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Critical Care Amy Butler, DVM, MS, DACVECC Ohio State University Shock - Recognition, Pathophysiology and Treatment What is shock? Shock is often defined as oxygen delivery to the tissue that is insufficient to meet tissue requirements. This may be due to altered hemodynamics, such that the circulatory system is unable to provide adequate pressure to drive perfusion. Or, shock can occur when tissues are receiving adequate flow, but there is either not enough oxygen in the blood or the tissues are unable to extract and utilize the oxygen. In fact, there is not a true definition for shock since it is not a true diagnosis. Shock is a syndrome of clinical signs that has multiple underlying causes. Classically, the signs that indicate the shock state are:
The hallmark of shock is that cellular oxygen delivery is insufficient to meet demand. Initially, peripheral vascular beds will vasoconstrict to shunt flow to the "essential organs" (brain and heart). This results in reduced perfusion and oxygen delivery to the affected vascular beds. In the dog, the GI tract is considered the shock organ since it takes the brunt of vasoconstriction. Unless shock is rapidly reversed, tissue beds enter an anaerobic state. The products of cellular metabolism build up in tissues, including lactate, acids, nitric oxide, CO2 and adenosine. As ATP stores decrease, membrane pumps are unable to maintain electrochemical gradients, leading to cellular edema. Over time, cellular death will occur, resulting in cell lysis, inflammation, free radical formation and local activation of coagulation. As the by-products of cellular metabolism continue to accumulate, these local factors can eventually overwhelm the vasoconstriction induced by the sympathetic nervous system. This results in vasodilation, systemic hypotension, decompensate, and entry of metabolic byproducts, cytokines, free radical and activated white blood cells into systemic circulation. Many compensatory mechanisms are induced in the shock state. The goals of the compensatory mechanisms are to maintain perfusion to the core organs and restore vascular volume. These include:
The earliest stage of shock is the compensated phase. During this period of time, compensatory mechanisms are able to maintain blood flow to the important organs through peripheral vasoconstriction. Clinical signs are the "classic" signs of shock, and include pale mucous membranes, poor pulse quality and cold extremities secondary to vasoconstriction. Tachycardia is a result of SNS activation, as the body tries to maintain cardiac output. Blood pressure is usually normal to high as a result of vasoconstriction. Remember that the overall goal of compensation is to maintain blood pressure, and a normal blood pressure does NOT mean that perfusion is normal. Over time, the body is either able to "fix" the blood volume and return to normal homeostasis, or it goes into decompensated shock. This phase occurs when local tissue beds that were vasoconstricted begin to vasodilate. Vasodilation leads to pooling of blood and maldistribution of flow to "non-essential" organs. Clinical signs include grey mucous membranes, bradycardia, loss of vasomotor tone leading to hypotension, and severely altered mentation. The patient is often stuporous to comatose. Ventricular arrhythmias can be seen on an ECG. It is important to realize that the progression from compensated to decompensated shock can occur over minutes to hours depending on the cause and severity of injury, and that patients can present anywhere along this spectrum. Cats present a special challenge since they do not always display the classic signs of shock like dogs do. The shocky cat often presents with bradycardia, hypothermia and hypotension, even in the early stages of shock. The causes for this are unknown, although it is documented that cats have species specific alterations in vascular tone and in vascular response to injury. Treatment of the decompensated shock patient may result in resolution of clinical signs of shock, but the patient may decompensate again soon after resuscitation. This is the result of inflammatory mediators and free radicals being flushed back into systemic circulation, setting up DIC and the systemic inflammatory response syndrome, and eventually multi-organ dysfunction. In short, there was simply too much tissue damage to fix despite appropriate shock therapy. Causes of shock Multiple classification systems and etiologies of shock have been described. The classic approach will be used here
The treatment of shock depends on rapid determination of the underlying cause. For example, the 12 year old Poodle with a Grade V/VI heart murmur and pulmonary crackles in shock is likely to be cardiogenic in origin. The cat with a PCV of 6% is likely to have anemic shock. The causes and treatment principles of the various shock categories are listed below.
Many adjunctive therapies have been described. The most of these include:
Shock resuscitation is aimed at improving tissue oxygen delivery such that homeostasis can be maintained. Therapy should always be titrated to effect and halted once the endpoints of resuscitation are achieved. Over-zealous fluid administration can cause more harm than good, and complete shock volumes should not be given unless necessary. Therefore, it is important to constantly monitor endpoints of resuscitation during shock therapy. These include: Heart rate - This is the easiest modality to measure. For the patient in compensated shock, the heart rate should decrease during resuscitation. In cats, heart rate should increase to normal if presented with bradycardia. Unfortunately, ongoing pain or stress can obscure the response to therapy. Pulse quality - This should improve with shock therapy. However, pulse quality is a relatively imprecise indicator of blood pressure since pulse pressure is merely the difference between the systolic and diastolic pressures. A normal pulse quality does not mean that the animal is fine, but a poor pulse quality usually indicates ongoing issues. Mucous membrane color - MM color reflects the degree of tissue perfusion. If there is on-going vasoconstriction, MM color will remain poor. However, vasodilatory conditions such as sepsis may cause normal color even in the face of severe shock. Additionally, ongoing pain can contribute to peripheral vasoconstriction even without shock. Mental status - Improvements in mentation often lag behind normalization of other parameters, so it should not be used as the sole measure of shock resuscitation. However, improvements in mentation are expected as shock is resolved. Mental status can be difficult to asses in patients with CNS disease or head trauma. Arterial blood pressure - This modality is one of the most frequently used to assess shock states, but the astute clinician also should realize the limitations of blood pressure measurement. A normal blood pressure does not mean that the patient is fine, and an abnormal blood pressure definitely means that something is not right. Out of all parameters, blood pressure is the most protected by compensation for shock. Normalization of blood in conjunction with normalization of heart rate, mucous membrane color and mentation indicate the shock resuscitation has been successful. PCV/TS - These are insensitive indicators of shock resuscitation. Even with severe blood loss, redistribution of fluid from the interstitial to intravascular compartments takes time. Further changes in PCV will occur with fluid administration, or PCV can be falsely elevated due to splenic contraction. PCV can be useful for determining the need for blood transfusions. Urine output and specific gravity - Urine output is an excellent indicator of renal blood flow, provided that the patient does not have pre-existing renal disease. The normal urine output for a patient on IV fluids is 1-2 ml/kg/hr. The well-hydrated patient should have a urine SG of 1.012-1.020. Unfortunately, shock states can cause acute renal failure or impaired concentrated ability, which limit the usefulness of this as a monitoring tool. Additionally, evidence of good renal perfusion does not necessarily equal normal perfusion in other tissues. Acid-base balance - Shock states are usually associated with metabolic acidosis. Successful treatment of shock should cause an improvement in pH and base excess back towards normal. Failure of base excess to return to normal is associated with a worse prognosis. Lactate - This is a good marker of tissue perfusion, especially in the GI tract. Lactate is produced by tissues undergoing anaerobic metabolism. Remember that the measured value is the balanced between lactate production and clearance. Decreased clearance (i.e., liver disease) can cause elevations in lactate. Additionally, severely underperfused tissue can have lactate trapped, resulting in falsely low blood concentrations. Lactate has been shown to be an important prognostic marker. Failure to reduce lactate concentrations have been strongly correlated with a worse prognosis for multiple diseases. The important point is that multiple parameters should be assessed to judge response to shock resuscitation. No single marker has been shown to be strongly correlated with successful treatment, therefore, the entire patient should be reassessed frequently (every 10-15 minutes) during the resuscitation period. A Refresher on IV Fluid Therapy The objective of this lecture to aid the practitioner in answering the following fluid therapy questions:
