Rhabdomyolysis

What is Rhabdomyolysis?

Rhabdomyolysis is a condition in which your skeletal muscles (the muscles that allow your body to move) break down. As a result, parts of the muscle cells like myoglobin (a protein that stores oxygen in your muscles), other muscle proteins, and electrolytes (substances that conduct electricity in your body) leak into your body’s fluids and bloodstream. When you hear the term rhabdomyolysis, it comes from Greek words that mean ‘striped muscle breakdown.’ Common signs of this disease include muscle weakness, aching muscles, swelling, and possibly dark red-colored urine, due to myoglobin being present. This disorder’s severity can vary greatly, from a mild increase in a certain muscle enzyme to medical emergencies like trapped muscle groups (compartment syndrome), low body fluid levels, clotting disruption (Disseminated intravascular coagulation), kidney injury caused by myoglobin, and irregular heartbeats.

A blood test showing elevated levels of an enzyme called creatine phosphokinase (CPK) may indicate rhabdomyolysis, but unfortunately, no specific threshold level of this enzyme is universally used for diagnosis. Many doctors, however, consider a diagnosis if CPK levels are three to five times the normal upper limit, which is approximately 1000 IU per liter. Importantly, rhabdomyolysis is a major cause of sudden kidney failure. Catching it early generally means a better outlook for acute kidney injury caused by rhabdomyolysis.

Various things can cause rhabdomyolysis, including direct injuries and other non-injury related causes. Some specific causes can be major accidents, earthquakes, or other large disasters. However, not every muscle injury will result in rhabdomyolysis and kidney failure. We should also consider other reasons for acute kidney failure, like dehydration, infections, certain drugs, and sustained immobility. Other common causes of rhabdomyolysis without injury include seizures, alcohol use, certain drugs, and being bedridden for prolonged durations.

There have been instances of this condition throughout history. For example, people have experienced muscle breakdown after eating certain types of quail known to consume toxic plants. Similarly, people have reported symptoms of rhabdomyolysis after eating certain birds in Italy that aren’t affected by toxic plants. In more recent history, cases of rhabdomyolysis have been documented during war times.

Rhabdomyolysis can be caused by a variety of factors like trauma, overexertion, lack of oxygen to muscles, infections, abnormalities in metabolism and electrolytes, toxins, certain drugs, and even genetic defects. If someone repeatedly experiences rhabdomyolysis, physicians should examine muscle metabolism to uncover any underlying issues. Damage to muscles can come from direct injury or metabolic issues that harm the muscle’s cell membrane or deplete its energy source, ATP. A drop in ATP can disrupt the way calcium is controlled within the cell. This disruption can lead to persistent contraction, energy depletion, and activation of different enzymes eventually leading to the muscle fiber’s destruction and leakage of cell content.

Often, people with rhabdomyolysis experience muscle pain, dark-colored urine, and weakness, although less than 10% of patients show these characteristic signs. Most often, individuals are not aware they have rhabdomyolysis since it usually presents as abnormalities in lab results without any obvious symptoms. A frequent lab finding in rhabdomyolysis is a high level of the enzyme CPK, which is made by your muscles. Unfortunately, the level of CPK doesn’t necessarily correlate with the severity of muscle damage and kidney failure. Generally, CPK levels higher than 5000 international units per liter suggest significant muscle injury. Treating rhabdomyolysis typically involves providing supportive care, including adequate hydration, to prevent sudden kidney failure.

What Causes Rhabdomyolysis?

Rhabdomyolysis, a serious condition where damaged muscle breaks down quickly, can be caused by two main types of factors: traumatic or physical, and non-traumatic or nonphysical.

Determining the cause of rhabdomyolysis requires a thorough health history assessment, physical exam, and laboratory tests. It’s important to note that the different causes may be more or less common depending on where you are and the behaviors of the community you’re in.

Traumatic or physical causes include anything that physically harms the muscles. This could be due to injury from accidents, long periods of immobility, or abuse. For example, people who’ve been in serious accidents, had prolonged surgeries, or have been physically restrained for a long time are at greater risk. This also applies to those who engage in extremely strenuous exercise, especially without proper training, or are involved in high-intensity events such as fires, explosions, or encounters with high voltage electricity.

