Endocrinology

Diabetic Ketoacidosis

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Diabetic ketoacidosis/ketoacidemia (DKA) is an absolute or relative insulin deficiency resulting in ketone body production and decreased serum total CO2 concentration. This potentially life-threatening metabolic disturbance occurs most commonly in type 1 diabetics, but may also occur in type 2 diabetics.

Absolute or relative insulin deficiency results in hyperglycemia, glycosuria, and intracellular starvation, leading to release of counterregulatory hormones (glucagon, epinephrine, cortisol, and growth hormone). This results in lipolysis, proteolysis, glycogenolysis, gluconeogenesis, and insulin resistance. Glycogenolysis and gluconeogenesis exacerbate the already-present hyperglycemia. A negative cycle of progressive ketoacidemia and insulin resistance, associated with a surge of counterregulatory hormones, leads to increasing insulin resistance, hyperglycemia, dehydration, electrolyte losses, potential brain swelling, and may result in metabolic death.

Figure 14.1 ▪ Diffuse Brain Swelling; Diabetic Ketoacidosis.

A noncontrast head computed tomographic scan shows obliteration of all cerebrospinal fluid spaces including ventricles and basal cisterns with blurring of the margins of gray and white matter, typical for diffuse cerebral edema and herniation around the brainstem. These findings were seen in a patient with new-onset diabetes who initially presented with a normal mental status, severe ketoacidemia without shock, and received isotonic saline 60 mL/kg over 2 hours. Progressively diminished arousability and hypertension were unrecognized signs of raised intracranial pressure until irregular respirations and a decrease in heart rate ensued. (Photo contributor: Geetha Chari, MD.)

Figure 14.2 ▪ Brain Swelling Seen at Autopsy; Diabetic Ketoacidosis (DKA).

A dorsal view of the brain shows severe brain swelling with flattened gyri and effaced sulci. Evidence of brain swelling with herniation was seen on the brain’s ventral surface. Pretreatment brain herniation is rare, but brain swelling prior to treatment (incompletely understood cause[s]) appears common among pediatric patients with DKA. This 17-year-old known diabetes patient collapsed at home and developed hypertension, bradycardia, and agonal respirations on arrival of first responders. Such patients underscore the need for careful volume resuscitation, fluid and electrolyte management, and timely administration of insulin in those with DKA, because they likely present with some degree of brain swelling even before treatment begins. (Photo contributor: M.G.F. Gilliland, MD.)

Clinical Features

Key findings include polyuria, nocturia, polydipsia, no change in appetite, polyphagia or decreased appetite, varying degrees of dehydration, weight loss, abdominal pain, vomiting, hyperventilation, Kussmaul breathing (which is clinically visible and may be confused with respiratory distress from primary respiratory diseases such as pneumonia), subnormal body temperature (in severe DKA; may also occur in sepsis), altered mental status (which may be caused by shock, profound ketoacidemia or raised intracranial pressure [ICP]), the fruity odor of ketones on the breath, and Candida infections (eg, vaginitis or perineal yeast). Typical laboratory findings include hyperglycemia (may only be modest with serum glucose <300 mg/dL), glycosuria, ketonemia, ketonuria, metabolic acidosis/acidemia, and compensatory hypocarbia. Enuresis, urinary incontinence, apparent or actual hyponatremia, hypernatremia, hypokalemia, hypophosphatemia, hypomagnesemia, increased serum urea nitrogen, increased serum creatinine, hypertriglyceridemia, and increased serum amylase may also be present. Increased lipase in the absence of pancreatitis may occur. Initially, potassium, magnesium, and phosphorus may be increased or normal; however, close monitoring is required because serum concentrations of these ions may decrease significantly with treatment as they move intracellularly, and total body depletion of one or more of these ions becomes manifest.

Figure 14.3 ▪ Candidiasis as a Presenting Sign of Diabetes.

