Infection Control & Hospital Epidemiology (2019), 40, 301–306 doi:10.1017/ice.2018.360
Original Article
Analyzing the impact of duration of ventilation, hospitalization, and ventilation episodes on the risk of pneumonia
Martin Wolkewitz PhD1, Mercedes Palomar-Martinez MD, PhD2, Francisco Alvarez-Lerma MD, PhD3, Pedro Olaechea-Astigarraga MD4 and Martin Schumacher PhD1 1Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Frieburg, Germany, 2Universitat Autonoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain, 3Service of Intensive Care Medicine, Parc de Salut Mar, Barcelona, Spain and 4Service of Intensive Care Medicine, Hospital de Galdakao-Usansolo, Bizkaia, Spain
Abstract
Objective: To study the impact of duration of mechanical ventilation, hospitalization and multiple ventilation episodes on the development of pneumonia while accounting for extubation as a competing event.
Design: A multicenter data base from a Spanish surveillance network was used to conduct a retrospective analysis of prospectively collected intensive care patients followed from admission to discharge. Setting: Spanish intensive care units (ICUs).
Patients: Mechanically ventilated adult patients from 158 ICUs with 45,486 admissions, 48,705 ventilation episodes, and 314,196 ventilator days.
Methods: Competing-risk models were applied to account for extubation plus 48 hours as a competing event for acquiring ventilator- associated pneumonia (VAP).
Results: Time in the ICU before mechanical ventilation was associated with an increased VAP hazard rate and with longer intubation time. This indirect prolongation of intubation increased the cumulative risk to eventually acquire VAP. For instance, comparing 3–4 versus 0 days, the adjusted VAP hazard ratio was 1.40 (95% confidence interval [CI], 1.19–1.64) and the adjusted extubation hazard ratio was 0.64 (95% CI, 0.61–0.68), which leads to an adjusted VAP subdistribution hazard ratio (sHR) of 2.13 (95% CI, 1.83–2.50). Similarly, due to prolonged intu- bation, multiple ventilation episodes increase the risk for VAP; the adjusted sHR is 1.52 (95% CI, 1.35–1.72) for the second episode compared to the first episode, and the adjusted sHR is 1.54 (95% CI, 1.03–2.30) for the third episode compared to the first episode. The Kaplan-Meier method produced an upward biased estimated cumulative risk for VAP.
Conclusions:Acompeting-risk analysis is necessary to receive unbiased risk estimates and to quantify the indirect effect of intubation time on the cumulativeVAP risk. Our findings may guide physicians to improve medical decisions related to the harms and benefits of the duration of ventilation.
(Received 4 April 2018; accepted 15 December 2018)
Pneumonia is among the most common and potentially avoidable complications that occur among ventilated patients in intensive care units (ICUs). It is associated with prolonged length of hospital stay and increased hospital mortality, especially if it is caused by multidrug-resistant pathogens.1,2 Thus, understanding the risks for ventilator-associated pneumonia (VAP) and identifying high-risk patients is clinically important. Appropriate statistical models to evaluate the risks for VAP are
needed because the definition as well as the occurrence of VAP are closely connected with several time-related issues. First, VAP is defined as pneumonia occurring in a mechanically ventilated
Author for correspondence: Martin Wolkewitz, Email:
wolke@imbi.uni-freiburg.de Cite this article: Wolkewitz M, et al. (2019). Analyzing the impact of duration of
ventilation, hospitalization, and ventilation episodes on the risk of pneumonia. Infection Control & Hospital Epidemiology, 40: 301–306,
https://doi.org/10.1017/ice.2018.360
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved.
patient after 48 hours of endotracheal intubation.1,2 It is common practice in randomized clinical trials3 as well as in epidemiological studies (eg, studies following the protocol of the European Centre for Disease prevention and Control4) to consider the at-risk time for VAP as the period between 48 hours after intubation and 48 hours after extubation. This at-risk time is directly linked to ‘ventilator-days at risk’ as the appropriate denominator in calcu- lating VAP rates.5 To account for the at-risk time, commonly used statistical models (eg, Kaplan-Meier techniques and standard Cox proportional hazard models) are applied.3 However, such models fail to account for competing events, which leads to overestimated risks.6,7 Second, reintubation (especially after unsuccessful extuba- tion) and multiple ventilation episodes are considered risk factors for VAP.8,9 Third, the presence of an endotracheal tube is the principle risk factor for VAP, and the cumulative risk increases with the duration of mechanical ventilation.2 However, previous
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