CME

Evaluating postoperative fever

Kristopher R. Maday, MS, PA-C; John B. Hurt, MS, PA-C; Paul Harrelson, MSPAS, PA-C; John Porterfield, MD

ABSTRACT
Downloaded from https://journals.lww.com/jaapa by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3fgGGXf0fUkCdWFxPGOzeAGk+MYbSLOJuy1HksQQx26w= on 09/03/2018

Fever is one of the most common postoperative com-

plications seen in medical and surgical settings. Clini-
cians taking care of these patients need to be able to

SURGICAL INSTRUMENTS © CSP_REDCARPETT

differentiate between a normal physiologic response
to surgery and one that may be pathologic. Pathologic

THERMOMETER © EMOTIVE IMAGES

causes should be further separated into infectious and
noninfectious causes. A systematic approach to febrile
postoperative patients can help clinicians make better use
of resources, limit costly workups, and improve patient
outcomes.
Keywords: surgery, fever, complications, postoperative
management, deep vein thrombosis, adrenal insufficiency

Learning objectives
Describe infectious and noninfectious causes of postopera-
tive fever and methods to distinguish between mechanisms.
Identify life-threatening causes 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

Y
ou 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 obstruct-
ing 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
At the University of Alabama at Birmingham, Kristopher R. Maday is
an assistant professor and academic coordinator of the PA program,
John B. Hurt and Paul Harrelson are assistant professors in the
PA program, and John Porterfield is an assistant professor in the
Department of Surgery. The authors have disclosed no potential
conflicts of interest, financial or otherwise.
DOI: 10.1097/01.JAA.0000496951.72463.de
Copyright © 2016 American Academy of Physician Assistants
$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 mortal-
ity. The challenge is to identify which patients need imme-
diate 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 blood-
stream, cytokines act on the preoptic area of the
hypothalamus to increase prostaglandin production,
raising the thermoregulatory set point for the body
temperature.5

JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 23

Copyright © 2016 American Academy of Physician Assistants

CME
Key points
Fever is one of the most common postoperative complica-
tions seen in medical and surgical settings.
Fever can be a normal physiologic response to surgery or
have a pathologic cause such as infection, DVT, certain
medications, or endocrine derangement.
Clinicians need to be vigilant in identifying the pathologic
causes of postoperative fever that do require workup.
The specific influential pyrogenic cytokines that affect
postoperative temperature regulation are serum interleu-
kin-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.
Wind 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 com-
mon following intubation and general anesthesia.9 Atel-
ectasis 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
24 www.JAAPA.com
Copyright © 2016 American Academy of Physician Assistants
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 pulmo-
nary 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 pneu-
monia, which dramatically increases postoperative
morbidity and mortality.
Water Urinary tract infections (UTIs) are the most com-
mon nosocomial infections in the United States, account-
ing 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 leu-
kocyte 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. aerugi-
nosa (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 contin-
gent upon the degree of patient illness, comorbid condi-
tions, 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.
Wound Surgical site infections (SSIs) are defined by the
CDC as infections that occur at or near the surgical inci-
sion within 30 days of surgery or within 90 days if pros-
thetic 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 ery-
thema, warmth, tenderness, and purulent drainage from
the incision 5 to 10 days after surgery.18 The National
Nosocomial Infection Surveillance System Risk Index for
Volume 29 • Number 10 • October 2016
 Evaluating postoperative fever

