Multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation.

Abstract

Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definition's subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients' ventilator settings after a period of stable or decreasing support.
We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital contributed 100 randomly selected patients ventilated 2-7 days and 100 patients ventilated >7 days. All patients were independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.
Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2-8.0 and 6.0, 95% CI 5.1-7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2-7.7 and 5.0, 95% CI 4.1-5.9), and days to hospital discharge (4.7, 95% CI 2.6-7.5 and 3.0, 95% CI 2.1-4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3-3.2) but VAP was not (OR 1.1, 95% CI 0.5-2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.
Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but is faster, more objective, and a superior predictor of outcomes.

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Multicenter Evaluation of a Novel Surveillance Paradigm
for Complications of Mechanical Ventilation
Michael Klompas1,2*, Yosef Khan3, Kenneth Kleinman1, R. Scott Evans4,5, James F. Lloyd5, Kurt
Stevenson3, Matthew Samore4, Richard Platt1,2for the CDC Prevention Epicenters Program
1Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, United States of America, 2Infection
Control Department, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America, 3Department of Medicine, The Ohio State University Medical
Center, Columbus, Ohio, United States of America, 4Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, United States of
America, 5Department of Medical Informatics, Intermountain Healthcare, Salt Lake City, Utah, United States of America
Abstract
Background: Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and
inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might
circumvent the VAP definition’s subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons
more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for
ventilator-associated complications (VAC) defined by sustained increases in patients’ ventilator settings after a period of
stable or decreasing support.
Methods: We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital
contributed 100 randomly selected patients ventilated 2–7 days and 100 patients ventilated .7 days. All patients were
independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive
care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of
patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.
Results: Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator
days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2–8.0 and 6.0, 95% CI
5.1–7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2–7.7 and 5.0, 95% CI 4.1–5.9), and days to hospital
discharge (4.7, 95% CI 2.6–7.5 and 3.0, 95% CI 2.1–4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3–3.2)
but VAP was not (OR 1.1, 95% CI 0.5–2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP
and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.
Conclusions: Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but
is faster, more objective, and a superior predictor of outcomes.
Citation: Klompas M, Khan Y, Kleinman K, Evans RS, Lloyd JF, et al. (2011) Multicenter Evaluation of a Novel Surveillance Paradigm for Complications of
Mechanical Ventilation. PLoS ONE 6(3): e18062. doi:10.1371/journal.pone.0018062
Editor: Benjamin Cowling, University of Hong Kong, Hong Kong
Received November 8, 2010; Accepted February 21, 2011; Published March 22, 2011
Copyright: ? 2011 Klompas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was funded by the Centers for Disease Control and Prevention Epicenters Program (grant #1U01CI000344). The funders had no role in study
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: mklompas@partners.org
Introduction
Mechanically ventilated patients are at risk for a wide array of
preventable pulmonary complications including pneumonia,
barotrauma, fluid overload, pulmonary embolism, pneumothorax,
and atelectasis. Measuring quality of care for ventilated patients,
however, has focused almost exclusively on ventilator-associated
pneumonia (VAP). Indeed, many groups including legislatures,
accreditation agencies, and consumer organizations advocate
public reporting of VAP rates with a view to benchmarking
hospitals and catalyzing improvements in care.
