Fever and Neutropenia by Dr. Katie Greenzang and Dr. Jonathan Marron.
Hello, I'm Katie Greenzang, and I'm a Pediatric Oncologist.
And I'm Jonathan Marron, also a Pediatric Oncologist.
Today, we'll be talking to you about management of patients with febrile neutropenia.
This is a situation encountered quite often with oncology patients who typically receive
treatments that simultaneously drop their neutrophil count and impair their immune system.
The lessons you learn today will apply primarily to the care of hospitalized children with solid
tumors, hematologic malignancies, and brain tumors. But the same principles apply to the care
of these patients in the emergency department, outpatient clinic, or intensive care unit.
So why is this important? When patients are neutropenic, their immunologic defenses
are down putting them at increased risk for development of serious bacterial infections.
Review of Febrile Neutropenia.
The management of febrile neutropenic patients on bone marrow transplant and
other services such as hematology or immunology may be slightly different,
so speak to your fellow or attending. The general principles however, are the same.
Before going any further, it's important to know how to calculate the absolute neutrophil count or
ANC. The ANC is calculated by multiplying the total white blood cell count by the sum of the
percentage of neutrophils and bands. Be careful with your units and decimal places. We typically
define neutropenia as an absolute neutrophil count of less than 500 cells per microliter.
Patients with neutropenia are at risk of serious bacterial infections.
While patients with neutropenia can develop infections from a variety of causes,
typically bacterial pathogens are due to normal body flora
such as translocation of bacteria from the gut or skin flora getting into a central line.
Unfortunately, neutropenic patients can get very sick very quickly in the setting of a
bacterial infection. Though not every fever in a patient with neutropenia is due to bacteremia,
we empirically treat for bacteremia with IV antibiotics given the very
high morbidity and mortality from serious bacterial infections in these patients.
Probably the most important thing to safely manage these patients is to have a plan in place
before a patient develops a fever. Make sure that you are comfortable with the fever plan for each
neutropenic patient that you're caring for. If you are unsure of what you should do if one of
your patients were to spike a fever, be sure to proactively speak with your fellow or attending.
The last thing you want to do is have to figure out,
in the heat of the moment, when you find out that a patient has spiked a fever.
Let's consider that very situation and go through how febrile neutropenia is managed.
Management of Febrile Neutropenia.
One of your patients has a single fever to 100.4 degrees Fahrenheit.
How do you know what to do? First, how do we define fever in the oncology population? Fever is
defined as a single oral temperature of at least 38.5 degrees Celsius, which is equivalent to 101.4
degrees Fahrenheit or a sustained oral temperature of greater than or equal to 38.0 degrees Celsius
or 100.4 degrees Fahrenheit for greater than 1 hour. A sustained temperature is
demonstrated by two separate temperature measurements at least one hour apart.
Please note, the temperatures are taken on oncology patients only orally, never rectally,
particularly in neutropenic patients. The small amount of trauma to the mucosa caused by the
placement of a rectal thermometer can lead to tearing of the skin and entry of bacteria
into the bloodstream. So if you are the resident, how should you reply to the nurses page about the
single fever of 100.4? Make sure to let the nurse know that you've received the page and are aware
of the fever and then go examine the patient. Since this was only a single fever less than 38.5,
we typically wouldn't start antibiotics, but we still should take this opportunity
to gather more information about the patient that will help in our assessment and decision making.
What information would be helpful? We also want to know the duration of fever,
but also about the other vital signs-- heart rate, respiratory rate, oxygen saturation and blood
pressure. We also want to know about the child's hemodynamics, how are their pulses and perfusion,
and mental status? These all help to begin to draw a picture of how clinically ill the patient is.
We want to confirm, also, that we know the child's cancer diagnosis.
Fever in some cancers is treated differently than others.
Lastly, we want to ask about other symptoms just as we would with any other patients. Things like
cough, rhinorrhea, shortness of breath, nausea and vomiting, diarrhea, abdominal pain, and dysuria.
At this point, we're looking both for red flags that could be warning
signs that a patient is sick or getting sick, and also for any focal findings
that might highlight the source of the fever. Red flags include poor perfusion,
abnormal or unstable vital signs, hypotension, acute abdominal tenderness, or erythema,
tenderness, or discharge at the central line sites, and finally, altered mental status.
Sites important to check on the physical exam will vary based on the patient's clinical symptoms and
history, but should always include peripheral pulses and perfusion, hearts, lungs, abdomen,
all central line sites, keeping an eye out for erythema, tenderness, or discharge, and rectum.
Just as oncology patients should never have rectal temperatures, we also never perform
internal rectal exams. Instead, always perform an external rectal exam by palpating for masses
or tenderness around the rectum. In patients with headaches or other neurological symptoms,
always do a brief neurological exam and assess mental status.
Because febrile patients with neutropenia can get sick so rapidly, one very important thing is
to know when to call for help. You should always feel comfortable contacting the oncology fellow.
He or she will probably want to know about all fevers anyway,
but certainly call or page your fellow if you're ever worried about a patient's clinical status.
Also, consider an ICU evaluation for a patient you're worried about. Finally, carefully consider
the inputs of the oncology nurses. If they're worried about a patient, you should be too.
