Peripheral Perfusion Versus Lactate Targeted Fluid Resuscitation in Septic Shock: ANDROMEDA-SHOCK PHYSIOLOGY STUDY
试验速览
- 阶段
- 不适用
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Amount of resuscitation fluids
研究概览
简要总结
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.
详细描述
GENERAL OBJECTIVE To demonstrate that a CRT-targeted FR is associated with less positive fluid balances, organ dysfunctions, and similar improvement of markers of tissue hypoperfusion and hypoxia, when compared to a lactate- targeted FR.
SPECIFIC OBJECTIVES
- To determine if normalization of CRT is associated with less fluid resuscitation and positive 24-h fluid balances as compared to lactate-targeted resuscitation.
- To determine if normalization of CRT is associated with less organ dysfunctions as compared to lactate-targeted resuscitation.
- To determine if CRT-targeted resuscitation compared to lactate-targeted resuscitation leads to similar improvement in markers of tissue hypoperfusion or hypoxia at the end of fluid resuscitation
- To determine if normality of all the selected hypoperfusion variables (central venous oxygen saturation (ScvO2), central venous to arterial carbon dioxide pressure difference (P(cv-a)CO2), and CRT) at different time-points in septic shock patients can predict the absence of tissue hypoperfusion and hypoxia.
For this Research Project, several variables of tissue hypoperfusion that can only be assessed by special perfusion-monitoring techniques were included.
Sublingual microcirculatory assessment: Sublingual microcirculatory alterations have been well described in septic shock patients. Functional capillary density and microvascular blood flow are decreased, while heterogeneity is markedly enhanced. These alterations have been shown to be prognostic, with a rapid improvement in survivors but a progressive decline in nonsurvivors. A microcirculatory flow index (MFI) ≤ 2.5 and a proportion of perfused vessels (PPV) < 80% will be considered as categorical of microcirculatory hypoperfusion Liver blood flow: Plasma disappearance rate (PDR) of indocyanine green (ICG), with a non-invasive transcutaneous assessment of ICG clearance. Normal range is 18% to 25% per minute with a value < 15%/min categorically abnormal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
CRT guided resuscitation
Fluid resuscitation will be aimed at normalizing capillary refill time (CRT) during the intervention period. Fluid challenges will be administered at a rate of 500 ml of crystalloids over 30 minutes, with reassessment of CRT until achieving normal values, or the patient becomes fluid unresponsive, or a safety issue develops.
干预措施: CRT guided resuscitation (Other)
Lactate guided resuscitation
Fluid resuscitation will be aimed at normalizing or decreasing lactate levels by more than 20% every 2 hours during the intervention during the intervention period. Fluid challenges will be administered at a rate of 500 ml of crystalloids over 30 minutes, with reassessment of lactate every 2 hours until reaching target, or the patient becomes fluid unresponsive, or a safety issue develops.
干预措施: Lactate guided resuscitation (Other)
结局指标
主要结局
Amount of resuscitation fluids
时间窗: at six hours
The total amount of fluids administered as fluid challenges from baseline to 6 hours after starting protocol
次要结局
- Sublingual microcirculation(at baseline, 6 hours and 24 hours)
- Multiple organ dysfunction(At 24 hours, 48 hours and 72 hours)
- Hepato-splanchnic blood flow(At baseline, 6 hours and 24 hours)
- Ccv-aCO2/Da-vO2 ratio(At baseline, 6 hours and 24 hours)
- Muscle tissue oxygenation(At baseline, 6 hours and 24 hours)
- Lactate/Pyruvate ratio(At baseline, 6 hours and 24 hours)
- Total fluid balance(at 24 hours)
研究者
Glenn Hernández
Titular Professor
Pontificia Universidad Catolica de Chile