Peripheral Perfusion Targeted Fluid Management

Peripheral Perfusion Targeted Fluid Management in Critically Ill Patients: a Pilot Study

• Impaired peripheral perfusion is related to worse outcome in critically ill patients. Although this is known, these parameters have never been used as target for hemodynamic therapy.
• We hypothesize that targeting of fluid administration on parameters of peripheral perfusion might prevent excessive fluid administration, leading to less formation of tissue edema, less respiratory dysfunction and shorter duration of mechanical ventilation in critically ill patients.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Severe Sepsis
• Intervention / Treatment: Other: PPTFM

Detailed Description

Rationale: Currently, fluid administration of critically ill patients is aimed at optimizing conventional hemodynamic parameters such as stroke volume and cardiac output. Fluid is infused repeatedly until patients become "non-responsive", i.e. cardiac output does not increase anymore. However, the ultimate goal of hemodynamic therapy should be to improve peripheral (i.e. tissue) perfusion. Recently we have shown that 1) increasing stroke volume does not always have an effect on peripheral perfusion and 2) that peripheral perfusion is not impaired when stroke volume can still be increased with fluid infusion. Furthermore, repeated administration of fluid in order to reach a maximum cardiac output can lead to an enormous accumulation of fluid in the patient. This leads to formation of lung edema and respiratory dysfunction and is associated with prolonged mechanical ventilation and ICU-stay. Recently, techniques have been developed which allow bedside assessment of peripheral perfusion. Although impaired peripheral perfusion was related to worse outcome, these parameters have never been used as target for hemodynamic therapy.

Objective: To study whether peripheral perfusion targeted fluid management (PPTFM) leads to less fluid administration, improved respiratory function and shorter mechanical ventilation.

Study design: The study is a pilot study and is designed as a randomized controlled trial. The study will be conducted as a single-center study at the Intensive Care of the Erasmus Medical Center.

Study population: We aim to include 40 adult patients who are admitted to the Intensive Care with hemodynamic instability (defined as mean arterial pressure < 65 mmHg and an arterial lactate concentration > 3.0 mmol/l) due to severe sepsis and septic shock.

Intervention: In the intervention group fluid management is targeted on peripheral perfusion parameters while in the control group fluid is administered in order to optimize cardiac output.

Main study parameters/endpoints: The main study endpoints are daily fluid balance and duration of mechanical ventilation.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is a possible risk that in the treatment group the patients will remain hypovolemic. To ensure that this will not occur, fluids will be administrated in this group, irrespective of peripheral perfusion parameters, until cardiac index is 2,5 L/min/m2. Assessment of peripheral perfusion is performed with non-invasive optical techniques that impose no burden to the patient.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 CE Rotterdam
      • Recruiting
      • ErasmusMC
      • Contact: Jasper v Bommel, MD,PhD; Email: j.vanbommel@erasmusmc.nl
      • Principal Investigator: Jasper v Bommel, MD,PhD
      • Sub-Investigator: Michel v Genderen, Msc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult patients (>18 years) admitted to the intensive care with 1) hemodynamic instability due to severe sepsis, and 2) a mean arterial pressure < 65 mmHg and 3) an arterial lactate concentration > 3.0 mmol/L will be considered for participation

Exclusion Criteria:

• moribund.
• severe coagulation disorder (contraindication for central venous catheter placement).
• severe peripheral vascular disease (interfering with peripheral perfusion measurement).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; The fluid management algorithm of the control group is based on the standard care procedure of our ICU as recommended in guidelines: the patient's fluid status is assessed by performing a fluid challenge with a bolus of 250 ml colloids. When the patients is fluid responsive (i.e. showing an increase in stroke volume > 10% ) he will receive an additional bolus of 250 ml of colloids. After each fluid challenge, patients will be revaluated for fluid responsiveness to access need of further fluid administration.
EXPERIMENTAL: PPTFM; The fluid management algorithm of the intervention group uses identical therapy (i.e. fluids) yet targeted at different endpoints (i.e. peripheral perfusion parameters). After evaluation of peripheral perfusion, only patients with a "bad peripheral perfusion" (i.e. 3 out of 4 criteria considered as bad) will receive a fluid challenge, the same way as in the standard care procedure (i.e. bolus of 250 ml of fluid). After each fluid challenge, patients will be re-evaluated for peripheral perfusion to access further need in fluid challenges. To ensure that no hypovolemia will occur in the intervention group, fluid will be administered irrespectively of peripheral perfusion parameters, if cardiac index falls below a value of 2,5 L/min/m2.	Other: PPTFM; Peripheral Perfusion Targeted Fluid Management; Other Names: CRT; PFI; delta Temp; StO2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid balance during Intensive Care Unit stay	Total and daily fuid balance for a maximal time period of 72 hours	untill 72 hours after admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRT (Capillary refill time)	Parameter of peripheral perfusion	Within 72 hours after admission
Systemic hemodynamic variables	Heart Rate; Mean Arterial Pressure; Cardiac Index; Cardiac output; Stroke Volume; Central Venous Pressure; Systemic Vascular Resistance	Untill 72 hours after admission to the ICU
Respiratory function	FiO2; PEEP; Breathing Frequency; pCO2; pO2	Untill 72 hours after admission to the ICU
PFI (Peripheral Flow Index)	Parameter of peripheral perfusion	Untill 72 hours after ICU admission
Tskindiff (Forearm-to-Fingertip temperature skin difference)	Parameter of peripheral perfusion	Untill 72 hours after ICU admission
StO2 (Peripheral tissue oxygenation)	Parameter of peripheral perfusion	Untill 72 hours after ICU admission

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Michel E Genderen, Drs, Erasmus Medical Center

Publications and helpful links

General Publications

• Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med. 2009 Mar;37(3):934-8. doi: 10.1097/CCM.0b013e31819869db.
• Lima A, van Bommel J, Sikorska K, van Genderen M, Klijn E, Lesaffre E, Ince C, Bakker J. The relation of near-infrared spectroscopy with changes in peripheral circulation in critically ill patients. Crit Care Med. 2011 Jul;39(7):1649-54. doi: 10.1097/CCM.0b013e3182186675.
• van Genderen ME, Engels N, van der Valk RJ, Lima A, Klijn E, Bakker J, van Bommel J. Early peripheral perfusion-guided fluid therapy in patients with septic shock. Am J Respir Crit Care Med. 2015 Feb 15;191(4):477-80. doi: 10.1164/rccm.201408-1575LE. No abstract available.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ANTICIPATED): January 1, 2014
• Study Completion (ANTICIPATED): January 1, 2014

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (ESTIMATE): July 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: critically ill patients; peripheral perfusion; fluid administration
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: NL34607.078.10