Fluids are divided into two main groups: crystalloids and colloids. Crystalloids contain solutes (variable amounts of electrolytes), water and may contain dextrose. They distribute throughout the extracellular fluid compartments rapidly, and will slowly equilibrate with the intracellular fluid compartments. They are characterized based on their tonicity (isotonic, hypotonic, hypertonic) and by their effects on acid-base status (alkalinizing or acidifying). Colloids contain large molecules that cannot (or slowly) escape from the intravascular space, thus, they have a smaller volume of distribution compared to crystalloids. The colloids are classified based on their origin (synthetic vs. natural). Isotonic crystalloid solutions: All of these solutions are approximately isosmolar to blood and replace electrolytes as well as water. Their volume of distribution is predominantly the extracellular space. Following administration of a crystalloid bolus, 65-75% of that fluid will leave the intravascular space and redistribute to the interstitial space within 30 minutes. This is the basis for the 3:1 rule (replace 1 part blood lost with 3 parts crystalloid). Clinical indications for isotonic crystalloid therapy are many, but the most common uses are shock resuscitation, rehydration and replacement of isotonic losses. 0.9% NaCl: This is considered an acidifying solution, but not just because it has an acidic pH. The acidifying effects are due to the high chloride concentration (154 meq/L) compared to plasma (110 meq/L) which will, over time, create hyperchloremia and thus acidosis. Because of it's high chloride and sodium content compared to plasma (see table below), it is considered the fluid of choice for Addisonian crisis and hypochloremic metabolic alkalosis (as occurs with upper GI obstruction). It is often used in management of the DKA patient as those patients are usually total body sodium depleted. Normosol-R and Plasmalyte 148: These similar buffered solutions are considered alkalinizing as they both contain acetate and gluconate, which are broken down by a number of tissues to bicarbonate. These have similar electrolyte compositions and contain magnesium. There are no specific indications or contraindications for use of either, although research has shown that rapid blousing of acetate containing solutions in animals at a deep plane of anesthesia caused temporary hypotension. Lactated Ringer's Solution (LRS): This is an alkalinizing solution that uses lactate as the bicarbonate precursor, a process that occurs in the liver. Therefore, end-stage liver disease is a potential contraindication as hyperlactatemia could result. LRS has the lowest osmolarity and lowest sodium concentration (130 meq/L) compared to other isotonic crystalloids. The only major contraindication for use of LRS is in-line (i.e., via the same catheter) administration with blood products. The calcium in LRS will chelate the anticoagulant in the blood products and could lead to thrombosis. A common question is: which isotonic crystalloid is the best for the shocky patient? Millions of dollars and decades of research have been performed to answer this question. The answer is… they are all pretty equivalent. It doesn't matter which one you use, so long as you use one of them. Hypotonic Crystalloids Examples of these include 5% dextrose in water (D5W), 0.45% NaCl (½strength), 0.45% NaCl with 2.5% dextrose (½ and ½) and Normosol-M. While some of these solutions (D5W, ½ and ½) are similar in osmolarity to blood, they are considered hypotonic solutions. This is because the dextrose is rapidly taken up by the cells, leaving a hypotonic solution. Hypotonic crystalloids rapidly redistribute within the total body water, leaving very little in the intravascular space. These fluids are used for replacing a free water loss (hypernatremia) and for maintenance fluid therapy. They should never be used for fluid resuscitation from shock, as they do not provide meaningful expansion of the intravascular volume. 0.45% NaCl (with or without dextrose): These fluids are used for maintenance fluids, or to expand free water (for the hypernatremic patient). They can also be used for patients with end-stage renal or heart failure, as they contain lower sodium concentrations (77 meq/L) and may help to prevent volume overload. They may also be used for patients receiving bromide therapy. Higher chloride containing solutions can decrease bromide levels through decreased renal retention of bromide. 5% dextrose in water: Since D5W is basically sterile water, this fluid is normally used to replace free water in the hypernatremic patient. Care should be used to not decrease sodium concentrations faster than 0.5-1.0 meq/hr as neurological sequealae may develop. D5W contains only 170 kcal/L from dextrose, and is not sufficient to meet energy requirements. For example, an average sized cat requires 220 kcal/day and would need almost 1.3L/day, or 54 ml/hr, to meet its RER. Normosol-M: This solution is similar to Normosol-R in that it contains magnesium, and utilizes acetate and gluconate as buffers. It also has 13 meq/L of potassium, which could cause cardiovascular problems if large amounts are rapidly bloused. It is intended for maintenance fluid therapy once replacement requirements have been met. Hypertonic solutions 7% NaCl (HTS - hypertonic saline) is used for rapid expansion of the intravascular volume. HTS pulls fluid primarily from the interstitial compartment. The advantage is that only small volumes are required to increase intravascular volume quickly. Its use is primarily for treatment of the head trauma patient and in shock resuscitation. Anti-inflammatory effects have also been documented. The volume expansion provided by HTS is short lived, as the sodium redistributes throughout the extracellular compartment quickly. HTS is available as both 7-7.5% and 23% solutions. The 23% solution MUST be diluted prior to administration. HTS should be administered no faster than 1ml/kg/min as vagally mediated bradycardia or arrest could occur. Synthetic Colloids 6% Hetastarch (HES) and Hextend: Both are made with hydroxyethyl stach, a polydispersed starch complex. Hetastarch is dissolved in 0.9% NaCl, while Hextend is dissolved in modified LRS. The volume of distribution is primarily within the intravascular space, depending on the vascular permeability. Administration increases intravascular volume by 1-1.4x, and the duration of action is almost 24 hours. Indications include volume resuscitation and oncotic support for hypoprotenemia. At doses greater than 20 ml/kg/day, a dose dependent coagulopathy has been reported. However, this has not been shown to increase risk of clinical bleeding in veterinary patients. Voluven: As of January, the manufacturers of HES have suspended production due to the above mentioned coagulopathy. At OSU, we have started stocking Voluven, another form of HES with a lower C2:C6 substitution ratio. This reduces the likelihood of coagulopathy even with doses greater than 20ml/kg/day. The cost per 500ml bag is $44, compared to Pentastarch at $62/bag. Natural Colloids Blood products will be considered elsewhere during this lecture series. Human Albumin (HA): Is used to increase oncotic pressure. Albumin distributes throughout the extracellular fluid volume, so relatively large doses must be given. Initially, administration of HA results in an increase in intravascular volume of 3-5x until redistribution occurs. It has not been proven to be superior to isotonic crystalloids for shock resuscitation. Its use in veterinary medicine is controversial due to transfusion and delayed immunologic reactions. What route of delivery should be used? The intravenous route should be used for all patients with: cardiovascular compromise or shock, moderate to severe dehydration, or for patients with significant ongoing losses. If venous access cannot be obtained (especially in small/pediatric patients), the intraosseus route can be used, or a vascular cutdown can be performed. The subcutaneous route should not be used in the shocky patient as peripheral vasoconstriction will severely limit absorption. In the mildly dehydrated patient, the subcutaneous route is sufficient. How fluid should be given, and how fast? The three phases of fluid delivery are resuscitation, replacement and maintenance. The resuscitation phase is the rapid restoration of intravascular volume by administration of intravenous fluids. This is used to address hypovolemia, and is not required in all patients. Signs of hypovolemic shock, such as tachycardia (bradycardia in the cat), pale mucous membranes, altered mentation, cool extremities and poor pulses, indicate the need for resuscitation. For isotonic crystalloids or colloids, the shock doses should be divided into aliquots of 1/4 to 1/3 of the total volume and repeated as needed to resolve signs of shock. Shock doses are listed below:
Once shock signs are alleviated, as evidenced by normalization of heart rate and pulse quality, improved mentation, pinker mucous membranes, and reduction in lactate concentrations, resuscitation therapy should cease. Shock doses should be given over a 15-20 minute period, reassessing the patient after each aliquot is given The replacement phase is aimed at replacing the extravascular volume lost during fluid shifts that occur to maintain intravascular volume. Fluid losses, such as those that occur with vomiting, diarrhea, renal disease and excessive insensible losses will initially lead to dehydration (loss of TBW), and finally to signs of hypovolemia. Again, if signs of hypovolemia are present, fluid resuscitation should precede replacement. Isotonic crystalloids should be used for replacement. Clinical signs of dehydration include tacky mucous membranes, decreased skin turgor, sunken eye position within the orbit, and prolonged CRT. Signs of hypovolemia are almost always present in patients with >10% dehydration. To calculate dehydration, the estimated percent dehydration should be multiplied by body weight (in kg) to estimate the replacement amount in liters. This should be replaced over 8-24 hours. After replacing the estimated replacement amount, the patient should be re-assessed and fluid requirements recalculated. Fluids should always be titrated to effect. Replacement fluids should also be used for ongoing fluid losses. Ongoing losses can be estimated by weighing diarrhea or vomitus. Daily fluctuations in body weight can be very useful indicators of fluid status. Maintenance fluids are based on the physiological fluid requirement. There are multiple formulas to calculate maintenance requirements, but allometric scaling best predicts fluid requirements in very small and very large patients. Formulas include: The choice of crystalloid fluids depends on the volume status and electrolyte concentrations of the patient. Hypotonic crystalloids can be used as indicated, especially in the hypernatremic or hyperchloremic patient.
