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Determinants of natriuretic peptides in early septic shock

Background and objectives

Circulating natriuretic peptides (atrial natriuretic peptide, brain natriurelic peptide) are sensitive indicators of the severity of heart failure. Comparable high plasma levels of natriuretic peptides has been found in severe heart failure (NYHA III-IV) and patients with septic shock (Am Heart J 1993, 126:466–468). Impaired heart function, changes of cardiopulmonary hemodynamics and proinflammatory cytokines, ie interleukin-6 (IL-6) or tumor-necrosis-factor-α (TNF-α) might contribute to the modulation of natriuretic peptide release (Am Heart J 1997, 79:1128–1131). Therefore, we studied the interrelation between IL-6, soluble TNF-receptors (TNF-R-p55, TNF-R-p75), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as well as heart function, cardiopulmonary and systemic hemodynamics in patients at the first two days following the diagnosis of septic shock.


Patients without acute renal failure (ARF) fullfilling criteria of septic shock (APACHE 28.4 ± 16.9; ELEBUTE 19.2 ± 4.2; n = 17). Determination of IL-6, TNF-R-p55, TNF-R-p75, ANP and BNP in plasma as well as cardiac index (CI), mean arterial pressure (MAP), right atrial pressure (RA), heart rate (HR), systemic vascular resistance (SVR) and mean pulmonary arterial pressure (PAP). Mean ± SD; r2 = Pearsons correlation coefficient.


IL-6 was significantly correlated to ANP (P < 0.01). During the first 2 days following diagnosis, IL-6 and ANP concordingly decreased (4033 ± 5657 vs 1978 ± 4751 pg/ml and 28.3 ± 16.6 vs 23.3 ± 15.1 pg/ml, respectively). BNP remained unchanged (12.4 ± 15.7 vs 12.8 ± 17.2 pg/ml), on both days inversely correlated to CI (P < 0.05). Accordingly, no significant differences of CI (4.5 ± 0.9 vs. 4.5 ± 1.0 l/min/m2) or SVR (533.6 ± 136.9 vs 595.7 ± 210.2 dyn × s × cm-5) could be determined. The fall of ANP from day 1 to 2 was independent of changes in RA (11.2 ± 4.2 vs. 11.8 ± 3.5 mmHg), HR (136.8 ± 27.2 vs. 142.4 vs. 62.6 bpm) or PAP (27.0 ± 6.6 vs 28.3 ± 4.6 mmHg). There was no significant change from day 1 to 2 of TNF-R-p55 (7.6 ± 3.5 vs 8.3 ± 6.0 pg/ml) and TNF-R-75 (11.0 ± 6.2 vs 12.9 ± 8.6 pg/ml). On day 2, ANP and BNP significantly correlated to CI (r2 = -0.682 and r2 = -0.574, respectively; P < 0.05), while CI inversely depend on SVR (r2 = -0.801; P < 0.05). No significant negative correlation could be calculated between ANP, BNP and SVR or MAP.


Patients in early septic shock without ARF showed a directly correlated, concordant decrease of IL-6 and ANP independent of changes in RA, HR, PAP or CI. Vasodilative BNP release was inversely correlated to CI. Thus, interleukin-6 and left ventricular heart function might play a different role in the regulation of ANP- and BNP release in early septic shock.

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Witthaut, R., Busch, C., Fraunberger, P. et al. Determinants of natriuretic peptides in early septic shock. Crit Care 2 (Suppl 1), P062 (1998).

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