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Dilemmas in Fluid Therapy

The Goldilocks Principle

Jon Palmer, VMD, DACVIMChief, Neonatal Intensive Care Service

New Bolton Center, University of Pennsylvania, USA

Pandemic “Indian Cholera”

1831-1832 23,000 victims in Britain Began in Russia Arrived in London Dec Over by May

Standard care Blood-letting With or without emetics

William O'Shaughnessy 22-year old Recent medical graduate

Edinburgh University 1829 Denied license to practice London

Unemployed Clinical Chem lab in London Analyzed blood Cholera victims

At request of medical board Blood dark – oral fluids could correct

Presented findings to medical community Board of Health Westminster Medical Society

He suggested oral, colonic or IV fluids Had been tried in Russia - unsuccessfully

Thomas Latta Scottish physician, in Leith Read paper/letters, heard talks Tried new therapy

First tried enteral fluids “…injecting copiously into the larger intestine …”

Then Latta said: ‘having no precedent to direct me, I proceeded with much caution’ – IV fluids

Critically ill woman Moribund Unresponsive to all other treatments Revived in 30 minutes – began to talk

Thomas Latta Left Hospital

Left for 6 hrs. House Officer took over care Patient relapsed – died

Tried on other patients 3 of 15 survived Lancet – “a favorable result” Later report 25 of 156 survived

Medical Society Hearings “New treatment” tried on a few of 23,000 victims Renounced new treatment as malpractice

Thomas Latta – died within a year (TB)

William O’Shaughnessy Joined the civil service – India Medical marijuana

Tetanus cases Rabies

Telegraph system Using rivers in India

Knighted IV fluids not used again for half a century

Fluid Dynamics in the Fetus

and Foal

Fluid PhysiologyFetus/Neonate

Unique characteristics of Fetus/ Neonate

Interstitium

Lymph flow

Capillary endothelial permeability


Interstitium Heterogeneous space Dynamically controls its fluid content Compliance 10X adult (fetal lamb)


Lymph flow Thoracic duct lymph flow

Fetal lamb - 0.25 mL/minute/kg 5x the adult rate

Lymph flow - subcutaneous Puppies 2X adult dogs (per kg)

Pulmonary lymph flow Newborn lambs and puppies > adults

Neonate – local/ whole body lymph flow > adult Increased interstitial volume Higher capillary permeability


Capillary endothelial permeability Filtration rate in fetal lambs vs adults

Fluid 5x Proteins 15x

Why? Poor precapillary tone Higher capillary hydrostatic pressure Higher filtration The role of the glycocalyx?

Filtration related to hydrostatic pressure Precapillary tone lambs – develops during 1st week Doesn’t develop in a uniform manner

Fluid PhysiologyAt Birth

Arterial blood pressure increases Studied in lambs Last weeks – increases 20% During labor – increases another 18% At birth – increases another 12%

Transmitted to capillaries Increased transcapillary filtration

Poor precapillary tone

Fluid PhysiologyAt Birth

Other reasons for fluid shifts Direct compression of the fetus

Increased venous pressure Vasoactive hormones

Arginine vasopressin Norepinephrine Cortisol Atrial natriuretic factor

Fluid PhysiologyBorn Fluid Overloaded

Fluid shifts From fetal fluids / maternal circulation Accumulating in the fetal interstitium

All Neonates Are Born Fluid Overloaded Rate of loss of this fluid - species variation

Foal – weeks Other species

10-15% body weight rapidly after birth Important not to replace fluid loss

Poor outcomes with persistent fluid overload

Why?

Related to the Colloids vs. Crystalloids

Question

Classic Compartment Model

Intracellular fluid compartment Extracellular fluid compartment

• Intravascular• Interstitial

Ernest Starling 1896• Semipermeable membrane • Hydrostatic and oncotic pressure gradients• Principal determinants of transvascular exchange

30 Years Ago - Promise

Assumptions:

Plasma volume 20% of the extracellular fluid Volume equivalence for resuscitation hypovolemia 20 ml colloid to 100 ml crystalloid

Transfusion of hyperoncotic colloid solutions Absorb fluid from the interstitial fluid Increase intravascular volume

