ENDOCRINE SYSTEM
B. Diabetic Ketoacidosis
1. Definition. Diabetic ketoacidosis (DKA) is an emer
gency condition that, if left untreated, can have lifethreatening consequences. DKA occurs as a
DIABETES MELLITUS ■ 509
result of relative or absolute insulin deficiency and is diagnosed when blood glucose is greater than 200 mg/dL, venous pH is less than 7.3, or bicarbonate is less than 15 mmol/L, and ketonemia/ketonuria are present (von Saint Andrevon Armin et al., 2013).
DKA remains the leading cause of morbidity and mortality in children with type 1 diabetes and is the leading cause of hospital admissions. DKA events most often occur when there is nonadherence to insulin regimen or intercurrent illness, stress, or sur
gery (Brashers et al., 2014).
2. Pathophysiology
a. When the balance of insulin and counter
regulatory hormones are disrupted in the body, DKA occurs. In the absence of insu
lin, hyperglycemia occurs as tissue uptake of glucose is inhibited and glucose produc
tion by the liver is increased. Glycogenolysis (breakdown of glycogen), gluconeogenesis (synthesis of glucose from noncarbohydrate sources), proteolysis, and lipolysis contribute to the metabolic changes in DKA (Brashers et al., 2014; Sperling et al., 2014). Insulin defi
ciency leads to lipolysis and overproduction of ketone bodies such as betahydroxybutyrate and acetoacetates. Bicarbonate buffering does not happen and there is a resultant metabolic acidosis. Counterregulatory hormones (glu
cagon, cortisol, catecholamines, and GH) are released in times of stress, and they also contrib
ute to hyperglycemia. Glycosuria occurs with osmotic diuresis once the renal threshold for glucose is exceeded (usually around 180 mg/
dL; von Saint Andrevon Arnim et al., 2013).
Passive electrolyte losses (magnesium, phos
phorus, sodium) occur secondary to diuresis, but most concerning is the total body loss of potassium, which can reach up to 3 to 5 mEq/
kg (Brashers et al., 2014). Hyperosmolality results secondary to hyperglycemia and free water loss with diuresis. Dehydration occurs secondary to osmotic diuresis and vomiting (Brashers et al., 2014; Sperling et al., 2014).
There is a total body fluid shift from the intra
cellular space to the extracellular space to help compensate for the dehydration. Nausea and vomiting occur secondary to ketoacidosis and this worsens the electrolyte imbalances. Serum osmolarity can become very high, putting patients at risk for the development of CE and stroke.
3. Etiology is related to inadequate endogenous insulin secretion or inadvertent omission of insulin.
Initial presentation is often precipitated by nonad
herence to insulin, stress, emotional or psychologi
cal problems, infection, surgery, or trauma (Sperling et al., 2014). Often, adolescents do not comply with their treatment plan and are repeatedly admitted in DKA due to familial or personal stress and inability to cope with their chronic illness.
4. Risk factors include a previous history of diabe
tes with poor control or compliance, young or ado
lescent age, ethnic minority, lack of health coverage, delayed treatment, lower body mass index, and infection (Brashers et al., 2014).
5. Signs and symptoms (Table 6.3) include polyuria, polydipsia, polyphagia, and hyper
glycemia, generally with a serum glucose level greater than 200 mg/dL, and presence of ketones in urine. Other symptoms include weight loss, weakness and lethargy, nausea and vomit
ing, abdominal pain, dehydration, tachycardia, hypovolemia, poor perfusion, shock, glycosuria, ketonuria, rapid deep respirations (Kussmaul’s respirations), and stupor that can lead to coma.
However, DKA can occur with normoglycemia or hypoglycemia if severe vomiting is present.
Also, indicative of DKA is the presence of aci
dosis demonstrated by a pH less than 7.30, and serum bicarbonate less than 15 mmol/L (Klein, Sathasivam, Novoa, & Rapaport, 2011). Serum sodium levels may be high, low, or normal with total body sodium depletion secondary to urinary losses or dilutional hyponatremia (fluid shifts from intracellular space to extracellular space) secondary to hyperglycemia. Serum potassium may be high, low, or normal with total body potassium depletion. In acidosis with increased osmolality, potassium shifts from intracellular space to extr cellular space creating more avail
able potassium for use by the body. Insulin and acidosis correction shifts potassium back into the intracellular space and levels may fall. Elevated serum triglycerides are present. The white blood cell (WBC) count is elevated with a shift to the left (Sperling et al., 2014).
