Recombinant Human Brain Natriuretic Peptide for the Recovery Stage of Septic Shock

Recombinant Human Brain Natriuretic Peptide for the Recovery Stage of Septic Shock: An Interventional Pilot Study

As infection control improves and circulation stabilizes, treatment de-escalation of septic shock begins, accompanied by fluid redistribution from interstitial spaces to the vasculature, increasing cardiac volume load. Synthetic recombinant human BNP (rh-BNP) plays a role in inducing vasodilation, particularly in the venous system, alleviating cardiac congestion, and enhancing natriuresis and diuresis. Thus the investigators designed a single-center, prospective physiological study to evaluate the efficacy of standard rh-BNP infusion in reducing venous return and enhancing fluid removal, with a secondary objective of assessing the maintenance of perfusion pressure and tissue perfusion.

Inclusion criteria:

1. Age >18 years.

2. Septic shock in recovery phase with decreasing vasopressor requirements, which is defined as:

   1. Fulfilling the Sepsis-3 definition of septic shock at initial stage.
   2. Hemodynamic stability achieved after adequate initial resuscitation and individualized hemodynamic optimization.
   3. Controlled infection source with 48-hour trend of improving temperature, white blood cell count, and procalcitonin.
   4. 48-hour trend of decreasing vasopressor requirements and transition to negative fluid balance.
   5. Adequate perfusion with warm extremities, and capillary refill time <3 seconds.

3. Ongoing pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and sinus rhythm.

4. Volume indicators above the lower limit of normal range, with global end-diastolic volume index (GEDI) >680 mL/m2 and central venous pressure (CVP) >8 mmHg.

5. Signs of cardiac dysfunction: BNP>200[10] or NT-proBNP >900 pg/ml[6] or reduced ejection fraction (LVEF) < 50%.

6. No bolus dose of diuretics had been administered in the previous 6 hours.

7. Informed consent obtained from patient/legal representative.

Exclusion Criteria:

1. Pregnancy or lactation.
2. Arrhythmia.
3. Advanced renal dysfunction (Acute Kidney Injury [AKI] stage 3 or Chronic Kidney Disease [CKD] stage 3b or higher) based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
4. Inadequate ultrasound window preventing acquisition of diagnostic-quality images.
5. Trauma or neurological diseases (including intracerebral hemorrhage and cerebral infarction).
6. Pre-existing severe heart failure (New York Heart Association [NYHA] class III-IV) or acute myocardial infarction within the past 30 days.
7. Concurrent enrollment in interventional trials that could confound study outcomes.

Criteria for withdrawing from the study:

1. Withdrawal of the informed consent.
2. Severe hemodynamic deterioration necessitating the discontinuation of all vasodilatory medications.
3. Treating clinician's decision.