Influence of Intrathecal Dexamethasone Administration for Proximal Femoral Fractures

NCT03856502 | Completed

• 1 other identifier: 662809198348
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Spinal anesthesia blocks acute pain in older patients with femur fracture. Delirium is a common complication seen after femur fracture, affecting approximately 10-16% of patients. It is associated with increased mortality at 1st year, delayed rehabilitation efforts, prolonged length of hospital stay, poorer functional outcomes, and increased risk of nursing home placement. Intrathecal dexamethasone administration improves quality of anesthesia in patients with femur fracture compared to conventional spinal anesthesia.

Conditions

Femoral Fracture; Cognition Disorders; Cortisol; Hypersecretion

Keywords

spinal anesthesia; femoral fracture; dexamethasone

Outcome Measures

Primary Outcomes (2)

• postoperative cognitive change

  Assessed using a simplified Confusion Assessment Method scoring scale, a clinical instrument for delirium assessment used by non-psychiatric medical staff after surgery for excluding delirium. Delirium is defined in terms of 4 possible diagnostic criteria (1. acute onset or fluctuating course; 2- inattention; 3- disorganised thinking; 4- altered level of consciousness (may be defined as alert, lethargic, stupor or coma cognitive state)) and is defined as present when 1 plus 2 and either 3 or 4 diagnostic criteria are positive.

  Confusion Assessment Method scoring was assessed in 4 measure points: 1. one hour after surgery, 2. on the 3rd postoperative day at 9 am, 3. on the 5th postoperative day at 9 am, 4. on the 10th postoperative day at 9 am

• cortisol concentrations changes

  Determined from patient's blood plasma assessed by Roche Elecsys Immunoassay System and defined from the laboratory reference points (185-624)nmol/L equal for each measure point; for single measuring 0,5 ml of patient's blood was taken

  Measured in 5 measure points: 1. one hour before surgery, 2. one hour after surgery, 3. on the 3rd postoperative day at 6 am, 4. on the 5th postoperative day at 6 am, 5. on the 10th postoperative day at 6 am

Secondary Outcomes (10)

• perioperative pain intensity: Visual Analogue Scale score

  Visual Analogue Scale scoring (scores: 0-10) was assessed in 5 measure points every 3 hours when patient was awake: 1. 1 h before surgery, 2. 1 h after surgery, 3. on the 3rd postoperative day, 4. on the 5th postoperative day, 5. 10th postoperative day

• glucose concentrations changes

  Measured in 5 measure points (units: mmol/L): 1. one hour before surgery, 2. one hour after surgery, 3. on the 3rd postoperative day at 6 am, 4. on the 5th postoperative day at 6 am, 5. on the 10th postoperative day at 6 am

• Blood loss

  During the surgical repairment and up to the removal of drainage systems (2nd postoperative day)

• Number of Participants with pulmonary embolism

  During surgical reconstruction and during postoperative follow-up of up to ten postoperative days

• Number of Participants with heart failure

  During surgical reconstruction and during postoperative follow-up of up to ten postoperative days

Study Arms (2)

group that received dexamethasone (DLSA)

EXPERIMENTAL

The study group of 30 patients ASA status 2 or 3 received 8 mg of dexamethasone with 12,5 mg of 0,5% of levobupivacaine intrathecally for surgical reconstruction of proximal femoral fracture. Spinal anaesthesia was performed in sitting position using middle approach in intervertebral space L2-L3 or L3-L4 with spinal needles 22-27 GA.

Drug: 8 mg of dexamethasone; Drug: 12,5 mg of 0,5 % of levobupivacaine

group without dexamethasone (LSA)

ACTIVE COMPARATOR

The control group of 30 patients ASA status 2 or 3 received 12,5 mg of 0,5% of levobupivacaine intrathecally for surgical reconstruction of proximal femoral fracture. Spinal anaesthesia was performed in sitting position using middle approach in intervertebral space L2-L3 or L3-L4 with spinal needles 22-27 GA.

Drug: 12,5 mg of 0,5 % of levobupivacaine

Interventions

8 mg of dexamethasone DRUG

Effect of intrathecally administered dexamethasone in spinal anaesthesia for surgical correction of the hip fracture.

Also known as: Dexamethasone KRKA, Chirocaine Abbott

group that received dexamethasone (DLSA)

12,5 mg of 0,5 % of levobupivacaine DRUG

Local anaesthetic standardly used in spinal anaesthesia for surgical correction of the hip fracture by the particular hospital's protocol.

