Clinical guidelines Fever in the Picu

Clinical Evidence and Guidelines
Fever in the ICU
Rob Parker
March 13, 2018

Outline
 What is a Fever
 Causes of Fever
 Timing of Fever
 Workup of Fever Based on Its Suspected Source

What is Fever
 Fever is defined as having a temperature above the body’s
normal range due to an increase in the set point
 Ranges of fever are vast
– Temperature in the rectum is at or over 37.5–38.3 °C (99.5–100.9 °F)
– Temperature in the mouth is at or over 37.7 °C (99.9 °F)
– Temperature under the arm or in the ear is at or over 37.2 °C (99.0 °F)
 Fevers can oscillate by >1.0 °C and change depending on time
of day (low in early morning, peak in early afternoon/late
evening)
 However, these definitions are not universally accepted and are
not widely translatable to a PICU

Hyperthermia vs Pyrexia
 Pyrexia, also referred to as fever, is an adaptive response
to a physiologic stress that is tightly regulated through
endogenous pyrogenic and anti-pyretic pathways, and is
associated with an increase in the hypothalamic set
– This type of fever is responsive to anti-pyretics
 Hyperthermia reflects a pathologic increase in body
temperature that is not associated with an increased
hypothalamic set point
– This type of fever does not respond to antipyretics

Pathophysiology of Fever
 A pyrogen is any substance that
causes fever
– Fever producing cytokines are also
known as pyrogenic cytokines
 Exogenous pyrogens are largely
comprised of microbes or toxins
– LPS from gram negatives are a classic
example
 Endotoxins from microbes produce toll
like receptor(TLR) ligands that can bind
to macrophages and activate cells
– Toxic shock syndrome toxin (TSST-1)
from gram positives can act as direct
toxins as well as “super antigens”
interacting with MHC II and T cell
subsets to release pyogenic cytokines
 Endogenous pyrogens are
inflammatory cytokines produced in
response to a foreign substance
Ravikumar M, Hageman DJ, Tomaszewski WH, Chandra GM, Skousen JL,
Capadona JR. The Effect of Residual Endotoxin Contamination on the
Neuroinflammatory Response to Sterilized Intracortical Microelectrodes. J
Mater Chem B. 2014;2(17):2517-2529.

Contributions of important cytokines to immunologic responses
Source Critical functions
Cytokine
IL-1
Macrophage; Many
cells
Fever, induces other cytokines, T cell stimulation, Induces metalloproteinases and prostaglandins,
Increases adhesion molecule expression
IL-2 T cells Increase T cell proliferation, activates B cells
IL-4 T cells
Signal for immunoglobulin switch, increases IgE, Decreases production of proinflammatory cytokines, Suppresses delayed type
hypersensitivity (Th1 cells)
IL-6 Many cells B and T cell proliferation, acute phase reactants, Induces natural protease inhibitor (TIMP)
IL-12 Macrophages Increase IFN-gamma production and Th1 cell differentiation
IL-13 T cells Similar to IL-4
IL-15 T cells; Macrophages Induces TNF-alpha release from synovial macrophages, induces mitogenesis, and inhibits apoptosis
IL-17 T cells; Innate lymphoid cells Activates neutrophils and a variety of stromal cells to regulate host defense and also matrix disruption
IL-23 Dendritic cells; Macrophages Promotes T cell differentiation, particularly of the Th17 type
TNF-alpha T cells; Macrophages
Cachexia, induces other cytokines, T cell stimulation; Induces metalloproteinases and prostaglandins; Increases
adhesion molecule expression
IFN-gamma T cells Adhesion molecules, HLA-DR expression, activation of T cells, NK cells, macrophages
Colony-stimulating factors
GM-CSF
Macrophages; Fibroblasts; T
cells
Myeloid differentiation, macrophage activation
G-CSF Macrophages Granulocyte differentiation and activation
M-CSF Macrophages Myeloid differentiation, macrophage activation
Chemokines
C-X-C family Many cells Activate neutrophils, chemotactic to neutrophil (IL-8, ENA-78, etc) and T cells
C-C family Many cells Chemotactic for monocytes and T cells (MCP-1, MIP-1, etc)
Growth factors
TGF-beta Many cells
Fibroblast proliferation, collagen and TIMP synthesis; Decrease metalloproteinases, decreases T cell proliferation; Angiogenesis, decreased
proinflammatory cytokines
FGF, VEGF Many cells Fibroblast proliferation, angiogenesis
PDGF Many cells Fibroblast proliferation

