Intravenous Fluids

Intravenous Fluids:Intravenous Fluids: Composition & UsesComposition & Uses

Srinidhi Jayaram, PGY1Srinidhi Jayaram, PGY1

Body Fluid CompartmentsBody Fluid Compartments

Total Body Water (TBW): 50Total Body Water (TBW): 50--70% of total body wt.70% of total body wt.Avg. is greater for males.Avg. is greater for males.Decreases with age. Highest in newborn, 75Decreases with age. Highest in newborn, 75--80%. By 80%. By first year of life TBW ~ 65%.first year of life TBW ~ 65%.Most in muscle, less in fat.Most in muscle, less in fat.TBW= ECF + ICFTBW= ECF + ICFICF ~ 2/3 & ECF ~ 1/3ICF ~ 2/3 & ECF ~ 1/3ECF = Intravascular (1/3) + Interstitial (2/3)ECF = Intravascular (1/3) + Interstitial (2/3)

Electrolyte PhysiologyElectrolyte Physiology

Primary intravascular/ECF Primary intravascular/ECF cationcation is Nais Na++. Very small . Very small contribution of Kcontribution of K++, Ca, Ca2+2+, and Mg, and Mg2+2+..Primary intravascular/ECF anion is Primary intravascular/ECF anion is ClCl--. Smaller . Smaller contribution from HCOcontribution from HCO33

--, SO, SO4422-- & PO& PO44

33--, organic acids, , organic acids, and protein.and protein.Primary ICF Primary ICF cationcation is Kis K++. Smaller contribution from . Smaller contribution from MgMg2+2+ & Na& Na++..Number of Number of intravascintravasc anions not routinely detected.anions not routinely detected.

ICF (ICF (mEqmEq/L)/L) ECF (ECF (mEqmEq/L)/L)

CationsCations KK++(15(1500--154154))NaNa+ + (6(6--1010))MgMg+2+2

(40)(40)

NaNa++(142) (142) CaCa+2 +2 (5)(5)KK+ + ((44--5)5)MgMg+2+2

(3)(3)

AnionsAnions Organic POOrganic PO

44

--33

((100100--106)106)

protein (protein (4040--60)60)SOSO

44

--22

(17)(17)HCOHCO

33

--

((1010--13)13)organic acids (4)organic acids (4)

ClCl--(10(1033--10105)5)HCOHCO

33

--

(24(24--2727))protein (15)protein (15)POPO

44

--33

((33--5), SO5), SO

44

--22

(4) (4) Organic acids (2Organic acids (2--55))

Basic Fluid and Electrolyte LossesBasic Fluid and Electrolyte Losses

AvgAvg water loss in stool 150water loss in stool 150--400 ml.400 ml.AvgAvg loss in urine 800loss in urine 800--1500 ml1500 mlAvgAvg insensible loss 8insensible loss 8--12 ml/kg (6012 ml/kg (60--75% 75% respresp + 25+ 25--40% skin)40% skin)A pt deprived of all external access to water must still A pt deprived of all external access to water must still excrete a minimum of 500excrete a minimum of 500--800 ml urine/day in order 800 ml urine/day in order to excrete products of catabolism in addition to to excrete products of catabolism in addition to mandatory insensible loss.mandatory insensible loss.These losses are increased in states of stress/These losses are increased in states of stress/dzdzInsensible losses increase with Insensible losses increase with hypermetabolismhypermetabolism, , hyperventilation, and fever.hyperventilation, and fever.

Basic Fluid and Electrolyte RequirementsBasic Fluid and Electrolyte Requirements

Daily fluid requirements of healthy children and Daily fluid requirements of healthy children and adults can be estimated (100adults can be estimated (100--5050--20/420/4--22--1 or 1 or 35ml/kg/d for adults).35ml/kg/d for adults).This will vary depending on ptThis will vary depending on pt’’s renal and cardiac s renal and cardiac function.function.These requirements will increase in states of These requirements will increase in states of dzdz/stress as fluid losses increase./stress as fluid losses increase.Requirements vary around what is necessary to Requirements vary around what is necessary to maintain homeostasis and maintain homeostasis and euvolemiaeuvolemia..

