Research Article| Volume 124, P72-80, June 2019

The study protocol for a randomized, controlled trial of acupuncture versus a sham procedure versus standard care alone for the treatment of delirium in acutely hospitalized older adults with a medical illness


      • Acupuncture improves cognitive function and reduces agitation in dementia.
      • We hypothesized that acupuncture may be effective in the treatment of delirium in patients with an acute illness.
      • We have planned a randomized study that will evaluate both the specific and the non-specific effects of acupuncture on delirium, as well as its safety and cost-effectiveness.



      Many hospitalized older adults experience delirium, but treatment options are limited. Acupuncture has been shown to improve cognitive function and reduce agitation in dementia. We hypothesize that acupuncture, when compared with a sham intervention, will reduce the duration and severity of delirium, normalize delirium biomarkers, and improve clinical outcomes related to delirium in acutely hospitalized older adults with a medical illness.


      This three-arm, prospective, randomized, clinical trial will evaluate adults aged over 65 years who are acutely hospitalized to an internal-medicine ward and diagnosed with delirium or subsyndromal delirium. The 288 patients (96 in each of three groups) will be randomly allocated to receive either daily true acupuncture with usual care, a daily sham procedure with usual care, or usual care only in a 1:1:1 distribution for up to one week or until the patient is delirium-free for over 48 h. Other delirium and clinical interventions will remain unchanged. Delirium will be diagnosed using DSM-5 criteria and its severity will be assessed using the long Confusion Assessment Method Severity (CAM-S) tool.


      The primary study outcome will be the daily CAM-S score over 7 days between the three groups. Secondary outcomes will include time to first resolution of the delirium (over 7 days), the proportion of days spent delirium-free, daily antipsychotic use, daily pain scores, sleep quality, morning serum cortisol and T3 levels, and midnight urinary cortisol/creatinine ratio, all determined twice a week, and delirium-related complications. Hospital mortality, duration of hospital stay and functional status at discharge will also be compared between the three groups. Adverse events potentially related to acupuncture will be evaluated daily. The cost-effectiveness of acupuncture will be estimated.


