Shock/SIRS/Sepsis/MODS Flashcards
Shock definition
Shock is defined as an inadequate production of energy at the cellular level
– secondary to decreased delivery of oxygen and nutrients to tissues
Cryptic shock
term cryptic shock has been used to describe ill or injured patients with high lactate concentrations without hypotension
Goal of Shock tx
aims to improve tissue perfusion and restore optimal oxygen and nutrient delivery to tissues.
Resuscitation endpoints
Normalization of arterial blood pressure
lactate concentration and central venous oxygen saturation
POCUS as a means of dynamically assessing intravascular volume
Shock fluids
shock dose is approximately 60 to 90 ml/kg in dogs and approximately 45 to 60 ml/kg in cats, which reflects the approximate blood volumes in each species
– A common recommendation in small animals is to begin shock treatment using a bolus of 10 to 20 ml/kg administered over 15 to 30 minutes
Isotonic fluids for Shock boluses
– Rapid redistribution with short-lived intravascular volume expansion effect.
– Caution with use in patients with decreased colloid osmotic pressure or increased vascular permeability due to increased risk of pulmonary and interstitial edema
Normal Saline, LRS, Plyte, Norm-R
Synthetic colloids for shock boluses
Does: 2–5 ml/kg IV over 10–30 minutes
– Sustained intravascular volume expansion.
Increased risk of coagulation disturbances with use of large doses.
– May cause or exacerbate preexisting acute kidney injury
HES, Vetstarch
Hypertonic solutions for shock boluses
Dose: 3–5 ml/kg of 7%–7.5% NaCl solution over 10–20 minutes
– Monitor electrolytes, particularly sodium. Use with caution in chronic hyponatremia.
– Can exacerbate interstitial volume depletion in dehydrated patients.
– Good for small-volume resuscitation, particularly in septic shock, hemorrhagic shock, and traumatic brain injury.
3% HTS, 7.5% HTS
Blood products for shock boluses
10–20 ml/kg given IV over 2–4 hours (can be given faster in rapidly decompensating patients up to a rate of 1.5 ml/kg/min over 15–20 min
– Ideal for patients presenting in acute hemorrhagic shock
–
Canine and feline pRBCs
Canine and feline FFP
Canine and feline fresh whole blood (where donors available)
Adverse effects of aggressive crystalloid resuscitation
– patients with severe hypoproteinemia or kidney or cardiac dz
– Bc crystalloids redistribute into the interstitium, organ edema can occur and may be life threatening
– Pulmonary edema and ALI are among the most commonly seen adverse effects of shock resuscitation, particularly in patients with increased vascular permeability secondary to systemic inflammation or sepsis.
GIT effects of aggressive crystalloid fluid therapy
decreased motility, increased intestinal permeability predisposing the patient to bacterial translocation, and increased risk for abdominal compartment syndrome
Cardiac effect from aggressive crystalloid fluid therapy
– increased risk of ventricular arrhythmias, disruption of cardiac contractility, and decreased CO
– demonstrated by Starling’s myocardial performance curve; when beyond a designated point on the curve, further increases in end-diastolic volume cause a decrease in CO
Coag effects of aggressive crystalloid fluid therapy
Coagulation disturbances can also occur as a result of dilution of coagulation factors and decreased blood viscosity; however, these effects are significantly less than changes caused by synthetic colloids
Effects of aggressive resuscitation with crystalloids on endothelial glycocalyx
“Overzealous resuscitation with crystalloids has also been shown to negatively impact the health of the endothelial glycocalyx.
Recent studies have demonstrated that the volume of crystalloids administered in patients with septic shock is independently associated with the degree of glycocalyx degradation.”
Synthetic colloids
– increase the colloid osmotic pressure of serum, creating a force that opposes the hydrostatic pressure in the vasculature and helps retain fluid in the vascular space
Adverse effects of Synthetic Colloids
Coag adveserve effects of Synthetic Colloids
All colloidal plasma substitutes are known to interfere with the physiologic mechanisms of hemostasis either through a nonspecific effect correlated to the degree of hemodilution or through specific actions of these macromolecules on platelet function, coagulation proteins, and the fibrinolytic system.