Surveillance and public reporting of VAP, however, is
problematic.[1,2] The surveillance definition for VAP requires
patients to fulfill radiologic (new and persistent infiltrate,
consolidation, or cavitation), systemic (fever, abnormal white
blood cell count, or delirium), and pulmonary criteria (any two of
change in secretions, worsening oxygenation, rales or bronchial
breath sounds, and new onset of cough or dyspnea).[3] Positive
cultures of pulmonary secretions are optional. In practice,
applying this definition is complicated, time consuming, and
subject to substantial interobserver variability.[4,5] There is poor
correlation between clinical diagnoses of VAP and histologically
confirmed infection [6–10] and an inconsistent correlation with
patients’ outcomes.[11,12] Many patients diagnosed with VAP are
found to have other complications at autopsy.[13] Requiring
positive cultures adds little accuracy since endotracheal aspirates,
broncholaveolar lavage, and protected specimen brush samples all
have relatively poor sensitivity and specificity relative to histolo-
gy.[14–18] Indeed, hospitals’ VAP rates can vary markedly
depending upon which methodology intensivists select to culture
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patients’ pulmonary secretions.[19] Hospitals’ rates also vary
depending upon the prevalence of patients with common
conditions that can mimic VAP in the hospitals’ intensive care
population.[20,21]
The complexity, unreliability, and limited focus of VAP
surveillance make VAP a poor basis for internal quality assessment
or external benchmarking. Shifting the emphasis of surveillance
from VAP in particular to ventilator-associated complications
(VAC) in general offers many potential advantages including a)
circumventing the inaccuracy of clinical signs to diagnose VAP, b)
emphasizing the importance of preventing all complications of
mechanical ventilation rather than pneumonia alone, and c)
facilitating an objective surveillance definition that might ease the
burden of data collection and make interfacility comparisons more
meaningful.
We hypothesized that surveillance for increases in patients’
ventilator settings after a period of stable or decreasing ventilator
settings might be a good indicator of a VAC. Surveillance for
increases in ventilator settings not only shifts the emphasis of
surveillance to detecting multiple complications of mechanical
ventilation rather than just pneumonia, but is also easier, faster,
more objective, and more amenable to electronic assessment
compared to the complicated weighing of clinical factors required
for VAP surveillance. Furthermore, basing VAC surveillance upon
increases in ventilator support sets a threshold effect for severity of
complications: only patients with severe enough complications to
merit a sustained increase in ventilator support are captured by
this definition. It is unknown, however, whether this surveillance
approach predicts patients’ outcomes. Good quality measures
should not only be objective and easy to gather but should also
predict patients’ outcomes and be able to reflect meaningful
changes in quality of care.
We undertook a multicenter study to compare outcomes for
patients who meet criteria for VAC compared to those who meet
criteria for VAP using the traditional definition of the United
States Centers for Disease Control and Prevention. In particular,
we compared time for surveillance and patients’ duration of
mechanical ventilation, length of stay in the intensive care unit and
hospital, and mortality. We also conducted a qualitative analysis of
a subset of patients meeting criteria for VAC and VAP to try to
determine a possible etiology for their events.
Materials and Methods
Setting, patients, and ethics review
This study was conducted using retrospective data from three
large academic medical centers in different regions of the United
States. The institutional review boards of Brigham and Women’s
Hospital (Boston, Massachusetts), The Ohio State University
Medical Center (Columbus, Ohio), and LDS Hospital (Salt Lake
City, Utah) approved the study. The review boards waived the
need for informed consent since the study involved medical record
review alone, all results are reported in aggregate without any
personally identifiable information, and because consent was not
practicable given the retrospective nature of the study and the high
morbidity and mortality rate of the target population.
We assessed medical and surgical patients over age 18 on
mechanical ventilation during calendar years 2006 and 2007. We
had sufficient resources to review 600 patients in total. We
therefore randomly selected 200 ventilated patients per hospital
but enriched the sample with patients with longer durations of
mechanical ventilation in order to maximize the frequency of
events and hence power. In particular, each hospital randomly
selected 100 patients ventilated for 2–7 days and 100 patients
ventilated for .7 days. Each patient was then assessed for VAC
and for VAP.
Definitions
VAC and VAP were assessed by different reviewers blinded to
each others’ conclusions. VAC was manually assessed using
electronically generated tables with a single line for each calendar
day the patient was on mechanical ventilation. Each line listed the
patient’s minimum positive end expiratory pressure (PEEP) and
fraction of inspired oxygen (FiO2) for that calendar day. VAC was
defined as an increase in the patient’s daily minimum PEEP by
2.5 cm H2O sustained for $2 days or an increase in the daily
minimum FiO2 by $15 points sustained for $2 days after a
minimum of 2 days of stable or decreasing daily minimum PEEPs
and FiO2s respectively. Patients with persistently elevated PEEP
($7.5 cm H2O) or FiO2 ($70%) during the first three days of
mechanical ventilation (suggesting intubation for a severe,
progressive respiratory disorder) were only eligible if they
subsequently stabilized and only required minimal ventilator
support (PEEP #5 cm H2O and FiO2 #40%) for $2 days. The
thresholds for defining stability prior to eligibility for VAC, the
magnitude of ventilator setting increases, and the minimum
duration of elevated settings were determined in advance by the
investigators based on prior operational experience with a
quantitative method for applying the CDC’s VAP definition that
incorporated changes in ventilator settings.[22] The thresholds
were set at the minimum level felt to represent a meaningful
change in ventilator support.
