Hyperosmolar coma E14.01

In 1880, Won Frerichs and Dreschfeld were the first to describe the clinical picture of a diabetic with hyperglycemia and glucosuria, but without the classic Kussmaul respiration and without evidence of acetone in the urine (Adeyinka 2021).

Hyperosmolar coma (HOK) is a clinical condition that results from a complication of diabetes mellitus (Adeyinka 2021).

It is characterized, according to the American Diabetic Association, by:

• Hyperglycemia > 600 mg / dl (not uncommon with BG- values > 1,000 mg / dl [van Aken 2007]).
• hyperosmolality > 320 mOsm / l
• Dehydration

Significant ketoacidosis, on the other hand, is absent (Adeyinka 2021).

Hyperosmolar coma (HOK [van Aken 2007)] or HHS = hyperglycemic hyperosmolar state [Kasper 2015]) together with ketoacidotic com a (DKA = diabetic ketoacidosis [Kasper 2015]) belong to the group of forms of hyperglycemic coma(Herold 2020).

HOK is relatively rare and accounts for only about 10-20% of all hyperglycemic comas (Waldhäusl 2013).

It affects 90 - 95 % of type 2 diabetics and predominantly diabetics with obesity (Adeyinka 2021).

As the initial diagnosis of diabetes mellitus (DM), HOK manifests in 30 - 40 % (Mehnert 2003), with HOK as the initial diagnosis predominantly affecting children and adolescents (Stoner 2017).

In approximately 30 % of patients with hyperglycemic coma, features of diabetic ketoacidosis are also found in addition to the features of HOS (Mehnert 2003).

A HOK can be triggered by:

• Infections of the:
  • Airways
  • Gastrointestinal tract
  • Urogenital tract

Infections are with 50 - 60 % the most frequent cause of a HOK. This is caused by water loss, release of endogenous catecholamines, etc.

• Medications such as:
  • atypical antipsychotics
  • beta blockers
  • Glucocorticoids
  • Thiazide diuretics
• cardiovascular insult:
  • Apoplexy
  • Myocardial infarction
  • angina pectoris

In this case, the stress reaction leads to the release of counter-regulatory hormones, which cause an increase in BG and, as a result, osmotic diuresis and dehydration. (Adeyinka 2021)

In HOK, there is decreased peripheral glucose utilization: insulin deficiency causes increased glucose production by glycogenolysis and gluconeogenesis in the liver and impairs glucose utilization in skeletal muscle .

Hyperglycemia results in osmotic diuresis, leading to volume depletion intravasally (Kasper 2015).

Hypertonic dehydration leads to neurological symptoms, and hypovolemia causes a decrease in glomerular filtration and consecutively exacerbates glycemic imbalance (van Aken 2007).

Excessive ketoneogenesis is prevented by low levels of:

• Cortisol
• Glucagon
• catecholamines
• growth hormones (van Aken 2007)

HOK occurs predominantly in older diabetics (van Aken 2007).

A typical feature of hyperosmolar coma is its gradual onset (Herold 2020).

Not infrequently, weeks before decompensation there is already:

• Lack of drive
• Pruritus
• visual disturbances
• Perceptual disturbances

In the further course, the typical symptoms of an HOK occur:

• Extremely high BG value, usually > 600 mg / dl (Reitgruber 2021)
• Tachycardia (caused by vasodilation [Berndt 2015])
• Hypotension (Kasper 2015)
• Signs of dehydration such as:
  • detachable, stagnant skin folds
  • dry oral cavity (dehydration is caused by osmotic diuresis [Berndt 2015])
  • muscle cramps (caused by fluid and electrolyte loss [Berndt 2015])
  • Blood pressure drop (also caused by fluid and electrolyte loss [Berndt 2015])
  • Polyuria (primary; caused by osmotic diuresis [Berndt 2015]).
  • Oligo-anuria (secondary)

[Haak 2018)

• Neurological symptoms due to dehydration and hypernatremia if present (Sohal 2020) such as:
  • Hemianopsia
  • Paresis
  • Convulsions

(van Aken 2007)

In addition to the above symptoms, there may also be symptoms of the precipitating disease such as apoplexy, myocardial infarction, pneumonia, sepsis etc (Kasper 2015).

With regard to diagnostics, a detailed medical history, if necessary a medical history of others, a detailed physical examination and laboratory findings (see below) are decisive (Adeyinka 2021).

In addition to the internal medicine admission laboratory should be determined:

• Glucose (hourly)
• HbA1C (in case of so far unknown DM)
• Serum osmolality
• sodium:

Pseudohyponatremia may exist because the osmotic gradient produced by hyperglycemia draws water from the intracellular to the extracellular space. Sodium levels are therefore determined using the following formula:

Corrected sodium = measured sodium + (((serum glucose - 100) / 100) x 1.6 [Adeyinka 2021]).

• Potassium:

Potassium level may be elevated but may also be decreased due to extracellular shift of potassium caused by low insulin level (Adeyinka 2021).

