1. Description of the problem

What every clinician needs to know

Lactic acidosis associated with critical illness is commonly a byproduct of a much larger problem. In 1976 Cohen and Woods classified lactic acidosis based on etiology. Type A is due to clinical evidence of tissue hypoperfusion. Type B occurs in the absence of clinical evidence of tissue hypoperfusion. Type B is further divided into subgroups B1 – underlying disease/physiologic state; B2 – medication or toxin; and B3 – inborn errors of metabolism.

In critically ill patients, lactic acidosis is typically associated with increased lactate production (hypoperfusion, mitochondrial dysfunction), and/or decreased metabolism/clearance. Approximately 1400 mmol of lactic acid is produced daily. The kidneys metabolize up to 30% with no significant elimination. The liver is very efficient in lactate metabolism and elimination and serum lactate levels should remain in the normal range until about 75% of hepatic function is lost.

Clinical features

The clinical features of lactic acidosis are similar to other forms of metabolic acidoses. These may include respiratory compensatory signs such as tachypnea and Kussmaul respirations. Other clinical features are related to the underlying cause of lactic acidosis, such as signs of hypoperfusion.

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  • Hyperventilaton (rapid shallow or Kussmaul respirations).

  • Hypotension.

  • Altered mental status.

  • Cyanosis.

  • Tachycardia.

  • Fever or hypothermia.

  • Seizure (generalized seizures can cause a transient lactic acidosis).

  • Signs of hypovolemia (dry mucous membranes, decreased capillary refill, skin tenting, oliguria).

  • Abdominal pain (especially with mesenteric ischemia).

Key management points
  • There may only be subtle clinical findings, therefore one needs to have a high suspicion in clinically relevent situations (e.g. infection, CHF exacerbation) and draw a lactate level.

  • Identify likely etiology for lactic acidosis.

  • Start appropriate therapy immediately. For the majority of patients with lactic acidosis, this will consist of appropriate resuscitation in concert with treating the underlying problem (inotropes for heart failure, antibiotics for sepsis).

  • Followup with repeat lactate level to evaluate for treatment effectiveness.

2. Emergency Management

Stabilizing the patient
  • Suspect potential clinical cause for lactic acidosis.

  • Screen for elevated lactate level (blood gas lab or point of care – both are faster than central lab).

  • While waiting for lab results, appropriate management of serious physiologic derangements. Follow the ABCs of resuscitation.

  • During the immediate resuscitation, order appropriate lab and other tests necessary to identify the cause of the lactic acidosis.

  • Monitor serial lactate levels as one variable guide to treatment effectiveness.

Management points not to be missed

Hypoperfusion/Shock treatment: The goal is to restore adequate tissue perfusion. Treatment depends on the shock state:

Septic shock

  • Broad spectrum antibiotics.

  • Start early goal directed therapy.

  • Source control.

  • Follow accepted endpoints of resuscitation available.

  • Follow serial lactate, mixed or central venous saturation trends.

Hypovolemic – hemorrhagic shock

  • Restore circulating volume. If actively bleeding, then blood products are first choice. If no active hemorrhage, use crystalloid.

  • Hemorrhagic shock: control the bleeding, may need surgical intervention or gastroenterology for GIB.

  • Follow accepted endpoints of resuscitation available.

  • Follow serial lactate, mixed or central venous saturation trends.

Cardiogenic shock

  • Cardiology consult for evaluation of PTCA if STEMI.

  • Consider starting inotropes and/or vasopressors.

  • Consider intra-aortic balloon counter pulsation.

  • Follow accepted endpoints of resuscitation available.

  • Follow serial lactate, mixed or central venous saturation trends.

Medication or poisoning

  • Support hemodynamics and protect airway.

  • Rapid determination of toxin or medication (e.g. toxic alcohol, metformin, acetaminophen).

  • Rapid administration of antidote or therapy (e.g. fomepizole, dialysis, n-acetylcysteine).

  • Follow serial lactate, mixed or central venous saturation trends.

3. Diagnosis

Diagnostic criteria and tests

Due to multiple metabolic and respiratory buffering mechanisms, lactic acidosis is not required to exist in the setting of acidemia. However, it is important to understand the entire acid-base status of the critically ill patient.

Lab tests:

ABG: will give big picture of acidosis/alkalosis and the primary determinant (metabolic vs. respiratory).

Electrolytes: Na, K, Cl, iMg, iCa.

Weak acids: Phosphorus and albumin.

Lactate: either point of care or from an ABG. Venous samples are acceptable. Capillary samples are also acceptable on certain point of care analyzers.

