Clinical Impact of the Implementation Strategies Used to Apply the 2013 Pain, Agitation/Sedation, Delirium or 2018 Pain, Agitation/Sedation, Delirium, Immobility, Sleep Disruption Guideline Recommendations: A Systematic Review and Meta-Analysis
Open accessAbstract
OBJECTIVES: To summarize the effectiveness of implementation strategies for ICU execution of recommendations from the 2013 Pain, Agitation/Sedation, Delirium (PAD) or 2018 PAD, Immobility, Sleep Disruption (PADIS) guidelines. DATA SOURCES: PubMed, CINAHL, Scopus, and Web of Science were searched from January 2012 to August 2023. The protocol was registered with PROSPERO (CRD42020175268). STUDY SELECTION: Articles were included if: 1) design was randomized or cohort, 2) adult population evaluated, 3) employed recommendations from greater than or equal to two PAD/PADIS domains, and 4) evaluated greater than or equal to 1 of the following outcome(s): short-term mortality, delirium occurrence, mechanical ventilation (MV) duration, or ICU length of stay (LOS). DATA EXTRACTION: Two authors independently reviewed articles for eligibility, number of PAD/PADIS domains, quality according to National Heart, Lung, and Blood Institute assessment tools, implementation strategy use (including Assess, prevent, and manage pain; Both SAT and SBT; Choice of analgesia and sedation; Delirium: assess, prevent, and manage; Early mobility and exercise; Family engagement and empowerment [ABCDEF] bundle) by Cochrane Effective Practice and Organization of Care (EPOC) category, and clinical outcomes. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. DATA SYNTHESIS: Among the 25 of 243 (10.3%) full-text articles included (n = 23,215 patients), risk of bias was high in 13 (52%). Most studies were cohort (n = 22, 88%). A median of 5 (interquartile range [IQR] 4–7) EPOC strategies were used to implement recommendations from two (IQR 2–3) PAD/PADIS domains. Cohort and randomized studies were pooled separately. In the cohort studies, use of EPOC strategies was not associated with a change in mortality (risk ratio [RR] 1.01; 95% CI, 0.9–1.12), or delirium (RR 0.92; 95% CI, 0.82–1.03), but was associated with a reduction in MV duration (weighted mean difference [WMD] –0.84 d; 95% CI, –1.25 to –0.43) and ICU LOS (WMD –0.77 d; 95% CI, –1.51 to 0.04). For randomized studies, EPOC strategy use was associated with reduced mortality and MV duration but not delirium or ICU LOS. CONCLUSIONS: Using multiple implementation strategies to adopt PAD/PADIS guideline recommendations may reduce mortality, duration of MV, and ICU LOS. Further prospective, controlled studies are needed to identify the most effective strategies to implement PAD/PADIS recommendations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Psychotropics that cause sedation, fatigue, cognitive deficits, mobility impairment, depression, and anorexia may be replaced by aerobic or PRT.
“For example, psychotropics that cause sedation, fatigue, cognitive deficits, mobility impairment, depression, and anorexia may be replaced by aerobic or PRT [[569], [570], [571], [572]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [571]
Some drugs can impair exercise engagement and adaptation, necessitating adjustments in exercise prescriptions, behavioral support, and monitoring.
“Some drugs can impair exercise engagement and adaptation, necessitating adjustments in exercise prescriptions, behavioral support, and monitoring.”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [571]
Psychotropics that cause sedation, fatigue, cognitive deficits, mobility impairment, depression, and anorexia may be replaced by aerobic or progressive resistance training.
“For example, psychotropics that cause sedation, fatigue, cognitive deficits, mobility impairment, depression, and anorexia may be replaced by aerobic or PRT [[569], [570], [571], [572]].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [571]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · BMJ · doi:10.1136/bmj.n71 · Cited by 108,283 · see citing works
Bias in meta-analysis detected by a simple, graphical test
Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997) · BMJ · doi:10.1136/bmj.315.7109.629 · Cited by 56,722 · see citing works
Meta-analysis in clinical trials
DerSimonian, R., & Laird, N. (1986) · Controlled Clinical Trials · doi:10.1016/0197-2456(86)90046-2 · Cited by 39,552 · see citing works
Wan, X., Wang, W., Liu, J., & Tong, T. (2014) · BMC Medical Research Methodology · doi:10.1186/1471-2288-14-135 · Cited by 11,735 · cited 3× · see citing works
“The median number of PAD/PADIS guideline elements reported per study was two (IQR 2–3).”
