Attributable Mortality Of Ventilator-associated Pneumonia Research Articles

Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19.

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV+), and pandemic non-COVID-19 group (PandeCOV-) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV- group, and 1,687 in the PandeCOV+ group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV-, and PandeCOV+ groups, respectively. Except for the higher risk of developing VAP, the PandeCOV- group shared similar VAP characteristics with the control group. PandeCOV+ patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

Attributable Mortality of Ventilator-associated Pneumonia. Replicating Findings, Revisiting Methods

Rationale: Estimating the impact of ventilator-associated pneumonia (VAP) from routinely collected intensive care unit (ICU) data is methodologically challenging.Objectives: We aim to replicate earlier findings of limited VAP-attributable ICU mortality in an independent cohort. By refining statistical analyses, we gradually tackle different sources of bias.Methods: Records of 2,720 adult patients admitted to Ghent University Hospital ICUs (2013–2017) and receiving mechanical ventilation within 48 hours after admission were extracted from linked Intensive Care Information System and Computer-based Surveillance and Alerting of Nosocomial Infections, Antimicrobial Resistance, and Antibiotic Consumption in the ICU databases. The VAP-attributable fraction of ICU mortality was estimated using a competing risk analysis that is restricted to VAP-free patients (approach 1), accounts for VAP onset by treating it as either a competing (approach 2) or censoring event (approach 3), or additionally adjusts for time-dependent confounding via inverse probability weighting (approach 4).Results: A total of 210 patients (7.7%) acquired VAP. Based on benchmark approach 4, we estimated that (compared with current preventive measures) hypothetical eradication of VAP would lead to a relative ICU mortality reduction of 1.7% (95% confidence interval, −1.3 to 4.6) by Day 10 and of 3.6% (95% confidence interval, 0.7 to 6.5) by Day 60. Approaches 1–3 produced estimates ranging from −0.7% to 2.5% by Day 10 and from 5.2% to 5.5% by Day 60.Conclusions: In line with previous studies using appropriate methodology, we found limited VAP-attributable ICU mortality given current state-of-the-art VAP prevention measures. Our study illustrates that inappropriate accounting of the time dependency of exposure and confounding of its effects may misleadingly suggest protective effects of early-onset VAP and systematically overestimate attributable mortality.

The importance of oral hygiene for patients on mechanical ventilation.

The importance of oral hygiene for patients on mechanical ventilation.

Attributable mortality of ventilator-associated pneumonia – Authors' reply

We thank Anne-Cornélie de Pont for her comments. In our study1 we selected randomised controlled trials published between 1998 and 2010, reporting rates of both ventilator-associated pneumonia and mortality (during stay in an intensive-care unit [ICU]). This selection yielded six decontamination studies, which is indeed less than the 36 randomised trials included in a different meta-analysis.2 However, of the 36 studies, only six were published after 1998, of which no data were available for one3 and one had no data for ventilator-associated pneumonia.

