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Diabetic ketoacidosis and hyperosmolar, hyperglycaemic state


Essentials

  • 1

    Diabetic ketoacidosis (DKA) consists of the triad of ketonaemia, hyperglycaemia and acidaemia—a high anion-gap metabolic acidosis.

  • 2

    DKA is caused by insulin omission or error, intercurrent illness (including infection) or is a presenting feature of new diabetes.

  • 3

    Key management components of DKA include:

    • fluids (0.9% normal saline) to replace deficits of sodium of 7 to 10 mmol/kg and water 100 mL/kg

    • soluble insulin infusion at 0.1 unit/kg/h to a maximum of 6 units/h to suppress ketogenesis, reduce blood sugar and help correct the electrolyte abnormalities

    • potassium replacement, providing the serum (potassium) is less than 5.5 mmol/L and there is urine output (note anuria is rare in DKA)

    • education—all patients on insulin need to know the ‘sick day rules’, plus be familiar with regular home testing for capillary blood sugar.

  • 4

    Meticulous monitoring and documentation of treatment in DKA are essential.

  • 5

    Hyperosmolar hyperglycaemic state (HHS) is characterized by hypovolaemia, marked hyperglycaemia (>30 mmol/L) without ketonaemia or acidosis, and a raised osmolality usually >320 mOsmol/kg.

  • 6

    Mortality and morbidity of HHS are greater than with DKA, usually related to the older age of patients, co-morbidities and complications, such as stroke.

  • 7

    Treatment of HHS is similar to DKA except:

    • lower dose insulin infusion rate is used at 0.05 unit/kg/h

    • this infusion rate is titrated against the serum osmolarity rather than ketoacids

    • 0.9% normal saline is used and only changed to half normal (0.45%) saline if the osmolality and glucose are not declining

    • low-molecular-weight heparin (LMWH) thromboprophylaxis is indicated.

Introduction

Diabetic ketoacidosis (DKA) is an acute, potentially life-threatening complication in an insulin-dependent diabetic and in some type II diabetics. It consists of the triad of ketonaemia, hyperglycaemia and acidaemia—a high anion-gap metabolic acidosis. Although DKA is preventable, its prevalence and suboptimal management may highlight shortfalls in the quality of care for patients with diabetes. The mortality rate in developed countries has dropped to <1%.

Hyperosmolar hyperglycaemic state (HHS) is characterized by hypovolaemia, marked hyperglycaemia (>30 mmol/L) without ketonaemia or acidosis, and a raised osmolality usually >320 mOsmol/kg. It comes on more insidiously and has a worse prognosis with an increased mortality of around 15% to 20% and greater morbidity, in part related to underlying chronic medical disorders, and often occurring in an older population.

Epidemiology and aetiology

An annual incidence of DKA of approximately 1:170 patients with type I diabetes is reported, or 2 episodes per 100 patient years of diabetes, for a prevalence of 4.6 to 8 episodes per 1000 patients with diabetes. The mortality rate in developed countries is under 1% most commonly due to cerebral oedema particularly in children/young adults, severe hypokalaemia, adult respiratory distress syndrome (ARDS) and co-morbid conditions such as sepsis or acute myocardial infarction (MI).

DKA may be the presenting feature of new diabetes mellitus (3% to 25% DKA), but it more usually follows intercurrent illness in a patient with known autoimmune type I diabetes (35% DKA); when there has been an insulin error with poor compliance or inadequate insulin (30% DKA); and/or for instance an insulin infusion pump blockage. A variant of type II diabetes is also ‘ketosis-prone (type II) diabetes’, usually in the obese with a strong family history. This was originally described in Africans and African Americans, but is now noted worldwide.

