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Beyond Pneumonia

Beyond Pneumonia

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Published by: Prof Dr Dr Ernst Hanisch on Jul 28, 2013
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Beyond pneumonia: improving care for ventilated patients
In the ongoing quest to improve care for ventilated patients, a thorough understanding of the potential hazards faced by this population is indispensible. Merely knowing which harms might befall these patients is not sufficient. Understanding their relative frequencies and severities is crucial to inform complete and cost effective prevention strategies. Accurately measuring the frequency and severity of harms, however, is surprisingly complicated. Estimating frequency is hindered by the subjectivity and limited accuracy of definitions for conditions such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and thromboembolic disease. Estimating attributable morbidity and mortality is hindered by the difficulty disentangling the independent contributions of the complication of interest, patients’ underlying illnesses, time spent in hospital and on mechanical ventilation before developing the complication, and concurrent additional hazards of critical care. Investigators have developed several sophisticated statistical strategies to adjust for these potential confounders. These include matching protocols, multistate models, and marginal structural models.1–5 In The Lancet Infectious Diseases, however, Wilhelmina Melsen and colleagues present an innovative and clinically intuitive method6 that takes advantage of data from randomised controlled trials to estimate the attributable mortality of ventilator-associated pneumonia and to tease apart the relative contributions of pneumonia versus prolonged intensive care to mortality risk. Melsen and colleagues6 estimated mortality associated with ventilator-associated pneumonia by assessing the extent to which prevention measures can lower ventilator-associated pneumonia rates and intensive care unit (ICU) mortality rates. They pooled together data from 6284 individuals enrolled in 24 randomised trials of different ventilatorassociated pneumonia prevention interventions. The pooled interventions lowered ventilator-associated pneumonia rates by 30% overall (95% CI 21–38) and ICU mortality by 4% (–6 to 12). They therefore estimated that if one were theoretically able to eliminate 100% of ventilator-associated pneumonias that ICU mortality would decrease by 13% (4% multiplied by 100% divided by 30%). This finding implies that only 13% of the mortality risk in ICU patients is due to ventilator-associated pneumonia. Although this low figure probably reflects the beneficial impacts of antibiotic therapy, it is nonetheless sobering and alerts us that we need to look beyond pneumonia prevention alone to make further substantive effects on ICU mortality. Melsen and colleagues1 also completed a competing risks analysis that sheds light on the relative contribution of ventilator-associated pneumonia itself versus general complications of intensive care on patients’ prognoses. The competing risks analysis enabled the authors to estimate the impacts of ventilatorassociated pneumonia on intensive care length of stay and mortality both independently and in combination. They showed that ventilator-associated pneumonia decreased the daily probability of discharge from the ICU by 26% (95% CI 20–32), indicating that the disorder extends length of stay in the ICU. The ventilatorassociated pneumonia cause-specific hazard ratio (HR) of dying in the ICU was 1·13 (95% CI 0·98–1·31) but combining the effect of prolonged length of stay with the ventilator-associated pneumonia cause-specific mortality increased the estimated mortality HR to 2·20 (1·91–2·54). This implies that most of the mortality noted in patients with ventilator-associated pneumonia is due to extra time spent in the ICU rather than directly due to the condition itself. This observation carries important lessons for prevention. We learn that extended time spent in the ICU is hazardous in patients with and without ventilator-associated pneumonia and that interventions that can decrease length of stay are probably potent strategies to mitigate both non-specific and ventilatorassociated pneumonia-specific ICU mortality. In this regard, Melsen and colleagues’ analysis anticipates the the US Centers for Disease Control and Prevention’s (CDC) new definitions for ventilator-associated event surveillance.7 CDC’s new definitions deliberately broaden the focus of routine surveillance from pneumonia alone to complications of mechanical ventilation in general in recognition that ventilated patients are at risk for many severe complications in addition to pneumonia. Both Melsen and colleagues’ analyses and CDC’s new definitions challenge us to enlarge our vision of what

Published Online April 25, 2013 http://dx.doi.org/10.1016/ S1473-3099(13)70111-7 See Online/Articles http://dx.doi.org/10.1016/ S1473-3099(13)70081-1

www.thelancet.com/respiratory Published online April 25, 2013 http://dx.doi.org/10.1016/S1473-3099(13)70111-7


Michael Klompas


it takes to improve outcomes for patients in ICUs. Interventions focused solely on preventing ventilatorassociated pneumonia alone are not sufficient. General strategies that expedite extubation and ICU discharge merit prioritisation. In this light, improved sedative management, ventilator weaning, and early mobilisation protocols deserve special mention. These interventions have repeatedly been shown to decrease duration of mechanical ventilation, length of stay in intensive care, long-term functional outcome, and sometimes even mortality.8–13 These potent interventions are the means to help translate Melsen and colleagues’ insights into better outcomes for mechanically ventilated patients. *Michael Klompas, Lingling Li
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 133 Brookline Avenue, Boston MA 02215, USA (MK, LL); Department of Medicine, Brigham and Women’s Hospital, Boston, MA (MK) mklompas@partners.org
MK has received honoraria from Premier Healthcare Alliance for lectures on VAP surveillance. LL declares that she has no conflicts of interest. 1 Wolkewitz M, Beyersmann J, Gastmeier P, Schumacher M. Modeling the effect of time-dependent exposure on intensive care unit mortality. Intensive Care Med 2009; 35: 826–32. Nguile-Makao M, Zahar JR, Francais A, et al. 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. Intensive Care Med 2010; 36: 781–89.












Schumacher M, Wangler M, Wolkewitz M, Beyersmann J. Attributable mortality due to nosocomial infections. A simple and useful application of multistate models. Methods Inf Med 2007; 46: 595–600. Bekaert M, Vansteelandt S, Mertens K. Adjusting for time-varying confounding in the subdistribution analysis of a competing risk. Lifetime Data Anal 2010; 16: 45–70. Bekaert M, Timsit JF, Vansteelandt S, et al. Attributable mortality of ventilator associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med 2011; 184: 1133–39. Melsen WG, Rovers MM, Groenwold RHH, et al. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013; published online April 25. http://dx.doi.org/10.1016/S1473-3099(13)70081-1. US Centers for Disease Control and Prevention. Ventilator-associated event protocol. 2013. http://www.cdc.gov/nhsn/acute-care-hospital/vae/index. html (Feb 25, 2013). Ely EW, Baker AM, Dunagan DP, et al. Effect on the duration of mechanical ventilation of identifying patients capable of breathing spontaneously. N Engl J Med 1996; 335: 1864–69. Kress JP, Pohlman AS, O’Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: 1471–77. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371: 126–34. Strom T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010; 375: 475–80. Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 2009; 373: 1874–82. Morris PE, Griffin L, Berry M, et al. Receiving early mobility during an intensive care unit admission is a predictor of improved outcomes in acute respiratory failure. Am J Med Sci 2011; 341: 373–77.



www.thelancet.com/respiratory Published online April 25, 2013 http://dx.doi.org/10.1016/S1473-3099(13)70111-7

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