Edward Cooper, VMD, MS, DACVECC Professor, Emergency and Critical Care The Ohio State University Body fluid compartments Fluid Pharmacology Phases of fluid therapy Resuscitation Replacement Maintenance Fluid therapy during anesthesia Subcutaneous fluids (2/3) (1/3) (2/3) (1/3) (3/4) (1/4) (3/4) (1/4) (2/3) (1/3) (3/4) (1/4) Barriers between compartments ICF and ECF = Cell membrane Freely permeable to water, impermeable to electrolytes unless by transport Impermeable to proteins unless by transport Movement of fluid dictated by osmotic gradients ISF and IVF = Endothelium Freely permeable to water and electrolytes based on concentration gradients Relatively impermeable to proteins, larger molecules Movement of fluid dictated by Starling s forces 1
Osmotic forces Starling s forces Fluid type? Crystalloids Colloids Blood products Extensive research no clear victor Fluid volume? Also subject of great debate Fluid rate? Depends on objective of fluid therapy Resuscitation vs replacement vs maintenance Varying electrolyte composition in water Categorized based on tonicity Hypotonic (0.45% NaCl, D5W, Norm M) Isotonic (0.9% NaCl, Plasmalyte, etc) Hypertonic (7% NaCl) Categorized by effects on acid-base Acidifying (0.9% NaCl) Alkalinizing (LRS, Plasmalyte, Norm R) Species Na K Cl Ca ++ Mg Osm Dog 135-145 4-5 110 5.4 3 280-305 Cat 140-155 4-5 120 5.1 2.5 295-320 Horse 130-140 3.5-4 105 5.5 1.9 286-305 Cow 130-140 3.5-4 102 5.0 2.0-2.5 286-305 Fluid Na K Cl Ca Mg Osm Bicarb Precurs D5W 0 0 0 0 0 287 0 0.45% NaCl 77 0 77 0 0 154 0 0.9% NaCl 154 0 154 0 0 308 0 LRS 130 4 109 3 0 278 28 lactate P-148, Norm R 140 5 98 98 0 3 294 27 acetate 23 gluconate 3% NaCl 513 0 513 0 0 1026 0 7% NaCl 1198 0 1198 0 0 2396 0 Osmolality less than that of blood Net increase in free water Volume of distribution - total body water Examples Dextrose 5% in water Dextrose allows initial match to blood osmolarity Dextrose not effective osmol metabolized leaving free water 0.45% NaCl ± 2.5% Dextrose Dextrose used for same reason as D5W Normosol M maintenance fluid 2
Clinical indications Replacing free water deficit (hypernatremia) Heart disease and renal disease Impaired ability to handle sodium load Maintenance fluid therapy Lower Na +, higher K + matches daily needs Potentially applied after replacement NEVER RESUSCITATION! Cannot administer rapidly never bolus! Dramatic change in blood osmolarity, RBC damage Osmolality ~ equal to that of blood Replaces electrolytes as well as water Volume of distribution - extracellular space Redistribution within 20-30 minutes Only 1/4-1/3 remains in vascular space Non-balanced acidifying electrolyte solution Normal saline (0.9% NaCl) Balanced alkalinizing electrolyte solutions Plasmalyte, LRS, Norm-R Effects on acid-base balance 0.9% NaCl is acidifying why? ph 5.0 (4.0-7.0) Not a major factor unless large amounts administered HyperCl - (154meq/L) compared to plasma (~110) Increase in Cl - relative to Na + Bicarb loss to maintain electroneutrality? Potential to worsen existing acidosis Beneficial with hypochloremia Effects on acid-base balance Balanced e-lyte solns are alkalinzing Why? ph LRS 6.5 (6.0-8.0), P-lyte 5.5 7.4 (5.0-8.0) Provide bicarbonate precursors: Acetate (P-lyte): NaC 2 H 3 O 2 + 2O 2 CO 2 + H 2 O + NaHCO 3 - Gluconate (Norm R): NaC 6 H 11 O 7 + 5 ½O 2 5CO 2 + 5H 2 O + NaHCO 3 - Lactate (LRS): NaC 3 H 5 O 3 + 3O 2 2CO 2 + 2H 2 O + NaHCO 3-2C 3 H 5 O 3 + 2H + C 6 H 12 O 6 (gluconeogenesis) C 3 H 5 O 3 + H + +3O 2 3CO 2 + 3H 2 O Clinical indications Correction of acid-bases disorders Rehydration Replacement of ongoing losses Resuscitation Adverse effects Creation of acid-base disorders Tissue edema Osmolality of solution greater than that of blood Shift of fluid from interstitium into vascular space Rapid volume expansion (4-6x volume given) Rapidly redistribute across ECF (10-30 min) Only transient impact on blood volume Ultimately reduction in ICV with slight increase in ECV Typically given as 7-7.5% solution 23% solution MUST be diluted! Have mystical anti-inflammatory effects? 3