Colloid and Crystalloid Solutions

Colloids in theory• More effective in expanding intravascular volume

Stays within the intravascular space Maintain colloid oncotic pressure

• 1:5 ratio of colloids to crystalloids Crystalloids

• Inexpensive • Available

But significant interstitial edema Occur with both types of fluids

Major Studies Saline versus Albumin Fluid Evaluation (SAFE) Efficacy of Volume Substitution and Insulin

Therapy in Severe Sepsis (VISEP) Scandinavian Starch for Severe Sepsis/Septic

Shock (6S) Synthetic Colloids vs Crystalloids Crystalloid versus Hydroxyethyl Starch Trial

(CHEST) Colloids Versus Crystalloids for the

Resuscitation of the Critically Ill (CRISTAL)

Type of Fluid Colloid vs Crystalloids HES:crystalloid all studies volume used

Approximately 1:1.3 (not 1:5) But colloids retain fluids = negative outcome

Reversal of shock No difference volume or speed

Toxicity of HES Coagulopathy Kidney injury – tubular uptake Hepatic failure in the HES group Severe persistent pruritus Tissue storage of HES

Why don’t colloids work as expected?

Why is there increased transcapillary filtration

before birth?

Myburgh JA, Mythen MG. Resuscitation Fluids. N Engl J Med 2013;369:1243-51

EGL Barrier

Endothelial glycocalyx Carbohydrate-rich layer Proteoglycans and glycoproteins Bound plasma proteins, mainly albumin

Hydrostatically forced fluid Forces albumin and other osm particles into web Forms a gradient with more caught outside Any protein making it through washed into interstitium Layer of fluid on luminal side of endothelium – protein free Forms oncotic gradient Not effected by interstitial protein content

Best Practice & Research Clinical Anaesthesiology 28 (2014) 227‐234.

Endothelial Glycocalyx Complex, multicomponent, biochemical structure Functions

Molecular sieve Lubrication layer

RBC motion Inhibitor of inflammation Shear sensor

Plasma flow‐induced fluid shear strain Size

15‐20% of the radius of the smallest capillaries Larger vessels – thicker Frequent fluctuations, ill‐defined boundary Total volume > 1 L average person

Endothelial Glycocalyx Backbone molecules

Membrane‐bound proteins (proteoglycans) Structural, core protein anchored to membrane (GAGs)

Glycosylated proteins (glycoproteins) Receptors, selectins, integrins, etc.

Synthesized and assembled in cell Shuttled in vesicles to cell surface Endoplasmic reticulum to Golgi apparatus to cell

membrane “Decorated” by soluble molecules

Derived from the cell From plasma

Endothelial Glycocalyx

Molecular sieve Fence‐like meshwork Size exclusion of plasma molecules Semipermeable filter to large solutes

Soluble components caught in meshwork Albumin

Composition/thickness continuously fluctuate Bushes planted in a hexagonal array Anchoring to intracellular actin cortical

cytoskeleton

Capillary Types

Continuous non‐fenestrated capillaries Skin, connective tissues, muscles, lung

parenchyma, nervous system, etc. Luminal glycocalyx layer continuous Some specializations

CNS – Blood Brain Barrier Reabsorption not occur

The steady state Starling principle

Capillary Types Continuous fenestrated capillaries

Lymph node, endocrine glands, choroid plexus, gut mucosa

Bi‐directional passage of fluid Absorption of fluid into a capillary is required

Glomerular capillary – uniquely fenestrated Sinusoidal tissues

Liver, spleen, bone marrow Interendothelial gaps, discontinuous glycocalyx Do not filter soluble molecules

Interstitial fluid has protein concentration of plasma

Fluid Type and the EGL Transvascular fluid filtration

Depends on endothelial glycocalyx If intact with normal capillary pressures

Crystalloids freely pass Colloids are held back

If damaged neither are held back Intravascular hypovolemia

Low capillary pressures No filtration crystalloids or colloids

Damage EGL – loss of filtering ability Hypervolemia Rapid fluid administration Sepsis (inflammatory mediators, TNF) Ischemia/Reperfusion

From: http://www.hubrecht.eu

EGL – Damage by Hypervolemia Theory

Volume sensed by atria Release natriuretic peptides (ANP) Which activates metalloproteinases

From: Myburgh JA, Mythen MG. Resuscitation Fluids. N Engl J Med 2013;369:1243-51.

