Crush Injury, Crush Syndrome, Traumatic Rhabdomyolysis, Muscle Reperfusion syndrome

1. Description of the problem

Crush injury is a direct injury resulting from the crush.

Crush Syndrome is the systemic manifestation of muscle cell damage resulting from pressure or crushing.

Initially described by Bywaters and Beall in 1941in a patient who initially appeared to be unharmed but subsequently died of renal failure.

Crush Injury: Compression of extremities or other parts of the body that causes muscle swelling and/or neurological disturbances.

Crush Syndrome: Crush injury with systemic manifestations. Systemic manifestations are caused by a traumatic rhabdomyolysis due to muscle reperfusion injury when compressive forces on the tissues are released.This can cause local tissue injury, organ dysfunction, and metabolic abnormalities, including acidosis, hyperkalemia, and hypocalcemia.

Clinical features

Some or all of the following clinical signs and symptoms may be present:

• Cardiovascular instability

  Hypotension and hypovolemic shock. This may be caused from the massive fluid shift from the extracellular fluid space into the damaged cell s or associated injuries causing blood loss.

  Arrhythmia and negative inotropy secondary to hyperkalemia, hypocalcemia and hyperphosphatemia

  Cardiomyopathy

• Renal failure

  Secondary to circulatory shock and intravascular volume depletion leading to renal cortical ischemia.

  Release of myoglobin, urate, phosphate and purine by the muscle cells causes precipitation in the distal convoluted tubules, causing tubular obstruction.

• Metabolic acidosis with lactic acidosis

• Disseminated intravascular coagulopathy

• Hypothermia

• Myoglobinuria

• Skin injury and swelling

• Paralysis and paresthesia

• Pulses may or may not be present.

• Compartment syndrome

• Acute lung injury / ARDS

Key management points

Primary survey with focus on airway, breathing and circulation.

Establishing intravenous access and initiation of fluid resuscitation prior to releasing the crushed extremity, especially if the time of entrapment is > 4 hours.

If extrication is impossible short-term use of tourniquet on the affected limb is recommended until intravenous access can be obtained.

Acute limb amputation should be avoided until extrication is impossible.

Continue with fluid resuscitation while transfer to a medical facility is initiated.

Monitor the crushed limb for the 5 P’s: Pain, Pallor, Paresthesia, Pain with passive movement and Pallor.

Combat hypotension with aggressive hydration.

Prevention of renal failure is important. Alkaline diuresis and mannitol therapy is recommended. Hemodialysis is also recommended for acute renal failure.

Electrolyte abnormalities (hypokalemia / hypocalcemia / hyperphosphatemia) need to be monitored and treated accordingly.

Monitoring for cardiac arrhythmia is recommended.

Correction of acidosis with alkalinization of the urine is critical.

Monitoring for compartment syndrome is also recommended. If present it should be treated with fasciotomy. Fasciotomies should not be performed if the compartment syndrome has been present for > 24 hours.

Open wounds should be treated with antibiotics, tetanus toxoid and debridement of necrotic tissue.

Hyperbaric oxygen therapy may be useful.

2. Emergency Management

The management of crush syndrome should focus on preventing the systemic complications of the syndrome. It is important to understand the pathophysiology of the process and treat accordingly.

Extrication

Extrication should be prompt as the time of entrapment of a limb is directly proportional to the development of crush syndrome. Basic Life Support measures should be started with assessment of airway, breathing and circulation, especially establishment of intravenous access. If possible, fluid resuscitation should be started prior to extrication, especially in limbs trapped > 4 hours. Attention should also be focused on the possibility of concomitant injury (fractures, organ damage, spinal injury and obvious hemorrhage). High-flow oxygen should be started and the patient should be transferred to a medical facility as soon as possible.

Applying tourniquets for more than 2 hours may cause rhabdomyolysis and neurovascular damage, and hence the current consensus is to avoid using tourniquets. There are some theoretical benefits to applying tourniquets, especially in the patient in whom intravenous access cannot be obtained prior to extrication of the entrapped limb. Tourniquets may delay the onset of reperfusion syndrome in a crushed limb as well as control hemorrhage. But if applied, tourniquets should not be released before medical facilities are available.