IV Fluid/Electrolyte TherapyIV Fluid/Electrolyte Therapy

Three key concepts in consideration of fluid and Three key concepts in consideration of fluid and electrolyte management: electrolyte management:

cell membrane permeabilitycell membrane permeabilityosmolarityosmolarityelectroneutralityelectroneutrality

Cell membrane permeability refers to the ability of a Cell membrane permeability refers to the ability of a cell membrane to allow certain substances such as cell membrane to allow certain substances such as water and urea to pass freely, while charged ions water and urea to pass freely, while charged ions such as sodium cannot cross the membrane and are such as sodium cannot cross the membrane and are trapped on one side of it.trapped on one side of it.

OsmolarityOsmolarity is a property of particles in solution.is a property of particles in solution. If a If a substance can dissociate in solution, it may substance can dissociate in solution, it may contribute more than one equivalent to the contribute more than one equivalent to the osmolarityosmolarity of the solution.of the solution. For instance, For instance, NaClNaCl will will dissociate into two dissociate into two osmoticallyosmotically active ions: Na and active ions: Na and Cl.Cl. One One millimolarmillimolar NaClNaCl yields a 2 yields a 2 milliosmolarmilliosmolarsolution.solution.ElectroneutralityElectroneutrality means that the overall number of means that the overall number of positive and negative charges balances.positive and negative charges balances. For For instance, in conditions like renal tubular acidosis instance, in conditions like renal tubular acidosis where HCO3where HCO3-- is lost, chloride is retained leading to a is lost, chloride is retained leading to a

hyperchloremichyperchloremic statestate..

Expected Expected osmolarityosmolarity of plasma can be calculated of plasma can be calculated according to the following formula:according to the following formula:OsmolarityOsmolarity ((mOsmmOsm/kg) = 2/kg) = 2××[mEq/L Na[mEq/L Na++] + glucose+ BUN] + glucose+ BUN

Concentration of sodium is the major determinant.Concentration of sodium is the major determinant.Normal serum Normal serum osmolarityosmolarity ranges from about 280 to ranges from about 280 to 295 295 mOsmmOsm/kg./kg.Maintenance fluids must be determined for basic Maintenance fluids must be determined for basic requirements, then existing volume or electrolyte requirements, then existing volume or electrolyte deficits must be evaluated to determine the deficits must be evaluated to determine the appropriate IV fluid to use and the volume to appropriate IV fluid to use and the volume to administer.administer.

Types of IV FluidTypes of IV Fluid

Crystalloid:Crystalloid: Balanced salt/electrolyte solution; forms Balanced salt/electrolyte solution; forms a true solution and is capable of passing through a true solution and is capable of passing through semipermeablesemipermeable membranes. May be isotonic, membranes. May be isotonic, hypertonic, or hypotonic.hypertonic, or hypotonic.

Normal Saline (0.9% Normal Saline (0.9% NaClNaCl), Lactated Ringer), Lactated Ringer’’s, s, Hypertonic saline (3, 5, & 7.5%), RingerHypertonic saline (3, 5, & 7.5%), Ringer’’s s solution.solution.

However, hypertonic solutions are considered plasma However, hypertonic solutions are considered plasma expanders as they act to increase the circulatory expanders as they act to increase the circulatory volume via movement of intracellular and interstitial volume via movement of intracellular and interstitial water into the intravascular space.water into the intravascular space.

Colloid:Colloid: HighHigh--molecularmolecular--weight solutions, draw fluid weight solutions, draw fluid into intravascular compartment via into intravascular compartment via oncoticoncotic pressure pressure (pressure exerted by plasma proteins not capable of (pressure exerted by plasma proteins not capable of passing through membranes on capillary walls). passing through membranes on capillary walls). Plasma expanders, as they are composed of Plasma expanders, as they are composed of macromolecules, and are retained in the intravascular macromolecules, and are retained in the intravascular space.space.

Albumin, Albumin, HetastarchHetastarch, , PentastarchPentastarch ((PentaspanPentaspan®®), ), Plasma, Plasma, DextranDextran..

Free HFree H22O solutions:O solutions: provide water that is not provide water that is not bound by macromolecules or organelles, free to pass bound by macromolecules or organelles, free to pass through.through.

D5W (5% dextrose in water), D10W, D20W, D5W (5% dextrose in water), D10W, D20W, D50W, and Dextrose/crystalloid mixes.D50W, and Dextrose/crystalloid mixes.

