Postoperative Pyrexia | Postoperative Fever

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Introduction

Postoperative pyrexia is a persistently elevated or fluctuating temperature >38°C after surgery. It can also be defined as a temperature >38°C for two consecutive postoperative days or higher than 39°C for any postoperative day.¹

In most cases, this is due to non-concerning causes and self-resolves. A single elevated temperature is rarely concerning; however, in some cases, pyrexia may indicate a more serious cause that requires rapid assessment and management.

Within the first 24 – 48 hours, a raised temperature in the absence of any other clinical signs is part of a normal physiological response.

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Aetiology

Normal physiological response

Postoperative pyrexia in the first 48 hours is most commonly due to a normal inflammatory response.

Tissue damage during surgery triggers the release of inflammatory cytokines (most notably interleukin-1, TNF-alpha, and interferon), which induce an inflammatory response that leads to pyrexia.^2-4 This usually resolves within 2-4 days.

Atelectasis

Atelectasis can cause a low-grade fever postoperatively. Intubation and anaesthesia can result in airway compression and reduced surfactant, leading to partial collapse of the lung in the early postoperative period.⁵

Atelectasis in the postoperative period is very common, occurring in as much as 90% of patients undergoing general anaesthesia.⁶

Infection

Infection can cause pyrexia (usually 48 hours to 7 days following surgery).

Common causative organisms include:

• Staphylococcus aureus and coagulase-negative staphylococci: in orthopaedic, vascular, and plastic surgeries
• Enterococcus, gram-negative bacilli, and anaerobes: in abdominal and pelvic procedures ⁷

Infection in the first 48 hours is most commonly preoperative, and fever after five days is commonly due to a peri or postoperative cause.

Pneumonia

Pneumonia is a common cause of postoperative fever, particularly in the early postoperative period. Immobilisation following surgery and postoperative pain can reduce chest expansion, leading to the accumulation of secretions. Atelectasis can reduce mucociliary clearance, decrease alveolar ventilation, and increase local inflammation, thereby increasing the risk of bacterial colonisation.

Hospital-acquired pneumonia within 5 days is typically caused by Streptococcus pneumoniae, whereas Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa typically cause pneumonia later than 5 days.⁸ Contributing factors include immunocompromise, pulmonary co-morbidities, and endotracheal intubation.

Clinical features include:

• Tachypnoea
• Cough
• Decreased breath sounds and inspiratory crepitations on auscultation

Urinary tract infections

Urinary tract infections (UTIs) are a common cause of pyrexia, and catheterisation increases the risk of infection. The most common causative organism is Escherichia coli, followed by Staphylococcus saprophyticus.⁹

Clinical features include:

• Suprapubic pain
• Dysuria
• Frequency
• Urgency
• Cloudy urine

Surgical site infections

Surgical site infections (SSIs) occur when the wound becomes colonised by microbes (either from endogenous flora or exogenous agents):

• Endogenous microbes are introduced by direct contact from surrounding structures or haematogenous spread
• Exogenous microbes may be introduced by an operator, instrument, graft, or airborne transmission

SSIs can affect the skin or subcutaneous tissue (most common), tissue deep to the subcutaneous fat, such as muscle and fascia, or organs and their associated organ cavities.⁷

Clinical features include:

• Tenderness
• Erythema
• Swelling
• Discharge from the surgical site
• Purulent output from the surgical drain

In the context of recent abdominal surgery, particularly bowel surgery, an intra-abdominal infection should be considered. Signs may also include diffuse abdominal pain, guarding and rebound tenderness.

Toxic shock syndrome

Toxic shock syndrome can rarely occur due to infection with Group A Streptococcus (S. pyogenes) or Staphylococcus aureus. These bacteria release exotoxins that activate the immune system, resulting in the release of inflammatory cytokines and subsequent septic shock.¹⁰ TSS occurs rapidly, typically within 48 hours of surgery.

Deep-seated infection

In the very late postoperative period (7 – 28 days), deep wound infections, abscesses, necrotising fasciitis, infected grafts or prostheses, and osteomyelitis can occur.

Clinical features include:

• Pain at the surgical site
• Erythema
• Swelling
• Discharge from the surgical site
• Purulent output from the surgical drain
• Severe pain in the affected limb
• Tenderness overlying the bone
• Restriction of movement

C. difficile infection can occur secondary to broad-spectrum antibiotic use, immunocompromise, and multiple comorbidities.

Venous thromboembolism

Venous thromboembolism can occur at any point postoperatively due to multiple factors. Surgery can result in vessel injury, venous stasis, and hypercoagulability (Virchow’s triad), leading to deep venous or pulmonary vascular thrombosis.¹²

Clinical features of deep vein thrombosis (DVT) include:

• Calf and leg swelling: >3 cm than the other leg
• Tenderness: particularly along the deep venous system
• Dilation of superficial veins

Clinical features of a pulmonary embolism (PE) include:

• Cough
• Haemoptysis
• Pleuritic chest pain
• Tachycardia
• Tachypnoea
• Hypoxaemia
• Concurrent DVT

Thrombosis

Post-operative myocardial infarction (MI) or stroke can also cause fever, both in the first 48 hours and in the first seven days. This is now relatively rare due to early risk identification and perioperative risk reduction.