Non-traumatic or nonphysical causes relate more to factors that disrupt the body’s normal function, like poor oxygen supply to the muscles, changes in the levels of certain body salts (electrolytes), and abnormal metabolism. Many medications and illicit drugs can lead to rhabdomyolysis, as can various infections. Other conditions that can cause rhabdomyolysis include abnormal levels of electrolytes in the body, some endocrine disorders (issues with hormones), certain muscle disorders, bite from insects or snakes, poisoning, certain autoimmune conditions, some blood disorders, and problems with body temperature regulation.

Trauma, immobility, severe infections, and heart surgeries are among the most common causes of rhabdomyolysis. However, the use of certain cholesterol-lowering drugs is increasingly being linked to the condition. While the occurrences of muscle damage from these medications vary, the condition could get severe enough to cause rhabdomyolysis. Doctors usually recommend stopping the medication as a way to treat this. If muscle damage persists even after stopping the medication, it might indicate a severe autoimmune muscle disease. It’s also advisable to avoid other medications that can make muscle damage worse and to use the lowest effective dose of the cholesterol-lowering drugs, especially for patients who have experienced drug-induced rhabdomyolysis before. It’s worth noting that in some cases, despite thorough investigation, doctors may not be able to identify a specific cause for rhabdomyolysis.

Risk Factors and Frequency for Rhabdomyolysis

Rhabdomyolysis, a serious condition where muscle tissue breaks down rapidly, is reported in about 25,000 cases per year in the USA. Between 5 to 30% of these cases result in acute kidney injury (AKI). It’s interesting to note that rhabdomyolysis accounts for about 15% of all AKI cases. Although it can affect people of any age, it is most common in adults.

• Factors such as being male, African-American, obese, or over 60 years old can increase the risk of rhabdomyolysis.
• The most common cause of rhabdomyolysis in children is infection, accounting for 30% of cases.
• Patients with rhabdomyolysis may often have more than one risk factor.
• Rhabdomyolysis associated with a significant increase in a muscle enzyme called CPK or resulting in ICU admission significantly impacts patient outcomes.
• Even in cases without kidney injury, the mortality rate is around 20%. This figure jumps to 50% when kidney injury is involved.
• Crush syndrome, often related to traumatic injury, can occur in 30 to 50% of rhabdomyolysis cases. Although children are at a lower risk, adults with this complication face higher mortality rates.

Of note, the American College of Cardiology defines rhabdomyolysis related to statin intake as muscle symptoms accompanied by a high creatine kinase level. About 0.5% of patients taking statins may experience significant muscle breakdown, with a higher risk if they are also taking other medications such as gemfibrozil, cyclosporine, cytochrome P450 inhibitors, or steroids. Despite the low incidence of rhabdomyolysis from statins, muscle-related side effects remain a common reason for stopping this therapy.

Unfortunately, the exact incidence of rhabdomyolysis caused by immobilization, alcohol intoxication, fractures, strenuous muscle exercises, and insect bites is unclear due to the sporadic nature of these events.

Signs and Symptoms of Rhabdomyolysis

Rhabdomyolysis is a medical condition that can present different symptoms in different individuals. Common signs include muscle pain, weakness, and urine that’s darker than normal. However, over half of people with rhabdomyolysis won’t experience all of these symptoms. It’s most common for adults with the condition to experience muscle pain, with about 50% reporting this complaint. Around 30-40% notice their urine becoming darker.

There are a variety of other symptoms a person might have, such as muscle cramps, stiffness, swelling, tiredness, stomach pain, nausea, heart palpitations, and fever. The cause of the rhabdomyolysis often influences the symptoms a person experiences. For example, if it’s caused by drug use, insect bites, heat exertion, surgery, accidents, medication changes, antibiotic use or certain supplements, this might affect how it manifests. People with muscle diseases (myopathies) might experience weakness as their main complaint.

• Muscle pain
• Muscle weakness
• Dark-colored urine
• Cramps, stiffness, swelling in muscles
• Fatigue
• Abdominal pain
• Nausea
• Palpitations and fever

Rhabdomyolysis can also impact the body more globally. For example, symptoms may include fever, tiredness, nausea, confusion, agitation, delirium, and changes in urine color or output. In those who’ve suffered trauma, checking blood circulation and nerve function in the limbs is a priority, as rhabdomyolysis can lead to reduced blood flow and nerve damage.

In a patient who is unconscious and has dark-colored urine, testing can help determine if the color change is due to blood or proteins in the urine like myoglobin. This protein can be verified if no red blood cells are present in the urine. Spotting rhabdomyolysis early is crucial to prevent further complications.

