Avaliação da estabilidade de anticoagulação entre a Varfarina e a Femprocumona / Oral anticoagulation stability assessment with Warfarin and Phenprocoumon

Fundamentos: A varfarina e a femprocumona são os anticoagulantes orais mais utilizados; no entanto, até então, não existem estudos randomizados comparando a estabilidade da anticoagulação entre estes dois fármacos. Objetivos: Comparar a varfarina e femprocumona quanto à estabilidade na manutenção de anticoagulação em nível terapêutico (razão normatizada internacional [RNI] entre 2,0 e 3,0) e avaliar a incidência de complicações hemorrágicas e tromboembólicas decorrentes de anticoagulação inadequada.Métodos: Ensaio clínico, randomizado, duplo-cego, incluindo pacientes em tratamento vigente com anticoagulante oral, porém com RNI abaixo do alvo terapêutico nas últimas três semanas, randomizados para uso de varfarina ou femprocumona. O ajuste da dose da medicação foi realizado conforme algoritmo pré-estabelecido. Resultados: Foram randomizados 62 pacientes, sendo 31 em cada grupo, durante as cinco primeiras semanas de estudo. Verificou-se que a femprocumona se mostrou mais instável comparada à varfarina. A partir da sexta aferição de RNI, o grupo femprocumona apresentou melhora na estabilidade do valor do RNI, porém não houve significância estatística. Também não houve diferença significativa em relação aos efeitos colaterais dos fármacos. Conclusão: A varfarina demonstrou maior eficácia na estabilidade do RNI em relação à femprocumona.

Background: Although warfarin and phenprocoumon are the most widely used oral anticoagulants, there a r e n o r a n d o m i z e d s t u d i e s c o m p a r i n g t h e anticoagulation stability of these two drugs.Objectives: To compare warfarin and phenprocoumon in terms of therapeutic anticoagulation maintenance stability (international normalized ratio [INR] between 2.0 and 3.0) and evaluate the incidence of thromboembolic and hemorrhagic complications arising from inadequate anticoagulation.Methods: Randomized double-blind clinical trial with patients undergoing current oral anticoagulant treatment but with INR below the therapeutic target during the past 3 weeks, randomized for warfarin or phenprocoumon. Medication dosages were adjusted in compliance with a predetermined algorithm.Results: With 62 patients randomized into two groups of 31 each during the first five weeks of the study, phenprocoumon was found to be more unstable than warfarin. From the sixth INR measurement onwards, the stability of the INR value improved in the phenprocoumon group, but with no statistical significance. There were no significant differences in the side effects of the drugs.Conclusion: Warfarin demonstrated greater effectiveness for INR stability than phenprocoumon.

Brazilian guidelines for community-acquired pneumonia in immunocompetent adults - 2009.

Community-acquired pneumonia continues to be the acute infectious disease that has the greatest medical and social impact regarding morbidity and treatment costs. Children and the elderly are more susceptible to severe complications, thereby justifying the fact that the prevention measures adopted have focused on these age brackets. Despite the advances in the knowledge of etiology and physiopathology, as well as the improvement in preliminary clinical and therapeutic methods, various questions merit further investigation. This is due to the clinical, social, demographical and structural diversity, which cannot be fully predicted. Consequently, guidelines are published in order to compile the most recent knowledge in a systematic way and to promote the rational use of that knowledge in medical practice. Therefore, guidelines are not a rigid set of rules that must be followed, but first and foremost a tool to be used in a critical way, bearing in mind the variability of biological and human responses within their individual and social contexts. This document represents the conclusion of a detailed discussion among the members of the Scientific Board and Respiratory Infection Committee of the Brazilian Thoracic Association. The objective of the work group was to present relevant topics in order to update the previous guidelines. We attempted to avoid the repetition of consensual concepts. The principal objective of creating this document was to present a compilation of the recent advances published in the literature and, consequently, to contribute to improving the quality of the medical care provided to immunocompetent adult patients with community-acquired pneumonia.

