This presentation focuses on a recently published paper aiming to create an algorithm for the investigation of patients with new onset fever or instability

1. “A Novel Comprehensive Algorithm for Evaluation of
PICU Patients With New Fever or Instability”
Pediatric Critical Care Medicine- June 2023, Vol 24, Issue 6
By Fatima Farid
Ped Resident Yr 5
Journal Club

2. Fever in the PICU – Why do we worry more?
2
VS
VS

3. Background
• Temperature is one of the most important vital signs for all patients, including intensive
care units!
• The fever in the ICU could be:
• A continued manifestation of the disease/disorder that prompted the ICU admission
• Due to interventions or therapies provided during ICU stay
• New-onset fever due to SIRS, septic, metabolic or a neuroendocrine response
• Rarely due to flare-up of an underlying dormant disease or disorder
3
Achaiah NC, Bhutta BS, AK AK. Fever in the Intensive Care Patient. [Updated 2023 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570583/

4. 4
Ventilator-
associated
pneumonia
(VAP)
Catheter-
related
bloodstream
infection
(CRBSI)
Catheter-
associated
urinary tract
infection
(CAUTI)
Clostridoides
difficile colitis
Surgical
wound-
related
infection
CNS/ heart/
bone/ soft
tissue/ etc
infection
Achaiah NC, Bhutta BS, AK AK. Fever in the Intensive Care Patient. [Updated 2023 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570583/

5. 5
Cerebral
infarction/
hemorrhage
ARDS/ PE/
chemical
pneumonitis
Acalculous
cholecystitis/
pancreatitis/
gut ischemia
MI/ DVT/
thrombophle
bitis
Adrenal
insufficiency
Drug fever/
drug
withdrawal
fever
Achaiah NC, Bhutta BS, AK AK. Fever in the Intensive Care Patient. [Updated 2023 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK570583/
Thyroid
storm/
pheochrom
ocytoma
Post- op
fever/
transfusion
or drug
allergy
Cancer
SJS

6. Is liberal culturing the best approach to fever w/up?
• No
• Negatives:
• Avoidable antibiotic usage
• Additional 2ry diagnostics
• Extended length of stay (LOS)
• Inflation of healthcare costs
• Delayed diagnosis of alternative causes of fever
6

7. A possible solution
• Use a decision- support tool !
• These may:
• Improve clinical care
• Reduce errors
• Minimize medical overuse and costs
• Create uniformity in clinical practice
• Reduce risk of implicit physician biases
7

8. June 2023 - Volume 24 - Issue 6
8

9. • Single center study at John
Hopkins Children’s Center in
Baltimore
• Quaternary care academic PICU
with 40 beds for medical, surgical
and cardiac cases
9

10. Background
10
In 2014: a “blood culture
decision- support tool” led
to safe 46% decline in
blood cultures
In 2018: an “endotracheal
culture decision- support
tool” led to 41% decline in
ET cultures & Abx usage for
ventilatory- associated
infections
But by late 2018:
• An increase in the frequency of
blood cultures from 90 to 100/
1,000 patient days
• Trend of sending urine cultures
isolated without urine routine
testing
• Relatively stable 20 respiratory
cultures/ 1,000 patient days

11. Research Purpose
• Aims:
• Promote judicial microbiological testing by reducing cognitive bias from habitual or reflex
ordering practices
• Encourage broader consideration of fever etiologies
• Targets:
1. Decrease blood culture rates by 10%
2. Decrease urine cultures & increase urine analysis by 20 %
3. Sustain reduced rate of ET cultures
11

12. Method
Analysis of clinician
bias towards excess
culturing
Algorithm
development by
multi- disciplinary
experts
Study of pre- VS.
post- algorithm
implementation
practice
12

13. 13

14. Guideline
Formation
Final algorithm
Societal
guidelines
Contemporary
evidence
Unit blood &
ETT guidelines
14
Common
non-
infectious
causes of
fever
Special
considerations
for neonates +
immunocompr
omised
Screened by
stakeholders from
CCU, NICU, oncology,
ped surgery & ped
neurosurgery
Distributed to the
practitioners

15. 15
New Fever/ Hypothermia:
- New/ first fever is at least 48 hours since last
fever. Any 2 readings should be 1 hr apart.
- Immunocompetent:
- 38 C x 2
- 38.5 C x 1
- < 36 C x 2
- Immunocompromised:
- 38 C x 2
- 38.3 C x 1
- < 36 C x 2
- Neonates < 2 months GA:
- Hyperthermia 38 C x 1
- Hypothermia < 36 C x 2
- Increased need for temperature support

16. 16
New instability or sepsis:
- Rigors, hypothermia
- Hypotension (absolute or relative hypotension in
patient on anti-hypertensive medications)
- Use of vasoactive medications
- Tachycardia, mental status changes, poor
perfusion
- Glucose instability, worsening organ dysfunction
(lactemia, acute kidney injury, metabolic acidosis)
- Abnormal WBC
- New apnea or bradycardia, concern for NEC/SIP
in neonates

17. 17
* Immunocompromised: may have masked signs of sepsis, particularly patients on > 1 mg/kg/day steroids, induction
chemotherapy for HLH, induction or reduction therapy for Burkitt Lymphoma
* Differential time-to-positivity is a useful way to distinguish catheter-related bloodstream infections from bacteremia
unrelated to central line care. To be valid, equal volumes of blood must be obtained simultaneously from each lumen and a
peripheral source and inoculated in the same culture media.
* Consider blood cultures from central line lumens and peripherally to distinguish line infections from bacteremia and to
inform possible salvage of the central line. If considering catheter salvage, re-culture every lumen daily until negative.