EGL – Damage by Hypervolemia Studies

Acute blood loss Add HES or albumin to maintain normovolemia Almost 100% retained

Hypervolemia – HES or albumin Infuse same volume without loss 60% colloid escapes into interstitium Glycocalyx is decreased

Fetus/Neonate?

Fluid TypeCrystalloids vs Colliods

Depend on state of endothelial glycocalyx layer Colloid increases intravascular volume

Resuscitation from hemorrhage No difference intravascular volume

Sepsis Inflammatory states Trauma Hypervolemia

Crystalloids and colloids will have the same effect

Albumin Albumin within the Endothelial Glycocalyx Layer

Determinant of its filter function Works as long as plasma albumin > ½ normal Congenital analbuminaemia/ acquired hypoalbuminaemia

Other proteins become important Albumin

In health - about 40% intravascular In inflammation

Intravascular albumin will decrease Extravascular proportion will increase

Transcapillary escape rate of albumin (TCERA) Index of ‘vascular permeability’ normal 5% per hour 2x during surgery > 20% per hr in septic shock

No Absorption Rule Glycocalyx model

Transendothelial protein concentration difference not result in fluid absorption No absorption rule

Observations explained by this: Hypoalbuminaemia marker of disease severity

Treatment of hypoalbuminaemia no benefit Not improve outcome

ARDS have low plasma albumin Giving hyperoncotic albumin solution

No improvement in pulmonary edema ARDS patients

Improvement of alveolar:arterial oxygen tension With negative fluid balance Not with hyperoncotic albumin solution

Capillary Filtration

When Cap pressure high Fluid leaks at interendothelial clefts Directed as a jet through small strand breaks Washing protein away making COP very low One-way valve

If Cap pressure drops Fluid jet slows Protein diffuses into cleft COP differences cleft:cap lumen decrease No out flow but also no reabsorption

Capillary Filtration

COP of fluid used Does not change fluid flow out/in capillary

Giving fluids with normal/high capillary pressure Endothelial glycocalyx will degrade Predispose to edema formation

Bolus resuscitation Transient peaks of capillary pressure Cause transient hyperfiltration Lose infused volume to the tissues Using a colloid solution will not provide protection!

Lymphatic Flow ~50% of lymph fluid enter vasculature in local lymph nodes Lymph then has a higher protein concentration

To thoracic duct Other lymphatic/vascular connections

Function when needed Lymphatic contractility

Enhanced by adrenergics Suppressed by inflammatory mediators

Discontinuous capillary circulations 25% of the cardiac output Liver, spleen and bone marrow

Lymph in the thoracic duct 50% originates from the liver Resuscitated hyperdynamic sepsis

Proportion of blood flow to the liver increased 50% Loss of protein increases without pathologic changes in vessels

Endothelial Glycocalyx“Capillary Leak”

Normovolemia Endothelial glycocalyx layer healthy Colloids remain intravascular Crystalloids leak

Hypervolemia (fluid therapy, fetal fluid shifts) Endothelial glycocalyx damaged Colloids and crystalloids leak

Hypovolemia Colloids and crystalloids remain intravascular

Sepsis Endothelial glycocalyx damaged Colloids and crystalloids leak with fluid therapy

Fluid Type Albumin

Saline versus Albumin Fluid Evaluation (SAFE) 2004 7000 patients – overall no differences Septic patients – trend increased survival

Albumin Italian Outcome Sepsis (ALBIOS) study 2014 No benefit from maintaining normal albumin level Reduced mortality in Septic Shock subgroup

Role in glycocalyx functioning Albumin level important for normal filtering

Transcapillary escape rate of albumin (TCERA) Index of ‘vascular permeability’ Normal TCERA - 5% per hour Septic shock - 20% or more Low albumin

Increased escape? Catabolism?

