Postoperative fever

Postoperative fever is a core temperature of 38.0 degrees Celsius or more on two occasions, or 38.3 degrees Celsius or more once, within 30 days of an operation. It is common and often self limiting, but may signal infection, thromboembolism, a leak, a reaction to a drug or transfusion, or a rare emergency such as malignant hyperthermia. The timing since surgery directs the differential.

Clinical relevance. Up to half of patients have a fever in the first 48 hours, and most have no infection. Fever after day 3 is more often infective. A missed anastomotic leak or necrotising infection carries high mortality.

Mechanisms. Surgery releases interleukin 1, interleukin 6 and tumour necrosis factor, which produce fever without infection. Infection, tissue necrosis, haematoma, thrombosis, drugs and transfusion release pyrogens or act through immune mechanisms. Malignant hyperthermia is hypermetabolism from uncontrolled skeletal muscle calcium release triggered by volatile anaesthetics and suxamethonium.

Classification by timing.

• Immediate (intraoperative to 24 hours): malignant hyperthermia, transfusion reaction, aspiration pneumonitis, necrotising infection (group A streptococcus, clostridia), inflammatory response to surgery, atelectasis, bacteraemia from instrumentation.
• Acute (days 1 to 3): atelectasis and pneumonia, urinary tract infection, line infection, aspiration, early surgical site infection, drug fever, alcohol withdrawal, pancreatitis.
• Subacute (days 4 to 7): wound infection, anastomotic leak, intra-abdominal abscess, pneumonia, catheter related infection, venous thromboembolism, Clostridioides difficile infection.
• Delayed (after 1 week): abscess, deep wound or implant infection, osteomyelitis, cholecystitis, sinusitis, drug fever, thromboembolism, graft versus host disease, thyroid storm, adrenal insufficiency, HIV related causes.

Key distinctions. Fever within 48 hours with no focal signs and stable observations is usually physiological. A rising fever with tachycardia, ileus or abdominal pain, even without peritonism, suggests a leak. Fever with rash or eosinophilia suggests drug fever.

History.

• Type, urgency and duration of surgery, anaesthetic, intraoperative events (aspiration, contamination, transfusion, hypotension), bowel preparation and antibiotic prophylaxis.
• Timing, pattern and height of fever, rigors, associated cough, sputum, dyspnoea, dysuria, abdominal pain, diarrhoea, headache, calf pain, rash and wound pain.
• Drugs and transfusions: antibiotics, heparin, anticonvulsants, beta lactams, antiarrhythmics, allopurinol, new drugs within 2 to 3 weeks, and blood products.
• Lines and devices: central venous catheter, urinary catheter, drains, nasogastric tube, tracheal tube.
• Comorbidities: diabetes, immunosuppression, HIV, tuberculosis, alcohol dependence, thyroid disease, adrenal insufficiency, previous venous thromboembolism, valvular disease and prosthetic material.
• Family history of anaesthetic complications (malignant hyperthermia).

Examination (head to toe, repeated daily).

• Vital signs including oxygen saturation, urine output and mental state.
• Wound and drain sites: erythema, collection, discharge, dehiscence, crepitus. Remove the dressing.
• Chest: crackles, bronchial breathing, effusion. Abdomen: distension, tenderness, peritonism, bowel sounds, drain contents (bile, pus, enteric content, urine).
• Line sites and catheter: phlebitis, pus. Calves: swelling, tenderness. Sacrum and heels: pressure injury.
• Parotids, sinuses, mouth, throat, ears and eyes (endophthalmitis in candidaemia).
• Skin rash, jaundice, lymph nodes, murmurs and splenomegaly. Muscle rigidity and masseter spasm.

Red flags.

• Fever with hypotension, tachycardia over 100 beats/min, confusion, lactate over 2 mmol/L or oliguria (sepsis).
• Fever within hours of anaesthesia with rising end tidal carbon dioxide, tachycardia, muscle rigidity, dark urine, temperature rising by more than 2 degrees Celsius each hour (malignant hyperthermia).
• Pain out of proportion, skin discolouration, bullae or crepitus (necrotising infection).
• Abdominal pain, distension, ileus, high drain output or bilious or faecal discharge (leak).
• Fever with new murmur, embolic phenomena (endocarditis), or an implant.
• Fever within 4 hours of a transfusion with hypotension, back pain or haemoglobinuria.
• Calf swelling, pleuritic chest pain or hypoxia (venous thromboembolism).
• Profuse watery diarrhoea with abdominal distension (severe Clostridioides difficile infection).

Special groups. Older adults may be afebrile with sepsis and present with delirium. Neutropenic patients need immediate antibiotics. Cardiac and orthopaedic surgery carry implant risk. Pregnant patients after caesarean section need assessment for endometritis and wound infection.

Non-infective (early).

• Surgical inflammatory response, atelectasis, haematoma, tissue necrosis.
• Malignant hyperthermia, neuroleptic malignant syndrome, serotonin syndrome.
• Transfusion reaction (febrile non-haemolytic, acute haemolytic, transfusion related acute lung injury, bacterial contamination).
• Drug fever (beta lactams, sulphonamides, phenytoin, heparin, anticonvulsants), heparin induced thrombocytopenia.
• Alcohol or drug withdrawal, thyroid storm, adrenal insufficiency, pheochromocytoma crisis.

