APPROACH TO EQUINE CRITICAL CARE^∗

Peggy S. Marsh

Critical care is provided in disease states of crisis or extreme complexity and involves thoughtful judgment and timely intervention. Typically, acute life-threatening conditions require this type of care. Because of the intricate, time-consuming, and often urgent nature of such situations, specially trained personnel are often best suited to deliver optimal care. This type of care is generally needed for days, rather than just a few minutes or hours, and therefore a team of health care providers is required. The provision of optimal diagnostic and monitoring alternatives is facilitated by access to a wide range of equipment. Segregating patients that need immediate as well as continuous attention in a particular area of a hospital or clinic, such as an intensive care unit (ICU), allows better use of resources. However, these are not absolute requirements for providing critical care. Adherence to a foundation principle that calls for serial evaluations of the entire patient, with particular attention to maintaining or restoring homeostasis for that individual, is at the heart of critical care medicine.

In equine practice there are no definitive universal guidelines to identify patients that would benefit from being treated in a centralized ICU by a team of specialized health care providers. In human medicine various studies have evaluated the potential benefits of such care. Most have shown increased efficiency, shorter duration of stay, and sometimes decreased cost when critical care patients are treated in a central hospital unit and managed by a specialized team of health care providers. The decision as to which equine patients would benefit from such care is based on a wide variety of criteria, including type of illness or trauma, degree of illness, availability of personnel and facilities, biosecurity measures, cost, and client preference. In veterinary medicine there is no clear evidence demonstrating when such care might improve outcome and efficiency or reduce cost.

Even with a wide range of inciting problems, there are some aspects of critical care medicine that are common in all critically ill individuals. Therapeutic goals for all patients include providing appropriate care for the primary problems, anticipating complications and initiating appropriate preventive therapy, and providing appropriate supportive care for all vital body systems.

The purpose of this chapter is to provide an outline of therapeutic guidelines for use in equine patients with life-threatening medical problems or patients with complex disease processes that simultaneously involve multiple body systems. Diagnosis and therapy of many specific critical care topics are covered in more detail in other chapters of this book, and the reader will be referred to the relevant chapters as appropriate. The goal for this chapter is to outline an approach to the entire patient and all body systems that will facilitate creation of an action plan to help restore systemic function in the critically ill equine patient.

EQUINE INTENSIVE CARE UNIT

Comprehensive care for critically ill horses can be provided anywhere, with some creativity and a large commitment of time; however, it can be argued that moving such patients to a hospital setting with experienced clinicians and a variety of diagnostic and therapeutic equipment allows for better use of resources and improved care. Equine ICUs are becoming increasingly prevalent in clinical practice. Common features include housing of patients according to type or severity of illness with appropriate biosecurity precautions; readily available equipment for diagnosing, monitoring, and treating the seriously compromised horse; and 24-hour staffing with professionals who have the knowledge and experience to treat these patients. The goals of these units are to pool resources, thereby increasing efficiency and reducing cost, and to improve patient outcomes.

The decision to offer ICU services should be based on the population needs and the economic environment of the hospital and community. Several recent studies describe the general case population and commonly performed procedures and treatments of patients admitted on an emergency basis to large university referral centers.^1,2 Because equine emergencies are relatively common among patients requiring critical care, such information provides an initial database for understanding population dynamics. In general, these studies revealed that although acute abdominal crisis is the most common type of case encountered, many cases will not require surgical intervention. Also, a variety of other problems presented as emergencies, and the required skills to deal with these included experience with dysfunction of most all body systems. Reviewing the anticipated distribution of cases within a given area, as well as the monthly distribution of cases, is important. Such reviews ensure an appropriate allocation of staff and equipment tailored to the needs of the population.

Human ICU treatment requires a multidisciplinary team that includes intensivists (i.e., physicians who specialize in critical illness care), nurses, respiratory care therapists, dieticians, pharmacists, and other consultants from a broad range of specialties, such as surgery, internal medicine, and anesthesiology. Compared with human medicine, the number of equine cases is limited and is handled without the same degree of clinician specialization. The most common advanced training programs in equine practice are anesthesia, internal medicine, and surgery. Individuals trained in these areas typically have experience with critically ill equine patients. More recently, specialty training in the area of equine emergency and critical care has been developed. Although the care of many extremely sick horses is performed in the general practice setting, it is useful to know that the number of veterinarians with extensive experience and specialty training in the area of critical care is growing.

Besides clinicians, intensive and continuous care usually is provided by licensed veterinary technicians. In general, good nursing care is pivotal to successful outcomes. The technical staff should be trained to identify subtle changes in patient status and feel comfortable using a range of equipment. The ability to perform common techniques and to recognize changes in condition early is essential.

The equipment used for the care of critically ill equine patients should be based on the anticipated case population and the maximal level of care required for that population. Purchasing a ventilator would be a poor economic decision if mechanical ventilation is performed rarely. Renting medical equipment that might be needed only occasionally or seasonally may be a more practical choice. Box 7-1 lists some equipment to consider when equipping an equine ICU. Regular review of equipment and training for all personnel on new equipment are essential.

Commonly performed procedures in equine critical care include monitoring, fluid administration, and pain control. Monitoring includes not only close, astute observation and serial physical examinations but also the use of appropriate equipment and laboratory support to monitor systemic health as appropriate for that patient. Fluid administration encompasses routine administration of a wide range of products, including crystalloids, synthetic colloids, blood, and blood substitutes. The selection of appropriate analgesia may vary widely depending on the origin of pain (e.g., musculoskeletal versus abdominal) and the possible adverse effects of different medications. All of these considerations should be based on the specific needs of the equine patient.

Emergency drugs should be readily available and mobile, possibly in a crash cart or box in the ICU. Table 7-1 lists several emergency drugs and dosages used in adult horses. Keeping a specific list such as this one readily available in the crash cart for easy reference is advisable. In addition, assembling packs for specific anticipated emergency situations, such as all the necessary items for delivering supplemental oxygen or supplies to perform an urgent tracheotomy, and placing these packs in key areas are recommended.

