The Rule of 20

The goal of fluid therapy (see Fluid Therapy) is to provide adequate perfusion (intravascular volume) and hydration (interstitial volume) without overloading the interstitial space. Peripheral perfusion can be assessed by physical parameters such as heart rate, mucous membrane color, pulse quality, and mentation, as well as by measured parameters such as blood pressure, central venous pressure, urine output, and blood lactate measurements. Hydration can be assessed by physical parameters such as mucous membrane and corneal moistness and skin turgor, and by measured values such as body weight. Animals with systemic inflammatory response syndrome (SIRS) diseases may require more fluid than expected because of peripheral vasodilation and loss of endothelial integrity, making the administration of colloids with crystalloid solutions optimal. When treating fluid deficits, intravascular deficits should be addressed rapidly first; interstitial deficits should be treated using standard calculations to correct dehydration and monitor ongoing losses.

Albumin provides the major intravascular oncotic pull in the normal vasculature. In conditions in which there has been massive blood loss or leakage of plasma proteins due to an exudative process, albumin is lost from the intravascular space. This loss of intravascular oncotic pressure combined with increased capillary permeability associated with many SIRS diseases requires treatment using synthetic colloids that have a higher molecular weight than that of albumin. Colloid oncotic pull (COP) can be measured with colloid osmometry but is not commonly available in veterinary practice. Formulas are available to calculate COP based on plasma protein levels, but they are not reliable predictors of measured COP. Normal COP in dogs is ~20 mmHg. In patients with moderate to severe decreases in COP or in total proteins, natural and synthetic colloids should be administered. Examples of natural colloids include plasma, concentrated human or canine albumin, and stroma-free hemoglobin. Examples of synthetic colloids include dextrans and hydroxyethyl starches. Newer understanding of the endothelial cell function and the impact of the endothelial glycocalyx may present novel therapeutic options in the future.

Part of the oncotic activity normally provided by albumin can be provided by synthetic colloids, but only albumin can perform other functions such as drug, cation, and hormone transport, as well as contribute to acid/base balance. Albumin can be lost with a variety of diseases (GI, renal, or SIRS); in addition, it is a negative acute-phase protein, so production of albumin drops during critical illness. Interstitial albumin stores are drawn upon to replace serum albumin, and a low serum albumin reflects a total body deficit of albumin. Albumin levels <2 g/dL have been associated with a poor prognosis; however, it is not known whether restoring albumin levels improves survival. Plasma and albumin transfusions are often administered to supplement the albumin to reach a target of 2 g/dL, but large volumes of plasma are required. Lyophilized canine serum albumin is now available in 100-g vials, making replacement of albumin more cost-effective and with lower total volumes than plasma transfusions. Human albumin products have been used in critically ill dogs but may result in severe organ dysfunction when given to healthy dogs. Interstitial albumin stores must be replenished as well as intravascular levels, so multiple units of plasma or albumin may be necessary to increase serum albumin levels.

The goal is to maintain glucose between 80 and 120 mg/dL. Septic animals are at an increased risk of hypoglycemia that can be severe enough to cause hypotension or neurologic dysfunction ranging from weakness to stupor or seizures. Other causes of hypoglycemia include inadequate nutrition, glycogen storage diseases, heat stroke, young age, small size, severe liver disease or portosystemic vascular anomalies, certain neoplasias, hypoadrenocorticism, and iatrogenic insulin administration. Dextrose supplementation is warranted in any animal that is hypoglycemic. Solutions with a dextrose concentration >5% are best administered through a central line. Animals with clinical hypoglycemia despite administration of solutions with high dextrose concentrations should be assessed for insulinoma and may benefit from glucagon infusions. A difference of >20 mg/dL in blood glucose values and abdominal fluid glucose values has high sensitivity and specificity for septic peritonitis in animals who have not recently had surgery.

Insulin treatment of hyperglycemia in diabetic animals is important to offset ketoacidosis or hyperosmolar complications. Constant-rate infusion (CRI) of regular insulin can result in the slow and controlled lowering of blood glucose (to help avoid rapid changes of blood osmolality); close monitoring of blood glucose levels should be performed. Tight control of increased blood glucose has improved neurologic outcome after head trauma in critical human surgical patients but not in human medical patients; in addition, increased incidences of hypoglycemia may occur with tight glucose control. Acutely traumatized animals are prone to insulin resistance because of large amounts of circulating cortisol and epinephrine and may develop hyperglycemia severe enough to require treatment with insulin. The benefit of tight blood glucose control has not been clearly demonstrated in veterinary medicine.

