Sleep and Cognition After Ambulatory Hip and Knee Arthroplasty

Sleep and rest are key elements in postoperative rehabilitation and recovery. There are complex relations between major surgery, sleep disturbance and complications. Major surgery leeds to severe postoperative sleep disturbances, initially reducing REM sleep time and disturbing the remaining sleep stages. Major surgery is again a risk factor for postoperative delirium and other cognitive impairment. The underlying mechanisms includes pain, opioid medication, sleep disturbances and neuroinflammation, along with external factors as noise during hospitalisation. The physiologic stress from sleep disturbances and sleep deprivation is associated with blood-brain barrier impairment, inflammation, decreased restitution, altered nociceptive function. Likewise, undiagnosed and untreated sleep apnea is a risk for postoperative complications and is itself affected by anesthesia and some analgesics (i.a. opioids).

Fast-track surgery development has led to restitution period shortening, optimized pain management reducing opioid use, postoperative inflammatory stress response reduction and less delirium. Evolution of hip and knee arthroplasty(THA/TKA), organisation, optimized pain management and pharmacologic modification of inflammatory response by high dose steroid has permitted to perform these surgeries in an outpatient setting.

Previous studies of fast-track THA/TKA using multimodal opioid-sparring analgesia, however neither using high dose steroids nor in an out patient setting, have demonstrated REM sleep period reduction from a normal range of 18% preoperatively to 1% postoperatively. However, changes in sleep architecture after THA/TKA in at setting attempting to minimise abnormal sleep by means of ambulatory surgery added to perioperative reduction of inflammatory response to surgery, pain and opioid use by high dose steroid, haven't been studied.

The purpose of this study is to investigate how much an optimized ambulatory THA/TKA , reducing pain and inflammatory response to surgery and opioid use by high doses steroid can conserve the preoperative sleep architecture.

Study Overview

• Status: Unknown
• Conditions: Delirium; Sleep Disturbance; Arthroplasty Complications

• Study Type: Observational
• Enrollment (Anticipated): 16

Contacts and Locations

• Study Contact: Name: Alexandre Garioud, MD; Phone Number: +4542705009; Email: alexandre.garioud@gmail.com
• Study Contact Backup: Name: Henrik Kehlet, Dr.med,Phd; Phone Number: + 45 3545 4774; Email: henrik.kehlet@regionh.dk

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital
    • Contact: Alexandre Garioud, MD; Phone Number: +4542705009; Email: alexandre.garioud@gmail.com
    • Contact: Nicolai B Foss, Dr.med,Phd; Phone Number: +45 36 32 53 28; Email: nicolai.bang.foss@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

16 adult attending scheduled hip or knee arthroplasty in an ambulatory fast-track setting with spinal anesthesia corresponding to the above mentioned inclusion criteria.

Description

Inclusion Criteria:

• ASA classification I or II
• Scheduled hospital discharge same day after surgery
• Adult person following the patient 24 hours at the patients habitation
• Informed consent and signature.
• Patient speaks and understands Danish

Exclusion Criteria:

• Hospital discharge later than same day after surgery
• No consent form patient
• Alcohol or drug abuse
• Anxiolytic og antipsychotic treatment
• Preoperative opioid treatment
• Soporific treatment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in postoperative REM sleep time compared to preoperative	Polysomnography	One night 2 to 4 night preoperatively, and the first and second postoperative night.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes Remaining sleep stages and sleep variables (i.a. apnea)	Polysomnography	One night 2 to 4 night preoperatively, and the first and second postoperative night.
Presence and severity of postoperative delirium compared to preoperative	Confusion Assessement Method-Severity (CAM-S). High scores, better outcome.	One night 2 to 4 night preoperatively, and after the second postoperative night.
Presence and severity of postoperative cognitive impairment compared to preoperative	Mini Mental State Examination (MMSE), High scores, better outcome.	One night 2 to 4 night preoperatively, and after the second postoperative night.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective measurement of tiredness	questionnaire. Better sleep, better outcome.	One night 2 to 4 night preoperatively, and after the second postoperative night.
Subjective measurement of sleep quality	Pittsburgh Sleep Quality Index. Lower score, better outcome.	One night 2 to 4 night preoperatively, and after the second postoperative night.
Changes in preoperative inflammatory marker level (CRP) compared to postoperative.	Blod samples	One night 2 to 4 night preoperatively, and after the second postoperative night.
Subjective measurements of pain at rest and after mobilisation.	questionnaire. Visual Analogue Scale(VAS). Lower score, better outcome.	Immediately after surgery, and after the first and second postoperative night.
Registration of opioid use.	questionnaire. Less opioid use, better outcome.	Immediately after surgery, and after the first and second postoperative night.

