Septic Shock Clinical Trial
Official title:
Peripheral Perfusion Versus Lactate Targeted Fluid Resuscitation in Septic Shock: ANDROMEDA-SHOCK PHYSIOLOGY STUDY
Persistent hyperlactatemia has been traditionally considered as representing tissue hypoxia,
and lactate normalization is recommended as a resuscitation target by the Surviving Sepsis
Campaign (SSC). However, other sources contribute to hyperlactatemia such as sustained
adrenergic activity and impaired lactate clearance. Only hypoperfusion-related
hyperlactatemia might be reversed by optimizing systemic blood flow.
Fluid resuscitation (FR) is used to improve cardiac output (CO) in septic shock to correct
hypoperfusion. Nevertheless, if persistent hyperlactatemia is not hypoxia-related, excessive
FR could lead to flow overload. In addition, kinetics of recovery of lactate is relatively
slow, and thus it might be a suboptimal target for FR.
Peripheral perfusion appears as a promising alternative target. Abnormal capillary refill
time (CRT) is frequently used as trigger for FR in septic shock. Studies demonstrated the
strong prognostic value of persistent abnormal peripheral perfusion, and some recent data
suggest that targeting FR on CRT normalization could be associated with less fluid loading
and organ dysfunctions. The excellent prognosis associated with CRT recovery, the
rapid-response time to fluid loading, its simplicity, and its availability in
resource-limited settings, constitute a strong background to promote studies evaluating its
usefulness to guide FR .
The study hypothesis is that a CRT-targeted FR is associated with less positive fluid
balances, organ dysfunctions, and at least similar improvement of tissue hypoperfusion or
hypoxia, when compared to a lactate-targeted FR. To test this hypothesis, the investigators
designed a clinical physiological, randomized controlled trial in septic shock patients.
Recruited patients will be randomized to FR aimed at normalizing CRT or normalizing or
decreasing lactate >20% every 2 h during the study period. Fluid challenges (500 ml in 30 min
intervals) will be repeated until perfusion target is achieved, or dynamic predictors of
fluid responsiveness become negative, or a safety limit is reached. The design of our study
is aimed at: a) determining if CRT targeted resuscitation is associated with less fluid
resuscitation and fluid balances; b) determining if this strategy is associated with less
organ dysfunctions; and c) if it results in similar improvement in markers of tissue
hypoperfusion or hypoxia such as hepato-splanchnic blood flow or microcirculatory perfusion.
Status | Recruiting |
Enrollment | 46 |
Est. completion date | December 31, 2019 |
Est. primary completion date | September 30, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 90 Years |
Eligibility |
Inclusion Criteria: - Septic shock diagnosed at ICU admission according to the Sepsis-3 Consensus Conference [35], basically septic patients with hypotension requiring norepinephrine (NE) to maintain a mean arterial pressure (MAP) of 65 mmHg, and serum lactate levels > 2 mmol/l after initial fluid resuscitation. - Less than 24 h after fulfilling criteria for septic shock - Positive fluid responsiveness assessment Exclusion Criteria: - 1. Pregnancy - Anticipated surgery or dialytic procedure during the first 6h after septic shock diagnosis - Do-not-resuscitate status - Child B or C liver cirrhosis - Active bleeding - Severe concomitant acute respiratory distress syndrome (ARDS) |
Country | Name | City | State |
---|---|---|---|
Chile | Pontificia Universidad Catolica de Chile | Santiago | Metropolitana |
Lead Sponsor | Collaborator |
---|---|
Pontificia Universidad Catolica de Chile | Comisión Nacional de Investigación Científica y Tecnológica |
Chile,
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* Note: There are 38 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Amount of resuscitation fluids | The total amount of fluids administered as fluid challenges from baseline to 6 hours after starting protocol | at six hours | |
Secondary | Total fluid balance | Balance of fluids in the first 24h (inputs-outputs) | at 24 hours | |
Secondary | Multiple organ dysfunction | Sequential Organ Failure Assessment (SOFA) scores assessed at baseline, 24 hours, 48 hours and 72 hours. The scale range is from 0 points to 24 points, where 0 points represent normality and no organ dysfunction, and 24 points severe organ dysfunction for the six organs evaluated. More than 10 points is considered severe organ dysfunction. The six organs evaluated in the Sequential Organ Failure Assessment score are: lungs, cardiovascular system, coagulation, liver, kidneys, and central nervous system. All six organs are evaluated from 0 (normal function) to 4 (severe dysfunction) and these sub-scores are summed to get the total SOFA score. |
At 24 hours, 48 hours and 72 hours | |
Secondary | Sublingual microcirculation | Evaluation of sublingual microcirculation by SDF: Videos will be taken at the sublingual mucosa with the SDF device. Two parameters will be calculated systematically by off-line video analysis according to consensus recommendations: MFI (normal value 3.0, with <2.5 considered as abnormal (range 0-3); and PPV where 100% is normal, with <80% representing clear abnormalities (range 0-100%) | at baseline, 6 hours and 24 hours | |
Secondary | Hepato-splanchnic blood flow | Evaluation of hepato-splanchnic blood flow by ICG clearance: calculation of plasma dissapearance of ICG with normal values >18% in 15 minutes | At baseline, 6 hours and 24 hours | |
Secondary | Muscle tissue oxygenation | Evaluation of muscle tissue oxygen saturation by NIRS (normal value >75%) | At baseline, 6 hours and 24 hours | |
Secondary | Ccv-aCO2/Da-vO2 ratio | Assessed by the Ccv-aCO2/Da-vO2 ratio as a marker of tissue hypoxia: normal value <1 | At baseline, 6 hours and 24 hours | |
Secondary | Lactate/Pyruvate ratio | Assessed by the L/P ratio as another marker of tissue hypoxia. Normal value 10 | At baseline, 6 hours and 24 hours |
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