– decreases in the activity of von Willebrand’s factor and its associated factor VIII and ristocetin cofactor activities, as well as some degree of platelet dysfunction
What dose of Synthetic Colliods is know to cause coag abnormalities?
that the administration of more than 20 ml/kg/day of hetastarch in animals can cause coagulation derangements
Hypertonic solutions
crystalloid solution is any saline solution that has an effective osmolarity exceeding that of normal plasma
– causes intravascular volume expansion due to the osmotic gradient generated by the sudden, dramatic increase in plasma osmolarity after administration
Other Advantagous of Hypertonic solutions
#3
– immunomodulatory effects, such as decreased neutrophil activation and adherence, stimulation of lymphocyte proliferation, and inhibition of proinflammatory cytokine production by macrophages.
– also improves the rheologic properties of circulating blood, reduces endothelial cell swelling, and helps reduce intracranial pressure in patients with traumatic brain injury
– improves myocardial function and causes coronary vasodilation, thereby improving overall cardiac function
Adverse effects of Hypertonic Fluids
#4
= hypernatremia and hyperchloremia
– risk for hypernatremia-induced osmotic demyelination syndrome
cautiously in patients with preexisting cardiac or pulmonary abnormalities because the increase in intravascular volume and hydrostatic pressure may lead to volume overload or pulmonary edema.
– can also cause significant interstitial (and intravascular) volume depletion, particularly in patients that are already dehydrated.
Albumin
– maintenance of colloid osmotic pressure and endothelial integrity, wound healing, metabolic and acid-base functions, coagulation, and free radical scavenging.
– often low in critically ill patients because of loss, vascular leak, third-spacing, and decreased production as a result of shifting of hepatic production toward acute-phase proteins.
Blood products
(whole blood, fresh frozen plasma [FFP], or packed red blood cells [pRBCs])
– hemorrhagic shock secondary to trauma, nontraumatic hemoabdomen, gastrointestinal bleeding, rodenticide intoxication, or other primary or secondary coagulopathies
– FWB transfusions carry the benefit of increased levels of clotting factors, fibrinogen, and platelets compared with component therapy
Hypotensive resuscitation
Restoration of a lower-than-normal systolic blood pressure (approximately 80 to 90 mm Hg) helps facilitate control of hemorrhage and reduces the risk of rebleeding but ensures preserved blood flow to vital organs such as the kidney and GI tract.
– temporary solution and is only meant to bridge the gap between presentation and definitive hemostatic control (usually via surgical intervention)
Fluid challenge
– administration of fluids to patients that are hemodynamically unstable in order to assess their response to fluid therapy
– helps guide therapy, particularly when hypovolemia may be subtle, while minimizing the risk of volume overload that can occur as a result of overzealous or unnecessary fluid therapy.
Urosepsis
sepsis associated with a complicated urinary tract infection (UTI).
– infection can be the kidney, bladder, prostate, or genital tract
– pyometra, prostatic abscessation or suppuration, testicular abscessation, renal abscessation and vaginal abscessation
uncommon in vetmed
local host defense mechanisms typically prevent ascending UTIs:
x7
- normal micturition,
- extensive renal blood supply,
- normal urinary tract anatomy (i.e., urethral lengthhigh pressure zones within the urethra),
- urethral and ureteral peristalsis,
- mucosal defense barriers,
- antimicrobial properties of the urine,
- systemic immunocompetence
Most common uropathogen
E. coli
laboratory changes with urosepsis
specifically related to the urinary tract, including azotemia, an active urine sediment and a positive urine bacterial culture
Pyelonephritis causing Urosepsis
– one or both kidneys may be enlarged and painful, and the animal may have signs of polyuria, polydipsia, and vomiting. Azotemia may be present and blood work often reveals a neutrophilic leukocytosis with a left shift and a metabolic acidosis.
–urinalysis may reveal impaired urine concentrating ability, bacteriuria, pyuria, proteinuria, hematuria, and/or granular casts
Bladder rupture resulting in Urosepsis
penetrating injuries, neoplasia, aggressive catheterization, cystocentesis, rupture secondary to prolonged urethral obstruction, injury to the urinary tract during abdominal surgery, or excessive force during bladder expression.
