Ignite Creation Date:
2024-05-05 @ 4:35 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00270673
Status:
COMPLETED
Last Update Posted:
2008-04-25
First Post:
2005-12-23
Brief Title:
Early Lactate-Directed Therapy in the Intensive Care Unit ICU
Sponsor:
Erasmus Medical Center
Organization:
Erasmus Medical Center
Study Overview
Official Title:
Early Lactate-Directed Therapy on the ICU A Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2008-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Blood lactate levels have long been related to tissue hypoxia a severe condition in critically ill patients associated with the development of organ system failure and subsequent death Increased blood lactate levels and failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality However evidence of improved clinical outcome of lactate-directed therapy is limited and difference in the use of blood lactate monitoring in the intensive care unit exists between hospitals This warrants a study on the efficacy of early blood lactate-directed therapy In this study the efficacy of 8 hours of early lactate-directed therapy therapy aimed at resolving tissue hypoxia that is guided by serial blood lactate levels will be compared with 8 hours of control group therapy without lactate measurement
Detailed Description:
Tissue hypoxia can be defined as a state in which tissue oxygen demand is not met by tissue oxygen delivery DO2 The presence and persistence of tissue hypoxia is related to the development of organ system failure and subsequent death However definite clinical indicators of tissue hypoxia are lacking In experimental conditions a mismatch between oxygen delivery and oxygen demand resulting from either a progressive decrease of any of the components of oxygen delivery hemoglobin level arterial oxygen saturation and cardiac output or an increase in oxygen demand leads to increases in blood lactate levels However as lactate is a normal end product of metabolism other processes not related to tissue hypoxia have also been linked to increases in blood lactate levels In clinical conditions increased blood lactate levels and a failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality Even in hemodynamically stable patients with hyperlactatemia a condition referred to as compensated shock or occult hypoperfusion lactate levels are related to morbidity and mortality In our retrospective pilot study performed in the general ICU of the Erasmus MC n 931 we found 40 mortality in patients with blood lactate levels of 3 mmoll or higher in the early hours of ICU admission Blow at al implemented a treatment protocol to increase oxygen delivery guided by blood lactate levels in hemodynamically stable trauma patients with occult hypoperfusion Failure to correct hyperlactatemia after lactate-directed therapy correlated with increased mortality Rossi et al studied lactate-directed therapy in children undergoing congenital heart surgery However while showing a reduction in morbidity and mortality they used a historical control group Only one randomized controlled trial has been performed evaluating lactate-directed therapy This study of Polonen et al showed a decrease in morbidity and length of stay in post-cardiac surgery patients using lactate 2mmoll and mixed venous oxygen saturation SvO2 70 as goals of therapy Thus a relevant body of clinical evidence does not yet support routine monitoring of blood lactate levels and lactate-directed therapy in all critically ill patients As some investigators have even posed strong arguments that increased blood lactate levels are not related to the presence of tissue hypoxia in critically ill patients some clinicians use increased blood lactate levels to guide therapy whereas others hardly measure lactate levels The limited evidence of efficacy and the variable clinical use of blood lactate monitoring in different hospitals thus warrants a study on the clinical efficacy of blood lactate monitoring and blood lactate-directed therapy in the ICU
In general a monitor cannot influence outcome without an associated treatment protocol to guide treatment We will therefore study the clinical efficacy of repeated blood lactate measurements in combination with a predefined treatment protocol aimed at resolving tissue hypoxia during the first hours of intensive care treatment This pragmatic approach and also the early timing of the intervention are supported by the study of Rivers et al in which optimizing the balance between oxygen delivery and demand early in the treatment of patients with severe sepsis and septic shock resulted in a 16 absolute mortality reduction
The pre-defined treatment protocol will consist of components to
1 reduce oxygen demand 2 increase oxygen delivery and to 3 recruit the microcirculation
1 Reduction of metabolic oxygen demand has been successfully accomplished by preventing hyperthermia adequate analgesia or sedation and mechanical ventilation
2 Increasing oxygen delivery can be achieved by increasing any of the components of oxygen transport arterial oxygen saturation cardiac output and hemoglobin level However the oxygen delivering capabilities of stored red blood cells have been debated and adverse effects of red blood cell transfusion have been reported Best evidence suggests a restrictive transfusion policy in the ICU transfusion threshold 434 mmoll with an exception of severe ischemic cardiac disease