Hypokalemia can be a contributing factor in weakness and ileus of critically ill animals. These animals commonly have reduced oral intake and/or increased GI and urinary losses of potassium that require potassium supplementation in the IV fluids. Hyperkalemia can be a life-threatening complication of urinary tract rupture or obstruction, renal failure, reperfusion injury, or massive cellular death. Hyperkalemia commonly results in bradyarrhythmias and can be temporarily treated with calcium gluconate and insulin, concurrently with dextrose and/or sodium bicarbonate. The underlying pathology that led to hyperkalemia must be addressed. Other important electrolytes to monitor include sodium, ionized calcium, phosphorus, magnesium, and chloride; all can be increased or decreased in critically ill animals and may affect other body systems (such as neurologic acid/base balance, serum osmolality, the cardiovacular system, and RBCs). The anion gap (AG) can be calculated when blood electrolytes are measured: AG = [Na] + [K] – [HCO₃] – [Cl]. Normal AG values are between 12 and 24 mEq/L. An increased AG indicates there is some unmeasured anion present in the blood, which may include ketones, lactate, uremic compounds, or toxins (eg, salicylates, ethylene glycol, ethanol, methanol, indomethacin, isoniazid, paraldehyde, propylene glycol). The most common cause of metabolic acidosis is lactic acidosis caused by poor perfusion leading to anaerobic metabolism. Lactate production results in an equimolar production of hydrogen ions and subsequent alterations in blood gas values (metabolic acidosis). Lactate measurements can be easily performed with handheld or benchtop analyzers. Resolution of hyperlactatemia with adequate fluid resuscitation is often associated with improved survival. Treatment involves maximizing blood flow and tissue oxygen delivery. Rarely is the administration of sodium bicarbonate (NaHCO₃) warranted for perfusion-related acidosis. Once perfusion and hydration are corrected, the acid-base status is reassessed.

If severe metabolic acidosis (as occurs with ketosis or uremia) persists and HCO₃ remains below ~12 mEq/L after perfusion has been restored, slow administration of fluids with NaHCO₃ supplementation is warranted, restoring serum values to >15 mEq/L. The dosage of NaHCO₃ is calculated as follows:

mEq NaHCO₃ = 0.3 × (target NaHCO₃ [eg, 15] - patient NaHCO₃) × body weight in kg

Serum bicarbonate levels are carefully monitored to meet patient requirements.

Pulmonary function can be compromised in critical illness for a variety of reasons (pneumonia, acute respiratory distress syndrome, thromboembolism, congestive heart failure, etc). Early diagnostic tests (eg, imaging, blood work, tracheal washes, urine blastomycosis antigen testing, etc) for targeted therapeutics will help limit extension of pulmonary disease. Aspiration pneumonia is a particular challenge, because it is most commonly a "second hit" disease (secondary to another systemic illness); therapeutics (such as antiemetics, prokinetics, or use of nasogastric tubes) to prevent aspiration pneumonia should be used whenever appropriate. Arterial blood gas measurement is the "gold standard" method to detect hypoxemia or hypercarbia. Pulse oximetry (SpO₂) is a noninvasive way to determine the oxygen saturation of hemoglobin. Supplemental oxygen and/or therapeutic ventilation may be indicated with SpO₂ values <96%. Hypercarbia can be detected using end-tidal CO₂ through an endotracheal tube or nasal catheter and has been shown to correlate with arterial CO₂ levels in animals. Serial monitoring is recommended in the initial management of animals with respiratory compromise to determine the adequacy of oxygen supplementation and the need for mechanical ventilation. If hypoxemia is unresponsive to oxygen supplementation (PaO₂ <60 mmHg or SpO₂ <90%) or hypercarbia is present (PaCO₂ >60 mmHg), or if respiratory effort (work of breathing) is substantially increased, manual or mechanical ventilation is necessary. Ventilation should not be delayed until respiratory failure or arrest. Prognosis for animals that require ventilation is variable; those with hypoxemia from congestive heart failure or hypoventilation from metabolic disease (eg, hypokalemia) or cervical spinal disease have a better prognosis than those that require ventilation for hypoxemia due to primary pulmonary disease. Invasive (arterial sampling) and noninvasive (ETCO₂/SpO₂) blood gas measurements should be performed during mechanical ventilation to determine need for adjustment of the ventilator settings.

A decline in an animal’s level of consciousness warrants investigation to exclude metabolic causes, such as hypoglycemia, hyperglycemia, hepatic encephalopathy, acidosis, electrolyte or osmotic derangements, or sudden development of hypertension, hypotension, or shock. An increase in intracranial pressure can result from intracranial hemorrhage, fluid overload (cerebral edema), primary brain/meningeal disease, and/or ischemia. The drugs the animal is receiving should be carefully evaluated for adverse effects that can lead to altered mentation or level of consciousness. Cerebral edema may be responsive to medical management with furosemide and concurrent mannitol therapy. Steroids may be indicated in certain inflammatory diseases (eg, meningitis, neoplasia), and antibiotics in infectious disease (eg, toxoplasmosis). Craniotomy may be needed in animals not responsive to medical management. Cerebral perfusion pressure = mean arterial pressure – intracranial pressure. Elevating the head 15° and avoiding procedures that may increase venous pressure and subsequently intracranial pressure is essential. Maintaining normal oxygenation/ventilation, blood pressure, glucose level, and serum osmolality is essential for animals with brain disease. Neurologic status may be evaluated using a scoring system assessed on a regular basis, such as the modified Glasgow Coma Scale; lower scores are associated with a poorer prognosis.

