Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock

NCT07481097 | Not Yet Recruiting

• 1 other identifier: Mean Systemic Filling Pressure
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy of a hemodynamic resuscitation protocol guided by the Venous Return Gradient (Pmsf - CVP), measured via the non-invasive arm cuff technique, in reducing the incidence of Acute Kidney Injury (AKI) in patients with septic shock compared to standard care and to assess the precision and reproducibility of the non-invasive arm cuff Pmsf measurement in the septic shock population and to determine the correlation between the systemic Venous Return Gradient and the renal micro-circulatory Resistance Index (RRI).

Conditions

Acute Kidney Injury Due to Sepsis

Keywords

sepsis; acute kidney injury; resuscitation; mean systemic filling pressure; renal resistive index

Outcome Measures

Primary Outcomes (1)

• To compare the incidence of Acute Kidney Injury (AKI) in septic shock in both groups after 7 days of inclusion in the study. (AKI defined by KDIGO criteria: Creatinine increase ≥ 0.3 mg/dl within 48h OR ≥ 1.5x baseline within 7 days)

  To compare the incidence of Acute Kidney Injury (AKI) in septic shock in both groups after 7 days of inclusion in the study. (AKI defined by KDIGO criteria: Creatinine increase ≥ 0.3 mg/dl within 48h OR ≥ 1.5x baseline within 7 days)

  7 days

Secondary Outcomes (6)

• Renal Resistive Index (RRI): Measured and recorded at T0 (Baseline), T24, T48, and T72 hours

  72 hours

• Serum Lactate Clearance: Measured and recorded at T0, T6, T12, and T24 hours.

  24 hours

• Serum Creatinine level: Measured and recorded daily for 7 days.

  7 days

• Cumulative Fluid Balance: Calculated and recorded daily for 7 days.

  7 days

• Vasopressor Free Days: Recorded at Day 28.

  28 days

Study Arms (2)

Group A: Standard Care (Control Group)

NO INTERVENTION

Patients in this group will be managed according to the Surviving Sepsis Campaign (SSC) 2021 Guidelines

Group B: Pmsf-Guided Resuscitation (Intervention Group).

ACTIVE COMPARATOR

The Pmsf will be measured using the transient stop-flow arm cuff method. A pneumatic tourniquet cuff is placed on the upper arm. The cuff is inflated to a pressure 50 mmHg higher than the systolic arterial pressure for a duration of 60 seconds. The invasive arterial pressure and the ipsilateral peripheral venous pressure are recorded. Three consecutive measurements are performed with a 5-minute interval. Measurement Technique (RRI): Renal Doppler will be performed using a convex probe. The inter-lobar arteries will be visualized, and RRI will be calculated. Therapeutic Algorithm: State 1: Low Gradient and Low Pmsf AND RRI ≤ 0.70: Absolute Hypovolemia. Administer fluid bolus (250-500 ml crystalloid) to recruit stressed volume. State 2: Low Gradient and High Pmsf AND RRI ≥ 0.70: Vasoplegia with relative hypovolemia. Initiate or increase Norepinephrine. State 3: Adequate Gradient but High RRI ≥0.70: Renal Congestion. Discontinue fluids immediately Consider administration of diuretics

Other: Hemodynamic measurements during reduction in Norepinephrine and fluid boli.

Interventions

Hemodynamic measurements during reduction in Norepinephrine and fluid boli. OTHER

State 1: Low Gradient and Low Pmsf AND RRI ≤ 0.70: Absolute Hypovolemia. Administer fluid bolus (250-500 ml crystalloid) to recruit stressed volume. State 2: Low Gradient and High Pmsf AND RRI ≥ 0.70: Vasoplegia with relative hypovolemia. Initiate or increase Norepinephrine. State 3: Adequate Gradient but High RRI ≥0.70: Renal Congestion. Discontinue fluids immediately Consider administration of diuretics

Group B: Pmsf-Guided Resuscitation (Intervention Group).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (Age 18 years or older) admitted to the Intensive Care Unit.
• Primary diagnosis of Septic Shock defined according to the Third International Consensus Definitions for Sepsis (Sepsis-3): Sepsis with persisting hypotension requiring vasopressors to maintain MAP 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L despite adequate volume resuscitation.
• Patients must be mechanically ventilated and sedated to ensure baseline hemodynamic stability.
• Presence of an invasive arterial catheter and a central venous catheter.