– abdominal fluid to peripheral blood creatinine and/or potassium ratios are often diagnostic of uroperitoneum,
– presence of bacteria on cytology
Prostatic infection resulting in Urosepsis
– prostatic fluid contains a zinc-associated antibacterial factor that is important in serving as a natural defense mechanism
– bacterial colonization of the prostate can occur through both ascension of urethral flora, reflux of urine into prostatic ducts, inoculation of bacteria through biopsy needles, or by the hematogenous route
– Suppurative prostatitis and prostatic abscessation most common causes
– E. coli was the most common bacteria
Pyometra resulting in urosepsis
can occur in both dogs and cats diagnosed with pyometra with or without uterine rupture.
– E. coli is the most common bacteria
– UTIs are common complications of pyometra
MODS definition
MODS was defined as the presence of altered organ function in an acutely ill patient such that homeostasis cannot be maintained without intervention
Sepsis definition
sepsis defined as SIRS caused by an infectious agent.
– when body’s response becomes dysregulated, fatal organ dysfunction results
6 steps
Healthy animals response to infection
– bacterial invaders are rapidly detected by cells of the innate immune system.
– Macrophages bind to microbes via a variety of pathways;
–pattern recognition receptors may bind to pathogen‐associated molecular patterns (PAMPs), alarm signals sent during the initial insult known as danger‐associated molecular patterns (DAMPs) may be recognized, or both may occur
– macrophages kill and phagocytize the bacterial cells and perform “clean‐up” of cellular debris generated by the initial injury
– process initiates the release of numerous pro‐and anti‐inflammatory cytokines
– balance of proinflammatory and anti‐inflammatory mediators ensures that the appropriate cells are sent to the injured site and that homeostasis is restored
3
Prominent proinflammatory cytokines (3) and proinflammatory chemical signalers (2):
– tumor necrosis factor (TNF) alpha, IL‐1 and IL‐6
– chemical signalers include nitric oxide and chemokines → signal for leukocytes to migrate to site of infection
Sepsis proinflammatory and anti-inflammatory imbalance
overabundance of cytokines causing systemic illness potentially unrelated to the initial insult
Sepsis‐induced immunoparalysis
– When the proinflammatory response is exhausted, patients enter an anti‐inflammatory mediator‐influenced period that can result in immunosuppression
Apoptosis
programmed cell death
4
Consequences of Cell damage in sepsis
– endothelial repercussions,
– primarily separation of the tight junctions between cells,
– disruption of the endothelial glycocalyx, and thrombosis of the microvasculature.
– vessels leak = organ edema resulting in additional damage while thrombi disrupt perfusion through the microvasculature.
– All organ systems are at risk.
Acute
Patient Physiologic and Laboratory Evaluation (APPLE) score for
Higher APPLE full scores also predict mortality following traumatic injury in both cats and dogs
SIRS typical CS
– Hyper/hypothermia, unexplained sinus tachy- or bradycardia, and tachypnea
– depressed mentation or abnormal mucus membrane color, skin temperature, and femoral pulse quality
Thermoregulation definiton
the balance between heat loss and heat production.
– Metabolic, physiologic, and behavioral mechanisms are used by homeotherms to regulate heat loss and production.
– control center for the body is located in CNS in the preoptic area of the anterior hypothalamus (AH).
Fever vs Non febrile Hyperthermia
– true fever is the body’s normal response to infection, inflammation, or injury and is part of the acute-phase response
– Nonfebrile hyperthermia is a result of an imbalance between heat production and heat loss.
PathPhys of Thermoreguation
Changes in ambient and core body temperatures are sensed by the peripheral and central thermoreceptors, and information is conveyed to the AH via the nervous system.
– thermoreceptors sense body is below or above its normal temperature and subsequently cause the AH to stimulate the body to increase heat production and reduce heat loss through conservation if the body is too cold or to dissipate heat if the body is too warm
Patients factors that affect their ability to regulate temperature
4 examples
- Cachectic
- anesthetized patients,
- or those with severe neurologic impairment, may not be able to maintain a normal set point or generate a normal response to changes in core body temperature.
