03 Oct 08

Impaired plasma B-type natriuretic peptide clearance in human septic shock

Posted in BNP, Sepsis at 19:10 by Laci

By R Pirracchio, N Deye, A Lukaszewicz, A Mebazaa, B Cholley, J Mateo et al

Crit Care Med 2008; 36:2542-2546

High B-type natriuretic peptide (BNP) levels are reported in the context of septic shock. We hypothesized that high BNP levels might be related to an alteration in BNP clearance pathway, namely neutral endopeptidase (NEP) 24.11. NEP 24.11 activity was measured in septic shock and in cardiogenic shock patients. We further evaluated whether baseline plasma BNP can predict fluid responsiveness and whether BNP can still be released in plasma despite high initial BNP levels, in response to overloading.

Material and Methods
Prospective observational study. Patients in severe sepsis (S) or in septic shock (SS) needing a fluid challenge were included. Stroke volume (SV) and BNP were measured before (SV1, BNP1) and 45 mins after (SV2, BNP2) a standardized fluid challenge. DeltaBNP was defined as the difference between BNP2 and BNP1. NEP 24.11 activity was determined by fluorometry in 12 SS and 4 S patients before fluid challenge and in 5 cardiogenic shock patients.

Results
Twenty-three patients (61 +/- 18 years old, Simplified Acute Physiology Score II: 54 +/- 21; 19 SS, 4 S; BNP1: 1371 +/- 1434 pg/mL) were studied. BNP1 concentrations were significantly higher in SS than in S (1643 +/- 1437 vs. 80 +/- 35 pg/mL; p = 0.002). There was no correlation between baseline BNP and fluid responsiveness. Nine of the 11 patients with BNP1 >1000 pg/mL were fluid responders. DeltaBNP was greater in fluid nonresponders than in fluid responders (22 +/- 27% vs. 6 +/- 11%, p = 0.028). Plasma BNP was higher in SS than in cardiogenic shock patients (1367 +/- 1438 vs. 750 +/- 346 respectively; p = 0.027). NEP 24.11 activity was lower in SS than in S patients (0.10 +/- 0.06 nmole/mL/min vs. 0.50 +/- 0.22 nmole/mL/min, p <0.0001) cardiogenic shock patients (0.10 +/- 0.06 nmole/mL/min vs. 0.58 +/- 0.19 nmole/mL/min; p = 0.002).

Conclusion
High levels of BNP might be related to an alteration in BNP clearance. During sepsis, high BNP levels are not predictive of fluid nonresponsiveness. Nevertheless, in fluid nonresponders, acute ventricular stretching can result in further BNP release.

07 Sep 08

Prognostic value of plasma N-terminal probrain natriuretic peptide levels in the acute respiratory distress syndrome

Posted in ALI/ARDS, BNP at 19:28 by Laci

By EK Bajwa, JL Januzzi, MN Gong, BT Thompson, DC Christiani

Crit Care Med 2008;36:2322-2327

Patients with acute respiratory distress syndrome suffer from profound cardiac and pulmonary derangement, including right ventricular strain and noncardiogenic pulmonary edema, which may potentially alter concentrations of cardiac natriuretic peptides. We sought to determine whether N-terminal probrain natriuretic peptide (NT-proBNP) levels are elevated in acute respiratory distress syndrome and whether they can serve as a marker of prognosis in this setting.

Design
Prospective study.

Setting
Tertiary-care academic medical center.

Patients
One hundred seventy-seven acute respiratory distress syndrome subjects enrolled in a prospective intensive care unit cohort.

Interventions
None

Measurements and main results
NT-proBNP was measured from blood taken within 48 hrs of acute respiratory distress syndrome onset. Patients were followed for the primary outcome of 60-day mortality and secondary outcomes of organ dysfunction and ventilator-free days. Seventy patients died (40%). Median NT-proBNP level was 3181 ng/L (interquartile range 723-9246 ng/L). NT-proBNP levels were significantly higher among nonsurvivors (p < .0001). Receiver operating curve analysis revealed an optimal NT-proBNP cut-point of 6813 ng/L for predicting death. Patients with levels above the cut-point had significantly higher odds of mortality on multivariable analysis (odds ratio 2.36, 95% confidence interval 1.11-4.99, p = .02) than those with levels below the cut-point. Kaplan-Meier survival analysis showed that this difference emerged early and was sustained (p < .0001). Patients with elevated NT-proBNP also had higher organ dysfunction scores (p < .0001) and fewer ventilator free days (p = .03) than those with lower NT-proBNP levels.

