HYPERLACTATEMIAHYPERLACTATEMIA

Renie Traiforos, R3Renie Traiforos, R3

Lab roundsLab rounds

August 28, 2008August 28, 2008

OUTLINEOUTLINE

CaseCase Definitions – lactate, hyperlactatemia, Definitions – lactate, hyperlactatemia,

lactic acidosis.lactic acidosis. PathophysiologyPathophysiology Causes of elevated lactate/lactic acidosis.Causes of elevated lactate/lactic acidosis. Significance of elevated lactateSignificance of elevated lactate Source of blood for sampling the lactate??Source of blood for sampling the lactate?? Summary/take home messageSummary/take home message

CASECASE

57 yr old female c/o difficulty breathing x 2 57 yr old female c/o difficulty breathing x 2 days. Hx of cough, sore throat & nasal days. Hx of cough, sore throat & nasal congestion.congestion.

Past med significant for smoking & ?COPDPast med significant for smoking & ?COPD Brought in by EMS – worsening SOB and Brought in by EMS – worsening SOB and

chest pain.chest pain. Initial assessment: diaphoretic, appears Initial assessment: diaphoretic, appears

slightly distressed. RR 22-24, HR 128, slightly distressed. RR 22-24, HR 128, 113/79, T36.9113/79, T36.9

CASE – cont’dCASE – cont’d

Hgb 180, Wbc 37, bands 13, platelets Hgb 180, Wbc 37, bands 13, platelets 178,178,

creatinine 189, Na 128, K 4.9, Cl 90, creatinine 189, Na 128, K 4.9, Cl 90, CO2 20CO2 20

ABG 7.26/46/90/20/-7. lactate 3.5ABG 7.26/46/90/20/-7. lactate 3.5 CXR – large LLL consolidationCXR – large LLL consolidation

CASE – cont’dCASE – cont’d

Worsens in the ED (Incr RR, then Worsens in the ED (Incr RR, then fatigued, more tachycardic, fatigued, more tachycardic, developed hypotension) developed hypotension)

Rpt ABG: 7.17/53/92/19/-11. lactate 5Rpt ABG: 7.17/53/92/19/-11. lactate 5 Intubated for impending respiratory Intubated for impending respiratory

failure. ICU admissionfailure. ICU admission..

DEFINITIONSDEFINITIONS

LACTATE: LACTATE: A three carbon intermediary A three carbon intermediary of carbohydrate metabolism, generated of carbohydrate metabolism, generated from pyruvate with lactate dehydrogenase from pyruvate with lactate dehydrogenase as a catalyst.as a catalyst.

Under normal circumstances, it made in Under normal circumstances, it made in skeletal muscle, brain, skin & erythrocytes skeletal muscle, brain, skin & erythrocytes and it metabolized in the liver & kidney.and it metabolized in the liver & kidney.

N levels: <2 mmol/L (various cutoffs N levels: <2 mmol/L (various cutoffs reported)reported)

HYPERLACTATEMIA then is a blood HYPERLACTATEMIA then is a blood lactate level greater than 2 mmol/L.lactate level greater than 2 mmol/L.

Sometimes see this subdivided into Sometimes see this subdivided into

““mild to moderate” is 2-4 mmol/L and mild to moderate” is 2-4 mmol/L and “severe” hyperlactatemia is > 4 “severe” hyperlactatemia is > 4 mmol/Lmmol/L

DEFINITIONSDEFINITIONS

LACTIC ACIDOSISLACTIC ACIDOSIS: : [lactate] >4 mmol/L + metabolic [lactate] >4 mmol/L + metabolic

acidosisacidosis Occurs when lactate production Occurs when lactate production

exceeds lactate use or metabolismexceeds lactate use or metabolism Classically seen as a wide anion gap Classically seen as a wide anion gap

metabolic acidosismetabolic acidosis

LACTATE FORMATIONLACTATE FORMATION

Glycolysis converts glucose into pyruvate.Glycolysis converts glucose into pyruvate. Pyruvate may be transported across Pyruvate may be transported across

mitochondrial membranes and metabolized mitochondrial membranes and metabolized in Krebs cycle (aerobic cond’ns). in Krebs cycle (aerobic cond’ns).

