Shock

Shock is the result of a defect in tissue perfusion that leads to inadequate oxygenation, a reduced supply of nutrients and accumulation of metabolites which cause cellular damage. In the course of shock, the oxygen availability (O₂A) is reduced as a result of haemodynamic changes and a reduction in total oxygen content. The lack of supply of nutrients to cells reduces the synthesis of adenosine triphosphate (ATP) in the mitochondria which decreases the energy available for all cellular functions. The reduction of available energy and the alteration of tissue perfusion impede the normal removal of catabolites produced by cellular activity.

Regardless of its aetiology, shock is not due to a single pathophysiological problem, but to a dynamic set of alterations to cells, organs and apparatuses which may be involved in different ways and for different durations. For these reasons there is no single drug that can be used to treat shock but the clinician must determine the type and stage of the condition in order to institute effective treatment. The alterations caused by shock, if severe and prolonged for hours or, in a worst case scenario, even for days, may cause the patient's death.

PATHOPHYSIOLOGY

The effects produced by shock are:

• oxygen deficiency;
• unmet nutritional needs;
• accumulation of metabolites.

The body's responses to stressful events, such as intense sports, are similar to the pathophysiological changes that take place in the course of shock. After intense exertion, the subject may experience increases in heart rate and respiratory frequency, peripheral vasoconstriction and diversion of the blood to vital organs such as the lungs, heart and brain. These signs are common to many forms of shock. The endocrine and metabolic responses are very similar; what changes are the magnitude of the responses and their duration in time. A stressful event can, therefore, lead to shock due to persistence of the stimulus over time, or when the stressful event is severe enough to induce a bodily response that is incompatible with life because of its severity and duration.

The hypothalamus, which is not controlled by the neocortex and is, therefore, independent of volition, after stimulation induced by the cytokines released at the site of injury or affected tissue, may respond rapidly, thereby promoting the release of catecholamines and antidiuretic hormone (ADH, secreted by the neurohypophysis). Alternatively, the hypothalamus may modulate a slower response by liberating so-called releasing factors. Through the portal circulation, the releasing factors reach the anterior pituitary gland where they induce the release of hormones such as corticotrophin and growth hormone. The tissue perfusion deficit and reduced oxygen availability at the cellular level stimulate further release of cytokines and induce the liberation of tissue necrosis factor and interleukins.

Cytokines cause hypotension, reduce myocardial contractility, increase heart rate and breathing frequency, aggravate lactic acidosis, promote adhesion of leucocytes to the endothelium, attract other cytokines, activate neutrophils and induce the release of interleukin-6 which activates other inflammatory cells typical of the acute phase. Cytokines also stimulate platelet activation, which induces the release of histamine and serotonin, bronchoconstriction, an increase in capillary permeability and a lowering of blood pressure. The activation of leucocytes by the cytokines causes endothelial damage with an increase in vascular permeability and thrombosis. The increase in leucocyte adhesion contributes to microvascular occlusion.

The tumour necrosis factor released into the ischaemic tissues, where perfusion and O₂A are insufficient, also depresses myocardial contractility. As a result of peripheral vasoconstriction, the blood is diverted to the vital organs (heart and brain), thereby causing hypoperfusion of the kidneys, liver, gastrointestinal tract and lungs. If prolonged, the hypoperfusion can cause acute renal failure with metabolic acidosis, acute tubular necrosis and glycosuria. At the gastrointestinal level, ulcers that facilitate bacterial translocation and sepsis may develop, whereas, in the lungs, vasoconstriction alters the oxygenation/perfusion ratio thereby impeding oxygenation of the blood. If the process is not corrected by appropriate treatment, multiple organ failure and death of the patient may ensue.

CLASSIFICATION

Shock can be classified into three main types on the basis of the major imbalance:

• hypovolaemic;
• distributive;
• cardiogenic.

