The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery

Postoperative Cognitive Dysfunction Clinical Trial

Official title:

The Influence of Postoperative Analgesia on Systemic Inflammatory Response and Postoperative Cognitive Disfunction in Elderly Patients After Surgical Repair of Femoral Fractures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02848599
• Other study ID #: 25-1:6563-3/2014
• Status: Completed
• Phase: Phase 2
• Start date: July 2016
• Est. completion date: September 2017

Study information

• Verified date: August 2020
• Source: Osijek University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether epidural levobupivacaine applied for the purpose of post-operative analgesia compared to systemic analgesia with morphine leads to better pain control, stronger suppression of the inflammatory response and the production of inflammatory mediators, faster recovery of patients and consequently less incidence of postoperative cognitive dysfunction (POCD) in elderly patients after surgical treatment of femoral fractures.

Description:

The research will be carried out at the Department of Surgery at Clinical Hospital Centre(CHC) Osijek after approval by the Ethics Committee of CHC Osijek and will be organized as a prospective randomized trial. Respecting the including and excluding criteria for participation in the study, the research will include 70 patients aged 65 years and over who are undergoing surgery for proximal femur fractures and will be operated with the same operating technique (osteosynthesis with nail). All participants will receive the same type of anesthesia and one of two forms of post-operative analgesia, so it will be divided into two groups (35 patients) depending on which form of post-operative analgesia receive. Randomization will be performed by drawing an envelope in which the specified one or other form of post-operative analgesia will be written. The study will be stopped in case of serious complications life-threatening (excessive sedation, respiratory insufficiency, hemodynamic instability and profound hypotension, heart rhythm disorders), which could possibly be related to the administration of drugs used for postoperative analgesia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: September 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• patients age 65 and over

• fracture of the proximal femur

• preoperative assessment American Society of Anesthesiologists(ASA) score I - ASA III

• a written consent of the patient to participate in research

Exclusion Criteria:

• patient non-compliance

• ASA status IV and IV above

• patients younger than 65 years

• dementia, Parkinson's disease, cerebrovascular accident history; simultaneous head injuries,the use of opioids and benzodiazepines longer than a month before the surgery; alcoholism; serious liver disease (class C according to Child-Pugh's classification); severe kidney disease that require dialysis

• result of MMSE test (Mini-Mental State Examination) under 17

• the existence of any contraindications for the implementation of regional anesthesia and one or other form of post-operative analgesia.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Femoral Fractures
• Postoperative Cognitive Dysfunction

Intervention

Drug:
• morphine

• levobupivacaine

Locations

Country	Name	City	State
Croatia	Clinical Hospital Centre Osijek	Osijek

Sponsors (1)

Lead Sponsor	Collaborator
Osijek University Hospital

Country where clinical trial is conducted

Croatia, 

References & Publications (23)

Žura M, Kozmar A, Šakic K, Malenica B, Hrgovic Z. Effect of spinal and general anesthesia on serum concentration of pro-inflammatory and anti-inflammatory cytokines. Immunobiology. 2012 Jun;217(6):622-7. doi: 10.1016/j.imbio.2011.10.018. Epub 2011 Nov 3. — View Citation

Cunningham C. Systemic inflammation and delirium: important co-factors in the progression of dementia. Biochem Soc Trans. 2011 Aug;39(4):945-53. doi: 10.1042/BST0390945. Review. — View Citation

Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. — View Citation

Hansen MV. Chronobiology, cognitive function and depressive symptoms in surgical patients. Dan Med J. 2014 Sep;61(9):B4914. — View Citation

Kampe S, Weinreich G, Darr C, Eicker K, Stamatis G, Hachenberg T. The impact of epidural analgesia compared to systemic opioid-based analgesia with regard to length of hospital stay and recovery of bowel function: retrospective evaluation of 1555 patients undergoing thoracotomy. J Cardiothorac Surg. 2014 Nov 23;9:175. doi: 10.1186/s13019-014-0175-8. — View Citation

Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. One-year health care costs associated with delirium in the elderly population. Arch Intern Med. 2008 Jan 14;168(1):27-32. doi: 10.1001/archinternmed.2007.4. — View Citation

McDaniel M, Brudney C. Postoperative delirium: etiology and management. Curr Opin Crit Care. 2012 Aug;18(4):372-6. doi: 10.1097/MCC.0b013e3283557211. Review. — View Citation

Morrison RS, Magaziner J, Gilbert M, Koval KJ, McLaughlin MA, Orosz G, Strauss E, Siu AL. Relationship between pain and opioid analgesics on the development of delirium following hip fracture. J Gerontol A Biol Sci Med Sci. 2003 Jan;58(1):76-81. — View Citation

Peng L, Xu L, Ouyang W. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One. 2013 Nov 13;8(11):e79624. doi: 10.1371/journal.pone.0079624. eCollection 2013. — View Citation