Spinal injury that is severe enough to cause paralysis (particularly with lack of deep pain sensation) and inability to ventilate and ambulate, and that has not responded to medical management (such as anti-inflammatory medications) warrants immediate imaging and surgical intervention. Loss of deep pain is associated with a poor return to function. Serial neurologic examinations should be performed in any animal with neurologic disease.

Blood pressure should be monitored via direct or indirect methods. The goal is to maintain organ perfusion by maintaining a minimum mean arterial blood pressure >60 mmHg (systolic >90 mmHg). In hypotensive animals with adequate cardiac function, treatment consists of intravascular volume infusion (see Fluid Therapy), oxygen administration, and pain control. Hypotension unresponsive to intravascular volume replacement can be due to one or more of the following: hypoglycemia, acidosis, alkalosis, electrolyte disorders (eg, potassium, calcium, magnesium), brain-stem pathology, cardiac arrhythmias, metabolic toxins (eg, hepatic, renal), ongoing fluid loss, relative hypoadrenocorticism (eg, cortisol deficiency), heart or pericardial disease, excessive vasodilation, and excessive vasoconstriction. The need for cardiac support with positive inotropes should be assessed. An experienced ultrasonographer may be able to assess ventricular and/or capacitance vessel size to provide an estimate of preload and contractility. Once intravascular volume (central venous pressure >8 cm H₂O) and cardiac function are assessed as adequate, vasopressor therapy with CRI of dopamine (5–15 mcg/kg/min) or norepinephrine (0.05–2 mcg/kg/min), beginning at the lower end of the dosage range and increasing by increments of 0.2–0.5 mcg, is recommended. Stroma-free hemoglobin can be infused for its pressor effects. Objective measurements of global perfusion may also include lactate monitoring; animals with a significantly increased lactate concentration may have a poorer prognosis. Studies have demonstrated that serial lactate monitoring as pathology is treated is more useful than a single measurement. Central venous oxygen measurement is another objective measurement of global perfusion; normal values are 70–80 mmHg, whereas lower values may indicate increased oxygen extraction.

Hypertension is a relatively uncommon condition in veterinary medicine, but it can lead to catastrophic problems such as retinal detachment or neurologic derangements from intracranial hemorrhage. Hypertension can exacerbate proteinuria in animals with chronic kidney disease. Moderate to severe hypertension can be treated with oral antihypertensive agents such as angiotensin-converting enzyme inhibitors (eg, benazepril), calcium channel blockers (eg, amlodipine), direct arterial dilators (eg, hydralazine), or systemic injectable antihypertensive agents such as nitroprusside (0.5–10 mcg/kg/min), titrated to effect. Blood pressure must be monitored constantly to assess response to therapy with nitroprusside. Chronic hypertension that is rapidly decreased may result in decreased renal perfusion.

The American College of Veterinary Internal Medicine classifies risk of target-organ damage from hypertension into four categories based on systolic blood pressure: I: <150 mmHg = minimal risk; II: 150–159 mmHg = mild risk; III: 160–179 mmHg = moderate risk; and IV: >180 mmHg = severe risk.

The electrical and mechanical systems of the heart should be evaluated separately. Specific antiarrhythmic drug therapy should be instituted based on an accurate ECG diagnosis when perfusion is compromised by an arrhythmia and the first-line therapy of oxygen supplementation and analgesics has been unsuccessful in controlling the arrhythmia. Arrhythmias can occur for a variety of reasons, such as SIRS diseases, splenic disease, organ torsion (eg, gastric dilatation-volvulus), and electrolyte abnormalities (eg, hyperkalemia); the underlying condition must be treated/investigated as well. Some ventricular rhythms (such as ventricular premature contractions and accelerated idioventricular arrhythmias) may not necessarily require immediate therapy. Indications for treatment of a ventricular rhythm include tachycardia (rates >160–180 bpm), clinical signs of poor perfusion (low blood pressure, poor pulse quality, etc), multiform arrhythmias, and R-on-T phenomenon. Other tachyarrhythmias may respond to class I, II, III, or IV antiarrhythmics; bradyarrhythmias can be challenging to treat medically and may require pacemaker placement. An echocardiogram can be performed to evaluate cardiac contractility in SIRS diseases and to detect underlying cardiac diseases. If cardiac contractility is decreased, dobutamine at 5–10 mcg/kg/min (dogs) or 2.5–5 mcg/kg/min (cats) should be considered to provide inotropic support if there is evidence of poor cardiac output. Recent studies have demonstrated that dogs with mitral valve disease and dilated cardiomyopathy have a poorer prognosis if their cardiac troponins (cTnI) and/or natriuretic peptide (NT-pro-BNP) is increased. However, these tests are not available in all hospitals and do not necessarily direct therapy, or diagnose or differentiate disease processes.