When evaluating the acid-base status, lactic acidosis is usually present in the setting of an elevated anion gap. However, there are limitations to the anion gap, and each analyzer/hospital has its own range of “normal” mostly depending on the type of electrodes used. The anion gap can be erroneously interpreted as “normal” in the setting of hypoalbuminemia. By calculating the strong ion difference and strong ion gap, one can fully appreciate the contribution lactate has to the entire acid-base milieu.

Another method that is clinically equivalent, is correcting the anion gap for hypoalbuminemia.

Normal lab values

Normal lactate: 0.5-2 mmol/L or meq/L.

Intermediate Lactate: 2-4 mmol/L.

High Lactate: more than 4 mmol/L.

Point of care analyzers have been shown to be clinically equivalent to blood gas analyzers and the central lab. Venous, arterial and capillary results are also clinically similar.

Confirming the diagnosis

Elevated lactate level will confirm the suspicion of lactic acidosis. The clinical relevancy of this should be taken in context with the clinical presentation, underlying disease state and any previous lactate levels for comparison.

Other possible diagnoses

When the etiology of lactic acidosis is uncertain, a systematic approach can be helpful. It is important to follow serial lactate levels. Rapidly clearing lactic acidosis may have been the result of a seizure or occult hypoglycemia. For persistent lactic acidosis consider the following:

  • Could this be a toxic ingestion (e.g. ethanol, methanol, cyanide)?

  • Could this be a result from medication (e.g. antiretroviral agents, beta agonists, metformin, nitroprusside, acetominophen, iron, isoniazid)?

  • Could this be thiamine deficiency? Is the patient an acoholic, on a fad diet, chronically malnourished? Thiamine replacement is a relatively benign treatment and rapid resolution supports this diagnosis.

  • Is the patient having an asthma exacerbation? Hyperlactatemia can be caused by increased work of breathing as well as beta agonists.

  • Does this patient have MELAS syndrome? Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode. Usually presents between the ages of 4 and 15.

Confirmatory tests

Using a physicochemical approach to acid base analysis can help with complicated or multiple metabolic etiologies. The traditional anion gap, (Na+ + K+) – (Cl + HCO3), does not account for the effect of weak acids. However, accounting for the effect of pCO2, weak acids (mostly albumin and phosphates), and the strong ion difference (SID – strong ions are ions that are completely or almost completely disassociated at physiologic pH), one can identify if lactate is the primary etiology of the metabolic acidosis or if there are other unmeasured ions – the Strong Ion Gap (SIG).

Algorithm 1

Algorithm 2

Algorithm 3

[|#Algorithm Start#|]AGc = ((Na+ + K+) – (Cl + HCO3)) – 2 x (albumin(g/dL)) – 0.5 x (phosphate (mg/dl)) – lactate (mEq/l).

SIDa = Apparent strong ion difference

SIDe = Effective strong ion difference (takes into account weak acids)

SIG = Strong Ion Gap represents unmeasured ions. SIG should be less than 2 in healthy patients.

AGc = Anion gap corrected for albumin – has been shown to be as clinically useful as the SIG.

4. Specific Treatment

Treatment is directed towards the underlying condition that produced the lactic acidosis. Medications such as dichloroacetate, which promote mitochondrial oxidation of pyruvate and decrease lactate production, have not been shown to be clinically effective.

Drugs and dosages

Alkalinizing agents:

Sodium bicarbonate: not recommended to treat lactic acidosis primarily. In severe metabolic acidosis with refractory hypotension, hyperkalemia or acute kidney injury, bicarbonate solutions may be beneficial, though this is still controversial. Dose varies and should be titrated to effect desired, such as pH. Total body bicarbonate deficit can be calculated from the following formula; however, this formula has limitations and should only be used as a general guide to initiating the starting dose. Deficit HCO3- (mEq) = 0.5 x weight (kg) x [24 – serum HCO3- (mEq/L)].

Tromethamine (THAM): a non-CO2 generating buffer. Limited information. In small ICU studies, THAM did not lower potassium, caused mild hyponatremia, and did not increase pCO2 when compared to NaHCO3-. Therefore, it may be potentially useful for hypernatremia and hypercarbic or mixed respiratory/metabolic acidotic patients.


Thiamine (Vitamin B1): Thiamine deficiency has long been associated with Wernicke encephalopathy. Lactic acidosis may be associated with thiamine deficiency in rare cases. Hypoperfusion does not necessarily need to be present for this to occur. The adult dose 100 mg IV x 1. Subsequent daily doses of 50 mg/d IV are required. Death has occurred in cases with suspected Wernicke encephalopathy when given alone, therefore dextrose containing fluids should be administered along with thiamine.


