Plasma interleukin-6 response is predictive for severity and mortality in canine systemic inflammatory response syndrome and sepsis

BACKGROUND: Sepsis is still a major cause of death in both human and veterinary medicine. Early diagnosis is essential for appropriate treatment. Identification of patients at risk for developing sepsis is already possible in human medicine through the measurement of plasma interleukin-6 (IL-6) levels. In veterinary medicine, however, this has been investigated only in canine experimental models. OBJECTIVES: The purpose of this study was to measure IL-6 plasma levels in dogs with naturally occurring systemic inflammatory response syndrome (SIRS) and sepsis and to analyze the value of IL-6 as a predictive parameter for severity and mortality. METHODS: Included in the study were 79 dogs that had been admitted to the small animal clinics of Munich and Berlin from July 2004 to July 2005 and that satisfied the diagnostic criteria for SIRS and sepsis as defined using established parameters. Measurement of plasma IL-6 levels on days 0, 1, and 2 was performed by the use of a colorimetric bioassay based on IL-6-dependent cell growth. RESULTS: Septic foci were identified in 43 patients (septic group), and 36 patients were enrolled in the SIRS group. The frequency of positive blood cultures was 11%. The overall mortality rate was 48%. Higher plasma IL-6 levels on the day of admission were significantly correlated with a more severe degree of disease, increased mortality rate, and earlier fatality. CONCLUSIONS: Plasma IL-6 concentration is predictive of outcome in canine SIRS and sepsis and may be a valuable laboratory parameter for assessing critically ill dogs.     

Thromboelastography: a tool for measuring hypercoagulability, hypocoagulability, and fibrinolysis

Objective: To describe the technique of thromboelastography (TEG) and review the applications of this coagulation test in humans and small animals. Data sources: Data sources included scientific reviews and original research publications. Human data synthesis: TEG in humans has been used for documentation of hypercoagulable and hypocoagulable states and has been shown to be beneficial in patient management. Veterinary data synthesis: Clinical evaluation of TEG in veterinary medicine is limited; however, recent reports have documented evidence of hypercoagulability in dogs with parvovirus and protein‐losing nephropathy. Additionally, many of the research models may be relevant to veterinary patients. Conclusions: TEG provides information about coagulation that is not available through routine coagulation tests. The application of TEG monitoring to veterinary patients shows promise; however, prospective clinical studies are needed.     

Hemostatic changes in dogs with naturally occurring sepsis

Sepsis is a frequent source of morbidity and mortality in critically ill patients. The goal of this case control study was to measure hemostatic changes in dogs with naturally occurring sepsis. Blood was collected within 24 hours of admission from 20 dogs that fulfilled the criteria for sepsis. Sepsis was defined as histologic or microbiological confirmation of infection and 2 or more of the following criteria: hypo- or hyperthermia, tachycardia, tachypnea, or leukopenia, leukocytosis, or > 3% bands. Culture and sensitivities were performed on appropriate samples from all septic dogs. Twenty-eight control dogs were enrolled on the basis of normal results of physical examination, CBC, serum biochemistry, and coagulation profile. Plasma samples were analyzed for prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (FDP), D-dimer (DD) concentrations, antithrombin (AT) activity, and protein C (PC) activity. Data were compared between groups by chi-square or independent t-tests. PC (P < .001) and AT (P < .001) activities were significantly lower in dogs with sepsis compared to controls. Dogs with sepsis had significantly higher PT (P = .007), PTT (P = .005), D-dimer (P = .005), and FDP (P = .001) compared to controls. Platelet counts were not significantly different between groups. Ten of the 20 septic dogs (50%) died, but no association was identified between any of the measured variables and outcome. These findings are consistent with previous studies in animals with experimentally induced disease and in clinical studies of humans. On the basis of these results, further investigation of the role of AT and PC in canine sepsis is warranted.     

Paecilomycosis in dogs and horses and a review of the literature

We reviewed 14 cases of paecilomycosis in a tertiary care veterinary hospital and all reports of the disease in the veterinary literature. Paecilomycosis is a rare disease primarily of dogs, horses, reptiles, and humans. Clinical manifestations in veterinary patients vary but include disseminated disease and diskospondylitis, particularly in dogs: pneumonia in dogs, horses, and reptiles; keratitis in horses; and miscellaneous local infections. It is important to have an appropriate index of suspicion because the diagnosis can be difficult, particularly in localized disease where it is difficult to determine whether a positive culture represents an etiology or a contamination with an environmental saprophyte. Spinal radiographs, transtracheal washes, histopathology, and fungal culture have proven to be valuable diagnostic tools. The prognosis for paecilomycosis is poor, although some treatment success has been reported, and success rates could improve if additional information were available regarding fungal species occurring in veterinary patients and drugs to which these fungi are susceptible.     

