Sepsis-induced Cardiomyopathy, the Recovery Phase of Septic Shock
Conditions
Brief summary
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.
Interventions
DRUGLyophilized Recombinant Human Brain Natriuretic Peptide
rh-BNP is reconstituted to a concentration of 10 μg/mL and administered as an initial intravenous bolus of 2 μg/kg over 15 minutes, followed by a continuous infusion at a rate of 0.01 μg/kg/min. Patients should receive at least the first 500μg dose infusion, with a recommended duration of 72 hours. The specific timing of discontinuation will be determined by the attending physician. Prior to rh-BNP administration, measure: PiCCO indices, hemodynamic parameters, venous return, tissue perfusion, echocardiographic parameters, ultrasound indices, 2-hour averaged urine output and fluid balance. Repeat all above-mentioned measurements at 30 minutes post-initiation.
Sponsors
Tibet Kangzhe Pharmaceutical Development Co., Ltd
Sichuan Provincial People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The pressure gradient of venous return | From baseline to 30 minutes after rh-BNP initiation. | Pmsf - CVP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Perfusion pressure | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Absolute and relative changes in perfusion pressure (MAP - CVP) |
| CVP | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Absolute and relative changes in CVP |
| GEDI and global and left-ventricular preload (LVEDV) | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Absolute and relative changes in GEDI and global and left-ventricular preload (LVEDV) |
| Lactate clearance | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Absolute and relative changes in lactate clearance |
| Duration of invasive mechanical ventilation | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Duration of invasive mechanical ventilation |
| ICU lengths of stay | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | ICU lengths of stay |
| Renal microvascular resistance | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | Absolute and relative changes in renal microvascular resistance |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety outcome | From baseline to 30 minutes, 24 hours, 48 hours and 72 hours after rh-BNP initiation. | The safety outcome was hemodynamic instability, defined as a sustained (≥15 minutes) decrease in systolic blood pressure ≥ 10 mmHg or MAP ≥ 5 mmHg compared with baseline, or a requirement for ≥ 0.1 µg/kg/min increase in norepinephrine to maintain MAP ≥ 65 mmHg. |
Contacts
Primary ContactLingai Pan, MD
Outcome results
None listed