Postoperative Fever Case File
Eugene C. Toy MD, Donald Briscoe, MD, FA AFP, Bruce Britton, MD, Joel J. Heidelbaugh, MD, FA AFP, FACG
Case 38
On the third postoperative day following an uneventful open appendectomy under spinal anesthesia, a 70-year-old man with history of hypertension and benign prostatic hyperplasia (BPH) suddenly developed a temperature of 102.5°F (39. 1°C) accompanied by chills and vomiting. Just before surgery, a urethral catheter was placed, which was removed 24 hours later, only to be replaced when he was unable to urinate on his own on the second postoperative day. Physical examination is unremarkable except for costovertebral angle tenderness and suprapubic tenderness. He has no abdominal guarding or rebound tenderness.
⯈ What is the most likely cause of postoperative fever?
⯈ What is the next diagnostic step?
⯈ What is the most appropriate treatment at this time?
ANSWER TO CASE 38
Postoperative Fever
Summary: A 70-year-old man with history of hypertension and BPH who underwent open appendectomy under spinal anesthesia develops fever, chills, and vomiting on the third postoperative day. Physical examination shows costovertebral tenderness and suprapubic tenderness. He has a urethral catheter in place because of a problem in voiding.
- Most likely cause of postoperative fever: Urinary tract infection (UTI) with probable pyelonephritis
- The next diagnostic step: Urinalysis (UA) and urine culture
- Treatment: Antibiotics
ANALYSIS
Objectives
- Identify the different causes of postoperative fever based on the timing of onset, nature of surgery, and patient's risk factors.
- Understand the different clinical presentations that point to the etiology of postoperative fever.
Considerations
This 70-year-old man with history of hypertension and BPH is at high risk for UTI because he recently underwent a pelvic procedure under spinal anesthesia and because he has urinary retention secondary to BPH. In addition, the use of a urethral catheter poses an additional risk for bacterial seeding of the urinary bladder. Suprapubic pain and costovertebral tenderness are physical findings suggestive of UTI, most likely acute pyelonephritis. For those without a urethral catheter, symptoms such as dysuria, urgency, and frequency are common. UTI is high on the list of causes of fever in the third postoperative day, although it could also occur anytime during the postoperative period. Urinalysis may detect presence of bacteriuria, pyuria, nitrites, and leukocyte esterase. Urine culture would determine the type of offending organism, the most common of which are Escherichia coli, Proteus, Klebsiella, Staphylococcus epidermidis, Pseudomonas, and Candida. In this patient, the urethral catheter needs to be changed now and discontinued as soon as he is able to void on his own. Symptomatic patients and those who are at high risk for infection are usually treated with appropriate IV antibiotics according to the most likely pathogens. The antibiotics subsequently can be adjusted based on culture results. Blood cultures should be ordered if urosepsis is suspected. Most importantly, it is crucial to address and treat the cause of urinary retention ( eg, BPH, kidney stone) to prevent recurrence and avoid complications.
Approach To:
Postoperative Fever
DEFINITIONS
DRUG FEVER: Fever that coincides with the administration of a particular drug and cannot otherwise be explained by clinical and laboratory findings. Resolution of the fever occurs with discontinuation of the suspected drug. Drugs that are usually implicated are β-lactams, sulfa derivatives, anticonvulsants, allopurinol, heparin, and amphotericin B.
MALIGNANT HYPERTHERMIA: A rare autosomal dominant disorder characterized by fever of greater than 104°F (40°C), tachycardia, metabolic acidosis, rhabdomyolysis, and calcium accumulation in skeletal muscle leading to rigidity. This may occur up to 24 hours after exposure to anesthetic agents such as halothane and succinylcholine. Treatment includes discontinuing offending agents and supportive therapy, such as antipyretics, oxygen hyperventilation, cooling blankets, sodium bicarbonate for acidosis, and dantrolene IV.
SURGICAL SITE INFECTION (SSI): A concept introduced by the Centers for Disease Control and Prevention (CDC) and various consensus panels to replace the term surgical wound infection. This refers to any infection that occurs in the site of surgery within 30 days of an operative procedure or within 1 year with implants. SSIs are classified as superficial, deep, or organ/ space infections. SSI is a common nosocomial infection.
CLINICAL APPROACH
Fever (defined as >38°C/l00.4°F) is the most common postoperative complication, occurring in 50% of major surgery in the immediate postoperative period. As an integral part of informed consent prior to surgery, patients need to be made aware by the physician of the possibility of experiencing postoperative febrile episodes. In addition, adequate preoperative evaluation, which includes performing a history and physical examination to identify risk factors, medications, nutritional status, and comorbid conditions, is imperative to avoid possible life-threatening situations during the perioperative period. Preoperative and perioperative strategies can be used to reduce the risk of developing a postoperative fever (Table 38-1 ). Fortunately, postoperative fever typically resolves spontaneously and most of the time does not necessarily indicate the presence of infection.
