Etiology
The differential diagnosis is largely influenced by the time elapsed between the surgical procedure and the onset of the fever. Up to 80% of patients with fever in the first postoperative day will have a self-limiting etiology, and spontaneous resolution would be expected.[5]
If the fever does not resolve, appears after the first 48 hours, or is associated with characteristic symptoms and signs of an underlying condition, further investigation is required.
A prospective cohort study of elective surgical patients found that surgical site infection is the most common postoperative complication (during the 30-day postsurgical period), followed by urinary tract infection, and pneumonia.[6] Surgical site infections occur in approximately 1% to 3% of patients undergoing inpatient surgery, depending on the type of operative procedure performed.[7][8][9]
Any fever presenting in an organ transplant recipient or in an immunosuppressed patient requires urgent investigation.
Postoperative period: 0 to 48 hours
Fever in the first 48 hours is usually due to an inflammatory response to the surgery itself. Direct tissue trauma causes the release of the cytokines interleukin (IL)-1, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and IL-6.[10][11] Sutures also elicit a foreign body inflammatory response. The greater the tissue damage, the more pronounced the subsequent increase in temperature.[5][12] The fever is self-limiting and resolves within 2 to 4 days.[5][13]
Other causes of fever during the first 48 hours after surgery include:
Vascular causes: myocardial infarction is the most common complication occurring in the first 24 hours postoperatively.[6] Postoperative stroke usually presents in the first 48 hours. Infarction of the operated tissue presents in the immediate postoperative period.
Infection: community-acquired infections, hospital-acquired pneumonia caused by aspiration during the perioperative period, and toxic shock syndrome, (a rare complication of bacterial wound infection), may present in the first 48 hours after surgery.[14][15]
Drug-induced: drugs cause fever through hypersensitivity reactions, idiosyncratic reactions, alterations in thermoregulation, or by a direct pharmacological action. This effect can be seen at any time within the first 7 days of drug administration.[16] The most common drugs causing fever are hydroxyurea, propylthiouracil, iodides, heparin, allopurinol, immune globulins, salicylates, phenytoin, hydralazine, procainamide, furosemide, and thiazide diuretics. Several antibiotics also may cause fever including beta-lactam antibiotics, cephalosporins, sulfonamides, vancomycin, rifampin, and fluoroquinolones.[11][17]
Malignant hyperthermia: a rare but potentially life-threatening reaction to inhalation anesthetics that usually occurs intraoperatively or in the immediate postoperative period. It is produced by an acceleration of muscle metabolism and presents with high fever, hypercapnia, muscle rigidity, and tachycardia and tachypnea.[18] The condition can be triggered by any inhalation anesthetic or succinylcholine.
Blood transfusion reaction: although the onset of blood transfusion reactions can vary depending on the mechanism, the majority occur during or immediately following administration of blood or blood products. The reaction and subsequent fever are immune-mediated.[19]
Trauma: complications produced by trauma during surgery usually present in the first 48 hours. Those that cause fever are hematomas, seromas, and subarachnoid hemorrhage. Hematomas produce local swelling, pain or, rarely, compartment syndromes of the operated compartment. Compartment syndrome of the extremities due to a hematoma is most likely to occur following orthopedic trauma surgery. Compartment syndrome of the orbit is very rare, and is most likely to be seen following eye surgery or surgery for facial trauma.
Pre-existing conditions: the stress of surgery can exacerbate hyperthyroidism and even precipitate a thyroid storm. Physical pressure on a pheochromocytoma during surgery, even if indirectly transmitted, can increase the release of catecholamines from the tumor. Either effect can produce a fever.
Transplant rejection: if the patient has undergone an organ transplant, hyperacute rejection can present within minutes to hours of the transplantation.
Postoperative period: >48 hours to 7 days
If the onset of fever occurs later than 48 hours, an infectious etiology is likely, and becomes more likely with each additional day. Ninety percent of cases of postoperative fever presenting 5 days or later have an identifiable infection.
