Fluids, Electrolytes and Shock

1. Fluids, Electrolytes and Shock Tom Archer, MD, MBA UCSD Anesthesia

2. Outline • Three fluid compartments (ICF, ISF, IVF) • Three membranes • Osmosis– theory and clinical • Shock-- tissue needs and cardiac output • Water and electrolytes in general (3 overlapping systems) • Hyponatremia– appropriate and inappropriate secretion of ADH • Hypernatremia and K+ disorders

3. Three fluid compartments Intracellular fluid (ICF) Interstitial fluid (ISF) Intravascular fluid (IVF)

4. Fractions to remember:2/3, 2/3, 3/4 • TBW (42 L) = 2/3 of body weight (70 kg). • ICF (28 L) = 2/3 of TBW. • ECF (14 L) = 1/3 of TBW. • Interstitial fluid (ISF, 10.5 L) = ¾ of ECF • Intravascular fluid (IVF, 3.5 L) = ¼ of ECF.

5. Three membranes Cell membrane Non- brain capillary endothelium Brain capillary endothelium (“blood-brain barrier– BBB”)

6. Solutes Ions: Na+ , Cl-, K+, PO4--- Sugars: glucose, mannitol Large molecules (colloids): albumin, hetastarch

7. Two types of membranes • Non-brain capillary endothelium is permeable to everything but colloid, therefore, only colloid is osmotically active at non-brain capillary membrane.

8. Two types of membranes • Cell membrane and healthy BBB are only permeable to water, therefore, all ions, sugars and large molecules are osmotically active at cell membrane and BBB.

9. Blood-brain barrier • Behaves just like the cell membrane– a tight, lipid rich membrane which is impermeable to everything but water (and lipophilic drugs).

10. Osmosis • What is osmosis? • Answer: diffusion of water down its concentration gradient.

11. For all osmosis questions: • What is the solute? • What is the membrane? • Is the membrane permeable to the solute? • If not, solute will "pull" water across the membrane.

12. Clinical examples of osmotic effects • Brain trauma: mannitol to shrink normal brain to make room for mass lesion. • Brain trauma or blood loss: Hypertonic saline to shrink normal brain or expand ISF and IVF. • Hyperglycemia causes osmotic diuresis and hypovolemia. • Hyperglycemia causes brain dehydration (with potential for cerebral edema with rapid correction of hyperglycemia).

13. Multi-modal approach to cerebral protection / resuscitation after TBI: Monitoring Normovolemia Avoid hyperglycemia and hyperthermia Seizure prophylaxis Artificial ventilation, oxygenation ICP monitoring Sedation, analgesia, posture, paralysis PaCO2 management Osmotic Rx (serum mOsm = 320) Furosemide Hyperventilation Barbiturate coma Surgical decompression

14. Edema vs. Osmotic effects • Edema can be purely hydrostatic (6 hours head down during surgery) • Edema can be d/t low oncotic pressure (hypoalbuminemia in cirrhosis) • Can be due to both factors.

15. Intravenous fluids • “Crystalloids” • Normal saline (just NaCl). • Lactated ringers • Plasmalyte • Normosol • Last 3 have K+ and other stuff (acetate, Mg++, etc.)

16. Practical aspects • Crystalloids enter entire ECF: ISF (3/4 of ECF) and IVF (1/4 of ECF). • 3 or 4:1 for replacement of blood loss with crystalloid • Colloids only enter IVF (in short term– 16 hour half-time for entrance into ISF) • 1:1 replacement of blood loss with colloid

17. Homeostatic systems for water, electrolytes and circulation • Renin-angiotensin-aldosterone system (RAAS) • Osmoreceptors, thirst, ADH (V1 vasocon and V2 tubular) • Sympathetic nervous system • Aortic, carotid, atrial and ventricular stretch receptors--Atrial Natriuretic Peptide (ANP), Brain Natriuretic Peptide (BNP), vasogenic intestinal peptide… and others. • Kidney (glomerulus, tubules, collecting duct, glomerulo-tubular balance, macula densa).

18. Colson P Anesth and Analg 1999

19. Fast and slow components of fluid volume homeostasis. • RAAS: angiotensin II is fast / aldosterone is slow. • ADH (“arginine vasopressin”): ADH in high concentration is immediate vasopressor on V1 receptor. • ADH in low concentration retains free water (slowly) in collecting duct via V2 stimulation.