You may not qualify if:

• Known pre-existing chronic kidney disease (CKD Stage 4 or 5) or patients on chronic renal replacement therapy.
• Contraindications to arm cuff inflation, including upper limb trauma, -lymphedema, arteriovenous fistula, or peripheral vascular disease.
• Severe valvular heart disease, specifically severe tricuspid regurgitation, which invalidates CVP interpretation.
• Intra-abdominal hypertension (Intra-abdominal pressure greater than 15 mmHg) which mechanically alters venous return independent of blood volume.
• Moribund patients with a predicted mortality within 24 hours.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University Hospitals

Asyut, Asyut Governorate, 71511, Egypt

Location

Related Publications (27)

• Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, Yealy DM, Huang DT, Angus DC; ProCESS and ProGReSS-AKI Investigators. The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. Am J Respir Crit Care Med. 2016 Feb 1;193(3):281-7. doi: 10.1164/rccm.201505-0995OC. PMID: 26398704; PMCID: PMC4803059.

  BACKGROUND

• Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17(5):R207.

  BACKGROUND

• Higuera-Juan F, Blanco-García R. Renal Resistive Index as a Target for Hemodynamic Management in Septic Shock. Med Intensiva. 2019;43(8):499-500.

  BACKGROUND

• Bossard G, Bourgoin P, Corbeau J, Huntzinger J, Beydon L. Early detection of postoperative acute kidney injury by Doppler renal resistive index in cardiac surgery with cardiopulmonary bypass. Br J Anaesth. 2011;107(6):891-8.

  BACKGROUND

• Liu J, Xie H, Ye Z, Li F, Wang L. Incidence and Risk Factors of Sepsis-Associated Acute Kidney Injury: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2020;7:599.

  BACKGROUND

• KDIGO Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.

  BACKGROUND

• Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Med. 2021;47(11):1181-1247.

  BACKGROUND

• Rozemeijer S, de Wit N, de Grooth HJ, et al. Renal perfusion pressure and renal resistive index in patients with septic shock. Ann Intensive Care. 2019;9:126.

  BACKGROUND

• Darmon M, Schortgen F, Vargas F, et al. Diagnostic accuracy of Doppler renal resistive index for reversibility of acute kidney injury in critically ill patients. Intensive Care Med. 2011;37:68-76.

  BACKGROUND

• Schnell D, Deruddre S, Harrois A, et al. Renal resistive index better predicts the occurrence of acute kidney injury than cystatin C. Shock. 2012;38(6):592-7.

  BACKGROUND

• Viazzi F, Leoncini G, Derchi LE, Pontremoli R. Ultrasound Doppler renal resistive index: a useful tool for the management of the hypertensive patient. J Hypertens. 2014;32(1):149.

  BACKGROUND

• Le Dorze M, Bouglé A, Deruddre S, Duranteau J. Renal Doppler ultrasound: a new tool to assess renal perfusion in critical illness. Shock. 2012;37(4):360-5.

  BACKGROUND

• Aya HD, Rhodes A, Fletcher N, Grounds RM, Cecconi M. Transient stop-flow arm arterial-venous equilibrium pressure measurement: determination of precision of the technique. J Clin Monit Comput. 2016;30:55-61.

  BACKGROUND

• Wijnberge M, Sindhunata DP, Pinsky MR, Vlaar AP, Ouweneel E, Jansen JR, et al. Estimating mean circulatory filling pressure in clinical practice: a systematic review comparing three bedside methods in the critically ill. Ann Intensive Care. 2018;8:73.