Attributable mortality of ventilator-associated pneumonia

Wilhemina Melsen and colleagues estimated the attributable mortality of ventilator-associated pneumonia from individual patient data derived from randomised prevention studies. On the basis of the search terms “ventilator-associated pneumonia” and “randomisation” the investigators identifi ed 45 trials, of which 24 were included. They state that the included studies are reliable representatives of all studies of prevention of ventilator-associated pneumonia. However, the analysis included only six decontamination studies. This point is remarkable, because a meta-analysis of 36 randomised trials concluded that treatment with a combination of topical and systemic antibiotics reduces the incidence of respiratory tract infections from 40% to 19%, and overall mortality from 30% to 24%, with four patients needed-totreat to prevent one infection, and 18 to prevent one death. From these data suggesting that a 53% reduction in respiratory tract infections leads to a 6% reduction in mortality, the attributable mortality of respiratory infections is 11%, which is similar to the 13% calculated by Melsen and colleagues. Furthermore, Melsen and colleagues state that mortality after ventilator-associated pneumonia is mainly caused by prolonged exposure to risk of death due to increased length of stay in an intensive-care unit (ICU). However, this assumption contradicts previous fi ndings. In a case-control study, Klompas and colleagues elegantly showed that ventilator-associated pneumonia signifi cantly prolonged both median duration of mechanical ventilation and median length of stay in an ICU by 6 days. However, hospital mortality did not diff er signifi cantly. Indeed, mortality is not proportional to length of ICU stay—severely ill patients dying early during their ICU admission have a shorter length of stay than do those recovering after prolonged mechanical ventilation. In a retrospective analysis of 543 mechanically ventilated patients, Hayashi and colleagues also reported signifi cantly prolonged mechanical ventilation and length of stay in an ICU without an increase in mortality in patients with ventilatorassociated complications; however, they did note that patients with ventilator-associated complications more often had chronic obstructive pulmonary disease and acute kidney injury than did those with no complications. In patients with ventilator-associated pneumonia, underlying illness and complicating organ failure could have a greater eff ect on mortality than does length of ICU stay.

Ventilatorassoziierte Pneumonie

Ventilator-associated pneumonia (VAP) is a severe, not entirely preventable complication of invasive ventilation. Timely and adequate antibiotic treatment is important; therefore, intensivists often initiate broad spectrum antibiotic regimens upon clinical suspicion of VAP. Criteria for the diagnosis of VAP are not perfect and a clear distinction of VAP from ventilator-associated tracheobronchitis is not always possible due to the limitations of chest x-rays in ventilated patients. The attributable mortality of VAP is likely overestimated. All these aspects increase the need to reevaluate the diagnosis of VAP on a daily basis. Microbiology data are helpful in the decision to de-escalate or stop antibiotics. The prudent use of antibiotics and implementation of a number of preventive measures are key for management of VAP in ICUs. These steps will help to minimize the development of multidrug-resistant pathogens and, in turn, may help guarantee more antibiotic options for future patients.

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies

Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. None.

Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies*

To assess the attributable mortality of ventilator-associated pneumonia using results from randomized controlled trials on ventilator-associated pneumonia prevention. A systematic search was performed in PubMed, Embase, Web of Science, and Cochrane Library from their inception until July 2010. In addition, a reference and related article search was performed. Randomized ventilator-associated pneumonia prevention studies in which all patients were mechanically ventilated and from which ventilator-associated pneumonia and mortality rates of intervention and control group could be extracted were included. Fifty-three papers were identified describing 58 comparisons. Statistical significant reductions in ventilator-associated pneumonia incidences were reported in 20 of the 58 comparisons, whereas none of these trials reported a significant reduction of mortality. Pooled estimates of the relative risk reductions of both ventilator-associated pneumonia and mortality were calculated and the attributable mortality was estimated as the ratio between the relative risk reductions of mortality and ventilator-associated pneumonia. Effects of study quality, diagnostic methods used, and effectiveness of preventing ventilator-associated pneumonia on the mortality rate of ventilator-associated pneumonia were assessed in subgroup analyses. The overall attributable mortality of ventilator-associated pneumonia was estimated as 9%. In subgroup analyses, the attributable mortality varied between 3% and 17%. Based on the results of 58 randomized studies on ventilator-associated pneumonia prevention, the attributable mortality rate of ventilator-associated pneumonia was estimated to be 9% and ranged between 3% and 17% in subgroup analyses. Together with the results of other recent studies, there is cumulative evidence that the attributable mortality resulting from ventilator-associated pneumonia is approximately 10%.

