July 1
Fluids and electrolytes Joel Topf, MD Nephrology Attending St. John Hospital
http:// PBFluids .com
<ul><li>The lungs serve to maintain the composition of the extracellular fluid with respect to oxygen and carbon dioxide, ...
<ul><li>Answer: </li></ul><ul><li>The percentage of admissions that get either: </li></ul><ul><ul><li>IV fluids or  </li><...
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)...
67% 28 L 25% 11 L 8% 3 L Blood volume = 5 L
Hemoconcentration <ul><li>Mr. Jones drank too much and puked his guts out.  </li></ul><ul><li>On admission his hct is 65%....
Intravenous fluids Dextrose Saline Ringers Lactate Plasma expanders Crystalloids
Dextrose solutions <ul><li>The convention for naming dextrose solutions is grams percent (g%) </li></ul><ul><li>To convert...
Dextrose solutions <ul><li>The glucose concentration in D 5 W is so high to make the fluid isosmotic to plasma </li></ul><...
Saline  <ul><li>Isotonic saline is the primary fluid for volume resuscitation </li></ul><ul><li>Sodium concentration  154 ...
Lactated ringers <ul><li>Contains Na, Cl, K, and Ca at physiologic concentrations </li></ul><ul><ul><li>Do not use with hy...
Dextrose Saline Ringers Lactate Plasma expanders
Mr. Jones is down 1.9 L <ul><li>How much D5W will it take to replace the intravascular volume? </li></ul><ul><li>Dextrose ...
Mr. Jones is down 1.9 L <ul><li>How much 0.9% NaCl (or LR) will it take to replace the intravascular volume? </li></ul><ul...
Mr. Jones is down 1.9 L <ul><li>How much blood/albumin will it take to replace the intravascular volume? </li></ul><ul><li...
What type of IVF would you use? <ul><li>Patient is post-op from a hysterectomy. She had EBL of 280 mL and her current vita...
Bicarbonate drips <ul><li>Do not add bicarb to normal saline </li></ul><ul><li>An amp of bicarb has 50 mmol Na per 50  mL ...
 
<ul><li>Answer: </li></ul><ul><li>The percentage of admissions that need both: </li></ul><ul><ul><li>IV fluids and </li></...
<ul><li>Don’t give a drowning man a glass of water </li></ul><ul><li>Don’t use IVF and diuretics </li></ul><ul><ul><li>Exc...
Proper use of diuretics: Loops <ul><li>Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the...
 
Proper use of diuretics: Loops <ul><li>Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the...
Loop diuretic resistance <ul><li>Chronic use of loop diuretics results in hypertrophy of distal convoluted tubule </li></u...
Loop diuretic resistance Situation Mechanism of diminished response Therapeutic response Renal failure Impaired delivery t...
Furosemide drips <ul><li>High dose furosemide causes </li></ul><ul><ul><li>Electrolyte abnormalities </li></ul></ul><ul><u...
Proper use of diuretics: Thiazides <ul><li>Thiazide diuretics lose much of their effectiveness with a GFR < 50 mL/min </li...
Electrolyte  Emergencies
Sodium is different <ul><li>Most ions must be regulated because of direct effects of the ion. </li></ul><ul><ul><li>Arrhyt...
The movement of water in the body <ul><li>The movement of water into and out of cells is governed by tonicity (sodium): </...
Why we care about osmolality <ul><li>Alterations in cell size disrupt tissue function. </li></ul>
Low sodium: hyponatremia <ul><li>Hyponatremia is defined as a sodium concentration less than 135 mEq/L. </li></ul><ul><ul>...
Pseudohyponatremia:  high osmolality <ul><li>Elevated glucose (or mannitol) raise plasma tonicity which draws water from t...
Pseudohyponatremia:  high osmolality <ul><li>Correcting the sodium for hyperglycemia. </li></ul><ul><ul><li>Add 1.6 to the...
Pseudohyponatremia:  Normal osmolality <ul><li>Increased protein or lipids can cause a lab error causing a falsely lowered...
True hyponatremia:  water intake > water excretion <ul><li>Intake </li></ul><ul><ul><li>Psychogenic  polydipsia </li></ul>...
 
 
True hyponatremia:  water intake > water excretion <ul><li>Intake </li></ul><ul><ul><li>Psychogenic  polydipsia </li></ul>...
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 •  CH...
Concentrated urine Na + 600 900 Excess ADH:    • SIADH •  CHF •  Volume depletion
Etiology of Hyponatremia: 3 steps to generating dilute urine <ul><ul><li>1. Delivery of water to the diluting segments of ...
