Shock: physiology and pathophysiology (Proceedings)

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 tachycardia (although bradycardia often occurs in cats), tachypnea, pale mucous membranes, cold extremities, poor peripheral pulses and altered mentation.

What happens during shock?

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. Tissue beds enter an anaerobic state, causing the products of cellular metabolism build. 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:

• Mobilization of fluid from the interstitial to intravascular space. This occurs primarily in shock states with low blood volume, especially hypovolemic shock, but can potentially occur in all shock states.

• Activation of the sympathetic nervous system (SNS). This results in release of norepinephrine and epinephrine. There are many effects of the SNS, including tachycardia, vasoconstriction which may preferentially affect certain tissue beds, and positive inotropy. Activation of the SNS also results in retention of sodium (and therefore water) by the kidneys.

• Activation of the renin-angiotensin-aldosterone system (RAAS). This results in multiple effects, the most important (and immediate) of which are retention of sodium and water by the kidneys, and peripheral vasoconstriction.

• Release of Antidiuretic hormone (ADH). This results in retention of water and urine concentration. ADH is also a powerful vasoconstrictor.

Stages of shock

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

• Hypovolemic shock is one of the most common etiologies, and means that blood volume is low. This can be due to two major causes: hemorrhage (either external or internal) and dehydration. Dehydration does not always cause hypovolemia, but in severe cases can lead to it.

• Cardiogenic shock occurs when the heart is unable to put enough blood forward to maintain perfusion and oxygen delivery. Examples of cardiogenic shock include dilated cardiomyopathy, mitral regurgitation and myocardial failure

• Obstructive shock occurs when there is an obstruction to flow. Usually this is an obstruction to venous return, although arterial obstruction (such as with a saddle thrombus) can also cause obstructive shock. GDV, pericardial effusion, venous thrombosis and tension pneumothorax are all causes of obstructive shock.

• Distributive shock is a combination of various types of shock. (Mal)distributive shock usually occurs as a result of sepsis, although anaphylaxis can cause it as well. The hallmark of distributive shock is peripheral vasodilation and vascular pooling. The patient may have red instead of pale mucous membranes. Patients with septic shock may also have elements of hypovolemia (from fluid losses or tissue edema), cardiogenic (from myocardial dysfunction) and obstructive (from DIC) shocks.

• Hypoxemic and anemic shock occur when there is insufficient oxygen content to meet tissue needs. This can be that there are not enough red blood cells to carry the oxygen (anemic), or that the oxygen cannot get into the blood (hypoxemic). Hypoxemic shock is usually the result of pulmonary pathology.

• Neurogenic shock is a specialized form of distributive shock. Massive sympathetic release causes severe systemic vasoconstriction, which results in decreased forward flow and signs of shock despite adequate blood volume. Causes are severe spinal cord or CNS injury, head trauma, status epilepticus, strangulation and airway obstruction.

• Metabolic shock is caused when the cells have sufficient oxygen for normal metabolism, but are unable to use that oxygen. This is usually the result of disruption of the Krebs cycle or the electron transport chain. Causes include hypoglycemia, cyanide toxicity or mitochondrial dysfunction (as occurs with sepsis).

Treatment of Shock

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.

• Hypovolemic shock can be treated by replacing blood volume, either with crystalloids, colloids, or blood products as indicated. More information on this will be presented in the next session.

• Cardiogenic shock can be treated by reducing vascular volume (Furosemide 2mg/kg in dog; 1mg/kg in cats; PRN), causing peripheral vasodilation if indicated (nitroglycerin) or improving inotropy (Dobutamine).

• Obstructive shock can only be treated by relieving the obstruction, whether that is by decompressing the GDV, tapping the pericardial effusion or the pneumothorax, or otherwise de-obstructing flow. Vascular loading with IV fluids can also be of benefit, especially if decreased regional blood flow is the cause of shock (as occurs with GDV).

• Distributive shock can be very difficult to diagnose and treat. If vasodilation and hypotension are present, treatment with vasopressors (such as dopamine, vasopressin or norepinephrine infusions) can be beneficial. These patients may also respond to fluid loading, which is the first line treatment for septic shock.

• Anemic or hypoxemic shock can be treated with relative ease. RBC transfusions or Oxyglobin can be given in cases of anemia shock (more on this later). Hypoxemic shock will usually respond to supplemental oxygen, although mechanical ventilation may be indicated in more severe cases.

• Neurogenic shock is difficult to treat. The only known treatment is to treat the underlying cause. This may include administration of mannitol 1 g/kg IV or hypertonic saline in case of head trauma or CNS disease to reduce intracranial pressure.

• Treatment of metabolic shock is also aimed at correcting the underlying cause. Give dextrose 0.5g/kg IV bolus for hypoglycemia, but otherwise treatment is symptomatic and supportive.

Unfortunately, the cause of shock is not always readily apparent. What should the clinician do with the unknown cause of shock? With the exception of cardiogenic shock, it is never wrong to try an IV bolus of crystalloids. The “shock dose” of crystalloids should be given in ¼ - 1/3 aliquots over a 10-15 minute period. If cardiogenic shock is suspected (heart murmur on auscultation +/- crackles), a test dose of furosemide can be administered. The test dose for dogs is 2 mg/kg IV or IM, and for cats is 1 mg/kg IV or IM. IV fluids should not be routinely administered in cardiogenic shock.

Many adjunctive therapies have been described. The most of these include:

• Steroids. The proposed benefit of steroids include stabilization of lysosomal membranes, prevention of lipid peroxidation, scavenging and stabilization of free radicals, and maintenance of adrenoreceptor function. Disadvantages are many, and include alterations of GI blood flow, immunosuppression, vasodilation, and impaired wound healing. Multiple studies have failed to show any benefit of high dose steroid administration in any shock state. Low dose steroid administration (at physiologic doses) may be beneficial in anaphylactic or septic shock.

• Antibiotics should be administered only when indicated. In dogs, severe shock states are associated with GI tract hypoperfusion. This may cause ischemia-induced sloughing of the mucosal barrier, which allows bacteria to translocate from the gut lumen to the blood vessels. This often manifests as raspberry jam-like diarrhea which may have flecks of mucosa. If bloody diarrhea accompanies shock, broad spectrum antibiotics may be indicated.

• Analgesia is always indicated if shock is accompanied by pain. The physiologic response to pain is similar to that to shock, in that SNS activation causes tachycardia and peripheral vasoconstriction. Not administering opioids can make shock resuscitation more difficult since the physical manifestations of the pain response can easily be confused with prolonged shock. Hydromorphone, oxymorphone, buprenorphine, fentanyl or morphine (except in cats) can all be used with success. Butorphanol is generally not sufficient for treatment of severe pain. NSAIDs should be avoided.

Monitoring treatment

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.

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.

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.