Diabetic ketoacidosis and diabetic ketoacidotic coma

Diabetic ketoacidosis is an acute complication of diabetes mellitus, which is characterized by hyperglycemia (more than 14 mmol/l), ketonemia and the development of metabolic acidosis.

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Epidemiology

Diabetic ketoacidosis usually develops in diabetes mellitus type 1. The incidence of diabetic ketoacidosis ranges from 5 to 20 cases per 1000 patients with diabetes mellitus.

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Causes diabetic ketoacidosis and diabetic ketoacidotic coma

The development of diabetic ketoacidosis is based on a severe insulin deficiency.

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Causes of insulin deficiency

• late diagnosis of diabetes;
• insulin withdrawal or insufficient dose;
• gross violation of diet;
• intercurrent diseases and interventions (infections, injuries, operations, myocardial infarction);
• pregnancy;
• the use of drugs that have insulin antagonist properties (glucocorticosteroids, oral contraceptives, saluretics, etc.);
• pancreatectomy in individuals who have not previously suffered from diabetes mellitus.

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Pathogenesis

Insulin deficiency leads to decreased utilization of glucose by peripheral tissues, liver, muscles and adipose tissue. The glucose content in cells decreases, resulting in activation of glycogenolysis, gluconeogenesis and lipolysis processes. Their consequence is uncontrolled hyperglycemia. Amino acids formed as a result of protein catabolism are also included in gluconeogenesis in the liver and aggravate hyperglycemia.

Along with insulin deficiency, excessive secretion of counter-insular hormones, primarily glucagon (stimulates glycogenolysis and gluconeogenesis), as well as cortisol, adrenaline and growth hormone, which have a fat-mobilizing effect, i.e., stimulate lipolysis and increase the concentration of free fatty acids in the blood, are of great importance in the pathogenesis of diabetic ketoacidosis. Increased formation and accumulation of FFA decay products - ketone bodies (acetone, acetoacetic acid, b-hydroxybutyric acid) leads to ketonemia, accumulation of free hydrogen ions. The concentration of bicarbonate in plasma decreases, which is spent on compensating for the acid reaction. After depletion of the buffer reserve, the acid-base balance is disturbed, metabolic acidosis develops. Accumulation of excess CO2 in the blood leads to irritation of the respiratory center and hyperventilation.

Hyperventilation causes glucosuria, osmotic diuresis with the development of dehydration. In diabetic ketoacidosis, the body's losses can be up to 12 liters, i.e. 10-12% of body weight. Hyperventilation increases dehydration due to water loss through the lungs (up to 3 liters per day).

Diabetic ketoacidosis is characterized by hypokalemia due to osmotic diuresis, protein catabolism, and decreased activity of K ⁺ -Na ⁺ -dependent ATPase, which leads to a change in membrane potential and the release of K ⁺ ions from the cell along a concentration gradient. In individuals with renal failure, in whom the excretion of K ⁺ ions in the urine is impaired, normo- or hyperkalemia is possible.

The pathogenesis of the disorder of consciousness is not fully understood. Impaired consciousness is associated with:

• hypoxic effect of ketone bodies on the brain;
• cerebrospinal fluid acidosis;
• dehydration of brain cells; due to hyperosmolarity;
• CNS hypoxia due to an increase in the level of HbA1c in the blood and a decrease in the content of 2,3-diphosphoglycerate in erythrocytes.

Brain cells have no energy reserves. The cells of the cerebral cortex and cerebellum are most sensitive to the absence of oxygen and glucose; their survival time in the absence of O2 and glucose is 3-5 minutes. In compensation, cerebral blood flow decreases and the level of metabolic processes decreases. Buffer properties of cerebrospinal fluid also belong to compensatory mechanisms.

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Symptoms diabetic ketoacidosis and diabetic ketoacidotic coma

Diabetic ketoacidosis usually develops gradually, over several days. Common symptoms of diabetic ketoacidosis are symptoms of decompensated diabetes mellitus, including:

• thirst;
• dry skin and mucous membranes;
• polyuria;
• weight loss;
• weakness, adynamia.

Then symptoms of ketoacidosis and dehydration join in. Symptoms of ketoacidosis include:

• acetone smell from the mouth;
• Kussmaul's breathing;
• nausea, vomiting.

Symptoms of dehydration include:

• decreased skin turgor,
• decreased tone of the eyeballs,
• lowering blood pressure and body temperature.

In addition, signs of acute abdomen are often observed, caused by the irritating effect of ketone bodies on the gastrointestinal mucosa, small-point hemorrhages in the peritoneum, dehydration of the peritoneum and electrolyte disturbances.

In severe, uncorrected diabetic ketoacidosis, disturbances of consciousness develop, including stupor and coma.

The most common complications of diabetic ketoacidosis include:

• cerebral edema (develops rarely, more often in children, usually leads to the death of patients);
• pulmonary edema (often caused by incorrect infusion therapy, i.e. the introduction of excess fluid);
• arterial thrombosis (usually caused by increased blood viscosity due to dehydration, decreased cardiac output; myocardial infarction or stroke may develop in the first hours or days after the start of treatment);
• shock (it is based on a decrease in the volume of circulating blood and acidosis, possible causes are myocardial infarction or infection with gram-negative microorganisms);
• addition of a secondary infection.

