Na Disorders: Not so Elementary, Watson.tlcveterinaryforum.com/wp-content/uploads/2015/10/Sodium-Disorders... · If severe or rapid in onset: -Obtundation Coma ... Postobstructive

Na+ Disorders: Not so Elementary, Watson.

Polly A. Glover, DVM, DACVECC Animal Emergency Critical Care at The Life Centre

TLC Veterinary Forum October, 2015

Topics

Total Body Water

Osmolality & Osmotic Pressure

Regulation of Plasma Osmolality

Hypernatremia

Hyponatremia

Sodium Concentration [Na+] Disorders

Why do they matter?

Alterations in plasma [Na+] are associated with poor outcomes in critically ill humans & veterinary patients

Even changes within the normal range carry an increased mortality risk

Is increased risk a function of [Na+] changes being detrimental or are [Na+] changes a hallmark of more severe disease processes?

[Na+] Disorders

Most cases of Na+ disorders are problems with water handling in the body (osmoregulation) rather than increases or decreases in [Na+]

Total Body Water (TBW)

Body water = 60% of adult animal’s body weight

0.6 x lean BWkg = Liters of TBW

Intracellular Fluid (ICF) = 2/3 of TBW

Extracellular Fluid (ECF) = 1/3 of TBW -Interstitial space = 75% of ECF -Intravascular space = 25% of ECF



Osmole = 1 mole of any fully dissociated substance dissolved in H2O

NaCl = Na + Cl = 1 mole Na + 1 mole Cl = 2 moles total

Osmolality = Concentration of osmoles in a mass of a substance (mOsm/kg of H2O)

Osmolarity = Concentration of osmoles in a volume of solvent (mOsm/L of H2O)

In physiologic systems, no appreciable difference – use ‘osmolality’ for remainder of presentation


Every molecule dissolved in TBW contributes to osmolality

Molecular size, weight, charge and composition DO NOT matter

The NUMBER of dissolved molecules determine osmolality & therefore osmotic pressure

Most abundant molecules in ECF: -Na+ -Glucose -Urea


Effective osmoles: Do not freely cross semi-permeable cell membrane (Na+, K+); exert osmotic pressure across cell membrane

Ineffective osmoles: Freely cross semi-permeable cell membrane (glucose, urea); do not normally exert osmotic pressure across cell membrane

Osmotic pressure causes H2O to move from area of lower osmolality (higher [H2O]) to area of higher osmolality (lower [H2O]) down its concentration gradient

Occurs until osmolality in compartments equal


Na+, glucose, urea = main determinants of plasma osmolality in healthy dogs & cats

Plasma Osmolality

Dog: 290 – 310 mOsm/kg

Cat: 290 – 330 mOsm/kg

Measured plasma osmolality via freezing-point depression osmometry

Calculated plasma osmolality =

2 (Na+ + K+) + (BUN/2.8) + (Glucose/18)

*2.8 and 18 are conversion factors (mg/dL to mmol/L)

Regulation of Plasma Osmolality

Hypothalamic osmoreceptors sense changes in plasma osmolality

Osmolality changes of 2-3 mOsm/kg induce compensatory mechanisms to return plasma osmolality to hypothalamic set point

Two major physiologic mechanisms: 1. Antidiuretic hormone system (ADH) 2. Thirst

ADH/Vasopressin

Small peptide secreted by posterior pituitary gland

Two major stimuli for release: 1. Elevated plasma osmolality 2. Decreased effective circulating volume (ECV)

ECV = Volume of arterial blood effectively perfusing tissue. Dynamic quantity – not a measureable, distinct compartment.

ADH/Vasopressin

Increased plasma osmolality hypothalamic osmoreceptor shrinkage neural impulses to posterior pituitary ADH release

Low ECV Aortic arch & carotid bodies’ baroreceptor cells stimulated neural impulses to posterior pituitary ADH release

ADH/Vasopressin

No ADH renal tubular collecting ducts relatively impermeable to H2O

ADH activates V2 receptors on collecting duct cells to insert AQP-2 molecules into membrane

AQP-2 molecules form water pores H2O moves into cells down osmotic gradient into hyperosmolar renal medulla

If no hyperosmolar renal medulla (renal ‘washout’) – ADH will not work!

ADH/Vasopressin

Circulating ADH & its effects on the normal kidney are the primary

physiologic determinants of free H2O retention & excretion.

