Adrenal Insufficiency
The adrenal cortex is divided into three zones: the outermost glomerulosa, which produces aldosterone (mineralocorticoid), the middle fasciculata, which produces cortisol (glucocorticoid), and the innermost reticularis, which produces dehydroepiandrosterone (DHEA) and androstenedione (adrenal androgens). Cortisol production is regulated primarily by pituitary adrenocorticotropic hormone (ACTH) secretion, which in turn is regulated by the hypothalamic release of corticotrophin releasing hormone (CRH).
Lesions of the hypothalamus, pituitary, or adrenal cortex may cause adrenal insufficiency. In general, primary adrenal insufficiency (originating from the adrenal gland) results in inadequate production of both aldosterone and cortisol. Secondary adrenal insufficiency (originating from the pituitary) results in inadequate production of cortisol. Congenital adrenal hyperplasia (CAH), an inherited defect in steroid biosynthesis (most often 21-hydroxylase deficiency), is a relatively common cause. Other etiologies include autoimmune adrenalitis, adrenal hemorrhage in meningococcemia, trauma, HIV infection, tumor, infiltrative disease, tuberculosis, and bilateral adrenalectomy.
Central (hypothalamic or pituitary) adrenal insufficiency may be idiopathic, or secondary to CNS tumors, congenital abnormalities, or trauma. Exogenous steroid therapy is a frequent cause of adrenal insufficiency. Glucocorticoid treatment for more than 7–10 days places the patient at risk.
Adrenal insufficiency can result in a life-threatening emergency caused by relative or absolute deficiencies of cortisol and aldosterone. Crisis occurs when the adrenal gland fails to adequately respond to stress with an up to tenfold increase in cortisol secretion. This rise in cortisol secretion is dependent on increased ACTH release. Crisis may be precipitated by bacterial or viral infections, or dental or surgical procedures. Prompt recognition of the presenting symptoms and immediate treatment is imperative.
Clinical Presentation
The initial complaints are often nonspecific. The presentation may be gradual, with subtle complaints such as weakness, fatigue, malaise, anorexia, poor growth, and weight loss. With aldosterone deficiency (as occurs in primary adrenal insufficiency), salt craving may be reported and the blood pressure may be normal or low. Alternatively, there may be an acute presentation, with fever, weakness, lethargy, abdominal pain, nausea, vomiting (possibly bilious), guarding and rebound tenderness, dehydration, hypotension, and/or shock. Seizures, secondary to hypoglycemia or hyponatremia, may also occur. The presentation may also be fulminant, and sudden death can occur.
With primary adrenal insufficiency a subtle physical examination finding is skin hyperpigmentation, most often found on the lips and buccal mucosa, nipples, groin, palmar or axillary creases, and areas of old scars or friction (knees, elbows, knuckles). Skin hyperpigmentation is a sign of increased ACTH secretion, so it does not occur with secondary or tertiary adrenal insufficiency (due to pituitary or hypothalamic disease). Other possible signs include petechiae and purpura (overwhelming sepsis, usually meningococcemia), hypoglycemic seizures (glucocorticoid insufficiency), midline craniofacial malformations (e.g., septo-optic dysplasia, cleft lip/palate, holoprosencephaly), and micropenis (hypopituitarism). Central adrenal insufficiency is often associated with other hypothalamic/pituitary hormone deficiencies, which may manifest as growth failure, delayed pubertal progression, micropenis (secondary to growth hormone deficiency), and, in the case of CNS lesions, diabetes insipidus.
Primary adrenal insufficiency is usually associated with deficient aldosterone production with resultant significant losses of sodium and water and retention of potassium. These patients present with more severe hyponatremia, hyperkalemia, and volume depletion. As aldosterone production is primarily regulated by the renin-angiotensin enzyme system; central secondary or tertiary adrenal insufficiency are not associated with aldosterone deficiency. Autoimmune Addison’s disease (a type of primary adrenal insufficiency) may also be associated with mucocutaneous candidiasis, hypothyroidism, hypokalemia, hepatitis, vitiligo, alopecia, and pernicious anemia.
The use of steroids for more than 7–10 days can cause suppression of the patient’s endogenous hypothalamic–pituitary–adrenal axis. The abrupt withdrawal of steroids can then result in clinical adrenal insufficiency or acute adrenal crisis, as the patient is unable to mount an ACTH response or respond to ACTH. Acute insufficiency can also occur when there is a physiologic stress (surgery, infection, trauma) without an appropriate increase in the exogenous dose of glucocorticoids.
