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Shock in the cat

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Category: Schede
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  • Disciplina: Medicina d'urgenza
  • Specie: Gatto

Cats have always been considered an unusual species. Old adages, such as that “cats have seven (or nine) lives”, are present in all cultures, a testimony to the extraordinary resilience of this species. In the last 30 years the continuing evolution in our understanding of cats has made clear that cats should not be treated as small dogs. This is true in every field of Veterinary Medicine, and Emergency and Critical Care (ECC) is no exception to this rule. This presentation deals with feline shock. Particularities of shock, specific to the cat, in terms of pathophysiology, clinical signs, diagnosis and treatment, are briefly described.

 

SHOCK DEFINITION AND CLASSIFICATION

The most recent definition of shock describes this condition as a life threatening, generalized maldistribution of blood flow resulting in failure to deliver and/or utilize adequate amounts of oxygen leading to tissue dysoxia (Antonelli et al, 2007).

This definition highlights the fact that in all types of shock the final pathway consists in the poor delivery and/or inadequate use of oxygen by the different tissues. Several mechanisms may be responsible for this process and this sets the basis for the classification of shock into different types. Many classifications of shock have been described; the classification here presented, which identifies 4 main types of shock, is one of the most commonly used:

  • Hypovolemic shock, characterized by impaired tissue perfusion due to an intravascular volume deficit; e.g. haemorrhage or severe dehydration.
  • Cardiogenic shock, mainly caused by an abnormal heart function leading to poor tissue perfusion; e.g. decompensated hypertrophic cardiomyopathy.
  • Distributive shock, characterized by alterations in the vascular tone, mainly vasodilatation, which leads to blood flow maldistribution with hyperperfusion of some tissues and underperfusion of others. In this type of shock the microcirculation is particularly affected. Distributive shock is commonly complicated by hypovolemia and decreased cardiac function. Examples of this type of shock include septic and anaphylactic shock.
  • Obstructive shock, characterized by a mechanical obstruction of blood outflow from the heart; examples include the presence of severe pulmonary thromboembolism, pericardial tamponade or tension pneumothorax.

 

SHOCK IN THE CAT

In terms of response to shock the cat presents several differences compared to the dog. First of all, in the cat the blood volume is significantly lower (50-60 ml/kg versus the 80-90ml/kg in the dog). This means that the cat depends critically on a higher heart rate in order to maintain its cardiac output. Once bradycardia is present signs of inadequate perfusion may in fact develop earlier in the cat than in the dog. In most of the species studied, the physiological response to a decrease in cardiac output is tachycardia, due to baroreceptor stimulation.  In the cat it is known that the stimulation of cardiac vagal afferents occurs with severe haemorrhage, producing a reflex bradycardia (Oberg & Thorén, 1970). It is also known that in the cat, and not in the dog, the administration of endotoxin leads to pulmonary vasoconstriction and hypertension, causing elevation of the central venous pressure (CVP) and a decreased cardiac output (CO) (Hall & Hodge, 1971).

Cats also seem to have an endotoxin-induced systemic inflammatory response which is in some ways different from what happens in the dog. In a recent study, low-dose endotoxin was administered to normal cats (DeClue et al, 2009). The authors reported that markers of systemic inflammation such as temperature, plasma TNF activity, IL-6, CXCL-8 and IL-10 concentrations resulted significantly increased following endotoxin infusion. Increases in blood glucose, lactate and creatinine concentrations were also reported. In contrast, white blood cell counts were significantly decreased. Haemodynamic and pathological changes were also reported in the same study. A biphasic hypotensive response occurred following endotoxin infusion, without a concomitant tachycardia. Patchy alveolar congestion, multifocal acute alveolar epithelial necrosis and mild pulmonary oedema were reported in the lungs. This is in accordance with the knowledge that the lung is the “shock organ” in cats, differently than in the dog in which the “shock organ” is considered to be the liver. This notwithstanding, in this study endotoxin infusion was also associated with acute centrilobular hepatocellular necrosis. Finally, and similarly to what has been described in humans, mild lymphocyte apoptosis in the spleen and/or intestinal Peyer's patches were also noted.

