Maguy Bernard

Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial

BACKGROUNDnReduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.nnnMETHODSnIn this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.nnnFINDINGSnNine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001).nnnINTERPRETATIONnA procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.nnnFUNDINGnAssistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia

ObjectiveTo assess the predictive capacity for the diagnosis of ventilator-associated pneumonia (VAP) of serum procalcitonin levels before and on the day it is suspected.Design and settingSingle-center observational study in the intensive care unit of axa0teaching hospital.Patients and participantsConsecutive patients whose serum procalcitonin levels were available on the day that VAP was clinically suspected (day 1) and at some time within the preceding 5xa0days (“before”).Measurements and resultsSerum procalcitonin levels were determined on day 1 and “before”. Among the 73 suspected episodes VAP was confirmed by quantitative bronchoalveolar lavage cultures in 32 and refuted in 41. Respective median “before” procalcitonin levels were 1.89 ng/ml (interquartile range 0.18–6.01) and 2.14 (0.76–5.75) in patients with and without VAP, but their respective median day-1 procalcitonin levels did not differ: 1.07u202fng/ml (0.39–6.57) vs. 1.40 (0.67–3.39). On day 1 axa00.5u202fng/ml procalcitonin threshold had 72% sensitivity but only 24% specificity for diagnosing VAP. Between “before” and day 1, procalcitonin increased in 41% and 15% of patients with and without VAP, respectively. Thus axa0procalcitonin rise on day 1, compared to its “before” level, had 41% sensitivity and 85% specificity for diagnosing VAP, with respective positive and negative predictive values of 68% and 65%.ConclusionsCrude values and procalcitonin rise had poor diagnostic value for VAP in this particular setting and thus should not be used to initiate antibiotics when VAP is clinically suspected.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

Objective:Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. Design:Single-center prospective study. Setting:University hospital. Patients:Two hundred seventy-six patients scheduled for elective major aortic surgery. Interventions:Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL·min−1. Measurements and Main Results:Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng·mL−1, p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. Conclusions:Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

Usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock

BACKGROUNDnNo prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover.nnnMETHODSnThis was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO.nnnRESULTSnNeither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively.nnnCONCLUSIONnIn patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover.

Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection

Objective: To study the contribution of lactate and procalcitonin (PCT) serum measurements for the diagnosis and the risk-stratification of patients with suspected infection presenting to the ED. Methods: Single-center one year observational study on 462 consecutive patients. Multivariate analysis to assess variables associated with sepsis, severe sepsis, septic shock and severe outcome. Results: Multivariate analysis (Odds ratio [95% CI]), showed that PCT was the best independent variable to identify sepsis (3.98 [2.60–6.10]), while lactate was the best to diagnose severe sepsis (10.88 [6.51–18.19]). Patients with both lactate above 2 mmol·L−1 and PCT above 0.8u2009ng·mL−1 had an enhanced risk of severe outcome. Conclusions: the dosages of lactate and PCT are complementary for the diagnosis and risk-stratification of patients evaluated in the ED for suspected infection.

Procalcitonin measurement in routine emergency medicine practice: comparison between two immunoassays.

Abstract Background: Accurate identification of bacterial infections in patients presenting at the emergency department is crucial for early and rational antibiotic treatment. In this situation, using a cut-off of 0.25 μg/L for procalcitonin allows for carefully monitoring of febrile patients. Most previous studies have been performed with the reference B·R·A·H·M·S PCT KRYPTOR® assay. The goal of this study was to compare this test with the VIDAS B·R·A·H·M·S PCT® assay and to validate clinically relevant cut-off thresholds. Methods: This prospective study was conducted in adults presenting to the emergency departments of a tertiary hospital. We included 305 consecutive patients that had procalcitonin requested. Procalcitonin was measured first with the KRYPTOR, then with the VIDAS systems. Statistical analysis consisted in Passing and Bablok and Bland-Altman plots. Results: In the overall cohort, 176 patients had procalcitonin concentrations measured using both methods and were well correlated. The Bland-Altman plot exhibited a bias of 0.108 [95% confidence interval: –0.044 to 0.260]. The concordance at different procalcitonin cut-off thresholds, respectively of 0.1, 0.25, 0.5 and 2 μg/L, indicated that above 0.25 μg/L, the κ coefficient was >0.80. Conclusions: A highly significant correlation was observed between the two automated assays. Procalcitonin concentrations obtained from both methods led to the same clinical interpretation. Clin Chem Lab Med 2010;48:501–4.

Release of brain natriuretic-related peptides (BNP, NT-proBNP) and cardiac troponins (cTnT, cTnI) in on-pump and off-pump coronary artery bypass surgery.

BackgroundWe studied the kinetic release of cardiac troponins (cTnI and cTnT) and B-type natriuretic peptides (BNP and NT-proBNP) in patients undergoing off-pump or on-pump coronary artery bypass surgery.MethodsTwenty-five consecutive patients were prospectively enrolled. The patients were divided into three groups: beating heart (I), and cardiopulmonary bypass (CPB) with warm (II) or cold cardioplegia (III). Plasma samples were obtained before anesthesia induction until the sixth day after surgery.Results and ConclusionsThe data were analyzed first for off-pump versus the CPB procedures and second for warm versus cold cardioplegia. The plasma troponin releases appeared to be significantly higher in the CPB groups in comparison to the beating heart group (P < 0.001 and P < 0.002 for cTnI and cTnT peak values, respectively). The peak of the B-type natriuretic peptide release appeared to be more delayed in the groups undergoing CPB than in the beating heart group (day 6 versus days 2 and 4 for NT-proBNP and BNP, respectively). Taken together, our results indicated that the new generation of cTnT assays seemed to be more sensitive than the cTnI assays for the diagnosis of myocardium injury. A lower increase in the cTnT values in the warm cardioplegic group indicated less damage of the myocardium than with cold cardioplegia. Our data also confirm better preservation of the myocardium with off-pump cardiac surgery than with CPB.

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

IntroductionTo date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications.MethodsPCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction.ResultsIn the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest.ConclusionPCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

Abstract Background: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. Methods: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. Results: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 μg/L threshold. No significant bias was observed (–0.04 and –0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110–134 min, p<0.0001). Conclusions: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of COPD exacerbations: a multicenter prospective blinded study

Background Exacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes. Patients and methods This prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit. Results A total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77–1.48) versus 0.83 nmol/L (0.63–1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57–0.89), 0.83 nmol/L (0.62–1.12) and 0.95 nmol/L (0.75–1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10–2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%–58%) and a specificity of 79% (95% CI, 74–84). Conclusion MR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.