- Neonatal dogs and cats have a poorly developed thermoregulatory center and lack significant muscle mass. They require higher ambient temperatures to maintain normal body temperature.
7
Heat gain mechanisms
- shivering
- increased production of catecholamines/Thyroxine
- Decrease loss
- vasoconstriction
- Piloerection
- postural changes
- heat seeking
6
Heat loss mechanisms
- Panting
- Vasodilation
- postural changes
- cool seeking behavior
- perspiration
- grooming (cats)
Classification of Hyperthermia: True Fever
Production of endogenous pyrogens
2
Classification of Hyperthermia: Inadequate heat dissipation
- Heat stroke
- Hyperpyrexic syndromes
3
Classification of Hyperthermia: Exercise-induced hyperthermia
- Normal exercise
- Hypocalcemic tetany (eclampsia)
- Seizure disorders
Classification of Hyperthermia:
Pathologic or pharmacologic origin
- Lesions in or around the anterior hypothalamus
- Malignant hyperthermia
- Hypermetabolic disorders
- Monoamine metabolism disturbances
True fever
normal body response to invasion or injury and is part of the acute-phase response.
– acute-phase response = increased neutrophil numbers and phagocytic ability, enhanced T and B lymphocyte activity, increased acute-phase protein production by the liver, increased fibroblast activity, and increased sleep
– initiated by exogenous pyrogens that lead to the release of endogenous pyrogens
Exogenous pyrogens
– variety of subtances that can initiate fever
–they primarily cause the release of endogenous pyrogens by the host
Ex: bacterial, viral, fungi, protozoa, pharmalogical agents
Endogenous pyrogens
– responds to stimulation by an exogenous pyrogen, proteins (cytokines) released from cells of the immune system trigger the febrile response.
– Macrophages are the primary immune cells involved, although T and B lymphocytes and other leukocytes may play significant roles.
– proteins produced are called endogenous pyrogens or fever-producing cytokines
Fever-producing cytokines
- interleukin 1,
- interleukin 6,
- tumor necrosis factor-α
Cytokine febrile response to neoplastic cells
in anterior hypothalamus, stimulate the release of prostaglandins (PGs), primarily PGE2 and possibly PGF2α
Heat stroke
– result of inadequate heat dissipation
– Exposure to high ambient temperatures may increase heat load at a faster rate than it can be dissipated from the body
– will not respond to antipyretics
– must undergo immediate total body cooling to prevent organ damage or death.
4
Mechanisms of Heat loss
- Radiation : electromagnetic or heat exchange between objects in the environment
- Conduction : between the body and environmental objects that are in direct contact with the skin, as determined by the relative temperatures and gradients
- Convection: the movement of fluid, air, or water over the surface of the body
- Evaporation : disruption of heat by the energy required to convert the material from a liquid to a gas, as with panting
Hyperpyrexic syndrome
associated with moderate to severe exercise in hot and humid climates
– may be more common in hunting dogs or dogs that “jog” with their owners
– heavy exercise may lead to vasodilation to increase blood flow to skeletal muscles but simultaneous vasoconstriction of cutaneous vessels, thus compromising peripheral heat loss
Exercise-induced hyperthermia
3 examples
– body temperature will rise with sustained exercise of even moderate intensity because of heat production associated with muscular activity
– Eclampsia results in extreme muscular activity that can lead to significant heat production and result in severe hyperthermia
– Sz disorders from organic, metabolic, or idiopathic causes are encountered often in small animals
– first treatment priority should be to stop the seizures, but when significant hyperthermia is present, total body cooling is also recommended as soon as possible
Pathologic and pharmacologic hyperthermia
– Hypothalamic lesions may obliterate the thermoregulatory center
– Malignant hyperthermia leads to a myopathy and subsequent metabolic heat production secondary to disturbed calcium metabolism that is initiated by pharmacologic agents such as inhalation anesthetics (especially halothane) and muscle relaxants (e.g., succinylcholine)
– Hypermetabolic disorders may also lead to hyperthermic states.
