RESUMO
BACKGROUND: Gentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values. OBJECTIVES: Determine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 µg/mL. ANIMALS: Sixty-five horses (2002-2010) receiving once-daily gentamicin with TDM performed (N = 99 sets). METHODS: Retrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25-35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7-9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease. RESULTS: Peak concentrations resulting from doses ≥7.7 mg/kg were 5.74 µg/mL (SE 2.1 µg/mL) greater than peaks from doses <7.7 mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 µg/mL if dose was ≥7.7 mg/kg (P = .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P = .039). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest gentamicin dosage should be individually determined in horses using TDM, but support an initial once-daily dose of 7.7-9.7 mg/kg IV to achieve peaks >32 µg/mL and trough concentrations <2 µg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.
Assuntos
Antibacterianos/uso terapêutico , Gentamicinas/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/farmacocinética , Feminino , Gentamicinas/administração & dosagem , Gentamicinas/sangue , Gentamicinas/farmacocinética , Doenças dos Cavalos/sangue , Cavalos , Hospitais Veterinários , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: There is a markedly reduced half-life of transfused RBCs when donor and recipient cats or humans are cross-match incompatible. Only 10-20% of horses have naturally occurring alloantibodies. Therefore, cross-match testing before blood transfusion is not always performed. HYPOTHESIS: Cross-match incompatibility predicts shortened RBC survival time as compared to that of compatible or autologous blood. ANIMALS: Twenty healthy adult horses. METHODS: Prospective trial. Blood type, anti-RBC antibody screen (before and 1 month after transfusion) and major and minor cross-match determined 10 donor-recipient pairs. Two pairs were cross-match compatible, the remainder incompatible. Donor blood (4 L) was collected into citrate phosphate dextrose adenine-1, labeled with NHS-biotin, and transfused into recipients. Samples were collected at 1 hour and 1, 2, 3, 5, 7, 14, 21, 28, and 35 days after transfusion, and biotinylated RBCs were detected by flow cytometry. Horses were monitored for transfusion reaction during transfusion and daily for 5 days. RESULTS: Cross-match incompatibility was significantly associated with decreased RBC survival time (P < .001). The half-life of transfused incompatible (cross-match >1+) allogenic equine RBCs was 4.7 (95% CI, 3.2-6.2) days versus 33.5 (24-43) days for compatible pairings. Cross-match incompatibility was associated with acute febrile transfusion reaction (P = .0083). At day 30, only 1 horse had developed novel anti-RBC antibodies. CONCLUSIONS AND CLINICAL IMPORTANCE: Cross-match incompatibility was predictive of febrile transfusion reaction and shortened transfused RBC survival, but did not result in production of anti-RBC antibodies at 30 days. Cross-match testing before transfusion is recommended.
Assuntos
Antígenos de Grupos Sanguíneos/classificação , Incompatibilidade de Grupos Sanguíneos/veterinária , Tipagem e Reações Cruzadas Sanguíneas/veterinária , Envelhecimento Eritrocítico , Eritrócitos , Cavalos/sangue , Animais , Incompatibilidade de Grupos Sanguíneos/sangue , Transfusão de Sangue/veterináriaRESUMO
BACKGROUND: Information about treatment protocols, adverse effects and outcomes with intrapleural recombinant tissue plasminogen activator (rTPA) use in horses with fibrinous pleuropneumonia is limited. HYPOTHESIS/OBJECTIVES: Describe factors that contribute to clinical response and survival of horses treated with rTPA intrapleurally. ANIMALS: Horses with bacterial pneumonia and fibrinous pleural effusion diagnosed by ultrasonography, that were treated with rTPA intrapleurally. METHODS: Retrospective multicenter case series from 2007-2012. Signalment, history, clinical and laboratory evaluation, treatment, and outcome obtained from medical records. Regression analysis used to identify associations between treatments and outcomes. RESULTS: Thirty three hemithoraces were treated in 25 horses, with 55 separate treatments. Recombinant tissue plasminogen activator (375-20,000 µg/hemithorax) was administered 1-4 times. Sonographically visible reduction in fibrin mat thickness, loculations, fluid depth, or some combination of these was seen in 32/49 (65%) treatments. Response to at least 1 treatment was seen in 17/20 (85%) horses with sonographic follow-up evaluation after every treatment. Earlier onset of rTPA treatment associated with increased survival odds. No association was found between cumulative rTPA dose or number of rTPA doses and survival, development of complications, duration of hospitalization or total charges. Clinical evidence of hypocoagulability or bleeding was not observed. Eighteen horses (72%) survived to discharge. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment with rTPA appeared safe and resulted in variable changes in fibrin quantity and organization within the pleural space. Recombinant tissue plasminogen activator could be a useful adjunct to standard treatment of fibrinous pleuropneumonia, but optimal case selection and dosing regimen remain to be elucidated.
