The Randomized Controlled Trial of Inferior Vena Cava Ultrasound-guided Fluid Management in Septic Shock Resuscitation

The primary aim of this study is to evaluate the 30-day mortality outcome of the septic shock patients who are treated with ultrasound-assisted fluid management using change of the inferior vene cava (IVC) diameter during respiratory phases in the first 6 hours compared with those treated with "usual-care" strategy.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Procedure: IVC Ultrasound-guided; Drug: Antibiotics; Drug: Vasopressor

Detailed Description

Septic shock (SS) is globally prevalent in with high mortality rate.The current focuses on initial treatment of this condition emphasize on the early recognition, prompt administration of antibiotic, and restoration of hemodynamic with aggressive fluid resuscitation and vasopressor. Regarding the initial fluid therapy, administration of empirical crystalloid at the dose of 30 ml/kg is recommended in the guideline. The ultrasound-assisted management of shock patients has been introduced in the past decade and now is widely used. By using the measurement of inferior vena cava (IVC) diameter change during respiratory phases, physicians can predict the fluid responsiveness in the shock patients and tailor the fluid therapy during the resuscitation.Unfortunately, clinical outcome related to the use of this concept in SS resuscitation has not been well studied. Inadequate resuscitation with fluid therapy is related with higher mortality; however, fluid bolus or positive fluid balance that may result from "too aggressive" fluid administration is also associated with increased mortality in SS patients. The primary aim of this study was to evaluate the 30-day mortality outcome of the SS patients who were treated with ultrasound-assisted fluid management using change of the IVC during respiratory phases in the first 6 hours compared with those who were treated with "usual-care" strategy. The secondary outcomes were to compare the rate of the need for mechanical ventilation (MV) and renal replacement therapy (RRT) as well as the 6-hours lactate clearance and the change in Sequential Organ Failure (SOFA) score in 72 hours.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Pathum Wan, Bangkok, Thailand, 11130
      • Emergency Medicine Unit, King Chulalongkorn Memorial Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient who attended the emergency department with septic shock (defined by those who require a vasopressor to maintain a mean arterial pressure (MAP) of 65 mm Hg or greater and whose serum lactate level greater than 2 mmol/L in the absence of hypovolemia.)

Exclusion Criteria:

• 1) Congestive pulmonary edema or known to have poor systolic cardiac function (left ventricular ejection fraction ≤ 40%).
• 2) Known to have right heart pathologies.
• 3) Having or suspected to have marked ascites, significant bowel dilatation or the conditions that can cause abdominal hypertension.
• 4) Body mass index ≥ 30 kg/square meter.
• 5) Having concomitant attack of severe airway disease (eg. Asthma, COPD) that may have confounded the IVC interpretation due to the positive intrathoracic pressure.
• 6) IVC can not be identified or its diameter cannot be measured correctly.
• 7) Having end-stage renal diseases with or without dialysis.
• 8) Having non-infectious diseases as final diagnoses.
• 9) Pregnant women.
• 10) Have been referred or treated from other healthcare facility.
• 11) Having active hemorrhages.
• 12) Duplicated cases.
• 13) who had "do-not-resuscitate" living will.
• 14) Declined to consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IVC Ultrasound-guided; The treating physician will promptly assess the IVC diameter to obtain the collapsibility index (IVCCI) (or distensibility index, IVCDI) of an eligible patient. A previous study showed that IVCCI > 40% were strongly associated with fluid responsiveness. Accordingly, the patient will be given 10 ml/kg of bolus of 0.9% normal saline solution (NSS) each time when the IVCCI > 40% is discovered and serial measurements will be done after each intravenous bolus is achieved until the IVCCI < 40 % during our protocol. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.	Procedure: IVC Ultrasound-guided; IVC is identified in longitudinal section in the subcostal area of a patient using the curvilinear probe of standard ultrasound. The selected area of IVC diameter measurement is set at 2 centimeters distal to the confluence of hepatic vein by M-mode coupled by two-dimensional mode on frozen screen images using the Sonosite® X-porte.; Drug: Antibiotics; Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.; Other Names: Antimicrobials; Drug: Vasopressor; The threshold to the need of a vasopressor is set at mean arterial pressure below 65 mmHg if a patient's condition does not response to the fluid therapy.; Other Names: Norepinephrine, dopamine, epinephrine
NO_INTERVENTION: Usual care; Patients will be promptly and empirically treated by 30 ml/kg loading of NSS in this treatment arm. After the NSS bolus, treatment with either the additional intravenous fluid or a vasopressor is given depended on physicians' discretion during the 6-hour study period. Prompt empirical antibiotics will be given to the patients within one hour before the treatment allocation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day Mortality	30-day mortality related to septic shock	30 day after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change of 6-hour Lactate	The percentage change in blood lactate at 6 hour after initiation of treatment, calculated by [(Initial blood lactate level at presentation - blood lactate level at 6 hours after treatment)/Initial blood lactate level at presentation] x 100%. The higher positive value means the more relative reduction of blood lactate after treatment from that of initial presentation and indicates a better clinical outcome.	6 hours after treatment
6-hour Cumulative Amount of Intravenous Fluid (mL)	Cumulative amount of intravenous fluid (mL) during the first 6 hours after treatment.	6 hours after treatment
72-hour Cumulative Amount of Intravenous Fluid (mL) After Treatment	Cumulative amount of intravenous fluid (mL) during the first 72 hours after treatment.	72 hours after treatment
Change in Sequential Organ Failure Assessment (SOFA) Score in 72 Hours After Treatment	The change in Sequential Organ Failure Assessment (SOFA) score between the score at initial presentation and 72 hours after treatment, determined by SOFA score at presentation minus the SOFA score at 72 hours after treatment. The possible minimum and maximum value of the change in SOFA score are -24 and +24, respectively. The higher value means the more relative reduction in SOFA score at 72 hours and indicates a better clinical outcome.	72 hours after treatment

Collaborators and Investigators

• Sponsor: Chulalongkorn University
• Investigators: Principal Investigator: Khrongwong Musikatavorn, MD, Emergency Unit, Faculty of Medicine, Chulalongkorn Hospital

Publications and helpful links

General Publications

• Musikatavorn K, Plitawanon P, Lumlertgul S, Narajeenron K, Rojanasarntikul D, Tarapan T, Saoraya J. Randomized Controlled Trial of Ultrasound-guided Fluid Resuscitation of Sepsis-Induced Hypoperfusion and Septic Shock. West J Emerg Med. 2021 Feb 10;22(2):369-378. doi: 10.5811/westjem.2020.11.48571.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 18, 2017
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): July 31, 2020

Study Registration Dates

• First Submitted: January 3, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (ESTIMATE): January 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Septic Shock; Mortality; Resuscitation; Inferior vene cava diameter
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dopamine Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Mydriatics; Anti-Bacterial Agents; Norepinephrine; Epinephrine; Dopamine; Vasoconstrictor Agents
• Other Study ID Numbers: 589/59

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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