Lactate by jack.

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Dr.JAKEER HUSSAIN

Transcript of Lactate by jack.

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Dr.JAKEER HUSSAIN

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NORMAL LACTATE: Unstressed: 1-0.5 mmol/LStressed: < 2 mmol/L

HYPERLACTATEMIA: 2-5 mmol/L

LACTIC ACIDOSIS:usually > 5 mmol/L with associated metabolic acidosis

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LACTATE PRODUCTION-ANAEROBIC GLYCOLYSIS

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HYPERLACTATAEMIALactate production exceeds lactate consumption.

Addition of a number of protons equivalent to the number of excess lactate ions

Coexisting acidemia contributes to decreased lactate removal by the liver

Severe hypoxia and acidemia can convert the liver into a net lactate-producing organ.

HYPERLACTATEMIA is defined as a persistent, mild to moderate (2-4 mmol/L) increase in blood lactate concentration without metabolic acidosis

LACTIC ACIDOSIS is characterized by persistently increased blood lactate levels (usually >5 mmol/L) in association with metabolic acidosis.

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COHEN AND WOODS DIVIDED LACTIC ACIDOSIS INTO 2 CATEGORIES, type A and type B

TYPE A is lactic acidosis occurring in ass’ with clinical evidence of poor tissue perfusion or oxygenation of blood (eg, hypotension, cyanosis, cool and mottled extremities).

It can be caused by the overproduction of lactate or the underutilization of lactate.

IN CASES OF OVERPRODUCTION: circulatory, pulmonary, & hemoglobin transfer disorders are commonly responsible.

TYPE B is lactic acidosis occurring when no clinical evidence of poor tissue perfusion or oxygenation exists. However, in many cases of type B lactic acidosis, occult tissue hypoperfusion is now recognized to accompany the primary etiology.

Type B1 occurs in association with systemic disease, such as renal and hepatic failure, diabetes and malignancy.

Type B2 is caused by several classes of drugs and toxins, including biguanides, alcohols, iron, isoniazid, zidovudine, and salicylates.

Type B3 is due to inborn errors of metabolism.

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CAUSES OF LACTIC ACIDOSIS

TISSUE HYPOPERFUSION, HYPOXIA

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CAUSES OF LACTIC ACIDOSIS

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CAUSES OF LACTIC ACIDOSIS

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DRUGS Nucleoside reverse transcriptase inhibitors (NRTIs) used in the treatment of HIV-positive patients

cause injury to the mitochondria, which can lead to lactic acidosis. However,

NRTI-induced lactic acidosis is rare and is often associated with hepatic steatosis.

Acute ethanol intoxication can precipitate lactic acidosis, as ethanol oxidation increases the conversion of

pyruvate to lactate and inhibits other pathways of pyruvate accumulation.

Underlying alcoholic liver disease and thiamine deficiency may exacerbate the lactic acidosis.

Propylene glycol has also been associated with lactic acidosis as it is oxidised by alcohol

dehydrogenase in the liver to lactate and pyruvate. It is used as a diluent in many medications such as

phenytoin, phenobarbital, lorazepam, diazepam, digoxin and nitroglycerin and, as such, is the most

common alcohol intoxication in ICUs.

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MESENTERIC ISCHAEMIAThe diagnosis of mesenteric ischaemia can be challenging to make in the critically ill due to lack of clinical and diagnostic signs, difficulty transferring unstable patients for diagnostic imaging and concern about the deleterious effects of inappropriately administering contrast agents.

An ischaemic bowel can produce large amounts of lactate, and the presence of lactic acidosis in the setting of acute abdominal disease has been proposed as an indicator of mesenteric ischaemia.

lactate increases within 1 hour of induced intestinal ischaemia.

elevated lactate at the time of diagnosis of mesenteric ischaemia is a predictor of mortality.

However, although plasma lactate is a very sensitive marker (100%) for detecting acute mesenteric ischaemia, the low specificity of this marker (42%) is a particular problem in the critically ill

Have suspicion for mesenteric ischaemia in a deteriorating patient with an elevated lactate in the absence of a convincing alternative diagnosis, as identification of mesenteric ischaemia is frequently made first at laparotomy in the critically ill.

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CARDIAC SURGICAL PATIENTSHyperlactaemia during cardiopulmonary bypass is relatively frequent and is associated with an increased postoperative morbidity.

this ‘on pump’ hyperlactaemia is secondary to inadequate peripheral oxygen delivery (DO2 ), which creates a condition similar to cardiogenic shock leading to both direct lactate formation by dysoxic tissues and to catecholamine release, insulin resistance and hyperglycemia-induced lactate production. The use of epinephrine after cardiopulmonary bypass precipitates lactic acidosis in some patients.

This phenomenon is probably beta agonist mediated, is associated with increased whole body blood flow and resolves after substitution of norepinephrine.

However, there is emerging evidence that the severity of lactic acidosis following cardiac surgery is related to certain genetic polymorphisms in tumour necrosis factor and interleukin-10 genes.

