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The 6 Ps of limb ischemia is a mnemonic device to help identify symptoms, which include, pain, pulselessness, pallor, poikilothermia, paresthesias, and paralysis.

The symptoms of limb ischemia can appear over hours or days. Recognizing the condition is critical to improving the chances of limb preservation.

The main symptoms of acute limb ischemia are called "the six Ps" and include:

1. Pain
   • Symptoms range from muscle burning or cramping to severe pain.
   • Even if a person lies down, their affected limb may hurt, and elevating the limb may make it worse.
   • The pain may be severe enough that touching the skin with clothes will be uncomfortable.
   • After about six to eight hours, muscles become tender to palpation.
2. Pulselessness or pulse deficit
   • Loss of pulses in the affected limb.
3. Pallor
   • Due to a lack of blood flow, the skin on the affected limb becomes pale.
   • It is important to note that acutely ischemic limbs do not always appear pale. The extremity may develop a blue or mottled appearance as the ischemia progresses.
4. Perishingly cold or poikilothermia
   • Coldness in the affected limb.
   • The limb will lose its ability to self-regulate its temperature and will become the same temperature as its surroundings.
5. Paresthesias
   • Prickling and numbness in the affected limb, which is typically described as a pins and needles sensation.
6. Paralysis
   • Inability to move the affected limb.

Gangrene can develop in the later stages of limb ischemia.

The six Ps have been used as a mnemonic device to remember a patient's presentation with limb ischemia. However, not all of these will be present in all patients.

What is limb ischemia?

Limb ischemia is defined as a decrease in the blood flow to the limb (limb perfusion) that endangers the limb's viability. The occlusion of a blood vessel reduces blood flow, compromising oxygen, and nutrient delivery to tissues.

Ischemia causes permanent damage to peripheral nerves and skeletal muscles within about six hours.

Limb ischemia can occur as a result of a blood clot, air bubble, or fat. It is one of the most common vascular surgery emergencies, affecting 14 to 16 people per 100,000 people each year. The incidence rises with age, and it affects both men and women equally.

Main causes of limb ischemia

• Acute arterial thrombosis (blood clots)
• Embolism
• Arterial trauma
• Atherosclerosis (a buildup of plaque in the arteries)
• Smoking
• Older age
• High cholesterol
• High blood pressure
• Diabetes
• Family history of cardiovascular disease
• Obesity
• Sedentary lifestyle

3 different types of ischemia

• Chronic ischemia: A limb with a lack of blood flow that has been present for more than two to four weeks. With rest, the patient will develop ulcers and pain. The patient will not experience acute pain, and the limb is not in imminent danger.
• Acute ischemia: A sudden reduction in the blood flow to a limb, often resulting from a traveling blood clot (embolism) or a limb injury.
• Acute on chronic ischemia: Ischemia is caused by a buildup of plaques in the arteries of a limb, resulting in a chronic lack of blood flow in the foot. When one of those plaques ruptures or a clot form in that system, the ischemia becomes acute. This event increases pain or clinical findings of the six Ps.

Even doctors have difficulty distinguishing "chronic ischemia," "acute on chronic ischemia," and "acute ischemia."

While chronic peripheral artery disease is the most common cause of limb ischemia, it can occur in relatively healthy blood vessels due to trauma or other clot formations. In contrast to chronic ischemia, which develops slowly over time, acute ischemia occurs suddenly and is a medical emergency.

Rutherford criteria for grading limb ischemia

Table 1. Acute limb ischemia Category Symptoms Prognosis

I-Viable
No sensory loss and muscle weakness
Limb viable, not immediately threatened

IIA-Threatened
Minimal sensory loss but no muscle weakness
Limb marginally threatened, salvageable if promptly treated

IIB- Immediate
Sensory loss with pain at rest and mild to moderate muscle weakness
Limb immediately threatened, salvageable with immediate revascularization

III-Irreversible
Profound sensory loss and paralysis
Limb irreversibly damaged, major tissue loss or permanent nerve damage inevitable

Table 2. Chronic limb ischemia Grade Category Symptoms

0
0
Asymptomatic

1
Mild claudication

I
2
Moderate claudication

3
Severe claudication

II
4
Ischemic rest pain

III
5

• Minor tissue loss
• Focal gangrene
• Non-healing ulcer
• Pedal ischemia

6

• Major tissue loss
• The affected foot may not be saved

Rutherford criteria summary

Grade I ischemia

• Pallor
• Reduced capillary refill (the refilling of tiny blood vessels or capillaries after they are blanched by applying pressure on the skin)
• Pain
• Intact motor and sensory sensations

Grade II ischemia

• Beginning of paraesthesia
• Diminishing motor function
• Delayed capillary refill, greater than five seconds
• The limb feels cold

Grade III ischemia

• The limb is completely pale
• No capillary refill
• No motor or sensation
• No pulses
• The limb is unsalvageable and requires a primary amputation

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How can limb ischemia be diagnosed?

The six Ps are commonly used as a protocol to diagnose possible limb ischemia. Doctors may, however, order additional tests, such as:

Imaging

• Formal angiogram: Regarded as the gold standard for limb ischemia. An angiogram is a type of X-ray that can be used for both diagnostic and therapeutic purposes. An angiogram uses X-rays taken during the injection of a contrast agent to detect blockages.
• Computed tomography angiography (CTA): Regarded as being close to the level of formal angiography (96 percent sensitive, 95 percent specific). In CTA, a special dye is injected intravenously, and computed tomography scans produce images of blood vessels and tissues in a specific area of the body.
• Duplex ultrasound: The level of occlusion, patency of the distal vessel, echogenicity of the thrombus, and quality of the vessel wall at the level of occlusion can all be determined using ultrasound. Duplex ultrasound may provide imaging data that is as useful for surgical planning as angiography data.

