Prescribing IV fluids in the cat

The historical background

Although intravenous (IV) fluid administration was first popularized during the cholera pandemic of the 19^th century, fluid “therapy” is still one of the most controversial topics in both human and veterinary medicine 1. Cholera causes severe vomiting, diarrhea and profound dehydration, resulting in hypovolemia and hemoconcentration (hence the name “blue cholera”, as the elevated packed cell volume gave some individuals a bluish hue to the skin). Doctors started to treat affected patients with IV fluids and noted a good response, to the extent that the “new therapy” became widespread 2. The cholera pandemic also coincided with the medical profession starting to recognize the notion of “circulatory shock”, and so the use of IV fluids in treating patients with shock quickly gained popularity 3. The invention of the sphygmomanometer in the early 20^th century allowed shock to be associated with hypotension, and IV fluids were then recommended for hypotensive states, whether to counteract hypovolemia due to hemorrhage from trauma, “surgical shock” or anesthesia-induced hypotension. For the better part of the 20^th century administering IV fluids was considered “benign” with no major side effects, which contributed to its widespread administration and application beyond its original indications 3.

Fluids are drugs

The current definition for “drug” is a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body (Oxford online dictionary). Extensive research over the past four decades has led to the appraisal of fluid “therapy” administration and a better understanding of its potential harms. Indeed, many studies have demonstrated that when the wrong type of fluid is used (e.g., hydroxyethyl starches in patients with kidney injury), at the wrong dose (e.g., aggressive crystalloid administration in trauma patients) or for the wrong duration (e.g., continuation in patients that are eating and drinking), detrimental and potentially fatal side effects may occur 4,5. Hence the concept that fluids are drugs, with indications, contraindications and potential side effects, is becoming mainstream in both human and veterinary medicine 5. Therefore, it is only logical to take the same precautions when prescribing fluids as one would with any other drug, including analgesics, anesthetics, or antibiotics.

Although IV volume depletion can be fatal, mammalian species are well equipped to handle IV fluid losses, through complex neuro-hormonal reactions known as the “fight or flight response” – but they are much less equipped to deal with volume overload, as iatrogenic volume overload does not exist in nature 2. Therefore inducing volume overload, especially in the critically ill patient, will likely lead to interstitial edema, which in turn decreases tissue oxygenation (oxygen needs to travel further from the capillary to the cell), contributes to organ swelling and ischemia (especially in encapsulated organs such as the kidney) and eventually multi-organ dysfunction and death 6.

How does the cat handle IV fluids?

Recommendations for administration of IV fluids in small animal patients are largely extrapolated from human medicine 7. Furthermore, until the late 20^th century, fluid administration practices in cats were similar to dogs 7 – yet the adage “cats are not small dogs” is very true, particularly when it comes to IV fluid administration (Figure 1).

Given that the domestic cat originated in the desert, where fluid conservation capabilities are key (for example, the Dorcas gazelle can concentrate its urine to the point where it excretes solid uric acid pellets 8), and the feline kidney is known for its ability to concentrate urine 9. Therefore, the cat can cope relatively well with dehydration (as is sometimes seen with cats that display severe dehydration disproportionate to their general condition). On the other hand, the feline species does not seem to tolerate volume overload (as evidenced with the development of pleural effusion, pulmonary edema, and ascites following excess fluid administration). While the cause is not well understood, it is probably multifactorial, with potential contributing factors being that cats have a smaller blood volume (55-60 mL/kg) relative to dogs and people 10, are prone to occult (asymptomatic) cardiomyopathies 11 that can decompensate with fluid administration, and are relatively slow at eliminating IV fluids 12.