Extensive candidiasis involving perianal and inguinal areas with extension to the abdomen and thighs were seen in this infant presenting with diabetic ketoacidosis. Perineal Candida in a diapered infant can occur at any age. However, severe, recurrent or intransigent Candida dermatitis despite appropriate treatment and/or presence of oral candidiasis (distinctly uncommon after 12 months of age) should alert the physician to the possibility of diabetes or immune deficiency. (Photo contributor: Binita R. Shah, MD.)

The degree of dehydration varies in DKA. Severe DKA (ie, severe ketoacidemia) does not necessarily mean that severe dehydration is present; the degree of ketonemia and the degree of dehydration should be individually assessed. Raised ICP is the most common cause of morbidity and mortality; thus, monitoring for neurologic symptoms is essential. Avoid excessive volume administration, which can exacerbate brain swelling. Efforts to assign a volume of deficit should be made (Table 14.1).

Table 14.1 ▪ How to Estimate Degree Dehydration (Volume of Deficit) in DKA

	Degree of Dehydration
Guidelines	Mild	Moderate	Severe
Volume of deficit (mL/kg)*
>2 years	30	60	≥90
≤2 years	50	100	≥150
Clinical measures
Peripheral perfusion†
Palpation of peripheral pulses (pulse volume)	Normal	Normal to decreased	Decreased to absent
Capillary refill time (s)‡	<2	2 to 3	≥3
Skin temperature (tactile)	Normal	Normal to cool	Cool to cold
Heart rate	Normal to mildly increased	Moderately increased	Moderately to severely increased
Blood pressure	Normal	Normal to increased	Decreased to increased
Blood urea nitrogen (mg/dL)	Normal to mildly increased, eg, <20	Mildly increased, eg, 20 to 25	Moderately to severely increased, eg, >30
Predicted Na+ (mEq/L)	Usually normal	Usually normal	Normal to increased
Glucose (mg/dL)	Mildly increased, eg, ˜400	Moderately increased, eg, ˜600	Severely increased, eg, >800

Figure 14.4 ▪ Acanthosis Nigricans and Diabetes.

(A, B) Acanthosis nigricans is a cutaneous finding of abnormal texture (“velvety”) with darkened pigmentation of the skin that occurs in neck and flexural skin folds (A, B) most often associated with insulin resistance. In pediatric patients, it is most commonly associated with obesity and type 2 diabetes, or an increased risk for developing this disease. (Photo contributors: Amrit P. Bhangoo, MD [A] and Binita R. Shah, MD [B].)

Emergency Department Treatment and Disposition

Airway, breathing, and circulation must be addressed and insulin therapy begun. In rare cases where tracheal intubation is indicated, it should be accomplished using techniques that are protective for patients at risk for raised ICP. In addition, such patients are often profoundly hypocarbic (some patients have Paco2 values in the single digits). Their degree of compensatory hyperventilation should be maintained once the patient is intubated to avoid further decreases in blood and possibly cerebrospinal fluid (CSF) pH, which itself may contribute to brain swelling.

Figure 14.5 ▪ Obesity and Diabetes.

(A, B) Obesity is one of the risk factors for diabetes type 2 and patients may present with hyperosmolar hyperglycemic syndrome. Two different patients with diabetes with obesity and striae are shown. Striae (stretch marks) occur due to a rapid stretching of the skin (eg, rapid weight gain), and most common location is abdomen, breasts, hips, thighs, buttocks, and flank. Striae appear as parallel streaks of red, thinned skin which become white and scar-like in appearance over time. (Photo contributor: Binita R. Shah, MD.)

