What is the Delirium Bibliography? The searchable Delirium Bibliography page is one of our most popular features, allowing you to quickly gain access to the literature on delirium and acute care of older persons. It is primarily intended for clinicians and researchers interested in exploring these topics. The NIDUS team keeps it updated for you on a monthly basis!
How to Search for Articles: Search by author, title, year, and/or keywords. Each article is indexed by keywords taken from MEDLINE and other relevant databases. Click on the title of the article to read the abstract, journal, etc.
Reference Information
- Title
- Pharmacological interventions for the treatment of delirium in critically ill adults
- Authors
- Burry, L. Hutton, B. Williamson, D. R. Mehta, S. Adhikari, N. K. Cheng, W. Ely, E. W. Egerod, I. Fergusson, D. A. Rose, L.
- Year
- 2019
- Journal
- Cochrane Database Syst Rev
- Abstract
BACKGROUND: Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population. OBJECTIVES: Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients. SEARCH METHODS: We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings. SELECTION CRITERIA: We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of ‘nodes’ (i.e. drug classes) and ‘edges’ (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high. MAIN RESULTS: We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha2 agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha2 agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha2 agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo. AUTHORS’ CONCLUSIONS: We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha2 agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha2 agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.
- PMID
- Keywords
- Page(s)
- Volume
- 9
- Issue
| Title | Authors | Journal | Year | Keywords |
|---|---|---|---|---|
| Factors Associated with Length of Stay in Hospital Patients with and Without Dementia. | Möllers, T. Perna, L. Ihle, P. Schubert, I. Bauer, J. Brenner, H. | Journal of Alzheimer's Disease | 2019 |
adult |
| Does a Year Have 6 Months or 12? Implications for Delirium Detection Among Hospitalized Older General Medicine Patients. | Zhou, W. Ngo, L. H. Inouye, S. K. Gallagher, J. Husser, E. K. Fick, D. M. Marcantonio, E. R. | Journal of General Internal Medicine | 2018 |
adult |
| Serum soluble fibrinogen-like protein 2 concentration predicts delirium after acute pancreatitis. | Xu, W. B. Hu, Q. H. Wu, C. N. Fan, Z. K. Song, Z. F. | Brain Behav | 2019 |
acute pancreatitis |
| Use of the brief Confusion Assessment Method in a veteran palliative care population: A pilot validation study. | Wilson, J. E. Boehm, L. Samuels, L. R. Unger, D. Leonard, M. Roumie, C. Ely, E. W. Dittus, R. S. Misra, S. Han, J. H. | Palliat Support Care | 2019 |
cognition |
| Relative cerebral hyperperfusion during cardiopulmonary bypass is associated with risk for postoperative delirium: a cross-sectional cohort study. | Thudium, M. Ellerkmann, R. K. Heinze, I. Hilbert, T. | BMC Anesthesiology | 2019 |
Cardiac surgery |
| Prediction of postoperative delirium by comprehensive geriatric assessment among elderly patients with hip fracture. | Tao, L. Xiaodong, X. Qiang, M. Jiao, L. Xu, Z. | Ir J Med Sci | 2019 |
Comprehensive geriatric assessment |
| The Overlap Between Falls and Delirium in Hospitalized Older Adults: A Systematic Review. | Sillner, A. Y. Holle, C. L. Rudolph, J. L. | Clin Geriatr Med | 2019 |
Delirium |
| Depth of sedation as an interventional target to reduce postoperative delirium: mortality and functional outcomes of the Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients randomised clinical trial. | Sieber, F. Neufeld, K. J. Gottschalk, A. Bigelow, G. E. Oh, E. S. Rosenberg, P. B. Mears, S. C. Stewart, K. J. Ouanes, J. P. P. Jaberi, M. Hasenboehler, E. A. Wang, N. Y. | British Journal of Anaesthesia | 2019 |