In hypovolaemic shock, the main imbalance is the loss of circulating blood volume, in cardiogenic shock it is heart failure and in distributive shock circulatory changes occur. A patient may have more than one type of shock simultaneously. For example, a heart patient may also suffer a traumatic event and develop severe bleeding which causes hypovolaemic shock; in its turn the hypovolaemic shock worsens the cardiac decompensation, resulting in the simultaneous presence of cardiogenic shock. The type of shock and its stage must be determined in order to be able to make a diagnosis of the disease process in progress and implement effective emergency treatment. This diagnosis is made by evaluating at least the following vital signs:

• mucous membrane colour and capillary refill time;
• pulse and its characteristics;
• heart rate and sounds;
• respiratory rate and breathing pattern;
• central and peripheral temperature (rectal and interdigital);
• state of the sensorium.

The patient's ventilation, circulation and consciousness can be evaluated through the analysis of these vital parameters. Patients in shock may have one or more altered parameters; the extent of the alteration and the number of altered parameters indicate the severity of the disease process and its stage. When possible, in addition to controlling the above-mentioned clinical vital signs, the clinician should always measure the blood pressure to determine the type of fluid therapy suitable for resuscitation. A hypovolaemic patient with a mean arterial pressure below 70 mmHg or systolic blood pressure below 90-100 mmHg requires rapid restoration of circulating fluid with aggressive fluid therapy (referred to as a “shock dose”).

After measuring the vital signs, when diagnosing cardiocirculatory insufficiency it may be useful to measure the concentration of lactate in the blood, so as to quantify tissue perfusion objectively. The blood lactate concentration is also a useful parameter in the following hours or days, to verify the effectiveness of the treatment implemented. Proper treatment can reduce the values as early as 1 hour after the start of treatment. The lactate concentration can be measured in a peripheral blood sample (if there is not severe impairment of local circulation) or better still in a central blood sample. Central blood samples are also useful for assessing central venous saturation (ScvO₂), which provides information about the body's ability to oxygenate tissues (however, blood-gas analyses are needed for quantification). ScvO₂is one of the parameters used in humans to evaluate the effectiveness of treatment in the course of sepsis and septic shock. Another very useful examination during the initial evaluation of the patient is oximetry at an available mucous membrane(e.g., lips or tongue). Pulse oximetryindicates the capacity of the lungs and circulation to oxygenate the blood. It provides continuous real-time data,which are useful for evaluating the effectiveness of the treatment instant by instant.

Hypovolaemic shock may be caused by severe bleeding, vomiting or diarrhoea, a loss of fluids in the third space and, more rarely, hypoadrenocorticism. Patients in a state of hypovolaemic shock have pale or whitish mucous membranes, depending on the severity of the hypovolaemia and the peripheral vasoconstriction or vasodilatation. Peripheral vasoconstriction causes a prolonged capillary refill time because the blood needs more time to fill the vascular bed of the mucous membrane following removal of finger pressure. In hypovolaemic shock, the peripheral vasoconstriction that diverts the blood from the muscles, skin and gastrointestinal tract to the heart and brain is a consequence of stimulation of baroreceptors in the aorta and carotid artery, which perceive less distension of the vessel wall. As a result they send signals to the vasomotor centrelocated in the medulla oblongata which inhibits the parasympathetic nervous system. The reduction of vagal tone, in addition to causing peripheral vasoconstriction, also increases the heart rate and myocardial contractility. Furthermore, the baroreceptors stimulate release of antidiuretic hormone or vasopressin from the neurohypophysis, which causes water retention in the distal convoluted tubules of the kidney. If prolonged, vasoconstriction leads to a decrease in the temperature of the extremities and tissue acidosis due to a reduction in available oxygen to below the necessary amount (VO₂). The decrease in the volume of circulating blood reduces the stroke volume (SV; the volume of blood expelled from the left ventricle during each systole), causing a decrease in cardiac output (CO) and in oxygen availability and increased mortality. Excessive peripheral vasodilation, such as that found in the irreversible stage of shock, can prolong the capillary refill time due to excessive dilation of the peripheral capillaries. In hypovolaemic shock, it is common to observe an increased heart rate (HR) because the body tries to compensate for the reduction in SV by increasing the number of ventricular ejections per minute. In fact the CO is the product of the SV multiplied by the HR and is calculated using the following formula: CO = SV x HR. The increased respiratory rate commonly found in states of shock is usually due to the increased oxygen demand of tissues that are insufficiently or poorly perfused. The state of the sensorium can be normal, depressed or, in severe cases, stuporous, because of altered perfusion and brain oxygenation. In some cases, patients may manifest sensorial excitation as a result of pain stimuli which lead to the release of catecholamines such as adrenaline and noradrenaline. In addition to having a vasomotor effect, catecholamines stimulate the cells of the juxtaglomerular apparatus of the kidney where they promote the release of renin. In its turn, renin activates the renin-angiotensin-aldosterone system leading to the formation of angiotensin II, which induces splanchnic vasoconstriction and the release of aldosterone which causes reabsorption of sodium and chlorine. Angiotensin II also induces the release of noradrenaline from the adrenal glands and the neurons of the sympathetic nervous system.