Diretrizes brasileiras para pneumonia adquirida na comunidade em adultos imunocompetentes - 2009 / Brazilian guidelines for community-acquired pneumonia in immunocompetent adults - 2009

A pneumonia adquirida na comunidade mantém-se como a doença infecciosa aguda de maior impacto médico-social quanto à morbidade e a custos relacionados ao tratamento. Os grupos etários mais suscetíveis de complicações graves situam-se entre os extremos de idade, fato que tem justificado a adoção de medidas de prevenção dirigidas a esses estratos populacionais. Apesar do avanço no conhecimento no campo da etiologia e da fisiopatologia, assim como no aperfeiçoamento dos métodos propedêuticos e terapêuticos, inúmeros pontos merecem ainda investigação adicional. Isto se deve à diversidade clínica, social, demográfica e estrutural, que são tópicos que não podem ser previstos em sua totalidade. Dessa forma, a publicação de diretrizes visa agrupar de maneira sistematizada o conhecimento atualizado e propor sua aplicação racional na prática médica. Não se trata, portanto, de uma regra rígida a ser seguida, mas, antes, de uma ferramenta para ser utilizada de forma crítica, tendo em vista a variabilidade da resposta biológica e do ser humano, no seu contexto individual e social. Esta diretriz constitui o resultado de uma discussão ampla entre os membros do Conselho Científico e da Comissão de Infecções Respiratórias da Sociedade Brasileira de Pneumologia e Tisiologia. O grupo de trabalho propôs-se a apresentar tópicos considerados relevantes, visando a uma atualização da diretriz anterior. Evitou-se, tanto quanto possível, uma repetição dos conceitos considerados consensuais. O objetivo principal do documento é a apresentação organizada dos avanços proporcionados pela literatura recente e, desta forma, contribuir para a melhora da assistência ao paciente adulto imunocompetente portador de pneumonia adquirida na comunidade.

Community-acquired pneumonia continues to be the acute infectious disease that has the greatest medical and social impact regarding morbidity and treatment costs. Children and the elderly are more susceptible to severe complications, thereby justifying the fact that the prevention measures adopted have focused on these age brackets. Despite the advances in the knowledge of etiology and physiopathology, as well as the improvement in preliminary clinical and therapeutic methods, various questions merit further investigation. This is due to the clinical, social, demographical and structural diversity, which cannot be fully predicted. Consequently, guidelines are published in order to compile the most recent knowledge in a systematic way and to promote the rational use of that knowledge in medical practice. Therefore, guidelines are not a rigid set of rules that must be followed, but first and foremost a tool to be used in a critical way, bearing in mind the variability of biological and human responses within their individual and social contexts. This document represents the conclusion of a detailed discussion among the members of the Scientific Board and Respiratory Infection Committee of the Brazilian Thoracic Association. The objective of the work group was to present relevant topics in order to update the previous guidelines. We attempted to avoid the repetition of consensual concepts. The principal objective of creating this document was to present a compilation of the recent advances published in the literature and, consequently, to contribute to improving the quality of the medical care provided to immunocompetent adult patients with community-acquired pneumonia.

Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common infectious disease in intensive care units (ICUs). The best diagnostic approach to resolve this condition remains uncertain. OBJECTIVES: To evaluate whether quantitative cultures of respiratory secretions are effective in reducing mortality in immunocompetent patients with VAP, compared with qualitative cultures. We also considered changes in antibiotic use, length of ICU stay and mechanical ventilation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 4), which contains the Acute Respiratory Infections Group's Specialized Register; MEDLINE (1966 to December 2007); EMBASE (1974 to December 2007); and LILACS (1982 to December 2007). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing respiratory samples processed quantitatively or qualitatively, obtained by invasive or non-invasive methods from immunocompetent patients with VAP, and which analyzed the impact of these methods on antibiotic use and mortality rates. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and selected trials from the search results, and assessed studies for suitability, methodology and quality. We analyzed data using Review Manager software. We pooled the included studies to yield the risk ratio (RR) for mortality and antibiotic change with 95% confidence intervals (CI). MAIN RESULTS: Of the 3931 references identified from the electronic databases, five RCTs (1367 patients) met the inclusion criteria. Three studies compared invasive methods using quantitative cultures versus non-invasive methods using qualitative cultures, and were used to answer the main objective of this review. The other two studies compared invasive versus non-invasive methods, both using quantitative cultures. All five studies were combined to compare invasive versus non-invasive interventions for diagnosing VAP. The studies that compared quantitative and qualitative cultures (1240 patients) showed no statistically significant differences in mortality rates (RR = 0.91, 95% CI 0.75 to 1.11). The analysis of all five RCTs showed there was no evidence of mortality reduction in the invasive group versus the non-invasive group (RR = 0.93, 95% CI 0.78 to 1.11). There were no significant differences between the interventions with respect to the number of days on mechanical ventilation, length of ICU stay or antibiotic change. AUTHORS' CONCLUSIONS: There is no evidence that the use of quantitative cultures of respiratory secretions results in reduced mortality, reduced time in ICU and on mechanical ventilation, or higher rates of antibiotic change when compared to qualitative cultures in patients with VAP. Similar results were observed when invasive strategies were compared with non-invasive strategies.