All attempts should be made to preserve the crushed limb. Amputations should be considered only as a life-saving measure. If extrication is impossible, amputation prior to release of the crushing force would delay onset of reperfusion syndrome and the systemic effects of crush syndrome.

Fluid resuscitation

Intravenous access and fluid resuscitation is the mainstay of treatment. This should start before the start of extrication and reperfusion syndrome. Aggressive resuscitation using warm Normal Saline is recommended to reverse metabolic acidosis, improve coagulation cascade and prevent renal failure. Ringer’s Lactate should be avoided as it contains potassium. Dextrose should be avoided until resolution of shock and establishment of normovolemia. A Foley catheter should be inserted as early as possible.

Some general guidelines for fluid resuscitation:

• 1 to 1.5 l/h for young adults

• 20 cc/kg/h for children

• 10 cc/kg/h for elderly

Target urine output

• Adults: > 50cc / h

• Children: > 2cc/kg/h

Algorithm for managing crush injury

During Extrication

This may last 4-6 hours or longer. Start intravenous fluids (preferably Normal Saline) at 1L/h.

After Extrication:

Arrange for transfer to hospital.

Insert invasive monitoring (central line and arterial line) and Foley catheter. Monitor blood pressure and urinary output closely.

Continue resuscitation with normal saline at 1L/h.

Once normovolemia achieved, alternate with 5% dextrose solution.

Some general guidelines for fluid resuscitation:

• 1 to 1.5 l/h for young adults

• 20 cc/kg/h for children

• 10 cc/kg/h for elderly

Target urine output

• Adults: > 50 cc / h

• Children: > 2 cc/kg/h

After Hospital Admission:

Sodium bicarbonate (50 meq/L) is added to every second or third dextrose bottle to keep urine pH > 6.5. Monitor for target urine output at all times.

After Evidence of adequate urine output:

Start 20% mannitol (1-2 gm/kg body weight) over 4 hours.

Urine output needs to be maintained at 8 L/day (except in elderly) and may require infusion of 12 L/day.

Metabolic Alkalosis:

If arterial blood pH is > 7.45 (secondary to bicarbonate administration) acetazolamide can be given as an I.V. bolus of 500 mg.

Correct electrolyte abnormalities aggressively:

Hyperkalemia, hyperphosphatemia and hypocalcemia should be aggressively treated.

End Point:

Usually by Day 3 – myoglobin is eliminated from the urine.

CAUTION:

Mannitol should not be given to patients with anuria.

Blood osmolar gap should be maintained below 55 mOsm/kg (less than 1000 mg/d mannitol in blood).

Mannitol dose should be kept below 200 g/d (leads to acute renal failure in higher doses).

3. Diagnosis

Diagnostic criteria

Early diagnosis is crucial in patients, especially if they develop rhabdomyolysis. Patients who sustain soft tissue injury or ischemia–reperfusion injury are at risk of developing rhabdomyolysis, myoglobinuria, and renal failure. Patients may present with painful, swollen extremities and should be monitored for compartment syndrome. Physical examination is usually difficult and unreliable. Dark, tea-colored urine that is dipstick positive for blood despite the absence of red blood cells on microscopy is suggestive of myoglobinuria and rhabdomyolysis.

Patients who are believed to be at risk on the basis of history and physical examination should have their urine output monitored and serial serum creatine kinase levels drawn. Other labs of importance are serum blood urea nitrogen, creatinine, uric acid, potassium, phosphorus and calcium.

Release of myoglobin into the circulation is an important indicator of significant muscle injury. Normal levels are less than 85 ng/ml (but depends on normal laboratory values). Initially serum myoglobin values are higher than urine ones. Once myoglobin is cleared from the body these results are flipped. Thus it is best to follow both these values during the disease process. Creatinine phosphokinase values are a marker of muscle damage and can be very high in crush injuries.