A female infant with CAH is usually diagnosed soon after birth because of ambiguous genitalia, ranging from mild clitoromegaly to a completely penile urethra with labioscrotal folds. A male infant with CAH typically has normal external genitalia and is therefore not often diagnosed in the immediate newborn period, unless a positive screen is reported. The patient may present at 1–3 weeks of life (or later infancy) with fatigue, poor feeding, and vomiting, resembling the clinical picture of sepsis. Alternatively, there may be a fulminant presentation with dehydration, shock, or sudden death. There may be a family history of consanguinity, CAH, or neonatal deaths. On physical examination, hyperpigmentation (as described above) may be noted, while a completely virilized girl will not have testes detected.
Diagnosis
The key to diagnosing acute adrenal crisis is to maintain a high degree of suspicion, especially in a previously well infant who has mild to moderate illness but deteriorates quickly. The prominent gastrointestinal symptoms of adrenal crisis can resemble gastroenteritis (diarrhea is frequent), an acute abdomen (involuntary guarding and rebound tenderness), and intestinal obstruction (bilious vomiting). An elevated 17-OH progesterone confirms the diagnosis.
If impending or acute adrenal crisis is suspected, do not delay treatment while waiting for confirmatory laboratory tests. Initiate diagnostic testing and treatment simultaneously. Obtain blood for CBC, electrolytes, glucose, and serum cortisol, plasma renin activity, ACTH, and aldosterone while establishing IV access.
Acute primary adrenal insufficiency may cause hyponatremia, hypochloremia, and hyperkalemia with peaked T-waves on ECG. Hypoglycemia and neutropenia (WBC <5000/mm3) can occur, although these can also be signs of sepsis. In addition, there is increased plasma renin, increased urinary excretion of sodium if the patient is aldosterone-deficient (i.e., salt-wasters), and decreased urinary excretion of potassium.
Normally, patients in shock have an elevated serum cortisol level (> 15 mcg/dL), but with adrenal insufficiency, the serum cortisol is inappropriately low.
ED Management
Once the diagnosis is suspected, therapy includes immediate, aggressive fluid management and steroid replacement. Obtain a fingerstick glucose measurement and assess possible hyperkalemia (aldosterone deficiency or resistance) by looking for peaked T-waves on EKG. Infants with CAH may tolerate hyperkalemia better than older children. If needed, definitive assessment of adrenal function can be performed after the acute emergency has passed.
Acute Crisis
Glucocorticoid Stress Dose
Give a stat dose of hydrocortisone (Solu-Cortef), IV push/IM (0–3 years of age: 25 mg; ≥3–12 years of age: 50 mg; ≥12 years of age: 100 mg), followed by the same dose as a 24-hour IV infusion or div q 4–6h. The response is usually rapid.
Fluid Management
Clinical assessment tends to underestimate the severity of the hypovolemia. Consider the patient to be at least 10% dehydrated. Start an IV and give 20 mL/kg of normal saline over 30 minutes. Repeat the boluses until the patient becomes normotensive. Once the blood pressure is normal, continue with D5 NS for patients with salt-losing adrenal insufficiency. Change non-salt-losers to D5 ½ NS, if the electrolytes are normal.
Total fluid requirements are in the range of 1.5–2 times maintenance; reassess as therapy continues. Add potassium (10–20 mEq/L) once the patient voids, as the administration of cortisol will rapidly induce kaliuresis and a fall in the serum potassium. If the patient is hypoglycemic (blood glucose <70 mg/dL), give 2–4 mL/kg of D10 (maximum dose 25 g), infused slowly at a rate of 2–3 mL/min, and recheck the glucose in 15 minutes. Repeat the D10 if the hypoglycemia persists (blood glucose <70 mg/dL).
Shock
If shock persists despite the crystalloid boluses, give a plasma expander, such as plasmanate (20–40 mL/kg) or a vasopressor, such as dopamine (see Shock, pp. 28–36). Vasopressors may be ineffective unless preceded by adequate cortisol replacement.
Mineralocorticoid Replacement
Mineralocorticoid replacement is not necessary during the acute ED treatment because high-dose glucocorticoids interact with mineralocorticoid receptors and normal saline is given (steps 1 and 2). Once the patient is stable and can take oral fluids, give 9α-fluorocortisol (Florinef) 0.1–0.3 mg PO to salt-wasters. Supplemental oral sodium may also be necessary.