MethodInfluentialDevlin, J. W., Skrobik, Y. K., Gélinas, C., Needham, D. M., Slooter, A. J. C., Pandharipande, P. P., Watson, P. L., Weinhouse, G. L., Nunnally, M., Rochwerg, B. N., et al. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003299 · Cited by 4,074 · see citing works
Self-citationBarr, J. A., Fraser, G. L., Puntillo, K., Ely, E. W., Gélinas, C., Dasta, J. F., Davidson, J. E., Devlin, J. W., Kress, J. P., Joffe, A. M., et al. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182783b72 · Cited by 3,785 · see citing works
Self-citationGRADE guidelines: 9. Rating up the quality of evidence
Guyatt, G. H., Oxman, A. D., Sultan, S., Glasziou, P., Akl, E. A., Alonso-Coello, P., Atkins, D., Kunz, R., Brozek, J., Montori, V., et al. (2011) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2011.06.004 · Cited by 1,336 · see citing works
Barriers and Strategies in Guideline Implementation—A Scoping Review
Fischer, F., Lange, K., Klose, K., Greiner, W., & Kraemer, A. (2016) · Healthcare · doi:10.3390/healthcare4030036 · Cited by 906 · see citing works
Delirium in the intensive care unit
Girard, T. D., Pandharipande, P. P., & Ely, E. W. (2008) · Critical Care · doi:10.1186/cc6149 · Cited by 628 · see citing works
Sedation and Delirium in the Intensive Care Unit
Reade, M. C., & Finfer, S. R. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1208705 · Cited by 619 · see citing works
The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families
Ely, E. W. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002175 · Cited by 514 · see citing works
Intensive care unit quality improvement: A “how-to” guide for the interdisciplinary team*
Curtis, J. R., Cook, D. J., Wall, R. J., Angus, D. C., Bion, J., Kacmarek, R. M., Kane‐Gill, S. L., Kirchhoff, K. T., Levy, M. M., Mitchell, P. H., et al. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000190617.76104.ac · Cited by 365 · see citing works
Self-citationSedation, delirium and mechanical ventilation: the ‘ABCDE’ approach
Morandi, A., Brummel, N. E., & Ely, E. W. (2010) · Current Opinion in Critical Care · doi:10.1097/mcc.0b013e3283427243 · Cited by 357 · see citing works
Trogrlić, Z., van der Jagt, M., Bakker, J., Balas, M. C., Ely, E. W., van der Voort, P. H. J., & Ista, E. (2015) · Critical Care · doi:10.1186/s13054-015-0886-9 · Cited by 271 · see citing works
Management of pain in cardiac surgery ICU patients: Have we improved over time?