TABLE 7-1 Emergency Drug Chart for Adult Horses

Monitoring equipment commonly used in an ICU includes an electrocardiogram, a blood pressure monitor, a stallside glucometer and a lactate analyzer, a stallside electrolyte and chemistry analyzer, an ultrasound unit, a centrifuge for hematocrit determination, a refractometer for determining total protein and urine specific gravity, and urine test strips for urinalysis. Other monitoring tools to consider are a microscope with 100× magnification, equipment for cytological examination (including Gram stains), and a blood gas and electrolyte monitoring unit. A colloid osmometer is useful for determining colloid oncotic pressure in sick horses. If mechanical ventilation is routine, further monitoring units, including capnographs and pulse oximeters, are useful. Standard operating protocol should be established for each piece of equipment, and regular maintenance should be performed.

Advanced imaging is becoming more common, and the use of ultrasound has become an essential component of diagnosing and monitoring critically ill patients. Ultrasound can be used for identifying and monitoring effusions, intestinal distention, and motility; identifying umbilical structures; monitoring pregnancy; and visualizing ocular structures, among other anatomic areas. To enable imaging of a wide variety of structures, access to a variety of transducers ranging from 2.5 to 10 MHz, as well as a rectal probe, is recommended.

Oxygen ports for supplementation through nasal insufflation or for mechanical ventilation should be available. When installing a new ICU, the practitioner should consider placements of ports for oxygen, vacuum, and air, as well as a remote gas source and a pipeline system to allow delivery of oxygen. Compressed gas cylinders can be used, but these must be stored and handled appropriately to prevent injury. For each cylinder type, knowledge of the capacity of the cylinder and the flow rate enables calculation of the amount of time provided. The small portable E cylinders contain 655 L of oxygen when full and can provide oxygen for 260 minutes when set at a flow rate of 5 L/min. Adult horses may require flow rates of 10 to 15 L/min to have any significant effect on the fraction of oxygen inspired (FIO₂). Larger G or H cylinders containing 5290 or 6910 L, respectively, allow oxygen supplementation for longer periods.

The design of the ICU should accommodate the care of horses with a wide variety of problems. All stalls should have the equipment necessary for hanging large volume (e.g., 5 L) fluid bags. In addition, the design should include one or two stalls for easy unloading of down horses, and the structure must be able to withstand hoisting. If care of neonatal patients is expected to be routine, large foaling stalls should be available. These stalls may feature mobile separators to facilitate treatment of foals while allowing them access to their dams.

A central office facilitates oversight of the entire unit. For larger ICU facilities video monitoring of stalls from the central office is optimal. Sufficient storage space should be available to protect equipment that is not in use. A separate food preparation area should be available for preparation of enteral feeding. Staff members should pay attention to cleanliness in this area and particularly should refrain from washing their hands or contaminated material in the sink used for food preparation.

Although grouping critically ill patients in a single location allows for the greatest efficiency of personnel and equipment, maintaining biosecurity is essential. Grouping patients with similar disorders is therefore recommended. Strict disinfection and isolation protocols should be in place to prevent nosocomial infections and the spread of infectious disease. Thorough hand washing is an important component of most biosecurity protocols. Hand rubbing with an alcohol-based solution is more effective than hand washing with an antiseptic, probably because it does not require rinsing and drying of hands.³ Adoption of this practice significantly reduces cross-contamination among patients.

Guidelines for the judicious use of antibiotic regimens are available for human ICUs, and some of these guidelines apply to equine ICUs. These guidelines usually include recommendations for initial empirical selection of effective antibiotic regimens based on history, disease process, possibility of nosocomial infection, and knowledge of specific isolates for the hospital. Once culture results are available, therapy can be modified. Other methods that have been proposed to minimize antibiotic resistance and superinfections include cycling of antibiotics and restricted use of potent, broad spectrum therapies.

Salmonella organisms also can be a cause of nosocomial infection in the equine hospital. Salmonella shedding is greater in horses with colic, and the use of common equipment such as stomach tubes and pumps may promote transmission. Careful attention to hospital design and disinfection practices can help minimize the risk of hospital outbreaks.

COMMON PHYSIOLOGIC FEATURES OF CRITICAL ILLNESS

Despite differing problems, the common denominator in the treatment of many critically ill patients is the need to maintain adequate delivery of oxygen to meet metabolic demand. Methods to return to a fully functional state include serial systemic evaluations, even when the problem appears focal; attention to minimize adverse affects of treatments; and restoration of homeostasis, in particular working toward adequate delivery of oxygen and nutrients to cells.

Often a disease affects a single organ, and therapy can be focused on a specific process in that organ. A simple bacterial bronchopneumonia is often resolved with a course of appropriate antimicrobial medication and possibly the use of a nonsteroidal agent to help control inflammation. However, it is not unusual for the infection to induce fevers. Fevers may cause generalized malaise as well as inappetence. In horses fevers may be associated with signs of colic and altered gastrointestinal function. Although this is an obvious and relatively simple example of how a focal lesion creates systemic effects, it elucidates the need for evaluation of the entire body, even in patients with an obvious primary problem. Severely ill patients require sequential, thorough, and systemic evaluations. These evaluations are fundamental in critical care medicine.

A more severe consequence of focal problems causing systemic effects can occur when the initial insult is recognized as foreign by the body, and the various components of the immune system become activated to eliminate the threat. Most of the time this process is appropriate, and the various inflammatory mediator or coagulation cascades are activated in an orderly fashion. However, sometimes the progression is not balanced, and activation of certain systems, such as those governing inflammation and coagulation, can lead to unchecked release of mediators and a generalized reaction. In sick horses the most commonly cited example of this is systemic inflammatory response syndrome (SIRS), which can occur as a consequence of endotoxemia. These aspects of equine medicine are discussed in detail in Chapter 15.

Therapeutic misadventures can occur. The adverse affects of some therapeutic modalities can inadvertently cause significant systemic issues. A common example of this problem may be seen with the use of antibiotics in sick horses. It is not unusual for critically ill patients that are being treated with appropriate antimicrobial agents to develop significant, potentially life-threatening colitis. Understanding the potential effects of prescribed medication, carefully monitoring the patient’s clinical progression, and making adjustments to the treatment plan and management strategies may ameliorate some of these problems.

Many severe problems cause alteration of normal body function and lead to misdistribution of supplies needed to maintain cellular metabolism. When the delivery or utilization of oxygen is inadequate to the metabolic needs of tissue beds, the term dysoxia is used. Clinically, this syndrome is recognized as shock. If left untreated, such states may lead to metabolic acidosis, organ dysfunction, and death.

