Handbook of Critical Care Drug Therapy

Editors: Susla, Gregory M.; Suffredini, Anthony F.; McAreavey, Dorothea; Solomon, Michael A.; Hoffman, William D.; Nyquist, Paul; Ognibene, Frederick P.; Shelhamer, James H.; Masur, Henry

Title: Handbook of Critical Care Drug Therapy, 3rd Edition

Copyright 2006 Lippincott Williams & Wilkins

> Table of Contents > Chapter 6 - Endocrine Therapies

Chapter 6

Endocrine Therapies

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TABLE 6.1. Corticosteroid Potencies

Agent Equivalent Dose Relative Mineralocorticoid Effecta Biologic Half-Life
Short-Acting
Cortisone 25 mg ++ 8 h
Hydrocortisone 20 mg ++ 8 h
Intermediate-Acting
Prednisone 5 mg + 18 h
Prednisolone 5 mg + 18 h
Methylprednisolone 4 mg 0 18 h
Long-Acting
Dexamethasone 0.75 mg 0 36 h
aRange of mineralocorticoid effect is from ++ (highest) to 0 (none).

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TABLE 6.2. Thyroid, Pituitary, and Adrenal Hormonal Replacement

Agent Indications Dosage Comments
Thyroid
Levothyroxine (T4, L-thyroxine) Hypothyroidism, myxedema coma Initial replacement: 25 50 g PO qd Converted to T3 in periphery
Maximum replacement: 200 g PO qd Follow TSH for normalization and patient's clinical status
In critically ill with myxedema coma: 200 500 g IV/day slowly For stupor or coma, treat with 200 500 g IV bolus followed by 75 g/day; consider hydrocortisone 50 100 mg IV q8h 5 d as adjunctive therapy for hypocortisolism
Half-life: euthyroid, 6 d; hypothyroid, 8 d; hyperthyroid, 3 d
IV dose = 75% of PO dose (for replacement therapy)
Preferred over T3 for critically ill patients
Many experts prefer the lower doses initially for safety, especially in the elderly, comatose, and those with heart disease
May precipitate angina or arrhythmias
Liothyronine (T3, triiodothyronine) Hypothyroidism, myxedema coma Replacement: 25 75 g PO qd Assessment of therapy is more difficult; wait at least four hours after IV dose
Myxedema coma: 12.5 25 g IV q6h Half-life: euthyroid, 24 h; hypothyroid, 38 h; hyperthyroid, 17 h
Pituitary/Adrenal
Synthetic ACTH (cosyntropin) Screening test for adrenal insufficiency 250 g (25 units) IV/IM Some authors recommend using smaller doses such as 1 g for assessment of HPA axis
Normal function is indicated by control cortisol level >5 g/dl and 30 min post level >18 g/dl with an increase of 7 g/dl above control
Small doses of prednisone will not affect cortisol response
Dexamethasone does not affect cortisol response
Fludrocortisone Mineralo-corticoid replacement in primary adrenal insufficiency 50 200 g PO qd Titrated to achieve normal serum potassium and blood pressure
Not required in secondary adrenal insufficiency
Hydrocortisone Replacement 25 mg IV/PO q AM and

12.5 mg IV/PO q PM

 For equivalent corticosteroid dosages, see Table 6.1
Stress 50 100 mg IV/PO q8h For treatment of adrenal insufficiency complicating critical illness, maximum dose of glucocorticoid should be equivalent to hydrocortisone 300 mg/d
Preoperative 1 d preoperatively: 25 mg IV/PO at 6 PM and midnight For patients who may have adrenal insufficiency
Day of operation: 50 mg IV during surgery
Postoperative: 50 mg IV q8h 24 h, then 25 mg IV/PO q8h 24 48 h
Desmopressin Diabetes insipidus Intranasal: 10 40 g in 1 3 divided doses daily May cause hypertension, water retention, headache, abdominal cramps; swelling and burning may occur at the injection site after SC administration
SC/IV: 2 4 g in 2 divided doses daily
HPA, hypothalamic-pituitary-adrenal; IM, intramuscular; IV, intravenous; PO, by mouth; SC, subcutaneous; TSH, thyroid stimulating hormone

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TABLE 6.3. Therapy for Thyrotoxicosis

Drug Indication Dosage/Route Comment
Thiourea Agents Used when radioisotopes are NOT indicated: e.g., children, young adults, pregnancy, mild thyrotoxicosis, small goiters

Preparing hyperthyroid patients for surgery and elderly patients for radioactive iodide treatment

 Inhibit thyroid hormone synthesis

Low incidence of posttreatment hypothyroidism

Complications: agranulocytosis (0.1% to 0.4% of patients)

