Microvascular Fluid Management And its Effects

1. Microvascular Fluid Management And its Effects SABM Annual Meeting Los Angeles CA Sept 20th 2013 Dave Fitzgerald CCP President, AmSECT

2. Conflict of Interest DisclosureDavid C Fitzgerald, CCP • Salary: none • Royalty: none • Receipt of Intellectual Property Rights/Patent Holder: none • Consulting Fees (e.g., advisory boards): none • Fees for Non-CME Services Received Directly from a Commercial Interest or their Agents (e.g., speakers’ bureau): none • Contracted Research: none • Ownership Interest (stocks, stock options or other ownership interest excluding diversified mutual funds): none • Other: Terumo Cardiovascular- non-CME presentation

3. Pre Game Plan (The Big 3) • When ever possible the members of the Cardiac surgical team should communicate • (The Surgeon, Anesthesia, and Perfusion) should meet prior to surgery and discuss the best course of action for optimizing the case and avoiding Allogeneic Blood Products. • The Team Approach to Blood Management !

4. Edema “3rd Spacing” “Capillary Leak Syndrome”Fluid Extravasation or Leucophlegmatia Also known as dropsy or hydropsy, is the increase of interstitial fluid in any organ causing swelling and dysfunction. Generally, the amount of interstitial fluid is determined by the balance of fluid or homeostasis, and increased secretion of fluid into the interstitium or impaired removal of this fluid may cause edema and 3rd spacing. The Generation of interstitial fluid is regulated by the Starling equation of tissue fluid which states that it depends on the balance of osmotic pressure and of hydrostatic pressure which act in opposite directions across the semipermeablecapillary walls. Consequently, anything that increases oncotic pressure outside blood vessels (for example, inflammation), or reduces oncotic pressure in the blood (states of low plasmaosmolality, for example, hemodilution) will cause edema. Increased hydrostatic pressure inside the blood vessel (for example, in heart failure) will have the same effect. If the permeability of the capillary walls increases, more fluid will tend to escape out of the capillary, which can happen when there is inflammation. Abnormal removal of interstitial fluid is caused by dysfunction or obstruction of the lymphatic system.This may be due to, for example, pressure from a cancer or enlarged lymph nodes, lack of muscle contraction (ie during surgery) or infiltration of the lymphatics by infection (such as elephantiasis). There are two types: exudate and transudate.

5. *You should never give a patient IV fluid unless there is excessive volume loss from Urination or Bleeding *Perspiration and Insensible loss are negligible in the perioperative setting and may amount to 1L in 4hrs. But if you must give volume to the patient: There are two types of fluids that are used for intravenous administration; Crystalloids and Colloids *Crystalloidsare aqueous solutions of mineral salts or other water-soluble molecules. *Colloidsgenerally contain larger insoluble molecules, such as Albumin, Gelatins and Blood itself is a Colloid.

6. Types of Crystalloids used in Surgery • Ringers (drawbacks) • Ringers Lactate • Hartmann's Solution • Normal Saline .9%NACL • Half Normal Saline.45% NACL • D5W 5% dextrose in Water • Plasmalyte A • Plasmalyte 148 • Normosol

7. For Every 1000 mLs of Crystalloid Fluid Given to Patients Only 200-300 mLs will remain Intravascular in 30-45 mins Dilution leads to organ dysfunction and coagulopathy Hct 40% Hct 23% Hemodiluted Hct = +/- 23% Normal Hct = 40+/-% Chappell Fluid Article: Trauma patient study by Lowell et. al.

8. Anesthesia Can Help out a lot Here! • Hypotension is NOT always Hypovolemia! • Push the SVR not the Starling Curve! normal 800-1200. • Hemodilution (HD) is the Enemy! It leads to Organ Edema and Organ Dysfunction that leads to Morbidity and Mortality! • HD creates to a Dilutional Anemiaand a Dilutional Coagulopathy that leads to Blood Products and that leads to M&M! • Give as little Volume as necessary and keep Patient tight if possible

9. What is Blood? “Your Body your Blood”

11. The Big Picture about Whole Blood Choices/ Alternatives Publication Vol 4 Issue 2, Center for Bloodless Medicine and Surgery, University of Miami / Jackson Med Ctr.

