Effect of Dynamic Arterial Elastance and Assisted Fluid Management Software Guided Resuscitation in Septic Shock: Pilot Study (DAFM shock)

Effect of Dynamic Arterial Elastance and Assisted Fluid Management Software Guided Adjustment of Vasopressor and Fluid Therapy in Septic Shock Resuscitation; A Pilot Study

To investigate the benefit of using the AFM and Eadyn-guided fluid and vasopressor therapy in septic shock resuscitation for mechanically ventilated patients compared with the standard of care. The investigators hypothesize that using the AFM and Eadyn-guided fluid/vasopressor titration in septic shock patients who underwent mechanical ventilation might reduce the time to shock reversal.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Septic Shock; Fluid Over-load; Dynamic Arterial Elastance
• Intervention / Treatment: Other: The standard care for septic shock; Device: The AFM and Eadyn - guided resuscitation group

Detailed Description

Hypotension in the context of an intensive care unit has been associated with a higher risk of death and multiorgan dysfunction. Vascular leakage and systemic vasodilatation are brought on by systemic inflammation from infections. These are the hallmarks of septic shock in which 90% of cases of shock are mostly distributive and hypovolemic. Early vasopressors and fluid therapy are increasingly used at the start of vasodilatory shock resuscitation since this method improves the rate of shock control within 6 hours in septic shock resuscitation. Norepinephrine is the first-line vasopressor for vasodilatory shock. However, resuscitation with an accurate amount of fluid and vasopressor is challenging in clinical practice. Fluid overload and overuse of vasopressors are prevalent and increase mortality. Together with a higher dose of norepinephrine, it may increase the risk of ischemic complications.

A new hemodynamic monitoring device (Hemosphere(R) - Edward Lifescience, California, USA) provides two novel parameters for hemodynamic monitoring: the new device with artificial intelligence developed by a retrospective cohort (used for training) and a prospective (local hospital cohort used for external validation). The feature of Hemosphere(R), including dynamic arterial elastance (Eadyn) and stroke volume change prediction (∆SVpredict) as the assist fluid management (AFM) based on arterial pressure waveform analysis by the monitoring software, was detected in arterial line waveform without any complication of a safety issue.

The ratio of pulse pressure to stroke volume (PP/SV) is defined by dynamic arterial elastance (Eadyn), the reciprocal of compliance within the range of 0.8 to 1.0 is the optimization of arterial load that can predict arterial pressure response to fluid administration and vasopressor weaning. The prediction of the stroke volume changes following the upcoming fluid therapy (∆SVpredict) uses stroke volume variation parameters and closed-loop feedback data, which should be less than 10% to indicate optimal fluid administration. Consequently, this technique offers a useful means of evaluating arterial tone related to preload responsiveness parameters predicting the hemodynamic response to increases in cardiac preload.

However, several studies show the benefit of this tool in perioperative patients, and the evidence on the benefit of using this monitoring to guide septic shock resuscitation is limited. In a previous study, Eadyn can predict a decrease in mean arterial pressure linked to a reduction in norepinephrine dosage. This study aimed to investigate the benefit of using AFM and Eadyn-guided fluid and vasopressor therapy in septic shock resuscitation compared with the standard of care

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ranistha Ratanarat, MD; Phone Number: +66 2419 7767; Email: ranittha@gmail.com
• Study Contact Backup: Name: Nuwara Pornawalai, MD; Phone Number: +66 2419 7767; Email: nuwara.por@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Recruiting
    • Siriraj Hospital, Mahidol University
    • Principal Investigator: Ranistha Ratanarat, MD
    • Contact: Ranistha Ratanarat, MD; Phone Number: +66896685287; Email: ranittha@gmail.com; ranittha@hotmail.com
    • Contact: Nuwara Pornawalai, MD; Email: nuwara.por@gmail.com
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Not yet recruiting
      • Faculty of Medicine Siriraj Hospital
      • Contact: Nuwara Pornawalai, MD; Phone Number: +66 2419 7767; Email: nuwara.por@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All Thai consecutive patients older than 18 years with a diagnosis of sepsis or septic shock in medical ICU, defined by clinically suspected or confirmed infection and MAP <65 mmHg according to the criteria of the Surviving Sepsis Campaign 2021(11)with onset of shock in less than 24 hours.
• Already receiving or planning for mechanical ventilation
• Already receiving or planning for arterial catheter placement for invasive arterial pressure monitoring
• All patients will receive an echocardiogram with a cut point of LVEF > 30% to be included in the study

