Microcirculation Properties of Albumin for Fluid Resuscitation in Septic Shock

Study Overview
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Brief Summary
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The sublingual microcirculation is impaired in sepsis and septic shock. Sidestream dark field imaging technology has been developed into a clinical tool to help the clinician assess the microcirculation at the bedside. The ideal resuscitation fluid has not been identified. The investigators aim to use this new bedside technology to establish the microcirculation properties of two popular resuscitation fluids.

Detailed Description
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Sepsis and septic shock are diseases of the microcirculation. Recent developments in microcirculation imaging have illustrated the extent of the impairment of the microcirculation in these diseases of critical care. Heterogenous flow, stagnation and microthrombi can all be seen clearly in the sublingual region using a sidestream dark field imaging device. One of the key treatments for sepsis and septic shock is timely administration of intravenous fluids. Which fluid is administered is a matter for debate which has not been settled by several large trials. De-resuscitation has become increasingly important as physicians realise the implications and associated risks of excess fluid administration in ICU. Avoiding excess fluid administration at the resuscitation stage is therefore desirable. One of the prevailing theories about the function of albumin or colloid resuscitation is that it remains in the the intravascular space for a longer period of time, thereby continuing to benefit the patient and avoiding administration of excess fluid. However, recently albumin was tested against crystalloid for resuscitation and was shown to be effective but with no improvement in survival. It is possible, however, that albumin is having an initial beneficial effect at a microcirculation level. Macrohaemodynamic improvements are not necessarily matched by improvements in blood flow and oxygen delivery to cells, this has been referred to as haemodynamic incoherence. This randomised, prospective study aims to compare crystalloid and albumin resuscitation at a microcirculation level.

Official Title
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The Effect of Fluid Resuscitation With 20% Albumin Versus Crystalloid on the Microcirculation of Patients With Sepsis

Conditions
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Sepsis, Severe, Sepsis, Septic Shock

Intervention / Treatment
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* Other: 20% Albumin
* Other: Crystalloid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sepsis; suspected source of infection, tachycardia, tachypneic, hyperlactatemia, hypotensive requiring vasopressors, febrile >38.5degrees Celsius Fluid responsive; pulse pressure variability >10% or passive leg raise positive Exclusion Criteria: Fluid overloaded; pulmonary oedema, significant peripheral oedema Heart Failure, cardiogenic shock, recent MI Receiving regular albumin 20%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional 20% Albumin<br>Septic patients requiring a fluid bolus randomised to receive 100ml 20% albumin as boluses until they are stable or no longer require fluid resuscitation. | Other: 20% Albumin<br>* 100ml boluses 20% Albumin<br>|
| Active Comparator: Control Crystalloid<br>Septic patients requiring a fluid bolus randomised to receive 250ml boluses of crystalloid fluid until they no longer require fluid resuscitation. | Other: Crystalloid<br>* 250ml bolus of crystalloid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Microcirculation parameters in response to a fluid bolus | functional capillary density, perfused capillary density after fluid bolus Proportion Perfused vessels Microvascular Flow Index Total Vessel Density | Baseline at recruitment before fluid given, during bolus, after bolus: immediately after, 60 minutes after and 24 hours after to determine if immediate, delayed or sustained change in microcirculation parameters is influenced by fluid bolus | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of vasopressor administration |  | 28 days | 
| Duration of Mechanical ventilation |  | 28 days | 
| ICU length of stay |  | though to stud completion; up to 1 year | 
| 28 day mortality |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microcirculation, sidestream dark field