12. Systemic and Pulmonary Circulation Around the body to the Organ Systems

13. Where the Volume Goes andUnder what Pressure,“Everything is Hydrokinetic”

14. Arteries to Veins

15. VASCULAR ANATOMY

16. But This is! Where the Rubber Meets the Road

17. What is Microcirculation? Microcirculation deals with the flow of blood from arterioles to capillaries or sinusoids to venules. Blood flows freely between an arteriole and a venule through a vessel channel called a thoroughfare channel. Capillaries extend from this channel and structures called precapillary sphincters control the flow of blood between the arteriole and capillaries. The precapillary sphincters contain muscle fibers that allow them to contract. When the sphincters are open, blood flows freely to the capillary beds where gases and waste can be exchanged with body tissue. When the sphincters are closed, blood is not allowed to flow through the capillary beds and must flow directly from the arteriole to the venule through the thoroughfare channel. It is important to note that blood is supplied to all parts of the body at all times but all capillary beds do not contain blood at all times. Blood is diverted to the parts of the body that need it most at a particular time. For ex. when you eat a meal blood is diverted from other parts of your body to the digestive tract, or the Fight or Flight response ie: Tiger! CO = 5 lpm to 20 lpm

18. What Sizes

19. Arterioles Small precapillary resistance vessels (10-50 µ) composed of an endothelium surrounded by one or more layers of smooth muscle cells. Richly innervated by sympathetic adrenergic fibers and highly responsive to sympathetic vasoconstriction via both a 1 and a 2 postjunctional receptors. Represent the major site for regulating SVR systemic vascular resistance. Primary function within an organ is flow regulation, thereby determining oxygen delivery and the washout of metabolic by-products. Regulate, in part, capillary hydrostatic pressure and therefore influence capillary fluid exchange.

20. Vaso-Action of the Arterioles in Regulating SVR ***Norm= 800-1200d/cm2***

21. What are capillaries? Capillaries walls are thin and are composed of endothelium (a single layer of overlapping flat cells). Oxygen, carbon dioxide, nutrients and wastes are exchanged through the thin walls of the capillaries. The flow of blood is controlled by structures called precapillary sphincters. These structures are located between arterioles and capillaries and contain muscle fibers that allow them to contract. When the sphincters are open, blood flows freely to the capillary beds of body tissue. When the sphincters are closed, blood is not allowed to flow through the capillary beds

22. Capillary Size • Capillaries are so small that red blood cells can only travel through them in single file. • 5-10 microns in diameter.

23. Capillaries • Small exchange vessels (5-10 µ) composed of highly attenuated (very thin) endothelial cells surrounded by basement membrane – no smooth muscle. • Three structural classifications: Continuous (found in muscle, skin, lung, central nervous system) – basement membrane is continuous and intercellular clefts are tight (i.e., have tight junctions); these capillaries have the lowest permeability. Fenestrated (found in exocrine glands, renal glomeruli, intestinal mucosa) – perforations (fenestrae) in endothelium result in relatively high permeability. Discontinuous(found in liver, spleen, bone marrow) – large intercellular gaps and gaps in basement membrane result in extremely high permeability.  Large surface area and relatively high permeability to fluid and macromolecules make capillaries the primary site of exchange for fluid, electrolytes, gases, and macromolecules.In some organs, precapillary sphincters (a circular band of smooth muscle at entrance to capillary) can regulate the number of perfused capillaries.

24. Capillary "Type" • Permeability varies with type of capillary • Capillary type varies with organ function • 1. Tight (brain) 2. Continuous (skeletal muscle, skin) 3. Fenestrated (secretory glands, kidney, gut) 4. Discontinuous (liver, spleen, bone marrow)

27. Chappell Fluid Article

28. And this is the Gate Keeper

29. I Mean this is the Gate Keeper! The Glycocalyx

30. The Glycocalyx The Endothelial Glycocalyx, is a gel-like layer that coats the inner surface of the endothelium throughout the entire vascular tree less than 100nm thick and is made up of negatively charged carbohydrate polymeric glycoproteins and plasma soluble molecules produced by bacteria, epithelia and other cells. Think of it as a non-stick Teflon coating on the luminal endothelial surfaces. The slime on the outside of a fish is considered to be a glycocalyx. The glycocalyx layer contains very fine hair-like structures that contribute to cell-cell recognition and transmit intracellular adhesion changes and shear forces to the endothelium, ultimately regulating nitric oxide release, it consists of a wide range of enzymes and proteins that regulate leukocyte and thrombocyte adherence. Its principal role in the vasculature is to maintain plasma and vessel wall homeostasis.

31. The Glycocalyx Glycocalyx has multiple functions: it mediates nitric oxide synthesis and superoxide dysmutation, it acts as a protective "sieving" barrier, inhibits platelet adherence, and coagulation, and it regulates inflammation by preventing leukocyte adhesion to the vessel walls. One of its most important functions is to keep the endothelial wall responsive to changes in vascular fluid dynamics within the vascular endothelium as it shields the vascular walls from direct exposure to blood flow shear stress, while serving as a vascular permeability barrier.