Clinical indications Resuscitation Head trauma/cerebral edema Correction of acute hyponatremia Potential adverse effects Short duration of volume expansion Reflex bradycardia Seen with overly rapid administration (> 0.5-1ml/kg/min) Dramatic volume expansion and parasympathetic stim Contraindicated in dehydration? Osmosis is osmosis: volume expansion will be achieved Worsen intercellular dehydration? General principles Large molecules which do not readily cross capillary membranes and stay in vascular space Contribute to oncotic pressure which helps to maintain blood volume Normal oncotic pressure is 20-25 mm Hg Albumin is the most important colloid in blood Disease states can lead to decreased albumin, reduced oncotic pressure and edema formation Synthetic Hydroxyethyl starch Dextrans Gelatins Natural Albumin concentrate Plasma Whole blood Hydroxyethyl starch (Vetstarch) Wide range of molecular size in crystalloid solution Small molecules (#) dictate oncotic pressure, large molecules affect duration Volume of distribution is (mostly) vascular space Depends on vascular permeability Increases vascular volume by 1-1.5x volume given Prolonged vascular expansion compared to crystalloids Clinical indications Resuscitation sustained vascular expansion Oncotic support for hypoproteinemia Adverse affects Dose-dependent coagulopathy Dilution of clotting factors Impaired platelet aggregation, interference with clotting factors Dose needed to affect coagulation > 20-50 ml/kg/day? Associated with increased risk of clinical bleeding? Renal injury Mechanism unclear tubular obstruction or cell accumulation? Concern for increased risk of AKI and kidney failure in critically ill human patients Conflicting evidence in veterinary medicine, should avoid if existing kidney disease Why give albumin? Colloid osmotic pressure (80% of total COP) Carrier functions Bilirubin toxicity from bilirubin with albumin An assortment drugs Electrolytes e.g. Ca +2 Free radical and bacterial toxin scavenger Wound healing/tissue repair Synthetic colloids can augment COP but not these other functions Typically reserved for albumin < 1.5 g/dl 4
Canine Plasma ~4g/dL albumin in plasma Expand vascular volume equivalent to amount given Not very efficient for raising albumin or COP ~40-70 ml/kg plasma needed to increase albumin by 1g/dL! Can be given as a CRI More practical for smaller patients? Adverse effects Potential for transfusion reaction May be limited by cost and availability Crystalloid Colloids Type Advantages Disadvantages Hypotonic Isotonic Hypertonic Synthetic Natural -Inexpensive -Readily available -Use for maint, replace, and resusc -Acid/base correction -Prolonged vascular expansion -Support oncotic pressure -Rapidly leaves vascular space -Tissue edema -Inflammatory effects -Acid/base disturbance -Availability -More costly -Coagulopathy/AKI (synthetic) -Hypersensitivity Resuscitation Rapid restoration of vascular volume by administration of intravenous fluids Used to address hypovolemia Replacement Restoration of extravascular fluid deficit (rehydration) and ongoing losses Maintenance Administration of fluid based on physiological water requirement Hypovolemia reduction in intravascular volume Acute blood loss or cavitary effusion, severe dehydration, etc Clinical signs Tachycardia Pale mucous membranes Prolonged CRT Cool distal extremities Diminished pulse quality Tachypnea Depressed mentation Genesis of shock