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CompletedNCT03810118REFILLUpdated May 27, 2020

Fluid Challenge Infusion and Response

An interventional study of fluid challenge in Neurosurgery, Cardiovascular System and Anesthesia, General, sponsored by Humanitas Clinical and Research Center. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-05-27.

Sponsored by Humanitas Clinical and Research Center · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
49
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

It is unclear if the rate of administration of the fluid challenge could affect the rate of fluid responsiveness.

The role of this small-dose (the so called mini-FC) has been recently tested to assess if the infusion of a small amount of fluids (100 ml in 1 minute) could predict the final effect of the residual aliquot (i.e., 250 ml of FC test subdivided as follows: 100 ml in 1 minute and 150 ml in 9 minutes). Both the sudden increase in the stroke volume and the reduction of PPV and SVV after a bolus of 100 ml of crystalloids administered in 1 minute showed high sensitivity and specificity in predicting the final outcome of the FC.

The primary aim of the present study is assess whether the does the rate of infusion of fluid challenge affect fluid responsiveness in neurosurgical supine patients.

The secondary aim is to assess the reliability of the changes in SV, PPV and SVV after a mini-FC test in predicting the final fluid responsiveness.

Read the detailed description

Dedicated algorithms and protocols of anaesthetic care regarding fluid therapy are key factors to prevent perioperative hypovolaemia and/or hypervolemia, which are known to increase morbidity and length of hospital stay.

Fluid therapy is commonly used in critically ill and surgical patients to restore hemodynamics. The aim of volume expansion is to increase cardiac index and oxygen delivery and to improve tissue oxygenation. However, this occurs only in a situation of preload dependency (i.e. when the ventricle operates on the steep part of the Frank-Starling's curve). Moreover, giving fluids to a non-volume-responsive patient (preload independency) can result in detrimental pulmonary and interstitial oedema. Fluid responsiveness (i.e., increase in stroke volume, SV, after fluid challenge, FC, administration) can be detected in 35-50% of both critically ill and surgical patients. The FC consists in assessing the hemodynamic effects of giving a small amount of fluid in a short period of time. The FC allows restoring fluid depletion when indicated, while minimizing the risk of overloading, which makes it the gold standard for assessing fluid depletion in patients undergoing surgery.

Then, FC administration should be based on predictors of fluid responsiveness. Static indexes, such as the central venous pressure, do not seem appropriate, whereas dynamic indexes, such as pulse pressure variation (PPV) and stroke volume variation (SVV), reliably predict the effect of FC administration during controlled mechanical ventilation only in case of a tidal volume (VT) of at least 8 mL/kg, which unfortunately are rarely found in both critically ill and surgical patients.

To overcome this VT-related limitation of PPV and SVV, the prediction of fluid responsiveness can be also achieved by applying functional hemodynamic tests aiming at increasing venous return and enhancing right ventricle preload dependence.

For example, when a FC is performed using a rapid infusion rate and a relatively "small" dose, its effect is sufficient to test whether the patient is on the ascending part of the cardiac function curve, hence showing an increase in cardiac output (CO).

The role of this small-dose (the so called mini-FC) has been recently tested to assess if the infusion of a small amount of fluids (100 ml in 1 minute) could predict the final effect of the residual aliquot (i.e., 250 ml of FC test subdivided as follows: 100 ml in 1 minute and 150 ml in 9 minutes). Both the sudden increase in the stroke volume and the reduction of PPV and SVV after a bolus of 100 ml of crystalloids administered in 1 minute showed high sensitivity and specificity in predicting the final outcome of the FC. However, the mini-FC has been tested, insofar, only in small-sized studies, needing further investigations to be confirmed.

Moreover, the response to the FC is transitory, and as such also its clinical effect. The study of Aya et al. pointed out that the effect of the FC is dissipated in about 10 minutes in both responders and non-responders and that a dose of 4 ml/kg of crystalloids is the lowest one to evocate a significant hemodynamic effect. It remains unclear, however, what the best approach to FC administration should be and, in fact, wide variability exists at this regard among studies performed both in the perioperative setting and in the intensive care unit (ICU). In fact, the rate of fluid administration is not fixed. A recent systematic review showed a significant heterogeneity. In a subgroup of 35 studies three (8.6%) reported an infusion rate of 1 ml/kg/min. In another group of 32 studies, the FC was administered in 30 minutes in 7 (21.8%) studies, in 20 minutes in 2 (6.2%) studies, in 13 minutes in 1 (3.1%) study, in 10 minutes in 15 studies (46.8%), in 5 minutes in 4 (12.5%) studies, in 3 minutes in 1 (3.1%) study, and in 2 minutes in 2 (6.2%) studies. The median (IQR) time of infusion was 10 (5-20) minutes.

