Understanding Shock and Oxygen Delivery (DO2)

• Echo is a useful tool; students should recognize echo views and structures.
• Shock and congestive heart failure share similar pathophysiology with a few differences.
• Therapies for heart failure often address excessive activation of certain systems.

Neurohumoral Systems in CHF

• Norepinephrine: increased
• Renin-angiotensin system: increased
• Renal sodium excretion: decreased
• Vasopressin: increased
• B-type natriuretic peptide: increased
• Parasympathetic tone: decreased
• Blood pressure: decreased or no change
• Systemic hypertension as a cause of CHF is more common in humans than veterinary patients.
• Mitral valve disease in dogs typically presents with normal blood pressure.
• Dilated or hypertrophic cardiomyopathy often present with low blood pressure due to forward heart failure.

Recognizing Shock

• One of the main goals is being able to recognize shock and intervene quickly for better outcomes.
• The sooner shock is recognized and treated, the better the chance of reversing the situation.
• In shock, patients may be weak, in external recumbency, tachypneic, with dilated eyes and an abnormal sensorium.
• After treatment of shock, patients should have a more comfortable body position and a more alert demeanor.

Classic Signs of Shock

• Tachycardia, increased pulse rate
• Tachypnea
• Pale and cool skin
• Mucous membrane pallor
• Delayed capillary refill time
• Reduced urine output
• Weak arterial pulses or abnormal pulse pressure
• Muscle weakness
• Pupillary dilation
• Abnormal sensorium
• Abnormal sensorium presents as not paying attention to the surroundings and just trying to maintain homeostasis.

Objectives for Understanding Shock

• Know the classic clinical signs and findings.
• Know compensatory mechanisms well enough to write an essay.
• Differentiate the causes of shock.
• Know pros and cons of therapy for each cause of shock (fluids, blood products, steroids, pressors, antithrombotics).
• Know endpoints of therapy for shock.

Definition of Shock

• Shock is a clinical syndrome resulting from insufficient cardiac output to fill the arterial tree with blood under sufficient pressure, leading to inadequate blood flow to organs and tissues.
• Shock leads to a deficiency of oxygen in the tissues.
• It is a severe hemodynamic or metabolic dysfunction characterized by reduced tissue perfusion, impaired oxygen delivery (DO2), inadequate cellular utilization, or inadequate cellular energy production.
• Reduced tissue perfusion and impaired delivery of oxygen to the tissues are the most commonly observed issues.

Oxygen Delivery (DO2)

• Oxygen delivery (DO2) is cardiac output (CO) times the oxygen content of arterial blood (CaO2).
• DO2 = CO x CaO2

Determinants of Cardiac Output

• Cardiac Output (CO) is determined by heart rate and stroke volume.
• CO = HR x SV
• Heart rate is influenced by the autonomic nervous system, with sympathetic stimulation increasing HR and parasympathetic stimulation decreasing it, as well as heart disease and drugs.
• Stroke volume is affected by preload, afterload, and myocardial contractility.

Determinants of Oxygen Content (CaO2)

• Oxygen content (CaO2) is determined by the amount of oxygen bound to hemoglobin and dissolved in plasma.
• CaO2 = (1.34 x Hgb x SaO2) + (0.003 x PaO2)
• Most oxygen is bound to hemoglobin.

Major Mechanisms for Shock

• Inadequate blood volume is the most common cause.
• Inadequate cardiac performance, inadequate vascular tone, and tissue defects in oxygen utilization are less common.

Shock Classification

• Etiology/Clinical disease (hemorrhagic/hypovolemic, traumatic, cardiogenic, septic, neurogenic, anaphylactic) aids in overall therapy.
• Volume status (normovolemic, hypovolemic, hypervolemic) helps determine fluid/diuretic administration.
• Descriptive (hypovolemic, cardiogenic, vasculogenic, distributive) is least useful but may help Rx decisions.

Compensatory Mechanisms in Shock

• Tachycardia and increased pulse rate is due to sympathetic release triggered by baroreceptors.
• Kidneys sense decreased perfusion and make less urine, leading to reduced urine output (oliguria).
• The renin-angiotensin system is triggered by decreased renal perfusion, leading to aldosterone release to retain sodium and water, and vasoconstriction by angiotensin II.
• Mucous membrane pallor is due to peripheral vasoconstriction, mediated by sympathetic tone, angiotensin, and antidiuretic hormone (vasopressin).
• Sympathetic activation results in pupillary enlargement.
• Muscular weakness is due to reduced perfusion, leading to anaerobic metabolism and lactate formation, resulting in hyperlactateemia and lactic acidosis.
• Lungs sense changes in blood oxygen and acidosis, resulting in tachypnea to blow off acid.
• Reduced GI perfusion leads to GI stasis.
• Compromised GI tract permeability can lead to bacterial translocation.