Definitive therapy required; relapses after these agents discontinued
Propylthiouracil 100 300 mg PO q6 8h (<200 mg/d during pregnancy) Drug of choice during pregnancy

Complication (rare): hepatic necrosis
Methimazole 80 120 mg PO qd Less frequent dosing than propylthiouracil

Lower incidence of hepatitis
Iodide Thyroid storm Inhibits thyroid hormone release
Lugol's solution (7 mg l/drop) 3 10 gtts PO tid

 Cannot be used as sole therapy
SSKI (35 mg I/drop) 5 gtts PO qid
Other Agents
Radioactive iodine (l131) Generally used in older patients (>25 years) because of theoretical risk of carcinogenesis Destroys cells that concentrate iodine

Never used in pregnant patients
Propranolol Antagonism of peripheral effects of hormone

Symptomatic relief of tremor, tachycardia, etc.

Initial treatment of choice for thyroid storm

 10 40 mg PO q6 8h

1 mg IV aliquots up to 0.15 mg/kg

3 5 mg/h infusion

 Dose adjusted to response in heart rate (goal is 100 beats/min)

Other -blockers may be equally effective
Dexamethasone Thyroid storm 2 mg IV q6h Inhibits thyroid hormone release
IV, intravenous; PO, by mouth

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TABLE 6.4. Ketoacidosis and Hyperosmolar Coma

Syndrome Situation Therapy Comments
Diabetic ketoacidosis Fluid deficit Initially isotonic fluids, 1 L rapidly, then 1 L/h after clinical response of patient Rate and type of fluid is adjusted according to laboratory results and patient response

0.45% NaCl can be alternated with 0.9% NaCl

Dextrose may be added to the IV fluids when the blood glucose falls below 300 mg/dl
  Hyperglycemia Regular insulin 6 10 U/h IV infusion Blood glucose must be monitored every 2 h

Insulin infusion rate should be titrated to reduce blood glucose by 60 100 mg/dl/h to glucose of 300 mg/dl
  Hypokalemia Potassium 10 40 mEq/h Serum potassium may be elevated acutely in the presence of acidosis, but total body potassium is reduced
      Correction of acidosis and insulin administration will reduce serum potassium levels
      Administration should begin when the measured potassium level is in the normal range
      Administer with caution to patients with renal insufficiency
      Administer as the chloride or phosphate salt
  Acidosis Bicarbonate Usually unnecessary unless pH <6.9 or arrhythmias are present
  Hypophosphatemia Potassium phosphate or sodium phosphate Guide by serum phosphate level
Hyperosmolar nonketotic coma Dehydration 1 L 0.45% NaCl rapidly, then 1 L/h for several h A major free water deficit is usually present

Rehydration is the major therapy

Neurologic status should be monitored frequently because of the possibility of cerebral edema from too rapid a fall in serum osmolality
  Hyperglycemia Regular insulin 3 5 U/h IV infusion Goal of insulin therapy is to achieve a blood glucose of 250 300 mg/dl
      Patients are quite sensitive to the effects of insulin; blood glucose should be lowered at a rate of 60 100 mg/dl/h
      Because blood glucose can fall precipitously, insulin infusion rates should be more conservative than in patients with diabetic ketoacidosis
Alcoholic Ketoacidosis     Usually when PO intake stopped

Management is correction of fluid, electrolyte, and acid-base abnormalities that affect the chronic alcoholic

Blood glucose usually is <200 mg/dl
IV, intravenous; PO, by mouth

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TABLE 6.5. Insulin Preparations

Preparation Onset Peak Duration Comments
Short-Acting
Regular IV: 10 30 min

SC: 30 60 min

 IV: 30 min

SC: 2 3 h

 IV: 1 h

SC: 5 7 h

 Preferred for ketoacidosis and other conditions with rapidly changing requirements

Only form of insulin that can be given IV
Semilente SC: 30 90 min SC: 4 10 h SC: 12 16 h Not for IV administration
Lispro SC: 0.25 h SC: 0.5 1.5 h SC: 2.5 5 h Not for IV administration
Insulin aspart SC: 0.25 h SC: 1 3 h SC: 3 5 h Not for IV administration
Insulin glulisine SC: 0.5 1.5 h SC: 1 2.5 h Not for IV administration
Intermediate-Acting
NPH SC: 1 2 h SC: 4 12 h SC: 18 24 h Not for IV administration
Lente SC: 1 2.5 h SC: 7 15 h SC: 18 24 h Not for IV administration
Long-Acting
Protamine zinc SC: 6 8 h SC: 18 24 h SC: 36 h Not for IV administration
Ultralente SC: 4 8 h SC: 10 30 h SC: 36 h Not for IV administration
IV, intravenous; SC, subcutaneous

