Urgent considerations

See Differentials for more details

Deep vein thrombosis (DVT)

Acute-onset, asymmetrical, tender leg oedema (with associated swelling and redness) may be a sign of new DVT, which can be a threat to life if it embolises to the lung.[17] Patients may also report localized pain over the deep venous system or dilated superficial veins over the foot and leg.

[Figure caption and citation for the preceding image starts]: Deep vein thrombosis (DVT) of the right leg with associated swelling and rednessFrom the collection of James Heilman, MD. [Citation ends].com.bmj.content.model.assessment.Caption@65c0c212

Massive venous thrombosis can be associated with a limb-threatening syndrome referred to as phlegmasia cerulea dolens, in which the venous congestion leads to such a degree of interstitial oedema that compartment syndrome, arterial compromise, and gangrene can occur.[18]

For patients with a high pre-test probability of DVT, determined by Wells clinical prediction rules,​​ duplex ultrasound is the first-line test in most instances, particularly if a thrombosis in the popliteal, superficial femoral, or common femoral veins is suspected. [ Modified Wells score for deep vein thrombosis (DVT) Opens in new window ] If the pre-test probability is low, a negative D-dimer test allows ultrasound to be safely excluded.[17][19]

In the absence of contraindications, therapeutic anticoagulation should be initiated immediately on diagnosis.[17][19]​ Further treatment, such as thrombolysis, thrombectomy, and/or fasciotomy, may be necessary for massive thrombosis.[19][20]

Heart failure

Acute-onset heart failure, which may present with dyspnoea and lower-extremity oedema (usually bilateral), requires urgent evaluation to establish the underlying aetiology of the cardiac dysfunction.[21]

Emergency diagnoses such as myocardial ischaemia, pericardial effusion with cardiac tamponade, constrictive pericarditis, valvular disease, or cardiomyopathy should be considered when new symptoms of heart failure develop rapidly.[22] Complaints of chest pain, shortness of breath, orthopnoea, or paroxysmal nocturnal dyspnoea may provide a clue that the peripheral oedema arises from an acute cardiac cause.

Evidence of pulmonary oedema, elevated jugular venous pressure, heart murmurs, pericardial friction rubs, or pulsus paradoxus further support a cardiac aetiology of the oedema. ECG, chest x-ray, cardiac troponins, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and echocardiography would be appropriate to evaluate for suspected acute cardiac disease when peripheral oedema is a component of the presenting syndrome.[23][24]

Exacerbation of pre-existing chronic heart failure is noticed by the patient as fluid retention and increased lower-extremity oedema.[22] A cause for the decompensation should be sought. Worsening of symptoms of oedema from known heart failure requires treatment to regain euvolaemia, usually loop diuretics, and institution of other measures to improve and preserve cardiac function.[22][25] Pericardial effusions with tamponade require pericardiocentesis.[26]

New-onset renal disease

Frequently, the presenting symptom of nephrotic syndrome is peripheral oedema, which starts in the legs and may become severe involving the entire body (anasarca), and peri-orbital oedema.[27]​ Patients may also report frothy urine. Initial investigations should include testing for proteinuria, serum creatinine and serum albumin. Severe protein-wasting renal disease or acute renal failure with volume overload requires early nephrology evaluation.

Myxoedema coma

Peripheral oedema is one of the features seen with profound hypothyroidism, an endocrinological emergency.[28]​ In this setting, oedema would not occur in isolation but rather as part of a multi-system disorder. Other signs or symptoms may include mental status changes, lethargy, constipation, weight gain, coarse hair, dry skin, and cold intolerance.[29]​ Treatment requires intravenous thyroid hormone replacement.​

Acute hepatic venous obstruction

Venous obstruction at the level of the liver (including Budd-Chiari syndrome and hepatic veno-occlusive disease) can cause peripheral oedema, typically in association with abdominal pain, hepatomegaly, and ascites.[30] While obstruction can be caused by a variety of pathological processes, thrombus formation would be associated with rapid onset of symptoms. The combination of peripheral oedema, hepatomegaly, ascites, and abdominal pain, along with elevated transaminases and possibly jaundice, should prompt evaluation of the blood flow through the liver with imaging such as duplex ultrasound. Computed tomography or magnetic resonance imaging can also be used. A similar picture of hepatic congestion can be seen with cardiac disease, and this should be maintained in the differential diagnosis for this presentation.

