COMO TRATAR A EXACERBAÇÃO DA DPOC?

Apresentação em tema: "COMO TRATAR A EXACERBAÇÃO DA DPOC?"— Transcrição da apresentação:

1 COMO TRATAR A EXACERBAÇÃO DA DPOC?
X Curso Nacional de Atualização em Pneumologia Fernando Lundgren – HGOF - Recife

2 Potenciais Conflitos de Interesse CFM nº 1
Potenciais Conflitos de Interesse CFM nº 1.59/00 de 18/5/2000 e ANVISA nº 120/2000 de 30/11/2000 1. Nos últimos doze meses recebi apoio financeiro da indústria farmacêutica, em forma de passagem ou apoio didático para participação em evento médico, ou pesquisa clínica. Consultor da BI/Pfizer Novartis ; Boehringer-Inghelheim ; Pfizer ; GSK ; Aché; Astra Zeneca 2. Sou funcionário de entidade governamental. Coordenador de Residência Médica em Pneumologia do HOF- PE Membro do Comitê Estadual de Pneumologia 3. Sou membro de organização não-governamental destinada a defesa de interesses de profissionais de saúde. Membro da comissão de DPOC da SBPT Membro do projeto GOLD para a DPOC Diretor de Divulgação e Defesa Profissional da SBPT Data da última modificação: 31 de março de 2009

3 Definição Exacerbação
Exacerbação é um agravo das condições do paciente, do seu estado de estabilidade e de sua situação diária, este agravo é agudo e necessita tratamento adicional ao utilizado COPD exacerbations: definitions and classifications Eur Respir J 2003; 21: Suppl. 41, 46s–53s S. Burge*, J.A. Wedzicha# COPD exacerbations: definitions and classifications. S. Burge, J.A. Wedzicha. #ERS Journals Ltd 2003. ABSTRACT: Chronic obstructive pulmonary disease (COPD) is defined independently of exacerbations, which are largely a feature of moderate-to-severe disease. This article is the result of a workshop that tried to define exacerbations of COPD for use in clinical, pharmacological and epidemiological studies. The conclusions represent the consensus of those present. This review describes definitions, ascertainment, severity assessments, duration and frequency, using varying sources of data including direct patient interview, healthcare databases and symptom diaries kept by patients in studies. The best general definition of a COPD exacerbation is the following: an exacerbation of COPD is a sustained worsening of the patient9s condition, from the stable state and beyond normal day-to-day variations that is acute in onset and may warrant additional treatment in a patient with underlying COPD. A more specific definition for studies where a bacteriological cause of exacerbation is being studied is included, as well as simpler definitions for retrospective identification from database sources. Prospective diary card assessments are best recorded as changes from an agreed baseline, rather than absolute symptom severities. Diary cards identify many unreported exacerbations, which on average have similar severities to reported exacerbations. A scale for exacerbation severity is proposed that incorporates in- and outpatient assessments. Exacerbation duration, which also relates to severity, is defined from diary card reports. Healthcare utilisation is not an adequate substitute for severity, depending on many unrelated social and comorbidity factors. It is an outcome in its own right. S. Burge, J.A. Wedzicha Eur Respir J 2003; 21: Suppl. 41, 46s–53s.

4 Impacto das exacerbações na DPOC
Pacientes com exacerbações freqüentes Declínio da função pulmonar Queda da qualidade de vida Maior processo inflamatório Maior mortalidade Patients with frequent exacerbations of COPD result in higher mortality, poorer QOL, increased airway inflammation, and a more rapid decline in lung function versus those with less frequent exacerbations. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Reference Wedzicha JA, Seemungal TA. COPD exacerbations: defining their cause and prevention. Lancet. 2007;370: Wedzicha JA, Seemungal TA. Lancet. 2007;370:

