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Level 2 of 6Must-remember

The febrile patient: assessment and empirical management

Assess, manage and stay safe — enough on its own

The card — assess, manage, caution

Assessment— look, ask, measure

  • Measure the temperature properly: record the number, the site and the time, and use the same site thereafter — rectal readings run about 0.4°C above oral, unadjusted-mode tympanic about 0.8°C below rectal, and oral readings are falsely low in mouth-breathers and the tachypnoeic.
  • Know the thresholds: mean oral temperature is 36.6°C (95% confidence interval 35.7–37.3°C), so above 37.7°C is the 99th percentile and defines fever, most services use the rounder 38.0°C, formal fever-of-unknown-origin criteria use 38.3°C, hyperpyrexia is above 41.5°C, and 37.6°C is not automatically normal — in a patient on corticosteroids or a biological agent it may be the equivalent of 39.4°C in a healthy adult.
  • Ask the history that reshapes the differential: duration and pattern of fever, every localising symptom (cough, sputum, pleuritic pain, dysuria, loin pain, abdominal pain, diarrhoea, jaundice, headache, neck stiffness, joint pain, sore throat, rash, ear or wound discharge), travel, freshwater immersion, mosquito, tick and mite bites, animal-urine contact, unpasteurised dairy, sick contacts, recent transfusion, sexual exposure, and any new medicine — drug reactions should be considered in anyone acutely febrile on a new medication, especially anticonvulsants and antimicrobials.
  • Ask about immunosuppression explicitly: neutropenia, systemic anti-cancer therapy, corticosteroids, anticytokine or biological therapy, HIV, transplantation, splenectomy, cirrhosis, chronic kidney disease, diabetes and indwelling devices — low-grade fever in such a patient is of considerable concern and demands early and rigorous evaluation.
  • The question is not how high the fever is but whether the patient is septic: treat as sepsis until disproved if systolic blood pressure is below 90 mmHg, mean arterial pressure below 65 mmHg, or the systolic has fallen more than 40 mmHg from the usual value.
  • The other sepsis red flags: new confusion or reduced conscious level; respiratory rate above 22–25/min or oxygen saturation below 92% on air; capillary refill over 3 seconds with cold mottled peripheries, or the converse warm vasodilated shock; urine output below 0.5 mL/kg/h; a raised lactate; a non-blanching rash; hypothermia; and fever in a patient on systemic anti-cancer therapy or other significant immunosuppression.
  • Measure the bedside tests that grade severity: capillary glucose in anyone with altered consciousness, lactate (above 2 mmol/L indicates risk and above 4 mmol/L severe illness irrespective of blood pressure), oxygen saturation, respiratory rate and a full blood count with differential.Not available at your setup — Arterial blood gas.
  • The absence of fever never excludes infection: newborns, elderly patients, those in chronic hepatic or renal failure and those taking glucocorticoids, NSAIDs or anticytokine agents may have active disease without fever, and hypothermia can develop in septic shock — 35.4°C in an unwell patient is worse news than 39.5°C.