Blood products:Blood products: whole blood, packed whole blood, packed RBCsRBCs, FFP, , FFP, cryoprecipitate, platelets, albumin. Essentially all cryoprecipitate, platelets, albumin. Essentially all colloids.colloids.

Composition of common IV FluidsComposition of common IV Fluids

TABLE 61-5 -- Fluids Used for Resuscitation

NaCl(0.9%)

RINGER'SLACTATE

NaCl(3%)

ALBUMIN (5%)

HETASTARCH (6%)

DEXTRAN 70 + NaCl

Na(mEq/L) 154 130 513 130–160 154 154

Cl (mEq/L) 154 109 513 130–160 154 154

K(mEq/L) 0 4 0 0 0 0

Osmolarity(mOsm/L)

308 275 1025 310 310 310

Oncotic P(mm Hg)

0 0 0 20 30 60

Lactate(mEq/L)

0 28 0 0 0 0

MaximumDose(mL/kg/24 hr)

None None Limitedby serumNa+

None 20 20

Cost (L) $1.26 $1.44 $1.28 $100 $27.30 $35.08

IVF can supply 3 things: fluid, electrolytes, & calories. IVF can supply 3 things: fluid, electrolytes, & calories. In the In the nonstressednonstressed, fasting state, the 150g per day in , fasting state, the 150g per day in D5W at 125ml/h can provide enough carbohydrate to D5W at 125ml/h can provide enough carbohydrate to limit proteolysis.limit proteolysis.The most common uses for IVF:The most common uses for IVF:

Acutely expand intravascular volume in Acutely expand intravascular volume in hypovolemichypovolemic statesstatesCorrect electrolyte imbalancesCorrect electrolyte imbalancesMaintain basal hydrationMaintain basal hydration

Commonly used IV FluidsCommonly used IV Fluids

Normal Saline (0.9% Normal Saline (0.9% NaClNaCl): ): Isotonic salt water. Isotonic salt water. 154 154 mEqmEq/L Na/L Na+;+; 154 154 mEqmEq/L /L ClCl--; 308mOsm/L. ; 308mOsm/L. Cheapest and most commonly used resuscitative Cheapest and most commonly used resuscitative crystalloid. High [crystalloid. High [ClCl--] above the normal serum 103 ] above the normal serum 103 mEqmEq/L imposes on the kidneys an appreciable load of /L imposes on the kidneys an appreciable load of excess excess ClCl-- that cannot be rapidly excreted. A that cannot be rapidly excreted. A dilutionaldilutional acidosis may develop by reducing base acidosis may develop by reducing base bicarbbicarb relative to carbonic acid. Thus exist the risk of relative to carbonic acid. Thus exist the risk of hyperchloremichyperchloremic acidosis. Only solution that may be acidosis. Only solution that may be administered with blood products. Does not provide administered with blood products. Does not provide free water or calories. Restores free water or calories. Restores NaClNaCl deficits.deficits.

Lactated RingerLactated Ringer’’s (RL): s (RL): Isotonic, 273 Isotonic, 273 mOsmmOsm/L. /L. Contains 130 Contains 130 mEqmEq/L Na/L Na++, 109 , 109 mEqmEq/L /L ClCl--, 28 , 28 mEqmEq/L /L lactate, and 4 lactate, and 4 mEqmEq/L K/L K++. Lactate is used instead of . Lactate is used instead of bicarbbicarb because itbecause it’’s more stable in IVF during storage. s more stable in IVF during storage. Lactate is converted readily to Lactate is converted readily to bicarbbicarb by the liver. by the liver. Has minimal effects on normal body fluid composition Has minimal effects on normal body fluid composition and pH. More closely resembles the electrolyte and pH. More closely resembles the electrolyte composition of normal blood serum. Does not provide composition of normal blood serum. Does not provide calories.calories.