VAP was assessed by infection preventionists blinded to
patients’ VAC determinations. Between one and three infection
preventionists in each site applied the CDC’s National Healthcare
Safety Network definition for ventilator-associated pneumonia to
patients’ charts.[3] The CDC definition requires patients to meet
radiographic, systemic, and pulmonary criteria. Radiographic
criteria include new or progressive and persistent infiltrate,
consolidation, or cavitation. Systemic criteria include temperature
.38uC, leukopenia or leukocytosis, or delirium. Pulmonary
criteria require at least two of a change in sputum (new purulence,
change in character, increased secretions or increased suctioning
requirement); new or worsening cough, dyspnea, or tachypnea;
rales or bronchial breath sounds; and/or worsening gas exchange
(oxygen desaturations, increased oxygen requirements, or in-
creased ventilator demand).
Time for Surveillance
Two of the three study sites assessed the average time required
to assess for VAP and VAC status. Both the VAC reviewer and the
VAP reviewer tallied the total number of hours needed to perform
surveillance for the site’s 200 patients.
Statistical analyses
Days of mechanical ventilation, days in the intensive care unit,
days in the hospital, and hospital mortality were compared for
patients with and without VAC and for those with and without
VAP. Raw outcomes were compared using Wilcoxon signed rank
test for durations and Fisher’s exact test for mortality. We then did
separate matched analyses for each of VAC and VAP to control
for patients’ pre-morbid duration of mechanical ventilation (the
major risk factor for complications). All patients with VAC or VAP
(‘‘cases’’) were respectively and independently matched to as many
patients without VAC or VAP (‘‘controls’’) as possible. Controls’
minimum duration of mechanical ventilation was at least equal to
the matched cases’ duration of mechanical ventilation prior to
onset of VAC or VAP.[23] Patients were additionally matched on
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the basis of hospital, unit type (medical versus surgical), and
Charlson comorbidity index. We then applied linear and logistic
regression models corrected for matching in order to compare
days from event to extubation, intensive care discharge, and
hospital discharge in cases versus controls.[24] The day of event
was defined as the day of VAC or VAP in cases, and the ventilator
day on which the matched case patient developed VAC or VAP in
controls. The regression models included age, sex, hospital, unit
type, and Charlson comorbidity index as covariates. Time
variables were log transformed in order to increase normality.
The matched analyses of days from event to extubation, intensive
care discharge, and hospital discharge were repeated amongst
survivors only to assess whether an association between VAC and
mortality might simply reflect terminal increases in ventilator
support in patients with irreversible pulmonary disease. All
calculations were performed using SAS version 9.2 (SAS Institute,
Cary, NC).
Qualitative analysis of VAC and VAP events
A critical care physician independently reviewed 52 patients
with VAC or VAP randomly selected from one hospital. The
physician was asked whether the patient suffered a significant
episode of respiratory deterioration, and if so, the likely etiology.
The physician reviewer was blinded to patients’ VAC and VAP
determinations.
Results
During the study period, the three study hospitals provided
mechanical ventilation to 11,256 patients (5,887 ventilated 0–2
days, 3,181 ventilated 2–7 days, 2,188 ventilated .7 days).
Evaluable data was available for 597 patients supported for 6,347
ventilator-days. The characteristics of these patients are summa-
rized in Table 1. Of these, 9% met the CDC definition for VAP
(8.8 per 1000 ventilator days) and 23% met the definition for VAC
(21.2 per 1000 ventilator days). In the two hospitals that recorded
time required for surveillance, the VAP reviewer required
260 hours to assess 400 patients (mean 39 minutes per patient).