Shock usually results from oxygen delivery that is insufficient to meet tissue oxygen consumption. Oxygen delivery can be defined as cardiac output multiplied by arterial oxygen content (DO₂ = CO × CaO₂). Cardiac output is measured as heart rate times stroke volume. Oxygen content is determined by both the amount of oxygen carried by hemoglobin in the red blood cells as well as the amount of oxygen dissolved within plasma. The formula for calculating arterial oxygen content is as follows:

It is important to note that the majority of oxygen that is delivered to tissues is carried in the red blood cells bound to hemoglobin and the commonly monitored partial pressure of oxygen (PaO₂; dissolved oxygen) represents only a small portion of total oxygen. This highlights the need to monitor anemia during critical illness.

The clinical condition of shock may be described or classified in several different ways, such as by stage of shock or by underlying etiology. The stages of shock include compensated, uncompensated, and irreversible. During the initial phase of compensated shock, vital organ function is maintained and blood pressure remains normal to increased. This is also called warm shock. During this time various compensatory mechanisms are activated, including baroreceptors and chemoreceptors, the renin-angiotensin system, humoral responses, and internal fluid shifts. When activation of these mechanisms fails to restore normal tissue oxygenation, microvascular perfusion becomes marginal and cellular function deteriorates. All of this leads to hypotension, the hallmark of shock. During this phase vasoconstriction predominates, and the term cold shock is used. When lack of perfusion becomes severe and is refractory to all attempts to correct it, organ dysfunction and failure occur. At this point the process is often irreversible despite all therapeutic attempts.

The categories of etiologies of shock include hypovolemia, cardiogenic, distributive, obstructive, and dissociative. It is important to consider these differential diagnoses of shock to help determine management strategies, but the goal for treatment of shock resulting from any cause is to improve perfusion. Attempting to restore normal physiology may be misguided in critically ill patients because such efforts can result in substantial iatrogenic risks; however, early goal-directed therapies have been shown to improve outcome.

BASIC STEPS

An understanding of the physiologic and pathologic processes that may be occurring in critically ill patients is key to a successful outcome. The goal is to evaluate the patient, recognize current problems, anticipate impending issues, and then create an action plan. Because critical illness is generally dynamic, the plan also must also be dynamic. In the often highly emotionally charged period of initial patient evaluation, a systematic, thorough approach to each patient is beneficial. A basic 12-step plan for assessing and treating a critically ill patient is outlined in Box 7-2.

BASIC PROCEDURES IN ADULT EQUINE CRITICAL CARE

Joanne Hardy

Critical care for adult horses varies depending on the underlying problem being addressed. Expertise in a variety of technical procedures is advisable to facilitate diagnostic and therapeutic efforts.

VASCULAR ACCESS AND ADMINISTRATION OF FLUIDS

Intravenous catheters are available in varying materials, constructions, lengths, and diameters (Table 7-2). In choosing a catheter, the practitioner should consider the desired fluid rate, fluid viscosity, the length of time the catheter will remain in the vein, the severity of the systemic illness, and the size of the animal. The rate of fluid flow is proportional to the diameter of the catheter and inversely proportional to the length of the catheter and the viscosity of the fluid. Standard adult horse catheter sizes are usually 14 gauge in diameter and 5.25 inches in length. For more rapid administration rates, larger-bore catheters, such as 12- or 10-gauge, could be used, with the caveat that these larger sizes may be more traumatic to the vascular endothelium, which increases the risk of thomobosis, Plasma, blood products, and synthetic colloids, because of their increased viscosity, flow more slowly; if the horse requires volume replacement, the practitioner can combine administration of these fluids with a balanced electrolyte solution.

TABLE 7-2 List of Available Catheter Materials

Teflon catheters should be changed every 3 days, whereas polyurethane catheters may remain in the vein for up to 2 weeks. Regardless of the type of catheter, the site of vascular access should be closely monitored several times daily (discussed in more detail later in this chapter). Horses that are very ill (e.g., bacteremic, septicemic, endotoxic) are more likely to experience catheter problems and benefit from polyurethane or silicone catheters.

One also must consider the catheter construction (Table 7-3). Through-the-needle catheters are most common for standard-size adult horses. An over-the-wire catheter is best used in foals and miniature horses or when catheterizing the lateral thoracic vein. Short and long extension sets are available, as well as small- and large-bore diameters. Using an extension set that screws into the hub of the catheter is best, to prevent dislodgment. In horses with low central venous pressures (CVPs), disconnection of the line can result in significant aspiration of air and cardiovascular collapse. Double extensions are available for horses that require administration of other medication with the fluids.

TABLE 7-3 List of Commercially Available Catheter Constructions

Common sites for insertion of intravenous catheters in horses include the jugular, lateral thoracic, cephalic, and saphenous veins. The lateral thoracic vein makes an acute angle as it enters the chest at the fifth intercostal space; therefore an over-the-wire catheter is best to use when catheterizing this vein. Catheters placed in any location other than the jugular vein require more frequent flushings (every 4 hours) because they tend to clot more easily. Leg catheters usually are bandaged because they are more prone to dislodgment than jugular catheters.

In adult horses a catheter is usually not covered with a bandage so that potential problems can be quickly identified. The practitioner may need to apply bandages to foals if they are tampering with the catheter. A triple-antibiotic ointment may be applied at the insertion site to decrease infection. Catheters should be flushed with heparinized saline (10 IU/ml) four times per day if they are not used for fluid administration. When administering a medication, the clinician should wipe the injection cap with alcohol before inserting the needle and change the injection cap daily. The clinician should culture catheters if catheter site infection is suspected for identification of the causative organism and to facilitate early recognition of possible nosocomial infection.

Coil sets are used for stallside fluid administration for most adult horses. These are advantageous because they allow the horse to move around, lie down, and eat without restraint. An overhead pulley system with a rotating hook prevents fluid lines from becoming tangled.

Administration sets are used for short-term fluid or drug administration and are available at 10 drops/ml and 60 drops/ml. When using a calibrated fluid pump, one should take care to use the appropriate set calibrated for the brand of pump. Long coiled extension sets can then be used to connect fluids to the horse. Foal coil sets that deliver 15 drops/ml are also available.

Special foal fluid administration sets are available as pressurized bags that allow delivery of fluids at 250 ml/hr. These bags can be placed in a special harness on the foal’s back, thereby preventing entanglement with the mare.