D5W/D5W/¼¼NS: NS: Hypertonic, 406 Hypertonic, 406 mOsmmOsm/L. Provides /L. Provides 170 calories/L from 5% dextrose. Provides free water 170 calories/L from 5% dextrose. Provides free water for insensible losses and some Nafor insensible losses and some Na++ to promote renal to promote renal function and excretion. With added Kfunction and excretion. With added K++ this is an this is an excellent maintenance fluid in excellent maintenance fluid in postoppostop period. period. Prevents excess catabolism and limits proteolysis. Prevents excess catabolism and limits proteolysis. Hypertonic Saline (3% Hypertonic Saline (3% NaClNaCl): ): 1026 1026 mOsmmOsm/L & /L & 513 513 mEqmEq/L Na/L Na++. Increases plasma . Increases plasma osmolalityosmolality and and thereby acts as a plasma expander, increasing thereby acts as a plasma expander, increasing circulatory volume via movement of intracellular and circulatory volume via movement of intracellular and interstitial water into the intravascular space. Risk of interstitial water into the intravascular space. Risk of hypernatremiahypernatremia thus careful thus careful neuroneuro--monitoring and VS.monitoring and VS.

Determining Fluid DeficitDetermining Fluid Deficit

Clinical Assessment of Severity of Dehydration

Percent Dehydration Infant Child Clinical Signs and Symptoms

Mild 5% 3-4%

Increased thirst, tears present, mucous membranes moist, ext. jugular visible when supine, capillary refill > 2 seconds centrally, urine specific gravity > 1.020

Moderate 10% 6-8%

Tacky to dry mucous membranes, decreased tears, pulse rate may be elevated somewhat, fontanelle may be sunken,oliguria, capillary refill time between 2 and 4 seconds, decreased skin turgor

Severe 15% 10%

Tears absent, mucous membranes dry, eyes sunken, tachycardia, slow capillary refill, poor skin turgor, cool extremities, orthostatic to shocky, apathy, somnolence

Shock >15% >10%

Physiologic decompensation: insufficient perfusion to meet end- organ demand, poor oxygen delivery, decreased blood pressure.

Volume deficits are best estimated by acute changes Volume deficits are best estimated by acute changes in weight. Less than 5% loss is very difficult to in weight. Less than 5% loss is very difficult to detect clinically and loss of 15+% will be associated detect clinically and loss of 15+% will be associated with severe circulatory compromise.with severe circulatory compromise.Mild deficit represents a loss of ~ 4% body wt.Mild deficit represents a loss of ~ 4% body wt.Moderate deficit Moderate deficit ------ a loss of ~ 6a loss of ~ 6--8% body wt.8% body wt.Severe deficit Severe deficit ------ a loss of ~ >10% body wt.a loss of ~ >10% body wt.Volume deficit may be a pure water deficit or Volume deficit may be a pure water deficit or combined water and electrolyte deficit.combined water and electrolyte deficit.

Pure water deficit is reflected biochemically by Pure water deficit is reflected biochemically by hypernatremiahypernatremia, increase in plasma , increase in plasma osmolalityosmolality, , concentrated urine, and low urine [Naconcentrated urine, and low urine [Na++] (<15mEq/L).] (<15mEq/L).Treatment involves replacement of enough water to Treatment involves replacement of enough water to restore plasma [Narestore plasma [Na++] to normal.] to normal.The excess NaThe excess Na+ + for which water must be provided for which water must be provided can be estimated from the following equation:can be estimated from the following equation:

∆∆Na = (140 Na = (140 ––

plasma Na) plasma Na) ××

TBWTBW(Recall (Recall ------

TBW = ECF + ICF = 50TBW = ECF + ICF = 50--70% body wt.)70% body wt.)

∆∆Na represents the total Na represents the total mEqmEq Na Na ++ in excess of in excess of water. Divide water. Divide ∆∆NaNa++ by 140 to obtain the amount of by 140 to obtain the amount of water required to return serum Nawater required to return serum Na++ to 140mEq/L.to 140mEq/L.

This fluid deficit must be corrected in addition to This fluid deficit must be corrected in addition to giving maintenance fluids for ongoing obligatory giving maintenance fluids for ongoing obligatory losses.losses.Combined water and electrolyte deficit is commonly Combined water and electrolyte deficit is commonly associated with GIT losses, diuretic therapy, adrenal associated with GIT losses, diuretic therapy, adrenal insufficiency, excessive diaphoresis, burns, stomas, insufficiency, excessive diaphoresis, burns, stomas, and 3and 3rdrd spacing following trauma or surgery.spacing following trauma or surgery.Urine NaUrine Na++ is often < 10mEq/L as a result of sodium is often < 10mEq/L as a result of sodium conservation from conservation from aldosteronealdosterone on renal tubules.on renal tubules.Decreased blood Decreased blood volvol diminishes renal perfusion and diminishes renal perfusion and often produces often produces prerenalprerenal azotemiaazotemia: increased BUN & : increased BUN & Cr with BUN increased greater relative to Cr.Cr with BUN increased greater relative to Cr.