5 Causas de Exacerbação na DPOC
Infecciosas (50%) Bacteriana Viral Bactérias atípicas Não Infecciosas (20%) Fatores ambientais Uso errado da medicação Causa desconhecida (30%) TEP 25% Hospital 20% Residência Pneumotórax Câncer Arritmia Insuficiência cardíaca Infectious Etiology of Acute Exacerbations of Chronic Bronchitis Sanjay Sethi Chest 2000;117; Infectious agents are a major cause of acute exacerbations of chronic bronchitis (AECB) and COPD. Several respiratory viruses are associated with 30% of exacerbations, with or without a superimposed bacterial infection. Atypical bacteria, mostly Chlamydia pneumoniae, have been implicated in < 10% of AECB. The role of bacterial pathogens when isolated from the respiratory tract during AECB has become better defined by application of several newer investigative techniques. Bacterial pathogens can be isolated in significant concentrations from distal airways in 50% of AECB. Specific immune responses to surface exposed antigens of the infecting pathogen have been shown to develop after an exacerbation. Emerging evidence from molecular epidemiology and measurement of airway inflammation further support the role of bacteria in AECB. When properly defined, 80% of AECB are likely to be infectious in origin. Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD* A Systematic Review and Metaanalysis Jacques Rizkallah, MD; S. F. Paul Man, MD, FCCP; and Don D. Sin, MD, FCCP Background: Nearly 30% of all exacerbations of COPD do not have a clear etiology. Although pulmonary embolism (PE) can exacerbate respiratory symptoms such as dyspnea and chest pain,and COPD patients are at a high risk for PE due to a variety of factors including limited mobility,inflammation, and comorbidities, the prevalence of PE during exacerbations is uncertain. Methods: A systematic review of the literature was performed to determine the reported prevalence of PE in acute exacerbations of COPD in patients who did and did not require hospitalization. The literature search was performed using MEDLINE, CINAHL, and EMBASE, and complemented by hand searches of bibliographies. Only cross-sectional or prospective studies that used CT scanning or pulmonary angiography for PE diagnosis were included. Results: Of the 2,407 articles identified, 5 met the inclusion criteria (sample size, 550 patients). Overall, the prevalence of PE was 19.9% (95% confidence interval [CI], 6.7 to 33.0%; p ). In hospitalized patients, the prevalence was higher at 24.7% (95% CI, 17.9 to 31.4%; p ) than those who were evaluated in the emergency department (3.3%). Presenting symptoms and signs were similar between patients who did and did not have PE. Conclusions: One of four COPD patients who require hospitalization for an acute exacerbation may have PE. A diagnosis of PE should be considered in patients with exacerbation severe enough to warrant hospitalization, especially in those with an intermediate-to-high pretest probability of PE. (CHEST 2009; 135:786–793) Journal of Epidemiology and Community Health 2009;63: Environmental factors and hospitalisation for chronic obstructive pulmonary disease in a rurJournal of Epidemiology and Community Health 2009;63: al county of England V Sauerzapf1, A P Jones1, J Cross2 1 School of Environmental Sciences, University of East Anglia, Norwich, UK  2 School of Allied Health Professions, University of East Anglia, Norwich, UK Correspondence to: Dr A Jones, School of Environmental Sciences, University of East Anglia, Norwich, Norfolk NR4 7TJ, Background: Chronic obstructive pulmonary disease (COPD) is a major global cause of morbidity and mortality. Studies in urban areas have shown associations between air pollutants and hospital admissions for COPD. Whether temporal variations in air quality are associated with hospital admissions for COPD in a rural region with lower concentrations of air pollutants than previously studied was investigated. Methods: Daily COPD admissions were recorded for patients attending three hospitals in the county of Norfolk, UK, between January 2006 and February Records were combined with daily information on concentrations of six air pollutants (carbon monoxide, nitric oxide, nitrogen dioxide, oxides of nitrogen, ozone and fine particulates), airborne pollens, temperature and influenza incidence. A case–crossover analysis was used to examine the association between air pollution and daily admissions. Results: There were 1050 admissions for COPD over the study period. After adjustment for temperature, pollen and respiratory infections, each 10 µg/m3 increase in CO was associated with a 2% increase in the odds of admission. V3alues of 17%, 22% and 9% were observed for NO, NO2 and oxides of nitrogen respectively. No associations were observed with O3 or particulates. Conclusion: Among a population of a less urbanised area than previously investigated, this study found evidence that ambient pollutant concentrations were still associated with the risks of hospital admission for COP Journal of Epidemiology and Community Health 2009;63: Prevalence of Pulmonary Embolism in Acute Exacerbations of COPD* A Systematic Review CHEST 2009; 135:786–793 Infectious Etiology of Acute Exacerbations of Chronic Bronchitis Chest 2000; 117;

6 Avaliação da gravidade da Exacerbação
Sinais e sintomas clínicos Local de tratamento Presença de infecção bacteriana Marcadores séricos S.Daiana Current Opinion in Pulmonary Medicine :126–132

7 Gravidade das Exacerbações
As exacerbações apresentam gravidades diferentes Leve Moderada Grave Local de tratamento depende da gravidade Residência Enfermaria UTI Tratamento depende da gravidade

8 Indicação para tratamento Hospitalar
Aumento rápido dos sintomas em intensidade (dispnéia em repouso) DPOC muito grave e grave Início de novos sinais físicos (cianose, edema perifërico) Falha de resposta ao tratamento inicial Doenças associadas Exacerbações frequentes Arritimia Incerteza diagnóstica Idoso Indications for hospital management of acute exacerbations include the following: Marked increase in intensity of symptoms, such as sudden development of resting dyspnoea Severe underlying COPD Onset of new physical signs (e.g., cyanosis, peripheral oedema) Failure of exacerbation to respond to initial medical management Significant comorbidities Frequent exacerbations Newly occurring arrhythmias Diagnostic uncertainty Older age Insufficient home support Reference Global Strategy for Diagnosis, Management, and Prevention of COPD Available at: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2008