  • Undress the patient completely and inspect all the skin — front, back, buttocks, perineum, palms, soles, conjunctivae and mouth — the step most often omitted and the one most likely to change management within minutes.
  • Three skin findings demand action within minutes: non-blanching purpura (meningococcaemia until disproved), an eschar or tâche noire (a necrotic lesion covered with a black crust) in a skin fold, waistband, axilla or groin (scrub typhus and other rickettsioses), and skin sloughing with a positive Nikolsky sign and mucosal erosion (Stevens–Johnson syndrome / toxic epidermal necrolysis).
  • Be precise about the rash: non-palpable purpura is flat and non-blanching with petechiae under 3 mm and ecchymoses over 3 mm, whereas palpable purpura indicates vasculitis with haemorrhage.
  • Search systematically for the source: meningism, sinus tenderness, tympanic membranes, dentition, pharynx, temporal artery tenderness over 50, all lymph node groups, consolidation, effusion, a new or changing murmur with peripheral stigmata of endocarditis, the right upper quadrant (amoebic liver abscess presents with fever alone in 10–15% of cases), loin tenderness, hepatosplenomegaly, masses, a single hot swollen joint (septic arthritis until aspirated) and the calf, because pulmonary embolism causes fever.
  • Look for the patterns that cost nothing to seek: rigors (bacteraemia, pyogenic collections, cholangitis, pyelonephritis, malaria), tertian fever every third day (*Plasmodium vivax*) and quartan every fourth (*P. malariae*), the Pel–Ebstein pattern of fever lasting 3–10 days followed by afebrile periods of 3–10 days (Hodgkin disease and other lymphomas), biphasic saddleback fever in dengue, and temperature–pulse dissociation or relative bradycardia (typhoid fever, brucellosis, leptospirosis, some drug-induced fevers, factitious fever).
  • Decide fever versus hyperthermia at the first fork: in fever the hypothalamic set point is raised and paracetamol produces some fall even in hyperpyrexia, whereas in hyperthermia the set point is unchanged, no pyrogens are involved, the skin is hot but dry, the temperature may exceed 41.5°C and keep rising, antipyretics do nothing and the illness can be rapidly fatal.
  • Hyperpyrexia above 41.5°C occurs in severe infection but most commonly accompanies central nervous system haemorrhage, so consider CNS haemorrhage or hyperthermia rather than assuming infection.
  • Adjust for age and host: in the elderly a normal 37.4°C may represent a substantial rise and confusion, falls, incontinence, immobility and anorexia may be the only manifestations; neonates may be septic while hypothermic, and in children hypotension is a late sign so compensated shock shows tachycardia, prolonged capillary refill and cool peripheries at a normal blood pressure; paediatric red features include pale, mottled or ashen skin, unrousable or unresponsive to social cues, grunting, respiratory rate above 60, marked recession, reduced skin turgor, a non-blanching rash, bulging fontanelle, neck stiffness, status epilepticus, focal neurology, and age under 3 months with a temperature of 38.0°C or more.