Conclusions
NT-proBNP levels are elevated among acute respiratory distress syndrome patients and parallel the severity of the syndrome and likelihood for morbidity and mortality. This demonstrates the potential utility of this biomarker for prognosis in this disease.

Prognostic value of brain natriuretic peptide in acute pulmonary embolism

Posted in BNP, Venous thromboembolism at 19:27 by Laci

By G Coutancel, O Le Page, T Lo and M Hamon

Critical Care 2008;12:R109

The relationship between brain natriuretic peptide (BNP) increase in acute pulmonary embolism (PE) and the increase in mortality and morbidity has frequently been suggested in small studies but its global prognostic performance remains largely undefined. We performed a systematic review and meta-analysis of data to examine the prognostic value of elevated BNP for short term all-cause mortality and serious adverse events.

Methods
The authors reviewed PubMed, BioMedCentral, and the Cochrane database and conducted a manual review of article bibliographies. Using a prespecified search strategy, we included a study if it used BNP or N-Terminal Pro-Brain Natriuretic Peptide (NT-pro BNP) biomarkers as a diagnostic test in patients with documented pulmonary embolism and if it reported death, the primary endpoint of the meta-analysis, in relation to BNP testing. Studies were excluded if they were performed in patients without certitude of PE or in a subset of patients with cardiogenic shock. Twelve relevant studies involving a total of 868 patients with acute PE at baseline were included in the meta-analysis using a random-effects model.

Results
Elevated BNP levels were significantly associated with short-term all-cause mortality (odds ratio [OR], 6.57; 95% confidence interval (CI), 3.11 to 13.91), with death resulting from pulmonary embolism (OR, 6.10; 95% CI, 2.58 to 14.25), and with serious adverse events (OR, 7.47; 95% CI, 4.20 to 13.15). The corresponding positive and negative predictive values for death were 14% (95%, 11 to 18) and 99% (95% CI, 97 to 100), respectively.

Conclusions
This meta-analysis indicates that while elevated BNP levels can help to identify patients with acute pulmonary embolism at high risk of death and adverse outcome events, the high negative predictive value of normal BNP levels is certainly more useful for clinicians to select patients with a likely uneventful follow-up.

14 Apr 08

The use of N-Terminal pro-B Type Natriuretic Peptide in a pre-operative setting to predict left ventricular systolic dysfunction on echocardiogram

Posted in Anesthesia, BNP, Echocardiography, Heart failure/Cardiogenic shock at 13:28 by Laci

By P B Messer, R Singh, F T McAuley, G Handley, B Peaston and C P Snowden

Anaesthesia 2008;63:482-487

Heart failure is a major risk factor for adverse postoperative events following non-cardiac surgery. The use of transthoracic echocardiogram as a pre-operative investigation to assess cardiac dysfunction has limitations in this setting. The N-Terminal fragment of B-Type natriuretic peptide (NT proBNP) has been used in screening for heart failure. We have investigated the use of NT proBNP as a screening tool for left ventricular systolic dysfunction to reduce the requirement for pre-operative echocardiograms. Ninety-eight pre-operative non-cardiac surgical patients scheduled to undergo echocardiography were assessed clinically and with an NT proBNP measurement. Echocardiogram was used to define two groups of patients depending on the presence or absence of abnormal left ventricular function and the NT proBNP level was compared between the groups using non-parametric and receiver-operator-characteristic (ROC) curve analysis. In terms of pre-operative screening, a NT proBNP of <38.2 pmol.l−1 had a 100% negative predictive value in predicting patients with normal left ventricular systolic function and would have prevented the requirement for echocardiogram in 43% of pre-operative patients. NT proBNP was superior to electrocardiological and clinical criteria for detection of a normal echocardiogram. This may have significant impact in the pre-operative assessment of patients undergoing non-cardiac surgery.

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