F l u i d Th e r a p y i n L u n g

Disease
a, b
Elizabeth Rozanski, DVM *, Alex Lynch, BVSc(Hons)

KEYWORDS
 Extravascular lung water  Pulmonary contusion  Pulmonary edema  Pneumonia
 Crystalloids

KEY POINTS
 Fluid therapy for patients with known or suspected lung disease should be tailored to in-
dividual patients, with some patients benefitting from fluid restriction.
 Colloids should be used judiciously if at all in patients with lung injury due to the potential
of magnifying lung injury.
 Point-of-care ultrasound may be useful for identifying pulmonary infiltrates.
 Radiographic detection of pulmonary edema is a late finding.
 If the disease process is definitively known, it should be easier to titrate fluid therapy.

OVERVIEW

Fluid therapy is widely considered one of the most vital aspects of patient manage-
ment in small animal practice. Fluids are used to treat hypovolemia, correct dehydra-
tion, and provide maintenance fluid needs in patients unable to drink normally.
Patients with known or suspected pulmonary disease commonly present a conun-
drum for clinicians when determining if or when fluid therapy is indicated due to con-
cerns that fluid therapy could magnify respiratory disease. This is not an all-or-none
rule when it comes to providing fluid support in dogs and cats with known or sus-
pected cardiopulmonary disease. Fluid therapy may constitute crystalloids or colloids.
The most commonly used crystalloids are isotonic replacement fluids (eg, lactated
Ringer solution and 0.9% saline), but hypertonic crystalloids (eg, 7.5% hypertonic sa-
line) can also be used for rapid intravascular volume replacement. Hypotonic crystal-
loids contain lower concentrations of sodium and are not appropriate for volume
replacement. They have applications as maintenance fluids in patients not maintaining

Disclosure Statement: The authors have nothing to disclose.

a
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University,
55 Willard Street, North Grafton, MA 01536, USA; b Small Animal Clinical Sciences, College
of Veterinary Medicine, University of Florida, 2015 Southwest 16th Avenue, Gainesville, FL
32608, USA
* Corresponding author.
E-mail address: Elizabeth.rozanski@tufts.edu

Vet Clin Small Anim - (2016) -–-

http://dx.doi.org/10.1016/j.cvsm.2016.10.013 vetsmall.theclinics.com
0195-5616/16/ª 2016 Elsevier Inc. All rights reserved.
2 Rozanski & Lynch

normal voluntary water intake. Colloidal solutions, especially synthetic starch solu-
tions, are also used in veterinary medicine, although in parallel to human medicine,
their use has declined in recent years perhaps reflecting fears of acute kidney injury.1,2
Although not the focus of this article, the key player in fluid movement was histori-
cally considered the Starling equation; recently it has become clear that although hy-
drostatic and oncotic forces are important, other factors are also important in fluid
movement in biological organisms, including the health and integrity of the endothelial
glycocalyx.3 Alterations in this glycocalyx layer are understood to affect the movement
of solutes and capillary fluid dynamics.3
Fluid therapy could theoretically worsen lung function by increasing hydrostatic
pressure. Elevated hydrostatic pressure could lead to extravasation of crystalloid
fluids into the interstitium or decrease plasma oncotic pressure, similarly promoting
extravasation of fluid and increased extravascular lung water (EVLW). Additionally,
in patients with an altered or dysfunctional endothelium, leakage of water or larger
molecules could occur have a further negative impact on lung function. In normal pa-
tients, is difficult to create volume overload because compensatory mechanisms
result in the elimination of excessive fluids. Specific tissue safety factors in the lung
limit the risk of EVLW accumulation under such circumstances. The nondistensible na-
ture of the pulmonary interstitium physically limits further fluid transudation from ves-
sels. This is combined with the maintenance of a colloid osmotic gradient when
transudation does occur, promoting water flux away from the interstitium into pulmo-
nary vessels. Finally, the regional lymphatics enable removal of any excessive water
accumulation in the local region.4
In the short term (minutes to hours), fluid therapy is of less concern in promotion of
lung injury/dysfunction than in long-term therapy, where there is increased risk for pos-
itive water balance, potentially in excess of liters of fluid (Fig. 1). The incidence of volume
overload or even a positive fluid balance is not known in dogs and cats. Wiedemann and
colleagues5 compared a liberal versus restrictive fluid strategy in critically ill people with
acute respiratory distress syndrome managed in ICUs. No differences in overall survival
were identified but fewer ventilator and ICU days were reported in the restricted fluid
group.5 Other studies have also consistently identified that a negative or neutral fluid
balance after resuscitation is associated with better lung function. Consequently, con-
servative fluid approaches are currently preferred in the ICU after initial resuscitation in
the emergency setting, unless there is a compelling reason for more fluids.