Body temperature is considered part of the initial clinical database and should be measured regularly in every critically ill animal. A variety of diseases can result in increased or decreased body temperature. Temperature is measured most accurately and consistently with a rectal thermometer.

Increased temperatures can be seen with environmental exposure (eg, heat stroke), increased activity (eg, exercise, excitement), and infectious, inflammatory, or neoplastic diseases. Severe increases of temperature (>105.5° [40.8°C]), particularly when prolonged, can lead to severe metabolic disease such as hemorrhagic diathesis, disseminated intravascular coagulation, and SIRS diseases, which may lead to multiorgan dysfunction. Effective means of cooling animals include fluid therapy, using wet towels with fans, and placing alcohol in paw pads. Animals should not be immersed in cold water, because this causes peripheral vasocontriction and decreases core heat dissipation. Fever of unknown origin warrants a systemic evaluation (see Fever of Unknown Origin).

Hypothermia is most commmonly associated with anesthesia in small animals; however, severe systemic disease (particularly in cats) and environmental exposure may be contributing factors. Mild hypothermia can be a common sequela of severe cardiovascular disease and is a prognostic marker in cats with limb thromboembolism. Temperature is a vital parameter to monitor and treat in cats with clinical signs of shock, and active warming is an essential component of therapy. Therapeutic hypothermia may have some neuro-sparing effects in animals with traumatic brain injury or in postresuscitation (CPR) care; however, further investigation is needed. In animals with induced hypothermia, blood flow to most organs can be significantly decreased, and coagulation may be affected.

Altered body temperature is part of the definition of SIRS-type diseases; other parameters include an increased or decreased heart rate, increased or decreased WBC count, and an increased respiratory rate.

Disseminated intravascular coagulation (DIC) can develop in any animal that has undergone a period of relative vascular stasis as occurs during shock, severe tissue or capillary damage such as that which occurs with trauma, exposure of capillary endothelial cells to circulating inflammatory mediators as occurs during sepsis or SIRS, or moderate to severe alterations in body temperature. In the early stages of DIC, there may be few or no clinical signs. However, as DIC progresses, its effects are obvious and catastrophic. The goal is to detect DIC in the early stages and to slow or prevent its progression.

Early DIC is characterized by a hypercoagulable stage in which serum antithrombin (AT) levels are decreased and the coagulation cascade is activated by any of the precipitating causes. Activation of the coagulation cascade throughout the body rapidly depletes the clotting factors and the blood platelet count as platelets are incorporated into the clots. At this stage, the prothrombin time and partial thromboplastin time may be decreased, but this is a challenging stage to identify and diagnose. However, this rapidly progresses to a hypocoagulable stage as the coagulation factors are consumed. In this late stage, the prothrombin time and partial thromboplastin time (or activated clotting time) are prolonged, and fibrinogen degradation products are increased.

Treatment of DIC focuses on treating the underlying disease and removing the stimulus for continued activation of the coagulation cascade. In the early hypercoagulable stages, treatment focuses on maximizing the function of AT, which is the most abundant natural inhibitor of the serine proteases of the coagulation cascade. When AT levels are adequate, heparin can be administered SC (50–100 U/kg, tid). If AT levels are <60% of normal, then plasma transfusions should also be given to increase the level to ≥80%. In animals with diseases known to predispose to DIC, coagulation parameters and platelet counts should be monitored. Thomboelastography (TEG) provides another means of global assessment of the clotting cascade and may be a useful tool with suspected hypo- or hypercoagulable states; hypercoagulable states are challenging to diagnose, and TEG is one of the few methods that may provide an accurate assessment.

Thrombosis occurs without DIC when there are alterations in Virchow’s triad: endothelial injury, blood stasis, and hypercoagulable states. Abnormalities in one or more of these components may be seen with vascular anomalies, atrial enlargement, severe systemic illness (SIRS, immune-mediated hemolytic anemia), trauma, neoplasia, renal disease, hyperadrenocorticism, and as a primary disease in Greyhounds. The most common severe manifestations of hypercoagulability are aortic and pulmonary thromboemboli. Pulmonary thromboemboli should be suspected when significant hypoxemia is present with minimal lung changes on thoracic radiographs. Anticoagulation therapy and oxygen support should be implemented, and oxygenation and ventilation monitored. Arterial thromboembolism can occur in cats with underlying heart disease. Antithrombotics are warranted in these cases; options include aspirin and/or clopidogrel, heparin (low molecular weight or unfractionated), or warfarin. Most of these drugs require close monitoring of clotting times to achieve therapeutic goals. This disease can be painful, and opioid medications are often warranted as well as monitoring for reperfusion injury.

