Therapeutic Management of Anaphylactic Shock in Animals

Therapeutic Management of Anaphylactic Shock in Animals

Anaphylaxis is defined as the acute onset of a hypersensitivity reaction causing the release of mediators from mast cells and basophils. Anaphylaxis may be a life-threatening condition that can involve one or more organ systems. Often, a specific cause for anaphylaxis is not known. Anaphylaxis may be brought on by anaphylactic or anaphylactoid reactions; treatment is the same regardless of reaction type.

Anaphylactic shock is a rare, life-threatening, immediate allergic reaction to food, an injection, or an insect sting. The most common signs occur within seconds to minutes after exposure to the antigen. Dogs differ from other domestic animals in that the major organ affected by anaphylactic shock is the liver, rather than the lungs. Therefore, gastrointestinal signs are the major signs of anaphylactic shock rather than respiratory signs. These signs include sudden onset of diarrhea, excessive drooling, vomiting, shock, seizures, coma, and death. The dog’s gums may be pale, and the limbs may feel cold. The heart rate is generally very fast, but the pulse is weak.

Anaphylaxis is an extreme emergency. If you think that your dog is having an anaphylactic reaction, seek emergency veterinary assistance immediately. A veterinarian can give intravenous injections of epinephrine (adrenalin) to counteract the reaction. Treatment for other associated problems, such as difficulty breathing, may also be needed.

The term “shock” refers to a clinical syndrome rather than a specific disease entity. Although different sources may differ in exactly how they define “shock,” it is usually understood to mean a significant compromise in oxygen delivery to the tissues and particularly failure of the circulatory system to deliver blood flow to the tissues (circulatory compromise/tissue hypoperfusion). Tissue hypoperfusion, if untreated, leads to organ dysfunction and ultimately organ failure. Shock is present in the later stages of most fatal illnesses as circulatory failure is part of the final common pathway leading towards death. However, if shock is recognised and appropriately treated at an early stage, successful treatment is possible – these patients provide some of the most rewarding cases you may treat!

Circulatory shock may be further subdivided dependent on cause – this is important as different forms of shock require different treatments.

Shock is commonly categorised into:

Hypovolaemic shock – Tissue hypoperfusion occurs secondary to a lack of circulating blood volume. This is the commonest form of shock seen in veterinary patients and can occur secondary to haemorrhage (internal or external) or severe acute fluid loss into the gastrointestinal tract, through the kidneys or into or a “third” space (peritoneal/pleural cavity).

Distributive shock – The body displays generalised inappropriate vasodilation leading to alteration in distribution of blood flow between the tissues. Even in the face of a normal blood volume, tissue perfusion may be significantly reduced if all blood vessels are dilated. This kind of shock occurs with global release of inflammatory mediators such as in sepsis or SIRS (systemic inflammatory response syndrome) or rarely anaphylaxis. Other terms that may be used include septic or toxic shock but these are essentially subgroups of distributive shock.

 Cardiogenic shock – Failure of the heart as a pump. This occurs secondary to a number of cardiac diseases including advanced (late stage) cardiomyopathies and valvular disease and severe arrhythmias. However, in veterinary medicine, patients with cardiac disease more commonly present with signs of congestive heart failure and breathing difficulties rather than overt hypoperfusion and shock.

 Obstructive shock – Obstruction to blood flow. This form of shock is rare in veterinary patients but may be seen with pericardial effusion (where the pressure in the pericardial sac reduces venous return to the right side of the heart) or massive pulmonary thromboembolism.

Hypovolaemic shock is the commonest form of shock seen in veterinary patients and represents a loss of fluid from the circulating blood volume. It is very important that this form of fluid loss can be distinguished from that seen with dehydration. Both hypovolaemic shock and dehydration are treated with fluid therapy but the precise rate of fluid administration chosen depends on which is being treated.

To understand the difference between hypovolaemia and dehydration, a brief review of body fluid compartments is necessary. Roughly speaking 60% of the body is water and this is divided between intracellular and extracellular water. The extracellular water is further subdivided into interstitial and intravascular water.

Hypovolaemia occurs when fluid is lost primarily from the intravascular compartment – a relatively small total loss of fluid has profound physiological consequences with the development of hypovolaemic shock. In this circumstance, treatment with fluids centers around rapid replacement of the lost volume to restore tissue perfusion. Conversely dehydration represents fluid loss from all three body fluid compartments. It commonly occurs with more gradual fluid losses where there is time for water to move between body fluid compartments. Total body fluid losses may be much larger than with hypovolaemia but as the fluid losses are borne between all the compartments, it has much less profound and immediate physiological effects.

Diagnosis of Shock

The diagnosis of shock revolves around a careful physical examination which may be supplemented by measurement of haemodynamic parameters (e.g., blood pressure) or bloodwork (e.g., lactate – a marker of anaerobic respiration).