Gélinas, C. (2007) · Intensive and Critical Care Nursing · doi:10.1016/j.iccn.2007.03.002 · Cited by 188 · see citing works
Hsieh, S.-J. J., Otusanya, O., Gershengorn, H. B., Hope, A. A., Dayton, C., Levi, D., García, M. L., Prince, D. Z., Mills, M. G., Fein, D., et al. (2019) · Critical Care Medicine · doi:10.1097/ccm.0000000000003765 · Cited by 173 · see citing works
Frequency, Severity, and Treatment of Agitation in Young versus Elderly Patients in the ICU
Fraser, G. L., Prato, B. S., Riker, R. R., Berthiaume, D., & Wilkins, M. L. (2000) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.20.1.75.34663 · Cited by 160 · see citing works
Secular trends and evaluation of complex interventions: the rising tide phenomenon
Chen, Y., Hemming, K., Stevens, A. J., & Lilford, R. J. (2015) · BMJ Quality & Safety · doi:10.1136/bmjqs-2015-004372 · Cited by 102 · see citing works
Effect of ABCDE Bundle Implementation on Prevalence of Delirium in Intensive Care Unit Patients
Bounds, M., Kram, S. J., Speroni, K. G., Brice, K., Luschinski, M. A., Harte, S. E., & Daniel, M. G. (2016) · American Journal of Critical Care · doi:10.4037/ajcc2016209 · Cited by 100 · see citing works
A Systematic Review of Risk Factors for Sleep Disruption in Critically Ill Adults
Honarmand, K., Rafay, H., Le, J., Mohan, S., Rochwerg, B. N., Devlin, J. W., Skrobik, Y. K., Weinhouse, G. L., Drouot, X., Watson, P. L., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004405 · Cited by 98 · see citing works
Self-citationLéone, M., Ragonnet, B., Alonso, S., Allaouchiche, B., Constantin, J., Jaber, S., Martin, C., Fabbro-Péray, P., & Lefrant, J. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e31826571f2 · Cited by 95 · see citing works
Al‐Qadheeb, N. S., Balk, E. M., Fraser, G. L., Skrobik, Y. K., Riker, R. R., Kress, J. P., Whitehead, S., & Devlin, J. W. (2014) · Critical Care Medicine · doi:10.1097/ccm.0000000000000224 · Cited by 87 · see citing works
Self-citationDevlin, J. W., Skrobik, Y. K., Rochwerg, B. N., Nunnally, M., Needham, D. M., Gélinas, C., Pandharipande, P. P., Slooter, A. J. C., Watson, P. L., Weinhouse, G. L., et al. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003298 · Cited by 87 · see citing works
Self-citationDeng, L., Cao, L., Zhang, L., Peng, X., & Zhang, L. (2020) · Journal of Critical Care · doi:10.1016/j.jcrc.2020.08.019 · Cited by 86 · see citing works
Dissemination and Implementation Research Funded by the US National Institutes of Health, 2005–2012
Tinkle, M. B., Kimball, R., Haozous, E. A., Shuster, G. F., & Meize‐Grochowski, R. (2013) · Nursing Research and Practice · doi:10.1155/2013/909606 · Cited by 79 · see citing works
Faust, A. C., Rajan, P., Sheperd, L. A., et al. (2016) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000001393 · Cited by 78 · see citing works
Effectiveness of Bundle Interventions on ICU Delirium: A Meta-Analysis*
Zhang, S., Han, Y., Xiao, Q., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004773 · Cited by 76 · see citing works
Balas, M. C., Weinhouse, G. L., Denehy, L., Chanques, G., Rochwerg, B. N., Misak, C., Skrobik, Y. K., Devlin, J. W., & Fraser, G. L. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003307 · Cited by 72 · see citing works
Self-citationKram, S. L., DiBartolo, M. C., Hinderer, K. A., & Jones, R. A. (2015) · Dimensions of Critical Care Nursing · doi:10.1097/dcc.0000000000000129 · Cited by 67 · see citing works
Kotfis, K., Zegan-Barańska, M., Żukowski, M., et al. (2017) · BMC Anesthesiology · doi:10.1186/s12871-017-0415-2 · Cited by 59 · see citing works
