomyolysis is a syndrome that is characterised by the destruction of striated (skeletal) muscle leading to the release of cellular contents into the circulating blood plasma (Vanholder et al, 2000). Although there are a number of different causes for this condition, most appear to follow a common pathway of one of two routes, ultimately resulting in the destruction of myocytes and causing their contents, including potassium, phosphate, myoglobin and creatinine kinase (CK) to leak into the circulation in large quantities (Khan, 2009).
The two pathways that most commonly cause rhabdomyolysis are the depletion of adenosine triphosphate (ATP) or the direct effects of cellular damage at a site of injury.
The first, which is more common, is the depletion of ATP, which leads to a failure of the sodium potassium and calcium pumps located within the sarcolemma (membrane) of a myocyte. These two pumps control the internal environment of a cell by removing sodium and calcium and maintaining the homeostatic balance within. Both of these pumps rely on ATP as their source of energy and in rhabdomyolysis, the end result of a number of conditions, there is a failure to produce a sufficient quantity of ATP. When this occurs, the internal environment of the cell suffers significant raises in sodium and calcium, which, in turn, significantly increases enzyme activity within the cell, leading to the breakdown of the cellular membrane. This then leads to the cell contents being released into the extrastitial space and subsequently into the circulation.
The other primary cause is by direct cell injury as seen in various forms of trauma: this causes direct sarcolemmic injury, leading to cell death and the subsequent release of cellular contents (Bosch et al, 2009).
The severity of rhabdomyolysis can range from an asymptomatic elevation of serum muscle enzymes to life-threatening electrolyte imbalances associated with ARF (Dekeyser et al, 2009). The severity is dependent on the nature of the underlying cause and the quantity of muscle involved. As the amount of myoglobin present within circulating plasma exceeds normal levels it crosses the glomerulus, entering renal tubules and resulting in a dark or ‘cola’ colored urine called myoglobinuria.
Rhabdomyolysis with ARF
Acute renal failure, associated with myoglobinuria, is the most serious potential complication of rhabdomyolysis and can present as a life-threatening situation (Bosch et al, 2009). Estimations for the number of patients that suffer ARF secondary to rhabdomyolysis vary widely from 10–50% (Huerta-Alardin et al, 2005), although two studies put the overall risk at 17.5% and 16.5% respectively (Ward, 1988; Fernandez et al, 2005).
As already discussed, during the cellular breakdown characteristic of rhabdomyolysis, large quantities of myoglobin are released from the cellular environment into the extrastitial space and subsequently into the circulation (Khan, 2009). Myoglobin, a protein found within muscle cells, acts in a similar way to haemoglobin by carrying and storing oxygen, and releasing it when required (Tortora and Derrickson, 2011).
In a normal physiological state there is only a small quantity of myoglobin present within the circulation, which is loosely bound to plasma preventing it from crossing the glomerulus and entering the renal tubules (Hunter et al, 2006). However, when just as little as 100 g of skeletal muscle is damaged, the myoglobin present within plasma exceeds the protein's binding ability and, now present in large quantities, it can cross freely across the glomerulus, entering the renal tubules (Hunter et al, 2006; Khan, 2009). As myoglobin progresses through the tubules water is reabsorbed, increasing the concentration, which can lead to the formation of casts, creating an obstructive blockage (Walter and Catenacci, 2008).
Other mechanisms that lead to ARF in rhabdomyolysis include renal vasoconstriction, which can be exacerbated in hypovolaemia, and tubular damage by oxidative injury precipitated by the haem group of myoglobin causing lipids to breakdown (lipid peroxidation), which in turn causes tubular cytotoxicity (Hunter et al, 2006).
A point worth noting here is that glomerular filtration rate (GFR) falls steadily from the age of 40 years in most healthy older people and renal blood flow falls by around 10% per decade (Bowker et al, 2006); therefore, the elderly or any patient who already has chronic kidney disease, with a decreased renal function should be considered to be at a much higher risk of suffering the effects of rhabdomyolysis and subsequently developing ARF (Walter and Catenacci, 2008).
