Procalcitonin Implementation Guide

Procalcitonin Implementation in
Your Hospital
Implementing changes in a complex healthcare organization can be challenging. This implementa- Implementation best practices
tion guide provides a road map for protocol development, integrating Procalcitonin (PCT) into clini-
1. Education, education, education
cal practice, and recommendations for evaluating the process and impact of testing.
It is vital to provide tailored education to all clinicians involved with PCT testing including members of the Antibiotic
Stewardship Committee, pharmacy, critical care, emergency medicine, hospitalists, infectious disease and laboratory.
Education and support
2. Pharmacy and Antibiotic Stewardship Committee involvement
Research shows that behavior changes based on improving both knowledge and attitudes are more sustainable than
manipulating behavior alone. Focus on practical “need to know” content, and then follow up with “nice to know” Studies have demonstrated that when the antibiotic advisor is a pharmacist, antibiotic consumption improves.1-3
information or provide additional materials for self-directed study. In addition, an Antibiotic Stewardship Committee that reviews rapid diagnostic testing results and provides feedback
to providers can help clinicians act upon the results.

Resourses 3. Order set/protocol development

Your Medical Science Liaison (MSL) will serve as a PCT expert and scientific resource guiding you and your team through Order sets standardize and expedite the ordering process and helps clinicians ensure that critical components of care
PCT implementation. Your MSL will provide education, guidance on order sets and help with protocol development to are not overlooked. They also help to control test utilization and prevent unnecessary testing.
ensure a full understanding of PCT kinetics, clinical applications and how it can aid in antibiotic decision making. 4. Assess PCT testing impact: Pre- and post outcome assessment

The MSLs provide clinical support throughout the implementation process (table below). Your facility will choose the A pre- and post-assessment measures the occurrence of predetermined outcomes before and after PCT testing is
teaching methods that will work best with your workflow. Options include instructor-led sessions which are most effective, implemented. This allows the implementation team to assess the implementation strategy as well as the impact of
along with, computer-based training, small group teaching and discussion, or a combination. PCT testing. This assessment should be based on predefined metrics, e.g. antibiotic consumption, adverse drug
events, C-diff rates, hospital/ICU length of stay, health economics, etc.
Pre-implementation During Implementation 3-6 Months After Implementation 5. Assess compliance and offer feedback
• Provide information and education • Interdepartmental education • Grand rounds lecture by a physician Feedback and pharmacy oversight will help guide clinician practice which may lead to improved clinical and health
to antibiotic stewardship committee, (Similar to pre-implementation guest speaker
economic outcomes.
sepsis committee, ICU, ED, ID, education)
• Webinar, video clips for learning on
pharmacy, lab
• Roving Q&A at all ordering demand
• Procalcitonin kinetics, interpretation departments
of results, scientific evidence
• Review and learn from case studies
• Repeat interdepartmental education
PLAN DO
• Continuing literature support as Plan the change strategy… on a small scale Do a test-run of the intervention
• Examples of order sets and AN
• Pocket-size reference cards requested PL
protocols from hospitals that
distribution

DO
use PCT
• Abbreviated bibliography of recent

AC
PCT literature sent electronically ACT STUDY

T
Y
with active links Act on knowledge gained, make any ST U D Study feedback to confirm or to adjust the plan
adjustments necessary, then plan the
• References: hospitals, clinicians,
revisions and incorporate them in the roll out
lab personnel

2 3
 Establish critical values and reference ranges
Key steps to consider:
1. Discuss whether to establish critical values and reference ranges. There is not one specific cut-off for PCT.
The cut-offs are determined based on where and how PCT is used (ED, surgery, monitoring, neonatology, etc.).
In addition, a trend can provide more information than one absolute value.
Example:
1. Repeat 6-12 hours after initial draw if baseline <0.25 (or another pre-defined low value per your hospital policy)
and suspicion of infection is present.
2. Draw Q am x2 to monitor trend.
3. Determine who will be responsible for following PCT.
- For clinical decision making: Intensivist/hospitalist/ED physician and/or clinical pharmacists
- For antibiotic de-escalation: Intensivist/hospitalist and/or clinical pharmacist
- From a quality standpoint: QI/QA
- Who will monitor for spending/cost savings: Pharmacy for de-escalation, QI/QA for sepsis
Create an implementation strategy
2. Customize any additional elements based on organizational factors and potential barriers.
• Recruit team members that are immediately affected by the change and who have the ability to influence others’
reception of the protocol change - Are there any other labs that can be eliminated from current work-up?
- After implementation, track if there are fewer orders for blood cultures, etc.
Physician leadership Antibiotic Stewardship Committee Clinical pharmacy
Clinical laboratory Informatics Quality management