Disease states that result in relative hypocoagulability may include anticoagulant rodenticide ingestion, fulminant liver failure, severe thombocytopenia, snake bites, dilutional hypocoagulability from fluid and colloid administration, and congenital defects in the coagulation cascade such as von Willebrand disease, hemophilia A or B platelet defects (Boxers), or hyperfibrinolysis (Greyhounds). Therapy should be specific to the inciting cause; plasma products are often necessary to correct life-threatening coagulopathies.

Because Hgb carries most of the oxygen in the blood, maintaining adequate Hgb levels is essential to maintaining adequate oxygen delivery. When anemia is associated with clinical signs of tachycardia, increased respiratory rate, altered mentation, severe lethargy/weakness, and hypotension, then packed RBCs, whole blood, or stroma-free hemoglobin should be administered to bring the PCV to >20% or the Hgb level to >7 g/dL. In some cases of hemolytic or chronic anemia, the PCV can be maintained at a lower percentage before transfusion is required if there are no corresponding clinical signs. In animals that require multiple blood sampling (such as diabetic patients) or very small animals, blood sampling should be minimized to prevent iatrogenic blood loss. Optimal hemoglobin levels have not been determined; however, conservative transfusion managment in people (Hgb goal of 7 g/dL or PCV of 20%) has improved survival benefit over more liberal transfusion goals (Hgb of 10 g/dL or PCV of 30%).

Except in the case of acute, life-threatening hemorrhage, before an RBC-containing blood product is administered, a crossmatch should be performed to ensure a safely administered transfusion. Even type-specific or "A-negative" blood may not be antigenically appropriate for some dogs, because many antigens are present on canine RBCs. If multiple transfusions are anticipated, blood typing should be performed as well. Only type-specific blood should be administered to cats. In dogs and cats with acute cavitary (pleural or peritoneal) hemorrhage, blood may be salvaged from the cavity with aspiration (via centesis or exploratory surgery when indicated) and an autologous blood transfusion administered through a blood filter.

Rarely, disease states may result in altered hemoglobin (such as methemoglobinemia) or altered oxygen-carrying capacity (such as carboxyhemoglobinemia), often recognized by altered mucous membrane color (muddy or brick-red, respectively). Despite normal measured hemoglobin concentrations, oxygen is not being delivered to tissues in these animals, and oxygen supplementation is necessary along with treatment of the underlying disease.

An alternative means to increase oxygen-carrying capacity of the blood is a commercial stroma-free hemoglobin-based oxygen carrier (HBOC) such as Oxyglobin^®. Monitoring PCV is not an adequate assessment of oxygen delivery after use of HBOCs.

Animals with a PCV >55% (other than sight hounds and at high altitudes) may have microvascular sludging (due to the altered blood rheology) and hypertension (which impairs microvascular delivery of oxygen to the tissues). This occurs most commonly with hemorrhagic gastroenteritis. Treatment with IV fluids, and phlebotomy in cases of absolute polycythemia, are performed to improve microvascular flow and oxygen delivery to the tissues.

In animals that have had a hypotensive episode, are receiving potentially nephrotoxic medications, or have primary renal compromise, renal function should be evaluated daily. Urinalysis performed on a sample collected before fluid administration will help to assess renal function. Normal urine output is 1–2 mL/kg/hr and can be closely monitored with an indwelling urinary catheter. Animals in polyuric renal failure are most often managed medically; however, animals in oliguric (<0.8 mL/kg/hr), anuric (<0.03 mL/kg/hr), or relative oliguric (less than expected) renal failure may require peritoneal or hemodialysis to maintain fluid and electrolyte balance. Serial measurement of serum BUN, creatinine, electrolytes, and phosphorus will detect changes and help guide therapy. Serial urinalyses to detect glucosuria, proteinuria, or renal tubular casts help evaluate acute tubular injury before the damage progresses to overt renal failure and azotemia. If urine output monitoring with a catheter is not possible, then estimating urine output by measuring absorbent pads or litterboxes is neccesary. Body weights should be recorded regularly. Additional necessary diagnostics may include urine culture and susceptibility testing, urine protein to creatinine ratio, or specific testing for renal-specific disease (eg, ethylene glycol, leptospirosis). Animals may also be monitored using a scoring system to provide additional "objective" monitoring: the International Renal Interest Society has a staging system to monitor dogs and cats with chronic renal disease based on serum creatinine, blood pressure, and proteinuria.

