Determination of serum albumin, analytical challenges: a French multicenter study.

Among the biological markers of morbidity and mortality, albumin holds a key place in the range of criteria used by the High Authority for Health (HAS) for the assessment of malnutrition and the coding of information system medicalization program (PMSI). If the principle of quantification methods have not changed in recent years, the dispersion of external evaluations of the quality (EEQ) data shows that the standardization using the certified reference material (CRM) 470 is not optimal. The aim of this multicenter study involving 7 sites, conducted by a working group of the French Society of Clinical Biology (SFBC), was to assess whether the albuminemia values depend on the analytical system used. The albumin from plasma (n=30) and serum (n=8) pools was quantified by 5 different methods [bromocresol green (VBC) and bromocresol purple (PBC) colorimetry, immunoturbidimetry (IT), immunonephelometry (IN) and capillary electrophoresis (CE)] using 12 analyzers. Bland and Altman's test evaluated the difference between the results obtained by the different methods. For example, a difference as high as 13 g/L was observed for the same sample between the methods (p <0.001) in the concentration range of 30 to 35 g/L. The VBC overestimates albumin across the range of values tested compared to PBC (p <0.05). PBC method gives similar results to IN for values lower than 40 g/L. For IT methods, one of the technical/analyzer tandem underestimates the albumin values inducing a difference of performance between the immunoprecipitation methods (IT vs IN, p <0.05). Although, the albumin results are related to the technical/analyzer tandem used. This variability is usually not taken into account by the clinician. Thus, clinicians and biologists have to be aware and have to check, depending on the method used, the albumin thresholds identified as risk factors for complications related to malnutrition and PMSI coding.

Physiological modeling for indirect evaluation of drug tissular pharmacokinetics under non-steady-state conditions: an example of antimicrobial prophylaxis during liver surgery.

Cefazolin, a time-dependent first-generation cephalosporin with non-linear binding to albumin, is widely recommended for antimicrobial prophylaxis during liver surgery to decrease the incidence of postoperative wound infections. The recommended protocol (2 g IV at anesthesia induction followed by 1 g 4 h later) is expected to maintain the free cefazolin concentration in exposed intratissular fluids above its minimal inhibitory concentration (MIC) for potentially encountered microorganisms, from skin incision to skin closure. Since this dosing protocol fails to take into account either of patients status (total body weight and renal function) or of surgical and anesthetic consequences (variations of cardiac output and regional blood flows, progressive decrease of plasma albumin concentration) on cefazolin tissular pharmacokinetics, a physiological modeling study was conducted to investigate protocol suitability for liver surgery in six populations: obese (body mass index >34), renal insufficiency (GFR = 10, 30 or 50 ml min(-1)) and high intraoperative blood loss (three times that usually observed during this surgery) and none of these features referred to as controls. A previously validated physiologically based pharmacokinetic (PB-PK) model for cefazolin in humans was used and then further adapted to simulate obese or renal insufficiency patients as well as the consequences of general anesthesia and liver surgery on cefazolin pharmacokinetics. Clinical data required for simulation (intraoperative kinetics of percent expired isoflurane and plasma albumin concentration, mean intraoperative blood loss) were obtained from 10 patients who underwent right hepatectomy in our institution. Using a fixed MIC of 2 microg ml(-1) against potentially encountered bacteria, it was concluded that the recommended dosing schedule was suitable in all tested populations, including obese patients, although prolongation of the interval between injections appeared advisable for renal insufficiency patients. Furthermore, when a MIC of 3 microg ml(-1) was considered, the recommended cefazolin-dosing regimen failed to maintain sufficient free cefazolin concentrations in the interstitial fluids during surgery in all tested populations except renal insufficiency patients (GFR < 50 ml min(-1)).

Emergency department triage of patients with acute chest pain: definition of cardiac troponin I decisional value to manage patients without electrocardiographic evidence of ischemia.