The VAC reviewer required 12 hours to assess 400 patients (mean
1.8 minutes per patient).
Patients’ raw outcomes are summarized in Table 2. Both VAC
and VAP were significantly associated with more days of
mechanical ventilation, longer stays in the intensive care unit,
and longer stays in hospital compared to VAC and VAP negative
patients respectively. VAC positive patients were more likely to die
than VAC negative patients but there was no difference in
mortality between VAP positive versus VAP negative patients.
The matched analysis is presented in Table 3. Cases were
matched to between 1 and 5 control patients. All but four VAP
patients and eight VAC patients were successfully matched. There
were no significant differences in the age, sex, or co-morbidity
profiles of cases and controls. Both VAC and VAP were
significantly associated with prolonged mechanical ventilation,
intensive care stay, and hospital length-of-stay compared to
matched controls. However, the adjusted odds ratio of death for
patients with VAC was 2.0 (95% CI 1.3–3.2, P=.003) whereas the
adjusted odds ratio of death for patients VAP was 1.1 (95% CI,
0.5–2.4, P=.78).
The matched analysis amongst survivors only is presented in
Table 4. Both VAP and VAC were again significantly associated
with prolonged ventilator days, intensive care days, and hospital
days.
The frequency of overlap between patients with VAC and those
with VAP is presented in Figure 1 along with median ventilator,
intensive care unit, and hospital lengths of stay according to
overlap pattern. The sensitivity and specificity of VAC relative to
VAP were 56% (95% CI, 43–69%) and 95% (95% CI, 92–97%)
respectively. Patients that met criteria for both VAC and VAP had
the longest lengths of stay, those who met criteria for only one of
these two conditions had similar intermediate lengths of stay, and
those who were negative for both VAC and VAP had the shortest
lengths of stay.
The physician’s qualitative analysis of patients flagged with
VAC and VAP is shown in Table 5. Similar proportions of VAC
and VAP events were attributed to pneumonia (23% of VACs and
33% of VAPs), pulmonary edema (18% of VACs and 22% of
VAPs), acute respiratory distress syndrome (16% of VACs and
11% of VAPs), and atelectasis (11% of VACs and 11% of VAPs).
Table 1. Patient Characteristics.
Patients 597
Male328 (53%)
Age (mean) 57.5
Unit type
Medical 299 (50%)
Surgical286 (48%)
Mixed 12 (2%)
Comorbidities
Coronary artery disease 117 (20%)
Cerebrovascular disease80 (13%)
Congestive heart failure 185 (31%)
Chronic obstructive lung disease203 (34%)
Rheumatologic disease 20 (3%)
Liver disease142 (24%)
Diabetes139 (23%)
Renal insufficiency 133 (22%)
Cancer200 (34%)
Ventilator-associated pneumonia (VAP)
Overall 55 (9%)
Ventilated #7 days
Hospital A 4 (4%)
Hospital B3 (3%)
Hospital C0 (0%)
Ventilated .7 days
Hospital A 28 (28%)
Hospital B 13 (13%)
Hospital C 7 (7%)
Ventilator-associated complications (VAC)
Overall135 (23%)
Ventilated #7 days
Hospital A9 (9%)
Hospital B 8 (8%)
Hospital C 7 (7%)
Ventilated .7 days
Hospital A 47 (47%)
Hospital B34 (34%)
Hospital C 30 (30%)
doi:10.1371/journal.pone.0018062.t001
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Discussion
In this multicenter retrospective study, a novel objective
measure for complications of mechanical ventilation predicted
patients’ ventilator, intensive care, and hospital days as well as the
traditional CDC surveillance definition for VAP. The novel
definition for ventilator-associated complications, however, was a
superior predictor of hospital mortality. Surveillance using the
novel definition was faster than conventional surveillance,
requiring a mean of 1.8 minutes per patient versus 39 minutes
per patient for VAP. Qualitative analysis of both VAC and VAP
events suggested that they were both predominantly attributable to
similar frequencies of pneumonia, pulmonary edema, acute
respiratory distress syndrome, and atelectasis.
