Informative Article
Lactic Acidosis In Critically Ill Patients
Shafali Nandwani, *Mahip Saluja, **Mayank Vats ,**Yatin Mehta
Department of Medicine, * Department of Pulmonary Medicine, Subharti Medical College, Meerut-250002, **Department of Pulmonary
and Critical Care, Indraprastha Apollo Hospital, New Delhi-110044 Abstract:
Lactic acidosis is defined as increase in blood lactate levels in association with acidemia. It should be suspected in all patients presenting with shock & decreased mayocardial contractility. The patients with lactic acidosis have highmortality. However, the prognosis and case fatality are completely dependent on underlying disease in each patient withlactic acidosis being an independent indicator of severity of shock. All efforts should be directed towards treatment ofunderlying cause and concomitant correction of acidosis.
Key Words: Lactate, Pyruvate, Lactic acidosis,THAM.
Adinine Dinucleotide Phosphate (NAD/NADH). (The Lactic acidosis was first described in literature normal ratio of lactic acid: pyruvic acid is 10:1).
in the year 1920. Clausen in the year 1925 identifiedaccumulation of lactic acid as a cause of metabolicacidosis. However, till the year 1960 it was notrecognized as significant clinical problem. In year 1976,Cohen & Woods classified lactic acidosis on the basisof presence or absence of adequate tissue oxygenation.
Lactic acidosis is the most common under diagnosedlife threatening form of metabolic acidosis present in0.5% to 3.8% critically ill patients.
Lactic acidosis is a pathological state diagnosed when the serum concentration of lactate or lactic acid
is persistently 5mmol/L or greater and there is
significant acidemia and serum pH< 7.35. (Normal
lactate concentration is 2.0 mmol/L).
Formation of Lactic acid:
There is constant production and metabolism of lactate in the body. Red blood cells, brain and skinare major sources of lactic acid at rest while duringexercise skeletal muscles release significant amountof lactic acid.
Kidney and liver utilize lactic acid and convert Fig.I: Kreb’s cycle showing formation of lactic acid.
it into carbon dioxide and water and use it forgluconeogenesis. Normally there is fine balance between lactic acid production and utilization.
Lact ic acid a nd pyr uvic acid are inter convertible and the reaction is catalyzed by the
enzyme lactate dehydrogenase in the presence of
Nicotinamide Adinine Dinucleotide / Nicotinamide
----------------------------------------------------------------------------- Corresponding Author: Dr Mahip Salu ja, Associa te pr ofessor,
Department of Pulmonary Medicine, Subharti Medical College , Phone No.: 9837360657
Fig. II: Metabolic fate of lactic anion.
E mail : [email protected]
People’s Journal of Scientific Research 43 Vol.3(1), Jan 2010 Lactic Acidosis In Critically Ill Patients ----------------------------------------- S Nandwani, M Saluja, M Vats & Y Mehta Classification of Lactic Acidosis (Cohen &
of lactic acid or its diffusion in to total body fluid. This is associated with fall in bicarbonate concentration, They classified lactic acidosis into two types- which rapidly returns to normal once GTCS subsides.
As the acidosis is abrupt and transient, secondary TYPE A: It occurs in hypoperfusion and hypoxia.
response of hyperventilation may not develop and even • Tissue hypoxia is seen in carbon monoxide poiso- if magnitude of acidosis is high, bicarbonate therapy is ning, severe asthma and severe anemia.
Hypoperfusion occurs in state of shock (cardioge- (nic, hemorrhagic, septic, regional ischemia) 2. Tissue hypoxia: It is the predominant cause of
TYPE B: It occurs when there is no clinical evidence
lactic acidosis in critically ill patients. Prolonged hypoxia of hypoperfusion. It is further subdivided into 3 will lead to overproduction and underutilization of lactic acid leading to lactic acidosis. Patients with hypotension (i) B1is associated with acquired diseases like
either due to septic, hypovolumic or cardiogenic shock, diabetes mellitus, grand mal seizures, hepatic failure, may develop lactic acidosis due to poor perfusion of septicemia, malignancies, pheochromocytoma, post skeletal muscles and overproduction of lactic acid. The cardiopulmonary bypass, renal failure, thiamine degree of lactic acidosis correlates well with the duration and severity of shock and is a prognostic factor (ii)B2 is associated with metabolites, drugs and toxins
like acetaminophen, biguanides, cocaine, diethyl ether,epinephrine, norepinephrine, ethanol, ethylene glycol, 3. Cardio-respiratory arrest: It is another cause
isoniazid, lactulose, methanol, nalidixic acid, niacin, leading to severe acidemia due to combined lactic nitroprusside, antiretroviral therapy, paraldehyde, acidosis and respiratory acidosis due to cardiac arrest parenteral nutrition, terbutaline, theophyline etc.
