Emergency Department (ED) Flow-directed Fluid Optimization Resuscitation Trial (EFFORT)

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01128413
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The short term goal of this study is to evaluate a non-invasive approach that optimizes intravenous (IV) fluid administration according to heart performance and results in surrogate improvements in morbidity and mortality via lactate clearance. Additional objectives include comparative assessments of methods for determining volume responsiveness and establishing a prevalence of volume responsive shock in the Emergency Department (ED).

Condition or Disease	Intervention/Treatment	Phase
Shock	Device: Cheetah NICOM® PLRT; Device: USCOM ® (Ultrasound Cardiac Output Monitor); Device: Inferior Vena Cava (IVC) Ultrasound Collapsibility; Behavioral: CURVES Questionnaire; Biological: Lactate Clearance; Biological: 500ml Normal Saline Bolus; Biological: Clinician Discretion Intravenous Fluid Management	N/A

Detailed Description

Patients will be randomized to Routine Care (RC) or Fluid Optimizations (FO) arms. Both arms will have interval Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT).

In the FO arm, patients having a PLRT demonstrating a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) patients will receive a 500ml normal saline bolus. If the NICOM® PLRT shows a SVI or CI <15% patients will receive a saline lock. If bolused, NICOM® PLRT will be performed within 10 minutes after the bolus with the decision to re-bolus or saline lock according to repeated NICOM® PLRT measurements. If saline locked, NICOM® PLRT will be performed every 30 minutes with the decision to re-bolus or saline lock according to repeated NICOM® PLRT measurements.

In the RC arm, IV fluid administration will be per the treating clinicians discretion. The Cheetah NICOM®PLRT will be performed before and after each clinician fluid bolus.

