logging in or signing up Lactate Overview fergua Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Copy Does not support media & animations WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 3002 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: December 13, 2007 This Presentation is Public Favorites: 3 Presentation Description No description available. Comments Posting comment... By: elsaied_sh (19 month(s) ago) thannnnnnnnnnnnnnnnks Saving..... Post Reply Close Saving..... Edit Comment Close By: KHALIDSHAH (27 month(s) ago) As i am an intensivist..can i download it for my personal knowledge..thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: drrupii (42 month(s) ago) Hi Dr.Ferguson, I am anesthesiologist intensivist in Semarang-Indonesia. I am interest with your presentation, because in my place many people "afraid" and misperception about lactate. So if you don't mind please send me your slide for education only,espescially in my place.Thank you Saving..... Post Reply Close Saving..... Edit Comment Close By: ntqphuong (46 month(s) ago) thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: survivesepsis (53 month(s) ago) Dr Ferguson I would really like to be able to download this presentation. Can you send it to me or a link that would allow. I will embed your name in any of your slides so that it is clearr they are yours. Saving..... Post Reply Close Saving..... Edit Comment Close loading.... See all Premium member Presentation Transcript Slide1: Will the real please step forward? Dr. Andrew Ferguson MEd FRCA DIBICM FCCP Attending IntensivistDogma….: Dogma…. A concept or principle accepted as absolute truth on the basis of unquestioned acceptance of an authority's statement to that effect rather than on the basis of logical reasoning or demonstrated proof A blind belief in things often without a material base Slide3: Useless end-product or essential fuel?The traditional view…: The traditional view… “ current thinking continues to interpret hyperlactacidemia as hypoxia and to support stimulation of cardiac output and enhancement of oxygen delivery as therapy” James JH, Luchette FA, McCarter F, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999; 354: 505-508So doesn’t that mean that…?: So doesn’t that mean that…?Hyperlactataemia (> 2mmol/L): Hyperlactataemia (> 2mmol/L)Basal lactate production: Basal lactate production Total = 1290 mmol / 24 hours for 70 kgHow is lactate produced?: How is lactate produced? If pyruvate production > oxidation in CAC then lactate formation increases PDH SO… Anything that increases glycolysis can increase lactataemia once pyruvate oxidation is overwhelmed NOT just anaerobic metabolism!: SO… Anything that increases glycolysis can increase lactataemia once pyruvate oxidation is overwhelmed NOT just anaerobic metabolism!In the anaerobic state…: In the anaerobic state…Another way to look at it…: Another way to look at it… Schurr A. Lactate: the ultimate cerebral oxidative energy substrate? Journal of Cerebral Blood Flow & Metabolism 2006; 26: 142-152Lactate/pyruvate ratio: Lactate/pyruvate ratio Lactate/pyruvate = K x (NADH/NAD) x H+When lactate hypoperfusion: When lactate hypoperfusionWhen lactate hypoperfusion: When lactate hypoperfusionEpinephrine and lactate production: Epinephrine and lactate productionSlide16: Muscle tissue central to this 40% of total cell mass of body b2 receptors 99% of muscle adrenergic receptors In stress and resuscitated sepsis: Adrenaline activates glycolysis producing ATP Adrenaline activates Na/K-ATPase using ATP Increased glycolysis increases lactate Lactate not produced if Na/K-ATPase blocked Independent of tissue hypoxia Lactate overproduction blocked by b2 blockade Epinephrine and lactate productionSlide17: Reduced lactate clearance Conflicting data depending on technique and initial lactate Possibly contributes to mild hyperlactataemia Unlikely to play major role in cases where production is near normal Pyruvate dehydrogenase dysfunction PDH shifts pyruvate to Kreb’s cycle not to lactate Sub-normal levels in muscle in sepsis Function restored by dichloroacetate which also reduces lactate level Protein catabolism AA’s converted to pyruvate then lactate Inhibition of mitochondrial respiration Sepsis, drugs e.g. metformin (rare), cyanide, antiretrovirals When lactate hypoperfusionLactate Metabolism: Lactate Metabolism LIVER 60% KIDNEYS 30% Excretion