Pyrogenic Cytokines
 Specific cytokines produced upon activation of TLR that cause
fever
– Unless challenged by infection or trauma, cytokines do not seem
to play a role in normal physiologic functions, including
temperature regulation or endocrine functions
 IL-1, IL-6, tumor necrosis factor (TNF), interferon alpha, and
ciliary neurotrophic factor are the primary pyrogenic cytokines
– IL-1 and TNF are particularly pyrogenic
 Inflammation, trauma, or antigen-antibody complexes induce
the production of IL-1, TNF, and IL-6, and each or all three
cytokines trigger the hypothalamus to raise the set-point to
febrile levels

Pathogenesis of Fever
Roth J, Blatteis CM. Mechanisms of fever production and lysis: lessons
from experimental LPS fever. Compr Physiol. 2014;4(4):1563-604.
1. The sequence starts with the entry of
an exogenous pyrogen, ex. LPS, into
the host through a break in one of its
natural barrier
2. This exogenous agent is transported to
the liver and there activates Kupffer
cells (Kc) and, on the way, other
mononuclear phagocytic cells to
produce endogenous pyrogens (IL-1,
IL-6, and TNF)
3. These then are released into the
bloodstream (2) and transported to the
POA (3), where they induce the
expression of COX-2 and, hence,
PGE2
4. PGE2, in turn, inhibits the activity of
warm-sensitive neurons (W), causing
heat conservation (and reflexly heat
production [not shown]) and thereby
acting as the proximal mediator of fever
(4)

Do anticytokine therapies mask infection by
preventing fever?
 Anticytokine therapies, such as IL-1 receptor antagonist,
anakinra; TNF-alpha inhibitors; an IL-6 receptor inhibitor;
anti-IL-12 antibodies; or anti-IL-23 antibodies
 TNF-alpha antagonism by infliximab or adalimumab or
etanercept
 Acetaminophen or ibuprofen
 Patients can present with fever despite being treated with an
anticytokine agent is due to the other cytokines that can cause
fever (eg, IL-1, TNF-alpha, IL-6, interferons, and others) that
are not affected by a specific anticytokine agent
– Fevers are often reduced

ICU Fever
 In general, a fever in the ICU is >38.3 °C
 Systematic review of observational studies in febrile
critically ill adults reported five different definitions of
pyrexia among the nine included studies, with 38.3 °C
being the most frequently cited threshold
 Multinational survey of 139 ICUs in 23 countries found 14
discreet temperature thresholds used to define pyrexia
with a range of 37–40 °C and a median (interquartile range)
of 38.2 °C (38.0–38.5 °C)

 Normal temperature in healthy participants is 37.0°C (98.6°F) with temperature
variation by 0.5 to 1.0°C, according to circadian rhythm and menstrual cycle
 A variety of environmental forces in an ICU can alter temperature, such as
specialized mattresses, hot lights, air conditioning, cardiopulmonary bypass,
peritoneal lavage, dialysis, and continuous hemofiltration
 Thermoregulatory mechanisms can also be disrupted by drugs or by damage to the
central or the autonomic nervous systems
 “As a broad generalization, it is reasonable in many ICUs to consider everyone with a
temperature of >38.3°C (?101°F) to be febrile and to warrant special attention to
determine whether infection is present”
– These guidelines are from 2008 but are the most recent consensus guidelines
– They are currently being reviewed
Crit Care Med 2008; 36:1330–1349