Approach to the Dyspneic Patient Dyspnea is defined as the sensation of difficulty with breathing, or is often referred to in human medicine as shortness of breath. Since veterinary patients cannot report sensations, we commonly use the term respiratory distress. Patients in respiratory distress have an exaggerated work of breathing. Normally, only 3% of the total energy expend by the body goes towards breathing. In patients with severe respiratory distress, that percentage can climb to upwards of 40%. There are 4 major categories of respiratory distress etiology. These include: upper airway disease, lower airway disease, parenchymal disease and pleural space disease. Many other disease conditions, such as pain, stress, hyperthermia, anemia, CNS disease or compensation for a metabolic acidosis, can mimic dyspnea without true pulmonary pathology. The hallmark signs of dyspnea are open mouth breathing, cyanosis, abdominal effort, increased respiratory rate and effort, flaring nostrils, and orthopneic stance. More subtle signs can include hiding, weight loss, loss of appetite, decreased activity, and lethargy. Upper Airway Disease Clinical Signs: Upper airway disease can often be diagnosed by its classic obstructive breathing pattern. The obstructive pattern is associated with long, slow inspiration, stridor or stertor (depending on whether the obstruction is fixed or dynamic), increased effort +/- abdominal component, and orthopnea. Severe hyperthermia may be present, especially in dogs. Thoracic auscultation usually reveals referred upper airway sounds, found best by ausculting over the trachea. Obstruction can also cause non-cardiogenic pulmonary edema, resulting in pulmonary crackles. Pathophysiology: While most upper airway obstruction is associated with inspiratory dyspnea, intrathoracic upper airway obstruction can cause expiratory distress. Narrowing of the airway is responsible for reduced and turbulent air flow. As the patient works harder to breathe against the obstruction, further edema and inflammation result, creating a viscous cycle. Airway obstruction reduces the amount of exhaled CO2 and inhaled O2, and hypercapnemia with hypoxemia is a common feature. Etiologies: In dogs, the most common reasons for airway obstruction are laryngeal paralysis, brachycephalic airway syndrome and collapsing trachea. In cats, nasopharyngeal polyps, severe nasal disease, and tracheal masses are more common. Both species can have airway obstruction as a result of foreign bodies, intraluminal or extraluminal masses, abscesses or granulomas, or strictures. Treatment: The primary treatment for upper airway obstruction is sedation and supplemental oxygen. Sedation lessens the work of breathing, reduces airway collapse and lessens obstruction. Butorphanol 0.1-0.2 mg/kg IV or IM is a good choice for the unstable patient. If the patient is cardiovascularly stable, acepromazine 0.02-0.05 mg/kg IV or IM can be with or instead of butorphanol. Sedation should be titrated to effect. Upper airway obstruction tends to be oxygen responsive, but hypercapnemia may still be present. If the patient does not responds to initial sedation and oxygen, or if it is in severe distress, induction and intubation are appropriate. Emergency tracheostomy may also be indicated if a mass is present in the upper airways and the patient cannot be intubated. Diagnostics: Once the patient is stable, appropriate diagnostics include sedated upper airway exam (looking for elongated soft palate, nasopharyngeal polyps, laryngeal paralysis or masses), and otic exam, and thoracic and cervical radiographs. CT, rhinoscopy or tracheal fluoroscopy may be required for difficult to diagnose cases or to determine the extent of lesions. Lower Airway Disease Clinical signs: Lower airway disease is associated with expiratory distress, defined by normal inspiration and exaggerated, prolonged expiration. Expiratory wheezes are usually present on thoracic auscultation. A marked abdominal "push" may be present. Cats may present with a history of coughing. A heart murmur is usually not ausculted unless severe airway disease has led to cor pulmonale. Pathophysiology: In lower airway disease, edema and cellular infiltration of the bronchiole walls leads to thickening and weakening of the bronchial walls, excessive secretion and mucus plugging. Further narrowing is caused by acute bronchospasm. As the patient inhales, radial traction on the lungs pulls the airways open and allows air to enter the alveolus. During expiration, negative intrathoracic pressure causes the airways to collapse, trapping air inside the alveolus. Since the alveolus is already full on the next Inspiratory cycle, the result in decreased gas exchange and hypoxemia. These changes are further complicated in the presence of secondary bacterial infections. Etiologies: Expiratory dyspnea is most common in cats, and is pathognomonic for feline asthma. These cats typically have a history of a non-productive cough, "coughing up hairballs", or open mouth breathing after exercise, and are typically young to middle aged. Dogs can develop chronic bronchitis with secondary bacterial infections. Treatment: The initial therapies are sedation and supplemental oxygen. As above, opioids should be used in the non-stable patient. Butorphanol is more sedating than other opioids, and a dose of 0.1-0.2 mg/kg IV or IM can be administered. Physical exam should be very brief to minimize stress. If the patient struggles, stop! This is not the patient you want to fight with to place an IV catheter. Albuterol 2 puffs via facemask should be administered. Albuterol is a fast-acting local ?2 agonist. If an albuterol inhaler is not available, terbutaline 0.01 mg/kg SQ can be administered. Aminophylline and theophylline are much slower to act, and the negative effects of atropine and epinephrine outweigh their benefits. Steroids are a feature of long-term asthma control, but take time to work and are not immediately indicated in asthma treatment. Once the patient has been stabilized, steroid therapy can be initiated. Diagnostics: Thoracic radiographs should be taken only once the patient is stable. Cats with asthma will have a flattened diaphragm, over-inflated lungs, and may have right middle lung lobe atelectasis secondary to airway trapping. The hallmark of lower airway disease in both cats and dogs is the presence of the bronchiolar pattern on thoracic radiographs, including the presence of "doughnuts" and "tramlines" that indicate infiltration of bronchiolar walls. Airway cytology and culture can be used to rule out secondary bacterial infections. Mycoplasma is a common infectious agent, but requires special growth media. Doxycycline is the antibiotic of choice for treatment. Most times, lower airway disease is based on the presence of compatible clinical signs, radiographic findings, and the absence of cardiac disease. Pulmonary Parenchymal Disease Clinical Signs: Parenchymal disease does not have a specific respiratory pattern. Respirations are usually short, rapid and deep, but may mimic any of the other respiratory patterns. The patient may be in severe distress, cyanotic, and/or have a marked abdominal component. The best way to diagnose parenchymal disease on physical exam is to auscult the presence of crackles. A heart murmur may be ausculted in patients with cardiogenic edema. Dogs will commonly have a history of a cough (productive or not), while cats rarely cough with parenchymal disease. Bradycardia and hypothermia may be noted in the cat with congestive heart failure. Fever may be present in the patient with pneumonia. A thorough history should be taken to cover the most common causes of parenchymal disease, including any history of vomiting or recent boarding (pneumonia), potential trauma (contusions or non-cardiogenic edema), or heart disease (cardiogenic). Pathophysiology and Etiology: Crackles are the sound of collapsed alveoli and lower airways "popping" open at the end of inspiration, and indicate fluid filled alveoli. There are only a few types of fluid that can be present: blood (pulmonary contusions or hemorrhage), pus (pneumonia), or water (cardiogenic or non-cardiogenic edema). Pulmonary contusions are most commonly the result of blunt force trauma to the lungs, which causes rupture of vessels and bleeding into the alveoli. Pulmonary hemorrhage can occur as a result of coagulopathy. Pneumonia can be spread by the hematogenous route, but is more commonly associated with aspiration and vomiting. Cardiogenic edema is caused by left sided heart disease and increased pulmonary venous pressures. Non-cardiogenic edema is associated with severe seizures, head trauma, strangulation, airway obstruction and electrocution. Cardiogenic edema is low in protein and is caused by increased hydrostatic pressure within the pulmonary veins and capillaries. Non-cardiogenic edema is thought to be caused by endothelial injury and vascular leak of protein-rich fluid into the alveolus. Treatment: As above, the initial treatments of choice are sedation and supplemental oxygen. Since these patients are more likely to be cardiovascularly unstable, butorphanol is preferred over acepromazine. However, trauma patients may require stronger analgesia than that offered by butorphanol. In those cases, I will reach for methadone 0.2-0.5 mg/kg IV or hydromorphone 0.1-0.2 mg/kg IV. If a heart murmur is present, or if heart disease is strongly suspected, a single dose of furosemide 2 mg/kg (dogs) or 1 mg/kg (cats) IV or IM is not likely to cause harm. Once further history and diagnostics have been collected, additional treatment may be indicated. The goal of initial treatment is to get the patient stable enough for radiographs. If that patient is severely dyspneic and does not quickly respond to treatment, then the patient should be anesthetized, intubated and mechanically ventilated. Positive end-expiratory pressure (PEEP) of 5 cmH2O can help to recruit alveoli. Diagnostics: A thorough history is often the first step in diagnosis. Physical exam will also aid in making the diagnosis. Look carefully for other signs of trauma (bruising, especially episcleral or in the inguinal region) or injury. A burn at the lip commisures indicates electric shock. As above, the presence of a heart murmur is helpful, but does not always mean that cardiogenic edema is present. Fever may indicate infectious disease. Thoracic radiographs are the best way to help determine the underlying cause. An interstitial to alveolar or alveolar pattern suggests parenchymal disease. The following radiographic distributions can be useful in helping to determine the underlying cause:
Additional Treatment: Definitive treatment will be dictated by the diagnosis. Furosemide is indicated in cases of cardiogenic edema, but not in non-cardiogenic edema or pneumonia. IV fluid therapy and broad spectrum antibiotics are indicated for treatment of suspected pneumonia. There is no specific treatment for pulmonary contusions and non-cardiogenic edema other than supportive care and oxygen therapy. Pleural Space Disease Clinical signs: The restrictive pattern is the hallmark of pleural space disease. This is a short, shallow, rapid breathing pattern. The lungs may take on a "sprung" appearance, where the chest wall seems wider than normal, especially with pneumothorax. On auscultation, lung sounds and/or heart sounds may be dull. If pleural effusion is present, lung sounds will be loudest dorsally and a fluid line may be ausculted. If pneumothorax is present, lung sounds will be loudest ventrally. Borborygmi may be noted on thoracic auscultation in patients with diaphragmatic hernia. A heart murmur or gallop may be ausculted in patients with heart disease. Pathophysiology: The presence of air, fluid, organs or masses in the pleural space prevents expansion of the lungs by increasing intrapleural pressure above intrapulmonary pressure. As a result, the tidal volume is greatly increased, and animals must breathe must faster than normal to maintain an adequate respiratory minute volume. Progressive collapse of alveoli leads to hypoventilation, VQ mismatching and hypoxemia. Etiology: There are 4 things that can be in the pleural space: air, fluid, organs and masses. Pneumothorax is usually caused by trauma (either blunt or penetrating), but may be spontaneous due to rupture of bullae or severe parenchymal disease. Pleural effusion can be caused by hemothorax (rare), infection (pyothorax), heart failure, neoplasia or accumulation of chyle. Rarely, overhydration or hypoalbuminemia can cause pleural effusion. Diaphragmatic hernia (congenital or traumatic) and large intrathoracic masses can also cause clinically relevant pleural space disease. Treatment: Again, oxygen and sedation are the initial treatments. Diuretics are not effective for rapid removal of pleural effusion. Once the patient is appropriately sedated, thoracocentesis should always be performed prior to radiographs if pleural space disease is suspected. A chest tap should be performed at the 7th or 8th rib space, with the needle directed perpendicular to the chest wall. Continue to remove fluid or air until as much as possible is gone. If negative pressure cannot be achieved, if more than 2 taps are required in a one hour period or more than 3 taps are required in a 24 hour period, a chest tube should be placed. Thoracocentesis has a low rate of complications, but can cause hemorrhage, lung injury or introduce infection if not performed sterilely. In cases with long-standing pleural effusion, rapid and fatal re-expansion pulmonary edema can occur. Diagnosis: The presence of pneumothorax should prompt a search for pulmonary disease if there is no history of trauma. Traumatic pneumothorax generally resolves without surgical intervention, although some injuries can take up to a week to heal. The causes of pleural effusion are many, but the etiology can be narrowed with cytology of the fluid. Below is a table of the common causes of pleural effusion and their cytologic characteristics. In cats especially, echocardiogram may be required to differentiate causes of modified transudate. If thoracocentesis is negative, thoracic radiographs looking of an underlying cause of the restrictive pattern should be performed. Diaphragmatic hernias will require surgery to repair. A blanket waiting period of 24 hours after the onset of traumatic diaphragmatic hernia is no longer recommended - patients should be taken to surgery as soon as they are stable.