Strict aseptic technique should be observed when examining or treating animals that are neutropenic or receiving immunosuppressive drugs. These animals should be isolated from other animals and handled by a single person who adheres to appropriate barrier nursing techniques (washes hands, wears gloves and gown before handling the animal, etc). All veterinary staff should be encouraged to wash hands between patients, treat wounds in a clean manner, and administer IV injections only after swabbing an IV port with an alchohol swab. Educating hospital staff on appropriate patient handling techniques may help limit development of nosocomial infections, which develop 48 hr after hospital admission.

Ultimately, antibiotic selection should be based on the results of culture and susceptibility testing, but empiric treatment, based on site of infection and suspected type of bacteria, is necessary pending these results. Empiric therapy may be based on common organisms found at the affected site and/or Gram stain and cytologic examination, which should be performed immediately. Repeat culture and susceptibility testing may be necessary in animals not responding to therapy as expected or if prolonged antibiotic therapy is anticipated.

In animals that have sustained a hypotensive episode or have a GI disease that would allow bacterial translocation, broad-spectrum bacterial coverage should be provided until the results of culture are available or the risk of systemic infection has passed.

An antibiotic protocol should be established for veterinary hospitals to minimize the number of antibiotics administered empirically on a routine basis to reduce the development of resistant organisms in the hospital environment and to improve their susceptibility patterns. Limiting use of specific classes of antibiotics or having rotating schedules may help limit development of microbial resistance. Periodic environmental cultures and facility-based monitoring of culture and susceptibility results for evidence of nosocomial infections and bacterial resistance patterns can help identify and control sources of infection and limit development of resistance. A first-generation cephalosporin (eg, cefazolin, 22 mg/kg, tid) is useful for gram-positive and gram-negative infections; an alternative choice is an aminopencillin with a β-lactamase inhibitor (such as clavulanic acid or sulbactam), which has good gram-negative, gram-positive, and anaerobic coverage at 20–30 mg/kg, tid. If a resistant bacteria is suspected, gentamicin (3–5 mg/kg/day, IV) can be given to more specifically target gram-negative organisms after hydration and perfusion have normalized; a fluoroquinolone (eg, enrofloxacin at 5–10 mg/kg, IV, once or twice daily) is an alternative. The once-daily dosage is less likely to cause toxicity and has the same antibacterial effect as a divided dosage schedule. Metronidazole (7.5–15 mg/kg) given slowly IV over 20 min every 6–8 hr is used for suspected anaerobic infections. If multiple antibiotics are started, the antimicrobial spectrum should be narrowed and antibiotic choice adjusted as soon as the organism's susceptibility pattern is identified. Recurrent infections should be investigated for an underlying pattern of resistance, nidus of infection, or immune-compromising disease.

Newer generations and classes of antibiotics, such as carbapenems (eg, imipenim), third-generation cephalosporins (eg, ceftazidime), and vancomycin should be reserved for use in animals with bacterial infections demonstrated to be resistant to other antibiotics.

WBC counts performed on a semiregular basis (every 48–72 hr) may indicate an appropriate response to infection/inflammation or patient deterioration.

Various molecular or "bio" markers have been investigated in SIRS-type diseases to help understand and stratify disease. High mobility group box 1 protein and C-reactive protein have been associated with poor outcome or diagnosis of SIRS-type disease; however, how that information affects therapy has yet to be determined. Plasma interleukin 1B and IL-6 have been demonstrated to have some prognostic value in cats with sepsis.

Critically ill animals, even those without a primary GI disease, are prone to gastric atony, ileus, and gastric ulceration. Auscultation for bowel sounds should be performed three times a day. Metoclopramide (1–2 mg/kg/day as a CRI) is useful because of its central antiemetic effects and its ability to increase progressive gastric and intestinal motility. Other motility modifiers to consider include cisapride, ranitidine, and erythromycin. Motility modifiers should be avoided if gastric or intestinal obstruction is suspected or has been confirmed.

Placement of a nasogastric tube to allow removal of accumulated gas and fluid reduces the possibility of aspiration of refluxed gastric contents and allows continuous decompression. The nasogastric tube also can be used to introduce small amounts of a glucose and electrolyte solution or a liquid diet to provide nutrition directly to enterocytes, which helps prevent gastric ulceration and intestinal mucosal compromise with secondary bacterial translocation. Antiemetics are used in animals that continue to vomit frequently despite placement of a nasogastric tube, thus improving patient comfort and reducing the incidence of aspiration, vagal-induced collapse, and bradycardia that can accompany the vomiting reflex. Metoclopramide blocks the dopaminergic receptors in the chemoreceptor trigger zone (CRTZ) and central vomiting center and acts peripherally by promoting gastric emptying. Ondansetron and dolasetron are potent antiemetics that block serotonin receptors and act at the CRTZ and the central vomiting center; they are administered at 0.6–1 mg/kg/day. Maropitant is an NK₁ receptor antagonist that blocks vomiting at the CRTZ, vomiting center, and peripheral receptors, administered at 1 mg/kg/day, SC, or 2 mg/kg/day, PO. Vomiting refractory to all other treatments in an otherwise stable animal with normal blood pressure can be treated with chlorpromazine (dogs: 0.05–1 mg/kg, IV, every 4–8 hr; cats: 0.01–0.025 mg/kg, IV, every 4–8 hr). A combination of antiemetics that have different mechanisms of action is often required to arrest refractory emesis in severe illness; in animals that require multiple antiemetics, an obstructive disease should be excluded.

