Opioid-Free Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series

NCT04437589 | Completed

• 1 other identifier: OPIOIDANALGESIA1
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Cranio-cervical instability (CCI) has been well identified in diseases regarding connective tissue, such as Ehlers-Danlos Syndrome/Hipermobility Type (EDS-HT). These patients frequently suffer from severe widespread pain with very difficult management and control. Chronic neuroinflamation, opioid-induced hyperalgesia, and central sensitization phenomena may explain this complex painful condition. A retrospective, observational, consecutive case series study is designed to determine if opioid-free anesthetic management shows a reduction in postoperative pain and opioid rescues needs in comparison with opioid-based anesthesia management for patients with EDS-HT undergoing crano-cervical fixation.

Conditions

Ehlers-Danlos Syndrome; Craniocervical Syndrome

Keywords

Craneocervical -instability; Craneocervical -fixation; Opioid induced hyperalgesia; Free-opioid-anesthesia; Ehlers-Danlos Syndrome; Joint Hipermobility syndrome; Central sensitization phenomena

Outcome Measures

Primary Outcomes (24)

• Age

  Patient's age when the surgery was performed (in years)

  Baseline

• Sex

  Patient sex classified in two groups: female (1) and male (2)

  Baseline

• PO Analgesia

  Postoperative analgesia is a nominal variable which indicates the type of analgesia administered to the patient. There are 4 options: Lidocaine-Ketamine-Dexmetodimine (LKDi) as group 1, PCA morphine infusion pump as group 2, Ketamine perfusion as group 3 and Methadone-Ketamine as group 4.

  Baseline

• Preoperative EVA

  Escala Visual Analógica de dolor (EVA) is an analogic visual scale to measure the patients pain. It has a range between 0 and 10. Higher values mean more pain. The Preoperative EVA measures the pain before the surgery. If there is more than one measure the result is presented as the mean of all measurements.

  Baseline

• Preoperative Opioids

  The preoperative opioids is a categorical variable that indicates if the patient took opioids before the surgery. There are 4 options: * No opioids or eventually taken as option 0 * Weak opioids (tramadol, codeine, trapentadol) as option 1 * Strong opioids (fentanile, oxicodone, morphine, buprenorphine) as option 2 * A combination of strong opioids as option 3

  Baseline

• Postoperative EVA 1

  Escala Visual Analógica de dolor (EVA) is an analogic visual scale to measure the patients pain. It has a range between 0 and 10. Higher values mean more pain. The postoperative EVA 1 is measured 1 day after surgery.

  1 day after surgery

• Postoperative EVA 2

  Escala Visual Analógica de dolor (EVA) is an analogic visual scale to measure the patients pain. It has a range between 0 and 10. Higher values mean more pain. The postoperative EVA 2 is measured 2 day after surgery.

  2 days after surgery

• Postoperative EVA 4

  Escala Visual Analógica de dolor (EVA) is an analogic visual scale to measure the patients pain. It has a range between 0 and 10. Higher values mean more pain. The postoperative EVA 4 is measured 4 day after surgery.

  4 days after surgery

• Postoperative EVA 6

  Escala Visual Analógica de dolor (EVA) is an analogic visual scale to measure the patients pain. It has a range between 0 and 10. Higher values mean more pain. The postoperative EVA 6 is measured 6 day after surgery.

  6 days after surgery

• Sufentanil doses 1

  Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 1 day after surgery. Sufentanil doses 1 is a categorical variable with 4 levels: * From 0 to 2 pills (equal or less than 30mcg/day) as level 1. * From 2 to 4 pills (from 30mcg/day to 60mcg/day) * From 5 to 10 pills (from 75mcg/day to 150 mcg/day) * More than 10 pills (more than 150mcg/day)

  From surgery release till first day of hospitalization

• Sufentanil doses 2

  Number of pills of sufentanil that the patient has token besides the main treatment. The variable is 2 days after surgery. Sufentanil doses 2 is a categorical variable with 4 levels: * From 0 to 2 pills (equal or less than 30mcg/day) as level 1. * From 2 to 4 pills (from 30mcg/day to 60mcg/day) * From 5 to 10 pills (from 75mcg/day to 150 mcg/day) * More than 10 pills (more than 150mcg/day)

  From first day of hospitalization till second day of hospitalization

• Sufentanil doses 4

  Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 4 days after surgery. Sufentanil doses 4 is a categorical variable with 4 levels: * From 0 to 2 pills (equal or less than 30mcg/day) as level 1. * From 2 to 4 pills (from 30mcg/day to 60mcg/day) * From 5 to 10 pills (from 75mcg/day to 150 mcg/day) * More than 10 pills (more than 150mcg/day)

  From second day of hospitalization till fourth day of hospitalization

• Sufentanil doses 6

  Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 6 days after surgery. Sufentanil doses 6 is a categorical variable with 4 levels: * From 0 to 2 pills (equal or less than 30mcg/day) as level 1. * From 2 to 4 pills (from 30mcg/day to 60mcg/day) * From 5 to 10 pills (from 75mcg/day to 150 mcg/day) * More than 10 pills (more than 150mcg/day)

  From fourth day of hospitalization till sixth day of hospitalization

• Rescue Methadone

  Rescue Methadone is a categorical variable that indicates if the patient required the use of methadone as a secondary treatment besides the main one. The variable has 4 levels: * No rescue as level 0 * 5mg/day as level 1 * From 10mg/day to 15mg/day as level 2 * More than 15mg/day as level 3