  BACKGROUND

• Adda I, Lai C, Teboul JL, Guérin L, Gavelli F, Monnet X. Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock. Crit Care. 2021;25:302.

  BACKGROUND

• Malbrain MLNG, Van Regenmortel N, Saugel B, et al. Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy. Ann Intensive Care. 2018;8:66.

  BACKGROUND

• Cecconi M, Aya HD, Geisen M, Ebm C, Fletcher N, Grounds RM, et al. Changes in the mean systemic filling pressure during a fluid challenge in postsurgical intensive care patients. Intensive Care Med. 2013;39:1299-305.

  BACKGROUND

• Guérin L, Teboul JL, Persichini R, Dres M, Richard C, Monnet X. Effects of passive leg raising and volume expansion on mean systemic pressure and venous return in shock in humans. Crit Care. 2015;19:411.

  BACKGROUND

• Maas JJ, Geerts BF, van den Berg PC, Pinsky MR, Jansen JR. Assessment of venous return curve and mean systemic filling pressure in postoperative cardiac surgery patients. Crit Care Med. 2009;37(3):912-8.

  BACKGROUND

• Magder S. Volume and its relationship to cardiac output and venous return. Crit Care. 2016;20:271.

  BACKGROUND

• Guyton AC, Polizo D, Armstrong GG. Mean circulatory filling pressure measured immediately after cessation of heart pumping. Am J Physiol. 1954;179:261-7.

  BACKGROUND

• Persichini R, Lai C, Teboul JL, Adda I, Guérin L, Monnet X. Venous return and mean systemic filling pressure: physiology and clinical applications. Crit Care. 2022;26(1):150.

  BACKGROUND

• Kopitkó C, Medve L, Gondos T. The value of renal resistive index in the assessment of acute kidney injury in septic shock: an observational cohort study. BMC Anesthesiol. 2019;19:210.

  BACKGROUND

• Prowle JR, Ishikawa K, May CN, Bellomo R. Renal blood flow, fractional excretion of sodium and acute kidney injury: time for a new paradigm? Curr Opin Crit Care. 2020;26(6):546-552.

  BACKGROUND

• Ostermann M, Hall A, Crichton S. Low mean perfusion pressure is a risk factor for progression of acute kidney injury in critically ill patients. BMC Nephrol. 2017;18:151.

  BACKGROUND

• Meyhoff TS, Moller MH, Hjortrup PB, et al. Lower vs Higher Fluid Volumes During Initial Management of Sepsis: A Systematic Review with Meta-Analysis and Trial Sequential Analysis. Chest. 2020;157(6):1478-1496.

  BACKGROUND

• Peerapornratana S, Manrique-Caballero CL, Gómez H, Kellum JA. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, and clinical outcomes. Kidney Int. 2019;96(5):1083-1099.

  BACKGROUND

MeSH Terms

Conditions

Sepsis; Acute Kidney Injury

Interventions

Norepinephrine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Mark Wageh Debais, assistant lecturer

CONTACT

+201032090320; markwageh@aun.edu.eg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Intervention Group: The treating physician will be informed of the Pmsf and RRI values by the operator to adjust therapy according to the protocol. Control Group: The treating physician will remain blinded to the Pmsf and RRI values; these values will be recorded by the operator for analysis but will not be revealed to the clinical team, who will manage the patient strictly by standard SSC guidelines. Outcome Assessors (Blinded): The investigators responsible for collecting clinical outcome data (e.g., diagnosing AKI, calculating fluid balance, recording mortality) will be blinded to the patient's group assignment. Data Analysts (Blinded): The statisticians performing the final analysis will receive a coded database (e.g., Group A vs. Group B) and will remain blinded to the actual group identities until the analysis is complete.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer

Model Details: a prospective, single-center, single-blind (blinded outcome assessor), parallel-group Randomized Controlled Trial.

Study Record Dates

• First Submitted: March 15, 2026
• First Posted: March 18, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)