Risk factors for surgical site infection include: prolonged hospital stay, anemia, immunosuppressive medication, history of alcohol misuse, obesity, depression, history of congestive heart failure, HIV/AIDS, malnutrition, and smoking.[7][20]
Infections introduced by surgery
Pneumonia, urinary tract infection (UTI), and superficial surgical site infections are the most common infections that present in this time frame.[6]
Patients who have undergone neurosurgery may develop meningitis. Aseptic meningitis (a tissue inflammatory response to surgery) is more common, but all patients are treated as having bacterial meningitis until infection is excluded. Patients who have undergone head and neck surgery may develop otitis media.
Infections introduced through invasive access
Urinary catheter-associated UTI, pneumonia (due to endotracheal intubation), and catheter-related intravascular infections (due to intravascular access) are the most common. Superficial thrombophlebitis (at the site of catheter placement) and acalculous cholecystitis (due to hematogenous spread of bacteria) are also relatively common.
Other causes of infection
Infections introduced by transfusion of blood and blood products are very rare. Acute bacterial infections caused by transfusion include Yersinia, Pseudomonas, Staphylococcus, Salmonella, enterococci, and Clostridium species. West Nile virus and parasitic infections can also rarely be transmitted. Cytomegalovirus is common, but is asymptomatic except in immunocompromised patients.[21]
Adrenal insufficiency should be considered in patients with postoperative fever as it increases the risk of infection. Adrenal crisis itself can also cause fever.
Noninfectious causes
Possibilities during this time frame include:
Myocardial infarction
Drug-induced fever
Gout and pseudogout: patients with underlying gout or pseudogout can have an acute exacerbation following surgery[22]
Pancreatitis can occur as a result of any surgical intervention. The pathophysiology is poorly understood
Alcohol withdrawal usually begins during this time and patients with a history of alcohol abuse should be closely observed
Vascular causes: fat embolism presents from 48 to 72 hours, whereas thromboembolism presents later, usually during or after the second postoperative week. Cavernous sinus thrombosis is a rare complication that can occur in patients who have undergone recent head and neck surgery.
Atelectasis has a high prevalence in the postoperative period and therefore its coexistence with fever is not surprising. However, atelectasis correlates poorly with postoperative fever, and the relationship is coincidental rather than causative.[23][24][25]
Postoperative period: >7 days to 28 days
Infections are the main cause of fever presenting in this time frame:
UTIs, pneumonia, and catheter-related intravascular infections (due to intravascular access) remain common[6]
Clostridium difficile infection usually appears in the second week and there is typically a history of antecedent antibiotic use[26]
Wound cellulitis can present at any time after the first 48 hours, but deep wound infections and abscesses typically appear after the first week.[6] Necrotizing fasciitis is a rare, deep wound infection that is indistinguishable from cellulitis in the early stages. Symptoms include warm, tender, erythematous skin. As the infection progresses, patients show signs of sepsis and develop severe pain beyond the margins of the cellulitis. Patients might also have a thin wound discharge, skin crepitus, fluctuance, induration, bullae formation, and skin necrosis.[27]
Foreign-body infections start to manifest after the first week. These include infections of orthopedic hardware, endovascular devices, prosthetic valves, grafts, and stents
Osteomyelitis occurring as a complication of orthopedic surgery may appear as early as the second postoperative week (although some cases present months after surgery)
Sialadenitis usually presents after the first postoperative week, and is more common in older, debilitated, or malnourished patients with poor oral hygiene
Sinusitis usually presents after the first postoperative week and is most commonly associated with prolonged nasogastric tube insertion.
Noninfectious causes of fever presenting in this time frame:
Acute transplant rejection typically appears in the second postoperative week, or later.
Patients with underlying malignancy are at increased risk of developing a postoperative fever, which typically presents in the second postoperative week or later.
Deep venous thrombosis and pulmonary embolism produced by prolonged immobility typically present after the first week.[6] Cavernous sinus thrombosis can present in this time frame. Acute transplant rejection typically appears in the second postoperative week or later.
Postoperative period: >4 weeks
The predominant cause of fever in this time frame is infectious. The most common infections seen are foreign-body infections.
Osteomyelitis due to implant infection following orthopedic surgery can present weeks or even months after the surgery.
Infectious endocarditis can present as early as 5 weeks postoperatively, but any patient with a valve replacement has a lifelong increased risk of developing this infection.
The presentation of other surgical site infections may be delayed until 4 weeks postoperatively if caused by less virulent bacterial strains, but this is unusual.
Acute transplant rejection can present in this time frame.
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