      This novel randomized study will evaluate both the specific and the non-specific effects of acupuncture on delirium, and related outcomes, and its safety. Potential mechanism(s) of action for acupuncture in reducing delirium will be explored and healthcare-related costs estimated. Positive study results may prove pivotal in facilitating a multimodal, non-pharmacologic, integrative approach to delirium treatment among older, medical inpatients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Maturitas
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Heyman N.
        • Nili F.
        • Shahory R.
        • Seleznev I.
        • Ben Natan M.
        Prevalence of delirium in geriatric rehabilitation in Israel and its influence on rehabilitation outcomes in patients with hip fractures.
        Int. J. Rehabil. Res. 2015; 38: 233-237
        • Davis D.H.
        • Barnes L.E.
        • Stephan B.C.
        • et al.
        The descriptive epidemiology of delirium symptoms in a large population-based cohort study: results from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).
        BMC Geriatr. 2014; 14: 87
        • Hsieh S.J.
        • Madahar P.
        • Hope A.A.
        • Zapata J.
        • Gong M.N.
        Clinical deterioration in older adults with delirium during early hospitalisation: a prospective cohort study.
        BMJ Open. 2015; 5: e007496
        • Inouye S.K.
        • Marcantonio E.R.
        • Metzger E.D.
        Doing damage in delirium: the hazards of antipsychotic treatment in elderly persons.
        Lancet Psychiatry. 2014; 1: 312-315
        • Goldberg A.
        • Straus S.E.
        • Hamid J.S.
        • Wong C.L.
        Room transfers and the risk of delirium incidence amongst hospitalized elderly medical patients: a case–control study.
        BMC Geriatr. 2015; 15: 69
        • Noriega F.J.
        • Vidán M.T.
        • Sánchez E.
        • et al.
        Incidence and impact of delirium on clinical and functional outcomes in older patients hospitalized for acute cardiac diseases.
        Am. Heart J. 2015; 170: 938-944
        • Leslie D.L.
        • Inouye S.K.
        The importance of delirium: economic and societal costs.
        J. Am. Geriatr. Soc. 2011; 59: S241-S243
        • Inouye S.K.
        Delirium in older persons.
        N. Engl. J. Med. 2006; 354: 1157-1165
        • Van Eijsden W.A.
        • Raats J.W.
        • Mulder P.G.
        • van der Laan L.
        New aspects of delirium in elderly patients with critical limb ischemia.
        Clin. Interv. Aging. 2015; 10: 1537-1546
        • Kazmierski J.
        • Banys A.
        • Latek J.
        • Bourke J.
        • Jaszewski R.
        Cortisol levels and neuropsychiatric diagnosis as markers of postoperative delirium: a prospective cohort study.
        Crit. Care. 2013; 17: R38
        • Colkesen Y.
        • Giray S.
        • Ozenli Y.
        • Sezgin N.
        • Coskun I.
        Relation of serum cortisol to delirium occurring after acute coronary syndromes.
        Am. J. Emerg. Med. 2013; 31: 161-165
        • Shiwa T.
        • Oki K.
        • Yamane K.
        • et al.
        Significantly high level of late-night free cortisol to creatinine ratio in urine specimen in patients with subclinical Cushing's syndrome.
        Clin. Endocrinol. (Oxf.). 2013; 79: 617-622
        • Hipp D.M.
        • Ely E.W.
        Pharmacological and nonpharmacological management of delirium in critically ill patients.
        Neurotherapeutics. 2012; 9: 158-175
        • NICE-Guidelines
        Delirium: Prevention, Diagnosis and Management.
        2010 (
        • Sternberg S.A.
        • Chandran A.
        • Sikka M.
        Alternative therapy use by elderly African Americans attending a community clinic.
        J. Am. Geriatr. Soc. 2003; 51: 1768-1772
        • Ryder P.T.
        • Wolpert B.
        • Orwig D.
        • Oarter-Pokras O.
        • Black S.A.
        Complementary and alternative medicine use among older urban African Americans: individual and neighborhood associations.
        J. Natl. Med. Assoc. 2008; 100: 1186-1192
        • Loera J.A.
        • Reyes-Ortiz C.
        • Kuo Y.-F.
        Predictors of complementary and alternative medicine use among older Mexican Americans.
        Complement. Ther. Clin. Pract. 2007; 13: 224-231
        • Langevin H.M.
        • Churchill D.L.
        • Wu J.
        • et al.
        Evidence of connective tissue involvement in acupuncture.
        FASEB J. 2002; 16: 872-874
        • Zeng B.Y.
        • Salvage S.
        • Jenner P.
        1st ed. Effect and Mechanism of Acupuncture on Alzheimer's Disease. vol. 111. Elsevier Inc., 2013
        • Zhang M.
        • Xv G.H.
        • Wang W.X.
        • Meng D.J.
        • Ji Y.
        Electroacupuncture improves cognitive deficits and activates PPAR-gamma in a rat model of Alzheimer's disease.
        Acupunct. Med. 2017; 35: 44-51
        • Zhu H.
        • Dong K.
        • Wu Y.
        • et al.
        [Influence of acupuncture on isoprostane in patients with Alzheimer's disease].
        Zhongguo Zhenjiu. 2010; 30: 18-21
        • Yang M.-H.
        • Lin L.-C.
        • Wu S.-C.
        • Chiu J.-H.
        • Wang P.-N.
        • Lin J.-G.
        Comparison of the efficacy of aroma-acupressure and aromatherapy for the treatment of dementia-associated agitation.
        BMC Complement. Altern. Med. 2015; 15: 93
        • Lin L.C.
        • Yang M.H.
        • Kao C.C.
        • Wu S.C.
        • Tang S.H.
        • Lin J.G.
        Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.
        J. Am. Geriatr. Soc. 2009; 57: 1022-1029
        • Yang M.H.
        • Wu S.C.
        • Lin J.G.
        • Lin L.C.
        The efficacy of acupressure for decreasing agitated behaviour in dementia: a pilot study.
        J. Clin. Nurs. 2007; 16: 308-315
        • Matsumoto-Miyazaki J.
        • Ushikoshi H.
