Diabetic Emergencies: Diabetic Ketoacidosis in Adults, Part 4

The administration of bicarbonate in severe acidosis (pH less than 7.0) remains controversial.⁸ Severe metabolic acidosis exerts a negative inotropic effect on the heart, induces vasodilation and hypotension, reduces glucose uptake and utilization, and promotes ventricular arrhythmias.⁶ On the other hand, bicarbonate therapy may lead to worsening of hypokalemia (especially at the beginning of bicarbonate administration), intracellular acidosis in the central nervous system (paradoxical acidosis),²⁷ and metabolic alkalosis.⁶ One study showed that bicarbonate administration had no benefits for patients with DKA and initial pH 6.9-7.15.²⁸ However, in this trial the number of patients with pH in this range was very small. Based on existing evidence and expert opinion, it may be prudent to administer 50 mmol of bicarbonate in 200 ml water with 10 mEq of potassium chloride over 1 hour in patients whose pH is 6.9-7.0 or serum bicarbonate less than 5 mEq/L. In patients with pH less than 6.9, doubling of the above bicarbonate dose is recommended. Arterial pH should be monitored 2 hours later and the dose should be repeated if pH remains lower than 7.0.^8,10

Electrolyte replacement

Replacement of sodium and chloride deficits is achieved by the administration of normal saline as described above. Particular attention should be paid to potassium restoration. As mentioned, serum potassium concentrations are usually normal or increased despite the significant total body deficit. During treatment of DKA potassium levels are decreased, sometimes very quickly, because correction of acidosis and the insulin infusion move potassium into the intracellular compartment. Hypokalemia may cause severe arrhythmias and cardiac arrest. If potassium levels are less than 3.3 mEq/L at any point during therapy, insulin should be stopped and potassium should be administered.^6,10

Potassium replacement must be performed as follows:⁹

• Low potassium (less than 3.3 mEq/L): insulin should be immediately discontinued; give 20-30 mEq of potassium per hour until potassium levels exceed 3.3 mEq/L; then resume insulin infusion.
• Potassium levels between 3.3 and 5.3 mEq/L: add 20-30 mEq of potassium in each liter of intravenously administered fluid to keep serum potassium between 4 and 5 mEq/L.
• Potassium levels above 5.3 mEq/L: potassium is not administered until levels reach the normal value. Repeat potassium measurement in 2 hours.

Potassium is replaced as KCl. Some authors recommend replacement of one third of the potassium with KPO₄ to avoid excessive chloride administration and to prevent hypophosphatemia.⁶ Special attention is needed in patients with impaired renal function or anuria to avoid hyperkalemia.

It should be noted that the goal of treatment is not immediate restoration of the total potassium deficit. This can be done progressively and completed with feeding.

Phosphate depletion is common in DKA, and serum phosphate levels may decline during treatment with insulin because phosphate is taken up intracellularly. However, phosphate replacement should be reserved only for patients with severe hypophosphatemia (serum levels < 1.5 mg/dl [0.48 mmol/L]) providing that serum calcium levels are normal.⁸ Oral phosphate repletion is always preferable to intravenous repletion and should be commenced as soon as patients are able to take food by mouth.⁹ The management of DKA is depicted in Figure 1.2 .

The protocol in Table 1.5 is suggested for the monitoring of patients with DKA and should be meticulously completed (see Table 1.3). (It may vary between clinics.)¹

Complications of DKA include hypoglycemia (due to overtreatment), hypokalemia, cerebral edema, non-anion gap hyperchloremic acidosis, fluid overload, rhinocerebral mucormycosis, thrombotic events, rhabdomyolysis, and acute respiratory distress syndrome.^1,6,8,10

Administration of large doses of insulin for the management of DKA was associated with hypoglycemia, which sometimes was severe. Hypoglycemia is less commonly seen with the use of low-dose insulin regimens and with regular blood glucose monitoring as well as a fluid change to glucose 5% solution when blood glucose falls below 250 mg/dl (13.9 mmol/L).⁸

Hypokalemia can be prevented with appropriate potassium replacement and frequent monitoring. As mentioned above, insulin infusion should be discontinued when serum potassium falls to levels lower than 3.3 mEq/L at any stage of treatment and immediate potassium administration should begin.^8,10

