Hyperglycaemic Emergencies

The hyperglycaemic emergencies

Diabetic ketoacidosis

Hyperglycaemic hyperosmolar state

Precipitating factors 

Clinical features 

Treatment of hyperglycaemic emergencies at primary-care level 

Management of hyperglycaemic emergencies in hospital

General

Investigations

Treatment

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(See Strength of Recommendations Taxonomy (SORT) for explanation of Grade A-C)

SEMDSA 2017 Recommendations
Blood beta-hydroxybutyrate is the preferred test for the diagnosis and monitoring of diabetic ketoacidosis	B
Hyperglycaemic emergencies should ideally be managed in a high-care/ICU setting with standardised protocols for management and monitoring	C
A protocol that incorporates the following principles should be followed: fluid resuscitation avoidance of hypokalemia insulin administration avoidance of rapidly falling serum osmolality search for precipitating cause	C
Administration of sodium bicarbonate in patients with a pH > 6.9 is not recommended	B
The insulin infusion rate must be maintained, even when blood glucose has normalised, until DKA has resolved Avoid hypoglycaemia by changing the IV fluid to dextrose when the plasma glucose is < 14 mmol/L	B
Urinary ketones alone should not be used to confirm the resolution of DKA as this can be misleading Use a combination of clinical and biochemical measurements to confirm resolution instead	B
When transitioning to subcutaneous insulin, care must be taken to overlap this with insulin infusion	B

The hyperglycaemic emergencies, diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS), should be suspected whenever patients have hyperglycaemia, especially if they are systemically unwell or are known to have diabetes.

These conditions have significant morbidity and mortality, and emergency treatment with intravenous fluids and insulin is essential.

THE HYPERGLYCAEMIC EMERGENCIES

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is characterised by uncontrolled hyperglycaemia, high anion gap metabolic acidosis and increased total body ketones. In South Africa, DKA carries a higher mortality than in the developed world. It can present at any age, although it is more common in young patients. It is important to note that urine ketone measurement is not reliable in the diagnosis of DKA.¹ Urinary ketones are commonly detected during fasting, exercise or pregnancy even in the absence of any metabolic derangements.

In DKA, the two main ketones produced are acetoacetate (AcAc) and betahydroxybutyrate (BOHB). Urinary dipsticks only measure one of these ketone bodies and is also associated with false positive results.² BOHB can be measured by a lab or a validated point of care testing (POCT) device. POCT lends itself ideally for use in the primary health care setting. Uncontrolled hyperglycaemia in the presence of a BOHB level of >3.0 mmol/L indicates unequivocal DKA, whereas a level of <1 mmol/L excludes ketosis.³

The diagnosis of DKA can be made on the following criteria:

1. Hyperglycaemia - plasma glucose prior to insulin administration > 13.9 mmol/l
2. Acidosis - indicated by blood pH < 7.3 or bicarbonate below 18 mmol/litre
3. Ketonaemia - indicated by blood beta-hydroxybutyrate > 3 mmol/litre

Hyperglycaemic hyperosmolar state

The hyperglycaemic hyperosmolar state (HHS) is characterised by the slow development of marked hyperglycaemia (usually > 50 mmol/l), hyperosmolality and severe dehydration. Ketonuria may be slight or absent. The condition usually affects middle-aged or older patients and carries a high mortality. The initial treatment is the same as for DKA.

PRECIPITATING FACTORS

The clinician should attempt to identify the precipitating factor for DKA once resuscitation has been initiated. The most common precipitating factor is infection. Other precipitants include discontinuation of insulin, myocardial infarction and cerebrovascular accident. In elderly patients, restricted water intake can lead to dehydration and precipitate HHS. Drugs such as diuretics may exacerbate this. Note that a hyperglycaemic crisis can be the presenting feature of both type 1 and type 2 diabetes, (e.g. ketosis prone diabetes). In a significant proportion of patients, no precipitant can be identified.

CLINICAL FEATURES

DKA usually develops acutely (within days), whereas HHS usually evolves over a longer time period (several days to weeks). For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, vomiting, dehydration, weight loss, weakness and change in mental status. This can vary from mild confusion to profound lethargy or coma, with the latter being more common in HHS. 

Focal neurological signs and seizures may occur in HHS but the presence of this should always alert the clinician to a possible underlying condition, rather than attributing it to the metabolic derangement. Patients with DKA may complain of diffuse abdominal pain even in the absence of primary abdominal pathology. Physical findings may include Kussmaul breathing, and/or features of hypovolemic shock. History taking and examination should not delay the initial management and investigations. Rapid treatment is essential.

Once initial resuscitation has been established, the patient should be managed at an institution experienced in the management of these conditions, ideally in a high care setting. Table I provides a summary of the characteristics of DKA and HHS, to aid with the recognition of these conditions.