Underlying Pathology
Identify and treat any underlying cause of the stress. Infections are the most common precipitating factor.
Complications
ICU monitoring may be necessary, especially if the patient remains comatose or hypotensive, or the underlying pathology takes a fulminant course (sepsis). Complications of excessive fluid, salt, or steroid replacement include hypernatremia, hypokalemia, pulmonary edema, congestive heart failure, and hypervolemia.
Stress Dosing in Adrenal Insufficiency
Patient Taking Maintenance Corticosteroids (e.g., Patient With CAH or Addison’s Disease)
For a minor illness, such as low-grade fever (<38.8 °C; 102 °F), give 25 mg/m2 div q 6 h of hydrocortisone. A stress dose is not necessary for afebrile patients. For a moderate illness, such as fever ≥102 °F (>38.8 °C), vomiting, anesthesia, or a bacterial infection, give 50 mg/m2 div q 6h. If the patient cannot tolerate oral medications, give the same dose IM or IV. Admission will be necessary if the patient cannot subsequently tolerate oral steroids.
Patient Taking Pharmacologic Doses of Steroids (for Asthma, Nephrotic Syndrome, ITP, Leukemia, Collagen Vascular Diseases, etc.)
Most pharmacologic doses are greater than physiologic doses. However, if the current steroid dose is less than the recommended stress dose (see below), a stress dose is still necessary. If the stress is a serious infection, with an etiology that may be adversely affected by high-dose steroids (such as fungal infection in a patient with cystic fibrosis), consult with pediatric infectious disease and endocrine specialists. If a patient receiving a tapering dose of corticosteroids develops symptoms of adrenal insufficiency, increase the dose to the most recent dose at which he or she was asymptomatic, then initiate a more gradual taper after consulting with a pediatric endocrinologist.
Patient Who Has Recently Completed a Steroid Course
A history of completing a 7–10-day, or longer, course of corticosteroids in the previous six months places a patient at risk for developing adrenal insufficiency. If the patient is symptomatic for an acute adrenal crisis, treat as above. If the adrenal status is uncertain, treat for presumed adrenal insufficiency, as noted above.
For all of the above scenarios, continue the oral stress dose, 25–50 mg/m2 of hydrocortisone for the duration of the stress, and then taper quickly, over 4–7 days, to the previous or maintenance dose. If the patient has symptoms of adrenal insufficiency during a taper, the tapering schedule may be too rapid. Increase the dose to the most recent dose at which the patient was asymptomatic. Then, initiate a more gradual taper after consulting with a pediatric endocrinologist.
Advise the family of a steroid-dependent child to obtain and wear a MedicAlert bracelet or carry a card that indicates the presence of adrenal insufficiency, the current steroid dose (as well as the indication and the steroid doses that should be used for stress), and the prescribing physician’s name and contact numbers. In addition, instruct the family members and/or caretakers to administer emergency intramuscular hydrocortisone (infant 25 mg, child 50 mg, adult 100 mg) in the event the patient has persistent vomiting or altered mental status. Remind the caretakers to check expiration dates, new prescriptions, and to have the hydrocortisone easily available in the event of an emergency.
Indications for Admission
Vomiting, inadequate oral intake, or postural vital sign changes in a patient known to be at risk for adrenal insufficiency
Medication compliance at home is uncertain
Electrolyte abnormalities
Bibliography
Diabetes Insipidus
Diabetes insipidus (DI) is characterized by an inability to concentrate urine in the presence of hyperosmolality/hypernatremia. DI can be caused by either vasopressin (ADH) deficiency (central DI) or resistance of the ADH receptor (nephrogenic DI). ADH controls water homeostasis by activating reabsorption of water from urine.
A variety of acquired hypothalamic and pituitary lesions are associated with central DI, including tumors (craniopharyngioma, optic glioma, germinoma), infiltrative disorders (Langerhans cell histiocytosis, sarcoidosis, granulomatous disease), operative trauma to the posterior pituitary gland, autoimmune lymphocytic hypophysitis, drugs (ethanol, phenytoin, opioids, alpha-adrenergics), infections (meningitis/encephalitis), trauma (basilar skull fractures), and vascular lesions (aneurysm). The etiology of central DI may also be genetic, congenital, or idiopathic.