Uveitis associated with septic peritonitis in a cat

Objective – To report a case of bilateral uveitis believed to be a consequence of septic peritonitis in a 19‐month‐old cat. Case Summary – Bilateral anterior uveitis with suspicion of extension to the posterior segment was documented in a previously healthy young cat during hospitalization for severe septic peritonitis. Based on medical history and other findings uveitis was believed to result from concurrent abdominal sepsis, due either to metastatic seeding of bacterial organisms or to effects of bacterial toxins and inflammatory mediators on the blood‐aqueous barrier. The cat was surgically and medically managed, and made a full recovery with respect to both his ocular and his abdominal disease. New or Unique Information Provided – Ocular complications secondary to systemic sepsis are well documented in people but seldom reported in the veterinary literature. To the authors' knowledge this is the first report of uveitis linked to septic peritonitis in any veterinary species and the first to report sepsis‐related uveitis in a cat. Ocular inflammatory disease in the context of critical illness deserves attention as a potential significant source of morbidity. The development of ocular inflammatory disease may serve as a sentinel lesion for systemic sepsis and other life‐threatening conditions.     

An updated view of hemostasis: mechanisms of hemostatic dysfuntion associated with sepsis

Objective: To review the current understanding of mechanisms involved in normal hemostasis and to describe the changes associated with pro‐inflammatory disease processes such as sepsis. Data sources: Original research articles and scientific reviews. Human data synthesis: Organ damage caused by sepsis is created in part by the interdependent relationship between hemostasis and inflammation. Markers of coagulation have been found to have prognostic value in human patients with sepsis and there are both experimental and clinical investigations of the therapeutic potential of modulating the hemostatic system in sepsis. Improvement of 28‐day all‐cause mortality in severe sepsis by treatment with recombinant human activated Protein C strongly supports the interdependence of hemostasis and inflammation in the pathophysiology of sepsis. Veterinary data synthesis: Publications reporting clinical evaluation of the hemostatic changes occurring in septic dogs or cats are minimal. Experimental animal models of sepsis reveal significant similarity between human and animal sepsis and may provide relevance to clinical veterinary medicine until prospective clinical evaluations are published. Conclusions: It is now apparent that inflammation and the coagulation system are intimately connected. Understanding this relationship provides some insight into the pathogenesis of the hemostatic changes associated with sepsis. This new updated view of hemostasis may lead to the development of novel therapeutic approaches to sepsis and disseminated intravascular coagulation in veterinary medicine.     

犬品种之间的药物遗传和代谢差异

描述动物物种的相关药理学遗传差异的资料非常有限。尽管在兽医药学的遗传信息缺乏,但品种对内在的和外在的物质的具体反应已经有许多物种的报告。这一发现强调了当前跨越品种获得洞察基因型和表型变异的重要性。本文提供了有关犬品种在生理学,药物反应,药物药代动力学和代谢特性方面的差异的文献总结。了解这些品种差异将改善犬的人口预测（为了犬的药物产品）,当推断从犬到人类的毒理学数据时可能是有价值的。     

Acute pancreatitis in dogs

Objective: To summarize current information regarding severity assessment, diagnostic imaging, and treatment of human and canine acute pancreatitis (AP). Human‐based studies: In humans, scoring systems, advanced imaging methods, and serum markers are used to assess the severity of disease, which allows for optimization of patient management. The extent of pancreatic necrosis and the presence of infected pancreatic necrosis are the most important factors determining the development of multiple organ failure (MOF) and subsequent mortality. Considerable research efforts have focused on the development of inexpensive, easy, and reliable laboratory markers to assess disease severity as early as possible in the course of the disease. The use of prophylactic antibiotics, enteral nutrition, and surgery have been shown to be beneficial in certain patient populations. Veterinary‐based studies: The majority of what is currently known about naturally occurring canine AP has been derived from retrospective evaluations. The identification and development of inexpensive and reliable detection kits of key laboratory markers in dogs with AP could dramatically improve our ability to prognosticate and identify patient populations likely to benefit from treatment interventions. Treatment remains largely supportive and future studies evaluating the efficacy of surgery, nutritional support and other treatment modalities are warranted. Data sources: Current human and veterinary literature. Conclusions: Pancreatitis can lead to a life‐threatening severe systemic inflammatory condition, resulting in MOF and death in both humans and dogs. Given the similarities in the pathophysiology of AP in both humans and dogs, novel concepts used to assess severity and treat people with AP may be applicable to dogs.     