Normal lab values

Laboratory derangements usually seen are:

Creatine kinase > 10,000 U/L

Oliguria (urine output) < 400 mL/24 hrs

Blood urea nitrogen > 40 mg/dL

Serum creatinine > 2 mg/dL

Uric acid > 8 mg/dL

Potassium > 6 meq/L

Phosphorus > 8 mg/dL

Calcium < 8 mg/dL

Normal Values

Creatine kinase: 8-150 U/L

Blood urea nitrogen: 7-20 mg/dL

Serum creatinine: 0.5-1.4 mg/dL

Uric acid: 2.0-7.5 mg/dL

Potassium: 3.5-5.3 meq/l

Phosphorus: 2.5-4.8 mg/dL

Calcium: 8.8-10.3 mg/dL

Release of myoglobin into the circulation is an important indicator of significant muscle injury. Normal levels are less than 85 ng/ml (but depends on normal laboratory values). Initially serum myoglobin values are higher than urine ones. Once myoglobin is cleared from the body these results are flipped. Thus it is best to follow both these values during the disease process.

Creatinine phosphokinase values are a marker of muscle damage and can be very high in crush injuries.

Other possible diagnoses

Tumor lysis syndrome

Heat stroke

Exertional rhabdomyolysis

High-voltage electrical injury

Diagnostic tests

Serum and urine myglobin

Creatinine phosphokinase

Standard urine dipstick (heme-positive urine in the absence of red blood cells suggests myoglobinuria. This test is positive only 50% of the time, and thus a normal urine dipstick does not rule out myoglobinuria).

4. Specific Treatment

Extrication

Extrication should be prompt as the time of entrapment of a limb is directly proportional to the development of crush syndrome. Basic Life Support measures should be started with assessment of airway, breathing and circulation, especially establishment of intravenous access. If possible, fluid resuscitation should be started prior to extrication, especially in limbs trapped > 4 hours. Attention should also be focused on the possibility of concomitant injury (fractures, organ damage, spinal injury and obvious hemorrhage). High-flow oxygen should be started and the patient should be transferred to a medical facility as soon as possible.

Applying tourniquets for > 2 hours may cause rhabdomyolysis and neurovascular damage. and hence the current consensus is to avoid using tourniquets. There are some theoretical benefits to applying tourniquets. especially in the patient in whom intravenous access cannot be obtained prior to extrication of the entrapped limb. Tourniquets may delay the onset of reperfusion syndrome in a crushed limb as well as control hemorrhage. But if applied. tourniquets should not be released before medical facilities are available.

All attempts should be made to preserve the crushed limb. Amputations should be considered only as a life-saving measure. If extrication is impossible. amputation prior to release of the crushing force would delay the onset of reperfusion syndrome and the systemic effects of crush syndrome.

Fluid resuscitation

Intravenous access and fluid resuscitation is the mainstay of treatment. This should start before the start of extrication and reperfusion syndrome. Aggressive resuscitation using warm Normal Saline is recommended to reverse metabolic acidosis, improve coagulation cascade and prevent renal failure. Ringer’s Lactate should be avoided as it contains potassium. Dextrose should be avoided until resolution of shock and establishment of normovolemia. A Foley catheter should be inserted as early as possible.

Some general guidelines for fluid resuscitation:

• 1 to 1.5 l/h for young adults

• 20 cc/kg/h for children

• 10 cc/kg/h for elderly

Target urine output

• Adults: > 50 cc / h

• Children: > 2 cc/kg/h

During extrication

This may last 4-6 hours or longer. Start intravenous fluids (preferably Normal Saline) at 1L/h.

After extrication

Arrange for transfer to hospital.

Insert invasive monitoring (central line and arterial line) and Foley catheter. Monitor blood pressure and urinary output closely.

Continue resuscitation with normal saline at 1L/h.

Once normovolemia achieved, alternate with 5% dextrose solution.

