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), ketonomy and the development of metabolic acidosis.

[1]

Epidemiology

Usually, diabetic ketoacidosis develops in type 1 diabetes mellitus. The frequency of diabetic ketoacidosis varies from 5 to 20 cases per 1000 patients with diabetes mellitus.

[2], [3], [4]

Causes of the diabetic ketoacidosis and diabetic ketoacidotic coma

With the basis of the development of diabetic ketoacidosis there is a sharply depleted insulin deficiency.

[5],

Causes of Insulin Deficiency

• late diagnosis of diabetes mellitus;
• cancellation or insufficiency of the insulin dose;
• gross violation of diet;
• intercurrent diseases and interventions (infections, injuries, surgeries, myocardial infarction);
• pregnancy;
• use of drugs that have the properties of insulin antagonists (glucocorticosteroids, oral contraceptives, saluretics, etc.);
• pancreatectomy in persons who have not previously had diabetes.

[6],

Pathogenesis

Insulin deficiency leads to a decrease in the utilization of glucose by peripheral tissues, liver, muscles and fat tissue. The content of glucose in the cells decreases, resulting in the activation of glycogenolysis, gluconeogenesis and lipolysis. Their consequence is an uncontrolled hyperglycemic. The amino acids that result from the catabolism of proteins are also involved in gluconeogenesis in the liver and aggravate hyperglycemia.

Along with insulin deficiency, excessive secretion of the contrinsular hormones, especially glucagon (stimulates glycogenolysis and glyco-neogenesis), as well as cortisol, adrenaline and growth hormone, which possess fat-mobilizing action, i.e. Stimulating lipolysis and increasing the concentration of free fatty ones, is of great importance in the pathogenesis of diabetic ketoacidosis. Acids in the blood. The increase in formation and accumulation of the decomposition products of SLC-ketone bodies (acetone, acetoacetic acid of b-hydroxybutyric acid) leads to ketonemia, the accumulation of free hydrogen ions. In plasma, the concentration of bicarbonate is reduced, which is used to compensate for the acid reaction. After depletion of the buffer reserve, acid-base balance is disrupted, metabolic acidosis develops. Accumulation of excess CO2 in the blood leads to irritation of the respiratory center and hyperventilation.

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

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

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

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

There are no energy reserves in brain cells. The cells of the cerebral cortex and cerebellum are most sensitive to the absence of oxygen and glucose; their time of experiencing in the absence of O2 and glucose is 3-5 minutes. Compensatory decreases in cerebral blood flow and the level of metabolic processes decreases. The compensatory mechanisms include the buffer properties of the cerebrospinal fluid.

[7], [8], [9]

Symptoms of the diabetic ketoacidosis and diabetic ketoacidotic coma

Diabetic ketoacidosis develops, as a rule, gradually, for several days. Frequent symptoms of diabetic ketoacidosis - - symptoms of decompensated diabetes mellitus, including:

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

Then they are joined by the symptoms of ketoacidosis and dehydration. Symptoms of ketoacidosis include:

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

Symptoms of dehydration include:

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

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

With severe, uncorrected diabetic ketoacidosis, violations of consciousness develop up to the sopor and coma.

The most common complications of diabetic ketoacidosis include:

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

[10], [11], [12]

Diagnostics of the diabetic ketoacidosis and diabetic ketoacidotic coma

The diagnosis of diabetic ketoacidosis is based on an anamnesis of diabetes mellitus, usually type 1 (but it should be remembered that diabetic ketoacidosis can develop in people with previously unidentified diabetes mellitus, in 25% of cases ketoacidotic coma is the first manifestation of diabetes mellitus with which the patient gets to the doctor), the characteristic clinical manifestations and data of laboratory diagnostics (especially the increase in the level of sugar and beta-oxybutyrate in the blood, if it is impossible to analyze the ketone bodies in the blood, They eat ketone bodies in the urine).

Laboratory manifestations of diabetic ketoacidosis include:

• hyperglycemia and glucosuria (in people with diabetic ketoacidosis, glycemia is usually> 16.7 mmol / L);
• the presence of ketone bodies in the blood (the total concentration of acetone, beta-oksibaslyana and acetoacetic acids in the blood serum with diabetic ketoacidosis usually exceeds 3 mmol / l, but can reach 30 mmol / l at a rate of up to 0.15 mmol / l Beta- oxybutyric and acetoacetic acids with mild diabetic ketoacidosis is 3: 1, and in case of severe - 15: 1);
• metabolic acidosis (diabetic ketoacidosis is characterized by a concentration of bicarbonate and serum <15 meq / L and arterial blood pH <7.35 .In severe diabetic ketoacidosis - pH <7.
• disorders of electrolyte balance (often moderate hyponatremia due to the transition of intracellular fluid to the extracellular space and hypokalemia due to osmotic diuresis.The level of potassium in the blood can be normal or increased as a result of the release of potassium from cells in acidosis);
• other changes (leukocytosis is possible up to 15000-20000 / μl, not necessarily associated with infection, increased hemoglobin and hematocrit).