20. Schrier RW The American Journal of Medicine (2006) Vol 119 (7A), S47–S53

21. Juan A. Oliver and Donald W. Landry Curr Opin Crit Care 13:376–382. 2007 Lippincott Williams & Wilkins.

22. “Syndrome of Inappropriate ADH”A Garbage Term? • Seen in neurological disease or injury. • Seen in pulmonary disease (tumors, TB, etc.) • ADH release by pain, stress, opioids and nausea is also “inappropriate.” • Excessive and counter-productive ADH release in CHF and cirrhosis is also “inappropriate.”

23. Big picture– Shock (1) • Inadequate circulation and supply of nutrients to tissues– either at the macro or micro level. • Intravascular volume loss (hemorrhage, burns, GI losses). Preload problem. • Cardiogenic (pump failure). • Spinal cord transection / anaphylaxis. Preload and afterload problems. • Microcirculatory failure by RBC sludging, stasis or microcirculatory coagulation (sepsis, DIC).

24. Causes of shock • Preload (How do we judge preload? CVP?, PAOP?, LVEDP?, LVEDV?, SPV?, PPV?, SVV?) • Pump (contractility, dP/dT) • Afterload (SVR) • Microcirculatory (endothelial) failure (sepsis, pre-eclampsia, DIC, ARDS, hyperglycemia, etc.)

25. Obesity, hyperglycemia, sepsis and pre-eclampsia all “activate” (damage) endothelium, white cells and platelets, leading to white cell adhesion and infiltration, thrombosis and edema (inflammation). WBC WBC Obesity, hyperglycemia, sepsis or pre-eclampsia Platelet Platelets Protein (edema) Archer TL 2006 unpublished

26. Big picture– Shock (2) • Hemodynamic manipulations of HR, SV, SVR, preload, afterload, contractility, etc. may provide limited help to microcirculation deranged by sepsis (for example). • Hemodynamic manipulations may simply “buy us time” and support patient while we treat the underlying cause of the shock. • Endothelium must heal!

27. Different recipes for optimizing macrocirculation in sepsis. “Early goal-directed therapy of septic shock.” Rivers E et al N Engl J Med, Vol. 345, No. 19 · November 8, 2001

28. Like the giant plant in “Little Shop of Horrors”, body tissues say, “Feed me!”

29. “Feed me!” Arteriole Capillary Hungry tissue says, “Feed me!” to pre-capillary sphincter.

30. Case #1“The patient is overloaded…”“The patient is dry…” • 24 yo male, previously healthy, 4 days s/p GSW abdomen with shock, peritonitis, sepsis, hypotension. Controlled ventilation. BP = 90/60, HR = 130. • Weight gain 4 kg since admission. • Albumin = 1.9. BUN / creat = 48 / 1.9. • PAOP = 5 mm Hg. • Systolic pressure variation: 18%

31. Is the patient “dry”? Systolic pressure variation (together with pulse pressure variation and stroke volume variation) are new “dynamic” indices of whether or not the cardiac output will increase with a volume bolus. Michard F, Anesthesiology 2005; 103:419–28

32. Is the patient “dry”? Positive pressure ventilation sequentially (1-2-3) reduces vena cava blood flow, PA blood flow and arterial pressure. Michard F, Anesthesiology 2005; 103:419–28

33. Case #1“The patient is overloaded…”“The patient is dry…” • Patient has low INTRAVASCULAR volume, but also has excessive INTERSTITIAL fluid (edema). • This is totally consistent with the “leaky capillary” picture of sepsis. • Systolic pressure variation >13% suggests fluid bolus will increase CO. CO is “fluid responsive”.

34. The Three Hyponatremias • Isotonic (proteins or lipids dilute Na+ on bulk basis). Often called “artifactual.” “Watery” portion of serum has normal tonicity. • Hypertonic (osmotic agent “sucks” water out of ICF, diluting Na+, but tonicity stays high). • Hypotonic. By far the most common (and hardest to understand).

35. Isotonic hyponatremia • Hyperproteinemia or hyperlipidemia dilutes out the Na+. [Na+] in the water portion of the blood is normal. • Glycine solution with TURP. • Treatment is to work up and treat underlying cause

36. Isotonic hyponatremia (“artifactual”). Protein or lipid takes up some of the plasma volume. Aqueous “portion” of plasma has normal [NaCl]. Protein or lipid “phase” [NaCl] = 0 Serum (combined) [NaCl] = 123 Aqueous “phase” [NaCl] = 135 Osmolarity (tonicity) normal

37. Hypertonic Hyponatremia-- causes • Due to hyperglycemia, mannitol or glycerol. • Decreased [Na+] in serum, but osmolality is high (>290), due to sugar in the blood. • Sugar has “sucked” water out of cells, into the ECF. Water dilutes Na+.

