Fluids And Electrolytes July1

July 1

Fluids and electrolytes Joel Topf, MD Nephrology Attending St. John Hospital

http:// PBFluids .com

The lungs serve to maintain the composition of the extracellular fluid with respect to oxygen and carbon dioxide, and with this their duty ends. The responsibility for maintaining the composition of this fluid in respect to other constituents devolves on the kidneys. It is no exaggeration to say that the composition of the body fluids is determined not by what the mouth takes in but what the kidneys keep: they are the master chemists of our internal environment. Which, so to speak, they manufacture in reverse by working it over some fifteen times a day. When among other duties, they excrete the ashes of our body fires, or remove from the blood the infinite variety of foreign substances that are constantly being absorbed from our indiscriminate gastrointestinal tracts, these excretory operations are incidental to the major task of keeping our internal environments in the ideal, balanced state.
Homer W. Smith From Fish to Philosopher

Answer:
The percentage of admissions that get either:
IV fluids or
Diuretics

Question: What is 100%?

Answer: The percentage of hospital days that patients get electrolytes drawn

Question: What is 100%?

Fluids and electrolyte issues are ubiquitous The ability to screw up is ubiquitous 132 4.4 108 17 106 34 3.8

Fluids: Total body water

Ideal weight : Females: 45 kg Males: 50 kg Adjusted weight : ideal weight + 0.4 (actual body weight – ideal weight) + 2.3 kg for every inch over 5 feet

67% 28 L 25% 11 L 8% 3 L Blood volume = 5 L

Hemoconcentration
Mr. Jones drank too much and puked his guts out.
On admission his hct is 65%. Up from a recent hematocrit of 40%.
How much water was lost from his vascular space?

Intravenous fluids Dextrose Saline Ringers Lactate Plasma expanders Crystalloids

Dextrose solutions
The convention for naming dextrose solutions is grams percent (g%)
To convert this to conventional mg/dL multiply the g% by 1,000
Example
D5W contains 5g of glucose per 100 mL or
50 g per liter (200 Kcal/liter)
The glucose concentration of D 5 W is 5,000 mg/dL

Dextrose solutions
The glucose concentration in D 5 W is so high to make the fluid isosmotic to plasma
To convert from mg/dL to mmol/L
Divide the mg/dL by the molecular weight of glucose (180) to get mmol/dL
Multiply by 10 to convert mmol/dL to mmol/L
5000 mg/dL 180 mg/mmol 27.8 mmol/dL 10 dL/L 277 mmol/L

Saline
Isotonic saline is the primary fluid for volume resuscitation
Sodium concentration 154 mmol/L
pH of 5.5
When given in large volumes can cause a non-anion gap (hyperchloremic) metabolic acidosis
Dilutional acidosis

Lactated ringers
Contains Na, Cl, K, and Ca at physiologic concentrations
Do not use with hyperkalemia
Do not use with hypercalcemia
Lactate is used to supply alkali
Do not use with lactic acidosis
pH=6.6
The Contents
Sodium: 130 mmol/L
Chloride: 109 mmol/L
Lactate: 28 mmol/lL
Potassium: 4 mmol/L
Calcium: 6 mg/dL

Dextrose Saline Ringers Lactate Plasma expanders

Mr. Jones is down 1.9 L
How much D5W will it take to replace the intravascular volume?
Dextrose distributes in proportion to total body water.
8% of TBW is intravascular
1.9/0.08 = 23.75 L
23.75 liters

How much 0.9% NaCl (or LR) will it take to replace the intravascular volume?
Saline distributes among extracellular compartments.
25% of ECC is intravascular
1.9/0.25 = 7.6 L
7.6 liters

How much blood/albumin will it take to replace the intravascular volume?
Blood/albumin is limited to the intravascular space.
1.9/1.0 = 1.9 L
1.9 liters

What type of IVF would you use?
Patient is post-op from a hysterectomy. She had EBL of 280 mL and her current vitals are BP 113/78, HR 105.
Patient in the Shock-Trauma room of the ED after an MVA vs Peds. His BP is 78/40, HR 140 with a thready pulse.
Patient who is NPO due to resolving pancreatitis. Vital signs are stable. The patient is euvolemic.
Sodium is 163. The patient cannot tolerate oral liquid.

Bicarbonate drips
Do not add bicarb to normal saline
An amp of bicarb has 50 mmol Na per 50 mL (1000 mmol/L)
Add bicarbonate to:
D 5 W: 3-4 amps per liter
0.45 NS: 1-2 amps per liter
Sterile water: 3-4 amps per liter

Answer:
The percentage of admissions that need both:
IV fluids and
Diuretics
Question: What is very few?

