2. Fluids and Electrolytes Bruce R. Wall, MD, FACP Texas Health Dallas Presbyterian October 14 th, 2010

3. RBF=1000ml/min; RPF=600ml/min GFR=120ml/min or 172.8L/day

4. Key Concepts Volume status (EABV) “think” saline in ECF Cannot be measured in the lab… TBW (Total Body Water) “think” [Na+ mEq/L] Laboratory result… must examine the patient IV FLUID orders: Volume - Water - K+ - Acid/base

5. 3 Key Concepts in Fluid and Electrolyte Physiology Cell membrane permeability Osmolality Electroneutrality

6. Cell Membrane Permeability

7. Osmolarity vs Osmolality Osmolarity is defined as the concentration of the solute per liter of solution Osmolality is concentration of the solute/kg solvent (usually plasma or urine) Sodium accounts for 97-98% of plasma osmolality (range 287  7 mOsm/Kg) mOsm/kg = 2X[Na+ mEq/L] + (glucose mg/dL)/18 + (BUN mg/dL)/2.8

8. Electroneutrality Primary extracellular cation is SODIUM Primary intracellular cation is POTASSIUM Plasma (ECF) is the only compartment readily accessible

11. Body Fluid Compartments Adult humans are 50% - 70% water Women and the elderly have higher % of body fat than young men, and thus less water. For all practical purposes, assume that TBW = 0.60 X WT (kg)

12. Body Fluid Compartments 70 kg male (TBW=0.6 X wt) IntraCellFluid28L (70 kg X 40% = 28) ECF14L (70 kg X 20% = 14) Extravascular10.5L (70 kg X 15% = 10.5) Intravascular6.3L (70 kg X 9% = 6.3)

13. *Plasma Intracellular Extracellular Na + 16%81%3% EABV Distribution of Sodium

14. Body Fluid Compartments The composition of the ECF is roughly the same as the interstitial space with the exception of proteins which are trapped within the vascular lumens. The distribution of fluid between these two spaces is determined by Starling Forces.

15. Volume Homeostasis ECF Volume is linked to total body sodium Important: Total body sodium is not concentration Concentration depends not only on amount of sodium but also the amount of water Total body sodium is regulated by the kidneys Input minus output equals accumulation…

16. Volume Depletion (a.k.a Hypovolemia) Decreased ECF volume is always sensed as a decrease in the “Effective Arterial Blood Volume (EABV)” The EABV signals the kidney whether to reabsorb or excrete sodium. No direct measure of the EABV, it is determined by blood volume, cardiac output, and systemic vascular resistance Decreased “EABV” results in Na + retention and expansion of ECF volume

17. Clinical Signs of Hypovolemia Orthostatic hypotension Tachycardia Flat neck veins Dry mucous membranes Absent axilliary sweat Decreased skin turgor Decreased CVP

18. Common IV Fluids SolutionGlucoseNa + K+K+ Ca ++ Cl - LactatePO 4 = Mg ++ D5W500000000 NS015400 000 D5NS5015400 000 D5½NS507700 000 LR0130431092800

19. Management of Hypovolemia The primary fluid prescribed for hypovolemia is Normal Saline In the management of hypovolemia, there is no place for ½NS or D5W…. Transfusion Albumin Hetastarch (Hespan ®) or Plasmanate ®

20. IV fluids: continued Addition of an isotonic fluid (0.9% NaCl) expands the ECF but doesn’t change the IntraCellularFluid Addition of a hypotonic fluid (D5W) will cause movement of water into the cells. Addition of a hypertonic fluid (3% saline) will cause movement of water out of the cells.

21. Why is Normal Saline the “drug of choice”? If you give 1 Liter of Normal Saline (0.9% NaCl), the NaCl is restricted to the ECF, therefore the entire liter stays in this space. 75% (750 ml) in the interstitial fluid and 25% (250 ml) in the intravascular space.