Effectiveness of Implementing a Wake Up and Breathe Program on Sedation and Delirium in the ICU
Khan, B. A., Fadel, W. F., Tricker, J. L., et al. (2014) · Critical Care Medicine · doi:10.1097/ccm.0000000000000660 · Cited by 58 · see citing works
Moraes, F. D. S., Marengo, L. L., Moura, M. D. G., Bergamaschi, C. D. C., Fiol, F. D. S. D., Lopes, L. C., Silva, M. T., & Barberato-Filho, S. (2022) · Medicine · doi:10.1097/md.0000000000029499 · Cited by 58 · see citing works
Kamdar, B. B., Combs, M. P., Colantuoni, E., King, L. M., Niessen, T. M., Neufeld, K. J., Collop, N. A., & Needham, D. M. (2016) · Critical Care · doi:10.1186/s13054-016-1433-z · Cited by 53 · see citing works
Trogrlić, Z., van der Jagt, M., Lingsma, H. F., Gommers, D. A. M. P. J., Ponssen, H. H., Schoonderbeek, J., Schreiner, F. A. G., Verbrugge, S. J. C., Duran, S., Bakker, J., et al. (2019) · Critical Care Medicine · doi:10.1097/ccm.0000000000003596 · Cited by 50 · see citing works
A Scoping Review of Implementation Science in Adult Critical Care Settings
McNett, M., O’Mathúna, D. P., Tucker, S., Roberts, H., Mion, L. C., & Balas, M. C. (2020) · Critical Care Explorations · doi:10.1097/cce.0000000000000301 · Cited by 48 · see citing works
Implementing a Multicomponent Intervention to Prevent Delirium Among Critically Ill Patients
Martínez, F. T., Donoso, A. M., Marquez, C., & Labarca, E. (2017) · Critical Care Nurse · doi:10.4037/ccn2017531 · Cited by 43 · see citing works
Larsen, L. K., Møller, K., Petersen, M., et al. (2020) · Intensive and Critical Care Nursing · doi:10.1016/j.iccn.2020.102816 · Cited by 39 · see citing works
Effects of the ABCDE bundle on the prevention of post‐intensive care syndrome: A retrospective study
Lee, Y., Kim, K., Lim, C., & Kim, J. (2019) · Journal of Advanced Nursing · doi:10.1111/jan.14267 · Cited by 32 · see citing works
Brennan, K. J., Sanchez, D., Hedges, S., Lynch, J. M., Hou, Y. C., Sayfe, M. A., Shunker, S., Bogdanoski, T., Hunt, L., Alexandrou, E., et al. (2022) · Australian Critical Care · doi:10.1016/j.aucc.2022.08.005 · Cited by 22 · see citing works
Implementing the 2013 PAD Guidelines: Top Ten Points to Consider
Balas, M. C., Davidson, J. E., & Pun, B. T. (2013) · Seminars in Respiratory and Critical Care Medicine · doi:10.1055/s-0033-1342985 · Cited by 20 · see citing works
Movements and trends in intensive care pain treatment and sedation: What matters to the patient?
Wøien, H. (2020) · Journal of Clinical Nursing · doi:10.1111/jocn.15179 · Cited by 19 · see citing works
Sullinger, D., Gilmer, A., Jurado, L. V., Zimmerman, L. H., Steelman, J., Gallagher, A., Dupre, T., & Acquista, E. (2016) · Annals of Pharmacotherapy · doi:10.1177/1060028016668627 · Cited by 18 · see citing works
Effects of ABCDE Bundle on Hemodynamics in Patients on Mechanical Ventilation
Ren, X., Li, J., Peng, C., et al. (2017) · Medical Science Monitor · doi:10.12659/msm.902872 · Cited by 17 · see citing works
Impact of Pain, Agitation, and Delirium Bundle on Delirium and Cognitive Function
Wang, X., Lv, D., Yun-Fang, C. H. E. N., Na, C. H. E. N., Li, X., Cheng-Fei, X. U., Yin, L. I., & Tian, L. (2022) · Journal of Nursing Research · doi:10.1097/jnr.0000000000000497 · Cited by 17 · see citing works
Pain, Agitation, and Delirium Guidelines
Jablonski, J., Gray, J. R., Miano, T. A., Redline, G., Teufel, H., Collins, T. A., Pascual-Lopez, J. L., Sylvia, M. L., & Martin, N. D. (2017) · Dimensions of Critical Care Nursing · doi:10.1097/dcc.0000000000000239 · Cited by 16 · see citing works
Bardwell, J., Brimmer, S., & Davis, W. D. (2020) · AACN Advanced Critical Care · doi:10.4037/aacnacc2020451 · Cited by 15 · see citing works