Don’t give a drowning man a glass of water
Don’t use IVF and diuretics
Except
Hypercalcemia
Hyperkalemia

Proper use of diuretics: Loops
Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the loop of Henle
They block chloride in the tubular fluid from binding
So loop diuretics (like all diuretics except spironolactone) must get from the blood into the tubular fluid
Secretion in the proximal tubule
Secretion is dependent on renal function
Must increase the dose as renal function deteriorates
Age + BUN

Proper use of diuretics: Loops
Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the loop of Henle
They block chloride in the tubular fluid from binding
So the loop diuretic (like all diuretics except spironolactone) must get from the blood into the tubular fluid
Secretion in the proximal tubule
Secretion is dependent on renal function
Must increase the dose as renal function deteriorates
Age + BUN
Cr x 20

Loop diuretic resistance
Chronic use of loop diuretics results in hypertrophy of distal convoluted tubule
Increased distal reabsorption of sodium and fluid attenuate diuretic response
Addition of a thiazide diuretic can restore loop sensitivity

Loop diuretic resistance Situation Mechanism of diminished response Therapeutic response Renal failure Impaired delivery to tubular fluid Increased dose Nephrotic Syndrome Protein binding in the urine. Sodium avid nephron Increased dose Heart Failure Sodium avid nephron Increased frequency Cirrhosis Sodium avid nephron Increased frequency

Furosemide drips
High dose furosemide causes
Electrolyte abnormalities
Ototoxicity
Volume depletion
In a meta analysis Salvadore and Rey found continuous infusions for CHF:
More diuresis
Less ototoxicity
No change in electrolyte abnormalities
Give 40-80 mg bolus of furosemide
Start infusion at 20 mg/hour
Titrate drip to desired diuresis
May need to repeat the loading doses when titrating the drip
Maximum of 40 mg/hr
Salvador DR, Rey NR, Ramos GC, Punzalan FE. Cochrane Database Syst Rev. 2004;(1):CD003178

Proper use of diuretics: Thiazides
Thiazide diuretics lose much of their effectiveness with a GFR < 50 mL/min
This can be overcome with higher doses
50-100 mg of HCTZ with GFR 30-50
200 mg of HCTZ with GFR < 30
Metolazone (Zaroxolyn)
2.5-20 mg daily
Half-life is 2 days

Electrolyte Emergencies

Sodium is different
Most ions must be regulated because of direct effects of the ion.
Arrhythmias from high (or low) potassium
Weakness from high magnesium
Tetany from low calcium
Sodium is not like that.
The problems with high or low sodium have little to do with direct effects of the ion.
Disregulation of sodium causes changes in cell volume.

The movement of water in the body
The movement of water into and out of cells is governed by tonicity (sodium):
intracellular compartment extracellular compartment

Why we care about osmolality
Alterations in cell size disrupt tissue function.

Low sodium: hyponatremia
Hyponatremia is defined as a sodium concentration less than 135 mEq/L.
Pseudohyponatremia is when the sodium concentration is low (< 135) but osmolality is high or normal.
True hyponatremia is when both the sodium and the osmolality are low.

Pseudohyponatremia: high osmolality
Elevated glucose (or mannitol) raise plasma tonicity which draws water from the intracellular compartment diluting plasma sodium.
Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.

Pseudohyponatremia: high osmolality
Correcting the sodium for hyperglycemia.
Add 1.6 to the sodium for every 100 mg/dL the glucose is over 100.
Example: Na = 126 mEq/L. Glucose = 600 mg/dL:
600 - 100 = 500. So the glucose is five 100’s over 100
5 x 1.6 = 8
126 + 8 =134
True sodium equals 134 mEq/L
To remember 1.6 think “Sweet 16”
Underestimates true adjusted sodium

Pseudohyponatremia: Normal osmolality
Increased protein or lipids can cause a lab error causing a falsely lowered sodium.
Hyperlipidemia
Hypercholesterolemia
TPN with lipids
IV immunoglobulin infusions

True hyponatremia: water intake > water excretion
Intake
Psychogenic polydipsia

True hyponatremia: water intake > water excretion
Intake
Psychogenic polydipsia
Excretion
Renal failure
ADH
SIADH
CHF
Volume depletion
Cirrhosis
Adrenal insufficiency
Hypothyroidism

Urine Osmolality 50 1200 Healthy Kidneys Concentrated urine Na + Dilute urine Na +

isosthenuria Urine Osmolality 50 1200 Healthy Kidneys 150 900 Chronic Kidney Disease 600 900 Excess ADH: • SIADH • CHF • Volume depletion 50 150 Absence of ADH: Diabetes insipidis 300 ESRD or acute renal failure