Nephrogenic DI is caused by renal unresponsiveness to ADH. The defect may be congenital or secondary to hypercalcemia, hypokalemia, drugs (lithium, amphotericin, cisplatin, rifampin, methicillin), or chronic renal disease (ureteral obstruction, polycystic kidney disease, renal medullary cystic disease, sickle cell disease).
Normal plasma osmolality ranges between 275 and 295 mOsm/kg. Normally, at a serum osmolality of <280 mOsm/kg, the plasma vasopressin level is ≤1 pg/mL. Above 280 mOsm/kg, the normal threshold for vasopressin release, the plasma vasopressin level rises in proportion to the plasma osmolality, up to a maximum concentration of 20 pg/mL (at a blood osmolality of 320 mOsm/kg). Peak antidiuretic effect is achieved at a vasopressin concentration of 5 pg/mL.
Vasopressin secretion is also induced by hypovolemia, but in contrast to the increases in vasopressin secretion with minor changes in plasma osmolality, no change in vasopressin secretion occurs until the blood volume decreases by approximately 8%. Vasopressin secretion is inhibited by glucocorticoids, so that enhanced vasopressin activity occurs in primary or secondary glucocorticoid insufficiency and contributes to the hyponatremia in these conditions.
Clinical Presentation
Diabetes insipidus causes renal loss of free water, which leads to excessive urine output and thirst. Water loss is compensated for by increasing water intake, so that dehydration is unusual in an awake patient who has free access to water and whose sensation of thirst is intact. Infants, children with developmental delay or altered mental status, and patients whose thirst centers are affected by the primary process (hydrocephalus, postconcussive syndrome) are at an increased risk for hypernatremic dehydration.
An infant with DI is usually irritable but eager to suck, often exhibiting a distinct preference for water over milk and presenting with failure to thrive. An older child commonly presents with polyuria and polydipsia. Nocturia, secondary enuresis, constipation, and a preference for ice water are common. Recurrent episodes of dehydration and hypernatremia can result in poor growth and mental retardation, while polyuria and large volumes of urine can cause dilation of the urinary tract, impaired bladder function, and chronic renal failure.
Central nervous system symptoms, such as irritability, altered consciousness, increased muscle tone, convulsions, and coma can occur secondary to hypernatremia. These findings correlate with the degree and rapidity of the rise in serum sodium.
Diagnosis
The cardinal diagnostic features of diabetes insipidus are:
a high rate of dilute urine flow (urine output >4 mL/kg/h) over at least two hours;
clinical signs of dehydration (weight loss, hypotension), which may not be as apparent because of the hypernatremia;
mild to marked degree of serum hypernatremia (>145 mEq/L);
hyperosmolality (>300 mOsm/kg);
low urine osmolality (<300 mOsm/kg) and low specific gravity (<1.010), despite a normal or elevated serum osmolality.
If there is severe dehydration or a low glomerular filtration rate, urine output decreases and urine osmolality increases above the serum; this may temporarily obscure the diagnosis.
Other causes of polyuria include psychogenic polydipsia (nocturia unusual), organic polydipsia (hypothalamic lesion), osmotic diuresis (diabetes, IV contrast administration, chronic renal insufficiency), hyperglycemia associated with diabetes mellitus, diuretic use, and postoperative diuresis, as well as ADH unresponsiveness due to hypercalcemia or hypokalemia. With a urinary tract infection (pp. 692–696), there will be symptoms such as urgency, frequency, and dysuria. Diabetes insipidus may be distinguished from these other diagnoses by the history, serum and urine electrolytes and osmolality, BUN, and creatinine.
A large urinary volume can lead to bladder distention, which can then mimic obstructive uropathy.
ED Management
If DI is suspected, obtain a basic metabolic panel, serum osmolality, urinalysis and urine culture, urine electrolytes, and urine osmolality. A serum osmolality >300 mOsm/kg with a urine osmolality <300 mOsm/kg are highly suggestive of the diagnosis of DI. Perform a complete neurologic examination, with visual field assessment, if possible. Admit the patient and consult with a pediatric endocrinologist who will initiate vasopressin treatment if the serum sodium is >145 mmol/L and the osmolality is >295 mOsm/kg.
Arrange for an MRI of the pituitary gland with and without gadolinium. Normally, the posterior pituitary is seen as an area of enhanced brightness on T1-weighted images following the administration of gadolinium. This “bright spot” is absent in both central and nephrogenic diabetes insipidus, due to vasopressin deficiency in the former and enhanced vasopressin release in the latter. In primary/psychogenic polydipsia, the posterior bright spot is normal.