The superior association of VAC with mortality compared to
VAP might be due to the threshold effect inherent in the VAC
definition. Only patients whose complications were severe enough
to merit an increase in ventilator support met criteria for VAC
Table 2. Comparison of outcomes for ventilator-associated complication positive and negative patients and ventilator-associated
pneumonia positive and negative patients.
VAC Positive VAC NegativePVAP Positive VAP NegativeP
Number of patients 135462– 55 542–
Duration of ventilation (median days)13.06.0
,.00113.5 7.0
,.001
ICU length of stay (median days)16.38.0
,.00118.0 9.0
,.001
Hospital length of stay (median days) 21.0 16.0
,.00124.617.0
,.001
Hospital mortality (% of patients) 38%23% .00127%26% 1.000
Abbreviations:
VAC – ventilator associated complications; VAP – ventilator associated pneumonia.
doi:10.1371/journal.pone.0018062.t002
Table 3. Results of linear and logistic regression models comparing patient outcomes for ventilator-associated complication or
ventilator-associated pneumonia relative to matched patients without ventilator-associated complications or ventilator-associated
pneumonia respectively.
VAC Positive
(95% CI)
VAC Negative
(95% CI)P
VAP Positive
(95% CI)
VAP Negative
(95% CI)P
Patients matched127 32951188
Age (mean) 56.5 58.8 NS60.4 58.0NS
Male 56%57% NS61% 56% NS
Comorbidities
Coronary artery disease 19% 20% NS10%14%NS
Cerebrovascular disease9%14%NS16%16%NS
Congestive heart failure31%32%NS18%28%NS
Chronic obstructive lung disease31%32%NS 31%29% NS
Rheumatologic disease4% 4%NS2%3%NS
Liver disease 17%17%NS6%15%NS
Diabetes24%24%NS14%26%NS
Renal insufficiency 57%42%NS 39%37%NS
Cancer 49%41%NS 39%36% NS
Charlson index (mean) 2.72.7NS 2.92.9 NS
Duration of ventilation (days)14.7 (13.2–16.4)9.0 (8.2–9.9)
,.00116.9 (14.2–20.2) 11.0 (9.5–12.8)
,.001
ICU length of stay (days) 17.6 (15.7–19.6)13.0 (11.9–14.3)
,.001 20.9 (17.7–24.7) 14.9 (13.1–17.1)
,.001
Hospital length of stay (days)25.4 (22.7–28.4) 23.4 (21.5–25.4) .14 30.5 (15.6–36.4)26.8 (24.0–30.0) .16
Days from event to extubation*9.7 (8.4–11.2) 3.7 (3.3–4.1)
,.00110.3 (7.9–13.4) 4.5 (3.7–5.4)
,.001
Days from event to ICU discharge*11.8 (10.3–13.5) 6.8 (6.2–7.6)
,.001 13.2 (10.7–16.4)7.5 (6.5–8.7)
,.001
Days from event to hospital discharge* 16.4 (14.2–18.8)13.4 (12.1–14.8).0119.7 (16.0–24.3) 15.0 (13.4–16.8).02
Hospital mortality (odds ratio)2.0 (1.3–3.2)– .003 1.1 (0.51–2.4)– .78
*Date of event in cases defined as the ventilator day on which VAC or VAP began. Date of event in controls defined as the ventilator day on which the matched case
patient developed VAC or VAP.
Abbreviations:
VAC – ventilator associated complications; VAP – ventilator associated pneumonia; ICU – intensive care unit.
Model adjusted for age, sex, hospital, unit type, and Charlson comorbidity index.
doi:10.1371/journal.pone.0018062.t003
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whereas patients with stable ventilator support could still be
labeled with VAP on the basis of more subjective criteria such as
rales, delirium, and changes in the quality and quantity of
pulmonary secretions. Indeed, about half of patients labeled with
VAP did not meet criteria for VAC. By definition, these patients
had stable ventilator settings despite their purported pneumonias.