Failure to Generate dilute urine <ul><li>Lack of water delivery to the diluting segments. </li></ul><ul><ul><li>Renal fail...
Failure to Generate dilute urine <ul><li>Ineffective solute reabsorption in the diluting segments: </li></ul><ul><ul><li>T...
Failure to Generate dilute urine <ul><li>Permeable collecting ducts (ADH) </li></ul><ul><ul><li>Volume related ADH </li></...
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 inc...
The problem with compensation The starting point is after compensation has reduced the amount of intracellular solute and ...
Damned if you do. <ul><ul><li>Without treatment patients have cerebral edema. </li></ul></ul><ul><ul><li>Correction of sod...
Damned if you do. <ul><ul><li>Without treatment patients have cerebral edema. </li></ul></ul><ul><ul><li>Correction of sod...
Symptomatic vs. Asymptromatic <ul><li>Uncompensated, symptomatic </li></ul><ul><ul><li>Treat aggressively with 3% saline <...
Symptomatic vs. Asymptromatic <ul><li>Use the etiology of hyponatremia as a clue to duration of hyponatremia </li></ul><ul...
Clock and calendar are unreliable measures of chronicity
Chronic vs acute <ul><li>Prospectively collected case series of 53 postmenopausal women. </li></ul><ul><li>Average duratio...
Conservative therapy for asymptomatic hyponatremia <ul><li>Do no harm. </li></ul><ul><li>Fluid restrict the patient. </li>...
<ul><li>151 consecutive euvolemic hyponatremic patients admitted to through the ED </li></ul><ul><li>Na from 115 to 132 </...
Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8.
Introducing the vaptans <ul><li>Non-peptide vasopressin competitive antagonists </li></ul><ul><li>Three vasopressin recept...
Conivaptan marketed as Vaprisol® <ul><li>First licensed ADH antagonist </li></ul><ul><li>Dual V1a (vasopresssor) and V2 (a...
9%  of patients had overly rapid (>12 mmol/L in 24 hours)  correction of hyponatremia Potent CYP3A4 inhibitor: Caution wit...
Conivaptan <ul><li>No data in liver disease </li></ul><ul><li>No current indication in heart failure </li></ul><ul><ul><li...
Conivaptan <ul><li>Only available as an IV agent </li></ul><ul><li>Requires continuous infusion </li></ul><ul><ul><li>20 m...
 
<ul><li>Two identical studies SALT 1 (US Study) and SALT 2 (European Study) </li></ul><ul><li>Randomized double blind plac...
Sodium < 130 Sodium 130-134
Acute symptomatic hyponatremia <ul><li>In patients with neurologic symptoms due to hyponatremia: Use 3% NaCl. </li></ul><u...
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: <ul><li>The formula predicts serum sodium following one liter of any infusion. </li></ul><ul><ul...
Change in sodium formula: Examples <ul><li>46 yo AA female 3 days post-op from TAH develops seizures and is unresponsive. ...
Change in sodium formula: Limitations <ul><li>Under estimates change in sodium  </li></ul><ul><li>Assumes no urine output ...
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...
Hyponatremia summary <ul><li>The primary issues: </li></ul><ul><ul><li>Is it true hyponatremia </li></ul></ul><ul><ul><ul>...
Hypernatremia <ul><li>Hypernatremia is defined as a sodium > 145 mEq/L. </li></ul><ul><li>Hypernatremia is associated with...
Causes of hypernatremia <ul><li>Water excretion exceeds water intake </li></ul><ul><li>Two step process </li></ul>Generati...
Consequences and compensation
Treatment <ul><li>Provide water </li></ul><ul><ul><li>Enteral water is preferred </li></ul></ul><ul><ul><li>D 5 W results ...
<ul><li>Use the change in sodium formula to calculate the fluid volume. </li></ul>The amount of fluid <ul><li>TBW= kg x % ...
Treatment <ul><li>For routine hypernatremia correct the fluid deficit over 48 hours. </li></ul><ul><li>Patients with DI ha...
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Fluids And Electrolytes July1

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  • Homer Smith is one of the pre-eminant evolutionary biologists of the 20th century. He did comparative biology on the kidney and elucidated much of basic renal physiology
  • So a passing interest is more than just a good idea it is essential
  • Matt Carrington Jennifer Strange Walter Dean Jennings III
  • Fluids And Electrolytes July1

    1. 1. July 1
    2. 2. Fluids and electrolytes Joel Topf, MD Nephrology Attending St. John Hospital
    3. 3. http:// PBFluids .com
    4. 4. <ul><li>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. </li></ul>Homer W. Smith From Fish to Philosopher
    5. 5. <ul><li>Answer: </li></ul><ul><li>The percentage of admissions that get either: </li></ul><ul><ul><li>IV fluids or </li></ul></ul><ul><ul><li>Diuretics </li></ul></ul>
    6. 6. Question: What is 100%?