Lactate blood samples will be drawn at time zero, 1 hour, 3 hours, 6 hours, and/or ED departure and compared between arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Emergency Department (ED) Flow-directed Fluid Optimization Resuscitation Trial (EFFORT)
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluid Optimization (FO) Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT) that demonstrates a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) will receive a 500ml normal saline bolus. NICOM® PLRT with SVI or CI <15% will receive a saline lock. If bolused, NICOM® PLRT will be performed within 10 minutes after the bolus with the decision to re-bolus or saline lock according to repeated NICOM® PLRT measurements. If saline locked, NICOM® PLRT will be performed every 30 minutes with the decision to re-bolus or saline lock according to repeated NICOM® PLRT measurements. Additionally, USCOM®, IVC Ultrasound collapsibility, CURVES Questionnaire, and repeat lactate measurements will be performed.	Device: Cheetah NICOM® PLRT; Cheetah NICOM® (non-invasive cardiac output monitoring)PLRT (passive leg raise testing) protocol: The patient while in a semi-recumbent position (legs level, torso up 45 degrees) will have 3 minutes of stroke volume and cardiac index monitoring. Following the 3 minutes, the patient will be placed in a leg raised position (torso level, legs up 45 degrees) for 3 minutes of stroke volume and cardiac index monitoring. NICOM® PLRT will be performed within 10 minutes after any fluid bolus in both arms with results blinded to the Routine Care arm. If saline locked or maintenance IV fluid rate, NICOM® PLRT will be performed every 30 minutes in both arms with results blinded to the Routine Care arm.; Device: USCOM ® (Ultrasound Cardiac Output Monitor); Patients while in the Cheetah NICOM® PLRT semi-recumbent position (legs level, torso up 45 degrees) will have simultaneous USCOM® stroke volume and cardiac index monitoring. Following the 3 minutes of Cheetah NICOM® PLRT semi-recumbent positioning, the patient will be placed in a leg raised position (torso level, legs up 45 degrees) and have simultaneous USCOM® stroke volume and cardiac index monitoring. USCOM® monitoring will be blinded to the Routine Care arm unless used as part of a provider's routine practice. USCOM® changes in SVI or CI with PLRT will be calculated after the patient leaves the ED.; Device: Inferior Vena Cava (IVC) Ultrasound Collapsibility; Patients while in the Cheetah NICOM® PLRT semi-recumbent position (legs level, torso up 45 degrees) will have a simultaneous 6-12 second ultrasound recording of their IVC. These recordings will be reviewed later by an ultrasonographer and graded for volume responsiveness. The reviewing ultrasonographer will be blinded to the Cheetah NICOM® PLRT results.; Behavioral: CURVES Questionnaire; The CURVES (CardiovascUlar Response & Volume Estimation in Shock) Questionnaire consists of multiple provider questions aimed at defining the presumed shock etiology and anticipated responses to interventions. This will be administered to both arms.; Biological: Lactate Clearance; Lactate samples will be drawn at time 0, 1, 3, & 6 hours (or at ED departure if before 6 hours). Time 0 lactate will be revealed to the Routine Care arm and subsequent lactates revealed to the Routine Care arm only if serial lactates are part of the provider's routine practice.; Biological: 500ml Normal Saline Bolus; Patients randomized to the experimental arm and having a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) via Cheetah NICOM®PLRT will be given a 500ml normal saline fluid bolus.
Active Comparator: Routine Care (RC) Patients randomized to receive routine ED care will receive IV fluid administration per the treating clinicians discretion. The Cheetah NICOM®PLRT, USCOM®, IVC Ultrasound collapsibility, and CURVES Questionnaire will be performed and repeat lactate measurements will only be revealed to the routine care arm if they are used as part of the provider's routine care.	Device: Cheetah NICOM® PLRT; Cheetah NICOM® (non-invasive cardiac output monitoring)PLRT (passive leg raise testing) protocol: The patient while in a semi-recumbent position (legs level, torso up 45 degrees) will have 3 minutes of stroke volume and cardiac index monitoring. Following the 3 minutes, the patient will be placed in a leg raised position (torso level, legs up 45 degrees) for 3 minutes of stroke volume and cardiac index monitoring. NICOM® PLRT will be performed within 10 minutes after any fluid bolus in both arms with results blinded to the Routine Care arm. If saline locked or maintenance IV fluid rate, NICOM® PLRT will be performed every 30 minutes in both arms with results blinded to the Routine Care arm.; Device: USCOM ® (Ultrasound Cardiac Output Monitor); Patients while in the Cheetah NICOM® PLRT semi-recumbent position (legs level, torso up 45 degrees) will have simultaneous USCOM® stroke volume and cardiac index monitoring. Following the 3 minutes of Cheetah NICOM® PLRT semi-recumbent positioning, the patient will be placed in a leg raised position (torso level, legs up 45 degrees) and have simultaneous USCOM® stroke volume and cardiac index monitoring. USCOM® monitoring will be blinded to the Routine Care arm unless used as part of a provider's routine practice. USCOM® changes in SVI or CI with PLRT will be calculated after the patient leaves the ED.; Device: Inferior Vena Cava (IVC) Ultrasound Collapsibility; Patients while in the Cheetah NICOM® PLRT semi-recumbent position (legs level, torso up 45 degrees) will have a simultaneous 6-12 second ultrasound recording of their IVC. These recordings will be reviewed later by an ultrasonographer and graded for volume responsiveness. The reviewing ultrasonographer will be blinded to the Cheetah NICOM® PLRT results.; Behavioral: CURVES Questionnaire; The CURVES (CardiovascUlar Response & Volume Estimation in Shock) Questionnaire consists of multiple provider questions aimed at defining the presumed shock etiology and anticipated responses to interventions. This will be administered to both arms.; Biological: Lactate Clearance; Lactate samples will be drawn at time 0, 1, 3, & 6 hours (or at ED departure if before 6 hours). Time 0 lactate will be revealed to the Routine Care arm and subsequent lactates revealed to the Routine Care arm only if serial lactates are part of the provider's routine practice.; Biological: Clinician Discretion Intravenous Fluid Management; Clinicians caring for patients randomized to the Routine Care arm will within 10 minutes after any fluid bolus be asked to decide via their clinical discretion if they want to re-bolus, saline lock, or place the patient on a maintenance IV fluid rate. If the patient is on a saline lock or maintenance fluid rate, clinicians will be asked every 30 minutes to decide via their clinical discretion to re-bolus, saline lock, or place the patient on a maintenance IV fluid rate.

