Transcript Evolving Strategies for Hyponatremia Management in the ICU

Evolving Strategies for Hyponatremia
Management in the ICU
Mazen Kherallah, MD, FCCP
Infectious Disease & Critical Care Medicine
Assistant Professor, University of North Dakota
Critical Care Patients at Increased Risk of
Hyponatremia*





Increased age1
Up to 30% of patients with subarachnoid hemorrhage2
Up to 30% of ICU patients3
Over 30% of AIDS patients4
Postoperative patients
 – 25%-35% of pituitary surgery for tumor resection5
 ~30% of acute spinal cord injury6
 Psychiatric inpatients: 6%-17%7
*Data not exclusive to patients with euvolemic hyponatremia.
1. Hawkins RC. Clin Chim Acta. 2003;337:169-172; 2. Mayer SA. The Neurologist. 1995;1:71-85;
3. DeVita MV et al. Clin Nephrol. 1990;34:163-166; 4. Tang WW et al. Am J Med. 1993;94:169-174;
5. Bhardwaj A. Ann Neurol. 2006;59:229-236; 6. Peruzzi WT et al. Crit Care Med. 1994;22:252-258;
7. Siegler EL et al. Arch Intern Med. 1995;155:953-957.
Mortality Related to Hyponatremia Among
Hospitalized Patients
25%
20%
15%
10%
5%
0%
Anderson1
Terzian2
[Na+] <130 mEq/L
1. Anderson RJ et al. An Intern Med. 1995,102: 164-168
2. Terzian C et al. J Gen Intern Md. 1994,9:89-91
3. Tierney WM et al. J Gen Intern Med. 1986;1: 380-385
Tierney3
Normonatremia
Morbidities in Hospitalized Patients with
Symptomatic Hyponatremia
60%
50%
Altered
Sensorium
40%
30%
20%
10%
Seizures
Nausea & Gait Disturbance
Vomiting
& Falls
0%
•
•
•
•
Dysarthria
Coma
Single center, retrospective over 4 years (1997-2001)
168 patients with serum [Na+] <115 mEq/L
Symptoms of hyponatremic encephalopathy in 89 of 168 patient (53%)
No documented symptoms in 79 of 168 patients (47%)
Nzenue CM et al. J Natl Med Assoc. 2003;95: 335-343
Mechanisms of Hyponatremia
↓
[Na+]
𝑁𝑎
=
↑𝐻2𝑂
↓
[Na+]
↓𝑁𝑎
=
𝐻2𝑂
Brain CT Scan: Cerebral Edema
Normal CT Scan
Fatal Hyponatremia
Case I
 44 year old man with schizophrenia is brought to the ED from his group home after
a witnessed tonic-clonic generalized seizure.
 He was well until earlier in the day at which time he became progressively
somnolent.
 His medications include haloperidol, quetiapine and citalopram.
 On exam he is afebrile, BP 120/78, HR 92. He is somnolent but arousable and
following commands, is euvolemic, and there are no focal findings.
 His urine output is 120 ml/hour
Serum
Urine
Na
116 mEq/L
Na
35 mEq/L
K
3.9 mEq/L
K
15 mEq/L
Creat
0.8 mg/dL
Osm
92 mOsm/kg
Osm
240 mOsm/kg
Question
What is the most likely etiology of this man’s
hyponatremia?
a)
b)
c)
d)
e)
Syndrome of inappropriate antidiuresis
Psychogenic polydipsia
Pseudohyponatremia
Adrenal insufficiency
Cerebral sat wasting
The Diagnosis of Hyponatremia:
Three Critical Questions
Is it real?
Is water excretion
appropriate?
Is ADH excretion
“appropriate”?