    7. 7. Answer: The percentage of hospital days that patients get electrolytes drawn
    8. 8. Question: What is 100%?
    9. 9. Fluids and electrolyte issues are ubiquitous The ability to screw up is ubiquitous 132 4.4 108 17 106 34 3.8
    10. 10. Fluids: Total body water
    11. 11. 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
    12. 12. 67% 28 L 25% 11 L 8% 3 L Blood volume = 5 L
    13. 13. Hemoconcentration <ul><li>Mr. Jones drank too much and puked his guts out. </li></ul><ul><li>On admission his hct is 65%. Up from a recent hematocrit of 40%. </li></ul><ul><li>How much water was lost from his vascular space? </li></ul>
    14. 14. Intravenous fluids Dextrose Saline Ringers Lactate Plasma expanders Crystalloids
    15. 15. Dextrose solutions <ul><li>The convention for naming dextrose solutions is grams percent (g%) </li></ul><ul><li>To convert this to conventional mg/dL multiply the g% by 1,000 </li></ul><ul><li>Example </li></ul><ul><ul><li>D5W contains 5g of glucose per 100 mL or </li></ul></ul><ul><ul><li>50 g per liter (200 Kcal/liter) </li></ul></ul><ul><ul><li>The glucose concentration of D 5 W is 5,000 mg/dL </li></ul></ul>
    16. 16. Dextrose solutions <ul><li>The glucose concentration in D 5 W is so high to make the fluid isosmotic to plasma </li></ul><ul><li>To convert from mg/dL to mmol/L </li></ul><ul><ul><li>Divide the mg/dL by the molecular weight of glucose (180) to get mmol/dL </li></ul></ul><ul><ul><li>Multiply by 10 to convert mmol/dL to mmol/L </li></ul></ul>5000 mg/dL 180 mg/mmol 27.8 mmol/dL 10 dL/L 277 mmol/L
    17. 17. Saline <ul><li>Isotonic saline is the primary fluid for volume resuscitation </li></ul><ul><li>Sodium concentration 154 mmol/L </li></ul><ul><li>pH of 5.5 </li></ul><ul><ul><li>When given in large volumes can cause a non-anion gap (hyperchloremic) metabolic acidosis </li></ul></ul><ul><ul><li>Dilutional acidosis </li></ul></ul>
    18. 18. Lactated ringers <ul><li>Contains Na, Cl, K, and Ca at physiologic concentrations </li></ul><ul><ul><li>Do not use with hyperkalemia </li></ul></ul><ul><ul><li>Do not use with hypercalcemia </li></ul></ul><ul><li>Lactate is used to supply alkali </li></ul><ul><ul><li>Do not use with lactic acidosis </li></ul></ul><ul><ul><li>pH=6.6 </li></ul></ul><ul><li>The Contents </li></ul><ul><ul><li>Sodium: 130 mmol/L </li></ul></ul><ul><ul><li>Chloride: 109 mmol/L </li></ul></ul><ul><ul><li>Lactate: 28 mmol/lL </li></ul></ul><ul><ul><li>Potassium: 4 mmol/L </li></ul></ul><ul><ul><li>Calcium: 6 mg/dL </li></ul></ul>
    19. 19. Dextrose Saline Ringers Lactate Plasma expanders
    20. 20. Mr. Jones is down 1.9 L <ul><li>How much D5W will it take to replace the intravascular volume? </li></ul><ul><li>Dextrose distributes in proportion to total body water. </li></ul><ul><ul><li>8% of TBW is intravascular </li></ul></ul><ul><ul><li>1.9/0.08 = 23.75 L </li></ul></ul>23.75 liters
    21. 21. Mr. Jones is down 1.9 L <ul><li>How much 0.9% NaCl (or LR) will it take to replace the intravascular volume? </li></ul><ul><li>Saline distributes among extracellular compartments. </li></ul><ul><ul><li>25% of ECC is intravascular </li></ul></ul><ul><ul><li>1.9/0.25 = 7.6 L </li></ul></ul>7.6 liters
    22. 22. Mr. Jones is down 1.9 L <ul><li>How much blood/albumin will it take to replace the intravascular volume? </li></ul><ul><li>Blood/albumin is limited to the intravascular space. </li></ul><ul><ul><li>1.9/1.0 = 1.9 L </li></ul></ul>1.9 liters
    23. 23. What type of IVF would you use? <ul><li>Patient is post-op from a hysterectomy. She had EBL of 280 mL and her current vitals are BP 113/78, HR 105. </li></ul><ul><li>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. </li></ul><ul><li>Patient who is NPO due to resolving pancreatitis. Vital signs are stable. The patient is euvolemic. </li></ul><ul><li>Sodium is 163. The patient cannot tolerate oral liquid. </li></ul>
    24. 24. Bicarbonate drips <ul><li>Do not add bicarb to normal saline </li></ul><ul><li>An amp of bicarb has 50 mmol Na per 50 mL (1000 mmol/L) </li></ul><ul><li>Add bicarbonate to: </li></ul><ul><ul><li>D 5 W: 3-4 amps per liter </li></ul></ul><ul><ul><li>0.45 NS: 1-2 amps per liter </li></ul></ul><ul><ul><li>Sterile water: 3-4 amps per liter </li></ul></ul>
    25. 26. <ul><li>Answer: </li></ul><ul><li>The percentage of admissions that need both: </li></ul><ul><ul><li>IV fluids and </li></ul></ul><ul><ul><li>Diuretics </li></ul></ul>Question: What is very few?