METHODS OF EVALUATING FOR PULMONARY EDEMA/VOLUME OVERLOAD

Lung Compliance
Normal lung function is dependent on lung mechanics as well as gas exchange. The
most important pulmonary complication of fluid therapy is pulmonary edema, which
may be cardiogenic or noncardiogenic in origin. Pulmonary edema decreases lung
compliance and subsequently leads to an increased work of breathing. Lung compli-
ance is a measure of the distensibility of the lung and is given by the formula, change in
volume (mL)/change in pressure (cm H2O). Compliance may be measured during tidal
breathing and is referred to as dynamic compliance. It is more common to measure
compliance during pauses in breathing (ie, inspiratory pause maneuver in mechani-
cally ventilated patients) and is then termed, static compliance. Lung compliance is
easily measured in intubated patients but is difficult, although not impossible, to mea-
sure in awake patients.6,7 Static lung compliance can be measured with a spirometer
and anesthesia machine in intubated patients or in patients ventilated with critical care
ventilators by preset programs (Fig. 2).
 Fluid Therapy in Lung Disease 3

Fig. 1. A shepherd receiving hemodialysis for treatment of volume overload after devel-
oping a 13-kg weight gain during treatment of severe polytrauma, which included multiple
fractures and pulmonary contusions.

Extravascular Lung Water

An important concept when discussing fluid therapy in the face of known or suspected
pulmonary disease is the concept of EVLW.8 EVLW is defined as fluid within the lung
that is outside the vasculature. EVLW was originally measured by comparing wet and
dry weights of the lungs at necropsy; this obviously does not permit repeated

Fig. 2. Measure of lung function using a critical care ventilator.

4 Rozanski & Lynch

sampling. More recently, EVLW may be calculated using indicator methods; these
techniques may be repeated to follow trends over time. Increases in EVLW decrease
lung compliance and subsequently increase the work of breathing. EVLW increases in
response to overzealous fluid therapy in most cases even before there is clinical or
radiographic evidence of pulmonary edema.9 Evaluation of EVLW has been performed
in dogs in research settings, and it may become feasible in clinical cases in the
future.10 In human medicine, and presumably in veterinary medicine, it is necessary
to correct for ideal body weight.8 Overweight and obese patients do not have larger
lungs and calculations based on actual body weight may underestimate the degree
of increase in pulmonary water.
Focused Ultrasound
Point-of-care ultrasonography has become commonplace in veterinary medicine.
Initial investigations focused on the detection of free fluid in the abdomen, but recent
studies have highlighted the ability of ultrasound with a trained ultrasonographer to
detect the presence of pulmonary edema.11 Ultrasound has the advantages of being
portable and reproducible while limiting exposure to radiation. In veterinary medicine,
current work has highlighted the ability to detect the presence of B-lines (lung
rockets)12 but it seems likely that over the coming years, the ability to detect the early
onset of pulmonary edema associated with resuscitation will increase as well. A
learning curve is expected when becoming used to this technique because other pul-
monary changes (eg, contusions and pneumonia) may also be identified in patients
depending on anatomic location and operator skill. In human medicine, the fluid
administration limited by lung sonography (FALLS) protocol is growing in utility in help-
ing guide resuscitative efforts, whereas similar protocols are in development in veter-
inary medicine.13

RIGHT HEART FUNCTION

Although often overshadowed by the work of the left heart, right heart function is also
important to consider when determining fluids in resuscitation.14 Cardiac output is
related to the Frank-Starling mechanism. Within physiologic limits, cardiac output in-
creases with increases in diastolic volume (ie, venous return to the right atrium). Under
supraphysiologic conditions, increasing right diastolic volume does not improve car-
diac output but leads to volume overload (congestion). Therefore, assessment of right
heart function is warranted prior to massive fluid boluses; patients with a volume over-
loaded/dilated right heart may not benefit from increasing preload.

