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The ABCDEF Bundle in the ICU
Anthony Massaro MDDirector, Medical Intensive Care Unit
Division of Pulmonary and Critical CareBrigham and Women’s Hospital
Anthony Massaro, MD
• Harvard Medical School
• Medicine Residency @BWH
• Pulmonary Critical Care Medicine Fellowship @Harvard Program
• Instructor of Medicine@ HMS
– Clinical focus: Critical Care, Acute Respiratory Failure
– Research focus: Quality Improvement
Disclosures
• I have no financial disclosures
Objectives
• Goals of the ABCDEF Bundle implementation
• Individual elements of Bundle
– Data to demonstrate importance of bundle element
• What is the impact of effective adoption of the bundle?
• ABCDEF Bundle in the age of Covid
Intensive Care Unit Admission Sequelae
• Short Term
– Pain
– Agitation
– Delirium
– Immobility
– Sleep Disruption
• Long Term
– PICS
Post Intensive Care Syndrome (PICS)
• New or worsening function after critical illness
– Physical
• ICU acquired weakness
– Psychiatric
• Depression, anxiety, PTSD
– Cognitive
• Similar deficits to TBI or dementia
Factors Influencing PICS Development
Pre-Existing Conditions
Disease Process
ICU InterventionsTreatments
ABCDEF Bundle - Aims
• Provide care which reduce the short and long term sequelae of hospitalization with critical illness
• aka “Liberation Bundle”• Aka “A2FBundle”
• ICU Liberation Project– Society of Critical Care Medicine– https://www.sccm.org/ICULiberation/ABCDEF-
Bundles
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility and Exercise
F Family Engagement & Empowerment
ABCDEF (A2F) Bundle
• Bundles in ICU Care
– Sepsis
– CVC Placement
– Ventilator management
• Similarities to other ICU care bundles
– Interdependent
– Evidence based
– Multidisciplinary
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
• Key differences with ABCDEF Bundle
– Applicable to all ICU patients
– Applicable every day
– Focuses on symptoms assessment, prevention, management (not a specific disease process or procedure)
ABCDEF (A2F) Bundle
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
Goals of ABCDEF Bundle
• Short term outcomes– Reduce delirium– Reduce MV days– Reduce ICU and hospital LOS– Decrease mortality– Improve functional status at d/c hospital
• Long term outcomes– Reduce sequela which manifest as Post ICU Syndrome
• Support the 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep Disruption (PADIS)
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
Assess, Prevent and Manage Pain
• Why important?
– Common
– Long term sequela
• Delirium
• PTSD
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018Barr et al. Crit Care Med Vol 41 (1) Jan 2013
ICU Care is Associated with Pain Procedure N (%) Pre-procedural
Pain IntensityDuring Procedure Pain Intensity
Difference Median
p value
Chest tube removal 292 (6.1) 2 (0-4) 5 (3-7) 2.5 (0.5-4) <0.0001
Wound drain removal 75 (1.6) 2 (0-4) 4.5 (2-7) 2 (0-4.5) <0.0001
A line 199 (4.1) 1 (0-2.5) 4 (2-6) 2.75 (0-5) <0.0001
ETT suctioning 767 (15.9) 1 (0-4) 4 (1-6) 1.5 (0.4) <0.0001
Tracheal suctioning 302 (6.3) 1 (0-3.5) 4 (1-6) 1 (0-4) <0.0001
Peripheral IV 315 (6.5) 1 (0-3) 3 (1-5.5) 1 (0-3) <0.0001
Peripheral blood draw 328 (6.8) 0.5 (0-3) 3 (1-5) 1 (0-3) <0.0001
Turning 873 (18.1) 1.75 (0-4) 3 (0.25-6) 1 (0-2.5) <0.0001
Respiratory exercises 439 (9.1) 2 (0-4) 3 (1-5) 1 (0-2) <0.0001
Positioning 371 (7.7) 1 (0-4) 3 (0-5) 1 (0-2) <0.0001
Wound care 301 (6.3) 2 (0-4) 3 (1-6) 0.5 (0-2) <0.0001
Mobilization 526 (10.9) 1 (0-3) 2 (0-5) 0 (0-2) <0.0001