Plasma Substitutes Used to maintain or raise the plasma COP but …

Displace albumin from the circulation By elevating COP

Suppress hepatic albumin synthesis Traditional Starling

Great importance to the COP of plasma But clinical studies show

No difference between the COP of plasma Septic and non-septic patients

COP does not influence pulmonary transcapillary filtration In patients with pulmonary edema

Not found to be a determinant of outcome In intensive care cases

COP Paradox Rx albumin vs HES vs saline

• Can transiently raised plasma COP with albumin, HES• Not change fluid balance • Not change development of peripheral or pulmonary edema

In patients with acute lung injury• Plasma substitute resuscitation

Worsened the total thoracic compliance compared with saline• Type of fluid used for volume loading

Does not affect pulmonary permeability or edema

Properties other than the effect on COP contribute to the capillary ‘sealing’ effect of albumin

COP“Capillary Leak”

If capillary pressure is normal Colloid infusion

Preserves plasma COP Increases capillary pressure Increases capillary filtration

Crystalloid infusion Lowers plasma COP Increases capillary pressure Increases capillary filtration more than colloids

Colloids normal individual Keep vascular volume higher than crystalloids

COP“Capillary Leak”

If low capillary pressure – shock Infusion of colloid

Increases plasma volume (inside EGL - lumen) Infusion of crystalloid

Increases vascular volume (lumen and EGL) Results is 1:1.3 ratio colloid:crystalloid volume

Capillary filtration Close to zero in both cases

Effect on volemia is equal – no clinical difference

COP of plasma/colloid Not help volume resuscitation

Colloids

Only indicated for intravascular hypovolemia Without inflammation

No better than crystalloids For hypoperfusion For capillary hypotension/vasodilation Any time disruption of Endothelial Glycocalyx Layer

Should not be used as a fluid preload Neither should crystalloids

Not helpful in cases with low COP

Type of Fluid Colloid vs Crystalloids

Human regulations on colloid use: Do not use critically ill Do not use sepsis

Research misconduct Joachim Boldt

Scientific fraud (2012) 89 of 102 reports retracted

Fluid Dynamics Consequences

Response to Hemorrhage

Response to Volume Loading

Response to Hypoxia

Fluid Dynamics Response to Hemorrhage

Perinatal blood loss

Premature placental separation

Rupture of umbilical vessels

Long bone fractures

Gastrocnemius rupture

Necrotizing enterocolitis


30% loss of blood Adult horses, dogs, cats, and sheep

With out fluid therapy - 24 to 48 hours Fetus or neonate is shorter

Fetal sheep blood volume 2x adults within 30 minutes 100% within 3 to 4 hours


Neonatal kittens and rabbits Greater blood loss per kg before BP

decrease Translocation fluid and protein From the interstitial space

Tolerate blood loss better than adults

Fluid Dynamics Response to Volume Loading

Rapid intravascular infusions crystalloids Fetal lambs - 6 to 7% retained at 30-60 min

Adults – 20% to 50% retained at 30-60 min

Rapid transfer into the interstitial space High interstitial compliance

High capillary filtration coefficient Suppression of the endothelial glycocalyx?


Fluid Overload – lack of intravascular retention

Adults (dogs, sheep)

The adult clears the fluid load hours

Renin

Vasopressin

Atrial natriuretic factor


Fluid Overload – lack of intravascular retention

Neonates (puppies, lambs)

24 to 36 hr. to clear fluid load

Volume load escapes vasculature space quickly

Escape volume sensors detection

No diuretic response

Urine flow rapidly returns to normal

Before clearing volume load


After fluid loading (fetal lambs, neonatal lambs) Increase thoracic duct lymph flow

Increase by 3.5 times (max flow rate) Angiotensin II augments lymph flow

Fluid therapy – rapid infusion Increases CVP Dramatic decrease in lymphatic flow Result in edema

Thoracic Lymph Flow

From: Brace RA et.al.

Fetal lamb

Adult sheep

Thoracic Lymph Flow

Fetal lamb

With large volume intravenous infusion

↑↑ Lymph flow as

much as 340%

Limited by CVP

From: Brace RA et.al.

Fluid Dynamics Response to Hypoxia

Moderate/severe hypoxemia (fetal lambs) Increases arterial and venous pressures

Poor precapillary tone Increase capillary pressure

Destroy endothelial glycocalyx layer??

Greater fluid shift interstitial space

Leading to excessive fluid overload

Fluid Dynamics Response to Hypoxia

All neonates Fluid overloaded at birth

With hypoxia/asphyxia (and with fluid therapy) Greater degree of fluid overload

Hypovolemic with concurrent fluid overload

Are our patients getting better because of our therapy or

despite our therapy???

