You receive a call from the nurse regarding a 47-year-old man who had an uncomplicated laparoscopic sigmoid colectomy 2 days ago for a nearly obstructing but benign polyp. The patient just spiked a fever of 39.1° C (102.4° F). On your initial evaluation, he is tachycardic with a heart rate of 109 beats/minute and BP of 143/87 mm Hg. His Spo2 is 94% on room air and his respirations are 18 and unlabored. What is your next best step?
Adult postoperative fever, defined as an elevation of body temperature to greater than 38.3° C (100.4° F) following major surgical procedures, is a common complication in hospitalized patients. Incidence rates of postoperative fever vary widely between surgical subspecialties and have been shown to range between 14% and 91%.1 Most cases (72%) of postoperative fever occur within the first 48 hours; gynecologic studies have shown that up to 90% of patients with postoperative fever have no infectious or pathologic cause for the fever despite an extensive costly evaluation.2,3 In fact, one gynecologic study found the total charge for a postoperative fever infectious workup was more than $2,000 per event.4 In contrast, almost 90% of patients who developed fever after postoperative day 4 were found to have an identifiable infectious source and required therapeutic intervention.2 These patients must be identified promptly to limit postoperative complications and mortality. The challenge is to identify which patients need immediate screening and a thoughtful infectious evaluation, and which can be skillfully managed with observation and watchful waiting.
PHYSIOLOGIC RESPONSE TO SURGERY
Surgery of any type causes significant cellular injury and inflammation. This natural but often detrimental inflammatory response is primarily driven by cytokine release from macrophages, endothelial cells, and the reticuloendothelial system that are stimulated by tissue damage during surgery.5 Once released into the bloodstream, cytokines act on the preoptic area of the hypothalamus to increase prostaglandin production, raising the thermoregulatory set point for the body temperature.5
The specific influential pyrogenic cytokines that affect postoperative temperature regulation are serum interleukin-I (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), and interferon-gamma. In patients undergoing cardiovascular surgery, IL-6 levels have been shown to most directly correlate with the magnitude of the fever curve in the early postoperative period.6,7 The more tissue damage, the greater the cytokine release, so patients undergoing major surgery are more likely to develop postoperative fever than those undergoing minimally invasive procedures.8
This physiologic adaptation to surgery often is evident in the first 48 hours after surgery and is responsible for most postoperative fevers. Patients whose temperatures spike in the first 2 postoperative days should be assessed for life-threatening conditions and monitored for signs of clinical deterioration. This physiologic response to surgery is a normal step in healing; costly laboratory workup or pharmaceutical treatment will not improve overall outcomes.
THE SEVEN W'S OF POSTOPERATIVE FEVER
Clinicians need to be vigilant in identifying the pathologic causes of postoperative fever that do require workup. The seven W's (Table 1) can help with this evaluation.
Postoperative patients spend the majority of their day sitting or lying in bed, which leads to incomplete expansion and resulting atelectasis.9 Patients may have poor inspiratory effort due to sedation or pain and may be unable to clear the pulmonary secretions that are common following intubation and general anesthesia.9 Atelectasis itself also triggers an inflammatory response and is one of the most common complications seen in the early postoperative period, with incidence rates as high as 90%.9 Atelectasis has long been considered the leading cause of postoperative fever, but newer studies have shown no association between the degree of atelectasis and postoperative fever.10,11 Incidence of atelectasis peaks within the first 48 hours following surgery while the patient is recovering from anesthesia and starting to mobilize, which coincides with the pathophysiologic response to surgery and cytokine surges.
Identification and treatment of atelectasis are important in the early management of postoperative patients because rates of healthcare-associated pneumonia increase after the first 48 hours.9 Signs and symptoms of atelectasis include decreased breath sounds, crackles, tachypnea, dyspnea, cough, hypoxemia, and dependent infiltrates on chest radiography.9
Treatment for atelectasis consists of increased pulmonary hygiene: deep inspiration assisted by incentive spirometry, early mobilization, chest physiotherapy, and bronchodilators.9 Use a multimodality approach to aid lung recruitment and avoid healthcare-associated pneumonia, which dramatically increases postoperative morbidity and mortality.
Urinary tract infections (UTIs) are the most common nosocomial infections in the United States, accounting for up to 40% of all of hospital-acquired infections.12,13 Many patients undergoing surgical procedures require a urinary catheter during and after surgery, which increases the risk of postoperative UTI.
