Overview.
Diabetic hyperosmolar coma (HNDC) is a rare serious acute complication of diabetes mellitus, most commonly seen in elderly patients with no history of diabetes mellitus or type 2 diabetes mellitus, but also seen in patients with type 1 diabetes mellitus. The patient’s original insulin secretion is insufficient, and the blood glucose rises sharply under the action of triggers, which promotes the aggravation of glucose metabolism disorder, resulting in the extracellular fluid in a state of hypertonicity, hypovolemic hyperosmolar dehydration occurs, and neurological abnormalities are often seen (including coma in 25%-50% of the patients).
Etiology
1. Stress and infection
Stress such as cerebrovascular accident, acute myocardial infarction, acute pancreatitis, gastrointestinal bleeding, trauma, surgery, heat stroke or hypothermia. Infections, especially upper respiratory tract infections, urinary tract infections, etc. are most often induced.
2. Insufficient water intake
Decreased sensitivity of the thirst center in the elderly, bedridden patients, patients with mental disorders or coma, and young children who cannot actively ingest water.
3. Excessive water loss and dehydration
Such as severe vomiting, diarrhea, extensive burns, neurological and surgical dehydration treatment and dialysis treatment.
4. High sugar intake and input
Such as large amount of intake of sugar-containing beverages, high-sugar food, intravenous input of large amounts of glucose solution when the diagnosis is unknown or missed, complete intravenous high nutrition, as well as the use of sugar-containing solutions for hemodialysis or peritoneal dialysis and other cases. Especially in some endocrine diseases combined with impaired glucose metabolism, such as hyperthyroidism, acromegaly, cortisolism, pheochromocytoma patients are more likely to be induced.
5. Drugs
Many drugs can be a trigger, such as the use of glucocorticoids, thiazides or furosemide (tachycardia) and other diuretics, propranolol, phenytoin sodium, chlorpromazine, cimetidine, glycerol, azathioprine and other immunosuppressants, etc., can cause or aggravate the body’s insulin resistance to elevate blood glucose, dehydration aggravated, some drugs such as thiazide diuretics and inhibition of insulin secretion and reduce insulin sensitivity. Some drugs such as thiazide diuretics also inhibit insulin secretion and reduce insulin sensitivity, which can induce HNDC.
6. Other
For example, acute and chronic renal failure, diabetic nephropathy, etc., due to the decrease of glomerular filtration rate, the clearance of blood glucose also decreases, which can also be a trigger.
Symptoms
The onset of the disease is insidious, often preceded by polyuria, polydipsia, thirst, weight loss, but polyphagia is not obvious, or on the contrary, loss of appetite, so it is often overlooked. Water loss gradually worsens with the progress of the disease, and neuropsychiatric symptoms appear, manifesting as drowsiness, hallucinations, disorientation, and in some patients, there are symptoms of focal neurological impairment (hemiparesis or hemianopsia) and/or epilepsy, and finally fall into a coma. At the time of presentation, there is often significant water loss or even shock, and there is no acidosis-like deep breathing.
Examination
1. Blood sugar and urine sugar
This disease is mainly characterized by significant high blood glucose and high urinary glucose. Blood glucose mostly exceeds 33mmol/L (600mg/dl), and urine glucose is strongly positive. If the patient is severely dehydrated or has renal function damage that raises the renal glucose threshold, the urine glucose may not be strongly positive, but the urine glucose negative is rare.
2. Blood electrolytes
Generally, blood sodium is normal or elevated, or reduced; blood potassium is normal or reduced, or elevated; overall sodium and potassium are reduced. Patients may also have loss of calcium, magnesium and phosphorus. The level of the patient’s blood sodium and potassium depends on the amount of their loss and their distribution status inside and outside the cells, as well as the degree of their water loss.
3. Blood urea nitrogen and creatinine
are often significantly elevated to a degree that reflects severe dehydration and renal insufficiency. Urea nitrogen (BUN) can reach 21-36mmol/L (60-100mg/dl), creatinine (Cr) can reach 163-600μmol/L (1.7-7.5mg/dl), and BUN/Cr ratio can reach more than 30:1 (normal people are mostly in the range of 10:1-20:1).
4. Plasma osmolality
Significant elevation is an important feature and diagnostic basis of HNDC.
5. Acid-base imbalance
About half of the patients have mild or moderate metabolic, high anion gap acidosis. The anion gap is elevated by a factor of 1, blood HCO3- is higher than 15 mmol/L, and pH is higher than 7.3. The elevated anions are mainly organic acids such as lactic acid and ketoacid, but also contain a small amount of sulfuric acid and phosphoric acid.
6. Blood and urine ketones
Blood ketone is mostly normal or mildly elevated, quantitative measurement is not more than 50mg/dl, when measured by dilution method, there are few plasma diluted to 1:4 or more still positive. Urine ketones are mostly negative or weakly positive.
7. Blood leukocyte count
The blood leukocyte count of HNDC patients is often increased, up to 50×109/L; the hematocrit is increased, reflecting dehydration and hemoconcentration.
8. Imaging examination
Urine culture, chest X-ray and electrocardiogram are optional according to the condition.
Diagnosis
1. Symptoms and signs
(1) History The patients are mostly elderly, and 90% of them have combined renal lesions.
(2) The onset of the disease is slow, and there is often a gradual worsening of diabetes mellitus (polyuria, polydipsia, malaise), reflecting a gradual increase in blood glucose and plasma osmolality.