The etiology of postoperative fever could be infectious or noninfectious (Tables 38-2 and 38-3). Most postoperative fevers are not infectious, but require a good thorough history and physical to rule infectious causes out. The mnemonic "5 Ws" helps in remembering the most common causes of postoperative fever in roughly the order of frequency: wind (pneumonia), water (UTI), wound (SSI), walking (deep venous thrombosis [DVT]), and wonder drugs (drug fever). When a surgical patient develops fever, the differential diagnosis and investigative methods
Abbreviation: DVT, deep venous thrombosis.
are directed by the timing of the fever, the type of surgery performed, the preexisting clinical conditions, and the presenting symptoms. Comorbid conditions that increase risk for infectious postoperative fevers include increasing age, frailty, smoking, diabetes, and immunosuppression. A thorough physical examination should be initiated, followed by inspection of the surgical site, a review of all medications, and a consideration of hospital-related causes (IV lines and catheters). In the absence of significant risk factors and clear lack of clinical and physical signs of infection, laboratory tests may not be required.
Tissue trauma during surgery stimulates an inflammatory response that leads to release of pyrogenic cytokines (ie, interleukin, tumor necrosis factor, interferons) from the tissues. In general, more extensive surgical procedures are associated with more tissue trauma and a greater degree of fever response. Elevated levels of bacterial endotoxins and exotoxins that are released from the endogenous gut flora of the colon as a result of surgical complications also elicit the same inflammatory response. This reaction leads to elevation of the thermoregulatory set point and production of fever (temperature >100.4°F (38°C]). This explains why suppression of cytokine release by nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or acetaminophen may alleviate fever and enhance patient comfort.
There are few causes of fever in the immediate postoperative period. Medications and blood products are commonly associated with fevers immediately postoperative. A dangerous cause in this period is malignant hyperthermia, which is an inherited disorder characterized by markedly elevated temperature, up to 104°F (40°C), typically within 30 minutes after induction of inhalational anesthesia (ie, halothane) or depolarizing muscle relaxant (ie, succinylcholine). Another cause of immediate postoperative fever is bacteremia, which occurs more commonly in urologic procedures that involve instrumentation, for example, transurethral resection of the prostate. Gram-negative bacteria are the most common pathogen. Within 30 to 45 minutes, the patient develops chills and temperature that could exceed
104°F (40°C). Accompanying symptoms such as tachycardia, tachypnea, oliguria, and hypotension are common.
If fever occurs within 36 hours postlaparotomy, there are two important infectious etiologies to keep in mind-bowel injury with leakage of gastrointestinal contents into the peritoneum and invasive soft-tissue wound infection caused by β-hemolytic streptococci or Clostridium species. The former is accompanied by hemodynamic instability. Much less common in this setting is toxic shock syndrome caused by Staphylococcus aureus.
Within the first 48 to 72 postoperative hours, atelectasis (partial collapse of peripheral alveoli) causes 90% of pulmonary complications of surgery, particularly following abdominal and thoracoabdominal procedures. Contrary to popular belief, its close association with early postoperative fever is probably coincidental. The alveolar collapse is compounded by the loss of functional residual capacity in almost all patients and 50% reduction of vital capacity intraoperatively. Chest x-ray may reveal discoid infiltrate and an elevated hemidiaphragm. Although fever is not likely a consideration, hypoxemia, pneumonia, and scarring that can lead to bronchiectasis can be a consequence of atelectasis.
Instructing the patient on deep inspiration and coughing, the use of incentive spirometry, and the provision of adequate pain control can facilitate the opening of the alveoli. Without resolution of atelectasis, pneumonia may ensue. Patients who are on mechanical ventilators are at highest risk for pneumonia (ventilatorassociated pneumonia). Fever associated with productive cough, pulmonary crackles, worsening oxygenation, elevation of white blood counts (WBCs), positive sputum culture, and new infiltrates in chest x-ray are the usual indicators of pulmonary infection. Postoperative pneumonia is typically polymicrobial. Enterobacteriaceae and S aureus or Enterobacteriaceae and streptococci are common bacterial combinations. Appropriate use of broad-spectrum IV antibiotic therapy is the treatment. Aspiration as the possible cause of pneumonia should be suspected in the elderly, those who reside in a nursing home, and those with neurologic dysphagia, compromised cough reflex, altered mentation, endotracheal intubation, and gastroesophageal reflux disease (GERD). Antibiotics are typically given following a witnessed aspiration and discontinued after 48 to 72 hours with no development of infiltrates. Gram-negative coverage is required for aspiration pneumonia, with the current agents of choice being piperacillin/tazobactam, meropenem, or cefepime with metronidazole. Vancomycin can be considered to cover for methicillin-resistant S aureus (MRSA). It is also around this time that UTI should be entertained as part of differential diagnosis. Mild UTIs can be treated with similar agents or with a third generation cephalosporin or fluoroquinolone. For severe cases or if drug-resistant bacteria are suspected, carbapenems are recommended.