Patients suffering from distributive shock have symptoms similar to those described for hypovolaemic shock. To diagnose this condition correctly it is necessary to determine the origin of the disease process (e.g., trauma or sepsis). Special attention is given to septic shock, characterized by hypotension that is resistant to adequate fluid therapy  for resuscitation. In this type of shock, the hypotension is caused by the activation of potassium channels, an increased concentration of nitric oxide and a decreased concentration of vasopressin; myocardial contractility is reduced as a result of inflammatory cytokines.

Cardiogenic shock may be the result of anterograde or retrograde heart failure. Anterograde heart failure occurs when the CO is reduced because of cardiac causes (e.g. canine or feline dilated cardiomyopathy, patent ductus arteriosus, subaortic stenosis); retrograde heart failure (e.g. mitral valve endocardiosis, ventricular septal defects, tricuspid valve endocardiosis) causes an increase in venous pressure that leads to oedema (pulmonary or splanchnic). Patients with cardiogenic shock of anterograde origin may show symptoms similar to those of patients with hypovolaemic shock because the CO is reduced. Patients with retrograde heart failure usually have an increase in blood pressure and may manifest pulmonary oedema or abdominal effusion, depending on the predominantly involved valve.

It is very important to distinguish between cardiogenic shock of anterograde origin and hypovolaemic shock, because aggressive fluid therapy, which can be useful for hypovolaemic shock, may be deleterious in cardiogenic shock of anterograde origin. Even in the course of cardiogenic shock of retrograde origin, aggressive fluid therapy can worsen the symptoms and increase the risk of death (due to exacerbation of the interstitial and cellular oedema). After diagnosing cardiogenic shock, it is important to distinguish which type of heart failure is occurring, because while the retrograde type often benefits from therapy with diuretics, in the anterograde type the use of these drugs could impair the already deficient CO, thereby reducing the O₂A and increasing the risk of death.

After diagnosing the type of shock, its stage must be determined in order to implement the appropriate therapy, in terms of both timing and extent, and monitor the patient during hospitalisation. The evaluation of the stage and its monitoring are also useful for prognostic purposes and to explain to the owner the emergency nature of the treatments to be given, or vice versa, the stability of the patient.

STAGING

Three stages of shock can be recognized: compensated, decompensated and irreversible. The symptoms of the compensated stage of shock are characteristic of a hyperdynamic phase influenced by the release of catecholamines and are:

• increased heart rate;
• normal or increased blood pressure;
• increased intensity of the pulse (hyperdynamic pulse);
• increased respiratory rate;
• hyperaemic mucous membranes;
• shortening of the capillary refill time (< 2 sec);
• increase in the difference between central and peripheral temperature;
• sensorial excitation.

In the decompensated stage, there is reduced tissue perfusion resulting in cellular hypoxia and increased anaerobic metabolism with the production of lactic acid and an increase in the concentration of lactate in the blood. The presence of inflammatory cytokines causes the loss of integrity of the vascular wall with a consequent reduction in blood pressure and tissue perfusion. At this stage, the skin, gastrointestinal system, muscles, kidneys, liver and lungs are perfused less in order to favour blood supply to the heart and brain. Furthermore, at this stage there is a higher risk of gastrointestinal ulcers, kidney failure and bacterial translocation.

