ICU Grand RoundsAugust 8th, 2003

Dr. G Alvarez

Dr. B. Cartwright

Hypo Na: Not SIADH!

Case Presentation

• 29 y.o. Irish Tourist arrived Sydney 28/7/03– “cold” resolving over a week before flight– dry cough, rhinorrhea, itchy eyes– driving from airport, vomited twice– stayed @ home most of day and slept

Case Presentation

• 29/7: walking around Opera house and gardens

– slept on grass, anorexic, lethargy, light headed– saw MD @ Martin place, BP 95/60– that evening, witnessed TC seizure for 2 min

• Emergency– GCS 10, BP 97/66, P92 sinus, T 36 39C– delirious and combative

Case Presentation• Emergency

– Given Ceftriaxone 2gm IV, NS @ 250/hr– CT head Normal– ABG: 7.44/34 co2 /84 o2 /23 ho3– Toxic screen negative– hgb 122, wbc 2.86, plt 186,

– Na 112, Cl 76. – LFT/Ca/Po4/glc/Cr/Coag/ESR N

What do You want now?

• Physical Exam

Dehydrated

• Laboratory Exam

– Posm 262

– Uosm 460

– UNa 106

– UrineK <10

Case Presentation• 30/7 @ 0730

– Intubated b/c GCS 7, hypotensive

• 30/7 @0900– I thought she was dehydrated– volume and eventually Noradrenaline– correct Na to “safe” range 120mmol/L– correct 120 to 140 over 48hours– aim 10mmol/L first 24 hours– gave her 200mg hydrocortisone, then 100mg q6

Case Presentation• EEG

– generalized delta wave slowing– minimal activity 2nd to sedation?– NO seizure activity

• Lumbar puncture– Normal glucose and protein– No wbc or rbc seen– started on Ceftriaxone and Acyclovir

Case Presentation

• PiCCO inserted– CI 5.05– SVRI 1072– ITBVI 695 NorAD @ 0.08ug/kg/min– EVWLI 10– MAP 75– FiO2 25%

SO, what do you think now?

• I spoke with patient on medical floor– April/2000 admitted to Cairns Hospital with

diagnosis of viral gastroenteritis– malaise, N/V, fever, arthralgias and myalgias

• Cuts her vacation short and returns to Ireland

The 3 years before her return

• Over the next year– crampy stomach pain, N/V and diarrhoea– anorexia, wt loss and weakness– postural dizziness and low BP– GI Physician: endoscopy showed reflux

esophagitis, IBS and Rx PPI– “I craved salty foods like bacon and chips”– “people told me I really kept my tan a long time”

Back to the case

• Random am Cortisol: 43! (155-599)

• ACTH 536 (0-50)

• Neurology involved, wanted MRI b/c poor pupils reflex and didn’t know what was going on?– Normal MRI

The rest of the tests

• TSH, free T4 Normal

• Troponin 0.5• Procalcitonin 17.3 (I stopped Ab and acyclovir)• CSF viral PCR negative• Legionella, Chlamydia, Mycoplasma serology

The happy end of the story

• Extubated the next day to room air

• Still delirious but improved each day

• Transferred to ward Day 3

• Switched to oral steroid and mineralcorticoid replacement

• Discharged home august 8th, 2003

Lets talk Low Sodium

• Figure out Volume status?

• Order Urine Osm, electrolytes and Posm

• Euvolemic HyponatremiaSIADH

polydipsia (Uosm <80)

post-surgical, narcotics or sedatives

Endocrine: hypothyroid and hypoadrenal

Why does endocrine failure cause low Na?

• HypoThyroid Cardiac output and GFR ADH secretion to hemodynamic stimulus

• HypoAdrenal1. ADH (a) indirectly 2nd volume depletion

(b) directly b/c co-secreted with CRF

2. mineralcorticoids

Distributive Shock

• Septic– Hyperdynamic not hypodynamic

• Neurogenic• Anaphylaxis• Hypoadrenal

• All characterised by low systemic vascular resistance and low filling pressures

Hypothalamic-pituitary-adrenal axis

• copes with stresses such as infections, hypotension, and surgery

• anterior pituitary amplifies requests from the hypothalamus

• likewise the adrenal cortex responds to corticotropins to produce cortisol

• negative feedback system

Cortisol

• 5-10% free; rest bound to binding globulin

• role in– metabolism CHO, protein– secretion of adrenal androgen/aldosterone– immune response– negative feedback control of:

• corticotropin, CRH, ADH by glucocorticoid Rcs

Adrenal Insufficiency

• Primary versus Secondary

• Abrupt versus slow onset

• Abrupt primary more likely to occur in the ICU setting such as adrenal haemorrhage or necrosis with sepsis

Differential diagnosis of adrenal insufficiency - ACUTE

• PRIMARY– adrenal haemorrhage,

necrosis or thrombosis

– occurs in sepsis, coagulopathy and antiphospholipid syndrome

– post-adrenal surgery for Cushing’s

• SECONDARY– postpartum pituitary

necrosis (Sheehan)

– bleed into pituitary adenoma

– head trauma with pituitary injury

Differential diagnosis of adrenal insufficiency - CHRONIC

• Primary– autoimmune– TB– adreno-

myeloneuropathy– systemic fungal

infections– AIDS– metastatic carcinoma– isolated deficiency

• Secondary– pituitary tumour– craniopharyngioma– pituitary surgery– lymphocytic

hypophysitis– empty sella syndrome– hypothalamic syndrome– long term steroids

Addison’s disease

• In 1855, Thomas Addison described the clinical syndrome of adrenal insufficiency

• In his 43-page monograph, "On the Constitutional and Local Effects of Disease of the Suprarenal Capsules," Addison [15] described 10 cases marked by "anemia . . . feebleness of the heart action . . . a peculiar change of color in the skin occurring in connection with a diseased condition of the 'suprarenal capsules'."

Addison’s disease

• rare, may occur at any age, and affects both sexes equally

• Must involve >90% of adrenal glands

• Previously caused by chronic granulomatous infections such as TB but majority now autoimmune related idiopathic atrophy

• Some also have antibodies to thyroid, parathyroid, and/or gonadal tissue

• increased incidence of chronic lymphocytic thyroiditis, premature ovarian failure, type 1 diabetes mellitus, and hypo- or hyperthyroidism– Two or more of above = polyglandular autoimmune syndrome

Primary adrenalinsufficiency

• destruction of the adrenal cortex

• medulla is usually spared

• but synthesis of adrenaline in the adrenal medulla depends on the presence of high local cortisol concentrations

Primary adrenalinsufficiency

• Presentation– tiredness, weakness, depression

– Commonly misdiagnosed as chronic fatigue syndrome

– anorexia, weight loss (parents thought Anorexia nervosa!)

– dizziness, orthostatic hypotension– nausea, vomiting, diarrhoea– hyponatraemia, hyperkalaemia, hypoglycaemia,

anaemia, lymphocytosis, eosinophilia– hyperpigmentation, vitiligo

Adrenal Insufficiency in ICU

• Need to consider if vasopressor resistant shock with any other features on history or exam as given above

• Especially if associated with abdominal pain, vomiting, confusion, hypotension, typical electrolyte changes and no apparent source of infection

• A plasma cortisol of <25 is diagnostic but need to investigate further if <150mcg/dL

Further tests to investigate a low serum cortisol

• ACTH, CRH levels

• Adrenal antibody levels

• Stimulation response tests

• Will localise pathology along hypothalamic-pituitary-adrenal axis

Management in ICU

• Identify cause

• Replacement steroids: hydrocortisone 200-300mg over the course of the first 24hours

• Correct hypovolaemia and hyponatraemia with isotonic saline

• Supplemental glucose

Long term management

• Symptomatic adrenal insufficiency: Glucocorticoid replacement in the morning, titrated to urinary cortisol levels to reduce side effect profile

• Primary adrenal insufficiency: aldosterone replacement with fludrocortisone

• MedicAlert bracelet + carry steroids for injury / stress / febrile illness

“Sepsis-induced adrenal deficiency syndrome”

• Adrenal insufficiency in septic shock

– Occurs but definition, prevalence and characteristics remain controversial

– Mechanism = mix of: Corticotropin resistance versus reduced glucocorticoid synthesis

• Studies have shown

– a low serum cortisol response to ACTH is associated with a longer length of stay and more severe organ dysfunction

– Nonsurvivors of severe sepsis had lower basal plasma cortisol concentrations

Steroid replacement

• a short corticotropin test at presentation in septic patients can help identify those with relative adrenal insufficiency

• low-dose glucocorticoids reduce mortality rates and the need for vasopressor agents.

• Precisely which patients, how much steroid and other treatment/s is still unclear