Exclusion Criteria:

• Active, immediate, life-threatening cardiac arrhythmia, defined as ventricular tachycardia and ventricular fibrillation
• Acute cerebral vascular event, including both acute ischemic stroke or intracranial hemorrhage
• Acute coronary syndrome
• cardiogenic shock, acute heart failure
• Severe asthma exacerbation
• Fluid intolerance: hypoxemia (P:F ratio < 150)
• Life-threatening gastrointestinal hemorrhage
• Pregnancy
• Requirement for immediate surgery within 2 hours of randomization
• Advanced-stage cancer with predicted survival of less than 6 months
• Oliguric AKI with signs of volume overload

Withdrawal or termination criteria

• The patient and legal representative request for withdrawal
• The attending physician requested a withdrawal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: the standard of care group; The standard of care group will be treated according to according to septic shock guidelines 2021; In brief A vasopressor with optimal ideal fluid (at least 30 ml/kg) will be given to achieve the hemodynamic target (MAP ≥ 65 mm Hg) by fluid challenge technique guided by MAP and central venous pressure (CVP) changes after fluid challenge. Fluid-responsive tests can be used as a subsidiary, depending on the attending physician. Early Norepinephrine (NE) infusion can be used with a standard dose of 0.05 mcg/k/min and titrated at the rate of 0.01-0.02 mcg/kg/min every 10 min until 0.25 mcg/kg/min was achieved; then, the second line vasopressor will be added and adjusted to the target of vasopressor. Hydrocortisone can be given according to septic shock guidelines.	Other: The standard care for septic shock; The standard of care group will be treated according to according to septic shock guidelines 2021; In brief A vasopressor with optimal ideal fluid (at least 30 ml/kg) will be given to achieve the hemodynamic target (MAP ≥ 65 mm Hg) by fluid challenge technique guided by MAP and central venous pressure (CVP) changes after fluid challenge. Fluid-responsive tests can be used as a subsidiary, depending on the attending physician. Early Norepinephrine (NE) infusion can be used with a standard dose of 0.05 mcg/k/min and titrated at the rate of 0.01-0.02 mcg/kg/min every 10 min until 0.25 mcg/kg/min was achieved; then, the second line vasopressor will be added and adjusted to the target of vasopressor. Hydrocortisone can be given according to septic shock guidelines. After MAP of 65 achieved, tissue perfusion including urine output, capillary refill time, and serum lactate will be assessed
Experimental: AFM and Eadyn - guided resuscitation group; Patients randomized to this arm are treated with the standard of care for patients with septic shock as described for 'the standard of care' arm, along with the AFM and Eadyn - guided resuscitation group, as detailed under 'Interventions'	Other: The standard care for septic shock; The standard of care group will be treated according to according to septic shock guidelines 2021; In brief A vasopressor with optimal ideal fluid (at least 30 ml/kg) will be given to achieve the hemodynamic target (MAP ≥ 65 mm Hg) by fluid challenge technique guided by MAP and central venous pressure (CVP) changes after fluid challenge. Fluid-responsive tests can be used as a subsidiary, depending on the attending physician. Early Norepinephrine (NE) infusion can be used with a standard dose of 0.05 mcg/k/min and titrated at the rate of 0.01-0.02 mcg/kg/min every 10 min until 0.25 mcg/kg/min was achieved; then, the second line vasopressor will be added and adjusted to the target of vasopressor. Hydrocortisone can be given according to septic shock guidelines. After MAP of 65 achieved, tissue perfusion including urine output, capillary refill time, and serum lactate will be assessed; Device: The AFM and Eadyn - guided resuscitation group; A fluid challenge using a stroke volume change prediction (∆SVpredict) and Eadyn guide. If the ∆SVpredict is more than 10%, isotonic crystalloid of 500 ml will be administered in 30 minutes, and the machine's response will be awaited. If ∆SVpredict is still more than 10%, continuous fluid loading was reapplied until SVV was less than 10% (fluid therapy will be stopped if ∆SVpredict is less than 10%) and dynamic arterial elastance (EAdyn) reaches the goal of 0.8-1.0 along with a vasopressor will be administered and titrated every 10 minutes until the target MAP > 65 mmHg is reached. After MAP of 65 achieved, tissue perfusion including urine output, capillary refill time, and serum lactate will be assessed; Other Names: hemosphere; dynamic arterial elastance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to shock reversal	the time from diagnosis of septic shock until the achievement of sustained MAP of ≥65 mmHg with evidence of adequate tissue perfusion (continuation of urine flow ≥ 0.5 ml/kg/h or normalized or continuing decrease in serum lactate ≥10% from the previous value) without any vasopressor infusion	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay		28 days
hospital length of stay		28 days
a time-to-goal achievement for septic shock resuscitation	MAP ≥ 65 mmHg with vasopressors and optimized tissue perfusion	28 days
time to NE titrating		48 hours
maximum dose of vasopressors		48 hours
volume of fluid therapy during resuscitation		48 hours
fluid before randomization		48 hours
fluid accumulation at 24 hours		24 hours
fluid accumulation at 72 hours		72 hours
fluid accumulation at 7 days		7 days
28-day hospital mortality		28 days
shock reversal at 6 hours	Shock reversal is defined as mean arterial pressure at or more than 65 mmHg with one of the following: -Reduction of serum lactate level of 20% or more -Hourly urine output of 0.5 mL/kg or more	6 hours
rate of new initiation of renal replacement therapy		28 days
time to initiation of renal replacement therapy		28 days
Vasopressor-free day	Number of days that patient is alive after successful discontinuation of vasoactive agents in the first 28 days, with the day of randomization defined as Day 1. Successful discontinuation of vasoactive agents is defined as discontinuation of vasoactive agents without resumption until Day 28 or until hospital discharge, whichever is first. In case of multiple periods of vasoactive agents use, the days from the final discontinuation of vasoactive agents are counted. All 28-day non-survivors are counted as 0, irrespective of their use of vasoactive agents at the time of death, and censored observations after 28 days	28 days
Ventilator-free day	Number of days that patient is alive after successful liberation of mechanical ventilation in the first 28 days, with the day of randomization defined as Day 1. Successful liberation of mechanical ventilation is defined as the discontinuation of mechanical ventilation (either via orotracheal or tracheostomy tube) for 48 hours or more. Non-invasive positive pressure ventilation is not regarded as mechanical ventilation. In case of multiple periods of mechanical ventilation, the days from the final successful liberation of mechanical ventilation within 28 days are counted. All 28-day non-survivors are counted as 0, irrespective of their ventilation status at the time of death, and censored observations after 28 days	28 days
Renal replacement therapy(RRT)-free day	Number of days that patient is alive after successful discontinuation of renal-replacement therapy in the first 28 days, with the day of randomization defined as Day 1. Successful discontinuation of renal-replacement therapy is defined as discontinuation of all modes of renal-replacement therapy without resumption for at least 7 days and until Day 28 or until hospital discharge, whichever is first. Hemoperfusion according to treatment protocol in 'Standard of care and hemoperfusion with HA-330' arm is not counted as renal-replacement therapy. All 28-day non-survivors are counted as 0, irrespective of their use of renal-replacement therapy at the time of death, and censored observations after 28 days	28 days
Serum lactate at 0 hours, 1 hour, and 6 hours		6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event	ischemic complication and arrhythmia	28 days