Practical Transfusion Medicine Objectives:
Components of Transfusion Therapy Red Blood Cells The average canine red blood cell has a life span of 120 days, and slightly less for the cat (60-120 days, depending on reference). Red blood cells are present in many products, including fresh whole blood (FWB), whole blood (WB) and packed red blood cells (pRBCs). The life span for transfused red blood cells is shorter than for normal red blood cells, but there is no consensus on how long these products last. Transfusion longevity depends on the underlying disease process, the presence of immune-mediated disease and the oxidative status of the animal. The dose of RBCs depends on the product. Whole blood products are dosed at 2 ml/kg (or 1 ml/pound) to increase the PCV by 1%. pRBCs are dosed at 1 ml/kg to increase PCV by 1%. The goal is NOT to transfuse to a normal PCV, but to transfuse to normalization of clinical signs. A common question regarding RBC transfusion is: when should I give a transfusion? Again, the clinical condition of the patient should dictate this. A patient who rapidly goes from a PCV of 45% to 20% will be sicker than a patient who is chronically at a PCV of 17%. In general, tachycardia, elevated lactate, severe lethargy, ST segment depression or other signs of tissue hypoxia should guide transfusion. I typically aim to increase the PCV by 5-10%, and then reassess the patient to determine if additional RBCs are needed. Clotting Factors Plasma contains many protein components. These include the clotting factors (stable and labile), von Willebrand factor (vWF) and fibrinogen (factor I). The products that contain clotting factors are FWB (all factors), FFP (all factors), FP (stable only) and cryoprecipitate (FVIII only). The vitamin-K dependent clotting factors (II, VII, IX, and X) are considered stable factors, whereas factors V and VIII are labile factors, meaning that their amounts decrease with storage. The most common reason for coagulopathy in veterinary medicine is anti-coagulant rodenticide toxicity (ACR). This can be treated with any product except for cryoprecipitate. Patients with von Willebrand disease can be treated with FFP, FWB or cryoprecipitate. If the cause of the clotting disorder is unknown, FFP is the best treatment. The dose of plasma (either fresh or frozen) to improve clotting times is 10-15 ml/kg repeated as needed until PT and aPTT have normalized. If FWB is used for this purpose, the dose must be doubled as the plasma fraction is roughly ½ of the amount transfused (the other ½ being the RBCs). There is significant debate over when clotting times need to be corrected. A rough rule of thumb is that if the patient is bleeding or at high risk of bleeding (clotting times significantly prolonged, invasive procedure), then transfusions should be given. Albumin Unfortunately, transfusions are a very poor way of increasing albumin levels. To increase albumin by 1.0 g/dl, approximately 40 ml/kg of plasma must be given. Each unit of plasma can be 125-250 ml/unit, depending on the source of the unit. This makes plasma transfusions impractical and expensive for most patients. Remember that albumin distributes through the entire extracellular fluid compartment, not just the intravascular volume. Therefore, very large amounts must be given. Human albumin is a more efficient method of increasing albumin, although significant debate exists about its safety in veterinary patients. The best way to increase albumin is to ensure an adequate nutritional plan. Platelets Platelets are by far the most difficult blood component to transfuse. FWB, platelet-rich plasma (PRP) and lyophilized platelet (LP) products are available. Remember that regular plasma does NOT contain platelets are they are unable to survive either refrigeration or freezing unless special precautions are taken. While both PRP and LP contain active platelets, there is no information on how long those platelets are active once they are transfused. There is no information available on the longevity or activity of platelets in FWB. Von Willebrand Factor vWF is a multimer that is carried in circulation by Factor VIII, and functions in platelet activation and aggregation. Additional stores of vWF are released by platelets and vascular endothelium during coagulation. von Willebrands Disease (vWD) is a decreased amount of circulating vWF, and is manifested as bleeding tendencies. Sources of vWF are FFP, FWB, and cryoprecipitate. Lyophilized cryoprecipitate is available as well, although care must be taken to order the appropriate size. Some vials are made from 125ml plasma, while others are made from 250ml plasma. The dose of FFP or FWB is the same as for correction of clotting factor disorders. The dose of cryoprecipitate is 1 unit per 5-10kg, again depending on the size of the plasma vial from which it is made. Indications for use: The following lists the indications for the most commonly available blood products.
What to Do If You Don't Have A Blood Bank Donor Selection If a blood bank is not immediately available, your practice will rely on use of donor animals, and you will use fresh whole blood for the majority of your patients. Prior to use of ANY animal for blood donation, consider the following: Dogs: Donor dogs should be ideally large (30-50 kg), young (between 1-7 year old), and tolerant of restraint. They should be screened before blood collection to be DEA 1.1 and 1.2 negative, healthy and transmissible-disease free (Ehrlichia canis/platys, Brucella canis, Babesia canis, and Dirofilaria immitis). At a minimum, they should be heartworm negative and on year-round prevention. Cats: Donor cats should be at least 5 kg, young, indoors, vaccinated and negative for FeLV and FIV. Similar to dogs, a blood type, complete blood cell count and chemistry panel should be done prior to enrollment as a donor. In addition they should have no signs or symptoms of Feline Infectious Peritonitis, and ideally have a low titer. Preferably they should live in a low risk environment for all infectious feline disease (indoor only small population households). In hospital donors can have blood drawn up to every 10 days (if ABSOLUTELY necessary), however, a minimum of three to four weeks between donations is a more common and safer practice. All donors should be well-vaccinated, have monthly flea and heartworm prevention, and live in a disease-free environment. Drawing and storing blood Ideally, a peripheral catheter should be inserted after the donor has been sedated (if required) and replacement intravenous crystalloids administered (three times the volume of blood withdrawn can be administered over 20-30 minutes) after the donation is complete. Dogs can be sedated with opioids or opioid/ benzodiazepine combinations. Cats can be sedated with ketamine/diazepam for the procedure, or can be given alpha-2 agonists (bradycardia may require anticholinergics/and or reversal agents) and reversed when the procedure is finished. Dogs can be collected using the standard 16-ga needle connected to the transfusion pack by gravity, or by vacuum assistance. Cats can be collected using a butterfly catheter and 60ml syringe. Do not allow air to enter the collection system through the needle after completion of the transfusion. The system must remain closed to potential contamination. All blood collected to be used as stored components should be collected into CPDA-1 at a rate of 14 ml anticoagulant to 100 ml of blood. Blood collected for immediate transfusion can be collected into ACD. The actual collection should be done in an aseptic manner (i.e. shave, sterile prep, wear sterile gloves). How much blood can be removed from a donor? Up to 15% of the blood volume can be removed safely, and up to 20% can be removed if followed by fluid therapy. Removal of 30% of blood volume will produce signs of hypovolemic shock. The blood volume of the dog is ~90 ml/kg and the blood volume of the cat is ~60 ml/kg. Therefore, the dog can have 13.5 ml/kg and the cat can have 40-50ml TOTAL removed safely. FWB should be used within 4 hours of removal. WB can be stored in the refrigerator at 4-6ºC after collection. Red cell life is 35 days with CPDA-1. Blood can also be sedimented and the plasma component stored in the freezer. If you plan to separate blood, special collection systems should be used so that the system is not opened and exposed to air. Household freezers do not reach the low temperatures required for FFP, so this plasma is considered FP only. In-house Blood Typing and Cross-Matching If typing cards are available, these should always be used prior to blood transfusion (and only for products containing RBCs unless prior plasma transfusions have resulted in reactions). Ideally, the blood type of the donor is known in advance. If your practice does not have blood typing cards available, skip to the cross-matching portion of this section. Canine Blood Types and Typing DEA 1.1/1.2 negative is considered the universal donor. Typing cards check only for DEA 1.1; one of the most important antigens, but not the only antigen that can cause transfusion reactions. Each typing card has three wells identified as "DEA 1.1 Positive Control", "DEA 1.1 Negative Control", and "Patient Test". One drop of whole blood (in EDTA/purple top) and one drop of phosphate buffered saline (PBS) are mixed in each well, being careful to avoid cross contamination between the wells. In the "Patient Test" well, the monoclonal antibody is reconstituted to form an antiserum and then mixed with whole blood from the patient. The presence of agglutination in the "Patient Test" well indicates that the patient is EITHER DEA 1.1 positive or is auto-agglutinating. Dogs who are auto-agglutinating should always receive 1.1 negative blood, because the typing cards are difficult to interpret when autoagglutination is present. Bitches which have whelped and any dog that has had a prior transfusion (> 7 days previous) should have a crossmatch performed prior to transfusion. One rule of thumb is that all dogs should be able to receive one blood transfusion without a reaction. Feline Blood Types and Typing Typing felines prior to transfusion is mandatory. Type B blood is rarely stored, but ideally, a B cat should be available to the practice to donate as needed (Rex breeds, British Shorthairs, Maine Coons etc). Type A red cells given to a B cat are catastrophic, and Type B given to a Type A cat may cause a severe reaction. On the feline blood typing card, RBCs from type A cats will agglutinate with anti-A monoclonal antibodies and RBCs from type B cats will agglutinate with anti-B solution. Erythrocytes from type AB cats will agglutinate with both anti-A and anti-B reagents. The third well on the card serves as the auto-agglutination saline screen and must be negative in order to interpret results. Rapid Cross-Matching If blood typing equipment is not available, then a rapid cross-match is the easiest way to determine if recipient and donor are compatible. These are not as complex or as complete as the cross-matching performed in referral laboratories, but will be sufficient if time is of the essence. This is only required for transfusions containing RBCs. It requires an EDTA sample (purple top) from both the recipient and donor animals.