Fluid Therapy
DI can be treated with meticulous fluid management, initiated immediately in the ED, once the diagnosis is established. Use a flow sheet to document fluid intake and output, replacement of urine output and insensible losses, vital signs, urine specific gravity, and serum electrolytes. The components of fluid management include:
insensible fluid loss replacement (400 – 600 mL/m2/day) with D5 ½ NS;
urine output replacement, mL per mL, with D5W or D2.5 ¼ NS IV or free water orally;
correction fluid to lower the serum sodium to the normal range; Use the following equation (over 8–24 h):
Treatment of DI in Infants
Since the primary source of nutrition in infants is in liquid form, there is a risk of hyponatremia in infants with DI treated with vasopressin or DDAVP. Instead, use a low-solute formula (PM 60/40) or breast milk to reduce urine output by reducing renal solute load.
Treatment of Nephrogenic DI
The goals of therapy are to maintain normal growth and development by providing adequate calories, to decrease urine volume, and to avoid severe dehydration and hyponatremia. Medications used to decrease the polyuria include:
Thiazide Diuretics
Thiazides promote sodium excretion by interfering with sodium reabsorption in the distal tubule of the nephron and by altering inner medullary osmolality. A thiazide plus an amiloride diuretic is the most commonly used combination for the treatment of congenital X-linked nephrogenic diabetes insipidus. Give hydrochlorothiazide (2 mg/kg/day divided bid; 100 mg/day maximum for children, 200 mg/day maximum for adults).
Amiloride Diuretics
Amiloride counteracts the thiazide-induced hypokalemia. The dose is 0.625 mg/kg/day in patients weighing 6–20 kg; in adolescents, give 5–20 mg/day, up to a maximum of 40 mg/24 hours.
Indications for Admission
Hypernatremia
Inability to drink oral fluids or to keep up with losses
Titration of dosing
Bibliography
Diabetic Ketoacidosis
Diabetic ketoacidosis (DKA) is defined as hyperglycemia (glucose >200 mg/dL), the presence of ketones in the urine or blood, and metabolic acidosis (pH <7.3 or serum bicarbonate <15 mEq/L). DKA may be the initial presentation of new-onset type 1 diabetes mellitus (DM) or a complication in a previously diagnosed patient. DKA occurs less frequently in patients with type 2 DM. Infection is the most common precipitating factor, but trauma, pregnancy, emotional stress, and noncompliance are other causes. An absolute or relative insulin deficiency is present, along with increased levels of counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines), leading to deranged metabolism, hyperglycemia, osmotic diuresis, hypertonic dehydration, and finally, ketoacidosis. In ketoacidosis, the acidosis is secondary to ketonemia with β-hydroxybutyrate and its redox partner, acetoacetate.
Clinical Presentation
The patient usually presents with abdominal pain, nausea, vomiting, dehydration, fatigue, and hyperpnea. Isolated vomiting can also be a presentation of DKA. The history often reveals polydypsia, polyuria, nocturia, enuresis, and, with new-onset diabetes, recent weight loss or lack of weight gain in a growing child. Characteristic Kussmaul breathing (deep sighing breathing) can be present, but the respirations may be depressed if the patient is severely acidotic (pH ≤6.9). Neurologic findings range from drowsiness to coma and are related to the level of hyperosmolality and the degree of volume depletion and acidosis.
DKA is categorized as mild (pH 7.2–7.3), moderate (pH 7.1–7.2), or severe (pH <7.1)
Diagnosis
In the known diabetic, consider DKA when the patient complains of abdominal pain, vomiting, or malaise. The diagnosis may be more difficult to make in a patient presenting for the first time (Table 7.1). In addition to acidosis and ketonemia, significant hyperglycemia (>500 mg/dL) is common, although DKA can occur with a glucose of 200–300 mg/dL.
| Coma | Ketonuria (without hyperglycemia) |
| CNS trauma, infection, bleeding | Anorexia of any etiology |
| Hypoglycemia | Fasting states |
| Lactic acidosis | Gastroenteritis with vomiting |
| Nonketotic hyperosmolar coma | Salicylate poisoning |
| Sedative-hypnotic or narcotic overdose | |
| Hyperglycemia | Metabolic acidosis |
| Hypernatremia | Salicylate poisoning |
| Iron toxicity | Severe gastroenteritis with hypovolemia |
| Salicylate poisoning (glucose <300 mg/dL) | Other ingestions: ethanol, ethylene glycol, iron, isoniazid, methanol |
| Sepsis | |
| Stress |
In DKA, sodium stores are depleted but serum sodium may be low, normal, or high, depending on the water balance. The measured sodium is lower than the true value because of the shift of water into the extracellular space (sodium decreases 1.6 mEq/L per each 100 mg/dL rise in glucose over 100 mg/dL) and the increase in serum lipid and protein levels (pseudohyponatremia). In addition, the low sodium level may reflect water retention secondary to increased secretion of antidiuretic hormone.