Infective: respiratory and urinary. Aspiration pneumonia, hospital acquired pneumonia, ventilator associated pneumonia, empyema, urinary tract infection (catheter associated), pyelonephritis, bacteraemia.

Infective: surgical site. Superficial and deep wound infection, necrotising soft tissue infection, intra-abdominal abscess, anastomotic leak with peritonitis, empyema, mediastinitis, infected haematoma, infected prosthesis, graft or mesh, osteomyelitis, septic arthritis, endometritis, surgical peritonitis. Infective: line and device related. Central line infection, peripheral cannula phlebitis, endocarditis, infected pacemaker, ventriculitis or meningitis after neurosurgery.

Infective: other. Clostridioides difficile infection, sinusitis from nasogastric tube, parotitis, acalculous cholecystitis, cholangitis, pancreatitis, perforation, HIV and tuberculosis reactivation, fungal infection (candidaemia in the critically ill), cytomegalovirus.

Thromboembolic. Deep vein thrombosis, pulmonary embolism, septic thrombophlebitis, mesenteric ischaemia, myocardial infarction, stroke.

Other. Pancreatitis, gout and pseudogout, haematoma resorption, retroperitoneal bleeding, graft versus host disease and malignancy.

Step 1. Review time since surgery, the operation, vital signs and trend, and whether the patient is septic. Find the source with a directed examination, remembering lines, wounds, chest, urine, abdomen and calves.

Step 2. First line tests for fever after 48 hours, or earlier when unwell:

• full blood count and film, CRP, urea, creatinine, electrolytes, liver tests, glucose, lactate, blood gas
• blood cultures (two sets from separate sites before antibiotics)
• urinalysis and urine culture (when symptoms or catheter)
• chest radiograph
• coagulation screen if septic
• wound and drain fluid cultures

Step 3. Targeted tests.

• Respiratory: sputum culture, repeat chest radiograph or CT for consolidation, effusion or collapse.
• Line related: peripheral and line blood cultures drawn at the same time (a line culture positive by over 2 hours earlier than peripheral culture supports line source), and line tip culture after removal.
• Abdominal: CT abdomen and pelvis with intravenous and oral or rectal contrast for leak, collection, ischaemia or free gas (free gas is expected for up to 7 days after laparotomy). Ultrasound for biliary and pelvic causes. Drain fluid amylase and creatinine.
• Thromboembolic: duplex ultrasound of the legs, and CT pulmonary angiography directed by clinical probability (Wells score) and D-dimer (low specificity after surgery).
• Stool: Clostridioides difficile toxin and nucleic acid test for diarrhoea.
• Transfusion reaction: clinical check, repeat crossmatch, direct antiglobulin test, haemolysis screen (haemoglobin, bilirubin, LDH, haptoglobin, urine haemoglobin), and culture of the blood unit.
• Malignant hyperthermia: blood gas (mixed acidosis), potassium, creatine kinase (rises over hours), myoglobinuria.
• Echocardiography (transoesophageal if needed) for suspected endocarditis with implants or bacteraemia.
• Other: procalcitonin (supports bacterial infection and helps decide when to stop antibiotics), thyroid function, cortisol, and drug review. Lumbar puncture after neurosurgery when meningitis is possible.

Interpretation. CRP over 150 mg/L on day 3 to 4 raises concern for infection or collection, and a falling CRP is reassuring. Raised procalcitonin is less specific in the first 2 days after major surgery. Culture results help therapy only when taken before antibiotics.

Limitations. Normal imaging does not exclude early leak. CT is hard to interpret in the first week after laparotomy. Blood cultures are negative in many deep infections.

Immediate priorities. Assess airway, breathing and circulation. Start oxygen to keep saturation over 94% (88 to 92% in carbon dioxide retainers). Resuscitate sepsis with 30 mL/kg isotonic crystalloid for hypotension or lactate of 4 mmol/L or more, and give antibiotics within 1 hour.

Malignant hyperthermia.

• Stop volatile agents and suxamethonium, call for help, hyperventilate with 100% oxygen at high flow (10 L/min or more) through a clean circuit.
• Dantrolene 2.5 mg/kg IV rapid bolus, repeated every 5 minutes up to 10 mg/kg or more until heart rate, rigidity and end tidal carbon dioxide fall.
• Dantrolene maintenance 1 mg/kg every 6 hours for 24 to 48 hours; give extra doses if signs recur.
• Monitor temperature, potassium, creatine kinase, blood gas, urine output and coagulation. Avoid calcium channel blockers.
• Cool actively (cold fluids, ice, surface cooling) to under 38.5 degrees Celsius, treat hyperkalaemia with calcium chloride 10% 10 mL IV and insulin with glucose, and treat arrhythmias without calcium channel blockers. Admit to critical care for 24 to 48 hours.

