Procalcitonin in intensive care units: the PRORATA trial
2010; Elsevier BV; Volume: 375; Issue: 9726 Linguagem: Inglês
10.1016/s0140-6736(10)60696-4
ISSN1474-547X
Autores Tópico(s)Emergency and Acute Care Studies
ResumoLila Bouadma and colleagues1Bouadma L Luyt CE Tubach F 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: 463-474Summary Full Text Full Text PDF PubMed Scopus (818) Google Scholar nicely showed that a strategy based on the daily measurement of procalcitonin concentration allowed for a reduction of antibiotic consumption in intensive care units (ICUs). Although this held true for most infections, the PRORATA trial mainly included patients with pneumonia and showed that measuring procalcitonin concentrations allowed the clinician to better adhere to the international guidelines on antibiotherapy duration.2Mandell LA Wunderink RG Anzueto A et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.Clin Infect Dis. 2007; 44: S27-S72Crossref PubMed Scopus (4651) Google Scholar, 3Joseph S Solomkin JE Mazuski JS et al.Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.Clin Infect Dis. 2010; 50: 133-164Crossref PubMed Scopus (1051) Google Scholar These results remind us that patients in ICUs are frequently overtreated, or at least treated for a too long. But had the patients in the control group been managed according to current recommendations,2Mandell LA Wunderink RG Anzueto A et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.Clin Infect Dis. 2007; 44: S27-S72Crossref PubMed Scopus (4651) Google Scholar, 3Joseph S Solomkin JE Mazuski JS et al.Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.Clin Infect Dis. 2010; 50: 133-164Crossref PubMed Scopus (1051) Google Scholar this trial would have had negative results. Before implementing costly biological analyses that could be unduly overinterpreted, we should increase educational efforts to better diffuse accepted guidelines.Another concern is that the PRORATA trial was designed to exclude a 10% difference in mortality between procalcitonin-guided and control groups. This 10% cutoff is questionable, since no study in an ICU setting has ever shown such a dramatic difference in mortality—we are happy when intensive insulin therapy is associated with a 3% reduction in mortality,4van den Berghe G Wouters P Weekers F et al.Intensive insulin therapy in the critically ill patients.N Engl J Med. 2001; 345: 1359-1367Crossref PubMed Scopus (8109) Google Scholar or activated protein C with a 6% reduction.5Bernard GR Vincent JL Laterre PF et al.for the Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study groupEfficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5035) Google Scholar Should we accept a 3·8% increase with a procalcitonin-guided strategy? Obviously, this 3·8% increase is not statistically significant, but the design and the power of the trial means that the trial cannot definitely exclude such a negative impact on mortality attributable to the procalcitonin strategy.We must not hide behind procalcitonin or other sophisticated biomarkers and must always ask ourselves about the appropriateness of pursuing antibiotics in any given patient.I declare that I have no conflicts of interest. Lila Bouadma and colleagues1Bouadma L Luyt CE Tubach F 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: 463-474Summary Full Text Full Text PDF PubMed Scopus (818) Google Scholar nicely showed that a strategy based on the daily measurement of procalcitonin concentration allowed for a reduction of antibiotic consumption in intensive care units (ICUs). Although this held true for most infections, the PRORATA trial mainly included patients with pneumonia and showed that measuring procalcitonin concentrations allowed the clinician to better adhere to the international guidelines on antibiotherapy duration.2Mandell LA Wunderink RG Anzueto A et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.Clin Infect Dis. 2007; 44: S27-S72Crossref PubMed Scopus (4651) Google Scholar, 3Joseph S Solomkin JE Mazuski JS et al.Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.Clin Infect Dis. 2010; 50: 133-164Crossref PubMed Scopus (1051) Google Scholar These results remind us that patients in ICUs are frequently overtreated, or at least treated for a too long. But had the patients in the control group been managed according to current recommendations,2Mandell LA Wunderink RG Anzueto A et al.Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.Clin Infect Dis. 2007; 44: S27-S72Crossref PubMed Scopus (4651) Google Scholar, 3Joseph S Solomkin JE Mazuski JS et al.Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.Clin Infect Dis. 2010; 50: 133-164Crossref PubMed Scopus (1051) Google Scholar this trial would have had negative results. Before implementing costly biological analyses that could be unduly overinterpreted, we should increase educational efforts to better diffuse accepted guidelines. Another concern is that the PRORATA trial was designed to exclude a 10% difference in mortality between procalcitonin-guided and control groups. This 10% cutoff is questionable, since no study in an ICU setting has ever shown such a dramatic difference in mortality—we are happy when intensive insulin therapy is associated with a 3% reduction in mortality,4van den Berghe G Wouters P Weekers F et al.Intensive insulin therapy in the critically ill patients.N Engl J Med. 2001; 345: 1359-1367Crossref PubMed Scopus (8109) Google Scholar or activated protein C with a 6% reduction.5Bernard GR Vincent JL Laterre PF et al.for the Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study groupEfficacy and safety of recombinant human activated protein C for severe sepsis.N Engl J Med. 2001; 344: 699-709Crossref PubMed Scopus (5035) Google Scholar Should we accept a 3·8% increase with a procalcitonin-guided strategy? Obviously, this 3·8% increase is not statistically significant, but the design and the power of the trial means that the trial cannot definitely exclude such a negative impact on mortality attributable to the procalcitonin strategy. We must not hide behind procalcitonin or other sophisticated biomarkers and must always ask ourselves about the appropriateness of pursuing antibiotics in any given patient. I declare that I have no conflicts of interest. Procalcitonin in intensive care units: the PRORATA trial – Authors' replyDjamel Mokart and Marc Leone point out potential difficulties for interpreting procalcitonin concentrations in immunocompromised patients. In our trial, these patients had significantly lower antibiotic exposure in the procalcitonin group than in the control group (3·6 days), without significant differences in mortality and relapse rates. However, we agree that more trials are needed to confirm that a procalcitonin-guided strategy can reduce antibiotic use without adversely affecting outcomes in that specific subset of patients. Full-Text PDF
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