A Trial To Assess Risk of Delirium in Older Adults Undergoing Hip Fracture Surgery With Spinal or General Anesthesia

Delirium Clinical Trial

Official title:

A Randomized Controlled Trial To Assess Risk of Delirium in Older Adults Undergoing Hip Fracture Surgery With Spinal or General Anesthesia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02190903
• Other study ID #: 818017
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Est. completion date: April 2015

Study information

• Verified date: July 2018
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot project will address the gaps in knowledge regarding the effect of anesthetic technique on the risk of delirium through an adequately-powered trial employing standardized regimens for treatment and outcome assessment to test the hypothesis that use of spinal versus general anesthesia decreases the risk of delirium after hip fracture surgery.

Description:

Objectives Overall objectives Overall Objectives Specific Aims

1. To compare the effect of spinal versus general anesthesia on rates of postoperative delirium after hip fracture surgery. We hypothesize that rates of delirium after hip fracture surgery will be lower among patients receiving spinal versus general anesthesia.

2. To develop, field-test, and conduct a qualitative evaluation of protocols and procedures for a planned multicenter trial to test the association of anesthesia technique with survival and recovery of function in activities of daily living ambulatory ability at six months after hip fracture.

Primary outcome variable(s) The primary outcome variable is the rate of delirium after hip fracture surgery.

Background Delirium, or a disturbance of consciousness and a change in cognition that develop over a short period of time, (1) complicates 2.6 million hospitalizations among U.S. adults aged 65 or older each year. (2,3) Patients who experience delirium during hospitalization face increased risks morbidity, mortality, and functional disability. (4) Each year, delirium accounts for $6.9 billion in Medicare hospital expenditures. (5) Delirium occurs in 35% to 65% of the 320,000 older U.S. adults hospitalized for hip fracture each year. (6) While adverse survival and functional outcomes are common after hip fracture, (7) a single episode of delirium doubles the odds of both new functional dependence and new ambulatory disability at six months after fracture, and triples the odds of death or new nursing home placement. (8) Compared to general endotracheal anesthesia, spinal anesthesia may decrease the incidence of postoperative delirium after hip fracture surgery. Small randomized trials of anesthesia type for hip fracture have suggested a 50% lower risk of acute confusion after hip fracture surgery with spinal anesthesia, (9) but the heterogeneity of outcome definitions and measurement strategies employed by past trials, along with their use of historical anesthesia practices limit their applicability to current practice.

As a result of these limitations, clinical equipoise continues to exist regarding the optimal anesthetic technique for hip fracture care. Compared to general anesthesia, spinal anesthesia may offer potential benefits not limited to decreased delirium. These may include decreased intraoperative blood loss, and decreased risks of postoperative thromboembolic events, respiratory infections and malignant hyperthermia. At the same time, spinal anesthesia may be associated with greater hypotension than general anesthesia, and may carry small risks of bleeding and infection at the site of the spinal injection and discomfort during block placement. Relative to spinal anesthesia, general anesthesia may offer benefits of hemodynamic stability. At present, while spinal anesthesia has been demonstrated in a retrospective observational study to be associated with lower in-hospital mortality after hip fracture (10), a meta-analysis of randomized trials was inconclusive with regard to mortality differences. (9) Reflecting this state of clinical equipoise patterns of anesthesia care differ widely by country and by provider, reflecting a large role of provider practice style in determining anesthesia care for hip fracture. For example, in a recent survey of UK anesthesiologists, 76% indicated that they routinely performed hip fracture surgeries with spinal anesthesia (11). In contrast, recent U.S. data suggest that approximately 80% of hip fracture surgeries are performed with general anesthesia, with wide variability in practice across hospitals.(10) While these variations may in part reflect differences in patient preferences, the current state of knowledge regarding the risks and benefits of differing types of anesthesia is inadequate to support appropriately informed medical decision-making by either patients or health care providers. The UKs national institute for Health and Care Excellence (NICE) strongly recommend further clinical trials to provide additional information regarding the clinical and cost effectiveness of differing anesthesia types for hip fracture, stating that they were unable to identify any recent randomised controlled trialsthat fully address this question and that the [available] evidence is old and does not reflect current practice.

Study Design Phase II

Design This is a randomized, controlled trial of spinal versus general anesthesia to test the effect of anesthesia type on rates of postoperative delirium after hip fracture surgery.

Study duration It is expected that this study will begin enrollment in June 2013. The enrollment of all subjects is projected to be completed in May 2014 with data analysis to follow. The study will hope to be completed by June 2015.

The length of participation for each subject will be about 5 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject is aged 18 and older.

2. Subject is scheduled to undergo surgical treatment of an acute femoral neck or pertrochanteric hip fracture.

3. Subject can speak English

4. Subject has ability to sign informed consent

Exclusion Criteria:

1. Subject has a pathological or periprosthetic fracture.

2. Subject has concurrent conditions anticipated at the time of admission to require surgical treatment (e.g. multiple trauma, acute cholecystitis).