Calibrated pumps allow delivery at various rates. These pumps have alarms that signal air in the line, an empty fluid bag, or catheter problems. The maximal fluid rate that these pumps can deliver is 999 ml/hr, which is insufficient for most adult horses. The pumps are useful for recumbent foals or for combined drug infusions. For large volume fluid delivery, peristaltic pumps are available that can deliver up to 40 L/hr. One must supervise these pumps constantly when in use because they continue to run even if fluids run out. Large-bore catheters should be used to prevent trauma resulting from the jet effect on the endothelium of the vein.

BASIC FLUID THERAPY

Fluid administration for maintenance or replacement is one of the mainstays of equine critical care and should be readily available in any equine hospital. The availability of commercial materials and fluids for use in large animals makes fluid administration easy and cost-effective in most situations. This section provides a review of available materials and principles that should be followed when planning fluid administration.

Designing a Fluid Therapy Regimen

Fluids can be administered for maintenance or replacement purposes. Horses usually receive maintenance regimens orally, and electrolyte formulations are available for this purpose. Intravenous maintenance fluids are lower in sodium and higher in calcium, potassium, and magnesium than replacement fluids. Replacement regimens replace fluids lost through dehydration and ongoing losses. When designing a fluid therapy regimen, the clinician must consider the following questions:

• What volume of fluid must be given?

• What type of fluid will be given?

• What will be the rate of administration?

The volume of fluids to give equals the maintenance requirements plus the correction for dehydration and ongoing losses.

MAINTENANCE

In the adult horse maintenance fluid requirements have been estimated at 60 ml/kg/day. This figure probably overestimates the actual needs of a resting, fasted animal but appears to be safe in most situations. In horses with renal failure, in which elimination of excess fluids is problematic, monitoring of body weight and CVP is indicated. If weight gain, edema, or increased CVP is evident, the fluid administration rate should be decreased.

DEHYDRATION

Evaluation of dehydration is at best a subjective estimate, and the clinician must understand that this estimate must be adjusted on the basis of monitoring parameters. Table 7-4 lists useful parameters for evaluating acute, extracellular dehydration.

TABLE 7-4 Parameters Used for Estimation of Dehydration in the Horse

After obtaining an estimate of dehydration, the clinician can calculate the amount of fluids to be given as follows:

ONGOING LOSSES

Sometimes the clinician can measure and record ongoing losses (e.g., for nasogastric reflux), but ongoing losses usually must be estimated. The clinician monitors the patient to determine whether the calculated fluid volume is meeting the ongoing losses. Patients receiving fluids intravenously should be monitored at least twice a day, including assessment of heart rate and measurement of packed cell volume and total protein; the clinician should monitor patients more frequently (every 2, 4, or 6 hours) depending on the severity of cardiovascular compromise. The clinician should also monitor creatinine concentration once daily when initially elevated to ensure adequate return to normal. Additional means of monitoring adequate fluid delivery may include measurement of CVP, arterial blood pressure, and urine output.

TYPE OF FLUID

The type of fluid to administer depends on evaluation of the chemistry profile and disease state. The first step is to decide on the baseline fluid (saline or balanced electrolyte solution), and the second step is to decide on the types of additives to add to the baseline fluid, which depends on specific deficits or excesses, such as hyponatremia or hypernatremia, hypokalemia or hyperkalemia, hypocalcemia or hypercalcemia, hypoglycemia, and acid-base disorders.

Two categories of fluids commonly are used for fluid replacement: 0.09% saline and balanced electrolyte solutions (BESs). Table 7-5 lists the composition of various commercially available fluids. In general, BESs are chosen when serum electrolytes are close to normal. All BESs contain some potassium. Saline is higher in sodium and much higher in chloride than serum concentrations and is used when sodium is lower than 125 mEq/L. Saline also is used in disease processes associated with high potassium levels, such as hyperkalemic periodic paralysis or renal failure, in which a potassium-free solution is preferable. In cases of long-term fluid maintenance therapy (greater than 4 to 5 days), if the oral route is not available, the practitioner should consider half-strength basic fluids to which potassium and calcium are added. Long-term fluid therapy with routine BESs results in hypernatremia, hypokalemia, hypomagnesemia, and hypocalcemia.

TABLE 7-5 Crystalloid Solutions Available for Fluid Therapy

In horses routine fluid replacement includes calcium and potassium supplementation, in particular when the horse receives no oral intake because of gastrointestinal disease. Both electrolytes are important for smooth muscle function and vascular tone. Recently, magnesium supplementation also has received interest, particularly with fasting and ileus.^1,2

Horses with metabolic acidosis also may require bicarbonate supplementation. Because the most common cause of nonrespiratory acidosis is lactic acidemia resulting from poor perfusion, providing fluid replacement should be the first and principal means of correcting this problem. Rules of thumb for bicarbonate supplementation in acute metabolic acidosis are as follows:

• Normal respiratory function: If the horse is unable to exhale the generated carbon dioxide (CO₂) because of a respiratory problem, the acidosis will worsen.

• pH lower than 7.2: In acute acidosis associated with dehydration, fluid replacement results in restoration of urine output, and renal compensation follows and usually is complete if the pH is greater than 7.2.

• Half of the calculated amount is rapidly administered, followed by the remainder over 12 to 24 hours.

• Intravenously administered bicarbonate and calcium-containing solutions are incompatible.

In chronic metabolic acidosis, particularly with ongoing losses of bicarbonate (e.g., diarrhea), the horse usually requires the full calculated amount, partly because the bicarbonate loss is distributed over all fluid compartments, not just the extracellular fluid. Orally administered bicarbonate is a good means of dealing with ongoing losses in horses with diarrhea.

Bicarbonate can be given orally as a powder, where

RATE OF ADMINISTRATION

For patients in severe shock, the clinician should give a shock dose of fluids in the first hour (60 to 80 ml/kg), which can be done only with pressurized bags or a pump.

In other situations the rate of administration is based on 24-hour requirements and estimates as a volume per hour. Keeping tally of the fluids given is important to ensure that the correct amount is administered.

ORALLY ADMINISTERED FLUIDS

Oral fluid therapy should be administered using the fluid composition shown in Table 7-6. One should administer calcium separately because it causes precipitation of the solution. This electrolyte solution meets daily needs for an adult horse and can be given through a small, preplaced nasogastric feeding tube or by intermittent intubation.