dose Hemorrhagic shock manifests after ~30% volume loss Only 1/4-1/3 of crystalloid remains within the vascular space V = 80-90 ml/kg (dog blood volume) X 0.3 (presumed loss) 1/3-1/4 (expansion factor) V = ~80-90 ml/kg V = 40-60 ml/kg (cat blood volume) X 0.3 (presumed loss) 1/3-1/4 (expansion factor) V = ~40-60 ml/kg Could give an entire blood volume! Genesis of shock dose Hemorrhagic shock manifests after ~30% volume loss Hypertonic saline expands vascular volume by 5-7x the administered volume V = 80-90 ml/kg (dog blood volume) X 0.3 (presumed loss) 5-7 (expansion factor) V = ~3-6 ml/kg V = 40-60 ml/kg (cat blood volume) X 0.3 (presumed loss) 5-7 (expansion factor) V = ~2-4 ml/kg 5
Genesis of shock dose Hemorrhagic shock manifests after ~30% volume loss Hetastarch expands vascular volume by 1-1.5x the administered volume V = 80-90 ml/kg (dog blood volume) X 0.3 (presumed loss) 1.0 1.5 (expansion factor) V = ~20-30 ml/kg V = 40-60 ml/kg (cat blood volume) X 0.3 (presumed loss) 1.0 1.5 (expansion factor) V = ~10-15 ml/kg Hypertonic saline/hetastarch (turbostarch) Rapid expansion of HS, sustained effect of HES Reduces volume of HES administered Decreased risk of coagulation effects Dilute 23.4% HS with HES, ~ 1:2 Fast formulation: 18 ml HS + 42 ml HES Dilutes HS to 7%, HES to 4.2% Shock dose - 4-6 ml/kg Administration of shock dose? Serves as a guideline, titrate to effect Some fraction over some period of time Classic approach: large volume fast 1/4 1/3 shock does (20-30 ml/kg, 10-15 ml/lb) over 10-20 minutes Revised approach? Evidence to suggest more rapid fluid administration may be less effective at expanding the vascular volume Smaller bolus over longer period may be more effective Consider 10-15 ml/kg over 20-30 min The slowlus After bolus (slowlus) need to reassess patient Repeat as necessary to normalize/ achieve desired targets Mucous membranes, CRT Heart rate, pulse quality Arterial blood pressure Lactate (absolute vs change) Hypoproteinemia Higher consideration for colloid Hemorrhage Consideration for blood products if suspected greater than 30% blood loss or poor response to crystalloid/colloid Active/ongoing hemorrhage Concern to worsen hemorrhage with acute volume expansion Sudden increase in pressure, disruption of clot A more gentle approach to resuscitation Smaller boluses over a longer period of time (slowlus) Change targets to minimally acceptable blood pressure Systolic 90-100 mm Hg, mean 65-75 mm Hg Let other parameters ride until hemostasis achieved Dehydration Ongoing losses Maintenance requirement Oncotic support 6
Gradual reduction in extravascular volume Lost in attempt to restore vascular volume GI and renal losses, insensible losses, etc Most commonly isotonic, can be hypotonic Clinical signs Tacky mucous membranes Decreased skin turgor Sunken eyes Reduction in body weight Increased specific gravity Progression to hypovolemia and shock % Dehydration Clinical Condition <5% Subclinical, undetectable 5-8% Mild. Tacky MM, sl dec in skin turgor. Typically not accompanied by signs of CV compromise. Alert and responsive. 8-10% Moderate. Marked dec in skin turgor, eyes sunken. Often accompanied by mild signs of CV compromise. Depressed and reluctant to respond. 