In the cat, the splenic contraction that occurs in response to hypovolaemia is not as pronounced as in the dog. Cats are also more sensitive to hypothermia than dogs, making the treatment of hypothermia a more fundamental necessity in the management of feline shock. Other specific differences are present however their description goes beyond the scope of this presentation.  Nevertheless it is now clear that for some specific characteristics cats respond to shock differently than dogs.

 

DIAGNOSIS

The diagnosis of shock is based on a combination of clinical signs, laboratory and imaging data. The first assessment should always be complemented with history findings, which may help to explain the aetiology of shock (e.g. a history of hypertrophic cardiomyopathy, trauma, vomiting and diarrhoea suggestive of a gastrointestinal problem, etc.).

Clinical signs of shock
Cats in a state of shock may present clinical signs differing from those in dogs or humans. Cats tend to present the classical shock triad: hypotension, bradycardia and hypothermia. Each component of the triad is a different manifestation of the same disease, being simultaneously the cause and aggravating factor of the other two components. This triad can be present in all types of shock but is particularly frequent in septic shock (Brady et al, 2000). In hypovolemic shock an initial compensated phase can be evident, characterized by tachycardia, pale mucous membranes (MM) and a bounding pulse which becomes weaker with the progression of the condition. These signs can also be mistaken with severe pain, especially in trauma patients, consequently analgesia should be provided as soon as possible (see treatment below). Obstructive shock has a more diverse presentation, however pulmonary oedema, weak to absent pulse and especially pleural effusion, combined with hypotension, are a common finding. Other possible signs of shock are dyspnoea, depressed mentation, increased capillary refill time (CRT), jaundice, increased jugular vein refill time following digital compression and oliguria.

In the diagnostic plan for feline shock the presence of  a heart disease should be ruled out as soon as possible, as the treatment of cardiogenic shock differs greatly from the treatment of other types of shock. In fact, it is the only type of shock that is treated with low fluid administration, if any at all. Signs that could alert for a cardiac origin of shock include auscultation of a heart murmur, gallop sounds or arrhythmias.

Minimum data base
The clinical assessment is completed with some diagnostic tests. Although what constitutes an emergency database in shock will change from practice to practice, some tests are universal. These include the measurement of blood pressure (non-invasively or ideally invasively, although the latter is seldom performed in critically ill cats when they arrive at the hospital), packed cell volume (PCV), total protein (TP), glucose, blood urea nitrogen (BUN), serum electrolytes, acid-base status and urine specific gravity.  This emergency database can help to identify the aetiology of shock and the presence of several co-morbidities (e.g. hyperkalaemia). The measurement of CVP is useful to assess both the preload and the function of the right heart, to help in diagnosing the cause of shock (hypovolemic shock will tend to have a low CVP while obstructive and cardiogenic shock tend to have the opposite; in distributive shock the CVP findings are more diverse) and as a guide for fluid therapy, helping to avoid fluid overload. The response of CVP values to the initial bolus of fluids can also be helpful in estimating the severity of hypovolemia. The normal CVP of cats is 0-5 cm H2O.  CVP is normally measured with a central venous catheter placed in the cranial vena cava, although the caudal vena cava (CVC) can also be used. Recently, new non-invasive ultrasound based techniques, such as the respiratory kinetics of CVC, have been used to assess the degree of right ventricular preload in humans (Marcelino et al, 2006). Their use in cats may prove useful as a central line is not routinely placed in the first approach to the patient.