How to Obtain temperature
 Gold standard is thermistor in either PA
catheter or bladder catheter
– Esophageal probes in distal 1/3 of esophagus
are nearly equal in accuracy
 Rectal temperatures can be used in leu of a
central measuring device
– Readings from the rectum are often a few
tenths of a degree higher than core
temperature
 Oral temperatures are often easier to obtain
but are not suggested
– Can be confounded by mouth breathers,
heated gases, or fluid ingestion
 Tympanic membrane temperature is believed
to reflect the temperature of the
hypothalamus and, thus, the core body
temperature
– Poor consistency and lots of variables in
obtaining accurate measurements
 Infrared thermometry, axillary thermometry
and chemical dot thermometry should not be
used in the ICU (level 2)

Is a fever always bad?
 Fever complicates up to 70 percent of all intensive care unit
(ICU) admissions and is often due to an infection or another
serious condition
 In an adult study of over 24,000 patients, fever ≥39.5ºC (103ºF)
was associated with an increase in mortality (20 versus 12
percent)
 Even in pediatric patients, fever is associated with longer
length of stay, longer length of mechanical ventilation and
increased morbidity and mortality
 Fever can be an appropriate adaptive response to infection
 Elevated peak temperatures in ICU patients with infections were
associated with decreased hospital mortality

Differential Diagnosis of Fever

Degrees of Fever
 Fevers between 38.3ºC (101ºF) and 38.8ºC (101.8ºF)
– May be infectious or noninfectious
– Widest differential
 Fevers between 38.9 (102ºF) and 41ºC (105.8ºF)
– Assumed to be infectious
 Fevers ≥41.1ºC (106ºF)
– Usually noninfectious
– Include drug fever, transfusion reactions, adrenal insufficiency,
thyroid storm, neuroleptic malignant syndrome, heat stroke, and
malignant hyperthermia

SCCM and IDSA Recommendations
 A new onset of temperature of >38.3°C is a reasonable trigger for a
clinical assessment but not necessarily a laboratory or radiologic
evaluation for infection (level 3)
 A new onset of temperature of 36.0°C in the absence of a known
cause of hypothermia (e.g., hypothyroidism, cooling blanket, etc.) is a
reasonable trigger for a clinical assessment but not necessarily a
laboratory or radiologic evaluation for infection (level 3)
 Critical care units could reduce the cost of fever evaluations by
eliminating automatic laboratory and radiologic tests for patients with
new temperature elevation (level 2).
 Instead, these tests should be ordered based on clinical assessment.

What we actually do
 Survey of medical and nursing
staff in 35 paediatric intensive
care units and transport teams in
the United Kingdom and Ireland
with goal to establish attitudes
towards the management of
children with fever
 462 respondents (291 nurses;
171 doctors) answered eight
questions regarding thresholds for
temperature control in usual
clinical practice, indications for
paracetamol use, and readiness
to participate in a clinical trial of
permissive temperature control
Brick T, Agbeko RS, Davies P, et al. Attitudes towards fever amongst UK paediatric
intensive care staff. Eur J Pediatr. 2017;176(3):423-427.

Don’t Just Sit There, Do SOMETHING!
 Approximately one half of
parents consider a temperature
of less than 38°C (100.4°F) to
be a fever, and 25% of
caregivers would give
antipyretics for temperatures of
less than 37.8°C (100°F).
 The most common indications
for initiating antipyretic therapy
by pediatricians are a
temperature higher than 38.3°C
(101°F) and improving the
child’s overall comfort
Sullivan JE, Farrar HC. Fever and antipyretic use in children.
Pediatrics. 2011;127(3):580-7.
 It should be emphasized that
fever is not an illness but is, in
fact, a physiologic mechanism
that has beneficial effects in
fighting infection.
 Fever retards the growth and
reproduction of bacteria and
viruses, enhances neutrophil
production and T-lymphocyte
proliferation, and aids in the
body’s acute-phase reaction
There is no evidence that
reducing fever reduces
morbidity or mortality from a
febrile illness.

