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eonatal foals have a larger volume of total body water, Monitoring Replacement CrystaUoid Therapy
N comprising approximately 75 to 83.3 % of body weight, as Assessment of fluid status should include physical examination
compared to 60 to 70% of body weight in the adult horse. 1-5 In
findings, including those that reflect intravascular volume sta-
addition, the extracellular fluid (ECF) compartment is rela-
tus. These perfusion parameters include mentation, heart rate,
tively larger in foals, occupying approximately 39.4 + 2.9 L/kg
extremity temperature, pulse quality, capillary refill time (Fig
of body weight, as opposed to approximately 22 to 29 I_/kg in
1), jugular refill time, mucous membrane color, as well as urine
the adult. 6-~1Neonatal foals are expected to have a higher turn-
production. Hemodynamic monitoring, including measure-
over of body water, as they have a higher metabolic rate than
ment of central venous pressure, arterial blood pressure, colloid
adult horses. Foals have a relatively greater surface area and
osmotic pressure, blood lactate, PrO2 and acid base status
reduced renal concentrating ability in the postpartum period as
compared to adult animals. 12,13 should also be performed. Central venous pressure (CVP) is the
luminal blood pressure of the intrathoracic cranial (or caudal)
Normal urine output in neonatal foals is reported to be ap-
vena cava. It is regulated by central venous blood volume (ve-
proximately 6 mIA~g/h. ~z This high output is related to a large
nous return), venous tone, and cardiac output. CVP can be
mtake of water, in the form of milk. Milk consists of approxi-
measured using a plastic manometer with a three-way stopcock
mately 89 to 90 % water, and healthy foals consume between 15
fastened to extension tubing that is continuous with a central
to 30% of body weight in milk per day. ~,~4 Reflecting this high
venous catheter (Fig 2). Catheters which are 20 to 30 cm in
water intake and urine excretion, normal unne specific gravity
length (such as an Arrow intravenous catheter, Arrow Interna-
in newborn foals, after the first 24 hours postpartum, is usually
tional, Inc, Reading, PA), should be utilized for measurement of
hyposthenuric (<1.008) and is reported to range from 1.001 to
1.027.i2,13 CVP (Fig 3). Placement of the catheter within the cranial vena
cava can be confirmed through thoracic radiography (Fig 4).
Serial monitoring of CVP is useful in evaluating responses to
Fluid Replacement (Volume Resuscitation) fluid boluses. Increase in CVP may be caused by volume over-
load, as might occur with excessive volume replacement or
Fluid deficits can be replaced using crystalloids, colloids, or
right heart failure. There are a number of additional causes of
both (please see discussions below). Briefly, crystalloids are
increased CVP, including increases in pleural or pericardial
pressures or false elevations as might occur with catheter oc-
From the School of Veterinary Medicine, University of California, Davis, clusion or the presence of air in the lines. Normal CVP in
Davis, CA, USA neonatal foals is <10 to 12 cm of water (<9 mmHg). 17 CVP
Address reprint requests to Dr. K. Gary Magdeslan, One Shields Ave, values within the normal range do not rule out hypovolemia,
2108 Tupper Hall, School of Veterinary Medicine, Department of Medi- but overzealous fluid administration will result in increases in
cine and Epidemiology, University of California, Davis, Davis, CA 95616.
Copyright 2003, Elsevier Science (USA). All rights reserved. CVP, and negative results are indicative of hypovolemia. Nor-
1534-7516/03/0201-0001 $35.00/0 mal blood lactate in 24-hour foals is less than 2 to 2.5 mmol/L
doi:l 0.1053/$1534-7516(03)00021-0 (Ref 15, Magdesian, personal observations). Blood lactate ele-
vation occurs most commonly because of absolute or relative Maintenance Fluid Requirements
tissue hypoxia, as with hypovolemia or cytopathic hypoxia,
Exact maintenance fluid requirements in the perinatal foal are
respectively. However, it should be remembered that increases
unknown. There are currently a number of different protocols
in blood lactate concentration may also occur with hypermeta-
bolic states (as with sepsis), decreased clearance (liver failure), used to estimate fluid requirements in this age group of
inhibition of pyruvate dehydrogenase (as with thiamine defi- horses. 16-1s One report recommends a maintenance fluid re-
ciency), and catecholamine surges or inflammatory mediators quirement of 80 to 120 mL/kg/day, which translates to 3 to 5
associated with SIRS. As with CVP, serial measurement of lac- mlJkg/h. Palmer estimates maintenance fluid requirements by
tate, evaluating for trends and alterations, is probably more using the following calculations: 16
important than one particular measurement. Arterial blood 100 mL/kg per day for the first 10 kg of body weight
pressure is discussed m the manuscript on hemodynamic mon- + 50 mL/kg per day for the second 10 kg of body weight
itoring. Fluid balance should also be evaluated through moni- + 20-25 mL/kg per day for the remainder of body weight
toring of water intake and urine output in critically ill foals;
output is measured through means of a urinary catheter (Fig 5), Based on this formula, a 50-kg foal would require approxi-
while input reflects both enteral and parenteral water intakes. mately 100 mldh of fluids for maintenance needs once rehy-
Milk is approximately 89 to 90 % water. Fluid input should be drated. Foals on either protocol should be monitored for ade-
approximately equal to urine output, in addition to estimations quacy of fluid provision.