Surgical Site Infections was developed in 2001 and uses

TABLE 1. Postoperative fever evaluation
three variables that have been shown to increase the risk
of developing an SSI: Causes Time (hr) Clinical approach
• American Society of Anesthesiologists physical status Wind
classification score of 3 to 5, indicating that the patient Atelectasis <48 Incentive spirometry, pulmonary
is a high-risk surgical candidate toilet, early mobilization
• contaminated or dirty procedure Pneumonia >48 Chest radiograph, sputum culture,
• an operative duration that is greater than the 75th antibiotics
percentile for that procedure.19
Water
This index also identifies use of a laparoscope, when
appropriate, as a negative risk factor.19 Other patient- UTI >48 Removal of catheter, urinalysis,
specific factors that increase risk for SSI are older age, urine culture, antibiotics
poor nutrition, history of diabetes, smoking, obesity, Wound
other concomitant infections, impaired immune status, SSI >72 Screening complete blood cell
and previous history of colonization.20 count with differential and antibi-
SSIs can be classified as superficial (skin and subcutane- otics (for a superficial SSI) and
ous tissue only), deep (involving fascia and muscle), and radiography, OR or interventional
organ/space infection.17 Collect specimens of the purulent radiology drainage, culture, and
drainage for culture because they typically are needed for antibiotics (for a deep or organ/
microorganism identification and antimicrobial sensi- space SSI)
tivities to tailor treatment. Avoid routine culture swabs Walking
of incisions, which can be contaminated with skin flora. DVT >72 Venous Doppler ultrasound,
Patients with signs of severe illness (such as high fever, sequential compression devices
leukocytosis, or hemodynamic instability) out of propor- Wonder drugs
tion to skin findings may need radiographic studies, such
as ultrasound or CT, to identify deep or organ/space Medications Any Review medication history and
patient history, stop suspected
infections. In these cases, operative or interventional
medications, provide supportive
drainage is needed so the pathogen can be identified and care
appropriate antibiotics selected.
The most common pathogens that cause SSI are skin Withdrawal
flora, such as species of Streptococcus, Staphylococcus, Delirium >72 Review patient history, administer
and Enterococcus.21 Patients who may need antimicrobial tremens benzodiazepine, consult psychiatry
prophylaxis before surgery include those with a history “Wonky” glands
of past infections with drug-resistant organisms and those Adrenal <12 Review patient history and medi-
who have been hospitalized within the previous 12 months insufficiency cation history, administer fluid
in order to determine the need to cover for Gram-negative resuscitation and glucocorticoids
organisms. Rare life-threatening wound infections, such Thyroid <48 Review patient history, administer
as Clostridium spp causing gangrene or group A beta- storm a beta-blocker, a thionamide, and
hemolytic streptococcal infections causing necrotizing iodine and consult endrocrinology
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 oping postoperative DVT include those undergoing
patient-specific risk factors until culture data are available abdominal-pelvic surgery or lower extremity orthopedic
for tailored treatment. surgery, patients with major trauma or spinal cord injury,
Walking Postoperative patients account for 20% of all patients with cancer, and those who are obese.25 DVT
hospital-acquired deep vein thromboses (DVTs).22 Patients incidence increases after postoperative days 3 to 5, but
often are sedentary for the first few postoperative days may occur sooner in high-risk patients. Patients also can
due to pain and also may be immobilized after certain have a febrile response to a pulmonary embolism (PE)
surgeries. The resulting venous stasis, combined with the without signs or symptoms of a DVT; PE can be a cause
postoperative inflammatory cascade, increases patient of sudden death in a postoperative patient. Patients with
risk for DVT. The problem for clinicians is that 10% to suspected DVT should be screened with a lower extrem-
80% of hospitalized patients with DVT are asymptom- ity Doppler ultrasound and started on therapeutic anti-
atic.23 The only objective finding that may be apparent is coagulation when clinically safe.
fever due to inflammation of the deep venous system with Wonder drugs Medications are the most common
local vascular irritation.24 Patients at high risk for devel- noninfectious cause of fever in postoperative patients,

JAAPA Journal of the American Academy of Physician Assistants www.JAAPA.com 25

Copyright © 2016 American Academy of Physician Assistants

CME
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 pres-
ent in perioperative patients with a fever greater than 40°
C (104° F):
• Serotonin syndrome is caused by medications interact-
ing with selective serotonin reuptake inhibitors (SSRIs),
resulting in increased serotonergic neurotransmission and
overstimulation of central and peripheral serotonin recep-
tors.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 rigid-
ity, 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, dis-
continuing any medication that could be causing the
reaction, and providing supportive care to prevent febrile
complications.
Withdrawal Alcohol consumption is a significant prob-
lem 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 symp-
toms 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 condi-
tion, which has a mortality of up to 4%, begins about
72 hours after the last alcohol ingestion. The constella-
tion 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
26 www.JAAPA.com
Copyright © 2016 American Academy of Physician Assistants
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
“Wonky” glands Two endocrinologic causes of fever in
postoperative patients require specific mention and
consideration: adrenal insufficiency and thyrotoxicosis.
The hypothalamic-pituitary-adrenal axis has many endo-
crine 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 sup-
port 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, hypo-
glycemia, 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 physi-
ology 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 med-
ications 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 clin-
ical manifestations of thyroid storm include tachycardia,
altered mental status, hyper- or hypotension, and hyper-
thermia (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
LIFE-THREATENING CAUSES
Most of the causes of fever in the postoperative setting
are not life-threatening and mainly revolve around nor-
mal physiologic responses to acute stress, prevention of
complications, and management of simple infections.
However, clinicians caring for patients in the postoperative
Volume 29 • Number 10 • October 2016

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
• sepsis
• pulmonary embolism
• serotonin syndrome
• malignant hyperthermia
• neuroleptic malignant syndrome
• delirium tremens
• adrenal insufficiency
• thyroid storm.
OUTCOME
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.
CONCLUSION
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 tak-
ing 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. JAAPA
Earn Category I CME Credit by reading both CME articles in this issue,
reviewing the post-test, then taking the online test at http://cme.aapa.
org. Successful completion is defined as a cumulative score of at least
70% correct. This material has been reviewed and is approved for
1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The
term of approval is for 1 year from the publication date of October 2016.
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Volume 29 • Number 10 • October 2016