    26. 27. <ul><li>Don’t give a drowning man a glass of water </li></ul><ul><li>Don’t use IVF and diuretics </li></ul><ul><ul><li>Except </li></ul></ul><ul><ul><ul><li>Hypercalcemia </li></ul></ul></ul><ul><ul><ul><li>Hyperkalemia </li></ul></ul></ul>
    27. 28. Proper use of diuretics: Loops <ul><li>Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the loop of Henle </li></ul><ul><li>They block chloride in the tubular fluid from binding </li></ul><ul><ul><li>So loop diuretics (like all diuretics except spironolactone) must get from the blood into the tubular fluid </li></ul></ul><ul><ul><ul><li>Secretion in the proximal tubule </li></ul></ul></ul><ul><ul><ul><li>Secretion is dependent on renal function </li></ul></ul></ul><ul><ul><li>Must increase the dose as renal function deteriorates </li></ul></ul><ul><ul><ul><li>Age + BUN </li></ul></ul></ul>
    28. 30. Proper use of diuretics: Loops <ul><li>Loop diuretics block the Na-K-2Cl co-transporter in the thick ascending limb of the loop of Henle </li></ul><ul><li>They block chloride in the tubular fluid from binding </li></ul><ul><ul><li>So the loop diuretic (like all diuretics except spironolactone) must get from the blood into the tubular fluid </li></ul></ul><ul><ul><ul><li>Secretion in the proximal tubule </li></ul></ul></ul><ul><ul><ul><li>Secretion is dependent on renal function </li></ul></ul></ul><ul><ul><li>Must increase the dose as renal function deteriorates </li></ul></ul><ul><ul><ul><li>Age + BUN </li></ul></ul></ul><ul><ul><ul><li>Cr x 20 </li></ul></ul></ul>
    29. 31. Loop diuretic resistance <ul><li>Chronic use of loop diuretics results in hypertrophy of distal convoluted tubule </li></ul><ul><ul><li>Increased distal reabsorption of sodium and fluid attenuate diuretic response </li></ul></ul><ul><ul><li>Addition of a thiazide diuretic can restore loop sensitivity </li></ul></ul>
    30. 32. 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
    31. 33. Furosemide drips <ul><li>High dose furosemide causes </li></ul><ul><ul><li>Electrolyte abnormalities </li></ul></ul><ul><ul><li>Ototoxicity </li></ul></ul><ul><ul><li>Volume depletion </li></ul></ul><ul><li>In a meta analysis Salvadore and Rey found continuous infusions for CHF: </li></ul><ul><ul><li>More diuresis </li></ul></ul><ul><ul><li>Less ototoxicity </li></ul></ul><ul><ul><li>No change in electrolyte abnormalities </li></ul></ul><ul><li>Give 40-80 mg bolus of furosemide </li></ul><ul><li>Start infusion at 20 mg/hour </li></ul><ul><li>Titrate drip to desired diuresis </li></ul><ul><ul><li>May need to repeat the loading doses when titrating the drip </li></ul></ul><ul><li>Maximum of 40 mg/hr </li></ul>Salvador DR, Rey NR, Ramos GC, Punzalan FE. Cochrane Database Syst Rev. 2004;(1):CD003178
    32. 34. Proper use of diuretics: Thiazides <ul><li>Thiazide diuretics lose much of their effectiveness with a GFR < 50 mL/min </li></ul><ul><ul><li>This can be overcome with higher doses </li></ul></ul><ul><ul><li>50-100 mg of HCTZ with GFR 30-50 </li></ul></ul><ul><ul><li>200 mg of HCTZ with GFR < 30 </li></ul></ul><ul><ul><li>Metolazone (Zaroxolyn) </li></ul></ul><ul><ul><ul><li>2.5-20 mg daily </li></ul></ul></ul><ul><ul><ul><li>Half-life is 2 days </li></ul></ul></ul>
    33. 35. Electrolyte Emergencies
    34. 36. Sodium is different <ul><li>Most ions must be regulated because of direct effects of the ion. </li></ul><ul><ul><li>Arrhythmias from high (or low) potassium </li></ul></ul><ul><ul><li>Weakness from high magnesium </li></ul></ul><ul><ul><li>Tetany from low calcium </li></ul></ul><ul><li>Sodium is not like that. </li></ul><ul><ul><li>The problems with high or low sodium have little to do with direct effects of the ion. </li></ul></ul><ul><ul><li>Disregulation of sodium causes changes in cell volume. </li></ul></ul>