Increased catecholamines/cortisol (resulting in coronary vasoconstriction and vascular shear stress), hypercoagulability, and hypertension can lead to coronary artery plaque rupture.^13-14 Postoperative hyper/hypotension, tachycardia, and anaemia can also result in an oxygen supply-demand mismatch, which can lead to myocardial ischemia.¹⁴

Most postoperative strokes are cardioembolic, resulting from perioperative hypercoagulable states and atrial fibrillation (AF). Hypoperfusion can also lead to a stroke, particularly where there is haemodilution and anaemia.¹⁵

Other causes

Other less common causes of postoperative pyrexia include:

• Drug-induced: can occur within 7 days of a drug being started. These include beta-lactam antibiotics (e.g. penicillins and cephalosporins), heparin, aspirin, and some anti-epileptics (e.g. phenytoin)
• Hematoma or seroma: usually fluctuant masses with or without tenderness and overlying redness
• Transfusion reaction: can include febrile non-haemolytic transfusion reaction or, more seriously, anaphylaxis
• Gout: exacerbation from surgery
• Pancreatitis
• Alcohol withdrawal: particularly if not given chlordiazepoxide
• Fat embolism: particularly with long bone fractures
• Transplant rejection (rare)

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Risk factors

The predisposing factors are dependent on the cause.

Infection

Risk factors for infection include poorly controlled diabetes, prolonged hospital stay, traumatic injury, immunosuppressive medications, IV drug use (IVDU), obesity, human immunodeficiency virus, malnutrition, and smoking.²

Venous thromboembolism

Risk factors for VTE include being bedridden for >3 days, active cancer, previous VTE, recent trauma, increasing age, immobilisation, and pre-existing thrombophila.¹²

Myocardial infarction/stroke

Risk factors for MI and stroke include pre-existing coronary or cerebrovascular disease, anaemia, poorly controlled diabetes, renal failure, increasing age, AF, valvular disease, heart failure and infection.¹⁴

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Clinical features

As postoperative pyrexia has many potential causes, a thorough history and examination are essential to make a diagnosis, appropriately investigate, and manage any serious complications.

History

The history should include thorough details of their current admission, including the type of surgery performed, intra- or postoperative complications, need for blood products, placement of prosthesis or grafts, and postoperative recovery (including length of immobility).

The reason for the surgery and admission is essential. A preoperative infection is likely to contribute to postoperative pyrexia for several days (e.g. appendicitis, cholecystitis).

Ask about the onset and duration of the fever and associated features such as pain and swelling.

Take a full surgical history and systems review (looking for an infectious source), including an abdominal and respiratory history.

Other key elements

Other important areas to cover in the history include:

• Past medical history: hyperthyroidism and cancer can cause non-infectious pyrexia, and immunosuppression increases the risk of neutropenic sepsis
• Medication history: to exclude possible drug causes
• Social history: poor oral intake, IVDU, smoking, and high BMI can increase the risk of infection ²

Clinical examination

A full assessment of the surgical site, surgical devices/lines, catheters, surgical drains, and other appropriate systems (e.g. abdominal examination, respiratory examination) should be performed. If there is evidence of acute illness, assess using an ABCDE approach.

All wound dressings should be removed (if the wound isn’t visible) to assess for superficial infection and collection.

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Investigations

Fever during the first 48 hours doesn’t usually require further investigation unless there are other suspicious signs. Further investigation is needed if there are additional indications of a serious underlying cause, e.g. underlying immunocompromise, or if the pyrexia occurs after 48 hours.¹

Bedside investigations

Relevant bedside investigations include:

Laboratory investigations

Relevant laboratory investigations include:

• Full blood count: specifically looking for a raised WCC indicating infection
• Urea and electrolytes: may show acute kidney injury, and guide antibiotic dosing dependent on renal function
• Liver function tests: enzymes may be deranged in systemic illness
• CRP and ESR: raised in infection, and may be raised in MI and VTE
• Troponin: in suspected MI
• D-dimer: in suspected VTE
• Blood cultures: in suspected sepsis (± additional cultures if a line infection is suspected)
• Wound cultures

Imaging

Relevant imaging includes:

• Chest X-ray: for pneumonia or atelectasis
• CT imaging: may be appropriate if a collection or anastomotic leak is suspected

Further investigations should be guided by clinical suspicion and senior input.

