What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Adult patients (mean age ~70 years) with sepsis complicated by heart failure (SCHF) diagnosed by Surviving Sepsis Campaign Guidelines (n=1182). Intervention: Recombinant human brain natriuretic peptide (rhBNP) plus conventional Western therapy (CWT) vs. Conventional Western therapy (CWT). Primary outcome: 28-day mortality (RR 0.73, 95% CI 0.58–0.92, p=0.006).

March 9, 2026Open Access

Clinical efficacy and safety of recombinant human brain natriuretic peptide in the treatment of sepsis complicated by heart failure: a systematic review and meta-analysis

Key Result

Adjunctive recombinant human brain natriuretic peptide reduced 28-day mortality by 27% compared to conventional therapy in adults with sepsis complicated by heart failure.

Key Points

This study aims to assess the effectiveness and safety of recombinant human brain natriuretic peptide in sepsis complicated by heart failure.
Conducted a systematic review and meta-analysis of RCTs
Searched 8 databases for relevant trials
Included ten Chinese RCTs with 1,182 patients
Measured primary outcomes like 28-day mortality and left ventricular ejection fraction
Utilized Trial Sequential Analysis and the GRADE framework for quality assessment.
RhBNP reduced 28-day mortality (RR = 0.73)
Improved left ventricular ejection fraction by 4.91
Increased total clinical effective rate (RR = 1.26)
Enhanced cardiac output by 0.47
No significant difference in adverse events (RR = 0.77).

Study Design

Type

Meta-Analysis (n=1,182)

Multicenter

Structured PICO

Does recombinant human brain natriuretic peptide (rhBNP) combined with conventional Western therapy reduce 28-day mortality and improve LVEF in adult patients with sepsis complicated by heart failure?

Population

1,182 adult patients (≥18 years) diagnosed with sepsis complicated by heart failure (SCHF) pooled from 10 Chinese RCTs. Pooled mean age 69.9-70.1 years, 56-57% male.

Intervention

Recombinant human brain natriuretic peptide (rhBNP) combined with conventional Western therapy (CWT)

Comparator

Conventional Western therapy (CWT) alone (encompassing infection source control, antimicrobial treatment, fluid resuscitation, vasopressors, corticosteroids, inotropic support, blood product transfusion, sedative and analgesic management, glycemic control, mechanical ventilation, renal replacement therapy, and nutritional support)

Outcome

28-day mortality and left ventricular ejection fraction (LVEF)hard clinical

Adjunctive rhBNP may offer survival and cardiac function benefits in sepsis complicated by heart failure, though current evidence is of low certainty and requires confirmation by larger, multinational RCTs.

Main Result

Effect estimate: RR 0.73 (95% CI 0.58–0.92)

p-value: p=0.006

Limitations

All studies were single-center and conducted only in China, limiting generalizability.
Low to very low certainty of evidence due to risk of bias, imprecision, and inconsistency.
Inconsistent definition and reporting of secondary endpoints like adverse events.
Limited sample sizes and heterogeneity across studies.
Potential publication bias and language bias as most studies published in Chinese.

Abstract

Heart failure is among the most prevalent organ dysfunctions in sepsis and carries a high mortality rate. Currently, no specific drugs are available. Recombinant human brain natriuretic peptide (rhBNP) has demonstrated efficacy in treating isolated heart failure. This study aims to evaluate the feasibility of using rhBNP in the management of sepsis complicated by heart failure (SCHF). Eight databases were searched for qualified randomized controlled trials (RCTs) from inception to 19 July 2025, with no language restrictions. The primary outcomes included 28-day mortality and left ventricular ejection fraction (LVEF). The secondary outcomes included total clinical effective rate (TCER), APACHE II scores, cardiac output (CO), and adverse events (AEs). The meta-analyses were conducted by R (version 4.5.0). We utilized the Trial Sequential Analysis (TSA) software to perform TSA. Subsequently, the quality of the evidence was assessed using the GRADE framework (the Grading of Recommendation, Assessment, Development, and Evaluation system). This study was registered with PROSPERO (CRD 42023491344). Ten Chinese RCTs involving 1,182 patients were included. Pooled analysis showed that rhBNP combined with conventional Western therapy (CWT) was associated with reduced 28-day mortality (RR = 0.73, 95% CI: 0.58–0.92, p = 0.006) and APACHE II scores (MD = -4.18, 95% CI: -7.80 to -0.55, p = 0.024), and improved TCER (RR = 1.26, 95% CI: 1.12–1.41, p < 0.0001), LVEF (MD = 4.91, 95% CI: 2.56–7.26, p < 0.0001), and CO (MD = 0.47, 95% CI: 0.21–0.74, p = 0.0005). However, rhBNP did not significantly reduce AEs (RR = 0.77, 95% CI: 0.54–1.08, p = 0.13). The certainty of evidence was graded as low for CO and AEs, and very low for 28‑day mortality, LVEF, TCER, and APACHE II scores. Adjunctive rhBNP may offer cardiac and survival benefits in sepsis complicated by heart failure, but the evidence is of low certainty, non‑generalizable, and safety concerns persist. These hypothesis‑generating findings require confirmation by rigorously designed, multinational RCTs.

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