TABLE 7-6 Fluid Composition for Orally Administered Fluid Therapy

For Every L of Water, add:
FOR EVERY 21 L OF WATER
Electrolyte	Amount
NaCl	10 g
NaHCO3	15 g
KCl	75 g
K2HPO4	60 g

Fluids Used to Expand Circulating Blood Volume

ISOTONIC CRYSTALLOIDS

Intravenous administration of isotonic crystalloids immediately reconstitutes circulating volume. However, because the fluids are crystalloids, they distribute to the entire extracellular compartment within a matter of minutes. Because the extracellular fluid compartment is three times the volume of blood, one must administer three times as much isotonic crystalloid to gain the desired amount of volume expansions. The dose is 60 to 90 ml/kg/hr, and the fluid types usually are BESs such as lactated Ringer’s solution.

HYPERTONIC CRYSTALLOIDS (7.2% NaCl)

Hypertonic crystalloids are approximately eight times the tonicity of plasma and extracellular fluid; their immediate effect is to expand the vascular volume by redistribution of fluid from the interstitial and intracellular spaces. However, this effect is short lived. As the electrolytes redistribute across the extracellular fluid, fluids shift again and the patient becomes hypovolemic again. Because the principal effect is fluid redistribution, a total body deficit still exists that must be replaced. The duration of effect of hypertonic solutions is directly proportional to the distribution constant, which is the indexed cardiac output. The dose is 4 ml/kg, administered as rapidly as possible, and the fluid is 5% or 7% saline. Because of its short duration of effect, one must follow hypertonic saline administration with isotonic volume replacement.

COLLOIDS

Colloids are fluids that contain a molecule that can exert oncotic pressure. These molecules do redistribute to the extracellular fluid but at a much slower rate than crystalloids, so that the duration of effect is prolonged compared with that of crystalloids. Table 7-7 describes the different colloids available.

TABLE 7-7 Characteristics of Colloid Solutions Available for Fluid Therapy

A disadvantage of natural colloids (plasma or albumin) is that they are more antigenic and can cause allergic reactions. Synthetic colloids have a much lower antigenicity, but they can cause bleeding disorders because of their tendency to coat platelets or by causing a decrease in coagulation factor. In the horse Dextran 40 can cause anaphylactoid reactions. Hetastarch administration can cause a decrease in coagulation factors and prolong clotting times, particularly at high doses (20 ml/kg).³ The dose is 10 ml/kg of 6% solutions.

Synthetic colloids do not register on a refractometer. Accurate evaluation of oncotic pressure requires use of a colloid osmometer. If one is not available, the clinician must use clinical evaluation (e.g., observing presence of edema and poor circulatory volume and pressure).

BLOOD SUBSTITUTES

Blood substitutes are hemoglobin solutions. Currently, only one commercial hemoglobin solution (oxyglobin, which is made from bovine hemoglobin) is available. The major advantage of oxyglobin is that it does not depend on 2,3-diphosphoglycerate for oxygen-carrying capacity, such that it can be stored and is immediately able to transport oxygen. The duration of effect is approximately 18 hours in horses, after which point another dose or a blood transfusion must be considered.^4,5 Unfortunately, cost limits the usefulness of oxyglobin in horses.

WHOLE BLOOD

Whole blood is the ideal fluid for blood loss or platelet loss, provided that it is fresh blood and has been crossmatched. It is important to remember that stored blood loses its oxygen-carrying capacity and that it can take several hours to restore it after administration.

Ideally, the ICU should maintain blood donors that are free of antigenic determinants, particularly Aa and Qa, and of isoantibodies. The practitioner can perform a major and minor crossmatch to select an appropriate donor, provided that complement is added to the test for hemolysin detection. Interpretation of the minor crossmatch may be difficult if autoagglutination is present. If crossmatch is unavailable, one can use a non-Thoroughbred gelding. A volume of 20 ml/kg can be safely collected every 3 weeks in adult horses,³ and whole blood can be collected in sodium citrate using sterile technique. Commercial blood collection kits are also available. Complications of blood transfusion include acute anaphylactic reactions, allergic reactions, hemolysis, fever, tachypnea, and hypocalcemia caused by citrate chelation.

MONITORING ARTERIAL BLOOD PRESSURE

The practitioner can measure arterial blood pressure by direct catheterization of a peripheral artery or by indirect measurements that depend on a cuff placed over an artery and cuff inflation until blood flow is occluded. Measurement of arterial blood pressure is one of the indirect estimates of tissue perfusion, using the mean pressure as the driving pressure. Horses may have low mean arterial pressure (MAP) as a result of hypovolemia, SIRS, heart failure, or any of a wide variety of disorders.

Most monitoring equipment provides an estimation of systolic arterial pressure, diastolic pressure, and MAP. MAP is a calculated value determined by integrating the area under the pressure waveform and dividing this by the duration of the cardiac cycle.

Pulse pressure is the difference between systolic and diastolic pressure and is responsible for the palpable pulse. A bounding pulse pressure results from an increased systolic pressure, a decreased diastolic pressure, or both.

Ultimately, the clinician is interested in oxygen delivery to tissues, which depends on adequate perfusion of tissues, which in turn depends on functional capillary density and blood flow in capillaries. In the clinical arena measurement of tissue perfusion or of tissue blood flow is impractical. Therefore clinicians use blood pressure as an estimate of adequate blood flow and tissue perfusion. The problems with this assumption are as follows:

Direct or Invasive Blood Pressure Measurement

An over-the-needle catheter configuration is preferable for direct or invasive blood pressure measurement to prevent bleeding at the site of puncture. A small (20- or 22-gauge) catheter is preferable to minimize hematoma formation on catheter removal. The radial artery over-the-needle catheter (Arrow International, Reading, Pa.) with a wire guide is suitable for arterial catheterization of peripheral vessels in the horse. As an alternative, an over-the-wire catheter sheath that calls for a Seldinger technique for insertion (Seldinger technique transradial artery catheter, Arrow International) may be used. The catheter is connected to noncompliant tubing filled with heparinized saline, which is linked to a pressure transducer.

Suitable arteries for arterial catheterization in the horse include the transverse facial, facial, and greater metatarsal arteries. In the standing horse the transverse facial or the facial artery are most practical (Figure 7-1).

FIGURE 7-1 An adult horse with an arterial catheter in the tranverse facial artery for direct blood pressure monitoring.