But Fever Can Make you Look Bad
 Physical signs such as pallor, mottled
appearance, ashen or blue skin color,
reduced activity (poor feeding, no
smile, decreased response to stimuli,
lethargy, weak high-pitched cry),
tachypnea and tachycardia, capillary
refill time >3s, and a reduced urine
output are all concerning for SBI
 Fever may by itself alter respiratory
rate and heart rate; therefore, using
age-specific, temperature-corrected
cut-offs for respiratory rate has been
shown to result in more accurate
detection of lower tract respiratory
infections than fixed thresholds
Barbi E, Marzuillo P, Neri E, Naviglio S, Krauss BS. Fever in Children:
Pearls and Pitfalls. Children (Basel). 2017;4(9)

What about response to Acetaminophen?
 Our data show that patients
with a variety of known viral
and bacterial diseases
demonstrate similar ranges
of temperature response to
acetaminophen treatment.
 Temperature
responsiveness to
antipyretic administration
cannot be reliably used to
distinguish between different
diagnoses.

Ok, it’s a fever. Now
what should we do?

When to Start Looking for
an Infectious Cause of
Fever
 Fever occurred in 82 patients (40.6%)
during anytime of their PICU
 In 76 febrile patients (92.7%), fever
occurred in the first 48 hours of
admission and was associated with the
admission diagnosis in all cases
 If the fever occurs more than 48 hours
after admission, there is a greater
likelihood that there is a new infectious
process occurring
 If the new fever was found to be
infectious, VAP, UTI, and blood stream
infection were most common if a source
was found; however, 60% of the cases
had no microbial growth despite elevated
inflammatory markers and clinical signs

Do we need a blood culture?
 The bloodstream is a common site of infection in critical
illness
– Infection from LRTI, abdominal and urinary sources can easily
invade bloodstream
– Most common pathogens are E. coli, S. aureus, and S.
pneumoniae
 Because a bacteremia can have a profound affect on
prognosis and therapy, blood cultures should be
performed for patients with new fever, even when the
clinical findings do not strongly suggest a noninfectious
cause

Do we need a blood culture?
 Objectives
– To identify predictors of bacteremia in critically ill patients
– Retrospective study in adult ICU in 2007 – 2008
– 1444 patients, 231 with blood cultures drawn
– 45 out of 231 patients (19.5%) had positive blood cultures
 Results
– Fever alone cannot be considered a solid predictor of bacteremia
– CRP and WBC had low predictive values for bacteremia, while elevated procalcitonin
correlated with positive BCx
– No associations between bacteremia and immunodeficiency or diabetes
– Bacteremia was not associated with the presence of a surgical wound or mechanical
ventilation
 All cultures <72hrs from surgery were sterile
– Limiting repeated blood cultures for persistent fever had no effect on clinical outcome

SCCM and IDSA Recommendations for Work Up
 Blood Cultures:
– Obtain three to four blood cultures within the first 24 hrs of the
onset of fever (level 2)
– Additional blood cultures should be drawn thereafter only when
there is clinical suspicion of continuing or recurrent bacteremia or
fungemia or for test of cure, 48 –96 hrs after initiation of
appropriate therapy for bacteremia/fungemia (level 2)
– For patients without an indwelling vascular catheter, obtain at
least two blood cultures (level 2)
– If the patient has an intravascular catheter, one blood culture
should be drawn by venipuncture and at least one culture should
be drawn through an intravascular catheter (level 2)

Pediatric bacterial blood cultures: Recommended
blood volume
Patient Weight (kg) Recommended blood volume per
culture (mL)
Volume of blood equal to 1
percent of patient's total
blood volume (mL)*
<8.5 1 2
8.5 – 13.5 3 6 to 10
13.5 - 27 5 10 to 20
27 – 40 10 20 to 30
40 – 55 15 30 to 40
>55 20 >40
1.Kaditis AG, O'Marcaigh AS, Rhodes KH, et al. Yield of positive blood cultures in pediatric oncology patients by a new
method of blood culture collection. Pediatr Infect Dis 1996; 15:615.
2.Specimen collection, transport, and processing: Bacteriology. In: Manual of Clinical Microbiology, 10th ed, Versalovic
J, Carroll KC, Funke G, et al (Eds), ASM Press, Washington, DC 2007.