Puntillo et al. Am J Respir Crit Care Med. 2014 Vol 189 (1)
Pain – Assessment
• Management of pain for adult ICU patients should be guided by routine pain assessment (PADIS).– Good Practice Statement
• Tools• Self Reported
– 1-10 scale = gold standard
• CPOT (Critical Care Pain Observation Tool)
• BPS (Behavioral Pain Score)
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
Pain – Prevent / Manage
• Pain should be treated before a sedative agent is considered (PADIS).– Good Practice Statement
• Suggest using an assessment-driven, protocol-based, stepwise approach for pain and sedation in critically ill adults (PADIS)– conditional recommendation, moderate quality of
evidence
• Consider Nonpharmacologic interventions– conditional recommendation, very low to low quality
of evidence
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
SAT (Spontaneous Awakening Trial)
• Stop continuous IV sedatives
• Stop continuous IV narcotics (unless needed for pain control)
• Restart ½ dose
• Sedation minimization strategy
Impact of Spontaneous Awakening Trial
Variable Intervention Control P value
N=68 N=60
median (interquartile range)
Duration of MV (days) 4.9 (2.5-8.6) 7.3 (3.4-16.1) 0.004
LOS
ICU 6.4 (3.9-12.9) 9.9 (4.7-17.9) 0.02
Hospital 13.3 (7.3-20.0) 16.9 (8.5-26.6) 0.19
Kress et al. NEJM Vol 342 (20)
SAT paired with SBT – ABC Trial
Variable Intervention Control P value
N=167 N=168
median (interquartile range)
Ventilator-free days 14.7 (0.9) 11.6 (0.9) 0.02
LOS
ICU 9.1 (5.1-17.8) 12.9 (6.0-24.2) 0.01
Hospital 14.9 (8.9-26.8) 19.2 (10.3 to NA) 0.04
Mortality
28 Day 47 (28%) 58 (35%) 0.21
1-year 74 (44%) 97 (58%) 0.01
Girard et al. Lancet 2008 Jan 12;371 (9607):126-34
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
Oversedation – Poor Outcomes
Sedation and long term mortalityIn mechanically ventilated criticallyIll adults.
N-259Multicenter, longitudinal
Every 4 hrs sedation and daily delirium Assessment
Early = First 48 hrsDeep sedation <=-3 RASS
Shehabi et al. Intensive Care Med (2013) 39:910–918
Oversedation – Poor Outcomes
Early = First 48 hrsDeep sedation <=-3 RASS
Shehabi et al. Intensive Care Med (2013) 39:910–918
• Assessment of Agitation / Sedation (PADIS recommendation)–Current and subsequent sedation
status should be assessed using valid and reliable scales• RASS (Richmond Agitation and Sedation
Scale)• Riker Sedation-Agitation Scale
Choice of Analgesia and Sedation
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
• Suggest light sedation (vs deep sedation) in critically ill mechanically ventilated patients (PADIS)– conditional recommendation, low quality of evidence.– Strategies to minimize sedation
• SAT• Goal directed sedation management
• Using either propofol or dexmedetomidine over benzodiazepines in critically ill mechanically ventilated patients (PADIS)– conditional recommendation, low quality of evidence
Choice of Sedation - Treatment
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
SLEAP Trial• SLEAP – Sedation Lightening and Evaluation of a Protocol• Study design:
– Protocolized sedation vs– Protocolized sedation with SAT
• n=430• 16 tertiary care medical and surgical ICU• Outcomes:
– Primary• Time to extubation
– Secondary• ICU LOS, Hospital LOS• ICU, Hospital mortality• ICU Organ failure• Delirium• Unintentional device removal• Sedation and opioid dose
JAMA. 2012;308(19):1985-1992. doi:10.1001/jama.2012.13872
Mechanical Ventilation DurationProtocolized Sedation vs SAT
JAMA. 2012;308(19):1985-1992. doi:10.1001/jama.2012.13872