Determination of arterial oxygen and CO content
Because shock ultimately results from a decreased oxygen delivery to the tissues (DO2), tests that could measure oxygen as well as the oxygen consumption by tissues (VO2) would ideally be useful in such patients. DO2 is equal to the product of CO by the arterial oxygen content of blood (CaO2), according to the following equation:

DO2 = CO x CaO2, where CaO2 = (Hg/dl x1,34 xSaO2) + (Pa O2 X 0,003)

(Hg = haemoglobin; SaO2 = arterial haemoglobin oxygen saturation; PaO2 =free oxygen dissolved in arterial blood)

DO2 can be calculated from a simple arterial blood gas analysis (which provides the components that determine CaO2) and from the patient’s CO. Until recently the placement of a pulmonary artery catheter (PAC) (Swan-Ganz catheter) was the only clinical approach possible to determine CO, by means of a thermodilution method. Although the use of a PAC provides measurement of important haemodynamic variables, its use implies the need for specialized equipment and can be associated with the occurrence of severe adverse events (e.g. pulmonary artery rupture). In addition, in humans the use of a PAC did not contribute to a significant improvement in survival (Chatterjee, 2009). The thermodilution technique to determine CO has been described in anaesthetized cats and has been shown to be useful (Beaulieu et al, 2009).

Recently, new techniques for the determination of CO have become available, including echocardiography derived cardiac output assessment, Pulse Contour Analysis of CO (PiCCO) (Shih  et al, 2011) and other ultrasound based methods (USCOM® device) (Critchley et al, 2005). At the time of writing this article only a few studies have addressed the use of these techniques in small animal patients and these were mainly performed in dogs, such as in the case for PiCCO (Shih et al, 2011).

Assessment of tissue perfusion
Parameters that assess global tissue perfusion are normally monitored in cats with shock. These include the measurement of lactate and base deficit. The values of lactate have been shown to predict prognosis in small animal critical patients. In fact more important than the initial value of lactate is the degree of lactate clearance as therapy is instituted, as it has been shown that this correlates better with prognosis (Abramson et al, 1993). The values of mixed venous oxygen saturation or SvO2 (the haemoglobin oxygen saturation in blood retrieved from the pulmonary artery) are also an accurate index of tissue oxygenation (Ladakis et al, 2001). Because SvO2 is not normally measured in veterinary patients, other alternatives were sought. The measurement of central venous oxygen saturation or ScvO2 has been shown to correlate with ScvO2 even for different cardiac indexes (el-Masry et al, 2009). Once a central venous catheter is in place, ScvO2 can be used as an estimate of SvO2 and consequently of the balance between O2 supply/demand at tissue level. Prospective studies that address the use of ScvO2 instead of SvO2 in cats have not yet been published, while such studies have recently been performed in female dogs with pyometra, sepsis and septic shock (Conti-Patara et al, 2012). In this study, ScvO2 determined at ICU admission was related to death (P = 0.001); this parameter, together with a base deficit, were found to be the best discriminators between survivors and nonsurvivors.  

In humans, the use of techniques to monitor deficits in peripheral perfusion, such as tissue oxygen measurement methods and gastric and sublingual mucosal tonometry, have been reported with success (De Backer et al, 2010). The use of these techniques to monitor peripheral perfusion and microcirculation in small animal patients is currently being investigated.

Other diagnostic tests
Diagnostic tests should also be conducted to identify the possible aetiology of shock. This may include performing thorax and abdominal X-rays,  abdominal, cardiac and thoracic ultrasound, ECG, diagnostic tests for specific diseases (e.g. FIP) and cytology and culture from several types of samples (e.g. blood, urine, abdominal and thoracic fluid, etc.). In trauma patients the use of  FAST (Focused Abdominal Scan for Trauma) with an ultrasound probe can be very useful in diagnosing the cause of occult bleeding and major soft tissue injuries. Rarely, advanced imaging techniques (CT/MRI scans), spinal or joint taps or even surgery (e.g. exploratory laparotomy) may be used in order to determine the underlying aetiology of shock.

 

TREATMENT

The main goal of shock treatment is to maximize DO2 to tissues. The treatment of shock should initially consist in the ABCs of resuscitation (A for Airway, B for Breathing and C for Circulation) like in every emergency case. In the case of cardiopulmonary arrest, cardiopulmonary cerebral resuscitation (CPCR) should be started immediately. The reader is advised to look for the recent published guidelines of the RECOVER initiative, that address the most recent developments and guidelines for small animal CPCR (Fletcher  et al, 2012). Oxygen should be supplemented with a minimally stressful form of supplementation (“flow-by”, nasal prongs, and Crowe collar) and a venous access should be established as soon as possible. One or two peripheral, short, large gauge, over-the-needle catheters (to maximize fluid flow) are initially used, because they are faster and easier to place than a central venous catheter. If the veins are so collapsed that the initial IV access attempt fails, a venous cut-down or the use of the intra-osseous route are good alternatives to provide an access for drug and fluid administration.