Pneumonia severity index class v patients with community-acquired pneumonia: characteristics, outcomes, and value of severity scores.

BACKGROUND: Community-acquired pneumonia (CAP) with a pneumonia severity index (PSI) score in risk class V (PSI-V) is a potentially life-threatening condition, yet the majority of patients are not admitted to the ICU. The aim of this study was to characterize CAP patients in PSI-V to determine the risk factors for ICU admission and mortality, and to assess the performance of CAP severity scores in this population. METHODS: Prospective observational study including hospitalized adults with CAP in PSI-V from 1996 to 2003. Clinical and laboratory data, microbiological findings, and outcomes were recorded. The PSI score; modified American Thoracic Society (ATS) score; the confusion, urea, respiratory rate, low BP (CURB) score, and CURB plus age of >/= 65 years score were calculated. A reduced score based on the acute illness variables contained in the PSI was also obtained. RESULTS: A total of 457 patients were included in the study (mean [+/- SD] age, 79 +/- 11 years), of whom 92 (20%) were admitted to the ICU. Patients in the ward were older (mean age, 82 +/- 10 vs 70 +/- 10 years, respectively) and had more comorbidities. ICU patients experienced significantly more acute organ failures. The mortality rate was higher in ICU patients, but also was high for non-ICU patients (37% vs 20%, respectively; p = 0,003). A low level of consciousness (odds ratio [OR], 3.95; 95% confidence interval [CI], 2 to 5) and shock (OR, 24.7; 95% CI, 14 to 44) were associated with a higher risk of death. The modified ATS severity rule had the best accuracy in predicting ICU admission and mortality. CONCLUSIONS: Most CAP patients PSI-V were treated on a hospital ward. Those admitted to the ICU were younger and had findings of more acute illness. The PSI performed well as a mortality prediction tool but was less appropriate for guiding site-of-care decisions.

Impact of alcohol abuse in the etiology and severity of community-acquired pneumonia.

BACKGROUND AND STUDY OBJECTIVES: Alcohol consumption is known to affect both systemic and pulmonary immunity, predisposing the patient to pulmonary infections. The aim of this study was to compare the etiology of disease, the antibiotic resistance of Streptococcus pneumoniae, the severity of disease, and the outcome of patients with alcohol abuse to those of nonalcoholic (NA) patients who have been hospitalized for community-acquired pneumonia (CAP). METHODS: From 1997 to 2001, clinical, microbiological, radiographic, and laboratory data, and follow-up variables of all consecutive patients who had been hospitalized with CAP were recorded. Patients were classified as alcoholic (A) [n = 128] or ex-alcoholic (EA) patients (n = 54) and were compared to NA patients (n = 1,165). RESULTS: S pneumoniae was found significantly more frequently in all patients with alcohol misuse. As regards the rates of antibiotic resistance, invasive pneumococcal disease, and other microorganisms, no differences were found. The severity criteria for CAP according to the American Thoracic Society were more frequent in A patients, but mortality did not differ significantly. Multivariate analysis showed an independent association between pneumococcal CAP and alcoholism (A patients: odds ratio [OR], 1.6; p = 0.033; EA patients: OR, 2.1; p = 0.016). CONCLUSIONS: We found an independent association between pneumococcal infection and alcoholism. Current alcohol abuse was associated with severe CAP. No significant differences were found in mortality, antibiotic resistance of S pneumoniae, and other etiologies.

Risk and prognostic factors of ventilator-associated pneumonia in trauma patients.

OBJECTIVE: To assess the risk and prognostic factors of ventilator-associated pneumonia in trauma patients, with an emphasis on the inflammatory response. DESIGN: Case-control study. SETTING: Trauma intensive care unit. PATIENTS: Of 190 consecutive mechanically ventilated patients, those with microbiologically confirmed pneumonia (n = 62) were matched with 62 controls without pneumonia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiological, and outcome variables were recorded. Cytokines were measured in serum and blind bronchoalveolar lavage specimens at onset of pneumonia. Multivariate analyses of risk and prognostic factors for ventilator-associated pneumonia were done. Increased severity of head and neck injury (odds ratio, 11.9; p < .001) was the only independent predictor of pneumonia. Among patients with pneumonia, serum levels of interleukin-6 (p = .019) and interleukin-8 (p = .036) at onset of pneumonia were higher in nonresponders to treatment. Moreover, serum levels of tumor necrosis factor-alpha (p = .028) and interleukin-6 (p = .007) at onset of pneumonia were higher in nonsurvivors. Mortality in the intensive care unit was 23% in cases and controls. Nonresponse to antimicrobial treatment (odds ratio, 22.2; p = .001) and the use of hyperventilation (p = .021) were independent predictors of mortality in the intensive care unit for patients with pneumonia. CONCLUSIONS: Severe head and neck trauma is strongly associated with ventilator-associated pneumonia. A higher inflammatory response is associated with nonresponse to treatment and mortality among patients with pneumonia. Although pneumonia did not influence mortality, nonresponse to treatment independently predicted mortality among these patients.