A Assess, Prevent and Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium: Assess, Prevent & Manage
E Early Mobility & Exercise
F Family Engagement & Empowerment
Delirium
• Syndrome of acute brain dysfunction characterized by inattention, fluctuating mental status, altered level of consciousness or disorganized thinking
Delirium
• Common– 81% of MV Patients
• Ely et al. JAMA 2004;291:1753-1762
• Impact – Increased
• Mechanical ventilation• ICU LOS• Hospital LOS• Cost• Mortality –
– Strongly associated with increased mortality even when adjusted for severity of disease
• Post – ICU Cognitive impairment
Jorge I F Salluh et al. BMJ 2015;350:bmj.h2538
Delirium – Impact on MV Duration
Jorge I F Salluh et al. BMJ 2015;350:bmj.h2538
Delirium – Impact on ICU LOS
Jorge I F Salluh et al. BMJ 2015;350:bmj.h2538
Delirium – Impact on Hospital Mortality
Assessment of Delirium
• Most commonly used scales
– Confusion Assessment Method – ICU
– Intensive Care Delirium Screening Checklist
Delirium Prevention– PADIS Guidelines• Recommendation. Using a multicomponent,
nonpharmacologic intervention that is focused on (but not limited to) reducing modifiable risk factors for delirium, improving cognition, and optimizing sleep, mobility, hearing, and vision in critically ill adults– conditional recommendation, low quality of evidence.
• Interventions include:– Improved wakefulness (minimize sedation)
• “B” and “C” component of bundle
– Reduce immobility (early rehabilitation / mobilization)• “E” component of bundle
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
Delirium Prevention – PADIS Guidelines
• Suggest not using haloperidol, an atypical antipsychotic, dexmedetomidine, a HMG-CoA reductase inhibitor (i.e., statin), or ketamine to prevent delirium in all critically ill adults
– conditional recommendation, very low to low level of evidence.
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
Delirium Treatment – PADIS Guidelines• Suggest not using haloperidol or an atypical
antipsychotic to treat subsyndromal delirium.– conditional recommendation, very low to low level of
evidence
• Suggest not routinely using haloperidol, an atypical antipsychotic, or a HMG-CoA reductase inhibitor (i.e., a statin) to treat delirium.– conditional recommendation, low quality of evidence
• Suggest dexmedetomidine in ventilated adults if agitation is precluding weaning/extubation.– conditional recommendation, low quality of evidence
Devlin et al. Crit Care Med 2018; 46:e825-873 September 2018
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement
• Prospective cohort study
• Intervention: Mobilization (mobility team)
• Enrolled within 48 hrs intubation
• Prior to ICU admission– Able to walk without assistance
– No prior cognitive impairment
• Primary outcome: Proportion of patients receiving PT– Only patients who survived to discharge included in
analysis
Morris et al Crit Care Med 2008 Vol 36; No 8
Early Intensive Care Mobility Therapy
Variable Intervention Control P value
N=145 N=135
median (confidence intervals)
Day to first out of bed 8.5 (6.6-10.5) 13.7 (11.5-15.7) <0.001
Day to first out of bed (adj) 5.0 (4.3-5.9) 11.3 (9.6-13.4) <0.001
Mechanical ventilation 7.9 (6.4-09.3) 9.0 (7.5-10.4) .298
Mechanical ventilation (adj) 8.8 (7.4-10.3) 10.2 (8.7-11.7) .163
LOS
ICU 7.6 (6.3-8.8) 8.1 (7.0-9.3) 0.084
ICU (adj) 5.5 (4.7-6.3) 6.9 (5.9-8.0) 0.025
Hospital 14.9 (12.6-17.1) 17.2 (14.2-20.2) 0.048
Hospital (adj) 11.2 (9.7-12.8) 14.5 (12.7-16.7) 0.006
Adjust for BMI, APACHE II and vasopressors