As a dog’s blood volume reduces, a number of homeostatic mechanism act to maintain cardiac output and tissue perfusion by increasing heart rate and stroke volume (compensated shock). These will be successful up to a critical point where the blood volume is so decreased they are no longer effective (decompensated shock). Careful examination of a dog’s perfusion parameters will allow an accurate assessment of the severity of hypovolaemic shock. The perfusion parameters are heart rate, pulse quality, mucous membrane colour and capillary refill time – all 4 perfusion parameters should be checked each time the patient is examined.

The table above provides a fairly accurate assessment of what happens to the perfusion parameters as a dog progresses through hypovolaemic shock and can be adapted for other species. Pulse quality is assessed by both the amplitude (height) and duration (width) of the pulse. Many different terms are used to describe pulse quality. The tall and narrow pulses found in early hypovolaemic shock are sometimes called “bounding” or “hyperkinetic” whereas the very short and narrow pulses seen in late shock may be described as “weak” or “thready.”

The tachycardia seen with hypovolaemia is a sinus tachycardia (i.e., on an ECG complexes all appear normal). Maximum rate for a sinus tachycardia is approximately 220 bpm as at heart rates higher than this cardiac output will actually start to fall as there is insufficient time for ventricular filling.

Distributive shock: The hallmark of distributive shock is inappropriately red mucous membranes. For example consider a dog with a heart rate of 200 bpm and poor pulse quality. If this animal had uncomplicated hypovolaemic shock their mucous membranes should be pale as they undergo peripheral vasoconstriction with diversion of the remaining blood volume to the important internal organs. Red mucous membranes in this patient should suggest inappropriate vasodilation and the presence of distributive shock.

Cardiogenic shock: Animals with cardiogenic shock typically have respiratory signs as well due to concurrent congestive heart failure. However, occasionally animals with tachyarrhythmias present in shock without concurrent heart failure – their heart rates are likely to be higher than the maximum achieved during hypovolaemia (a sinus tachycardia). Inappropriate bradycardia in a collapsed patient with poor pulse quality should also prompt assessment for an underlying cause (e.g., hyperkalaemia).

Obstructive shock: This is the least common kind of shock. Diagnosis relies on an index of suspicion for an underlying disease such as pericardial effusion that may lead to obstructive shock.

More than one kind of shock may coexist in the same patient and although assessment of uncomplicated hypovolaemic shock is relatively straightforward, some patients present more of a challenge.

Pathophysiology

Anaphylactic reactions are classified into 4 separate categories: type I, or immunologic IgE mediated; types II and III, which are immunologic IgE independent; and type IV, or nonimmunologic. Most anaphylaxis patients are likely to have type I reactions, but it is unclear why.

Anaphylactic Reaction: Immunologic IgE Mediated

In immunologic IgE-mediated reactions, patients do not show clinical signs at the initial allergen exposure. Upon reexposure, IgE antibodies are produced, and the allergen forms a “bridge” that cross-links these antibodies via a high-affinity receptor, FcεRI, located in the membrane of mast cells and basophils. After binding, antibodies cause mast cell and basophil activation and start the immediate hypersensitivity reaction. Cross-linking induces a membrane change, causing an influx of calcium ions into the cell that initiates degranulation and, thus, a release of mediators (eg, histamine). Interactions between mediators and host organs cause clinical signs to appear.

Anaphylactoid Reaction: Immunologic IgE Independent

In contrast, immunologic IgE-independent reactions occur through IgG antibody production. Allergen exposure activates IgG antigen binding to low-affinity receptors on macrophages. IgE-independent reactions require more antigen exposure and do not result in the release of histamine as a mediator. Furthermore, IgE-independent reactions do not require initial allergen exposure.

Anaphylactoid Reaction: Nonimmunologic Anaphylaxis

Nonimmunologic reactions may occur via degranulation of mast cells and basophils without immunoglobulins. They may be triggered by external influences, such as physical factors, drugs, and external toxins.

Chemical Mediators

Mediators stored in mast cells and basophils (ie, histamine, heparin, proteases such as tryptase and chymase, and cytokines) are released during degranulation (Figure 1), which causes an increased production of phospholipase A and thus arachidonic acid and its metabolites. Downstream activation of this cascade leads to an increase in newly synthesized mediators, such as prostaglandins, leukotrienes, and plasma activating factor. These newly synthesized mediators induce an inflammatory response. The release of inflammatory and vasoactive mediators leads to shock.

Histamine

Once an antigen has bound to the primed IgE receptors, histamine is released. Histamine is the principal mediator stored in granules of mast cells and basophils. It is released quickly during anaphylaxis and can be found in elevated concentrations in circulating plasma less than 1 minute after allergen interaction.³ Histamine acts through 3 receptors (H1R, H2R, H3R) to promote signs of shock. H1R increases smooth muscle contraction, causing vasodilation and increased vascular permeability. It also stimulates the conversion of l-arginine into nitric oxide, which leads to vasodilation and therefore decreases venous return. H2R increases gastric acids, increases heart rate and ventricular contractility, and further promotes vasodilation. H3R inhibits norepinephrine release, thus increasing the degree of systemic shock. Without norepinephrine, vasodilation can persist and lead to clinical hypotension. Clinical signs of histamine release include rhinitis, pruritus, dyspnea, hypotension, and tachycardia.