Laboratory evaluation

Not useful for diagnosis but critical for monitoring coexisting conditions and anticoagulant therapy response, including:

• Complete blood count
• Basic metabolic panel
• Prothrombin time or partial thromboplastin time
• Creatine kinase

Because other vascular and nonvascular comorbid diseases are commonly present in patients with acute limb ischemia, laboratory, and radiographic testing may be required in addition to anticoagulation and surgery.

In any patient with suspected or proven acute limb ischemia, doctors consider these diagnosis modalities.

• Infection or gangrene
• Abnormal glucose levels
• Myocardial infarction
• Arrhythmia
• Renal disease
• Dehydration or low urine output
• Congestive heart failure

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What are the treatment options for limb ischemia?

The treatment of acute limb ischemia will be determined by the results of the diagnostic tests and scans, as well as the location of the ischemia. Medication or surgeries are used to treat the condition.

Limb ischemia is frequently the tip of the iceberg in a patient with a poor clinical status and multiple comorbidities. Many patients suffer from dehydration, cardiac failure, hypoxia, and pain, which should be treated along with limb ischemia modalities.

Treatment options

• According to the 2012 American College of Chest Physicians guidelines, anticoagulant therapy should begin with a heparin bolus and infusion once the diagnosis of acute limb ischemia has been made through medical history and physical examination.
• Heparin prevents the thrombus from growing larger and lowers the likelihood of another clot forming in areas of relatively stagnant flow. Obtaining imaging or other diagnostics should not be used to postpone the decision to start heparin.
• Medications, such as anticoagulants and clot-dissolving drugs, can be used if the ischemia has been caused by a blood clot.

Several techniques are frequently used to restore blood flow.

The revascularization strategy used is determined by the extent and location of the occlusion, the presence of collaterals, the patient's comorbid illnesses, and surgical risk, and the availability of treatment options. 

Although the emergency physician does not usually determine the treatment plan, knowing the options can help determine the appropriateness of transfer and inform patients of their options.

• Catheter-directed thrombolysis: Patients with acute occlusion (14 days) who received thrombolysis had marginally better amputation-free survival and shorter hospitalizations, but chronically ischemic limbs were better treated with surgical revascularization.
• Percutaneous mechanical thrombectomy: In patients with acute limb ischemia and a salvageable limb, it can be used as an adjunct to thrombolysis. Several devices have been created to carry out this procedure. The risks of using it include bleeding, distal embolization of the clot with downstream occlusion, and vessel damage.
• Surgical thromboembolectomy: A surgical procedure is used to remove a clot from an artery. This procedure is frequently performed in conjunction with a percutaneous approach to completely remove a clot. This is yet another option to manage an acutely occluded salvageable limb.
• Surgical bypass or balloon angioplasty: When used as the first-line treatment option, studies show that both bypass surgery and balloon angioplasty have comparable amputation-free survival rates. If angioplasty fails, surgery may still be a viable option.
• Amputation: The only option for limbs that cannot be saved. These limbs are clinically insensate, immobile, or rigid and may show signs of gangrene. Primary amputation may benefit people who are nearing the end of their lives or have chronic immobility.

Management is complicated. Here is an outline of a possible timeline for these management options synchronized with the Rutherford grading system.

Initial management

• Conservative. Typically includes analgesia and heparin (anticoagulant).

Rutherford I

• Following a diagnostic workup. Catheter-directed thrombolysis, thrombectomy, or bypass can all be used to try to revascularize the vessel.

Rutherford II

• Urgent revascularization is required, and imaging should not be delayed. It is typically accomplished through thrombectomy or bypass surgery. If an underlying vascular lesion is present, surgery should be attempted.

Rutherford III

• Amputation of affected areas is required due to irreversible damage with dead, nonviable tissue.

Surgical or percutaneous intervention may be deemed inappropriate in some patients due to the patient’s preferences or comorbidities. In these cases, symptomatic relief and conservative measures (such as continuing heparin infusion) and palliative care input should be implemented.

Possible side effects of treatment options

• Ischemia-reperfusion injury:
  • Following the restoration of blood flow to previously ischemic tissues, there is a paradoxical exacerbation of cellular dysfunction and death. Blood flow must be restored to save ischemic tissues.
  • Correction of underlying abnormalities is part of the treatment. Certain patients may require hemodialysis and cardiopulmonary support.
• Compartment syndrome:
  • Compartment syndrome causes ischemia, which leads to muscle and nerve necrosis.
  • Emergency fasciotomy is used to treat the condition. Fasciotomy is a procedure that involves cutting the fascia to relieve pressure in the muscle compartment.

The outcome of limb ischemia

Despite significant advances in care and increased diagnostic recognition, limb ischemia is still associated with rates of limb loss of up to 30 percent and in-hospital mortality rates of up to 20 percent.

Similarly, approximately 15 to 20 percent of patients die within one year of presentation, usually as a result of the medical illnesses that led to their presentation. The majority of deaths are due to cardiopulmonary complications, highlighting the severity of these patients' preexisting medical conditions.

The six Ps mnemonic has limitations. Patients are unaware that they have limb ischemia and present late. In patients with lower limb symptoms, a high index of suspicion and pulse palpation at the foot would help avoid misdiagnosis of limb ischemia.

Finally, public awareness campaigns are needed to educate the public about the importance of reporting on time. If a person believes they are suffering from acute limb ischemia, they must seek treatment right away. The sooner they receive treatment, the more likely it is that their limb will be saved. If a person has intermittent symptoms of limb ischemia, they should see a specialist before the situation becomes an emergency.