NCT00590707 |
| Delirium Incidence and Functional Outcomes After Transcatheter and Surgical Aortic Valve Replacement. | Shi, S. M. Sung, M. Afilalo, J. Lipsitz, L. A. Kim, C. A. Popma, J. J. Khabbaz, K. R. Laham, R. J. Guibone, K. Lee, J. Marcantonio, E. R. Kim, D. H. | J Am Geriatr Soc | 2019 |
aortic valve replacement |
| Effect of perioperative administration of dexmedetomidine on delirium after cardiac surgery in elderly patients: a double-blinded, multi-center, randomized study. | Shi, C. Jin, J. Qiao, L. Li, T. Ma, J. Ma, Z. | Clin Interv Aging | 2019 |
anesthesia |
| Perspectives on the Delirium Experience and Its Burden: Common Themes Among Older Patients, Their Family Caregivers, and Nurses. | Schmitt, E. M. Gallagher, J. Albuquerque, A. Tabloski, P. Lee, H. J. Gleason, L. Weiner, L. S. Marcantonio, E. R. Jones, R. N. Inouye, S. K. Schulman-Green, D. | Gerontologist | 2019 |
*Burden |
| Association of Persistent Intense Thirst With Delirium Among Critically Ill Patients: A Cross-sectional Study. | Sato, K. Okajima, M. Taniguchi, T. | J Pain Symptom Manage | 2019 |
Thirst |
| Role of Epileptic Activity in Older Adults With Delirium, a Prospective Continuous EEG Study. | Sambin, S. Gaspard, N. Legros, B. Depondt, C. De Breucker, S. Naeije, G. | Front Neurol | 2019 |
Ncse |
| Surgical delay is a risk factor of delirium in hip fracture patients with mild–moderate cognitive impairment. | Pioli, G. Bendini, C. Giusti, A. Pignedoli, P. Cappa, M. Iotti, E. Ferri, M. A. Bergonzini, E. Sabetta, E. | Aging Clinical and Experimental Research | 2019 |
age |
| Cerebrospinal Fluid Spermidine, Glutamine and Putrescine Predict Postoperative Delirium Following Elective Orthopaedic Surgery. | Pan, X. Cunningham, E. L. Passmore, A. P. McGuinness, B. McAuley, D. F. Beverland, D. O'Brien, S. Mawhinney, T. Schott, J. M. Zetterberg, H. Green, B. D. | Sci Rep | 2019 | |
| The impact of the Hospital Elder Life Program on the treatment of asymptomatic bacteriuria: An unexpected benefit. | O'Donnell, A. J. Walsh, T. L. Tang, A. Weinberg, L. | Geriatr Nurs | 2019 |
Asymptomatic bacteriuria |
| Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium. | Nielsen, R. M. Urdanibia-Centelles, O. Vedel-Larsen, E. Thomsen, K. J. Moller, K. Olsen, K. S. Lauritsen, A. O. Eddelien, H. S. Lauritzen, M. Benedek, K. | Neurocrit Care | 2019 |
Brain diseases |
| Delirium risk factors and associated outcomes in a neurosurgical cohort: a case-control study. | Morshed, R. A. Young, J. S. Safaee, M. Sankaran, S. Berger, M. S. McDermott, M. W. Hervey-Jumper, S. L. | World Neurosurg | 2019 |
Delirium |
| Biomarker Predictors of Delirium in Acutely Ill Patients: A Systematic Review. | Michels, M. Michelon, C. Damasio, D. Vitali, A. M. Ritter, C. Dal-Pizzol, F. | J Geriatr Psychiatry Neurol | 2019 |
Cam |
| Predicting postoperative delirium severity in older adults: The role of surgical risk and executive function. | Lindroth, H. Bratzke, L. Twadell, S. Rowley, P. Kildow, J. Danner, M. Turner, L. Hernandez, B. Brown, R. Sanders, R. D. | Int J Geriatr Psychiatry | 2019 |
aging |
| Subsyndromal delirium is associated with poor functional outcome after ischaemic stroke. | Klimiec-Moskal, E. Lis, A. Pera, J. Slowik, A. Dziedzic, T. | European Journal of Neurology | 2019 |
aged |
| SF-36 scores predict postoperative delirium after surgery for cervical spondylotic myelopathy. | Kin, K. Yasuhara, T. Tomita, Y. Umakoshi, M. Morimoto, J. Date, I. | J Neurosurg Spine | 2019 |
CCI = Charlson Comorbidity Index |
| Effects of massage on outcomes of adult intensive care unit patients: a systematic review. | Jagan, S. Park, T. Papathanassoglou, E. | Nurs Crit Care | 2019 |
Complementary and alternative therapies |
