Bringing the ABCDEF Bundle to Life and Saving
Lives Through the Process*
Brian J. Anderson, MD, MSCE
Mark E. Mikkelsen, MD, MSCE
Pulmonary, Allergy & Critical Care Division
Center for Clinical Epidemiology and Biostatistics
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA
W
hat began 20 years ago as a single intervention
to assess ventilated patients daily for a spontane-
ous breathing trial (SBT) (B) (1) later matured
into a combined intervention of daily awakening via seda-
tion interruption and an SBT (AB) (2). As the evidence for
delirium prevention and early mobilization emerged, a bun-
dle was born, one that had the potential to improve the lives
of the critically ill in the short and long term. The ABCDE
bundle was designed to incorporate sedative choice (C),
delirium assessment and management (D), and early mobi-
lization (E) (3).
In its current form, the ABCDEF bundle combines the
assessment, prevention, and treatment of pain; both daily
sedation interruption and SBTs; choice of sedation and anal-
gesia agents with a focus on targeting minimal sedation and
avoiding benzodiazepines; delirium monitoring and manage-
ment; early mobilization; and family engagement. Implemen-
tation of components of the ABCDE bundle (1, 2, 4–12) and
the bundle itself (13–16) has been associated with reductions
in mortality, ventilator duration, and delirium. These achieve-
ments were realized despite less than ideal bundle compli-
ance (13, 16). Imagine what could be achieved if the ABCDEF
bundle was provided uniformly to all critically ill patients, and
we begin to understand the vision of the Society of Critical
Care Medicine’s ICU Liberation Initiative, described in detail
at www.iculiberation.org.
In this issue of Critical Care Medicine, Barnes-Daly et al (17)
sought to optimize ABCDEF bundle compliance and through
the process, improve the quality and quantity of life of the medi-
cally and surgically critically ill at Sutter Health in California.
Guided by important preceding work that provided a roadmap
for how to optimize ABCDE bundle implementation (18), the
*See also p. 171.
Key Words: ABCDEF bundle; critical illness; delirium; ICU liberation;
quality improvement; sedation
Supported, in part, by National Institutes of Health (NIH) grant F32-
GM116637 (Dr. Anderson) and the NIH Loan Repayment Program (Dr.
Mikkelsen). Drs. Anderson and Mikkelsen received support for article re-
search from the National Institutes of Health (NIH). Dr. Anderson’s institu-
tion received funding from the NIH.
Copyright © 2017 by the Society of Critical Care Medicine and Wolters
Kluwer Health, Inc. All Rights Reserved.
DOI: 10.1097/CCM.0000000000002124
Critical Care Medicine www.ccmjournal.org 363
Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Sutter Health team expertly designed and implemented the
ABCDEF bundle (the 2014 version, Table 1) using an interpro-
fessional team consisting of two nurses, a pharmacist, a physical
therapist, a respiratory care practitioner, and an ICU physician.
Members of the team underwent a 12-week training program
that included training on interprofessional team concepts and
clinical aspects of the ABCDEF bundle, before being deployed
into ICUs at seven community hospitals within a large health
system in CA.
The ICUs were open, medical-surgical ICUs. Three were
staffed by intensivists and all had remote electronic ICU RN and
physician staff support. The target population included ventilated
and nonventilated ICU patients deemed eligible for the bundle.
Important exclusion criteria included active drug and alcohol
withdrawal, hemodynamic or respiratory instability, receipt of
neuromuscular blockade, active coronary ischemia, and specific
surgical conditions (e.g., open abdomen). The team hypothesized
that bundle compliance would be high and would translate into
improved in-hospital survival and delirium-free/coma-free days
(DFCFD) during the ICU stay. To determine the association of
bundle compliance with outcomes, the authors used multivariable
regression and adjusted for age, illness severity (Acute physiology
and chronic health evaluation [APACHE] III), and proportion of
days of mechanical ventilation.
Between January 1, 2014, and December 31, 2014, the
team implemented the bundle in 6,064 ICU patients. Despite
90% of the patients being urgent or emergent ICU admis-
sions, only 1,438 (23.7%) required mechanical ventilation
during their hospitalization and the median ICU and hos-
pital length of stay (LOS) were 3 and 5 days, respectively.
Furthermore, in contrast to national benchmarks and poten-
tially related to generalizability, in-hospital mortality was
relatively low at 9.7%.
The primary findings were two-fold. First, compliance with
the ABCDEF bundle was extremely high, with mean total com-
pliance approaching 90% and mean partial compliance around
95% (definitions summarized in Table 1). As shown in Supple-
mental Table 6 in (17), these compliance rates were achieved
across all seven hospitals. Although the implementation team
designed their study to optimize compliance, based on prior
implementation studies (13, 16), wherein postimplementation
compliance ranged from 50% for delirium assessments to 71%
and 84% for a sedation interruption and SBT, respectively (13),
at best, these results are breathtaking.
Second, each 10% increase in total bundle compliance was
associated with a 7% (odds ratio [OR], 1.07; 95% CI, 1.04–1.11;
p < 0.001) increased odds of in-hospital survival and each 10%
increase in partial bundle compliance was associated with a
15% (OR, 1.15; 95% CI, 1.09–1.22; p < 0.001) increased odds
of in-hospital survival. Notably, the observed survival benefits
were confined to patients without a palliative care consultation.
Editorials