Normal BUN/Cr ratio is ~ 10:1. With Normal BUN/Cr ratio is ~ 10:1. With prerenalprerenalazotemiaazotemia it may increase to 20it may increase to 20--25:1.25:1.These combined water and electrolyte deficits are These combined water and electrolyte deficits are corrected by choosing the appropriate IVF for the ptcorrected by choosing the appropriate IVF for the pt’’s s electrolyte imbalance and the magnitude of the electrolyte imbalance and the magnitude of the deficit may be estimated as in the previous tables, deficit may be estimated as in the previous tables, clinically.clinically.The composition of the correction fluid should take The composition of the correction fluid should take into account the plasma [Nainto account the plasma [Na++]. If it is normal, fluid ]. If it is normal, fluid and and lytelyte losses are probably isotonic, and the losses are probably isotonic, and the replacement fluid should be isotonic NS or its replacement fluid should be isotonic NS or its equivalent. equivalent.

Thus replacement therapy should be planned in 2 Thus replacement therapy should be planned in 2 steps:steps:1. Na1. Na+ + deficit should be calculateddeficit should be calculated2. Volume deficit should be estimated from clinical 2. Volume deficit should be estimated from clinical

S/S and change in body wt.S/S and change in body wt.However, avoid volume overload. Hormonal and However, avoid volume overload. Hormonal and circulatory responses to surgery result in circulatory responses to surgery result in postoppostop NaNa++

and water conservation by the kidneys that is and water conservation by the kidneys that is independent of the status of the ECF volume.independent of the status of the ECF volume.BUTBUT……consider replacement therapy consider replacement therapy vsvs resuscitation.resuscitation.

Resuscitative IV FluidsResuscitative IV Fluids

Principle of trauma & surgery: Crystalloids; isotonic Principle of trauma & surgery: Crystalloids; isotonic balanced salt solutions. balanced salt solutions. NS or RL.NS or RL.Amount given based upon body wt, clinical picture, Amount given based upon body wt, clinical picture, and vital signs. ?shock.and vital signs. ?shock.Generally a bolus of 500Generally a bolus of 500--2000cc is given depending 2000cc is given depending on the above, then rates are run at 1.5on the above, then rates are run at 1.5--2x 2x maintenance or 10maintenance or 10--20cc/kg/d on top of maintenance. 20cc/kg/d on top of maintenance. Continuous clinical r/a of vitals and response to fluids Continuous clinical r/a of vitals and response to fluids already given is required for ongoing IVF therapy.already given is required for ongoing IVF therapy.Resuscitative IVF therapy is for initial stabilization Resuscitative IVF therapy is for initial stabilization and overlaps with further replacement therapy.and overlaps with further replacement therapy.

Controversy exists over the use of colloids and Controversy exists over the use of colloids and hypertonic solutions as resuscitative fluids.hypertonic solutions as resuscitative fluids.The large volumes of crystalloid sometimes necessary The large volumes of crystalloid sometimes necessary to stabilize pts may lead to peripheral edema that to stabilize pts may lead to peripheral edema that may impair wound healing.may impair wound healing.Colloids offer the theoretical advantage of expanding Colloids offer the theoretical advantage of expanding the intravascular space with less volume, and have the intravascular space with less volume, and have been shown to increase blood pressure more rapidly been shown to increase blood pressure more rapidly than crystalloids. than crystalloids. 1 L of 1 L of dextrandextran increases increases intravascintravasc volvol by 800ml; 1 L by 800ml; 1 L of of hetastarchhetastarch by 750ml; 1 L 5% albumin by 500ml; by 750ml; 1 L 5% albumin by 500ml; and 1 L NS by 180 ml.and 1 L NS by 180 ml.