Dichloroacetate (DCA): DCA’s role in the treatment of lactic acidosis is more of a historical one. DCA is a halogenated organic acid that is very effective at lowering lactate concentrations by inhibiting pyruvate dehydrogenase. The result is a shift from the production of lactate (from pyruvate in glycolysis) to increased oxidation in the mitochondria. However, a prospective randomized trial using dicholoracetate for treatment of lactic acidosis in humans did not improve hemodynamics or survival when compared to placebo. Subsequent studies have demonstrated similar outcomes. Serious neurologic side effects have limited its use.

Refractory cases

Refractory cases need to have the underlying cause of lactic acidosis aggressively managed. This could be surgical exploration/debridement for sepsis, placement of an intra-aortic balloon pump for cardiogenic shock or initiation of hemodialysis for treatment of certain toxins. Dialysis for refractory lactic acidosis has been reported to be an effective adjunct for metformin toxicity and severe thiamine deficiency.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

Depending on the severity and duration of lactic acidosis, the expected response to the appropriate therapy will vary. If the etiology is severe sepsis or septic shock, even with early recognition and aggressive goal directed treatment, mortality is still approximately 30%. In conditions where hypoperfusion is thought to be the etiology of lactic acidosis, the elevated lactate is directly related to the amount of oxygen debt. There are several variables that will affect outcome. The duration of hypoperfusion, severity of hypoperfusion, etiology of hypoperfusion, condition of the microvascular system, mitochondrial injury and underlying state of health are all important considerations.

Incorrect diagnosis

Lactic acidosis is not a specific marker for any disease. Rather it is a marker for severity of illness. However, In patients with jejunal-ileal bypass or other types of “short bowel syndrome,” D-lactate may be produced. D-lactate is not associated with hypoperfusion but may produce an anion gap metabolic acidosis with a “normal” range of lactate. Since the common assays for lactate only measure L-lactate, D-lactate will not be measured. Thus one should suspect D-lactatic acidosis in the proper clinical setting in which the patient presents with an anion gap metabolic acidosis that can’t be explained by L-lactate, ketones or toxic metabolites.

Acidemia caused by D-lactate occurs when colonic overgrowth of Gram positive anaerobes, such as lactobacilli, metabolize carbohydrates and other complex sugars into D-lactic acid, which then is slowly absorbed into the systemic circulation. Since L-lactate dehydrogenase does not convert D-lactate into pyruvate, the D-lactate will accumulate and may cause acidemia. Symptoms are usually neurologic in nature with altered mental status, ataxia, slurred speech and memory loss. These symptoms are more common after large carbohydrate laden meals.


Disposition and followup is dependent on the primary etiology of the lactic acidosis. Serial lactate levels can be monitored to evaluate lactate clearance. Lactate clearance of at least 30% over 6 hours has been associated with improved outcomes compared to those patients who either are unable to clear lactate at this rate, or have rising lactate levels in sepsis.


As mentioned previously, lactic acidosis can arrise from several etiologies. It is generally due to clinically evident tissue hypoperfusion (Type A) or the absence of clinically evident tissue perfusion (Type B). Type B1 is from underlying disease states (e.g. asthma, liver failure, systemic inflammation, malignancy, thiamine deficiency, hypophosphatemia, d-Lactic acidosis, hypoglycemia). Type B2 is from toxins or medication (e.g. alcohols, cyanide, antiretrovirals, metformin, beta-2 receptor agonists, salicylates, nitroprusside, carbon monoxide, propofol), and B3 is inborn errors of metabolism (e.g. MELAS and others).

Lactate production

In the cytoplasm of virtually all cells, glucose metabolism starts with glycolysis, an anaerobic pathway. The product of glycolysis is pyruvate, which then diffuses into the mitochondria and becomes part of the Krebs cycle through an aerobic pathway. In the absence of adequate oxygen, pyruvate is not metabolized in the Krebs cycle, but rather converted in the cytoplasm to lactate by lactate dehydrogenase (LDH). Lactate then diffuses out of the cell and enters the surrounding tissue and eventually the circulation. Thus, the most important determinant of pyruvate and lactate production is glycolytic flux.

Lactate can be generated aerobically and then “shuttled” back to the mitochondria to support oxidative phosphorylation and can also be converted to pyruvate for future oxidation. This is done with mitochondrial LDH. This lactate shuttle has been demonstrated in skeletal muscle, myocardial and liver cells.