Assessment of Hyponatremia:
Three Critical Questions
1. Is it real?
Plasma Osmolality
Normal or High
Pseudohyponatremia
Hyperglycemia
Azotemia, ETOH Intoxication
92
Low
mOsm/kg
(< 100
mOsm/kg)
Psychogenic polydipsia
240
Low
mOsm/kg
2. Is water excretion appropriate?
Urine Osmolality
High
(>100 mOsm/kg)
3. Is ADH secretion appropriate? (Volume Status)
Hypovolemia
Euvolemia
Hypervolemia
Appropriate ADH Secretion
Inappropriate ADH
Maladaptive ADH Secretion
Total body water ↓
Total body Na+ ↓↓
Total body water ↑
Total body Na+ ↔
Total body water ↑↑
Total body Na+↑
U[Na+] >20 mEq/L
Renal Losses
Diuretic excess
Mineralocorticoid
deficiency
Bicarbonaturia with
tubal acidosis and
metabolic alkalosis
Ketonuria
Osmotic diuresis
U[Na+] <20 mEq/L
U[Na+] >20 mEq/L
Extrarenal losses
Vomiting
Diarrhea
Third spacing of
fluids
Burns
Pancreatitis
Trauma
Glucocorticoid deficiency
Hypothyroidism
Syndrome of inappropriate
ADH secretion
U[Na+] >20 mEq/L
Acute or chronic
renal failure
U[Na+] 20 <mEq/L
Nephrotic syndrome
Cirrhosis
Cardiac failure
Case II
 46-year-old woman admitted to
Neurocritical Care Unit confused and
mildly lethargic secondary to subarachnoid
hemorrhage
 Past medical history: hypertension, tobacco
smoker
 BP 170/78 mm Hg, HR 71 bpm
 0.9% saline administered at 100 mL/h
 CVP 6-8 mm Hg
 Mildly positive fluid balance
 Remained confused and disoriented, but
lethargy gradually resolved
In the Step-Down Unit
 Day 9 post-SAH
 Patient transferred to step-down unit
 Central venous IV catheter discontinued
 IV fluid: normal saline administered at 100 mL/h through peripheral IV
 Day 10 post-SAH
 The patient appeared to be more confused
 Serum [Na+] = 126 mEq/L
Serum
Urine
Na
126 mEq/L
Na
45 mEq/L
K
3.6 mEq/L
K
17 mEq/L
Creat
0.7 mg/dL
Osm
292 mOsm/kg
Osm
258 mOsm/kg
Question
What is the most likely etiology of this patient’s
hyponatremia?
a)
b)
c)
d)
e)
SIADH
Psychogenic polydipsia
Pseudohyponatremia
Adrenal insufficiency
Cerebral sat wasting
Assessment of Hyponatremia:
Three Critical Questions
1. Is it real?
Plasma Osmolality
Normal or High
258
Low
mOsm/kg
2. Is water excretion appropriate?
Urine Osmolality
Low
(< 100 mOsm/kg)
Pseudohyponatremia
Hyperglycemia
Azotemia, ETOH Intoxication
Psychogenic polydipsia
High
292
(>100 mOsm/kg)
mOsm/kg
3. Is ADH secretion appropriate? (Volume Status)
Hypovolemia
Euvolemia
Hypervolemia
Appropriate ADH Secretion
Inappropriate ADH
Maladaptive ADH Secretion
Total body water ↓
Total body Na+ ↓↓
Total body water ↑
Total body Na+ ↔
Total body water ↑↑
Total body Na+↑
U[Na+] >20 mEq/L
Renal Losses
Diuretic excess
Mineralocorticoid
deficiency
Bicarbonaturia with
tubal acidosis and
metabolic alkalosis
Ketonuria
Osmotic diuresis
U[Na+] <20 mEq/L
U[Na+] >20 mEq/L
Extrarenal losses
Vomiting
Diarrhea
Third spacing of
fluids
Burns
Pancreatitis
Trauma
Glucocorticoid deficiency
Hypothyroidism
Syndrome of inappropriate
ADH secretion
U[Na+] >20 mEq/L
Acute or chronic
renal failure
U[Na+] 20 <mEq/L
Nephrotic syndrome
Cirrhosis
Cardiac failure
Question
How would you treat this patient?
