Differentials

Non-infectious causes of systemic inflammatory response syndrome (SIRS)

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SIRS can result as a non-specific finding from a host of other disease states, including post-operative recovery, trauma, burns, transplant rejection, hyperthyroidism, Addisonian crisis, blood product transfusion reactions, serum sickness, immunisations, and central nervous system infarction or haemorrhages.

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Specific tests are directed by clinical suspicion of underlying cause.

Associated medical interventions (e.g., catheterisation, surgical procedures, ventilation) can subsequently lead to superimposed infections to make sepsis a continual threat and possibility.

Myocardial infarction (MI)

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Symptoms suggesting MI are central, squeezing chest pain or pressure radiating down the left arm or into the jaw. Pain may be felt in the epigastric region.

Patients may present in cardiogenic shock with breathlessness and hypotension. A low-grade fever and raised C-reactive protein may also be present.

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Ischaemic changes on ECG.

Elevated creatine kinase-MB and troponin.

Pericarditis

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Patients present with sharp, stabbing, pleuritic chest pain (typically better on sitting up and leaning forward, and worse with lying down) and sometimes a low-grade fever.

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ECG may have upward concave ST-segment elevation globally and PR-segment depression.

Echo may demonstrate a pericardial effusion; absence of left ventricular wall motion abnormalities.

Myocarditis

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Patients typically present with a viral prodrome (which may include a low-grade fever), dyspnoea, or underlying autoimmune condition, such as systemic lupus erythematosus.

Medications such as antibiotics, thiazide diuretics, antiepileptics, digoxin, lithium, amitriptyline, and dobutamine may be suggestive of drug aetiology.

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ECG may show non-specific ST-segment and T-wave abnormalities.

Inflammatory markers may be elevated.

Two-dimensional echo demonstrates global and regional left ventricular motion abnormalities and dilatation.

Acute pancreatitis

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May present with abdominal pain radiating through to the back, low-grade fever, and hypovolaemia.

There may be a history of gallstones, alcohol use, or viral infections (e.g., mumps).

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Elevated serum amylase, lipase, glucose; low calcium.

Massive pulmonary embolism

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Typically presents with acute dyspnoea and hypotension. Symptoms may also include fever, decreased consciousness, syncope or pre-syncope, and pleuritic chest pain. Risk factors for thromboembolic disease may be evident.

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CT pulmonary angiogram shows a filling defect in the pulmonary arteries.

Leukaemia

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May present with fever, leukocytosis, anaemia, tachycardia, multi-organ dysfunction, and dyspnoea and thus meet diagnostic criteria for (suspected) sepsis.

The immunocompromise may additionally facilitate development of infections or the increased clinical suspicion of undiagnosed infection.

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Biopsies of blood smear, bone marrow, tumour, or lymph nodes may identify neoplastic cells.

Identification of a specific infectious agent is definitive in differentiating sepsis from SIRS.

Malignant hyperthermia

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This is a rare condition characterised by severe hyperthermia (>41.1°C [106°F]) and muscle rigidity following administration of anaesthetic agents (e.g., succinylcholine for intubation). Lactic acidosis, hyperkalaemia, rhabdomyolysis, hypoxia, and arrhythmias may also occur.[126]

Malignant hyperthermia is an inherited disorder (autosomal dominant) and a high index of suspicion is necessary if there is a positive family history.[126]

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The caffeine-halothane contracture test (CHCT) is most commonly used to screen for susceptibility, as ryanodine receptor gene (RYR1) identification is gaining in clinical importance.[127]

The CHCT requires muscle biopsy and testing in select regional laboratories after resolution of the episode.

Neither test is clinically useful to direct therapy in the acute situation.

Drug-induced fever and coma

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This includes neuroleptic malignant syndrome, serotonergic syndrome, delirium tremens, and metformin lactic acidosis.

History of causative drug use.

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Clinical diagnosis. Specific tests are not readily available.

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