9 Indicação para Unidade de Terapia Intensiva
Intensa dispnéia que não responde ao tratamento inicial na emergência Alteração no estado mental (confusão, letargia, coma) Agravo da hipoxemia (PaO2 < 40 mm Hg), e / ou hipercapnia (PaCO2 > 60 mmHg) Agravo da acidose respiratória (pH <7.25) apesar da oxigenoterapia e ventilação não invasiva Necessidade de ventilação invasiva Instabilidade hemodinâmica – uso de vasopressor Speaker Notes Indications for treatment in an intensive care unit for a patient with an acute exacerbation of COPD include: Severe dyspnoea that responds inadequately to initial emergency therapy Changes in mental status (confusion, lethargy, coma) Persistent or worsening hypoxaemia (PaO2 <5.3 kPa, 40 mm Hg), and/or severe/worsening hypercapnia (PaCO2 >8.0 kPa, 60 mmHg), and/or severe/worsening respiratory acidosis (pH <7.25) despite supplemental oxygen and noninvasive ventilation Need for invasive mechanical ventilation Haemodynamic instability—need for vasopressors Reference Global Strategy for Diagnosis, Management, and Prevention of COPD Available at: GOLD

10 Como predizer desfecho de EDPOC
794 EDPOC que procuravam emergência foram avaliados anos 2003 a 2004 Dois grupos: 353 – coleta de dados para derivação da regra – validação da regra Mortalidade do estudo = 7,9% Pacientes que eram internados na UTI não participaram da pesquisa

11 Preditores de mortalidade em Exacerbação da DPOC
Risco de Morte (OR e 95% IC) Análise multivariada Idade > 70 anos 4,5 (1,6-12,1) Sinais clínicos de gravidade Cianose 1,5 (0,7-3,0) Alteração do estado de alerta 5,1 (2,4-10,8) Edema de MMII 1,0 (0,4-2,0) Asterixis 1,7 (0,6-4,3) Uso de músculos inspiratórios acessórios 2,6 (1,1-6,2) Use de músculo abdominal na expiração 0,9 (0,4-1,9) Dispnéia basal 0-1 1,0 2-3 3,6(0,7-16,5) 4-6 6,5(1,4-29,3) Eur Respir J 2008; 32: 953–961 Predictors of outcomes in COPD exacerbation cases presenting to the emergency department N. Roche*, M. Zureik#, D. Soussan#, F. Neukirch#, D. Perrotin" and the Urgence BPCO (COPD Emergency) Scientific Committee and investigators+ ABSTRACT: The aim of the present prospective multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease (COPD) exacerbations in a real-life setting. All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included, except those who immediately required intensive care unit admission and/or ventilatory support. The data collected included patient characteristics, in-hospital outcomes (mortality and length of stay) and mode of discharge (unsupported or need for post-hospital assistance). The in-hospital mortality rate was 7.4% (59 out of 794). Independent prognostic factors were age, number of clinical signs of severity (among cyanosis, impaired neurological status, lower limb oedema, asterixis and use of accessory inspiratory or expiratory muscles) and dyspnoea grade in the stable state. The need for post-hospital support was also predicted by female sex. In order to construct and validate a prediction score for mortality based on these items, patients were randomly allocated to a derivation and a validation cohort. The prediction score showed good discrimination, with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort. Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease. Their use needs to be prospectively validated. Roche et al .Eur Respir J 2008; 32: 953–961

12 Escala de Gravidade da Exacerbação
Corte Pontos Idade > 70 1 Sinais Ausência sinal 1-2 2 ≥ 3 3 Dispnéia 0-1 2-3 4-5 Roche et al .Eur Respir J 2008; 32: 953–961

13 Ponto de Corte e mortalidade na EDPOC
Derivação Validação Pontos n = 353 n = 334 0 -1 ponto 1,7% (2) 0,00% (0) 2-3 pontos 4,6% (5) 4,8% (5) > 4 pontos 15,5% (19) 12,3% (14) Sensibilidade 0,73 0,74 Especificidade 0,68 Roche et al .Eur Respir J 2008; 32: 953–961

14 Tratamento em Residência da DPOC
Iniciar ou Aumentar BD Reavaliar em horas Melhora ou Resolução Continuar tratamento Rever manutenção Sem melhora Corticóide oral Heparina Agravo Encaminhar Hospital GOLD

15 Tratamento em Hospital
Avaliação inicial Sintomas / Radiografia / Gasometria Oxigenote rapia Gasometria após 30 minutos VNI Medicamentos Corticóide sistêmico Inalado ( se não for possível uso sistêmico) Broncodilatadores Aumentar dose e freqüência Associar Anticoli nérgico e β adrenérgico Considerar aminofilina Antibióticos Avaliar indicação Afastar complicações Pneumonia Pneumotórax TEP Heparina ICC Arritmia IAM GOLD