10-12% Severe. Almost always accompanied by signs of CV compromise. Very depressed, poorly responsive 12-15% Very severe, nearly incompatible with life. Definite shock. Moribund and minimally responsive. Replace dehydration over 4-24 hours Most commonly isotonic (replacement) fluid Some argue rapid replacement (4-8 hours) Quickly moves to interstitium, want to replace deficit as quickly as possible Some argue more gradual Rapid replacement will be lost through kidneys (dry sponge theory) Replace more slowly, especially if chronic process Rehydration calculation mls/hr = Estimated % dehydration X Body weight hours for rehydration Types of ongoing losses Vomiting, diarrhea Hemorrhage Excessive urinary losses (polyuria) Increased insensible losses (panting) Ideally losses are measured, otherwise estimated Can weigh fluids lost in disposable pads: 1gm = 1mL Should be replaced over the time frame lost by adding to maintenance and dehydration Based on physiological fluid requirement Urinary, GI and insensible losses Overall these loss are hypotonic Replacement fluid often used Easier to keep only a few types of fluid Higher sodium relative to water for maintenance needs Ok if heart and kidneys work, will get rid of excess Maintenance fluid requirement is more water and K + Should use a hypotonic rather than isotonic fluid supplemented with potassium Norm M, Plasmalye 56, 0.45% NaCl Many ways to calculate 2-4 mls/kg/hr 30*BW + 70/day 30 mls/lb/day (60 mls/kg/day) Linear relationship does not take into account surface area:volume ratios Overestimates fluid requirement in large patients Underestimates fluid requirement in small patients Exponential relationship may be more reflective of daily fluid requirement 132*BW 0.75 (dog) and 80*BW 0.75 (cat) 7
10 kg MC Schnauzer presenting for vomiting, lethargy and anorexia. Est 8% dehydration on presentation Initial fluid rate: Maintenance + Dehydration Maintenance = 132 X 10 3/4 = 31 ml/hr Dehydration = 10kg X 0.08 = 800ml, decide to replace in 12hr = 800 ml/ 12 = 67 ml/hr Initial rate = 98 ml/hr for first 12 hours, reassess q4-6 Over next 4 hours, vomits three times, approx 100 ml New fluid rate = Maintenance + Dehydration + Losses Ongoing losses = 100/4 = 25 ml New rate = 98 +25 = 123 ml/hr for next 4 hours, reassess High rates (10-20 ml/kg/hr) previously advocated to offset cardiovascular effects of anesthesia Decreased cardiac output, vasodilation Increased measured and insensible fluid losses Little evidence to support this practice, may have adverse effects Hypervolemia, volume overload Tissue edema, impaired uptake of O2 and nutrients Current recommendations Crystalloid anesthesia maintenance 3ml/kg/hr cats, 5 ml/kg/hr dogs Current recommendations Bolus therapy for hypotension Crystalloid 10-15 ml/kg dog, 5-10 ml/kg cats Colloid 3-5 ml/kg dog, 2-4 ml/kg cat Given over 15-20 minutes, reassess If repeated 1-2x without improvement to BP, consider adding pressor agent Norepinephrine Vasopressin Dopamine Administration of fluid for gradual absorption and distribution across fluid compartments Typically deposited in multiple sites Uptake of fluid dictated by: Hydration status Peripheral perfusion Body temperature Should only administer near-isotonic fluids Hypo/hypertonic solutions cause significant irritation and/or tissue injury (NO high concentration dextrose fluids!) Advantages Practical: minimal equipment required Less expensive than IV cath and fluids Can be administered on out-patient basis Preferred for: Mild to moderate dehydration Prevention of dehydration for anorexic/npo patient Unable to hospitalize Disadvantages Unreliable with peripheral vasoconstriction Not for resuscitation or replacement - shock/critically ill patient Limited options for fluid administration Potential for pain, irritation, necrosis, infection Dose??? Often done as ballpark estimate Cats and small dogs 50-100 ml Medium dogs 250-500 ml Large dogs 500-1000 ml Actual calculation? Example of 5 kg cat Maintenance fluid requirement: 80*5kg 3/4 = 267 ml/day Assuming 5% dehydration: 5kg*0.05 = 250 ml Would technically need to give ~500 ml to cover 24 hours! If still eating and drinking some, will try to give at least half of deficit with first dose, owners repeat at home if possible 8