Attributable Mortality of Ventilator-Associated Pneumonia

Measuring the attributable mortality of ventilator-associated pneumonia (VAP) is challenging and prone to different forms of bias. Studies addressing this issue have produced variable and controversial results. We estimate the attributable mortality of VAP in a large multicenter cohort using statistical methods from the field of causal inference. Patients (n = 4,479) from the longitudinal prospective (1997-2008) French multicenter Outcomerea database were included if they stayed in the intensive care unit (ICU) for at least 2 days and received mechanical ventilation (MV) within 48 hours after ICU admission. A competing risk survival analysis, treating ICU discharge as a competing risk for ICU mortality, was conducted using a marginal structural modeling approach to adjust for time-varying confounding by disease severity. Six hundred eighty-five (15.3%) patients acquired at least one episode of VAP. We estimated that 4.4% (95% confidence interval, 1.6-7.0%) of the deaths in the ICU on Day 30 and 5.9% (95% confidence interval, 2.5-9.1%) on Day 60 are attributable to VAP. With an observed ICU mortality of 23.3% on Day 30 and 25.6% on Day 60, this corresponds to an ICU mortality attributable to VAP of about 1% on Day 30 and 1.5% on Day 60. Our study on the attributable mortality of VAP is the first that simultaneously accounts for the time of acquiring VAP, informative loss to follow-up after ICU discharge, and the existence of complex feedback relations between VAP and the evolution of disease severity. In contrast to the majority of previous reports, we detected a relatively limited attributable ICU mortality of VAP.

Attributable mortality of ventilator-associated pneumonia

To critically discuss the attributable mortality of ventilator-associated pneumonia (VAP) and potential sources of variation. The review will cover the available estimates (0-50%). It will also explore the source of variation because of definition of VAP (being lower if inaccurate), case-mix issues (being lower for trauma patients), the severity of underlying illnesses (being maximal when the severity of underlying illness is intermediate), and on the characteristics and the severity of the VAP episode. Another important source of variation is the use of poorly appropriate statistical models (estimates biased by lead time bias and competing events). New extensions of survival models which take into account the time dependence of VAP occurrence and competing risks allow less biased estimation as compared with traditional models. Attributable mortality of VAP is about 6%. Accurate diagnostic methods are key to properly estimating it. Traditional statistical models should no longer be used to estimate it. Prevention efforts targeted on patients with intermediate severity may result in the most important outcome benefits.

Attributable mortality of ventilator-associated pneumonia: respective impact of main characteristics at ICU admission and VAP onset using conditional logistic regression and multi-state models

Methods for estimating the excess mortality attributable to ventilator-associated pneumonia (VAP) should handle VAP as a time-dependent covariate, since the probability of experiencing VAP increases with the time on mechanical ventilation. VAP-attributable mortality (VAP-AM) varies with definitions, case-mix, causative microorganisms, and treatment adequacy. Our objectives here were to compare VAP-AM estimates obtained using a traditional cohort analysis, a multistate progressive disability model, and a matched-cohort analysis; and to compare VAP-AM estimates according to VAP characteristics. We used data from 2,873 mechanically ventilated patients in the Outcomerea database. Among these patients from 12 intensive care units, 434 (15.1%) experienced VAP; of the remaining patients, 1,969 (68.5%) were discharged alive and 470 (16.4%) died. With the multistate model, VAP-AM was 8.1% (95% confidence interval [95%CI], 3.1-13.1%) for 120 days' complete observation, compared to 10.4% (5.6-24.5%) using a matched-cohort approach (2,769 patients) with matching on mechanical ventilation duration followed by conditional logistic regression. VAP-AM was higher in surgical patients and patients with intermediate (but not high) Simplified Acute Physiologic Score II values at ICU admission. VAP-AM was significantly influenced by time to VAP but not by resistance of causative microorganisms. Higher Logistic Organ Dysfunction score at VAP onset dramatically increased VAP-AM (to 31.9% in patients with scores above 7). A multistate model that appropriately handled VAP as a time-dependent event produced lower VAP-AM values than conditional logistic regression. VAP-AM varied widely with case-mix. Disease severity at VAP onset markedly influenced VAP-AM; this may contribute to the variability of previous estimates.