Concentrated urine Na + 600 900 Excess ADH: • SIADH • CHF • Volume depletion

Etiology of Hyponatremia: 3 steps to generating dilute urine
1. Delivery of water to the diluting segments of the nephron.
2. Functional diluting segments.
3. Collecting tubule impermeable to water (lack of ADH)
1400 285 100 50

Failure to Generate dilute urine
Lack of water delivery to the diluting segments.
Renal failure
Volume deficiency
Cirrhosis
Heart failure
Nephrotic syndrome

Ineffective solute reabsorption in the diluting segments:
Thick ascending limb of the loop of Henle (TALH)
Distal convoluted tubule.
Diuretics
Non-oliguric ATN

Permeable collecting ducts (ADH)
Volume related ADH
SIADH
Drug induced
Paraneoplastic
CNS
Pulmonary disease
Adrenal insufficiency
Hypothyroidism

Implications of hyponatremia

Adrogué and Madias NEJM 2000;342:1581.

The response to hyponatremia Low sodium concentration causes water to move into the cells. In the brain this causes an increase in ICP. Compensated chronic hyponatremia is essentially asymptomatic.

The problem with compensation The starting point is after compensation has reduced the amount of intracellular solute and the ICP Now, an over-eager intern sees the low sodium and starts an infusion of 3% NaCl to raise the sodium to normal. Sodium 108 The sodium draws water from the inside of the cells causing the brain to shrivel. The problem with interns This causes osmotic brain damage. Central pontine myelinolysis. This is lethal. Sodium 134

Damned if you do.
Without treatment patients have cerebral edema.
Correction of sodium puts patients at risk for OBD
To treat or not to treat? That is the question. T. Berl Damned if you don’t.

Symptomatic vs. Asymptromatic
Uncompensated, symptomatic
Treat aggressively with 3% saline
Critical care or nephrology consult.
Compensated, asymptomatic
Treat conservatively
Water restriction
Conivaptan / Tolvaptan
Demeclocycline
Lasix
Symptoms
Mental status changes
Nausea
Vomiting
Headache
Movement abnormalities
Seizures
Hypoxia/respiratory failure

Symptomatic vs. Asymptromatic
Use the etiology of hyponatremia as a clue to duration of hyponatremia
Patients with long standing disease processes are more likely to be chronic:
SIADH
CHF
Cirrhosis
Likely to cause acute hyponatremia:
Psychogenic polydipsia (water intoxication)
Thiazide diuretics
Post-operative hyponatremia
Marathons
COMMON RARE

Clock and calendar are unreliable measures of chronicity

Chronic vs acute
Prospectively collected case series of 53 postmenopausal women.
Average duration of hyponatremia: 5.2 days
All had severe neurologic symptoms.
Early aggressive therapy Late aggressive therapy Conservative therapy Ayus JC, Arieff AI. JAMA 1999; 281: 2299-2304. Symptomatic vs Asymptomatic

Conservative therapy for asymptomatic hyponatremia
Do no harm.
Fluid restrict the patient.
Check the urine Na plus K
If it is greater than the serum Na, furosemide may help.
Speed limit
0.5 mmol/L/hr
No more than 12 mmol in the first day.

151 consecutive euvolemic hyponatremic patients admitted to through the ED
Na from 115 to 132
Excluded patients with CHF, acute hyponatremia, or seizures
N = 122
Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8. 9.45 67.43

Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8.

Introducing the vaptans
Non-peptide vasopressin competitive antagonists
Three vasopressin receptors
V1a: Vasoconstriction
V1b: Cortisol modulation
V2: Water metabolism in the kidney
Treatment of hyponatremia and heart failure

Conivaptan marketed as Vaprisol®
First licensed ADH antagonist
Dual V1a (vasopresssor) and V2 (aquaporin) antagonist
Licensed December 2005 for the treatment of euvolemic hyponatremia

9% of patients had overly rapid (>12 mmol/L in 24 hours) correction of hyponatremia Potent CYP3A4 inhibitor: Caution with ketoconazole, itraconazole, clarithromycin, ritonavir and indinavir Placebo (n=21) Conivaptan 40mg/d (n=18) Baseline sodium 124.3 mmol/l 123.6 mmol/l Sodium at 48 hours 125.1 mmol/l 129.4 mmol/l Sodium at 96 hours 126.7 mmol/l 130.0 mmol/l Number with a Na rise of ≥ 6 mmol/L at 48 hours 0 (0%) 7 (38.9%) Number with a Na rise of ≥ 6 mmol/L at 96 hours 6 (28.6%) 12 (66.7%)

Conivaptan
No data in liver disease
No current indication in heart failure
Lowers wedge pressure
Increases urine output
Corrects hyponatremia
JE Udelson, WB Smith, Et al. Circulation. 2001;104:2417.