The patient with persistent fever 5 to 7 days after surgery needs to have a thorough examination of the operative site to check for signs of infection, which include erythema, pain, local edema, and purulent discharge. Surgical site infections (SSIs) have markedly decreased through wide practice of aseptic technique and team-based perioperative management protocols. Patients at high risk of wound infection are those who underwent lengthy surgical procedure, received blood transfusion, are malnourished, are immunosuppressed, and those who have diabetes mellitus. Prophylactic antibiotics should be given within 1 hour before surgery and discontinued within 24 hours after surgery to lower the risk of SSL Skin site infections may be treated with oxacillin or with vancomycin if MRSA is common in the institution or environment. Deep abdominal infections are often treated with a cephalosporin, such as cefoxitin, or a combination of fluoroquinolone plus metronidazole to cover anaerobic, enterococci, and enteric gram-negative bacilli infections.
Drug fevers are often associated with rash and/or lupus-like syndromes. They also may have renal, liver, lung, joint, or hematologic dysfunction associated with the drug toxicity. The risk of developing drug fever correlates with the number of drugs prescribed. Antimicrobial agents account for roughly one-third of all cases. Common antimicrobial agents associated with drug fever include minocycline, cephalosporins, fluoroquinolones, sulfonamides, and penicillins. Drug fever typically resolves within 72 to 96 hours after the discontinuation of the offending agent.
Purulent drainage and fluctuance indicate the presence of abscess, which requires incision and drainage. When cellulitis is confirmed, treatment with antibiotic is warranted. Gram-positive bacteria, such as S aureus, S epidermidis (especially with implants or devices), Streptococcus pyogenes, and Enterococcus, are important pathogens. Fungal etiology should not be ruled out in patients with severe comorbid conditions. On rare occasions, deep abscesses produce fever 10 to 15 days after surgery. A high level of suspicion leads to diagnostic imaging such as computed tomography (CT) scan of the body region most likely to be infected, which depends on the location of the surgery. Interventional radiology specialists could be called upon for radiologically guided drainage of the abscess, which is the definitive treatment. Antibiotics should include coverage for gram-negative enteric bacilli and anaerobes, especially when intra-abdominal or pelvic infections are suspected. Gallium scans may be helpful in finding sites of infection in patients without localizing symptoms and workup.
lntravascular catheter or line-associated infection needs to be entertained when the patient has had IV devices for 3 days or more, even when the site appears clean. Any unnecessary lines should be discontinued, as they are potential sites of infection. The catheter tip is cultured to reveal the offending organism that would direct treatment.
Fever caused by DVT usually occurs 1 to 4 weeks postoperatively. Half of the time patients with DVT are asymptomatic. Common complaints are unilateral leg swelling, tenderness, pain, and warmth. The Homan sign (pain in the calf on foot dorsiflexion) is demonstrated in some cases. When possible, surgical patients are encouraged to ambulate early; otherwise, subcutaneous heparin or low-molecular weight heparin are useful prophylactic measures. If the patient is at high risk for bleeding, intermittent pneumatic compression devices can help. Diagnosis is made by duplex ultrasound. Patients who develop pulmonary embolism usually have concomitant DVT. The treatment of DVT and pulmonary embolism is initiated with low-molecular-weight heparin or unfractionated heparin, followed by warfarin.
The type of surgery also provides a clue as to the associated risks of fever associated surgical morbidity. In general, laparoscopic surgery comparatively causes fewer cases of fever than open surgery due to less tissue trauma. Pleural effusion develops in all patients undergoing cardiothoracic surgery and 5% of those patients acquire pneumonia. Particularly unique to abdominal surgery is deep abdominal abscess and pancreatitis. Obstetric and gynecologic surgery could be complicated by postpartum endometritis/deep pelvic abscess, necrotizing fasciitis, and pelvic thrombophlebitis. SSI is the most common infectious cause of fever in orthopedic surgery. Prostatic and perinephric abscess are more commonly seen in urologic procedures. Arterial embolization, or " blue toe'' syndrome due to emboli from an infected vascular graft can occur following vascular surgery, especially in grafts involving the groin and the legs. Endovascular aortic aneurysm repair may be complicated by"postimplantation syndrome" characterized by self-limited fever, elevated C-reactive protein (CRP) levels, leukocytosis, and negative blood cultures. Patients undergoing genitourinary procedure are at greater risk of having UTI. Meningitis is a common cause of fever following a neurosurgical procedure. Neurosurgery patients, who are usually immobilized and less aggressively anticoagulated to avoid brain hemorrhage, have the highest incidence of DVT.