Some general guidelines for fluid resuscitation:

• 1 to 1.5 l/h for young adults

• 20 cc/kg/h for children

• 10 cc/kg/h for elderly

Target urine output

• Adults: > 50 cc / h

• Children: > 2 cc/kg/h

After hospital admission

Sodium bicarbonate (50 meq/L) is added to every second or third dextrose bottle to keep urine pH > 6.5. Monitor for target urine output at all times.

After evidence of adequate urine output:

Start 20% mannitol (1-2 gm/kg body weight) over 4 hours.

Urine output needs to be maintained at 8 L/day (except in elderly) and may require infusion of 12 L/day.

Mannitol also has the ability to decrease intracompartmental pressure in crushed limbs.

Mannitol should not be given to anuric patients and should be started after documenting urine output.

Mannitol also scavenges oxygen free-radicals and may help to prevent damage of renal parenchyma, cardiac and skeletal muscles that may be caused during reperfusion.

Metabolic alkalosis

If arterial blood pH is > 7.45 (secondary to bicarbonate administration) acetazolamide can be given as an I.V. bolus of 500 mg.

Electrolyte abnormalities

Hyperkalemia, hyperphosphatemia and hypocalcemia should be aggressively treated.

Rewarming

Patients who have been trapped have a high risk of hypothermia both primary and secondary. Although hypothermia may be protective, extremely low core temperatures has been associated with clotting abnormalities, hyperkalemia and cardiac arrhythmias. Studies have shown that less aggressive rewarming is associated with increased mortality. Aggressive rewarming methods should be employed as soon as possible (warm intravenous fluids, warm air blankets, heat lamps, warmed respiratory gases, bladder and peritoneal lavage may be considered, warm enemas and ultimately cardiopulmonary bypass may be considered in cases of profound hypothermia).

Analgesia

Pain is usually a late sign. (Early on crushed limbs are only mildly painful secondary to neuropraxia and may mask compartment syndromes.)

Potassium binders

Hyperkalemia is one of the most fatal complications of crush injury. Sodium polystyrene sulfonate should be given orally or rectally to prevent hyperkalemia during reperfusion. Usual dose used is 15 g per day.

Allopurinol

Allopurinol is a xanthine oxidase inhibitor and also reduces the production of oxygen free-radicals. Reducing uric acid production also may be protective and may help prevent renal parenchymal injury.

Other diuretics

Other diuretics (furosemide, dopamine, angiotensin converting enzyme inhibitors) have been used with very limited success.

Amiloride: is a potassium-sparing diuretic that inhibits sodium–hydrogen and sodium–calcium exchange. Reduction in intracellular calcium improves contractile and metabolic recovery during post-ischemic reperfusion.

Benzamil: An analogue of amiloride that is even more potent in its ability to block sodium calcium exchange

Calcium

Hypocalcemia is common. Administered calcium is rapidly sequestered in the injured muscle and does not correct serum calcium. Also, as the disease progresses and myocytes die, calcium is released into the systemic circulation, causing rebound hypercalcemia. Thus, correction of hypocalcemia and administration of calcium is not recommended unless required for cardiac arrhythmias and hyperkalemia.

Dialysis and Hemofiltration

Oliguria or anuria responsive to treatment, fluid therapy, volume overload, and a rising serum potassium (47 mEq/L) are indicators of the need for dialysis. Dialysis is usually required 2 or 3 times daily for 13–18 days to restore renal function and urine flow. All types of renal-replacement therapy (intermittent hemodialysis, continuous renal replacement therapy and peritoneal dialysis) should be considered depending on availability.

Sepsis

Sepsis is the major cause of mortality from crush injury. Wound infections, peritonitis or pneumonitis and open injuries should be treated aggressively and high-calorie feeding should be started to prevent nutritional deficiencies.