Outcome Measures

Primary Outcome Measures

1. Lactate Clearance [The median lactate clearance within 6 hours of the ED stay.]

   The median lactate clearance from time zero to within 6 hours of the ED stay.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hypotension (Systolic Blood Pressure ≤90mm Hg or Mean Arterial Pressure ≤ 65 mm Hg) after ≥ 20ml/kg fluids OR

• Vasopressor Use OR

• Lactate ≥ 2.5 mmol/L

Exclusion Criteria:

• Pulse Oximetry <90% despite supplemental oxygen or intubation

• Seizure in the last 24 hours

• Prisoner

• Pregnancy

• Age <18

• Allergy to coupling or ultrasound gel

• Inability to do passive leg raise

• Inability to obtain IV access

• Treating clinician discretion

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barnes-Jewish Hospital Emergency Department	St. Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Christopher V Holthaus, MD, Washington University School of Medicine
• Principal Investigator: Brian M Fuller, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Barbier C, Loubières Y, Schmit C, Hayon J, Ricôme JL, Jardin F, Vieillard-Baron A. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004 Sep;30(9):1740-6. Epub 2004 Mar 18.
• Blow O, Magliore L, Claridge JA, Butler K, Young JS. The golden hour and the silver day: detection and correction of occult hypoperfusion within 24 hours improves outcome from major trauma. J Trauma. 1999 Nov;47(5):964-9.
• Corley A, Barnett AG, Mullany D, Fraser JF. Nurse-determined assessment of cardiac output. Comparing a non-invasive cardiac output device and pulmonary artery catheter: a prospective observational study. Int J Nurs Stud. 2009 Oct;46(10):1291-7. doi: 10.1016/j.ijnurstu.2009.03.013. Epub 2009 May 6.
• Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep;30(9):1834-7. Epub 2004 Mar 25.
• Jones AE, Kline JA. Use of goal-directed therapy for severe sepsis and septic shock in academic emergency departments. Crit Care Med. 2005 Aug;33(8):1888-9; author reply 1889-90.
• Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. doi: 10.1001/jama.2010.158.
• Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008 Jul;134(1):172-8. doi: 10.1378/chest.07-2331. Review.
• Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009 Sep;37(9):2642-7. doi: 10.1097/CCM.0b013e3181a590da. Review.
• Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002 Jun;121(6):2000-8. Review.
• Monnet X, Teboul JL. Passive leg raising. Intensive Care Med. 2008 Apr;34(4):659-63. doi: 10.1007/s00134-008-0994-y. Epub 2008 Jan 23.
• Nguyen HB, Losey T, Rasmussen J, Oliver R, Guptill M, Wittlake WA, Corbett SW. Interrater reliability of cardiac output measurements by transcutaneous Doppler ultrasound: implications for noninvasive hemodynamic monitoring in the ED. Am J Emerg Med. 2006 Nov;24(7):828-35.
• Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42.
• Perera P, Mailhot T, Riley D, Mandavia D. The RUSH exam: Rapid Ultrasound in SHock in the evaluation of the critically lll. Emerg Med Clin North Am. 2010 Feb;28(1):29-56, vii. doi: 10.1016/j.emc.2009.09.010.
• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77.
• Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, Weiss JW. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005 May;45(5):524-8.
• Sinclair S, James S, Singer M. Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture: randomised controlled trial. BMJ. 1997 Oct 11;315(7113):909-12.
• Sinert R, Spektor M. Evidence-based emergency medicine/rational clinical examination abstract. Clinical assessment of hypovolemia. Ann Emerg Med. 2005 Mar;45(3):327-9.
• Thiel SW, Kollef MH, Isakow W. Non-invasive stroke volume measurement and passive leg raising predict volume responsiveness in medical ICU patients: an observational cohort study. Crit Care. 2009;13(4):R111. doi: 10.1186/cc7955. Epub 2009 Jul 8.

