Monitoring Resuscitation in Severe Sepsis and Septic Shock

Our hypothesis is that hemodynamic fluid resuscitation guided by dynamic parameters will improve outcome in patients with severe sepsis and septic shock, by limiting the deleterious effects of fluid overload.

Study Overview

• Status: Unknown
• Conditions: Hemodynamics
• Intervention / Treatment: Behavioral: Dynamic-parameters-guided fluid management; Behavioral: Standard-guided-fluid management

Detailed Description

To evaluate the efficacy of dynamic parameters versus static measures to guide fluid resuscitation we pretend to detect a 10% relative reduction in mortality. In addition, we pretend to observe an improvement on the length of resuscitation time, mechanical ventilation and vasopressor support-free days, ICU and hospital length of stay, organ failure and renal function.

• Study Type: Interventional
• Enrollment (Anticipated): 952
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Recruiting
      • Area de Critics. Hospital de Sabadell
      • Contact: Gemma Goma, RN; Phone Number: 21179 937231010; Email: ggoma@tauli.cat
      • Principal Investigator: Xaime Garcia, MD
      • Sub-Investigator: Guillem Gruartmoner, MD

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:

• Age > 18 years
• Clinical evidence of sepsis (microbiology confirmation, radiological or direct view - pus in biological fluid or surgical direct view-).

• ≥ 2 SIRS criteria:

  • Temperature < 36.0°C or > 38.0°C
  • Heart rate > 90 bpm
  • Respiratory rate > 20 rpm or PaCO2 < 32 mmHg or need of mechanical ventilation.
  • Leukocytes > 12.0 x109/L or < 4.0 x109/L

• Hemodynamic insufficiency defined as (at least one of the following):

  • Sustained systemic hypotension (systolic arterial pressure ≤ 90 mmHg or MAP < 65 mmHg) or a decrease in MAP of > 30 mm Hg in a hypertensive patient.
  • Need of vasopressors.
  • Tachycardia (HR > 110 bpm) or bradycardia (HR < 55 bpm)
  • Acute onset of oliguria, defined as a decreased urine output < 0.5 ml/kg/hr for ≥ 2 hours
  • Serum lactate > 2 mmol/l
  • Peripheral cyanosis, mottled skin, prolonged capillary refill
• Mechanical ventilation without any kind of inspiratory effort and Vt 7-10 mL/Kg, Pplateau < 30 mmH2O. Those patients with ARDS under mechanical ventilation will need to tolerate a tidal volume of at least 7 mL/Kg during 30 seconds while the plateau pressure remains < 30 mmH2O.
• Prior hemodynamic monitoring by arterial catheter.
• Central venous catheter.

Exclusion Criteria:

• Acute myocardial infarction < 7 days.
• Pregnancy
• Prior request of limited code status or expected life length lower than 3 months.
• Shock > 12h
• Cardiac arrhythmia
• Aortic valvular disease
• Inability to properly measure arterial pressure wave forms

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dynamic guide resuscitation; This arm follows a resuscitation protocol based on dynamic-parameters-guided fluid management.	Behavioral: Dynamic-parameters-guided fluid management; ● In preload-responsive patients defined by the following dynamic parameters: Patients fully adapted to mechanical ventilation* and with sinus rhythm.; PPV >12%. PPV: Pulse pressure variation PPV = (PPmax-PPmin)/ [(PPmax+PPmin)/2] x100 (during 5 respiratory cycles); SVV > 12% (15). SVV: Stroke volume variationA tidal volume (Vt) ≥ 7-10cc/kg in mechanically ventilated (in a controlled mode - control volume or control pressure) and well-adapted patients without any inspiratory effort should be guaranteed. Fluid loading must be performed with crystalloids (1omL/Kg) or colloids (5ml/Kg) every 30 minutes until PPV-SVV < 12%, while hypoperfusion signs are present. Continue resuscitation following Surviving Sepsis Campaign rules excluding more fluid administration (as described in the standard intervention once CVP>12). ● Non-preload responsive patients (defined as PPV or SVV < 12%) will resume the same protocol as responders when fluid response parameters are negative.
Active Comparator: Standard resuscitation; This arm follows a common resuscitation protocol based on Surviving Sepsis Campaign recommendations.	Behavioral: Standard-guided-fluid management; Fluid loading in patients with hypotension or elevated lactates until normalization of MAP (> 65mmHg) or CVP > 12mmHg. If CVP reaches > 12 mmHg and MAP remains < 65mmHg, norepinephrine should be started to reach MAP > 65mmHg. Once MAP is restored, if hypoperfusion signs persist (elevated lactate or urine output < 0.5mL/Kg/h), ScvO2/SvO2 must be measured. In order to reach a ScvO2 ≥70% or SVO2 ≥65%, consider giving blood transfusion if hemoglobin level (Hb) ≤ 7g/dL, and also consider dobutamine (initial dose 2,5 µg/kg/min, increased by 2,5 µg/kg/min every 30 min up to a maximum dose of 20 µg/kg/min, presence of arrhythmia, or FC>110bpm). At that point, if hypoperfusion signs remain present, consider restart protocol from the beginning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mortality at 28 days	28 days after hospital admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of resuscitation	Vasopressor use and fluid load between 0h to 6h; Vasopressor use and fluid load between 7h to 72h	72 hours after protocol inclusion
Ventilator-free days	From 1 to 28 days over 28 days in a month.	28 days after admission
Vasopressor-free days	From 1 to 28 days over 28 days in a month.	28 days after admission
Organ failure-free days	Cardiovascular, CNS, renal, hepatic, coagulation abnormalities. From 1 to 28 days over 28 days in a month.	28 days after admission
ICU length of stay		At ICU discharge (expected average 30 days after admission)
Hospital length of stay		At hospital discharge (expected average 45 days after hospital admission)
Renal function evolution	Creatinin clearance will be calculated every day for the first 3 days (Cockroft-Gault formula).	3 days after study enrollment
Mortality at 3 months		3 months after admission

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli

Publications and helpful links

Helpful Links

• Spanish webpage of the study

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): February 1, 2015
• Study Completion (Anticipated): May 1, 2015

Study Registration Dates

• First Submitted: November 29, 2012
• First Submitted That Met QC Criteria: December 10, 2012
• First Posted (Estimate): December 11, 2012

Study Record Updates

• Last Update Posted (Estimate): February 13, 2014
• Last Update Submitted That Met QC Criteria: February 12, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis
• Other Study ID Numbers: MORESS