While there is usually a total body potassium deficit, the initial serum potassium concentration may be normal or elevated because of hyperosmolality, insulin deficiency, and the shifting of potassium into the extracellular space. A low initial potassium level (<3.5 mEq/L) is an unusual and ominous finding.
Finally, in the absence of infection, the WBC count may be elevated (18,000–20,000/mm3), secondary to the increase in circulating catecholamines and hemoconcentration.
ED Management
After a rapid evaluation of the patient’s status, initiate therapy to correct fluid deficits, electrolyte imbalances, acidosis, and hyperglycemia. Avoid overly vigorous management, which can cause excessively rapid changes in glucose, osmolality, and pH, and therefore contribute to the development of complications, such as cerebral edema. Treat any concomitant pathology or complications (sepsis, increased ICP, or coma).
History
Determine the duration of the current illness and any precipitating factors such as infection, trauma, or stress. If the patient is a known diabetic, document the current insulin regimen (and adherence) and the time of the last injection.
Physical Examination
Focus the examination on the vital signs (including the presence of Kussmaul respirations), degree of dehydration, level of consciousness, fundoscopic examination, and possible sites of infection. Document the vital signs and neurologic status at least hourly.
Initial Laboratory Evaluation
Obtain blood for STAT glucose, electrolytes, BUN, creatinine, lactate, calcium, phosphorous, osmolality, beta-hydroxybutyrate, pH (venous or arterial), CBC, HgbA1c, and a bedside fingerstick glucose measurement. Also obtain a urinalysis and an ECG (check for peaked T-waves). Prior to beginning insulin therapy for a patient with new-onset diabetes, send additional blood for insulin, C-peptide, thyroid autoantibody titers and relevant autoantibodies (insulin autoantibodies [IAA], islet cell antibodies [ICA], and glutamic decarboxylase antibodies [GAD]). Also obtain blood cultures if infection is suspected.
Initial Management
Place the patient on a cardiorespiratory monitor and start and maintain a flow sheet. Perform a rapid assessment of level of consciousness and evaluate for signs of cerebral edema; repeat at least hourly. In general, the goals are slow, steady rehydration over 48 hours, a decrease in the serum glucose of 80–100 mg/dL/h, and a stable corrected sodium while the measured sodium increases.
Fluid Resuscitation
A patient with DKA has some degree of dehydration. However, significant dehydration can exist and the patient will continue to urinate until intravascular volume depletion affects the glomerular filtration rate. If available, the difference between a premorbid weight and present weight provides the best assessment of volume depletion. In general, a child with moderate to severe DKA is at least 7–10% dehydrated.
Insert two IV catheters so that maintenance and replacement fluids and the insulin drip can be managed separately. Initially, administer an isotonic saline fluid bolus (20 mL/kg) over approximately 60 minutes. Reassess the patient after the initial bolus (peripheral pulses, capillary refill) and repeat, if necessary, in order to maintain adequate peripheral perfusion.
Deficit Fluids
Calculate deficit fluids using recent weight loss or an estimation of percentage dehydration. Replace the total deficit with normal saline, divided evenly over 24–48 hours. Use a slower rate (over 48 hours) of fluid replacement for children under two years, or if there is severe acidosis, an elevated corrected sodium, significant hyperosmolality (>350 mOsm/kg), or a long prodromal illness. Subtract the amount of fluid given as a fluid bolus from the total deficit.
Maintenance Fluids
Calculate the daily maintenance fluid requirements and administer as normal saline. Replacement of ongoing losses may be necessary, especially if there is polyuria (>5 mL/kg/h). For a polyuric patient, measure the urinary losses every 4–8 hours, and then replace half of this volume over the next 4–8 hours with ½ NS in a separate “piggy-back” line. Also replace the volume of vomitus with ½ NS in this line.