Morris et al Crit Care Med 2008 Vol 36; No 8
• Intervention: Early physical exercise and mobilization (PT and OT) paired with SAT
• Control: SAT (and usual care)
• Inclusion criteria
– > 18 years of age
– MV < 72 hrs
– Baseline functional independence
• 104 patientsSchweickert et al Lancet 2009 Vol 373
Impact of Early MobilizationIntervention Control p value
(n=49) (n=55)
Return to independent functional status 29 (59%) 19 (35%) 0.02
ICU Delirium (days) 2.0 (0.0-6.0) 4.0 (2.0-7.0) 0.03
ICU acquired paresis at hospital discharge 15 (31%) 27 (49%) 0.09
Ventilator free days 23.5 (7.4-25.6) 21.1 (0.0-23.8) 0.05
ICU LOS 5.9 (4.5-13.2) 7.9 (6.1-12.9) 0.08
Hospital LOS 13.5 (8.0-23.1) 12.9 (8.9-19.8) 0.93
Hospital Mortality 9 (18%) 14 (25%) 0.53
Schweickert et al Lancet 2009 Vol 373
Benefits of early mobilization
• Reduced delirium
• Reduced mechanical ventilation days
• Reduced ICU LOS
• Reduced Hospital LOS
A Assess, Prevent & Manage Pain
B Both SAT and SBT
C Choice of Analgesia and Sedation
D Delirium – Assess, Prevent & Manage
E Early Mobility
F Family Engagement & Empowerment
Family Engagement / Empowerment
• Aligned with Patient Centered Care
• Potential benefits– Anxiety reduction
– Cognitive - increased familiar stimulation therefor reduced delirium
• Perceived downsides– Burden on medical care team
– Interferes with care
– Increased infection
Family Engagement - Interventions
• Family presence
– Open visitation policies
– Family involvement on rounds
– Family presence at codes / procedures
• Family participation
– Rounds
– Structured family meetings
– Participation in care
• Flexible (up to 12 hrs) vs Restricted (median 4.5 hrs)• Cluster-crossover randomized• Patients, family members, and clinicians• 36 adult ICUs• Outcomes
– Primary• No reduction in Incidence of delirum p=0.44
– Secondary (Patient related)• ICU infections, & day ventilator free days, ICU LOS, Hospital mortality all without
significant difference.
– Secondary (Family Member related)• Anxiety, Depression and Satisfaction all significantly improved
– Secondary (ICU Staff related)• Burnout unchanged
Rosa et al. JAMA. 2019:233(3):216-228
Impact on Family Members
• Post traumatic stress symptoms 33.1%
• Subgroups
– Felt information was incomplete (48.4%)
– Relative died in ICU (50%)
– Relative died after end-of-life decisions (60%)
– Shared in EOL decision making (81.8%)
Azoulay et al. Am J Respir Crit Care Med Vol 171. pp 987–994, 2005
Post Intensive Care Syndrome - Family
• Acute stress disorder
– 33% of parents with children in ICU
• Posttraumatic stress disorder (PTSD)
– Median 21%; range 13-56%
• Anxiety
– Median 40%; range 21-56%
• Depression
– Median 23%; range 8-42%
Davidson et al. Crit Care Med 2012 Vol. 40, No. 2
Impact of ABCDE(F) Implementation
Reference # ICU # Patients
2019 Hsieh et al. Crit Care Med 47 (7):885-893 2 1855
2019 Pun et al. Crit Care Med 47(1):3-14 68 15,226
2017 Barnes-Daly et al. Crit Care Med 45(2):171–178 7 6064
2014 Balas et al. Crit Care Med 42(5):1024–1036 7 269
Impact of the Bundle
• Aim: Association between bundle compliance and outcomes– Hospital survival– Delirium or coma free days
• Prospective cohort; ICU patients• 7 community hospitals
– Mechanical ventilation (MV) and non MV
• Utilized earlier ABCDEF definition (same processes / reorganized)• Higher bundle compliance was independently associated with improved
survival and more days free of delirium and coma after adjusting for age, severity of illness, and presence of mechanical ventilation.