Thirst

Hyperosmolality & decreased ECV stimulate thirst

Mechanisms similar to pathways for ADH secretion

Thirst + H2O consumption are main determinants of free H2O intake

Osmolality versus ECV

Normal physiologic conditions: -RAAS monitors & fine-tunes ECV -ADH system maintains plasma osmolality

Maintenance of ECV always prioritized over maintenance of normal plasma osmolality

Patients with poor ECV will have increased thirst & ADH release regardless of plasma osmolality

Hypernatremia

Plasma [Na+]

Normal plasma [Na+]:

-Dog: 145 - 150 mEq/L

-Cat: 155 - 160 mEq/L

*Moderate hypernatremia: [Na+] > 170

*Severe hypernatremia: [Na+] > 180 mEq/L

*Both species by convention

Hypernatremia (HyperNa+)

Most cases due to free or hypotonic H2O loss, not excessive Na+ intake or

retention

HyperNa+: Clinical Signs

In many cases, there are no specific signs.

All cells with Na+-K+/ATPase pumps shrink as H2O moves out of cell & down concentration gradient to interstitium

Neurons clinically least tolerant to changes in cell volume

If severe or rapid in onset: -Obtundation Coma -Head-pressing -Seizures -Death

HyperNa+: Adaptation

Slow development of hyperNa+ allows adaptation

Patient less symptomatic or asymptomatic

Brain has multiple ways to protect against & reverse neuronal H2O loss

HyperNa+: Early Adaptation

Within minutes to hours of hyperosmolar state:

Neuronal H2O lost to hyperNa+ circulation, neurons shrink

As plasma osmolality increases further, Na+ moves rapidly from CSF cerebral tissue

Minimizes brain volume loss – H2O follows Na+ into interstitium & neurons

Early fluid & ionic shifts protect brain from magnitude of volume loss expected for given plasma hyperosmolality

HyperNa+: Late Adaptation

Within 24 hours to 7 days:

Neurons accumulate organic solutes to increase ICF osmolality & shift H2O back into ICF

Idiogenic osmoles

-Inositol -Glutamine -Glutamate -Others

HyperNa+: Treatment

Hypernatremia should be treated, even if no clinical signs are present.

HyperNa+: Treatment

The most important questions:

1. What caused the hypernatremia?

2. How rapidly did the hypernatremia occur?

3. What are the neurologic, hydration, & IV volume statuses of my patient?

4. What IV crystalloid should I use?

5. What should the IV fluid rate (IVFR) be?

6. How often should I be monitoring plasma [Na+] & performing neurologic exams on my patient?

HyperNa+: Causes of Free Water Deficit

Denied H2O access for extended period

Prolonged panting – high environment/body temperature

Diabetes Insipidus

Hypodipsic hyperNa+ (Miniature Schnauzers)

HyperNa+: Causes of Hypotonic Fluid Deficit

GI loss: Vomiting, diarrhea

Third-space fluid loss

Renal disease: CKD, nonoliguric AKI

Postobstructive diuresis

Osmotic diuresis: Mannitol, diabetes mellitus

Activated charcoal + sorbitol

Low Na+ polyuria (diuretics)

HyperNa+: Causes of Na+ Excess

Hyperaldosteronism

Hyperadrenocorticism

Salt poisoning (rock salt, chemicals, seawater, brackish water, beef jerky, homemade play dough)

Sodium phosphate enemas

Hypertonic saline

NaHCO3 infusion

Parenteral nutrition

HyperNa+: Treatment

Must assess volume status of your patient! Hydration ≠ Perfusion

Hydration issues (dog & cat): Dry mucous membranes, loss of eye sheen, sunken eyes, skin tent, dandruff/dry coat, dry rectal mucosa, hard/firm feces

Early perfusion issues (dog): Tachycardia, normo- or hypertension, bounding/thready pulses, CRT < 1 second, typically normothermic

Early perfusion issues (cat): Bradycardia, normo- or hypotension, fair/weak pulses, CRT unreliable, normo- to hypothermic

HyperNa+: Treatment

In small animal medicine, most hyperNa+ patients will have hypotonic fluid losses resulting in some level of dehydration and/or intravascular volume depletion.

HyperNa+: Treatment

Must know onset of primary clinical signs!

-Profuse vomiting/diarrhea for 12 hours or 2-3 days?

-Outside in summer heat 1 hour ago or 24 hours ago?

-Large ingestion of beef jerky today or on NFL Sunday?

Rapidity of hyperNa+ onset will dictate how quickly you can normalize plasma [Na+] in your patient.

HyperNa+: Free H2O Loss Treatment

What crystalloid should I use? 5% dextrose in water (D5W)

Free H2O Deficit =

([current [Na+]p ÷ normal [Na+]p] – 1) x (0.6 x BWkg) current [Na+]p = patient’s current plasma [Na+]

normal [Na+]p = Patient’s normal plasma [Na+] BWkg = Patient’s body weight in kg

HyperNa+: Free Water Loss Treatment

Free water replacement alone will not correct clinical dehydration or hypovolemia

2/3 of volume administered will enter cells

Relatively safe to replace free water in hypernatremic patients – even those with renal & cardiac disease


What IVFR should I use?

