Appendix J: Glycaemic emergencies
Hypoglycaemia is a common complication of the management of type 1 diabetes. But the frequency of hypoglycaemia in type 2 diabetes is underestimated. Its clinical significance, especially in the elderly patient, is great. Hypoglycaemia can lead to falls, fractures, injuries, arrhythmias and, in severe cases, death. Symptoms may go unrecognised or may be mistaken for other conditions (e.g. TIA, vasovagal episodes).
Patients at risk of hypoglycaemia include:
- the elderly
- people with longstanding type 2 diabetes with CVD
- people with renal impairment and CKD
- people on monotherapy with insulin or long-acting sulphonylureas
- people on combination therapies with sulphonylureas and insulin
- patients using heavy machinery
- people with excessive alcohol intake
- people on beta blocker therapy (rare), in particular vasodilatory agents (e.g. propranolol, atenolol).
Hypoglycaemia occurs most frequently with:
- insulin therapy
- sulphonylurea therapy
- deficient carbohydrate intake
- unaccustomed exercise.
The risk of hypoglycaemia with each sulphonylurea relates to its pharmacokinetic properties. Long-acting preparations are associated with higher risks of hypoglycaemia (e.g. glibenclamide [Daonil, Glimel]). Studies have shown significantly lower rates of hypoglycaemia associated with the use of gliclazide (Diamicron) compared with other sulphonylureas.
Although many newer therapies for type 2 diabetes do not cause hypoglycaemia when used as monotherapy, their use in combination with insulin or sulphonylureas increases the risk of hypoglycaemia. The use of insulin analogs may limit, but not eradicate, the risk of hypoglycaemia.
Symptoms of hypoglycaemia vary between persons. Patients often learn to recognise their unique symptoms. The onset of symptoms usually occurs with a BGL <3.9 mmol/L. Common symptoms fall into two categories: adrenergic symptoms of trembling or shaking, sweating, hunger, lightheadedness and numbness around the lips and fingers, and neuro-glycopaenic symptoms of lack of concentration, weakness, behavioural change, tearfulness/crying, irritability, headache and dizziness.
Severe hypoglycaemia occurs clinically when a patient requires external assistance from another person to manage an episode of hypoglycaemia. A BGL <2.0 mmol/L puts the person at risk of severe hypogylcaemia.
Asymptomatic hypoglycaemia (or biochemical hypoglycaemia) occurs when BGL is low (<3.9 mmol/L) but above the normal threshold for detection of hypoglycaemia in most patients (~3.5 mmol/L).
Hypoglycaemic unawareness is of particular concern and refers to the clinical situation where a patient loses the ability to detect the early symptoms of hypoglycaemia. This results from repeated episodes of mild hypoglycaemia with eventual loss of adrenergic and neuro-glycopaenic symptoms. It can lead to confusion and marked behavioural change which is not recognised by the patient and may progress to loss of consciousness.
The cause needs to be identified and the episode dealt with by reinforcing education, counselling the patient and perhaps changing treatment.
Management of an episode of hypoglycaemia
If a patient with diabetes is showing signs of potential hypoglycaemia, first make sure the patient is safe (e.g. seated securely and not at risk of falling).
If possible, confirm that the symptoms are due to hypoglycaemia by performing a finger prick BGL.
If BGL is lower than 4.0 mmol/Land the patient is symptomatic, awake and can swallow, manage according to the Rule of 15:
- Provide 15 grams of quick-acting carbohydrate that is easy to consume (e.g. half can of regular – non diet – soft drink, half glass fruit juice, 3 teaspoons of sugar or honey, 6–7 jellybeans, 3 glucose tablets).
- Wait 15 minutes and repeat blood glucose check. If the level is not rising, suggest eating another quick-acting carbohydrate from the above list.
- If the patient’s next meal is more than 15 minutes away, provide some longer acting carbohydrate (e.g. a sandwich, 1 glass of milk or soy milk, 1 piece of fruit, 2–3 pieces of dried apricots, figs or other dried fruit, 1 tub of natural low-fat yoghurt, 6 small dry biscuits and cheese).
- Test glucose again during the next 2–4 hours.
Patients and carers should be made aware of the use of a similar Rule of 15.
