"Sepsis" TUMOR TIDBITS, A BIWEEKLY VETERINARY ONCOLOGY E-LETTER Volume 3; Number 26; July 19, 2002. Editor: Kevin A. Hahn, DVM, PhD, Dipl - ACVIM (Oncology) & Overall Nice Guy! ANNOUNCEMENTS * Sugar Land is OPEN for consultations with Dr. Janet Carreras. Our thanks to the veterinary communities of Sugar Land, Missouri City, Stafford, Katy and others for making this a successful venture for Gulf Coast Veterinary Oncology. * We're still enrolling dogs with lymphoma into a clinical trial using a novel antiangiogenic agent. It is for dogs with relapsed lymphoma and the criteria for entry are strict. Call or email us for additional details. Have a GREAT summer! ============================================ THIS WEEK'S TUMOR TIDBIT: SEPSIS ============================================ OVERVIEW Sepsis is the transient, intermittant, or continuous shedding of bacteria or other organisms into the blood. When it occurs in the normal individual, bacteremia is usually transient. Invasion of the circulatory system with bacteria as a result of concurrent infection or vascular access devices may lead to prolonged bacteremia and disastrous or overwhelming infection. In most healthy individuals, bacteria are removed from the circulatory system rapidly and effectively through phagocytosis by fixed-tissue macrophages in the spleen and liver. Persistent bacteremia only ensues when bacteria multiply at a rate that exceeds the ability of the reticuloendothelial system to remove them. Neutrophils are not a major component of the host defense mechanism in the circulation. Three patterns of bacteremia are possible: 1) transient--occurs frequently as during routine dentistry and is of no consequence in healthy patients; 2) intermittent--characterized by periodic showering of bacteria into the bloodstream, the most common scenario; 3) continuous--characterized by persistent showering of bacteria into the bloodstream. The circulatory system is affected most adversely, resulting in septic shock. Bacteremia may lead to endocardial or renal manifestations of disease. Development of endocardial disease requires prior damage to heart valves in combination with bacteremia for disease development. Ultimately, any organ system may be impaired as a result of effects from intermittent or continuous bacteremia. Signs may be varied and include generalized depression, fever, tachycardia, and tachypnea. With the advent of septic shock, hypothermia, low blood pressure, low urine output, and low toe-web temperature indicate more severe disease, but these signs are not specific for septicemia. Gastrointestinal signs may appear early as anorexia, progressing to vomiting, and severe bloody diarrhea later in the course of disease. Gram-negative bacteria are the most common cause of bacteremia, followed by gram- positive cocci and obligate anaerobes. Mixed infections are also common and may account for as many as 17% of cases. The most common isolates in dogs are Escherichia coli and coagulase-positive staphylococci (S. aureus or S. intermedius). Rare in both dogs and cats are isolates of Pseudomonas. Many factors have been cited as predisposing to bacteremia and sepsis. Patients presenting with established infections are at greatest risk. Diseases that can progress to septicemia and shock include pyothorax, peritonitis, pyometra, prostatic abscess, mastitis, biliary tract infection, pyelonephritis, urinary tract infection, and occasionally, hepatic or lung abscess. Any patient with depression of the immune response is at higher risk for developing bacteremia and sepsis. Noninfectious diseases that may predispose to bacteremia include hematologic malignancy, solid tumors, glucocorticoid therapy, trauma, surgery, diabetes mellitus, Cushing's disease, renal failure, hepatic failure, low body total protein, cytotoxic therapy (for neoplastic or inflammatory diseases), intravenous and urinary tract catheters, and burns. The most important factor influencing mortality from bacteremia and sepsis is the extent and severity of the underlying disease. Mortality as a result of bacteremia is less likely to occur in previously healthy individuals. Efforts to prevent the development of bacteremia should be directed toward the most seriously ill patients because these patients are at greatest risk and the most likely to die after becoming bacteremic. Attempts must be made to differentiate from other causes of fever, cardiac or renal disease, gastrointestinal disease, and abdominal pain or