1. Procalcitonin Guided Antibiotic Management for the Post-operative Open Heart Surgery Patient
Daizo Tanaka, MD; Shinya Unai, MD; Harrison T. Pitcher, MD
Nicholas Cavarocchi, MD; James T. Diehl, MD; Hitoshi Hirose, MD
Division of Cardiothoracic Surgery, Department of Surgery
Thomas Jefferson University Hospital

2. Diagnosis of infection in postop cardiac surgery patients
Systemic inflammation after cardiac surgery makes diagnosis of infection difficult.
Surgical trauma
Cardiopulmonary bypass
Prat C, Ricart P, Ruyra X, Domínguez J, Morillas J, Blanco S, Tomasa T, Torres T, Cámara L, Molinos S, Ausina V. Serum concentrations of Procalcitonin after cardiac surgery. J Card Surg 2008; 23:
Aouifi A, Piriou V, Blanc P, Bouvier H, Bastien O, Chiari P, Rousson R, Evans R, Lehot JJ. Effect of cardiopulmonary bypass on serum Procalcitonin and C-reactive protein concentrations. Br J Anaesth 1999; 83:602-7.
Conventional signs and markers of infection (fever, WBC count, CRP etc.) are inaccurate.

3. Procalcitonin (PCT)
More specific for infection than conventional markers
Aouifi A, Piriou V, Blanc P, Bouvier H, Bastien O, Chiari P, Rousson R, Evans R, Lehot JJ. Effect of cardiopulmonary bypass on serum Procalcitonin and C-reactive protein concentrations. Br J Anaesth 1999; 83:602-7.
Valuable for diagnosis of community-acquired pneumonia, urinary tract infection and sepsis
Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum Procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515-8.
Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Müller B. Effect of Procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomized, single-blinded intervention trial. Lancet 2004;363:600-7.
Only limited reports for postop cardiac surgery patients

4. Study design
Algorithm to manage postop patients suspected of infection
Retrospective study from Jan 2012 to Jan 2013
Postop cardiac surgery patients tested for PCT
Exclusion
PCT value on POD1
prolonged systemic malperfusion
immunosuppression

5. Algorithm TREGGER EVENT Increased WBC count Fever >101.4
Infiltration on chest x-ray
Positive urinalysis or culture
Increasing vasopressor requirement
Signs of sepsis/shock NO
Continue standard of care
Yes
Study confirmation of source
Cultures: blood, urine, sputum
Duplex ultrasound
Laboratory tests (Labs)
Start broad-spectrum antibiotics
Initial Procalcitonin (PCT) level
Trend PCT levels
Treat per standard of care

6. Treat per standard of care Initial Procalcitonin (PCT) level
Trend PCT
Treat per standard of care
Initial Procalcitonin (PCT) level
PCT < 2ng/ml
PCT ≥ 2ng/ml
Positive PCT with
Source confirmation
Trend PCT
Continue antibiotics
Follow-up cultures
Trend PCT
Continue antibiotics
Follow-up cultures
Worsening clinical picture
PCT < 2ng/ml
Increasing/positive PCT
No clinical improvement
Positive PCT
No source identified
Clinical improvement
Trend PCT
Continue antibiotics
CT chest/abdomen/pelvis
Consider repeat cultures
Discontinue antibiotics
No additional imaging
Positive PCT
Source not identified on imaging
Negative PCT
No clinical improvement
Positive PCT
Source identified on imaging
Trend PCT
Continue antibiotics
False negative PCT
Restart antibiotics
Improving clinical picture
Trend PCT
Treat per standard of care (consider operation)
False positive PCT
Discontinue antibiotics

7. Characteristics of patients
With infection
Without infection
P value
Number 16 17 -
Age (years old)
55.5 ± 13.1
61.2 ± 15.3
0.37
Male
14 (88%)
13 (76%)
Body mass index
28.3 ± 7.4
29.3 ± 6.2
0.68
Procedure
CABG 2 5
Valve 8
Other 9 4
PCT (ng/ml)
16.4 ± 26.5
4.1 ± 10.2
0.11
Temperature (F)
99.4 ± 1.6
100.1 ± 1.5
0.27
WBC count (B/L)
16.8 ± 9.0
13.1 ± 5.3
0.18

8. Sensitivity, specificity, predictive values with different cut-off of PCT value
Cut-off (ng/ml)
Sensitivity (%)
Specificity (%)
PPV (%)
NPV (%)
2.0 81 82
1.5 88
1.0 94 77 79 93

9. Receiver operating characteristics
1.0 ng/ml
PCT
1.5 ng/ml
WBC
2.0 ng/ml
Area under curve
PCT
0.864 (0.658 – 0.955)
WBC
0.605 (0.399 – 0.779) P
0.03
Sensitivity
Specificity

10. True positive PCT
All 15 true positive patients (PCT≥2ng/nl, +infection) were treated with ABX.
10/15 patients:
PCT was trended until <2ng/ml
3 patients:
ABX continued
(2 mediastinitis and 1 sepsis after AVR)
7 patients:
ABX discontinued, no recurrence

11. True negative PCT
12/14 true negative patients (PCT<2ng/ml, – infection) had empiric ABX discontinued by 72 hours.
12/14 patients:
ABX discontinued

12. False positive/negative PCT
Only one case with PCT<1ng/ml and +infection; mediastinitis (contained sternal abscess)
PCT values have been reported to be low in case of contained infection and abscess, and it could be the limitation of the PCT assay.
Aouifi A, Piriou V, Bastien O, Blanc P, Bouvier H, Evans R, Célard M, Vandenesch F, Rousson R, Lehot JJ. Usefulness of Procalcitonin for diagnosis of infection in cardiac surgical patients. Crit Care Med 2000;28:
3 cases of false positives (PCT≥2ng/ml and –infection); no positive culture was obtained
Trending of PCT level was effective in following up severity of infection.

13. Conclusion
PCT assays incorporated in the algorithm was able to predict infection with excellent sensitivity and specificity.
PCT value of 1 to 2ng/ml would be the best cut-off to diagnose infection.
can vary depending on timing and other condition
This PCT based algorithm potentially reduces hospital cost and length of stay.