22. Body Fluid Compartments 70 kg male (TBW=0.6 X wt) IntraCellFluid28L (70 kg X 40% = 28) ECF14L (70 kg X 20% = 14) Extravascular10.5L (70 kg X 15% = 10.5) Intravascular6.3L (70 kg X 9% = 6.3)

23. IV Fluids: what about 0.45% saline? Think of 0.45% NaCl as 500ml of saline and 500 ml of water. The saline distributes to the ECF compartment alone. 75% (375 ml) in the interstitial space and 25% (125 ml) in the intravascular space. The water distributes 66% (330 ml) to the intracellular space & 33% (170 ml) to the ECF. Of the 170 ml to ECF, only 25% or 42.5 ml stays in the intravascular space.

24. Fluid Prescriptions Thus of our 1L 0.45NaCl, only 125 + 42.5 = 167.5 ml stays in the intravascular space

25. When should you use hypotonic solutions? If there is a need to administer water to the patient (because of a water deficit state) Maintenance fluids (not volume replacement) D5W, D5¼NS or D5½NS may be used in combination with bicarbonate if there is a need to administer base.

26. Clinical Signs & Symptoms of Volume Expansion Jugular venous distension +/- S3 gallop Dyspnea Ascites – this could be debated Pulmonary edema Pleural effusions Peripheral edema (remember hypoalbuminemia)

27. Management of Hypervolemia Goal of treatment Removal of extracellular fluid Loop Diuretics Salt restriction (PO and IV) Dialysis/CVVHD Phlebotomy Rotating tourniquets

28. Pathways of Water Balance

29. Calculate the Water Deficit… [0.6] x (wt in Kg) X [{Na/140} – 1] The water deficit should be fixed in the form of water (D5W or tap water). Water repletion is over and above the maintenance fluids which may be either isotonic or hypotonic.

30. How do you write IV Fluid orders? Input – output = accumulation Volume balance Water balance Potassium (deficit, CKD, Mg++, presence of acidosis or alkalosis) Acid base (administration of bicarbonate or HCl)

31. Case I: Mild Hyponatremia Case I: Mild Hyponatremia 65 yo WF smoker @ small cell carcinoma No evidence of CHF on physical exam Na+ 122 mEq/l K+6.1 Mild respiratory acidosis GFR normal No dyrenium, amiloride, or aldactone Positive history for Lovenox (DVT) for 2 weeks

32. Case I: hyponatremia - continued PE: normal vitals (no tilt) comfortable at rest extremities - no edema no confusion Random U Na+ elevated at 40 mEq/L Uosm 600 TSH is WNL 1) Differential Diagnosis 2) IV fluid orders (NPO for cardiac evaluation)

33. Patient receives saline Diagnosis = SIADH IV saline administered: 1 liter = 300mosm Urine 600 mosm, provides for excretion of 300 mosm of sodium chloride in 500ml of urine Allows patient to “keep” 500 ml of water Sodium falls to 119 mEq/L

34. Case II: HIV possible sepsis 25 yo male with HIV Admitted with streptococcal sepsis with meningitis History of IVDA with baseline CKD ARF = BUN 80mg% creatinine 2.5mg% Volume depletion on exam NPO (unresponsive) Mild metabolic acidosis Sodium 133 mEq/L IV fluids?

35. Case III: history of CHF 70 yo diabetic, known CHF, mild CKD Admitted with acute coronary syndrome NPO for cardiac cath Recent increase in diuretics caused acute deterioration in GFR: BUN > 110 creat 2.2mg% Euvolemic on exam (maybe a little dry?) Na+ 125mmole/L IV Fluids?

