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Sedation Depth During Spinal Anesthesia and the Development of Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Repair


      To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium.


      We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (≥65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, ≥80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery.


      From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean ± SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5±1.5 days vs 1.4±4.0 days; P=.01).


      The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.
      Trial Registration: Identifier: NCT00590707
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        • Rasmussen LS
        • Moller JT
        Central nervous system dysfunction after anesthesia in the geriatric patient.
        Anesthesiol Clin North America. 2000; 18 (vi.): 59-70
        • Dyer CB
        • Ashton CM
        • Teasdale TA
        Postoperative delirium: a review of 80 primary data-collection studies.
        Arch Intern Med. 1995; 155: 461-465
        • Bitsch MS
        • Foss NB
        • Kristensen BB
        • Kehlet H
        Acute cognitive dysfunction after hip fracture: frequency and risk factors in an optimized, multimodal, rehabilitation program.
        Acta Anaesthesiol Scand. 2006; 50: 428-436
        • Sharma PT
        • Sieber FE
        • Zakriya KJ
        • et al.
        Recovery room delirium predicts postoperative delirium after hip-fracture repair.
        Anesth Analg. 2005; 101: 1215-1220
        • Zakriya K
        • Sieber FE
        • Christmas C
        • Wenz Sr, JF
        • Franckowiak S
        Brief postoperative delirium in hip fracture patients affects functional outcome at three months.
        Anesth Analg. 2004; 98: 1798-1802
        • Duppils GS
        • Wikblad K
        Acute confusional states in patients undergoing hip surgery: a prospective observation study.
        Gerontology. 2000; 46: 36-43
        • Marcantonio ER
        • Flacker JM
        • Michaels M
        • Resnick NM
        Delirium is independently associated with poor functional recovery after hip fracture.
        J Am Geriatr Soc. 2000; 48: 618-624
        • Holmes J
        • House A
        Psychiatric illness predicts poor outcome after surgery for hip fracture: a prospective cohort study.
        Psychol Med. 2000; 30: 921-929
        • Nightingale S
        • Holmes J
        • Mason J
        • House A
        Psychiatric illness and mortality after hip fracture [letter].
        Lancet. 2001; 357: 1264-1265
        • McCusker J
        • Cole MG
        • Dendukuri N
        • Belzile E
        Does delirium increase hospital stay?.
        J Am Geriatr Soc. 2003; 51: 1539-1546
        • Pandharipande P
        • Jackson J
        • Ely EW
        Delirium: acute cognitive dysfunction in the critically ill.
        Curr Opin Crit Care. 2005; 11: 360-368
        • Milbrandt EB
        • Deppen S
        • Harrison PL
        • et al.
        Costs associated with delirium in mechanically ventilated patients.
        Crit Care Med. 2004; 32: 955-962
        • Franco K
        • Litaker D
        • Locala J
        • Bronson D
        The cost of delirium in the surgical patient.
        Psychosomatics. 2001; 42: 68-73
        • Siddiqi N
        • Stockdale R
        • Britton AM
        • Holmes J
        Interventions for preventing delirium in hospitalised patients.
        Cochrane Database Syst Rev. 2007; (CD005563.)
        • Marcantonio ER
        • Flacker JM
        • Wright RJ
        • Resnick NM
        Reducing delirium after hip fracture: a randomized trial.
        J Am Geriatr Soc. 2001; 49: 516-522
        • Kalisvaart KJ
        • de Jonghe JF
        • Bogaards MJ
        • et al.
        Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.
        J Am Geriatr Soc. 2005; 53: 1658-1666
        • Morrison RS
        • Magaziner J
        • Gilbert M
        • et al.
        Relationship between pain and opioid analgesics on the development of delirium following hip fracture.
        J Gerontol A Biol Sci Med Sci. 2003; 58: 76-81
        • Edlund A
        • Lundstrom M
        • Brännström B
        • Bucht G
        • Gustafson Y
        Delirium before and after operation for femoral neck fracture.
        J Am Geriatr Soc. 2001; 49: 1335-1340
        • Bitsch M
        • Foss N
        • Kristensen B
        • Kehlet H
        Pathogenesis of and management strategies for postoperative delirium after hip fracture: a review.
        Acta Orthop Scand. 2004; 75: 378-389
        • Inouye SK
        • Viscoli CM
        • Horwitz RI
        • Hurst LD
        • Tinetti ME
        A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics.
        Ann Intern Med. 1993; 119: 474-481
        • Alagiakrishnan K
        • Wiens CA
        An approach to drug induced delirium in the elderly.
        Postgrad Med J. 2004; 80: 388-393
        • Marcantonio ER
        • Juarez G
        • Goldman L
        • et al.
        The relationship of postoperative delirium with psychoactive medications.
        JAMA. 1994; 272: 1518-1522
        • Pandharipande P
        • Ely EW
        Sedative and analgesic medications: risk factors for delirium and sleep disturbances in the critically ill.
        Crit Care Clin. 2006; 22 (vii.): 313-327
        • Pandharipande P
        • Shintani A
        • Peterson J
        • et al.
        Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients.
        Anesthesiology. 2006; 104: 21-26
        • Dubois MJ
        • Bergeron N
        • Dumont M
        • Dial S
        • Skrobik Y
        Delirium in an intensive care unit: a study of risk factors.
        Intensive Care Med. 2001; 27: 1297-1304
        • Aono J
        • Ueda W
        • Mamiya K
        • Takimoto E
        • Manabe M
        Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys.
        Anesthesiology. 1997; 87: 1298-1300
        • Parker MJ
        • Handoll HH
        • Griffiths R
        Anaesthesia for hip fracture surgery in adults.
        Cochrane Database Syst Rev. 2004; (CD000521.)
        • Bryson GL
        • Wyand A
        Evidence-based clinical update: general anesthesia and the risk of delirium and postoperative cognitive dysfunction.
        Can J Anaesth. 2006; 53: 669-677
      1. Sieber FE, Gottschalk A, Zakriya KJ, Mears S, Lee H. General anesthesia occurs frequently in elderly patients during spinal anesthesia and propofol based sedation. J Clin Anesth. In press.