A longitudinal serological survey of parvovirus infection in dogs

Serum samples collected from dogs routinely presented at a clinic between June 1974 and October 1980 were tested for the presence of haemagglutination inhibition (HI) titres to canine parvovirus. The first positive titre (>1:320) was demonstrated in serum collected in October 1979. The first confirmed clinical case of canine parvovirus enteritis was diagnosed by the authors in July 1979. In addition, between 1st December 1980 and 1st March 1981, serum samples were collected from 106 healthy dogs which were presented for canine parvovirus vaccination for the first time. Twenty-four dogs (approx. 23%) showed HI titres >1:320 indicating probable previous canine parvovirus infection. Therefore approx. 80% of dogs in the clinic area were at risk at that time and vaccination should have protected them from infection.     

Characterization of the use of antiemetic agents in dogs with parvoviral enteritis treated at a veterinary teaching hospital: 77 cases (1997-2000)

OBJECTIVE: To characterize the use of antiemetic agents in dogs with canine parvovirus (CPV)-associated enteritis in a veterinary teaching hospital. DESIGN: Retrospective case series. ANIMALS: 77 dogs with CPV-associated enteritis. PROCEDURE: Medical records of 560 dogs with confirmed CPV-associated enteritis that were admitted to a veterinary teaching hospital were reviewed. Exclusion criteria included vaccination against CPV infection within the preceding 2 weeks, hospitalization for < 24 hours or removal from the hospital against advice, or an incomplete record. Signalment, duration of hospitalization, and daily antiemetic administrations were assessed; WBC counts and clinical findings were used to classify dogs as having systemic inflammatory response syndrome (SIRS). RESULTS: 77 dogs were included in the study; 55 (71%) received antiemetics (53 received metoclopramide at least once). Seventy-one dogs survived, and 6 dogs died (all 6 received antiemetics). Compared with dogs that did not receive antiemetics, duration of hospitalization was significantly longer for antiemetic-treated dogs. Daily values of rectal temperature and heart and respiratory rates did not predict administration of antiemetics or duration of hospitalization; however, compared with survivors, SIRS developed more frequently among nonsurvivors. Assessment of emetic events recorded hourly for 17 dogs indicated that antiemetic treatment did not control emesis. CONCLUSIONS AND CLINICAL RELEVANCE: Many dogs with CPV-associated enteritis had persistent vomiting despite antiemetic administration. The apparent difference in duration of hospitalization between antiemetic-treated dogs and other dogs may reflect a difference in disease severity between groups, although antiemetic-associated adverse events (e.g., signs of depression, hypotension, and immune modulation) may prolong hospitalization.     

Influence of long-term treatment with tetracycline and niacinamide on antibody production in dogs with discoid lupus erythematosus

OBJECTIVE: To evaluate the effect of long-term treatment with tetracycline and niacinamide on antibody production in dogs by measuring postvaccinal serum concentrations of antibodies against canine parvovirus and canine distemper virus. ANIMALS: 10 dogs receiving long-term treatment with tetracycline and niacinamide (treatment group) and 10 healthy dogs (control group). PROCEDURE: The treatment group included 9 dogs with discoid lupus erythematosus and 1 dog with pemphigus foliaceus on long-term treatment (> 12 months) with tetracycline and niacinamide. The control group included 10 healthy dogs with no clinical signs of disease and no administered medications for the past 3 months. Blood samples were obtained from all dogs by jugular venipuncture. Serum antibody titers against canine parvovirus and canine distemper virus antigens were measured, using hemaglutination inhibition and serum neutralization, respectively, and compared between groups. RESULTS: A significant difference in antibody titers between treatment- and control-group dogs was not found. All dogs had protective antibody titers against canine distemper virus, and 8 of 10 dogs from each group had protective titers against canine parvovirus infection. CONCLUSION AND CLINICAL RELEVANCE: These results provide evidence that long-term treatment with tetracycline and niacinamide does not interfere with routine vaccinations and thus does not seem to influence antibody production in dogs.     