36. Case IV: DKA 45 yo WF IDDM X 20 yrs Non-functional glucometer… N&V for 18 hrs… indigestion/pain for 2 hrs No dyspnea No blood in emesis or stool ‘too sick’ to administer insulin PMH - DM HBP Lipids CKD

37. DKA: continued 130/60 tilting to 95/50 P110 R24 Afebrile Neck: veins impossible to assess Lungs: few rales, WOB increased Cor: I/VI m, soft S3, increased HR Abd:benign, non-distended Ext: 1+edema WBC 12K Hct 35% 2+proteinuria 5-10 WBC/HPF EKG: 2mm ST elevation III and AVF

38. DKA: continued Na+ 131 K+ 3.2 Cl- 104 HCO3 5mEq/l BUN 70 Creat 2.0 anion gap 22 mEq pH 7.18 pCO2 18 pO2 80 (1.5)(HCO3) + 8 [+/- 2mEq] = pCO2 Dx? Volume status? Na+? K+? acid/base issues? IV fluids?

39. Case V: Rhabdomyolysis 24 yo SWAT team member of GPD August 1998 “106 degrees in the shade” full gear running drill - collapse in field BP 100/60 P 130 T 102.8 rectal Skin warm Neck veins: nl Lungs: clear Cor: increased HR MS: tender back/gluteal region, no edema

40. Rhabdo: continued Urine looks red… scant volume… heme + U Na+ <10 FeNa+ low Na+ 149 K+ 5.9 Anion gap 22 Bun 15 Creat 2.4 Ca++ 6.5 Phos 8.5 CPK 50,000 “As you rapidly cool down the patient:” Diagnosis? Volume status? Cause of Hyperkalemia? IVF orders?

41. Case VI: Ascites 65 yo retired engineer with known cirrhosis ETOH exposure Hx GIB/varices Meds: Beta blocker Aldactone Furosemide (no NSAID’s) Decreased intake for several days; increasing abd pain - severe, diffuse, no radiation; minimal emesis no gross hemorrhage in stool

42. Ascites: continued PE: barely awake confabulates barely follows tremulous T 101.8 BP 90/60 red palms spider angiomata muscle wasting massive ascites very tender abdomen guaiac positive stool 1+ edema 2+ ankles Lab: WBC 20K Hct 34% Bili 4 albumin 2.4 INR 2.5 AG 12 Na+128 K+ 5.0 FeNa<1; ascites with 3000 WBC and positive gram stain BUN 80 Creat 3mg% Decreased U Na+ < 15

43. Ascites: continued Differential diagnosis? Volume status? Acid base status? IV fluids? (TPN?)

44. Case VII – Metabolic acidosis Patient with recurrent diarrhea complains of muscle weakness No carpopedal spam, Trousseau’s of Chvostek’s EKG reveals ST-segment and T-wave changes and PVC’s compatible with hypokalemia

45. Case VII: continued Plasma [Na+] = 140 meq/L [K+] = 1.3 meq/L [CL-] = 117 meq/L [HCO3] = 10 meq/L [albumin] = 4.1 g/dL (3.5 – 5 g/dL) [Ca++] = 6.3 mg/dL (8.8 – 10.5 mg/dL) arterial pH = 7.26 pCO2 = 23 mm Hg Correction MA effect K+? Correct hypo Ca++?

46. Case VIII: Chronic Li+ 40 yo female NPO X 48 hours post complicated cholecystectomy Admission [Na+] = 146 mmoles Developes profound hypotension requiring transfer to ICU (without myocardial infarction) Current [Na+] = 175 mmoles IV fluid orders?

47. Case IX: AKI 60 yo attorney ANURIC AKI SEPSIS MSOF: lungs, cardiac, liver, renal, bone marrow, nutrition, skin, CNS Intermittent HD [Na+] 130 [K+] 3.3 BUN 40 mg% Creat 5mg% IVF orders? TPN? Tube feeds?

48. Case X: acute water intoxication 20 yo SMU student brought to ER by fraternity Unresponsive hypothermic hypotensive Sodium 106 mEq/L Mild azotemia Calculated water load > 8 liters… IVF?