The reference unit for blood pressure is millimeters of mercury (mm Hg), meaning the force exerted by the blood against an area of the vessel wall to raise a column of mercury by a certain number of millimeters. Occasionally, centimeters of water (cm H₂O) is used. One mm Hg equals 1.36 cm H₂O. The mercury manometer is too slow, however, to record changes in blood pressure rapidly. Therefore a continuous method of pressure recording is preferable for clinical use. A transducer transforms the pressure signal to an electronic signal that can be displayed continuously. The transducer and flush device (Pressure Monitoring Kit with Truwave disposable pressure transducer; Edwards Lifescience, Irvine, Calif,) then can be used for continuous blood pressure measurement. One should place the transducer at the level of the heart base, as estimated by the point of the shoulder.

In addition to blood pressure measurement, invasive blood pressure measurement enables evaluation of the pressure waveform, which in turn can provide insight regarding the status of the stroke volume and peripheral vascular tone.

Indirect Measurement

Indirect blood pressure measurements depend on a cuff placed around the tail or the metatarsus. The diameter of the cuff influences the accuracy of the measurement, with cuffs that are too wide resulting in underestimation of the blood pressure. An ideal cuff width-to-circumference ratio of 0.25 to 0.35 has been recommended for use on the tail or limbs of horses. Cuff widths are available for neonate, pediatric, and adult horses. Once the cuff is in place, the practitioner measures blood pressure by recording the signal emitted by the changing blood frequency during the pulse wave. The following sections describe noninvasive blood pressure measurement methods.

DOPPLER

Doppler uses a small ultrasound probe placed on a peripheral artery, and a piezoelectric crystal within the probe converts the pulse wave into an audible signal. The probe must be placed over a shaved area (usually under the tail of the horse) after application of a coupling gel. Doppler allows measurement of only systolic pressure and is therefore not as useful as other methods.

OSCILLOMETRIC SPHYGMOMANOMETRY

Oscillometric sphygmomanometry relies on the recording of the change in oscillations generated by the change in blood flow during deflation of the cuff. Oscillations start as the cuff pressure reaches systolic pressure, are maximal at mean pressure, and disappear when the cuff reaches diastolic pressure. The meter records and displays systolic, diastolic, and mean pressures. When placing the meter on the tail, one can use tape or a bandage below the cuff to prevent its slipping, but should not restrain the cuff itself (Figure 7-2).

FIGURE 7-2 Indirect oscillometric blood pressure measurement in a horse using a cuff placed on the tail.

PHOTOPLETHYSMOGRAPHY

Photoplethysmography relies on the detection of arterial volume by attenuation of infrared radiation. Photoplethysmography originally was designed for use in human fingers and has been validated for use in small dogs and cats but has not been evaluated for use in horses.

TRANSESOPHAGEAL ULTRASOUND

Transesophageal ultrasound is a method of hemodynamic monitoring that uses a transesophageal probe with two ultrasound transducers (HemoSonic; Arrow International). An M-mode transducer continuously measures the aortic diameter, and a pulsed Doppler measures the flow velocity, providing hemodynamic measurements, including MAP. Although transesophageal Doppler echocardiography has been evaluated for determination of cardiac output in horses, the accuracy and repeatability of the combined probes for blood pressure determination have not been evaluated (Vingmed Sound, Horten, Norway).

MONITORING CENTRAL VENOUS PRESSURE

Central venous pressure is the pressure in the central veins of the patient and is most often measured within the intrathoracic portion of the cranial vena cava. The CVP is affected by vascular volume, venous tone, and cardiac function. Monitoring CVP is most useful for patients in which the veterinarian is attempting to maintain adequate vascular volume without fluid overload. For example, assessment of CVP may be useful in horses with oliguric or anuric renal failure, horses with large volume gastric reflux, and horses predisposed to edema formation.

Central venous pressure is measured by using an intravenous catheter placed in the jugular vein and terminating in the intrathoracic portion of the cranial vena cava. The catheter is attached via an extension set to a water manometer positioned such that the pressure at the level of the base of the heart or point of the shoulder is zero.

TRACHEOSTOMY

Box 7-3 lists the materials needed for an emergency tracheostomy pack. If possible, the clinician should clip, prepare, and infiltrate with local anesthetic the planned incision site. In cases of acute respiratory distress, this may not be possible, however. The clinician makes an 8- to 10-cm longitudinal incision at the junction of the proximal and middle third of the neck, just above the V made by the junction of the sternothyrohyoideus muscles. It is important to stay on midline to favor drainage, separating the sternothyrohyoideus muscles on the midline and exposing the trachea. The clinician makes a transverse incision between two tracheal rings, taking care not to damage the tracheal cartilages. If the head of the horse is supported in elevation during the procedure, the clinician should make the tracheal incision distal in relationship to the skin incision to keep from covering the incision when the head is lowered. In emergency situations a J-type tracheostomy tube is used because of its ease of insertion. When the horse is calm, or if the situation is not critical, a self-retaining tube is preferable for maintenance because J-tubes tend to fall out. If the animal is to be ventilated, a silicone-cuffed tube is preferable to allow for closed-system ventilation.

The tracheostomy tube should be cleaned daily and changed as needed. Petroleum gel applied around the incision prevents skin scalding. In general but particularly in foals, tracheostomy tubes should be removed as early as possible to avoid permanent tracheal deformity. To help decide when to remove the tube, the clinician can occlude the tube temporarily to see if the horse can breathe without it. After the tube is removed, the site should be cleaned of exudate twice daily and allowed to heal by second intention. The wound generally closes in 10 to 14 days and heals in 3 weeks.

THORACOCENTESIS

Thoracic drainage is an essential part of managing pleural effusion and can be lifesaving in cases of severe effusion. Pleural effusion is identified by typical increases in area of cardiac auscultation; dullness in the ventral area of auscultation; and, if unilateral, a discrepancy in auscultation between the two hemithoraxes. The clinician can use percussion, although ultrasound typically provides the best method of identifying fluid in the chest. Pleural fluid is drained through a cannula or by placement of a chest drain. The clinician clips, prepares, and infiltrates the site with a local anesthetic. An incision is made in the skin cranial to the proposed point of entry, and the trocar is inserted through the skin. The clinician moves the incision in a caudal direction to a point between two ribs and, using pressure, pushes the trocar into the chest. One hand serves as a stop to control depth of entry. After obtaining the fluid, the clinician places a Heimlich valve on the end of the tube and sutures the tube in place using a Chinese finger trap pattern.

Pneumothorax is classified as open (external wound) or closed. The pleural pressure equilibrates with atmospheric pressure, resulting in lung collapse. Tension pneumothorax develops when air continuously enters the chest without evacuation. The pleural pressure can reach supra-atmospheric levels and can be life threatening.