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Diagnostics diabetic ketoacidosis and diabetic ketoacidotic coma

Diagnosis of diabetic ketoacidosis is based on the history of diabetes mellitus, usually type 1 (however, it should be remembered that diabetic ketoacidosis can also develop in individuals with previously undiagnosed diabetes mellitus; in 25% of cases, ketoacidotic coma is the first manifestation of diabetes mellitus with which the patient comes to the doctor), characteristic clinical manifestations and laboratory diagnostic data (primarily an increase in the level of sugar and beta-hydroxybutyrate in the blood; if it is impossible to analyze ketone bodies in the blood, ketone bodies are determined in the urine).

Laboratory manifestations of diabetic ketoacidosis include:

• hyperglycemia and glucosuria (in individuals with diabetic ketoacidosis, glycemia is usually > 16.7 mmol/l);
• the presence of ketone bodies in the blood (the total concentration of acetone, beta-hydroxybutyric and acetoacetic acids in the blood serum in diabetic ketoacidosis usually exceeds 3 mmol/l, but can reach 30 mmol/l with a norm of up to 0.15 mmol/l. The ratio of beta-hydroxybutyric and acetoacetic acids in mild diabetic ketoacidosis is 3:1, and in severe - 15:1);
• metabolic acidosis (diabetic ketoacidosis is characterized by a serum bicarbonate concentration of < 15 mEq/l and arterial blood pH of < 7.35. In severe diabetic ketoacidosis, pH < 7.
• electrolyte imbalance (often moderate hyponatremia due to the transition of intracellular fluid into the extracellular space and hypokalemia due to osmotic diuresis. The potassium level in the blood may be normal or elevated as a result of the release of potassium from cells during acidosis);
• other changes (leukocytosis up to 15,000-20,000/μl is possible, not necessarily associated with infection, increased hemoglobin and hematocrit levels).

Also of great importance for assessing the severity of the condition and determining the treatment tactics is the study of the acid-base balance and electrolytes in the blood. ECG allows to identify signs of hypokalemia and heart rhythm disturbances.

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Differential diagnosis

In diabetic ketoacidosis and especially in diabetic ketoacidotic coma, it is necessary to exclude other causes of impaired consciousness, including:

• exogenous intoxication (alcohol, heroin, sedatives and psychotropic drugs);
• endogenous intoxications (uremic and hepatic coma);
• cardiovascular:
  • collapse;
  • Adams-Stokes attacks;
• other endocrine disorders:
  • hyperosmolar coma;
  • hypoglycemic coma;
  • lactic acidotic coma,
  • severe hypokalemia;
  • adrenal insufficiency;
  • thyrotoxic crisis or hypothyroid coma;
  • diabetes insipidus;
  • hypercalcemic crisis;
• cerebral pathology (often with possible reactive hyperglycemia) and mental disorders:
  • hemorrhagic or ischemic stroke;
  • subarachnoid hemorrhage;
  • episyndrome;
  • meningitis,
  • traumatic brain injury;
  • encephalitis;
  • cerebral sinus thrombosis;
• hysteria;
• cerebral hypoxia (due to carbon monoxide poisoning or hypercapnia in patients with severe respiratory failure).

Most often, it is necessary to differentiate diabetic ketoacidotic and hyperosmolar precoma and coma from hypoglycemic precoma and coma.

The most important task is to distinguish these conditions from severe hypoglycemia, especially at the pre-hospital stage, when it is impossible to determine the blood sugar level. If there is the slightest doubt about the cause of the comatose state, trial insulin therapy is strictly contraindicated, since in hypoglycemia, insulin administration can lead to the death of the patient.

Treatment diabetic ketoacidosis and diabetic ketoacidotic coma

Patients with diabetic ketoacidosis and diabetic ketoacidotic coma require urgent hospitalization in the intensive care unit.

After diagnosis and initiation of therapy, patients require constant monitoring of their condition, including monitoring of key hemodynamic parameters, body temperature, and laboratory parameters.

If necessary, patients undergo artificial ventilation, bladder catheterization, installation of a central venous catheter, nasogastric tube, and parenteral nutrition.

In the intensive care unit they carry out.

• express blood glucose analysis once an hour with intravenous administration of glucose or once every 3 hours when switching to subcutaneous administration;
• determination of ketone bodies in blood serum 2 times a day (if not possible, determination of ketone bodies in urine 2 times a day);
• determination of the level of K, Na in the blood 3-4 times a day;
• study of the acid-base balance 2-3 times a day until stable normalization of pH;
• hourly monitoring of diuresis until dehydration is eliminated;
• ECG monitoring;
• monitoring of blood pressure, heart rate (HR), body temperature every 2 hours;
• chest x-ray;
• general blood and urine tests once every 2-3 days.

The main directions of treatment of patients are: insulin therapy (to suppress lipolysis and ketogenesis, inhibition of glucose production by the liver, stimulation of glycogen synthesis), rehydration, correction of electrolyte disturbances and acid-base balance disturbances, elimination of the cause of diabetic ketoacidosis.