| Perioperative Dexmedetomidine Reduces Delirium in Elderly Patients after Lung Cancer Surgery. | Huyan, T. Hu, X. Peng, H. Zhu, Z. Li, Q. Zhang, W. | Psychiatr Danub | 2019 | |
| The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. | Hov, K. R. Neerland, B. E. Undseth, O. Bruun Bratholm Wyller, V. MacLullich, A. M. J. Qvigstad, E. Skovlund, E. Wyller, T. B. | Int J Geriatr Psychiatry | 2019 |
Delirium treatment |
| Delirium and Alzheimer disease: A proposed model for shared pathophysiology. | Fong, T. G. Vasunilashorn, S. M. Libermann, T. Marcantonio, E. R. Inouye, S. K. | Int J Geriatr Psychiatry | 2019 |
Alzheimer disease |
| Development and validation of a dynamic delirium prediction rule in patients admitted to the Intensive Care Units (DYNAMIC-ICU): A prospective cohort study. | Fan, H. Ji, M. Huang, J. Yue, P. Yang, X. Wang, C. Ying, W. | International journal of nursing studies | 2019 |
aged |
| Delirium and cognitive impairment among older patients in Norwegian emergency departments. | Evensen, S. Saltvedt, I. Ranhoff, A. H. Myrstad, M. Myrstad, C. Mellingsaeter, M. Wang-Hansen, M. S. Neerland, B. E. | Tidsskr Nor Laegeforen | 2019 | |
| Motor activity across delirium motor subtypes in geriatric patients assessed using body-worn sensors: a Norwegian cross-sectional study. | Evensen, S. Bourke, A. K. Lydersen, S. Sletvold, O. Saltvedt, I. Wyller, T. B. Taraldsen, K. | BMJ Open | 2019 |
accelerometer |
| Factors Associated With Delirium in Surgical Intensive Care Unit Patients Treated With Supplemental Melatonin: A Case-Cohort Study. | Cusimano, J. M. Welch, S. Perez-Protto, S. Lam, S. | Clin Neuropharmacol | 2019 | |
| Intraoperative blood transfusion predicts postoperative delirium among older patients undergoing elective orthopedic surgery: A prospective cohort study. | Chou, M. Y. Wang, Y. C. Peng, L. N. Liang, C. K. Chu, C. S. Liao, M. C. Lin, Y. T. Hsu, C. J. Chen, L. K. | Int J Geriatr Psychiatry | 2019 |
aged |
| Postoperative delirium in critically ill surgical patients: incidence, risk factors, and predictive scores. | Chaiwat, O. Chanidnuan, M. Pancharoen, W. Vijitmala, K. Danpornprasert, P. Toadithep, P. Thanakiattiwibun, C. | BMC Anesthesiology | 2019 |
Intensive care unit (ICU) |
| Differential Clinical Characteristics, Management, and Outcome of Delirium among Ward Compared with ICU Patients. | Canet, E. Amjad, S. Robbins, R. Lewis, J. Matalanis, M. Jones, D. Bellomo, R. | Intern Med J | 2019 |
Agitation |
| Vitamin D levels and risk of delirium: A mendelian randomization study in the UK Biobank. | Bowman, K. Jones, L. Pilling, L. C. Delgado, J. Kuchel, G. A. Ferrucci, L. Fortinsky, R. H. Melzer, D. | Neurology | 2019 | |
| Single-bed rooms in a geriatric ward prevent delirium in older patients. | Blandfort, S. Gregersen, M. Rahbek, K. Juul, S. Damsgaard, E. M. | Aging Clin Exp Res | 2019 |
Delirium |
| Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016. | Aloisi, G. Marengoni, A. Morandi, A. Zucchelli, A. Cherubini, A. Mossello, E. Bo, M. Di Santo, S. G. Mazzone, A. Trabucchi, M. Cappa, S. Fimognari, F. L. Incalzi, R. A. Gareri, P. Perticone, F. Campanini, M. Montorsi, M. Latronico, N. Zambon, A. Bellelli, | J Clin Psychiatry | 2019 | |
| Patient Safety Incidents Describing Patient Falls in Critical Care in North West England Between 2009 and 2017. | Thomas, A. N. Balmforth, J. E. | J Patient Saf | 2019 | |
| Have you SCAND MMe Please? A framework to prevent harm during acute hospitalisation of older persons: A retrospective audit. | Redley, B. Baker, T. | Journal of Clinical Nursing | 2019 |
acute disease |
| Low-Dose Ketamine Infusion to Decrease Postoperative Delirium for Spinal Fusion Patients. | Plyler, S. S. Muckler, V. C. Titch, J. F. Gupta, D. K. Rice, A. N. | J Perianesth Nurs | 2019 |
3d-cam |
| Nurses' experiences of caring for older patients afflicted by delirium in a neurological department. | Kristiansen, S. Konradsen, H. Beck, M. | Journal of Clinical Nursing | 2019 |