    35. 37. The movement of water in the body <ul><li>The movement of water into and out of cells is governed by tonicity (sodium): </li></ul>intracellular compartment extracellular compartment
    36. 38. Why we care about osmolality <ul><li>Alterations in cell size disrupt tissue function. </li></ul>
    37. 39. Low sodium: hyponatremia <ul><li>Hyponatremia is defined as a sodium concentration less than 135 mEq/L. </li></ul><ul><ul><li>Pseudohyponatremia is when the sodium concentration is low (< 135) but osmolality is high or normal. </li></ul></ul><ul><ul><li>True hyponatremia is when both the sodium and the osmolality are low. </li></ul></ul>
    38. 40. Pseudohyponatremia: high osmolality <ul><li>Elevated glucose (or mannitol) raise plasma tonicity which draws water from the intracellular compartment diluting plasma sodium. </li></ul>Hillier TA, Abbott RD, Barrett EJ. Am J Med 1999; 106: 399-403.
    39. 41. Pseudohyponatremia: high osmolality <ul><li>Correcting the sodium for hyperglycemia. </li></ul><ul><ul><li>Add 1.6 to the sodium for every 100 mg/dL the glucose is over 100. </li></ul></ul><ul><ul><li>Example: Na = 126 mEq/L. Glucose = 600 mg/dL: </li></ul></ul><ul><ul><ul><li>600 - 100 = 500. So the glucose is five 100’s over 100 </li></ul></ul></ul><ul><ul><ul><li>5 x 1.6 = 8 </li></ul></ul></ul><ul><ul><ul><li>126 + 8 =134 </li></ul></ul></ul><ul><ul><ul><li>True sodium equals 134 mEq/L </li></ul></ul></ul><ul><ul><ul><li>To remember 1.6 think “Sweet 16” </li></ul></ul></ul><ul><ul><li>Underestimates true adjusted sodium </li></ul></ul>
    40. 42. Pseudohyponatremia: Normal osmolality <ul><li>Increased protein or lipids can cause a lab error causing a falsely lowered sodium. </li></ul><ul><ul><li>Hyperlipidemia </li></ul></ul><ul><ul><li>Hypercholesterolemia </li></ul></ul><ul><ul><li>TPN with lipids </li></ul></ul><ul><ul><li>IV immunoglobulin infusions </li></ul></ul>
    41. 43. True hyponatremia: water intake > water excretion <ul><li>Intake </li></ul><ul><ul><li>Psychogenic polydipsia </li></ul></ul>
    42. 46. True hyponatremia: water intake > water excretion <ul><li>Intake </li></ul><ul><ul><li>Psychogenic polydipsia </li></ul></ul><ul><li>Excretion </li></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>ADH </li></ul></ul><ul><ul><ul><li>SIADH </li></ul></ul></ul><ul><ul><ul><li>CHF </li></ul></ul></ul><ul><ul><ul><li>Volume depletion </li></ul></ul></ul><ul><ul><ul><li>Cirrhosis </li></ul></ul></ul><ul><ul><ul><li>Adrenal insufficiency </li></ul></ul></ul><ul><ul><ul><li>Hypothyroidism </li></ul></ul></ul>
    43. 47. Urine Osmolality 50 1200 Healthy Kidneys Concentrated urine Na + Dilute urine Na +
    44. 48. 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
    45. 49. Concentrated urine Na + 600 900 Excess ADH: • SIADH • CHF • Volume depletion
    46. 50. Etiology of Hyponatremia: 3 steps to generating dilute urine <ul><ul><li>1. Delivery of water to the diluting segments of the nephron. </li></ul></ul><ul><ul><li>2. Functional diluting segments. </li></ul></ul><ul><ul><li>3. Collecting tubule impermeable to water (lack of ADH) </li></ul></ul>1400 285 100 50
    47. 51. Failure to Generate dilute urine <ul><li>Lack of water delivery to the diluting segments. </li></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>Volume deficiency </li></ul></ul><ul><ul><li>Cirrhosis </li></ul></ul><ul><ul><li>Heart failure </li></ul></ul><ul><ul><li>Nephrotic syndrome </li></ul></ul>
    48. 52. Failure to Generate dilute urine <ul><li>Ineffective solute reabsorption in the diluting segments: </li></ul><ul><ul><li>Thick ascending limb of the loop of Henle (TALH) </li></ul></ul><ul><ul><li>Distal convoluted tubule. </li></ul></ul><ul><li>Diuretics </li></ul><ul><li>Non-oliguric ATN </li></ul>