6. Classification of the presentation of DKA is based on the degree of acidosis (Klein et al., 2011)
a. Mild. Venous pH less than 7.30 and bicar
bonate less than 15 mmol/L
b. Moderate. Venous pH less than 7.20 and bicarbonate less than 10 mmol/L
c. Severe. pH less than 7.10 and bicarbonate less than 5 mmol/L
7. Interpretation of Diagnostic Studies
a. Hyperglycemia is due to insulin deficiency, decreased glucose uptake, gluconeogenesis, and an increase in the counterregulatory hormones.
b. Glycosuria occurs secondary to hyper
glycemia.
c. pH level less than 7.30 and bicarbonate less than 15 mmol/L are due to acetoacetic acid and betahydroxybutyrate dehydrogenase (ketones) production. Acidosis could also be due to poor perfusion and accumulation of lactic acid (lactic acidosis).
d. Ketonuria is the presence of ketones in the urine. Ketonemia is the presence of high serum ketone levels.
e. Serum osmolality is greater than 300 mOsm/
kg because of hyperglycemia and osmotic diure
sis, which leads to dehydration.
f. Electrolyte disturbances are related to electro
lyte loss with osmotic diuresis, shifts between extracellular and intracellular spaces, and met
abolic acidosis.
g. Islet cell antibodies and insulin autoantibod- ies are not diagnostic for DKA but may offer a screening tool for detecting patients with autoimmunity.
h. A glucose tolerance test has no role in the diag
nosis of DKA but can be used to diagnose glu
cose intolerance in a child with glucosuria and normal or mildly elevated serum glucose.
i. Glycosylated hemoglobin (HbA1) reflects blood glucose control over the last 120 days, or the life of red blood cells. Elevated levels are correlated with high serum glucose concen
trations and a level of greater than or equal to 6.5% is diagnostic for diabetes (Babler et al., 2013).
TABLE 6.3 Signs and Symptoms of Diabetic Ketoacidosis
Symptoms Underlying Mechanisms
Hyperglycemia Relative or absolute insulin deficiency
Metabolic acidosis (gap acidosis) Build up of B-hydroxybutyrate, acetoacetic acids, and acetone in the serum from incomplete oxidization of fatty acids
Dehydration, shock Osmotic diuresis secondary to hyperglycemia, vomiting
Kussmaul breathing Deep, rapid breathing; a compensatory mechanism to blow off carbon dioxide and normalize pH
Cardiac arrhythmia Hypokalemia, hyperkalemia
Sodium imbalance Total body sodium depleted secondary to sodium loss from osmotic diuresis Dilutional hyponatremia secondary to hyperglycemia, fluid drawn into extracellular
space, decreases sodium content
Potassium imbalance Acidosis causes potassium to shift from the intracellular space into extracellular space
Insulin and acidosis correction returns potassium to intracellular space Total body potassium depletion secondary to losses from osmotic diuresis Mental status changes Cerebral edema, level of acidosis, degree of dehydration
Hyperosmolality Hyperglycemia, osmotic diuresis
Ketonuria Lipolysis causes elevated ketone levels to rise above the renal threshold and spill into the urine
Glucosuria Glucose spills into the urine when blood glucose exceeds renal threshold
DIABETES MELLITUS ■ 511
j. CT scan is used to diagnose CE, an uncom
mon but ominous manifestation of DKA that clinically occurs in only about 1% of all cases (von Saint Andrevon Arnim et al., 2013).
8. Diagnoses
a. Differential diagnoses at presentation include adrenocortical dysfunction, highdose steroid usage, uremia or lactic acidosis, gastroenteritis with metabolic acidosis, pancreatitis, cystic fibro
sis, exogenous catecholamines, stress response (CIRCI), DI, encephalitis, alcoholic ketoacidosis, starvation, hyperosmolar syndrome, and inborn errors of metabolism.
b. Collaborative diagnoses and comorbidities i. Fluidvolume deficit related to osmotic diuresis secondary to hyperglycemia
ii. Low cardiac output related to fluid
volume deficit
iii. Potential for CE related to treatment and hyperosmolar state
iv. Potential for arrhythmias related to electrolyte imbalances
v. Acid–base imbalance related to ketoacidosis
vi. Electrolyte imbalances related to both osmotic diuresis and treatment
vii. Potential for hypoglycemia related to treatment
viii. Potential for selfcare deficits related to lifelong treatment and monitoring with possible noncompliance
ix. Alteration in body image related to chronic illness and future complications
x. Alteration in healing related to chronic hyperglycemia
xi. Potential for infection related to inflammatory response from chronic hyperglycemia
xii. Knowledge deficit regarding home management
xiii. Potential for depression related to chronic disease state
9. Treatment Goals
a. Correct fluid and electrolyte imbalances slowly
b. Correct metabolic acidosis
c. Infuse insulin to treat hyperglycemia and ketosis
d. Prevent neurologic complications
e. Maintain good glycemic control (long term) f. Treat underlying disorders
g. Educate and prevent recurrence 10. Management
a. Fluid. Cautious rehydration in DKA is imperative to prevent CE. For accurate rehy
dration, knowledge of preillness weight must be known. To calculate the percentage of dehydration present, subtract illness weight from preillness weight and divide this num
ber by preillness weight then multiply by 100% (Taketomo, Hodding, & Kraus, 2015). In most cases, the preillness weight is unknown, and fluid management is based upon estima
tion of mild, moderate, or severe dehydration.