Aerobic lactate production may be enhanced by hormones such as epinephrine and insulin. This is thought to be mediated through a beta-2 adrenergic receptor mediated process that increases Na+ K+ membrane pump activity. This process is activated by aerobic glycolytic flux and has been confirmed in humans with septic shock.

Inflammatory cytokines also promote an increase in lactate production by stimulating glucose uptake and glycolytic flux in tissue macrophages. This is thought to be an important mechanism of hyperlactatemia in the setting of inflammatory states.

Regardless of the etiology of the lactate production, in critical illness hyperlactatemia has been shown to be a reliable marker for severity of illness for more than 40 years.


The true incidence and prevalence of lactic acidosis is not known. It can be very difficult to determine. Published data for hospital and pre-hospital incidence rates are few, with small sample sizes. However, one recent 3 year observational, single center, multidisciplinary ICU study has provided a good starting point to understanding the scope of hyperlactatemia or lactic acidosis. After reviewing nearly 14,000 ICU admission episodes and more than 11,000 patients during a 3-year period, Khosravani and colleagues found the incidence of hyperlactatemia to be 40% and prevelance was 20 hyperlactatemia days per 100 days of ICU admission. The group also found significant differences between major admitting category, age and higher APACHE II scores. The mortality rate for those admitted with hyperlactatemia on admission was 20% vs. 5% for those who had normal lactate levels.

In 1994, Aduen and colleagues published the first large comparison of a point of care lactate analyzer with two accepted laboratory reference methods. They described various populations, including patients presenting to the ED for multiple reasons, non-hypotensive ward patients and ICU patients. In this one study, over 15 years ago, the incidence of hyperlactatemia (lactate > 2) in 489 non-hypotensive ward patients was 14%. Only one of these patients had a lactate greater than 4. The incidence of hyperlactatemia (lactate > 2) in 173 ED patients was 39%, with 11% greater than 4 mmol/L.


Prognosis of lactic acidosis depends on the etiology, duration and resolution of lactic acidosis. The underlying health state of the patient also is an important consideration. Multiple studies over the past 40 years have consistently demonstrated a direct correlation of mortality with elevated lactate levels, regardless of the etiology. More specifically, it appears that the ability and rapidity of lactate clearance may contribute more to a favorable outcome rather than an isolated presenting value.

Whether the etiology is trauma, septic shock or cardiac arrest, the body’s ability to rapidly clear lactate has been associated with improved outcomes. One example is in the setting of trauma patients, in which patients who were able to clear their lactate to normal levels (<2 mmol/L) within the first 24 hours had 100% survival rate. Compare these results to those that took 24-48 hours to normalize lactate (78% survival) and those that had persistent lactic acidosis after 48 hours (14% survival).

Physical exercise and self-limited seizures are two examples in which an elevated lactic acidosis may be present, but its duration is usually short and lactate is rapidly cleared to normal in these conditions. The prognosis that these patients will return to the same level of activity and function prior to their episode of lactic acidosis is very high.

Special considerations for nursing and allied health professionals.


What's the evidence?

1. Description of the problem

Huckabee, WE. “Abnormal resting blood lactate. I. The significance of hyperlactatemia in hospitalized patients”. Am J Med.. vol. 30. 1961. pp. 840-8. (Classic paper describing lactate metabolism as it relates to illness.)

Bellomo, R. “Bench-to-bedside review: Lactate and the kidney”. Crit Care.. vol. 6. 2002. pp. 322-6. (Very well written review of lactate metabolism in general and more specifically the contribution of the renal system.)

Emergency management

Rivers, E, Nguyen, B, Havstad, S. “Early goal-directed therapy in the the treatment of severe sepsis and septic shock”. N Engl J Med. vol. 345. 2001. pp. 1368-77(Seminal paper describing a goal-directed approach in the early treatment of severe sepsis and septic shock.)

Dellinger, RP, Levy, MM, Carlet, JM. “Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock”. Crit Care Med. vol. 36. 2008 Jan. pp. 296-327. (Internationally accepted guidelines in the treatment and management of septic shock.)

Pieracci, FM, Biffl, WL, More, EE. “Current Concepts in Resuscitation”. J Intensive Care Med. 2011 Feb 7. (Good review of endpoints of resuscitation and shock in general. Almost 200 references.)


Pyne, DB, Boston, T, Martin, DT. “Evaluation of the Lactate Pro blood lactate analyser”. Eur J Appl Physiol.. vol. 82. 2000. pp. 112-6. (Comparison of two handheld point of care lactate analyzers with a standard blood gas analyzer.)