The “feline shock triad”

To complicate things even further, the clinical manifestation of circulatory shock in cats differs from that commonly seen in dogs and people. Cats do not display a “compensated” shock state; instead they often present as bradycardic, hypotensive, and hypothermic 13. It is believed that this “feline shock triad” is the result of complex reflexes that have an overall protective nature. Hypothermia seems to be centrally mediated through stimulation of α1- and α2-adrenergic receptors in the hypothalamus. Paradoxically, there is a decrease in peripheral sympathetic tone, resulting in vasodilation which contributes to hypothermia and hypotension. Reduced cardiac filling seems to trigger bradycardia through the Bezold-Jarisch reflex to optimize cardiac output (a slower heart rate allows greater cardiac filling in the presence of reduced IV volume); however, this can eventually exacerbate hypotension. Severe hypothermia ultimately inactivates adrenergic receptors, thus perpetuating the vicious cycle of hypotension and bradycardia. Furthermore, cats seem to have a relatively larger overall body surface area when compared to dogs 14, so ill or injured cats left untreated can quickly become hypothermic. The current pathophysiological explanation for the feline shock triad relies on historical experimental studies, and although this phenomenon is seen in practice, little is known about the intricacies of feline circulatory shock, and further research is needed.

Prescribing fluids in the cat

Before prescribing any medication, it is essential to establish if there is an indication; fluids are no different in this regard. There are three general indications for prescribing IV fluids (Table 1), and therefore a clinician should ask the following questions when faced with a cat that potentially needs IV fluids:

1. Is the cat in non-cardiogenic circulatory shock?
2. Is the cat clinically dehydrated or likely to become dehydrated within the next few hours?
3. Does the cat require assistance to maintain adequate nutritional and fluid intake?

If the answer is no to all these questions, then IV fluids are not indicated. If the answer to one or more of these questions is yes, then prescribing fluids is warranted. The clinician should then follow a standard process to choose the correct type of fluid (and avoid contra-indicated fluids), the dose (or rate) and the duration of administration, and must be aware of any anticipated side effects. A comprehensive flow chart to aid decision-making in IV fluid prescription is presented in Figure 2a and 2b.

What fluid should be chosen?

The three general indications for prescribing fluids in the cat (other than the peri-operative setting) are IV volume expansion (although other terms are also used, including fluid resuscitation, preload optimization, and bolus therapy), replacement of (bodily) fluid losses other than from the IV space (also known as rehydration, or replacement therapy) and maintenance (delivering daily water requirements). These indications dictate the choice of fluid, as detailed in Table 1.

Crystalloids

Crystalloids are a group of water-based solutions containing mostly sodium chloride and a few other electrolytes in various concentrations. Based on their osmolality (concentration of electrolytes) and tonicity (distribution once delivered into the IV space) they are divided into isotonic (and often iso-osmolar or slightly hypo-osmolar), hypertonic (and hyperosmolar), and hypotonic (again iso-osmolar or slightly hypo-osmolar). Based on their composition, isotonic crystalloids are further divided into 1. buffered (containing a buffer such as lactate, acetate, or carbonate which alkalizes plasma once administered), balanced (the electrolyte composition mimics that of plasma), and polyionic (containing ions other than sodium and chloride) crystalloids, and 2. isotonic saline (0.9% NaCl solution, which is neither buffered or balanced and is acidifying due to its relatively high chloride content).

Isotonic crystalloids are by far the most versatile fluids. Their indications include IV volume expansion for non-cardiogenic circulatory shock, replacement of acquired (dehydration) and ongoing losses, and maintenance fluid requirements. Buffered balanced isotonic crystalloids, such as Lactated Ringer’s Solution, should be the first line fluid choice for cats in circulatory shock, with the exception of conditions causing hypochloremia and metabolic alkalosis (such as upper gastrointestinal obstruction) where isotonic saline is the preferred solution. Isotonic crystalloids should also be used with caution in the hemorrhaging feline patient (see below).