Mixing these stable patients with patients who do have
pronounced evidence of impaired oxygenation may be the reason
that VAP was not associated with increased mortality: patients
with benign disease may be ‘‘diluting’’ the mortality signal of
patients with more severe disease. As such, the relative insensitivity
of VAC relative to VAP may in fact be a strength of VAC
surveillance since it selects for patients with more severe and hence
meaningful complications.
The association of ventilator setting increases with mortality is
analogous to the partial pressure of arterial oxygen to fraction of
inspired oxygen ratio (PaO2/FiO2). A sustained decrease in the
PaO2/FiO2ratio is also an independent marker for mortality in
ventilated patients. Changes in ventilator settings are more suitable
for continuous population surveillance than changes in PaO2/
FiO2ratios, however, since ventilator settings are available on
every patient for every day of mechanical ventilation whereas
PaO2/FiO2ratios are only available when clinicians choose to
obtain an arterial blood gas, typically an intermittent event.
Concern that VAC is merely a marker for the manner in which
patients die on mechanical ventilation (i.e. progressive increases in
ventilator support for refractory hypoxemia) is allayed by the
consistent correlation between VAC and lengths of stay in the
analysis of survivors alone. Likewise, VAC is unlikely to be simply
a marker for severity of illness since by definition it is only
triggered by a deleterious change in patients’ respiratory status
after a period of stable or improving respiratory status. Worsening
oxygenation after a sustained period of stability or improvement is
more likely to indicate a complication than progression of
underlying disease.
The VAC definition can be rapidly applied either electronically
or manually. The dramatically lower time required for VAC
surveillance presumes the raw data is pre-organized into a linelist
with each patient’s daily minimum ventilator settings. Hospitals
without information systems to automatically generate linelists of
Table 4. Survivors only comparison of patient outcomes for patients with ventilator-associated complications or ventilator-
associated pneumonia relative to matched controls.
Outcome
VAC Positive
(95% CI)
VAC Negative
(95% CI)P
VAP Positive
(95% CI)
VAP Negative
(95% CI)P
Duration of ventilation (days)14.2 (12.5–16.0) 9.1 (8.2–10.0)
,.00116.5 (13.8–19.7) 10.1 (8.8–11.8)
,.001
ICU length of stay (days) 17.4 (15.4–19.7)13.1 (11.9–14.4)
,.001 21.6 (18.2–25.5) 14.3 (12.6–16.3)
,.001
Hospital length of stay (days) 25.4 (22.4–29.0)23.7 (21.6–25.9).2729.5 (24.3–35.7)27.1 (24.3–30.3) .43
Days from event to extubation*9.0 (7.5–10.7)3.8 (3.4–4.3)
,.0019.8 (7.5–12.9)3.8 (3.1–4.6)
,.001
Days from event to ICU discharge*11.6 (9.9–13.6) 7.4 (6.6–8.2)
,.00113.8 (11.1–17.0) 7.1 (6.2–8.1)
,.001
Days from event to hospital discharge* 18.1 (15.6–21.0)15.1 (13.7–16.7) .0320.7 (16.6–25.9)16.1 (14.3–18.2) .05
*Date of event in cases defined as the ventilator day on which VAC or VAP began. Date of event in controls defined as the ventilator day on which the matched case
patient developed VAC or VAP.
Abbreviations:
VAC – ventilator associated complications; VAP – ventilator associated pneumonia; ICU – intensive care unit.
Model adjusted for age, sex, hospital, unit type, and Charlson comorbidity index.
doi:10.1371/journal.pone.0018062.t004
Figure 1. Median ventilator, intensive care unit, and hospital lengths of stay according to overlap pattern between patients with
ventilator-associated complications (VAC) versus ventilator-associated pneumonia (VAP).
doi:10.1371/journal.pone.0018062.g001
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patients’ daily minimum PEEPs and FiO2s can have nurses or
respiratory therapists record these two values every 24 hours on a
dedicated spreadsheet by the bedside. Spreadsheets of this nature
enable infection preventionists to rapidly complete VAC surveil-
lance by consolidating and simplifying patients’ ventilator data for
rapid review. Hospitals can also consider providing visual plots or
statistical process control charts of daily minimum PEEPs and
FiO2s for clinicians at the bedside to rapidly alert them to evolving
VACs.