of insensible losses and water retention for growth. Even more elusive are the fluid requirements of the critically
Hydration parameters, those that reflect interstitial volume ill foal. These likely vary considerably, with a high degree of
status rather than intravascular volume, include skin turgot, interindividual variability. A foal experiencing a systemic in-
tear film production (corneal quality), eye positioning (sunken flammatory response syndrome (SIRS) associated with diarrhea
eyes reflecting dehydration), and mucous membrane texture. will certainly require more daily fluid than one with perinatal
Serial body weight measurements are very useful indicators of asphyxia syndrome and obtundation, recumbency, and com-
total body water changes. promised endothelial integrity.
Once dehydration and hypovolemia are corrected using re- Complications of Fluid Therapy
placement fluids (as described under 'Fluid Replacement'), the
Complications of paremeral fluid therapy include overhydra-
author recommends initiating fluid plans for critically ill foals
uon and phlebitis. Volume overload and overhydration will be
using one of the methods described here for maintenance. Sub-
sequently, the foal should be monitored serially using clinical reflected by: (1) significantly greater fluid input than output,
examination findings, monitoring tools such as central venous (2) increased CVP, (3) unexpected weight gain, (4) increased
pressure, arterial blood pressure, urine output, and blood lac- skin turgor, (5) peripheral edema as manifested by ventral
tate concentrations, as well as clinical pathologic markers such edema or chemosis, and/or (6) increased respiratory rate or
as total protein, colloid osmotic pressure, and hematocrit or deterioration of blood gases reflecting pulmonary edema. Ex-
packed cell volume. No one of these values will dictate fluid cessive fluid administration should be detected before develop-
needs alone, but rather the combination will monitor trends in ment of edema, and this is where CVP and monitoring of input
fluid balance and thus aid in directing fluid plans. For example, versus output of fluid volume is useful.
a normal hematocrit or total protein should not necessarily Neonatal foals are often supplemented with dextrose in flu-
imply adequate hydration, because these may be independently ids. Because neonatal foals with poor milk intakes are at risk for
low for other reasons, including anemia and protein loss, re- hypoglycemia, fluids should initially provide 4 to 8 mg/kg/min
spectively. Other techniques useful in monitoring fluid balance of dextrose.16 However, hyperglycemia should be avoided dur-
include measurements of body weight, serum albumin concen- ing volume resuscitation because of potential complications,
tration, BUN and creatinine, urine specific gravity, plasma os- such as intracellular acidosis and osmotic diuresis. Intensive
molarity, mixed venous oxygen saturation, thoracic radiogra- insulin therapy with tight regulation of blood glucose has re-
phy, and echocardiography. ceived recent attention in human critical care, and insulin may
In addition to 'replacement' and 'maintenance' fluid require- exert antiinflammatory effects. 19,2 To prevent hyperglycemia,
ments, on-going losses of fluid, as might occur with diarrhea or blood glucose concentrations should be monitored frequently
reflux, should be accounted for in fluid plans. in foals being supplemented with parenteral glucose in fluids.