    49. 53. Failure to Generate dilute urine <ul><li>Permeable collecting ducts (ADH) </li></ul><ul><ul><li>Volume related ADH </li></ul></ul><ul><ul><li>SIADH </li></ul></ul><ul><ul><ul><li>Drug induced </li></ul></ul></ul><ul><ul><ul><li>Paraneoplastic </li></ul></ul></ul><ul><ul><ul><li>CNS </li></ul></ul></ul><ul><ul><ul><li>Pulmonary disease </li></ul></ul></ul><ul><ul><li>Adrenal insufficiency </li></ul></ul><ul><ul><li>Hypothyroidism </li></ul></ul>
    50. 54. Implications of hyponatremia
    51. 55. Adrogué and Madias NEJM 2000;342:1581.
    52. 56. 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.
    53. 57. 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
    54. 58. Damned if you do. <ul><ul><li>Without treatment patients have cerebral edema. </li></ul></ul><ul><ul><li>Correction of sodium puts patients at risk for OBD </li></ul></ul>To treat or not to treat? That is the question. T. Berl Damned if you don’t.
    55. 59. Damned if you do. <ul><ul><li>Without treatment patients have cerebral edema. </li></ul></ul><ul><ul><li>Correction of sodium puts patients at risk for OBD </li></ul></ul>To treat or not to treat? That is the question. T. Berl Damned if you don’t.
    56. 60. Symptomatic vs. Asymptromatic <ul><li>Uncompensated, symptomatic </li></ul><ul><ul><li>Treat aggressively with 3% saline </li></ul></ul><ul><ul><li>Critical care or nephrology consult. </li></ul></ul><ul><li>Compensated, asymptomatic </li></ul><ul><ul><li>Treat conservatively </li></ul></ul><ul><ul><li>Water restriction </li></ul></ul><ul><ul><li>Conivaptan / Tolvaptan </li></ul></ul><ul><ul><li>Demeclocycline </li></ul></ul><ul><ul><li>Lasix </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Mental status changes </li></ul></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Headache </li></ul></ul><ul><ul><li>Movement abnormalities </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Hypoxia/respiratory failure </li></ul></ul>
    57. 61. Symptomatic vs. Asymptromatic <ul><li>Use the etiology of hyponatremia as a clue to duration of hyponatremia </li></ul><ul><ul><li>Patients with long standing disease processes are more likely to be chronic: </li></ul></ul><ul><ul><ul><li>SIADH </li></ul></ul></ul><ul><ul><ul><li>CHF </li></ul></ul></ul><ul><ul><ul><li>Cirrhosis </li></ul></ul></ul><ul><ul><li>Likely to cause acute hyponatremia: </li></ul></ul><ul><ul><ul><li>Psychogenic polydipsia (water intoxication) </li></ul></ul></ul><ul><ul><ul><li>Thiazide diuretics </li></ul></ul></ul><ul><ul><ul><li>Post-operative hyponatremia </li></ul></ul></ul><ul><ul><ul><li>Marathons </li></ul></ul></ul>COMMON RARE
    58. 62. Clock and calendar are unreliable measures of chronicity
    59. 63. Chronic vs acute <ul><li>Prospectively collected case series of 53 postmenopausal women. </li></ul><ul><li>Average duration of hyponatremia: 5.2 days </li></ul><ul><li>All had severe neurologic symptoms. </li></ul>Early aggressive therapy Late aggressive therapy Conservative therapy Ayus JC, Arieff AI. JAMA 1999; 281: 2299-2304. Symptomatic vs Asymptomatic
    60. 64. Conservative therapy for asymptomatic hyponatremia <ul><li>Do no harm. </li></ul><ul><li>Fluid restrict the patient. </li></ul><ul><ul><li>Check the urine Na plus K </li></ul></ul><ul><ul><li>If it is greater than the serum Na, furosemide may help. </li></ul></ul><ul><li>Speed limit </li></ul><ul><ul><li>0.5 mmol/L/hr </li></ul></ul><ul><ul><li>No more than 12 mmol in the first day. </li></ul></ul>
    61. 65. <ul><li>151 consecutive euvolemic hyponatremic patients admitted to through the ED </li></ul><ul><li>Na from 115 to 132 </li></ul><ul><li>Excluded patients with CHF, acute hyponatremia, or seizures </li></ul><ul><li>N = 122 </li></ul>Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8. 9.45 67.43
    62. 66. Renneboog B, Musch W, Et al. Am J Med 2006; 119: 71 e1-8.