49. Summary Most common error in writing IV Fluid orders: 1) administration of NS in pts with SIADH 2) inadequate volume replacement in sepsis or pre-renal azotemia

50. Questions? Next month: hemodialysis therapy…

51. Hyponatremic Patient SymptomaticAsymptomatic Acute (<48 hrs) Chronic (>48 hrs) Risk Factors for Neurologic Complications? Treatment of Hyponatremia

52. Symptoms and Signs of Hyponatremia Symptoms Lethargy Headache Apathy Muscle Cramps and weakness Anorexia Nausea Agitation Psychosis Signs Abnormal sensorium Depressed deep tendon reflexes Hypothermia Pathologic reflexes Pseudobulbar palsy Seizures *Tentorial Herniation *Cheyne-Stokes respiration *Coma Death

53. Acute Symptomatic Hyponatremia Duration <48 hrs Increase serum [Na] rapidly by approximately 2 mM/L/hr until resolution of symptoms. Full correction probably safe, but not necessary Hypertonic Saline 1-2 ml/kg/hr Coadministration of Furosemide Note: The sum of urinary cations (U Na + U K ) should be less than the concentration of infused sodium to ensure excretion of electrolyte free water.

54. Cerebral Adaptation to Hyponatremia

55. Duration >48 hrs or unknown Initial increase in serum [Na] by 10% or 10 mM/L Hypertonic Saline 1-2 ml/kg/hr Co-administration of Furosemide Perform frequent neurologic evaluations; correction rate may be reduced with improvements in symptoms Perform frequent measurement of serum and urine electrolytes At no time should correction exceed rate of 1.5 mM/L/hr, or increment of 15 mmol/day Change to water restriction upon 10% increase of [Na], or if symptoms resolve Chronic Symptomatic Hyponatremia Note: The sum of urinary cations (U Na + U K ) should be less than the concentration of infused sodium to ensure excretion of electrolyte free water.

56. Severe Hyponatremia (<125 mM/L) Symptomatic Asymptomatic Acute Duration < 48 hrs Chronic Duration > 48 hrs Emergency Correction Needed Hypertonic Saline 1-2 ml/kg/hr Coadministration of Furosemide Some Immediate Correction Needed Hypertonic Saline 1-2 ml/kg/hr Co-administration of Furosemide Change to water restriction upon 10% increase of [Na], or if symptoms resolve Perform frequent measurement of serum and urine electrolytes Do not exceed 1.5 mM/L/hr, or 20 mM/d Chronic Rarely < 48 hrs Long Term Management Identification and Treatment of Reversible etiologies Water Restriction Demeclocycline 300 mg to 600 mg bid Urea 15 to 60g qd V2 receptor antagonists No immediate correction needed Treatment of Severe Euvolemic Hyponatremia (<125 mmol/L)

58. Treatment of Asymptomatic Chronic Hyponatremia Fluid Restriction Pharmacologic Inhibition of Vasopressin Action Lithium Demeclocycline V-2 receptor antagonist Increase solute Excretion Furosemide + 2-3 g of NaCl/day Urea 30 g/d Increased dietary protein intake

59. Management of Non-Euvolemic Hyponatremia SM Lauriat, T Berl: The Hyponatremic patient: Practical Focus on Therapy. J Am Soc Nephrol, 1997, 8(11):1599-1607. Hypovolemic Hyponatremia Volume restoration with isotonic saline Identify and correct etiology of water and sodium losses Hypervolemic Hyponatremia Water Restriction Sodium Restriction Substitute loop diuretics instead of thiazide diuretics Treatment of stimulus for sodium and water retention V2-receptor antagonist

60. The Hypernatremic Patient

61. Guidelines for the Treatment of Symptomatic Hypernatremia Correct at a rate of 2 mM/L/hr Replace half of the calculated water deficit over the first 12- 24 hrs. Replace the remaining deficit over the next 24-36 hrs. Perform serial neurologic examinations - prescribed rate of correction can be decreased with improvement in symptoms Measure serum and urine electrolytes every 1-2 hrs. Note: If U[Na] + U[K] is less than the concentration of P[Na], then there are ongoing water losses that need to be replaced

62. Treatment of Hyponatremia Three Key Questions Is the patient symptomatic? What is the duration of Hyponatremia? Are there any risk factors for the development of neurologic complications?