a)
b)
c)
d)
e)
Fluid restriction (<2 L/d)
Salt tablets (NaCl 2 g/d)
Normal saline infusion
3% hypertonic saline
IV Conivaptan
Treatment Considerations
• Often unknown
• >2 days
• Acute reduction
in chronic state
• More brain
adaptation with
chronic
Acute or Chronic
Severity of
Hyponatremia
• Mild: >129
• Moderate:
121-129
• Severe <120
• Severe Symptoms or
Intracranial
Pathology: seizures,
impaired mental
status or coma
• Moderate:
confusion, lethargy,
• Mild: fatigue,
nausea, dizziness,
gait disturbances,
forgetfulness nd
muscle cramps
• Asymptomatic
Severity of
Symptoms
Treatment Goals
• Treat cerebral
edema
• Relieve symptoms
and prevent
progression of
neurologic
dysfunction
• Prevent osmotic
demyelination
syndrome
• 4-6 meq/24 hrs (<9
meq/L in any 24
hrs)
Treatment Strategies
• Treat pain,
nausea,
vomiting,..
• cessation of
therapy with
certain drugs
• glucocorticoids
to patients with
adrenal
insufficiency
Treat Underlying
Cause
Restoration of
Euvolemia
• Saline to patients
with true volume
depletion
• Diuretics in
edematous states
(such as heart
failure and
cirrhosis)
•Fluid restriction in
SIADH
Balancing the
Effect of ADH
Correction of Na
and Rate of
Correction
• Hypertonic
saline
• Normal saline
• Salt tablets
Sodium deficit= TBW (desired SNa-actual SNa)
Increase in SNa= (infusate [Na]-SNa) ÷ (TBW+1)
Treatment Options
• Rapid increase in Na 46 meq/L (in 6 hours)
• 3% saline 100 mL IV
bolus
• Repeat 1-2 X at 10
minutes intervals if
symptoms persist
• ≤ 9 meq/L in 24 hours
• (NS in hypovolemia)
• Hypertonic saline
• Increase Na 0.5-1
meq/hour in the first 4
hours
• 4-6 meq in 24 hours
Severe
Symptoms:
Seizure or
coma
Moderate
Symptoms:
Confusion
and/or
lethargy
Mild or
abscent
symptoms:
Na ≤120
meq/L
Mild or
abscent
symptoms:
Na > 120
meq/L
• Hypertonic saline
• Increase Na 0.5-1
meq/hour in the first 4
hours
• 4-6 meq in 24 hours
(<9 meqin any 24
hours)
• (NS in hypovolemia)
• Fluid restriction (<UO or
<800 ml/day)
• Salt tablets
• V2 receptors
antagonists
Treatment Course for This Patient
 A 20 mg loading dose of conivaptan followed by a
continuous infusion of 20 mg/d
 24 hour after the start of the loading dose, the serum [Na+]
increased from 126 to 132
 A second 24 hour contineous infusion given
SAH
Day
Serum [Na+]
(mEq/L)
24 Hour Fluid
Balance (L)
Conivaptan
Treatment Day
10
126
+0.2
1
11
132
-0.8
2
12
138
-1.2
3
Day 2 of Treatment
 The next day serum [Na+] increased from 132 to138 mEq/L
 Mental status: less confused
 Conivaptan discontinued
 Patient discharged to rehabilitation on SAH Day 13
Receptor-Mediated Effects of VAP
Receptor Subtype
Site of Action
Activation Effects
V1a
Vascular smooth muscle
cells
Platelets
Lymphocytes and
monocytes
Adrenal cortex
Vasoconstriction
Platelet aggregation
Coagulation factor release
Glyconeogenesis
V1b
Anterior pituitary
ACTH and ß-endorphin
release
V2
Renal collecting duct
principal cells
Free water absorption
Lee CR et al. AM Heart J. 2003;143:9-18
Hyponatremia in Acute Brain Injury
Therapeutic Options
Speed
Situation
Pluses
Minuses
Free water
restriction
Slow
Hard to
regulate
NS+furosemide
Sow
Electrolyte
depletion
Fludrocortisone
Slow
Fluid overload
AVP Inhibitor
Faster
Asymptomatic Reliable effect
hyponatremia
Infusion site
reactions
Mannitol
Fatsest
Symptomatic
hyponatremia
Reduce
Edema
Can worsen
hypovolemia
Electrolyte
depletion
Hypertonic
saline
Fastest
Symptomatic
hyponatremia
Reduce brain
edema
Fluid overload
Thank you