Early Co-Administration of Crystalloid Fluid and Norepinephrine for Preventing Acute Kidney Injury in Septic Shock

Official title

Early Co-Administration of 30 mL/kg Crystalloid Fluid and Norepinephrine for Preventing Acute Kidney Injury in Septic Shock: A Pretest-Posttest Clinical Study

Overview

Septic shock is a life-threatening condition that can cause severe circulatory failure and damage to vital organs, including the kidneys. One of the most serious complications of septic shock is acute kidney injury (AKI), which is associated with increased morbidity and mortality. This study aims to evaluate the effect of early co-administration of crystalloid fluid resuscitation (30 mL/kg body weight) and norepinephrine on preventing acute kidney injury and improving hemodynamic stability in adult patients with septic shock. Patients will receive standard initial fluid resuscitation combined with early norepinephrine infusion according to a predefined clinical protocol. Changes in blood pressure, urine output, and other hemodynamic parameters will be observed before and after the intervention. The findings of this study are expected to provide evidence to support early hemodynamic optimization strategies for reducing the risk of acute kidney injury in septic shock patients.

Detailed description

This study is a pretest-posttest interventional clinical study designed to evaluate the effectiveness of early co-administration of crystalloid fluid resuscitation and norepinephrine in patients with septic shock. Septic shock is characterized by persistent hypotension requiring vasopressor therapy despite adequate fluid resuscitation and is associated with a high risk of acute kidney injury.

Eligible participants are adult patients diagnosed with septic shock who meet the study inclusion criteria. All participants will receive crystalloid fluid resuscitation at a dose of 30 mL/kg body weight, followed by early initiation of norepinephrine infusion at an initial dose of approximately 0.05 µg/kg/min, titrated according to hemodynamic response and clinical judgment.

Hemodynamic parameters, including mean arterial pressure, heart rate, oxygen saturation, urine output, and central venous pressure (when available), will be measured before and after the intervention. Renal function indicators will be monitored to assess the occurrence of early acute kidney injury.

The primary objective of this study is to evaluate the effect of early combined fluid resuscitation and norepinephrine administration on the prevention of acute kidney injury. Secondary objectives include assessment of changes in hemodynamic stability following the intervention. The results of this study are expected to contribute to evidence-based management strategies for septic shock in resource-limited clinical settings.

Interventions

• Drug Norepinephrine
  Norepinephrine is administered as an intravenous infusion initiated early in patients with septic shock at an initial dose of approximately 0.05 µg/kg/min. The dose is titrated based on hemodynamic response to achieve and maintain adequate mean arterial pressure in accordance with standard clinical practice.
• Other Crystalloid Fluid Resuscitation
  Participants receive intravenous crystalloid fluid resuscitation at a total dose of 30 mL per kilogram of body weight as part of early management of septic shock. Fluid administration is provided according to institutional protocols and patient clinical condition.

Primary outcome measures

• Occurrence of Acute Kidney Injury [Time frame: Within 48 hours after intervention]

Secondary outcome measures (1)

• Change in Mean Arterial Pressure [Time frame: Within 30 minutes after intervention]

Eligibility criteria

Inclusion criteria

• Adult patients aged 18 years or older.
• Diagnosed with septic shock based on clinical criteria.
• Require fluid resuscitation and vasopressor support.
• Admitted to the intensive care unit or emergency department.
• Have complete baseline clinical and hemodynamic data.

Exclusion criteria

• Patients with end-stage renal disease or receiving chronic dialysis.
• Known pregnancy.
• History of severe chronic kidney disease.
• Patients with limitations of care or do-not-resuscitate orders.
• Incomplete clinical data for outcome assessment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mehta Y, Paul R, Rabbani R, Acharya SP, Withanaarachchi UK. Sepsis Management in Southeast Asia: A Review and Clinical Experience. J Clin Med. 2022 Jun 23;11(13):3635. doi: 10.3390/jcm11133635. PMID 35806919
• Monnet X, Lai C, Ospina-Tascon G, De Backer D. Evidence for a personalized early start of norepinephrine in septic shock. Crit Care. 2023 Aug 22;27(1):322. doi: 10.1186/s13054-023-04593-5. PMID 37608327
• Ospina-Tascon GA, Hernandez G, Alvarez I, Calderon-Tapia LE, Manzano-Nunez R, Sanchez-Ortiz AI, Quinones E, Ruiz-Yucuma JE, Aldana JL, Teboul JL, Cavalcanti AB, De Backer D, Bakker J. Effects of very early start of norepinephrine in patients with septic shock: a propensity score-based analysis. Crit Care. 2020 Feb 14;24(1):52. doi: 10.1186/s13054-020-2756-3. PMID 32059682
• Permpikul C, Tongyoo S, Viarasilpa T, Trainarongsakul T, Chakorn T, Udompanturak S. Early Use of Norepinephrine in Septic Shock Resuscitation (CENSER). A Randomized Trial. Am J Respir Crit Care Med. 2019 May 1;199(9):1097-1105. doi: 10.1164/rccm.201806-1034OC. PMID 30704260

Identifiers

NCT: NCT07418541 · 344/KEPK/USU/2025 · No.344/KEPK/USU/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