In open pneumothorax sealing of the chest must occur, followed by evacuation of air. The clinician can seal the chest with sheets of plastic wrapped around the site of entry or close the wound if possible. The chest is evacuated by placing a small trocar, or a 14-gauge catheter, in the dorsal twelfth intercostal space, and the trocar is removed once the air has been evacuated satisfactorily. In closed pneumothorax or tension pneumothorax, the catheter must be kept in place until the source of air entry can be sealed.

NASOGASTRIC INTUBATION

Nasogastric intubation is an essential and possibly lifesaving procedure performed in cases of equine colic. The horse should be adequately restrained, with a twitch and sedation if needed. The clinician should stand on the side of the horse, with the hand closest to the horse placed on the nose, and the thumb in the nostril. With the other hand, the clinician passes the tube in the ventral meatus, using the thumb to keep it directed correctly. If a hard structure is encountered, it is the ethmoidal area, and the tube should be redirected ventrally. On reaching the pharynx, the practitioner should feel a soft resistance. The tube can be turned 180 degrees to direct its curvature dorsally. The clinician stimulates the horse to swallow by gentle to-and-fro movement or by blowing in the tube. Keeping the head of the horse flexed at the poll is helpful. Once the horse swallows, the clinician pushes the tube into the esophagus. Blowing into the tube to dilate the esophagus facilitates insertion. If the horse coughs, the clinician withdraws the tube and repeats the procedure until the tube is positioned correctly. There are three ways to determine that the tube is placed correctly in the esophagus: gentle suction, which should elicit a negative pressure; shaking of the trachea, which should not elicit a rattle; and visual confirmation of correct placement. Direct observation is the safest method. The tube is advanced until it is in the stomach (fourteenth rib). If the clinician encounters difficulty in passing the cardia, 60 ml of mepivacaine may be injected into the tube. Once the tube is in place, the practitioner must force the horse to reflux if reflux is not spontaneous. Medication should never be administered by nasogastric tube to a horse with colic without checking first for reflux. To do this, one fills the tube with water using a pump and directs the end of the tube downward to verify the presence of gastric contents. Subtracting the amount pumped in from the amount obtained is useful to determine the net amount of reflux.

One removes the tube by first occluding it (putting a thumb on the end or folding it) to prevent its contents from spilling out in the pharynx and possibly the trachea as it is withdrawn. Gentle traction is then applied in a direction parallel to the nose. If bleeding occurs, a towel can be placed over the horse’s nose. The bleeding, even if severe, is self-limiting.

Nasogastric reflux is not normal. Occasionally, a small amount of reflux (1 L or less) is obtained if a horse has had a tube in place for a long time. When reflux occurs, the clinician should note the amount, character, and timing in relation to the onset of colic. In addition, the clinician should note the response to gastric decompression. Reflux originating from the small intestine is alkaline, whereas reflux composed of gastric secretions is acidic. Typically, reflux refers to small intestinal ileus, functional or mechanical. Lesions of the proximal small intestine produce large amounts of reflux early in the onset of the colic. With lesions of the distal small intestine (ileum), one initially obtains no reflux, and as the condition persists, one obtains reflux but usually several hours after the onset of the colic. Occasionally, large colon disease can be associated with reflux if the colonic distention exerts pressure on the duodenum as it curves over the base of the cecum.

The clinician should note the amount of reflux obtained because this factors into ongoing losses, and the volume of fluids given intravenously must be adjusted accordingly. Horses with functional ileus need gastric decompression usually every 4 hours, although if the condition is severe, they may require decompression every 2 hours. The nasogastric tube should be left in place only as long as required because some horses develop pharyngeal and laryngeal irritation associated with its presence.⁶ These horses then have pain when swallowing when they resume feeding.

ABDOMINOCENTESIS

Abdominocentesis is important for evaluating abdominal disease, whether it is colic, weight loss, or postoperative problems. Box 7-4 provides the materials needed to perform this procedure.

The clinician clips a 2×2–inch area approximately 3 cm caudal to the xyphoid and 1 to 2 cm to the right of midline. With sterile gloved hands, the clinician inserts an 18-gauge needle through the skin and gently advances it into the abdomen. If no fluid is obtained, another needle can be inserted next to the first one. If no fluid is obtained this time, a bitch catheter, cannula, or dialysis catheter may be tried. Obtaining fluid from very dehydrated horses is often difficult.

To insert a teat cannula, bitch catheter, or dialysis catheter, the clinician places a bleb of local anesthetic at the site, punctures the skin and abdominal wall with a 15-gauge scalpel blade using sterile technique, and then inserts the chosen device in the abdomen. Two points of resistance will be encountered: as the device goes through the abdominal wall and as it goes through the peritoneum. The clinician collects the fluid in ethylenediamine tetraacetic acid (EDTA; shaken out of the tube so that the amount in the sample is not excessive) and, if the fluid is cloudy, in a culture tube.

Normal values for abdominocentesis are as follows: total protein should be less than 2.5 g/dl, and white blood cells should be less than 5000 cells/μl. On cytologic examination neutrophils make up approximately 40% of cells, the rest being lymphocytes, macrophages, and peritoneal cells.

With intestinal strangulation, the protein increases first (in the first 1 to 2 hours) such that the fluid is clear but more yellow. After 3 to 4 hours of strangulation, red blood cells also leak, and the fluid is more orange. After 6 hours or more, white blood cells increase gradually, with the progression of intestinal necrosis.

Enterocentesis sometimes occurs and must be differentiated from intestinal rupture. With enterocentesis a cytologic examination reveals plant material, bacteria, and debris but no cells. The clinical condition of the horse is not consistent with rupture, although in early rupture clinical signs may not reflect rupture (2 to 4 hours are necessary for manifestation of signs). Cytologic examination of abdominal fluid with intestinal rupture shows neutrophils, bacteria, and bacteria that have been phagocytized by neutrophils.

Blood contamination can result from the procedure and must be differentiated from internal hemorrhage or severely devitalized bowel. Blood from skin vessels usually swirls in the sample and spins down when centrifuged, leaving the sample clear. If an abdominal vessel is punctured, blood also spins down. All fresh blood contamination shows platelets, which are not present with blood older than 12 hours. If the spleen is punctured accidentally, centrifugation reveals a packed cell volume higher than the peripheral packed cell volume. In internal hemorrhage blood is hemolyzed such that the supernatant is reddish after centrifugation; the sample has no platelets and shows erythrophagocytosis. Ultrasonography also reveals fluid swirling in the abdomen.