Pre-hospital rehydration

To eliminate dehydration, the following is administered:

Sodium chloride, 0.9% solution, intravenously by drip at a rate of 1-2 l/h in the 1st hour, then 1 l/h (in the presence of cardiac or renal failure, the infusion rate is reduced). The duration and volume of the administered solution are determined individually.

Further measures are carried out in the intensive care units.

Insulin therapy

An ICD is inserted in the intensive care unit.

• Soluble insulin (human genetically engineered or semi-synthetic) intravenously by slow jet stream 10-14 U, then intravenously by drip (in 0.9% sodium chloride solution) at a rate of 4-8 U/hour (to prevent insulin adsorption on the plastic, for every 50 U of insulin, add 2 ml of 20% albumin and bring the total volume to 50 ml with 0.9% sodium chloride solution. When glycemia decreases to 13-14 mmol/l, the insulin infusion rate is reduced by 2 times.
• Insulin (human genetically engineered or semi-synthetic) intravenously by drip at a rate of 0.1 U/kg/hour until diabetic ketoacidosis is eliminated (125 U are diluted in 250 ml of 0.9% sodium chloride, i.e. 2 ml of solution contains 1 U of insulin); when glycemia decreases to 13-14 mmol/l, the insulin infusion rate is reduced by 2 times.
• Insulin (human genetically engineered or semi-synthetic) IM 10-20 U, Zitem 5-10 U every hour (only if it is impossible to quickly establish an infusion system). Since comatose and pre-comatose states are accompanied by impaired microcirculation, the absorption of insulin administered IM is also impaired. This method should be considered only as a temporary alternative to IV administration.

When glycemia decreases to 11-12 mmol/l and pH > 7.3, switch to subcutaneous insulin administration.

• Insulin (human genetically engineered or semi-synthetic) - subcutaneously 4-6 U every 2-4 hours; the first subcutaneous administration of insulin is performed 30-40 minutes before the end of the intravenous infusion of drugs.

Rehydration

For rehydration use:

• Sodium chloride, 0.9% solution, intravenously by drip at a rate of 1 l during the 1st hour, 500 ml during the 2nd and 3rd hours of infusion, 250-500 ml in the following hours.

If the blood glucose level is < 14 mmol/l, glucose is added to the sodium chloride solution or the sodium chloride solution is replaced with a glucose solution:

• Dextrose, 5% solution, intravenously by drip at a rate of 0.5-1 l/h (depending on the volume of circulating blood, arterial pressure and diuresis)
• Insulin (human genetically engineered or semi-synthetic) intravenously by jet stream 3-4 U for every 20 g of dextrose.

Correction of electrolyte disturbances

Patients with hypokalemia are given a potassium chloride solution. Its rate of administration in diabetic ketoacidosis depends on the concentration of potassium in the blood:

Potassium chloride intravenously by drip 1-3 g/hour, duration of therapy is determined individually.

For hypomagnesemia, administer:

• Magnesium sulfate - 50% pp, intramuscularly 2 times a day, until hypomagnesemia is corrected.

Only in individuals with hypophosphatemia (with a blood phosphate level < 0.5 mmol/l) the following is administered:

• Potassium phosphate monobasic intravenously by drip 50 mmol phosphorus/day (for children 1 mmol/kg/day) until hypophosphatemia is corrected or
• Potassium phosphate dibasic intravenously by drip 50 mmol phosphorus/day (for children 1 mmol/kg/day) until hypophosphatemia is corrected.

In this case, it is necessary to take into account the amount of potassium introduced as part of the phosphate.

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Correction of acidosis

It has not been proven that the use of bicarbonate accelerates the normalization of metabolic parameters and makes treatment more successful.

Only in cases of severe acidosis (pH < 6.9), severe lactic acidosis or life-threatening hyperkalemia is the following administered:

• Sodium bicarbonate intravenously by jet stream 44-50 meq/h until pH reaches 7.1-7.15.

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Evaluation of treatment effectiveness

Signs of effective therapy for diabetic ketoacidosis include the elimination of clinical manifestations of diabetic ketoacidosis, achievement of target blood glucose levels, and the disappearance of ketoacidosis and electrolyte disorders.

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Errors and unjustified appointments

The introduction of a hypotonic solution at the initial stages of therapy for diabetic ketoacidosis can lead to a rapid decrease in plasma osmolarity and the development of cerebral edema (especially in children).

Administration of potassium even to moderate hypokalemia in individuals with oligo- or anuria may result in life-threatening hyperkalemia.

The use of phosphate in renal failure is contraindicated.

Unjustified administration of bicarbonates (in the absence of life-threatening hyperkalemia, severe lactic acidosis, or at pH > 6.9) may lead to side effects (alkalosis, hypokalemia, neurological disorders, tissue hypoxia, including the brain).

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Forecast

The prognosis of diabetic ketoacidosis depends on the effectiveness of treatment. Mortality in diabetic ketoacidosis remains quite high and is 5-15%, in people over 60 years old it reaches 20%.