Assuntos
Fibrinolíticos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Pleuropneumonia Contagiosa/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Feminino , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/mortalidade , Cavalos , Masculino , Pleuropneumonia Contagiosa/diagnóstico por imagem , Pleuropneumonia Contagiosa/microbiologia , Pleuropneumonia Contagiosa/mortalidade , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , UltrassonografiaRESUMO
BACKGROUND: Fibrinous parapneumonic pleural effusions are associated with decreased efficacy of pleural fluid drainage and increased risk of medical treatment failure in people, but similar associations have not been established in horses. HYPOTHESIS/OBJECTIVES: We hypothesized that fibrin deposition in the pleural cavity of horses with parapneumonic effusions increases the risk of poor outcome. ANIMALS: Seventy four horses with bacterial pleuropneumonia diagnosed by culture and cytology of tracheal aspirates, pleural fluid, or both, and pleural effusion diagnosed by ultrasonographic examination. METHODS: Retrospective study of cases was from 2002 to 2012. Information obtained from the medical records included signalment, history, sonographic findings, treatments, and outcome. The primary outcome investigated was survival and secondary outcomes were development of complications and surgical intervention. Fisher's exact test and logistic regression were applied for categorical variables. A t-test was used to find differences in continuous variables between groups. RESULTS: Seventy four horses met study criteria and 50 (68%) survived. Fibrinous pleural effusion was associated with higher respiratory rate and pleural fluid height at admission, necrotizing pneumonia, increased number of indwelling thoracic drains required for treatment, and decreased survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Fibrin accumulation in parapneumonic effusions is associated with increased mortality. Direct fibrinolytic treatment might be indicated in affected horses.
Assuntos
Doenças dos Cavalos/patologia , Derrame Pleural/veterinária , Pleuropneumonia Contagiosa/patologia , Animais , Antibacterianos/uso terapêutico , Feminino , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/mortalidade , Cavalos , Masculino , Derrame Pleural/complicações , Derrame Pleural/mortalidade , Derrame Pleural/patologia , Pleuropneumonia Contagiosa/tratamento farmacológico , Pleuropneumonia Contagiosa/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Pneumonia is observed in horses after long-distance transportation in association with confinement of head position leading to reduction in tracheal mucociliary clearance rate (TMCR). HYPOTHESIS/OBJECTIVES: Clenbuterol, a beta-2 agonist shown to increase TMCR in the horse, will ameliorate the effects of a fixed elevated head position on large airway contamination and inflammation in a model of long-distance transportation model. ANIMALS: Six adult horses. METHODS: A cross-over designed prospective study. Horses were maintained with a fixed elevated head position for 48 hours to simulate long-distance transport, and treated with clenbuterol (0.8 µg/kg PO q12h) or a placebo starting 12 hours before simulated transportation. TMCR was measured using a charcoal clearance technique. Data were collected at baseline and 48 hours, and included TMCR, tracheal wash cytology and quantitative culture, rectal temperature, CBC, fibrinogen, and serum TNFα, IL-10, and IL-2 levels. There was a 18-21 day washout between study arms, and data were analyzed using regression analysis and Wilcoxon rank-sum tests. RESULTS: Tracheal mucociliary clearance rate was significantly decreased after transportation in both treatment (P = .002) and placebo (P = .03) groups. There was a significant effect of treatment on TMCR, with the treatment group showing half the reduction in TMCR compared with the placebo group (P = .002). Other significant differences between before- and after-transportation samples occurred for serum fibrinogen, peripheral eosinophil count, quantitative culture, tracheal bacteria, and degenerate neutrophils, though no treatment effect was found. CONCLUSIONS AND CLINICAL IMPORTANCE: Treatment with clenbuterol modestly attenuates the deleterious effects of this long-distance transportation model on tracheal mucociliary clearance.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Clembuterol/farmacologia , Doenças dos Cavalos/fisiopatologia , Depuração Mucociliar/fisiologia , Traqueia/fisiopatologia , Agonistas Adrenérgicos beta/uso terapêutico , Animais , Contagem de Células Sanguíneas/veterinária , Clembuterol/uso terapêutico , Estudos Cross-Over , Citocinas/sangue , Fibrinogênio/análise , Cavalos , Estudos Prospectivos , Análise de Regressão , Meios de TransporteRESUMO
OBJECTIVE: Our objective was to evaluate ethnic differences in response to morphine and to determine whether any detectable differences were pharmacokinetically based. METHODS: This cohort study was carried out in a teaching hospital. Sixty-six young, healthy male subjects from 3 ethnic groups (Caucasians, native Indians, and Latinos; n = 22 in each group) consented to participate. All subjects received an intravenous morphine bolus of 0.08 mg/kg followed by 0.002 mg/kg. min infused for 30 minutes. Respiratory response was evaluated with the carbon dioxide rebreathing method before and at 25, 95, 180, and 360 minutes after morphine administration. Vital signs and opioid side effects were recorded, and serial blood samples were analyzed for morphine, morphine-3-glucuronide, and morphine-6-glucuronide (M6G). RESULTS: All 3 groups had suppression of the ventilatory response to hypercapnia, but the degree of blunting of the ventilatory response differed among groups. Compared with Caucasians, native Indians had an additional 18% reduction in ventilatory response after morphine administration (95% confidence interval, -35% to -2%). The incidence of side effects was similar in all groups (P =.18). Caucasians had higher plasma levels of M6G than did native Indians or Latinos. M6G areas under 6-hour concentration-versus-time curve were as follows: Caucasians, 12,065 +/- 4354; native Indians, 8464 +/- 4809; and Latinos, 9156 +/- 3764 ng. min/mL (P =.03). CONCLUSIONS: Ethnicity influences the response to morphine. Native Indians are more susceptible to morphine depression of the ventilatory response than Caucasians, despite the higher serum M6G levels in Caucasians.