Hyperosmolar coma

Hyperosmolar coma is a complication of diabetes mellitus, which is characterized by hyperglycemia (more than 38.9 mmol/l), blood hyperosmolarity (more than 350 mosm/kg), severe dehydration, and the absence of ketoacidosis.

[ 1 ]

Epidemiology

Hyperosmolar coma occurs 6-10 times less frequently than ketoacidotic coma. In most cases, it occurs in patients with type 2 diabetes, more often in the elderly. In 90% of cases, it develops against the background of renal failure.

[ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ]

Causes hyperosmolar coma

Hyperosmolar coma can develop as a result of:

• severe dehydration (due to vomiting, diarrhea, burns, long-term treatment with diuretics);
• insufficiency or absence of endogenous and/or exogenous insulin (e.g. due to inadequate insulin therapy or its absence);
• increased need for insulin (in case of severe violation of the diet or introduction of concentrated glucose solutions, as well as in infectious diseases, especially pneumonia and urinary tract infections, other severe concomitant diseases, injuries and operations, dative therapy with drugs that have insulin antagonist properties - glucocorticosteroids, sex hormone drugs, etc.).

[ 7 ]

Pathogenesis

The pathogenesis of hyperosmolar coma is not fully understood. Severe hyperglycemia occurs as a result of excess glucose intake, increased hepatic glucose production, glucose toxicity, suppression of insulin secretion and glucose utilization by peripheral tissues, and dehydration. It was believed that the presence of endogenous insulin prevents lipolysis and ketogenesis, but it is not sufficient to suppress hepatic glucose production.

Thus, gluconeogenesis and glycogenolysis lead to pronounced hyperglycemia. However, the concentration of insulin in the blood in diabetic ketoacidosis and hyperosmolar coma is almost the same.

According to another theory, in hyperosmolar coma, the concentrations of somatotropic hormone and cortisol are lower than in diabetic ketoacidosis; in addition, in hyperosmolar coma, the insulin/glucagon ratio is higher than in diabetic ketoacidosis. Plasma hyperosmolarity leads to suppression of the release of FFA from adipose tissue and inhibits lipolysis and ketogenesis.

The mechanism of plasma hyperosmolarity includes increased production of aldosterone and cortisol in response to dehydration hypovolemia; as a result, hypernatremia develops. High hyperglycemia and hypernatremia lead to plasma hyperosmolarity, which in turn causes pronounced intracellular dehydration. At the same time, the sodium content in the cerebrospinal fluid also increases. Disruption of water and electrolyte balance in brain cells leads to the development of neurological symptoms, cerebral edema, and coma.

[ 8 ], [ 9 ], [ 10 ], [ 11 ]

Symptoms hyperosmolar coma

Hyperosmolar coma develops over several days or weeks.

The patient experiences increasing symptoms of decompensated diabetes mellitus, including:

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

In addition, symptoms of dehydration are noted;

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

Characteristic neurological symptoms:

• hemiparesis;
• hyperreflexia or areflexia;
• disturbances of consciousness;
• convulsions (in 5% of patients).

In severe, uncorrected hyperosmolar conditions, stupor and coma develop. The most common complications of hyperosmolar coma include:

• epileptic seizures;
• deep vein thrombosis;
• pancreatitis;
• renal failure.

[ 12 ]

Diagnostics hyperosmolar coma

The diagnosis of hyperosmolar coma is based on the history of diabetes mellitus, usually type 2 (however, it should be remembered that hyperosmolar coma can also develop in individuals with previously undiagnosed diabetes mellitus; in 30% of cases, hyperosmolar coma is the first manifestation of diabetes mellitus), characteristic clinical manifestations of laboratory diagnostic data (primarily severe hyperglycemia, hypernatremia, and plasma hyperosmolarity in the absence of acidosis and ketone bodies. Similar to diabetic ketoacidosis, ECG can reveal signs of hypokalemia and cardiac arrhythmia.

Laboratory manifestations of hyperosmolar state include:

• hyperglycemia and glucosuria (glycemia is usually 30-110 mmol/l);
• sharply increased plasma osmolarity (usually > 350 mOsm/kg with a normal value of 280-296 mOsm/kg); osmolality can be calculated using the formula: 2 x ((Na) (K)) + blood glucose level / 18 blood urea nitrogen level / 2.8.
• hypernatremia (low or normal concentration of sodium in the blood is also possible due to the release of water from the intracellular space into the extracellular space);
• absence of acidosis and ketone bodies in the blood and urine;
• other changes (possible leukocytosis up to 15,000-20,000/μl, not necessarily associated with infection, increased hemoglobin and hematocrit levels, moderate increase in the concentration of urea nitrogen in the blood).