Hyperosmolality is present and in order to prevent CE, replacement should be done over 48 hours. Moderate DKA has an estimated dehy
dration of 7% to 10% and severe DKA has more than 10% dehydration. In most cases, dehydra
tion is estimated to be 10% in all patients with DKA (von Saint Andrevon Arnim et al., 2013).
When shock is present, it is necessary to admin
ister normal saline (NS) 10 mL/kg for volume expansion. Frequent reassessment is necessary and additional boluses may be required if poor perfusion persists. NS is an isotonic fluid but because children in DKA are hyperosmolar, NS is a hypotonic fluid.
b. Electrolytes. Potassium and phosphate replacement is imperative in DKA. If hyper
kalemia is present initially, an ECG should be performed and it is necessary to wait until urine output is achieved before potassium replace
ment is initiated. If a normal potassium level is present, initiate replacement with a combi
nation of potassium chloride and potassium phosphate as insulin will drive potassium and phosphate back into the cell, thus decreasing serum levels of potassium and phosphorous (Sperling et al., 2014). Attention should be paid to calcium levels during treatment as rising phosphorus levels will cause hypocalcemia.
A hyperchloremic metabolic acidosis can occur during treatment with high chloridecontain
ing fluids, and can be offset with the addition of potassium phosphate (K Phos) to fluid bags.
Sodium bicarbonate administration is not rou
tinely recommended and it should never be administered as a bolus as it can precipitate car
diac arrhythmias (Sperling et al., 2014; von Saint Andrevon Arnim et al., 2013).
c. Insulin. Rehydration will cause serum glucose to decrease and improve perfusion and acidosis, but an insulin infusion will always be required in DKA. Insulin is needed to normal
ize serum glucose levels, to suppress ketogen
esis and lipolysis, and to resolve ketoacidosis (Sperling et al., 2014). Insulin infusion should begin within an hour of initial fluid replacement at 0.1 units per kilogram of body weight per hour, and should continue until there is a resolu
tion of DKA or a closure in the anion gap. Blood glucose should drop at a rate of 80 to 100 mg/
dL per hour, and will occur faster than the res
olution of acidosis (Sperling et al., 2014). When the blood glucose falls to near 300 mg/dL with continued acidosis, the addition of 5% or 10%
dextrose fluid should be administered via IV and titrated based on hourly glucose parame
ters to keep blood glucose near 200 mg/dL (von Saint vonAndre Ornim et al., 2013). Insulin dosing may be decreased to 0.05 units/kg/hr if the blood glucose continues to fall despite the addition of 10% dextrose to the IV fluids and aci
dosis persists. IV insulin should continue until the pH is greater than 7.3, bicarbonate is greater than 15 mmol/L, and the child is tolerating oral intake (von Saint vonAndre Arnim et al., 2013). When transitioning to subcutaneous insu
lin, give subcutaneous insulin 30 to 60 minutes before discontinuing the continuous infusion.
d. The goal of insulin replacement therapy is to match the normal pattern of secretion by the body as closely as possible through basal dose therapy and to avoid wide shifts in glucose. It is done with a basal/bolus insulin regimen either through insulin pump or through multiple daily subcutaneous injections. There are more than 10 varieties of insulin formularies, which are most often categorized on the duration of action.
There are rapidacting insulins that have high and sharp peaks of effects with a short dura
tion of therapy. The intermediateacting insulin, neutral protamine Hagedorn (NPH), which has delayed peaks of action, was previously used in new onset type 1 diabetes to help cover hyper
glycemia (Sperling et al., 2014). Longacting insulin medications were developed to meet the demands for basal insulin needs, and they help patients and families better manage their diabetes (Sperling et al., 2014). During the initial diagno
sis time of type 1 diabetes, there is a honeymoon period that can last several months during which there is residual betacell function with minimal insulin requirements to maintain euglycemia and prevent ketoacidosis (Sperling et al., 2014).
e. Monitoring. Vital signs, blood pressure, intake and output, cardiovascular assessment with con
tinuous ECG monitoring, and neurologic checks are done hourly. Hourly glucometer determi
nation of blood glucose is done at the bedside.
