Managing Fever in the Presence of Neutropenia or Central Lines

Chadi ELtaha, MD PGY II - PEDS

Fever and Neutropenia

Muy Importante!



Fever in a patient with cancer or on chemotherapy is a medical emergency



Mortality is 1-5%

Definitions



Fever:

 Single oral T>101 o F (38.3

o C) OR  T=100.4

o F (38 o C) on two separate readings one hour apart  Oral is best; take axillary if oral temp impossible  No conversion needed  AVOID rectal temperature in any oncology patient at any time

Definitions



Neutropenia

:  ANC < 1500  Mild 1500-1000  Moderate 1000-500  Severe <500  Profound <200  Risk of infection in cancer patients is high if ANC<1000

Definitions

 Calculating the ANC:  Total WBC count x (% neutrophils + % bands)  WBC= 3.1, neutrophils 30%, bands 4%  What is the ANC?

 WBC= 2.4, neutrophils 0%, bands 0%  What is the ANC?

Risk

 Infection risk increases with:  Any break in the skin barrier  Any foreign body: central lines, indwelling ports, Foley catheters, NG tubes, shunts, rods, prostheses  Prolonged neutropenia

History

 Duration of fever? Accompanied by chills?

 Fatigue?

 Rhinorrhea?

 Cough?

 Abdominal pain or GI symptoms?

 Dysuria?

 Central line?

Physical Exam

 Thorough exam, including:  Oral exam for ulcerations  Perirectal exam for lesions  Nares for lesions, especially if NGT feeds  Skin exam  Central line for phlebitis, cellulitis

Admission Investigations

 CBC with diff, CRP, blood cultures from periphery x 1, blood cultures from all lumens of all central lines, CP14 (most chemo patients will have abnormalities)  urinalysis and culture (must be clean catch- catheterization contraindicated in neutropenia)  viral respiratory culture and rapid flu and RSV if indicated  If diarrhea, C. diff toxin, fecal WBCs, stool culture

Admission Investigations

 Radiologic Studies  CXR (debatable if no pulmonary symptoms)  Sinus CT if symptoms or if all other workup negative  Abdominal CT if significant abdominal pain (worry about neutropenic colitis, aka acute typhilitis)

Beware…

 CXR may not have an infiltrate apparent during neutropenia —may change after counts recover  Urinalysis may not have WBCs or leukocyte esterase during neutropenia — send a culture

Daily Labs

 CBC with differential to follow ANC  CRP if previously elevated  CP14 if indicated (if needs supplements or on TPN)  Blood cultures while febrile (can be from central line, don’t have to have peripheral)

Medications

 Ceftazadime or Cefepime 50 mg/kg/dose IV Q8 hours, max 2g/dose  Add Vancomycin 15 mg/kg/dose IV Q6 hours if signs of line infection.

 Add Gentamicin 5 mg/kg/day IV Q24 hours if hypotension and chills  Add Amphotericin B if persistent neutropenia and fever >4-5 days despite antibiotics  * Both Cefepime and Ceftazadime can cause neutropenia, even in healthy people!

To culture or not?

 Recollect blood cultures in these cases:  Before adding or changing an antibiotic  Persistent fever (get one culture per day while febrile, best to get when actually febrile, don’t always have to have a peripheral)  During times of clinical deterioration  If you are called with a positive culture  You don’t need 8 million cultures in a day!

What if something grows?

 Order another culture  Look at your antibiotics and see if you should have coverage  Follow-up on the sensitivities; should be available the next day  Tailor antibiotics if possible  If a true infection, ECHO

Contaminant or Not?

 Unlikely to be true pathogens: 

Corynebacterium,

non-anthracis

Bacillus

,

Propionibacterium acnes

 Uncertain significance:  Coagulase negative staph  If your patient was unstable, has a CVL, or this grows in multiple cultures, maybe so!

 Probably so: 

S. aureus, S. pneumo, Enterobacter, P. aeruginosa, C. albicans, Aspergillus

Consider…

 If multiple positive blood cultures, likelihood of true bacteremia increases  If cultures are repeatedly positive for coag neg staph or if peripheral and CVL cultures are positive at the same time, likelihood of true bacteremia increases

How long do you treat?

 Depends on the organism and if they have a central line that you want to keep  Depends on initial clinical appearance  Usually minimum of 14 days for CVL, sometimes longer; ask your friendly ID expert!

 Start counting your days of antibiotics from the date the first negative cx was drawn, not from first day of antibiotics

What if nothing grows?

 This will happen more often than not.

 You can stop antibiotics when  Afebrile for 48 hours  Counts recovered (ANC >500)  All cultures negative for 48-72 hours, and any positive cultures treated fully  Clinically stable  Your attending says so!

Fever and Central Lines in the Absence of Neutropenia

Types of Central Lines

Hickman catheter:  Seen more in infants and toddlers  Placed surgically in the chest wall; needs surginet  Benefits: always accessed, no needle stick to draw blood or infuse  Drawbacks: always accessed, increasing risk of infection, hanging on chest, gets pulled by frisky kids

0100…

 RN calls you because Ricky, a 3 yo with ALL, was found running in the hall with his IV pole behind him attached to his Hickman catheter. She thinks he might have pulled out the line some.

 What do you want to do?