3. Subject has severe cognitive impairment, as evidenced by a Montreal Cognitive Assessment Score (MOCA) of 15 or less.

4. Subject has clinical findings of delirium prior to surgery, as evidenced by a positive Confusion Assessment Method (CAM) evaluation;

5. Subject has contraindications to spinal anesthesia or volatile general anesthetics.

Related Conditions & MeSH terms

• Delirium
• Fractures, Bone
• Hip Fracture
• Hip Fractures
• Postoperative Complications

Intervention

Other:
• General endotracheal anesthesia
General Anesthesia Patients randomized to receive general anesthesia induction of anesthesia with intravenous lidocaine, propofol, fentanyl citrate and vecuronium or cisatracurium, following dosing guidelines defined by protocol. Following tracheal intubation, anesthesia will be maintained with sevoflurane in oxygen and air as defined by protocol. End-tidal gas monitoring (for carbon dioxide and sevoflurane) and maintenance, monitoring, and reversal of neuromuscular blockade will be as per HUP and PPMC routine. Immediate postoperative analgesia will be via IV dilaudid dosed intraoperatively as defined by protocol.
• Regional (spinal) Anesthesia
Patients randomized to receive spinal anesthesia will undergo spinal blockade using standard techniques and medications dosed as per protocol, and will include hyperbaric bupivicaine or tetracaine, fentanyl citrate, and epinephrine; algorithms for management of spinal-related hypotension will be defined by protocol. Intraoperative sedation will be achieved via continuous intravenous propofol infusion; supplemental oxygen will be provided by nasal cannula or facemask as needed.

Locations

Country	Name	City	State
United States	Hosptial of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

References & Publications (21)

American Psychiatric Association. Delirium, Dementia, and Amnestic and Other Cognitive Disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision). Washington, D.C.: American Psychiatric Association; 2000.

Blackman DK, Kamimoto LA, Smith SM. Overview: surveillance for selected public health indicators affecting older adults--United States. MMWR CDC Surveill Summ. 1999 Dec 17;48(8):1-6. — View Citation

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 Nov;12(3):189-98. — View Citation

Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009 Apr;5(4):210-20. doi: 10.1038/nrneurol.2009.24. Review. — View Citation

Hung WW, Egol KA, Zuckerman JD, Siu AL. Hip fracture management: tailoring care for the older patient. JAMA. 2012 May 23;307(20):2185-94. doi: 10.1001/jama.2012.4842. — View Citation

Inouye SK, Rushing JT, Foreman MD, Palmer RM, Pompei P. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med. 1998 Apr;13(4):234-42. — View Citation

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 Dec 15;113(12):941-8. — View Citation

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 Sep 15;119(6):474-81. — View Citation

Inouye SK. Delirium in older persons. N Engl J Med. 2006 Mar 16;354(11):1157-65. Review. Erratum in: N Engl J Med. 2006 Apr 13;354(15):1655. — View Citation

Kahan BC, Morris TP. Improper analysis of trials randomised using stratified blocks or minimisation. Stat Med. 2012 Feb 20;31(4):328-40. doi: 10.1002/sim.4431. Epub 2011 Dec 4. — View Citation

KATZ S, FORD AB, MOSKOWITZ RW, JACKSON BA, JAFFE MW. STUDIES OF ILLNESS IN THE AGED. THE INDEX OF ADL: A STANDARDIZED MEASURE OF BIOLOGICAL AND PSYCHOSOCIAL FUNCTION. JAMA. 1963 Sep 21;185:914-9. — View Citation

Kernan WN, Viscoli CM, Makuch RW, Brass LM, Horwitz RI. Stratified randomization for clinical trials. J Clin Epidemiol. 1999 Jan;52(1):19-26. Review. — View Citation

Marcantonio ER, Flacker JM, Michaels M, Resnick NM. Delirium is independently associated with poor functional recovery after hip fracture. J Am Geriatr Soc. 2000 Jun;48(6):618-24. — View Citation

National Clinical Guideline Centre (UK). The Management of Hip Fracture in Adults [Internet]. London: Royal College of Physicians (UK); 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK83014/ — View Citation

Neuman MD, Silber JH, Elkassabany NM, Ludwig JM, Fleisher LA. Comparative effectiveness of regional versus general anesthesia for hip fracture surgery in adults. Anesthesiology. 2012 Jul;117(1):72-92. doi: 10.1097/ALN.0b013e3182545e7c. — View Citation

Parker MJ, Handoll HH, Griffiths R. Anaesthesia for hip fracture surgery in adults. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD000521. Review. Update in: Cochrane Database Syst Rev. 2016;2:CD000521. — View Citation

Russo CA, Elixhauser A. Hospitalizations in the Elderly Population, 2003: Statistical Brief #6. 2006 May. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2006 Feb-. Available from http://www.ncbi.nlm.nih.gov/books/NBK63501/ — View Citation

Sandby-Thomas M, Sullivan G, Hall JE. A national survey into the peri-operative anaesthetic management of patients presenting for surgical correction of a fractured neck of femur. Anaesthesia. 2008 Mar;63(3):250-8. doi: 10.1111/j.1365-2044.2007.05328.x. — View Citation

Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. — View Citation

Sieber FE, Zakriya KJ, Gottschalk A, Blute MR, Lee HB, Rosenberg PB, Mears SC. Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair. Mayo Clin Proc. 2010 Jan;85(1):18-26. doi: 10.4065/mcp.2009.0469. Erratum in: Mayo Clin Proc. 2010 Apr;85(4):400. Dosage error in article text. — View Citation

Simon R. Restricted randomization designs in clinical trials. Biometrics. 1979 Jun;35(2):503-12. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Postoperative Delirium After Hip Fracture Surgery	Delirium will be assessed by the Confusion Assessment Method Instrument (CAM), a validated method of assessing delirium based on the presence of both (1) an acute onset of signs and symptoms with a fluctuating course AND (2) inattention; PLUS (3) disorganized thinking OR (4) an altered level of consciousness.	Up to 5 days post hip fracture surgery