Fluid therapy

 

Common controversies in fluid therapy (Fig. 1) for shock include the type of fluid (colloid versus crystalloid and in case of colloid, synthetic versus natural), the rate of administration and the end-points of resuscitation. Unfortunately, a universal recipe for a fluid therapy that can be used in all types of shock does not exist. In fact, the initial fluid of choice will depend on the patient’s condition and especially on its coagulation, electrolyte and acid-based status; heart, lung and kidney function; nature of the disease and ideally on the colloid osmotic pressure. The current recommendation is not to follow fluid therapy recipes but instead to individualize the fluid therapy to each patient.  Nevertheless some general assumptions can be made. Cats, in general, because of their lower blood volume compared to dogs, will need lower doses of fluid. The fluid should also be delivered at a slower rate. Depending of the condition, the most common initial fluid therapy for shock treatment is the administration of a warm (especially if the animal is hypothermic) bolus of 15-30 ml/kg of a balanced electrolyte solution such as Ringer Lactate, Normosol R® or Normal Saline (although this tends to be more acidifying) for 15-20 minutes.

Depending on the state of shock, but especially on if hypoproteinaemia is present or if hemodynamic parameters fail to improve with the crystalloids, the initial crystalloid bolus may be followed by a bolus of hetastarch (2-5 ml/kg) and/or hypertonic saline (HS) (2-3ml/kg) for 15-20 minutes. In severe, decompensated shock, the artificial colloid can be used from the start simultaneously with the crystalloid. Artificial colloids allow the correction of hypovolemia with lower amounts of administered fluid. Besides, the increase in intravascular volume obtained with colloids is maintained for longer periods of time. Colloids are more expensive than crystalloids and are associated with side effects such as coagulation abnormalities and renal injury. The use of artificial colloids should therefore be decided on an individual basis.  Hypertonic saline has many proposed benefits, including improvement in tissue hypoperfusion, decreased oxygen consumption, endothelial dysfunction, cardiac depression, and immunomodulating and antioxidant properties (Oliveira et al, 2002). Haemodynamic benefits resulting from the use of HS for feline hypovolemic shock have been demonstrated in an experimental study (Muir& Sally, 1989), although clinical studies on its use are currently lacking. The use of HS requires a careful monitoring of the rate of administration. In fact, in the cat, administration rates of HS under 15 minutes have been associated with bradycardia and cardiac arrest.

 

Should the presence of defects in coagulation be suspected, fresh frozen plasma (FFP) is the colloid of choice. To increase CaO2, besides oxygen supplementation, packed red blood cells (PRBC), fresh whole blood (FWB) or eventually Haemoglobin-Based-Oxygen-Carriers (HBOC) can be used (Fig. 2). The latter has not been approved for use in the cat by the manufacturer. When using HBOC for feline shock (a normal dose of 0.25-1 ml/kg for 5 minutes is recommended) it is important to monitor the  respiratory function, as these types of fluids have been associated with the development of pulmonary oedema and pleural effusion in this species, especially in the presence of heart disease (Weingart & Kohn, 2008). Possible mechanisms responsible for these complications are HBOC´s powerful capability to increase plasma oncotic pressure and its vasopressive effect caused by its nitric oxide (NO) chelating properties.  Future developments in the field of fluid therapy for shock will include the development of better colloid solutions (with fewer effects on the coagulation system and better pharmaceutical properties), a better definition for the role of hypertonic solutions and the development and/or refinement of new HBOC.

Resuscitation should be performed until several endpoints have been met. These include the normalization of several clinical signs (CRT, MM colour, HR, temperature, pulse) and laboratory data (e.g. lactate and base deficit levels). A urine output equal or higher than 1-2 ml/kg/hr is indicative of an adequate CO and renal perfusion.

