Upload
others
View
11
Download
1
Embed Size (px)
Citation preview
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
Fluid PhysiologyFetus/Neonate
Interstitium Heterogeneous space Dynamically controls its fluid content Compliance 10X adult (fetal lamb)
Fluid PhysiologyFetus/Neonate
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
Fluid PhysiologyFetus/Neonate
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
Fluid Dynamics Response to Hemorrhage
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
Fluid Dynamics Response to Hemorrhage
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 Dynamics Response to Volume Loading
Fluid Overload – lack of intravascular retention
Adults (dogs, sheep)
The adult clears the fluid load hours
Renin
Vasopressin
Atrial natriuretic factor
Fluid Dynamics Response to Volume Loading
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
Fluid Dynamics Response to Volume Loading
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
Fluid therapy Maintenance Requirements
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
Fluid therapy Maintenance Requirements
Holliday-Segar philosophy (1957)Maintenance fluid needs are related
to basal metabolism Metabolism produces
Heat Dissipated by insensible evaporation
Solutes Byproducts excreted in urine
Fluid therapy Maintenance Requirements
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
Sodium balance in the neonate
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
Sodium balance in the neonate
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”