    63. 67. Introducing the vaptans <ul><li>Non-peptide vasopressin competitive antagonists </li></ul><ul><li>Three vasopressin receptors </li></ul><ul><ul><li>V1a: Vasoconstriction </li></ul></ul><ul><ul><li>V1b: Cortisol modulation </li></ul></ul><ul><ul><li>V2: Water metabolism in the kidney </li></ul></ul><ul><li>Treatment of hyponatremia and heart failure </li></ul>
    64. 68. Conivaptan marketed as Vaprisol® <ul><li>First licensed ADH antagonist </li></ul><ul><li>Dual V1a (vasopresssor) and V2 (aquaporin) antagonist </li></ul><ul><li>Licensed December 2005 for the treatment of euvolemic hyponatremia </li></ul>
    65. 69. 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%)
    66. 70. Conivaptan <ul><li>No data in liver disease </li></ul><ul><li>No current indication in heart failure </li></ul><ul><ul><li>Lowers wedge pressure </li></ul></ul><ul><ul><li>Increases urine output </li></ul></ul><ul><ul><li>Corrects hyponatremia </li></ul></ul>JE Udelson, WB Smith, Et al. Circulation. 2001;104:2417.
    67. 71. Conivaptan <ul><li>Only available as an IV agent </li></ul><ul><li>Requires continuous infusion </li></ul><ul><ul><li>20 mg loading dose over 30 minutes </li></ul></ul><ul><ul><li>Then 20 mg over the rest of the day </li></ul></ul><ul><ul><li>40-80 as continuous infusion for up to 96 hours </li></ul></ul>
    68. 73. <ul><li>Two identical studies SALT 1 (US Study) and SALT 2 (European Study) </li></ul><ul><li>Randomized double blind placebo controlled trial </li></ul><ul><li>All patients had hyponatremia due to: </li></ul><ul><ul><li>SIADH </li></ul></ul><ul><ul><li>CHF </li></ul></ul><ul><ul><li>Cirrhosis </li></ul></ul><ul><li>Patients randomized to placebo or tolvaptan </li></ul><ul><li>Dose was titrated from 15 mg to a maximum of 60 mg to bring the Na up to 135. </li></ul><ul><li>Study drug was continued for 30 days and then stopped. </li></ul>
    69. 74. Sodium < 130 Sodium 130-134
    70. 75. Acute symptomatic hyponatremia <ul><li>In patients with neurologic symptoms due to hyponatremia: Use 3% NaCl. </li></ul><ul><li>Increase sodium until symptoms abate or 6 mmol/L, which ever comes first. </li></ul>
    71. 76. 12 Increase Na 12 mmol/L in the first 24 hours. Increase Na 12 mmol/L in the first 24 hours.
    72. 77. Change in sodium formula: <ul><li>The formula predicts serum sodium following one liter of any infusion. </li></ul><ul><ul><li>Works equally well in hyponatremia </li></ul></ul><ul><ul><ul><li>3% NaCl </li></ul></ul></ul><ul><ul><li>and hypernatremia </li></ul></ul><ul><ul><ul><li>D 5 W </li></ul></ul></ul><ul><li>In adults, using 3% NaCl the ∆Na should be pretty close to 10 mmol/L per liter </li></ul>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.