Saunders, AC, Feldman, HA, Correia, CE. “Clinical evaluation of a portable lactate meter in type I glycogen storage disease”. J Inherit Metab Dis.. vol. 28. 2005. pp. 695-701. (Nice study demonstrating that capillary lactate measurements obtained on a point of care lactate meter are very accurate when compared to venous sampling measured on standard central lab analyzers.)

Lavery, RF, Livingston, DH, Tortella, BJ. “The utility of venous lactate to triage injured patients in the trauma center”. J Am Coll Surg. vol. 190. 2000. pp. 656-64. (A nice study comparing venous and arterial samples in trauma patients that demonstrated they were clinically interchangeable.)

Moviat, M, van Haren, F, van der Hoeven, H. “Conventional or physicochemical approach in intensive care unit patients with metabolic acidosis”. Crit Care. vol. 7. 2003 Jun. pp. R41-5. (Nice critical care based study demonstrating the limitations of the uncorrected anion gap.)

Kellum, JA, Kramer, DJ, Pinsky, MR. “Strong ion gap: a methodology for exploring unexplained anions”. J Crit Care. vol. 10. 1995 Jun. pp. 51-5. (Classic acid-base paper describing the determination of the strong ion gap in the context of the physicochemical approach to acid-base derangements.)

Gunnerson, KJ, Saul, M, He, S, Kellum, JA. “Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients”. Crit Care. vol. 10. 2006 Feb. pp. R22(First large paper describing various outcomes of different etiologies of metabolic acidosis in critically ill patients using a physicochemical approach.)

Gunnerson, KJ, Srisawat, N, Kellum, JA. “Is there a difference between strong ion gap in healthy volunteers and intensive care unit patients?”. J Crit Care. vol. 25. 2010 Sep. pp. 520-4. (Recent study evaluating "normal" values in various patient populations in regards to the physicochemical approach to acid-base analysis.)

Specific treatment

Stacpoole, PW. “Lactic acidosis: the case against bicarbonate therapy”. Ann Intern Med. vol. 105. Aug 1986. pp. 276-9. (A compelling editorial by one of the world's experts in lactate metabolism eschewing the routine use of bicarbonate in the treatment of lactic acidosis.)

Cooper, DJ, Walley, KR, Wiggs, BR. “Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study”. Am J Med. vol. 56. 1974 Feb. pp. 162-8. (One of the first reports of the inability of bicarbonate therapy to improve outcome in patients with lactic acidosis.)

Hoste, EA, Colpaert, K, Vanholder, RC. “Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis”. J Nephrol. vol. 18. 2005 May-Jun. pp. 303-7. (Nice paper demonstrating the effectiveness and properties of THAM when used as a buffer compared to sodium bicarbonate.)

Stacpoole, PW, Wright, EC, Baumgartner, TG. “A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactate Acidosis Study Group”. N Engl J Med. vol. 327. Nov 26 1992. pp. 1564-9. (Classic paper demonstrating that by preventing lactic acidosis production by blocking pyruvate dehydrogenase did not improve outcomes in critically ill patients with lactic acidosis.)

Disease monitoring, follow-up and disposition

Nguyen, HB, Rivers, EP, Knoblich, BP. “Early lactate clearance is associated with improved outcome in severe sepsis and septic shock”. Crit Care Med. vol. 32. 2004 Aug. pp. 1785-6. (One of the first well done trials demonstrating the importance of lactate clearance and the role of serial lactate measurements in septic shock.)

Luft, FC. “Lactic Acidosis Update for Critical Care Clinicians”. J Am Soc Nephrol.. vol. 12. 2001. pp. S15-S19. (Good review of pathophysiology of lactic acidosis.)

Grunert, S, Schmidts, M, Kenzel, S. “D-lactic acidosis: "right-left disorientation" in laboratory testing: acute encephalopathy in a child with carbohydrate malabsorption syndrome”. J Pediatr Gastroenterol Nutr. vol. 50. 2010 Jan. pp. 106-7. (Recent review of the literature and case report of D-lactic acidosis.)

Aduen, J, Bernstein, WK, Khastgir, T. “The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations”. JAMA. vol. 272. 1994 Dec 7. pp. 1678-85. (Novel study describing point of care lactate testing and also describing the incidence and outcome of various patient populations including the emergency department, ward patients and ICU patients.)

Khosravani, H, Shahpori, R, Stelfox, HT. “Occurence and adverse effect on outcome of hyperlactatemia in the critically ill”. Crit Care. vol. 13. 2009. pp. R90(Recent and very large observational study of more than 11,000 ICU patients with lactate levels on ICU admission.)