Hypertonic saline (HTS) is a hyperosmolar agent which rapidly draws fluid from the interstitial space into the circulation. It therefore acts as a rapid, low-volume IV expander before it redistributes between the IV and interstitial space over 30-40 minutes. Hypertonic saline is also used to treat cerebral edema and increased intracranial pressure by drawing fluid out of the cerebral parenchyma. Therefore, it is particularly useful for the feline trauma patient, where head trauma is often present. Concentrations of commercially available HTS vary between 1-23% depending on the country, and hence the dose also varies significantly; the reader is advised to consult on the local availability of HTS and corresponding dose rates.

Hypotonic crystalloids have a relatively narrow spectrum of use, mainly as maintenance fluids, for treating pure water loss (e.g., diabetes insipidus), and dysnatremias. Products include, but are not limited to, 5% dextrose/glucose solution and half-strength saline (0.45% NaCl) with 2.5% dextrose/glucose solution. Patients that only require daily “maintenance” fluids may benefit from hypotonic crystalloids as they have a relatively lower sodium content. However, having one fluid for replacement and another for maintenance is often impractical and can lead to errors, so for patients not at risk of sodium overload, isotonic crystalloids are often used as maintenance fluids. Hypotonic crystalloids should never be used for IV volume expansion, as they rapidly leave the IV space (and are therefore ineffective at restoring tissue perfusion) and can lead to life-threatening volume overload, including cerebral edema.

Colloids

Colloids are a group of solutions containing compounds with relatively large molecular weights that generate colloid osmotic pressure and retain fluid within the IV space through the Gibbs-Donnan effect. They are therefore used mostly as IV volume expanders, although they do have other indications.

Synthetic colloids contain either a chemically modified starch (hydroxyethyl starch), gelatin (usually bovine gelatin), or fermented sugars (dextrans; only available in a very limited number of countries) suspended in isotonic saline or a buffered balanced crystalloid solution. The use of synthetic colloids (namely hydroxyethyl starches) has received a lot of negative attention recently, with substantial evidence of their harmful effect in people, leading to severe restrictions in their use 15. Veterinary evidence regarding the harmful properties of hydroxyethyl starches remains less convincing, with very little evidence of their effects in cats 15. This discrepancy is probably due to differences in cohorts and study design rather than species-specific differences. Gelatins are less studied in both human and veterinary medicine. However, evidence of their potential harmful effects is emerging 16. The author warrants very careful decision-making when prescribing synthetic colloids, as their “superior” IV volume expanding effects remain questionable and their side effects documented.

Natural colloids refer to whole blood and its derivatives, including fresh frozen plasma and packed red blood cells. Blood products are indicated for IV volume expansion in the hemorrhaging patient regardless of the presence or absence of a coagulopathy. Feline fresh frozen plasma, when available, can be used as an IV volume expander, especially in animals requiring colloid osmotic support (septic or otherwise hypoalbuminemic patients). Other uses of blood products include acute and chronic anemias, and coagulopathies. Blood typing and cross matching is mandatory when transfusing cats, and monitoring for transfusion reactions should be performed throughout the procedure. The use of human serum albumin as an IV volume expander or for colloid osmotic support has been reported in cats, but side effects include type I and type III hypersensitivities 15. The risk-benefit ratio should therefore be considered when prescribing this product to critically ill cats. The geographical availability of human serum albumin varies widely.

Administration rates 

Depending on the indication for IV fluid administration, the dose rates will differ. Like any drug, prescribing insufficient IV fluid will be ineffective, while overdosing is associated with side effects. Doses and rates for the three main prescription scenarios are detailed in Table 1.

Intravenous volume expansion

Intravenous volume expansion is meant to increase the stroke volume in cats with IV volume depletion (absolute or relative hypovolemia resulting in circulatory shock) and restore adequate tissue perfusion. Circulatory shock is clinically manifested as changes in the six perfusion parameters (mentation, heart rate, pulse quality, mucous membrane color, capillary refill time and temperature). Each perfusion parameter is not specific and can be altered for reasons other than circulatory shock. However, shock in the cat usually leads to changes in most perfusion parameters, especially mentation, pulse quality and temperature (hypothermia). Other clinical point-of-care tests that can assist with diagnosing circulatory shock include non-invasive blood pressure, lactate measurement, and cardiovascular and global point-of-care ultrasound (Figure 3).