Tan, C. M., Camargo, M., Miller, F., et al. (2019) · BMJ Open Quality · doi:10.1136/bmjoq-2018-000421 · Cited by 14 · see citing works
Cinotti, R., Besnard, N., Desmedt, L. K. C., et al. (2020) · Burns · doi:10.1016/j.burns.2020.02.009 · Cited by 14 · see citing works
Brown, J. C., Querubin, J. A., Ding, L., et al. (2022) · Critical Care Explorations · doi:10.1097/cce.0000000000000679 · Cited by 14 · see citing works
Mo, Y., Zimmermann, A. E., & Thomas, M. C. (2016) · Journal of Pharmacy Practice · doi:10.1177/0897190015625396 · Cited by 13 · see citing works
Outcomes of protocolised analgesia and sedation in a neurocritical care unit
Mahmoud, L. N., Zullo, A. R., Thompson, B., & Wendell, L. C. (2018) · Brain Injury · doi:10.1080/02699052.2018.1469167 · Cited by 11 · see citing works
Assessment and Management of Delirium in Critically Ill Veterans
Kresevic, D. M., Miller, D., Fuseck, C. W., et al. (2020) · Critical Care Nurse · doi:10.4037/ccn2020137 · Cited by 9 · see citing works
Frawley, A., Hickey, J., Weaver, C., et al. (2019) · Anaesthesiology Intensive Therapy · doi:10.5603/ait.a2019.0004 · Cited by 7 · see citing works
Loberg, R. A., Smallheer, B., & Thompson, J. A. (2021) · Critical Care Nursing Quarterly · doi:10.1097/cnq.0000000000000387 · Cited by 6 · see citing works
Fish, J. T., Baxa, J., Draheim, R., et al. (2021) · Journal of Intensive Care Medicine · doi:10.1177/08850666211063404 · Cited by 6 · see citing works
Devabhakthuni, S., Kapoor, K., Verceles, A. C., et al. (2019) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/zxz265 · Cited by 4 · see citing works
Impact of a Multimodal Analgesia Protocol in an Intensive Care Unit: A Pre-post Cohort Study
de Souza, R. L. P., Abrão, J., Garcia, L. V., et al. (2022) · Cureus · doi:10.7759/cureus.22786 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Izquierdo, M., de Souto Barreto, P., Arai, H., Bischoff-Ferrari, H. A., Cadore, E. L., Cesari, M., Chen, L.-K., Coen, P. M., Courneya, K. S., Duque, G., et al. (2025) · The Journal of nutrition, health and aging · doi:10.1016/j.jnha.2024.100401 · Cited by 273 · see citing works
- Authors
- Hume, N. E., Zerfas, I., Wong, A., Klein-Fedyshin, M., Smithburger, P. L., Buckley, M. S., Devlin, J. W., & Kane-Gill, S. L.
- Affiliations
- University of Kentucky HealthCare (US)
- Michigan Medicine (US)
- Beth Israel Deaconess Medical Center (US)
- Health Sciences Library System, University of Pittsburgh, Pittsburgh, PA.
- University of Pittsburgh (US)
- Banner Health (US)
- Brigham and Women's Hospital (US)
- Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
- ORCID
- Venue
- Critical Care Medicine
- Published
- 2024-01-09
- Volume
- 52
- Issue
- 4
- Pages
- 626-636
- ISSN
- 0090-3493 (ISSN-L)
- PMC
- PMC10939834
- OpenAlex
- W4390779938
- Cited by
- 45
- References
- 57
- Citations by year
- 2026: 21 · 2025: 16 · 2024: 8
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R13AG072860)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- immobility, sleep disruption, implementation strategies, intensive care unit, delirium prevention, pain management, sedation, mechanical ventilation duration, ICU length of stay, mortality, early mobilization, family involvement, ABCDEF bundle, guideline implementation, critically ill adults, quality of evidence, risk of bias, heterogeneity
- MeSH terms
- Delirium, Humans, Intensive Care Units, Length of Stay, Psychomotor Agitation, Respiration, Artificial, Sleep Wake Disorders, Practice Guidelines as Topic, Pain Management
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