16 Broncodilatadores Doses elevadas de curta-ação
Aumentar freqüência e dose Controle por efeitos colaterais Associação de anticolinérgico + β2 adrenérgico Pode ser iniciado se não utilizada Manter tratamento habitual Não suspender medicação GOLD Incorporating Tiotropium Into a Respiratory Therapist-Directed Bronchodilator Protocol for Managing In-Patients With COPD Exacerbations Decreases Bronchodilator Costs Gail S Drescher MA RRT, Bettye J Carnathan RRT, Susan Imus RRT, and Gene L Colice MD BACKGROUND: Tiotropium is used in maintenance treatment of chronic obstructive pulmonary disease (COPD), but there are no guidelines on when to start tiotropium followin g an exacerbation. OBJECTIVE: To determine whether the addition of tiotropium to a respiratory-therapist-directed bronchodilator protocol affects bronchodilator costs for patients hospitalized for COPD exacerbation. METHODS: We retrospectively analyzed data on the number and type of bronchodilator treatments administered to all patients admitted for COPD exacerbation during the 3-month period (January through March 2006) after tiotropium was added to our bronchodilator protocol, and compared that data to a historical control period (January through March 2004) before tiotropium was available in our hospital. We compared the costs of bronchodilator treatments, baseline patient characteristics, comorbidities, concomitant medications, length of stay, adverse events, and inhospital deaths. RESULTS: Baseline characteristics, comorbidities, and concomitant medications were similar in the 2004 control group (n 181) and the 2006 intervention group (n 174). The mean SD number of bronchodilator treatments per admission was significantly higher in the control period ( ) than in the intervention period ( ). That difference correlated to a reduction in combination therapy (short-acting inhaled 2 agonist plus ipratropium), which decreased from a per-admission average of in the control period to in the intervention period. Calculated bronchodilator costs were significantly lower in the intervention period than in the control period. Length of stay also significantly decreased, from d to d. There were no adverse events related to tiotropium. Pulmonary-related in-hospital deaths were not significantly different between the 2 periods. CONCLUSIONS: Early addition of maintenance-treatment tiotropium to a respiratory-therapist-directed bronchodilator protocol for patients hospitalized for COPD exacerbation reduced costs and produced no safety concerns. Key words: tiotropium bromide, chronic obstructive pulmonary disease, COPD exacerbation, respiratory herapist-directed bronchodilator protocol, costs, 2 agonist, long-acting inhaled bronchodilator, anticholinergic. [Respir Care 2008;53(12):1678 –1684. Iniciar BD de longa-ação na emergência CONCLUSIONS: Early addition of maintenance-treatment tiotropium to a respiratory-therapist-directed bronchodilator protocol for patients hospitalized for COPD exacerbation reduced costs and produced no safety concerns. Gene L Colice et al Respir Care 2008;53(12):1678 –1684.

17 Tempo de Permanência Hospitalar
2003 – Média de permanência – 32,5 dias Tratamento habitual sem uso de BD de longa ação Média de permanência – 17,2 dias Tratamento habitual associado ao Titrópio 18 µg +Budesonida 400 µg + Formoterol 12 µg Banco de dados de internamentos – Enfermaria de Pneumologia – Hospital Otávio de Freitas

18 Relative Risk (95% Confidence Interval)
Meta-analise da eficácia do corticóide sistêmico e risco de falência de tratamento 10 0.1 0.2 0.5 Relative Risk (95% Confidence Interval) 2 5 1 Favorece Placebo Favorece Corticóide Pooled summary (RR, 0.54; 95% CI, ) Bullard et al, 1996 Thompson et al, 1996 Davies et al, 1999 Niewoehner et al, 1999 Maltais et al, 2002 Aaron et al, 2003 Background: Treatment with systemic corticosteroids for exacerbations of COPD results in improvement in clinical outcomes. On hospitalization, corticosteroids are generally administered IV. It has not been established whether oral administration is equally effective. We conducted a study to demonstrate that therapy with oral prednisolone was not inferior to therapy with IV prednisolone using a double-blind, double-dummy design. Methods: Patients hospitalized for an exacerbation of COPD were randomized to receive 5 days of therapy with prednisolone, 60 mg IV or orally. Treatment failure, the primary outcome, was defined as death, admission to the ICU, readmission to the ICU because of COPD, or the intensification of pharmacologic therapy during a 90-day follow-up period. Results: A total of 435 patients were referred for a COPD exacerbation warranting hospitalization; 107 patients were randomized to receive IV therapy, and 103 to receive oral therapy. Overall treatment failure within 90 days was similar, as follows: IV prednisolone, 61.7%; oral prednisolone, 56.3% (one-sided lower bound of the 95% confidence interval [CI], 5.8%). There were also no differences in early (ie, within 2 weeks) treatment failure (17.8% and 18.4%, respectively; one-sided lower bound of the 95% CI, 9.4%), late (ie, after 2 weeks) treatment failure (54.0% and 47.0%, respectively; one-sided lower bound of the 95% CI, 5.6%), and mean ( SD) length of hospital stay ( and days, respectively). Over 1 week, clinically relevant improvements were found in spirometry and health-related quality of life, without significant differences between the two treatment groups. Conclusion: Therapy with oral prednisolone is not inferior to IV treatment in the first 90 days after starting therapy. We suggest that the oral route is preferable in the treatment of COPD exacerbations. Trial registration: Clinicaltrials.gov Identifier: NCT (CHEST 2007; 132:1741–1747) Speaker Notes Systemic corticosteroids are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. Results from this meta-analysis indicated that, compared with placebo, systemic corticosteroids reduced treatment failure by 46%, length of hospital stay by 1.4 days, and improved FEV1 by 0.13 L after 3 days of therapy. Steroid treatment also significantly increased the risk for hyperglycaemia (relative risk = 5.88). Reference Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2008;133: Chest Contemporary Management of Acute Exacerbations of COPD”, Quon BS et al, Vol 133,