Or under anaerobic conditions, pyruvate is Or under anaerobic conditions, pyruvate is oxidized to oxidized to lactatelactate by lactate by lactate dehydrogenase. This is a reversible dehydrogenase. This is a reversible reaction within the liver & kidney, requiring reaction within the liver & kidney, requiring the coenzyme NAD+ (the Cori cycle)the coenzyme NAD+ (the Cori cycle)

LACTATE FORMATIONLACTATE FORMATION

The Cori CycleThe Cori Cycle

Causes of HyperlactatemiaCauses of Hyperlactatemia

Elevated lactate can occur due to:Elevated lactate can occur due to: excessive tissue lactate production excessive tissue lactate production impaired hepatic metabolism of lactateimpaired hepatic metabolism of lactateIn most clinical cases it is probable that both processes are In most clinical cases it is probable that both processes are

contributing.contributing.

Almost always discussed in the texts as a Almost always discussed in the texts as a differential for lactic acidosis. But just differential for lactic acidosis. But just remember that depending on buffer remember that depending on buffer reserves and concurrent acid-base reserves and concurrent acid-base disturbances, hyperlactatemia may or may disturbances, hyperlactatemia may or may not be associated with acidemia.not be associated with acidemia.

CLASSIFICATION of LACTIC CLASSIFICATION of LACTIC ACIDOSISACIDOSIS

Cohen – Woods classification systemCohen – Woods classification system

Type A: Due to tissue hypoxiaType A: Due to tissue hypoxia Tissue hypoperfusion (global – shock, Tissue hypoperfusion (global – shock,

hypotension, cardiac arrest. regional – hypotension, cardiac arrest. regional – mesenteric ischemia)mesenteric ischemia)

Reduced tissue 02 delivery (hypoxemia, Reduced tissue 02 delivery (hypoxemia, severe anemia, CO poisoning)severe anemia, CO poisoning)

Anaerobic muscular activity (seizures, Anaerobic muscular activity (seizures, extreme exerciseextreme exercise))

LACTIC ACIDOSIS – LACTIC ACIDOSIS – classification classification

Type B: Not due to tissue hypoxia. 3 Type B: Not due to tissue hypoxia. 3 subtypes: subtypes:

B1B1- is due to systemic disorders (note – can - is due to systemic disorders (note – can lead to Type A) lead to Type A) Eg, renal or hepatic dysfunction, Eg, renal or hepatic dysfunction, sepsis, DM, neoplasms, severe malnutritionsepsis, DM, neoplasms, severe malnutrition

B2B2- is due to medications/intoxications. - is due to medications/intoxications. Eg, Eg, cyanide, salicylates, methanol, ethanol, ethylene cyanide, salicylates, methanol, ethanol, ethylene glycol, anti-retrovirals, INH, nitroprusside, biguanides.glycol, anti-retrovirals, INH, nitroprusside, biguanides.

B3B3 - is due to hereditary inborn errors of - is due to hereditary inborn errors of metabolism. metabolism. Eg, G-6-PD, biotin deficiency, Eg, G-6-PD, biotin deficiency, mitochondrial disorders.mitochondrial disorders.

Significance of elevated Significance of elevated lactatelactate

In a recent paper on severe sepsis and In a recent paper on severe sepsis and septic shock by Talan et al septic shock by Talan et al (Infec Dis Clin North (Infec Dis Clin North

America 2008),America 2008), it states that elevated lactate it states that elevated lactate levels in sepsis “are associated with poor levels in sepsis “are associated with poor prognosis”… and “hyperlactatemia is not prognosis”… and “hyperlactatemia is not always accompanied by a low bicarb level always accompanied by a low bicarb level and/or elevated AG and thus, a lactate and/or elevated AG and thus, a lactate level should be considered if severe sepsis level should be considered if severe sepsis is suspected.”is suspected.”

