Transcript No Slide Title

ICU Endocrine Emergencies
Bradley J. Phillips, MD
Burn-Trauma-ICU
Adults & Pediatrics
ICU - Endocrine Disorders
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Glucose metabolism
Thyroid dysfunction
Adrenal disorders
Pituitary disorder
Unusual
– Carcinoid crisis
– Hyperparathyroidism
ICU - Glucose Metabolism
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Hyperglycemia
Hypoglycemia
Diabetic Ketoacidosis (DKA)
Hyperglycemic Hyperosmolar Syndrome
Diabetes in the ICU
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Diagnosis
– Fasting glucose > 126
– Random glucose > 200 x 2
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Complications
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Diuresis and dehydration
Acidosis
Hyponatremia
Hypocalcemia
Immune dysfunction
DKA
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Presentation
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Anorexia, nausea, emesis, polyuria
Kussmaul breathing
“Fruity” breath
Deterioration mental status
Hypotension
Progressive acidosis
Chest and/or abdominal pain
DKA
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Occurs in absence or near-absence of insulin
NIDDM (type 2) at risk during catabolic stress
More common in adults than children
– 40% over 40
– 20% over 55
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Infectious cause most common
Mortality
– 5-10%
– Increases with age ( > 65 = 20-40%)
DKA
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Tests
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Hyperglycemia (> 250)
Ketonemia (ß-hydroxybutyrate)
Glycosuria and ketonuria
Acidosis (pH < 7.3) with anion gap
Low serum bicarbonate (< 15)
Moderate hyperosmolality
DKA - Associated Abnormalities
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Sodium
– variable
– fall by 1.6 for every 100 increase in glucose
– falsely low with hypertriglyceridemia
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Chloride
– hyper in ketoacidosis
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– hypo associated with severe emesis
Potassium
– high with acidosis
– at high risk for severe hypokalemia
DKA
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Management
– Fluid resuscitation
Normal saline 500-1000 cc/hr with bolus of 1L
 If UOP good and NA > 140, slow IVF and change to
.45 NS
 Add D5 once BS < 300
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– Insulin
0.4u/kg with 1/2 IV and 1/2 SQ
 IV qtt or hourly IV injections
 continue until ketones in urine resolved
 change to SQ once BS< 200, pH > 7.3, Bicarb > 18
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DKA
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Management
– Potassium
K< 3.5 add 40 meq/l
 K > 3.5 and < 5.5 20 meq/l
 check q 2 hrs
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– Replete hypophosphatemia
– Give bicarbonate if pH < 7.1
– Treat underlying cause
DKA
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Complications
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Hypotension and shock
Thrombosis
Cerebral edema
Renal failure
Hypoglycemia
Hyperglycemic Hyperosmolar
Syndrome
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Present with severe hydration without ketosis
and acidosis
Glucose > 1000
Coma, seizures, tremors, hemiplegia
Causes
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infection
MI
hemorrhage and trauma
burns
Treat the same as DKA
ICU - Thyroid Dysfunction
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Hypothyroidism
Myxedema coma
Thyrotoxicosis
– Thyrotoxic crisis
Hypothyroidism
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cold intolerance
hypothermia
apathy
depressed mental
status
weight gain
alopecia
dry coarse skin
arthralgia and myalgia
hoarseness
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enlarged tongue
goiter
periorbital edema
hyponatremia
hypoventilation
hypotension
cardiac dysfunction
bradycardia
pericardial effusion
Myxedema Coma
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Acute exacerbation of hypothyroidism
Highly lethal = 50%
Precipitating factors
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CVA
CHF
drugs (narcotics, diuretics, sedative)
surgery/trauma
GI hemorrhage
bowel obstruction
hypoadrenalism
Myxedema coma
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Non-pitting edema “doughy”
Severe sensorial depression
Airway obstruction
Respiratory muscle weakness
Severe hypoventilation
Thyrotoxicosis
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Etiology
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Graves
toxic goiter
thyroiditis
drugs
amiodarone
 iodine
 thyroxine (particularly IV)
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– Pituitary adenoma
– Molar pregnancy
Thyrotoxicosis
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Thyroid crisis / “storm”
– life-threatening 10-20% mortality
– precipitation factors
Infection
 Thyroid manipulation (operation, palpation)
 Metabolic disorders (DKA)
 Trauma
 MI
 PE
 Pregnancy
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Thyrotoxicosis Vs “Storm”
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Neuro
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– emotional lability
– tremors
– weakness
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CV
– tachycardia
– systolic HTN
– afib
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– delirium
– seizures
– coma
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GI
– diarrhea
CV
– CHF
– arrhythmias
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Thermo
– fevers
Thermo
– heat intolerance