Also known as: Chirocaine Abbott

group that received dexamethasone (DLSA); group without dexamethasone (LSA)

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• cooperative ASA 2 and ASA 3 status patients with proximal femoral fractures of one leg
• agreed to be enrolled in the study (Informed Consent signed)

You may not qualify if:

• patients refused to be enrolled in the study
• patients with pre-existing cognitive disturbances before surgery
• conditions or diseases with corticosteroid therapy, long term corticosteroid, diabetes mellitus, neurological conditions or tumors, neuroendocrine disorders or tumors
• breaking the study protocols
• patients who no longer wanted to be enrolled in the study
• unexpected events when the study already started

Sponsors & Collaborators

• General Hospital Sveti Duh: lead

Study Sites (1)

University Hospital "Sveti Duh"

Zagreb, 10000, Croatia

Location

Related Publications (24)

• 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.

  PMID: 22713634 BACKGROUND

• Membership of the Working Party; Griffiths R, Alper J, Beckingsale A, Goldhill D, Heyburn G, Holloway J, Leaper E, Parker M, Ridgway S, White S, Wiese M, Wilson I. Management of proximal femoral fractures 2011: Association of Anaesthetists of Great Britain and Ireland. Anaesthesia. 2012 Jan;67(1):85-98. doi: 10.1111/j.1365-2044.2011.06957.x.

  PMID: 22150501 BACKGROUND

• Borgeat A, Ekatodramis G. Orthopaedic surgery in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):235-44. doi: 10.1016/s1521-6896(03)00007-7.

  PMID: 12817917 BACKGROUND

• Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994 Feb;15(2):74-80. doi: 10.1016/0167-5699(94)90137-6.

  PMID: 7512342 BACKGROUND

• Buckingham JC. Stress and the hypothalamo-pituitary-immune axis. Int J Tissue React. 1998;20(1):23-34. No abstract available.

  PMID: 9561443 BACKGROUND

• Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25-44. doi: 10.1210/edrv-5-1-25.

  PMID: 6368214 BACKGROUND

• Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. doi: 10.1093/bja/85.1.109. No abstract available.

  PMID: 10927999 BACKGROUND

• Hogevold HE, Lyberg T, Kahler H, Haug E, Reikeras O. Changes in plasma IL-1beta, TNF-alpha and IL-6 after total hip replacement surgery in general or regional anaesthesia. Cytokine. 2000 Jul;12(7):1156-9. doi: 10.1006/cyto.2000.0675.

  PMID: 10880268 BACKGROUND

• Kehlet H. Manipulation of the metabolic response in clinical practice. World J Surg. 2000 Jun;24(6):690-5. doi: 10.1007/s002689910111.

  PMID: 10773121 BACKGROUND

• Bani-Hashem N, Hassan-Nasab B, Pour EA, Maleh PA, Nabavi A, Jabbari A. Addition of intrathecal Dexamethasone to Bupivacaine for spinal anesthesia in orthopedic surgery. Saudi J Anaesth. 2011 Oct;5(4):382-6. doi: 10.4103/1658-354X.87267.

  PMID: 22144925 BACKGROUND

• Kroin JS, Schaefer RB, Penn RD. Chronic intrathecal administration of dexamethasone sodium phosphate: pharmacokinetics and neurotoxicity in an animal model. Neurosurgery. 2000 Jan;46(1):178-82; discussion 182-3.

  PMID: 10626948 BACKGROUND

• Yao XL, Cowan MJ, Gladwin MT, Lawrence MM, Angus CW, Shelhamer JH. Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A2 activity. J Biol Chem. 1999 Jun 11;274(24):17202-8. doi: 10.1074/jbc.274.24.17202.

  PMID: 10358078 BACKGROUND

• Dong Y, Zhang X, Tang F, Tian X, Zhao Y, Zhang F. Intrathecal injection with methotrexate plus dexamethasone in the treatment of central nervous system involvement in systemic lupus erythematosus. Chin Med J (Engl). 2001 Jul;114(7):764-6.

  PMID: 11780346 BACKGROUND

• Williams BA, Hough KA, Tsui BY, Ibinson JW, Gold MS, Gebhart GF. Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine. Reg Anesth Pain Med. 2011 May-Jun;36(3):225-30. doi: 10.1097/AAP.0b013e3182176f70.