Causes of rhabdomyolysis
There are a broad range of causes for rhabdomyolysis and it is beyond the scope of this review to discuss them all in detail. Instead, Table 1 provides a list of some of the more common causes split into physical and non-physical, a common way of diving the predisposing factors for this condition (Vanholder et al, 2000). It should be clear to the pre-hospital practitioner that a number of conditions they encounter on a regular basis have the risk of going on to develop rhabdomyolysis.
| Physical | Non-physical | ||
|---|---|---|---|
| Trauma and compression |
|
Metabolic syndromes | |
| Occlusion or hypoperfusion |
|
Toxins |
|
| Excessive muscle activity |
|
Infections |
|
| Electrical current |
|
Electrolyte imbalances |
|
| Hyperthermia |
|
Endocrine disorders |
|
| Autoimmune disease |
|
||
‘Due to the broad range of predisposing conditions the pre-hospital clinician should keep an open mind to the potential for rhabdomyolysis being a cause or a complication of the condition afflicting their patient’
Single episodes often occur as a result of infections, drugs or physical factors such as compartment syndrome following crush injuries and pressure from hard surfaces in comatose patients, or patients who have fallen (Lane and Phillips, 2003). There is well-documented evidence of rhabdomyolysis occurring after exercise, particularly in extremes of heat or in those who have never trained before. There are also reports of it occurring after prolonged seizures (Dekeyser et al, 2009) and even a documented case of it being caused by multiple wasp stings (Ito et al, 2012).
Drugs typically linked with rhabdomyolysis are alcohol and opiates; however, any drug that causes states of extreme agitation can induce rhabdomyolysis (Lane and Phillips, 2003). There is also a documented link to the use of statins (Lane and Phillips, 2003; O’Mahony et al, 2008).
Due to the broad range of predisposing conditions the pre-hospital clinician should keep an open mind to the potential for rhabdomyolysis being a cause or a complication of the condition afflicting their patient. If the underlying pathophysiology is understood then the clinician should be able to identify the risk for rhabdomyolysis in the majority of cases without the need to memorise a list of potential causes.
Research conducted in an American emergency department (ED) identified that cocaine, exercise, and prolonged immobilisation were the leading causes of rhabdomyolysis (Fernandez et al, 2005).
Rhabdomyolysis in falls
Falls cost the NHS around £2.3 billion per year (National Institute for Health and Care Excellence (NICE), 2013) and it is estimated that 30% of people over 65 years and 50% of people over 80 years will fall at least once per year (NICE, 2013).
Falls represent a large workload for ambulance services with a survey published in 2006 showing that London Ambulance Service (the busiest in the country) responded to 60 064 falls in 2003–4, a figure that represented 8% of their total 999 workload (Snooks et al, 2006).
Another survey conducted recently, in which 11/13 of the United Kingdom (UK) ambulance services at the time responded, showed the proportion of falls patients left at home was between 7% and 65%, athough the 7% was abnormally low, with every other trust reporting at least 28.4% (Darnell et al, 2012).
As shown above, prolonged immobilisation is a leading cause of rhabdomyolysis and it has long been recognised that this immobilisation can be as a result of collapse, stroke or accidental fall with a prolonged period on the floor (Ratcliffe et al, 1984).
There are no specific guidelines for when rhabdomyolysis is likely to become an issue for those that have suffered a fall, this will depend on a potentially vast number of variables, which may include: the duration the patient has been on the floor, the type of surface, how much they have moved around whilst on the floor, age, previous renal failure, other co-morbidities, hydration status and other injuries suffered.
However, Ratcliffe et al (1984) showed in their survey of elderly collapse that a period as short as one hour was sufficient to see significant increases in creatine kinase (CK), indicative of muscle injury. Whilst this did not necessarily follow through to being a significant event, or go on to cause ARF, it should be noted that shorter time periods of just a few hours present a serious potential risk.
Recognition and testing
The classic triad presentation for rhabdomyolysis is muscle pain, weakness, and myoglobinuria (Huerta-Alardin et al, 2005); which can range from a light pink to a dark black colour. It must be noted, however, that this classic triad does not have to occur for rhabdomyolysis to be present (Walter and Catenacci, 2008) and it may be present in as few as 10% of patients (Huerta-Alardin et al, 2005).
Therefore, definitive testing for rhabdomyolysis is performed by measurement of serum CK with a five-fold increase being considered the minimum for when rhabdomyolysis has occurred (Dekeyser et al, 2009). CK levels rise within 2 to 12 hours of the onset of the muscle injury and peak at 1–3 days after the cessation of the injury and usually begin to fall at 3–5 days (Huerta-Alardin et al, 2005).
Another method which is used, is the measurement of serum or urine myoglobin; however, this has a number of limitations, which is why it is not considered to be definitive. These limitations include the fact that myoglobin is rapidly excreted and levels can return to normal in as little as 1–6 hours following injury with just a transient peak (Walter and Catenacci, 2008).
Another practice frequently used to test for the presence of myoglobin in the urine is to perform urinalysis with dipsticks. The dipsticks will respond to the myoglobin in the urine and show a positive trace for blood due to the fact that myoglobin is a haem-containing compound (Walter and Catenacci, 2008). However, these sticks do not distinguish between myoglobin, haemoglobin and red blood cells (Khan, 2009) and so may be misleading, especially in cases of trauma where there is a risk of haematuria from other causes.