GOAL-DIRECTED THERAPY AND BIOMARKERS

The concept of goal-directed therapy was initially associated mostly with resuscitation
strategies in patients with severe sepsis and septic shock.15 The approach involves
careful monitoring of patients usually using several pieces of clinical data to help un-
derstand the appropriateness of treatments provided to date. The approach has
strong links to the underlying physiology of oxygen delivery, where approaches to
maximizing oxygen delivery are performed in a somewhat sequential manner, in an
attempt to maximize positive outcome in critically ill people. This involves ensuring
normal oxygenation and ventilation, improving preload by administering intravenous
fluids, reducing afterload in hypertensive patients with antihypertensive drugs, aug-
menting afterload in hypotensive patients with vasopressors, improving contractility
with positive inotropes in patients affected by poor contractile function, and providing
red cells to anemic patients in the form of transfusions. The aim of this approach is to
 Fluid Therapy in Lung Disease 5

effectively audit a clinician’s ability to resuscitate an individual patient and act as a

reminder of alternative therapies that may be useful in patients refractory to standard
therapy (eg, consideration for vasopressors rather than relying on fluid therapy alone).
In the context of lung disease, this approach can be applied to ensure that patients are
achieving good endpoints of resuscitation without inadvertently providing excessive
fluids to patients potentially intolerant of such an intervention.
The biomarkers that can be used to gauge resuscitation include, but are not limited
to, heart rate, pulse quality, mucous membrane color, mentation, body temperature
(especially true in cats), lactate, blood pressure (remembering it is a late-stage indica-
tor of hypoperfusion), echocardiographic estimation of left ventricular volume, central
venous oxygen saturation, and mixed venous oxygen saturation. Respiratory bio-
markers that provide information about pulmonary function may provide information
related to a patient’s tolerance of fluids along with information related to the primary
disease. Commonly used biomarkers include pulse oximetry, arterial blood gas anal-
ysis, and capnography. More novel indicators of cardiac stretch, like N-terminal pro-
brain natriuretic peptide (NT pro-BNP), may find a role in the assessment of adequacy
of volume resuscitation in the future (Fig. 3). To date, this biomarker has been used to
help to characterize whether small animals with dyspnea are more or less likely to have
a cardiogenic or noncardiogenic cause for their signs, along with providing prognostic
information in dogs with confirmed heart disease. In theory, this biomarker has poten-
tial to help gauge whether the degree of ventricular stretch associated with preload
augmentation from fluids can be tolerated in certain patient populations like those
with lung disease. There is a paucity of information currently with respect to this appli-
cation of NT pro-BNP for animals compromised with lung disease.

SPECIFIC CLINICAL SCENARIOS

Heart Disease
In dogs and cats with suspected heart disease, fluid therapy may be challenging,
particularly if the extent of the potential heart disease is unknown. Heart disease is
a broad category with varying causes and degrees of decompensation. The presence
of a heart murmur, especially in cats, does not make fluid contraindicated or neces-
sarily limited when treating hypovolemia or dehydration. It is prudent to consider po-
tential heart disease patients in several categories; specifically, patients with active