All red cell products should be administered through a blood administration filter (170 ?m) using a non-rotary type fluid administration pump (peristaltic flow pumps are acceptable). A baseline TPR and PCV/TS should be collected prior to beginning a transfusion. Initial rate of administration should be slow (0.25-1 mL/kg/hr) for 15-20 minutes to monitor for transfusion reaction. Vital parameters (TPR) should be monitored every 15-30 minutes for the 1st hour, and then every hour until transfusion is completed. The calculated dose of red blood cell product should be administered within 4 hours of puncturing the donation bag. Total daily doses of red blood cell products should not exceed 22 mL/kg/day, unless severe ongoing losses are occurring (do not exceed 22 mL/kg/hr unless massive hemorrhage). If risk of volume overload is present, then maximum administration rate should be 4 mL/kg/hour. Patients who are experiencing severe and rapid blood loss should be administered red blood cell products as rapidly as needed to maintain adequate circulating volumes. Slow initial rates of transfusion are usually not employed in emergency situations. For example, the actively bleeding ACR patient should have the full dose of FWB or FFP within 20-30 minutes. A PCV/TS should always be performed within 60-90 minutes after completion of the transfusion to determine response. Transfusion Reactions Type I - Allergic/Anaphylactic reaction This is the most common transfusion reaction and is manifested by urticaria, pruritus, or fever. Anaphylaxis can occur, but is rare. Most of the time, the reaction is directed against an incompatible antigen located on the platelet or white blood cell remnants or some plasma protein component. If urticaria or fever is the only manifestation, the transfusion should be stopped temporarily, and diphenhydramine (2 mg/kg IM) administered. The transfusion can be reattempted after 20-30 minutes. If the fever or urticaria does not resolve within 30 minutes, Dexamethasone SP 0.25 mg/kg IV can be administered. Anaphylaxis should be treated with aggressive fluid resuscitation and antihistamines as described above if severe. Epinephrine (0.1 mL/kg or 1:100000 concentration IV) may also be necessary if severe bronchoconstriction and cardiovascular collapse are present. Restarting the transfusion is not recommended in this case. Type II - Acute Immunologic - Hemolytic Reaction Acute intravascular hemolysis is the most severe of the transfusion reactions and results in hemoglobinemia and hemoglobinuria. Signs may include restlessness, anxiety, nausea, muscle tremors, urticaria, fever, tachycardia, tachypnea, and seizures. Acute death, thromboembolic disease, or acute renal failure are possible. The most common situations where this would occur include Type A blood to a B cat, or DEA 1.1 positive blood to a negative dog previously sensitized through previous transfusion or breeding (negative female dog bred to positive male with exposure to positive fetal blood during whelping). The transfusion should be discontinued immediately. IV fluid therapy is always indicated to support glomerular filtration rates and renal blood flow. Administration of corticosteroids (Dex SP 0.25mg/kg IV) may be beneficial. Delayed Immunologic Reactions This transfusion reaction is uncommon in veterinary medicine. Rapid destruction of transfused RBC is the most common reaction in this category. Typically, DEA 3/5/7 antigen antibody reactions are involved through previous sensitization, or naturally occurring antibodies. Rapid drop in PCV within 3-7 days and evidence of extravascular hemolysis are the typical signs. Acute Non-Immunologic The most common problems associated with this category of reaction include vascular overload (cough, pulmonary edema, vomiting, urticaria, and serous nasal discharge). In addition, poor component handling can result in hemolysis (physical trauma to red cells during collection or administration, prolonged or inadequate storage, freezing, overheating, and mixing with non-isotonic fluids). If RBC damage is severe, then signs may similar to acute severe intravascular hemolysis, but more commonly reflect rapid transfused RBC destruction and extravascular hemolysis. Occasionally a pyrogenic substance from the plastic bag or tubing can cause a febrile response which is not immune mediated. Administration of RBC or plasma products with calcium containing crystalloids (LRS) can cause microembolization within the IV tubing to occur. Inappropriate plasma product storage or administration can result in poor viability of plasma/clotting proteins and ineffective response. Massive transfusion in severe/ catastrophic hemorrhage can result in hypocalcemia and/or anticoagulant toxicity. This is seldom encountered in veterinary medicine. Disease transmission can also occur if donors have not been carefully chosen and screened. Coagulation and Coagulation Testing Objectives:
Hemostasis is the physiologic process whereby bleeding is halted. The primary functions of the hemostatic system are to: 1) maintain blood in fluid state while in the vessels; 2) arrest bleeding at the site of injury and 3) remove the clot once healing is complete. This lecture is intended to investigate part 2 of the hemostatic functions. Hemostasis is divided into two subcategories. These are primary hemostasis, which is composed of platelet adhesion, activation and aggregation; and secondary hemostasis, which is coagulation factor activation. Primary hemostasis is initiated when disruption to the vascular endothelium exposes circulating platelets to collagen in the subendothelial matrix and von Willebrand factor released from disrupted endothelial cells. Adhered platelets degranulate to release a number of vasoactive and attractant factors (thromboxane, additional vWF, histamine, epinephrine, platelet activating factor, etc). This attracts and activates additional platelets, allowing formation of a platelet plug. This plug is unstable and short lived; secondary hemostasis is required to stabilize the plug and form a mature clot. Secondary hemostasis occurs on the surface of both the endothelium and the platelets, and requires activation of the clotting factors, which are circulating proteins. The end result of secondary hemostasis is cross-linked fibrin strands. Think of the fibrin as a net, holding down a group of platelets. The platelets plug the holes in the net to prevent additional fluid from leaking out, and the net prevents the platelets from floating away. In vitro, the "Y" diagram is used to describe secondary hemostasis. In vivo, the system functions quite differently. If we look at the "Y" diagram, it appears that the intrinsic and extrinsic systems contribute equally to the activation of the common pathway. In reality, factor VII is integral to activation of secondary hemostasis. Animals deficient in F VII have severe bleeding tendencies and usually die shortly after birth. In contrast, animals (especially cats) with complete F XII deficiency have a normal lifespan and are not coagulopathic. Even the names "primary" and "secondary" hemostasis are misnomers. The platelets and coagulation cascade are activated simultaneously, and each depends on the other for optimal function. So why use the "Y"? It is an easy way to explain laboratory testing for coagulation dysfunction. 
