Sean P. Keenan

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease - 2007 update

Chronic obstructive pulmonary disease (COPD) is a major respiratory illness in Canada that is both preventable and treatable. Our understanding of the pathophysiology of this complex condition continues to grow and our ability to offer effective treatment to those who suffer from it has improved considerably. The purpose of the present educational initiative of the Canadian Thoracic Society (CTS) is to provide up to date information on new developments in the field so that patients with this condition will receive optimal care that is firmly based on scientific evidence. Since the previous CTS management recommendations were published in 2003, a wealth of new scientific information has become available. The implications of this new knowledge with respect to optimal clinical care have been carefully considered by the CTS Panel and the conclusions are presented in the current document. Highlights of this update include new epidemiological information on mortality and prevalence of COPD, which charts its emergence as a major health problem for women; a new section on common comorbidities in COPD; an increased emphasis on the meaningful benefits of combined pharmacological and nonpharmacological therapies; and a new discussion on the prevention of acute exacerbations. A revised stratification system for severity of airway obstruction is proposed, together with other suggestions on how best to clinically evaluate individual patients with this complex disease. The results of the largest randomized clinical trial ever undertaken in COPD have recently been published, enabling the Panel to make evidence-based recommendations on the role of modern pharmacotherapy. The Panel hopes that these new practice guidelines, which reflect a rigorous analysis of the recent literature, will assist caregivers in the diagnosis and management of this common condition.

Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia.