Fig. 3. A point-of-care NT pro-BNP snap test confirming the presence (darker blue dot
[right]) of elevations in NT pro-BNP, consistent with heart failure in this cat.
6 Rozanski & Lynch

congestive heart failure (CHF), patients with recent CHF but are now out of heart fail-
ure; patients with no history of CHF but with known significant heart disease; and
those patients with either unknown or suspected heart disease. Classification systems
(eg, that of International Small Animal Cardiac Health Council) can be helpful to cate-
gorize individual patients and allow clinicians to make reasonable therapeutic recom-
mendations. In simple terms, increasing preload by providing fluids is less well
tolerated in patients with advanced heart disease by increasing the risk of EVLW
accumulation.
The speed with which fluids are administered also is an important factor to consider.
Rapid intravascular volume expansion leading to rapid alterations in preload are poorly
tolerated in patients with decompensated heart disease. In contrast, judicious rates of
fluid (eg, 1–2 mL/kg/h) may be tolerated in these patients without apparent ill effect if
close attention is paid to them. Subcutaneous fluids, although considered a fairly inef-
ficient method of administering fluids in general, can be poorly tolerated in animals
with advanced heart disease. This is especially relevant in cats with hypertrophic car-
diomyopathy that typically have a long asymptomatic preclinical phase. These cats
may be provided with subcutaneous fluids for other reasons (eg, azotemia, correct
fluid losses secondary to gastrointestinal losses) and subsequently develop cardio-
genic pulmonary edema. If possible, oral fluids are the safest choice for animals
with underlying cardiac disease but are not appropriate as a means of correcting fluid
deficits in already dehydrated patients or patients with impaired consciousness.

Pulmonary Contusion
Pulmonary contusions are common in traumatized dogs, and to a lesser extent in cats,
and reflect one of the biggest conflicts in fluid therapy.16 Resuscitation from hypovo-
lemia is often best accomplished with fluid therapy in the traumatized pet, whereas
contusions may be magnified by excessive fluid therapy. Pulmonary contusions
form in response to blunt or penetrating trauma and may be accompanied by the pres-
ence of current thoracic injuries, such as pneumothorax or rib fractures after damage
to capillaries in the pulmonary parenchyma. Capillary damage results in the extrava-
sation of blood into the interstitium and occasionally alveolar spaces. The hemorrhage
triggers an inflammatory response that further compromises gas exchange. Excessive
crystalloid therapy has been implicated in worsening lung injury by increasing capillary
pressure, potentially increasing the volume of fluid present in the tissues. Colloid ther-
apy has also been incriminated because leakage of larger colloidal molecules (eg,
hetastarch or pentastarch) could worsen lung injury by extravasating into the pulmo-
nary interstitium fostering subsequent water movement into the tissue.
No controlled studies in naturally occurring pulmonary contusions have been per-
formed in cats or dogs to determine the optimal fluid resuscitation technique. In exper-
imental animal models, the role of fluid therapy in pulmonary contusion with
concurrent hemorrhage has been extensively evaluated.17–19 Gryth and colleagues18
examined pigs with pulmonary contusions and noted pigs resuscitated with a lower-
volume strategy consisting of a hypertonic saline-dextran mixture had less EVLW and
a trend toward a higher PaO2 compared with those resuscitated with larger volumes of
lactated Ringer solution. In another study, traumatized pigs with induced contusions
were resuscitated to a mean arterial pressure of 70 mm Hg using 1 of 2 protocols:
normal saline, low-volume saline plus norepinephrine, or hypertonic saline-hetas-
tarch.19 When compared with a control group of uninjured pigs, all the study pigs
developed increased EVLW to varying extents.19 Pulmonary edema was apparent in
the saline and the hypertonic saline-hetastarch group.19 All treated groups had
decreased oxygenation ability, and compliance was lower in the saline and hypertonic
 Fluid Therapy in Lung Disease 7