GI ulceration often accompanies critical diseases such as hypotension, hypergastrinemia associated with liver and kidney disease, drug toxicities, neurologic disease, and respiratory disorders requiring ventilation. Histamine₂-receptor antagonists such as ranitidine and famotidine, and proton-pump inhibitors such as omeprazole and pantoprazole should be administered to treat gastric ulcers. However, changing the pH of the stomach can change its microbial flora. Agents such as sucralfate and barium are administered to bind to esophageal and gastric erosions and ulcers. Misoprostol may help prevent NSAID-induced ulceration when toxic levels of NSAIDs are ingested.

An active medications list should be kept with each animal's medical record and carefully reviewed daily for potential drug interactions, drug dosages, and possible adverse effects. If renal or hepatic function is compromised, or if protein (albumin) binding capacity is decreased, some drug dosages should be decreased to account for altered metabolism, elimination, or protein binding. The daily review also should ensure that the dosage has been calculated correctly and that it is appropriate for the animal’s current weight and body condition score. The sudden onset of any new clinical signs should be investigated in light of the medications and their potential adverse effects.

When nutritional needs are not met, animals rapidly develop a negative energy balance, which can result in GI dysfunction, organ dysfunction, poor wound healing, and even death. Direct enteral nutrition will improve the normal GI barrier, function, and motility. Enteral feeding is always preferred, and most animals tolerate trickle flow feeding techniques. Short-term options include syringe or forced feeding; however, this can lead to food aversion and is not comfortable for most critically ill animals. Easy to place and well-tolerated, short-term feeding tubes that allow trickle feeding include nasogastric, nasoesophageal, and nasojejunal. Nasogastric tubes also allow gastric suctioning to monitor GI function and may limit continued vomiting and risk of aspiration pneumonia; nasojejunal tubes can be challenging to place. Long-term feeding tubes include esophagostomy, pharyngostomy, gastrotomy, or jejunostomy tubes. Each of these tubes are well tolerated by most animals, and all require anesthesia to place; the esophagostomy is a minor surgical procedure, and gastrostomy tubes can be placed with endoscopic assistance.

Feeding by trickle flow is initiated with small volumes of a dilute veterinary liquid diet solution. If an animal has been starved for an extended period of time, nutrition should be increased slowly (by 25%–33% of daily caloric requirements per day) to avoid the hyperglycemia, hypokalemia, hypophosphatemia, and hypomagnesemia seen with refeeding syndrome.

For the first 12–24 hr, the diet should be calculated to provide ¼ to ⅓ of the daily caloric requirement and is diluted 1 part liquid diet to 2 parts water (or electrolyte solution). This volume is delivered by CRI over 12–24 hr or divided into small boluses every 2–4 hr. Before each bolus feeding and every 6 hr during a CRI, the feeding tube should be suctioned to determine whether any residual volume is present that would necessitate decreasing the volume infused or adding prokinetic agents. After suctioning or administering a liquid diet, the tube should be flushed with saline. If this initial feeding is tolerated, the concentration is increased to 2 parts liquid diet mixed with 1 part water during the next 12–24 hr. If this is tolerated, then the undiluted diet can be delivered to provide the full caloric requirements. As the animal recovers, bolus feeding can be introduced by gradually decreasing feeding frequency and increasing volumes.

When nutritional needs cannot be met by enteral feeding, parenteral feeding is used. Partial parenteral nutrition, consisting of amino acid and carbohydrate solutions, can be infused through a peripheral vein, providing part of the animal's caloric requirements in a readily metabolizable form. Total parenteral nutrition (including the lipid component) must be delivered through a central venous catheter, because high osmolarity of the solutions may cause phlebitis and RBC lysis. In animals with prolonged anorexia, vitamin supplementation may also be necessary.

Appetite stimulants, such as the serotonin antagonist cyproheptadine and the serotonin agonist mirtazapine, are commonly used but with varying success. Oral benzodiazepines may cause hepatotoxicity in cats and are not good alternatives; injectable benzodiazepines may be used as a short-term solution for animals with rapidly resolving disease. The use of appetite stimulants provides inconsistent food intake and is not recommended as the primary way to administer nutrition in critically ill animals.

