PERANAN LAKTAT PADA PASIEN KRITIS DI ICU Prof. Dr. dr. Made Wiryana, SpAn.KIC.KAO
History of Lactate Karl Scheele, 1780 found in sour milk Joseph Scherer the German physician-chemist after 70 years demonstrate the presence of lactate in human blood who had just died what we now call septic shock Carl Folwarczny, 1858, found lactate in the blood living patient Araki and Zilessen, increase lactate levels and tissue hypoxia ( Z Physiol Chem, 1891 )
Useless end-product or essential fuel?
BASIC CONCEPT OF HOMEOSTASIS THE QUALITY AND QUANTITY OF ORGAN/CELLULAR PERFUSION OR DELIVERY OF OXYGEN ( DO2 ) TO THE CELL DEPEND ON OXYGEN CONTENT AND CARDIAC OUTPUT FOR OXYGENATION AND PHOSPHORYLATION PROCESS IN MITOCHONDRIA DO2 = CaO2 x CO
Preload Contractility Afterload HR SV Hgb PaO 2 Sat % CO CaO 2 DO 2
PRINSIP PELAYANAN DI ICU Life Saving Resusitasi Terapi penyakit primer : medis dan pembedahan Supporting Terapi Closed Monitoring Support Psikologis Terhadap Pasien dan Keluarga
Lactate Levels THE EARLIEST, THE BETTER
Basal lactate production Total = 1290 mmol / 24 hours for 70 kg
Lactate Metabolism LIVER 60% MUSCLE KIDNEYS 10% 30% Excretion renal threshold = 5-6 mmol/l
Lactate Metabolism Produced by glycolysis in the muscles, skin, brain, intestine, and red blood cells Metabolised by the liver and lesser by the kidney Lactate can be transformed into oxaloacetate or alanine to produce glycogen and glucose by (glyco genesis, glucogenesis; Cori Cycle) Blood level less than 2 mmol/l although daily production is actually 1500 mmol/l
How is lactate produced? PDH If pyruvate production > oxidation in CAC then lactate formation increases
In the anaerobicstate
PLASMA + Larutan RINGER LACTATE Plasma Ringer laktat Laktat cepat dimetabolisme Na + = 140 meq/l Cl - = 102 meq/l SID= 38 meq/l Cation + = 137 meq/l Cl - = 109 meq/l 1 liter Laktat - = 28 meq/l SID = 0 meq/l 1 liter SID : 38
Normal ph setelah pemberian RINGER LACTATE Plasma = Na + = (140+137)/2 meq/l= 139 meq/l Cl - = (102+ 109)/2 meq/l = 105 meq/l Laktat - (termetabolisme) = 0 meq/l SID = 34 meq/l 2 liter SID : 34 lebih alkalosis dibanding jika diberikan NaCl 0.9%
UA = Unmeasured Anion: Laktat, acetoacetate, salisilat, metanol dll. K HCO 3 - SID K HCO 3 - Keto - SID A- A- Na + Na + Cl - Cl - Lactic/Keto asidosis Normal Ketosis
Why measure lactate? Diagnose of critical ill patients (severe sepsis) with elevated lactate as a diagnosis of tissue hypoperfusion Trigger for quantitative resuscitation if lactate is 4 mmol/l or more We suggest targeting resuscitation to normalize rapidly as possible
Why measure blood gas Diagnosis of hypoxia, hypo/hypercarbia, and acidosis Setting Mode of ventilation Value of oxygen content/ oxygen delivery Value of cardiac output Mixed venous O2
SURVIVING SEPSIS CAMPAIGN BUNDLES TO BE COMPLETED WITHIN 3 HOURS: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 ml/kg crystalloid for hypotension or lactate 4mmol/L TO BE COMPLETED WITHIN 6 HOURS: 5) Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/l (36 mg/dl): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated* *Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg, ScvO2 of 70%, and normalization of lactate
When lactate hypoperfusion Cardiogenic shock Haemorrhagic shock Septic shock if Catecholamine resistant Unresuscitated
When lactate hypoperfusion Accelerated aerobic glycolysis Carbohydrate metabolism > mitochondrial oxidative capacity Stimulated by catecholamines / cytokines e.g. leukocyte lactate in blood / lung (ARDS) Pyruvate build-up is the main issue Aggravated in sepsis by pyruvate dehydrogenase dysfunction
When lactate hypoperfusion 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
Hyperlactataemia (> 2mmol/L)
Hyperlactatemia Type A : Cause of tissue hypoxia (anaerobe) At a critical of oxygen delivery, oxygen consumption becomes limited, and this coincides with a sharp increase lactate level Type B : Aerobic metabolism Stimulating aerobic glucose metabolism and stimulating epinephrine/catecholamine has been shown to increase lactate levels Lactate Clearance???
Classification of lactic acidosis Type A Lactic Acidosis Associated with malperfusion / dysoxia Type B Lactic Acidosis In the absence of malperfusion / dysoxia B1 Disease states e.g. DKA, leukaemia, lymphoma, thiamine deficiency B2 Drugs e.g. metformin, cyanide, b agonists B3 Inborn errors of metabolism
Lactate and Acidosis The metabolism of glucose during hypoxia will increase production of lactate, ATP, and water H ion from water dissociation to maintain acid-base equilibrium by the addition of the strong ion lactate
How to Measure Lactate Levels Lactate can be measured by using various devices ( central laboratory or point-of-care blood gas analysers) The sampling site of the blood (arterial, venous, and capillary) does not seem to affect the results much When targeting changes in short intervals, it is not appropriate to use devices and sampling interchangeably
Clearance of Lactate The body is able to clear large lactate loads as shown the rapid decrease following exercise or return of circulation Several clinical conditions have been associated with impaired clearance: Liver dysfunction Cardiac surgery Increase glucose metabolism Sepsis
Prognosis Increased blood lactate have been related to morbidity and mortality In the ED and ICU blood lactate levels have a place in risk-stratification In the recent studies, not only one point in time measurements are related outcome but also the duration Lactate is a marker of recovery
Lactate as prognosticator in sepsis Dellinger et al, recommended measurement of lactate on initial presentation, elevated value signifying tissue hypoperfusion With aggressive resuscitation achieving lactate clearance 10% and ScvO2 70% increase survival rate Moreover studies: 10% in 2-6 hr increase in lactate clearance 11% decrease mortality Lactate clearance > 20% in 8 hour 22% Elevated initial and 24 hr significant predictors of mortality up to 67%
Reducing lactate levels by at least 20%/hour, significantly reduced ICU LOS, and also ICI mortality
So what do we do aboutit? Look for evidence of malperfusion If present augment CO & O 2 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!
Thank you