    73. 78. Change in sodium formula: Examples <ul><li>46 yo AA female 3 days post-op from TAH develops seizures and is unresponsive. </li></ul><ul><ul><li>Na = 108 </li></ul></ul><ul><ul><li>Weight = 65 kg </li></ul></ul><ul><li>You prescribe 3% NaCl </li></ul><ul><li>For every liter of 3% the Na will rise 10.1 mmol/L </li></ul><ul><ul><li>So 1 mmol/L per 100 cc of 3% </li></ul></ul><ul><li>Raise Na 6 mEq in 2 hours give 300 ml/hr for 2 hours or until symptoms resolve. </li></ul><ul><li>After that 50mL for 12 will increase serum Na by 6 mmol/L to get you to 12 mmol/L. </li></ul><ul><li>Check frequent serum Na, recheck change in Na calc. </li></ul>
    74. 79. Change in sodium formula: Limitations <ul><li>Under estimates change in sodium </li></ul><ul><li>Assumes no urine output </li></ul><ul><ul><li>The greater the urine output the more inaccurate the formula </li></ul></ul><ul><ul><li>In 40% of people who overcorrect, there is documented diuresis </li></ul></ul><ul><li>Assumes accurate calculation of total body water </li></ul>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
    75. 80. Fluids: Total body water
    76. 81. 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
    77. 82. Hyponatremia summary <ul><li>The primary issues: </li></ul><ul><ul><li>Is it true hyponatremia </li></ul></ul><ul><ul><ul><li>Check a spot glucose </li></ul></ul></ul><ul><ul><li>If it is true then: </li></ul></ul><ul><li>To treat or not to treat? </li></ul><ul><ul><li>Symptomatic: Treat with 3% </li></ul></ul><ul><ul><li>Asymptomatic: fluid restrict </li></ul></ul><ul><ul><ul><li>Tolvaptan / Conivaptan </li></ul></ul></ul><ul><ul><ul><li>Demeclocycline </li></ul></ul></ul><ul><ul><ul><li>Lasix and /or salt tablets </li></ul></ul></ul>
    78. 83. Hypernatremia <ul><li>Hypernatremia is defined as a sodium > 145 mEq/L. </li></ul><ul><li>Hypernatremia is associated with increased hospital mortality. </li></ul><ul><ul><li>Patients who present with hypernatremia typically get appropriate therapy. </li></ul></ul><ul><ul><li>In patients who develop hypernatremia while hospitalized don’t get therapy as often. </li></ul></ul>
    79. 84. Causes of hypernatremia <ul><li>Water excretion exceeds water intake </li></ul><ul><li>Two step process </li></ul>Generation <ul><ul><li>Generation </li></ul></ul><ul><ul><ul><li>Gain of sodium </li></ul></ul></ul><ul><ul><ul><li>Loss of water </li></ul></ul></ul>Maintenance <ul><ul><li>Maintenance </li></ul></ul><ul><ul><ul><li>Inability to ingest water </li></ul></ul></ul><ul><li>Without both of these processes there cannot be hypernatremia. </li></ul>
    80. 85. Consequences and compensation
    81. 86. Treatment <ul><li>Provide water </li></ul><ul><ul><li>Enteral water is preferred </li></ul></ul><ul><ul><li>D 5 W results in hyperglycemia </li></ul></ul><ul><ul><ul><li>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 </li></ul></ul></ul>
    82. 87. <ul><li>Use the change in sodium formula to calculate the fluid volume. </li></ul>The amount of fluid <ul><li>TBW= kg x % body water </li></ul><ul><ul><li>0.7 for well hydrated young males </li></ul></ul><ul><ul><li>0.6 for well hydrated young females </li></ul></ul><ul><ul><li>reduce by 0.1 for: </li></ul></ul><ul><ul><ul><li>Obesity </li></ul></ul></ul><ul><ul><ul><li>Elderly </li></ul></ul></ul><ul><ul><ul><li>Dehydration </li></ul></ul></ul><ul><ul><li>Each liter of D5 or free water lowers Na 4, so 6 liters will reduce the Na to 144. </li></ul></ul>
    83. 88. Treatment <ul><li>For routine hypernatremia correct the fluid deficit over 48 hours. </li></ul><ul><li>Patients with DI have large ongoing free water losses (200-300 mL/hr). </li></ul><ul><ul><li>Failing to account for these losses will result in a failure to correct the hypernatremia. </li></ul></ul><ul><li>Many of these patients have poor perfusion. </li></ul><ul><ul><li>Treat the shock and compromised perfusion without worrying about the Na. </li></ul></ul><ul><ul><li>After perfusion is restored treat the hypernatremia. </li></ul></ul>

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