Management— do this, in order

  • Answer four questions before prescribing anything: is this fever or hyperthermia, is the patient septic, is the patient neutropenic or otherwise immunosuppressed, and is there a specific immediately treatable diagnosis such as meningococcaemia, malaria, rickettsial infection or necrotising soft-tissue infection.
  • Resuscitate first: give oxygen, secure two points of intravenous access, and take blood cultures from the first venepuncture — two sets from two separate sites before antibiotics, three sets for suspected endocarditis or prolonged unexplained fever.Not available at your setup — Blood culture.
  • Check capillary glucose immediately in anyone with altered consciousness and correct it — adult 50% dextrose 50–100 mL IV; child 10% dextrose 2 mL/kg IV.Doctor / Nurse
  • Fluids: start balanced crystalloid or 0.9% sodium chloride as 500 mL boluses over 15 minutes in adults, reassessed after each, aiming for 30 mL/kg in the first hour if hypoperfusion persists, and 10–20 mL/kg boluses in children.
  • Three groups need reduced, titrated volumes: heart failure or severe valve disease, oliguric chronic kidney disease, and suspected dengue in the critical phase (5–10 mL/kg/h titrated against haematocrit, pulse pressure and urine output).
  • Persisting hypotension after fluid: noradrenaline titrated to a mean arterial pressure of 65 mmHg or more.Doctor / NurseNot available at your setup — Infusion pump.
  • If the patient is septic or neutropenic, give high-dose intravenous antibiotics within one hour of admission, after cultures, without waiting for a source or for test results — this applies to all febrile patients on systemic anti-cancer therapy.Doctor / NurseNot available at your setup — Blood culture.
  • Sepsis with unknown community-acquired source: ceftriaxone 2 g IV every 24 hours, adding metronidazole 500 mg IV every 8 hours if abdominal or pelvic; or piperacillin–tazobactam 4.5 g IV every 6–8 hours, which covers *Pseudomonas* and anaerobes in one agent.Doctor / Nurse
  • Bacterial meningitis aged 18–50: ceftriaxone 2 g IV every 12 hours plus vancomycin 15–20 mg/kg IV every 8–12 hours, with dexamethasone 0.15 mg/kg (about 10 mg) IV every 6 hours given with or before the first antibiotic dose; over 50, pregnant or immunosuppressed add ampicillin or amoxicillin 2 g IV every 4 hours for *Listeria*, and add aciclovir 10 mg/kg IV every 8 hours if encephalitis is possible.Doctor / Nurse
  • Febrile neutropenia: cefepime 2 g IV every 8 hours, or piperacillin–tazobactam 4.5 g IV every 6 hours, or meropenem 1 g IV every 8 hours — maximal doses of antipseudomonal beta-lactams must be used because neutrophils are absent; add vancomycin 15–20 mg/kg IV every 8–12 hours for suspected MRSA, an infected line or port, severe mucositis or haemodynamic instability.Doctor / Nurse
  • The specific treatable diagnoses: severe malaria — artesunate 2.4 mg/kg IV at 0, 12 and 24 hours then once daily (children under 20 kg 3 mg/kg), checking glucose hourly; suspected rickettsial illness — doxycycline 100 mg orally or IV twice daily; enteric fever — ceftriaxone 2 g IV every 24 hours; intra-abdominal or biliary sepsis — piperacillin–tazobactam 4.5 g IV every 6–8 hours or ertapenem 1 g IV every 24 hours.Doctor / Nurse
  • Paediatric antibiotics: ceftriaxone 50 mg/kg IV (maximum 2 g) every 12 hours for meningitis or severe sepsis, or 80 mg/kg IV once daily for other severe infection; in neonates under 1 month use cefotaxime 50 mg/kg IV every 6–8 hours plus ampicillin or amoxicillin 50 mg/kg IV every 6 hours with an aminoglycoside.Doctor / Nurse
  • Antipyresis with paracetamol first line: adult 1 g orally or per rectum every 6 hours to a maximum of 4 g in 24 hours, reduced to a maximum of 2 g in 24 hours in significant liver disease, malnutrition or weight under 50 kg; child 15 mg/kg per dose orally or rectally every 4–6 hours, maximum 4 doses in 24 hours.
  • Second-line antipyretic: ibuprofen 400 mg orally every 8 hours with food in adults, 10 mg/kg per dose orally every 6–8 hours in children — parenteral NSAID preparations and rectal suppositories may be used if the oral route is unavailable.
  • Antipyresis is strongly indicated where there is pre-existing cardiac, pulmonary or CNS impairment, and children with a history of febrile or non-febrile seizure should be aggressively treated to reduce fever.
  • In hyperpyrexia above 41.5°C add physical cooling — tepid sponging, fanning, ice packs to axillae and groins, cold intravenous fluid — stopping at about 38.5°C and slowing down if the patient shivers; in hyperpyretic patients with CNS disease or trauma, reducing core temperature mitigates the detrimental effects of high temperature on the brain.
  • In hyperthermia antipyretics are useless: cool actively, withdraw the precipitant, and give dantrolene 1–2.5 mg/kg IV to a maximum of 10 mg/kg/day for malignant hyperthermia and severe neuroleptic malignant syndrome, benzodiazepines for rigidity, and cyproheptadine 12 mg orally then 2 mg every 2 hours for serotonin syndrome.Doctor / Nurse
  • Source control matters as much as the drug: drain collections, remove infected lines and catheters, relieve an obstructed biliary or urinary tract, and arrange urgent surgical exploration for necrotising soft-tissue infection, suspected from pain out of proportion to the appearance of the limb.