Testing for Rhabdomyolysis

The key sign of acute rhabdomyolysis, a severe condition that causes muscle fibers to break down, is unusually high levels of a protein named creatine phosphokinase (CPK). In some cases, you might notice that your urine has a reddish-brown color; this changes because of the presence of another protein, myoglobin, in your urine. However, this is not present in all cases.

Your doctor will conduct some basic laboratory tests to check for this condition. These tests include checking your blood count, levels of various substances in your blood (such as CPK), and examining urine samples. They might also check your heart’s electrical activity using an electrocardiogram (EKG) and take a chest X-ray.

Normal CPK levels are usually between 20 to 200 IU/L. When your CPK levels are at least five times the upper limit of normal, this suggests rhabdomyolysis. CPK comes in four forms. One type, CK-MM, is specific to skeletal muscles. Two other types (CK-MB 1 and 2) relate to the heart muscle. The last one, CK-BB, is found in the brain.

With rhabdomyolysis, the myoglobin protein is released more than usual and is excreted in your urine, resulting in a tea-colored urine. However, only about half of patients with rhabdomyolysis have this symptom. Also, bear in mind that because myoglobin is broken down quickly in the body, it may not always be detected in your urine.

Rhabdomyolysis can also cause changes in the levels of certain substances in your blood, such as potassium, phosphate, and calcium. This is due to the excessive breakdown of muscle tissues. Hypocalcemia, or low calcium levels, can occur, as well as increased levels of uric acid, a waste product produced during the breakdown of food and cells. You might also experience changes in your body’s acid-base balance, which can lead to metabolic acidosis, a condition that occurs when your body produces too much acid or when the kidneys aren’t removing enough acid from the body.

Your EKG results could show changes in heart activity due to hyperkalemia (excess potassium in the blood) and hypocalcemia. Additionally, lab results could show elevated levels of certain white blood cells and inflammatory proteins (ESR and CRP).

One possible complication of rhabdomyolysis is acute kidney injury which can arise from various factors, such as loss of body fluids, drug effects, dehydration, and insufficient blood flow to the kidneys. The risk of this complication depends on the initial levels of CPK; patients with very high levels present an increased risk. Other factors, such as hydration status, initial serum creatinine levels (an indicator of kidney function), and levels of calcium, phosphate, and bicarbonate in the body, can also be predictors.

A serious complication involving blood clotting, known as disseminated intravascular coagulation (DIC), can sometimes happen in severe cases of rhabdomyolysis.

Doctors might also use imaging techniques like X-rays or CT scans to identify other issues such as fractures or swelling of muscle groups. However, more specialized testing such as MRI scans, muscle biopsies, or electromyography (a test for muscle and nerve function) is usually not necessary to diagnose rhabdomyolysis. These tests are generally reserved for cases where an inflammation of the muscles or recurrent rhabdomyolysis is suspected.

Treatment Options for Rhabdomyolysis

Managing rhabdomyolysis, a condition where a large amount of muscle tissue breaks down and releases substances into the blood that can damage the kidneys, is all about replenishing fluids in the body and protecting the kidneys. It starts by figuring out the main cause of the rhabdomyolysis and stopping it. Keeping up the hydration level is extremely important to help maintain better circulation and heart function. Regular check-ups help to correct any imbalances in the body’s electrolytes and identify any complications such as compartment syndrome, a painful and potentially serious condition caused by pressure build-up from internal bleeding or swelling of tissues.

Managing Rhabdomyolysis in Trauma Cases

For those who have rhabdomyolysis due to a traumatic event like a crush injury, it is crucial to start fluid replacement via an IV as soon as possible, preferably at the site of injury. A large amount of fluids may be needed to maintain proper blood volume and urine output. Fluid replacement helps to prevent kidney damage and the need for kidney dialysis. However, for patients trapped under debris for an extended time, fluid replacement may be challenging and kidney damage may have already occurred by the time they receive medical help. Too much fluid replacement can lead to fluid overload in patients who already have signs of kidney injury.

Once in the hospital, constant monitoring of urine output is necessary. Some doctors may recommend alkalinization of urine to prevent myoglobin, a blood pigment, from building up in the kidneys. However, this can be associated with a drop in blood calcium levels, and thus, close monitoring is required.

Medications like Mannitol, which increases urine production, may be used to help clear the kidneys in patients with crush injuries. It should only be used after adequate urine flow is established. Its use is controversial for patients already with acute kidney injury.