Sympathetic Nervous System

• Increased heart rate
• Increased inotropic state
• Vasoconstriction
• Increased blood pressure toward normal levels
• Hepatic glycogenolysis increases blood glucose

Additional Compensatory Mechanisms

• Baroreceptor response: increased CO
• Chemoreceptor response: increased ventilation
• Cerebral ischemic response: vasoconstriction via SNS
• Renal conservation of salt and water
• ADH release: water retention, vasoconstriction to raise BP
• Local vasoconstriction: reduced perfusion to cutaneous, renal, GI, muscular, mesenteric beds
• Renin-angiotensin-aldosterone system: vasoconstriction and sodium/water retention
• Other vasoactive compounds such as vasodilators and vasoconstrictors

Consequences of Reduced Cardiac Output and Compensatory Responses

• Metabolic acidosis: increased base deficit / dropping bicarb
• Elevated blood lactate: hyperlactatemia
• Vasodilator release: circulatory pooling and loss of effective circulating volume
• Reticuloendothelial cell depression: liver/spleen cannot clear endotoxin and bacteria
• Altered coagulation: capillary sludging, activation of tissue factor, complement activation, loss of protein C leading to DIC with thrombosis and consumptive coagulopathy
• Reduced GI perfusion: bacterial translocation
• Inflammatory cytokine release: tumor necrosis factor, interleukin I, platelet activating factor, and other cytokines (IL-6, IL-10)
• Cell death: DAMPS (mitochondrial DNA, formyl peptides), prostaglandins/leukotrienes, oxygen radical formation and damage
• Myocardial failure from cytokines (TNF), coronary thrombosis, low coronary perfusion, etc.
• Nitric oxide formation (iNOS) and other factors: loss of vascular tone, vascular endothelial damage, glycocalyx loss

Arachidonic Acid Pathway

• Tissue injury leads to release of membrane phospholipids, which go down the arachidonic acid pathway.
• The arachidonic acid pathway leads to the lipoxygenase pathway to leukotrienes or the COX pathway to prostacyclin (vasodilator) or thromboxanes (platelet activity).
• Oxygen-free radicals contribute to damage, especially in septic shock.

Differences in Cats

• Cats are not small dogs.
• Shock in cats typically presents as bradycardia, hypothermia, and hypoglycemia.
• Hypothermia affects the sinus node firing rate and contributes to the bradycardia.
• Cats have a smaller blood volume (45-60 mL/kg).

Cardiogenic Shock vs. Other Forms of Shock

• Fluid volume is typically excessive.
• Elevated ANP and BNP levels.
• Distended Jugular vein.
• Diuretics are indicated, whilst fluids are not.

Definitions Related to Shock

• Bacteremia: bacteria in the bloodstream
• Infection: inflammatory response to microorganisms
• SIRS: Systemic Inflammatory Response Syndrome
• Sepsis: SIRS with documented or strongly suspected infection
• Endotoxemia: endotoxin (LPS) in the bloodstream
• Severe sepsis: sepsis with organ dysfunction and hypoperfusion
• MODS: Multiple Organ Dysfunction Syndrome (e.g., respiratory failure plus kidney failure)
• Septic shock: severe sepsis with hypotension unresponsive to adequate fluid resuscitation

SIRS Criteria

• Abnormal temperature (fever or hypothermia)
• Abnormal heart rate (tachycardia or bradycardia)
• Tachypnea
• Leukocytosis, leukopenia, or significant left shift (bands)
• Cats are more likely to have bradycardia and hypothermia with sepsis than dogs.
• The presence of SIRS indicates the animal is in trouble and requires fast action.

Sepsis Arc

• Infection progresses to SIRS, then sepsis, severe sepsis with organ dysfunction, and eventually septic shock and possibly death.
• Early recognition of sepsis and starting antibiotics is crucial.

MODS

• Presence of organ dysfunction in 2 or more systems.
• Kidney dysfunction (creatinine rise > 0.5 mg/dL)
• Cardiovascular dysfunction (need for pressors to raise blood pressure)
• Respiratory dysfunction (need supplemental O2 or mechanical ventilation)
• Hepatic dysfunction (T. bili > 0.5 mg/dL)
• Coagulation dysfunction (Thrombocytopenia or clotting factor depletion)

Shock Scenarios

• Include hypovolemic, cardiogenic, septic, anaphylactic, and neurogenic.