FEAST StudyFluid Expansion As Supportive Therapy

Attempt to justify modernizing hospitals Attempt to deliver fluids expediently Children with poor perfusion

But not septic shock Bolus vs slow drip Backfired

Bolus fluids increased the risk of death No subgroup fluid resuscitation beneficial

FEAST Study

Fluid Expansion As Supportive Therapy NEJM 364(26):2483, 2011

Pediatric patients - fluid resuscitation Poor perfusion (1st hr. total, 2nd hr. total)

20 ml/kg boluses saline (20 ml/kg, 5 ml/kg) 20 ml/kg boluses albumin (20 ml/kg, 4.5 ml/kg) No boluses (1.2 ml/kg, 2.9 ml/kg)

Severe sepsis 40 ml/kg bolus saline 40 ml/kg bolus albumin

FEAST StudyPoor Perfusion Group

Children – 60 d to 12 yr – 3000+ Severe febrile illness Impaired consciousness Respiratory distress Impaired perfusion

Capillary refill time of ≥ 3 sec Lower limb temperature gradient Weak pulse volume Severe tachycardia

FEAST Study Poor perfusion group

51% moderate to severe acidosis 39% lactate > 5 mmol/l

Poor perfusion group deaths by 48 hr 10.6% albumin bolus group 10.5% saline bolus group 7.3% no bolus group RR bolus vs no bolus

1.45; 95% CI, 1.13 to 1.86; P = 0.003

FEAST Study No benefit from bolus fluid infusion Bolus fluids increased risk of death

No subgroup benefited Hypotension Severe metabolic acidosis

Increased mortality all subgroups All physiological derangement All microbial pathogen

Deaths not associated fluid overload Cardiovascular death Early use of vasopressors?

Fluid-Bolus Resuscitation Patients with compensated shock

Harmful? Mechanisms? Interruption catecholamine responses

Rapid increase in plasma volume Reperfusion injury?

Transient hypervolemia/hyperosmolality Exacerbate capillary leak Harmful edema

Bolus-fluid resuscitation in compensated shock If no clinical fluid deficit Practice with caution

Septic Shock Volume Resuscitation Immediate positive effect

Increased perfusion Patient “looks better” but …

Rapid infusion – adverse effects Fluid responder

CO increases Vasodilatation BP unchanged (perfusion?)

Increased shear stress Increases NO

Septic Shock Volume Resuscitation Increased cardiac filling pressure

Increased right atrial pressure Increase natriuretic peptide

cGMP-mediated vasodilatation Cleaves endothelial glycocalyx Endothelial barrier injury

Capillary leak At 3 hr. < 5% crystalloid intravascular Increased tissue edema Myocardial dysfunction

Once Shock Reversed Positive fluid balance = increased mortality

Acute load Rapid unload – diuresis

Patients who rapidly unload live Less severe disease? Can we influence outcome?

Dilemma Initially fluids are helpful in shock But once reversed – harmful

Restrictive fluid strategy Early use inopressors Reverse severe vasodilatory shock

Fluid Therapy Timing

Fluid substitution Electrolyte mix

Volume substitution Resuscitation shock

Timely Adequate

Bolus Therapy Timing Positive effects Negative effects

Are Fluid Boluses Needed?

Clinical guess Clinicians can’t guess correctly

Clinical examination

Hemodynamic indices (e.g. CVP)

50% improve outcome

50% cause harm

Are Fluid Boluses Needed?ProCESS

Protocol-based Care for Early Septic Shock NEJM 5/14 1341 patients with septic shock

Protocol-based EGDT CVP, inotropes, blood transfusions

Protocol based standard therapy Usual care

Resuscitation strategies differed significantly Monitoring: CVP, O2 etc. Intravenous fluids, vasopressors, inotropes and

blood transfusions

Are Fluid Boluses Needed?ProCESS

No differences despite intense monitoring 90 day mortality 1-year mortality Need for organ support

Goldilocks Principle “Just Right” Without available cues

“Targeted Fluid Minimization” - TFM Following initial resuscitation in septic shock Using “fluid responsiveness”

Type of Fluid

Saline vs balanced crystalloids

Crystalloids vs colloids

Plasma (albumin)

Saline vs Balanced Crystalloids Saline vs Balanced Crystalloids

Hyperchloremic acidosis Renal vasoconstriction Decreased renal artery

Flow velocity Blood flow Cortical tissue perfusion

Reduced GFR Salt and water retention

Greater interstitial edema Chloride-restrictive strategy

1533 ICU patients Significant decrease in AKI

Which Balanced Crystalloid?