Pöpping DM, Elia N, Van Aken HK, Marret E, Schug SA, Kranke P, Wenk M, Tramèr MR. Impact of epidural analgesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Ann Surg. 2014 Jun;259(6):1056-67. doi: 10.1097/SLA.0000000000000237. Review. — View Citation

Raats JW, van Eijsden WA, Crolla RM, Steyerberg EW, van der Laan L. Risk Factors and Outcomes for Postoperative Delirium after Major Surgery in Elderly Patients. PLoS One. 2015 Aug 20;10(8):e0136071. doi: 10.1371/journal.pone.0136071. eCollection 2015. — View Citation

Rade MC, Yadeau JT, Ford C, Reid MC. Postoperative delirium in elderly patients after elective hip or knee arthroplasty performed under regional anesthesia. HSS J. 2011 Jul;7(2):151-6. doi: 10.1007/s11420-011-9195-2. Epub 2011 Feb 11. — View Citation

Saczynski JS, Marcantonio ER, Quach L, Fong TG, Gross A, Inouye SK, Jones RN. Cognitive trajectories after postoperative delirium. N Engl J Med. 2012 Jul 5;367(1):30-9. doi: 10.1056/NEJMoa1112923. — View Citation

Seitz DP, Adunuri N, Gill SS, Rochon PA. Prevalence of dementia and cognitive impairment among older adults with hip fractures. J Am Med Dir Assoc. 2011 Oct;12(8):556-564. doi: 10.1016/j.jamda.2010.12.001. Epub 2011 Mar 8. Review. — 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

Steinman L. Modulation of postoperative cognitive decline via blockade of inflammatory cytokines outside the brain. Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20595-6. doi: 10.1073/pnas.1015282107. Epub 2010 Nov 22. — View Citation

Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013;106:161-78. doi: 10.1093/bmb/ldt006. Epub 2013 Apr 4. Review. — View Citation

van Harten AE, Scheeren TW, Absalom AR. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia. Anaesthesia. 2012 Mar;67(3):280-93. doi: 10.1111/j.1365-2044.2011.07008.x. Review. — View Citation

Vega P E, Nazar J C, Rattalino F M, Pedemonte T J, Carrasco G M. [Postoperative delirium among older people]. Rev Med Chil. 2014 Apr;142(4):481-93. doi: 10.4067/S0034-98872014000400010. Spanish. — View Citation

Wang W, Wang Y, Wu H, Lei L, Xu S, Shen X, Guo X, Shen R, Xia X, Liu Y, Wang F. Postoperative cognitive dysfunction: current developments in mechanism and prevention. Med Sci Monit. 2014 Oct 12;20:1908-12. doi: 10.12659/MSM.892485. Review. — View Citation

Wang Y, Sands LP, Vaurio L, Mullen EA, Leung JM. The effects of postoperative pain and its management on postoperative cognitive dysfunction. Am J Geriatr Psychiatry. 2007 Jan;15(1):50-9. — View Citation

Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010 Jul 28;304(4):443-51. doi: 10.1001/jama.2010.1013. — View Citation

Zywiel MG, Prabhu A, Perruccio AV, Gandhi R. The influence of anesthesia and pain management on cognitive dysfunction after joint arthroplasty: a systematic review. Clin Orthop Relat Res. 2014 May;472(5):1453-66. doi: 10.1007/s11999-013-3363-2. Review. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interleukin-6 Concentration in Peripheral Blood.	Measurement will be done before and 24 and 72 hours after the surgery.	Before, 24 and 72 hours after the surgery
Primary	Changes in Cognitive Function	Assessment of cognitive function will be done using the Mini-mental state examination (MMSE) rating scales before and 24,48,72,96 and 120 hours after the surgery at the same time every morning.; Mini-Mental State Examination Scale: minimum score is 0 and maximum score is 30; the severity of cognitive impairment: no cognitive impairment=25-30; mild cognitive impairment=19-24; moderate cognitive impairment=10-18; and severe cognitive impairment<9. Higher scores mean a better and lower scores mean a worse outcome.	Before, 24,48,72,96 and 120 hours after the surgery
Secondary	Changes in C-reactive Protein (CRP) Levels	Measurement will be done before and 24,72 and 120 hours after the surgery.	Before, 24,72 and 120 hours after the surgery
Secondary	Changes in Fibrinogen Concentrations in Peripheral Blood	Measurement will be done before and 24,72 and 120 hours after the surgery.	Before, 24,72 and 120 hours after the surgery
Secondary	Changes in Pain Intensity	Assessment will be done using Numeric Rating Scale (NRS). During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily. Median of 8 time points measurements during the first 24, 48 and 72 hours after the surgery will be reported. After that, median of 3 time points will be reported from the 4. to 6. postoperative day and on the day of discharge.; Minimum score 0 and maximum score 10 ( 0-No Pain; 1-3 Mild Pain; 4-6 Moderate Pain; 7-10 Severe Pain ). Higher scores mean a worse and lower scores mean a better outcome.	During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily until discharge
Secondary	Postoperative Hospital Stay	Duration of postoperative hospital stay in days	14 days