Caution— what harms

  • Never judge severity from the thermometer: severity is judged from perfusion, respiration, mentation and lactate, and qSOFA must not be used alone to screen or to rule sepsis out — current guidance recommends against it, because its sensitivity as a screen is poor.
  • Never let a normal temperature reassure you in the newborn, the elderly, the patient in hepatic or renal failure, or the patient on glucocorticoids, NSAIDs or anticytokine agents — and remember that latent *Mycobacterium tuberculosis* infection can disseminate in patients receiving anti-TNF therapy.
  • Never aspirin in children — risk of Reye syndrome with certain viral infections; the sole exception is Kawasaki disease under specialist direction.
  • Avoid NSAIDs in the hypotensive, dehydrated, bleeding or renally impaired patient and in suspected dengue, because oral aspirin and NSAIDs adversely affect platelets and the gastrointestinal tract; do not routinely alternate paracetamol and ibuprofen.
  • Do not exceed 2 g of paracetamol in 24 hours in significant liver disease, malnutrition or weight under 50 kg, and remember paracetamol hepatotoxicity in the alcohol-dependent.
  • Ceftriaxone must not be used in neonates under 1 month — it displaces bilirubin and precipitates with calcium-containing fluids.
  • If the patient is stable with no source, it is usually right not to prescribe: an empirical course of antimicrobials for unexplained fever is rarely helpful and may impair infectious disease diagnosis, for example by reducing the sensitivity of blood cultures.
  • Do not change the antibiotic because the fever has not settled in 24 hours: pyrexia may persist for up to five days after the start of specific therapy in enteric fever and the antirickettsial response takes 48–72 hours — judge response on pulse, blood pressure, respiratory rate, mental state, lactate and urine output.
  • But do not ignore fever that persists past that window: a patient still febrile after 4–5 days of treatment for pyelonephritis has a perinephric or renal abscess until disproved and needs imaging rather than a different antibiotic, and fever beyond 5–7 days of broad-spectrum antibacterial therapy in neutropenia means an antifungal such as voriconazole 200 mg IV or orally every 12 hours.
  • Do not order screening serologies or febrile agglutinins: they are of low yield and should not be done, including the single Widal titre, which cannot distinguish current infection from past exposure or vaccination — blood culture is the test that diagnoses enteric fever.
  • Do not stop the evaluation at an abnormal urinalysis: bacteriuria and pyuria are expected in catheterised patients, and asymptomatic bacteriuria in the elderly is a frequent false trail.
  • Do not accept one negative test: a single negative malaria film does not exclude malaria and must be repeated if fever continues, and transoesophageal echocardiography retains a roughly 10% false-negative rate for vegetations.
  • Do not delay the antibiotic for imaging or lumbar puncture in suspected meningitis — the antibiotic precedes the imaging and the tap, not the reverse — and do not repeat a CRP within hours, because it lags 6–12 hours.
  • Watch for the treatment complications: the Jarisch–Herxheimer reaction, in which some 15% of patients with early spirochaetal disease develop a febrile reaction with rigors, hypotension and worsening rash during the first 24 hours of therapy — it is not an allergy and the antibiotic must not be stopped; also overshoot hypothermia from over-vigorous cooling, NSAID kidney injury and gastrointestinal haemorrhage, and *Clostridioides difficile* infection; cooling blankets should not be used without oral antipyretics.

Refer / escalate

Escalate immediately and arrange transfer for any febrile patient with sepsis red flags (systolic below 90 mmHg, mean arterial pressure below 65 mmHg, a fall of more than 40 mmHg from the usual systolic, new confusion, respiratory rate above 22–25/min, saturation below 92%, capillary refill over 3 seconds, urine output below 0.5 mL/kg/h, raised lactate, hypothermia), a non-blanching rash, an eschar, skin sloughing with mucosal erosion, hyperpyrexia above 41.5°C, suspected hyperthermia, neutropenia or systemic anti-cancer therapy, a child with any red traffic-light feature or aged under 3 months with a temperature of 38.0°C or more, or suspected necrotising soft-tissue infection needing urgent surgical exploration.

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