32. A Non-Stick Coating Unless Disrupted The Glycocalyx can get damaged from sheer stress decreasing NO availability, increased oxidative stress, leakage of macromolecules, increased platelet adherence, thrombin generation, and increased leukocyte adhesion, all of which set the stage for thrombotic events. These damaged glycocalyx areas increase perivascular edema leading to a leakage of fluids and proteins which causing tissue damage and loss of capillaries.

33. Glycocalyx Shedding and Vascular Permeability. Its hypothesized that hypoxic perfusion of the glycocalyx is sufficient enough to initiate a degradation mechanism of the endothelial barrier. Studies found that flow of oxygen throughout the blood vessels did not have to be completely absent (ischemic hypoxia), but that minimal levels of oxygen were sufficient enough to cause the degradation. Shedding of the Glycocalyx can be triggered by Fluid Shear Stress (FSS) ie the start up motion of an RBC in a tight capillary bed or the crushing passage of a WBC, and inflammatory stimuli such as Tumor necrosis factor-alpha (TNF). Whatever the stimulus, shedding of the glycocalyx leads to a drastic increase in vascular permeability. This permeability enabling the passage of macromolecules and other harmful antigens leading to 3rd spacing and edema and organ edema and dysfunction.

34. OK What are Sinusoids then? • The liver, spleen and bone marrow contain vessel structures called sinusoids instead of capillaries. Similar to capillaries sinusoids are composed of endothelium. The individual endothelial cells however do not overlap as in capillaries and are spread out. Oxygen, carbon dioxide, nutrients, proteins and wastes are exchanged through the thin walls of the sinusoids. • Sinusoid Size • 30-40 microns in diameter.

35. OK on our way Out The Return Trip Venules Small exchange vessels (10-50 µ) composed of endothelial cells surrounded by basement membrane (smallest postcapillary venules) and smooth muscle (larger venules). Fluid and macromolecular exchange occur most prominently at venular junctions. Sympathetic innervation of larger venules can alter venial tone which plays a role in regulating capillary hydrostatic pressure. Terminal Lymphatics Composed of endothelium with intercellular gaps surrounded by highly permeable basement membrane and are similar in size to venules – terminal lymphatics end as blind sacs. Larger lymphatics also have smooth muscle cells. Spontaneous and stretch-activated vasomotion is present which serves to "pump" lymph. Sympathetic nerves can modulate vasomotion and cause muscle contraction. One-way valves direct lymph away from the tissue and eventually back into the systemic circulation via the thoracic duct and subclavian veins (Normally 2-4 liters/day is returned)

36. (Physiology) Fluid Volume Management Circulation Lymphatics

37. Blood Volume & Fluid Compartments

38. BLOOD DISTRIBUTION

39. Cardiac Output & Delivering the Blood Volume to the Tissues And Oxygen Extraction

40. Meds IV fluids Transfusions Bleeding Diarrhea Fever Renal Failure Dialysis Surgery (!) Ventilator Maintaining Fluid HomeostasisFluid Balance is DynamicEspecially in illness and most especially in surgery

41. Volume/Fluid Management Time to Focus on the Real Problem! • That first I.V. Line (Let the games begin) • For every 1 liter of Crystalloid given • Only 200mls will stay Intravascular within 45 minutes, the rest of the 800mls will cross extravascularly causing Organ Edema/Dysfunction dropping the Viscosity and COP by Hemodilution • It’s a lot easier to add volume to the patient • than it is to take it off!

42. The “Epicenter” of Life & Fluid Balance

43. How Do Fluid Shifts Happen?

44. STARLINGS LAW

45. Fluid Movement Between Compartments

47. Tonicity • Osmolarity • Ions (osmotic force) • Proteins (oncotic force) • Hypotonic • Cells placed in a hypotonic solution swell • IsotonicJust right* • Hypertonic • Cells placed in a hypertonic solution shrink

48. Oncotic States

49. Advantages of Crystalloids Virtually free of adverse/allergic reactions No reported adverse effects on hemodynamics or prolonged extubation times Increased urine output Cheap and readily available G. Myers NS CA

50. Disadvantages of Crystalloids Reduce colloid osmotic pressure Increase perioperative water content in heart and lungs During bleeding replacement is 3 times blood lost As much as 70-80% of infused volume can go into the extravascular space G. Myers NS CA