19 Corticóide na Exacerbação da DPOC
Corticóide sistêmico – dose entre 30 a 40 mg prednisolona dia CHEST 2007; 132:1741–1747 Corticóide inalatório – Budesonida – dose entre 4 a 6 mg dia Steroids in acute exacerbations of chronic obstructive pulmonary disease: are nebulized and systemic forms comparable? Hakan Gunena, Arzu Miricib, Mehmet Meralc and Metin Akgu¨nc Current Opinion in Pulmonary Medicine 2009,15:133–137 Purpose of review Systemic corticosteroids are strongly recommended in the treatment of exacerbations of chronic obstructive pulmonary disease (COPD). As COPD patients are usually elderly and are relatively immobile, side effects of systemic corticosteroids frequently outweigh their beneficial effects. On the contrary, nebulized corticosteroid solutions have a negligible systemic side-effect profile. In this review, as an alternative to systemic corticosteroids, the place of nebulized corticosteroids in exacerbation periods of COPD was summarized. Recent findings The number of trials in the literature is increasing. Regarding the available data, high dose nebulized budesonide was found as effective as systemic corticosteroids in exacerbations of COPD. The side-effect profile, blood glucose level in particular, is better for nebulized budesonide. Summary Findings from recent studies are giving a positive impression on the role of high dose nebulized budesonide in exacerbations of COPD. However, larger and statistically high powered trials testing different types of nebulized corticosteroid solutions with varying dosages are still lacking. Before recommending the routine use of nebulized corticosteroids in exacerbations, present findings need to be confirmed with further studies of high quality. Oral or IV Prednisolone in the Treatment of COPD Exacerbations* A Randomized, Controlled, Double-blind Study Ynze P. de Jong, MD; Steven M. Uil, MSc; Hans P. Grotjohan, MD, PhD; Dirkje S. Postma, MD, PhD; Huib A.M. Kerstjens, MD, PhD; and Jan W.K. van den Berg, MD, PhD, FCCP Background: Treatment with systemic corticosteroids for exacerbations of COPD results in improvement in clinical outcomes. On hospitalization, corticosteroids are generally administered IV. It has not been established whether oral administration is equally effective. We conducted a study to demonstrate that therapy with oral prednisolone was not inferior to therapy with IV prednisolone using a double-blind, double-dummy design. Methods: Patients hospitalized for an exacerbation of COPD were randomized to receive 5 days of therapy with prednisolone, 60 mg IV or orally. Treatment failure, the primary outcome, was defined as death, admission to the ICU, readmission to the ICU because of COPD, or the intensification of pharmacologic therapy during a 90-day follow-up period. Results: A total of 435 patients were referred for a COPD exacerbation warranting hospitalization; 107 patients were randomized to receive IV therapy, and 103 to receive oral therapy. Overall treatment failure within 90 days was similar, as follows: IV prednisolone, 61.7%; oral prednisolone, 56.3% (one-sided lower bound of the 95% confidence interval [CI], 5.8%). There were also no differences in early (ie, within 2 weeks) treatment failure (17.8% and 18.4%,respectively; one-sided lower bound of the 95% CI, 9.4%), late (ie, after 2 weeks) treatment failure (54.0% and 47.0%, respectively; one-sided lower bound of the 95% CI, 5.6%), and mean ( SD) length of hospital stay ( and days, respectively). Over 1 week, clinically relevant improvements were found in spirometry and health-related quality of life, without significant differences between the two treatment groups. Conclusion: Therapy with oral prednisolone is not inferior to IV treatment in the first 90 days after starting therapy. We suggest that the oral route is preferable in the treatment of COPD exacerbations. Trial registration: Clinicaltrials.gov Identifier: NCT (CHEST 2007; 132:1741–1747) Current Opinion in Pulmonary Medicine :133–137

20 Conduta nas exacerbações: pontos fundamentais
Pacientes que apresentam exacerbação da DPOC, com sinais clínicos de infecção das vias aéreas (aumento do volume e mudança da cor da expectoração e/ou febre) podem se beneficiar do tratamento antibiótico (Evidência B). GOLD