The symptoms associated with the decompensated stage of shock are:

• increased heart rate;
• reduced blood pressure;
• weak pulse or pulse difficult to feel;
• pale mucous membranes;
• increased or decreased respiratory rate;
• prolonged capillary refill time (> 2 sec);
• cold extremities and skin;
• drop in rectal temperature;
• depression of the sensorium.

The irreversible stage  of shock can be the result of ineffective treatment or lack of response by the patient due to the ongoing state of shock and the continuous presence of cytokines in the circulation with a drastic reduction of O₂A  and the possible death of cells in some tissues and organs. At this stage one or more organs may fail (multiple organ failure syndrome). The prognosis is poor with a high risk of imminent respiratory and cardiac arrest.

The symptoms associated with the irreversible stage of shock are:

• decreased heart rate;
• severe hypotension;
• capillary refill time increased or difficult to determine;
• pulse weak or absent;
• reduced heartbeat;
• cyanotic or whitish mucous membranes;
• reduced respiratory rate, respiratory failure;
• reduced cardiac output;
• oliguria and kidney failure;
• severe depression of the sensorium, stupor or coma.

TREATMENT

To increase survival in patients with shock, there must be an attempt to increase O₂A by optimising CO and the total oxygen content in the blood (CaO₂). O₂A is influenced by two main components: CO and CaO₂ (Fig. 1).

The CO depends on the stroke volume, heart rate and myocardial contractility. CaO₂  depends on the amount of haemoglobin and the partial pressure of arterial oxygen (paO₂). Unfortunately, in order to quantify the haemodynamic component of O₂A, in other words the CO, a thermodilution catheter (Swan-Ganz catheter) must be placed into the pulmonary artery. However, if the components of the CO are known and the clinical parameters that influence it can be evaluated, appropriate therapy can be given to optimise the CO. The first component of the CO, the stroke volume, is dependent on preload i.e. the circulating blood volume that reaches the right heart. This can be assessed clinically by studying the blood volume (e.g. by observing the filling of the jugular vein). The stroke volume can be quantified approximately by measuring the central venous pressure. The central venous catheter may be placed in the cranial vena cava through the jugular vein or the medial saphenous vein.

Fluids can be administered intravenously to increase the blood volume whereas diuretics are normally used to reduce it, for example in the course of hypervolaemia and pulmonary oedema caused by retrograde heart failure. Heart rate and contractility can be supported with drugs that control heart rate and inotropism.

To quantify the component that concerns oxygenation, i.e. CaO₂, arterial blood-gas analysis must be conducted. The blood-gas analysis must be carried out on arterial blood because in order to calculate the CaO₂we must know the value of the partial oxygen pressure and its saturation in the arterial region as shown in the following formula:

CaO₂= (1.3 x Hb x SaO₂) + (0.03 x PaO₂)

(CaO₂ = total oxygen content, Hb = haemoglobin, PaO₂ = partial pressure of arterial oxygen)

An analysis of the formula shows that the CaO₂ is greatly influenced by the amount of haemoglobin in the blood of the patient, so if we want to increase the survival of patients with shock, we must make an attempt to reach haemoglobin values greater than or equal to 7-8 g/dl or, better still, greater than 9-10 g/dl.

The treatment of shock, regardless of the aetiopathogenesis,  can therefore be summarised by the VIP acronym: ventilation, infusion and perfusion.

Ventilation. The patient must be adequately ventilated and oxygenated in order to obtain an O₂A of between 600-900  l/m^₂/min. If the patient is not breathing, orotracheal intubation is needed and two long insufflations must be made with 100% oxygen to expand the chest. If the patient does not resume spontaneous ventilation,  cardiopulmonary-cerebral resuscitation must be performed. If the patient is breathing spontaneously, the level of oxygenation must be checked:

• normal: paO₂≥ 80 mmHg, SaO₂≥ 95%
• hypoxaemia: paO₂< 80 mmHg, SaO₂< 95%
• severe hypoxemia: paO₂≥ 80 mmHg, SaO₂≥ 95%

(paO₂ = partial pressure of oxygen in the blood expressed in mmHg, SaO₂ = percentage of oxygen saturation of arterial haemoglobin)

When hypoxaemia is diagnosed, oxygen must be administered. Some examples of oxygen therapy are given below:

• oxygen mask: 5-6 litres/min;
• endonasal plugs: 50-100 ml/kg/min;
• transtracheal tube: 50-100 ml/kg/min;
• oxygen tent: keep FiO₂(fraction of inspired oxygen) at 40%;
• source of oxygen (tube) near the nasal cavities (flow by):
  • cats and small dogs 1-3 litres/min.
  • medium sized dogs 3-5 litres/min.
  • large and giant breed dogs 5-15 litres/min.

