Procalcitonin – D Dimer for sepsis?

The following discussion is taken from a presentation given at JC by Dr Dave Hewson, ST5 Anaesthetics, in which he explores the utility of PROCALCITONIN:

Does our antibiotic use matter?

  • The evidence would seem to show that it does “…Antibiotic resistance becomes more prevalent by using prolonged courses of broad-spectrum antimicrobial agents for treatment of severe sepsis patients (i.e. on ICU)…”[1]
  • Antibiotic consumption and acquired resistance is associated with increased mortality, morbidity, length of hospitalization, and health care costs[2]

How to limit antibiotic use?

  • Based on the Surviving sepsis guidelines: A 7 to 10 day course is a grade-2C recommendation
  • With the caveat that the “decisions to continue, narrow, or stop antimicrobial therapy must be made on the basis of clinician judgment and clinical information”[3].

Are Biomarkers the answer?

After all they should be…

  • Easily and cheaply identifiable
  • Highly sensitive and specific to aid diagnosis
  • Indicate severity
  • Indicate prognosis for outcome/trajectory

There are multiple candidates, CRP, Pentraxin, TNF-ɑ…the list goes on….and there is

PROCALCITONIN is :

  • A peptide precursor of calcitonin
  • 116 amino acids
  • Produced by parafollicular cells of thyroid and neuroendocrine cells of lung and gut
  • Normal levels < 0.1 ng/mL
  • Increased 2-3 hours after bacterial endotoxin release
  • Falls with successful treatment
  • Fails to rise to same extent with viral infection

And would seem to be an ideal agent (minor downside is elevation in cases of pancreatitis inhalational injury and connective tissue disorders.

So how could we use it in ICU? Can PCT be used for surveillance on ICU?

 PASS TRIAL[4]

  • A Danish multi-centre RCT of 1200 patients “to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of PCT, could reduce the time to appropriate therapy, thus improving survival.”
  • Patients randomised to standard care or drug-escalation algorithm with daily PCT and antibiotics commenced if PCT >1ng/mL.
  • Outcomes: Death (0.6 CI -4.7 to +5.9), LoS (1 day longer p = 0.004), Ventilator rate (increased), GFR < 60 mL/min/1.73m (increased)
  • PCT surveillance and antibiotic escalation did not improve survival and led to organ-related harm and prolonged ICU length of stay

 

Can PCT guide whether to commence antibiotics?

A single centre RCT[5]

  • Randomising 509 patients “to test the usefulness of PCT serum level for the reduction of antibiotic consumption in intensive care unit patients.”
  • Patients randomised to standard care or a PCT group where antibiotics were only initiated if a single measured PTC was above >1ng/mL.
  • 8% of the cases in which no infection was confirmed had a PCT >1ng/mL and 14.9% of the cases with confirmed infection had PCT <0.25 ng/mL.
  • The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low.

 

Can PCT guide when to stop antibiotics?

Multiple Studies…

  • Annane D, et al: Procalcitonin levels to guide antibiotic therapy in adults with non-microbiologically proven apparent severe sepsis: a randomised controlled trial. BMJ Open 2013, 3:e002186.
  •  Bouadma L, et al: Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 2010, 375:463-474.
  •  Hochreiter M, et al: Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Crit Care 2009, 13:R83.
  •  Nobre V et al: Use of procalcitonin to shorten antibiotic treatment duration in septic patients – A randomized trial. Am J Respir Crit Care Med 2008, 177:498-505.
  •  Schroeder S, et al: Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg 2009, 394:221-226.
  • Svoboda P, et al: Can procalcitonin help us in timing of re-intervention in septic patients after multiple trauma or major surgery? Hepatogastroenterology 2007, 54:359-363.

And an RCT

 Prkno A, et al. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis. Critical Care 2013, 17:R291

Which showed …

“median length of antibiotic treatment of 6 days in the PCT-guided group compared to 8 days in the control group, resulting in a median reduction of approximately 2 days.”

 

Does it’s use improve outcome?

Not really …

 

TAKE HOME MESSAGE

  • PCT-guided treatment may reduce the duration of antibiotic therapy in ICU patients with severe sepsis without affecting their outcome.
  • PCT-guided algorithms for treatment of sepsis patients differ substantially among published studies.
  • PCT cannot be used to diagnoses sepsis, assist the decision to commence antibiotics, used as a surveillance tool, or dramatically improve patient mortality.
  • There is no evidence that restricting antibiotic usage by using PCT in the ICU limits the spread of antibiotic resistance

 

[1] Goldmann DA, et al: Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals – A challenge to hospital leadership. JAMA 1996, 275:234-240.

[2] Goossens H: Antibiotic consumption and link to resistance. Clin Microbiol Infect 2009, 15:12-15

[3] Dellinger R et al: Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013, 41:580-637

[4] Jensen JU, et al. The PASS trial. Crit Care Med 2011, 39: 2048-2058.

[5] Layios, N, et al. Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients. Critical care medicine 2012; 40 (8): 2304-2309

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