 Intravascular Devices and Fever:
– Relative risk of bloodstream infection caused by various intravascular
devices ranges widely
 Short-term, noncuffed central venous catheters: 2–5 per 1,000 catheter days
 Arterial catheters 2–3 per 1,000 catheter days
 Small, peripheral intravenous catheters 0.1 cases per 1,000 catheter days
– Examine the patient at least daily for inflammation or purulence at the
exit site or along the tunnel (level 2)
– Any expressed purulence from the insertion site should be Gram
stained and cultured (level 2)
– If there is evidence of a tunnel infection, embolic phenomenon,
vascular compromise, or septic shock, the catheter should be removed
and cultured and a new catheter inserted at a different site (level 2)
– At least two blood cultures should be obtained. One specimen should
be obtained from the suspected catheter (level 1)

 Question: Can a quality
improvement initiative safely
reduce unnecessary blood
culture use in critically ill
children?
 Pre and post intervention
retrospective cohort study
– 2204 pre (1807 BCx drawn for
11,196 pt days)
– 2356 post (984 BCx drawn for
11,204 pt days)
– Utilized fever/sepsis screening
algorithm to determine need for
blood cultures

 Episodes of suspected infection and
septic shock were detected by the
presence of a set of clinical events
occurring concomitantly (ie, within a 24-
hour time window) during a PICU visit
 Anchor time point for an episode was the
time of a new (ie, first dose) broad-
spectrum antibiotic or ≥48 hrs from prior
administration of a broad-spectrum
antibiotic
 Episodes were defined as:
– (1) suspected infection: recorded
temperature ≥ 38.5°C or <36.0°C
within 24 hours (ie, before or after) of
receiving a new broad-spectrum
antibiotic
– (2) suspected septic shock: recorded
temperature ≥ 38.5°C or <36.0°C and
vasopressor administration within 24
hours of receiving a new broad-
spectrum antibiotic

 There were fewer BCx drawn, fewer drawn
from CLVs and less antibiotics used
 There were no significant differences in in-
hospital mortality (2.0% vs 1.6%; P = .23) or
mortality in the subgroup of patients with
suspected septic shock occurrences (12.2% vs
10.0%; P = .51).
 Both hospital 7-day readmission rates (4.9%
and 4.4%; P = .42) and PICU 7-day
readmission rates (3.1% and 3.1%; P = .98)
were not significantly different.
 “A systematic approach to blood cultures
may help to optimize laboratory use in
critically ill children. This clinical decision
support initiative decreased the total
number of cultures and the proportion
drawn from CVCs with stable
postintervention mortality rates and
readmission rates and, most importantly,
no increase in episodes of suspected
septic shock after intervention or mortality
associated with episodes of suspected
septic shock”

 Pulmonary Infections and ICU-Acquired Pneumonia:
– In an ICU, it can be difficult to determine whether fever is due to
pneumonia when a patient has another noninfectious process
that results in abnormal radiographic findings and gas exchange
– Physical examination, chest radiograph, and examination of
pulmonary secretions comprise the initial evaluation
– A chest imaging study should be obtained (level 1)
– Obtain one sample of lower respiratory tract secretions for direct
examination and culture before initiation of or change in
antibiotics (level 2)