Diseases of Hemostasis Disorders of Primary Hemostasis These can be divided into two broad categories: thrombocytopenia (decreased platelet numbers) and thrombocytopathia (decreased platelet activation/aggregation). Thrombocytopenia is caused by decreased production, increased consumption, or destruction. Sequestration can occur (as with snakebite envenomation) but is rare. The most common cause of thrombocytopenia is destruction, whether primary immune-mediated (ITP) or secondary immune-mediated (such as secondary to tick-borne disease, neoplasia, etc.). Decreased production is caused by bone marrow aplasia or secondary to neoplastic processes affecting the bone marrow. Increased consumption is usually associated with DIC. Mild thrombocytopenia can also occur from platelet loss, as occurs with severe hemorrhage. Thrombocytopathia can occur from inherited defects in platelet activation (such as occurs with greyhounds), decreased vWF, or from drug administration such as aspirin or other NSAIDs. Platelet counts are normal, but platelet function is altered. It is uncommon to see spontaneous bleeding in these patients (unless vWD is of more severe forms), but bleeding may be excessive during surgical procedures or with trauma. Of these causes, vWD and ITP (either primary or secondary) are the most common. ITP is an immune-mediated destruction of the platelets. Primary ITP, where no underlying cause can be determined, is associated with platelet counts that tend to be < 20,000 cells/?l. Tick borne disease causing a secondary ITP tends to have higher platelet counts, near the 40,000-80,000 cells/?l range. The hallmark sign of severe thrombocytopenia is petechial hemorrhages that tend to occur on mucosal surfaces, including nasal, gingival, gastrointestinal and bladder mucosa. Spontaneous bleeding usually occurs with platelet counts < 20,000 cells/?l. Multiple forms of vWD exist. In Type I disease, all sizes of vWF multimers are present, but in decreased amounts. This is the most common form, and bleeding is mild to moderate. Breeds affected include the Doberman Pinscher, Basset, Cocker, English Setter, German Shepards, Golden Retrievers, Poodles, Shetland Sheepdogs, Welsh Corgis and many others. In Type II disease, large multimers are absent (which are the most hemostatically active). Bleeding is typically severe, and this form usually affects German shorthair and wirehair pointers. In Type III disease, there is either a complete absence of all sized multimers or only trace amounts. Bleeding is severe. Predisposed breed include the Scottish terrier, Shetland sheepdog, Dutch Kooiker, Chesapeake Bay retriever, and Golden retriever. Unless significant hemorrhage is present, platelet numbers are normal. vWF is often confused with Factor VIII. Remember that Factor VIII levels are normal, and that this factor serves as a carrier to protect vWF from destruction. Disorders of Secondary Hemostasis Decreased production of the Vitamin K dependent clotting factors can occur with severe hepatic dysfunction or failure. This can also be seen with anti-coagulant rodenticide (ACR) toxicity. Prolongations of clotting times tend to be much more severe with ACR than with liver failure. There are also a number of inherited disorders of coagulation. Hemophilia A (lack of Factor VIII) and Hemophilia B (lack of Factor IX) occur occasionally in veterinary medicine. Hemophilia A tends to affect large breed dogs (especially German Shepards), and Hemophilia B tends to affect small breed dogs, although any breed can be affected with either disease. Factor VII deficiencies have been reported in the Beagle. Increased consumption of clotting factors can occur in the late, or hypocoagulable phases of DIC. Loss of factors can occur in severe hemorrhage and subsequent hemodilution with non-clotting factor containing solutions, such as pRBCs, crystalloid, or synthetic colloid solutions. Additionally, synthetic colloid solutions such as hetastarch can cause decreased levels of Factor VIII and platelet dysfunction. Very rarely do these lead to clinical bleeding. The hallmarks of disorders of secondary hemostasis are ecchymotic hemorrhages and cavitary bleeding. Hemorrhage can occur into any cavity, especially the pleural, pericardial and peritoneal spaces. ACR toxicity in particular can result in bleeding into any part of the body, including pulmonary hemorrhage, and bleeding into the eyes, joints, tracheal membranes, ventricles of the brain, GI tract and bladder. Practical Coagulation Testing For all coagulation testing, needle sticks should be as atraumatic as possible. While using a vacutainer has long been considered the standard for drawing blood for coagulation testing, this is not strictly necessary. Samples can be drawn from a needle and syringe, and then rapidly transferred to the appropriate collection tube. Plastic tubes are more likely to cause platelet clumping; therefore, glass tubes should be used if the platelet count is in question. Finally, a recent study published in AJVR showed no significant difference in PT/aPTT drawn through a catheter versus that drawn with a needle stick. Platelet Counts: If an automated platelet count is available, ensure that no clots are present in the sample. A blood smear should always be used to confirm platelets counts. The feathered edge of the smear should be evaluated for platelet clumping. Clumping can greatly reduce the reported platelet numbers on the CBC. If an automated platelet count is not available, platelet numbers can be estimated from the blood smear provided that clumping is not present. The number of platelets per high power field (100x) can be counted and multiplied by 10,000-15,000. This will give a rough estimate of the platelet count. Buccal Mucosa Bleed Time (BMBT): This test can be used to determine if a primary hemostatic disorder is the cause for bleeding. It is inexpensive to perform, although it is strongly recommended that a BMBT kit is used for the test. To perform the BMBT, the test kit should be placed against the gently everted buccal mucosa. The blade from the test kit is deployed, providing a standard depth and length incision. Blotting paper is used to remove blood from under the site, but should not touch the incision itself. Normal BMBT is < 4 minutes in the dog, and <3 minutes in the cat, depending on the test kit. Limitations of the BMBT are considerable inter- and intra-operator error, it does determine the etiology of the abnormality, and it is not correlated to predicted risk of bleeding from surgical procedures. Prothrombin Time (PT): The PT reflects activation of the extrinsic (F VII) and common pathways (F X, V, II and I). Blood should be drawn into a citrated (blue top) tube and filled to the bottom of the top of the label (blood: citrate ratio of 9:1) The amount of blood drawn is important since dilution with citrate can alter clotting times. PT is the first parameter to increase with ACR toxicity, although overt bleeding does not occur until both PT and aPTT are elevated. Activated Partial Thromboplastin Time (aPTT): The aPTT reflects activity of the intrinsic (F XII, XI, IX, VIII) and common pathways. Blood should be drawn into a citrated tube as described above. The SCA-2000 coagulation analyzer is the most common machine used in private practice to determine clotting times. These machines cost roughly $2-3000. Cartridges cost around $4.00 each, and are stored at room temperature. Shelf life of the cartridges is 30 days at room temperature, or 60 days refrigerated. Cartridges that are kept in the refrigerator need approximately 10 minutes to warm up before use. Activated Clotting Time (ACT): The ACT is a rough estimate of the aPTT, although very low platelet counts can affect it as well. The ACT is performed by placing 2ml of whole blood into a pre-warmed (body temperature at 37 C) glass tube containing diatomaceous (Fullers) earth (grey top tube). After 60 seconds (keeping the tube at 37 C), the tube should be inverted every 10-15 seconds to check for clot formation. The test stops when a clot is noted in the tube. The normal range is 60-110 seconds in dog. A specialized heating block can be used to keep the tube warm. Alternately, a cup of water warmed to body temperature can be used. Proteins Induced by Vitamin K Antagonism (PIVKA): Inactive precursors of vitamin K dependent coagulation factors are stored in the liver. In the absence of vitamin K, which is required to activate these factors, the precursors build up and can spill over into the blood. Without vitamin K to activate them, there is depletion of activated coagulation factors, which leads to prolongation of clotting times and clinical bleeding. The human PIVKA test actually measures concentrations of these inactive PIVKA whereas the veterinary test marketed as the PIVKA is actually just a modified prothrombin time (PT). The veterinary PIVKA does not offer any advantage over simply measuring PT. It has also been shown to be elevated secondary to a number of disease conditions and is not specific for anticoagulant rodenticide toxicity. vWF Assays: vWF antigen ELISA assays are useful for the diagnosis of Type I and Type III vWD. Dogs with Type I vWD generally have vWF antigen levels that are less than 15% while dogs with Type III vWD have no detectable vWF. The quantitative nature of these assays makes them unsuitable as stand-alone assays for the diagnosis of Type II vWD. In academic or referral settings, thromboelastrography and platelet function analysis are available, but these are not yet readily available to the general practitioner. What to Do with the Actively Bleeding Patient? In private practice, a microscope for estimation of platelet counts, a BMBT kit and an ACT can be used to help diagnose most clotting disorders. While they may not be 100% diagnostic, at least using these tests will help to determine therapy. Unfortunately, red top clotting times and toenail trim tests are not accurate for diagnosis of coagulopathy. These are too dependent on inter- and intra-operator variability. Additionally, cross-contamination of EDTA from filling blood tubes (i.e., filling the EDTA tube first) can alter coagulation times. Take for example the middle aged Golden Retriever with epistaxis. The platelet smear can help to rule in or out severe thrombocytopenia. The ACT can help to determine if a disorder of secondary hemostasis is the cause. Severe prolongations in ACT (> 4 min) are likely to be associated with ACR toxicity. A BMBT can be used to determine if thrombocytopathia is the underlying cause for hemorrhage. The below table can be used to help with diagnosis of hemostatic disorders.
Small Animal Toxicology Decontamination Decontamination involves emptying the GI tract to reduce toxin exposure or increase elimination. This is the most fundamentally important way to treat a potential toxicity. The 4 main methods of decontamination are induction of emesis, gastric lavage, enemas and administration of activated charcoal. Induction of emesis Induction of emesis should be performed with recent toxin exposure. However, emesis should NOT be induced if the animal has ingested substances such as cleaning agents (caustics), petroleum products or detergents. It should not be recommended if the animal is comatose, dyspneic, or obtunded due to the risk of aspiration. Do not induce emesis if the animal is actively productively vomiting. Induction of vomiting if often of little benefit after 2-4 hours due to stomach emptying, but may be attempted if the animal is stable. Owners should be discouraged from inducing vomiting at home. Make sure to save stomach contents for testing if the toxin is unknown! Dogs