Neuro
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GI
– emesis
– diarrhea
– jaundice
Thyroid - Diagnostic Tests
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TSH
Free T4 ( or FTI)
T3 –RIA (Radioimmune Assay)
Thyrotoxicosis Differential
Diagnosis
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Check free T4
– if high, r/o euthyroid hyperthyroxinemia
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etiology
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high TBG (pregnancy, estrogen)
acute illness
liver disease
drug-induced (amiodarone, heparin, narcotics, antipsychotics)
differeriate with history/clinical exa,
– If low, check T3 to r/o T3 toxicosis
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Radioactive iodine uptake test
Therapy - Hyperthyroidism
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Uncomplicated hyperthyroidism
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outpatient
methimazole or PTU
B-blockers for adrenergic
+/- I31 ablation
Severe hyperthyroidism
– possible hospitalization
restricted activity
 compliance with medications
 education
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Management of Thyroid “Storm”
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Always ICU management
Supportive
– Fever reduction
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decreases metabolic rate
decreases percentage of free T4
tylenol avoid salicylates (alters protein binding)
– Aggressive fluid resuscitation
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large losses from sweating, emesis, diarrhea
replete glucose and vitamins
? Hemodynamic monitoring
– rate control - first line digoxin
– avoid B-Blockers
Management of Thyroid “Storm”
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Pharmacologic control
– Antithyroid drugs
methimazole or PTU
 give po/NGT/rectally
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– Inhibit release of T4 and T3
SSKI or Lugol’s solution
 initial of dose of antithyroid drug must be given
 consider lithium
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Management of Thyroid “Storm”
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Pharmacologic control
– Inhibit conversion of T4 to T3
consider steroids or PTU
 ipodate sodium (Oragrafin) highly effective
 caution long-term use (“escape”
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– Reduction of hyperadrenergic state
propranolol (historical)
 cautious of B-blockers in CHF
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– Removal of T4
plasmaphresis or hemoperfusion
 emergent thyroidectomy
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ICU Complications of
Hyperthyroidism
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Atrial arrthythmias
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most convert within 3 weeks of euthyroidism
never after 4 months
no prospective study on anticoagulation
CVA age-dependent not atrial fib -dependent
CHF
Malnutrition/dehydration
Metabolic failure
Drug metabolism
Therapy - Hypothyroidism
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Uncomplicated
– outpatient treatment
– full dose 1.7 ug/kg
– age dependent
young 50-100 ug/d
 old 12.5 to 25 ug/d
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– check TSH at 4-6 weeks
– change doses 12.5 to 25 ug increments
Therapy - Hypothyroidism
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Profound or myxedema coma
– endocrine emergency
– supportive care
correct hypothermia
 blood volume restoration
 monitor electrolytes (free water clearance impaired)
 glucose replacement
 check for drug toxicity (digoxin etc)
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– r/o underlying infection
Therapy - Hypothyroidism
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Thyroxine replacement
– loading dose 300-500 uq IV
no CV complications in critically ill
 ? Higher mortality in high T3 toxicosis
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– maintenance 50-100 ug/d
Hypothyroidism in Surgical
Patients
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Historical complications peri-op more common
Recent studies
– mild-moderate - little influence
– no increased cardiopulmonary difficulties, wound
healing impairment, or infections
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Critically ill
– ? respiratory dysfunction and vent weaning
– T4 and T3 reduced, TSH high/low/normal
– Controlled studies of T4/T3 administration
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no benefit overall in trauma, burns
? Benefit in organ transplantation
Adrenal disorders
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Adrenal insufficiency
Pheochromocytoma and “ crisis”
Aldosterone deficiency
Adrenal Insufficiency
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Incidence
– General population 40-60/million
– ICU
1-20%
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SICU
0.66%
– SICU trauma
– SICU nontrauma
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0.23%
0.98%
SICU
– > 14 days
– age > 55
– > 14 days and age > 55
– Blunt adrenal injury 5%
6%
1.7%
11%
Risk Factors - AI
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Age > 55
Malnutrition
Prolonged hospital or ICU stay
Chronic alcoholism
High APACHE score
Stress in form of trauma, surgery, infection,
and dehydration
Presentation of AI
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Non-ICU
– insidious
– nonspecific (weakness, wt loss, lethargy, GI
symptoms)
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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