Many patients with UTIs are asymptomatic and do not require treatment. In these cases, treatment does not improve outcomes and can increase rates of antimicrobial resistance.14
Symptoms of UTI include fever, suprapubic or flank pain, costovertebral angle tenderness, and urinary urgency. Risk factors for developing a symptomatic UTI that requires treatment include length of catheterization, unsterile placement or care of a urinary catheter, female sex, older age, history of diabetes, and history of previous UTIs.15
Obtain a urinalysis and urine culture with sensitivity for patients with symptoms suggestive of a UTI. Positive results requiring treatment include pyuria, positive leukocyte esterase, positive urine nitrites, and bacterial culture showing more than 105 cfu/mL of the offending organism.16 The most common causative organisms implicated in catheter-associated UTI are E. coli (27%), Enterococcus spp (15%), Candida spp (13%), P. aeruginosa (11%), and Klebsiella spp (11%); empiric treatment should be aimed at these pathogens with tailoring to specific organisms once culture data are available.12 Empiric treatment while awaiting culture data is contingent upon the degree of patient illness, comorbid conditions, previous culture results, and local resistance pattern. In particularly difficult cases, consult the infectious disease specialist, microbiology laboratory, and hospital pharmacy to determine appropriate regimens.
Surgical site infections (SSIs) are defined by the CDC as infections that occur at or near the surgical incision within 30 days of surgery or within 90 days if prosthetic materials have been implanted.17 The overall incidence rate of SSI is less than 2%, with an overall mortality of 3%.17 Most patients with SSIs develop erythema, warmth, tenderness, and purulent drainage from the incision 5 to 10 days after surgery.18 The National Nosocomial Infection Surveillance System Risk Index for Surgical Site Infections was developed in 2001 and uses three variables that have been shown to increase the risk of developing an SSI:
- American Society of Anesthesiologists physical status classification score of 3 to 5, indicating that the patient is a high-risk surgical candidate
- contaminated or dirty procedure
- an operative duration that is greater than the 75th percentile for that procedure.19
This index also identifies use of a laparoscope, when appropriate, as a negative risk factor.19 Other patient-specific factors that increase risk for SSI are older age, poor nutrition, history of diabetes, smoking, obesity, other concomitant infections, impaired immune status, and previous history of colonization.20
SSIs can be classified as superficial (skin and subcutaneous tissue only), deep (involving fascia and muscle), and organ/space infection.17 Collect specimens of the purulent drainage for culture because they typically are needed for microorganism identification and antimicrobial sensitivities to tailor treatment. Avoid routine culture swabs of incisions, which can be contaminated with skin flora. Patients with signs of severe illness (such as high fever, leukocytosis, or hemodynamic instability) out of proportion to skin findings may need radiographic studies, such as ultrasound or CT, to identify deep or organ/space infections. In these cases, operative or interventional drainage is needed so the pathogen can be identified and appropriate antibiotics selected.
The most common pathogens that cause SSI are skin flora, such as species of Streptococcus, Staphylococcus, and Enterococcus.21 Patients who may need antimicrobial prophylaxis before surgery include those with a history of past infections with drug-resistant organisms and those who have been hospitalized within the previous 12 months in order to determine the need to cover for Gram-negative organisms. Rare life-threatening wound infections, such as Clostridium spp causing gangrene or group A beta-hemolytic streptococcal infections causing necrotizing fasciitis, should be considered in patients who are critically ill and require ICU transfer. Empiric antibiotic treatment should be guided by individual hospital antibiogram and patient-specific risk factors until culture data are available for tailored treatment.
Postoperative patients account for 20% of all hospital-acquired deep vein thromboses (DVTs).22 Patients often are sedentary for the first few postoperative days due to pain and also may be immobilized after certain surgeries. The resulting venous stasis, combined with the postoperative inflammatory cascade, increases patient risk for DVT. The problem for clinicians is that 10% to 80% of hospitalized patients with DVT are asymptomatic.23 The only objective finding that may be apparent is fever due to inflammation of the deep venous system with local vascular irritation.24 Patients at high risk for developing postoperative DVT include those undergoing abdominal-pelvic surgery or lower extremity orthopedic surgery, patients with major trauma or spinal cord injury, patients with cancer, and those who are obese.25 DVT incidence increases after postoperative days 3 to 5, but may occur sooner in high-risk patients. Patients also can have a febrile response to a pulmonary embolism (PE) without signs or symptoms of a DVT; PE can be a cause of sudden death in a postoperative patient. Patients with suspected DVT should be screened with a lower extremity Doppler ultrasound and started on therapeutic anticoagulation when clinically safe.
Medications are the most common noninfectious cause of fever in postoperative patients, and can cause fever immediately after administration or hours or days later. Antimicrobials and heparin account for almost one-third of cases of drug-related fever in hospitalized patients.26 Most of these drug-related fevers are transient and require no specific workup or treatment.
Three specific medication-related conditions may present in perioperative patients with a fever greater than 40° C (104° F):
- Serotonin syndrome is caused by medications interacting with selective serotonin reuptake inhibitors (SSRIs), resulting in increased serotonergic neurotransmission and overstimulation of central and peripheral serotonin receptors.27 Signs and symptoms of serotonin syndrome include fever, altered mental status, hyperreflexia, myoclonus, and mydriasis.27
- Malignant hyperthermia, which occurs in genetically susceptible patients when they are exposed to volatile anesthetics, causes profound calcium accumulation that leads to cellular hypermetabolism.28 Symptoms include muscle rigidity, acid-base disturbances, and hyperthermia, which can occur in the OR or can manifest as a later sign.28
- Neuroleptic malignant syndrome is a dysautonomic condition thought to be caused by dopamine receptor blockade in the hypothalamus that leads to muscle rigidity, altered mental status, and hyperthermia.29 Most commonly caused by the typical neuroleptic medications, it also can be caused by antiemetic medications such as metoclopramide and promethazine that are commonly used to manage postanesthesia nausea.