renal threshold = 5-6 mmol/L MUSCLE 10%What happens to the lactate?: What happens to the lactate? Gluconeogenesis 20% – Cori cycle in liver 2 CH3 CHOH COO- + 2H+ = C6H12O6 Glucose production uses 6 ATP from b oxidation of fatty acids LACTATE SHUTTLE: aerobic lactate used to move carbons for oxidation/gluconeogenesis at critical time Hyperlactataemia = adaptive response Lactate is a “stress fuel” used by heart and brain Reduced lactate in heart reduces cardiac function in shock Oxidation 80% CH3 CHOH COO- + H+ + 3 O2 = 3 CO2 + 3 H2O Classification of lactic acidosis: Classification of lactic acidosisPrognostic value: Prognostic value Source doesn’t matter High lactate still a marker of severe physiological stress and risk of death High lactate often not hypoxia related but represents metabolic changes of severe stressSo what do we do about it?: So what do we do about it? Look for evidence of malperfusion If present augment CO & O2 delivery BUT don’t do this just for the lactate level TREAT the malperfusion not the lactate Consider the other reasons for high lactate Lactate is the messenger…don’t shoot it! References: References Levy B. Lactate and shock state: the metabolic view. Curr Opin Crit Care 2006; 12: 315-321 Cohen RD, Simpson R. Lactate metabolism. Anesthesiology 1975; 43: 661-673 De Backer D. Lactic acidosis. Intensive care Med 2003; 29: 699-702 Levy B, Gibot S, Franck P, Cravoisy A, Bollaert P-E. Relation between muscle Na+K+ ATPase activity and raised lactate concentration in septic shock: a prospective study. Lancet 2005; 365:871-875 Trzeciak S, Dellinger RP, Chansky ME, Arnold RC, Schorr C, Milcarek B, Hollenberg SM, Parrillo JE. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33: 970-977 James JH, Luchette FA, McCarter F, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999; 354: 505-508 Matejovic M, Radermacher P, Fontaine E. Lactate in shock: a high-octane fuel for the heart? Intensive Care Med 2007; 33: 406-408 Schurr A. Lactate: the ultimate cerebral oxidative energy substrate? Journal of Cerebral Blood Flow & Metabolism 2006; 26: 142-152 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Lactate Overview fergua Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINTLite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: Embed: Flash iPad Copy Does not support media & animations WordPress Embed Customize Embed URL: Copy Thumbnail: Copy The presentation is successfully added In Your Favorites. Views: 3002 Category: Science & Tech.. License: All Rights Reserved Like it (0) Dislike it (0) Added: December 13, 2007 This Presentation is Public Favorites: 3 Presentation Description No description available. Comments Posting comment... By: elsaied_sh (19 month(s) ago) thannnnnnnnnnnnnnnnks Saving..... Post Reply Close Saving..... Edit Comment Close By: KHALIDSHAH (27 month(s) ago) As i am an intensivist..can i download it for my personal knowledge..thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: drrupii (42 month(s) ago) Hi Dr.Ferguson, I am anesthesiologist intensivist in Semarang-Indonesia. I am interest with your presentation, because in my place many people "afraid" and misperception about lactate. So if you don't mind please send me your slide for education only,espescially in my place.Thank you Saving..... Post Reply Close Saving..... Edit Comment Close By: ntqphuong (46 month(s) ago) thanks Saving..... Post Reply Close Saving..... Edit Comment Close By: survivesepsis (53 month(s) ago) Dr Ferguson I would really like to be able to download this presentation. Can you send it to me or a link that would allow. I will embed your name in any of your slides so that it is clearr they are yours. Saving..... Post Reply Close Saving..... Edit Comment Close loading.... See all Premium member Presentation Transcript Slide1: Will the real please step forward? Dr. Andrew Ferguson MEd FRCA DIBICM FCCP Attending IntensivistDogma….: Dogma…. A concept or principle accepted as absolute truth on the basis of unquestioned acceptance of an authority's statement to that effect rather than on the basis of logical reasoning or demonstrated proof A blind belief in things often without a material base Slide3: Useless end-product or essential fuel?The traditional view…: The traditional view… “ current thinking continues to interpret hyperlactacidemia as hypoxia and to support stimulation of cardiac output and enhancement of oxygen