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TABLE 6.6. Hyperglycemia: Regular Insulin Sliding Scales

Subcutaneous (SC) Dosing
Blood glucose concentration (mg/dL) SC regular insulin (units)
<180
180 240 2
240 300 4
300 360 6
360 400 8
>400 10 12
IV Continuous Dosing
Blood glucose concentration (mg/dL) IV infusion rate (U/h)
<120
120 179 0.5 1
180 240 1 2
241 300 2
301 360 3
361 400 4
>400 6 8
Administer insulin not more than every 4 hours.

Not for patients with shock or other hypoperfusion states.

Monitor serum glucose every 2 to 4 hours; may alternate with finger stick glucose measurements.

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TABLE 6.7. Amylin Analog

Conversion of Pramlintide to Insulin Unit Equivalents
Prescribed Pramlintide Dose ( g) Insulin Unit Equivalents Using U-100 Syringe (Units) Corresponding Volume (ml)
15 2.5 0.025
30 5 0.05
45 7.5 0.075
60 10 0.1
120 20 0.2
Pramlintide is an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Pramlintide is not indicated for acute glucose management in critically ill patients and should be discontinued in this setting. Pramlintide therapy should only be restarted after the patient's critical illness has resolved, and the patient is consuming a stable caloric intake. Titration of the patients's insulin dose, oral hypoglycemic dose, and pramlintide may be required in this setting. Patients should be monitored at regular intervals to assess the effect on blood glucose.

Pramlintide Dosage and Administration

Pramlintide should be administered using a 0.3 ml, U-100 insulin syringe. The pramlintide dose may be prescribed in micrograms, but it will be administered in Units indicated on the U-100 insulin syringe. Table 6.7 outlines the conversion of the pramlintide dose prescribed in micrograms to the administration dose in Units.

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TABLE 6.8. Oral Hypoglycemic Agents

Agent Starting Dosage Onset/Duration Comments
Sulfonylurea
Glimepiride 1 2 mg PO qd Onset: 2 3 h

Duration: 24 h

 Lower dosage in elderly and those with hepatic or renal disease because of risk of hypoglycemia
Glipizide 5 mg PO qd Onset: 1 h

Duration: 10 24 h

 As potent as glyburide

Contraindicated in patients with renal or hepatic impairment
Glyburide 2.5 mg PO qd Onset: 1.5 h

Duration: 18 24 h

 Prolonged biologic effect despite short half-life (1 2 h)
-Glucosidase Inhibitor
Acarbose 25 mg PO tid Onset: unknown

Duration: unknown

 Delays glucose absorption from GI tract

Not recommended in patients with renal impairment

GI side effects
Miglitol 25 100 mg PO tid Onset: unknown

Duration: unknown

 Delays glucose absorption from GI tract

Not recommended in patients with renal impairment

GI side effects
Bioguanide
Metformin 500 mg PO bid Onset: 1 3 h

Duration: 24 h

 May increase serum levels of cimetidine

May decrease absorption of vitamin B12 and folic acid causing deficiencies

May cause lactic acidosis, especially in patients with renal impairment; stop drug in setting of excessive ethanol ingestion, hypoxemia, shock, hepatic failure or surgery
      GI side effects
Meglitinides
Repaglinide 0.5 4 mg PO tid before meals Onset: unknown

Duration: unknown

 Take 15 30 min before meals

Starting dose in patients with severe renal function is 0.5 mg
Nateglinide 60 120 mg PO tid before meals Onset: unknown

Duration: unknown

 Take 15 30 min before meals

Use with caution in patients with chronic liver disease
Thiazolidinedione
Pioglitazone 15 45 mg PO qd Onset: unknown

Duration: unknown

 Usually used in combination with sulfonylureas, metformin, or insulin

Check LFT before beginning therapy
      Contraindicated in liver disease when ALT >2.5 ULN
      Can cause fluid retention and may exacerbate HF
      Drug interactions with CYP450 3A4 substrates
Rosiglitazone 2 8 mg PO qd Onset: unknown

Duration: unknown

 Usually used in combination with sulfonylureas, metformin, or insulin

Check LFT before beginning therapy
      Contraindicated in liver disease when ALT >2.5 ULN
      Contraindicated in renal impairment
      Can cause fluid retention and may exacerbate HF
ALT, aminotransferase; GI, gastrointestinal; HF, heart failure; LFT, liver function tests; PO, by mouth; ULN, upper limit of normal

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