Hypovolemic Shock

• Loss of circulating blood volume due to hemorrhage, GI losses, reduced intake of fluids, diuresis, third spacing of fluids, or Addison's disease.
• A 10% blood loss results in little to no change in MAP, and spontaneous recovery is likely.
• A 15-20% blood loss results in low normal MAP between 80-90 mmHg, and spontaneous recovery is possible.
• A 20-30% blood loss results in an initial MAP of 60-80 mmHg, with severe hypotension and early shock, treatmen is often reversible during this stage.
• A 30-40% blood loss results in an initial MAP of 50-70 mmHg, shock may be irreversible and fatal even with treatment.

Third spacing of fluids

• Occurs when fluid leaks from capillaries into subcutaneous tissue and becomes inaccessible to the body

Treatment of Hypovolemic Shock

• Administer oxygen.
• Determine and remove the inciting cause, such as stopping hemorrhage or surgically removing infection.
• Give IV fluids rapidly, in bolus, unless the patient has cardiogenic shock.
• Use a large bore catheter.
• Administer a total volume of 90 ml/kg in an hour for dogs, often given in 20 ml/kg boluses serially, and 60 ml/kg in an hour for cats, with the same 20 ml/kg bolus approach.
• After giving sufficient fluids, if shock persists, administer pressors or inotropes.
• If ongoing bleeding, consider Tranexamic acid as an antifibrinolytic agent.

Fluid Therapy for Hypovolemic Shock

• Use crystalloid boluses up to 90 ml/kg for dogs, administering 20 ml/kg, then reassess for shock; repeat if needed.
• Consider pressors, blood, or colloids if needed.
• Use 60 ml/kg for cats, similar stepwise fashion with 20 ml/kg boluses.
• Recheck physical exam, PCV, TS, and lactate levels at each reassessment point. Lactate levels should improve within 30 minutes of improving the shock scenario.

Crystalloid Fluids

• Replacement fluid types can be used in shock, including 0.9% NaCl, Lactated Ringer's solution, and Plasmalyte A.
• Maintenance fluid types are typically not used in shock, including Plasmalyte 56 and 0.45 NaCl in 2.5% dextrose (KCL added).
• Hypertonic Saline is also an option – 7.5%NaCl

Distribution of body Fluid

• Intracellular fluid is 66% of body fluid
• Extracellular fluid is 33% of body fluid
• Of the extracellular fluid, 75% is interstitial and 25% is intravascular

Crystalloids

• Are inexpensive
• Are easy to administer
• Has Persistence in intravascular space limited (½ to ⅕ administered volume remains in intravascular space by 1 hour)
• There are a variety of choices for electrolytes
• They have few adverse reactions
• Can cause fluid overload you give too much

Hypertonic Saline

• 7.5% hypertonic saline.
• Administer 4 ml/kg over > 10 minutes to achieve rapid expansion of intravascular volume; the fluid is pulled in from the interstitial space.
• Effects will not persist unless followed by or given with crystalloids.
• Used in very large animals or head trauma cases to minimize cerebral edema; also used in large breed dogs (GDV).
• Potential side effects: hyperosmolarity, hemolysis, hypernatremia, hyperchloremia, and hypotension or VPCs if given too fast.

Colloids

• Large, oncotically active particles.
• Maintain intravascular colloid osmotic pressure (COP).
• Smaller volume to achieve plasma volume expansion (3:1 compared to crystalloids).
• Greater persistence in the intravascular space.
• Commonly administered in 20 ml/kg total dose.
• 1-2 ml/kg/hr as a CRI
• Examples: Hetastarch, Dextrans, Gelatin, Albumin (Canine albumin vs Human albumin), and Hemoglobin-based oxygen carriers (HBOC) - Oxyglobin.
• Disadvantages can include More expensive than crystalloids, renal toxicity, Coagulopathy, Anaphylactic reactions, Not cleared quickly, No clear survival benefit, Reduced survival in human trauma cases

Blood Products

• Indicated for low PCV, TS, or is there active bleeding.
• Packed RBCs are indicated for Low PCV
• Fresh Frozen Plasma contains clotting factors and protein.
• Frozen Plasma contains aprotien.
• Platelet Rich Plasma are platelets that are only effective for a few hours
• Cryoprecipitate contains Clotting factors without the volume.

