The effectiveness of non-pharmacological interventions in reducing the incidence and duration of delirium in critically ill patients: a systematic review and meta-analysis
To evaluate the effect of non-pharmacological interventions versus standard care on incidence and duration of delirium in critically ill patients.
We searched electronic and grey literature for randomised clinical trials up to March 2018. Two reviewers independently screened, selected and extracted data. Meta-analysis was undertaken using random effects modelling.
We identified 15 trials (2812 participants). Eleven trials reported incidence of delirium. Pooled data from four trials of bright light therapy showed no significant effect between groups (n = 829 participants, RR 0.45, 99% CI 0.10–2.13, P = 0.19, very low quality evidence). Seven trials of various individual interventions also failed to report any significant effects. A total of eight trials reported duration of delirium. Pooled data from two trials of multicomponent physical therapy showed no significant effect [n = 404 participants, MD (days) − 0.65, 99% CI − 2.73 to 1.44, P = 0.42, low quality of evidence]. Four trials of various individual interventions also reported no significant effects. A trial of family voice reorientation showed a beneficial effect [n = 30, MD (days) − 1.30, 99% CI − 2.41 to − 0.19, P = 0.003, very low quality evidence].
Current evidence does not support the use of non-pharmacological interventions in reducing incidence and duration of delirium in critically ill patients. Future research should consider well-designed and well-described multicomponent interventions and include adequately defined outcome measures.
KeywordsCritical care Delirium Meta-analysis Non-pharmacological interventions Systematic review
The authors acknowledge Mrs Patricia Watt, Mrs Brenda Allen and Mr Richard Fallis from Queen’s University Belfast medical library for their invaluable help in developing a search strategy and locating full text of manuscripts. The authors also thank E. Alvarez, R. Simons, L. Denehy, P. Black and C. Smith for providing additional information on their studies. This work was funded by a Doctoral Fellowship Award to LB by the Northern Ireland Health and Social Care research and development division. Funding was provided by Public Health Agency (Grant no. EAT/5092/14).
Compliance with ethical standards
Conflicts of interest
The lead author (LB) has been paid an honorarium for a presentation on non-pharmacological interventions for delirium management in critically ill patients by Orion Pharmaceuticals. Other authors report no conflict of interest.
- 6.Lat I, McMillian W, Taylor S, Janzen JM, Papadopoulos S, Korth L, Ehtisham A, Nold J, Agarwal S, Azocar R, Burke P (2009) The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med 37(6):1898–1905. https://doi.org/10.1097/CCM.0b013e31819ffe38 CrossRefPubMedGoogle Scholar
- 9.Milbrandt EB, Deppen S, Harrison PL, Shintani AK, Speroff T, Stiles RA, Truman B, Bernard GR, Dittus RS, Ely EW (2004) Costs associated with delirium in mechanically ventilated patients. Crit Care Med 32:955–962. https://doi.org/10.1097/01.CCM.0000119429.16055.92 CrossRefPubMedGoogle Scholar
- 11.Devlin JW, Bhat S, Roberts RJ, Skrobik Y (2011) Current perceptions and practices surrounding the recognition and treatment of delirium in the intensive care unit: a survey of 250 critical care pharmacists from eight states. Ann Pharmacother 45:1217–1229. https://doi.org/10.1345/aph.1Q332 CrossRefPubMedGoogle Scholar
- 12.Page VJ, Ely EW, Gates S, Zhao XB, Alce T, Shintani A, Jackson J, Perkins GD, McAuley DF (2013) Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 1(7):515–523. https://doi.org/10.1016/S2213-2600(13),70166-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.van den Boogaard M, Slooter AJC, Bruggermann RJM, The REDUCE Study Investigators et al (2018) Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA 319(7):680–690. https://doi.org/10.1001/jama.2018.0160 CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Collet MO, Caballero J, Sonneville R et al (2018) Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study. Intensive Care Med 44:1081–1089. https://doi.org/10.1007/s00134-018-5204-y CrossRefPubMedGoogle Scholar