3 Administration after intravascular volume resuscitation of nitroglycerin reverses microcirculatory shutdown and shunting in septic shock patients In severe heart failure and cardiogenic shock microcirculatory alterations are also frequently encountered and vasodilation may reverse this condition Although the components of this treatment protocol are not innovative and will also be available in the standard therapy group guiding of this treatment by serial measurements of blood lactate levels is
Intensive care extensively impacts on health care resources Lactate-directed therapy aims at prevention of multiple organ failure MOF and subsequent death Patients with MOF account for a disproportionately high part of the ICU budget Moreover in general costs per ICU day are higher for non-survivors than for survivors Reduction in the use of ICU health care resources by lactate-directed therapy could thus result in an important economical benefit In some hospitals serial lactate measurements are routinely used on intensive care units In our retrospective pilot study we found that in 2004 the Erasmus MC intensive care unit performed on average 12 lactate measurements per patient per admission This resulted in a total of 28715 measurements with estimated external budget costs of 336000 If lactate-directed therapy appears equally or less effective than standard therapy blood lactate measurement in the ICU may not be indicated and resources could thus be saved Therefore both a positive and negative outcome of this randomized controlled trial would be clinically and economically relevant
The main research question of this study is in patients with increased initial blood lactate levels on admission to the ICU
1 will early lactate-directed therapy reduce mortality primary endpoint
2 will early lactate-directed therapy reduce morbidity
3 will early lactate-directed therapy reduce consumption of health care resources
In general a monitor cannot influence outcome without an associated treatment protocol to guide treatment We will therefore study the clinical efficacy of repeated blood lactate measurements in combination with a predefined treatment protocol aimed at resolving tissue hypoxia during the first hours of intensive care treatment This pragmatic approach and also the early timing of the intervention are supported by the study of Rivers et al in which optimizing the balance between oxygen delivery and demand early in the treatment of patients with severe sepsis and septic shock resulted in a 16 absolute mortality reduction
The pre-defined treatment protocol will consist of components to
1 reduce oxygen demand 2 increase oxygen delivery and to 3 recruit the microcirculation
1 Reduction of metabolic oxygen demand has been successfully accomplished by preventing hyperthermia adequate analgesia or sedation and mechanical ventilation
2 Increasing oxygen delivery can be achieved by increasing any of the components of oxygen transport arterial oxygen saturation cardiac output and hemoglobin level However the oxygen delivering capabilities of stored red blood cells have been debated and adverse effects of red blood cell transfusion have been reported Best evidence suggests a restrictive transfusion policy in the ICU transfusion threshold 434 mmoll with an exception of severe ischemic cardiac disease
3 Administration after intravascular volume resuscitation of nitroglycerin reverses microcirculatory shutdown and shunting in septic shock patients In severe heart failure and cardiogenic shock microcirculatory alterations are also frequently encountered and vasodilation may reverse this condition Although the components of this treatment protocol are not innovative and will also be available in the standard therapy group guiding of this treatment by serial measurements of blood lactate levels is
Intensive care extensively impacts on health care resources Lactate-directed therapy aims at prevention of multiple organ failure MOF and subsequent death Patients with MOF account for a disproportionately high part of the ICU budget Moreover in general costs per ICU day are higher for non-survivors than for survivors Reduction in the use of ICU health care resources by lactate-directed therapy could thus result in an important economical benefit In some hospitals serial lactate measurements are routinely used on intensive care units In our retrospective pilot study we found that in 2004 the Erasmus MC intensive care unit performed on average 12 lactate measurements per patient per admission This resulted in a total of 28715 measurements with estimated external budget costs of 336000 If lactate-directed therapy appears equally or less effective than standard therapy blood lactate measurement in the ICU may not be indicated and resources could thus be saved Therefore both a positive and negative outcome of this randomized controlled trial would be clinically and economically relevant
The main research question of this study is in patients with increased initial blood lactate levels on admission to the ICU
1 will early lactate-directed therapy reduce mortality primary endpoint
2 will early lactate-directed therapy reduce morbidity
3 will early lactate-directed therapy reduce consumption of health care resources
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None