Lactic acidotic coma E87.2

Synonyms

Coma due to lactic acidosis; coma due to lactic acidosis;

First described by

In 1780, the Swedish chemist Scheele succeeded in isolating lactate from sour milk.(Glowatzki 2015).

Lactic acidosis was first described by Clausen in 1925 (Romy 2012). However, it was not until 1961 through publications by Huckabee that lactic acidosis received increasing clinical attention (Oberdisse 1977).

Daughaday et al. described non-ketotic acidosis in diabetics in 1962.

Adolf Kußmaul (1822-1902) was the first to describe the special respiration in coma diabeticum in 1874, which was later named after him and is known as Kußmaul respiration (Kluge 2003).

Lactic acidosis is defined as an accumulation of lactate in the serum > 5 mmol / l, which leads to a decompensated, severe metabolic acidosis with a pH < 7.25 (Rau 2011).

One speaks of a lactic acidotic coma if, in addition to the above findings, there is also a systolic blood pressure < 90 mmHg (Schoenenberger 2008).

The normal value for lactate in the blood is between 0.5 - 1.8 mmol / l. Values between 2.5 - 5 mmol / l are referred to as hyperlactatemia (Rau 2011).

Diabetic coma is divided into:

• diabetic ketoacidosis (DKA)
• hyperosmolar non-ketoacidotic coma (HHS)
• Lactic acidosis (Berndt 2015).

Lactic acidosis is divided into:

• Type A - Lactic acidosis:

This is a so-called acquired, anaerobic form (Renz 2009). As a result of severe hypoxia with disturbed tissue perfusion, there is a reduced supply of oxygen to the tissue (Hien 2007), which leads to an increased production of lactate (Renz 2009).

• Type B - Lactic acidosis:

In type B, the aerobic form, metabolic causes are found (Renz 2009). Both an increased production of lactate and a disturbed utilization of lactate are present (Hien 2007).

Among metabolic acidoses, lactic acidosis is the most common form (Renz 2009).

In Germany, 51 cases of lactic acidosis occurred in diabetics between 1990 and 2002 according to the regulatory authority.Lactic acidotic coma is very rare overall in diabetics treated with metformin and can generally be prevented by careful patient selection with attention to contraindications (Kasper 2015). The incidence here is approximately 1 - 5 cases per 100,000 patient-years (Hien 2007).

In about 15 % of cases, lactic acidosis occurs in conjunction with a ketoacidotic derailment (Hien 2007).

Type A lactic acidosis can be triggered by:

• severe hypoxia such as with:
  • septic, cardiogenic or hypovolemic shock (Hien 2007)
  • bronchial asthma
  • severe anaemia
  • regional perfusion disorders (e.g. mesenteric ischemia, compartment syndrome, etc.)
  • CO poisoning (Berndt 2015)

Type B is triggered by metabolic changes e.g. in:

• Hyperthyroidism
• liver insufficiency (Scheurlen 2013)
• administration of contrast media (e.g. pyelography [Herold 2020])
• intoxication with ethanol or methanol
• severe tissue necrosis (Johnsen 2011)
• severe infections such as cholera or malaria
• Neoplasms
• renal insufficiency
• sepsis
• Vit. B1 deficiency
• epilepsy
• medications such as
  • Biguanide
  • Paracetamol
  • Salicylates
• strong muscular activity (Hien 2007)
• inborn errors of metabolism such as:
  • Fructose- 1,6- diphosphatase deficiency
  • Glucose- 6- phosphatase deficiency
  • Pyruvate carboxylase deficiency
  • Pyruvate dehydrogenase deficiency

(Berndt 2015)

Lactate represents the end product of the anaerobic glucose metabolism, which can be introduced into the citrate cycle in an oxygen-dependent manner and is thus available for gluconeogenesis.

The formation of lactate can take place in all tissues, the degradation only in liver, kidney and brain (Renz 2009).

If hypoxia of the tissues occurs, each organ produces lactate from glycolysis and lactic acidosis occurs. This in turn reduces vascular and cardiac contractility and a vicious circle ensues (Hien 2007).

Lactate breakdown is inhibited from a pH < 7.2. From a pH < 7.0, the liver itself produces lactates.