Efforts should be made to prevent an excessive amount of potassium in the blood. If there is severe potassium elevation, treatments like glucose and insulin administration or specific potassium-lowering medications might be needed.

Patients needing long-term IV fluid should also have a urinary catheter placed to monitor urine output accurately. Fluid replacement should continue until signs of muscle breakdown in the urine are gone and muscle enzyme levels are decreasing. In severe cases, kidney dialysis might be necessary.

Managing Non-traumatic Rhabdomyolysis

Rhabdomyolysis caused by non-traumatic reasons needs similar treatment. Adequate hydration with fluids through an IV should be provided based on what caused the rhabdomyolysis. The aim is to maintain a decent volume of urine output and a downward trend in muscle enzyme levels. In severe cases, alkaline diuresis (increased urine output and alkalinization) can be considered if the patient doesn’t have any signs of kidney damage.

Managing Electrolyte Imbalance in Rhabdomyolysis

Rhabdomyolysis can cause levels of several electrolytes (substances needed in the body for many functions), including potassium, calcium, uric acid, and phosphate, to become imbalanced in the blood. Treatments depend on the electrolyte involved and the symptoms the patient is experiencing. For example, high potassium levels can be managed by avoiding fluids containing potassium and using bicarbonate in the fluids. Higher than normal uric acid levels can be managed with medication like allopurinol if the level is quite high.

Other Treatments

If the patient has sepsis (a serious infection), appropriate use of antibiotics and blood pressure-boosting medicines may be needed. An urgent consultation with an orthopedic surgeon may be needed in the case of compartment syndrome. A specific diet might also be essential for people with inherited muscle diseases to improve their symptoms.

What else can Rhabdomyolysis be?

While diagnosing certain medical conditions, doctors need to consider some other potential diagnoses as well, such as:

• Hypothermia (dangerously low body temperature)
• Malignant hyperthermia (a severe reaction to certain drugs used during surgery)
• Neuroleptic malignant syndrome (a reaction to certain psychiatric medications)
• Sepsis (a life-threatening complication of an infection)
• Inflammatory myositis (inflammation of muscle tissue)
• Inherited myopathies (muscular diseases inherited through the genes)
• Guillain-Barré syndrome (a neurological disorder where the body’s immune system attacks your nerves)
• Hyperosmolar conditions (excessively high levels of certain substances in the body’s fluids)

What to expect with Rhabdomyolysis

The outlook for rhabdomyolysis, a condition where muscle tissue breaks down and releases a damaging protein into the blood, can differ based on what’s causing it. However, even when patients develop a condition known as AKI (Acute Kidney Injury), which is when the kidneys suddenly stop working properly, most people have positive outcomes and their kidney function completely recovers.

Possible Complications When Diagnosed with Rhabdomyolysis

Common Complications and Risks:

• Sudden kidney damage or failure
• Imbalances of electrolytes, minerals needed for bodily functions
• Irregular heartbeat
• Increased pressure within a muscle compartment that compromises blood flow
• A condition causing blood clots to form throughout the body’s small blood vessels
• Severe kidney disease that requires dialysis or transplant
• Infections due to an extended stay in the hospital

Recovery from Rhabdomyolysis

Individuals who have survived traumatic rhabdomyolysis, a condition where a large amount of muscle breakdown occurs, may need surgeries related to the bone (orthopedic) or blood vessels (vascular). Even if they recover from rhabdomyolysis with or without Acute Kidney Injury (AKI) – a situation where the kidneys suddenly stop working, they still need rehabilitation. This is crucial to improve their ability to move and function normally again.

Preventing Rhabdomyolysis

If you have a condition called rhabdomyolysis, it’s important to be aware of the risk factors and understand how to avoid it happening again in the future. This condition involves damage of the muscles which can release harmful substances into the blood. If your doctors suspect that your muscle damage is caused by inflammation or metabolic issues (meaning problems with the chemical reactions that your body needs to function properly), they may need to do additional tests, like a biopsy which is a procedure where a small sample of your muscle tissue is removed and studied.

If you have survived a specific type of this condition known as ‘traumatic rhabdomyolysis crest syndrome’, which is caused by a severe injury, you might need psychological support and potentially medication. It might come as a shock when diagnosed, but there’s no need to worry as doctors are equipped with strategies to deal with these situations.

Your doctors should also inform you about other available alternatives that can help manage the condition. As this can be a genetic condition, meaning it can run in the family, it would be wise for your family members to also get checked for potential heritable causes. This is to ensure early detection and timely management if any of your family members are also at risk.