Hyponatremia in the Neurosurgical ICU: Who, Why, When

1
Hyponatremia in the Neurosurgical ICU Who, Why,
When?

• Stephan A. Mayer, MDAssociate Professor of
  Clinical Neurology and Neurological
  SurgeryDirector, Neurological Intensive Care
  Unit Columbia University Medical Center
  Department of NeurologyDivision of Stroke and
  Critical CareNew York, New York

2
Disclosure

• Research support
• Novo Nordisk A/S
• Medivance, Inc.
• Consulting
• Novo Nordisk A/S
• Stock Options
• Radiant, Inc.
• Medivance, Inc.
• Speaking Honoraria
• Novo Nordisk A/S
• ESP Pharma
• Astellas Inc.

3
Hyponatremia in CNS Disease

• Subarachnoid hemorrhage (SAH)
• Intracerebral hemorrhage (ICH)
• Massive cerebral infarction
• Severe traumatic brain injury
• Meningitis/encephalitis
• Others

Tendency to Develop Hyponatremia
CNScentral nervous system.
4
Why Is Hyponatremia Bad in Acute Brain Injury?

• In the old days, neurosurgeons assumed that brain
  edema could be treated with fluid restriction,
  dehydration, and negative fluid balance
• We now know that ICP and tissue water content
  correlate primarily with water balance, not fluid
  balance
• Free water tends to flow down its osmotic
  gradient into areas of injured brain
• Tissue damageideogenic osmoles

ICPintracranial pressure.
5
NICU Fluid Management Principles
Free Water Neuro-ICU No-No

• Give only isotonic crystalloids
• Normal saline
• Ringers lactate solution
• Avoid all sources of free water
• NO D5W or half-normal saline
• NO half-concentrated feeds
• Maintain euvolemia
• Positive fluid balance
• CVP gt5 mm Hg

CVPcentral venous pressure NICUNeurosurgical
ICU.
6
ICP Housekeeping Issues

• Elevate head of bed 30
• Use only isotonic fluids (0.9 saline)
• Control fevers aggressively
• Seizure prophylaxis
• No routine steroids

Option 3 saline (1 mL/kg/h) or mannitol for
target osmolality of 300 to 320 mOsm/L
7
Why Do Neuro Patients Become Hyponatremic?
8
Cerebral Salt Wasting (CSW)?

• Several case reports in the 1950s linked
  hyponatremia after brain injury with cerebral
  salt wasting
• Patients developed hyponatremia, hypovolemia,
  and natriuresis
• Corrected only with administration of large
  volumes of isotonic saline
• Misconception CSW is a specific, isolated
  phenomenon that afflicts a small number of
  patients (like diabetes insipidus)

9
Syndrome of Inappropriate ADH Release (SIADH)

• Subsequently SIADH was described in lung cancer
  and CNS disease
• CNS control of antidiuretic hormone (ADH) release
  recognized
• Release of ADH is inappropriate relative to
  serum normal to low serum osmolality
• MISCONCEPTION hyponatremia in patients with CNS
  disease is universally attributed to SIADH

10
Hyponatremia Following SAH

• Occurs in up to one third of patients
• Gradual onset over several days
• Time course parallels that of vasospasm
• More common with severe hemorrhage

MCA aneurysm
11
ADH Levels After SAH
14
Normonatremic
12
Hyponatremic
10
8
Plasma AVP (pg/mL)
6
4
2
0
0
3
6
9
12
Day After Hemorrhage
Diringer et al. Ann Neurol. 199231543-550.
12
SIADH Physiology in SAH
Diringer et al. Ann Neurol. 199231543-550.
13
Etiology of Hyponatremia After SAH

• Initially attributed to SIADH
• Reports of elevated ADH in blood and CSF of SAH
  patients1
• Hyponatremia from SIADH was corrected with
  fluid restriction
• The results were disastrous

CSFcerebrospinal fluid. 1. Mather et al. J
Neurol Neurosurg Psychiatry. 198144216-219.
14
Impact of Fluid Restriction on Cerebral
Infarction After SAH
Death occurred more frequently among patients
with hyponatremia (12 of 27 patients) than among
normonatremic patients (6 of 19 patients Plt.01)
Number of Patients
21
81
33
Wijdicks et al. Ann Neurol. 198517137-140.
15
Natriuresis After SAH

• Hyponatremic patients found to have low blood
  volume1
• Model of hyponatremia in SAH2
• Negative sodium balance
• Reduction in intravascular volume
• Suppression of renin levels
• No change in aldosterone levels

1. Nelson et al. J Neurosurg. 198155938-941 2.
Nelson et al. J Neurosurg. 198460233-237.
16
Substantial Volume Resuscitation Is Required in
SAH Patients

• Normovolemic therapy1
• 1.5 to 2.0 liters/day of crystalloid
• Plasma volume fell by 50
• Negative sodium balance preceded hyponatremia
• Hypervolemic therapy2
• 5.0 to 10.0 liters/day of crystalloid
• Plasma volume did not fall
• Neutral sodium balance maintained

1. Wijdicks et al. Ann Neurol. 198518211-216
2. Diringer et al. Ann Neurol. 199231543-550.
17
Hypervolemic Therapy Prevents Negative Sodium
Balance After SAH
Hyper CVP ?8
Normo CVP ?5