After the indication of Aya et al., 4 ml/kg of crystalloids is the standard dose for the FC in our center. However, it is unclear if the rate of administration could affect the rate of fluid responsiveness. We, therefore, will perform a study to address this issue in a sample of neurosurgical patients.

The primary aim of the present study is assess whether the does the rate of infusion of fluid challenge affect fluid responsiveness in neurosurgical patients.

The secondary aim is to assess the reliability of the changes in SV, PPV and SVV after a mini-FC test in predicting the final fluid responsiveness.

02

Conditions studied

  • Neurosurgery
  • Cardiovascular System
  • Anesthesia, General
03

In context

Lead sponsor

Humanitas Clinical and Research Center is the lead sponsor of 33 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Adult patients aged ≥ 18 years;
  2. Scheduled for elective supine neurosurgery and requiring invasive arterial monitoring;
  3. Glasgow coma scale 15 at recruitment

Exclusion criteria

Exclusion Criteria:

  1. Any recurrent cardiac arrhythmias;
  2. Reduced left (ejection fraction \<30%) or right (systolic peak velocity of tricuspid annular motion \<0.17 m/s) ventricular systolic function;
  3. Intra-operative use of vasopressors or inotropes before FC administration or between the first and the second bolus of fluids.
  4. Chronic use beta-blocking agents.
05

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
49 participants (actual)

Study arms

  • Experimental
    Treatment

    All the enrolled patients will receive the same mini-fluid challenge test of 100ml and then will complete the 4 ml/kg fluid challenge in either 10 or 20 minutes

    Diagnostic Test: fluid challenge

Interventions

  • Diagnostic testfluid challenge

    4 ml/kg fluid challenge infused over in either 10 or 20 minutes

06

What researchers measure

Primary outcomes

  1. Percentage of fluid responders

    Percentage of patients showing an increase in the stroke volume above the predefined threshold of fluid responsiveness after the infusion of the fluid challenge (\>10%).

    Time frame: 10 or 20 minutes from the start

  2. Pharmacodynamic effect of the FC

    AUC

    Time frame: 10 or 20 minutes from the start

  3. Pharmacodynamic effect of the FC

    dmax

    Time frame: 10 or 20 minutes from the start

  4. Pharmacodynamic effect of the FC

    Tmax

    Time frame: 10 or 20 minutes from the start

  5. Pharmacodynamic effect of the FC

    d1

    Time frame: 10 or 20 minutes from the start

  6. Pharmacodynamic effect of the FC

    d5

    Time frame: 10 or 20 minutes from the start

07

Study locations

1 site
  • Humanitas Research Hospital
    Rozzano, Milano 20089, Italy
08

References and documents

Publications

  • Mahjoub Y, Lejeune V, Muller L, Perbet S, Zieleskiewicz L, Bart F, Veber B, Paugam-Burtz C, Jaber S, Ayham A, Zogheib E, Lasocki S, Vieillard-Baron A, Quintard H, Joannes-Boyau O, Plantefeve G, Montravers P, Duperret S, Lakhdari M, Ammenouche N, Lorne E, Slama M, Dupont H. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth. 2014 Apr;112(4):681-5. doi: 10.1093/bja/aet442. Epub 2013 Dec 29. PubMed 24374504 ↗
  • Biais M, de Courson H, Lanchon R, Pereira B, Bardonneau G, Griton M, Sesay M, Nouette-Gaulain K. Mini-fluid Challenge of 100 ml of Crystalloid Predicts Fluid Responsiveness in the Operating Room. Anesthesiology. 2017 Sep;127(3):450-456. doi: 10.1097/ALN.0000000000001753. PubMed 28640019 ↗
  • Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRea Group. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500. PubMed 21792056 ↗
  • Aya HD, Ster IC, Fletcher N, Grounds RM, Rhodes A, Cecconi M. Pharmacodynamic Analysis of a Fluid Challenge. Crit Care Med. 2016 May;44(5):880-91. doi: 10.1097/CCM.0000000000001517. PubMed 26683506 ↗

Individual participant data

Plan to share: Undecided

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 27, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03810118
Lead sponsor
Humanitas Clinical and Research Center
Responsible party
Antonio Messina (ICU senior consultant, Humanitas Clinical and Research Center) — Principal investigator
First posted
Jan 18, 2019
Start date
Apr 8, 2019
Primary completion
Feb 21, 2020
Completion
May 1, 2020
Last update
May 27, 2020

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.

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