Gastric lavage should be performed in patients that have ingested caustic materials, have an increased risk of aspiration, are seizuring or if emesis cannot be induced by routine methods. Gastric lavage requires general anesthesia and the placement of a well-cuffed endotracheal tube. Gastric lavage should not be performed without placing an ETT due to the high risk of aspiration. Once the patient is properly anesthetized, measure the length of a stomach tube to the last rib. Mark this on your tube. Pass the tube to the pre-measured mark, double check to ensure that the tube is in the stomach, and begin lavage with large volumes of warm water. Two tubes, one for egress and one for ingress, can be used. Continue until the lavage fluid is clear. Enemas Enemas are useful to clear toxins from the lower GI tract or with enterohepatic recycling (such as metaldehydes) by speeding GI transit time. Large volumes of warm water should be used. Many activated charcoal products contain sorbitol, which helps to increase GI motility. Products containing sorbitol should only be given once due to the risk of severe diarrhea and electrolyte disturbances. Over-the-counter human enemas, especially FleetR enemas, are toxic to pets and should not be recommended. Activated Charcoal Activated charcoal acts by binding charged molecules in the GI tract. Mixing activated charcoal with food will render it inactive, as the charcoal will bind charged molecules in the food instead of the toxin. ToxibanR is the most commonly used activated charcoal product. The dose is 1-3g/kg, or 6-10ml/kg of the reconstituted product. Keep in mind that Toxiban will cause false positive on ethylene glycol kit tests, so do not administer prior to drawing blood. As we all know, administration of Toxiban is often very messy. An alternative is Universal Animal Antidote (UAA) gel. It is a thick paste that is much easier to give and requires lower volumes. The dose is 1-3ml/kg orally. Activated charcoal should be repeated q4-6 hours for toxins with enterohepatic recycling (especially chocolate, marijuana and bromethalin). Do not give repeated doses of sorbitol-containing products. Any oral medications should be started at least 2 hours after activated charcoal administration. Don't forget to warn owners to expect black feces for 24-48 hours after ingestion. Of all of the decontamination methods, activated charcoal administration is likely the MOST important. SPECIFIC TOXINS Non-Steroidal Anti-Inflammatory Drug toxicities Types of NSAIDs include:
Recent evidence suggests that COX-2 also has some constitutive functions, including maintenance of stomach and colon mucosa and healing of GI ulcers. There are additional isoforms of COX that have recently been discovered, including neuronal, ocular and osteogenic forms. The viewpoint that COX-1 is all good and COX-2 is all bad appears to be changing as we investigate its function more. Early treatment includes decontamination of the GI tract, IV fluid diuresis (for large ingestions) and administration of misoprostol (2-5 mcg/kg TID). Misoprostol works by providing an analogue of PGE2, which acts to maintain GI and renal blood flow. Misoprostol is only helpful when the active form of NSAID is present, and tends not to be useful once the drug has been eliminated (3-4 drug half-lives). While I don't always use it, I typically use it for only the first 3 days post-NSAID ingestion. After that time, GI ulcerations may be present but misoprostol will be ineffective and may actually worsen vomiting and diarrhea. Fluid diuresis should be continued for 3-4 drug half-lives (usually 48 hours). Once GI ulceration is present, treatment includes anti-emetics, proton pump inhibitors and sucralfate therapy. Renal failure tends to be reversible in mild cases, although long term renal insufficiency can occur depending on the degree of damage. Acetaminophen (TylenolR) toxicity Acetaminophen toxicity is one of the most frequently encountered toxicities in small animal medicine. Owners will often administer the product to pets, or the pet may get into the medication on its own. It is far more toxic in cats than in dogs. The mode of action is through a cytochrome P450 induced production of an active metabolite (N-acetyl benzoquinomeime) that binds to glutathione, a natural anti-oxidant. Feline hemoglobin is uniquely sensitive to oxidation, resulting in the formation of methemoglobinemia. In dogs, low glutathione levels lead to hepatic necrosis and lower levels of methemoglobin. Acetaminophen is available in children's (80mg), regular strength (325mg) and extra strength (500mg) doses. The toxic dose in the cat is 50mg/kg, while in the dog it is 150-200mg/kg. Therefore, a single regular strength TylenolR is lethal to a cat! Signs of toxicity in the cat are much more common due to less capacity for glucuronidation. Dogs will eliminate the drug 10 times faster than cats. Typical clinical signs in the cat include anorexia, salivation, dyspnea, hypothermia, depression, weakness and coma. Facial and forelimb edema occur through an unknown mechanism. Mucus membranes, blood and urine are often chocolate colored due to the formation of methemoglobinemia and methemoglobinuria. Signs will typically occur within 1-4 hours of ingestion. Clinical signs in the dog include vomiting, abdominal pain and dark urine and mucus membranes. Diagnosis is based on history, physical exam findings, the presence of methemoglobinemia, prominent Heinz bodies on peripheral smears (cats) and elevated liver enzymes. Metabolic acidosis may also be present due to inadequate oxygen carrying capacity and tissue hypoxia. Treatment consists of standard decontamination, supportive care, and therapy directed at reducing oxidative stress. Remember to handle cats carefully as they can stress and die easily! Methemoglobin is unable to carry oxygen, resulting in tissue hypoxia. Oxygen therapy is often beneficial. The antidote is N-acetylcysteine (MucomystR), which may be given IV or PO. N-acetylcysteine directly binds with acetaminophen metabolites to enhance elimination and serves as a glutathione precursor. If given IV, dilute to a 5% solution with 5% dextrose. The dose is 140mg/kg IV or PO loading dose, then 70mg/kg q 6 hours for 7 treatments. Blood transfusions may be necessary as the reticuloendothelial system removes damaged red blood cells from circulation. Transfusions will also improve the blood oxygen carrying capacity. Other proposed therapies include administration of ascorbic acid (Vitamin C) 30mg/kg PO or SQ QID, to help to reduce methemoglobinemia; and cimetidine (5-10 mg/kg IV or IM TID) to reduce metabolism of acetaminophen by the cytochrome P-450 system. The benefit of these therapies has not been investigated. The prognosis is guarded to poor in cats, with rapidly progressive methemoglobin concentrations, methemoglobin concentrations > 50% and progressive rises in liver values being poor prognostic indicators. The prognosis is more favorable in dogs. As a reminder, we should never recommend the use of acetaminophen in cats. Due to the potential for toxicity, its use should be avoided in the dog. Ethylene Glycol Ethylene glycol is contained in many antifreeze preparations. It is rapidly metabolized via alcohol dehydrogenase to glycoaldehyde, glycolic acid, glycoxalic acid and oxalic acid, producing a severe metabolic acidosis and acute renal failure. Oxalic acid may combine with calcium to form calcium oxalate (monohydrate) crystals in the kidneys and other organs. The toxic dose is 4-6ml/kg in the dog and 1.5ml/kg in the cat. Three stages of intoxication occur. Stage I occurs within 30 minutes to 12 hours of ingestion and consists of neurological signs, including depression, ataxia, knuckling, stupor and coma. Other signs include anorexia, vomiting, polyuria and polydipsia. Stage II occurs 12-24 hours post ingestion and consists of tachypnea and tachycardia, which frequently go unnoticed by the owner. Stage III is the renal phase, occurring at 24-72 hours post ingestion. Signs include severe depression, vomiting, diarrhea, dehydration, azotemia and oliguric or anuric renal failure. Diagnosis is made by history, physical exam findings, laboratory values and specific testing. Frequent laboratory abnormalities include severe metabolic acidosis, high anion gap, increased serum osmolality, hypocalcemia, and hypo- or hyperphosphatemia. Azotemia typically occurs at 12 hours in the cat and 36-48 hours in the dog. The presence of calcium oxalate crystals in the urine can occur as early as 6 hours post-ingestion, but this finding is not consistently present. In-house test kits (EGT Test Kit) test for glycol levels greater than 50mg/dl. However, this test will cross-react with a variety of glycols, including the propylene glycol found in certain moist foods, Toxiban, paintballs, and non-toxic antifreezes. Therefore, a positive test doesn't always mean that the animal got into antifreeze! In addition, it is only reliable for the first 18 hours after ingestion. These kits are not reliable in cats as the toxic level in cats is much less than that detected by the kit. Quantitative testing for ethylene glycol levels can be performed at most human hospitals, and is much more sensitive and specific. It is relatively inexpensive (< $75 at most hospitals). Treatment consists of decontamination, supportive care, and directed therapy. Decontamination should be performed immediately if ethylene glycol ingestion is suspected. Once a diagnosis is made, therapy should be instituted promptly. 4-Methylpyrazole (fomepizole or AntizolR) is a competitive inhibitor of alcohol dehydrogenase and is the preferred treatment. For dogs the recommended dose is 20mg/kg IV once, then 15mg/kg at 12 and 24 hours, then 5mg/kg at 36 hours. Fomepizole is not labeled for use in cats, but it has been shown to be effective at much higher doses. The dose for cats is 124mg/kg IV once, then 31.25mg/kg IV at 12, 24 and 36 hours. Fomepizole can be overwhelmed by massive toxin overdoses, such as those that occur with malicious poisoning. If fomepizole is too cost prohibitive, therapy with ethanol can be attempted. Ethanol has multiple problems, including worsening of acidosis, diuresis, and respiratory and CNS depression. IV Ethanol therapy requires mixing a 7% solution. Mix 107ml 100 proof vodka in 1L Normosol-R or saline with 5% dextrose. Administer a loading dose 600mg/kg IV, then 100-200mg/kg IV CRI. IV Ethanol should be administered for 24-36 hours. Conversely, oral Ethanol (80 proof alcohol) at 2.2ml/kg (1ml/lb) PO q4h for 24 hours can be used. Ethylene glycol testing should be performed at the end of therapy. If positive, treatment should be continued. In addition to directed therapy, supportive care should be administered. IV fluids should be given at 2-3 times maintenance rate. Weight, CVP, and urine output should be monitored carefully. Early and directed treatment typically results in a good outcome for most patients. However, one clinical study found that all patients that were azotemic upon admission did not survive. Therefore, it is very important that clients seek early, aggressive medical attention. Moldy Garbage Intoxication (aka Garbage Gut) Garbage gut is fairly common in free-roaming dogs. Ingestion of spoiled foods can cause a variety of syndromes, including botulism, food poisoning, and Penitrem A toxicity. Botulism is relatively rare in veterinary medicine. Clinical signs include vomiting, hypersalivation and abdominal pain progressing to ascending flaccid paralysis. Ingestion of E. coli, Staph spp, Strept spp. Salmonella spp., clostridium and Bacillus spp. can lead to altered GI permeability and motility from release of endotoxins. Clinical signs include severe vomiting, diarrhea (which may become bloody), dehydration, fever and signs of endotoxic shock. The signs of endotoxic shock include