distension such as that caused by organ enlargement, neoplasia, cystic structures, pancreatitis, and peritonitis. DIAGNOSTIC RESULTS Neutrophilia progressing to neutropenia occurs in severe cases. Thrombocytopenia and severe hemoconcentration may be observed. Serum biochemical analysis may reveal hyperkalemia secondary to acidosis, shock, poor renal perfusion, and tissue necrosis. Hypoglycemia may occur early in septic patients because of the presumed "insulinlike" effect of endotoxin. Electrolyte abnormalities vary depending on the etiology and duration of disease. High BUN and liver enzymes. The presence of bacteria in urine or positive urine cultures. Metabolic alterations, including metabolic acidosis, occur rapidly. Blood cultures are indicated in any critically ill animal that develops fever, neutropenia, left shift, shifting leg lameness, recent or changing cardiac murmur, or other signs of sepsis that cannot be explained by a preexisting condition. Blood culture is indicated in patients with suspected bacteremia to confirm that infection exists, to identify the causative organism, and to facilitate optimal antimicrobial therapy. TREATMENT & OTHER CONSIDERATIONS Successful treatment of septicemia and septic shock depends on early diagnosis, identification and elimination of the bacterial nidus and aggressive hemodynamic support. Physical examination may reveal superficial abscesses. Blood, sputum, urine, and wound discharges should be obtained for bacterial culture. Wounds should be debrided aggressively and abscesses drained. Surgical management should be elected when indicated (e.g., pyometra, prostatic abscess, peritonitis, gastrointestinal tract perforation). appropriate antibiotic treatment is necessary to eliminate the source of bacterial by-products such as endotoxins and exotoxins. Nutritional support should be instituted to combat the catabolic effects of sepsis. The owner should be made aware that the fatality rate, even with appropriate therapy, is high and related to the underlying cause of sepsis and physical condition of the patient. Hypovolemia/shock is treated by intravenous fluids to correct hypovolemia as well as metabolic changes (acidosis, electrolyte abnormalities). Volume replacement at a rate up to 90 ml/kg is started based on extent of disease. Isotonic fluids such as lactated Ringer's or Normosol-R are recommended. If the patient is hypoglycemic, the use of 5% dextrose in a polyionic replacement fluid is indicated. Plasma and dextran solutions are fluids of choice because protein loss to the extravascular space is extensive. antibiotic therapy is warranted and should be started as soon as a diagnosis of septicemia is made. The antibiotic should be broad spectrum and initially should be administered in high doses by the intravenous route. Aminoglycosides, chloramphenicol, and cephalosporins are good first choice antibiotics alone or in combination. Secondary choices include penicillins, erythromycin and metronidazole. Ultimately, antibiotic choice should be based on results of culture and sensitivity testing. Controversy exists regarding the use of corticosteroids in sepsis. Most authors agree that the properties of corticosteroids (stabilizing lysosomal membranes, decreasing vascular permeability, protecting against endotoxin, restoring of intestinal wall permeabiltiy) make them a useful adjunct to therapy for peritonitis. Nonsteroidal antiinflammatory drugs have been documented to be beneficial in the treatment of septicemia in dogs. Feeding should begin via feeding tube after enterostomy or gastrotomy tube placement. Consider evaluation of serum albumin with replacement of protein losses if albumin falls below 2.0 gm/dl. Death from septicemia, hypovolemia, and electrolyte disturbances occurs in a high percentage of patients. SUGGESTED READING * The 5 Minute Veterinary Consult. By Tilley LP & Smith FWK. Lippincott, William & Wilkins, 2002. * Veterinary Oncology, From "The Practical Veterinarian Series". By Hahn KA. Butterworth-Heinemann Press, 2002. * Current veterinary therapy XII. By Bonagura JD. Philadelphia, WB Saunders, 1995:137-139. ============================================ I hope this info helps and don't hesitate to call or email us at Gulf Coast Veterinary Oncology! Kevin Kevin A. Hahn, DVM, PhD Diplomate American College of Veterinary Internal Medicine (Oncology) & Overall Nice Guy Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: http://www.gcvs.com Email: mailto:drhahn@gcvs.com