Bronchial colonization and postoperative respiratory infections in patients undergoing lung cancer surgery.

STUDY OBJECTIVES: To evaluate the risk factors associated with postoperative respiratory infection in patients undergoing lung cancer surgery, with special emphasis on the perioperative pattern of airway colonization. DESIGN: Prospective cohort study. SETTING: Department of Pneumology and Thoracic Surgery of a tertiary hospital. PATIENTS: Seventy-eight consecutive patients undergoing lung cancer surgery were evaluated. Patients were followed up until hospital discharge or death. INTERVENTIONS: Fiberoptic bronchoscopies with bilateral protected specimen brush or bronchial aspirates were performed during anesthesia prior to the initiation of the surgical procedure. RESULTS: Sixty-five patients (83%) had perioperative bronchial colonization by either potentially pathogenic microorganisms (PPMs) [28 patients, 36%] or non-potentially pathogenic microorganisms (56 patients, 72%). The 24 patients (31%) with a postoperative respiratory infection (pneumonia, purulent tracheobronchitis, or pleural empyema) had significantly higher perioperative bronchial colonization by PPMs (15 patients [63%] vs 13 patients [24%], p = 0.003) and a higher bacterial index (mean +/- SD, 3.6 +/- 3.3 vs 0.9 +/- 1.4; p = 0.003), compared to patients without infection. The agreement between pathogens found in perioperative evaluation and during postoperative infection was total in 5 patients (21%), partial in 5 patients (21%), and no concordance in 14 patients (58%). In the multivariate analysis, the presence of perioperative airway colonization by a PPM (odds ratio [OR], 6.9; p = 0.001) and a higher postoperative pain score (OR, 4.1; p = 0.014) were independent predictors of postoperative respiratory infection. CONCLUSION: Adequate control of postoperative pain, as well as the conditions that potentially cause airway colonization by PPMs, could be beneficial in preventing postoperative respiratory infections after lung cancer surgery.

Respiratory nosocomial infections in the medical intensive care unit.

Intensive care unit (ICU)-acquired lower respiratory tract infections include acute tracheobronchitis and hospital-acquired and ventilator-associated pneumonia (VAP). Nosocomial pneumonia is the second most common hospital-acquired infection and the leading cause of death in hospital-acquired infections. The mortality rate in VAP ranges from 24% to 76% in several studies. ICU ventilated patients with VAP have a 2- to 10-fold higher risk of death than patients without it. Early oropharyngeal colonization is pivotal in the etiopathogenesis of VAP. The knowledge of risk factors for VAP is important in developing effective preventive programs. Once the physician decides to treat a suspected episode of ICU-acquired pneumonia, some issues should be kept on mind: first, the adequacy of the initial empiric antibiotic therapy; second, the modification of initial inadequate therapy according to microbiological results; third, the benefit of combination therapy; and finally, the duration of the antimicrobial treatment. Additionally, a protocolized work-up to identify the causes of non-response to treatment is mandatory. All these issues are discussed in depth in this article.

Non-infectious and unusual infectious mimics of community-acquired pneumonia.

Noninfectious or unusual infectious diseases may present with clinical, radiological and laboratorial characteristics of community-acquired pneumonia (CAP). Usually their presence is only suspected after treatment failure, leading to inappropriate interventions, unnecessary costs and risks related to the untreated potentially life-threatening disease. The present study aimed to assess the noninfectious or unusual infectious diseases that may be misdiagnosed as CAP that progresses with treatment failure. Sixteen hospitalized patients with presumptive diagnosis of CAP and treatment failure were described. The most prevalent symptoms were fever and cough. Radiological pattern of air-space disease was observed in 10 (62%) patients. The diagnosis was established by autopsy (12%) or invasive procedures (88%), as follows: open lung biopsy (nine), flexible fiberoptic bronchoscopy (two), transthoracic fine needle aspiration (two) and bone marrow aspiration (one). Eight patients had noninfectious diseases: pulmonary embolism, cryptogenic organizing pneumonia, Wegener's granulomatosis, hypersensitivity pneumonitis, bronchocentric granulomatosis, neoplastic disease and acute leukemia. The unusual infectious diseases were: tuberculosis, cryptococcosis, actinomycosis, histoplasmosis and paracoccidioidomycosis. Patients with noninfectious or unusual infectious diseases may present with symptoms and radiological findings that mimic CAP. These diseases should always be suspected in patients who do not respond to initial empirical antimicrobial treatment, especially young patients or those without comorbidity.