Similar to asthma, lactic acidosis associated with the administration of epinephrine in this setting does not have the adverse implications of lactic acidosis associated with shock.

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SEPSIS There has been much debate whether the hyperlactaemia of sepsis results from net increased cellular production or reduced net clearance.

It is likely that, in such patients, the cause of lactic acidosis is multifactorial. As these patients are often haemodynamically unstable, lactate production can increase as a result of inadequate oxygen delivery from hypoperfusion.

Other mechanisms thought to contribute to development of lactic acidosis in sepsis include increased pyruvate production, release of lactate from lung parenchyma, decreased pyruvate dehydrogenase (PDH) activity, and reduced clearance of lactate.

Tissue hypoxia may not be a major mechanism for regional lactate production during sepsis:

hyperlactaemia is thought to be linked to the severity of the septic cellular inflammatory response and hypermetabolic state. Net lactate production from the hepatosplanchnic bed is uncommon in septic patients and nuclear magnetic resonance spectroscopy suggests that hyperlactaemia may occur without tissue hypoxia.

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METFORMIN-ASSOCIATED LACTICACIDOSIS (MALA) Metformin is an oral biguanide used widely in type 2 diabetes mellitus, as it has been shown to decrease cardiovascular morbidity and mortality.

Metformin associated lactic acidosis is a rare, but very serious, complication of its use. Two years after its introduction into the US market, an incidence of MALA of 2–9 cases per 100000 patients treated with metformin each year together with a mortality of up to 50% was reported.

A recent study in an Australian tertiary intensive care unit found an incidence of MALA of 6 per 1000 ICU admissions, and a mortality of 29%.

A European study found that MALA accounted for 0.84% of all ICU admissions & associated with a mortality of 30%.

In most cases, MALA occurs when the contraindications of metformin have been overlooked or, more

commonly, when acute renal failure develops and leads to metformin accumulation.

Risk factors for developing

LACTIC ACIDOSIS WHILE ON BIGUANIDE TREATMENT >>>> age >60 years, decreased cardiac, hepatic or renal function, diabetic ketoacidosis, surgery, respiratoryfailure, ethanol intoxication and fasting.

The pathophysiology of MALA remains unclear, thought that biguanides may inhibit oxidative metabolism, and increase the concentration of NADH, reduce gluconeogenesis and suppress gastrointestinal absorption of glucose

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LUNG INJURYThe lung is a primary source of lactate production in patients with ARDS, pulmonary release of lactate being directly related to the severity of lung injury, supporting the view that the primary contributors are the tissues with the most inflammation or injury.

The increased lactate production by the injured lung is not only secondary to anaerobic metabolism in the hypoxic regions of the lung but also may be due to altered glucose metabolism and a direct effect of cytokines on pulmonary cells.

Laboratory studies suggest that both metabolic and respiratory acidosis protect the lung against injury, whereas correction of acidosis compounds the injury.

Two ventilator trials demonstrating a positive impact on mortality in ARDS by limiting tidal volume and airway pressures differed widely on how they regarded the resultant hypercapnic acidosis.

Whereas Amato et al allowed elevation of the PaCO2 (permissive hypercapnia) and resultant acidosis, the ARDSnetgroup aggressively corrected the hypercapnic acidosis by increasing the respiratory rate and allowing administration of sodium bicarbonate.

There is growing evidence that not only may hypercapnic acidosis beneficial be in lung injury, but also the ARDSnetintervention aimed at correcting the acidosis may be deleterious. These findings have not only promoted a

greater tolerance of acidosis in ARDS but also increased reluctance to buffer the acidosis exogenously towards

‘normal’ values.

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CLINICAL PRESENTATIONPatients present with clinical signs appropriate to their primary disorder.

In critically ill patients with shock, however, the severity of lactic acidosis can be a valuable monitor of the efficacy of resuscitation. Repeated measures of ABGs and blood lactate concentrations are required.

In HYPOVOLAEMIC SHOCK, resolving lactic acidosis with the clinical signs of improving perfusion is indicator of successful resuscitation.

Conversely, failure of lactic acidosis to resolve in hypovolaemic shock suggests inadequate resuscitation or another undetected or unresolved clinical problem.

In patients c severe lactic acidosis, a blood lactate concentration of 5mmol/L indicated a mortality approaching 80%

Survival was best in patients whose hyperlactaemia resolved.

LACTIC ACIDOSIS MAY ALSO OCCUR IN CRITICALLY ILL PATIENTS IN THE ABSENCE OF SHOCK hypermetabolic states where accelerated aerobic glycolysis may contribute (trauma, burns, sepsis), conditions with increased muscle activity(seizures) and during exogenous lactate administration (lactate-buffered haemofiltration fluid). In many of these patients (e.g. patients with seizures) very high blood lactate concentrations have no prognostic implications

because the acidosis Is rapidly cleared.

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L-LACTATE is the most commonly measured level, as it is the only form produced in human metabolism.

Its excess represents increased anaerobic metabolism due to tissue hypoperfusion.