Many observers have questioned the validity of comparing VAP
rates between hospitals as well as the clinical significance of reports
of ‘‘zero’’ VAP rates in some hospitals. [1,2,25–27] The
distribution in VAC rates between the hospitals in this study
compared with the spread in VAP rates is informative. Amongst
patients ventilated for 7 days or less, the observed VAP rates
varied from 0 to 4% but when VAC rates were calculated, the
range was only 7 to 9%, suggesting a measure that is both more
uniform and able to detect complications in populations with
ostensibly zero VAPs. A similar narrowing of the distribution
between hospitals was observed for patients ventilated .7 days.
A potential criticism of VAC relative to VAP is that it does not
indicate specific etiologies for patients’ decompensations that can
be used to inform future care improvement efforts. The ostensible
specificity of a VAP diagnosis, however, is illusory. In this study,
qualitative analysis by a critical care physician confirmed only one
third of VAPs and identified many additional pneumonias missed
by VAP criteria. Poor correlation between VAP clinical criteria
and patients’ true underlying disorders is consistent with prior
investigations.[13,28] Indeed, it is striking that similar proportions
of VAC events and VAP events were attributed to same array of
significant complications including pulmonary edema, acute
respiratory distress syndrome, and atelectasis in addition to
pneumonia. This implies that VAP surveillance both misses and
mislabels many important complications. Lumping many compli-
cations together as pneumonia risks missing important alternative
domains for care improvement initiatives. Labeling patients’
adverse events as VACs rather than pneumonias is a more frank
and therefore useful description of what can and cannot
confidently be discerned by surveillance.
In addition, shifting the focus of surveillance from pneumonia
alone to complications in general emphasizes the importance of
preventing all complications of mechanical ventilation, not just
pneumonia. Hospitals should consider treating VACs as sentinel
events that catalyze a multidisciplinary, open-minded evaluation of
what might have precipitated the patient’s deterioration. Shifting
focus from pneumonia alone to complications in general sidesteps
arguments about whether or not implicated patients truly had
pneumonia (a distraction that sometimes overshadows critical
analyses of VAPs at present) and instead invites caregivers to try to
work out what did go wrong. A sentinel analysis might conclude
that the patient’s deterioration was due to VAP but could just as
well attribute decompensation to poor fluid management,
barotrauma, thromboembolic disease, or lobar collapse secondary
to mucous plugging. Ideally, open-minded analyses of complica-
tions will generate broader and more nuanced views as to what
practices can be improved. Grouping VACs by suspected etiology
might reveal patterns of potentially modifiable precipitants.
Ultimately, this process should lead to a broader ‘‘ventilator
bundle’’ with added measures to promote early extubation,
encourage protective lung ventilation, prevent pulmonary edema,
minimize blood transfusions, and better manage secretions. The
Institute for Healthcare Improvement’s bundle anticipates this
direction: it includes thromboembolism and stress ulcer prophy-
laxis in addition to pneumonia specific measures such as elevating
the head of the bed.[29]
There are important limitations to this work. It is a purely
observational, retrospective study limited to three medical centers.
VAP assignments were made by infection preventionists from
chart reviews – different infection preventionists conducting
prospective surveillance might have made different determina-
tions. VAP surveillance time estimates should be treated as
approximations since they measure time for retrospective chart
review rather than daily, prospective, bedside assessments. The
results of this investigation need to be reproduced prospectively in
different settings to assure validity and generalizability.
The thresholds for stability prior to VAC eligibility, minimum
changes in ventilator settings, and duration of changes merit
further evaluation. In particular, the 2 day window of stable or
decreasing ventilator settings prior to VAC eligibility might need
to be lengthened to avoid mislabeling patients who require
staggered increases in ventilator support when intubated for
respiratory failure from a disease that continues to progress after
intubation. Increasing the minimum thresholds for rises in
ventilator settings and duration of increased ventilator support
might further improve correlation between VAC and adverse
outcomes.