Pharmacovigilance in veterinary medicine in Chile: a pilot study

Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study. J. vet. Pharmacol. Therap. 34 , 108–115. In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6‐month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under‐reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs’ presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus, Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR‐presenting drug detection and drug safety improvement.     

The effect of staphylococcal antigen on the output of cells from the popliteal lymph node of immunized sheep

Serum samples collected from dogs routinely presented at a clinic between June 1974 and October 1980 were tested for the presence of haemagglutination inhibition (HI) titres to canine parvovirus. The first positive titre (> 1:320) was demonstrated in serum collected in October 1979. The first confirmed clinical case of canine parvovirus enteritis was diagnosed by the authors in July 1979.

In addition, between 1st December 1980 and 1st March 1981, serum samples were collected from 106 healthy dogs which were presented for canine parvovirus vaccination for the first time. Twenty-four dogs (approx. 23%) showed HI titres > 1:320 indicating probable previous canine parvovirus infection. Therefore approx. 80% of dogs in the clinic area were at risk at that time and vaccination should have protected them from infection.     

Cholestasis Associated With Extrahepatic Bacterial Infection in Five Dogs

Intrahepatic cholestasis associated with severe extrahepatic bacterial infection is well recognized in humans. A similar syndrome is not well characterized in veterinary medicine. Five dogs with severe extrahepatic bacterial infection that developed histologically confirmed intrahepatic cholestasis were selected from the authors' case files. The types of infections included pneumonia, peritonitis secondary to a rectal tear, urinary tract infection, bite wounds, and vegetative endocarditis. Escherichia coli was involved in two of the dogs, mixed infection in one dog, and a gram-positive cocci in the other two dogs. Total bilirubin concentrations ranged from 3.5 to 33.5 mg/dl. Serum liver enzyme activities showed only mild to moderate increases: alkaline phosphatase (ALP, 41-750 IU/l), alanine aminotransferase (ALT, 25-235 IU/l), and aspartate aminotransferase (AST, 99-255 IU/l). Fasting serum bile acids concentration was markedly elevated in the one dog in which it was measured (259 mumol/l). Histologically, the cholestasis was characterized by bile pigment accumulation in hepatocytes, canaliculi, and/or Kupffer's cells. Inflammatory parenchymal changes, when present, were minimal. The findings of hyperbilirubinemia, only a slight increase in the liver enzyme activities, and minimal inflammatory changes in liver tissue specimens in the five dogs with extrahepatic bacterial infections are similar to the findings in intrahepatic cholestasis associated with extrahepatic bacterial infection in humans.     

Stray dogs as sentinels for canine parvovirus

An attempt to determine the prevalence of canine parvovirus in the stray dog population of Franklin County, Ohio (U.S.A.) was made by sampling dogs during the first 6 months of 1981. Serum and fecal samples, which were collected from 209 strays at time of euthanasia, were tested by serum hemagglutination inhibition (HI) and fecal hemagglutination (HA) techniques to determine canine parvovirus experience (seropositive) or fecal virus shedding, respectively. Sera collected from 93 strays for an unrelated study conducted in 1979 were used as the comparison group. All of the 1979 sera were HI negative (< 1:80) whereas, 139 of 201 (69.2%) sera suitable for testing from the 1981 group of strays were HI positive (? 1:80). The fecal HA results from the 1981 group revealed 26 of the 209 (12.4%) dogs were shedding parvovirus at time of euthanasia (HA titers ? 1:64). Of these 26 of the 209 (12.4%) dogs were shedding parvovirus at time of euthanasia were found to be seropositive. These results indicate that the stray population of Franklin County, Ohio, was not exposed in 1979, but by 1981 had experienced and for the most part, had recovered from canine parvovirus as indicated by a 69.2% seropositive dog population with 12.4% active virus shedders. The stray dog population, if sampled regularly, could thus serve as a sentinel for canine parvovirus activity in a community.     