 CLINICAL DIAGNOSIS OF VAP
1. Imaging test evidence (new or progressive and persistent infiltrate, Consolidation, Cavitation,
Pneumatoceles in infants ≤1 year old
2. Fever (>38.0°C or >100.4°F) or Leukopenia (≤4000 WBC/mm3) or leukocytosis (>12,000
WBC/mm3)
3. 2 or more of:
1. New onset of purulent sputum or change in character of sputum, or increased respiratory secretions, or
increased suctioning requirements
2. New onset or worsening cough, or dyspnea, or tachypnea
3. Rales or bronchial breath sounds
4. Worsening gas exchange (e.g., O2 desaturations (e.g., PaO2/FiO2 <240), increased oxygen requirements, or
increased ventilator demand)
 MICROBIOLOGIC METHODS TO DIAGNOSE VAP/HAP
1. Suggest noninvasive sampling with semiquantitative cultures to diagnose VAP, rather than invasive
sampling with quantitative cultures and rather than noninvasive sampling with quantitative cultures
(weak)
2. For patients with suspected VAP whose invasive quantitative culture results are below the diagnostic
threshold, suggest withholding/stopping antibiotics (weak)
 USE OF BIOMARKERS TO DIAGNOSE VAP/HAP
1. With suspected HAP/VAP, we recommend using clinical criteria alone, rather than using serum PCT
and/or CRP plus clinical criteria (strong)

 INITIAL TREATMENT OF VAP/HAP
1. With suspected VAP, we recommend including coverage for S. aureus,
Pseudomonas aeruginosa, and other gram-negative bacilli (strong)
1. Regimen including piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or
meropenem (weak)
2. Suggest including MRSA tx only in those with strong risk factors
2. Patients being treated empirically for HAP, we recommend prescribing an
antibiotic with activity against S. aureus, P. aeruginosa and other gram-negative
bacilli
 LENGTH OF THERAPY
1. Patients with VAP/HAP, we recommend a 7-day course of antimicrobial therapy
rather than a longer duration (strong)
2. We suggest that antibiotic therapy be de-escalated to narrowest therapy rather
than fixed (strong)
3. For patients with HAP/VAP, we suggest using PCT levels plus clinical criteria to
guide the discontinuation of antibiotic therapy, rather than clinical criteria alone
(weak)

 HAP has a rate of 5 to 10 per
1000 hospital admissions
 VAP constitutes 20% of
nosocomial infection in
paediatric ICU
 Early onset VAP:
– S. pneumoniae, H. influenzae,
S. aureus, E. coli and K.
pneumoniae
 Late onset VAP:
– S. aureus, P. aeruginosa, K.
pneumoniae and Enterobacter
spp
 Types of outcome
measures
1. Clinical Cure
2. Treatment failure rates
3. Mortality rate
4. Relapse rate
5. Length of hospital stay
6. Need for change in
antibiotics
7. Adverse events

 Urinary Tract Infection:
– Catheter-associated bacteriuria or candiduria usually represents colonization, is rarely
symptomatic, and is rarely the cause of fever or secondary bloodstream infection, even in
immunocompromised patients, unless there is urinary tract obstruction, the patient has had
recent urologic manipulation or surgery, or is granulocytopenic
– For patients at high risk for urinary tract infection (kidney transplant patients,
granulocytopenic patients, or patients with recent urologic surgery or obstruction), if clinical
evaluation suggests a patient may have symptomatic urinary tract infection, obtain urine for
microscopic exam, Gram stain, and culture (level 2)
– Patients who have urinary catheters in place should have urine collected from the sampling
port of the catheter and not from the drainage bag (level 2)
– Cultures from catheterized patients showing >103 cfu/mL represent true bacteriuria or
candiduria, but neither higher counts nor the presence of pyuria alone are of much value in
determining if the catheter-associated bacteriuria or candiduria is the cause of a patient’s
fever; in most cases, it is not the cause of fever (level 1)
– Gram stains of centrifuged urine will reliably show the infecting organisms and can aid in the
selection of anti-infective therapy if catheter-associated urosepsis is suspected (level 1)