Potassium
Correction of the acidosis will exacerbate the hypokalemia. If the serum potassium is <5.0 mEq/L, add 20 mEq K acetate/L and 20 mEq K phosphate/L, once urine output is documented. If a serum potassium level is unavailable, obtain an ECG to look for evidence of hyperkalemia (peaked T-waves, shortened QT interval) or hypokalemia (flattened T-waves, widened QT interval). If the patient is hypocalcemic, use KCL instead of K phosphate. Measure the phosphorus and calcium every 4–6 hours and repeat the ECG every 2–4 hours.
Insulin and Glucose
After the initial fluid resuscitation, begin an insulin drip with the goal of decreasing the blood sugar by 80–100 mg/dL/h. Start the insulin drip at 0.1 units/kg/h. Do not give an insulin bolus. Add 100 units of regular insulin to 100 mL of normal saline (resultant concentration = 1 unit/mL), and infuse at 0.1 mL/kg/h. Prior to running the drip, allow 50 mL of the mixture to flow through the IV in order to saturate insulin binding sites in the tubing. Start the insulin drip at 0.05 units/kg/h if the patient is markedly hyperglycemic (glucose >1000 mg/dL), is under two years of age, or has recently received a subcutaneous dose of insulin.
Add D5 to the fluids when the glucose reaches 250–300 mg/dL, but continue the insulin infusion. Adjust the rate of the drip to maintain a blood glucose of 120–180 mg/dL. Lower the rate by one-half (0.5 units/kg/h) if the glucose is falling below this level. If the patient is becoming hypoglycemic at this rate, increase the dextrose in the IV solution to D7.5–D12.5. Calculate the glucose requirement per unit of insulin; most patients require 3–5 g of glucose/unit of insulin. Once the acidosis is resolved (pH >7.30, bicarbonate >15 mEq/L) and the patient can tolerate a PO diet, begin subcutaneous insulin. Stop the insulin drip one hour after the subcutaneous insulin dose.
Bicarbonate
Do not use sodium bicarbonate unless the venous pH is <6.9 with associated hemodynamic compromise. The dose is 0.5–1 mEq/kg by IV infusion over one hour, not as an IV push. Mix a 50 mL ampule of sodium bicarbonate with 250 mL sterile water to create a concentration of 44 mEq/300 mL.
Example Calculation
Patient with DKA who weighs 40 kg and has 10% dehydration:
Initial Fluid Bolus
Fluid Deficit
Maintenance Fluids
Insulin
Initial Fluids
Continue normal saline until the osmolality is <310 mOsm/kg and the sodium rises to approximately 140 mEq/L as the blood sugar falls, then change to ½ NS. However, if the corrected sodium is >160 mEq/L, consult with a pediatric endocrinologist and use a lower sodium concentration in the IV fluid.
Laboratory Assessments
Repeat the glucose and venous pH hourly. Obtain electrolytes, osmolality, BUN, and creatinine every two hours until the trend is normalizing, then every four hours until normal. Calculate the corrected sodium with each set of laboratory values:
Obtain calcium and phosphorus levels every 4–6 hours until the DKA is resolving. Obtain an ECG every 2–4 hours, looking for peaked T-waves (hyperkalemia).
Even with meticulous care, a patient with DKA is at risk for developing cerebral edema. Risk factors include age under three years, an elevated BUN, severe acidosis, and failure of the serum sodium to rise as expected as the glucose falls. Signs and symptoms of increased ICP (pp. 527–529) classically occur 6–18 hours into treatment and include headache, vomiting, lethargy, disorientation, fundoscopic changes (absent venous pulsations, blurring of optic disk margins), and decorticate or decerebrate posturing. Any neurologic signs at presentation, prior to treatment, reflect the patient’s hyperosmolality.
If the patient complains of headache and becomes lethargic during treatment, but has a normal fundoscopic examination, obtain a stat CT scan of the head. If the patient is unresponsive, posturing, has pupillary changes, or has milder symptoms with fundoscopic abnormalities, immediately treat for increased intracranial pressure (pp. 527–529) with mannitol 1 g/kg IV over ten minutes, endotracheal intubation if airway protection is compromised because of the patient’s mental status, and elevation of the head to 30°. Alternatively, use 3% saline, 5 mL/kg over 30 minutes.
Also observe the patient for other problems associated with therapy for DKA, such as fluid overload with edema or CHF.
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