The authors have not been able to identify any reliable method that is routinely practiced for the pre-hospital recognition of rhabdomyolysis, nor does there appear to be any reliable near patient testing for CK that is routinely used for this purpose. For this reason, having a good understanding of the condition, an appreciation of the risk factors and an open mind to the potential for this condition are key in pre-hospital management.
One further investigation that is advocated is gaining an electrocardiogram (ECG). As discussed above, the death of muscle cells releases high levels of potassium into the circulation, this can lead to a hyperkalaemic state (Criner et al, 2002). The pre-hospital recognition of hyperkalemia is challenging; however, an ECG can, but will not necessarily, show changes in hyperkalemia. The classic change is thought to be peaked T waves, although this can be very difficult to determine. Other changes that can occur are a prolonged PR interval, widening QRS and reduced or no P waves. In patients with an already abnormal baseline ECG the only sign of hyperkalemia may be a bradycardia. Cardiac conduction disturbances are much more likely when there has been a rapid rise in potassium levels, for example in acute renal failure (Rull, 2011).
Management
Management of symptomatic rhabdomyolysis, or rhabdomyolysis with ARF should be managed in a hospital environment. The hospital management focuses around the prevention of ARF wherever possible and may include a combination of the following depending on the cause and severity of symptoms:
There is a lack of good randomised controlled trials looking at the management of rhabdomyolysis (Khan, 2009) and there are calls for the traditional use of manitol and sodium bicarbonate to be properly trialed as an increasing number of studies suggest they may not produce the benefit previously thought (Huerta-Alardin et al, 2005).
The current pre-hospital guidelines for paramedics practicing in the UK recognises the risk that rhabdomyolysis presents in heat stroke patients; however, it does not provide any advice on pre-hospital management (Joint Royal Colleges Ambulance Liaison Committee (JRCALC), 2013).
As much of the focus of management is around the early administration of intravenous (IV) fluids to avoid progression of ARF (Bosch et al, 2009), recommendations have been made that this could be initiated in the pre-hospital environment (Khan, 2009).
Implications for paramedic practice
Due to the diverse nature of the causes of rhabdomyolysis, it is likely that most paramedics in the UK will, at some point, encounter this condition, either as the cause for contact, or where it may be a complicating factor to another presentation, for example the elderly patient who has fallen and been immobile on the floor.
Against a backdrop where more ambulance services are encouraging a ‘see and treat’ agenda, complications such as rhabdomyolysis should become common knowledge for those practicing in the pre-hospital arena, otherwise the risks for this potentially life-threatening condition could be easily overlooked.
Due to a lack of previous research, it has not been possible to provide, or to suggest, guidelines for exactly when rhabdomyolysis should be suspected; however, a good understanding is required on the part of any pre-hospital practitioner of the pathophysiology involved.
It is the belief of the authors that this is particularly true for elderly fallers who have been immobile for any period of time over one hour. There is also a consideration that advanced practitioners, such as paramedic practitioners who frequently deal with this patient group, should be given increased training and tools to help screen for this condition.
It is also the recommendation of the authors that future work should be undertaken to determine whether or not rhabdomyolysis should be included as a condition with current UK clinical practice guidelines for paramedics.
Conclusions
Rhabdomyolysis is a potentially life-threatening condition which has a broad range of causes, many of which are frequently encountered in paramedic practice. Chief of which are illicit drug use, excessive exercise and prolonged immobilisation, such as that seen in the elderly faller confined to the floor, where just one hour can be enough to trigger the condition. This last patient group in particular should be considered carefully, as there may not always be an obvious need to initiate transport, and only with a thorough assessment with a good understanding of pathophysiology will the risk of rhabdomyolysis be identified.
As definitive diagnosis takes place from laboratory testing not available in the out-of-hospital environment and the classic triad of symptoms are rarely present together, recognising that the predisposing risks factors for the condition are present is key to safe pre-hospital practice.
There is currently a lack of high-quality evidence reviewing the management of the condition and even less evidence directing the pre-hospital management of the condition, but as the focus of in hospital care is upon early fluid administration to prevent the progression to ARF, it is reasonable to suggest that this could be extended to pre-hospital practice, especially for those facing a prolonged transport time with patients.
Currently, through anecdotal experience of the authors, this condition does not always feature in paramedic education curriculums and, in the setting where clinicians are being encouraged to take a ‘see and treat’ approach, this potentially serious condition should become a routine differential considered in all at risk groups.