(3) Dehydration and peripheral circulatory failure Hyperosmolar hyperglycemia syndrome (HHS) is often characterized by severe signs of dehydration, as evidenced by dryness of the skin and mucous membranes, sunken eyes, and rapid pulse rate, and in severe cases, a state of shock.
(4) Neuropsychiatric symptoms Patients often have different degrees of neuropsychiatric symptoms and signs, half of them have blurred consciousness, and one third of them are in a coma. The state of consciousness is related to the speed and degree of plasma osmolality, when the effective plasma osmolality exceeds 350mmol/L, 40% of the patients may have blurred consciousness or coma. In addition to coma, a variety of neurologic signs may be present, such as seizures, hemiparesis, visual disturbances, positive pathologic signs, or central fever.
Some patients have very high blood glucose, but the effective osmolality does not reach 320 mmol/L due to low blood sodium. Although these patients cannot be diagnosed as HNDC, they should still be treated as HNDC.
2. Laboratory tests
(1) Blood glucose and urine glucose Hyperglycemia, blood glucose mostly exceeds 33.3mmol/L, and urine glucose is mostly strongly positive.
(2) Blood ketone bodies and urine ketone bodies are mostly negative or weakly positive, but can be positive when combined with diabetic ketoacidosis (DKA).
(3) Electrolytes Blood sodium may be normal, elevated, or decreased, mostly >150 mmol/L; potassium may be normal, elevated, or decreased. Overall sodium and potassium are lost. It should be noted that hyperosmolar diuresis renal tubular reabsorption of sodium is inhibited, and intracellular water transfer to the extracellular, so that the blood sodium is reduced, blood glucose for every 5.6 mmol / L, blood sodium decreased by about 1.7 mmol / L, celiac blood can also make a pseudo-sodium drop. However, at the same time, if hyperosmolar diuresis loses more water than sodium, activation of the renin-angiotensin-aldosterone system (RAAS system) can cause sodium retention, which in turn may raise blood sodium.
(4) Effective plasma osmolality Effective plasma osmolality = 2 (Na + K) + blood glucose (mmol/L), effective plasma osmolality ≥ 320 mOsm/L is an important diagnostic criterion.
(5) Blood gas About half of the patients have AG-augmented metabolic acidosis, which is usually mild or moderate, pH is usually >7.3, and blood HCO-3 is mostly more than 15 mmol/L.
(6) Blood urea and creatinine Blood urea is often significantly elevated by dehydration and positively correlates with the degree of dehydration, and creatinine can be elevated several times.
Differential diagnosis
The main differential diagnosis is with DKA, see the table below.
DKA
HHS
Blood glucose
Mostly higher than 16.7mmol/L, usually between 16.7 and 33.3mmol/L
≥33.3 mmol/L
Effective plasma osmolality
Normal or slightly elevated
≥320mOsm/L
Urinalysis
Urine sugar strong positive; urine ketone body positive
Urine sugar strong positive; urine ketone body negative
Blood gas
Decreased, pH <7.3 or HCO3- <15mmol/L
Normal or slightly lower, pH ≥7.3 or HCO3-≥15mmol/L
Blood sodium
Reduced or normal
Mostly normal or significantly elevated
Treatment
1. Rehydration
Rehydration is a crucial step and plays a decisive role in prognosis. The degree of water loss in patients is more severe than that of DKA, and is estimated to be up to one-fourth of body fluids or more than one-eighth of body weight.
(1) Total amount of fluid rehydration Mostly 6-10L, one-third of the total amount should be replenished within 4 hours after admission, and the total amount should be replenished within 24 hours after admission. Due to the large amount of rehydration fluid, it should be replenished through the gastrointestinal tract as much as possible, and the intragastrointestinal rehydration can be based on plain water, which can serve to replenish the volume on the one hand, and lower the blood osmotic pressure on the other. Since the patient’s consciousness is usually poor, inferior nasal feeding is usually necessary, and this method is safe and effective.
(2) Types of fluid replenishment ① At the beginning of treatment, saline is recommended because it is isotonic but hypotonic compared to the patient’s blood. If combined with shock or insufficient blood volume, the use of colloidal fluid can be considered in addition to saline to expand the volume. ② The timing of the use of hemiosmotic fluid (0.45% sodium chloride) is controversial, and it is generally believed that this solution can be used when the blood Na>150mmol/L and there is no obvious hypotension. ③ Once the blood glucose drops to 13.9 mmol/L, 5% dextrose solution or sugar saline can be used and insulin can be added proportionally.
2. Insulin
Intravenous continuous drip small dose insulin treatment program is generally used, the rate of blood glucose drop should not be too fast, blood glucose drop too fast easily lead to the occurrence of cerebral edema. Patients can start subcutaneous injection of insulin after eating, but attention should be paid to detecting blood glucose after subcutaneous injection of insulin. Generally speaking, after subcutaneous injection of insulin, the glucose-lowering effect of insulin can overlap with that of intravenous insulin for at least 1 to 2 hours, because the former has a long onset of action and the latter has a fast metabolism. It should be noted that patients with this disease have higher sensitivity to insulin than diabetic ketoacidosis, and the chance of hypoglycemia may be higher.
3. Correct electrolyte disorders
Electrolyte disorders are mainly caused by the loss of sodium and potassium, and the loss of sodium can be corrected by replenishing NaCl-containing fluids, so the key to correct electrolyte disorders is to replenish potassium, and potassium supplementation is still dominated by potassium chloride in China.
4.Correct acidosis
Some patients have acidosis, if the degree is not serious, alkaline drugs should not be considered.
5.Correcting triggering factors