To achieve IV volume expansion a relatively large amount of fluid needs to be administered in a relatively short period of time (known as a “fluid challenge”) to elicit a fluid response; this is defined as an improvement in perfusion parameters (alongside blood pressure, point-of-care ultrasound and laboratory abnormalities). Non-response to an adequate fluid challenge, particularly when repeated 2-3 times (as often happens in practice) does not mean that the patient requires more IV fluids, but rather, the cat can be classified as a non-fluid responder and further fluid challenges should be discontinued. A lack of response to fluid challenge is well-recognized in critically ill people; and although the incidence of non-fluid responders in cats is unknown, it is empirically reported as “common”, especially in hypothermic cats (and cats in shock are often hypothermic). Indeed, caution should be employed when administering fluids to a hypothermic cat in shock, with some authors advising fluid restriction until rewarming to a temperature of least 36-37°C (96.8-98.6°F) is achieved 13. As IV volume depletion can contribute to hypothermia (as mentioned above), the author recommends small fluid challenges be administered to the hypothermic cat while rewarming takes place. Maintaining permissive mild hypothermia is also advocated until the cause of circulatory shock is reversed.

Not all causes of circulatory shock are equal. Cats with non-hemorrhagic hypovolemic shock (from severe vomiting, diarrhea, polyuria/polydipsia (PU/PD), or third space losses) will respond well to IV volume expansion. Hemorrhaging cats will also initially respond to fluids, but dilutional coagulopathy and clot dislodgement may exacerbate the hemorrhage. In patients with active uncontrolled hemorrhage, low volume resuscitation or permissive hypotension can be applied until damage control surgery is performed. Distributive shock is accompanied by vasodilation, but also increased vascular permeability (due to endothelial glycocalyx damage) and loss of fluid into the interstitial space. Therefore, cats in distributive shock (usually from sepsis) will initially respond to IV fluids due to a concurrent degree of absolute hypovolemia; this is, however, at the expense of further vascular leakage and interstitial edema. Anecdotally, cats in distributive shock will stop responding to fluid challenges at a later stage of stabilization, and vasopressors should be considered in these patients to counteract the vasodilation. Cats in obstructive shock (severe pneumothorax, cardiac tamponade, intestinal volvulus) will partially respond to fluid challenges, however, the shock will not be completely reversed until the obstruction is corrected.

Replacement of losses 

For cats that are not (or no longer) in circulatory shock but have acquired and/or have ongoing fluid losses, a replacement fluid administration plan is needed. Acquired losses are calculated on the degree of dehydration, which is based on a percentage of total body weight lost (Table 1). Since cats are often not weighed prior to fluid loss, dehydration needs to be estimated on the clinical findings (skin tenting, mucosal tackiness, etc.). This is subjective and challenging. Therefore, the author offers a simplified approach to estimating dehydration, relying more on close monitoring during fluid replacement rather than initial subjective estimation. Cats with clinical dehydration with no signs of circulatory shock should be considered mildly (~ 5%) dehydrated, whilst cats with signs of circulatory shock due to dehydration should be considered severely (~ 10%) dehydrated. Severely dehydrated cats with circulatory shock should first receive IV volume expansion and replacement therapy should start once shock is reversed. Monitoring of clinical parameters, weight gain, spontaneous feeding, hydration, and overall re-assessment of the replacement plan should be performed 2-3 times daily, with adjustments made accordingly.

Ongoing losses can be estimated based on clinical findings, weight loss and quantifying fluid loss (e.g., by weighing incontinence sheets, collecting urine in litter, ultrasound-guided bladder volume estimations, using urinary and fecal catheters, etc.).