Now let's return to our patients. In the scenario we've just discussed, the
patient had a single temperature of 100.4 which didn't meet our fever criteria. As the resident,
you should still go examine the patient to make sure she doesn't exhibit any of the warning signs
we just went over. But as long as that's not the case, we won't empirically start antibiotics.
Point of clarification. If a patient develops a single fever between 38 and 38.5 degrees Celsius
antipyretics such as acetaminophen should not be administered as they
may make it difficult to interpret the patient's temperature an hour later.
Accurate determination of fever an hour after the first elevated temperature
is critical to appropriate recognition and management of fever and neutropenia.
Now you receive a page that the same patient has a second fever to 100.7
a little over an hour after the last fever. Now what do we do?
This time, because the patient has a persistent temperature greater than 38 degrees Celsius for
over an hour, we would officially consider this patient to have both fever and neutropenia.
An additional lab should be drawn and broad spectrum antibiotics initiated. But how should you
choose what antibiotics to start and what labs and studies to order? In febrile neutropenic patients,
we must consider a few issues in making this decision. Again, this is never a decision
you should feel that you are making alone. Each patient should have a fever plan that is discussed
on daily rounds, and then again when the on-call team is getting sign out from the daytime team.
At Boston Children's Hospital, we have a set of guidelines for the treatment of
febrile neutropenia in oncology patients. This is available on the intranet and is posted throughout
the oncology work rooms. Though no one expects you to memorize this document, make sure that
you are aware of where it is so you can refer to it when you need to. If you are at an institution
other than Boston Children's, you probably have a similar guideline for your own institution.
Antibiotics.
A few important things should always be considered for each febrile patient.
The first is patient risk group. We divide patients with febrile neutropenia into those
whom we consider high risk or standard risk. High risk patients are those who have prolonged and/or
profound neutropenia, have Down syndrome, and/or have symptoms suggestive of a severe infection
such as sepsis or shock. The patient's diagnosis is also considered in defining risk group.
Secondly, we think about a patient's cancer diagnosis, ANC, and last chemotherapy.
Different chemotherapeutics cause neutropenia at different times and for different lengths of time.
Knowing what chemotherapy the patient had and when will help you to estimate the trajectory of
their neutrophil count with time. It's important to know not only the patient's current ANC, but
also how it has been trending over the past few days. Thirdly, we consider any history of prior
infections and/or episodes of febrile neutropenia. If a patient has recently had an invasive or
serious infection, it may be wise to consider an antimicrobial that covers their prior pathogen.
We also consider what antimicrobials the patient is currently receiving.
This informs the decision as to whether new antimicrobials need to be added, if current
medications should be changed, and what holes there may be in current antimicrobial coverage. We
also consider duration of symptoms to help better develop a differential diagnosis for the fever.
The most important intervention for a patient with fever and neutropenia
is early administration of broad spectrum antibiotics. Our goal is to have antibiotics
administered within one hour of fever detection. Different institutions use different empiric
antibiotics, but the general principles of selecting antimicrobials are universal.
Both the most common bacterial pathogens and the most dangerous pathogens must be covered.
In a neutropenic patient, we are concerned about impaired immunity,
disrupted mucosal barriers, and indwelling catheters. Antimicrobials should therefore provide
coverage against gram negative enteric flora, gram positive skin flora, and in the case of abdominal
pain, or perirectal pain, consider additional coverage of anaerobic enteric organisms.
Labs and Studies.
What labs and studies should you order in a febrile neutropenic patient?
Physical exam findings, symptoms, and patient history should guide your evaluation.
All patients must have a complete blood count with differential and blood cultures drawn
at the time of fever. Consider also obtaining a viral respiratory panel
or chest x-ray for patients with viral symptoms or abnormal findings on respiratory exam.
In neutropenic patients with abdominal pain, the can't miss diagnosis is typhlitis,
also called neutropenic entercolitis. For patients with abdominal pain, or diarrhea,
consider abdominal imaging and stool studies. If a patient has neurologic symptoms,
consider head imaging. For all of these concerns,
you should be discussing the appropriate workup and management with your on-call fellow.
Ongoing clinical assessment is important in ensuring that changes in a patient's
clinical status are noted promptly. While many patients with febrile neutropenia
have no localizing signs or symptoms and are managed sufficiently with empirical antibiotics,
some patients may develop more concerning symptoms that warrant further interventions
or more intensive monitoring. Patients with respiratory distress, vital sign instability,
and/or mental status changes should raise concerns for bacteremia or sepsis
and warrant consideration of an ICU evaluation as well as notification of the on-call fellow.
Don't forget initial stabilizing measures in a sick patient while awaiting help to
arrive such as supplemental oxygen as needed and fluid resuscitation.
Sick and/or persistently febrile patients may also require broader anti-microbial coverage.
Summary.
So to recap, fever and neutropenia is defined as a fever of 38.5 degrees Celsius once
or at least 38.0 sustained over an hour in an oncology patient with an ANC
less than or equal to 500. Vital signs, clinical exam, and risk stratification can
be used to guide initial management, tests, and antibiotics. Obtain blood cultures and
start broad spectrum antibiotics within one hour. Thank you for watching this video.