Excess EDTA in the sample falsely elevates the total protein. When performing an abdominocentesis, the clinician should shake out the EDTA from the tube to avoid this sampling error.

Abdominal surgery increases the total protein level and white blood cell count for some time after surgery. Typically, if no enterotomy occurred, the white blood cell count increases greatly for 4 to 7 days and returns to normal by 14 days. The total protein level may remain elevated for 3 to 4 weeks after surgery. Neutrophils appear to be nondegenerate. After an enterotomy or an anastomosis, degenerate neutrophils and occasional bacteria may be seen in the first 12 to 24 hours. Subsequently, the white blood cell count remains elevated for approximately 2 weeks, but on cytologic examination the neutrophils appear to be nondegenerate and no bacteria are apparent. The total protein level remains elevated for 1 month after surgery. If septic peritonitis is present, clinical signs are consistent with bacterial infection (i.e., fever, depression, anorexia, ileus, pain, endotoxemia). The white blood cell count and total protein level are elevated greatly. On cytologic examination greater than 90% of cells are neutrophils, and they appear to be degenerate. Free and phagocytized bacteria are visible.

TROCARIZATION OF THE LARGE COLON

Trocarization of the large colon is occasionally useful to decompress the abdomen for abdominal compartment syndrome (i.e., severe distention associated with pain and dyspnea). Box 7-5 lists the materials needed for this procedure.

Trocarization should be performed only for large colon distention and never to decompress the small intestine. Before deciding on trocarizatino, identifying the segment of intestine involved is important. In adult horses, such identification can be made by rectal palpation, and in foals or small horses, radiographs or ultrasound can be used. The distended segment of large colon also must be close to the body wall so that it can be reached safely.

The most common site for trocarization is the right upper flank area, just cranial to the greater trochanter at the location of the cecal base. The clinician clips, prepares, and infiltrates with a local anesthetic a 4 × 4-cm area of skin. With gloved hand, the clinician inserts a 14-g catheter with an extension tube perpendicular to the skin. The clinician places the end of the extension in water so that gas bubbles are visible when the tip of the catheter is positioned correctly. When gas is obtained, the trocar part of the catheter should be withdrawn slightly to keep from lacerating the bowel. It may be necessary to reposition the catheter several times when gas is not obtained. After decompression the clinician removes the trocar and infuses an antibiotic (e.g., gentamicin) while withdrawing the catheter.

Peritonitis and local abscessation are the two most common problems encountered after trocarization. The horse should be observed for 24 hours for signs of peritonitis. If the practitioner suspects peritonitis, confirmation is with abdominocentesis, and systemic broad spectrum antibiotics should be administered to the horse until the condition resolves. If a local abscess develops, the practitioner can drain it externally.

URINARY CATHETERIZATION

Measurement of urine output in adult horses is an infrequent procedure, compared with foals, but it may be useful in horses with of oliguric renal failure or when 24-hour volumetric measurements are needed. Male horses with neurologic disorders that make them unable to express their bladder may require bladder decompression.

In the mare, urine is easily collected by placing a Foley catheter that is connected to collection tubing. One can make a closed system by using a solution administration set and empty fluid bag. In geldings one can insert a male urinary catheter and suture it in place using a Chinese finger trap pattern. If the horse is recumbent and thrashing, leaving as little as possible of the catheter protruding to keep it from being pulled out is important. Normal horses produce 1 to 2 ml/kg/hr of urine.

SUPPORT OF CARDIOVASCULAR FUNCTION^∗

Peter R. Morresey

REVIEW OF CARDIOVASCULAR PHYSIOLOGY

Cardiac output, the volume of blood pumped through the heart per minute, is calculated as the product of heart rate and stroke volume. Heart rate is determined by a number of neurologic, endocrinologic, and physical factors. Stroke volume is the amount of blood expelled from the heart with each contraction (i.e., the difference between end-diastolic volume [maximal filling] and end-systolic volume within the ventricle [peak contraction]). The quantity of blood arriving as the arterial supply of a tissue depends on cardiac output.

Resistance to arterial blood flow varies among tissues. As a result, cardiac output is not evenly distributed throughout the body. Contraction of the smooth muscle of the arterioles largely determines that this resistance functions to maintain a pressure gradient across the tissue capillary beds, allowing flow from arterioles to venules. Systemic vascular resistance can be considered a measure of vasomotor tone and hence vascular capacity.

Delivery of oxygen to the tissues becomes inadequate when the cardiovascular system is dysfunctional, because the oxygen delivered is a product of blood flow through the tissue and arterial oxygen content. In patients with reduced blood flow and peripheral perfusion, fluid therapy is used to increase circulating volume. Increased venous return leads to an increased stroke volume, increasing cardiac output and therefore tissue blood flow. When fluid therapy fails to improve tissue perfusion as a sole therapeutic approach, the use of vasoactive drugs (e.g., vasopressors, inotropes) may be indicated.

CARDIOVASCULAR INSUFFICIENCY: SHOCK STATES

If the cardiovascular system fails to meet the demands of the animal for adequate oxygen delivery to tissues, a state of shock ensues. Shock is classified into four major types: hypovolemic shock, cardiogenic shock, obstructive shock, and distributive shock.¹ The first three of these categories of shock are associated with a decrease in cardiac output and uniform circulatory disturbances in the arterioles, venules, and capillaries. Anaerobic tissue metabolism ensues as a result of diminished oxygen delivery. The fourth type of shock, distributive or vasodilatory shock, is associated with a heterogenous disturbance of blood flow in the microcirculation and areas of shunting.²

Hypovolemic shock results from a loss of intravascular volume, whether by systemic dehydration with resultant hemoconcentration, loss of fluid into a third space, or by loss of whole blood through hemorrhage. Decreased circulating volume leads to diminished venous return, reducing cardiac preload. This reduction in preload decreases myocardial fiber length, with resultant decreased contractility and therefore cardiac output. Reduced tissue perfusion results.

Cardiogenic shock is the result of impaired ventricular function with resultant decreased cardiac output. Myocarditis, myocardial infarction, valvular pathology, or arrhythmias may be responsible.³ Inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-2 and IL-6, decrease the contractility of cardiac myocytes, effects shown experimentally to be mediated by nitric oxide.⁴

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