If the patient is symptomatic but the blood glucose or capillary glucose cannot be performed to confirm the episode is due to hypoglycaemia, treat the patient as if they have hypoglycaemia by administering 15 g of quick-acting carbohydrate. If there is no improvement after 15 minutes, the patient could have another cause for the episode and further medical assistance may be necessary.
If the patient cannot safely swallow 15 g of carbohydrate due to their depressed mental state, consider the administration of 1 vial of glucagon intramuscularly, if available. If not, further emergency medical assistance will be required.
If glucagon is administered, always review the monitored capillary glucose after 15 minutes to ensure effective management of the hypoglycaemia has occurred and the blood glucose remains above 4 mmol/L. Test again 1 hour after severe hypoglycaemia to ensure stable glucose levels.
Post-hypoglycaemia: Re-assess the patient’s circumstances, medication dosages, and dietary intake as well as overall need for glucose monitoring after any severe hypoglycaemic episode with both the patient and/or with their immediate family or support persons. Also ensure implications for driving competence, operation of machinery and other similar areas are discussed with the patient.
J.2 Hyperglycaemic emergencies
Severe hyperglycaemia has significant morbidity and mortality.
Hyperglycaemic emergencies should be preventable in people known to have diabetes, and their occurrence in this group signifies a major breakdown in medical management. Adequate early management of sick patients with diabetes will prevent the development of hyperglycaemic emergencies.
DKA, once thought to typify type 1 diabetes mellitus, can occur in patients with type 2 diabetes mellitus under stress such as during surgery, trauma or infections. The very young, older people and pregnant patients are also at greater risk of DKA.
Signs of DKA:
- ketotic breath
- disturbed conscious state and shock
Common precipitating factors:
- urinary tract infection
- myocardial infarction
DKA occurs when there is an absolute deficiency of insulin. For DKA to occur in type 2 diabetes, there needs to be significantly impaired insulin secretion as the result of ‘glucotoxicity’ together with severe insulin resistance, typically as the result of severe infection or other stresses.
This results in:
- increasing hepatic glucose production causing hyperglycaemia
- increasing peripheral lipolysis releasing free fatty acids. These are converted to ketoacids by the liver resulting in a metabolic acidosis
- hyperglycaemia-induced osmotic diuresis leading to sodium, potassium and phosphate depletion
- dehydration causing pre-renal failure.
The biochemical criteria for DKA are:
- venous pH <7.3 or bicarbonate <15 mmol/L
- presence of blood or urinary ketones.
Urinalysis can be used for initial assessment if blood ketone testing is not available.
The time-tested therapy for DKA is rehydration with saline-based intravenous fluid therapy, administration of intravenous insulin with subsequent administration of glucose as the BGL normalises, and adequate potassium replacement throughout to avoid hypokalaemia. Additionally associated problems arising from or precipitating the episode need to be addressed.186
Wherever possible the patient should be managed in a specialist medical unit. In remote rural practice this may not be possible. In this situation it is advisable to contact the most appropriate diabetes resource person for advice while commencing treatment promptly.
Table J.1. General outline for the management of DKA
- Blood glucose
- Arterial blood gases (venous in children)
- Electrolytes and renal function
- Urine glucose, ketones, microscopy and culture
- Chest X-ray
||Clinical and biochemical status. For example:
- 1/2 hourly: BP, pulse, urine output
- Hourly: capillary blood glucose
- 2 hourly: electrolytes especially potassium
|Fluids and electrolytes
||Most patients have a deficit of several litres (40 to 80 mL/kg). Normal (0.9%) saline is suitable.
If hypoperfusion is present, give 0.9% saline at 10 mL/kg and reassess. If central capillary refill remains >2 seconds, a further bolus of 10 mL/kg of 0.9% saline may be given.
Patients with DKA rarely require >20 mL/kg in total as a bolus.
Fluid replacement with normal saline and potassium should continue for at least the first 6 hours. If the blood glucose falls very quickly within the first few hours, or if the BGL reaches 12–15 mmol/L, change to normal saline with 5% dextrose and potassium.
Do not administer potassium supplement if the potassium level is greater than 5.5 mmol/L, or if the patient is anuric.
If the potassium level is 4.5–6 mmol/L, start KCl at 40–60 mmol/L if person’s weight is >30 kg or 40mmol/L if person’s weight is <30 kg.