21 Exacerbação Infecciosa da DPOC
Etiologia bacteriana em 50-70% dos casos Murphy TF et al. Chest 2000;118: Evidências baseadas em pesquisa viral por PCR 39 to 56% em exacerbados e 16% em estáveis Seemungal et al. AJRCCM 2001 Rohde et al. Thorax 2003;58:37-42 Em ventilação mecânica, vírus em 43%, único agente em 33% e misto em 10% Intensive Care Med Robert Cameron Airway Inflammation and Etiology of Acute Exacerbations of Chronic Bronchitis Chest 2000;118; Brydon J. B. Grant and Timothy F. Murphy Sanjay Sethi, Karen Muscarella, Nancy Evans, Karin L. Klingman, Study objectives: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. Design: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-a, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypeable Haemophilus influenzae (n 5 20), Haemophilus parainfluenzae (n 5 27), and Moraxella catarrhalis (n 5 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n 5 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. Setting: An outpatient research clinic at a Veterans Affairs Medical Center. Patients: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. Interventions: None. Measurements and results: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-a, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-a and NE when compared to pathogen-negative exacerbations. H parainfluenzaeassociated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. Conclusions: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB. Respiratory Viruses, Symptoms, and Inflammatory Markers in Acute Exacerbations and Stable Chronic Obstructive Pulmonary Disease . TERENCE SEEMUNGAL, RHIAN HARPER-OWEN, ANGSHU BHOWMIK, IVANA MORIC, GWENDOLYN SANDERSON, SIMON MESSAGE, PETER M AC CALLUM, THOMAS W. MEADE, DONALD J. JEFFRIES, SEBASTIAN L. JOHNSTON, and JADWIGA A. WEDZICHA The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV1 , 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study , A Wiethege, I Borg, M Kauth, T T Bauer, A Gillissen, A Bufe, G Schultze-Werninghaus Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are a common cause of hospital admission. Many exacerbations are believed to be due to upper and/or lower respiratory tract viral infections, but the incidence of these infections in patients with COPD is still undetermined. Methods: Respiratory syncytial virus (RSV), influenza A and B, parainfluenza 3, and picornaviruses were detected by nested reverse transcription polymerase chain reaction (RT-PCR) in upper (nasal lavage) and lower respiratory tract specimens (induced sputum). In a 2:1 case-control set up, 85 hospitalised patients with AE-COPD and 42 patients with stable COPD admitted for other medical reasons were studied. Results: Respiratory viruses were found more often in sputum and nasal lavage of patients with AE-COPD (48/85, 56%) than in patients with stable COPD (8/42, 19%, p<0.01). The most common viruses were picornaviruses (21/59, 36%), influenza A (15/59, 25%), and RSV (13/59, 22%). When specimens were analysed separately, this difference was seen in induced sputum (exacerbation 40/85 (47%) v stable 4/42 (10%), p<0.01) but was not significant in nasal lavage (exacerbation 26/85 (31%) v stable 7/42 (17%), p=0.14). In patients with AE-COPD, fever was more frequent in those in whom viruses were detected (12/48, 25%) than in those in whom viruses were not detected (2/37, 5%, p=0.03). Conclusion: Viral respiratory pathogens are found more often in respiratory specimens of hospitalised patients with AE-COPD than in control patients. Induced sputum detects respiratory viruses more frequently than nasal lavage in these patients. These data indicate that nasal lavage probably has no additional diagnostic value to induced sputum in cross-sectional studies on hospitalised patients with AE-COPD and that the role of viral infection in these patients is still underestimated. Intensive Care Med Robert Cameron Virus Infection in exacerbations of COPD requiring ventilation Abstract Objectives We aimed to characterise and quantify the incidence of common infectious agents in acute exacerbations of chronic obstructive pulmonary disease (COPD) requiring ventilation, with a focus on respiratory viruses. Design An epidemiological study conducted over 3 years. Setting A 12-bed intensive care unit (ICU). Participants ICU patients over 45 years of age with a primary diagnosis of COPD exacerbation requiring non-invasive ventilation (NIV) or ventilation via endotracheal tube (ETT). Materials and methods Nasopharyngeal aspirates (NPA) and posterior pharyngeal swabs (PS) were tested for viruses with immunofluorescence assay (IFA), virus culture (VC) and polymerase chain reaction (PCR). Paired virus and atypical pneumonia serology assays were taken. Blood, sputum and endotracheal aspirates were cultured for bacteria. Results 107 episodes in 105 patients were recorded. Twenty-three (21%) died within 28 days. A probable infectious aetiology was found in 69 patient episodes (64%). A virus was identified in 46 cases (43%), being the sole organism in 35 cases (33%) and part of a mixed infection in 11 cases (10%). A probable bacterial aetiology was found in 25 cases (23%). There was no statistically significant difference in clinical characteristics or outcomes between the group with virus infections and that without. Conclusion Forty-six (43%) of the patients with COPD exacerbation requiring mechanical ventilation had a probable viral pathogen. Prodromal, clinical and outcome parameters did not distinguish virus from non-virus illness. PCR was the most sensitive whilst virus culture was the least of virus assays.

