Management of Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

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Key points

  • Hyperglycemic emergencies are life-threatening complications of diabetes.

  • This article reviews diabetic ketoacidosis and hyperglycemic hyperosmolar state addressing historical context, epidemiology, clinical features, and guidelines for management.

Historical review of diabetic comas

The first detailed clinical description of diabetic coma in an adult patient with severe polydipsia, polyuria, and a large amount of glucose in the urine followed by progressive decline in mental status and death was reported by August W. von Stosch in 1828.5 This publication was followed by several case reports describing young and adult patients with newly diagnosed or with established diabetes who presented with an abrupt clinical course of excessive polyuria, glycosuria, coma, and death.6, 7

Epidemiology

Although DKA occurs more commonly in patients with autoimmune T1D, the cumulative number of cases of DKA reported in patients with T2D represents at least one-third of all cases.22 Global epidemiologic studies have reported on the incidence of DKA among patients with T1D. An analysis from the Prospective Diabetes Registry in Germany including 31,330 patients reported a DKA admission rate of 4.81 per 100 patient-years (95% confidence interval [CI], 4.51–5.14).23 Individuals with the highest risk

Precipitating cause

The most common precipitating causes of DKA reported in different epidemiologic studies worldwide are shown in Table 1. DKA is the initial presentation of diabetes in approximately 15% to 20% of adults and in approximately 30% to 40% of children with T1D.4, 37, 38 Infection is the most common cause of DKA around the world; however, poor adherence to insulin treatment is the most common precipitating cause of DKA in young patients with T1D and in inner city populations in the United States.39, 40

Pathophysiology

The 2 most important pathophysiologic mechanisms for DKA and HHS are significant insulin deficiency and increased concentration of counterregulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone (Fig. 1).62, 63, 64 The insulin deficiency of DKA can be absolute in patients with T1D or relative as observed in patients with T2D in the presence of stress or intercurrent illness.65 Insulin deficiency coupled with increased counterregulatory hormones lead to increased

Signs and Symptoms

Patients with DKA often present following a short clinical course characterized by fatigue and classic symptoms of hyperglycemia: polyuria, polydipsia, and weight loss. Gastrointestinal complaints are common with diffuse abdominal pain reported in 46% of patients and nausea and vomiting in up to two-thirds of patients.42 About one-half of patients present with lethargy and stupor, but less than 25% present with loss of consciousness.1 On physical examination, patients often present with signs

Symptoms and Signs

The majority of patients with HHS present with a history of polyuria, polydipsia, weakness, blurred vision, and progressive decline in mental status.50, 83 The typical patient with HHS is older than 60 years of age with an infection or acute illness who has delayed seeking medical attention. On physical examination, similar to DKA, patients with HHS frequently have clear signs of dehydration, dry mucous membranes and poor skin turgor, or hypotension.50

Laboratory Findings

The diagnostic criteria for HHS includes a

Common laboratory pitfalls

Patients with DKA frequently present with significant leukocytosis with white cell counts in the 10,000 to 15,000 mm3 range. A leukocyte count of greater than 25,000 mm3 or the presence of greater than 10% neutrophil bands is seldom seen in the absence of bacterial infection.64, 84 In ketoacidosis, leukocytosis is attributed to stress, dehydration, and demargination of leukocytes.

The admission serum sodium may be low because of the osmotic flux of water from the intracellular to the

Management of hyperglycemic crises

The American Diabetes Association algorithm for the management of hyperglycemic emergencies is shown in Fig. 2.1 Similar therapeutic measures are recommended for the treatment of DKA and HHS. In general, treatment goals include correction of dehydration, hyperglycemia, hyperosmolality, electrolyte imbalance, and increased ketonemia, and the identification and treatment of precipitating event(s). The average time to resolution is between 10 and 18 hours for DKA89, 90 and approximately 9 and

Fluid therapy

Intravenous (IV) fluids are a critical aspect of treatment of hyperglycemic emergencies. Treatment with IV fluids alone expands intravascular volume, restores renal perfusion, and reduces insulin resistance by decreasing circulating counterregulatory hormone levels.62 Isotonic saline (0.9% NaCl) is the preferred solution and is given at an initial rate of 500 to 1000 mL/h during the first 2 to 4 hours. A study comparing 2 IV fluid regimens with sodium chloride and lactate ringers found no

Transition to maintenance insulin regimen

Resolution of DKA is defined when glucose levels are lower than 250 mg/dL, venous pH is greater than 7.30, there is a normal anion gap, and serum bicarbonate is 18 mEq/L or greater.1 HHS resolution is achieved when effective serum osmolality is less than 310 mOsm/kg and the glucose level is 250 mg/dL or less (13.8 mmol/L) in a patient who has recovered mental alertness and regaining of mental status.1, 97

Because of the short half-life of intravenous insulin (<10 minutes),109 abrupt cessation of

Complications

Hypoglycemia is the most common complication during treatment, reported in 5% to 25% of patients with DKA.1, 4, 105 Lack of frequent monitoring and the failure to reduce insulin infusion rate and/or to use dextrose-containing solutions when blood glucose levels are less than 200 mg/dL are the most important risk factors associated with hypoglycemia during insulin treatment. Many patients with hypoglycemia do not experience adrenergic manifestations of sweating, nervousness, fatigue, hunger, and

Prevention

Medication noncompliance is a leading cause of DKA among both newly diagnosed and recurrent episodes of DKA.39, 40, 41 The mean cost of hospitalization is about $7500.40 In one-half of such episodes, patients report an inability to afford medication or to pay for transportation as the reason why medication was discontinued.41 Development of system-wide changes such as assistance programs to provide insulin to patients and reduce lapses in treatment may be a cost-effective way to reduce the rate

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      Dextrose-containing fluid is continued to keep blood glucose between 8.4-14 mmol/L (150-250 mg/dL). This allows for the prevention of hypoglycemia with continued insulin infusion to correct the ketoacidosis as it takes longer to resolve.1,2,5,6,12,30,39–41 Fluid resuscitation should be carefully monitored in several patient populations such as the elderly, patients with heart failure, and end-stage kidney disease.

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