The aim of this study was to define the use of a new cardiac troponin I (cTnI) assay for emergency patients with chest pain and no specific electrocardiographic changes consistent with the presence of ischemia. Patients (n = 106) admitted in Emergency/Cardiology Departments for chest pain and suspicion of acute coronary syndrome (ACS) were randomized into two diagnosis groups (ACS or non-ACS) by two independent cardiologists. cTnI measurements were performed at admission, and 6 hours and 12 hours later with a new generation assay (Access AccuTnI, Beckman Coulter). Using an upper reference limit of 0.04 microg/l, 27 patients had a cTnI elevation not related to the final diagnosis of ischemia; the positive predictive value (PPV) was 67% with specificity 48%. The decisional value was re-defined and set at 0.16 microg/l, a concentration corresponding to the 99th percentile of the non-ACS patient group. Precision (coefficient of variation) was 8% at this level, PPV 97% and specificity 98%. This new decisional value is now used in our institution and could be included in standard care guidelines to improve the management of patients presenting chest pain in emergency departments.

Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure.

OBJECTIVES: The aim of this study was to determine the value of serial B-type natriuretic peptide (BNP) assay for predicting post-discharge outcome of patients admitted for decompensated congestive heart failure (CHF). BACKGROUND: Patients hospitalized for decompensated CHF are frequently re-admitted. Thus, identification of high-risk patients before their discharge is a major issue that remains challenging. B-type natriuretic peptide measurement could be useful. METHODS: Serial BNP measurements were performed from admission to discharge in two samples of consecutive patients. Survivors were monitored for six months; the main end point combined death or first re-admission for CHF. RESULTS: Among the 105 survivors of the derivation study, all serial BNP values, percentage change in BNP levels, and predischarge Doppler mitral pattern correlated with the outcome. In contrast, clinical variables and left ventricular ejection fraction were poorly predictive. The predischarge BNP assay had the best discriminative power (area under the receiver operating characteristic [ROC] curve = 0.80) and remained the lone significant variable in multivariate analysis (hazard ratio [HR] = 1.14 [95% confidence interval [CI], 1.02 to 1.28], p = 0.027). Among the 97 survivors of the validation study, the predischarge BNP assay was also the most predictive parameter (area under the ROC curve = 0.83). The risk of death or re-admission increased in stepwise fashion across increasing predischarge BNP ranges (p < 0.0001). After adjustment for baseline covariables, the HRs were 5.1 [95% CI 2.8 to 9.1] for BNP levels between 350 and 700 ng/l and 15.2 [95% CI 8.5 to 27] for BNP levels >700 ng/l, compared with BNP <350 ng/l. CONCLUSIONS: High predischarge BNP assay is a strong, independent marker of death or re-admission after decompensated CHF, more relevant than common clinical or echocardiographic parameters and more relevant than changes in BNP levels during acute cares.

Comparative value of Doppler echocardiography and B-type natriuretic peptide assay in the etiologic diagnosis of acute dyspnea.

OBJECTIVES: We compared the accuracy of B-type natriuretic peptide (BNP) assay with Doppler echocardiography for the diagnosis of decompensated congestive left-heart failure (CHF) in patients with acute dyspnea. BACKGROUND: Both BNP and Doppler echocardiography have been described as relevant diagnostic tests for heart failure. METHODS: One hundred sixty-three consecutive patients with severe dyspnea underwent BNP assay and Doppler echocardiogram on admission. The accuracy of the two methods for etiologic diagnosis was compared on the basis of the final diagnoses established by physicians who were blinded to the BNP and Doppler findings. RESULTS: The final etiologic diagnosis was CHF in 115 patients. Twenty-four patients (15%) were misdiagnosed at admission. The BNP concentration was 1,022 +/- 742 pg/ml in the CHF subgroup and 187 +/- 158 pg/ml in the other patients (p < 0.01). A BNP cutoff of 300 pg/ml correctly classified 88% of the patients (odds ratio [OR] 85 [19 to 376], p < 0.0001), but a high negative predictive value (90%) was only obtained when the cutoff was lowered to 80 pg/ml. The etiologic value of BNP was low in patients with values between 80 and 300 pg/ml (OR 1.85 [0.4 to 7.8], p = 0.4) and also in patients who were studied very soon after onset of acute dyspnea. Among the 138 patients with assessable Doppler findings, a "restrictive" mitral inflow pattern had a diagnostic accuracy for CHF of 91% (OR 482 [77 to 3,011], p < 0.0001), regardless of the BNP level. CONCLUSIONS: Bedside BNP measurement and Doppler echocardiography are both useful for establishing the cause of acute dyspnea. However, Doppler analysis of the mitral inflow pattern was more accurate, particularly in patients with intermediate BNP levels or "flash" pulmonary edema.