D-LACTATE is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection.

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D LACTIC ACIDOSISD-lactic acidosis is a unique form of lactic acidosis that occurs in patients with short-bowel syndrome, a history of jejuno-ileal bypass surgery or chronic pancreatic insufficiency.

Patients typically present with a high-anion-gap metabolic acidosis & neurological manifestations including slurred speech and confusion, triggered by ingestion of large amounts of carbohydrate.

D-lactate is an end-product of the anaerobic metabolism of organic acids produced in the GI tract from bacterial metabolism of undigested fibre, sugar and starch.In the setting of carbohydrate malabsorption, the higher concentration of organic acids leads to a decrease in intraluminal pH favouring overpopulation of bacteria such as Lactobacillus, one of the main D-lactate-producing bacteria.

As D-lactate is metabolised slowly, it can accumulate following a large carbohydrate load.

D-lactic acidosis is characterised by a normal lactate level as the assay for lactate measures only L-lactate; a D-lactate level must be specifically requested if D-lactic acidosis is suspected.

CLINICAL PRESENTATION

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MANAGEMENTDIAGNOSE

CORRECT UNDERLYING CONDITION

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HYPERVENTILLATIONHYPERVENTILLATION is normal compensatory response to met acidosis in conscious Pt.

in MV Pts, -- hyperventilation is required to correct lactic acidosis partially.

difficult in pts c pul path

in few pts it worsens lactic acidosis,,, inc intrathoracic pressure, >>> dec venous return,

>>>decreases CO, WORSENS LACTIC ACIDOSIS.

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BICARBONATEThe use of bicarbonate therapy for the treatment of lactic acidosis continues to be controversial

SODIUM BICARBONATE also has adverse effects >>> acute hypercapnia and ionised hypocalcaemia which outweighs potential benefits in patients. Hypercapnia may increase intracellular acidosis (CO2 crosses cell membranes rapidly) hypocalcaemia decreases myocardial contractility bicarbonate is a hypertonic solution and include acute intravascular volume overload and cardiac depression bicarbonate increases lactate production by increasing the activity of the rate-limiting enzyme phosphofructokinase, shifts the haemoglobin–oxygen dissociation curve, increases oxygen affinity of haemoglobin andthereby decreases oxygen

delivery to tissues.

bicarbonate has never been shown to be beneficial in any clinical trial of patients with lactic acidosis and

its use in these patients is not recommended, regardless of the degree of acidaemia.

two specific subgroups of patients with lactic acidosis in whom bicarbonate may be considered. Patients with pulmonary hypertension and right heart failure (e.g. lung transplant recipients) may have pulmonary vasoconstriction,

which is exacerbated by acidosis. In these patients, although there are other useful therapies including inhaled nitric oxide & partial pH correction, it may improve right heart function.

Secondly, patients with significant ischaemic heart disease and lactic acidosis may be at increased risk of major arrhythmiasbecause severe acidosis lowers the myocardial threshold for arrhythmias. In both of these subgroups, slow bicarbonate infusions tokeep the arterial pH above 7.15 may be justified

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ALTERNATIVE THERAPIESCARBICARB is an equimolar mixture of sodium carbonate & sodium bicarbonate that does not generate

carbon dioxide and may therefore have fewer adverseeffects than bicarbonate. There is limited clinical

research associated with Carbicarb®, and though it has been shown to increase intracellular pH and have fewer haemodynamic adverse effects than bicarbonate it does not address the underlying

cause of lactic acidosis and is not in clinical usage.

DICHLOROACETATE (DCA) stimulates the phosphate dehydrogenase complex, the rate-limiting enzyme that

regulates entry of pyruvate into the tricarboxylic acid cycle, and thereby facilitates the oxidation of

lactate. Although it has been shown to increase arterial pH and decrease lactate concentrations,

a large multicentre randomised clinical trial in patients with lactic acidosis found no benefits for either haemodynamics or patient outcome.

This study is the best evidence currently available to support the view that correction of lactic acidosis in

critically ill patients without improving the underlying primary disorder has no overall impact on patient

outcome.

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ALTERNATIVE THERAPIESDIALYSIS/HAEMOFILTRATION

Haemofiltration and continuous renal replacement therapies (CRRT) have been promoted as treatments for lactic acidosis, with several theoretical advantages.

Bicarbonate-based haemodialysis can assist in treatment of acidosis through diffusion of bicarbonate from the dialysate into the serum without the risk of volume overload, hypernatraemia or hyperosmolality.

Studies have shown improvements in acid–base balance with bicarbonate-based CRRT,although controlled clinical trials showing an improvement in outcome are lacking.

A study of 10 critically ill patients with acute renal failure and stable lactate concentrations found that, following an infusion of sodium lactate, bicarbonate-buffered haemofiltration was ineffective, contributing to less than 3% of lactate clearance.

They concluded that continuous veno-venous haemofiltration with dialysis cannot meet lactate overproduction.

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Seminar is defined as process in whichone spoils his sleep for one night ,,,in an effort to make others sleep …….