Initial laboratory tests should include complete blood count (CBC), chemistry panel, urinalysis, betahydroxybutyrate, hemoglobin A1C, and a blood gas. Electrolytes, betahydroxybutyrate, and pH are monitored every 2 to 4 hours until stable, then every 4 to 6 hours until acidosis is resolved. A gradual rise in serum sodium as the glucose levels fall helps prevent rapid changes in serum osmolality and may prevent alteration in mental state. Intake and output, weights, and urine ketones are monitored daily.
11. Complications a. Acute
i. Hypoglycemia can occur during the treatment of DKA and should be treated with dextrosecontaining fluids as described earlier. Persistent acidosis can be related to inadequate fluid replacement, inadequate insulin dosing, insulin resistance, ineffec
tive method of delivery, or a malfunctioning insulin delivery system.
ii. Hypokalemia can occur because of inadequate potassium replacement and rapid fluid shifts.
iii. CE occurs in about 1% of episodes of DKA, but continues to have significant mortality and morbidity. It can be appar
ent on presentation, 4 to 12 hours after treatment has been initiated, or even up to 22 to 48 hours into treatment (von Saint Andrevon Arnim et al., 2013). Mounting evidence supports that many patients in DKA have subclinical CE visible only on CT scans. Symptoms include severe head
ache, altered mental status, hyperten
sion, bradycardia, and vomiting (Sperling et al., 2014). Risk factors for CE (Table 6.4) include first presentation, high serum BUN and CO2 (reflective of the degree of dehydration and acidosis), administration of insulin bolus doses, bicarbonate treat
ment, rapid glucose correction, aggressive fluid administration, and younger age at diagnosis. Treatment at recognition of CE should begin with administration of hyper
tonic saline or mannitol, elevate the head of the bed, and performing an emergent CT scan of the brain to evaluate CE (Klein et al., 2011). Fluid administration should
HYPERGLYCEMIC HYPEROSMOLAR SYNDROME ■ 513
be lowered and support of respiratory and neurologic status may become necessary with intubation for Glasgow Coma Scale less than 9.
iv. Fluid overload and congestive heart failure can occur as a result of aggressive fluid management during treatment.
v. Aspiration is possible if the level of con
sciousness is depressed.
b. Chronic
i. Chronic complications of repeated episodes of DKA can have lifealtering ramifications for children with diabetes.
Hyperglycemia with poor metabolic control can lead to a chronic state of proinflamma
tion, which leads to further insulin resis
tance. This state leads to harmful release of cytokines and impairment of the coagulation pathways (V. Srinivasan & Agus, 2014). The Diabetes Control and Complications Trial study revealed that intense glycemic control (which led to nearly normal glucose levels) significantly lowered the risk of serious long
term consequences of diabetes and had low risks of hypoglycemia (Sperling et al., 2014).
Other significant chronic problems include repeat episodes of hypoglycemia and hyper
glycemia, poor growth, hypertrophy and lipoatrophy of injection sites, limited joint mobility, candidiasis (opportunistic infec
tions), retinopathy, nephropathy, neuropa
thy (rare in childhood), and macrovascular disease (Sperling et al., 2014).
HYPERGLYCEMIC HYPEROSMOLAR SYNDROME
A. Pathophysiology
The incidence of hyperglycemic hyperosmolar syn
drome (HHS) continues to be infrequent in children, but the numbers are increasing. These escalating numbers are associated with a high mortality rate and delayed diagnosis. In HHS, insulin secretion is adequate enough to prevent lipolysis, but not substantial enough to pre
vent hyperglycemia, thereby producing a state of relative insulin deficiency. The stress response, which includes the release of glucagon, catecholamines, cortisol, and GH, worsen hyperglycemia by increasing gluconeogen
esis and glyconeolysis (Zeitler, Haqq, Rosenbloom, &
Glaser, 2011). Marked hyperosmolality with significant dehydration and electrolyte losses subsequently occurs.
The degree of hyperglycemia, hyperosmolality, and dehydration is much greater in HHS than in DKA and can cause significant sequelae. The absence of ketoac
idosis and typical associated physical symptoms seen in DKA may reflect the delay in treatment. This delay can lead to profound shock, kidney dysfunction, altered mental status or coma, rhabdomyolysis, hyperthermia, and ventricular arrhythmias (Price, Losek, & Jackson, 2016; Zeitler et al., 2011).