and respiratory arrest respectively. Similarly patients (iii)B3 is due to inborn errors of metabolism
with acute left ventricular failure with pulmonary edema (congenital lactic acidosis) e.g. Glucose-6 phosphate may develop acidosis due to reduced tissue perfusion dehydrogenase deficiency, fructose1-6 diphosphatase and respiratory acidosis due to respiratory failure.
deficiency, pyruvate carboxylase deficiency,organic Reduced partial pressure of oxygen (PaO ) seldom aciduria, Leigh’s disease, Alpers disease and causes lactic acidosis if cardiovascular status is normal because it is compensated by increased tissue perfusion.
In patients of type II respiratory failure secondary to Miscellaneous:
advanced chronic obstructive airway disease, seldom Spontaneous lactic acidosis or idiopathic lactic have lactic acidosis if there are no other confounding acidosis like chronic recurrent lactic acidosis may be factors. It is due to the fact that these patients have due to subclinical, regional hypoperfusion or coexistence chronic compensated respiratory acidosis and PaO , of various predisposing conditions or late manifested enzymatic defect.
D-lactic acidosis is rare and is caused by d-stereo 4. Carbon monoxide poisoning: It typica lly
isomer of lactic acid (d-lactic acid) which is synthesized produces lactic in the form of acidosis due to lack of by pathological gut flora. It can not be measured by compensa tor y mecha nism of incr eased tissue perfusion. Carbon monoxide binds to hemoglobin andas its affinity for hemoglobin is 40 times more than Clinically important causes of lactic acidosis are
that of oxygen, it leads to tissue hypoxia and lactic overproduction or underutilization of lactate or both the conditions co-existing together.
1. Vigorous exercise: The magnitude of increase in
5. Drugs and toxins: Some of drugs & toxins also
lactic acid concentration depends upon the type and lead to increased production of lactate. Alcohol severity of exercise. Same is also true following ingestion is a common cause of lactic acidosis as prolonged generalized tonic clonic seizures (GTCS).
ethanol oxidation increases the conversion of pyruvate Lactate level falls to normal immediately following to lactate and decreases the clearance of lactate.
cessation of exercise or GTCS due to rapid metabolism People’s Journal of Scientific Research 44 Vol.3(1), Jan 2010 Lactic Acidosis In Critically Ill Patients ----------------------------------------- S Nandwani, M Saluja, M Vats & Y Mehta Alcohol induced lactic acidosis is treated by Diagnosis:
correcting the hypoglycemia and electrolyte imbalance.
The major clues leading to the diagnosis of lactic Alkali therapy is rarely required in such cases.
Prolonged metformin therapy is associated with lactic • Increased anion gap (AG) metabolic acidosis acidosis for many reasons. It increases glycolysis inperipheral tissues, decreases pyruvate oxidation and Increased level of serum lactic acid (> 5 mmol/
Significant acidemia (arterial pH< 7 .35)
acidosis but it is not certain whether these drugs per se or associated hypotension produces lactic acidosis.
Fructose, frequently used in intravenous fluids and total Laboratory studies include: Arterial blood gas analysis parentral nutrition, leads to deficiency of thiamin andaccumulation of lactate. It also leads to inhibition of (ABG), calculation of anion gap (normal range of anion lactate utilization by liver and hence produces lactic gap is 10-12mmol/L), serum lactate assay (for serum acidosis. Sorbitol also gets converted into fructose and lactate assay sample must be transferred in ice filled leads to lactic acidosis by the same mechanism.
pack and analyzed within 4 hours- reference range for Epinephrine enhances hepatic glycogenolysis serum lactate is < 2mmol/L).
and glycolysis to lactate and reduces pyruvate utilization Diagnosis of lactic acidosis may be missed in resulting in lactic acidosis especially in massive doses.
patients with uremia and concomitant metabolic Septic patients because of hypotension and poor alkalosis if the clinical suspicion is not high.
peripheral perfusion are at risk of developing lactic One should always obtain plasma lactate levels in patients with acute respiratory failure when everbicarbonate concentration falls unexpectedly which 6. Terminal cirrhosis or hepato-cellular failure: It
may not be explained by respiratory failure alone.
may lead to lactic acidosis due to poor utilization of concomitant metabolic alkalosis, the clue to thediagnosis is unexpected increase in anion gap.