Crystalloids Crystalloids vsvs

Colloids for ResuscitationColloids for Resuscitation

Yet there is evidence that colloids may inhibit the Yet there is evidence that colloids may inhibit the coagulation system and cause coagulation system and cause anaphylactoidanaphylactoid rxnrxn’’ss..Some studies have found an increased risk of ARF Some studies have found an increased risk of ARF associated with associated with hetastarchhetastarch and and pentastarchpentastarch solutions solutions when given for when given for resuscresusc of sepsis, possibly due to of sepsis, possibly due to inadequate free water replacement.inadequate free water replacement.Overall metaOverall meta--analyses of IVF therapy and mortality analyses of IVF therapy and mortality have not supported a benefit for colloids over have not supported a benefit for colloids over crystalloids. crystalloids. Several metaSeveral meta--analyses have shown a trend toward analyses have shown a trend toward increased mortality in heterogeneous groups of increased mortality in heterogeneous groups of critically ill ptcritically ill pt’’s s resuscresusc’’dd with colloids.with colloids.

Given the available data, and potential risks of colloid Given the available data, and potential risks of colloid solutions, crystalloids still remain the cornerstone of solutions, crystalloids still remain the cornerstone of volume resuscitation, although ptvolume resuscitation, although pt’’s with profound s with profound volume deficits may benefit from colloids volume deficits may benefit from colloids in addition in addition to crystalloids.to crystalloids.

Maintenance IV FluidsMaintenance IV Fluids

Can be calculated by three methods:Can be calculated by three methods:1. Holliday1. Holliday--Segar method.Segar method.2. Caloric method.2. Caloric method.3. Body surface area method.3. Body surface area method.

Most commonly used is HollidayMost commonly used is Holliday--Segar method, most Segar method, most of you use it everyday and you probably donof you use it everyday and you probably don’’t even t even know itknow it……..4..4——22——1 or 1001 or 100——5050——20. 20. In the HollidayIn the Holliday--Segar method, fluid and electrolyte Segar method, fluid and electrolyte requirements are empirically based on caloric needs requirements are empirically based on caloric needs of the average hospital pt. This caloric expenditure is of the average hospital pt. This caloric expenditure is approximated based on body wt.approximated based on body wt.

For each kilogram in this range

Daily caloric cost per kilogram

Daily Maintenance Fluid Requirements

Hourly Maintenance Fluid Requirements

1-10 kg (1st 10kg) 100 kcal/kg/day 100ml 4ml

11-20 kg (2nd 10kg) 50 kcal/kg/day 50ml 2ml

>20 kg (each kg over) 20 kcal/kg/day 20ml 1ml

Na 3-5 mEq per 100 kcal/day

K 2-4 mEq per 100 kcal/day

Cl 2 mEq per 100 kcal/day

Maintenance electrolyte requirementsMaintenance electrolyte requirements

The HollidayThe Holliday--Segar method or 4Segar method or 4——22——1 can only be 1 can only be applied to patients above 2 weeks of age.applied to patients above 2 weeks of age.For every 100 kcal expended, a certain amount of For every 100 kcal expended, a certain amount of fluid is lost either through "insensible water loss" or fluid is lost either through "insensible water loss" or through renal function; a small amount is generated through renal function; a small amount is generated through oxidation of carbohydrates and tissue through oxidation of carbohydrates and tissue catabolism. catabolism. This method does not take into consideration caloric This method does not take into consideration caloric expenditures above maintenance or take into account expenditures above maintenance or take into account onon--going fluid losses.going fluid losses.This method is essentially a simplified/empiric This method is essentially a simplified/empiric application of the caloric method.application of the caloric method.

Monitoring endpoints for IVF therapyMonitoring endpoints for IVF therapy

Endpoint should be maintenance or reestablishment Endpoint should be maintenance or reestablishment of homeostasis.of homeostasis.In order to reestablish homeostasis in a pt, IVF In order to reestablish homeostasis in a pt, IVF therapy must not only provide a balance of water and therapy must not only provide a balance of water and electrolytes, but must ensure adequate oxygen electrolytes, but must ensure adequate oxygen delivery to all organs and renal perfusion as delivery to all organs and renal perfusion as evidenced by urine output.evidenced by urine output.Endpoints: normalization of VS, UO>0.5ml/kg/hr Endpoints: normalization of VS, UO>0.5ml/kg/hr (1ml/kg/hr for a child) and restoration of normal (1ml/kg/hr for a child) and restoration of normal mental status and lack of clinical signs of deficit.mental status and lack of clinical signs of deficit.Other endpoints include normalization of labs, such Other endpoints include normalization of labs, such as as BUN:CrBUN:Cr ratio and electrolyte values.ratio and electrolyte values.