Compartment syndrome

Compartment syndrome can rapidly threaten the viability of a limb, and should be investigated and managed aggressively when suspected. Typical clinical scenarios include trauma to the extremity due to fractures, soft-tissue injury, vascular compromise, and burn injuries.

Features that might alert the clinician to this diagnosis include unilateral oedema, severe pain in the extremity especially on passive stretch of the muscle, a compartment tense to palpation, muscle weakness, and hypoaesthesia. Where applicable, casts or occlusive dressings should be removed and any padding or circumferential dressings should be released immediately.

Measurement of compartment pressure is indicated whenever the diagnosis is uncertain in a patient at risk. The perfusion pressure of a compartment (the compartment delta pressure) is defined as the difference between the diastolic BP and the intra-compartmental pressure (i.e., diastolic BP minus compartment pressure). A delta pressure of ≤30 mmHg is considered a strong indicator for fasciotomy.[31][32][33] However, care should be taken when using this criterion in patients who are receiving vasodilatory medications and whose diastolic BP is low.

Sepsis

Peripheral oedema itself is not a typical presenting symptom for sepsis, unless the underlying cause is a focal infection in the limb.

In patients with sepsis, oedema may occur several days after the administration of large volume fluid resuscitation. Nevertheless, it is important to consider the possibility of sepsis in any patient with oedema who presents with possible signs of infection.[34]

Sepsis is a spectrum of disease, where there is a systemic and dysregulated host response to an infection.[35] Presentation ranges from subtle, non-specific symptoms (e.g., feeling unwell with a normal temperature, malaise, lethargy, nausea, or vomiting) to severe symptoms with evidence of multi-organ dysfunction and septic shock. Patients may have signs of tachycardia, tachypnoea, hypotension, fever or hypothermia, poor capillary refill, mottled or ashen skin, cyanosis, newly altered mental state or reduced urine output.[34] Sepsis and septic shock are medical emergencies.

Risk factors for sepsis include:[34]​

  • Age under 1 year

  • Age over 75 years

  • Frailty, impaired immunity (due to illness or drugs)

  • Recent surgery or other invasive procedures

  • Any breach of skin integrity (e.g., cuts, burns)

  • Intravenous drug misuse

  • Indwelling lines or catheters, and

  • Pregnancy or recent pregnancy

Early recognition of sepsis is essential because early treatment improves outcomes.[34][36][Evidence C][Evidence C]​​​​​ However, detection can be challenging because the clinical presentation of sepsis can be subtle and non-specific. A low threshold for suspecting sepsis is therefore important. The key to early recognition is the systematic identification of any patient who has signs or symptoms suggestive of infection and is at risk of deterioration due to organ dysfunction. Several risk stratification approaches have been proposed. All rely on a structured clinical assessment and recording of the patient’s vital signs.[34][37][38]​​[39][40]​​ It is important to check local guidance for information on which approach your institution recommends. The timeline of ensuing investigations and treatment should be guided by this early assessment.[39]

Treatment guidelines have been produced by the Surviving Sepsis Campaign and remain the most widely accepted standards.[36][41]

Recommended treatment of patients with suspected sepsis is:

  • Measure lactate level, and re-measure lactate if initial lactate is elevated (>2 mmol/L [>18 mg/dL]).

  • Obtain blood cultures before administering antibiotics.

  • Administer broad-spectrum antibiotics (with methicillin-resistant Staphylococcus aureus [MRSA] coverage if there is high risk of MRSA) for adults with possible septic shock or a high likelihood for sepsis.

  • For adults with sepsis or septic shock at high risk of fungal infection, empiric antifungal therapy should be administered.

  • Begin rapid administration of crystalloid fluids for hypotension or lactate level ≥4 mmol/L (≥36 mg/dL). Consult local protocols.

  • Administer vasopressors peripherally if hypotensive during or after fluid resuscitation to maintain MAP ≥65 mmHg, rather than delaying initiation until central venous access is secured. Noradrenaline (norepinephrine) is the vasopressor of choice.

  • For adults with sepsis-induced hypoxaemic respiratory failure, high flow nasal oxygen should be given.

Ideally these interventions should all begin in the first hour after sepsis recognition.[41]

For adults with possible sepsis without shock, if concern for infection persists, antibiotics should be given within three hours from the time when sepsis was first recognised.[36]

For adults with a low likelihood of infection and without shock, antibiotics can be deferred while continuing to closely monitor the patient.[36]

See Sepsis in adults and Sepsis in children.

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