If hypernatremia acute in onset, can correct plasma [Na+] rapidly with D5W – no idiogenic osmole formation

With more prolonged or unknown onset, use guidelines:

Moderate hyperNa+ (> 170 mEq/L): Decrease plasma [Na+] no more than 1.0 mEq/L/hr

Severe hyperNa+ (> 180 mEq/L): Decrease plasma [Na+] no more than 0.5 – 1.0 mEq/L/hr


If there are severe neurologic signs present, rapidly administer serial 10-20

mL/kg aliquots of D5W until clinical signs improve.

HyperNa+: Hypotonic Fluid Loss

What crystalloid & rate should I use?

Plasma [Na+] < 170 mEq/L typically can use balanced electrolyte replacement solution for rehydration & resuscitation purposes

Plasma [Na+] > 170 mEq/L resuscitate with IVF that has [Na+] that matches patient +/- 6 mEq/L

Plasma [Na+] > 170 mEq/L rehydrate with IVF that has [Na+] lower than patient but will not drop plasma [Na+] over 10 mEq/L in 24 hour period or 18 mEq/L over 48 hours

THIS IS VERY HARD TO DO!


Adding Na+ to a balanced electrolyte solution or 0.9% NaCl:

23.4% hypertonic saline = 4 mEq NaCl/mL solution

7.2% hypertonic saline = 1.2 mEq NaCl/mL solution

3% hypertonic saline = 0.5 mEq NaCl/mL solution

Add calculated volume to the fluid bag

Remember to factor in the Na+ already in the fluid bag!


What crystalloid & rate should I use?

Resuscitation must happen fast! Up to 90 mL/kg IVF in 10-20 mL/kg aliquots

If [Na+] not immediately known – do not delay therapy waiting for results, treat with balanced electrolyte solution

Rehydration should always occur over a time frame that closely mirrors the onset of dehydration (hours or days?)

Rehydration volume (L) = (% dehydration x BWkg) + 60 mL/kg/d

HyperNa+: Iatrogenic IVF

What to do when plasma [Na+] starts to steadily climb while on replacement IVF therapy for rehydration?

Change to maintenance solution or 0.45% NaCl + 2.5% dextrose +/- KCl if patient well hydrated

‘Piggy-back’ 0.45% NaCl + 2.5% dextrose with balanced electrolyte solution if patient still dehydrated

If cardiac or renal patient, recommend changing to 0.45% + 2.5% dextrose IVF earlier to prevent volume overload

HyperNa+: Therapeutic Considerations

Consider nasoesophageal or nasogastric tube placement for enteral H2O administration in patients not vomiting

Consider furosemide for natriuresis in neurologic crises

Desmopressin therapy for diabetes insipidus

Monitor blood pressure closely & treat PRN – hypertension typically improves and/or resolves with plasma [Na+] reduction

HyperNa+: Therapeutic Complications

Primary complication = Cerebral edema

Clinical Signs: Obtundation, head pressing, coma, seizures, other disorders of behavior/movement

Remember to check plasma [Na+] – clinical signs may be related to treatment or worsening hypernatremia!

Mannitol 0.5 – 1.0 g/kg IV over 20-30 minutes

Hypertonic saline (7.2%) 3-5 mL/kg IV over 20 minutes -If no mannitol -If mannitol ineffective

HyperNa+: Monitoring

Monitor vital parameters & neurologic status every 2-4 hours or more frequently if necessary

Monitor plasma [Na+] initially every 4 hours, or immediately after any large volume IVF bolus

Majority of patients require several days in 24 hour referral hospital – exception are some free water loss patients

Further diagnostics need to be performed to determine underlying disease process

Be sure real-time plasma Na+ levels available to guide therapy

Hyponatremia

Plasma [Na+]

Normal [Na+]:

-Dog: 145 - 150 mEq/L

-Cat: 155 - 160 mEq/L

Moderate hyponatremia: [Na+] < 130 mEq/L

*Severe hyponatremia: [Na+] < 120 mEq/L

*Both species by convention

Hyponatremia (HypoNa+)

Clinically detrimental hypoNa+ uncommon in critically ill dogs & cats

Almost always free H2O retention in excess of Na+

retention

May have Na+ loss

Generation typically requires H2O intake + decreased H2O excretion

HypoNa+: Adaptation

ICF/interstitial edema in CNS increase in intracranial hydrostatic pressure

enhances fluid movement into CSF CSF flows out of cranium

subarachnoid space central spinal canal venous circulation

HypoNa+: Adaptation

Swollen neurons expel solutes: Na+, K+, organic osmolytes

Decreases intracellular osmolality & encourages H2O loss into ECF

Ion expulsion occurs rapidly

Loss of organic osmolytes requires hours to days

HypoNa+: Treatment

The most important questions are the same as with hyperNa+:

1. What caused the hyponatremia?

2. How rapidly did the hyponatremia occur?

3. What are the neurologic, hydration, & volume statuses of my patient?

4. What IV crystalloid should I use?

5. What should the IV fluid rate (IVFR) be?

6. How often should I be monitoring plasma [Na+] & performing neurologic exams in my patient?

HypoNa+: Causes

Decreased ECV

Hypoadrenocorticism

Diuretics

GI parasitism

Syndrome of Inappropriate ADH secretion (SIADH)

Infectious/inflammatory disease

Psychogenic polydipsia

Pregnancy

Cerebral salt-wasting syndrome (CSW, humans)

Artifact: Lipemic, hyperproteinemic samples

HypoNa+: Pseudohyponatremia

Diabetes mellitus

Diabetic ketoacidosis – Balanced electrolyte solution or 0.9% NaCl

Hyperglycemic hyperosmolar syndrome – recommend 0.9% NaCl therapy

Mannitol administration

HypoNa+: Clinical Signs

Mild to moderate [Na+] change usually no specific signs

If severe (Na+ < 120 mEq/L) or rapid occurrence – CNS signs same as with hyperNa+

All cells with Na+/K+-ATPase pumps swell as H2O moves into relatively hyperosmolar cell from hypoosmolar ECF

Neurons least tolerant of over hydration

HypoNa+: Asymptomatic Treatment

HypoNa+ due to decreased ECV most often mild (Na+ > 130) & self-corrects with treatment of underlying disease

Avoid IVF with [Na+] less than that of patient

HypoNa+: Symptomatic Treatment

If a patient is symptomatic, whether acute or chronic, it requires emergency

therapy;

however….

the best management style is controversial.

HypoNa+: Symptomatic Treatment

Goal = Raise plasma [Na+] enough to resolve clinical signs without causing

complications

HypoNa+: Symptomatic Treatment #1

1. Mannitol (0.5 g/kg IV) or furosemide (0.5 mg/kg IV) for electrolyte-free H2O loss

2. Replace fluid loss with a replacement crystalloid unless patient is overhydrated

3. Raise plasma [Na+] < 10 mEq/L over 1st 24 hours

4. Rate per day more important than rate per hour

5. Raise plasma [Na] < 18 mEq/L over 48 hr


Calculate Na+ deficit: (target [Na+]p – patient [Na+]p) x (0.6 x lean BWkg)

Target [Na+]p = desired patient plasma [Na+]

Target [Na+] = no more then 10-15% higher than current plasma [Na+] in 1st 24 hours

Calculated deficit determines amount of 3% hypertonic Na+ (0.5 mEq/mL) to be infused


Human medicine strategy:

1. Raise [Na+] by 10-15% in first 24 hours

2. Rate of correction as great as 15 mEq/L in 1st 24 hours

3. Not more than 2 mEq/L/hr increase in plasma [Na+] for first few hours

HypoNa+: Fluid Resuscitation

Plasma [Na+] < 130 mEq/L resuscitate with IVF with [Na+] that matches patient +/- 6 mEq/L

Balanced electrolyte solution with 130 mEq/L Na+ = lactated Ringer’s solution (LRS)

Add Na+ to maintenance solution to make [Na+] = patient’s plasma [Na+]

HypoNa+: Therapeutic Complications

Major complication = Thalamic myelinosis (dogs)

Neuronal shrinking away from myelin sheath as H2O moves out of neuron during correction of hypoNa+

Clinical signs occur many days after intervention

Overzealous correction paresis, ataxia, dysphagia, obtundation, other neurologic signs

Typically when [Na+] < 110 mEq/L & recommended replacement rates exceeded

HypoNa+: Therapeutic Complications

What to do if clinical signs develop during therapy:

Discontinue any hyperosmolar fluids

Immediately check plasma [Na+]

Treat with addition of free water (D5W)

Decreasing plasma [Na+] in already hypoNa+ patients can be difficult without concurrent loop diuretic

Preparedness Pearls

Collect blood samples prior to administering IVF every time if possible

Run electrolytes promptly – particularly if neurologic patient

Take stock of your crystalloids – recommend having replacement & maintenance solutions available +/- D5W

Keep hypertonic saline on the shelf (7.0 - 23.4%)

Prepare clients for potential neurologic complications – particularly if hyponatremic

Remember: Slow & steady wins the race!

Questions?

Documents

Na Disorders: Not so Elementary, Watson.tlcveterinaryforum.com/wp-content/uploads/2015/10/Sodium-Disorders... · If severe or rapid in onset: -Obtundation Coma ... Postobstructive