If shock is present, emergency volume resuscitation is required (Figure 14.1 and Table 14.1). A requirement for more than 30 mL/kg of isotonic saline resuscitation fluid is uncommon and the need for emergency volumes in excess of 20 to 30 mL/kg of ideal body weight should raise suspicion of significant complicating illnesses such as septic shock, pancreatitis, or severe enteritis. Severe ketonemia causes vasoconstriction. Cool, sometimes mottled, skin may be attributable to a very low blood pH rather than hypovolemia. For this reason, if foot pulses are strong and blood pressure is appropriate but skin remains cool and/or mottled despite 10 to 20 mL/kg of resuscitation fluid in the presence of severe acidemia, further bolus volume resuscitation may not be warranted. In these cases, insulin and rehydration therapy is recommended with serial reassessments; impaired perfusion should resolve as ketonemia is corrected with insulin and gradual rehydration. For the remainder of hydration, use solutions as described in Figure 14.6.

Figure 14.6 ▪ Initial Fluid Therapy for DKA.

Monitor closely for signs of raised ICP, including lethargy, altered mental status, decreased arousability, age-inappropriate bed-wetting associated with lack of awareness, headache, hypertension, bradycardia or relative bradycardia for the clinical situation, pupillary sluggishness or unresponsiveness, anisocoria, new focal neurologic signs, and/or seizures. If raised ICP is suspected, treat with hypertonic (20% or 25%) mannitol 0.25 to 1 g/kg over 20 minutes and evaluate the patient for a decrease in volume delivery (ie, consider a decrease in the rate of intravenous [IV] fluid infusion). If hemodynamic instability is present, infusion of 3% NaCl (3-10 mL/kg) may be an alternative to use of an osmotic diuretic. Tracheal intubation with an appropriate degree of hyperventilation may also be required.

Initiate treatment with insulin as soon as possible (by the end of the first treatment hour) by continuous intravenous infusion of regular human insulin 0.1 unit/kg actual (not ideal) body weight per hour. An improvement in the base deficit by 1 mEq/L/hour indicates adequate insulin dosing and delivery. Failure to achieve this goal suggests an inadequate insulin dose or a problem with insulin delivery (eg, adsorption of insulin to IV tubing, infiltrated IV site, malfunction of the IV pump). The insulin dose should be increased by increments of 100% if ketoacidosis is not improving. If the patient is using an insulin pump and presents with DKA, treat with continuous IV insulin even if the pump appears to be functioning.

While DKA is most commonly triggered by treatment noncompliance, it is also important to rule out other triggers including infections, acute abdominal processes, depression, behavioral disorders, illicit drug use, pregnancy, psychosocial problems, and physical and sexual abuse.

Patients should be admitted to the ICU and after stabilization, a diabetes nurse educator and nutritionist should be involved in team care.

Pearls

Watch closely for altered mental status and signs of cerebral edema or increased ICP; treat suspected increased ICP with mannitol and then obtain head CT.
Do not assume that severe acidemia is necessarily associated with severe dehydration or that the parched oral mucosa commonly seen with Kussmaul breathing and severe acidemia is indicative of severe dehydration.
Give emergency volume resuscitation only in the presence of shock.
Failing to recognize that concomitant illness such as pancreatitis, sepsis, acute abdomen, etc may be present and masked.
A continuous infusion of insulin at effective doses must be given by the end of the first treatment hour. Deep intramuscular (IM) administration of regular insulin 0.1 units/kg given hourly may be used as a bridge to continuous IV infusion in situations where IV access or appropriate monitoring cannot be optimally achieved (eg, certain transport situations).
Do not give antiemetics as these can mask the neurologic status; vomiting and abdominal pain caused by DKA are treated by insulin and fluid administration; if vomiting and abdominal pain continue, consider confounding illness.
If serum glucose is <250 mg/dL in the presence of ketoacidosis, increase glucose delivery so that insulin can be continued to correct ketoacidosis.
Hyperosmolar hyperglycemic syndrome presents with marked hyperglycemia (usually >800 mg/dL), minimal or mild ketosis(less severe than DKA), and dehydration (typically more severe than DKA). The principles of management are similar as for DKA. Some patients have underlying diabetes (often type 2), but not all patients are diabetic. However, most patients will require insulin therapy during the acute illness.