Other Mediators

Heparin is also released from mast cell granules. The release of heparin inhibits clot formation by decreasing clotting factors. This may lead to a hypocoagulable state and predispose a patient to clinical bleeding.

Cytokines, such as interleukin-4 and interleukin-13, are synthesized and released in response to the arachidonic acid cascade. The release of cytokines leads to an increase in cellular responsiveness to inflammatory mediators, up to 6 times normal.

Prostaglandins released may cause bronchoconstriction, pulmonary and coronary vasoconstriction, and peripheral vasodilation. Clinically, airway obstruction, increased airway secretions, and decreased cardiac output may be noted (hypotension).

Platelet activating factor decreases coronary blood flow and myocardial contractility and increases pulmonary resistance, vasodilation, hypotension, and platelet aggregation. Decreases in myocardial contractility in conjunction with vasodilation can lead to profound hypotension.

Anaphylactic Shock

Shock is a state of low blood perfusion to tissues that causes inadequate delivery of oxygen and decreased cellular energy production. Shock is often brought on by hypovolemia, maldistribution of vascular volume, or failure of the cardiac pump (cardiogenic shock). Anaphylactic shock results from massive vasodilation secondary to mast cell degranulation, histamine release, and the rapid release of inflammatory and vasoactive mediators. Vasodilation in turn decreases the relative circulatory volume, decreasing perfusion and thus oxygen delivery to tissues. This leads to splenic contraction and tachycardia, and ultimately myocardial and cerebral hypoxemia, cardiovascular collapse, and death.

Treatment of Shock

Hypovolaemic shock: The treatment of hypovolaemic shock revolves around replacing intravascular volume. Isotonic replacement crystalloid fluids (e.g., Hartmann’s, lactated Ringers) are generally the first choice fluid. When treating shock, bolus doses of fluids are used with the size and duration of the bolus being determined by the clinical signs of the patient. Most animals with moderate to severe shock will receive a bolus of 20–40 ml/kg over 15–30 minutes which may be repeated. Very severely compromised patient may receive a “full” shock bolus of 60–90 ml/kg in a dog and 40–60 ml/kg in a cat although it is rare to use this as the initial dose especially in cats. This is approximately the same as the animal’s blood volume. Unfortunately there are no precise rules that allow accurate judgement of the correct amount of fluid to give in each patient; the most important thing is that following administration of the bolus the perfusion parameters of the patient are rechecked. If the perfusion parameters are within normal limits, the treatment has been effective; if the perfusion parameters are still abnormal, further fluid boluses may be required. The patient should also be monitored for complication of fluid therapy, especially evidence of dyspnoea. This is an especial concern in animals with concurrent heart disease which may not be able to tolerate a rapid increase in their intravascular volume. Other fluid therapy options for hypovolaemic shock include hypertonic saline, colloid therapy or blood products.

Distributive shock: In patients with distributive shock the underlying cause for the inflammatory stimulus should be aggressively sought as successful treatment involves addressing the underlying problem. Fluid therapy is also important in these patients and occasionally specific medications including blood pressure support with inotropes or pressors (e.g., dopamine) is required.

Cardiogenic shock: Cardiogenic shock is treated dependent on the underlying heart disease – fluid therapy is generally contraindicated in these patients.

Obstructive shock: Obstructive shock is treated by removal of the cause of vascular obstruction e.g., pericardiocentesis in a patient with pericardial effusion.

The case with diagnosed as anaphylactic shock in  Animal may be  treated with Epinephrine (1:10000) @ 0.01 mg/kg body weight I/V and Anistamin (Chlorphen aramine maleate) @10ml I/M daily are given for 3 days. The animal is treated with intravenous infusion of 5% dextrose and normal saline @ 30 lit /day in the ratio of 4:1 twice daily for 3 days. Intramuscularly dexamethasone @ 2mg/kg b.wt, the life saving Nonsteroidal anti-inflammatory drug is given daily for three days. Smith (2002) also recommended the treatment of anaphylactic shock in horse with epinephrine, dexamethasone and antihistaminic. In case of  hypocalcaemia, so intravenous infusion of Mifex containing calcium, magnesium phosphate and dextrose is given 100ml, slow I/V daily for 3 days. In order to improve the appetite, tonic Zigbo (Natural Remedies, Bangalore) @ 4 bolus orally is given twice daily till complete recovery. Intravenous infusion of Terramycin (Oxytetracycline of Pfizer) @ 5mg/kg b.wt twice daily is given to combat the secondary bacterial infection. The said animal  also given  the I/M injection of Trineurosol-H (Merind) (Vit- B1, B6 and B12) 5ml and Tonophosphan, (Intervet India Ltd.) 10ml for three days. Animal may be administered with  the Iodex ointment massage till she/he may be  moved on his/her legs. After four to five  days animal may be  able to stand up with physical support and made an uneventful recovery.

NB-Treatment of animal must be in the guidance of a registered veterinarian

Compiled  & Shared by- Team, LITD (Livestock Institute of Training & Development)

Image-Courtesy-Google

Reference-On Request.

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