Table I. Differentiation between the different types of hyperglycaemic coma

	DIABETIC KETO-ACIDOSIS (DKA)	HYPERGLYCAEMIC HYPEROSMOLAR COMA (HHS)
History	Known T1DM Newly-diagnosed DM	Known T2DM Newly-diagnosed DM
Precipitants	Infection, non-compliance on insulin	Infection, MI, CVA, diuretic use contribute to dehydration
Age frequency	Younger patients	Usually older persons
Onset	Hours to days	Days to weeks
Symptoms	Polyuria, polydipsia, anorexia, nausea, vomiting, abdominal pain	Polyuria, polydipsia, increasing somnolence
Signs	Kussmaul respiration –deep sighing breathing, dehydration, confusion, nausea, vomiting	Severe dehydration, mental status changes, focal neurological signs and/or seizures*
Urine ketones	Strongly positive	Positive or negative
Serum ketones	Strongly positive	Negative or only weakly positive
Blood glucose	Raised	Markedly raised
Blood pH	Decreased	Normal or slightly decreased
Serum bicarbonate	Low	Normal or slightly decreased

* Exclude underlying pathology

TREATMENT OF HYPERGLYCAEMIC EMERGENCIES AT PRIMARY-CARE LEVEL 

Rapid treatment is essential and should not be delayed.

The following steps should be followed when treating hyperglycaemic emergencies in the primary-care setting:

• Confirm the diagnosis and initiate management as per algorithm provided
• Intravenous (IV) fluids:
  IV fluid administration should ideally start with normal saline, but if not available can be achieved with other isotonic solutions.⁴ In a young patient with suspected DKA, infuse
  one litre of normal saline over the first hour. In older patients, change fluid to half normal saline after the first litre
• Administer hourly boluses of ten (10) units of regular insulin IV, until the patient is transferred to hospital. If IV access is problematic, insulin can be given intramuscularly (IM) or
  subcutaneously (SC) in the interim^5,6,7,8
• Arrange transfer to a hospital experienced in the management of hyperglycaemic emergencies
• Clear instruction should be provided for the continued management during transport

MANAGEMENT OF HYPERGLYCAEMIC EMERGENCIES IN HOSPITAL

Refer to: Management of Hyperglycaemic Emergencies and Diabetic Coma Chart for a suggested management algorithm and monitoring protocol.

GENERAL

• Patients should be managed in a high care/ICU setting, but management should not be delayed until a high care bed is available
• Mild DKA has been managed in an outpatient setting by means of insulin.^9,10 This is not recommended as the South African primary health care context differs markedly from those where this practice is accepted
• A thorough investigation for precipitating factors such as infective processes, (usually urinary tract and skin) and myocardial ischaemia etc. should be undertaken
• If infection is suspected, antibiotics should be initiated. The choice of antibiotics and continued use thereof should be based on the accepted antibiotic guidelines of the specific institution
• Should there be delay in the resolution of DKA (usually resolves < 48 hours) a meticulous search for occult infections should be undertaken. This includes otitis media and external, rhinocerebral mucormycosis, occult abscesses, pyelonephritis,cholecystitis, osteomyelitis and tuberculosis
• Prompt surgical intervention should not be delayed even in the presence of metabolic derangements
• An elevated white cell count should not be overinterpreted as this may occur solely on the basis of DKA
• Prophylactic antithrombotic treatment is essential
• Aspiration must be anticipated and prevented. Insert a nasogastric tube if the patient is comatose or has gastric dilatation
• Frequent reassessment of the patient’s condition is necessary. The responsible doctor must keep a meticulous flow chart of the hourly recordings of clinical and biochemical progress and treatment
• The rate of insulin infusion needs to be adjusted hourly until the expected rate of decline in blood glucose is achieved

INVESTIGATIONS

The following special investigations should ideally be performed:

Blood tests:

• Glucose, urea and electrolytes (calculate the anion gap), full blood count and differential, and glycated haemoglobin (HbA_1C)
• Venous blood gas
• Validated plasma, serum or capillary betahydroxybutyrate (BOHB)

Urine tests:

• Dipstick test for nitrites, blood and protein
• Microscopy, culture and sensitivity, if indicated

Chest X-ray:

ECG:

Other investigations, as appropriate, to investigate for the precipitant of the hyperglycaemic emergency (e.g. blood cultures, sputum culture and cardiac enzymes). Table II provides a list of the laboratory findings which are expected in hyperglycaemic emergencies.