- 16.Barr J, Fraser GL, Puntillo K, American College of Critical Care Medicine et al (2013) Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 41(1):263–306. https://doi.org/10.1097/CCM.0b013e3182783b72 CrossRefPubMedGoogle Scholar
- 17.Trogrlić Z, van der Jagt M, Bakker J, Balas MC, Ely EW, van der Voort PH, Ista E (2015) A systematic review of implementation strategies for assessment, prevention, and management of ICU delirium and their effect on clinical outcomes. Crit Care 19:157. https://doi.org/10.1186/s13054-015-0886-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Barnes-Daly MA, Phillips G, Ely EW (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 45:171–178. https://doi.org/10.1097/CCM.0000000000002149 CrossRefPubMedGoogle Scholar
- 22.Bannon L, McGaughey J, Clarke M, McAuley DF, Blackwood B (2016) Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research. Syst Rev 5:75. https://doi.org/10.1186/s13643-016-0254-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Higgins JPT, Green S (eds) (2011) The Cochrane handbook for systematic reviews of interventions version 5.1.0, updated March 2011. The Cochrane Collaboration. http://www.cochrane-handbook.org. Accessed 29 Oct 2018
- 25.Review Manager (RevMan) [Computer program] (2014) Version [Version 5.3]. Copenhagen: The Nordic Cochrane Centre, The Cochrane CollaborationGoogle Scholar
- 27.GRADEpro GDT: GRADEpro Guideline Development Tool [Software] (2015) McMaster University (developed by Evidence Prime, Inc.). http://gradepro.org
- 30.Simons KS, Laheij RJ, van den Boogaard M, Moviat MA, Paling AJ, Polderman FN, Rozendaal FW, Salet GA, van der Hoeven JG, Pickkers P, de Jager CP (2016) Dynamic light application therapy to reduce the incidence and duration of delirium in intensive care patients: a randomised controlled trial. Lancet Respir Med 4(3):194–202. https://doi.org/10.1016/S2213-2600(16)00025-4 CrossRefPubMedGoogle Scholar
- 31.Potharajaroen S, Tangwongchai S, Tayjasanant T, Thawitsri T, Anderson G, Maes M (2018) Bright light and oxygen therapies decrease delirium risk in critically ill surgical patients by targeting sleep and acid base balance disturbances. Psychiatry Res 261:21–27. https://doi.org/10.1016/j.psychres.2017.12.046 CrossRefPubMedGoogle Scholar
- 32.Van Rompaey B, Elseviers MM, Van Drom W, Fromont V, Jorens PG (2012) The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients. Crit Care 16:R73. https://doi.org/10.1186/cc11330 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Álvarez EA, Garrido MA, Tobar EA, Prieto SA, Vergara SO, Briceño CD, González FJ (2017) Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: a pilot randomized clinical trial. J Crit Care 37:85–90. https://doi.org/10.1016/j.jcrc.2016.09.002 CrossRefPubMedGoogle Scholar
- 37.Girard TD, Kress JP, Fuchs BD et al (2008) 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 371:126–134. https://doi.org/10.1016/S0140-6736(08)60105-1 CrossRefPubMedGoogle Scholar
- 38.Mehta S, Burry L, Cook D, SLEAP Investigators, Canadian Critical Care Trials Group et al (2012) Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomised controlled trial. JAMA 308:1985–1992. https://doi.org/10.1001/jama.2012.13872 CrossRefPubMedGoogle Scholar
- 41.Giraud K, Pontin M, Sharples LD, Fletcher P, Dalgleish T, Eden A, Jenkins DP, Vuylsteke A (2016) Use of a structured mirrors intervention does not reduce delirium incidence but may improve factual memory encoding in cardiac surgical ICU patients aged over 70 years: a pilot time-cluster randomized controlled trial. Front Aging Neurosci 8:228. https://doi.org/10.3389/fnagi.2016.00228 CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Rose L, Agar M, Burry LD, Campbell N, Clarke M, Lee J, Siddiqi N, Page VJ, Del-COrS Group (2017) Development of core outcome sets for effectiveness trials of interventions to prevent and/or treat delirium (Del-COrS): study protocol. BMJ Open 7:e016371-2017-016371. https://doi.org/10.1136/bmjopen-2017-01637 CrossRefGoogle Scholar
- 51.Liu X, Zhang K, Wang W, Xie G, Cheng B, Wang Y, Hu Y, Fang X (2016) Dexmedetomidine versus propofol sedation improves sublingual microcirculation after cardiac surgery: a randomized controlled trial. J Cardiothorac Vasc Anesth 30(6):1509–1515. https://doi.org/10.1053/j.jvca.2016.05.038 CrossRefPubMedGoogle Scholar
- 52.Poulsen LM, Andersen-Rnaberg NC (2018) Agents intervening against delirium in intensive care unit (AID-ICU). https://clinicaltrials.gov/ct2/show/NCT03392376. Accessed 30 Aug 2018