Sydney Ringer 1880s Ringer’s lactate - USA

Alexis Hartmann 1920s Hartmann’ solution - UK

Normosol-R, PlasmaLyte Formulations – “balanced”

Lactate, acetate, gluconate Gluconate

Not metabolized Diuresis

Fluid Therapy Critical Patients

Past focus on short-term goals Rapid correction of hypovolemia Emergency resuscitation Clinically immediately rewarding but …

Potential longer-term consequences Contribution to organ failure Long term mortality/morbidity

Challenge of Fluid TherapyGetting It Right

Give the appropriate dose of fluids Too little – harmful Too much – harmful

Achieve physiological targets But no clinical way to monitor

How close to the target? Overshot target?

Early Goal Directed Therapy Intensive monitoring not helpful

Timing Early positive fluid balance Late negative fluid balance

Dangerous to uncritically achieve clinical targets

Fluid TherapyThings I Try to Do

Bolus fluids but not too much No good stall side guide

Stop high rates fluids early Before legs warm Give IV nutrition

In as small a volume as practical Na restriction in neonates Cl restriction

Fluid TherapyThings I Try to Do

Watch weight increases as gauge? Confounding factors

Fluid restriction If good perfusion Signs fluid overload

Edema Weight gains

No good clinical guides Too much vs too little Be well aware of possible harm

Type of fluid Sodium restriction (3-4 mEq/kg/day) Chloride restriction

Goldilocks Principle

Getting it “Just Right”

No Jelly Belly

Fluid Therapy in the Neonate Hypovolemia - Septic Shock Crystalloid fluid boluses

20 ml/kg over 20 minutes – or less?? Re-evaluation tissue (regional) perfusion after each bolus

Improved pulse quality Warm legs?? Return of borborygmi Urine production Improved mental status

No good clinical guidelines Repeat fluid boluses???

If > 40-60 ml/kg is required, inopressor therapy? Large volumes – first 1 to 2 hr then stop unless large losses

This approach has been seriously questioned Avoid fluids > immediate needs

Reassessing the patient after each bolus

Fluid Bolus Example: 50 kg foal

20 mg/kg = 1000 ml Over 20 min Reassess – how?

Fluid therapy Maintenance Requirements

Metabolic rateDegree metabolism is supported by catabolism

Increase osmotic load Result in production of metabolic water

Insensible water loss Humidity Respiratory rate Body temperature Ambient temperature Surface to mass ratio


Gastrointestinal water lossUrine osmotic load

Increased with many medications Increased with hyperglycemia

Ability of the kidneys To concentrate this osmotic load

There is no "correct maintenance fluid rate" Maintenance needs vary from patient to patient


Holliday-Segar philosophy (1957)Maintenance fluid needs are related

to basal metabolism Metabolism produces

Heat Dissipated by insensible evaporation

Solutes Byproducts excreted in urine


Basal Metabolic Rate Higher per kg in neonate Higher per kg in smaller animal Varies with size Growing neonate based on wt MR0.75

Between species based on wt MR0.75

BMR can be estimated Based on surface area Based on experimental info in tables Based on age formulas (humans) Using Holliday-Segar formula

Fluid therapy Holliday-Segar Formula

Developed to estimate kcal expended But … fluid required in ml = kcal used

For each 100 kcal for metabolism require 100 ml fluid Insensible loss 35-40 ml Urinary excretion 65-60 ml

Usg = 1.010 Holliday-Segar Formula (wt < 100 kg)

1-10 kg wt = 100 ml/kg/day 4 ml/kg/hr

11-20 kg wt = 1000 ml + 50 ml/each kg > 10 kg ml/hr = 40 + 2 ml/each kg > 10 kg

> 20 kg = 1500 ml + 25 ml/each kg > 20 kg H-S used 20 ml/each kg > 20 kg/day ml/hr = 60 + 1 ml/each kg > 20 kg/hr

Holliday MA and Segar WE. Pediatrics 1957;19;823

Fluid therapy Maintenance Fluids

Using H-S formula Half calculated rate ≈ insensible loss Useful with oliguric renal conditions

