Definition

Sepsis-induced hypotension that persists despite adequate intravascular volume and cardiac output, and is attributable to low systemic vascular resistance.

Pathophysiology

• In sepsis, infectious agents trigger large-scale activation of monocytes, macrophages, and neutrophils that then interact with endothelial cells inducing a generalized inflammatory response.
• In the subset of septic patients described as having septic shock, the elaborate interaction of inflammatory cells and mediators decreases systemic vascular resistance and provokes maldistribution of blood flow (distributive effect). They also increase capillary permeability such that fluid shifts out of the intravascular space. To compensate for diminishing circulating volume, catecholamines increase cardiac output and myocardial contractility. In the face of severe arterial vasodilation, cardiac output is not sufficient to maintain oxygen delivery to tissues.
• Decreased oxygen delivery is compounded by the presence of interstitial edema and microvascular sludging. In due course, tissue hypoxia leads to organ failure and death.

Systems Affected

• Cardiovascular-increased cardiac output, arterial vasodilation, and maldistribution of blood flow with hypotension predominates; however, myocardial dysfunction secondary to circulating factors can be an important variable.
• Endocrine-may manifest as hyperglycemia and insulin resistance or as insufficient production of either corticosteroids or vasopressin.
• Gastrointestinal-mucosal necrosis, hemorrhage, and bacterial translocation.
• Hemic-microvascular thrombosis as well as hyper- and hypocoagulopathy.
• Hepatobiliary-hepatocellular enzyme leakage, cholestasis, reduced clearance of bacteria, and abnormal synthetic function.
• Nervous-altered mental status.
• Renal-ischemic tubular damage, oliguria, and development of acute kidney injury.
• Respiratory-enhanced microvascular permeability results in interstitial and alveolar edema; hypercoagulopathy may result in pulmonary thromboembolism.

Genetics

Unknown

Incidence/Prevalence

Unknown

Geographic Distribution

Unknown

Signalment

• Dogs and cats
• Any breed, age, or sex

Signs

Causes

• Septic peritonitis-gastrointestinal tract rupture, penetrating abdominal wound, infected urinary tract rupture.
• Respiratory and pleural space-pneumonia, pyothorax.
• Skin or soft tissue infections-infected wounds, foreign bodies.
• Urinary tract-pyelonephritis.
• Reproductive-prostatitis, pyometra.
• Cardiovascular-bacterial endocarditis.
• Musculoskeletal-septic arthritis, osteomyelitis.
• Iatrogenic sources of infection-catheters, implants, surgical sites.
• Central nervous system-meningitis, encephalitis.

Risk Factors

• Extremes of age
• Concurrent diseases such as diabetes mellitus, hyperadrenocorticism, and malignancy
• Immunosuppression
• Surgery, trauma, and burns
• Prior antibiotic therapy

Differential Diagnosis

• Other causes of distributive shock include drug or toxin reaction, anaphylaxis, and adrenal insufficiency.
• Hypovolemic shock.
• Cardiogenic shock.
• Heatstroke.

CBC/Biochemistry/Urinalysis

• Neutrophilia or neutropenia, left-shift, and toxic change
• Lymphopenia
• Thrombocytopenia
• Hematocrit and blood glucose are variable
• Hypoalbuminemia
• Elevated bilirubin and liver enzymes
• Electrolyte derangements
• Azotemia
• Isosthenuria and variably active urine sediment

Other Laboratory Tests

• Prolongation of the activated partial thromboplastin and prothrombin times, increased D-dimers and fibrin degradation products, and decreased levels of antithrombin and protein C.
• Blood gas analysis may reveal hypoxemia and acid-base disturbances.
• Serum lactate elevation.
• Cytology, gram stain, and culture and sensitivity on samples obtained from potential sites of infection may reveal etiologic organisms.
• Culture and sensitivity of urine and blood may be useful especially when the source of the sepsis is unknown.
• Low COP.
• ACTH stimulation test in patients not responding to standard therapy.

Imaging

• Thoracic radiographs may reveal a septic focus or cause for respiratory dysfunction.
• Echocardiography may document a vegetative valvular lesion and or characterize the adequacy of cardiac function.
• Abdominal ultrasonography may detect a septic focus.

Diagnostic Procedures

Thoracocentesis, abdominocentesis, tissue aspirates, and arthrocentesis when indicated may provide insight into underlying etiology.

Pathologic Findings

Abnormalities consistent with various underlying etiologies. Other abnormalities consistent with inflammation and tissue hypoxia.

Appropriate Health Care

• Emergency inpatient intensive care management.
• Resuscitation goals:
  • Maximize blood oxygen content by ensuring adequacy of ventilation and oxygen saturation of blood and correct anemia
  • Restore blood flow
  • Fluid therapy.
• Traditional endpoints of resuscitation, including restoration of normal vital signs (mentation, CRT, heart rate, peripheral pulse quality, and rectal temperature), BP, and urine output remain the standard of care. However, it has been documented that critically ill patients have evidence of ongoing tissue hypoxia despite normalization of these parameters, suggestive of occult oxygen debt and presence of compensated shock. There is evidence that normalization of vital signs, blood lactate, base deficit, and oxygen transport indices are more sensitive markers for adequacy of tissue perfusion than any of these variables alone. Until stronger support exists for preferential selection of one endpoint over the others, utilization of as many of these markers as are available on any given patient seems advisable.
• Identify and treat source of infection (antimicrobial therapy, surgery, or both).
• Maintain adequate organ function (guided by cardiovascular and laboratory monitoring).