• Bicarbonate:

Bicarbonate level is usually in the normal range (8- 12 mmol / l) as there is minimal formation of ketone bodies (Adeyinka 2021).

• Magnesium:

At times, a decreased magnesium level is found (Adeyinka 2021).

• Phosphate:

Phosphate levels are often elevated (especially in rhabdomyolysis [Adeyinka 2021]).

• Creatinine:

Creatinine levels and also BUN (urea / nitrogen) levels are usually elevated, indicating prerenal azotemia (Adeyinka 2021).

• Urine findings:

Glucosuria and ketonuria are present in most cases (moderate ketonuria is most suggestive of a starvation state [Kasper 2015]).Specific gravity is often elevated (Adeyinka 2021).

In HOK, metabolic acidosis with a small anion gap may exist as a result of increased lactic acid (Kasper 2015).

• Conditions that also present with altered mental status:
  • Hypoglycemia
  • Hyperammonemia
  • Hypernatremia
  • Hyponatremia
  • intoxication with alcohol or drugs
  • uremic encephalopathy
• Conditions that may cause hyperglycemia:
  • diabetic ketoacidosis

(Adeyinka 2021)

• Cerebral edema (when serum osmolality falls too rapidly).
• Rhabdomyolysis (Adeyinka 2021)
• Shock
• Sepsis
• thromboembolic events (Mehnert 2003)

In most cases, HOK is treated in the intensive care unit.

For intensive care therapy may be necessary:

• bladder catheter for balancing
• central venous catheter for ZVD measurement (Herold 2020)

Monitored should be:

• half-hourly:
  • Blood pressure
  • Heart rate (Haak 2018)
• hourly:
  • Blood glucose
• every 2 h:
  • Base excess
  • Bicarbonate
  • Sodium
  • Potassium
  • Glasgow Coma Scale
  • Blood gas analysis with pH- value (Herold 2020 / Haak 2018)

Prophylaxis required regarding:

• Thromboembolism
• Pressure ulcer
• Pneumonia (Herold 2020)

In the treatment of HOK - as far as the ketonemia is < 18 mg / dl (1 mmol / l) - initially no insulin is given. Volume replacement with 0.9% saline alone results in a reduction of the blood glucose level (Haak 2018). For more details on insulin therapy, see "Blood glucose" below.

• Potassium:

Hypokalemia must be compensated before insulin treatment may be necessary, as insulin shifts potassium to intracellular, posing a risk of hypoglycemic ventricular fibrillation (Herold 2020).

• Substitution of potassium at a pH of > 7.1:
  • for potassium > 4 - 5 mmol /l substitution of 10 - 15 mmol / l
  • with potassium 3 - 4 mmol / l substitution of 15 - 20 mmol / l
  • for potassium < 3 mmol / l substitution of 20 - 25 mmol / l (Herold 2020)

A maximum of 40 mmol of potassium chloride should be infused per 1,000 ml of NaCl 0.9% at a time (Haak 2018). Contraindication to potassium administration is anuria (Herold 2020).

If hypokalemia of < 3 mmol / l occurs during insulin therapy, any insulin administration should be discontinued (Herold 2020).

The target serum potassium should be > 3.5 mmol / l (Kasper 2015).

• Phosphate:

Elevated phosphate levels can usually be lowered by fluid administration and insulin alone, since phosphate is thereby returned to the cells on the one hand, and can be excreted by the kidneys on the other (Adeyinka 2021).

• Sodium:

In the presence of hypernatremia, a semi-isotonic saline solution or a hypoosmolar whole electrolyte solution are indicated (Herold 2020). However, sodium concentration should not fall faster than 180 mg/dl (10 mmol/l) in 24 h (Haak 2018).

• Creatinine and BUN:

Both values usually normalize with fluid administration (Adeyinka 2021).

• Blood glucose:

Blood glucose should not fall more than 90 mg / dl (5 mmol / l) per hour.

If BG does not drop further with i. v. administration of fluid alone or there is ketonemia of > 18 mg / dl (1 mmol / l), insulin infusion of 0.05 IU / kg / h should be started (Haak 2018).

Kasper (2015) previously recommends an insulin bolus of 0.1 IU / kg bw.

The CNS needs some time to normalize the water shifts triggered by the coma. Therefore, the patient may remain unconscious despite normalization of blood glucose, electrolytes, pH and volume balance. This disturbance usually disappears with a delay (Herold 2020).

The diet should start with a light diet. A small amount of normal insulin should be injected s.c. before each meal.... Subsequently, readjustment of DM is required (Herold 2020).

HOK is a potentially life-threatening condition. Mortality is approximately 20%, significantly higher than diabetic ketoacidosis (Adeyinka 2021).

Causes of early mortality, estimated at about 15%, are shock, sepsis or underlying disease. In late mortality (≥ 72 h), the cause is often found to be thromboembolic events or consequences of treatment. In HOK, more patients die from the disease causing the HOK than from the HOK itself (Mertens 2021).

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