Measure levels and adjust the dose at least 2 hourly.
- An intravenous bolus of 0.15 units/kg neutral insulin.
- An infusion of neutral insulin 100 units/L saline is commenced. Run 100 mL through the line before connecting to the patient to saturate insulin binding to the giving set. If a syringe pump is available add 50 units of neutral insulin to 50 mL of saline and flush the giving set. Commence the infusion at 0.05–0.15 units per kg per hour and adjust the dose depending on glycaemia (usual rates are 0.5–6 units per hour for a 70 kg adult).
- When blood glucose levels fall below 15 mmol/L set up a 5% dextrose infusion (50–100 mL per hour) and make appropriate adjustments to other intravenous fluids.
- DKA can be complicated by severe infection, arterial thrombosis, profound shock and lactic acidosis and cerebral oedema. Once treatment is initiated (unless the acidosis is mild and response rapid) transfer the patient to a specialist unit.
Hyperosmolar nonketotic coma
HONC occurs due to inadequate diabetes control in patients with type 2 diabetes. This is usually a result of illness or infection, however it can also be due to poor patient compliance. Older patients are at higher risk of HONC.
HONC develops because of relative rather than absolute insulin deficiency. Significant insulin deficiency causes hyperglycaemia due to increased hepatic gluconeogenesis. However, as absolute insulin deficiency is not present, peripheral lipolysis remains suppressed and the release of free fatty acids is low. Little substrate is available for generation of ketoacids and a metabolic acidosis does not occur.
The hyperglycaemia results in an osmotic diuresis leading to pre-renal failure. Eventually, severe intravascular volume depletion occurs resulting in a further deterioration of renal function. Consequently glomerular filtration diminishes preventing the further excretion of glucose. With ongoing increased hepatic glucose production, decreased peripheral glucose utilisation and reduced urinary glucose losses, severe hyperglycaemia results.
Signs of HONC:
- severe dehydration
- altered consciousness
Common precipitating factors:
- urinary tract infection
- myocardial infarction
The depletion of the total body water leads to the hyperosmolality of body fluids reflected by the extreme hyperglycaemia and increased plasma sodium. This hyperosmolar state affects consciousness and may cause coma.
General outline for the management of HONC
Wherever possible the patient with HONC should be managed in a specialist medical unit. In remote rural practice this may not be possible. In this situation it is advisable to contact the most appropriate diabetes resource person for advice while commencing treatment promptly.
Rapid correction of the hyperosmolar state is dangerous.
The priority is to correct the extracellular fluid deficit, then slowly correct the hyperglycaemia (with insulin) and water deficit (with low sodium fluids [e.g. 5% dextrose or 4% dextrose and normal saline]).
Monitor extracellular fluid status and plasma glucose, sodium and potassium.
It is important to note that blood glucose meters do not register very high glucose levels so access to a laboratory is necessary to monitor the correction of hyperglycaemia as well as to monitor sodium and potassium levels.
See Table J.2 for an outline of management of HONC.
Table J.2. General outline of management of HONC
|Recommendations and supporting evidence|
||SIGN Level of evidence
||1. Initial treatment – 0.9% NaCl at the rate of 15–20 mL/kg/h or 1–1.5 L during the first hour.
|2. Maintenance – guided by clinical state. 0.45% saline at 250–500 mL/h is appropriate in patients who are eunatraemic or hypernataemic, while 0.9% NaCl at a similar rate is appropriate in hyponatraemic subjects.
|3. When plasma glucose is 11.1 mmol/L in DKA or 16.7 mmol/L in HONC, 5% dextrose should be added to repletion continue insulin until ketonaemia resolves.
||188 189 190
||1. IV regular insulin 0.14 units/kg/h as continuous infusion, or a bolus of 0.1 units/kg followed by 0.1 units/kg/h.
||188 191 192
|2. If blood glucose does not fall by 10% in the first hour, give 0.14 units/kg as a bolus, then continue infusion at the previous rate.
|3. When the plasma glucose reaches 11.1 mmol/L in DKA or 16.7 mmol/L in HONC, insulin infusion rate should be reduced to 0.02–0.05 units/kg/h. Also, dextrose should be added to the intravenous fluids.