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Kirill Gromov; Anders Troelsen; Kehlet, Henrik, M.D., Ph.D.; Nicolai Bang Foss; Poul Jenum; Mette Grentoft; Henning Piilgaard Hansen
• Investigators: Study Director: Henrik Kehlet, Dr.med,Phd, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Aldecoa C, Bettelli G, Bilotta F, Sanders RD, Audisio R, Borozdina A, Cherubini A, Jones C, Kehlet H, MacLullich A, Radtke F, Riese F, Slooter AJ, Veyckemans F, Kramer S, Neuner B, Weiss B, Spies CD. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol. 2017 Apr;34(4):192-214. doi: 10.1097/EJA.0000000000000594. Erratum In: Eur J Anaesthesiol. 2018 Sep;35(9):718-719.
• Inouye SK, Kosar CM, Tommet D, Schmitt EM, Puelle MR, Saczynski JS, Marcantonio ER, Jones RN. The CAM-S: development and validation of a new scoring system for delirium severity in 2 cohorts. Ann Intern Med. 2014 Apr 15;160(8):526-533. doi: 10.7326/M13-1927.
• Keats AS. The ASA classification of physical status--a recapitulation. Anesthesiology. 1978 Oct;49(4):233-6. doi: 10.1097/00000542-197810000-00001. No abstract available.
• Krenk L, Rasmussen LS, Kehlet H. New insights into the pathophysiology of postoperative cognitive dysfunction. Acta Anaesthesiol Scand. 2010 Sep;54(8):951-6. doi: 10.1111/j.1399-6576.2010.02268.x. Epub 2010 Jul 12.
• Krenk L, Jennum P, Kehlet H. Postoperative sleep disturbances after zolpidem treatment in fast-track hip and knee replacement. J Clin Sleep Med. 2014 Mar 15;10(3):321-6. doi: 10.5664/jcsm.3540.
• Krenk L, Jennum P, Kehlet H. Sleep disturbances after fast-track hip and knee arthroplasty. Br J Anaesth. 2012 Nov;109(5):769-75. doi: 10.1093/bja/aes252. Epub 2012 Jul 24.
• Riedel B, Browne K, Silbert B. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction. Curr Opin Anaesthesiol. 2014 Feb;27(1):89-97. doi: 10.1097/ACO.0000000000000032.
• Ni P, Dong H, Zhou Q, Wang Y, Sun M, Qian Y, Sun J. Preoperative Sleep Disturbance Exaggerates Surgery-Induced Neuroinflammation and Neuronal Damage in Aged Mice. Mediators Inflamm. 2019 Mar 18;2019:8301725. doi: 10.1155/2019/8301725. eCollection 2019.
• He J, Hsuchou H, He Y, Kastin AJ, Wang Y, Pan W. Sleep restriction impairs blood-brain barrier function. J Neurosci. 2014 Oct 29;34(44):14697-706. doi: 10.1523/JNEUROSCI.2111-14.2014.
• McMahon WR, Ftouni S, Drummond SPA, Maruff P, Lockley SW, Rajaratnam SMW, Anderson C. The wake maintenance zone shows task dependent changes in cognitive function following one night without sleep. Sleep. 2018 Oct 1;41(10). doi: 10.1093/sleep/zsy148.
• de Raaff CAL, Gorter-Stam MAW, de Vries N, Sinha AC, Jaap Bonjer H, Chung F, Coblijn UK, Dahan A, van den Helder RS, Hilgevoord AAJ, Hillman DR, Margarson MP, Mattar SG, Mulier JP, Ravesloot MJL, Reiber BMM, van Rijswijk AS, Singh PM, Steenhuis R, Tenhagen M, Vanderveken OM, Verbraecken J, White DP, van der Wielen N, van Wagensveld BA. Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline. Surg Obes Relat Dis. 2017 Jul;13(7):1095-1109. doi: 10.1016/j.soard.2017.03.022. Epub 2017 Mar 30.
• Kehlet H. Fast-track hip and knee arthroplasty. Lancet. 2013 May 11;381(9878):1600-2. doi: 10.1016/S0140-6736(13)61003-X. No abstract available.
• Kehlet H, Lindberg-Larsen V. High-dose glucocorticoid before hip and knee arthroplasty: To use or not to use-that's the question. Acta Orthop. 2018 Oct;89(5):477-479. doi: 10.1080/17453674.2018.1475177. Epub 2018 May 21. No abstract available.
• Krenk L, Rasmussen LS, Hansen TB, Bogo S, Soballe K, Kehlet H. Delirium after fast-track hip and knee arthroplasty. Br J Anaesth. 2012 Apr;108(4):607-11. doi: 10.1093/bja/aer493. Epub 2012 Jan 24.
• Gromov K, Kjaersgaard-Andersen P, Revald P, Kehlet H, Husted H. Feasibility of outpatient total hip and knee arthroplasty in unselected patients. Acta Orthop. 2017 Oct;88(5):516-521. doi: 10.1080/17453674.2017.1314158. Epub 2017 Apr 20.
• Stephansen JB, Olesen AN, Olsen M, Ambati A, Leary EB, Moore HE, Carrillo O, Lin L, Han F, Yan H, Sun YL, Dauvilliers Y, Scholz S, Barateau L, Hogl B, Stefani A, Hong SC, Kim TW, Pizza F, Plazzi G, Vandi S, Antelmi E, Perrin D, Kuna ST, Schweitzer PK, Kushida C, Peppard PE, Sorensen HBD, Jennum P, Mignot E. Neural network analysis of sleep stages enables efficient diagnosis of narcolepsy. Nat Commun. 2018 Dec 6;9(1):5229. doi: 10.1038/s41467-018-07229-3.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2020
• Primary Completion (Anticipated): July 1, 2020
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: December 12, 2019
• First Submitted That Met QC Criteria: January 11, 2020
• First Posted (Actual): January 14, 2020

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 16, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Dyssomnias; Parasomnias
• Other Study ID Numbers: HVH01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No