Coma, hypoglycemic E15

Synonym(s)

Diabetic shock; coma due to hypoglycaemia; shock due to hypoglycaemia; sugar shock

First descriptor

The term "coma," in Greek "sound sleep, insomnia," has long been variously defined. For medicine, Frowein in 1976 and Brihaye in 1978 were the first to define the term as a state in which mental perception of oneself and one's surroundings is no longer possible. An international standardization can be found in Anonymus' "Glossary of Neurotraumatology" in 1979 (Moskopp 2015).

Shortly after insulin treatment began in 1922, hypoglycemia was first reported as a side effect of insulin therapy in Toronto (Plate 2008).

Todd's palsy was first described in 1849 by Irish physician Robert Bentley Todd (1809 - 1860) and referred to temporary postictal paralysis. Sometimes the term "Bravais phenomenon" (named after the French physician of the same name) is used for a temporary paresis (Krämer 2005).

A hypoglycemic coma is a state of unconsciousness triggered by absolute or relative insulin excess, in which mental perceptiveness is no longer present. Spontaneous movements are only possible in response to pain stimuli (Moskopp 2015).

Coma is usually classified using the Glasgow com a scale (GCS). However, since this scale does not sufficiently take into account the signs of brainstem dysfunction, the Neurotraumatology Committee WFNS (World Federation of Neurosurgical Societies) has assigned the severity of coma on the basis of the (most important) signs of life-threatening entrapment with brain dysfunction as follows:

• Coma Grade 1:

This denotes coma with no other disturbances.

• Coma Grade II:

Here, in addition to coma, there are also side signs, hemiparesis and / or unilateral loss of pupillary response.

• Coma grade III:

In coma grade III, stretching synergisms are found in addition to coma.

• Coma grade IV:

Here, in addition to coma, there is a bilateral loss of pupillary function.

(Moskopp 2015)

Exact data on the frequency of hypoglycemic shock are not available. Severe hypoglycaemia occurs most frequently in connection with diabetes mellitus. Type 1 diabetics experience an average of one severe hypoglycemia per year (Kasper 2015).

In type 2 di abetics, severe hypoglycemias occur at approximately 0.7 - 12 per 100 person-years. They are found particularly frequently in:

• elderly patients
• long duration of diabetes
• Patients with a history of hypoglycaemia (Silbert 2018).

The cause of hypoglycemic coma is always an absolutely or relatively elevated insulin level (Berlit 2005), which can be due to numerous triggers:

- reactive

- exogenous

- endogenous

- hormonal

For more details see Hypoglycemia

For a long time it was assumed that the neurons in the brain are deprived of glucose by hypoglycemia and that this leads to the death of the neurons. In the meantime, it has been proven that hypoglycemia actively kills neurons. This can be detected in the EEG by a flattening of the waves (Auer 2004).

If the glucose level falls below 18 mg / dl for a certain time, there is an abrupt energy failure with release of aspartate into the extracellular space of the brain. This floods the excitatory amino acid receptors on the neuronal dendrites. Calcium influx and membrane destruction occur in the cells, ultimately leading to neuronal necrosis.

Hypoglycemia can be differentiated from ischemia by the neuropathological distribution: hypoglycemic damage is found preferentially in the dentate gyrus located in the hippocampus and the superficial layers of the cortex. The brainstem and cerebellum are spared hypoglycemic brain damage (Auer 2004).

Hypoglycemic coma, unlike hyperglycemic coma, occurs suddenly, within minutes. Before the loss of consciousness, signs of hypoglycaemia may still be present, such as trembling, sweating, restlessness, ravenous appetite (Berlit 2005). For further details see. Hypoglycaemia.

In coma, the patient may exhibit the following symptoms:

• profound unconsciousness
• primitive automatisms such as:
  • Smacking
  • Grimacing
  • Grasping
• central respiratory and circulatory disturbances (Herold 2020)
• focal deficits in the form of transient paresis (so-called Todd paresis [Amiel 2021])
• seizure (Kasper 2015)
• in contrast to hyperglycemia find a:
  • hypertonic musculature
  • moist skin

(Berlit 2005)

In all cases of unexplained unconsciousness, the BG values should always be checked first, which are usually < 50 mg/dl in a hypoglycaemic coma (Herold 2020).

In addition to the patient's medical history, if this can be obtained, the laboratory values are important (see below), as is the diagnostic clarification of the cause of the hypoglycaemic coma (see "Laboratory" below).

• Blood glucose:

Before glucose administration, a blood sample should be taken - if possible - to confirm the diagnosis (Kasper 2015).

To clarify the cause of hypoglycaemia, the following should be determined:

• HbA1c
• C-peptide
• Plasma insulin
• Proinsulin
• Beta hydroxybutyrate level
• Cortisol (Kasper 2015)
• ACTH (Bansal 2020)
• Growth hormones (Kasper 2015)

• Investigations to find the cause:

72 h- starvation test:

The starvation test is used to detect hypoglycemia caused by inadequately high (pro) insulin release, such as can occur in endogenous hyperinsulinism or insulinoma (Krebs 2018).