INs – insensible losses = OUTs Helps gauge renal function Detect excessive/decreased urine Follow weight changes Help match INs with OUTs Beware: correction of fluid overload

Outs > Ins

Fluid therapy Maintenance Support

"Dry maintenance rate" Somewhat fluid restricting Spares kidneys during recovery period Renal pathology common in the neonate

Neonates If don't have excessive fluid loss Can have trouble handling fluid overload Dry maintenance rate helpful

Glucose infusion rate Use 10 – 20% solutions to give 4 – 8 mg/kg/min For average neonate just above maintenance rate

Larger the foal the greater the difference It is more important to deliver glucose needs

Sodium balance in the neonate

Positive Na balance important for growth Mother’s milk Na poor Neonates preconditioned to conserve Na

Retain 65% of ingested Na Proximal tubule not mature Distal tubule

Site of most avid Na conservation Sodium load

Neonate only able to excrete 10% of pediatric Puppies decreased ability to handle Na load


IV Na load adult dogs, puppies Adult Fxna = 9% Puppy Fxna = 2% Proximal tubules

Adult reabsorb 64% Na Puppy reabsorb 48% Na

Distal tubule Adult reabsorb 26% Na Puppy reabsorb 51% Na

Distal tubular compensation


Mechanism for Na conservation Studied for 50 years Becoming clearer

9 Na transport carrier systems Have different characteristics and distribution Failure of one results in compensation by others

Distal tubular enhanced Na absorption Epithelial Na Channel Aldosterone

Sodium balance in the neonate Normal Na intake

Require about 1 mEq/kg/day for growth Mare’s milk – 9 mEq/l From mare’s milk 1.8 mEq/kg/day 65% retention by neonate ~ 1 mEq/kg/day

Na supplementation – acute Extracellular volume expansion Edema Hypernatremia – with insensible losses

Na supplementation – chronic With supplementation Fxna will increase Time required varies

Species differences Longer with neonatal disease

Fluid TherapySodium considerations

Neonates easily sodium overloaded Perinatal disease compounds Na handling problems Sodium overload common sequela

Indiscriminate fluid therapy Normal foal

Nursing 10 - 20% of its body weight in mare’s milk Receives 1 - 3 mEq Na/kg/day

Colostrum 4.9 mEq Na/kg/day Neonate will use ~ 1 mEq Na/kg/day in growth

Interstitial expansion Increase cellular mass Bone growth

Fluid TherapySodium considerations

Goal - limit daily Na intake to < 3 mEq/kg/day 1 liter of Na based crystalloids – 50 kg neonate 1 liter of plasma – 50 kg neonate Drug infusions

Inopressors Insulin Antimicrobials CRIs

Parenteral nutrition Most amino acid sources

2 gm/kg/day amino acids Delivers approximately 1 mEq Na/kg/day.

Fluid Therapy Sodium considerations

Neonatal nephropathyCommon neonatal problem

Hypoxic ischemic disease SIRS – cytokine associated

Na wastingHigher Na requirement

Fluid Therapy Sodium considerations

ClinicallyUrine is only source of Na loss

Without reflux Without diarrhea (dysmotiliy) After growth requirements considered

Match Ins to urine loss + 1-2 mEq/kg (growth)

Fluid Therapy Sodium considerations Urinary Na loss

Total urine collection Total daily Na excretion monitored

Not have total urine collection Na requirements can be estimated

from urine Na concentrations Fxna

Na overload avoided While Na requirements are met

Fluid Therapy Potassium Supplementation

K requirements Difficult to estimate

Renal loss Growth requirements (anabolic) Catabolic K release K release from sepsis

Any neonate not consuming milk will require K Supplementation

Empirical – 3 mEq/Kg/day Begin before decrease

May need more depending Stress level/sepsis Deficit before beginning 6-9 mEq/Kg/day

Occasionally > 12 mEq/Kg/day Wean when begin milk

Maintenance Fluid Formula

Volume – based on H-S formula Sodium

4 mEq/kg/day max 1 mEq/kg/day in amino acids (TPN) Deliver 3 mEq/kg in fluids

Account for Na in drugs Mix Na fluids + D5W = Na needed

Potassium 3 mEq/kg/day

Commercial “maintenance fluids”

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