|4. Subcutaneously administered insulin analogs may be used in the medical ward or emergency room in mild–moderate DKA.
|5. Once DKA has resolved, patients can be started on a multiple dose insulin regimen. Patients who are unable to eat should continue to receive intravenous insulin infusion and fluid replacement.
|6. Some patients with type 2 diabetes may be treated with oral anti-diabetic agents and lifestyle modification after recovery.
||1. Adults with pH <6.9 may be given 100 mmol sodium bicarbonate in 400 mL sterile water with 20 mequiv KCI administered at a rate of 200 mL/h for 2 h until the venous pH is >7.0.
|2. Patients with pH ≥ 6.9 do not require bicarbonate therapy.
||196 197 198
|Abnormal phosphate level
||1. There is no indication for phosphate therapy in most patients with DKA. In patients with potential complications of hypophosphatemia the use of phosphate maybe justified. 20–30 mequiv/L potassium phosphate can be added to replacement fluids.
||188 189 199
|2. Potassium replacement may be given 1/3 as potassium phosphate and 2/3 as potassium chloride.
|Serum calcium level should be monitored in patients receiving phosphate infusion.
||Prophylactic use of heparin may be beneficial in DKA and full anticoagulation may be indicated where there are no contraindications in HONC.
||1. Education of the diabetic patient and care givers on the process of care and sick day management.
|2. Patients who use illicit drugs may benefit from drug rehabilitation.
Reproduced with permission from Elsevier from Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011;94(3):340–51.187
- Newton CA, Raskin P. Diabetic ketoacidosis in type 1 and type 2 diabetes mellitus: clinical and biochemical differences. Arch Intern Med 2004;164:1925–31.
- Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011;94:340–51.
- Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009;32:1335–43.
- Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001;24:131–53.
- Hillman K. Fluid resuscitation in diabetic emergencies—a reappraisal. Intensive Care Med 1987;13:4–8.
- Caputo DG, Villarejo F, Valle GB, Diaz Aguiar P, Apezteguia CJ. [Hydration in diabetic ketoacidosis. What is the effect of the infusion rate?]. Medicina (B Aires) 1997;57:15–20.
- Krentz AJ, Hale PJ, Singh BM, Nattrass M. The effect of glucose and insulin infusion on the fall of ketone bodies during treatment of diabetic ketoacidosis. Diabet Med 1989;6:31–6.
- Butkiewicz EK, Leibson CL, O’Brien PC, Palumbo PJ, Rizza RA. Insulin therapy for diabetic ketoacidosis. Bolus insulin injection versus continuous insulin infusion. Diabetes Care 1995;18:1187–90.
- Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med 1977;297:238–41.
- Della Manna T, Steinmetz L, Campos PR, et al. Subcutaneous use of a fast-acting insulin analog: an alternative treatment for pediatric patients with diabetic ketoacidosis. Diabetes Care 2005;28:1856–61.
- Mauvais-Jarvis F, Sobngwi E, Porcher R, Riveline JP, Kevorkian JP, Vaisse C, et al. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of beta-cell dysfunction and insulin resistance. Diabetes 2004;53:645–53.
- Maldonado M, Hampe CS, Gaur LK, D’Amico S, Iyer D, Hammerle LP, et al. Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes. J Clin Endocrinol Metab 2003;88:5090–98.
- Beigelman PM. Potassium in severe diabetic ketoacidosis. Am J Med 1973;54:419–20.
- Tattersall RB. The history of diabetes mellitus. 4th edn. In Holt RIG, Cockram CS, Flyvberg A, Goldstein BJ. eds. West Sussex, UK: Wiley-Blackwell, 2010.
- Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med 1999;27:2690–93.
- Winter RJ, Harris CJ, Phillips LS, Green OC. Diabetic ketoacidosis. Induction of hypocalcemia and hypomagnesemia by phosphate therapy. Am J Med 1979;67:897–900.
- Buyukasik Y, Ileri NS, Haznedaroglu IC, et al. Enhanced subclinical coagulation activation during diabetic ketoacidosis. Diabetes Care 1998;21:868–70.
- Nyenwe EA, Loganathan RS, Blum S, et al. Active use of cocaine: an independent risk factor for recurrent diabetic ketoacidosis in a city hospital. Endocr Pract 2007;13:22–9.
- Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 1983;57:177–80.