saline-hetastarch group, whereas the low-dose saline-norepinephrine group had

raised lactate levels.19 In human clinical practice, Simon and colleagues17 recommen-
ded that patients with pulmonary contusions should not be excessively fluid restricted
but rather treated with fluids to maintain adequate perfusion. Similar guidelines are
likely warranted in animals with contusions, with a focus on maintaining a normal
lactate value and other markers of normal perfusion and avoiding excessive intrave-
nous fluid therapy. Steroids are contraindicated in pulmonary contusions. Diuretics
are not indicted for treatment of pulmonary contusions, unless inadvertent volume
overload has occurred.
Pneumonia
Pneumonia is a common acquired condition in dogs but seen less commonly in cats.
In patients with normal voluntary water intake from eating and drinking, additional fluid
therapy does not hasten resolution of their pneumonia. In anorexic patients or dogs
with excessive water loss via panting, replacement of fluid loss and provision for main-
tenance needs are warranted. In patients with sepsis or septic shock, more careful
goal-oriented fluid goals are advised, with the realization that the volume of fluid
required in individual patients is difficult to gauge. Recent data in people support
earlier use of vasopressors in combination with conservative fluid therapy, rather
than larger volumes of fluids in patients with pulmonary sepsis.20,21 In dogs, similar
guidelines have not been published, but careful monitoring to avoid an excessive pos-
itive fluid balance is warranted, whereas consideration for vasopressor use is reason-
able. Improvement in preload via venoconstriction is an underappreciated role of
vasopressor agents over and above augmentation of systemic vascular resistance
resulting in improvement in arterial blood pressure.22 Constriction of the veins in the
body, which serve a capacitance-type role, promotes venous return, thereby second-
arily improving cardiac output by improving preload.
Metastatic Lung Cancer
Fluid therapy in these cases of metastatic cancer is typically palliative. Excessive fluid
therapy is unlikely either harmful or particularly helpful. Dehydration is likely to
compromise quality of life, so crystalloid administration to ensure fluid balance helps
maintain a good quality of life. No specific guidelines exist for fluid therapy with met-
astatic disease but judicious monitoring of patients is sensible as for any other hospi-
talized patients.
Interstitial Lung Disease
Interstitial lung diseases (ILDs) are recognized with increasing frequency in both dogs
and cats.23 ILD patients rarely require intravenous fluids, and there are no studies on
their use in people. In decompensated dogs and cats with ILD, a conservative rate of
fluids may be provided to help prevent dehydration. As a caveat, pulmonary hyperten-
sion is a common complication of ILD, and fluid therapy may worsen pulmonary hyper-
tension, so if the presence or absence of pulmonary hypertension is unknown, fluid
therapy should be particularly cautious. Dogs and cats are often initially suspected
of having CHF and may be treated aggressively with diuretics before the actual diag-
nosis is reached. In these patients, fluids to rehydrate the patients are warranted if they
are not eating and drinking on their own.
Pleural Space Disease
Fluids in pleural space disease reflect the underlying disease. In animals with right-
sided CHF, fluids should be avoided. Although diuretics are the front line in treatment
8 Rozanski & Lynch

of heart failure, removing the pleural effusion is more effective that expecting diuretics
alone to be effective. In pleural effusions from other causes, fluids may be useful to
maintain hydration or to treat hypovolemia, such as with hemothorax from anticoagu-
lant rodenticide toxicity or in cases of pyothorax. For traumatic pneumothorax, pulmo-
nary contusions are almost invariably associated with thoracic trauma, and
conservative fluids should be considered. In spontaneous pneumothorax, concurrent
hypovolemia or dehydration is uncommon and it is rare that fluid therapy is clearly
beneficial.

Pulmonary Thromboembolism
IV fluids may be beneficial in patients with pulmonary thromboembolism, unless the
right heart is already volume overloaded, at which point fluids are harmful.14 Echocar-
diography is helpful in establishing right heart function and volume status.24 If echo-
cardiography is unavailable, a small bolus of fluids could be tried with close
monitoring to see if there is a clear benefit to fluid resuscitation.

SUMMARY

Fluid therapy is warranted in many patients with pulmonary disease but should be
carefully titrated in individual patients. Excessive fluid therapy, in particular colloids
and crystalloids, can magnify lung injury, particularly in the presence of disturbances
in the microvasculature, as well as result in generalized volume overload (Fig. 4). Fluid
rates to correct dehydration and to provide for maintenance needs are well tolerated in
all animals except those with CHF. High volumes of fluids are poorly tolerated in many

Fig. 4. A massive volume overloaded French bulldog.

 Fluid Therapy in Lung Disease 9

cases of pulmonary disease, and higher rates should be used only if clearly indicted.
Echocardiography and potentially biomarkers show great promise for more careful
titration of fluid therapy.

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