depression, hypotension, collapse, hypo- or hyperthermia, and rapid or prolonged CRT. Penitrem A toxicity is one of the more common toxicities seen in small animal medicine. It is a neurotoxin that affects nerves by increasing the resting potential, facilitating transmission across motor end plates and prolonging the duration of depolarization. Clinical signs include panting, restlessness, hypersalivation, incoordination, and fine muscles tremors that start over the face and head and spread over the entire body. Late in the cause of the disease, tonic spasms, hyperthermia, ataxia, seizures and death can occur. Differential diagnoses include strychnine intoxication, mushroom intoxication and eclampsia. Diagnosis is typically made on history and physical exam findings. Induction of emesis, when appropriate, will often cement the diagnosis. Many patients will vomit a large volume of garbage or food that the owner has not fed. Laboratory findings are nonspecific, including leukocytosis or leukopenia late in the disease, elevations in amylase and lipase, or elevations in CK if tremors or seizures are present. Treatment of Penitrem A toxicity includes standard decontamination and supportive care. There are no specific antidotes. While activated charcoal should be administered, a cathartic is not normally necessary due to the presence of diarrhea. Aggressive crystalloid and colloid support should be instituted to treat shock. Broad-spectrum antibiotic therapy should also be instituted. Muscle tremors can be treated with Methocarbamol (Robaxin) 44.4-222mg/kg slow IV to effect. Seizures may require diazepam or barbiturates for control. GI protectants, including H2 blockers and sucralfate are beneficial. If vomiting is excessive, treatment with Prochlorperazine (0.5mg/kg IM), Metoclopramide (1-2 mg/kg/day CRI) or Ondansetron (0.1-0.2 mg/kg IV TID) can be instituted. The primary goal of treatment is supportive care and preventing the development of DIC, acute respiratory distress syndrome, multi-organ dysfunction and death. If therapy is instituted early in the course of disease, the progress is fair to good. Chocolate The mode of action of chocolate is through methylxanthine toxicosis. Both theobromine and caffeine are methylxanthine alkaloids present to varying degrees in chocolate. These lead to increases in cyclic AMP, potentiating and increasing catecholamine release; competitive antagonism of cellular adenosine receptors, leading to vasoconstriction and CNS stimulation; and increased intracellular calcium, causing increased smooth and skeletal muscle contractility. Typical clinical signs include vomiting and diarrhea, hyperactivity, polyuria and polydipsia, hyperthermia, hyperreflexia, muscle rigidity, tachypnea, tachycardia, seizures and death. The toxic dose of theobromine is 100mg/kg and the toxic dose of caffeine is 140mg/kg. Dangerous Quantities of Chocolate
Warning: These are approximate amounts only. Every animal has a different sensitivity to chocolate. If the animal is exhibiting any clinical signs, has ingested a quantity near the approximated toxic amount or has a history of cardiac, hepatic, renal, seizure disorders, recommend examination. There are significant amounts of caffeine in these products. Nestlé's milk chocolate contains approximately 19mg caffeine per ounce while Hershey's contains approximately 8 mg of caffeine per ounce. Caffeine is considered to enhance the clinical toxicity of chocolate. Reproduced from Plunkett. Emergency Procedures for the Small Animal Veterinarian, Saunders 2001. Diagnosis is typically based on history and physical exam. Many animals are already vomiting or having diarrhea by the time they are presented to the hospital. There is no specific antidote for chocolate ingestion. Standard decontamination, including enemas, and supportive care are recommended. IV fluids, treatment with diazepam or acepromazine for hyperactivity, and ECG and blood pressure monitoring are recommended. Ventricular arrhythmias can be treated with IV lidocaine CRI. Propranolol or metoprolol can be used to control sinus tachycardia. Many dogs will benefit from anti-emetics and GI protectants to neutralize the gastric irritation caused by caffeine toxicosis. The expected clinical course is 12-36 hours. The overall prognosis is good depending on severity of clinical signs. Seizures and arrhythmias are poor prognostic indicators. Rodenticides There are three major rodenticides: anti-coagulant, bromethalin and cholecalciferol. Cholecalciferol Cholecalciferol is the least common of the rodenticides. Brand names include Ortho Mouse-B-Gone, Rampage, Rat-B-Gone and Quintox. Cholecalciferol is metabolized to 25-hydroxyvitamin D in the liver, which is then converted in the kidney to the active form, 1,25-dihydroxyvitamin D. (Vitamin D3). Vitamin D3 promotes calcium retention, leading to lethal hypercalcemia and hyperphosphatemia resulting in mineralization of blood vessels, renal tubules, heart and lungs. Mineralization occurs when the Ca x P product is greater than 60. Clinical signs are seen at ingestion of 0.5-3mg/kg and lethal toxicosis is seen at 10-20mg/kg. Cats are more sensitive than dogs. Signs typically occur within 12-36 hours and include hemorrhage, vomiting, diarrhea, polyuria, polydipsia, lethargy and signs of acute renal failure. Unfortunately, many owners are unaware of ingestion until clinical signs occur. Laboratory findings include hyperphosphatemia, hypercalcemia, and azotemia. Abnormalities may occur as early as 12 hours post-ingestion, although elevations as long as 72 hours post-ingestion have been reported. Early treatment consists of standard decontamination with multiple doses of activated charcoal, and supportive care. Baseline calcium and phosphorous levels should be monitored every 12 hours for 4 days. Once hypercalcemia occurs, treatment with furosemide, prednisone, and phosphate binders (aluminum hydroxide) is recommended. For refractory hypercalcemia, treatment with either calcitonin (4 to 7 IU/kg SQ q4-6 hrs) or pamidronate (1.3-2mg/kg IV slow) should be instituted. Pamidronate is quite expensive but does not require the extensive monitoring and inpatient care required with calcitonin. Other signs related to renal failure (i.e., gastric ulcerations, seizures) should be managed as they occur. However, the prognosis is guarded to poor if absorption is allowed to occur. Bromethalin Bromethalin toxicosis is also fairly uncommon, but is seen more frequently than cholecalciferol. Brand names include Assault, Trounce and Vengeance. Bromethalin works by uncoupling oxidative phosphorylation, leading to decreased Na+/K+ ATPase activity. This produces demyelination and CNS dysfunction. Clinical signs include paresis or paralysis, extensor rigidity, tremors, seizures and death, and typically occur within 10-48 hours of ingestion. The toxic dose is 4.7mg/kg in the dog and 1.8mg/kg in the cat. Early treatment consists of standard decontamination, with multiple doses of activated charcoal and enemas. There is no specific antidote for bromethalin toxicity. Supportive care can be attempted, including treatment of seizures and mechanical ventilation. Death typically occurs secondary to respiratory failure. If neurologic signs develop, treatment is generally ineffective. Anticoagulant Rodenticides (ACRs) The majority of rodenticides are from the anti-coagulant family. The mode of action is inhibition of production of Vitamin K dependent coagulation factors (II, VII, IX, and X). First generation ACRs include warfarin and coumarin. These have a short half-life, and therapy is typically only needed for 7 days. Second generation ACR's include brodifacoums, bromadialone, diphacinone, chlorphacinone and valone. These are much longer acting and require treatment for 4-6 weeks. Ingestion results in massive hemorrhage 4-7 days after ingestion. Hemorrhage often occurs into cavities (hemoabdomen, hemothorax, hematuria), but patients can experience ecchymosis, epistaxis, hematemesis, hyphema, episcleral hemorrhage, hemomediastinum, etc. Clinical signs can include tachypnea, dyspnea, melena, bruising, weakness and pallor. Laboratory findings are typically related to hemorrhage, and anemia may be pronounced with severe bleeding. The platelet count is typically not affected. Early in the course of disease, prothrombin time (PT) is the most sensitive test for ACRs, with prolongations occurring within 2 days of ingestion. Activated partial thromboplastin times (aPTT) and activated clotting times (ACT) are prolonged later in the course of disease, usually after 4-7 days. However, if active hemorrhage is occurring, ACT will usually be greater than 4 minutes. Red-top clotting time is not sensitive for ACRs and should not be used for diagnosis. Early treatment includes induction of emesis and administration of activated charcoal. If decontamination is performed early or if the owner feels that only a small amount was ingested, a PT should be checked 2 days after ingestion. If it is normal, no therapy is needed. If it is prolonged, Vitamin K1 2.2mg/kg PO BID should be instituted for the appropriate length of time. If greater than 4 hours have passed since ingestion or a large amount was ingested, then Vitamin K1 therapy should be instituted. PT should always be rechecked 2 days after cessation of therapy. If the animal is actively bleeding, supportive care, fresh frozen plasma and blood transfusions should be instituted. Many clients will call stating that their pet got into "D-con", but oftentimes it is one of the other major brands. Always remember to have the client bring the package with them! All three classes of rodenticides are blue or green pellets or bricks - the type cannot be distinguished on appearance alone. If the package is unavailable, it is recommended to perform standard decontamination, then monitor calcium/phosphorous levels every 12 hours for 4 days and check a PT at 48 hours. Grapes and Raisins One of the newer topics in toxicology is the development of acute renal failure in dogs following ingestion of grapes or raisins. These can be commercial products, homegrown grapes or grape pressings left over from winemaking. The toxic principle is unknown. Ochratoxins, flavinoids, tannins and excessive amounts of monosaccharides have all been proposed as toxic components. Analyses of grapes and raisins involved in toxic cases have been negative for heavy metals, pesticides and known mycotoxins. The lowest documented toxic dose for grapes has been 0.7oz/kg, and for raisins 0.11oz/kg. However, some dogs are exposed and never show clinical signs. There have been reports of acute renal failure in cats and ferrets that have ingested grapes or raisins. Histological examination of kidneys from affected dogs has shown proximal renal tubular degeneration or necrosis. Mineralization of the kidneys and other organs has also been seen. Clinical signs typically begin within 2 days of ingestion, with most dogs showing clinical signs within six hours. Typical signs include nausea, vomiting, diarrhea and anorexia. Laboratory abnormalities include evidence of dehydration and azotemia. Hyperphosphatemia, hypermagnesemia and hyperkalemia have also been reported. If presented early, standard decontamination should be performed. The clinician should also consider early and aggressive fluid diuresis at twice maintenance rates for 48 hours. If there are no increases in BUN and creatinine, fluids can be weaned after 48 hours. Overall, the prognosis is guarded, and is significantly worse in patients that develop oliguria or anuria. All cases of grape and raisin ingestion should be treated as a potential toxicity, and grapes and raisins should not be given to dogs as treats.   | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