        • Némethy M
        • Paroli L
        • Williams-Russo PG
        • Blanck TJ
        Assessing sedation with regional anesthesia: inter-rater agreement on a modified Wilson sedation scale.
        Anesth Analg. 2002; 94: 723-728
        • Chisholm CJ
        • Zurica J
        • Mironov D
        • Sciacca RR
        • Ornstein E
        • Heyer EJ
        Comparison of electrophysiologic monitors with clinical assessment of level of sedation.
        Mayo Clin Proc. 2006; 81: 46-52
        • Patel S
        • Vargo JJ
        • Khandwala F
        • et al.
        Deep sedation occurs frequently during elective endoscopy with meperidine and midazolam.
        Am J Gastroenterol. 2005; 100: 2689-2695
        • Ying SW
        • Abbas SY
        • Harrison NL
        • Goldstein PA
        Propofol block of Ih contributes to the suppression of neuronal excitability and rhythmic burst firing in thalamocortical neurons [published correction appears in Eur J Neurosci. 2006;23(5):1403].
        Eur J Neurosci. 2006; 23: 465-480
        • Global Initiative for Chronic Obstructive Lung Disease
        Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD Web site. Medical Communications Resources, Inc, Gig Harbor, WA2008 (Accessed October 27, 2009.)
        • Folstein MF
        • Folstein SE
        • McHugh PR
        “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Inouye SK
        • van Dyck CH
        • Alessi CA
        • Balkin S
        • Siegal AP
        • Horwitz RI
        Clarifying confusion: the confusion assessment method: a new method for detection of delirium.
        Ann Intern Med. 1990; 113: 941-948
        • Katz S
        Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living.
        J Am Geriatr Soc. 1983; 31: 721-727
        • Lawton MP
        • Brody EM
        Assessment of older people: self-maintaining and instrumental activities of daily living.
        Gerontologist. 1969; 9: 179-186
        • Johansen JW
        Update on bispectral index monitoring.
        Best Pract Res Clin Anaesthesiol. 2006; 20: 81-99
        • Williams-Russo P
        • Sharrock NE
        • Mattis S
        • Szatrowski TP
        • Charlson ME
        Cognitive effects after epidural vs general anesthesia in older adults: a randomized trial.
        JAMA. 1995; 274: 44-50
        • Pereira J
        • Lawlor P
        • Vigano A
        • Dorgan M
        • Bruera E
        Equianalgesic dose ratios for opioids: a critical review and proposals for long-term dosing.
        J Pain Symptom Manage. 2001; 22: 672-687
        • Marcou TA
        • Marque S
        • Mazoit JX
        • Benhamou D
        The median effective dose of tramadol and morphine for postoperative patients: a study of interactions.
        Anesth Analg. 2005; 100: 469-474
        • Patanwala AE
        • Duby J
        • Waters D
        • Erstad BL
        Opioid conversions in acute care [published correction appears in Ann Pharmacother. 2007;41(3):531].
        Ann Pharmacother. 2007; 41: 255-266
        • Ibrahim AE
        • Taraday JK
        • Kharasch ED
        Bispectral index monitoring during sedation with sevoflurane, midazolam, and propofol.
        Anesthesiology. 2001; 95: 1151-1159
        • Ge SJ
        • Zhuang XL
        • Wang YT
        • Wang ZD
        • Li HT
        Changes in the rapidly extracted auditory evoked potentials index and the bispectral index during sedation induced by propofol or midazolam under epidural block.
        Br J Anaesth. 2002; 89: 260-264
        • Bruhn J
        • Bouillon TW
        • Radulescu L
        • Hoeft A
        • Bertaccini E
        • Shafer SL
        Correlation of approximate entropy, bispectral index, and spectral edge frequency 95 (SEF95) with clinical signs of “anesthetic depth” during coadministration of propofol and remifentanil.
        Anesthesiology. 2003; 98: 621-627