Table 1. Definitions of the ABCDEF Bundle Components and Compliance Measurementsa

Awakening Complete interruption of sedative infusions and analgesic infusions as long as the
patient was not having active pain
Breathing Patients receiving mechanical ventilation were placed on continuous positive airway
pressure or pressure-support ventilation 5/5 or blow-by for a minimum of 30 min
Choice of sedative/analgesics Statement by the pharmacist that pain, agitation, delirium guidelines were being
followed, including light sedation target, avoidance of benzodiazepines, and use of a
pain-first sedation approach
Delirium monitoring and management Confusion assessment method for the ICU was used to assess the patient on both the
current shift and prior shift
Early mobilization Patient was mobilized to maximum potential
Family engagement The patient or family participated in rounds or a family conference had been held
Total compliance Proportion of days during the patient’s ICU stay that he or she received all elements of
the ABCDEF bundle that the patient was eligible for on a given day
Partial compliance Proportion of the number of components the patient received on a given day divided by
the number of components the patient was eligible for on a given day, averaged over
the ICU stay
Components were considered compliant if they were accomplished during the previous 24 hr (rounds from prior day to rounds on present day).
a

Additionally, after adjustment, each 10% increase in total bundle
compliance was associated with a 2% increase in DFCFD (inci-
dent rate ratio [IRR], 1.02; 95% CI, 1.01–1.04; p = 0.004) and
each 10% increase in partial bundle compliance was associated
with a 15% increase in DFCFD (IRR, 1.15; 95% CI, 1.09–1.22; p
< 0.001).
Together, these results revealed that the Sutter Health team
brought the ABCDEF bundle to life, as nearly nine out of
every 10 eligible patients received the bundle in its entirety
and bundle compliance may have resulted in improve-
ments in acute brain dysfunction and survival. Although
the efforts of the Sutter Health team deserve our praise and
these results are worthy of our attention and serve to further
fuel an already raging fire, we should take the opportunity
to learn and improve as more and more healthcare systems
engage in the worthy efforts of ABCDEF bundle adoption
and implementation.
First, before expending one’s valuable time and energy, one
needs to know baseline metrics like the back of one’s hands.
Herein, the team needed to know the baseline compliance
measures for the components of the bundle to ensure that the
team was devoting their time and energy to a situation where
a gap existed. Unfortunately, the reader is left wanting in their
desire to understand how far the Sutter Health team came from
to get to 90% bundle compliance. Given prior work, the gap
was likely substantial, but we (including those who worked
tirelessly at Sutter Health) may never know the magnitude of
the accomplishment achieved.
Second, without baseline metrics for the outcomes of
interest (acute brain dysfunction and survival for ABCDEF-
eligible patients) to examine and account for temporal trends
preimplementation, it is reasonable to be circumspect of the
observed associations. In general, causal inference is always
challenging to invoke in a pre/postimplementation study
design, even with the use of robust analyses (i.e., difference-in-
difference designs). The study population and design herein
make this a legitimate threat.
Specifically, without preimplementation data to support
that survival improved after near uniform bundle implementa-
tion, one could reason that patients who were more likely to
survive were also those in whom it was easier to achieve partial
or total bundle compliance. This may be particularly relevant
because 76.3% of patients never required mechanical ventila-
tion during the ICU stay. This is an important observation, as
nonventilated patients may be less likely to benefit from the
bundle because they were not ventilated (B), likely were not
receiving continuous sedative or analgesic infusions (A and C)
and thus were likely at lower risk for delirium (D), more easy
to mobilize (E), and more likely to participate in rounds them-
selves (F). Although the authors adjusted for illness severity
using the APACHE III score in their logistic regression models,
the APACHE III score is unlikely to fully capture these funda-
mental differences. Demonstrating similar findings in stratified
analyses among ventilated and nonventilated patients would
have been reassuring and should be considered in similar stud-
ies in the future.
Last, whether the relationship between compliance and
DFCFD would persist if DFCDF were defined using a stan-
dardized timeframe (e.g., ventilator-free days within 28 d
[19] or DFCFD within 12 d [20]), rather than within the ICU
LOS, remains unclear. Although using a standardized time-
frame may require one to make assumptions after patients
are discharged from the ICU or the hospital, it minimizes
bias introduced due to differential lengths of follow-up. As
an example, if DFCFD were calculated only within the ICU
LOS as reported in the present study, a patient who was in
the ICU for 3 days and never experienced coma or delirium,
and a patient who was in the ICU for 7 days but experienced