than that of plasma, which has approximately 130 to 140 Acetate is metabolized primarily in muscle, and this may be an
mEq/L sodium and 90 to 102 mEq/L of chloride. This relative advantage for use in liver failure patients. 21 Another difference
increase in chloride causes saline to effect a mild acidosis, between Plasma-Lyte or Normosol-R and LRS is the relative
because of a relatively greater provision of strong anions as sodium to chloride ratio, with the former fluids having 140
compared to strong cations. Therefore, saline is useful in foals mEq/L sodium and 98 mEq/L chloride. This allows for a larger
with primary metabolic alkalosis, however, this is rarely en- strong ion difference (SID) in Plasma-lyte 148 (SID = 47 mEq/L
countered. Acidosis is common in critically ill foals, making as opposed to approximately - 4 mEq/L in Hartmann's or LRS),
saline a less than optimal fluid choice in these patients. which may be advantageous in patients with metabolic acido-
Plasma-Lyte 148 or Normosol-R. Plasma-Lyte 148 (Baxter sis. = The potassium content of Plasma-Lyte or Normosol is 5
Healthcare Corporation, Deerfield, IL) or Normosol-R (Abbott m E @ . A variety of other Plasma-lyte solutions exist, including
Laboratories, North Chicago, IL) are polyionic crystalloids that Plasma-Lyte A, Plasma-Lyte R, and solutions containing dex-
are similar to LRS with a few notable differences. They contain trose (Baxter Healthcare Corporation), which have slight vari-
magnesium, rather than calcium, and can therefore, be admin- ations on Plasma-Lyte i48.
istered along with plasma or blood products containing citrate. Isotomc bicarbonate. Isotonic bicarbonate solution can be
In addition, they contain acetate (27 mEq/L) and gluconate (23 made by adding 150 mEq of sodium bicarbonate (150 mEq of
mEq/L) as alkalinizers rather than lactate. = sodmm, 150 mEq of bicarbonate) to 1 liter of sterile water. This
Acetate: solution is a good fluid choice for foals with inorganic (hy-
NaC2H302 + 202 --+ CO2 + H20 + Na + + HCO3- ponatremic, hyperchloremic) metabolic acidosis, as well as
those with hyperkalemia, such as those with uroabdomen.
Gluconate:
Foals administered bicarbonate should be monitored for hypo-
2NaC6HnO7 + 1002 --->10CO 2 -~ 10H20 + 2Na + + 2HCO3- kalemia, decreases in ionized calcium, metabolic alkalosis, and
hypercapnia. Rapid administration of bicarbonate should be 148, and 100 mL of 5% dextrose in water would be adminis-
avoided for these reasons, as well as to avoid the possible de- tered. The proportion of isotomc crystalloid and D5W could be
velopment of paradoxical intracellular acidosis. Potentiation of changed depending on electrolyte and hydration status. Alter-
intracellular acidosis by rapid bicarbonate administration is an natively, commercial maintenance fluids are available.
equivocal phenomenon, which has been documented in Plasma-Lyre 56 or Normosol M. Plasma-Lyre 56 (Baxter
vitro. 23-26 A good rule of thumb is to administer half of the Healthcare Corporation, Deerfield, IL) or Normosol M (Abbott
estimated bicarbonate deficit (body weight in kg base defi- Laboratories, North Chicago, IL) are fluids that are hypoosmo-
cit X 0.4) over 1 to 2 hours @er replacement of fluid deficits, lar relative to the ECF, with an osmolarity of approximately 111
and then to reassess the base deficit. Bicarbonate administration m E @ . As expected, the sodium concentration is lower (40
should be performed with caution in foals with hypoventila- m E @ ) , and potassium, the primary intracellular cation, is
tion, as it may further increase PaCO2. higher (13 m E @ ) . Like their replacement counterparts, these
fluids contain magnesium rather than calcium. They contain
II. Maintenance Crystalloids only acetate (16 mEq/L) as the alkalinizing salt. One difference
Maintenance fluids are indicated in neonatal foals intolerant of from the analogous replacement fluids is that the sodium to
enteral feeding, as they provide an alternate source of free water chloride ratio is 1:1 in these maintenance fluids, which may
for distribution to the intracellular space in addition to the represent a slight disadvantage for acidotic patients with hyper-
ECF. They should be utilized only after the neonate is rehy- chloremia.
drated with replacement fluids. Replacement crystalloids may Sodium chloride (0.45 %) and dextrose in water (2.5%). This
be inappropriate for use as maintenance fluids in foals, because so-called "1/2 strength saline, 1/2 strength dextrose" crystalloid
of the large sodium content, especially in foals intolerant of is also a maintenance fluid. Like the above commercial fluids,
enteral milk intake, aT Maintenance fluids can be developed the sodium: chloride ratio is 1:1, however, the solution lacks
from replacement fluids through the administration of two- potassium or other electrolytes, as well as alkalinizing agents.
thirds the desired fluid rate as 5% dextrose in water (D5W) and The advantage of this solution is that it can be used directly off
one-third as replacement fluid. For example, if the fluid admin- the shelf without having to add dextrose. This solution may be
istration target is 150 mL per hour, then 50 mL of Plasma-Lyte ideal for maintenance of patients with hyperkalemia.