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

[13], [14]

Differential diagnosis

With diabetic ketoacidosis and especially with diabetic ketoacidotic coma, other causes of impaired consciousness should be excluded, including:

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

Most often it is necessary to differentiate diabetic ketoacidotic and hyperosmolar to precom and to whom with hypoglycemic precoma and coma.

The most important task is to distinguish these conditions from severe hypoglycemia, especially at the prehospital stage, when it is impossible to determine the level of sugar in the blood. In the presence of the slightest doubt in the cause of coma, trial insulin therapy is strictly contraindicated, since with hypoglycemia, the introduction of insulin can lead to the death of the patient.

Treatment of the diabetic ketoacidosis and diabetic ketoacidotic coma

Patients with diabetic ketoacidosis and diabetic ketoacidotic coma should be urgently hospitalized in the intensive care unit.

After establishing the diagnosis and initiating therapy, patients need constant monitoring of the condition, including monitoring of the main indicators of hemodynamics, body temperature and laboratory indicators.

If necessary, patients undergo artificial ventilation (IVL), urinary bladder catheterization, central venous catheter installation, nasogastric tube, parenteral nutrition.

In the resuscitation / intensive care unit is carried out.

• rapid blood glucose analysis 1 time per hour with intravenous glucose injection or once every 3 hours when switching to p / c injection;
• determination of ketone bodies in blood serum 2 r / day (if impossible - determination of ketone bodies in urine 2 r / day);
• determination of the level of K, Na in blood 3-4 r / day;
• study of acid-base state 2-3 r / day until stable pH normalization;
• hourly control of diuresis until elimination of dehydration;
• ECG monitoring;
• control of blood pressure, heart rate (heart rate), body temperature every 2 hours;
• chest radiography;
• the general analysis of a blood, urine 1 time in 2-3 days.

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

Rehydration at the prehospital stage

To eliminate dehydration, enter:

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

Further activities are carried out in intensive care units / intensive care units.

Insulin therapy

In the intensive care unit / intensive care unit is introduced ICD.

• Insulin soluble (human genetically engineered or semi-synthesized) intravenously slowly 10-14 U, then intravenously (in a solution of sodium chloride 09%) at a rate of 4-8 U / h (to prevent the adsorption of insulin on the plastic for every 50 units 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, insulin infusion rate is reduced by 2 times.
• Insulin (human genetically engineered or semi-synthetic) is injected intravenously at a rate of 0.1 U / kg / h until elimination of diabetic ketoacidosis (125 U of diluted in 250 ml of 0.9% sodium chloride, ie in 2 ml of the solution is contained 1 unit of insulin), with a decrease in glycemia to 13-14 mmol / L, the infusion rate of insulin is reduced by a factor of 2.
• Insulin (human genetically engineered or semi-synthetic) in the range of 10-20 units, 5-10 units each hour (only if the infusion system can not be installed quickly). Since comatose and precomatous conditions are accompanied by microcirculation disorders, the absorption of insulin injected in / m is also impaired. This method should be considered only as a temporary alternative to intravenous administration.

With a decrease in glycemia to 11-12 mmol / l and pH> 7.3, they switch to subcutaneous insulin administration.

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

Rehydration

For rehydragacim use:

• Sodium chloride, 0.9% rr, IV drip at a rate of 1 L for 1 hour, 500 ml for 2 and 3 hours of infusion, 250-500 ml for the following hours.

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

• Dextrose, 5% rr, IV drip at a rate of 0.5-1 L / h (depending on the volume of circulating blood, blood pressure and diuresis)
• Insulin (human genetically engineered or semi-synthetic) in / in struyno 3-4 units for every 20 g of dextrose.

Correction of electrolyte disturbances

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

Potassium chloride IV drip 1-3 g / h, the duration of therapy is determined individually.

When hypomagnesemia is administered:

• Magnesium sulfate - 50% pp, in / m 2 p / day, before correction of hypomagnesemia.

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

• Potassium phosphate monobasic iv drip 50 mmol phosphorus / day (children 1 mmol / kg / day) until the hypophosphataemia is corrected or
• Potassium phosphate dibasic IV drip 50 mmol phosphorus / day (children 1 mmol / kg / day) until the correction of hypophosphatemia.

In this case, it is necessary to take into account the amount of potassium introduced in the composition of phosphate

[15]

Correction of acidosis

It is not proven that the use of bicarbonate accelerates the normalization of metabolic indicators and makes treatment more successful.

Only with severe acidosis (pH <6.9), expressed lactic acidosis or life-threatening hyperkalemia, is administered:

• Sodium bicarbonate in / in struino 44-50 meq / h until a pH of 7.1-7.15.

[16], [17], [18], [19]

Evaluation of treatment effectiveness

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

[20], [21]

Errors and unreasonable appointments

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

The use of potassium even with moderate hypokalemia in persons with oligo- or anuria can lead to life-threatening hyperkalemia.

The appointment 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, neurologic disorders, hypoxia of tissues, including the brain).

[22], [23], [24], [25]

Forecast

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