Biguanides also inhibit the breakdown of lactate in the liver and kidneys. (Hien 2007)

The symptoms are distributed among different organs:

• respiratory:
  • compensatory hyperventilation (so-called kissing-mouth breathing )
• gastrointestinal:
  • Inappetence
  • nausea
  • vomiting
  • acute abdomen
• central nervous: From a blood lactate level of > 5 mmol / l and a pH < 7.25, there are altered states of consciousness with (Johnsen 2011)
  • confusion
  • fatigue
  • restlessness
  • up to coma (Hien 2007)
  • increased intracranial pressure (Rau 2011)
• cardiovascular:
  • arterial hypotension
  • Tachycardia
  • Hyperkalemia (results from compensatory potassium shift to the extracellular space [Johnsen 2011])
  • Cardiac arrhythmias (Rau 2011)
  • Late-stage hypothermia (Berndt 2015).

The diagnosis of lactic acidotic coma is made on the basis of the clinical picture, the (foreign) medical history and the laboratory findings.

In a lactic acidotic coma are found:

• lactate in the serum > 5 mmol / l
• pronounced acidosis with a pH < 7.25 (Rau 2011)
• compensatory decrease of the pCO2
• increased anion gap
• Hyperkalemia (can occur due to the compensatory shift of potassium to the extracellular space [Johnsen 2011])
• Increase in serum chloride (Berndt 2015).
• Blood glucose may be minimally elevated
• typically no ketone bodies (Scheurlen 2013)

For special questions, especially in hereditary forms, the determination of pyruvate or the lactate / pyruvate - ratio can be useful (Renz 2009).

In addition to determinations of the typical internal medicine admission laboratory may be required:

• Vit. B1 in case of a deficiency
• Thyroid hormones
• Blood cultures etc.

In the case of sudden unconsciousness, differential diagnosis may include:

• Cardiovascular e.g:
  • Shock
  • collapse
  • Adam Stokes seizure
  • Circulatory arrest
• Cerebral disorders e. g.:
  • subarachnoid haemorrhage
  • subdural / epidural haematoma
  • hypertonic mass haemorrhage
  • sinus thrombosis
  • meningitis
  • encephalitis
  • encephalomalacia
  • Craniocerebral trauma
  • Epilepsy
  • Generalized seizure
• Endocrine disorders e. g.:
  • hypoglycemic shock see hypoglycemic coma (hypertonic muscles, skin moist, breathing normal etc.)
  • Coma diabeticum
  • Addison crisis
  • diabetes insipidus
  • pituitary coma
  • hypercalcemic crisis
  • thyrotoxic crisis
  • myxedematous coma
  • ketoacidotic com a (ketone positive)
  • hyperosmolar com a (osmolarity > 320 mmol / l [Menche 2020])
• Toxic e.g:
• exogenous poisoning by
  • Alcohol
  • drugs, especially heroin
  • Psychotropic drugs
  • Sedatives
• endogenous poisoning by
  • Coma hepaticum
  • Uremia (Herold 2020)
• Anoxemic e. g.:
  • Hypercapnia in respiratory global insufficiency
  • Asphyxia (Herold 2020)
• Mental e. g.:
  • Hysteria (Herold 2020)

Successful treatment of lactic acidotic coma is only possible by eliminating the causes (Renz 2009).

Treatment depends on both the cause and the severity of lactic acidosis (Berndt 2015).

• Vit. B1 - deficiency:

This is particularly common in alcoholics and malnourished people. If a B1 deficiency is detected, the slow i.v. administration of thiamine is recommended (Berndt 2015).

• Biguanide-induced lactic acidosis:

In this case, the elimination of the substance should be carried out by dialysis. This not only removes the metformin from the body, but at the same time bicarbonate is added without sodium or volume load (Berndt 2015).

• Bicarbonate administration:

In lactic acidotic coma, the production of lactate is so pronounced that the acidosis can no longer be compensated by alkali substitution, as the sodium load would then be too high.

However, a pH of at least > 7.1 should be aimed for. The increasing sodium concentration can then be stimulated with diuretics (Hien 2007).

Another problem is the CO2 produced by buffering with bicarbonate, which can only be eliminated by increasing alveolar ventilation. The infusion should therefore be slow. Otherwise, elimination is not guaranteed and the CO2 level in the blood may increase, since the diffusion of CO2 through the cell membrane on the one hand increases intracellular acidosis and on the other hand influences cellular metabolism.