In septic shock, the use of an early goal directed therapy during the first 6 hours after diagnosis, with the aim of optimizing several haemodynamic and oxygenation parameters, has been recommended by recent guidelines developed for human patients (Dellinger et al, 2012). A recent study reported the use of this approach in dogs with septic shock (Conti-Patara et al, 2012), however clinical data on its use in the cat are still unavailable.

Once the desired endpoints have been achieved the animal can be started on a maintenance dose of crystalloid (1-2 ml/kg/hr); if COP is low or if a capillary leak syndrome is present the animal should be placed on hetastarch by constant rate infusion (CRI) at 0.25-1 ml/kg/hr.

Management ofhypothermia
In the cat hypothermia should be treated actively. After the first bolus of fluid (see above) the cat should be actively re-warmed and its blood pressure monitored. It is not uncommon for the clinician to find cats, with an initial presentation of severe shock, which following the first administration of a warmed bolus of fluids and re-warming show improvement in their blood pressure and in the clinical signs. In fact in some cats the improvement of haemodynamic parameters is only evident after re-warming is initiated.

After the administration of warmed fluids, re-warming should be performed carefully by passive and active techniques, to avoid side effects such as peripheral vasodilatation and burns. Re-warming techniques include the use of forced–air heating (Bair Hugger), circulating water blankets and the use of incubators or chambers with control of the internal temperature.

Ancillary therapies in felineshock
Pain control should never be overlooked as severe pain can mimic the haemodynamic characteristics of shock and is associated with a worse outcome. On this regard, opioids are the most common class of drugs used and are normally given through the IV route, as a bolus or CRI. µ Agonists such as fentanyl and morphine are typically chosen although in recent years buprenorphine has become increasingly popular. Other drug classes and/or routes of administration can also be added for the management of specific conditions and/or to improve pain management. The use of local anaesthetic blocks or the epidural administration of opioids and of local anaesthetics can for example be beneficial in some conditions, such as in the presence of pancreatitis. Ketamine is another agent that is also now commonly used to provide additional analgesia, thanks to its actions on the NMDA receptor. Ketamine used as an analgesic agent has several advantages. It can in fact prevent the “wind–up phenomenon” and the central sensitization of the central nervous system, thus improving pain management. Because of its sympathomimetic properties and its ability to maintain the respiratory drive, the administration of ketamine can be beneficial in cases of shock, unless the latter is caused by decompensated cardiomyopathy; in such case ketamine is contraindicated.  Ketamine can be used in bolus or in CRI, alone or combined with other agents, such as fentanyl and morphine.

For inotropic support dobutamine is the preferred drug in cats with shock associated with a decreased cardiac contractility and decreased CO (which excludes most cases of hypertrophic cardiomyopathy). In some cats this agent has been associated with the development of seizures, which however respond well to drug withdrawal and IV diazepam administration.

Vasopressors are indicated in shock when hypotension persists after intravascular fluid deficits and decreased CO have been corrected. Of all types of shock, septic shock is most probably the one which most benefits from the use of vasopressors. Vasopressors commonly used in feline shock are dopamine and norepinephrine and less frequently epinephrine. In humans the debate on which of these vasopressors is best in septic shock has been going on for years. The recent Surviving Sepsis Campaign International Guidelines for Management of Severe Sepsis and Septic Shock suggest that norepinephrine should be used as the first vasopressor of choice; should its administration not correct hypotension the second choice should then be epinephrine (Dellinger et al, 2012). In small animals, dopamine is commonly used as the first vasopressor instead of norepinephrine, as it possesses inotropic properties which can also be advantageous in the case of decreased CO. Dopamine is also used as it can theoretically increase hepatosplanchnic perfusion. This assumption has recently been questioned in studies performed in human vasoplegic septic patients (Guérin et al, 2005). In humans the most recent guidelines recommend the use of dopamine only in very specific circumstances (Dellinger et al, 2012). More recently the use of vasopressine has been reported for cardiac arrest (Buckley, Rozanski & Rush, 2011) and septic shock in dogs; for this latter condition most of the data comes however from experimental studies (Minneci et al, 2004). In humans, at the time of writing this article, the recommendation is that vasopressine can be added to norepinephrine for the treatment of hypotension in sepsis, but never as the first and only line of therapy (Dellinger et al, 2012).