Ventilator-associated pneumonia and mortality: A systematic review of observational studies*

To determine the attributable mortality of ventilator-associated pneumonia in a systematic review and meta-analysis of observational studies. Ventilator-associated pneumonia is generally believed to increase the mortality of patients. This notion is predominantly based on the results of observational studies. We performed a systematic search strategy using PubMed, Web of Science, and Embase from their inception through February 2007. In addition, a reference and related article search was performed. Studies were included if they reported mortality rates of patients with and without ventilator-associated pneumonia. Fifty-two studies with a total of 17,347 patients met the inclusion criteria. Pooling of all studies resulted in relative risk of 1.27 (95% Confidence Interval = 1.15-1.39), but heterogeneity was considerable (I2 statistic = 69%). The origin of heterogeneity could not be explained by differences in study design, study quality, and diagnostic approach. However, heterogeneity was limited for studies investigating only trauma patients (I2 = 1.3%) or patients with acute respiratory distress syndrome (I2 = 0%), with estimated relative risk of 1.09 (95% Confidence Interval = 0.87-1.37) among trauma patients and 0.86 (95% Confidence Interval = 0.72-1.04) among patients with acute respiratory distress syndrome. There is no evidence of attributable mortality due to ventilator-associated pneumonia in patients with trauma or acute respiratory distress syndrome. However, in other nonspecified patient groups, there is evidence for attributable mortality due to ventilator-associated pneumonia, but this could not be quantified due to heterogeneity in study results. More detailed studies, allowing subgroup analyses, are needed to determine the attributable mortality of ventilator-associated pneumonia in these patient populations.

The impact of ventilator-associated pneumonia on the Canadian health care system

Introduction Ventilator-associated pneumonia (VAP) is a cause of morbidity and mortality in critically ill patients. It is associated with increased health care costs and duration of mechanical ventilation. Using published data and information from public health care providers, we sought to determine the impact of VAP on the Canadian health care system. Methods Ventilator-associated pneumonia incidence, attributable mortality, and intensive care unit (ICU) utilization/resource data were obtained through Canadian published and institutional data. Ontario case cost methodology was used for the cost of a critical care bed which is CAN$2396 per day, excluding treatment costs. Antibiotic acquisition costs for Ontario were used. Physician reimbursement rates were obtained from the provincial ministries of health. Ventilator-associated pneumonia data, ICU resource data, and costs were combined to determine the impact of VAP. Results For the Canadian health care system; ICU utilization is 217 episodes per 100 000 population and 1150 days of mechanical ventilation per 100 000. The incidence of VAP is 10.6 cases per 1000 ventilator days (95% CI, 5.1-16.1). Ventilator-associated pneumonia increases ICU length of stay 4.3 days (95% CI, 1.5-7.0 days) per episode. The attributable mortality of VAP is 5.8% (95% CI, −2.4 to 14). The number of cases of VAP is estimated to be approximately 4000 cases per year (95% CI, 1900-6100). This results in 230 deaths per year with the lower and upper confidence intervals ranging from 0 to 580. Ventilator-associated pneumonia accounts for approximately 17 000 ICU days per year or around 2% of all ICU days in Canada. The cost to the health care system is CAN$46 million (possible range, $10 million to 82 million) per year. Conclusion The impact of VAP on the Canadian health care system is considerable. Eradication of this preventable nosocomial infection would save lives and conserve scarce health care resources.

Treatment Failure in Patients with Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is one of the most important infectious diseases in the intensive care unit (ICU). In some series the attributable mortality of VAP may reach 30%, and the adequacy of the initial empirical treatment greatly influences the prognosis. Treatment failure can be anticipated in approximately 30 to 40% of patients developing pneumonia during mechanical ventilation and this situation is associated with an adverse outcome in terms of morbidity. For these reasons, the lack of response to empirical antibiotic treatment should be recognized early in the course of VAP, and a clear strategy for clarifying the causes of failure should be implemented. Resolution of VAP depends not only on the accuracy of microbial diagnosis but also on comorbidities, the response of the host to the infection, concomitant infections, and the correct clinical diagnosis. Treatment failure can be defined by the pattern of resolution of VAP, which is clearly established in the literature.