the only source capable of replacing platelets. Because the COP Plasma-Lyte 148 (Baxter Healthcare Corporation) should be
of plasma is equivalent to the oncotic pressure of normal used instead.
horses, and because 60% or more of albumin may redistribute
extravascularly, foals with significant hypoproteinemia may re-
Synthetic Colloids
quire the use of synthetic colloids for additional oncotic sup-
port. Foals receiving plasma transfusions should be monitored Hydroxyethyl starch (Hetastarch). Hetastarch is the most
for signs of hypersensitivity and transfusion reactions, includ- commonly used synthetic colloid in horses (Fig 7).29,3.49 It is a
ing pyrexia, tachycardia, tachypnea, muscle tremors, colic, ur- modified branched-chain glucose polymer originating from
ticaria, and signs of anaphylaxis. Plasma should be adminis- amylopectin. It is available as a 6% aqueous solution in saline
tered through a blood administration set containing filtration (Abbott Laboratories) or lactated electrolyte solution (Hex-
devices. tend@, Abbott Laboratories). The COP of hetastarch is approx-
Whole blood. Whole blood transfusions may be indicated as imately 30 mmHg, making it a more cost-effective colloid than
the colloid of choice in cases of hemorrhagic shock, while plasma. The primary side effect associated with hetastarch ad-
washed dam erythrocytes are ideal for foals with neonatal iso- ministration is an induction of coagulopathies associated with
erythrolysis. Complications associated with blood transfusions reductions in coagulation factor VIII and yon Willebrand's fac-
include reactions due to incompatible red blood cells, as well as tor. Platelet counts and function may also be altered. Hypersen-
those associated with transfer of leukocytes. Citrate toxicity sitivity reactions are also rarely reported. Unlike dextrans,
and hypocalcemia are other potential side effects. Donor ani- hetastarch does not interfere with blood typing or cross match-
mals should be screened for blood-borne diseases. Red blood ing.
cells do not exert oncotic pressure, and therefore packed red There are no studies evaluating hetastarch in foals. Recom-
blood cells do not offer an advantage over whole blood from a mended doses of hetastarch based on studies conducted in
colloid standpoint. Whole blood should not be administered adult horses are up to 8 to 10 ml/kg/day. 29,3,5 Foals in need of
through the same lines as calcium containing fluids, and fluids rapid volume support may be bolused 3-5 ml/kg hetastarch in
without calcium such as Normosol-R (Abbott Laboratories) or addition to crystalloids. In addition to bolus administration,
hetastarch can be used as a slow infusion (0.5-1 mL/kg/h, up to drome, thrombocytopenia, or other hypocoagulable states
10 mldkg/day) for colloid support in hypooncotic animals. should not be administered hetastarch.
Until further research is available, larger doses of hetastarch Pentastarch. Pentastarch (DuPont Critical Care, McGaw,
should be used with caution. Foals with von Willebrand's syn- IL) is a narrow-range, medium molecular weight derivative of
Replacement
LRS 130 4 109 3 0 272-273 28 lactate
Saline (0.9%) 154 0 154 0 0 308 0
Ringers soln 147-148 4 156 4.5 0 310 0
Plasma-Lyte148 140 5 98 0 3 294 27 acetate
23 gluconate
Normosol R 140 5 98 0 3 294 27 acetate
23 gluconate
Maintenance
Plasma-Lyte 56 40 13 40 0 3 111 16
Normosol M 40 13 40 0 3 110 16
0.45% saline/2.5% dextrose 77 0 77 0 0 280 0
5% dextrose 0 0 0 0 0 252-253 0
hetastarch. The COP of pentastarch is 40 mmHg. It is more isoerythrolysis (NI) while awaiting blood transfusion. One case
homogenous than hetastarch in terms of size, excluding very report described the administration of 22 mI_/kg of polymerized
small or large molecules. Advantages over hetastarch include hemoglobin to a foal with NI. 55 In that foal, the Oxyglobin
fewer side effects on the coagulation and reticuloendothelial treatment maintained oxygen delivery for up to 18 hours before
(RE) systems. 51,52 Because of its narrower molecular weight washed red blood cells were administered.