Hyperbaric oxygen therapy

Hyperbaric oxygen therapy prevents secondary injury and keeps partially injured tissue viable. It increases the amount of oxygen dissolved in plasma. Hyperoxia is thought to have several benefits. The diffusion radius is greater, supplying oxygen to underperfused tissue. It also causes vasoconstriction and reduces capillary transudate and interstitial edema, thus slowing the progression to compartment syndrome. It also prevents neutrophil adhesion and prevents secondary injury. It is directly bactericidal to anaerobic organisms. It also enhances fibroblast differentiation, collagen synthesis and angiogenesis, leading to increased wound closure rates in hypoxic tissues.

Topical negative pressure therapy

This has been shown to improve wound healing. It has been found in animal studies to significantly decrease levels of circulating myoglobin, and hence progression to myglobinuric acute renal failure (ARF) and systemic crush syndrome are stopped.

Gastric pentadecapeptide BPC 157

This is an experimental drug that helps with wound healing. The mechanism of action is based on its ability to increase reticulin and collagen formation. Unfortunately this is not commercially available yet.

End Point

Usually by Day 3 – myoglobin is eliminated from the urine.

Fluid resuscitation:

• 1 to 1.5 l/h for young adults

• 20 cc/kg/h for children

• 10 cc/kg/h for elderly

Target urine output:

• Adults: > 50 cc / h

• Children: > 2 cc/kg/h

Sodium bicarbonate (50 meq/L) is added to every second or third dextrose bottle to keep urine pH > 6.5. Monitor for target urine output at all times.

20% mannitol (1-2 gm/kg body weight) over 4 hours.

If arterial blood pH is > 7.45 (secondary to bicarbonate administration) acetazolamide can be given as an I.V. bolus of 500 mg.

Kayexalate for hyperkalemia – maximum of 15G per day.

Patients who do not respond to hydration and forced diuresis usually require hemodialysis. Most patients who present with an initial serum creatinine of more than 1.7 mg/dL and up to one third of all patients with rhabdomyolysis require hemodialysis.

5. Disease monitoring, follow-up and disposition

• Obtain initial serum CPK.

• Monitor urine output hourly.

• Monitor urine pH hourly.

• Arterial blood gas every 4 hours

• Serial electrolytes every 6 hours

• BUN and creatinine every 8 hours

• Compartment pressures every 4 hours

• Invasive monitoring (central line and pulmonary artery catheter) may be required in patients with cardiac and pulmonary disease.

Intensive care support may be required for the complications of crush syndrome. Patients who become oliguric or anuric are likely to require dialysis. Patients with acute renal failure may require prolonged dialysis and may need follow-up.

Pathophysiology

The pathophysiology begins with muscle injury and muscle cell death.

• Immediate cell disruption.

• Direct pressure on muscle cells: The direct pressure causes muscle cells to become ischemic. Anaerobic metabolism ensues, generating lactic acid. Ischemia causes the cell membranes to leak.

• Vascular compromise: Large vessels are compressed, leading to loss of blood supply to muscle tissue.

• Injured muscle tissue releases toxins. The crushing force may serve as a protective mechanism, preventing these toxins from reaching the central circulation.

• Following extrication the toxins exert their effects systemically.

  Amino acids and other organic acids – acidosis, aciduria, and dysrhythmia

  Creatine phosphokinase – markers for crush injury

  Free radicals, superoxides, peroxides – formed when oxygen is reintroduced into ischemic tissue

  Histamine – vasodilation, bronchoconstriction

  Lactic acid – major contributor to acidosis and dysrhythmias

  Leukotrienes – lung injury (adult respiratory distress syndrome) and hepatic injury

  Lysozymes

  Myoglobin – precipitates in kidney tubules, especially in the setting of acidosis with low urine pH; leads to renal failure

  Nitric oxide – causes vasodilation, which worsens hemodynamic shock

  Phosphate – hyperphosphatemia causes precipitation of serum calcium, leading to hypocalcemia and dysrhythmias

  Potassium – hyperkalemia causes dysrhythmias

  Prostaglandins – vasodilation, lung injury

  Purines (uric acid) – may cause further renal damage

  Thromboplastin – disseminated intravascular coagulation

• Third spacing. Leaking cell membranes and capillaries cause intravascular fluids to accumulate in injured tissue.

