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ICU Endocrine Emergencies Bradley J. Phillips, MDBurn-Trauma-ICU Adults & Pediatrics.

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Presentation on theme: "ICU Endocrine Emergencies Bradley J. Phillips, MDBurn-Trauma-ICU Adults & Pediatrics."— Presentation transcript:

1 ICU Endocrine Emergencies Bradley J. Phillips, MDBurn-Trauma-ICU Adults & Pediatrics

2 ICU - Endocrine Disorders Glucose metabolism Glucose metabolism Thyroid dysfunction Thyroid dysfunction Adrenal disorders Adrenal disorders Pituitary disorder Pituitary disorder Unusual Unusual –Carcinoid crisis –Hyperparathyroidism

3 ICU - Glucose Metabolism Hyperglycemia Hyperglycemia Hypoglycemia Hypoglycemia Diabetic Ketoacidosis (DKA) Diabetic Ketoacidosis (DKA) Hyperglycemic Hyperosmolar Syndrome Hyperglycemic Hyperosmolar Syndrome

4 Diabetes in the ICU Diagnosis Diagnosis –Fasting glucose > 126 –Random glucose > 200 x 2 Complications Complications –Diuresis and dehydration –Acidosis –Hyponatremia –Hypocalcemia –Immune dysfunction

5 DKA Presentation Presentation –Anorexia, nausea, emesis, polyuria –Kussmaul breathing –“Fruity” breath –Deterioration mental status –Hypotension –Progressive acidosis –Chest and/or abdominal pain

6 DKA Occurs in absence or near-absence of insulin Occurs in absence or near-absence of insulin NIDDM (type 2) at risk during catabolic stress NIDDM (type 2) at risk during catabolic stress More common in adults than children More common in adults than children –40% over 40 –20% over 55 Infectious cause most common Infectious cause most common Mortality Mortality –5-10% –Increases with age ( > 65 = 20-40%)

7 DKA Tests Tests –Hyperglycemia (> 250) –Ketonemia (ß-hydroxybutyrate) –Glycosuria and ketonuria –Acidosis (pH < 7.3) with anion gap –Low serum bicarbonate (< 15) –Moderate hyperosmolality

8 DKA - Associated Abnormalities Sodium Sodium –variable –fall by 1.6 for every 100 increase in glucose –falsely low with hypertriglyceridemia Chloride Chloride –hyper in ketoacidosis –hypo associated with severe emesis Potassium Potassium –high with acidosis –at high risk for severe hypokalemia

9 DKA Management Management –Fluid resuscitation Normal saline cc/hr with bolus of 1L Normal saline cc/hr with bolus of 1L If UOP good and NA > 140, slow IVF and change to.45 NS If UOP good and NA > 140, slow IVF and change to.45 NS Add D5 once BS < 300 Add D5 once BS < 300 –Insulin 0.4u/kg with 1/2 IV and 1/2 SQ 0.4u/kg with 1/2 IV and 1/2 SQ IV qtt or hourly IV injections IV qtt or hourly IV injections continue until ketones in urine resolved continue until ketones in urine resolved change to SQ once BS 7.3, Bicarb > 18 change to SQ once BS 7.3, Bicarb > 18

10 DKA Management Management –Potassium K< 3.5 add 40 meq/l K< 3.5 add 40 meq/l K > 3.5 and 3.5 and < meq/l check q 2 hrs check q 2 hrs –Replete hypophosphatemia –Give bicarbonate if pH < 7.1 –Treat underlying cause

11 DKA Complications Complications –Hypotension and shock –Thrombosis –Cerebral edema –Renal failure –Hypoglycemia

12 Hyperglycemic Hyperosmolar Syndrome Present with severe hydration without ketosis and acidosis Present with severe hydration without ketosis and acidosis Glucose > 1000 Glucose > 1000 Coma, seizures, tremors, hemiplegia Coma, seizures, tremors, hemiplegia Causes Causes –infection –MI –hemorrhage and trauma –burns Treat the same as DKA Treat the same as DKA

13 ICU - Thyroid Dysfunction Hypothyroidism Hypothyroidism Myxedema coma Myxedema coma Thyrotoxicosis Thyrotoxicosis –Thyrotoxic crisis