range, pentastarch may be indicated for use in patients with
increased capillary permeability associated with SIRS. Pen-
tastarch shows promise for use in capillary leak syndromes, as it Conclusion
should be retained within the circulation to a greater extent There is little documentation supporting specific parenteral
than hetastarch, and it may aid in plugging leaky capillaries. 53
fluid management practices in neonatal foals. Current recom-
Fractions of colloids with molecular weights between 100 and
mendations are based on a combination of evidence, experi-
1000 kd may represent the ideal size for sealing of widened
ence, and extrapolation from adult horses and neonates of other
endothelial cell gap junctions. Smaller MW molecules ,nay po-
species. Available fluids include crystalloids, both replacement
tentiate third space accumulation of fluid, while larger mole-
and maintenance selections, as well as colloids. Understanding
cules could potentially interfere with sealing.54 Another advan-
the physiologic needs of the critical neonate is the best means of
tage of pentastarch is its potential for larger volume expansion
dictating fluid therapy, and continual reassessment of fluid
as compared to hetastarch.
balance, using clinical and clinicopathologic markers as well as
Dextrans. Dextrans are long glucose polymers produced monitoring tools, is of utmost importance in managing the ICU
from sucrose by the bacterium Leuconostoc mesenteroides (Fig
patient.
7). Dextran 70 is available as a 6% solution (6% Gentran 70,
Baxter Healthcare Corp) with a COP near 60 mmHg. The
higher colloid oncotic pressure of dextran 70 is misleading, as
References
many of the smaller molecules are rapidly eliminated, leaving a
comparable number of larger molecules as hetastarch. 1. Oftedal OT, Hintz HF, Schryver HF: Lactation in the horse: Milk
composition and intake by foals. J Nutr 113:2196-2206, 1983
Dextran 70 is associated with a higher rate of complications
2. Andrews FM, Nadeau JA, Saabye L, et al: Measurement of total body
than hetastarch. Allergic reactions and coagulation distur- water content m horses, using deuterium oxrde dilution. Am J Vet
bances appear to be more common. 51 Dextrans also mterfere Res 58:1060-1064, 1997
with crossmatching of blood products due to adherence to red 3. Forro M, Cieslar S, Ecker GL, et al: Total body water and ECFV
cell membranes and clumping of erythrocytes. For these rea- measured using bJoelectrical impedance analysis and indicator dilu-
tion in horses. J Appl Physiol 89:663-671, 2000
sons, the use of hetastarch is currently recommended over
4. Judson GJ, Frauenfelder HC, Mooney GJ: Plasma biochemical
dextrans for use in neonatal foals. changes in Thoroughbred racehorses following submaximal and
Hemoglobin-based products. Oxyglobin (Biopure, Cam- maximal exercise, in. Snow DH, Persson SGB, Rose RJ (eds): Equine
bridge, MA) contains polymerized bovine hemoglobin and is Exercise Physiology. Cambridge, Granta Edrtions, 1983, pp 408-415
labeled for increasing oxygen carrying capacity in dogs. Oxy- 5. Julian LM, Lawrence JH, Berlin NI, et al: Blood volume, body water
and body fat of the horse. J Appl Physiol 8:651-653, 1956
globin also provides a colloid effect (approximately 42 mmHg).
6. Fielding CL, Magdesian KG, EIliott DA, Craigmill AL, Wilson WD,
The shelf life of the product is 3 years at room temperature. Carlson GP: Pharmacokinetics and clinical utility of sodium bromide
Disadvantages of Oxygobhn include discoloration of mucous (NaBr) as an estimator of extracellular fluid volume in horses. J Vet
membranes and body fluids. It also interferes with several bio- Intern Med 17:213-217, 2003
chemical analyses and eliminates the ability to monitor hemat- 7. Evans JW: Effect of fasting, gestation, lactation and exercise on
glucose turnover in horses. J Anita Sci 33:1001-1004, 1971
ocrit or erythrocyte count. Scavenging of nitric oxide by Oxy-
8. Kohn CW, Muir WW, Sams R: Plasma volume and extracellular fluid
globin may result in regional tissue vasoconstriction, a volume in horses at rest and following exercise. Am J Vet Res
disadvantage that may counteract some of its oxygen carrying 59:871-874, 1978
benefits. Its ability to provide oxygen carrying capacity to 9. Muir WW, Kohn CW, Sam SR: Effects of furosemide on plasma
plasma is an advantage in low blood flow and ischemic tissues. volume and extracellular fluid volumes in horses. Am J Vet Res
39:1688-1691, 1978
Oxyglobin has been used in neonatal foals with neonatal
10. Carlson GP, Harold D, Rumbaugh GE: Volume dilution of sodMum
isoerythrolysis and anemia. Anecdotal reports suggest that a th~ocyanate as a measure of extracellular fluid volume in the horse.
dose of 5 to 7.5 mL/kg may be of benefit to foals with neonatal Am J Vet Res 40:587-589, 1979