Maintenance

Maintenance fluid administration is based on providing cats with their daily water requirements as determined by their caloric needs. Given that every kilocalorie of energy requires one milliliter of water, maintenance fluids are calculated using the formula for resting energy requirements with milliliters as units (Table 1). Ensuring the cat receives its daily water requirement does not equate to feeding, and cats should not be left on maintenance fluids for extended periods of time without receiving appropriate nutrition.

Duration

Intravenous volume expansion is intensive, but the duration is usually short, rarely exceeding 1-2 hours. After this, the cat has either responded and the shock reversed, or the cat has not responded adequately, and other means of stabilization are sought depending on the underlying cause of the shock.

Fluids losses are usually replaced over 24-48 hours. The more chronic the fluid loss, the slower the replacement (e.g., cats with chronic kidney disease), with some exceptions (for example cats with diabetic ketoacidosis are often rehydrated more quickly, e.g., 50% of estimated volume required given over ~6h, to allow initiation of insulin therapy). Longer replacement prescriptions are required for patients with severe ongoing losses which cannot be covered by oral hydration or IV maintenance fluids. These are usually cats with abdominal and/or thoracic drains, or less commonly cats with ongoing diarrhea, vomiting and PU/PD.

Maintenance fluid therapy should not exceed 24-48h. In general, cats hospitalized with anorexia have either a benign condition that resolves within this period with a spontaneous return of appetite, or a more severe disease that requires assisted feeding. Cats expected to remain anorexic for longer than 24-48h should receive nutrition, either spontaneously, with the help of appetite stimulants, or an appropriate feeding tube (Figure 4). This is particularly true in patients that are known to have been anorexic for a period of time prior to admission. Cats that are eating do not require maintenance fluids.

Contraindications and side effects

The side effects of various fluids are listed in Table 2. The main side effects of isotonic crystalloids include hemodilution (especially in the hemorrhaging patient) and volume overload, which leads to interstitial edema (and potentially pulmonary edema) 4. Hypertonic saline can additionally lead to hypernatremia, transient hypertension, and bradycardia. Hypotonic fluids will lead to edema if administered as a bolus. Synthetic colloids are additionally associated with acute kidney injury, non-dilutional coagulopathy, tissue accumulation, and increased mortality in people, with evidence suggesting this may also occur in small animals 15. Noteworthily, any fluid can be contraindicated (especially in patients with pre-existing volume overload, such as cardiac patients and oliguric or anuric patients) or can lead to side effects, if given at an incorrect dose rate or for the wrong indication.

Monitoring

It is important to note that every successful fluid prescription must be accompanied by adequate monitoring for efficacy and side effects (Table 1). The classical tools comprise physical exam findings (to assess IV volume and hydration status), non-invasive blood pressure measurements, and minimum laboratory database (packed cell volume, total proteins, venous blood gas with (or at least) lactate, urea/creatinine). Over the past two decades, point-of-care ultrasound has been added to daily practice as a tool for monitoring IV fluid administration 17. While this modality remains crucial for determining the indication for prescribing IV fluids, it is now also indispensable for preventing and diagnosing volume overload, which has traditionally been challenging to estimate using clinical parameters. Furthermore, it may be possible for an experienced clinician to screen patients for asymptomatic cardiomyopathies using ultrasound, which will help prevent additional volume overload in these cats 11.

Conclusion

Fluids are drugs and should be prescribed for every veterinary patient that needs them, but with very careful consideration in sick cats due to the “quirks” seen in this species. A prescription should include consideration of indication, fluid type, dose/rate, duration, side effects, and monitoring. Insufficient fluid administration can be fatal, and identifying fluid loss and the means of replenishing that loss is easy and readily available. On the other hand, volume overload can also be fatal, and recognition is often late and partial, with limited therapeutic options available. Overall, the clinician is urged to be rational when prescribing IV fluids to cats, and to focus on effective monitoring and timely discontinuation when fluids are no longer indicated.