UTI Diagnosis and Treatment
 Diagnosis:
– Fever (especially >39°C [102.2°F] or >48 hours), Ill appearance, Costovertebral angle
tenderness, Known immune deficiency, Known urologic abnormality
– Obtain a urine sample via catheterization or SPA along with a UA
 If a “bag” urine is fresh (<1hr from void) and does not contain leukocyte esterase and nitrites, it is
ok to watch and wait
– To diagnose a UTI, the UA should suggest infection (pyuria and/ or bacteriuria) and the
presence of at least 50,000 colony-forming units (cfu) per milliliter of a uropathogen
cultured from a urine specimen obtained through transurethral catheterization or SPA
 Treatment:
– Regimens include the combination of ampicillin and gentamicin; gentamicin alone; or a
third- or fourth-generation cephalosporin
– Ampicillin should be included if enterococcal UTI is suspected
– Uncomplicated UTI should be treated for 3 days; complicated UTI (ie, hospitalized,
young or with fever) should be treated for 10 days
 Currently a study is underway to determine which duration is suggested

 Postoperative Fever:
– Fever is a common phenomenon during the initial 48 hrs after
surgery and is usually noninfectious in origin
– A chest radiograph is not mandatory during the initial 72 hrs
postoperatively if fever is the only indication (level 3)
– A urinalysis and culture are not mandatory during the initial 72
hrs postoperatively if fever is the only indication.
 Urinalysis and culture should be performed for those febrile patients
having indwelling bladder catheters for >72 hrs (level 3)
– Surgical wounds should be examined daily for infection. They
should not be cultured if there is no symptom or sign suggesting
infection (level 2)

 Study
– All patients who had blood cultures drawn during the initial 48
hours postoperatively in a PICU
 Excluded if not first operation, discharged <48hrs, or had CVL in >24hrs
 Results
– 602 total patients; 66 febrile (>38C) w/ BCx drawn (111 BCx)
– 1 positive culture
 Conclusion
– “Fever in the first 48hrs in low risk postoperative patients is
unlikely to represent bacteremia. Blood cultures are unnecessary
in low risk patients with fever.”

 Study
– Objectives are to determine the incidence of
fever and the utilization and yield of tests
ordered in children
– Single center retrospective of ~7000
patients, 30.6% had fever (>38C)
 Results
– UC positive in 15.7% ; 92.0% had a urinary
catheter during surgery.
– BC positive in 0.69% of patients, all with a
central venous catheter.
– CXRs were considered infectious in 3.0% of
patients tested.
– Patients with PICU stay and/or fever
≥ 38.9 °C were more likely to undergo BC
and UC, but no more likely to have a positive
result compared those without PICU stay
and/or fever < 38.9°
 Conclusion
– “Early postoperative fever is common in
pediatric surgical populations and rarely
associated with an infectious source”

Fever after Neurosurgery
 Classic symptoms and signs of meningeal inflammation, such
as headache, photophobia, and nuchal rigidity, are usually not
helpful post surgery
 Microscopic and analytical examination of the cerebrospinal
fluid (CSF) is indicated in patients with fever
 Fever is common after neurosurgical procedures and is thought
to be due to disruption of the dura and/or inflammatory reaction
following breakdown of RBC’s in the cranial vault

 Central Nervous System Infection:
– Fever occurs in about 25% of neurosurgical patients with almost
half being noninfectious
– If altered consciousness or focal neurologic signs are
unexplained, lumbar puncture should be considered in any
patient with a new fever (level 3)
– For a patient with a new fever and new focal neurologic findings
suggesting disease above the foramen magnum, an imaging
study is usually required before lumbar puncture (level 2)
– In febrile patients with an intracranial device, CSF should be
obtained for analysis from the CSF reservoir (level 3)