Barnes-Daly et al. Critical Care Medicine. 45(2):171-178, February 2017.
• Prospective
• Multicenter• 68 ICU• Academic, Community, Federal, Private• Medical, Surgical, Cardiac and Neurologic ICUs
• Patients 15,226• ICU Duration > 24 hrs
• Objective: Determine the association between ABCDEF performance and outcomes• Evaluate both complete and dose related (proportional) performance
Pun et al. Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in over 15,000 Adults. Crit Care Med 47 (1): 3-14 January 2019
Operational Definitions of ABCDEF Performance
BundleElement
Days Eligible Performance in last 24 hrs if documented that patient received:
A All days >= 6 pain assessments using valid and reliable instrument
B1 Days when receiving continuous or intermittent sedative infusions
SAT
B2 Days when on ventilatory support SBT
C All days >=6 agitation-sedation assessments using valid and reliable instrument
D All days >=2 delirium assessments using valid and reliable instrument
E All days Mobility activities that were higher then range of motion
F Days when family present Family member / significant other was educated on ABCDEF bundle and/ or participated in at least one of the following: rounds; conference; plan of care or ABCDEF related activity
Study Outcomes
Outcomes
Patient-Related
ICU Discharge
Hospital Discharge
Death
Symptom-Related
Mechanical Ventilation
Coma
Delirium
Significant Pain
Restraints
System-Related
ICU Readmission
Discharge Destination
Outcome - Complete vs Incomplete Performance
Outcomes Complete bundle Performance p Value
Patient Related Adjusted Hazard Ratio (95% CI)
ICU Discharge 1.17 (1.05-1.30) <0.004
Hospital Discharge 1.19 (1.01-1.40) <0.033
Death 0.32 (0.17-0.62) <0.001
Symptom-Related
Adjusted Odd ratio (95% CI)
Mechanical Ventilation 0.28 (0.22-0.36) <0.0001
Coma 0.35 (0.22-0.56) <0.0001
Delirium 0.60 (0.49-0.72) <0.0001
Significant Pain 1.03 (0.88-1.21) 0.70
Restraints 0.37 (0.30-0.46) <0.0001
System-Related Adjusted Odd ratio (95% CI)
ICU Readmission 0.54 (0.37-0.79) <0.001
Discharge Destination 0.64 (0.51-0.80) <0.001
Patient-Related Outcomes – Proportional Performance
Symptom-Related Outcomes – Proportional Performance
Percent of Eligible ABCDEF Bundle Elements Performed
System-Related Outcomes – Proportional Performance
ABCDEF Bundle and Covid-19
• Effective Adoption Requires
– Clinicians familiar with the bundle / processes
– Time for interdisciplinary communication
– Frequent patient assessment
– Frequent patient interventions
– Access to Families
ABCDEF Bundle and Covid-19
• Effective Adoption Requires– Clinicians familiar with the bundle / processes
• ICU teams with reduced staffing• ICU teams with Providers, Nurses, Respiratory Therapists, Pharmacists, Physical Therapists not usually
in ICU
– Time for interdisciplinary communication• Increased patient census / team• Revised rounding practices
– Frequent patient assessment– Frequent patient interventions
• PPE shortages• Minimization of risk to healthcare workers
– Access to Families• Restrictive visitor policies
• Bundle completion remains important• Strategies to Optimize ICU Liberation (A to F) Bundle Performance in Critically Ill
Adults With Coronavirus Disease 2019. – Devlin, J. et al. (2020). Critical Care Explorations, 2, e0139.
doi:10.1097/CCE.0000000000000139
Summary
• ABCDEF Bundle– Interdependent, Evidence based, Interdisciplinary
– All patients / every day
• Effective adoption– Short term benefits
• Reduced - Delirium, Mechanical ventilation, ICU LOS, Hospital LOS, Mortality
– Long term benefits• Patients
• Family
Question 1
An 80 y.o. male with history of COPD is admitted to ICU with pneumonia and hypoxemic respiratory failure. Mechanical ventilation is initiated and he is started on continuous IV midazolam for sedation. Which of the following interventions is not indicated to minimize the risk of delirium?
a) Daily spontaneous awakening trial (SAT).b) Midazolam order titrated to RASS 0 to -1c) Initiation of haloperidol delirium prevention protocol.d) Mobilization at the earliest time possible.