Pathogenesis

DKA arises from an absolute or relative lack of insulin accompanied by an increase in counter-regulatory hormones, such as glucagon, cortisol and growth hormone. Insulin absence leads to increased hepatic gluconeogenesis and glycogenolysis, with an incomplete lack of insulin related to greater hyperosmolarity (in HHS). Lack of insulin and excess counter-regulatory hormones increase lipolysis and free fatty acid production as an alternate energy source. This leads to subsequent ketone body formation produced from acetyl coenzyme A, mainly in hepatic mitochondria, including acetone, beta-hydroxybutyrate and acetoacetate, and a reduced ability to prevent ketonaemia.

HHS is the other end of the hyperglycaemia spectrum from DKA, occurring with a relative rather than an absolute deficiency of insulin leading to a greater level of hyperglycaemia, therefore higher hyperosmolarity than is seen in DKA. The degree of dehydration is greater (typically 10% to 15% body weight), but significant ketosis does not occur. HHS is more insidious in onset than DKA and patients with HHS are typically older with pre-existing type II diabetes. However, HHS is seen in young adults and even teenagers.

Clinical features

Malaise and fatigue on a background of polyuria, polydipsia, weakness and fatigability are common, but gastrointestinal symptoms, such as nausea, vomiting and abdominal pain, may predominate. Lack of a history of diabetes does not rule out the diagnosis of DKA, as it may be a first presentation, often presaged by recent, unexplained rapid weight loss.

Laboured, sighing respirations with an increased rate and depth, known as Kussmaul breathing, are characteristic of DKA in association with dehydration causing decreased tissue turgor, a dry mouth and sweet foetor of pear drops (ketotic), which is not always noticed. The conscious level may be reduced, but coma is rare.

Look carefully for signs of an underlying precipitating cause. This can include chest, urine or skin infection, such as boils, as well as meningitis or an acute abdomen, although non-surgical upper abdominal pain is common in DKA. A silent MI is another potential cause. In those with HHS, look out for the complications of acute MI, stroke or arterial thrombosis.

The urine output should be measured regularly, which does not always require urinary catheterization. Likewise, invasive haemodynamic monitoring should not be instituted as a ‘routine’ for patients with DKA or HHS. It should be reserved for severe cases and those who fail to respond, or in the elderly who are at risk of fluid overload. In addition, venous blood gases are sufficient to monitor progress in DKA, rather than repeated arterial sampling.

Diagnostic criteria

Diabetic ketoacidosis

  • Metabolic acidosis with pH <7.3 or serum bicarbonate <15 mmol/L.

  • Ketonaemia >3.0 mmol/L, or marked ketonuria >2+on dipstick (note urinalysis may miss 3-beta hydroxybutyrate early).

  • Hyperglycaemia with blood glucose >11 mmol/L.

Hyperosmolar hyperglycaemic state

Note that there is no precise definition of HHS, but it is characterized by :

  • Hyperglycaemia. Serum glucose >30 mmol/L.

  • Hyperosmolality. Serum osmolality >320 mOsmol/kg. (If unable to measure regularly, use an approximation of the osmolarity = [2 × Na + glucose + urea].)

  • Significant dehydration with hypovolaemia.

  • Minimal ketonaemia (<3.0 mmol/L) with no more than 1 + ketonuria on urinalysis.

  • pH >7.30, bicarbonate >15 mmol/L.

Typical deficits per body weight

Diabetic ketoacidosis

  • Water 100 mL/kg

  • Sodium 7 to 10 mmol/kg

  • Potassium 3 to 5 mmol/kg.

Hyperosmolar hyperglycaemic state

  • Water 100 to 220 mL/kg

  • Sodium 5 to 13 mmol/kg

  • Potassium 4 to 6 mmol/kg.

Investigations

Blood testing

Measure both glucose and ketones in capillary blood hourly until they are near to the normal range. Or measure serum urea and electrolytes (U&Es), glucose and pH initially hourly, then 2-hourly once the serum glucose and capillary glucose are in agreement. Venous blood sampling is acceptable rather than repeated arterial punctures, but an intra-arterial line may be sited for repeat blood sampling (although it is not essential).

Send blood cultures if there is evidence of an underlying septic process, but remember that a mild leucocytosis is common in DKA, and should not be interpreted as signifying infection.

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