7. Neoplastic diseases: Leukemia predisposes to
lactic acidosis because of production of large amount
Differential diagnosis includes the common causes
of lactate by tumor cells and it resolves gradually after of increased anion gap acidosis like renal failure, diabetic ketoacidosis and rhabdomyolysis. They may 8. Congenital deficiency of enzymes: Enzymes
occur alone or co-exist with lactic acidosis which are involved in gluconeogenesis (glucose-6phosphate dehydrogenase, fructose 1, 6 pyruvate Treatment: The most important therapy in
carboxylase), pyruvate oxidation (Pyruvate management of lactic acidosis is correction of dehydrogenase) and key enzymes of oxidative underlying cause. In hypovolumic or cardiogenic shock, phosphorylation may also lead to development of rest oration of per fusion a nd adequate tissue oxygenation will reverse lactic acidosis. In septic shock,antibiotic treatment, surgical drainage/debridement will Clinical symptoms of lactic acidosis: Symptoms are
help in reversal of lactic acidosis. Giving intravenous non specific and are those of underlying primary thiamine in cases of total parentral nutrition will help in disorder. Lactic acidosis should be suspected in all resolution of lactic acidosis. In status asthmaticus, high critically ill patients who are hypovolumic, hypoxic, in dose of beta 2 agonist should be tapered gradually to septic or cardiogenic shock or if unexplained high anion reduce lactate levels. In shock, vaso constrictors should be added only after volume replacement as theyworsen the acidosis.
Clinical signs consistent with tissue hypoperfusion(peripheral vasoconstriction), hypotension, oliguria/ Alkali Therapy though theoretically appealing, but
anuria and altered sensorium are usually present in only few studies document safety and efficacy of bicarbonate in lactic acidosis. Correction of acidosis People’s Journal of Scientific Research 45 Vol.3(1), Jan 2010 Lactic Acidosis In Critically Ill Patients ----------------------------------------- S Nandwani, M Saluja, M Vats & Y Mehta with bicarbonate may reverse depressed cardiac over bicarbonate as it produces less carbon dioxide.
performance in critically ill patients. The side effects Clinical trials do not prove THAM to be more effective of bicarbonate therapy is acute hypercapnia which than bicarbonate. The dose of THAM should be increase intracellular acidosis and ionized hypocalcemia calculated by the formula (0.3 mol/L)=0.3 body weight which in turn decreases the myocardial contractility.
Bicarbonate is a hypertonic solution and causes volumeoverload and cardiac depression. It also increases the Carbicarb is an equimolar combination of sodium
lactate production by increasing the activity of rate carbonate and sodium bicarbonate that produces less limiting enzyme phosphofructokinase. Adverse effects carbon dioxide than sodium bicarbonate alone. It has of bicarbonate can be reduced by giving slow infusions theoretical advantage but trials have not demonstrated in preference to rapid boluses, by increasing minute any reduction in mortality or morbidity.
volume in patients on ventilator and by correctinghypocalcemia. Bicarbonate therapy is useful in patients Prognosis: Depends on etiology of shock/underlying
of ischemic heart disease as acidosis increases the risk disease which influences the survival but it has been of major arrhythmias due to lowering of the myocardial shown that serum lactate levels greater than 8 mmol/L threshold. In these patients bicarbonate infusion to keep are associated with mortality rate of more than 80%.
pH a bove 7. 10 can be justified. In all othercircumstances when lactic acidosis is accompanying Conclusion: Lactic acidosis is an important and
pulmonary oedema, cardiopulmonary arrest, grand mal frequently under diagnosed condition in critically ill seizures, biguanide therapy, ethanol ingestion, and patients. Timely correction of lactic acidosis can bring diabetic ketoacidosis, bicarbonate therapy is not marked change in outcome of patients in Intensive Care Haemodialysis is rarely indicated as a treatment for
lactic acidosis. It may be used in drug toxicity to speedup elimination of drug/toxin. It is helpful when fluid 1. Adr ogue HJ, Madias NE: Man agemen t of life overload and cardiac or renal insufficiency is present.
threatening acid base disorders. The New EnglandJournal of Medicine, 1998;338(1):26-34.