COMPREHENSION QUESTIONS
38.1 A 60-year-old man with adenocarcinoma of the colon underwent left hemicolectomy with primary anastomosis. Thirty hours after surgery, he was found to have a fever of 102°F (38.8°C), blood pressure of 90/60 mm Hg, heart rate of 140 beats/ min, respirations of 24 breaths/ min, and low urine output. Physical examination showed diffuse abdominal tenderness. The surgical site is clean and Gram stain did not show any organism. Urinalysis was negative and the complete blood count (CBC) showed leukocytosis. Which of the following is the most likely cause of this patient's fever?
A. Pneumonia
B. Intraperitoneal leak from bowel injury
C. Surgical site infection
D. Deep tissue abscess
38.2 An 84-year-old nursing home resident underwent emergency open cholecystectomy under general anesthesia. She has advanced Parkinson disease, hypertension, and diabetes, and was receiving nutrition via nasogastric tube (NGT). On the second postoperative day, she was noted to be coughing and vomiting. Four days later, she had a temperature of 102°F (38.8°C), heart rate of 90 beats/min, respiratory rate of 25 breaths/min, blood pressure of 120/70 mm Hg, and oxygen saturation of 87% on room air. She had a productive cough with what the nursing staff describes as "putrid sputum:' Lung auscultation showed crackles on the right and a chest radiograph revealed a patchy infiltrate in the right lung. Which of the following is the most appropriate next step in management?
A. Obtain an expectorated sputum sample for culture.
B. Treat empirically with antibiotics.
C. Insert a nasogastric tube.
D. Treat with a proton pump inhibitor (PPI).
38.3 A 42-year-old man underwent open reduction and internal fixation of a comminuted fracture of the right femur. He was doing well until the fifth postoperative day, when he complained of pleuritic chest pain and developed fever of 101°F (38.3°C), heart rate of 118 beats/min, respiration of 30 breaths/min, blood pressure of 130/85 mm Hg, and oxygen saturation of 85% on room air. His left ankle became edematous, warm, and tender. Which of the following is a risk factor for his condition?
A. Having an IV in his arm for more than 3 days
B. Failure to adequately use his incentive spirometer
C. Urinary bladder catheterization
D. Prolonged immobility
38.4 A 50-year-old woman with diabetes was recuperating from left inguinal hernia repair. Her glycosylated hemoglobin (HbA1c) prior to surgery was 10%. During postoperative follow-up a week after surgery, the surgical site was markedly erythematous, warm, and tender with pus. Which of the following is the next step in treatment?
A. Apply topical antibiotic to the surgical site.
B. Warm compresses alone will relieve the inflammation.
C. Open the surgical site and drain the infected material.
D. Send the patient home with prescription for oral antibiotics for 7 days.
ANSWERS
38.1 B. In the presence of severe hemodynamic changes and diffuse abdominal tenderness, intra peritoneal leak is the most common cause of fever in the first 36 hours after laparotomy.
38.2 B. This patient likely has aspiration pneumonia. She has risk factors including her age, functional status, recent general anesthesia, and advanced neurologic disease. She requires treatment with antibiotics which cover anaerobic bacteria. There is evidence that aspiration risk may not be reduced by placing a nasogastric tube before surgery but actually predisposes a person to aspiration pneumonia. Giving the patient a PPI does not treat and can increase risk of aspiration pneumonia. Expectorated sputum is unreliable for anaerobic cultures because of likely contamination by oral flora.
38.3 D. This patient has DVT and concomitant pulmonary embolism. Risk factors include prolonged immobility, vascular damage, and hypercoagulability.
38.4 C. Incision and drainage are the most important therapy for SSI Antibiotics are used solely in cases of significant systemic involvement.
CLINICAL PEARLS
⯈ Postoperative fevers in the first few days are common and usually resolve on their own .
⯈ A thorough risk assessment, history, and physical are needed to determine if laboratory testing and antibiotics are warranted .
⯈ The timing of the fever is useful in creating an effective differential diagnosis for postoperative fever.
⯈ Removal of all unnecessary medication, catheters, lines, and tubes should be discontinued in the postoperative febrile patient.
REFERENCES
Beilman G, Dunn D. Surgical infections. In: Brunicardi FC, Anderson DK, Billiar TR, et al., eds. Schwartz's Principles of Surgery. 9th ed. New York, NY : McGraw-Hill Education; 2010.
Libman H, Wilson P. Evaluation of Postoperative Fever, ACP Smart Medicine & AHFS DI Essentials, editorial changes 2014-06-27. P hiladelphia, PA: American College of P hysicians; 2015.
Narayan M, Medinilla S. Fever in the postoperative patient. Emerg Med Clin North Am. 2013 Nov;31(4):1045-1058.
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