1. Detection and Management of Fever and Infection in the CICU
John T. Berger, MD
Medical Director, Cardiac Intensive Care

2. Disclosures None Financial I am not an expert in infectious disease
The only infection I know anything about is critical pertussis

3. 48,277 Cases 4994 < 1 year 20 deaths 16 < 1 year

4. Pulmonary Hypertension in Pertussis
PH seen in 75% of patient who died

5. Leukoreduction in Critical Pertussis
14 Patients (11%)
Exchange transfusion (12), leukopheresis (1), both (1)
8 had pulmonary hypertension detected
4 had treatment on study day 0
No apparent survival benefit
Patients with WBC Count > 50K by leukoreduction status
Total
Survivors
Leukoreduction 13 8
No Leukoreduction 12 9

6. Objectives
Outline the diagnostic dilemmas of nosocomial infection and fever
Discuss the rise and fall of procalcitonin as biomarker for infection

7. Fever in the ICU Fever Prevalence 26-70%
Etiology equally split between infectious and noninfectious etiologies
Prolonged fever more likely to be infection
Fever a/w increased length of stay and possibly mortality
737 Adult ICU Patients
In septic patients, NSAIDS/Acetaminophen a/w increased mortality (2-2.5 odds ratio) versus non-septic patients with reduced mortality risk (OR ) Lee et al. Crit Care 2012, 16:R33

8. Fever in the PICU PICU – Netherlands – 202 Children
40% with fever during ICU stay
Only ½ with infection
Most within 48 hours of admission
Associated with increased PICU length of stay and mechanical ventilation
Gordjin et al. J Int Care Med 2009

9. Fever ≠ Infection
3 mon old s/p TOF repair. Temp 38.8 C, WBC 15,000; CXR unchanged
How many would send cultures on day 1 before exam?
Blood, Urine, Tracheal Aspirate
66 post op febrile patients with blood cultures in 1st 48 hours
1 positive culture (staph epid)
Kiragu PCCM :364
What about day 4?
Fever “merits clinical assessment by a healthcare professional… prior to any laboratory tests or imaging procedures”
Am College of Crit Care Med 2008

10. Sources of Fever Noninfectious Infectious Meningitis Brain Injury
Seizures
CVA
Meningitis
Otitis Media
Sinusitis
Infarction
Pulm Embolus
ARDS
Pericarditis
Heart Failure
CLA-BSI
Endocarditis
Ventilator associated LRTI
Surgical Site Infection
NEC
CAUTI
Pyelonephritis
Perineal or perirectal abscess
Pancreatitis
Acalculous cholecystitis
Ischemic colitis
Drugs
Transfusion Reactions
Endocrine Disorders (Adrenal insufficiency, thyrotoxicosis)
Malignancy
Inflammatory disorders
PICC or Femoral BSI
Cellulitis
Arthritis
Pressure Ulcer
DVT
Drug Eruptions

11. Environment, Low cardiac output, & hyperthermia
Wyndham. Ann NY Acad Sci, 1977

12. Fever and Infection Adult Canadian (Calgary) ICUs CICU at CNMC
18,989 admissions
Incidence of Fever fell from 50% to 25%
No change in BSI rate, Abx consumption
Niven et. al. CCM 2013, 41:1863
CICU at CNMC
1 CLABSI and 1 CAUTI in last year
Still lots of antibiotic use

13. Infection Related Ventilator Associated Complications (IVACS) (A name only the CDC could love)
Most commonly diagnosed nosocomial infection in PICU
Incidence varies / 1000 vent days
Accounts for ½ antibiotic use in PICU
Criteria for diagnosis neither sensitive or specific
CDC: Infection a/w increase in vent settings (PEEP by 2 cm H20 or Fio2 by 0.2)

14. Would you send a tracheal aspirate? Start Antibiotics?
4 mo old with RSV intubated for 3 days. New 38.5 C fever, WBC =14,000, but no change on CXR
7 yo old intubated for 6 days for ARDS / near drowning. New fever (38.9), WBC = 13,000 and no CXR changes

15. Tracheal Aspirates for IVAC
Survey of 118 MDs in PALISI (98% Attending)
65% -obtained tracheal aspirates as part of a standard r/o sepsis work up
42% without a standard collection method
“The RN or RT just does it”
CXR unchanged. NO change in vent settings reported.
Wilson PCCM 2014; 15:715

16. Percentage who would prescribe Antibiotics
IVAC Treatment
Percentage who would prescribe Antibiotics
RSV
ARDS
Gram Stain –Few PMN, Few GPC
34%
63%
2+MSSA, 2+PMN
79%
81%
2+MRSA, 2+PMN
91%
2+ Pseudomonas, 2+PMN
80%
87%
CXR unchanged. NO change in vent settings reported.
Wilson PCCM 2014; 15:715

17. Tracheal Aspirates
335 samples from 61 intubated PICU patients without regard for clinical status
Predicted to be intubated for > 48 hours
42% post op CV surgery or cardiomyopathy
None immunocompromised
Culture results not provided to clinical team
CDC Definition
> 104 cfu/ml = positive Cx
> 25 PMN / lpf
Willson et. al. PCCM 2014; 15:299

18. TA do not discriminate between colonization and infection
In Line Suction 90%
% Patients with > 25 PMN/lpf
Single catheter 40%
Willson et. al. PCCM 2014; 15:299

19. 40-90% Positive Cultures
CDC Clinical Criteria did not correlate with positive cultures
Fever, WBCs, Increase Secretions, Worse oxygenation, CXR changes
Typical Pathogens isolated
Staph A, Stenotrophamonas, Neisseria, Klebsiella, and Staph E – 80% of cultures
Willson et. al. PCCM 2014; 15:299

20. What to do?
BIOMARKERS

21. Procalcitonin Precursor protein of Calcitonin
Usually undetectable in healthy humans
Rises quickly in response to bacterial infection (IL-6, TNF-α) and less response in viral infection
Initial studies suggested as method to guide diagnose infection
Suggestions that it is better discriminator than CRP

22. Procalcitonin in PICU Single center study
64 of 225 eligible children with SIRS (25 with bacterial infection)
PCT and CRP drawn when found to have SIRS
Infection adjudicated by blinded investigators
Compared CRP to PCT
2.5 ng/ml PCT threshold
Simon PCCM 2008

23. Procalcitonin Variability
High Inter-patient variability
Increases seen with cardiopulmonary bypass and other inflammatory states
Use shifted to guide abx therapy
Schuetz et al. Curr Opin CCM 2013

24. Procalcitonin after Cardiac Surgery
53 patients –All > 3 months, None Infected
All significantly elevated for 3 days
Michalik Card in the Young 2006

25. Conclusions Fever common problem
Diagnosis of infectious etiologies not as straightforward as waiting for culture results
Antibiotic stewardship and rational discontinuation remain important awaiting the application of new biomarker strategies