22 Exacerbação – Infecção - Antibióticos
a) Tosse  b) Dispnéia  c) Volume e Purulência do Esputo  Tipo I : todos os 3 sintomas Tipo II : 2 dos 3 sintomas Tipo III: qualquer um dos 3 sintomas Critérios clássicos de indicação do uso de antibióticos na DPOC Na época do trabalho o uso de Corticóide não era considerada importante, os tipos II e III se agravassem passavam a fazer parte do grupo I Os antibióticos usados eram de menor potencia e espectro São postos em dúvidas quando avaliados com o tratamento atual Anthonisen NR et al. Ann Intern Med 1987;106:

23 Diferenciação Bactéria e Vírus
Provável infecção bacteriana Provável infecção viral VEF1 <35% predito) Várias exacerbações ou hospitalização prévia DPOC Presença de doenças associadas Anthonisen tipo I Escarro purulento Crescimento de bactéria patogênica Nova cepa bacteriana na cultura Admissão hospitalar Admissão em UTI ou Ventilação mecânica Elevação da Proteína C Reativa Nível de procalcitonina(>0.25ng/ml) Persistência de sintomas de exacerbação Anthonisen tipo II e tipo III Escarro mucóide Cultura de escarro negativa Eosinofilia do escarro Exacerbação leve Nível baixo de Proteína C-reativa Nível de procalcitonina (<0.1 ng/ml) Current Opinion in Pulmonary Medicine :126–132

24 Antibióticos recomendados
Tratamento Oral Alternativas Oral Tratamento Parenteral Grupo A Pacientes com um único sinal cardinal não deve receber antibiótico Grupo B β-lactâmicos Inibidores da β-lactamase Fluoroquinolones (gemifloxacina, levofloxacina, moxifloxacina) β-lactam/β-lactamase inibidores (Co-amoxiclav, ampicillina/sulbactam) Cefalosporins (2nd or 3rd geração) Fluoroquinolonas (levofloxacina, moxifloxacina) Grupo C Em pacientes com risco para pseudomonas Fluoroquinolonas (ciprofloxacino, levofloxacino – dose alta) Fluoroquinolonas (ciprofloxacino, levofloxacino – dose alta or β-lactamico com atividade para P aeruginosa The GOLD guidelines provide recommendations for antimicrobial therapy in patients with acute exacerbations of COPD. The guidelines generally favor the use of β-lactams, but recent-generation fluoroquinolones are recommended for patients with suspected Pseudomonas aeruginosa infection. Reference From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from: Grupo A: Exacerbação leve Grupo B: Exacerbação moderada Grupo C: Exacerbação grave com fatores de risco para P aeruginosa GOLD 2008

25 Meta-análise de Eficácia – antibiótico e risco de mortalidade
Weight (%) 0.67 [0.56, 0.80] 0.33 [0.07, 1.52] 0.70 [0.45, 1.11] 0.32 [0.15, 0.68] 1.03 [0.75, 1.41] 0.40 [0.22, 0.74] 0.57 [0.41, 0.79] 10 0.1 0.2 0.5 2 5 1 Favorece Placebo Favorece Antibiotico Placebo Grupo n/N RR 95% CI Estudo Antibiotico Grupo n/N Total eventos: 113 (Antibiotico Grupo), 170 (Placebo Grupo) Test for heterogeneity dri-square = df = 5 p = F = 67.7% Test for overall effect z= p= Total (95% CI) Alonso 1992 Anthonisen 1987 Elmes 1965a Jorgenson 1992 Pines 1968 Pines 1972 351 2/29 19/57 6/29 49/132 6/15 31/89 354 28/59 19/29 49/136 15/15 53/86 100.0 3.5 16.2 11.2 28.4 8.8 31.8 RR 95% CI Speaker Notes Most patients with an exacerbation of COPD are treated with antibiotics. However the value of their use remains uncertain. This meta-analysis included results from 917 patients and assessed multiple outcomes including mortality. Antibiotic therapy regardless of antibiotic choice significantly reduced mortality (relative risk = 0.23), treatment failure (relative risk = 0.47), and sputum purulence (relative risk = 0.56). Reference Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;2:CD Ram FS, et al. Cochrane Database Syst Rev. 2006;CD004403

26 Conduta nas exacerbações: pontos fundamentais
A ventilação não-invasiva por pressão positiva intermitente (VNPPI) nas exacerbações agudas melhora os gases arteriais e o pH, reduz a mortalidade hospitalar, diminui a necessidade de intubação e ventilação mecânica invasiva e reduz a permanência hospitalar (Evidência A). GOLD

27 Meta-análise de eficácia: VNI
Risco de intubação redução de 65% Risco de mortalidade hospitalar redução de 55% Bolt et al, 1993 Desinkpoulou et al, 1993 Servillo et al, 1994 Brochard et al, 1995 Kramer et al, 1995 Angus et al, 1996 Cellical et al, 1998 Plant et al, 2000 Olkensoy et al, 2002 CRC et al, 2005 Dharnja et al, 2005 Keenan et al, 2005 Pooled summary (RR.036: 96% CL ) Pooled summary (RR.045: 95% CL ) 0.01 0.1 10 100 RR 0,35 (95% Confidence Interval) 1 Favorece NIV Favorece tratamento sem VNI RR 0,45 (95% Confidence Interval) Favorece VNI Systemic corticosteroids, antibiotics, and NIV are recommended for patients with acute exacerbation of COPD. However, their clinical benefits in various settings are uncertain. Results from this meta-analysis indicated that NIV reduced the risk of intubation by 65%, in-hospital mortality by 55%, and the length of hospitalisation by 1.9 days. Reference Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and meta-analysis. Chest. 2008;133: Chest, “Contemporary Management of Acute Exacerbations of COPD”, Quon BS et al, Vol 133, 2008