• Responsible Party: Christopher Holthaus, MD, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01128413
• Other Study ID Numbers: EFFORT-10-0593
• First Posted: May 21, 2010
• Last Update Posted: Apr 1, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Christopher Holthaus, MD, Washington University School of Medicine: Shock; Resuscitation; Hemodynamics; Emergencies; Critical Care; Lactic Acid; Plasma volume
• Additional relevant MeSH terms: Emergencies

Study Results

Participant Flow

Recruitment Details	Patients screened and study performed in the ED from July 2010 to November 2013.

Arm/Group Title	Fluid Optimization (FO)	Routine Care (RC)
Arm/Group Description	Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT) that demonstrates a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) will receive a 500ml normal saline bolus. NICOM® PLRT with SVI or CI <15% will receive a saline lock.	Patients randomized to receive routine ED care. IV fluid administration will be per the treating clinicians discretion.
Period Title: Overall Study
STARTED	11	11
COMPLETED	7	10
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Fluid Optimization (FO)	Routine Care (RC)	Total
Arm/Group Description	Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT) that demonstrates a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) will receive a 500ml normal saline bolus. NICOM® PLRT with SVI or CI <15% will receive a saline lock.	Patients randomized to receive routine ED care. IV fluid administration will be per the treating clinicians discretion.	Total of all reporting groups
Overall Participants	11	11	22
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 63.6%	7 63.6%	14 63.6%
>=65 years	4 36.4%	4 36.4%	8 36.4%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	56	59	57
Sex: Female, Male (Count of Participants)
Female	6 54.5%	2 18.2%	8 36.4%
Male	5 45.5%	9 81.8%	14 63.6%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Lactate Clearance
Description	The median lactate clearance from time zero to within 6 hours of the ED stay.
Time Frame	The median lactate clearance within 6 hours of the ED stay.

Outcome Measure Data

Analysis Population Description

Only 9 total patients (5 Fluid Optimization; 4 Routine Care) stayed in the Emergency Department for a full 6 hours to allow calculation of a 6 hour lactate clearance. The rest of the patients left were dispositioned out of the ED before the 6 hour mark and therefore unable to calculate a 6 hour lactate clearance.

Arm/Group Title	Fluid Optimization (FO)	Routine Care (RC)
Arm/Group Description	Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT) that demonstrates a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) will receive a 500ml normal saline bolus. NICOM® PLRT with SVI or CI <15% will receive a saline lock.	Patients randomized to receive routine ED care. IV fluid administration will be per the treating clinicians discretion.
Measure Participants	5	4
Median (Inter-Quartile Range) [percent lactate clearance]	54	56

Adverse Events

Time Frame	24 hours
Adverse Event Reporting Description	Inpatient records reviewed for death within 24 hours of study enrollment, disability, worsening oxygenation and/or escalation of monitoring and/or supportive care believed to be directly related to excess IV fluid administration, electrode adhesive or ultrasound gel hypersensitivity, IV site infection or inflammation.
Arm/Group Title	Fluid Optimization (FO)		Routine Care (RC)
Arm/Group Description	Cheetah NICOM® (non-invasive cardiac output monitoring) Passive Leg Raise Testing (PLRT) that demonstrates a >/= 15% change in stroke volume index (SVI) or cardiac index (CI) will receive a 500ml normal saline bolus. NICOM® PLRT with SVI or CI <15% will receive a saline lock.		Patients randomized to receive routine ED care. IV fluid administration will be per the treating clinicians discretion.
All Cause Mortality
	Fluid Optimization (FO)		Routine Care (RC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluid Optimization (FO)		Routine Care (RC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Fluid Optimization (FO)		Routine Care (RC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)

Limitations/Caveats

Trial terminated early due to lack of resources leading to small numbers of subjects analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.