 Study
– 70 adult patients with meningitis after a neurosurgical
procedure
– Positive meningitis if >5 WBC/µL (>5 × 106/L) in nonbloody
spinal fluid
 If bloody, WBC:RBC ratio of >1:100 allowed inclusion
– Patients with positive cultures were included
– Patients with 5-25 WBC, no headache, change in mental
status, or fever, and negative cultures were excluded
 Results
– 20 instances of bacterial meningitis (more common after
paranasal sinus or spine surgery)
– 30 instances of chemical meningitis (more common with
posterior fossa surgery)
– 20 cases were indeterminant
– Chemical Meningitis:
 CSF rhinorrhea and otorrhea were not found
 Unusual to have a temperature >39.4°C.
 Did not have periods of unconsciousness, a new onset of seizure
disorders, and new focal neurological findings
 Patients with all of the following criteria can probably be
safely observed without administration of antimicrobials:
• Fever less than 39.4ºC (102.9ºF)
• CSF white blood count (WBC) less than 7,500/microL
• CSF glucose above 10 mg/dL
• No delirium, seizure, or surgical site inflammation

 Sinusitis:
– The most common risk factor for sinusitis is anatomic obstruction
of the ostia draining the facial sinuses with upwards of 85%
having evidence of sinusitis with NG/ND tubes for >1 week
– Pseudomonas (60%) and staph aureus and CONS (33%) are the
most common bacterial causes
– If clinical evaluation suggests that sinusitis may be a cause of
fever, a CT scan of the facial sinuses should be obtained (level
2)
– If the patient has not responded to empirical therapy, puncture
and aspiration of the involved sinuses under antiseptic
conditions should be performed (level 2)

Considerations for Empiric Therapy During
Diagnostics
 Recommendations for Empiric Therapy of Fever
– When clinical evaluation suggests that infection is the cause of
fever, consideration should be given to administering empirical
antimicrobial therapy as soon as possible after cultures are
obtained, especially if the patient is seriously ill or deteriorating
(level 1).
– Initial empirical antibiotic therapy should be directed against
likely pathogens, as suggested by the suspected source of
infection, the patient risk for infection by multidrug-resistant
pathogens, and local knowledge of antimicrobial susceptibility
patterns (level 1).

Marik, Paul E.
CHEST , Volume 117 ,
Issue 3 , 855 - 869

Conclusions
 Fever is very common in the PICU
 A fever should be measured by the most accurate means
possible (usually a rectal temp)
 The most widely accepted value for fever is >38.3°C
 Fever should trigger a clinician to examine the patient,
NOT reflexively order pan-cultures
 Peak temperature, response or lack of response to
antipyretics does not correlate with bacterial infection

Conclusions
 Blood cultures are the most likely culture to yield a result but
should be carefully considered whether needed
– Daily cultures are unnecessary
– Central and peripheral cultures should be obtained
 Respiratory cultures should be obtained if there is a worsening
in the clinical status of the patient
– A chest xray should be part of this workup
 Urinary sources are unlikely to be the cause of fever in critically
ill patients without risk factors
 Fever after neurosurgical procedures is common and does not
always need evaluation
 Postoperative fever is common and often does not need
evaluation within the first 48-72 hours

Nemours PICU Fever Pathway Broad Spectrum Antibiotics
•Any regimen including ceftriaxone,
cefotaxime, cefepime, piperacillin-
tazobactam, ciprofloxacin, or aztreonam
alone or in combination with vancomycin or
clindamycin
1. If CVL, prefer cefepime, vanco or gent
2. If abdominal, prefer zosyn, vanco or
gent
3. If CNS, prefer cefepime, consider flagyl
4. If already on broad spectrum, consider
imipenem, meropenem, vanco or
amikacin
Patient Weight (kg) Recommended blood volume per culture (mL)
<8.5 1
8.5 – 13.5 3
13.5 - 27 5
27 – 40 10
40 – 55 15
>55 20

Clinical guidelines Fever in the Picu

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