Collaborators and Investigators

• Sponsor: Mahidol University

Publications and helpful links

General Publications

• Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, Mira JP, Dequin PF, Gergaud S, Weiss N, Legay F, Le Tulzo Y, Conrad M, Robert R, Gonzalez F, Guitton C, Tamion F, Tonnelier JM, Guezennec P, Van Der Linden T, Vieillard-Baron A, Mariotte E, Pradel G, Lesieur O, Ricard JD, Herve F, du Cheyron D, Guerin C, Mercat A, Teboul JL, Radermacher P; SEPSISPAM Investigators. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014 Apr 24;370(17):1583-93. doi: 10.1056/NEJMoa1312173. Epub 2014 Mar 18.
• Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Aug 29;369(9):840-51. doi: 10.1056/NEJMra1208623. No abstract available. Erratum In: N Engl J Med. 2013 Nov 21;369(21):2069.
• Hatib F, Jian Z, Buddi S, Lee C, Settels J, Sibert K, Rinehart J, Cannesson M. Machine-learning Algorithm to Predict Hypotension Based on High-fidelity Arterial Pressure Waveform Analysis. Anesthesiology. 2018 Oct;129(4):663-674. doi: 10.1097/ALN.0000000000002300.
• Guinot PG, Bernard E, Levrard M, Dupont H, Lorne E. Dynamic arterial elastance predicts mean arterial pressure decrease associated with decreasing norepinephrine dosage in septic shock. Crit Care. 2015 Jan 19;19(1):14. doi: 10.1186/s13054-014-0732-5.
• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.
• 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.
• Messmer AS, Zingg C, Muller M, Gerber JL, Schefold JC, Pfortmueller CA. Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies. Crit Care Med. 2020 Dec;48(12):1862-1870. doi: 10.1097/CCM.0000000000004617.
• Maheshwari K, Malhotra G, Bao X, Lahsaei P, Hand WR, Fleming NW, Ramsingh D, Treggiari MM, Sessler DI, Miller TE; Assisted Fluid Management Study Team. Assisted Fluid Management Software Guidance for Intraoperative Fluid Administration. Anesthesiology. 2021 Aug 1;135(2):273-283. doi: 10.1097/ALN.0000000000003790.
• Kelly RP, Ting CT, Yang TM, Liu CP, Maughan WL, Chang MS, Kass DA. Effective arterial elastance as index of arterial vascular load in humans. Circulation. 1992 Aug;86(2):513-21. doi: 10.1161/01.cir.86.2.513.
• Lai CJ, Cheng YJ, Han YY, Hsiao PN, Lin PL, Chiu CT, Lee JM, Tien YW, Chien KL. Hypotension prediction index for prevention of intraoperative hypotension in patients undergoing general anesthesia: a randomized controlled trial. Perioper Med (Lond). 2024 Jun 15;13(1):57. doi: 10.1186/s13741-024-00414-7.
• Dong S, Wang Q, Wang S, Zhou C, Wang H. Hypotension prediction index for the prevention of hypotension during surgery and critical care: A narrative review. Comput Biol Med. 2024 Mar;170:107995. doi: 10.1016/j.compbiomed.2024.107995. Epub 2024 Jan 18.
• Monge Garcia MI, Jian Z, Settels JJ, Hunley C, Cecconi M, Hatib F, Pinsky MR. Performance comparison of ventricular and arterial dP/dtmax for assessing left ventricular systolic function during different experimental loading and contractile conditions. Crit Care. 2018 Nov 29;22(1):325. doi: 10.1186/s13054-018-2260-1.
• Zhou X, Pan W, Chen B, Xu Z, Pan J. Predictive performance of dynamic arterial elastance for arterial pressure response to fluid expansion in mechanically ventilated hypotensive adults: a systematic review and meta-analysis of observational studies. Ann Intensive Care. 2021 Jul 31;11(1):119. doi: 10.1186/s13613-021-00909-2.
• Kouz K, Monge Garcia MI, Cerutti E, Lisanti I, Draisci G, Frassanito L, Sander M, Ali Akbari A, Frey UH, Grundmann CD, Davies SJ, Donati A, Ripolles-Melchor J, Garcia-Lopez D, Vojnar B, Gayat E, Noll E, Bramlage P, Saugel B. Intraoperative hypotension when using hypotension prediction index software during major noncardiac surgery: a European multicentre prospective observational registry (EU HYPROTECT). BJA Open. 2023 May 4;6:100140. doi: 10.1016/j.bjao.2023.100140. eCollection 2023 Jun.
• Monge Garcia MI, Gil Cano A, Gracia Romero M. Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients. Crit Care. 2011;15(1):R15. doi: 10.1186/cc9420. Epub 2011 Jan 12.

Helpful Links

• sample size

Study record dates

Study Major Dates

• Study Start (Estimated): April 23, 2025
• Primary Completion (Estimated): April 8, 2027
• Study Completion (Estimated): April 8, 2028

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 22, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: septic shock; critical illness; dynamic arterial elastance; fluid overload; stroke volume change prediction; ischemic complication
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Critical Illness; Shock; Shock, Septic
• Other Study ID Numbers: SI 118/2025

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