Causes and predictors of nonresponse to treatment of intensive care unit-acquired pneumonia.

OBJECTIVE: To prospectively evaluate the predictive factors for the nonresponse to empirical antibiotic treatment and mortality in patients with intensive care unit-acquired pneumonia. DESIGN: A 1-yr prospective cohort of patients with suspicion of intensive care unit-acquired pneumonia. SETTING: Five medical and surgical intensive care units of Hospital Clinic in Barcelona. PATIENTS: A total of 71 patients with intensive care unit-acquired pneumonia were studied. The definition of nonresponse included at least one of the following: failure to improve the Pao2/Fio2 ratio or need of intubation because of pneumonia, persistence of fever or hypothermia and purulent respiratory secretions, worsening of pulmonary infiltrates, or occurrence of septic shock or multiple organ dysfunction not present at onset of pneumonia. INTERVENTIONS: Clinical assessment, including severity scores, blood and quantitative cultures of respiratory secretions, and cytokine measurements in serum and bronchoalveolar lavage at onset of pneumonia and 72 hrs after antimicrobial treatment. MEASUREMENTS AND RESULTS: A total of 44 patients (62%) fulfilled criteria of nonresponse, and at least one cause of nonresponse could be determined in 28 cases (64%): inappropriate treatment in ten (23%), superinfection in six (14%), concomitant foci of infection in 12 (27%), and noninfectious causes in seven cases (16%). The remaining 16 patients with no definite cause of nonresponse presented with septic shock, multiple organ dysfunction, or acute respiratory distress syndrome. Increased levels of interleukin-6 at onset of pneumonia (odds ratio, 9.7; p =.014) was an independent predictor of nonresponse to treatment. Likewise, increased level of interleukin-6 at follow-up (odds ratio, 27; p =.001) was the only independent predictor for hospital mortality. CONCLUSION: Increased systemic inflammatory response was the main predictor of nonresponse to treatment and mortality.

Má percepçäo da limitaçäo aos fluxos aéreos em pacientes com asma moderada a grave / Poor perception of airflow limitation in patients with moderate to severe asthma

Uma proporçäo significativa de amostra de asmáticos näo percebeu acuradamente a obstruçäo das via aéreas. Aléem disso, exame torácico mostrou ser um marcador inadequado da limitaçäo aos fluxos aéreos em asmáticos moderados a grave, estáveis e ambulatorial.

Ausência de correlaçäo entre a ausculta de sibilos e a gravidade da asma / Absence of correlation between wheezingauscultation and asthma severity

Objetivo: Avaliar a correlaçäo entre a presença, a intensidade e a fase ventilatória da ausculta de sibilos, com a gravidade da obstruçäo brönquica em asmáticos moderados a grave. Pacientes e métodos: Trinta e três pacientes com asma moderada a grave foram avaliados em ambulatório, durante seis semamas (sete visitas)por dois observadores distintos e independentes. O observador 1 realizou os exames clínicos e a classificaçäo clínica da gravidade da asma. O observador 2 obteve as escalas analógicas visuais de sintomas (EVAS)e as espirometrias. Os pacientes foram distribuídos emdois grupos de acordo com a presença (SP) ou a ausência (SA) de sibilos. A presença de sibilos foi comparada com o VEF, e o VEF1/CVF durante a visita inicial e em 231 observaçöes ao longo do estudo. Resultado: Os sibilos estavam presentes em 19 (cinqüenta e sete, seis por cento) pacientes e ausentes em 14 (quarenta e dois, quatro por cento) na avaliaçäo inicial. Observaram-se sibilos inspiratórios e expiratórios em onze (34,4 por cento) destes asmáticos, apenas expiratórios em sete (21,9 por cento) e unicamente inspiratórios em um (3 por cento). A mediana do VEF, foi de 56,6 por cento do previsto para o grupo SP e de 55 por cento para o grupo SA. A intensidade dos sibilos näo se associou ao VEF, ou ao VEF1/CVF. Conclusöes: Nem a presença nem a intensidade dos sibilos se correlacionaram com a intensidade da obstruçäo brônquica medida pelo VEF1, em asmáticos moderados e graves. Portanto, o método de ausculta isolado é insuficiente para determinar com precisäo a gravidade da asma. A mensuraçäo da funçäo pulmonar é essencial para monitorizaçäo segura de pacientes ambulatoriais com asma moderada a grave.