Infusion. When patients suffering from shock have a circulating blood volume that is insufficient to provide good CO, aggressive fluid therapy is required to restore effective circulation. In some cases, when the vascular bed is not appropriate for the circulating volume (e.g. vasodilation resulting in severe sepsis or septic shock), it may be useful to give vasoactive drugs (e.g. dobutamine, dopamine or noradrenaline) together with the fluid therapy. To restore an effective circulation quickly, crystalloid solutions can be infused at a fast rate: for example, 0.9% NaCl, lactated Ringer's solution or electrolyte solution for replenishment with sodium gluconate (Normosol-R). The preferred solutions in the course of metabolic acidosis are balanced solutions, such as the electrolyte solution for replenishment with sodium gluconate or lactated Ringer's solution.The infusion rate of crystalloid solutions in hypovolaemic shock, also known as “shock dose”, is 40-90 ml/kg/hour in dogs and 25-55 ml/kg/hour in cats; the infusion can be given intravenously or intraosseously   (Fig. 2).

Crystalloids leave the vascular bed quickly (after about an hour only 15-25% remains in the intravascular space) and can cause interstitial and intracellular oedema, especially in the lungs and the brain. When used to restore circulation quickly, the hypertonic crystalloid solutions (e.g. 7% NaCl) are administered as an intravenous bolus dose of 4-5 ml/kg/day, while the colloidal solutions (e.g. tetrastarch, dextran 70) are administered as an intravenous bolus dose of 10-20 ml/kg/day. Colloids are preferred over crystalloids when the circulation has to be restored quickly or when the oncotic pressure is low, such as when the total protein concentration is less than 3.5 g/dl. If colloids are used for the sole purpose of restoring the oncotic pressure, they can be administered at a dose of 2 ml/kg/hour as a constant rate infusion.

The effectiveness of fluid therapy at restoring the circulation can be assessed by measuring the blood pressure. The best measurements are obtained by invasive measurement of arterial blood pressure which does, however, require the insertion of an arterial catheter. Since this is difficult to achieve in traumatised, conscious patients, it is common to measure arterial blood pressure non-invasively by applying pneumatic cuffs at the base of the tail or at the extremities of the limbs. In order to ensure good tissue perfusion, the mean arterial blood pressure should be ≥ 80 mmHg (range,  80-120 mmHg) and the systolic blood pressure should be  ≥ 100 mmHg.

When aggressive fluid therapy is administered (at the above-mentioned shock doses) it is important to monitor at least the following perfusion parameters every 15 minutes during the infusion: heart rate (normal value is 70-160 bpm for dogs and 120-140 bpm for cats), capillary refill time (normal value is <2 seconds), colour of mucous membranes (pink) and pulse (full). When the above parameters are normal, fluid therapy can be administered at a maintenance rate (2 ml/kg/hour i.v.). In cats, colloids should be administered slowly: 5 ml/kg as an i.v. bolus over 15 minutes and to effect, even in the course of resuscitation fluid therapy. Colloids such as tetrastarch 6% and dextran 70 have an oncotic pressure slightly higher than that of the blood (about 30-40 mmHg); when administered in adequate quantities and at a proper rate, they reduce the risk of oedema and promote a more rapid expansion of circulating blood volume than crystalloids do. If given in excessive amounts, they can increase the bleeding time because of dilution of coagulation factors. During severe bleeding blood must be administered as quickly as possible (under positive pressure) to achieve a haematocrit ≥ 25%. When blood is used to correct a severe coagulopathy, it should be administered slowly.