        • Doufas AG
        • Bakhshandeh M
        • Haugh GS
        • Bjorksten AR
        • Greif R
        • Sessler DI
        Automated responsiveness test and bispectral index monitoring during propofol and propofol/N2O sedation.
        Acta Anaesthesiol Scand. 2003; 47: 951-957
        • Dahaba AA
        Different conditions that could result in the bispectral index indicating an incorrect hypnotic state.
        Anesth Analg. 2005; 101: 765-773
        • Chernik DA
        • Gillings D
        • Laine H
        • et al.
        Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam.
        J Clin Psychopharmacol. 1990; 10: 244-251
        • Girard TD
        • Pandharipande PP
        • Ely EW
        Delirium in the intensive care unit.
        Crit Care. 2008; 12: S3
        • Voyer P
        • Richard S
        • Doucet L
        • Carmichael PH
        Detecting delirium and subsyndromal delirium using different diagnostic criteria among demented long-term care residents.
        J Am Med Dir Assoc. 2009; 10: 181-188
        • Wei LA
        • Fearing MA
        • Sternberg EJ
        • Inouye SK
        The Confusion Assessment Method: a systematic review of current usage.
        J Am Geriatr Soc. 2008; 56: 823-830
        • Gustafson Y
        • Brännström B
        • Berggren D
        • et al.
        A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures.
        J Am Geriatr Soc. 1991; 39: 655-662
        • Gaudreau JD
        • Gagnon P
        Psychotogenic drugs and delirium pathogenesis: the central role of the thalamus.
        Med Hypotheses. 2005; 64: 471-475
        • White NS
        • Alkire MT
        Impaired thalamocortical connectivity in humans during general-anesthetic-induced unconsciousness.
        Neuroimage. 2003; 19: 402-411
        • Alkire MT
        • Haier RJ
        • Fallon JH
        Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness.
        Conscious Cogn. 2000; 9: 370-386
        • Steriade M
        • Deschenes M
        The thalamus as a neuronal oscillator.
        Brain Res. 1984; 320: 1-63
        • Deschênes M
        • Paradis M
        • Roy JP
        • Steriade M
        Electrophysiology of neurons of lateral thalamic nuclei in cat: resting properties and burst discharges.
        J Neurophysiol. 1984; 51: 1196-1219
        • Alkire MT
        • Pomfrett CJ
        • Haier RJ
        • et al.
        Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism.
        Anesthesiology. 1999; 90: 701-709
        • Franks NP
        General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal.
        Nat Rev Neurosci. 2008; 9: 370-386
        • Leventhal AG
        • Wang Y
        • Pu M
        • Zhou Y
        • Ma Y
        GABA and its agonists improved visual cortical function in senescent monkeys.
        Science. 2003; 300: 812-815

      Linked Article

      • Delirium: A Cognitive Cost of the Comfort of Procedural Sedation in Elderly Patients?
        Mayo Clinic ProceedingsVol. 85Issue 1
        • Preview
          Cognitive morbidity is a common complication of hospitalization in elderly patients.1,2 This morbidity takes several forms, with delirium, a confusional state defined clinically by acute and fluctuating changes in consciousness and attention, being the most frequent. The prevalence of delirium is about 20% in elderly hospitalized medical patients, can be as high as 60% after some types of surgery, and approaches 80% among patients admitted to a critical care unit.1,3,4 Delirium is also a costly complication in terms of length of stay and dollars, with a recent study5 estimating that the economic burden of delirium to the US health care system is more than $100 billion annually—enough for a small down payment on the health care legislation currently working its way through Congress.
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