Recent advances: Methylene blue, an oxidizing agent,
2. Agbenyega T, Angus BJ, Bedu-Addo G, Baffoe-Bonnie has been used to restore cellular Nicotinamide Adinine B, Guyton T, Stacpoole PW, Krishna S: Glucose andLactate kinetics in children with severe malaria. The Dinucleotide (NAD+) with a very limited success.
Journal of clinical Endocrinology and Metabolism, Glucose, insulin infusion, nitropruside infusion, hemodialysis, peritoneal dialysis have all been used in 3. Benjamin E: Continuous venovenous hemofiltration with order to treat lactic acidosis but their efficacy is dialysis and lactate clearance in critically ill patients.
unproven. Thiamine, lipoic acid and dichloroacetate Critical Care Medicine, 1997;25(1):4-5.
have been used as they increase the activity of 4. Broder G, Weil MH, Excess lactate: An index of pyruvate dehydrogenase enzyme, which converts reversibility of shock in human patients. Science, pyruvic acid to acetyl Co-A, but their clinical utility is not certain. Riboflavin, Coenzyme-Q, L-carnitine have 5. Clausen SW: Anhydremic acidosis due to lactic acid.
American Journal of Diseases in Children, 1925;29(6):761-766.
Dichloroacetate (DCA) is an activator of pyruvate
6. Cohen RD, Woods HF: Clinical and biochemical aspects dehydrogenase. It can lower concentration of lactic of lactic acidosis. Blackwell Scientific Publication, acid in patients by improving the lactate utilization but 7. Cohen RD, Woods HF: Lactic acidosis revisited, when used in large clinical trial it did not show any Diabetes, 1983;32(2):181-191.
effect on mortality. DCA, however, may be helpful in 8. Cuhaci B, Lee J, Ahmed Z: Sodium bicarbonate lactic acidosis in children with severe malaria.
controversy in lactic acidosis. Chest, 2000;118(3):882-884.
Tris hydroxymethyl aminomethane (THAM)
9. Cooper DJ, Walley KR, Wiggs BR, Russell JA: It is a weak alkali and theoretical has the advantage Bicarbonate does not improve harmodynamic is People’s Journal of Scientific Research 46 Vol.3(1), Jan 2010 Lactic Acidosis In Critically Ill Patients ----------------------------------------- S Nandwani, M Saluja, M Vats & Y Mehta clinically the patients who have lactic acidosis. Aprospective, controlled clinical Study. Annals of InternalMedicine, 1990; 112(7): 492-498.
10. Forsyth SM, Schmidt GA: Sodium bicarbonate for the treatment of lactic acidosis. Chest, 2000; 117(1):260-267.
11. Foulks CJ, Wright LF: Successful repletion of bicarbonate stores in ongoing lactic acidosis: a role for bicarbonate-buffered peritoneal dialysis. Southern Medical Journal,1981;74(9):1162-1163 12. Narins RG, Cohen JJ: Bicarbonate therapy for organic acidosis: the case for its continued use. Annals ofInternal Medicine, 1987;106(4):615-618.
13. Peretz DI, Scott HM, Duff J, Dossetor JB, MacLean LD, McGregor M: The significance of lacticacidemia in theshock syndrome. Annals of the New York Academy ofSciences, 1965; 119 (3 Chemistry): 1133-1141.
14. Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan C, Harman EM,Henderson GN, Jenkinson S: Natural history and courseof acquired lactic acidosis in adults. DCA-LacticAcidosis Study Group. The American Journal ofMedicine, 1994;97(1):47–54.
15. Stacpoole PW: Lactic acidosis. Endocrine and Metabolic Clinics of North America, 1993; 22(2): 221-245.
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People’s Journal of Scientific Research 47 Vol.3(1), Jan 2010


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