Inotropes and Vasopressors

• May be used when Blood volume OK, or if heart or vascular tone is abnormal
• Examples of those drugs are Dopamine, Dobutamine, Norepinephrine, Phenylephrine, and Milrinone or Inamrinone.
• Norepinephrine was first line vasopressor in 87.9% for dogs and 83.1% for cats
• Vasopressin was the most common second choice vasopressor
• Most ACVECC diplomats started vasopressor (after fluid Loading) for: Systolic BP < 90 mmHg or MAP < 60 to 65 mmHg

Receptor Specificity and CV Effects of Sympathomimetic Drugs

• Different inotropes stimulate different receptors and have different effects on blood pressure and cardiac output.
• Beta-1 agonists stimulate cardiac receptors, increasing heart rate and contractility.
• Beta-2 receptors stimulate vascular and bronchial receptors, causing vasodilation and bronchodilation.
• Alpha-1 receptors stimulate vascular receptors, causing vasoconstriction and increased blood pressure
• In hypovolemic shock, norepinephrine, is the ideal choice, having primarily has alpha and some beta 1 effects.

Fluid Choice

• Replace deficits with replacement crystalloids.
• After 24-48 hours, use Maintenance crystalloids.
• Hypertonic saline is acceptable in head trauma, Horse, big dog shock.
• Colloids can be used to droping TS but without coagulopathy, may reduce capillary leak but give if Albumin < 1.8-2.2.
• Pressors can be used to increase BP if blood volume is okay or cardiac bad .Use just give blood products for blood loss

Fluid Overload

• Fluid retention in the lungs
• Pulmonary edema, pleural effusion, or ARDS (Acute Respiratory Distress Syndrome)
• Peripheral fluid retention due to capillary leak or hypoalbuminemia
• Associated with worse outcome and more likely if repeated boluses of crystalloids

Summary of Treatment of Hypovolemic Shock

• Administer oxygen and determine/ remove inciting cause.
• Administer IV fluids rapidly, in bolus
• Crystalloids used until shock signs are resolving
• Consider colloids if marked hypoalbuminemia (< 1.8 g/dl).
• Blood products for anemia or coagulopathy
• Pressors or inotropes AFTER crystalloids if shock persists

Cardiogenic Shock

• Low cardiac output resulting from poor cardiac performance such as cardiac tamponade due to pericardial effusion, ruptured chordae tendinae (resulting in severe pulmonary edema), severe arrhythmia, myocardial infarction, pulmonary thromboembolism, or tension pneumothorax.
• Tension pneumothorax increases pressure in the pleural space collapsing the cava.

Cardiogenic Shock Definition

• Includes low cardiac output (usually < 2.2 L/min/M²), hypotension (Systolic BP < 90 mmHg, MAP 60-65 mmHg or less), signs of hypoperfusion (e.g., oliguria, altered mental status, pallor, high lactate, etc.), normal or elevated cardiac filling pressures (Often with PCWP > 15 mmHg), and it is due to a cardiac cause.

Treatment of Cardiogenic Shock

• Administer oxygen.
• Determine and remove inciting cause
• Treat bradycardia with pacing or anticholinergics.
• Treat tachycardias with drugs or defibrillation.
• Treat CHF with diuretics.
• Perform pericardiocentesis if appropriate.
• Perform centesis if marked ascites or pleural effusion.
• Administer inotropes or vasodilators in selected cases: Pimobendan vs Dobutamine vs Sodium Nitroprusside.
• Fluids are typically not indicated for cardiogenic shock.

Septic Shock Defined

• Severe sepsis with hypotension that is unresponsive to adequate fluid resuscitation
• Sepsis-induced hypotension despite adequate fluid resuscitation with hypoperfusion including, but not limited to, lactic acidosis, oliguria, and acute alteration in mental status

Septic Shock Concepts

• Gram-positive bacteria release various toxins.
• Gram-negative include endotoxin - E.g., lipopolysaccharide
• Can result from rickettsial, fungal, parasitic, or viral sources also possible.
• Most difficult to treat 50-70% survival in people
• Bacterial type (E. coli vs staph) usually reflects source of original infection
• Manifests as "Warm Shock" vs. "Cold Shock".
• The blood cultures need to be obtained rapidly from septic focus and broad spectrum antibiotics need to be commenced without waiting for results.

Clinical Descriptions Reflect the Progression of Septic Shock

• Warm or hyperdynamic shock: Tachycardia, Bounding pulses, Fever, Hyperglycemia, Injected mucous membranes, and Fast CRT
• Cold or hypodynamic shock: Tachycardia (except cats), Weak pulses, Hypothermia, Hypoglycemia, Pale mucous membranes, Delayed CRT

Septic Shock - Complicating Developments

• Inadequate circulating blood volume: reduced fluid intake, GI losses, splanchnic pooling, fluid loss from capillary leak, microthrombi, and reduced local tissue perfusion.
• Poor LV contractile function due to TNF, nitric oxide, other myocardial depressant factors, acidosis, and hypoxemia.
• Loss of vasomotor tone is associated with nitric oxide, prostaglandins, and inadequate steroid production or other vasodilators.
• Reduced ability of cells to utilize oxygen due to metabolic alterations.

