In 2016 the SOFA guideline was introduced, also called the Sepsis-related Organ Failure Assessment, to make a sepsis diagnosis easier and prevent mortality. According to this guideline, sepsis was defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Septic shock was defined as a subset of sepsis in which the circulatory and metabolic abnormalities would lead to a greater risk of mortality than sepsis alone. Patients with septic shock would be clinically identified by a need for vasopressors to maintain MAP greater than 65 mmHg and serum lactate greater than two mmol/L.

In February 2016 the Society of Critical Care Medicine published a JAMA article reformatting the definitions of sepsis in an attempt to overcome the shortcomings of the old definitions.The main changes are a new definition of sepsis, the replacement of the SIRS criteria with the quick Sepsis-related Organ Failure Assessment (qSOFA), and the complete removal of “severe sepsis” as an entity.The new definition of sepsis is that it is “life-threatening organ dysfunction caused by a dysregulated host response to infection.”Septic shock is “a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to increase mortality.”In essence this means that septic shock is sepsis plus the following, despite adequate fluid resuscitation:Vasopressors required to maintain a MAP > 65 mmHgSerum lactate > 2 mmol/lThe qSOFA score is a bedside prompt designed to identify patients with suspected infection who are at greater risk for a poor outcome outside of the intensive care unit. It uses the following three criteria:Hypotension (SBP < 100 mmHg)Tachypnoea (RR > 22)Altered mental status (GCS < 15)The presence of 2 or more of the qSOFA criteria near the onset of infection is associated with greater risk of death or a prolonged intensive care unit stay.

Interleukin-1, which is released by leukocytes and acts on the thermoregulatory centre of the hypothalamus, causes fever. Because prostaglandins mediate this process, antipyretics such as NSAIDs, paracetamol, and aspirin reduce prostaglandin levels by inhibiting cyclooxygenase enzymes. Malignant disease secretes interleukins, which cause the B-symptoms seen in lymphoma, for example. Bacterial toxins can also cause interleukins to be produced.Pyrexia of unknown origin (PUO) is defined as a fever of greater than 38.3 degrees Celsius that lasts for more than 2-3 weeks with no clear diagnosis despite extensive investigation.Investigation necessitates a thorough understanding of the conditions that can cause febrile illness, which may be missed during an initial investigation, as well as a thorough history, examination, and investigation centred on that list.Pyrexia of unknown origin has a wide differential diagnosis, which includes:InfectionBacterialPyogenic abscessTuberculosisInfective endocarditisBrucellosisLyme diseaseViralHIV Epstein Barr VirusCytomegalovirusParasiteToxoplasmosisMalignancy LeukaemiaLymphomaRenal cell carcinomaHepatocellular carcinomaVasculitides Still’s diseaseGranulomatosis with polyangiitis (formerly Wegener’s)Systemic lupus erythematosusGiant cell arteritisRheumatoid arthritisPolymyalgia rheumaticaMiscellaneous Drug induced fevers Familial Mediterranean feverThyrotoxicosisInflammatory bowel diseaseSarcoidosisFactitious fever Exaggerated normal circadian fluctuationThe patient might need to be admitted to the hospital for observation and further investigation. Because infection is still a possibility, blood cultures should be repeated on a regular basis, and inflammatory markers should be closely monitored. CT, PET, and MRI imaging have largely replaced diagnostic laparotomy as a diagnostic tool.