Evaluation of serum NT-pCNP as a diagnostic and prognostic biomarker for sepsis in dogs

Background: There is a need for diagnostic biomarkers that can rapidly differentiate dogs with sepsis from dogs with noninfectious forms of systemic inflammatory response syndrome (NSIRS). Objectives: To compare serum NT‐pCNP concentrations among dogs with various forms of sepsis, NSIRS, and healthy controls and to evaluate the use of serum NT‐pCNP for the diagnosis of various forms of sepsis in dogs. Animals: One hundred and twelve dogs including 63 critically ill dogs (sepsis n = 29; NSIRS n = 34) and 49 healthy control dogs. Methods: Prospective clinical investigation. Serum samples were collected for NT‐pCNP measurement from dogs with sepsis or NSIRS within 24 hours of intensive care unit admission or at the time of presentation for healthy dogs. Dogs with sepsis were subclassified based on the anatomic region of infection. Serum NT‐pCNP concentrations were compared among sepsis, NSIRS and healthy groups as well as among sepsis subgroups. The area under the curve (AUC), sensitivity, and specificity for identifying dogs with sepsis were determined. Results: Using a cut‐off value of 10.1 pmol/L, AUC, sensitivity, and specificity of NT‐pCNP for differentiating dogs with sepsis from dogs with NSIRS or healthy control dogs were 0.71 (95% CI, 0.58–0.85), 65.5% (45.7–82.1%), and 89.2% (80.4–94.9%), respectively. Serum NT‐pCNP had poor sensitivity for peritoneal sources of sepsis; AUC [0.92 (0.81–1.0)], sensitivity [94% (71–100%)], and specificity [89% (80–95%)] improved when these dogs were excluded. Serum NT‐pCNP concentration was not associated with survival in the sepsis group. Conclusions and Clinical Importance: Serum NT‐pCNP is a promising diagnostic biomarker for sepsis but is a poor indicator of septic peritonitis.     

Acute respiratory distress syndrome in dogs and cats: a review of clinical findings and pathophysiology

Objective: To review the clinical and pathophysiologic aspects of acute respiratory distress syndrome (ARDS) in dogs and cats. Data sources: Data from human and veterinary literature were reviewed through Medline and CAB as well as manual search of references listed in articles pertaining to acute lung injury (ALI)/ARDS. Human data synthesis: Since the term ARDS was first coined in 1967, there has been a abundance of literature pertaining to this devastating syndrome in human medicine. More complete understanding of the complex interactions between inflammatory cells, soluble mediators (e.g., tumor necrosis factor, interleukin (IL)‐6, IL‐8, platelet activating factor) and the clinical patient has provided for timely recognition and mechanistically based protective strategies decreasing morbidity and mortality in human patients with ARDS. Veterinary data synthesis: Although little is known, ARDS is becoming a more commonly recognized sequela in small animals. Initial case reports and retrospective studies have provided basic clinical characterization of ARDS in dogs and cats. Additionally, information from experimental models has expanded our understanding of the inflammatory mechanisms involved. It appears that the inflammatory processes and pathologic changes associated with ARDS are similar in dogs, cats, and humans. Conclusions: Unfortunately, current mortality rates for ARDS in small animals are close to 100%. As our capability to treat patients with advanced life‐threatening disease increases, it is vital that we develop a familiarity with the pathogenesis of ARDS. Understanding the complex inflammatory interactions is essential for determining effective preventative and management strategies as well as designing novel therapies for veterinary patients.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.     

The role of albumin replacement in the critically ill veterinary patient

Objective: To review the human and veterinary literature on the physiological role and effects of therapeutic albumin supplementation. Data sources: Data from human and veterinary literature was reviewed. Human data synthesis: Hypoalbuminemia often occurs in a variety of critical illnesses, and contributes to the development of life‐threatening complications, including pulmonary edema, delayed wound healing, feeding intolerance, hypercoaguability, and multiple organ dysfunction. Serum albumin concentration has been used as a prognostic indicator in cases of chronic hypoalbuminemia. The use of albumin replacement therapy in humans is sometimes controversial, but may be associated with improved morbidity and decreased mortality. Veterinary data synthesis: Unlike human literature, there is a paucity of controlled clinical studies in the literature regarding albumin supplementation in veterinary patients. Rather, the majority of published studies were performed in experimental animals or via retrospective analyses. One recent study evaluated the use of plasma to improve albumin concentration in dogs with hypoalbuminemia. Other older studies investigated wound healing in dogs with experimentally induced hypoalbuminemia. As in human medicine, serum albumin concentration may be helpful as a prognostic indicator in critically ill dogs. Conclusion: Albumin is one of the most important proteins in the body because of its role in maintenance of colloid oncotic pressure, substrate transport, buffering capacity, as a mediator of coagulation and wound healing, and free‐radical scavenging. Albumin replacement in veterinary medicine is difficult, but until prospective clinical trials determine the efficacy of albumin replacement are conducted, a suggested clinical guideline would be to maintain albumin concentration at or above 2.0 g/dl utilizing fresh frozen plasma.