14 Hypothyroidism cold intolerance cold intolerance hypothermia hypothermia apathy apathy depressed mental status depressed mental status weight gain weight gain alopecia alopecia dry coarse skin dry coarse skin arthralgia and myalgia arthralgia and myalgia hoarseness hoarseness enlarged tongue enlarged tongue goiter goiter periorbital edema periorbital edema hyponatremia hyponatremia hypoventilation hypoventilation hypotension hypotension cardiac dysfunction cardiac dysfunction bradycardia bradycardia pericardial effusion pericardial effusion

15 Myxedema Coma Acute exacerbation of hypothyroidism Acute exacerbation of hypothyroidism Highly lethal = 50% Highly lethal = 50% Precipitating factors Precipitating factors –CVA –CHF –drugs (narcotics, diuretics, sedative) –surgery/trauma –GI hemorrhage –bowel obstruction –hypoadrenalism

16 Myxedema coma Non-pitting edema “doughy” Non-pitting edema “doughy” Severe sensorial depression Severe sensorial depression Airway obstruction Airway obstruction Respiratory muscle weakness Respiratory muscle weakness Severe hypoventilation Severe hypoventilation

17 Thyrotoxicosis Etiology Etiology –Graves –toxic goiter –thyroiditis –drugs amiodarone amiodarone iodine iodine thyroxine (particularly IV) thyroxine (particularly IV) –Pituitary adenoma –Molar pregnancy

18 Thyrotoxicosis Thyroid crisis / “storm” Thyroid crisis / “storm” –life-threatening 10-20% mortality –precipitation factors Infection Infection Thyroid manipulation (operation, palpation) Thyroid manipulation (operation, palpation) Metabolic disorders (DKA) Metabolic disorders (DKA) Trauma Trauma MI MI PE PE Pregnancy Pregnancy

19 Thyrotoxicosis Vs “Storm” Neuro Neuro –emotional lability –tremors –weakness CV CV –tachycardia –systolic HTN –afib Thermo Thermo –heat intolerance GI GI –diarrhea Neuro Neuro –delirium –seizures –coma CV CV –CHF –arrhythmias Thermo Thermo –fevers GI GI –emesis –diarrhea –jaundice

20 Thyroid - Diagnostic Tests TSH TSH Free T4 ( or FTI) Free T4 ( or FTI) T3 –RIA (Radioimmune Assay) T3 –RIA (Radioimmune Assay)

21 Thyrotoxicosis Differential Diagnosis Check free T4 Check free T4 –if high, r/o euthyroid hyperthyroxinemia etiology etiology –high TBG (pregnancy, estrogen) –acute illness –liver disease –drug-induced (amiodarone, heparin, narcotics, anti- psychotics) differeriate with history/clinical exa, differeriate with history/clinical exa, –If low, check T3 to r/o T3 toxicosis Radioactive iodine uptake test Radioactive iodine uptake test

22 Therapy - Hyperthyroidism Uncomplicated hyperthyroidism Uncomplicated hyperthyroidism –outpatient –methimazole or PTU –B-blockers for adrenergic –+/- I31 ablation Severe hyperthyroidism Severe hyperthyroidism –possible hospitalization restricted activity restricted activity compliance with medications compliance with medications education education

23 Management of Thyroid “Storm” Always ICU management Always ICU management Supportive Supportive –Fever reduction decreases metabolic rate decreases metabolic rate decreases percentage of free T4 decreases percentage of free T4 tylenol avoid salicylates (alters protein binding) tylenol avoid salicylates (alters protein binding) –Aggressive fluid resuscitation large losses from sweating, emesis, diarrhea large losses from sweating, emesis, diarrhea replete glucose and vitamins replete glucose and vitamins ? Hemodynamic monitoring ? Hemodynamic monitoring –rate control - first line digoxin –avoid B-Blockers

24 Management of Thyroid “Storm” Pharmacologic control Pharmacologic control –Antithyroid drugs methimazole or PTU methimazole or PTU give po/NGT/rectally give po/NGT/rectally –Inhibit release of T4 and T3 SSKI or Lugol’s solution SSKI or Lugol’s solution initial of dose of antithyroid drug must be given initial of dose of antithyroid drug must be given consider lithium consider lithium