364 www.ccmjournal.org February 2017 • Volume 45 • Number 2

Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

coma or delirium on four of those 7 days, would both be
reported as having three DFCFD, and the outcome would
not accurately capture the burden of acute brain dysfunction.
Future confirmatory studies using standardized timeframes
are therefore needed.
In conclusion, through the use of an interprofessional team
model, the novel use of telemedicine, and a robust educational
platform, Barnes-Daly et al (17) brought the ABCDEF bundle
to life across seven community hospitals. As a result, of 6,064
ICU patients, nearly 5,400 received the entire ABCDEF bundle,
a powerful accomplishment and advancement by establish-
ing a new norm in bundle compliance. Combined with two
decades of cumulative research that supports ABCDEF bundle
implementation as a strategy to improve the quality and quan-
tity of life of the critically ill (1–16), the future is very bright for
our field and our patients.
REFERENCES
1. 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; 335:1864–1869
2. 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; 371:126–134
3. Morandi A, Brummel NE, Ely EW: Sedation, delirium and mechani-
cal ventilation: The ‘ABCDE’ approach. Curr Opin Crit Care 2011;
17:43–49
4. Kress JP, Pohlman AS, O’Connor MF, et al: Daily interruption of seda-
tive infusions in critically ill patients undergoing mechanical ventila-
tion. N Engl J Med 2000; 342:1471–1477
5. Minhas MA, Velasquez AG, Kaul A, et al: Effect of protocolized seda-
tion on clinical outcomes in mechanically ventilated intensive care unit
patients: A systematic review and meta-analysis of randomized con-
trolled trials. Mayo Clin Proc 2015; 90:613–623
6. 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; 373:1874–1882
7. Carson SS, Kress JP, Rodgers JE, et al: A randomized trial of intermit-
tent lorazepam versus propofol with daily interruption in mechanically
ventilated patients. Crit Care Med 2006; 34:1326–1332
Critical Care Medicine www.ccmjournal.org 365
Copyright © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Editorials
8. Pandharipande P, Shintani A, Peterson J, et al: Lorazepam is an inde-
pendent risk factor for transitioning to delirium in intensive care unit
patients. Anesthesiology 2006; 104:21–26
9. Riker RR, Shehabi Y, Bokesch PM, et al: Dexmedetomidine vs mid-
azolam for sedation of critically ill patients: A randomized trial. JAMA
2009; 301:489–499
10. Jakob SM, Ruokonen E, Grounds RM, et al: Dexmedetomidine vs mid-
azolam or propofol for sedation during prolonged mechanical ventila-
tion: Two randomized controlled trials. JAMA 2012; 307:1151–1160
11. Needham DM, Korupolu R, Zanni JM, et al: Early physical medicine
and rehabilitation for patients with acute respiratory failure: A quality
improvement project. Arch Phys Med Rehabil 2010; 91:536–542
12. Khan BA, Fadel WF, Tricker JL, et al: Effectiveness of implementing
a wake up and breathe program on sedation and delirium in the ICU.
Crit Care Med 2014; 42:e791–e795
13. Balas MC, Vasilevskis EE, Olsen KM, et al: Effectiveness and safety
of the awakening and breathing coordination, delirium monitoring/
management, and early exercise/mobility bundle. Crit Care Med
2014; 42:1024–1036
14. Dale CR, Kannas DA, Fan VS, et al: Improved analgesia, sedation,
and delirium protocol associated with decreased duration of delirium
and mechanical ventilation. Ann Am Thorac Soc 2014; 11:367–374
15. Strøm T, Martinussen T, Toft P: A protocol of no sedation for critically
ill patients receiving mechanical ventilation: A randomised trial. Lancet
2010; 375:475–480
16. Liu V, Herbert D, Foss-Durant A, et al: Evaluation following stag-
gered implementation of the “Rethinking Critical Care” ICU care
bundle in a multicenter community setting. Crit Care Med 2016;
44:460–467
17. Barnes-Daly MA, Phillips G, Ely EW: Improving Hospital Survival and
Reducing Brain Dysfunction at 7 California Community Hospitals:
Implementing PAD Guidelines via the ABCDEF Bundle in 6.064
Patients. Crit Care Med 2017; 45:171–178
18. Balas MC, Burke WJ, Gannon D, et al: Implementing the ABCDE
bundle into everyday care: Opportunities, challenges and lessons
learned for implementing the ICU pain, agitation and delirium (PAD)
guidelines. Crit Care Med 2013; 41:S116–S127
19. Schoenfeld DA, Bernard GR; ARDS Network: Statistical evaluation
of ventilator-free days as an efficacy measure in clinical trials of treat-
ments for acute respiratory distress syndrome. Crit Care Med 2002;
30:1772–1777
20. Pandharipande PP, Pun BT, Herr DL, et al: Effect of sedation with dex-
medetomidine vs lorazepam on acute brain dysfunction in mechani-
cally ventilated patients: The MENDS randomized controlled trial.
JAMA 2007; 298:2644–2653