delivery as therapy” James JH, Luchette FA, McCarter F, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999; 354: 505-508So doesn’t that mean that…?: So doesn’t that mean that…?Hyperlactataemia (> 2mmol/L): Hyperlactataemia (> 2mmol/L)Basal lactate production: Basal lactate production Total = 1290 mmol / 24 hours for 70 kgHow is lactate produced?: How is lactate produced? If pyruvate production > oxidation in CAC then lactate formation increases PDH SO… Anything that increases glycolysis can increase lactataemia once pyruvate oxidation is overwhelmed NOT just anaerobic metabolism!: SO… Anything that increases glycolysis can increase lactataemia once pyruvate oxidation is overwhelmed NOT just anaerobic metabolism!In the anaerobic state…: In the anaerobic state…Another way to look at it…: Another way to look at it… Schurr A. Lactate: the ultimate cerebral oxidative energy substrate? Journal of Cerebral Blood Flow & Metabolism 2006; 26: 142-152Lactate/pyruvate ratio: Lactate/pyruvate ratio Lactate/pyruvate = K x (NADH/NAD) x H+When lactate hypoperfusion: When lactate hypoperfusionWhen lactate hypoperfusion: When lactate hypoperfusionEpinephrine and lactate production: Epinephrine and lactate productionSlide16: Muscle tissue central to this 40% of total cell mass of body b2 receptors 99% of muscle adrenergic receptors In stress and resuscitated sepsis: Adrenaline activates glycolysis producing ATP Adrenaline activates Na/K-ATPase using ATP Increased glycolysis increases lactate Lactate not produced if Na/K-ATPase blocked Independent of tissue hypoxia Lactate overproduction blocked by b2 blockade Epinephrine and lactate productionSlide17: Reduced lactate clearance Conflicting data depending on technique and initial lactate Possibly contributes to mild hyperlactataemia Unlikely to play major role in cases where production is near normal Pyruvate dehydrogenase dysfunction PDH shifts pyruvate to Kreb’s cycle not to lactate Sub-normal levels in muscle in sepsis Function restored by dichloroacetate which also reduces lactate level Protein catabolism AA’s converted to pyruvate then lactate Inhibition of mitochondrial respiration Sepsis, drugs e.g. metformin (rare), cyanide, antiretrovirals When lactate hypoperfusionLactate Metabolism: Lactate Metabolism LIVER 60% KIDNEYS 30% Excretion renal threshold = 5-6 mmol/L MUSCLE 10%What happens to the lactate?: What happens to the lactate? Gluconeogenesis 20% – Cori cycle in liver 2 CH3 CHOH COO- + 2H+ = C6H12O6 Glucose production uses 6 ATP from b oxidation of fatty acids LACTATE SHUTTLE: aerobic lactate used to move carbons for oxidation/gluconeogenesis at critical time Hyperlactataemia = adaptive response Lactate is a “stress fuel” used by heart and brain Reduced lactate in heart reduces cardiac function in shock Oxidation 80% CH3 CHOH COO- + H+ + 3 O2 = 3 CO2 + 3 H2O Classification of lactic acidosis: Classification of lactic acidosisPrognostic value: Prognostic value Source doesn’t matter High lactate still a marker of severe physiological stress and risk of death High lactate often not hypoxia related but represents metabolic changes of severe stressSo what do we do about it?: So what do we do about it? Look for evidence of malperfusion If present augment CO & O2 delivery BUT don’t do this just for the lactate level TREAT the malperfusion not the lactate Consider the other reasons for high lactate Lactate is the messenger…don’t shoot it! References: References Levy B. Lactate and shock state: the metabolic view. Curr Opin Crit Care 2006; 12: 315-321 Cohen RD, Simpson R. Lactate metabolism. Anesthesiology 1975; 43: 661-673 De Backer D. Lactic acidosis. Intensive care Med 2003; 29: 699-702 Levy B, Gibot S, Franck P, Cravoisy A, Bollaert P-E. Relation between muscle Na+K+ ATPase activity and raised lactate concentration in septic shock: a prospective study. Lancet 2005; 365:871-875 Trzeciak S, Dellinger RP, Chansky ME, Arnold RC, Schorr C, Milcarek B, Hollenberg SM, Parrillo JE. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33: 970-977 James JH, Luchette FA, McCarter F, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999; 354: 505-508 Matejovic M, Radermacher P, Fontaine E. Lactate in shock: a high-octane fuel for the heart? Intensive Care Med 2007; 33: 406-408 Schurr A. Lactate: the ultimate cerebral oxidative energy substrate? Journal of Cerebral Blood Flow & Metabolism 2006; 26: 142-152