In septic shock, antibiotics should be administered as soon as possible (ideally in the first hour after septic shock has been diagnosed). At this initial stage the choice of antibiotics should be done empirically. Once culture results are available a re-evaluation of the antibiotic therapy can be performed, if necessary. The reassessment of the antimicrobial therapy should also occur daily during de-escalation, when appropriate. Possible empirical antibiotic combinations for feline septic shock include ampicillin 22 mg/kg IV every 8 hours or clindamycin 10 mg/kg IV every 12 hours associated with enrofloxacin 5 mg/kg IV once a day. The control of the source of infection should be undertaken, if possible and if the conditions of the patient allow it, during the first 12 hours of clinical presentation. The control of the source of infection may require the need for surgical debridement and abscess drainage.

Tight glucose control and low dose glucocorticoid treatment are recent treatment regimes that have been shown to improve prognosis in critically ill human patients. Recent clinical trials have shown a significant reduction in morbidity and mortality rates with the use of intensive insulin therapy to maintain strict normoglycaemia in critically ill patients. In fact recent guidelines on the management of sepsis in humans emphasize the maintenance of glucose levels lower than 180 mg/dl (Dellingeret al, 2012). At the moment of writing no studies have been published describing the use of tight glucose control in critically ill cats, although hyperglycaemia is frequently recognized in this clinical condition (Knieriem, Otto & Macintire, 2007).

Low dose glucocorticoid treatment has been recommended for the treatment of relative adrenal insufficiency (RAI). RAI has been reported in several types of critical illnesses, and its main manifestation is hypotension refractory to fluid and catecholamine therapy, although other clinical and laboratory signs are also present. A suspected case of RAI in a polytraumatized cat has been reported in the literature (Durkan et al, 2007). The animal developed hypotension refractory to fluid therapy and dopamine CRI which resolved with dexamethasone administration of 0.08 mg/kg IV. An ACTH stimulation test was performed, which demonstrated an abnormal low response of glucocorticoid secretion after ACTH administration. After steroid treatment the animal rapidly improved and was discontinued from the dopamine CRI. This report, together with others, highlight that RAI may indeed be a complication of critical illness in small animals and that further studies are needed in this area of research.  

Finally, for patients in shock early nutritional support (if possible by enteral route) should be provided as soon as all haemodynamic, acid base and electrolyte abnormalities are corrected, as this can significantly improve the patient´s morbidity and mortality. Last but not least, cats will most certainly benefit from adequate doses of “tender love and care”.

Cardiogenic shock

Cardiogenic shock requires a different approach. In this type of shock the goal is to improve oxygenation and ventilation and to optimize or correct the abnormal cardiac function. This normally is achieved with oxygen supplementation and the administration of several types of drugs, including furosemide, angiotensin converting enzyme inhibitors, antyarrhythmic drugs, inotropes such as dobutamine or pimobendan and lusitropic agents including diltiazem or beta-blockers. Depending on the clinical presentation, pleural and/or pericardial drainage and assisted ventilation may be required. Prevention and treatment of thromboembolism should be managed with appropriate anticoagulant therapies with drugs such as clopidogrel, aspirin, heparin (classic and low-molecular weight heparin) and warfarin. A complete description of feline cardiac disease management goes beyond the scope of this review. Interested readers should therefore retrieve additional information on this subject in the literature available elsewhere.

 

CONCLUSIONS

In conclusion, in the feline patient shock presents unique features that distinguish it from the same condition in humans and in dogs. However, thanks to the continuous evolution of our understanding of this magnificent species we are now in a better position to identify its specificities and to provide a better and more specific treatment. Hopefully, with our help, cats will no longer have to waste a significant number of their lives in order to survive this devastating condition.

             

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