38. Hypertonic hyponatremia– osmotically active sugar “draws” water into vascular space, diluting NaCl, but increasing overall osmolarity (tonicity). Glucose, mannitol, glycerol [NaCl] = 140 [NaCl] = 123 Osmolarity (tonicity) increased Water in ICF and interstitial ECF

39. Hypertonic Hyponatremia-- Rx • Insulin to slowly reduce blood glucose. • NS volume replacement. • Complications of rapid reduction of serum glucose and tonicity: hypoglycemia, cerebral edema

40. Four causes of increased ADH • Normal osmotic ADH release: osmoreceptors in hypothalamus release ADH via posterior pituitary in response to serum mOsm > 290. Makes physiological sense. Stress-related ADH release (pain, nausea, opioids, running a marathon). • Non-osmotic increased ADH (in hypovolemia): • “Defense of intravascular volume”-- severe volume contraction. Makes physiological sense. • Diuretics, GI losses, burns, hemorrhage, sweating, adrenal insufficiency. • Non-osmotic increased ADH (causing hypervolemia): • Pathological states (CHF, cirrhosis, pulmonary, CNS). These are classically called “SIADH”.

41. All these conditions are associated with increased ADH secretion. Achinger, Moritz, and Ayus • Dysnatremias: Why Are Patients Still Dying? Southern Medical Journal • Volume 99, Number 4, April 2006

42. Hypotonic hyponatremia– too much free water compared to NaCl. (Volume deficit with non-osmotic ADH release, or CHF, cirrhosis or SIADH) Free water ADH NaCl NaCl Osmolarity (tonicity) decreased

43. Stress- induced, non-osmotic ADH release: • This is why we DON’T give D51/4NS in surgery. • This is why we DO give NS, Normosol or LR. • We don’t give free water because of kidney’s reduced ability to excrete it (due to non-osmotic ADH release).

44. Hypotonic, Hypovolemic Hyponatremia-- Rx • Volume restoration with NS if hypovolemic (GI losses, diuretics). • Explanation: Severe hypovolemia causes non-osmotic ADH release. Body tries to “defend intravascular volume” by secreting ADH. • Volume restoration suppresses non-osmotic ADH release and cures hyponatremia by allowing free water excretion.

45. Hypotonic, Hypervolemic Hyponatremia-- Rx • Fluid restriction if hypervolemic (CHF, liver failure). • Diuretics (causing Na+ and water loss) are currently used for ECF overload. We want to get rid of water, but we get rid of Na+ as well. • Emerging Rx: “Aquaretics” are ADH V2 receptor antagonists which prevent inappropriate free water retention in CHF or cirrhosis. Courtesy Dr. Jaydeep Shah

47. Case #2:Perioperative hyponatremia • 34 yo female, no significant past medical history. • Elective L/S BTL 0900. During the surgery, D5 ¼ NS at 125 cc/ hr. • Pt in PACU until afternoon. “Too sedated to go home.” Got IV meperidine. No PO intake, IV D5 1/4 NS continued. • 2:45 AM next day, pt. C/O headache, verbal order for Tylenol #3. • At 9:00 AM, nurse tells surgeon of a sodium of 127 mEq/L. No • new orders, IV fluids were continued. • At 1:30 pm, pt. lethargic and pain medications, pain meds held. • At 3:30 pm, she had sz and respiratory failure. The patient intubated and ventilated. Serum sodium 122 mEq/L. Achinger, Moritz, and Ayus • Dysnatremias: Why Are Patients Still Dying? Southern Medical Journal • Volume 99, Number 4, April 2006

48. Case #2:Perioperative hyponatremia Stress, pain, nausea all cause increased ADH secretion from posterior pituitary. Free water administration with D5 1/4NS allows free water retention. Biggest danger in children, menstruating females and patients having suffered hypoxic episodes. Achinger, Moritz, and Ayus • Dysnatremias: Why Are Patients Still Dying? Southern Medical Journal • Volume 99, Number 4, April 2006

49. How aggressively do we Rx hyponatremic encephalopathy? • Depends on symptoms, not the [Na++]. • In symptomatic hyponatremic encephalopathy, use 3% saline until sx improve.

50. Case #3Hyponatremic encephalopathy • 31 yo female collapses 30 min after running marathon. Disoriented and SOB. • Crackles in all lung fields. CXR pulmonary edema. [Na+] = 126 mEq / L. • What is going on?