Here, serum insulin, blood glucose, insulin / glucose quotient and C- peptide are determined.

Results:

- Insulin and C- peptide show a parallel increase in endogenous secretion.

- C-peptide is decreased with exogenous insulin supply(hypoglycaemia factitia).

- Insulin and C-peptide are elevated when sulfonylureas are taken (e.g. with suicidal intent).

- Detection of proinsulin or glibenclamide in the normal range when taking sulfonylureas, elevated in insulinoma (Herold 2020)

Oral glucose tolerance test (oGTT):

This is performed before the 72 h starvation test. This can be used to objectify late hypoglycaemia occurring more than 5 h after food intake (Herold 2020).

Glucagon stimulation test (GST):

The GST is a complementary test that can determine the etiology of hypoglycemia. The test should be performed under steady state conditions.

After overnight fasting, the patient receives an i. v. injection of 1 mg glucagon over 2 min. Plasma glucose and insulin levels are measured at baseline and at well-defined time intervals.

Results:

• Normal:

The maximum insulin response occurs rapidly and does not exceed 100 uU / ml (4,033 ng / l). Serum glucose peaks at 140 + 24 mg / dl after approximately 20 - 30 min.

• Insulin-mediated cause:

Plasma glucose level rises to values of > 25 mg / dl (1.4 mmol / l) after glucagon.

• Insulinoma:

Approximately 15 - 30 min after injection, insulin levels rise to > 160 uU / ml (6,452.8 ng / l). However, some patients (8% in one study) with insulinoma do not secrete insulin.

• Anorexia / liver disease:

In this case, due to depleted hepatic glycogen stores, no hyperglycemic response to glucagon is possible. The insulin response may be slightly increased, but not to the extent seen in patients with insulinoma.

• Medications:

Medications such as diazoxide, diphenylhydantoin, and hydrochlorothiazide may cause false results on GST.

• Non-islet cell tumors:

Patients with non-islet cell tumors, such as hemangiopericytoma or meningeal sarcoma, sometimes show similar responses to patients with insulinoma.

• Indications:

Patients with liver cirrhosis and portocaval anastomosis may have peak insulin levels and therefore cannot be distinguished from patients with insulinoma.

Peak insulin levels may also occur in obese patients, patients with acromegaly, or those treated with aminophylline or sulfonylureas.

• Adverse effects:

The test may cause (severe) hypoglycaemia after 90 - 180 min and after vomiting. For this reason, a physician should be present throughout the test.

(Bansal 2020)

• Coma of other genesis such as:
  • Coma diabeticum
• Epilepsy
• Apoplexy (Herold 2020)

• Acute coronary syndrome:

Occurs clustered in elderly patients > 70 years in the first 10 days after hypoglycemic coma (Cruz 2020).

• Apoplexy:

Apoplexy risk increases with hypoglycemia (Cruz 2020).

Symptomatic treatment of hypoglycaemia should be started promptly, e.g. with:

• 40 - 100 ml 40 % glucose i.v.
• Repeat after 20 min
• followed by a 5 % glucose solution by infusion up to a BG of 200 mg / dl (Berlit 2005).

If i.v. administration is not possible, e.g. because the patient is being cared for by a layperson for the first time or is reacting aggressively due to hypoglycaemia, 1 mg glucagon can be injected i.m. or s.c. (Herold 2020).

Caution: In patients with glycogen deficiency, as is the case in alcohol-induced hypoglycaemia, glucagon is not effective, as the glycogen reserves are depleted and glucagon acts by stimulating glycogenolysis (Herold 2020 / Kasper 2015).

Among other things, glucagon stimulates insulin secretion and should therefore not be used in type 2 DM. If sulfonylurea-induced hypoglycemia is involved, glucagon can be given together with the somatostatin analogue octreotide, which causes suppression of insulin secretion (Kasper 2015).

This should be followed by a clarification of the cause with appropriate causal therapy (Berlit 2005).

Hypoglycemic coma is a condition that invariably leads to death if left untreated.

Severe hypoglycemia is bidirectionally associated with a doubling of risk for subsequent cardiovascular events, including death (Amiel 2021).

It is estimated that approximately 6-10% of type 1 diabetics die as a result of hypoglycemia (Kasper 2015). Of type 1 and 2 diabetics treated with insulin, approximately 2 - 4 % die from hypoglycemia (Balletshofer 2009).

In patients with hypoglycemic coma, significant EEG changes are seen in the event of renewed hypoglycemia (Maran 2017).

The diabetes patient must be informed in detail about the symptoms of hypoglycaemia and its prevention in training groups (Kasper 2015).

Type 1 diabetics should always carry an emergency glucagon kit. Relatives or caregivers should be informed in training groups about the symptoms of hypoglycemia as well as about the handling of the glucagon syringe (Haak 2018).

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