• Compartment syndrome

• The time to injury and cell death varies with the crushing force involved.

• Skeletal muscle can tolerate ischemia for up to 2 hours without permanent injury, reversible cell damage occurs by 2-4 hours and by 6 hours irreversible tissue necrosis starts.

• Direct injury from the crushing forces results in cell membrane failure and opening of intracellular sodium and calcium channels.

• This shifts calcium and sodium into hypoxic cells and damages myofibril proteins and results in worsened cell membrane dysfunction and release of ATP-inhibiting nucleases.

• Crush injury may cause hypovolemia by hemorrhagic volume loss and the rapid shift of extracellular volume into the damaged tissues.

• Acute renal failure is caused by hypoperfusion of the kidneys This may be worsened by cast formation and mechanical blockage of the nephrons by myoglobin.

• Reperfusion leads to increased neutrophil activity and the release of free radicals. Superoxide and hydrogen peroxide react to form the hydroxyl radical (OH), which damages cellular molecules and causes a lipid peroxidation. which leads to cell membrane destruction and cell lysis.

• Reperfusion also releases potassium, phosphorus, and myoglobin. Myoglobin is responsible for the ARF that can occur with the syndrome.

Epidemiology

Rhabdomyolysis occurs in up to 85% of patients with traumatic injuries.

10–50% of patients with rhabdomyolysis develop ARF.

Patients with rhabdomyolysis-induced renal failure have a mortality of approximately 20%.

Mortality is higher in patients with multiorgan dysfunction syndrome.

Victims of natural disasters are reported to have a 20% incidence of crush injury.

40% of extrication survivors are reported to have crush injuries.

Prognosis

• Crushed torso – Increases mortality rates

• Presence of ‘lethal triad of trauma’ (acidosis, coagulopathy, hypothermia) -Increases mortality rates

• Development of ARF (urine output <20 mL/h, urea >40 mg/dL and creatinine >200 mmol/L) -Increases mortality rates

• Physiological and anatomic based scoring systems – Increases mortality rates

• Number of limbs crushed (1 = 50%, 2 = 75%, 3 = 100%) – likelihood of developing ARF

• Initial serum CK > 5000 U/L – Likelihood of developing ARF and need for hemodialysis

• Dehydration at presentation – Likelihood of developing ARF

• Serum phosphorus – Likelihood of developing ARF

• Serum bicarbonate < 17 mmol/L – Likelihood of developing ARF

• Raised urea and creatinine on presentation – Likelihood of developing ARF and need for hemodialysis

• Hypocalcemia – Likelihood of developing ARF

• Raised peak serum uric acid – Likelihood of developing ARF

• Serum albumin – Below normal – General health status and susceptibility to ARF

• Hyperkalemia (+ hypocalcemia) – K > 7 mEq/L – Risk of arrhythmias and cardiac arrest (early sign) and predictor of developing ARF

• Serum lactate – Above normal – Presence of lactic acidosis

• Serum vs. urine myoglobin/time – Clinical course of the crush syndrome

• Microalbuminemia – Likelihood of developing ARF

• Serum amylase – Gut ischemia and possible development of SIRS

Special considerations for nursing and allied health professionals.

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What's the evidence?

Jagodzinski, NA, Weerasinghe, C, Porter, K. “Crush injuries and crush syndrome – a review. Part 1: the systemic injury”. Trauma. vol. 12. 2010. pp. 69-88.

Jagodzinski, NA, Weerasinghe, C, Porter, K. “Crush injuries and crush syndrome – a review. Part 2: the local injury”. Trauma. vol. 12. 2010. pp. 133-48.

Sever, MS, Vanholder, R, Lameire, N. “Management of crush-related injuries after disasters”. N Engl J. vol. 354. Med2006. pp. 1052-63.

Michaelson, M. “Crush injury and crush syndrome”. World J Surg. vol. 16. 1992. pp. 899-903.

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