Question 1 - Answer
Which of the following interventions is not indicated to minimize the risk of delirium?
a) Daily spontaneous awakening trial (SAT).b) Benzodiazepines titrated to RASS 0 to -1c) Initiation of haloperidol prevention protocol.d) Mobilization at the earliest time possible.
Daily interruption of sedation and goal targeted sedation titration are two well established strategies to minimize total sedation dose. Minimization of benzodiazepine dose is associated with reduced incidence of delirium. Early mobility studies have demonstrated reduced delirium rates. There is no evidence to support protocolizeduse of haloperidol to prevent delirium.
Question 2
An 65 y.o. female with stage IV non-small cell lung cancer is admitted to the ICU with a chemotherapy related pneumonitis and acute respiratory failure. At home she is on standing (and as needed oxycodone) to control pain from multiple rib and spine metastases. Mechanical ventilation is initiated. She is placed on continuous midazolam and fentanyl drip. Which of the following interventions would be most appropriate to minimize duration of mechanical ventilation?
a) Daily spontaneous awakening trial (SAT) with cessation of continuous IV midazolam and fentanyl.
b) Daily SAT with cessation of continuous IV midazolam and continuation of fentanyl to control any pain. When needed restart midazolam at prior dose.
c) Transition from midazolam and fentanyl to propofold) Assure that all sedation orders are written to titrate RASS to 0 to -
1 and opiate to titrate to pain..
Question 2
Which of the following interventions is most appropriate to minimize duration of mechanical ventilation?
a) Daily spontaneous awakening trial (SAT) with cessation of continuous IV midazolam and fentanyl.
b) Daily SAT with cessation of continuous IV midazolam and continuation of fentanyl to control any pain. When needed restart midazolam at prior dose.
c) Transition from midazolam and fentanyl to propofold) Assure that all sedation orders are written to titrate RASS to 0 to -1 and opiate
to titrate to pain.
Daily cessation of sedation is well established intervention to reduce mechanical ventilation days. In this case option A is not most appropriate since the patient is on chronic opiate at home and the SAT should be performed with continuation of continuous opiate to control baseline pain (equivalent to dose given at home). Option B directs restart of midazolam at prior dose and the continuous IV drip should be started at half the prior rate and then titrated. It is reasonable to consider transition from midazolam to propofol but the patient needs some opiate as pain must be addressed. Control of pain and titration of sedation to RASS 0 to -1 is the best answer.
References• Devlin, J. W., et al. (2018). "Executive Summary: Clinical Practice Guidelines for the
Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU." Crit Care Med 46(9): 1532-1548.
• Ely, E. W. (2017). "The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families." Crit Care Med 45(2): 321-330.
• Salluh, J. I., et al. (2015). "Outcome of delirium in critically ill patients: systematic review and meta-analysis." BMJ 350: h2538.
• Davidson, J. E., et al. (2017). "Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU." Crit Care Med 45(1): 103-128.
• Barnes-Daly, M. A., et al. (2017). "Improving Hospital Survival and Reducing Brain Dysfunction at Seven California Community Hospitals: Implementing PAD Guidelines Via the ABCDEF Bundle in 6,064 Patients." Crit Care Med 45(2): 171-178.
• Pun, B. T., et al. (2019). "Caring for Critically Ill Patients with the ABCDEF Bundle: Results of the ICU Liberation Collaborative in Over 15,000 Adults." Crit Care Med47(1): 3-14.
Critical Care Medicine: January 2017 - Volume 45 - Issue 1 - p 103–128