TREATMENT

Intravenous fluids

• DKA: The average fluid deficit in an adult presenting with DKA is 5-10 litres. Patients should receive 1-1.5 litres of fluid in the first hour^,11 and thereafter 250-500 ml per hour. The aim is to replace 50% of the fluid deficit during the first 12 hours after presentation, and the remainder within the next 12-16 hours.¹² Normal saline or Ringer’s lactate are good choices for initial fluid resuscitation. Hyperglycaemia is corrected faster than ketoacidosis,¹¹ and 5% dextrose solution should be used once the glucose falls to < 14 mmol/l to prevent hypoglycaemia. If hyperchloraemic (normal anion gap) acidosis occurs in the recovery phase of DKA, minimise hyperchloraemia by using 0.45% saline or 5% dextrose water
• HHS: If there is no cardiac compromise, the patient can be given one litre of normal saline in the first hour. The subsequent choice of fluid replacement and rate of infusion depends on serum sodium, state of hydration and urinary output. If the corrected serum sodium is normal or high, 0.45% saline infused at 250–500 ml/hour is appropriate. In patients with renal or cardiac compromise, frequent monitoring of serum electrolytes, central venous pressure and urine output is necessary to avoid fluid overload. The fluid replacement guideline is specific to adult patients. Please refer to paediatric guidelines for patients younger than 18 years. Paediatric patients are at increased risk of cerebral oedema if they are fluid overloaded

Table II. Laboratory findings in hyperglycaemic emergencies

	Diabetic Ketoacidosis (DKA)			Hyperglycaemic Hyperosmolar Coma (HHS)
	Mild	Moderate	Severe
Plasma glucose mmol/l	> 13.9	> 13.9	> 13.9	> 33.3
Serum HCO3 mmol/l	15 - 18	10 - 14	< 10	>18
Serum ketones	Positive	Positive	Positive	May be present
Anion gap	>10	>10	>12	Variable
Blood pH	7.25 – 7.30	7.00 – 7.24	< 7.00	> 7.30
Serum osmolality	Variable	Variable	Variable	> 320
Mental status	Alert	Alert/drowsy	Stupor/coma	Stupor/coma

Anion gap = Na+ - (CI- + HCO3-)
Osmolality = 2(Na⁺ + K⁺) + urea + glucose

Insulin

Intravenous short or rapid acting insulin is preferred for the treatment of hyperglycaemic emergencies. Serum potassium should always be checked before insulin infusion.

Continuous insulin infusion at a rate of 0,14 units/kg/hour in a high care or ICU setting with intensive glucose monitoring is the standard of care for the management of DKA.¹¹ However, treatment of DKA should not be delayed when ICU is not available. It is not advisable to use an insulin infusion outside of ICU or high-care due to the higher risk of hypoglycaemia. Other insulin regimens (IM or IV boluses of 10 units of regular insulin hourly,¹³as per institution protocol) may be used if the patient is nursed in the general ward. In either case, capillary glucose should be measured hourly to detect and prevent hypoglycaemia and to assist guiding the rate of insulin infusion. The insulin infusion should be titrated hourly (per institution protocol) in order to address the degree of hyperglycaemia appropriately and to prevent hypoglycaemia.

The switch to subcutaneous insulin can only be made when the hyperglycaemic emergency has resolved:

• The patient is fully conscious and eating
• Anion gap normalised, acidosis resolved (pH > 7.3 Bicarbonate > 18 mmol/l)
• Blood glucose < 15 mmol/l
• BOHB < 1 mmol/l

Potassium

Withhold potassium initially if the ECG and/or serum potassium level reveal marked hyperkalaemia. Start potassium therapy immediately if serum potassium is normal or low and/or the ECG is normal and the patient is passing urine. If the initial potassium is < 3.5 mmol/l, start replacement before insulin infusion to avoid severe hypokalaemia and its complications of arrhythmias or respiratory muscle weakness.¹¹ Four-hourly potassium monitoring will guide the need for replacement, as shown in Table III.

Table III. Guide to potassium replacement

Serum K+	Treatment
<3.0 mmol/l	- 40 mmol KCl per litre IV fluid
3.1 - 4.0 mmol/l	- 30 mmol KCl per litre IV fluid
4.1 - 5.5 mmol/l	- 20 mmol KCl per litre IV fluid
>5.5 mmol/l	- omit KCl

Bicarbonate

The use of bicarbonate in the treatment of DKA is controversial. In both prospective and retrospective studies of patients in DKA, treated with or without sodium bicarbonate, there were no differences in cardiac or neurological function, incidence of hypokalemia or hypoglycaemia, or rate of recovery from ketoacidosis.^14,15,16 There are no prospective randomised studies that have used bicarbonate in patients with a pH < 6.9. To date, evidence does not justify the use of bicarbonate in the treatment of DKA in general.¹⁷

Author: Daksha Jivan
Editors: Ankia Coetzee, Zaheer Bayat and Aslam Amod

References

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