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FN, sepsis and shock
1.
2.
3. Mild <1500/microL, moderate
<1000/microL, severe
<500/microL
Primarily useful for other forms
of neutropenia, such as viral-
induced or congenital/cyclical
Neutropenia is defined as an ANC
< 500/ microL in cancer patients
4. Definition:
An absolute neutrophil count (ANC) <
1500/microL
7.9 segs 8% L 82%
3.7 98 Bands 2% B 3%
23 M 4% E 1%
How do you calculate ANC?
Total WBC count x (% neutrophils + % bands)
100
5. Risks of infection related to
◦ Duration of neutropenia
◦ Degree of neutropenia
◦ Factors that predispose to infection
Mucosal and skin breakdown
Altered immune system
Central venous catheters
6. In a Neutropenic Patient
◦ A single oral temperature > 38.3 C
◦ A temperature of 38C for longer than one hour, or
two elevations greater than 38C in a 12 hour period
How about a rectal temperature?
◦ Due to associated risks of mucosal trauma and bad-
ass bacteremia, neutropenic patients should have
nothing introduced per rectum
Thermometer
Digital Exam
Suppository
Enema
7. In patients with cancer, infection is a
major cause of morbidity and
mortality
◦ Fever may be the first and only indication of
infection in a neutropenic patient
◦ Some patients may be afebrile, but are
hypothermic, hypotensive, lethargic, and/ or
confused.
Do not assume that if there is no
fever, there is no infection!
◦ Treat empirically if there are signs of clinical
deterioration in a neutropenic child, even if afebrile
8. Bacteremia is the most common cause!
◦ Approximately 20% of patients with fever and
neutropenia will have a positive blood culture
11. Thorough history
◦ Sick contacts
◦ Review of systems – little things mean a lot
Careful physical exam
◦ All skin – note even slight erythema
◦ Perirectal area (but no rectal exam)
◦ Mucosa
◦ Line sites, surgical sites, LP/BMA sites
Laboratory/ imaging studies:
CBC w/ diff
Blood/ fungal cultures (from all lumens of central line)
Symptom/history/risk based: chest x-ray, NP swabs,
lumbar puncture, urine cx, stool studies, wound cx
12. infectious or non-infectious insult leading
to an inflammatory
cascade, vasodilation, and capillary
endothelial leak, presenting with 2 or more
of the following:
◦ fever >38C or <36C,
◦ HR >90
◦ RR >20,
◦ WBC >12 or <4 or >10% bands
13.
14. What is shock?
◦ Inadequate oxygen delivery to meet the
metabolic needs of the tissues.
What shock isn’t:
◦HYPOTENSION
15. Compensated
◦ Vital organ system is preserved
Uncompensated
◦ Ability to regulate blood flow is compromised
Irreversible
◦ Damage of vital end organs leading to multiple
organ system failure
26. Inflammation is the normal host response to
infection
◦ It serves to localize and control bacterial invasion
and to initiate repair of injured tissue
Sepsis results when the inflammatory
response to infection becomes generalized
◦ It extends to involve healthy tissue remote from the
site of infection
27. Sepsis is a clinical syndrome due to a
systemic response to severe infection
Infection causes a release of
inflammatory mediators
These cause systemic inflammation and
widespread tissue injury
Maldistribution of intravascular volume
and depression of myocardial function
result in shock
28. Volume 20 cc/kg x 3 of crystalloid
May use colloid
◦ PRBCs if anemic
◦ 5% albumin if hypoalbuminemic
◦ Platelets if suspicion of active bleeding and
thrombocytopenic
If no response to 60 cc/kg, establish central
monitoring and initiate inotropic support
Antibiotics, antivirals, antifungals
◦ Important, but less important than fluids
30. Normal mental status
Normal blood pressure for age (reliable when
pulses are palpable)
Normal pulses-no difference between central
and peripheral pulses
Capillary refill < 2 seconds
31. Warm extremities
Urine output > 1 ml/kg/h
Normal glucose level
Normal calcium level
33. In
a patient with suspected septic
shock, how fast should you give
the initial 20ml/kg bolus?
◦A: As fast as possible!