Management of these specific medication-driven febrile syndromes revolves around identifying the cause, discontinuing any medication that could be causing the reaction, and providing supportive care to prevent febrile complications.
Alcohol consumption is a significant problem because 51% of adults over age 18 years admit to regularly drinking alcohol and 7.2% of these adults have been diagnosed with an alcohol use disorder.30-32 Of patients with an alcohol use disorder, 50% have symptoms of alcohol withdrawal during abstinence.30-32 Acute alcohol withdrawal symptoms may present within 6 hours of the patient's stopping alcohol use, and typically are mild with vague complaints of insomnia, anxiety, headache, and diaphoresis.33 These symptoms can easily be overlooked or misinterpreted as normal postoperative manifestations. If patients are not identified and treated, they may develop delirium tremens. This serious condition, which has a mortality of up to 4%, begins about 72 hours after the last alcohol ingestion. The constellation of symptoms includes hyperthermia (temperature greater than 40° C), altered mental status, agitation, hallucinations, or seizures.34 Because patients often are NPO for up to 12 hours before surgery, by the time they are postoperative, they are well into the risk period for developing acute alcohol withdrawal. Prevention is key, and involves proper preoperative social history and identification of postoperative symptoms. The acute treatment is an aggressive high-dose benzodiazepine regimen, either diazepam or lorazepam, until symptoms resolve; medications are then tapered over the next several days.34
Two endocrinologic causes of fever in postoperative patients require specific mention and consideration: adrenal insufficiency and thyrotoxicosis. The hypothalamic-pituitary-adrenal axis has many endocrine roles in the hours to days following surgery and is essential in maintaining homeostasis during this time. Cortisol and catecholamines are secreted by the adrenal glands to help blunt the inflammatory cascade and support hemodynamics following the stress of surgery. Patients with undiagnosed adrenal insufficiency, or those being treated with systemic corticosteroids before surgery without having a stress-dose adjustment, will not be able to mount a response to this stress and will develop signs and symptoms of acute adrenal insufficiency. These include hypotension, hyponatremia, hyperkalemia, hypoglycemia, and unexplained fever. Signs and symptoms usually manifest within the first few hours following surgery.35 Clinicians must be careful not to attribute this fever in the early postoperative period to normal physiology if the other manifestations of adrenal insufficiency are present.
Management of acute adrenal crisis is a bolus dose of glucocorticoids with either dexamethasone 4 mg IV or hydrocortisone 100 mg IV as well as crystalloid volume resuscitation.35
Thyrotoxicosis also may manifest postoperatively in patients with undiagnosed hyperthyroidism, or those with known hyperthyroidism who have not taken their medications due to NPO status. The hypothalamic-pituitary-thyroid axis in these patients already is hyperactive and the added physiologic stress of surgery may push this out of balance and precipitate thyroid storm. Common clinical manifestations of thyroid storm include tachycardia, altered mental status, hyper- or hypotension, and hyperthermia (greater than 40° C).36 Acute management of thyroid storm is a multimedication approach with beta-adrenergic blockade (propranolol 1 mg IV bolus), a thionamide (propylthiouracil 200 mg oral), and iodine solutions to blunt the physiologic effects and prevent the synthesis and release of new thyroid hormone.36
Most of the causes of fever in the postoperative setting are not life-threatening and mainly revolve around normal physiologic responses to acute stress, prevention of complications, and management of simple infections. However, clinicians caring for patients in the postoperative setting should always remember the causes of fever in surgical patients that have a higher mortality and require prompt identification and aggressive management, including:
- myonecrosis from Clostridium spp
- necrotizing fasciitis
- pulmonary embolism
- serotonin syndrome
- malignant hyperthermia
- neuroleptic malignant syndrome
- delirium tremens
- adrenal insufficiency
- thyroid storm.
The patient presented at the beginning of this article should have a chest radiograph, aggressive spirometry, and mobilization to aid in lung recruitment, as he likely has atelectasis (tachypnea and hypoxemia) and the fever is from the normal physiologic response to surgery.
Fever in a postoperative patient is a common occurrence. Clinicians should be able to differentiate between the normal physiologic response to surgery and a pathologic response. Fever in the first 2 postoperative days is expected and patients should be closely monitored, but not worked up. Pathologic causes need to be further separated into infectious and noninfectious causes. Suspected infectious causes should trigger a site-specific workup with empiric antibiotics started after cultures have been performed. Tailor antibiotics to the pathogen identified. Noninfectious causes must be considered based on the patient's past medical and social history and by perioperative medication reconciliation. By taking a systematic approach to patients with postoperative fever, clinicians will be able to make better use of resources, limit costly workups, and ultimately improve patient outcomes.
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