Blood is given when the haematocrit is below 20% or when the blood loss causes respiratory distress or there is a dangerous reduction of O₂A: 20 ml/kg blood raises the haematocrit by about 10%. The haemoglobin concentration should be between 7 and 8 g/dl, but preferably  ≥ 9-10 g/dl with a haematocrit ≥ 25%. The volume of blood to be transfused is calculated using the following formula:

• Dogs: kg x 85 x (desired Hct – recipient Hct)/donor Hct 
• Cats:  kg x 60 x (desired Hct – recipient Hct)/donor Hct

There are three types of fluid therapy for restoring circulation in the course of shock:

• rapid intravascular resuscitation
• resuscitation with hypotension
• resuscitation with above-normal goals

Rapid intravascular resuscitation is the fluid therapy most widely used and is indicated in patients with circulatory deficits resulting from a drop in circulating blood volume (e.g. due to severe diarrhoea and vomiting). See infusion.

Resuscitation with hypotension is used in the following cases:

• intracavitary haemorrhages;
• head injuries;
• pulmonary contusions;
• cardiogenic shock;
• oliguric renal failure.

The objective of this type of fluid therapy is to restore perfusion parameters while maintaining normal or below normal blood pressure: mean arterial pressure ≤ 80 mmHg. The fluid therapy is administered in small boluses: crystalloids: 10-20 ml/kg intravenously over 15 minutes to effect, colloids 5 ml/kg intravenously over 15 minutes to effect. After each bolus of fluid therapy, the perfusion parameters should be checked. If they are normal, the resuscitation fluid therapy can be stopped and maintenance with balanced electrolyte solutions can be provided.

Resuscitation with above-normal goals: in some patients it may be necessary to increase the O₂A to values that are ​​higher than normal, such as in the course of systemic inflammatory response syndrome (SIRS) and septic shock. In such cases, the fluids are administered at shock doses (see above) until perfusion and haemodynamic parameters are optimal.

Pump. To maintain the efficiency of the myocardial pump, CO and peripheral perfusion should be restored by re-establishing effective circulation with suitable fluid therapy; if this is not enough, drugs that act on the cardiovascular apparatus - such as dobutamine 5-15 mg/kg/min as a constant rate infusion or dopamine 5-10 mg/kg/min also as a constant rate infusion - can be administered. When contractility is impaired by cardiac diseases that alter rhythm or inotropism, it is necessary to administer cardioactive drugs such as atropine, β-blockers (e.g. atenolol) and ion channel blockers including sodium channel blockers (e.g. lidocaine), calcium channel blockers (e.g. diltiazem, verapamil) and potassium channel blockers (e.g. amiodarone).

Hypokinetic arrhythmias, such as atrioventricular blocks, sick sinus syndrome and atrial silence, may be treated with atropine at a dose of 20-40 mg/kg i.m. or i.v. and, in severe cases, with dobutamine as a constant rate infusion. Hyperkinetic supraventricular arrhythmias, such as sinus tachycardia, atrial tachycardia, junctional tachycardia or orthodromic reciprocating tachycardia, atrial fibrillation and atrial flutter, can be treated in an emergency with vagal manoeuvres or with verapamil 50 mg/kg/min i.v. in 2-3 minutes (maximum dose 0.15 mg/kg), propranolol 0.1-0.3 mg/kg as an i.v. bolus in dogs and 40-60 mg/kg as an i.v. bolus in cats and phenylephrine 5-10 mg/kg as an i.v. bolus. Hyperkinetic ventricular arrhythmias, such as sustained ventricular tachycardia, polymorphic ventricular tachycardia, bidirectional ventricular tachycardia, premature ventricular complexes and R on T alterations on the electrocardiographic trace, can be treated with potassium chloride, at a dose depending on the hypokalaemia, lidocaine at 2-4-8 mg/kg as an i.v. bolus followed by 40-80 mg/kg/min as a constant rate i.v. infusion in dogs and 0.25-1 mg/kg as an i.v. bolus followed by 10-40 mg/kg/min as a constant rate infusion in cats or amiodarone at 3-5 mg/kg as an i.v. bolus. Cardioactive drugs must be used only when a cardiac emergency has been diagnosed; otherwise, it is better to delay treatment until after an examination by a cardiologist.

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