Push is literal – you should actually be
pushing on the bag or syringe of fluid.
Your hand should hurt.
34. Volume
Volume
Volume
Volume
**Average requirement 40-60 ml/kg
Monitor for work of
breathing, rales, gallop, hepatomegaly
35. Dopamine
◦ First line drug
◦ Drip at 5-10 mcg/kg/min to start
◦ More beta adrenergic at low doses, alpha at high
doses
Epinephrine
◦ Fluid refractory, dopamine-resistant cold shock
Norepinephrine
◦ Fluid refractory, dopamine-resistant warm shock
◦ More alpha adrenergic
36. Risk for adrenal insufficiency
◦ CAH
◦ Previous steroid exposure
◦ Hypothalamic/pituitary abnormality
Shock despite epinephrine or norepinephrine
infusion
Send a cortisol level and initiate
hydrocortisone therapy at stress-level dosing
37.
38. Timely initiation of broad spectrum
empiric parental antibiotics
◦ Considerations in antibiotic choices:
Types of bacterial isolates found in the institution
Antibiotic susceptibility patterns
Patient’s drug allergies
Organ dysfunction (i.e. renal, hepatic)
Type of chemo regimen given and last time
administered (i.e. there is an association between Strep
viridans infection and high dose cytarabine therapy)
39. Good data supports the use of monotherapy
with a single antipseudomonal broad-
spectrum agent
However, many use combination therapy for
synergistic effects and possible reduction of
drug resistance
◦ Combination therapy: Aminoglycoside +
antipseudomonal penicillin, cefepime,
ceftazidime, or a carbapenem
40. Improves coverage of gram-positive organisms
◦ Febrile neutropenic patients are expected to
defervesce after 48-72h of broad-spectrum
antibiotics
◦ If the patient is still febrile after 48-72 hrs
of antibiotic coverage, the next drug we
add at MSKCC is Vancomycin
◦ It may be added at initiation of broad
spectrum antibiotics if there is a strong
suspicion of infection with a gram positive
organism
41. The efficacy of adding vancomycin at the
beginning of treatment has not been proven
◦ Up to 2/3 of bacterial isolates from blood in febrile
neutropenic cancer patients are gram + cocci
◦ Addition of Vancomycin at the start of treatment
has not shown an impact in either morbidity or
mortality
Empiric therapy is also discouraged because its use
increases the probability of colonization of infection
with Vancomycin-resistant enterococci (VRE)
42. Fungal treatment is generally added when
patients are persistently febrile after 5-7 days
of broad spectrum antibiotics and negative
blood cultures
◦ At MSKCC, we usually add Liposomal Amphotericin
(AmBisome) after 5-7 days of persistent fever
(Voriconazole alternative)
◦ Use of Amphotericin B therapy is limited
due to substantial toxicity, particularly
nephrotoxicity
43. Additional anaerobic coverage is generally
with metronidazole
◦ Indications include persistent diarrhea, positive
stool cultures (clostridium difficile), areas of
perianal infection (erythema, fissures, rectal pain/
possible typhlitis)
44. Length of treatment varies by center
At MSK, all antibiotics are continued until:
◦ ANC is >0.5 AND
◦ Patient is afebrile for at least 24 hours
If cultures are positive, length of treatment is
determined in consultation with ID
◦ This will also depend on type of infection and
intervention
45. Fever & Neutropenia is for real
Treat suspected sepsis immediately
◦ Fix the fluid overload later
◦ PUSH is literal. PUSH the fluid.
Choose antibiotics based on institution and
patient history
◦ You can always change later
Editor's Notes
Dopamine- Intermediate dosages from 5 to 10 μg/kg/min, known as the "cardiac dose", additionally have a positive inotropic and chronotropic effect through increased β1 receptor activation. Dopamine is used in patients with shock or heart failure to increase cardiac output and blood pressure.Dopamine begins to affect the heart at lower doses, from about 3 μg/kg/min IV.High doses from 10 to 20 μg/kg/min are the "pressor dose". This dose causes vasoconstriction, increases systemic vascular resistance, and increases blood pressure through α1 receptor activation, but can cause the vessels in the kidneys to constrict to the point that urine output is reduced.