Pain activates the stress hormone systems of the body and contributes to morbidity and mortality. Signs of pain are quite variable in animals; these may include decreased normal behavior (decreased appetite, ambulation, grooming, etc), development of abnormal behaviors (vocalizing, inappropriate urination, altered posture, signs of agitation or aggression, etc), reaction to touch, and altered objective physical parameters (increased heart rate, pale mucous membranes, dilated pupils, etc), which can mimic signs of shock. (Also see Systemic Pharmacotherapeutics of the Nervous System and see Pain Assessment and Management.) Animals that may not show obvious signs of pain but are known to have a painful condition should receive analgesics as part of their treatment (see Analgesics Used in Emergency Practice). Preemptive administration of analgesics is recommended, when possible. Pain should be assessed using a validated pain assessment tool and monitored on a regular basis during the course of hospitalization to ensure adequate analgesia.

Analgesia in critically ill animals can safely be provided by opioids titrated to effect. Opioids provide potent analgesia (given IV, IM, or SC) with minimal cardiovascular adverse effects, and their actions are reversible with antagonists (eg, naloxone). Long-acting opioids are best avoided in unstable animals. Reports of IV morphine causing hypotension due to histamine release do not seem to be clinically significant if the drug is given over 5–10 min or as a CRI. Other medications such as hydromorphone, oxymorphone, and fentanyl can be given without this risk. CRI provides constant analgesia and is often more convenient and less painful than intermittent IM or SC injections. In cats, injectable buprenorphine is absorbed systemically after sublingual administration. Neuroleptanalgesia can be provided by combination of an opioid with a sedative (eg, benzodiazepine) or tranquilizer (eg, acepromazine) in animals without contraindications to these medications.

For longterm control of pain, transdermal fentanyl patches or repository fentanyl injections are used but require up to 12 hr to reach therapeutic blood levels; analgesia must be provided by injection until adequate blood levels have been reached.

If pain is not adequately controlled with opioids alone, then ketamine, an NMDA receptor antagonist, can be delivered by CRI with the opioids. Ketamine may have variable effects on the cardiovascular system, making patient selection crucial, and it should not be used as a sole agent for pain relief. Lidocaine, a local anesthetic, can be used as an adjunct for systemic pain relief when delivered as a CRI and combined with ketamine and/or an opioid. Some investigation into using maropitant as an adjunctive analgesic agent is promising, because it decreased anesthetic requirements during noxious stimuli in dogs.

Local pain relief can be provided using local infiltrative or nerve blocks on extremities. Intermittent infusions of bupivicaine administered through thoracotomy tubes or abdominal catheters can provide pleural and peritoneal analgesia. Epidural injections by needle or infusions by catheter can provide pain relief from pelvic, hindlimb, and abdominal injuries or disease.

NSAIDs are rarely used in critically ill animals because of their effects on the GI tract, kidney, and liver; however, they may be appropriate in animals with significant fevers or orthopedic injury that are not systemically ill. Alpha-2 agonists (such as dexmedetomidine) provide sedation as well, but case selection is critical because of the significant cardiovascular adverse effects. Other oral classes of medication that are well tolerated for mild to moderate pain include tramadol, amantidine, and gabapentin. Adjuvant methods of pain relief may include placing ice packs on regions of swelling, acupuncture, laser therapy, or massage.

Providing nursing care to critically ill animals requires a skilled, knowledgeable, attentive, and highly trained nursing staff. Recumbent animals should be turned from one side to the other every 4 hr or maintained in variations of sternal recumbency to prevent decubital ulcers and atelectasis. Physical therapy 3–4 times a day is important to maintain range of motion and muscle tone and blood flow; this can be provided through massage, passive range of motion, encouraged activity, etc. Activity may also improve GI motility and provide a time when animals can urinate and defecate outside of their kennel. Catheters should be labeled and marked with the date of placement, and catheter sites should be inspected on a routine basis for signs of infection or displacement. When catheters are removed, the entrance site should be inspected for inflammation/infection. Urine and fecal soiling should be immediately cleaned. Recumbent animals require regular inspection and cleaning to prevent urine scalding of the skin; tail wraps minimize contamination from diarrhea. Nursing care must be tailored to the specific condition(s). A well-trained nursing staff can recognize deterioration or alterations in an animal often before the attending clinician because of the substantial amount of hands-on time with the patients.

Bandages, essential to cover wounds, should be changed whenever they become soiled or wet. Distal limb edema can be improved by placing light compression wraps that are changed every day. (Also see Wound Management.) Open wounds should be bandaged on arrival to prevent further contamination or nosocomial infection until surgical debridement can be done. Areas of skin swelling or bruising should be marked to determine progression or resolution of the pathology.

Owner visits should be encouraged. Animals should be handled and spoken to kindly to minimize stress and anxiety. Having familiar items such as toys or blankets from home are helpful for some pets. Consolidating several treatments at one time and turning down the lights at night, when the animal’s condition permits, allow the animal some time to rest and sleep undisturbed.