• Supplemental albumin to maintain a CVP gt8
  eliminated negative fluid balance, but had no
  effect on blood volume, after SAH

ANOVAanalysis of variance.Mayer et al.
Neurosurgery. 199842759.
18
Hypervolemic Therapy Prevents Negative Sodium
Balance After SAH
ANFatrial natriuretic factor.
Mayer et al. Neurosurgery. 199842759.
19
Atrial Natriuretic Factor Atriopeptin

• Circulating ANF markedly elevated after SAH
• ANF not elevated after elective aneurysm surgery
• ANF levels no different in patients with
  hyponatremia
• ANF causes natriuresis via an increase in GFR and
  inhibition of tubular sodium retention

GFRglomerular filtration rate. Diringer et al.
Stroke. 1988191119-1124.
20
Relationship of Increased GFR to Negative Sodium
Balance After SAH
500
R2.21, P.002
400
300
200
100
0
Day 1 Sodium Balance (mEq)
-100
-200
-300
-400
-500
-600
40
60
80
100
120
140
160
180
200
220
240
260
Day 1 GFR (mL/min)
Mayer et al. Neurosurgery. 199842759.
21
The Renin-Aldosterone System How Does It Work To
Preserve Intravascular Volume?
HypotensionHypovolemia
Renal hypoperfusion
? Afferent arteriolar stretch
? NaCl delivery to macula densa
? Sympathetic neural tone
? Renin release
Angiotensin I
Renin substrate
Converting enzyme
Angiotensin II
? Aldosterone secretion
? Systemic blood pressure
? Renal NA reabsorption
Extracellular volume expansion
Renin release
22
Renin and Aldosterone Levels after SAH
4.0
Normonatremic Hyponatremic Hypovolemic
3.2
Plasma Renin Activity (ng/mL/h)
2.4
1.6
NormalRange
0.8
0.0
0
3
6
9
12
70
60
50
40
Aldosterone (mg/dL)
30
20
NormalRange
10
0
0
3
6
9
12
Days After Hemorrhage
23
Summary of Neuroendocrine Changes Triggered by SAH
BNPbrain natriuretic peptide.Wijdicks et al.
Clinical Practice of Critical Care Neurology.
2003.
24
Unifying Hypothesis of Sodium and Water
Dysregulation After SAH
SAH
Primary Neurohormonal Alterations
Catecholamines
AVP
ANP
?
Physiologic Response
Blood Pressure and Cardiac Output
GFR and Sodium Excretion
Secondary Neurohormonal Alterations
Renin and Aldosterone
AVP
Homeostatic Derangements
Free Water Retention
Natriuresis
Hyponatremia
ECF and Plasma Volume Contraction
AVParginine vasopressin ECFextracellular
fluid GFRglomerular filtration rate. Mayer.
Neurologist. 1995171-85.
25
SIADH vs Cerebral Salt Wasting
26
Hyponatremia Therapeutic Options
Hospital transfer sodium is 128 mEq/L on D5
0.45 saline!

• Acute hyponatremia
• Free water restriction
• Normal saline plus furosemide
• Hypertonic saline
• Mannitol
• AVP inhibitor
• Chronic hyponatremia
• Fludrocortisone
• Demeclocycline

27
SAH Treatment With Fludrocortisone

• Prophylactic administration of 0.1 mg bid
• Reduction in sodium excretion
• No impact on serum sodium or intravascular
  volume1
• Administration of 0.3 mg/day reduced sodium and
  volume requirements2

1. Hasan et al. Stroke. 1989201156-1161 2.
Mori et al. J Neurosurg. 199991947-952.
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Nonpeptide AVP Receptor Antagonists
Lee et al. Am Heart J. 20031469-18.
29
Potential Role of a Vasopressin Antagonist in the
Neuro-ICU

• Reverse effects of inappropriately elevated
  levels of ADH
• Correct hyponatremia via a pure aquaresis
• No effect on intravascular volume
• Allow administration of large volumes of fluids
  to treat vasospasm without exacerbating
  hyponatremia
• Allow fine tuning of sodium level to avoid
  rebound drops in Na while weaning hypertonic
  saline
• Adjuvant to 20 mannitol or 23.4 hypertonic
  saline for rapid induction of hyperosmolar state
  to combat ICP or herniation syndromes

30
A Harmful Drop in Serum Osmolality upon
Discontinuation of Hypertonic Saline
31
Titratable Correction of Hyponatremia

• Small, repeated doses of AVP V2-receptor
  antagonists produce a titratable correction of
  hyponatremia that will allow physicians to stay
  within accepted guidelines for safe, controlled
  correction of hyponatremia more easily than
  current therapies such as 3 NaCl.

32
Emergency Treatment of Increased ICP

• Unmonitored patient with clinical signs of
  herniation
• Elevate head of bed 30
• Intubate and hyperventilate (PCO2 28-32)
• Osmotherapy
• Mannitol 20, 1.0 to 1.5 g/kg rapid IV infusion
• Hypertonic saline 23.4, 1.0-2.0 mL/kg IV
• AVP inhibitor aquaresis?
• CT scan and neurosurgical evaluation

PCO2partial pressure of carbon dioxide.