Febrile transfusion reaction. Stop the transfusion, keep the line open with isotonic saline, check the unit and patient identity, and send samples. For fever and chills without other features, paracetamol 1 g orally every 6 hours (maximum 4 g daily) and observation. Acute haemolysis, anaphylaxis or sepsis from contaminated blood needs resuscitation, adrenaline 0.5 mg IM for anaphylaxis (repeat every 5 minutes), broad spectrum antibiotics and critical care.

Empirical antibiotics (after cultures, in sepsis or an unwell patient with no clear source).

• Intra-abdominal or hospital acquired source: piperacillin with tazobactam 4.5 g IV every 6 hours (maximum 18 g piperacillin daily; every 8 hours for CrCl 20 to 40 mL/min and every 12 hours under 20 mL/min; monitor creatinine and full blood count).
• Resistant organism risk (previous extended spectrum beta lactamase, recent broad spectrum antibiotics, prolonged admission): meropenem 1 g IV every 8 hours.
• Meropenem renal dosing: 1 g every 12 hours for CrCl 26 to 50 mL/min, 500 mg every 12 hours for CrCl 10 to 25 mL/min, 500 mg every 24 hours under 10 mL/min. Monitor seizures and creatinine.
• Add vancomycin 25 mg/kg IV loading dose (maximum 3 g) then maintenance dosed by kidney function and levels when central line, implant, MRSA or skin source is likely.
• Severe penicillin allergy: ciprofloxacin 400 mg IV every 12 hours (maximum 1.2 g daily) plus metronidazole 500 mg IV every 8 hours (maximum 1.5 g daily), with vancomycin when indicated; monitor QTc, tendon pain and glucose; reduce the dose in kidney impairment.
• Hospital acquired pneumonia: piperacillin with tazobactam 4.5 g IV every 6 hours (every 8 hours for CrCl 20 to 40 mL/min; every 12 hours under 20 mL/min).
• Alternatively, ceftriaxone 2 g IV once daily (maximum 4 g daily) when community flora are likely. Review at 48 to 72 hours.
• Urinary tract infection: ceftriaxone 1 to 2 g IV once daily (maximum 4 g daily), changed after culture; remove or replace a urinary catheter that has been in place for over 48 hours.
• Source control (drain collections, remove infected lines and prostheses, return to theatre for leak) is part of treatment and often decides outcome.

Clostridioides difficile infection.

• Vancomycin 125 mg orally every 6 hours for 10 days (maximum 500 mg daily; no dose reduction for kidney impairment) or fidaxomicin 200 mg orally every 12 hours for 10 days.
• Stop the inciting antibiotic where possible. Avoid antimotility drugs.
• Severe or fulminant disease (hypotension, ileus, megacolon): vancomycin 500 mg orally or via nasogastric tube every 6 hours (maximum 2 g daily) plus metronidazole 500 mg IV every 8 hours, with urgent surgical review.

Venous thromboembolism. Give therapeutic anticoagulation after imaging confirms disease, or while awaiting urgent imaging when probability is high.

• Enoxaparin 1 mg/kg subcutaneously every 12 hours (1 mg/kg once daily if CrCl under 30 mL/min; maximum 100 mg for each dose in usual practice).
• Monitor platelets, creatinine, bleeding and anti-Xa level in obesity, pregnancy or kidney impairment.
• Seek surgical advice on bleeding risk.

Antipyretics. Paracetamol 1 g orally or IV every 6 hours as needed (maximum 4 g daily; 3 g daily if weight under 50 kg, malnutrition, alcohol excess or liver disease) for comfort. Do not give antipyretics routinely, because they mask the fever curve and do not treat the cause.

Drug fever. Stop the suspected drug when possible. Fever usually settles within 72 hours.

Withdrawal and endocrine causes. Treat the cause:

• alcohol withdrawal with diazepam 10 mg orally or IV every 1 to 2 hours as needed (maximum 60 mg in the first 6 hours without senior review) plus thiamine 200 to 300 mg IV every 8 hours
• adrenal insufficiency with hydrocortisone 100 mg IV then 50 mg every 6 hours
• thyroid storm with specialist care

Monitoring.

• Observations every 1 to 4 hours (or continuous) in sepsis, strict fluid balance, and daily examination of wounds, drains and lines.
• CRP and white cells daily for 3 days. Repeat cultures when fever persists after 72 hours of treatment.
• Review all antibiotics at 48 to 72 hours with narrowing or stopping (usually 5 to 7 days for most infections, longer for undrained collections, endocarditis, bone and implants).

Referral and escalation. The operating surgeon and a senior surgeon for suspected leak, collection or wound infection. Critical care for septic shock or malignant hyperthermia. Infectious diseases for line, implant and resistant infection. Haematology for transfusion reaction. Interventional radiology for drainage.

Admission criteria. Patients already inpatients stay in. Patients readmitted with fever after discharge need admission for sepsis, suspected leak, deep or implant infection, venous thromboembolism, severe diarrhoea, unreliable oral intake or poor social support.

Discharge and safety netting. Discharge when afebrile for 24 hours, source identified and treated, and oral antibiotics are in place if needed. Patients return for recurrent fever, wound discharge, abdominal pain, vomiting, calf swelling, breathlessness or diarrhoea.