ICU Clinical Presentation
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Refractory hypotension
High-output circulatory failure
– CI > 4
– tachycardia
– low SVR with normal wedge
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Electrolytes disturbances
– high K , low Na, and low glucose
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Febrile (> 39C)
Mental status changes
Dehydration
GI disturbances
“Clues” to AI
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History
– other endocrine abnormalities
– family h/o endocrine abnormalities
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Eosinophilia
AI Differential Diagnosis
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Sepsis
Neurogenic shock
Overdose of vasodilator
Severe anemia
AV shunt
Thyrotoxicosis
Beriberi
Pregnancy
Adrenal Insufficiency - AI
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Primary
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Central
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Relative
Adrenal Insufficiency - AI
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Primary
– autoimmune, infection, hemorrhage(bilateral),
medications (ketaconazole, etc), metastatic
carcinoma, lymphoma
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Central
– long-standing steroid use
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Relative
– increased degradation
– resistance
– increased demand
Primary AI
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Pathological process within adrenal gland
– 90% o f gland destruction
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Etiology
– Autoimmune - 65-80%
– Infectious - 35%
– Hemorrhagic
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Risk factors (Rao et al , Ann Intern Med, 1989)
– coagulopathy
– thromboembolic disease
– postoperative state
Central AI
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Central dysfunction
– pituitary (secondary)
– hypothalamus (teritary)
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Etiology
–  long-term glucocorticoid therapy
– uncommon
post-partum pituitary necrosis (Sheehan’s syndrome)
 transient ACTH deficiency (alcoholics)
 pituitary radiation
 empty sella syndrome
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Steroid and Potency
Glucocorticoid vs Mineralocorticoid
Steroid
Hydrocortisone
Prednisolone
Dexamethasone
Aldosterone
Fludrocortisone
Glucocorticoid Mineralocorticoid
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4
40
0.1
10
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0.7
2
400
400
Potential for HPA Suppression
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Higher risk for suppression
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higher glucocorticoid potency
short frequency of dosing
evening dosing
systemic therapy
duration > 1 week
Relative AI
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Relative
– increased degradation of glucocorticoids
drugs that activate hepatic metabolism
 treatment of hypothyroidism
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– resistance to glucocorticoid activity
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AIDS
– increased demand (stress response)
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numerous ICU studies
HPA Axis Assessment - Tests
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H-P Axis and Adrenal
– Low-dose ACTH stimulation (1 ug)
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Adrenal only
– Short ACTH stimulation test (250 ug)
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H -P Axis only
– Insulin-induced hypoglycemia test
– Metyrapone
– CRH stimulation
Laboratory Assessment
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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
Corticotropin-releasing hormone test (CRH)
Plasma renin and aldosterone measurements
Cosyntropin stimulation test
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Standard short
– baseline cortisol level
– 0.25 mg cosyntropin with level 60 minutes later
– peak > 20 or rise of 7 in critically ill
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Low-dose short ( more sensitive for central)
– more accurate and physiologic
– same as standard but only 1 ug dose
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Long
– differentiation of primary vs central
– replaced by ACTH measurement
HPA Axis Assessment - Test
Summary
Treatment
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Hemodynamically unstable
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Baseline cortisol
Treat with Hydrocortisone 100 IV bolus and q8
+/- cosyntropin testing
Isotonic IVF with D5
treat underlying disease or precipitating factors
Hemodynamically stable
– same as above
– cosyntropin testing
Treatment - Steroids
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Hydrocortisone
– provides glucocorticoid and mineralocorticoid
– physiological doses
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max 300 mg/day
– normal daily adrenal output
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AM 25 mg /PM 12..5 mg
Dexamethasone
– not cross-reactive with cortisol assays
– no mineralocorticoid activity
– useful while diagnostic testing being completed
Fludrocortisone (Florinef)
– uncommonly required for mineralocorticoid activity
Outcome
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Untreated = 100% mortality
Treated in critically ill = 50% mortality
Cortisol level
– positively correlated to severity of illness
– negatively correlated to survival
ICU Endocrine Emergencies
Questions…?
Bradley J. Phillips, MD
Burn-ICU
SBH-UTMB