[ 13 ], [ 14 ]

Differential diagnosis

Hyperosmolar coma is differentiated from other possible causes of impaired consciousness.

Considering the elderly age of patients, the differential diagnosis is most often made with cerebrovascular accident and subdural hematoma.

An extremely important task is the differential diagnosis of hyperosmolar coma with diabetic ketoacidotic and especially hypoglycemic coma.

[ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ]

Treatment hyperosmolar coma

Patients with hyperosmolar coma should be hospitalized in the intensive care unit. Once the diagnosis is established and therapy is initiated, patients require constant monitoring of their condition, including monitoring of the main hemodynamic parameters, body temperature, and laboratory parameters.

If necessary, patients undergo artificial ventilation, bladder catheterization, central venous catheter placement, and parenteral nutrition. The intensive care unit provides:

• express blood glucose analysis once an hour with intravenous glucose administration or once every 3 hours when switching to subcutaneous administration;
• determination of ketone bodies in the blood serum 2 times a day (if not possible, determination of ketone bodies in the 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, body temperature every 2 hours;
• chest x-ray,
• general blood and urine tests once every 2-3 days.

As with diabetic ketoacidosis, the main treatments for patients with hyperosmolar coma are rehydration, insulin therapy (to reduce glycemia and plasma hyperosmolarity), correction of electrolyte disturbances and acid-base balance disorders).

Rehydration

Enter:

Sodium chloride, 0.45 or 0.9% solution, intravenously by drip 1-1.5 l during the 1st hour of infusion, 0.5-1 l during the 2nd and 3rd, 300-500 ml in the following hours. The concentration of sodium chloride solution is determined by the sodium level in the blood. At a Na ⁺ level of 145-165 meq/l, a sodium chloride solution is administered at a concentration of 0.45%; at a Na ⁺ level < 145 meq/l - at a concentration of 0.9%; at a Na ⁺ level > 165 meq/l, the administration of saline solutions is contraindicated; in such patients, a glucose solution is used for rehydration.

Dextrose, 5% solution, intravenously by drip 1-1.5 l during the 1st hour of infusion, 0.5-1 l during the 2nd and 3rd, 300-500 ml - in the following hours. Osmolality of infusion solutions:

• 0.9% sodium chloride - 308 mosm/kg;
• 0.45% sodium chloride - 154 mosm/kg,
• 5% dextrose - 250 mOsm/kg.

Adequate rehydration helps reduce hypoglycemia.

[ 20 ], [ 21 ]

Insulin therapy

Short-acting medications are used:

Soluble insulin (human genetically engineered or semi-synthetic) intravenously by drip in a solution of sodium chloride/dextrose at a rate of 0.05-0.1 U/kg/h (while the blood glucose level should decrease by no more than 10 mosm/kg/h).

In case of a combination of ketoacidosis and hyperosmolar syndrome, treatment is carried out in accordance with the general principles of treatment of diabetic ketoacidosis.

[ 22 ], [ 23 ]

Evaluation of treatment effectiveness

Signs of effective therapy for hyperosmolar coma include restoration of consciousness, elimination of clinical manifestations of hyperglycemia, achievement of target blood glucose levels and normal plasma osmolality, and disappearance of acidosis and electrolyte disorders.

[ 24 ], [ 25 ], [ 26 ], [ 27 ]

Errors and unjustified appointments

Rapid rehydration and a sharp decrease in blood glucose levels can lead to a rapid decrease in plasma osmolarity and the development of cerebral edema (especially in children).

Considering the advanced age of patients and the presence of concomitant diseases, even adequate rehydration can often lead to decompensation of heart failure and pulmonary edema.

A rapid decrease in blood glucose levels can cause extracellular fluid to move into cells and worsen arterial hypotension and oliguria.

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

The administration of phosphate in renal failure is contraindicated.

[ 28 ], [ 29 ], [ 30 ], [ 31 ]

Forecast

The prognosis of hyperosmolar coma depends on the effectiveness of treatment and the development of complications. Mortality in hyperosmolar coma reaches 50-60% and is determined primarily by severe concomitant pathology.

[ 32 ]