Significance of elevated Significance of elevated lactatelactate

Studies have shown that anion gap does Studies have shown that anion gap does NOT accurately screen for either lactic NOT accurately screen for either lactic acidosis or hyperlactatemia in critically ill acidosis or hyperlactatemia in critically ill patientspatients (Adams et al, Emerg Med J 2006, and Iberti et al, Crit Care Med (Adams et al, Emerg Med J 2006, and Iberti et al, Crit Care Med 1990)1990)

ie – can see a clinically significant rise in lactate without a ie – can see a clinically significant rise in lactate without a wide anion gap metabolic acidosis and potentially even with wide anion gap metabolic acidosis and potentially even with no acidosis.no acidosis.

Lactic acidosis or lactate > 4 mmol/L has Lactic acidosis or lactate > 4 mmol/L has often been regarded as a sign of poor often been regarded as a sign of poor prognosis (in trauma, sepsis and other prognosis (in trauma, sepsis and other shock states)shock states)

Significance of elevated Significance of elevated lactatelactate

Not all high lactate levels predict Not all high lactate levels predict poor outcome though. Keep clinical poor outcome though. Keep clinical setting in mind. Eg: elevated lactate setting in mind. Eg: elevated lactate in setting of seizure – can be high (30 in setting of seizure – can be high (30 mmol/L!) but clear within few hrs - mmol/L!) but clear within few hrs - likely b/c problem only d/t excess likely b/c problem only d/t excess production not impaired lactate production not impaired lactate metabolism.metabolism.

Drawing a lactate levelDrawing a lactate level

any evidence for arterial vs central venous vs any evidence for arterial vs central venous vs venous sampling???venous sampling???

Good correlation b/t Good correlation b/t arterialarterial & & centralcentral venous samples venous samples (Middleton et al, Emerg Med J, 2006) – (Middleton et al, Emerg Med J, 2006) – this was true for pH, bicarb, BE & lactate values.this was true for pH, bicarb, BE & lactate values.

One study One study (Gallagher et al, Ann of Emerg Med 1997)(Gallagher et al, Ann of Emerg Med 1997) studied studied the agreement between the agreement between peripheral venousperipheral venous and and arterialarterial lactate levels and concluded lactate levels and concluded “caution should be used in substitution of V-“caution should be used in substitution of V-LACT for A-LACT”. LACT for A-LACT”. In particular found that N venous In particular found that N venous lactate closely correlate with arterial lactate but that elevated lactate closely correlate with arterial lactate but that elevated venous levels did not.venous levels did not.

Drawing a lactate levelDrawing a lactate level

Another study Another study (Lavery et al, J Am Coll Surg 2000)(Lavery et al, J Am Coll Surg 2000) found that in trauma patients venous found that in trauma patients venous lactate is “an excellent lactate is “an excellent approximation for” arterial lactate.approximation for” arterial lactate.

It is suggested that in the setting of It is suggested that in the setting of resuscitating a shock patient in the resuscitating a shock patient in the ED, better to follow central venous or ED, better to follow central venous or arterial lactate levels. Do we do this?arterial lactate levels. Do we do this?

TAKE HOME POINTSTAKE HOME POINTS

Elevated levels of lactate – many causes. Elevated levels of lactate – many causes. Often a sign of hypoxia. Often associated Often a sign of hypoxia. Often associated with bad outcomes.with bad outcomes.

Recognize that patient does not have to Recognize that patient does not have to have wide AG acidosis or acidosis at all to have wide AG acidosis or acidosis at all to have a significant hyperlactatemia. Espec have a significant hyperlactatemia. Espec true in early sepsis.true in early sepsis.

It may matter where you draw your lactate It may matter where you draw your lactate level from. ABG/CVBG often considered level from. ABG/CVBG often considered better than VBG. VBG okay if N level. better than VBG. VBG okay if N level.

QUESTIONS??????QUESTIONS??????