Future changes in ventilator management strategies or the
introduction of novel modes of ventilation might alter the
performance or feasibility of VAC criteria. There is also some
risk that clinicians may be loathe to increase patient’s ventilator
support, even when clinically indicated, to prevent their patient
from being labeled with VAC. However, we believe the risk of this
happening is low since failure to maintain patients’ oxygenation in
a safe zone is an egregious clinical error.
In recent years, hospitals have made admirable progress in
reducing their VAP rates.[25–27,30,31] The median VAP rate in
hospitals reporting to the National Safety Healthcare Network has
decreased from 4.6 per 1000 ventilator-days from 1992–2004 to
2.0 per 1000 ventilator-days in 2006–2008.[32,33] In addition,
multiple hospitals have reported extended periods without any
VAPs.[25–27] While these decreases may partly be due to the
subjectivity permitted by the current VAP definition, it is clear that
VAP is becoming a vanishing target upon which to focus
Table 5. Qualitative analysis of 52 patients flagged with
ventilator-associated complications or ventilator-associated
pneumonia.
Etiology of
VAC (N=44)
Etiology of
VAP (N=18)
Any pulmonary complication26 (59%)11 (61%)
Pneumonia10 (23%) 6 (33%)
Pulmonary edema8 (18%)4 (22%)
Acute respiratory distress syndrome7 (16%)2 (11%)
Atelectasis5 (11%)2 (11%)
Mucous Plugging1 (2%)0
Abdominal compartment syndrome1 (2%)0
Pulmonary embolus 1 (2%)0
Radiation pneumonitis 1 (2%)0
Sepsis syndrome 1 (2%)0
Poor pulmonary toilet 1 (2%)0
Abbreviations:
VAC – ventilator associated complications; VAP – ventilator associated
pneumonia.
doi:10.1371/journal.pone.0018062.t005
Surveillance for Ventilator Complications
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Page 7

surveillance and prevention efforts. Surveillance for VAC identifies
more patients who might have suffered complications of care
(almost three times as many patients met criteria for VAC
compared to VAP) and therefore constitutes a broader group upon
which to focus quality improvement efforts.
Most public health departments and funding agencies have
shied away from compelling hospitals to report VAP rates and
from making VAP a non-reimbursable event in light of the
complexity and subjectivity of VAP surveillance.[1] An alternative
measure is needed to promote quality assessment, benchmarking,
and care improvements for ventilated patients. VAC has many
features that make it a promising alternative: the definition’s
simplicity minimizes the extra burden upon hospital personnel to
complete surveillance, its objectivity makes it less susceptible to
gaming, and the close association between VAC and adverse
outcomes make it a meaningful target for prevention. VAC’s
emphasis on complications in general rather than pneumonia per
se sidesteps the inherent limitations of VAP diagnosis. This has the
additional advantage of inviting thoughtful case-by-case analyses
of affected patients to identify broad areas for improvements in
care beyond just pneumonia prevention alone. Further study is
now needed on the extent to which VAC rates can be lowered
through meaningful improvements in care.
Acknowledgments
The authors would like to thank the infection preventionists who assessed
patients for ventilator-associated pneumonia using the CDC definition:
Tricia Lemon RN, MPH of Tufts Medical Center; Lisa Hines RN, BS, CIC
of Ohio State University; Ruth Kleckner RN, BSN, Sharon Sumner RN,
BSN, and Caroline W. Taylor RN, MSN of Intermountain Medical Center.
PRIOR PRESENTATION
The findings of this study were first reported in part at the Fifth
Decennial Meeting on Healthcare Associated Infections sponsored by the
Centers for Disease Control and Prevention, the Society for Healthcare
Epidemiology of America, and the Association of Professionals in Infection
Control, March 18–22, 2010, Atlanta, GA.
Author Contributions
Acquisition of data: MK YK SE JL. Funding, administrative support, and
study supervision: KS MS RP. Conceived and designed the experiments:
MK YK KK SE RP. Analyzed the data: MK KK. Wrote the paper: MK.
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Surveillance for Ventilator Complications
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