• Determine how the test will be used clinically: antibiotic stewardship, differential diagnosis (rule-out bacterial infection), Feedback and evaluation
and which patient populations will be included (LRTI, COPD, sepsis, etc.) Encourage feedback throughout the implementation process. Once PCT has been incorporated into practice, survey
• Establish Alert and Critical Lab Values. staff members at all levels and ask them what went well, what didn’t go well from their perspective, and how the
process could be improved next time. Share what you learn with other implementation teams to facilitate future
• Develop and/or update order sets and protocols for each patient population.
process improvements.
• Establish a go-live target date.
Support a culture of information sharing. Learn from others’ experience, as they can learn from yours.
• Define education plan and timeline for Antibiotic Stewardship Committee, Sepsis Committee, Critical Care Committee,
Emergency Department, Pharmacy, Laboratory, etc. Long-term follow-up
• Define timeline and metrics for Pre / Post outcome assessment including duration of data collection, e.g. 4 months of Return to your baseline data. Collect data on the same parameters and compare pre- and post-implementation to
baseline data prior to starting PCT, then collect 4 months of data after implementation has been completed. Define determine if you met the goals described in the initial phase. Celebrate your successes! Bring the team together to
metrics, e.g. antibiotic consumption, adverse drug events, c-diff rates, hospital/ICU length of stay, health economic, etc. analyze where you might fall short to explore revising your implementation plan to address any shortcomings.
• Create a Communication Plan that outlines how to communicate implementation details with end-users. Include
go-live date, education dates, selected clinical applications, updates on order sets / protocol developments, etc.
Key steps to consider:

1. Add PCT as an order into EMR - this must be done early in the process to ensure it’s available when you go-live.
2. Develop onscreen prompts for ordering PCT, e.g. suspected bacterial infection, LRTI, sepsis, fever, etc.
3. Consider PCT as a pre-checked item for baseline and follow-up draws.

✓ How will order be triggered? ✓ How will results be monitored?

✓ Does test need to be repeated in a specific time frame? ✓ Is trending or tracking required?
✓ Do standard documents need to be updated? ✓ Do we need custom elements?

4 5
Procalcitonin implementation planning checklist Procalcitonin
Initiating antibiotic therapy for patients with suspected or confirmed lower respiratory tract infection (LRTI)4
Not
Preparation Yes No Required Comments
PCT (ng/mL) < 0.10 0.10 - 0.25 0.26 - 0.50 > 0.50
Recruit team members      
Ongoing
Confirm administrative support       Infection? Very Unlikely Unlikely Likely Very Likely

Develop action plan with dates       ABx Strongly ABx ABx ABx Strongly
Interpretation
Set goals       Discouraged Discouraged Encouraged Encouraged

Review research       Important Considerations: Antibiotic therapy should be considered regardless of PCT result if the patient is clinically unstable,
Explore laboratory options       is at high risk for adverse outcome, has strong evidence of bacterial pathogen, or the clinical context indicates antibiotic therapy is
warranted. If antibiotics are withheld, reassess if symptoms persist/worsen and/or repeat PCT measurement within 6-24 hours.
Identify health economic benefits      
In order to assess treatment success and to support a decision to discontinue antibiotic therapy, follow up samples should be
Assemble baseline data       tested once every 1-2 days, based upon physician discretion taking into account patient’s evolution and progress.
Custom elements PCT levels may not be elevated in patients infected by certain atypical pathogens, such as Chlamydophila pneumoniae and
Mycoplasma pneumoniae.
Custom elements

Not
Development Yes No Required Comments
Discontinuing antibiotics for patients with lower respiratory tract infection (LRTI), or suspected or
How test order will be triggered       confirmed sepsis5,6
How results will be monitored      
Change in PCT Level Current PCT Level
Create new flow sheet or revision
      Important Considerations: If clinical
to existing Decline from peak PCT > 80% LRTI ≤ 0.25 ng/mL
OR
picture has not improved and PCT
Check policies, procedures, protocols, and
      remains high, re-evaluate and consider
care paths for needed revisions Clinical Improvement Sepsis ≤ 0.50 ng/mL treatment failure or other causes.
Design education / support materials      
Custom elements      
Custom elements       PCT values rise in relation to sepsis severity, providing clinicians with a valuable tool for assessing
patients suspected of sepsis.7-9
Not
Implementation Yes No Required Comments
Inadequate Decline ≤ 80% from
infection control peak PCT had a
PCT can be measured on serum or
Identify targeted compliance threshold Peak
20% mortality rate10 plasma; the liquid chosen should be
12-24 hours
Conduct trial run pilot       consistent throughout a patient’s