Critically ill patients in the intensive care unit (ICU) are at high risk for infections associated with increased morbidity, mortality, and health care costs (1-3). The overall infection rate in critically ill patients approaches 40% and may be as high as 50% or 60% in patients who remain in the ICU for more than 5 days (4, 5). Respiratory tract infections account for 30% to 60% of all such infections. The incidence of pneumonia acquired in the ICU ranges from 10% to 65% (6-11). Among patients at high risk for ventilator-associated pneumonia (VAP) are those who have chronic obstructive pulmonary disease, burns, neurosurgical conditions, the acute respiratory distress syndrome, and witnessed aspiration; those who are reintubated; and those who receive paralytic agents or enteral nutrition (12, 13). The attributable morbidity and mortality of VAP are clinically important. In a prospective, matched cohort study, patients with VAP remained in the ICU 4.3 days (95% CI, 1.5 to 7.0 days) longer than patients who did not have VAP and had a trend toward an increased risk for death (absolute risk increase, 5.8% [CI, 2.4% to 14.0%]) (14). Six other studies using a matching strategy found a prolonged length of ICU stay associated with VAP (range, 5 to 13 days) and attributable mortality ranging from an absolute risk increase of 0% to 50% (15-20). Therefore, strategies to decrease the incidence of VAP could decrease morbidity, mortality, and health care costs and improve patient safety. A survey of the use of VAP prevention strategies identified differences across countries (21). For example, changing the ventilator circuit for each new patient was reported more frequently by French ICU directors than those in Canada (21). This survey also showed that some effective strategies were used infrequently, suggesting inadequate translation of randomized trial results into practice. One potential catalyst for knowledge translation is an evidence-based clinical practice guideline. Therefore, a Joint Planning Group of the Canadian Critical Care Society and Canadian Critical Care Trials Group commissioned the development of an evidence-based clinical practice guideline for the prevention of VAP. In this paper, we describe the methods used to create the guideline and the recommendations generated. Methods The Joint Planning Group selected an 11-member VAP Prevention Guideline Panel made up of 9 intensivists from university-affiliated and community hospitals, an ICU nurse, and an ICU respiratory therapist. Panel members were experts in critical care medicine (n= 9), VAP (n= 4), evidence-based medicine (n= 4), and guideline development (n= 3). The context was mechanically ventilated adult patients cared for in the ICU. The target audience was ICU clinicians in university-affiliated and community hospitals. To identify potentially relevant evidence, we searched 3 bibliographic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) to 1 April 2003 for randomized trials that evaluated interventions influencing VAP (Appendix). We had no language restrictions. We also reviewed personal files and practice guidelines on this subject previously published by the Centers for Disease Control and Prevention (22) and the American Thoracic Society (23). We included randomized trials and systematic reviews of randomized trials that 1) studied adult critically ill patients; 2) had VAP as an outcome; and 3) evaluated any of the following interventions: physical strategies (route of endotracheal intubation, systematic search for maxillary sinusitis, frequency of ventilator circuit changes, type of airway humidification, frequency of humidifier changes, endotracheal suctioning system, subglottic secretion drainage, chest physiotherapy, and tracheostomy timing), positional strategies (kinetic beds, semi-recumbent positioning, and prone positioning), and pharmacologic strategies (stress ulcer prophylaxis and prophylactic antibiotics, including selective decontamination of the digestive tract). Since study authors used various definitions of VAP, we used the definitions they provided. The most common definition was a new or persistent radiographic infiltrate plus fever, leukocytosis, change in the volume or color of sputum, or isolation of a pathogen. If available, histologic evidence of pneumonia was also used. A priori, we decided to review only systematic reviews of randomized clinical trials for antibiotic prophylaxis and only randomized clinical trials for all other topics. We excluded crossover and beforeafter studies. We also excluded randomized trials of ventilator weaning, including noninvasive mechanical ventilation, and nutritional interventions evaluating VAP because guidelines addressing these topics have recently been published (24, 25). In duplicate and independently, 3 pairs of panel members critically appraised each trial (26, 27) and systematic review (28). Each member of a pair compared his or her independent appraisal of a given trial or systematic review with that of the other member of the pair. For each randomized trial, we abstracted sample, allocation, intervention, co-interventions, exclusions after randomization, blinding of outcome assessment, definition of VAP, crude VAP events, relative risk for VAP, and other outcomes. For each intervention, we summarized the risk differences and calculated a pooled risk difference. For each systematic review, we abstracted number of trials, population, intervention, selection criteria, search strategy, validity assessment, method of pooling results, homogeneity assessment, VAP definition, pooled event rates, and other outcomes. Before the panel meeting, each pair of appraisers achieved consensus on the validity and results of the trials they reviewed. One month before the panel meeting, panel members received the evidence tables for review prepared by the 3 pairs of appraisers. A priori, panel members agreed to read all circulated documents and evidence tables in advance, to use levels of evidence to generate a status statement for each item, and to abide by the group process and consensus methods. The Canadian Critical Care Society appointed a chair to ensure that the panel achieved its objectives through group process (29). At the panel meeting, each member recorded any potential conflicts of interest (30). The pair of panel members responsible for critical appraisal of each intervention provided a structured written and oral presentation of the evidence. After the panel discussion, the initial evidence summary was revised if necessary. The panel members assigned levels of evidence, semi-quantitative scores to summarize the evidence and describe the intervention, and a status statement. We classified trials as level 1 if they had all of the following: concealed randomization, blinded outcome adjudication, an intention-to-treat analysis, and an explicit definition of VAP. Trials were classified as level 2 if any one of these characteristics was unfulfilled and as level 3 if allocation was not strictly randomized. We used a semi-quantitative score (0, 1, 2, or 3) to evaluate each intervention with respect to the validity of the randomized trials; the effect size of each intervention; the confidence intervals around the estimate of effect; the homogeneity of the trial results; and the safety, feasibility, and economic consequences of the intervention. The language of the status statement for each item was keyed to the levels of evidence and the semi-quantitative scores. We used the term recommended if there were no reservations about endorsing an intervention and the term considered if the evidence supported an intervention but there were minor uncertainties about the benefits, harms, or costs. No recommendation was made if evidence regarding an intervention was inadequate or if there were major uncertainties about the benefits, harms, or costs. After the panel meeting, the chair compiled the summaries and status statements and sent them to all panel members to check accuracy and clarity. In addition, the pairs of evidence appraisers wrote background documents for the interventions they appraised, including the rationale for each intervention, appraisal of randomized trials and systematic reviews, and harms and costs of the interventions. The chair and the writing committee organized the background documents, the evidence summaries, a table of the semi-quantitative scores, and the status statement for each item. We formatted the document with a structured abstract (31), a summary of the evidentiary basis for each recommendation, and a status statement for each item. We also created a quick reference guide. The draft guideline document was submitted for structured external review by the executives of the Canadian Critical Care Society and the Canadian Critical Care Trials Group and the respective executives of the Canadian Association of Critical Care Nurses, Canadian Society of Respiratory Therapists, Canadian Infectious Disease Society, and Canadian Thoracic Society. External reviewers were asked to critique whether the guideline was logical, clear, and practical and to critique the guideline development process. The panel revised the document on the basis of this feedback. The final guideline was returned to the external reviewers for further comments and official endorsement by their respective organizations. The final guideline was then piloted in 2 institutions. To record the agreement of each panel member with the final status statement for each item, we sent the final document to all panel members. Independently, blinded to each others ratings, panel members used a Likert scale from 1 to 9 that was anchored by disagree completely at the low end and agree completely at the high end. The panel will formally review and update this guideline every 2 years (32). The funding source played no role in study selection for this guideline and had no role in its development

Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure : A meta-analysis

OBJECTIVE To critically appraise and summarize the trials examining the addition of noninvasive positive pressure ventilation to standard therapy on hospital mortality and need for endotracheal intubation in patients admitted with acute respiratory failure. DATA SOURCES We searched MEDLINE (1966 to September 1995) and key references were searched forward using the Scientific Citation Index (SCISEARCH). Bibliographies of all selected articles and review articles were examined. Authors of all selected and review articles were contacted by letter to identify unpublished work. STUDY SELECTION a) POPULATION patients with acute respiratory failure; b) intervention: noninvasive positive pressure ventilation; c) outcome: mortality and/or endotracheal intubation; and d) design: randomized, controlled study. Two of us independently selected the articles for inclusion; disagreements were settled by consensus. Seven (three unpublished) of 212 initially identified studies were selected. DATA EXTRACTION Two authors independently extracted data and evaluated methodologic quality of the studies. DATA SYNTHESIS Noninvasive positive pressure ventilation was associated with decreased mortality (odds ratio = 0.29; 95% confidence interval 0.15 to 0.59) and a decreased need for endotracheal intubation (odds ratio = 0.20; 95% confidence interval 0.11 to 0.36). Sensitivity analysis suggested a greater benefit of noninvasive positive pressure ventilation in patients with chronic obstructive pulmonary disease (COPD). The inclusion/exclusion of unpublished trials did not influence these results. CONCLUSIONS The addition of noninvasive positive pressure ventilation to standard therapy in patients with acute respiratory failure improves survival and decreases the need for endotracheal intubation. However, this effect is restricted to patients whose cause of acute respiratory failure is an exacerbation of COPD. Further research is warranted to determine whether noninvasive positive pressure ventilation confers benefit in patients without COPD who have acute respiratory failure.

Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.

Background:Septic shock represents the major cause of infection-associated mortality in the intensive care unit. The possibility that combination antibiotic therapy of bacterial septic shock improves outcome is controversial. Current guidelines do not recommend combination therapy except for the express purpose of broadening coverage when resistant pathogens are a concern. Objective:To evaluate the therapeutic benefit of early combination therapy comprising at least two antibiotics of different mechanisms with in vitro activity for the isolated pathogen in patients with bacterial septic shock. Design:Retrospective, propensity matched, multicenter, cohort study. Setting:Intensive care units of 28 academic and community hospitals in three countries between 1996 and 2007. Subjects:A total of 4662 eligible cases of culture-positive, bacterial septic shock treated with combination or monotherapy from which 1223 propensity-matched pairs were generated. Measurements and Main Results:The primary outcome of study was 28-day mortality. Using a Cox proportional hazards model, combination therapy was associated with decreased 28-day mortality (444 of 1223 [36.3%] vs. 355 of 1223 [29.0%]; hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; p = .0002). The beneficial impact of combination therapy applied to both Gram-positive and Gram-negative infections but was restricted to patients treated with &bgr;-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin. Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days. Conclusion:Early combination antibiotic therapy is associated with decreased mortality in septic shock. Prospective randomized trials are needed.

Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia : Prevention

BACKGROUND Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in ventilated critically ill patients. PURPOSE To develop evidence-based guidelines for the prevention of VAP. DATA SOURCES MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews and Register of Controlled Trials. STUDY SELECTION The authors systematically searched for all relevant randomized, controlled trials and systematic reviews on the topic of prevention of VAP in adults that were published from 1980 to October 1, 2006. DATA EXTRACTION Independently and in duplicate, the panel scored the internal validity of each trial. Effect size, confidence intervals, and homogeneity of the results were scored using predefined definitions. Scores for the safety, feasibility, and economic issues were assigned based on consensus of the guideline panel. LEVELS OF EVIDENCE The following statements were used: recommend, consider, do not recommend, and no recommendation due to insufficient or conflicting evidence. DATA SYNTHESIS To prevent VAP: We recommend: that the orotracheal route of intubation should be used for intubation; a new ventilator circuit for each patient; circuit changes if the circuit becomes soiled or damaged, but no scheduled changes; change of heat and moisture exchangers every 5 to 7 days or as clinically indicated; the use of a closed endotracheal suctioning system changed for each patient and as clinically indicated; subglottic secretion drainage in patients expected to be mechanically ventilated for more than 72 hours; head of bed elevation to 45 degrees (when impossible, as near to 45 degrees as possible should be considered). Consider: the use of rotating beds; oral antiseptic rinses. We do not recommend: use of bacterial filters; the use of iseganan We make no recommendations regarding: the use of a systematic search for sinusitis; type of airway humidification; timing of tracheostomy; prone positioning; aerosolized antibiotics; intranasal mupirocin; topical and/or intravenous antibiotics. CONCLUSION There are a growing number of evidence-based strategies for VAP prevention, which, if applied in practice, may reduce the incidence of this serious nosocomial infection.

A retrospective review of a large cohort of patients undergoing the process of withholding or withdrawal of life support

OBJECTIVES To determine the proportion of patients who died as a result of the withdrawal or withholding of life support (WD/WHLS) in the intensive care units (ICUs) of three teaching hospitals and to describe the process involved by determining: a) why the decision was made to withdraw support (WDLS); b) when WDLS took place; and c) how the WDLS process was conducted. DESIGN Retrospective cohort study. SETTING Three university-affiliated ICUs. PATIENTS Four hundred nineteen patients who died in one of three academic, tertiary care ICUs over a 1-yr period. INTERVENTIONS Retrospective chart review. Data collected included age, gender, admitting diagnoses, comorbid disease, Acute Physiology and Chronic Health Evaluation II score, and mode of death (brain death, death due to withholding of life support, death due to WDLS, or death despite ongoing therapy). For those patients dying due to WDLS, the reason for WDLS, person initiating discussion, timing of WDLS, degree of organ dysfunction, order of withdrawal of life support modalities, and the use of sedatives and analgesics were recorded. MEASUREMENTS AND MAIN RESULTS Seventy percent of patients died by WD/WHLS and 8.4% were brain dead. Patients undergoing WD/WHLS were older and had a longer length of stay than patients dying from other causes. Poor prognosis was the most common reason given for WDLS, reflected by significant organ dysfunction at the time of WDLS. Future quality of life was a less frequently cited reason. Most patients undergoing WDLS did so early in their ICU stay, although time to WDLS appeared to reflect diagnostic group. Few meetings occurred before WDLS and death occurred soon after initiating WDLS. There was a preference of withdrawing mechanical ventilation last and large amounts of morphine (mean 21 +/- 33 [SD] mg/hr) and benzodiazepines (mean 8.6 +/- 11 mg/hr) were used. Little variability in practice was apparent among the studied ICUs. CONCLUSIONS Similar to other studies, WD/WHLS was the most common cause of death in academic ICUs and poor patient prognosis was considered the most important factor in deciding on WDLS. However, in contrast to other studies, future quality of life was not as frequently cited a reason for WDLS and larger amounts of morphine were used during WDLS. These discrepancies suggest areas for potential future research.

Does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review.

