Effect of Fluid Deresuscitation With Central Venous Pressure Target 0-4 mmHg in Septic Shock Patients

Effectiveness of Fluid Deresuscitation With Central Venous Pressure Target 0-4 mmHg on Capillary Perfusion Density, Acute Kidney Injury Stage, Cardiac Index, and the Intensive Care Unit Length of Stay in Septic Shock Patients After Resuscitation

A scientific research to prove the safety and effectiveness of TVS 0 - 4 mmHg as a target of resuscitation using furosemide, to improve Perfused Vessel Density (PVD) > 25 mm / mm2, AKI stage (based on KDIGO criteria), CI > 2.5 cc / min / m2 , prevent the incidence of intubation, reduce the duration of ventilator use <120 hours and reduce the length of ICU stay in patients with septic shock after resuscitation

Study Overview

• Status: Unknown
• Conditions: Septic Shock
• Intervention / Treatment: Procedure: Fluid resuscitation and furosemide administration (bolus and continuous) with central venous pressure target 8 - 10 mmHg; Procedure: Fluid deresuscitation and furosemide administration (bolus and continuous) with central venous pressure target 0 - 4 mmHg

Detailed Description

The study aims to evaluate the effectiveness of deresuscitation with target CVP 0 - 4 mmHg on septic shock patients in the ICU on capillary perfusion density, AKI stage (based on KDIGO criteria), the incidence of intubation, duration of use of mechanical ventilation, and length of stay in the ICU which can reduce the number of morbidity and mortality.

The study evaluates the difference in capillary perfusion density, AKI stage (based on KDIGO criteria), and the Cardiac index value between groups septic shock patients with CVP 0-4 mmHg on the 7th day after deresuscitation compared with the control group (CVP 8-10 mmHg on the first 7th day after being given deresuscitation).

The study evaluates the difference in the number of intubation incidents, duration of use ventilators, and care in the ICU between groups of patients with septic shock CVP 0 - 4 on day 28 after being given a degree of comparison with a control group (CVP 8-10 mmHg on day 28th after being deresuscitation).

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dita Aditianingsih, M.D, Ph.D; Phone Number: +628151819244; Email: ditaaditiaa@gmail.com
• Study Contact Backup: Name: Yohanes W.H. George, M.D.; Phone Number: +628121032069; Email: yohanesgeorge@yahoo.com

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Recruiting
      • Rumah Sakit Cipto Mangunkusumo
      • Contact: Dita Aditianingsih, M.D., Ph.D; Phone Number: +628151819244; Email: ditaaditiaa@gmail.com
      • Principal Investigator: Dita Aditianingsih, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Septic shock patients who meet the diagnosis criteria for quick SOFA and KDIGO 1 stage AKI (creatinine value 1.5 times OR creatinine value> 0.3 initial OR urine production <0.5 ml/kg/hour for 6-12 hours
• Patients, both men and women, in the age range of 18 - 60 years
• Patients who experience post clean operative sepsis
• Patients who agree to attend the study by signing informed consent

Exclusion Criteria:

• Patients with primary heart problems, right or heart failure suffer from congenital heart disease
• Have severe chronic obstructive pulmonary disease, patients with severe pleural effusion
• Patients who, based on ultrasound examination, found stones or tumors in the kidney during the study period
• CKD patients are based on history taking and physical examination
• DNR (do not resuscitate) patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Central Venous Pressure 8 - 10 mmHg; Furosemide deresuscitation or crystalloid loading until the CVP target 8-12 mmHg is reached	Procedure: Fluid resuscitation and furosemide administration (bolus and continuous) with central venous pressure target 8 - 10 mmHg; Crystalloid loading or furosemide administration with the CVP target 8-10 mmHg is reached in septic shock patients
EXPERIMENTAL: Central Venous Pressure 0 - 4 mmHg; Furosemide deresuscitation or crystalloid loading until the CVP target 0-4 mmHg is reached	Procedure: Fluid deresuscitation and furosemide administration (bolus and continuous) with central venous pressure target 0 - 4 mmHg; active fluid removal with furosemide bolus and continuous or crystalloid loading until the CVP target 0-4 mmHg is reached in septic shock patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Capillary Perfusion Density	Capillary Perfusion Density measurement using MicroScan every 24 hours during deresuscitation	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury Stage	AKI staging using KDIGO criteria every 24 hours during deresuscitation	7 days
Cardiac Index	cardiac index measurement using bio-impedance cardiometry every 24 hours during deresuscitation	7 days
Neutrophil Gelatinase-Associated lipocalin (NGAL)	NGAL measurement from urinary sample using NGAL ELISA method at 1st and 7th day during deresuscitation	1st and 7th day
Renal Resistive Index (RRI)	RRI measurement using renal doppler ultrasonography at 1st and 7th day during deresuscitation	1st and 7th day
Length of ICU stay	length of ICU stay in days during and after deresuscitation	28 days

Collaborators and Investigators

• Sponsor: Indonesia University

Publications and helpful links

General Publications

• Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
• Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, Jauregui L, Krell K, Pachl J, Takahashi T, Peckelsen C, Cordasco E, Chang CS, Oeyen S, Aikawa N, Maruyama T, Schein R, Kalil AC, Van Nuffelen M, Lynn M, Rossignol DP, Gogate J, Roberts MB, Wheeler JL, Vincent JL; ACCESS Study Group. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013 Mar 20;309(11):1154-62. doi: 10.1001/jama.2013.2194.
• Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL; International Surviving Sepsis Campaign Guidelines Committee; American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; Canadian Critical Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Japanese Association for Acute Medicine; Japanese Society of Intensive Care Medicine; Society of Critical Care Medicine; Society of Hospital Medicine; Surgical Infection Society; World Federation of Societies of Intensive and Critical Care Medicine. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. doi: 10.1097/01.CCM.0000298158.12101.41. Erratum In: Crit Care Med. 2008 Apr;36(4):1394-6.
• Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
• Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R. Fluid balance and acute kidney injury. Nat Rev Nephrol. 2010 Feb;6(2):107-15. doi: 10.1038/nrneph.2009.213. Epub 2009 Dec 22.
• Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care. 2008;12(3):R74. doi: 10.1186/cc6916. Epub 2008 Jun 4.
• Van Biesen W, Yegenaga I, Vanholder R, Verbeke F, Hoste E, Colardyn F, Lameire N. Relationship between fluid status and its management on acute renal failure (ARF) in intensive care unit (ICU) patients with sepsis: a prospective analysis. J Nephrol. 2005 Jan-Feb;18(1):54-60.
• Wang CH, Hsieh WH, Chou HC, Huang YS, Shen JH, Yeo YH, Chang HE, Chen SC, Lee CC. Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies*. Crit Care Med. 2014 Apr;42(4):954-61. doi: 10.1097/CCM.0000000000000050.
• Cordemans C, De Laet I, Van Regenmortel N, Schoonheydt K, Dits H, Huber W, Malbrain ML. Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance. Ann Intensive Care. 2012 Jul 5;2(Suppl 1 Diagnosis and management of intra-abdominal hyperten):S1. doi: 10.1186/2110-5820-2-S1-S1. eCollection 2012.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 14, 2019
• Primary Completion (ACTUAL): September 30, 2020
• Study Completion (ANTICIPATED): November 30, 2020

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (ACTUAL): November 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Septic Shock; Furosemide; Deresuscitation; Central Venous Pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: IndonesiaUAnes040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No