18. 18
* After 2 unsuccessful peripheral attempts, attempt an arterial puncture sample. If unable to obtain an arterial sample via
arterial puncture, obtain blood culture via central line. If unable to obtain central line culture, may consider changing the
patient’s arterial line set up and then obtaining an adequate specimen via arterial line. The arterial line should be the last
option for blood sampling.
* Burn patients may have inflammatory response due to burns/debridement/grafting procedures. Antibiotics should only be
used when absolutely needed (i.e., septic shock or identified infections). Antibiotics should be reviewed with PICU attending,
surgical burn attending, and following ID team.

19. 19

20. 20
* Consider the differential for instability in premature neonates such as IVH, widened PDA, or RDS

21. 21
* Examples of UTI risk factors: structurally abnormal urinary tract, high-grade hydronephrosis, neurogenic bladder

22. Measures
• Primary outcome:
1. Rates of blood (central, peripheral), ETT, urine routine & cultures measured per 1,000 PICU
patient- days (& also per CVC- days; ventilator- days; urinary catheter- days)
• Secondary outcomes:
1. Antibiotic usage
2. In- hospital mortality
3. Hospital & PICU LOS
4. 7- day hospital re- admission
5. Severity of illness using PRISM – III scores
22

23. Overview
4,298 children
PICU +
CICU
admissions
All ages <
25 years
23
Study Timeline:
July 1, 2018,  December 31, 2021
Regular electronic surveys were sent to
physicians to ask about use of the algorithm,
safety concerns, observed clinical benefits, and
feedback
Inclusion Criteria

24. Physician Feedback
Form
24

25. Statistical analysis
Statistical process control charts,
specifically U-charts, to analyze
testing and antibiotic rates
Defined the baseline period as the
24 months before algorithm
implementation (from July 1, 2018,
to June 30,2020)
Shifted centerlines if special cause
variation was demonstrated using
the aggregate point rule and
evidence of persistent shift if 8 of 9
points fell on one side of the
baseline rate
Compared the baseline monthly
rates to the postimplementation
rates beginning the month of a
centerline shift using incident rate
ratios (IRRs)
Evaluated testing rates, antibiotic
use rates, and clinical outcomes
using two-sided Z-tests for IRRs,
Mann-Whitney U tests for
nonnormally distributed variables,
and chi-square tests for categorical
variables
Conducted analyses in R Statistical
Software Version 4.1.2 (R Core
Team 2021; R Foundation for
Statistical Computing, Vienna,
Austria).
25

26. Results &
Discussion
26

27. 27
* Identical results when calculated per device- days

28. 28
Primary Outcome Analysis:
Blood:
- Mean blood culture rate declined by 17%
- Central blood culture rate declined by 22%
- Peripheral blood culture rate declined by 23%
ETT:
- Respiratory culture rate declined by 26%
Urine:
- Urine culture rate declined the most – by 36%
- Urine routine analysis increased by 18%

29. 29

30. Catheter- Associated UTI
• The most significant changes in their center were in urine testing
• Previously used to leave out urine routine- makes culture interpretation harder
• PICU reported no CAUTI from November 2020- May 2022; and CICU had only 1- likely
because the algorithm encourages removing unnecessary catheters/ lines +
encourages higher index of suspicion for risky cases (neonates, urology patients)
30

31. 31
Secondary Outcome Analysis:
Statistically Significant:
- Antibiotic initiation reduction by 12%
- Hospital length of stay reduction
- PICU length of stay reduction
- Stable risk of mortality pre- and post- algorithm implementation

32. 32
Secondary Outcome Analysis:
Static:
- In- hospital mortality
- 7- day hospital re- admissions
- PICU admission rates

33. Physician Feedback Assessment
• 46 out of 108 invited physicians participated
• 85% reported use of algorithm in the prior week
• No specific safety concerns were noted
• 61% reported the algorithm improved patient care in the prior week
• Suggestions for improvement were taken & algorithm was modified twice
33

34. Positive Comments
Helped them
remember
important Mx
steps
Increased
confidence
Clear
guidance
Reduced
unnecessary
cultures
Created
consistency
Made them
think twice
before ordering
cultures
Helped them
target the right
approach
34

35. Physician Suggestions
35

36. Discussion
• The algorithm promoted deliberate testing practices with more systematic consideration
of etiologies of fever
• No in- hospital mortality cases were associated with a missed opportunity to treat
infections related to the algorithms’ guidance
• The algorithm highlights time- sensitive infections that require prompt recognition and
treatment
• Weekly physician feedback was sought to avoid recall bias
36

37. Limitations
• Not all infectious disease testing
parameters were studied (i.e-
respiratory/ GI panels, CRP, FBC,
x- rays)
• The present algorithm focuses
on new symptoms, but cultures
may be obtained for persistent
symptoms
37

38. In Conclusion
The algorithm promoted judicious testing in a complex patient environment
38

39.  Thanks for listening 