Context:The results of studies on noninvasive positive pressure ventilation (NPPV) for acute hypoxemic respiratory failure unrelated to cardiogenic pulmonary edema have been inconsistent. Objective:To assess the effect of NPPV on the rate of endotracheal intubation, intensive care unit and hospital length of stay, and mortality for patients with acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema. Data Source:We searched the databases of MEDLINE (1980 to October 2003) and EMBASE (1990 to October 2003). Additional data sources included the Cochrane Library, personal files, abstract proceedings, reference lists of selected articles, and expert contact. Study Selection:We included studies if a) the design was a randomized controlled trial; b) patients had acute hypoxemic respiratory failure not due to cardiogenic pulmonary edema; c) the interventions compared noninvasive ventilation and standard therapy with standard therapy alone; and d) outcomes included need for endotracheal intubation, length of intensive care unit or hospital stay, or intensive care unit or hospital survival. Data Extraction:In duplicate and independently, we abstracted data to evaluate methodological quality and results. Data Synthesis:The addition of NPPV to standard care in the setting of acute hypoxemic respiratory failure reduced the rate of endotracheal intubation (absolute risk reduction 23%, 95% confidence interval 10–35%), ICU length of stay (absolute reduction 2 days, 95% confidence interval 1–3 days), and ICU mortality (absolute risk reduction 17%, 95% confidence interval 8–26%). However, trial results were significantly heterogeneous. Conclusion:Randomized trials suggest that patients with acute hypoxemic respiratory failure are less likely to require endotracheal intubation when NPPV is added to standard therapy. However, the effect on mortality is less clear, and the heterogeneity found among studies suggests that effectiveness varies among different populations. As a result, the literature does not support the routine use of NPPV in all patients with acute hypoxemic respiratory failure.

Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting

Over the past two decades, the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure by mask has increased substantially for acutely ill patients. Initial case series and uncontrolled cohort studies that suggested benefit in selected patients[1][1]–[

Patients readmitted to the intensive care unit during the same hospitalization: Clinical features and outcomes

OBJECTIVE To determine the clinical features and outcomes of patients readmitted to the intensive care unit (ICU) during the same hospital stay and the causes for these readmissions. DESIGN Multicenter, cohort study. SETTING Three ICUs from two teaching hospitals and four ICUs from four community hospitals. PATIENTS All ICU admissions were collected prospectively for a registry database in the seven ICUs. We retrospectively analyzed ICU admissions between January 1, 1995 and February 29, 1996. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS During the study period, 236 (4.6%) of the patients discharged alive from the ICU were readmitted to the unit. Patients with gastrointestinal (GI) and neurologic diagnoses had the highest readmission rate. Of the readmissions, 45% had recurrence of the initial disease, 39% experienced new complications, and 14% required further planned operation. Among patients readmitted for the same illness, cardiovascular and respiratory problems were the most frequent diagnoses. Of patients readmitted with a new diagnosis, 30% initially had GI diseases, while respiratory diseases accounted for 58% of the new complications. Readmissions within 24 hrs occurred in 27% of all readmissions. Patients requiring readmission had a higher hospital mortality rate (31.4%) compared with those not requiring readmission (4.3%, p < .001), even after adjustment for disease severity score (odds ratio = 5.93, p < .001). CONCLUSIONS Patients with GI and neurologic diseases are at greatest risk of requiring ICU readmission. Respiratory diseases are the major reason for readmission due to new complications. Readmitted patients have a high risk of hospital death that may be underestimated by the usual physiologic indicators on either initial admission or readmission. Further studies are required to determine if patients at risk for readmission can be identified early to improve the outcome.

Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy.

Objective:Although noninvasive positive pressure ventilation (NPPV) is a widely accepted treatment for some patients with acute respiratory failure, the use of NPPV in patients who have decided to forego endotracheal intubation is controversial. Therefore, the Society of Critical Care Medicine charged this Task Force with developing an approach for considering use of NPPV for patients who choose to forego endotracheal intubation. Data Sources and Methods:The Task Force met in person once, by conference call twice, and wrote this document during six subsequent months. We reviewed English-language literature on NPPV for acute respiratory failure. Synthesis and Overview:The use of NPPV for patients with acute respiratory failure can be classified into three categories: 1) NPPV as life support with no preset limitations on life-sustaining treatments, 2) NPPV as life support when patients and families have decided to forego endotracheal intubation, and 3) NPPV as a palliative measure when patients and families have chosen to forego all life support, receiving comfort measures only. For each category, we reviewed the rationale and evidence for NPPV, key points to communicate to patients and families, determinants of success and failure, appropriate healthcare settings, and alternative approaches if NPPV fails to achieve the original goals. Conclusions:This Task Force suggests an approach to use of NPPV for patients and families who choose to forego endotracheal intubation. NPPV should be applied after careful discussion of the goals of care, with explicit parameters for success and failure, by experienced personnel, and in appropriate healthcare settings. Future studies are needed to evaluate the clinical outcomes of using NPPV for patients who choose to forego endotracheal intubation and to examine the perspectives of patients, families, and clinicians on use of NPPV in these contexts.