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Management

Definite management is dependent on the underlying cause. Initial management of a yet unidentified postoperative fever may include:

Infection

Specific management is guided by the most likely cause and its severity if left untreated promptly. Management should occur early and often while waiting for the results of investigations.^{2, 10, 12}

Pneumonia

Investigations typically include urgent blood tests, an ABG (if concerns of respiratory failure) and a chest X-ray.

Management includes oxygen (if required), antibiotics and chest physiotherapy (to prevent atelectasis).

Urinary tract infection

Investigations typically include urine dipstick and urine culture.

Management includes antibiotics.

Surgical site infection (SSI)

Investigations typically include a septic screen, an assessment of the wound (± exploration in theatre), wound culture, and blood cultures.

Management typically includes a wound wash-out or drainage and IV antibiotics.

Abscess/collection

Investigations typically include CT or MRI, which can evaluate the site and extent of the collection.

Abscesses are typically managed with IV antibiotics and either aspiration or incision and drainage (including a surgical washout).

Seroma

Investigations typically include an ultrasound scan of the wound collection

Seromas can be managed conservatively with appropriate analgesia as they usually self-resolve and are not normally infectious. Aspiration and drainage is reserved if a seroma becomes particularly problematic.

Osteomyelitis and septic arthritis

Typical investigations include a septic screen and joint arthrocentesis with synovial fluid analysis. If exposed bone is present, a wound or bone sample for culture should also be taken. Imaging may include an X-ray of affected bones or an MRI.

Osteomyelitis and septic arthritis should be managed with empirical IV antibiotics, joint aspiration to dryness or surgical exploration in theatre with washout ± debridement.

Intra-abdominal infection (± anastomotic leak)

Investigations typically include VBG (for lactate and possible metabolic acidosis, indicating infection or ischaemia), and urgent CT abdomen and pelvis.

Management includes empirical IV antibiotics and laparotomy with washout (plus repair of anastomotic leak, if present).

Venous thromboembolism

Investigations typically include D-dimer (if below Wells’ criteria range), duplex ultrasound for suspected DVT, or CT pulmonary angiogram (or ventilation/perfusion (V/Q) scan) for suspected PE. 

VTE is typically managed with anticoagulation (with caution in recent surgery). Where there is haemodynamic instability, thrombolysis or thrombectomy should be considered (recent major surgery is a contraindication for thrombolysis).

Thrombosis

Myocardial infarction

Investigations typically include ECG and serial troponin levels.

Management typically includes dual antiplatelet therapy (caution may be needed post-operatively due to bleeding risk), analgesia, nitrates, ± angiography (dependent on the degree of infarction and risk stratification). Ensure a sufficient blood pressure for coronary artery perfusion.

Stroke

Investigations typically include ECG (to exclude AF as a cause) and non-contrast CT head.

Urgent senior support is required, as recent major surgery is an absolute contraindication for thrombolysis. Acute management otherwise may include antiplatelets.

Other causes of postoperative pyrexia

Cause	Clinical features	Management
Cavernous sinus thrombosis	Periorbital oedema and redness, proptosis, cranial nerve VI palsy, and ophthalmoplegia	IV antibiotics Urgent ophthalmology review
Meningitis	Neck stiffness, photophobia, and rash
Transfusion reaction (anaphylaxis)	Fever, headache, nausea and vomiting, wheezing, and tachycardia	Stop transfusion Inform blood bank Observations every 15 minutes
Toxic shock syndrome (TSS)	Fever, shock, and diffuse macular erythroderma	Sepsis 6 Wound and blood cultures IV antibiotics
Transplant rejection (rare) Hyperacute: intraoperative or immediately postoperative Acute: in the weeks after surgery	Symptoms dependent on the organ involved: Kidney: oliguria Lung: shortness of breath Liver: jaundice	Hyperacute: Hyperacute rejection causes irreversible damage, and the organ must be removed Acute: Monitoring Bloods and imaging specific to the transplanted organ Steroids Increased immunosuppression, i.e. increasing doses of tacrolimus and ciclosporin
Delirium tremens (rare)	Fever, tremors, agitation, confusion, and hallucinations	Benzodiazepine e.g. chlordiazepoxide Thiamine supplementation – to prevent Wernicke’s encephalopathy

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Prevention

The risk of postoperative pyrexia can be reduced by thorough clerking, identification of risk factors, and preoperative planning. Prevention methods may include:

• Smoking cessation before elective surgery
• Prophylactic perioperative antibiotics
• VTE prophylaxis (mechanical and/or chemical)
• Early postoperative mobilisation
• Chest physiotherapy and effective pain control to reduce atelectasis and respiratory infection
• Appropriate removal of catheters and cannulas
• Avoiding removal of wound dressings too soon or repeatedly

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Reviewer

Mr Philip C Bennett

Consultant Vascular Surgeon

The author wishes to express their appreciation for the contributions and assistance from Eléna Kappers, MA.

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Editor

Dr Jamie Scriven

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References

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