25 Pharmacologic control Pharmacologic control –Inhibit conversion of T4 to T3 consider steroids or PTU consider steroids or PTU ipodate sodium (Oragrafin) highly effective ipodate sodium (Oragrafin) highly effective caution long-term use (“escape” caution long-term use (“escape” –Reduction of hyperadrenergic state propranolol (historical) propranolol (historical) cautious of B-blockers in CHF cautious of B-blockers in CHF –Removal of T4 plasmaphresis or hemoperfusion plasmaphresis or hemoperfusion emergent thyroidectomy emergent thyroidectomy Management of Thyroid “Storm”

26 ICU Complications of Hyperthyroidism Atrial arrthythmias Atrial arrthythmias –most convert within 3 weeks of euthyroidism –never after 4 months –no prospective study on anticoagulation –CVA age-dependent not atrial fib -dependent CHF CHF Malnutrition/dehydration Malnutrition/dehydration Metabolic failure Metabolic failure Drug metabolism Drug metabolism

27 Therapy - Hypothyroidism Uncomplicated Uncomplicated –outpatient treatment –full dose 1.7 ug/kg –age dependent young ug/d young ug/d old 12.5 to 25 ug/d old 12.5 to 25 ug/d –check TSH at 4-6 weeks –change doses 12.5 to 25 ug increments

28 Profound or myxedema coma Profound or myxedema coma –endocrine emergency –supportive care correct hypothermia correct hypothermia blood volume restoration blood volume restoration monitor electrolytes (free water clearance impaired) monitor electrolytes (free water clearance impaired) glucose replacement glucose replacement check for drug toxicity (digoxin etc) check for drug toxicity (digoxin etc) –r/o underlying infection Therapy - Hypothyroidism

29 Thyroxine replacement Thyroxine replacement –loading dose uq IV no CV complications in critically ill no CV complications in critically ill ? Higher mortality in high T3 toxicosis ? Higher mortality in high T3 toxicosis –maintenance ug/d

30 Hypothyroidism in Surgical Patients Historical complications peri-op more common Historical complications peri-op more common Recent studies Recent studies –mild-moderate - little influence –no increased cardiopulmonary difficulties, wound healing impairment, or infections Critically ill Critically ill –? respiratory dysfunction and vent weaning –T4 and T3 reduced, TSH high/low/normal –Controlled studies of T4/T3 administration no benefit overall in trauma, burns no benefit overall in trauma, burns ? Benefit in organ transplantation ? Benefit in organ transplantation

31 Adrenal disorders Adrenal insufficiency Adrenal insufficiency Pheochromocytoma and “ crisis” Pheochromocytoma and “ crisis” Aldosterone deficiency Aldosterone deficiency

32 Adrenal Insufficiency Incidence Incidence –General population40-60/million –ICU1-20% SICU0.66% SICU0.66% –SICU trauma0.23% –SICU nontrauma0.98% SICU SICU –> 14 days6% –age > 551.7% –> 14 days and age > 5511% –Blunt adrenal injury5%

33 Risk Factors - AI Age > 55 Age > 55 Malnutrition Malnutrition Prolonged hospital or ICU stay Prolonged hospital or ICU stay Chronic alcoholism Chronic alcoholism High APACHE score High APACHE score Stress in form of trauma, surgery, infection, and dehydration Stress in form of trauma, surgery, infection, and dehydration

34 Presentation of AI Non-ICU Non-ICU –insidious –nonspecific (weakness, wt loss, lethargy, GI symptoms) ICU ICU –acute adrenal crisis –altered by co-existing disease –usually precipitated by physical stressor (trauma, surgery, infection, dehydration) –other causes AIDS, TB, or pituitary tumor

35 ICU Clinical Presentation Refractory hypotension Refractory hypotension High-output circulatory failure High-output circulatory failure –CI > 4 –tachycardia –low SVR with normal wedge Electrolytes disturbances Electrolytes disturbances –high K, low Na, and low glucose Febrile (> 39C) Febrile (> 39C) Mental status changes Mental status changes Dehydration Dehydration GI disturbances GI disturbances

36 “Clues” to AI History History –other endocrine abnormalities –family h/o endocrine abnormalities Eosinophilia Eosinophilia

37 AI Differential Diagnosis Sepsis Sepsis Neurogenic shock Neurogenic shock Overdose of vasodilator Overdose of vasodilator Severe anemia Severe anemia AV shunt AV shunt Thyrotoxicosis Thyrotoxicosis Beriberi Beriberi Pregnancy Pregnancy