Cerebral edema is a very rare complication in adults. It has been described in young adults presenting with DKA and is seen in 1–2% of children presenting with DKA. However, subclinical cerebral edema, demonstrable by computed tomography (CT) scanning or raised cerebrovascular fluid pressure, probably occurs in most cases during or even before treatment.^10,29 It is manifested by decline in consciousness level often progressing rapidly to coma, pupillary changes, vomiting, elevated diastolic blood pressure, decorticate or decerebrate posturing, cranial nerve palsies, Cheyne-Stokes respiration, and seizures. Typically it occurs within 8-24 hours after initiation of treatment and many patients deteriorate without warning. The mortality rate is high (70-90%) and may be partially related to delayed diagnosis and treatment. Mechanisms underlying this condition include rapid decline in plasma osmolality (greater than 3% per hour), high intravascular fluid replacement rate, use of hypotonic fluids, and high rate of decrease in blood glucose.^8,10 The diagnosis can be confirmed by CT or magnetic resonance scanning, which shows swelling of the brain with loss of structural details and squashing of the ventricular system. Treatment of cerebral edema includes administration of mannitol (0.3 g/kg given over 30 minutes and repeated hourly if there is no improvement to single doses of 1 g/kg). Dexamethasone is often given in high doses (4 mg every 6 hours intravenously) but its benefit remains unproven. Mechanical ventilation to remove carbon dioxide and improve acidosis has also been advocated.¹⁰

Non-anion gap hyperchloremic acidosis may occur because chloride is preferentially reabsorbed in the proximal renal tubules and chloride losses are less than sodium losses in DKA. Because replacement solutions have equal amounts of sodium and chloride, relative hyperchloremia may occur with treatment. The development of acidosis should not affect the treatment course and usually resolves.¹⁰

Fluid overload may be seen in patients with severe cardiac or renal impairment. In addition, acute respiratory distress syndrome has been reported in patients less than 50 years of age who are free of cardiac or renal disease. Manifestations include dyspnea, tachypnea, and central cyanosis. Arterial hypoxia is characteristic and chest radiograph reveals bilateral pulmonary infiltrates. The development of new pulmonary rates and an increased alveolar-arterial oxygen gradient are clues to diagnosis. Patients with this syndrome need mechanical support of ventilation and avoidance of fluid overload.^6,8

Rhinocerebral mucormycosis may develop in patients who develop recurrent episodes of DKA or another metabolic acidosis. This is caused by an opportunistic fungal infection starting in the paranasal sinuses and rapidly invading adjacent tissues (nose, sinuses, orbit, and brain). Treatment comprises of correction of acidosis, surgical excision of the affected tissues, and intravenous administration of antifungal agents.¹⁰

Diabetes is characterized by a propensity to thrombosis. Marked hyperglycemia is associated with decreased blood flow, increased blood viscosity, and increased coagulability. The role of prophylactic anticoagulation has not been clearly established. Because many patients present with some degree of renal failure, unfractionated heparin use is preferred for prevention of thromboembolism.¹⁰

Rhabdomyolysis is another possible complication of DKA. Hyperosmolality and hypoperfusion contribute to skeletal muscle damage. Recent data suggest that DKA is more common among users of cocaine, a common cause of rhabdomyolysis. Creatinine phosphokinase levels can be initially assessed in patients with DKA if clinically indicated.¹⁰

Many cases of DKA can be prevented by better access to medical care, proper education and effective communication with a healthcare provider during an intercurrent illness. Sick-day rules should be reviewed periodically with all patients (see Chapter 8). The patients and/or their family members must be able to determine blood glucose and β-OHB or urine ketones when blood glucose levels are above 300 mg/dl (16.7 mmol/L). Many hospitalizations can be avoided by devoting adequate resources to apply the measures described above.⁸ 

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Christina Kanaka-Gantenbein, MD, PhD
Associate Professor of Pediatric Endocrinology and Diabetology
First Department of Pediatrics, University of Athens
Agia Sofia Children's Hospital
Athens, Greece

Stavros Liatis, MD
Consultant in Internal Medicine and Diabetology
Laiko General Hospital

Konstantinos Makrilakis, MD, MPH, PhD
Assistant Professor of Internal Medicine and Diabetology
Athens University Medical School
Laiko General Hospital
Athens, Greece

Nikolaos Tentolouris, MD, PhD
Assistant Professor of Internal Medicine and Diabetology
University of Athens
Laiko General Hospital
Athens, Greece

A John Wiley & Sons, Ltd., Publication This edition first published 2011 © 2011 by John Wiley & Sons, Ltd.

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Diabetic Emergencies: Diagnosis and Clinical Management provides emergency room staff, diabetes specialists and endocrinologists with highly practical, clear-cut clinical guidance on both the presentation of serious diabetic emergencies like ketoacidosis, hyperosmolar coma and severe hyper- and hypoglycemia, and the best methods of both managing the emergencies and administering appropriate follow-up care.

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