Sepsis-Associated Myocardial Dysfunction: B-Type Natriuretic Peptide

Sepsis-Associated Myocardial Dysfunction: B-Type Natriuretic PeptideBackground: The 32-amino-acid B-type natriuretic peptide (BNP) and the 76-amino-acid N-terminal-pro-BNP (NT-proBNP) are the most extensively studied members of the family of natriuretic peptides. The prohormone pro-BNP is synthesized in bursts and cleaved into the active BNP and the biologically inactive NT-proBNP, which are constitutively released from ventricular myocytes. In contrast to A-type natriuretic peptide (ANP), BNP and NT-proBNP are not stored in granules, but BNP gene expression can increase very rapidly. The main stimulus for BNP synthesis and release is myocyte stretch. BNP exhibits natriuretic and vasodilatory effects, and counteracts the effects of the renin-angiotensinogen-angiotensin system. In the emergency department, BNP has been proven to be a helpful tool in distinguishing dyspnea caused by CHF from noncardiac dyspnea. fully

The measurement of a single BNP level significantly improves the management of patients presenting with acute dyspnea, and thus reduces hospital stay and medical costs. In the setting of acute dyspnea, a BNP level of < 100 pg/mL makes the diagnosis of CHF unlikely, whereas BNP levels of > 400 pg/mL or > 500 pg/mL are associated with a high probability of CHF. The intermediate range (BNP, 100 to 400 or 500 pg/mL) is a gray zone, where several conditions including stable left ventricular dysfunction and noncardiac conditions have to be considered. Studies in Critically Ill Patients: Several studies have addressed the questions whether BNP could accurately predict left-sided filling pressures and thus replace invasive monitoring for guidance of fluid resuscitation and vasopressor therapy, and whether BNP is of prognostic value in patients with sepsis.

However, in contrast to the rather uniform data on the impact of raised cardiac troponin levels in patients with sepsis, studies on the value of BNP testing in critically ill patients revealed conflicting results (Table 3). The pilot study by Witthaut and coworkers showed an inverse correlation between BNP and cardiac index (r = -0.56), whereas BNP correlated neither with stroke volume nor LVSWI, nor pulmonary capillary wedge pressure (PCWP). Plasma BNP levels in patients with septic shock were higher than those in control subjects, but absolute values were very low (Table 3), which might have been due to the uncommon type of assay employed or the fact that blood samples had been stored for several years before undergoing analysis.

Table 3—Studies on the Impact of BNP Measurement in Critically Ill Patients

Study Study Population(Age,} y) Severity of Disease SerumCreatinine

Level|

Assessment of LV Performance BNP Levels Mortality Relationships Among BNP, LV Performance, and Outcome
Witthautet al G1, 17 pts with septic shock (61 ± 2.7 yr); G2, 19 subjects without sepsis or heart disease (61 ± 2.1 yr) G1: APACHE II score, 28.4 ± 1.2; all mechanically ventilated G1, 97 ± 27 Mmol/L PAC: G1: CI,4.5 ± 0.2 L/min/ m2; G2: CI,

3.4 ± 0.5 L/min/ m2

G1, 12.4 ± 3.6 pg/ mL; G2, 5.5 ± 0.7 pg/mL 28 d: G1, 5/28 pts(29%) BNP correlated with CI (r = -0.56); APACHE II score not correlated with BNP
Charpentier et al 9 pts with severe sepsis and 25 pts with septic shock(56 yr) SAPS II score:43 ± 2.5; 18/34 pts (53%) mechanically ventilated NA TTE or TEE: 15/34 of pts with LVFAC < 0.5(44%) Day 1: LVFAC < 0.5, 425 ± 184 pg/mL; LVFAC > 0.5, 95.6 ± 30 pg/mLDays 3 and 4: nonsurvivors,

905 ± 246 pg/mL; Survivors,

181 ± 46 pg/mL

28 d: 10/34 pts(29%) Higher BNP levels in pts with LVFAC < 0.5 than in those with LVFAC > 0.5; higher BNP levels in nonsurvivors
Cuthbersonet al G1, 35 pts with sepsis (age, 66 yr; range, 55-74 yr); G2, 43 pts without sepsis (age, 66 yr; range, 55-74 yr) APACHE II score, 24 (range, 19-31); SAPS II score, 45 (range, 33-58) 137 Mmol/L (range, 92-222 Mmol/L) Not assessed At ICU admission:G1, 498 pg/mL (range, 242-884 pg/mL); G2, 213 pg/mL (range, 71-564 pg/mL)