Other than installing a lock…

 Inspect the chest for any changes  Be sure that he has surginet over his trunk to secure line  See if there is still blood return  Get a CXR and compare it to previous placement  If displaced, notify surgery team and discontinue use until repaired  Don’t keep kids hooked up if not necessary

Types of Central Lines

Port A Cath:  Seen more in older children and adolescents  Surgically placed in the chest wall  Benefits: cannot be pulled on because it’s subcutaneous, theoretically less infection  Drawbacks: requires needle stick to access or draw labs, can flip and make access difficult

2200…

 You are called because 10 yo Heaven’s port is not drawing back blood or flushing. She says that it hurts her.  What do you want to do?

Try…

 Deaccessing the port (need to flush with heparin before deaccessing in general)  Applying EMLA cream for comfort with needle sticks  Reaccessing the port  If you can’t get blood return, you can’t use it unless you have a radiology dye study to verify placement (considered bad form to infuse chemo or most anything subcutaneously!)

Types of Central Lines

PICC Lines (

P

eripherally

I

nserted

C

entral

C

atheter)  Placed by specially trained team of RNs  Benefits: OR not required for placement, allows for IVF, TPN, and prolonged antibiotics, allows for frequent blood draws  Drawbacks: Infection, bleeding, DVT, air embolism, breakage, requires weekly CXR for placement, not usually used for chemo

By the way..

 PICC handout and doctor consent form in PICU  Consent for deep sedation  Social service consult for OPAT (outpatient parental antimicrobial therapy)

1400…

 You need a CBC on a patient with a PICC line. Can the nurse draw it off the PICC line or do they have to stick the patient?

 Look at the original orders for the PICC line (in the order section). They tell you if you can draw off it or not. If you can’t find them, ask the PICC team or use these general guidelines…

PICC Guidelines

 Can draw labs off 3 Fr and bigger  Can transfuse blood through 3 Fr and bigger (risk of clotting off)  No contrast administered unless by specially trained RN (makes radiology techs nervous)  1.9 Fr get heparin flushes Q4 hours and after use (unless really tenuous, then may get continuous heparin)  3 Fr and bigger get NS flushes only  Dressing changes Q week and PRN nasty

Muy importante!

Fever in a child with a central line is bacteremia until proven otherwise

History

 Why do they have a central line? Are they already on antibiotics at home? Which ones, what doses?

 Other sources of fever?

 Line care, any problems with lines, any rash, cellulitis, pain associated with line?

 Fever, chills, nausea, fatigue?

Physical Examination

 Look at the line and look proximal to the line for any streaking, phlebitis  Look for any other sources  Listen for a murmur!

Labs

 CBC with diff, CRP, blood culture from periphery and from all lumens of the central line  Any applicable drug levels  CP14 depending on the drugs that they are on  Other investigations for fever as indicated

Other studies

 CXR for placement if needed  ECHO if murmur or a true positive blood culture to rule out endocarditis

WARNING



NEVER

try to push fluids or put Cath Flo in a central line that you think might be infected, you can release a septic emboli!



NEVER

treat any CVL infection with PO antibiotics 

ALWAYS

give antibiotics through the CVL if functioning

Medications

 Ceftazadime or Cefepime 150 mg/kg/day IV Q8 hours (covers Pseudomonas, Gram negatives and MSSA)  Vancomycin 15 mg/kg/dose IV Q6 hours (covers MRSA and coag neg staph)  What do you write after your Vanc order?

When should a line come out?

 For

sure

when there is a fungal infection  Probably when there is a gram neg bacillus, s aureus, or enterococci infection  Otherwise, consult with ID regarding safety of treating line  If patient unstable with a Gram negative infection, line has to come out, otherwise, may be able to treat  Should complete treatment before another line is placed

 A 12-year-old boy who has acute lymphoblastic leukemia (ALL) is undergoing reinduction chemotherapy and has an indwelling Broviac catheter. He has received multiple courses of antibiotics for episodes of fever and neutropenia. He recently completed a 6-week course of vancomycin for persistent coagulase-negative staphylococcal bacteremia. He is admitted to the hospital with a temperature of 39.5

°C and a white blood cell count of 0.2x10

3 /mcL (0.2x10

9 /L) (0% neutrophils). Blood culture grows gram-positive cocci that are resistant to vancomycin.

 Of the following, the MOST likely pathogen on the blood culture is 

A.

group B

Streptococcus

B.Klebsiella pneumoniae C.Listeria monocytogenes

D.

methicillin-resistant

Staphylococcus aureus

E.

vancomycin-resistant

Enterococcus

 A 4-year-old boy who has acute myelogenous leukemia is admitted for the treatment of fever and neutropenia. He has a Broviac catheter in place. His temperature on admission is 39.3

°C and absolute neutrophil count (ANC) is less than 0.1x10

3 /mcL (0.1x10

9 /L). No focus of infection is apparent on physical examination. After blood cultures are obtained, he is begun on treatment with piperacillin/tazobactam and gentamicin. Five days later, the cultures remain negative, ANC continues to be less than 0.1x10

3 /mcL (0.1x10

9 /L), and his daily maximum temperature continues to be greater than 39.3

°C.

 Of the following, the MOST appropriate management at this point is to

A.

add amphotericin B to the antibiotic regimen

B.

administer granulocyte transfusions

C.

change the antibiotic regimen to meropenem and amikacin

D.

continue the present antibiotic regimen

E.

stop the antibiotics and obtain another culture



THANK YOU