Hyperthermia
Hypermetabolic disorders
– Endocrine disorders such as hyperthyroidism and pheochromocytoma can lead to an increased metabolic rate or vasoconstriction, resulting in excess heat production, decreased ability to dissipate heat, or both
– thyroid hormone may also act directly on the hypothalamic set point resulting in a true fever as part of the hyperthermia
Benefits of Fevers
– a fever will reduce the duration of morbidity and decrease mortality from many infectious diseases.
– decreases ability of many bacteria to use iron, which is necessary for them to live and replicate
– Many viruses are heat sensitive and cannot replicate in high temperatures.
– may inhibit viral replication, increase leukocyte function, and decrease the uptake of iron by microbes (which is often necessary for their growth and replication)
Detriments of Fevers
Hyperthermia increases tissue metabolism and oxygen consumption, thus raising both caloric and water requirements by approximately 7% for each degree Fahrenheit
– fever in patients with noninfectious diseases such as TBI may carry a worse prognosis
– leads to suppression of appetite center in the hypothalamus; (thirst center usually remains unaffected)
– temps above 107 increases in cellular oxygen consumption that exceed oxygen delivery, resulting in the deterioration of cellular function and integrity. leading to potential DIC
Clin Path abnormalities with fevers
– liver (hypoglycemia, hyperbilirubinemia)
– kidneys (acute kidney injury)
– hypoxemia, hyperkalemia, skeletal muscle cytolysis, tachypnea, metabolic acidosis, tachycardia, tachypnea, and hyperventilation
– Exertional heat stroke and malignant hyperthermia may lead to severe rhabdomyolysis, hyperkalemia, hypocalcemia, myoglobinemia, myoglobinuria, and elevated levels of creatine phosphokinase
Nonspecific drug therapies for febrile patients
– Nonspecific therapy for true fever usually involves inhibitors of prostaglandin synthesis: NSAIDS
– They do not block the production of endogenous pyrogens
– Glucocorticoids should be resevered for pts with known causes to be noninfectious: ex immune-mediated
– Phenothiazines can be effective in alleviating a true fever by depressing normal thermoregulation and causing peripheral vasodilation
Cooling methods for non-specific febrile patients
– will reduce body temperature; however, the thermoregulatory center in the hypothalamus will still be directing the body to increase the body temperature.
– may result in a further increase in metabolic rate, oxygen consumption, and subsequent water and caloric requirements.
– unless fever is life threatening, this is counterproductive
febrile intensive care patient cause
Infectious vs noninfectious
– Nosocomial infection
– indwelling devices, catheters, compromised immune systems
Feline “shock organs”
lungs and respiratory tract
K9 “shock organs”
Liver and GIT
– histamine release within the GIT into portal vein induces hepatic vasodilation and an increase in hepatic blood flow.
– results in hepatic congestion and decreased venous outflow, further compromising blood flow from the hepatic circulation into the rest of the GIT
– reduced gastrointestinal venous return **affects cardiac output **and contributes to a global state of hypotensive and distributive shock
– Alters endothelial membrane permeability in the intestines → organ edema, fluid loss, hemorrhagic enteritis (that can start within minutes to hours following antigen exposure)
→ further contributing to hypovolemic shock
coagulopathy associated with systemic inflammation
involves:
1. increased expression of TF,
1. activation of ECs and disruption of the glycocalyx,
1. impairment of anticoagulant systems,
1. reduction of fibrinolysis.
Potential Lab findings in dogs with sepsis
– significantly prolonged aPTT and/or PT, along with higher FDP and D-dimer
– lower protein C and AT activities → consumptive
– TAFI is increased
sepsis-mediated thrombocytopenia
result of:
1. increased platelet consumption due to direct microbial–platelet interactions,
1. platelet–leukocyte aggregate formation,
1. and increased platelet sequestration secondary to microvascular thrombosis.
Which bacteria cause platelet aggregation?
– Escherichia coli and Streptococcus can directly interact with platelets through a variety of molecular interactions leading to platelet activation and aggregation.