  PMID: 21519308 BACKGROUND

• Benzon HT, Chew TL, McCarthy RJ, Benzon HA, Walega DR. Comparison of the particle sizes of different steroids and the effect of dilution: a review of the relative neurotoxicities of the steroids. Anesthesiology. 2007 Feb;106(2):331-8. doi: 10.1097/00000542-200702000-00022.

  PMID: 17264728 BACKGROUND

• Kopacz DJ, Lacouture PG, Wu D, Nandy P, Swanton R, Landau C. The dose response and effects of dexamethasone on bupivacaine microcapsules for intercostal blockade (T9 to T11) in healthy volunteers. Anesth Analg. 2003 Feb;96(2):576-82, table of contents. doi: 10.1097/00000539-200302000-00050.

  PMID: 12538215 BACKGROUND

• Macro M, Reznik Y, Leymarie P, Loyau G, Mahoudeau J. The effect of intrathecal dexamethasone injection on plasma cortisol level. Br J Rheumatol. 1991 Jun;30(3):238. doi: 10.1093/rheumatology/30.3.238. No abstract available.

  PMID: 2049597 BACKGROUND

• Bjorkelund KB, Hommel A, Thorngren KG, Gustafson L, Larsson S, Lundberg D. Reducing delirium in elderly patients with hip fracture: a multi-factorial intervention study. Acta Anaesthesiol Scand. 2010 Jul;54(6):678-88. doi: 10.1111/j.1399-6576.2010.02232.x. Epub 2010 Mar 15.

  PMID: 20236093 BACKGROUND

• Rasmussen LS, O'Brien JT, Silverstein JH, Johnson TW, Siersma VD, Canet J, Jolles J, Hanning CD, Kuipers HM, Abildstrom H, Papaioannou A, Raeder J, Yli-Hankala A, Sneyd JR, Munoz L, Moller JT; ISPOCD2 Investigators. Is peri-operative cortisol secretion related to post-operative cognitive dysfunction? Acta Anaesthesiol Scand. 2005 Oct;49(9):1225-31. doi: 10.1111/j.1399-6576.2005.00791.x.

  PMID: 16146456 BACKGROUND

• Mouzopoulos G, Vasiliadis G, Lasanianos N, Nikolaras G, Morakis E, Kaminaris M. Fascia iliaca block prophylaxis for hip fracture patients at risk for delirium: a randomized placebo-controlled study. J Orthop Traumatol. 2009 Sep;10(3):127-33. doi: 10.1007/s10195-009-0062-6. Epub 2009 Aug 19.

  PMID: 19690943 BACKGROUND

• 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. doi: 10.7326/0003-4819-113-12-941.

  PMID: 2240918 BACKGROUND

• Huang YF, Liang J, Shyu YL. Number of Comorbidities Negatively Influence Psychological Outcomes of the Elderly Following Hip Fracture in Taiwan. J Aging Health. 2016 Dec;28(8):1343-1361. doi: 10.1177/0898264315618922. Epub 2016 Jul 8.

  PMID: 26786859 BACKGROUND

• Drews T, Franck M, Radtke FM, Weiss B, Krampe H, Brockhaus WR, Winterer G, Spies CD. Postoperative delirium is an independent risk factor for posttraumatic stress disorder in the elderly patient: a prospective observational study. Eur J Anaesthesiol. 2015 Mar;32(3):147-51. doi: 10.1097/EJA.0000000000000107.

  PMID: 24979586 BACKGROUND

• Le Manach Y, Collins G, Bhandari M, Bessissow A, Boddaert J, Khiami F, Chaudhry H, De Beer J, Riou B, Landais P, Winemaker M, Boudemaghe T, Devereaux PJ. Outcomes After Hip Fracture Surgery Compared With Elective Total Hip Replacement. JAMA. 2015 Sep 15;314(11):1159-66. doi: 10.1001/jama.2015.10842.

  PMID: 26372585 BACKGROUND

MeSH Terms

Conditions

Femoral Fractures; Cognition Disorders

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Leg Injuries; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Livija Šakić, MD,PhD

  University Hospital Sveti Duh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PhD Anesthesiology, Reanimatology and Intensive Medicine

Study Record Dates

• First Submitted: November 2, 2018
• First Posted: February 27, 2019
• Study Start: November 11, 2012
• Primary Completion: May 26, 2016
• Study Completion: July 4, 2017
• Last Updated: February 28, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)