Therefore, buffer substances that do not lead to an increased formation of CO2 such as sodium carbonate, sodium hydrogen carbonate or tris (hydroxymethyl)-aminomethane (TRIS) are discussed

(Berndt 2015).

The massive losses of potassium that occur due to diuresis and acidosis must also be compensated for. This can best be done by hemodialysis. This should be carried out from a

pH < 7.0 and lactate values > 90 mmol / l (Hien 2007).

- Other indications for hemodialysis are:

- Biguanide-induced lactic acidosis (see above)

- hypothermia

- oliguria / anuria

- azotemia

(Berndt 2015)

Kluge (2018) reports a mortality of 80% for serum lactate levels > 10 mmol / l and 100% if the lactic acidosis persists for more than 48 h.

The mortality of lactic acidotic coma triggered by therapy with biguanides is also high and is up to 50 % (Reitgruber 2021).

Prophylaxis

To keep lactic acidotic coma as low as possible during treatment with metformin, it is essential to observe the contraindications.

These are:

• severe renal insufficiency with persistent eGFR < 30 ml / min.
• Conditions predisposing to tissue hypoxia such as respiratory failure, circulatory shock, severe heart failure (Mehnert 2003).
• decompensated heart failure
• severe liver dysfunction
• Fasting
• reduction diet
• alcoholism
• consumptive diseases
• acute and severe diseases
• gastrointestinal infections
• gravidity
• 48 h before and after a pyelography with contrast media, as otherwise there is a risk of lactic acidosis
• before and after surgery (see also diabetes and surgery)

(Herold 2020)

1. Berndt M et al. (2015) Diabetic coma and perioperative diabetes therapy. In: Marx N et al. The intensive care medicine. Springer Verlag Berlin / Heidelberg 1 - 30 DOI 10.1007/978-3-642-54675-4_78-1.
2. Glowatzki F (2015) The role of lactate-producing lactic acid bacteria in children with short bowel syndrome and D- lactate acidosis associated encephalopathy. Inaugural dissertation for the degree of Doctor of Medicine of the Department of Medicine, Justus Liebig University Giessen.
3. Herold G et al (2020) Internal Medicine. Herold Publishers 733, 746
4. Hien P et al (2007) Lactic acidosis. In: Diabetes handbook. A guide for clinic and practice. Springer Verlag Berlin / Heidelberg. https://doi.org/10.1007/978-3-540-48552-0_15
5. Johnsen J R (2011) Interaction of lactate with central glucose sensors and pancreatic ß-cells. Inaugural dissertation for the award of the doctorate of the University of Lübeck Medical Faculty.
6. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2413
7. Kluge F J et al (2003) Think clearly, feel warmly, act calmly: Adolf Kußmaul (1822-1902) and his significance for medicine in the 21st century. Z Rheumatol 62: 484-490
8. Kluge S et al (2018) Lactic acidosis - update 2018. Dtsch Med Wochenschr 143 (15) 1082 - 1085 DOI: 10.1055/a-0585-7986.
9. Menche N (2020) Internal medicine: white series. Elsevier Urban and Fischer Publishers 179 - 180.
10. Oberdisse K et al (1977) Handbook of internal medicine: seventh volume: metabolic diseases. Springer Verlag Berlin / Heidelberg / New York 682
11. Rau N (2011) Modulation of hunger and food intake by glucose and lactate in healthy volunteers.Inauguraldissertation zur Erlangung der Doktorwürde der Universität zu Lübeck Medizinische Fakultät.
12. Reitgruber D et al (2021) Lactic acidosis. In: internal intensive care medicine for beginners. Springer, Berlin, Heidelberg. 769 - 772 https://doi.org/10.1007/978-3-662-61823-3_40
13. Renz H (2009) Practical laboratory diagnostics: textbook on laboratory medicine, clinical chemistry and haematology. Walter de Gruyter Publishers Berlin / New York 22 - 23.
14. Romy W et al. (2012) Mortalitas asidosis metabolik lactate dan non sanglah. Sari Pediatri, vol. 13, no. 5, 352
15. Scheurlen P G (2013) Heidelberg pocket books: systematic differential diagnosis of internal diseases considering the subject catalogue. Springer Verlag Berlin / Heidelberg / New York 198
16. Schoenenberger R A et al (2008) Internal medicine emergencies: safely through the acute situation and the subsequent 48 hours. Georg Thieme Verlag Stuttgart 14