Septic Peritonitis in Cats – 83 Cases

• 69.9% Survival to hospital discharge
• Cats getting appropriate antimicrobials 4.4 times more likely to survive
• GI leakage as most common cause
• 56% Gram -
• 42% Gram +
• Polymicrobial 70% of the time

Treatment of Septic Shock

• Administer oxygen and IV crystalloid fluid bolus.
• Blood cultures and/or cultures of septic focus.
• Broad spectrum antibiotics
• Re-evaluate Vitals plus PCV, TS, Lactate; still signs of shock?
• More crystalloids? Colloids? Blood products?
• Use inotropes and/or vasopressors.
• Surgical debridement and/or drainage
• Heparin (plasma is at Attempt to prevent/treat DIC
• ? Severe acidosis, esp. if not improved on fluids
• ? anti-endotoxin (?)

Keys for Sepsis and Septic Shock

Initiate antibiotics within 1 hour of diagnosis is critical and improves survival.

• Delayed initiation of antibiotics reduces survival
• Picking the wrong antibiotic reduces survival – don't be too afraid of aminoglycosides if indicated
• Numbers 1-3 contingent on early recognition of sepsis/septic shock
• Early aggressive fluids in hour 1 is helpful
• Subsequent large volume fluids leads to fluid overload
• Fluid overload causes reduced survival, ARDS, and AKI
• The steroid controversy is tricky; mostly "don't give them"
• Steroids more likely to help if dependent on vasopressors
• Norepinephrine is currently the preferred vasopressor

Anaphylactic Shock

• Anaphylactic (or anaphylactoid) reaction to immediate hypersensitivity reaction (Type I) IgE mediated release of substances from mast cells and basophils
• Urticaria
• Facial swelling
• Erythema
• Itching
• Angioedema
• Vasodilation
• Bronchoconstriction
• Laryngeal edema, airway obstruction
• Pulmonary edema
• Vomiting
• Diarrhea
• Ataxia
• Coagulopathy
• Hypotension, hypovolemia, death
• Anaphylaxis in dogs often associated with spontaneous abdominal effusion +/- gall bladder edema

Anaphylactic reactions

• Anaphylaxis in dogs can be associated with spontaneous abdominal effusion (ascites)
• Up to 59% may have gall bladder wall edema
• 47% had insect exposure
• 76% had gastrointestinal signs
• 75% had cutaneous signs
• 69% had cardiovascular signs
• With rapid treatment, most dogs survived

Treatment of Anaphylactic Shock

• Epinephrine (mast cell stabilization) 0.01 mg/kg IM; may repeat q 5 to 15 minutes
• Oxygen and IV crystalloid fluid bolus
• Re-eval Vitals plus PCV, TS, Lactate
• More crystalloids? Probably yes if still shocky
• Corticosteroids? Likely OK, but give epinephrine first!
• Antihistamines? Likely OK, but give epinephrine first
• Bronchodilators? Perhaps intubate instead, especially if upper airway component due to pharyngeal swelling
• If ADEQUATE fluid resuscitation and ongoing shock, inotropes and/or vasopressors (norepinephrine)

Neurogenic Shock

• Loss of vasomotor tone with Increased vascular capacity leads to poolingMay see bradycardia if elevated intracranial pressure Causes: Anesthesia, Trauma, Ischemia to vasomotor centers, or CNS disease

Treatment of Neurogenic Shock

• Administer oxygen and IV crystalloid fluid bolus, there may be a role for hypertonic saline
• Reduce anesthesia level aned consider vasopressors early.
• If head trauma, ensure adequate blood pressure. The most effective treatment of head trauma, and consider surgical decompression.
• Re-evaluate vitals plus PCV, TS, Lactate. Consider :Mannitol or if hypovolemic and diuretics.

Ideal Resuscitation

• Target systolic BP > 90 mmHg, PCV > 22%, Total solids >3.5 g/dl, PaO2 > 70 mmHg, Lactate < 2 mmol/L, Good arterial pulse quality, mm color, CRT, Normothermia, pH > 7.25; bicarbonate > 15-17, Urine output > 1.5 ml/ kg/hr
• If those are met, control cardiac arrhythmias, perform Serial evaluation and if stable, nursing careUltrasound findings help assess fluid volumes.

Controversies in Shock

• Do or do not give Corticosteroids, Antibiotics, Sodium bicarbonate, Diuretics, Antithrombotics, or Plasma and blood products