Conivaptan
Only available as an IV agent
Requires continuous infusion
20 mg loading dose over 30 minutes
Then 20 mg over the rest of the day
40-80 as continuous infusion for up to 96 hours

Two identical studies SALT 1 (US Study) and SALT 2 (European Study)
Randomized double blind placebo controlled trial
All patients had hyponatremia due to:
SIADH
CHF
Cirrhosis
Patients randomized to placebo or tolvaptan
Dose was titrated from 15 mg to a maximum of 60 mg to bring the Na up to 135.
Study drug was continued for 30 days and then stopped.

Sodium < 130 Sodium 130-134

Acute symptomatic hyponatremia
In patients with neurologic symptoms due to hyponatremia: Use 3% NaCl.
Increase sodium until symptoms abate or 6 mmol/L, which ever comes first.

12 Increase Na 12 mmol/L in the first 24 hours. Increase Na 12 mmol/L in the first 24 hours.

Change in sodium formula:
The formula predicts serum sodium following one liter of any infusion.
Works equally well in hyponatremia
3% NaCl
and hypernatremia
D 5 W
In adults, using 3% NaCl the ∆Na should be pretty close to 10 mmol/L per liter
Change in sodium following one liter of any IVF. TBW = kg x 0.6 Na in 3% NaCl: 513 Na in 0.9% NaCl: 154 Na in 0.45% NaCl: 77 Na in 0.225% NaCl: 39 Adrogué and Madias NEJM 2000;342:1581.

Change in sodium formula: Examples
46 yo AA female 3 days post-op from TAH develops seizures and is unresponsive.
Na = 108
Weight = 65 kg
You prescribe 3% NaCl
For every liter of 3% the Na will rise 10.1 mmol/L
So 1 mmol/L per 100 cc of 3%
Raise Na 6 mEq in 2 hours give 300 ml/hr for 2 hours or until symptoms resolve.
After that 50mL for 12 will increase serum Na by 6 mmol/L to get you to 12 mmol/L.
Check frequent serum Na, recheck change in Na calc.

Change in sodium formula: Limitations
Under estimates change in sodium
Assumes no urine output
The greater the urine output the more inaccurate the formula
In 40% of people who overcorrect, there is documented diuresis
Assumes accurate calculation of total body water
Mohmand HK, Issa D, Et al. Abstract ASN 2006 Adrogué and Madias NEJM 2000;342:1581. Change in sodium following one liter of any IVF. TBW = kg x 0.6 Na in 3% NaCl: 513 Na in 0.9% NaCl: 154 Na in 0.45% NaCl: 77 Na in 0.225% NaCl: 39

Fluids: Total body water

100 kg 70 kg Ideal weight : Females: 45 kg Males: 50 kg Adjusted weight : ideal weight + 0.4 (actual body weight – ideal weight) + 2.3 kg for every inch over 5 feet 60% H 2 O 45% H 2 O

Hyponatremia summary
The primary issues:
Is it true hyponatremia
Check a spot glucose
If it is true then:
To treat or not to treat?
Symptomatic: Treat with 3%
Asymptomatic: fluid restrict
Tolvaptan / Conivaptan
Demeclocycline
Lasix and /or salt tablets

Hypernatremia
Hypernatremia is defined as a sodium > 145 mEq/L.
Hypernatremia is associated with increased hospital mortality.
Patients who present with hypernatremia typically get appropriate therapy.
In patients who develop hypernatremia while hospitalized don’t get therapy as often.

Causes of hypernatremia
Water excretion exceeds water intake
Two step process
Generation
Generation
Gain of sodium
Loss of water
Maintenance
Maintenance
Inability to ingest water
Without both of these processes there cannot be hypernatremia.

Consequences and compensation

Treatment
Provide water
Enteral water is preferred
D 5 W results in hyperglycemia
Note on D 5 W, since D 5 W distributes through the total body water 1 liter of D 5 W increases the intravascular space by only 83 mL

Use the change in sodium formula to calculate the fluid volume.
The amount of fluid
TBW= kg x % body water
0.7 for well hydrated young males
0.6 for well hydrated young females
reduce by 0.1 for:
Obesity
Elderly
Dehydration
Each liter of D5 or free water lowers Na 4, so 6 liters will reduce the Na to 144.

Treatment
For routine hypernatremia correct the fluid deficit over 48 hours.
Patients with DI have large ongoing free water losses (200-300 mL/hr).
Failing to account for these losses will result in a failure to correct the hypernatremia.
Many of these patients have poor perfusion.
Treat the shock and compromised perfusion without worrying about the Na.
After perfusion is restored treat the hypernatremia.

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Fluids And Electrolytes July1

by Joel Topf on Oct 13, 2008

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Fluids And Electrolytes July1 — Presentation Transcript