        • Miyata S.
        • et al.
        Acupuncture and traditional herbal medicine therapy prevent delirium in patients with cardiovascular disease in intensive care units.
        Am. J. Chin. Med. 2017; 45: 1-14
        • Levy I.
        • Attias S.
        • Ben-Arye E.
        • Bloch B.
        • Schiff E.
        Complementary medicine for treatment of agitation and delirium in older persons: a systematic review and narrative synthesis.
        Int. J. Geriatr. Psychiatry. 2017; 32: 492-508
        • Gaw A.
        • Chang L.
        • Shaw L.-C.
        Efficacy of acupuncture on osteoarthritic pain. A controlled double-blind study.
        N. Engl. J. Med. 1975; 293: 375-378
        • Assefi N.
        • Sherman K.
        • Jacobsen C.
        • Goldberg J.
        • Smith W.
        • Buchwald D.
        A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia.
        Ann. Intern. Med. 2005; 143: 10-19
        • Jian J.
        • Shao Y.
        • Wan L.
        • et al.
        Autopsy diagnosis of acupuncture-induced bilateral tension pneumothorax using whole-body postmortem computed tomography: a case report.
        Medicine. 2018; 97: e13059
        • Enblom A.
        • Johnsson A.
        Type and frequency of side effects during PC6 acupuncture: observations from therapists and patients participating in clinical efficacy trials of acupuncture.
        Acupunct. Med. 2017; : 1-9
        • Schiff E.
        • Levy I.
        • Arnon Z.
        • Ben-Arye E.
        • Attias S.
        First, keep it safe: integration of a complementary medicine service within a hospital.
        Int. J. Clin. Pract. 2018; 72
        • Liang S.
        • Lin Y.
        • Lin B.
        • et al.
        Resting-state functional magnetic resonance imaging analysis of brain functional activity in rats with ischemic stroke treated by electro-acupuncture.
        J. Stroke Cerebrovasc. Dis. 2017; 26: 1953-1959
        • Mcculloch M.
        • Nachat A.
        • Schwartz J.
        • Casella-Gordon V.
        • Cook J.
        Acupuncture safety in patients receiving anticoagulants: a systematic review.
        Perm. J. 2015; 19: 68-73
        • Zhou J.
        • Peng W.
        • Xu M.
        • Li W.
        • Liu Z.
        The effectiveness and safety of acupuncture for patients with Alzheimer disease: a systematic review and meta-analysis of randomized controlled trials.
        Medicine (Baltimore). 2015; 94: e933
        • Minchom A.
        • Punwani R.
        • Filshie J.
        • et al.
        A randomised study comparing the effectiveness of acupuncture or morphine versus the combination for the relief of dyspnoea in patients with advanced non-small cell lung cancer and mesothelioma.
        Eur. J. Cancer. 2016; 61: 102-110
        • Fønnebø V.
        • Grimsgaard S.
        • Walach H.
        • et al.
        Researching complementary and alternative treatments – the gatekeepers are not at home.
        BMC Med. Res. Methodol. 2007; 7: 7
        • Bellelli G.
        • Morandi A.
        • Davis D.H.J.
        • et al.
        Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people.
        Age Ageing. 2014; 43: 496-502
        • Inouye S.K.
        • Van Dyck C.H.
        • Alessi C.A.
        • Balkin S.
        • Siegal A.P.
        • Horwitz R.I.
        Clarifying confusion: the confusion assessment method. A new method for detection.
        Ann. Intern. Med. 1990; 113: 941-948
        • Kolanowski A.
        • Fick D.
        • Litaker M.
        • et al.
        Effect of cognitively stimulating activities on symptom management of delirium superimposed on dementia: a randomized controlled trial.
        J. Am. Geriatr. Soc. 2016; 64: 2424-2432
        • Morandi A.
        • Han J.H.
        • Meagher D.
        • et al.
        Detecting delirium superimposed on dementia: evaluation of the diagnostic performance of the Richmond Agitation and Sedation Scale.
        J. Am. Med. Dir. Assoc. 2016; 17: 828-833
        • Takakura N.
        • Yajima H.
        A double-blind placebo needle for acupuncture research.
        BMC Complement. Altern. Med. 2007; 7: 1-5
        • Vase L.
        • Baram S.
        • Takakura N.
        • et al.
        Can acupuncture treatment be double-blinded? An evaluation of double-blind acupuncture treatment of postoperative.
        PLOS ONE. 2015; 10: e0119612
        • Schlaeger J.M.
        • Takakura N.
        • Yajima H.
        • et al.
        Double-blind acupuncture needles: a multi-needle, multi-session randomized feasibility study.
        Pilot Feasibility Stud. 2018; 4: 1-8
        • Marcantonio E.R.
        Delirium in hospitalized older adults.
        N. Engl. J. Med. 2017; 377: 1456-1466
        • Tahir T.A.
        • Mahajan D.
        Medicine (United Kingdom). 2016; 44: 724-728
        • Craig P.
        • Dieppe P.
        • Macintyre S.
        • Michie S.
        • Nazareth I.
        • Petticrew M.
        Developing and evaluating complex interventions: the new Medical Research Council guidance.
        BMJ Clin. Res. Ed. 2008; 337: a1655
        • MacPherson H.
        • Altman D.G.
        • Hammerschlag R.
        • et al.
        Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement.
        PLoS Med. 2010; 7: e1000261
        • Inouye S.K.
        • Kosar C.M.
        • Tommet D.
        • et al.
        The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts.
        Ann. Intern. Med. 2014; 160: 526-533
        • Chung K.-F.
        • Yeung W.-F.
        • Yu Y.-M.
        • Kwok C.-W.
        • Zhang S.-P.
        • Zhang Z.-J.
        Adverse events related to acupuncture: development and testing of a rating scale.
        Clin. J. Pain. 2015; 31: 922-928
        • Moher D.
        • Hopewell S.
        • Schulz K.
        • et al.
        CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials.
        J. Clin. Epidemiol. 2010; 63: e1-e37