adult |
| Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium: A Network Meta-analysis. | Wu, Y. C. Tseng, P. T. Tu, Y. K. Hsu, C. Y. Liang, C. S. Yeh, T. C. Chen, T. Y. Chu, C. S. Matsuoka, Y. J. Stubbs, B. Carvalho, A. F. Wada, S. Lin, P. Y. Chen, Y. W. Su, K. P. | JAMA Psychiatry | 2019 | |
| Effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery the engages randomized clinical trial. | Wildes, T. S. Mickle, A. M. Abdallah, A. B. Maybrier, H. R. Oberhaus, J. Budelier, T. P. Kronzer, A. McKinnon, S. L. Park, D. Torres, B. A. Graetz, T. J. Emmert, D. A. Palanca, B. J. Goswami, S. Jordan, K. Lin, N. Fritz, B. A. Stevens, T. W. Jacobsohn, E. | JAMA | 2019 |
NCT02241655 |
| Perioperative Epidural Use and Risk of Delirium in Surgical Patients: A Secondary Analysis of the PODCAST Trial. | Vlisides, P. E. Thompson, A. Kunkler, B. S. Maybrier, H. R. Avidan, M. S. Mashour, G. A. | Anesth Analg | 2019 | |
| Effect of Intravenous Acetaminophen vs Placebo Combined with Propofol or Dexmedetomidine on Postoperative Delirium among Older Patients Following Cardiac Surgery: The DEXACET Randomized Clinical Trial. | Subramaniam, B. Shankar, P. Shaefi, S. Mueller, A. O'Gara, B. Banner-Goodspeed, V. Gallagher, J. Gasangwa, D. Patxot, M. Packiasabapathy, S. Mathur, P. Eikermann, M. Talmor, D. Marcantonio, E. R. | JAMA | 2019 |
NCT02546765 |
| The use of a screening scale improves the recognition of delirium in older patients after cardiac surgery - a retrospective observational study. | Smulter, N. Claesson Lingehall, H. Gustafson, Y. Olofsson, B. Engstrom, K. G. | J Clin Nurs | 2019 |
Assessments scales |
| Incidence and predictors of postoperative delirium in the older acute care surgery population: a prospective study. | Saravana-Bawan, B. Warkentin, L. M. Rucker, D. Carr, F. Churchill, T. A. Khadaroo, R. G. | Canadian Journal of Surgery | 2019 |
aged |
| Association of Duration of Surgery With Postoperative Delirium Among Patients Receiving Hip Fracture Repair. | Ravi, B. Pincus, D. Choi, S. Jenkinson, R. Wasserstein, D. N. Redelmeier, D. A. | JAMA Netw Open | 2019 | |
| Depression Predicts Delirium After Coronary Artery Bypass Graft Surgery Independent of Cognitive Impairment and Cerebrovascular Disease: An Analysis of the Neuropsychiatric Outcomes After Heart Surgery Study. | Oldham, M. A. Hawkins, K. A. Lin, I. H. Deng, Y. Hao, Q. Scoutt, L. M. Yuh, D. D. Lee, H. B. | American Journal of Geriatric Psychiatry | 2019 |
aged |
| Accuracy of the Delirium Observational Screening Scale (DOS) as a screening tool for delirium in patients with advanced cancer. | Neefjes, E. C. W. van der Vorst, Mjdl Boddaert, M. S. A. Verdegaal, Batt Beeker, A. Teunissen, S. C. C. Beekman, A. T. F. Zuurmond, W. W. A. Berkhof, J. Verheul, H. M. W. | BMC Cancer | 2019 |
Delirium |
| The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study. | Nagae, M. Egi, M. Furushima, N. Okada, M. Makino, S. Mizobuchi, S. | J Anesth | 2019 |
Delirium |
| Association between delirium, adverse clinical events and functional outcomes in older patients admitted to rehabilitation settings after a hip fracture: A multicenter retrospective cohort study. | Morandi, A. Mazzone, A. Bernardini, B. Suardi, T. Prina, R. Pozzi, C. Gentile, S. Trabucchi, M. Bellelli, G. | Geriatrics & Gerontology International | 2019 |
aged |
| Handover of anesthesia care is associated with an increased risk of delirium in elderly after major noncardiac surgery: results of a secondary analysis. | Liu, G. Y. Su, X. Meng, Z. T. Cui, F. Li, H. L. Zhu, S. N. Wang, D. X. | J Anesth | 2019 |
Delirium |
| Undiagnosed delirium is frequent and difficult to predict: Results from a prevalence survey of a tertiary hospital. | Lange, P. W. Lamanna, M. Watson, R. Maier, A. B. | J Clin Nurs | 2019 |
Undiagnosed delirium |