38 Adrenal Insufficiency - AI Primary Primary Central Central Relative Relative

39 Adrenal Insufficiency - AI Primary Primary –autoimmune, infection, hemorrhage(bilateral), medications (ketaconazole, etc), metastatic carcinoma, lymphoma Central Central –long-standing steroid use Relative Relative –increased degradation –resistance –increased demand

40 Primary AI Pathological process within adrenal gland Pathological process within adrenal gland –90% o f gland destruction Etiology Etiology –Autoimmune % –Infectious - 35% –Hemorrhagic Risk factors ( Rao et al, Ann Intern Med, 1989 ) Risk factors ( Rao et al, Ann Intern Med, 1989 ) –coagulopathy –thromboembolic disease –postoperative state

41 Central AI Central dysfunction Central dysfunction –pituitary (secondary) –hypothalamus (teritary) Etiology Etiology –  long-term glucocorticoid therapy –uncommon post-partum pituitary necrosis (Sheehan’s syndrome) post-partum pituitary necrosis (Sheehan’s syndrome) transient ACTH deficiency (alcoholics) transient ACTH deficiency (alcoholics) pituitary radiation pituitary radiation empty sella syndrome empty sella syndrome

42 Steroid and Potency

43 Glucocorticoid vs Mineralocorticoid SteroidGlucocorticoid Mineralocorticoid Hydrocortisone 11 Prednisolone 40.7 Dexamethasone402 Aldosterone Fludrocortisone10400

44 Potential for HPA Suppression Higher risk for suppression Higher risk for suppression –higher glucocorticoid potency –short frequency of dosing –evening dosing –systemic therapy –duration > 1 week

45 Relative AI Relative Relative –increased degradation of glucocorticoids drugs that activate hepatic metabolism drugs that activate hepatic metabolism treatment of hypothyroidism treatment of hypothyroidism –resistance to glucocorticoid activity AIDS AIDS –increased demand (stress response) numerous ICU studies numerous ICU studies

46 HPA Axis Assessment - Tests H-P Axis and Adrenal H-P Axis and Adrenal –Low-dose ACTH stimulation (1 ug) Adrenal only Adrenal only –Short ACTH stimulation test (250 ug) H -P Axis only H -P Axis only –Insulin-induced hypoglycemia test –Metyrapone –CRH stimulation

47 Laboratory Assessment Random cortisol level Random cortisol level –draw before steroids given –draw between 6-8 am –decadron generally consider not cross-reactive –positive if < 10 in normal or < 15 in critically ill –10-20 indeterminant Cosyntropin testing Cosyntropin testing Corticotropin-releasing hormone test (CRH) Corticotropin-releasing hormone test (CRH) Plasma renin and aldosterone measurements Plasma renin and aldosterone measurements

48 Cosyntropin stimulation test Standard short Standard short –baseline cortisol level –0.25 mg cosyntropin with level 60 minutes later –peak > 20 or rise of 7 in critically ill Low-dose short ( more sensitive for central) Low-dose short ( more sensitive for central) –more accurate and physiologic –same as standard but only 1 ug dose Long Long –differentiation of primary vs central –replaced by ACTH measurement

49 HPA Axis Assessment - Test Summary

50 Treatment Hemodynamically unstable Hemodynamically unstable –Baseline cortisol –Treat with Hydrocortisone 100 IV bolus and q8 –+/- cosyntropin testing –Isotonic IVF with D5 –treat underlying disease or precipitating factors Hemodynamically stable Hemodynamically stable –same as above –cosyntropin testing

51 Treatment - Steroids Hydrocortisone Hydrocortisone –provides glucocorticoid and mineralocorticoid –physiological doses max 300 mg/day max 300 mg/day –normal daily adrenal output AM 25 mg /PM mg AM 25 mg /PM mg Dexamethasone Dexamethasone –not cross-reactive with cortisol assays –no mineralocorticoid activity –useful while diagnostic testing being completed Fludrocortisone (Florinef) Fludrocortisone (Florinef) –uncommonly required for mineralocorticoid activity

52 Outcome Untreated = 100% mortality Untreated = 100% mortality Treated in critically ill = 50% mortality Treated in critically ill = 50% mortality Cortisol level Cortisol level –positively correlated to severity of illness –negatively correlated to survival

53 ICU Endocrine Emergencies Questions…? Bradley J. Phillips, MD Burn-ICU SBH-UTMB


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