PCT Plasma Concentration (ng/mL)

Study process, feedback & revise plan clinical course. Do not use citrate
      plasma tubes for specimen collection.
as needed; confirm “go-live” date
Train everyone involved in process just
      Approx. 24 Effective
before go-live PCT rises 3-6 hours hour half life treatment
Go-live       after bacterial
infection
Custom elements      
2 FOLD INCREASE
Custom elements       IN MORTALITY
Decline > 80% from
Not peak PCT had a
Evaluation Yes No Required Comments 10% mortality rate10
Day 0 Day 1 Day 2 Day 3 Day 4
Measure compliance and order patterns
Collect feedback and review formal
     
evaluation forms PCT Plasma
Evaluate entire process       Concentration
(ng/mL) Possible Interpretations 7-9,11
Make revisions as needed       Please Note: PCT levels below 0.5 ng/mL
< 0.05 - < 0.10 Normal level. do not exclude an infection, because local-
Collect data for longitudinal study       ized infections (without systemic signs) may
Custom elements       < 0.5 Low risk for progression to severe sepsis and/or septic shock. also be associated with such low levels. If
the PCT measurement is done very early
Custom elements      
Systemic infection cannot be excluded. PCT levels should be after the systemic infection process has
0.5 - 2.0 started (usually < 6 hours), these values
measured again within 6 to 24 hours.
may still be low.
> 2.0 High risk for progression to severe sepsis and/or septic shock.
See next page for additional notes.

6 7
PCT values may be elevated in certain conditions independent of bacterial infection. These include, but are not limited to:
∙ Injuries including major trauma, burns and heat stroke
∙ Acute medical conditions such as biliary pancreatitis, chemical pneumonitis, viral hepatitis and/or decompensated severe cirrhosis
(Child-Pugh Class 3), prolonged or severe cardiogenic shock, prolonged severe organ perfusion anomalies, and post-cardiac arrest
∙ Active medullary C-cell carcinoma, small cell lung carcinoma, and bronchial carcinoid
∙ Unusual infectious diseases including invasive fungal infections and acute plasmodium falciparum malaria
∙ Following interventions such as surgery with extra-corporeal circulation, treatment with drugs stimulating release of pro-inflammatory cyto-
kines or resulting in anaphylaxis, peritoneal or hemodialysis
The PCT reference ranges are valuable guidelines for the clinician but they should always be interpreted in context of the patient’s clinical
condition. PCT serum concentrations are elevated in clinically relevant bacterial infections and continue to rise with the increasing sever-
ity of the disease. However, as an expression of individually different immune responses and different clinical situations, the same focus of
infection may be associated with varying individual elevations in PCT concentrations. Antibiotic treatment should be started/continued on
suspicion of infection, particularly in high-risk patients.

PCT results should be evaluated in context of all clinical and laboratory findings. If results do not agree with clinical finding, additional testing
should be performed.

References
1. Pharmacists’ role in antimicrobial stewardship and relationship with antibiotic consumption in hospitals: An observational multicentre study. Available
online 16 July 2019. C. Ourghanlian et al. / Journal of Global Antimicrobial Resistance 20 (2020) 131–134
2. Teehan A et al. Hospital Pharmacy. June 8, 2020. Evaluation of a Pharmacist-Driven Procalcitonin Protocol for Lower Respiratory Tract Infections
Using a Clinical Decision Support System
3. Willmon J et al. Hospital Pharmacy. May 31, 2020. Impact of Pharmacist-Directed Simplified Procalcitonin Algorithm on Antibiotic Therapy in Critically
Ill Patients With Sepsis
4. Schuetz et al., Role of Procalcitonin in Managing Adult Patients With Respiratory Tract Infections, CHEST 2012; 141(4):1063–1073
5. Schuetz P., Christ-Crain M. et al., Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections:
the ProHOSP randomized controlled trial. Jama 2009; 302(10): 1059-1066.
6. Bouadma L., Luyt C. E. et al., Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre
randomised controlled trial. Lancet 2010; 375(9713): 463-474.
7. Harbarth et al., Am J Respir Crit Care Med 2001; 164: 396-402
8. Meisner M, Procalcitonin – Biochemistry and Clinical Diagnosis, ISBN 978-3-8374-1241-3, UNI-MED, Bremen 2010.
9. Müller B et al., Crit Care Med 2000, 28 (4): 977-983.
10. Schuetz et al., Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis
(MOSES) Study. Crit Care Med 2017; 45(5):781-789.
11. Morgenthaler NG et al: Detection of procalcitonin (PCT) in healthy controls and patients with local infection by a sensitive ILMA. Clin Lab
2002;48(5-6):263-270.

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