Nursing Care

• Maximize blood oxygen content:
  • Assess and stabilize the airway and breathing as necessary
  • Administer high-flow supplemental oxygen and provide ventilatory support as needed
  • Significant anemia (PCV <25%) should be corrected.
• Most septic patients are hypovolemic and require initial fluid resuscitation with an isotonic crystalloid such as lactated Ringer's solution, normal saline, Plasmalyte-A, and Normosol-R (30 mL/kg, dog; 20 mL/kg, cat over 15 minutes). If the patient is not significantly dehydrated, addition of 7.5% hypertonic saline (4 mL/kg over 15 minutes) may expedite the resuscitation.
  • After the initial bolus the patient's response is assessed. If vital signs and other resuscitation parameters return to normal, the patient must continue to be monitored to ensure stability. If vital signs and other resuscitation parameters transiently improve or if little or no improvement is seen, another crystalloid bolus should be infused and colloids such as HES (dose variable, dependent on type) considered.
  • HES will help maintain adequate COP and may reduce the amount of crystalloid required to achieve effective resuscitation. HES at high doses may exacerbate coagulopathy
  • Blood products should be administered based on patient need. Packed red blood cells are administered to anemic patients to improve oxygen carrying capacity. Plasma products are used to correct coagulation deficits and concentrated albumin products are most effective raising COP.
  • This process is repeated until the patient's resuscitation parameters normalize.
• Septic patients that have received large volumes of fluids may achieve an adequate circulating volume without normalization of BP and other perfusion parameters. It is important to recognize that continued aggressive fluid therapy in these patients will result in volume overload and that vasopressors and or positive inotropes are indicated. Monitor closely since infusion of large volumes may precipitate pulmonary edema in patients with capillary leak or low COP.

Activity

Minimize patient exertion.

Diet

Withhold oral intake until shock is resolved.

Client Education

Warn of the danger of imminent cardiac arrest and discuss a “code status” in advance whenever possible.

Surgical Considerations

Identify and remove the source of sepsis (e.g., septic peritonitis, abscess, pyothorax, pyometra, and soft tissue wounds).

Drug(s) Of Choice

• Once adequate circulating volume has been achieved, improvement in systemic BP and other clinical resuscitation parameters may require the use of one or more vasopressors and or positive inotropic agents:
  • Dopamine (5–20 µg/kg/minute), norepinephrine (0.05–2 µg/kg/minute), and vasopressin (0.5–2 mU/kg/minute) can be used for vasopressor support (dogs and cats). Monitor for tachyarrhythmia and excessive peripheral vasoconstriction
  • Dobutamine (2–20 µg/kg/minute) is primarily used as a positive inotrope in the subset of canine septic shock patients with decreased contractility or myocardial depression. Monitor for tachyarrhythmia. While dobutamine can be used safely in many feline patients, seizures have been observed in some cats at doses exceeding 5 µg/kg/minute.
• It is essential that intravenous, empiric, broad-spectrum antibiotic therapy be instituted early in septic patients; the spectrum should be narrowed when culture results become available. Empiric selection is based on the patient's underlying immune status, the suspected source and organism(s) responsible, specific antibiotic properties (tissue penetration, cidal versus static activity), and considerations for resistance (previous antibiotic use, hospital- or community-acquired infection).
• It is not unreasonable to empirically treat patients that are not responding adequately to standard therapy with 0.75–1.0 mg/kg q6h intravenous hydrocortisone after undergoing a standard ACTH stimulation test. Therapy should be continued in patients in whom relative adrenal insufficiency (hypoadrenocorticism) is documented.

Contraindications

N/A

Precautions

N/A

Alternative Drugs

N/A

Patient Monitoring

• Serial assessment of perfusion to optimize titration of fluids and vasoactive therapy:
  • Exam-mentation, mucous membrane color, CRT, pulse quality, muscle strength, temperature, and heart rate.
  • Hemodynamic monitoring-BP (frequently reveals a disproportionately low diastolic pressure), CVP (decreased due to hypovolemia and decreased preload; also allows for measurement of central venous oxygen saturation), and cardiac output.
  • Laboratory data-serum lactate and base deficit.
• Serial assessment of respiratory rate and effort, and pulmonary auscultation.
• Urine output as an indicator of glomerular filtration rate and renal blood flow.
• Continuous ECG to detect arrhythmia.
• Blood gas analysis and pulse oximetry to follow tissue oxygenation, ventilation, and acid-base balance.
• A minimum of daily packed cell volume, serum total protein, COP, blood glucose, serum electrolytes, hepatocellular enzymes, blood urea nitrogen, and serum creatinine to monitor effects of systemic tissue hypoxia.

Prevention/Avoidance

• Timely and effective treatment of wounds.
• Appropriate use of antimicrobial therapy.

Possible Complications

• Volume overload
• Pulmonary edema
• Vasculitis and peripheral edema
• Hypoglycemia
• Anemia and thrombocytopenia
• Coagulopathy
• Multiple organ dysfunction (cardiac, respiratory, renal, hepatic, gastrointestinal, pancreatic, adrenal, and brain)
• Cardiac arrest

Expected Course and Prognosis

Dependent on underlying etiology and ability to institute appropriate therapy.

See Also

• Disseminated Intravascular Coagulation
• Hypoadrenocorticism (Cushing's Disease)-Dogs
• Hypoadrenocorticism (Cushing's Syndrome)-Cats
• Shock, Cardiogenic
• Shock, Hypovolemic

Abbreviations

• ACTH = adrenocorticotropic hormone
• BP = blood pressure
• COP = colloid oncotic pressure
• CRT = capillary refill time
• CVP = central venous pressure
• ECG = electrocardiogram
• HES = hydroxyethylstarch

Client Education Handout Available Online