28 Mortalidade Exacerbação da DPOC
Characteristics and long-term outcome of acute exacerbations in chronic obstructive pulmonary disease: an analysis of cases in the Swedish Intensive Care Registry during 2002–2006 Internados em UTI=1009 Mortalidade 7,3% na UTI 26% 30 dias 69% 3 anos 14,5 meses sobrevida Readmissões 15,8% Acta Anaesthesiol Scand 2008; 52: 759–765Berkius Registro Nacional a Suécia Background: Chronic obstructive pulmonary disease (COPD) represents a major and growing health problem. The purpose of this work was to examine characteristics, resource use and long-term survival in patients with an acute exacerbation of COPD that were admitted to Swedish intensive care units (ICU). Methods: Patient characteristics at admission, length of stay (LOS), resource use and outcome were collected for admissions due to COPD during 2002–2006 in the database of the Swedish Intensive Care Registry. Vital status was secured for 99.6% of the patients. Kaplan–Meier survival estimates were computed for index admissions only. Results: We identified 1009 patients with 1199 admissions due to COPD (1.3% of all intensive care admissions). The mean (SD) age was 70.2 (9.1) years and the proportion of women were 61.5%. Mean (SD) Acute Physiology and Chronic Health Evaluation II probability of hospital death was 0.31 (0.19). Median LOS was 28 (interquartile range 52) h. The number of readmissions was 190 during the 5-year study. Older patients had fewer readmissions (OR 0.96, 95% CI: 0.95–0.98/year increase in age). ICU mortality was 7.3% (87 of 1199 admissions) and 30-day mortality was 26.0% (262 of 1009 index admissions). Median survival was 14.5 months and 31% of patients survived 3 years after the index admission. Conclusions: Short (30 days) and long-term survival is poor in acute COPD. Readmissions are frequent reflecting the severity of this chronic illness. Patients are less likely to be readmitted with increasing age which may be due to withholding of further intensive care Com 6 anos apenas 15% sobreviveram Crit Care Med 2006; 34:2317–2324) Berkius Acta Anaesthesiol Scand 2008; 52: 759–765

29 Mortalidade da DPOC após Exacerbação com atendimento em emergência
8% IAM This retrospective cohort study of emergency department patients who presented with an acute exacerbation indicated that mortality over time after the index event. Mortality was 5% at 30 days, 9% at 60 days, 11% at 90 days, 16% at 180 days, 23% at 1 year, 32% at 2 years, and 39% at 3 years. At the end of follow-up, 220 (46%) patients had died. On multivariate analysis, independent predictors of mortality were increasing age, having congestive heart failure, having a metastatic solid tumor, and hospital utilisation for COPD exacerbation during past year. Reference Kim S, Clark S, Camargo CA Jr. Mortality after an emergency department visit for exacerbation of chronic obstructive pulmonary disease. COPD. 2006;3:75-81. Arq.bras.cardiol 63(4):273-80, out. 1994 Kim S, et al. COPD. 2006;3:75-81.

30 Registro DESIRE do Hospital do Coração Pacientes: P > 6 Meses de Evolução Curva de Sobrevida Livre de Eventos Cardíacos Maiores* Dra.Amanda Sousa Brasília 180 360 540 720 900 1080 1260 1440 1620 1800 20 40 60 80 100 Sobrevida Livre de Eventos Maiores (%) Tempo após Procedimento Inicial (Dias) 91,4% Cum Survival * Eventos cardíacos Maiores = Óbito cardíaco, infarto do miocárdio e revascularização do vaso-alvo.

31 Conclusão Exacerbações são episódios graves para o DPOC Tratamento deve ser iniciado rápido e intensamente Oxigenoterapia deve ser realizada Broncodilatadores, corticóides e antibióticos devem ser utilizados Uso de BD de longa ação é útil CI em pacientes que não podem usar CS podem ser usados Uso de antibióticos ainda depende da avaliação clínica Purulência do escarro sugere infecção bacteriana Regras de diferenciação de gravidade podem ser úteis na escolha do local de tratamento A VNI modifica o risco de mortalidade

32 Líderes Nationais GOLD
Ireland Bangladesh Slovenia Brasil Saudi Arabia Australia Croatia Germany Taiwan ROC United States Thailand Portugal Austria Norway Malta Greece Moldova China Syria Canada South Africa United Kingdom Hong Kong ROC Yugoslavia Italy New Zealand Nepal Chile Israel Argentina Mexico Pakistan Russia United Arab Emirates Japan Peru Líderes Nationais GOLD Poland Korea Netherlands Egypt Switzerland India Venezuela Georgia France Macedonia Iceland Czech Republic Denmark Turkey Slovakia Belgium Singapore Spain Romania Columbia Ukraine Uruguay Sweden Kyrgyzstan Vietnam Albania