At 24 h: G1, 500 pg/mL (range, 239-1,017 pg/ mL); G2, 319 pg/ mL (range, 132808 pg/mL)

30 d: 27/78 pts(35%) Trend toward higher BNP levels in survivors(p = 0.28); higher ICU admission BNP levels in pts with sepsis than in pts without sepsis (p = 0.02); higher baseline BNP levels in pts with age > 65 yr (p = 0.04) and serum creatinine > 110 Mmol/L (p = 0.02).
Cuthbertsonet al Subgroup analysis:35 pts with sepsis

(age, 66 yr; range, 55-74 yr)

APACHE II score, 24 (range, 20-31); SAPS II score, 50 (range, 35-59) Su14 M N M L rvi

2 on (r iv 1о s о a o 298 l/L( survi l/L); ange, r1s,

m rang vor, 110 69M o

l/ e, m

) 0 9 o

/

Not assessed At ICU admission: survivors, 651 pg/ mL (range, 2421023 pg/mL); nonsurvivors, 377 pg/mL (range, 85-683 pg/mL)At 24 h: 500 pg/ mL (range, 2351,026 pg/mL); survivors, 662 pg/ mL (range, 3391,230 pg/mL); nonsurvivors, 377 pg/mL (range, 85-683 pg/mL) 30 d: 10/35 pts(29%) Trend toward higher BNP levels on ICU admission (p = 0.21) and at 24 h (p = 0.11) in survivors
Tung et al 49 pts with shock; G1, 7 pts with cardiogenic shock (CI, < 2.2 L/min/ m2; PCWP, > 18 mm Hg); G2, 42 pts with noncardiogenic shock APACHE II score, 21.8 ± 6.9; 36/49 pts (73%) mechanically ventilated Survivors, 159 Mmol/ L (range, 88-194 Mmol/L);

Nonsurvivors, 177 Mmol/L (range, 124-292 Mmol/L)

PAC: G1: CI,

1.6 ± 0.3 L/min/ m2; PCWP,

24 ± 4 mm Hg; G2: CI, 3.4 ± 1.3 L/min/m2; PCWP, 18 ± 7 mm Hg

1,133 ± 1,416 pg/ mL (median, 482 pg/mL); G1,

739 ± 471 pg/mL (median, 768 pg/ mL); G2,

1,199 ± 1,511 pg/ mL (median, 432 pg/mL)

In ICU: 19/49 pts

(38%)

No correlation

between BNP and CI (p = 0.59) and PCWP (p = 0.56), higher BNP levels in nonsurvivors than in survivors (p = 0.002), correlation between log BNP quartiles and ICU mortality

Forfia

etal

40 pts with CHF (n = 12), sepsis/ ARDS (n = 12), after abdominal/ vascular surgery (n = 13)/trauma (n = 3) with PAC indication (age, 62 yr; range, 52-73 y) Mechanical

ventilation, 26/40 pts (65%)

NA; two thirds of pts with renal insufficiency (acute, 25%; chronic, 75%) PAC: PCWP, 14 mm Hg (range, 10-22 mm Hg); CI, 3.1 L/min/m2 (range, 2.1-42 L/min/m2); TTE: LVEF, 50% (range, 20-60%) 420 pg/mL (range, 197-1,740 pg/mL) In-hospital: 14/40 pts

(35%)

Weak correlation between BNP and PCWP (r = 0.4); correlation between BNP and LVEF

(r = -0.49) and

estimated

creatinine

clearance

(r = -0.35);

estimated

creatinine

clearance

independent

predictor of BNP

levels

Jefic et al 41 pts with hypoxic respiratory failure (age, 66.5 ± 16 y); sepsis/septic shock in 20 pts APACHE II score, 18.5 ± 1; 39/41 pts (95%) ventilated NA; creatinine

clearance 60.5 ± 7 mL/min

PAC: 34 pts with LVSWI of < 35 g/m/m2; 18 pts with PCWP > 15 mm Hg LVSWI > 35 g/m/ m2, 639 ± 286 pg/mL; LVSWI < 35 g/m/m2,

916 ± 128 pg/mL

30 d: 17/40 pts (43%)§ Correlation BNP, and CI (r = -0.44), LVSWI (r = -0.62), creatinine clearance (r = -0.50), BNP not correlated with PCWP; BNP no different in survivors/nonsurvivors
This entry was posted in Cardiology and tagged cardiac troponins, myocardial dysfunction, natriuretic peptides, sepsis, septic shock.