  Baseline

• Morphine dosage 1

  For those cases in which an infusion PCA morphine pump was placed, mean dose 1 day after surgery of the administered morphine. Daily morphine dosage is a categorical variable of 4 levels: * Less than 30mg/day as level 1 * From 30mg/day to 60mg/day as level 2 * From 60mg/day to 150mg/day as level 3 * More than 150mg/day as level 4

  From surgery release till first day of hospitalization

• Morphine dosage 2

  For those cases in which an infusion PCA morphine pump was placed, mean dose 2 days after surgery of the administered morphine. Daily morphine dosage is a categorical variable of 4 levels: * Less than 30mg/day as level 1 * From 30mg/day to 60mg/day as level 2 * From 60mg/day to 150mg/day as level 3 * More than 150mg/day as level 4

  From first day of hospitalization till second day of hospitalization

• Morphine dosage 4

  For those cases in which an infusion PCA morphine pump was placed, mean dose 4 days after surgery of the administered morphine. Daily morphine dosage is a categorical variable of 4 levels: * Less than 30mg/day as level 1 * From 30mg/day to 60mg/day as level 2 * From 60mg/day to 150mg/day as level 3 * More than 150mg/day as level 4

  From second day of hospitalization till fourth day of hospitalization

• Morphine dosage 6

  For those cases in which an infusion PCA morphine pump was placed, mean dose 6 days after surgery of the administered morphine. Daily morphine dosage is a categorical variable of 4 levels: * Less than 30mg/day as level 1 * From 30mg/day to 60mg/day as level 2 * From 60mg/day to 150mg/day as level 3 * More than 150mg/day as level 4

  From fourth day of hospitalization till sixth day of hospitalization

• Nausea and vomiting

  Nausea and vomiting is a categorical variable that indicates if the patient reported having nausea or vomiting in the control postoperative visits. The variable has 2 states: Yes (1) or No (0).

  Baseline

• Intestinal ileus

  Intestinal ileus is a categorical variable that indicates if the doctor or nurse reported an intestinal ileus when performing the postoperative control visit. The variable has 2 states: Yes (1) or No (0).

  Baseline

• Constipation

  Constipation is a categorical variable that indicates if the patient reported having constipation in the control postoperative visits. The variable has 2 states: Yes (1) or No (0).

  Baseline

• Anxiolytic rescue agent

  The Anxiolytic rescue agent is a categorical variable that indicates if there was a need of applying an axiolytic as a rescue agent besides the main postoperative treatment. The variable has 5 levels: * Not required as level 0 * Eventually (1 time per day) as level 1 * Moderate (2 times per day) as level 2 * Frequent (3 times per day) as level 3 * Very Frequently (more than 3 times per day) as level 4

  Baseline

• Oral ketamine

  Oral ketamine is a categorical variable that indicates if the patient required the use of oral ketamine besides the main postoperative treatment. The variable has 2 states: Yes (1) or No (0).

  Baseline

• Chronic opioid and hospital discharge

  The Chronic opioid and hospital discharge variable is a categorical variable that resumes the patient state when discharged from the hospital. The variable compares the preoperative opioid dosage with the postoperative dosage prescription. The variable has 4 levels: * No opioids as level 0 * Decrease when compared to preoperative (between 20% and 30%) as level 1 * Same dose when compared to preoperative as level 2 * More dose when compared to preoperative as level 3

  Up to 6 days

Study Arms (2)

Exposure group

In this group the treatment applied for postoperative pain involves Free-opioid anesthesia (LKDi).

Control group

In this group the treatment applied for postoperative pain involves an opioid-based anesthesia.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients between 18-60 years with diagnosis of Hypermobility Syndrome undergoing Craneo-cervical fixation (CCF) between Sept, 2018 to March, 2020 to get stabilized craneo-cervical instability (CCI), and performed under opioid-based total intravenous anesthesia or opioid-free total intravenous anesthesia with lidocaine, ketamine and dexmedetomidine (LKD).

You may qualify if:

• Patients with a diagnosis of Hypermobility Syndrome undergoing Craneo-cervical fixation (CCF)
• Patients between 18-60 years.
• Patients enrolled in CCF surgery between September 2018 to March 2020 to get stabilized craneo-cervical instability (CCI).
• Patients under opioid-based total intravenous anesthesia or opioid-free total intravenous anesthesia with lidocaine, ketamine and dexmedetomidine (LKD).

You may not qualify if:

• CCF to stabilized post-traumatic or oncologic CCI.
• Lidocaine allergy.
• Advances heart-block.
• Epilepsy or convulsive syndrome non-medicated.

Sponsors & Collaborators

• Servei Central d'Anestesiologia: lead

Study Sites (1)

Centro Médico Teknon

Barcelona, 08022, Spain

Location

Related Publications (9)

• Castori M, Morlino S, Ghibellini G, Celletti C, Camerota F, Grammatico P. Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain. Am J Med Genet C Semin Med Genet. 2015 Mar;169C(1):84-96. doi: 10.1002/ajmg.c.31426. Epub 2015 Feb 5.

  PMID: 25655119 BACKGROUND

• Henderson FC Sr, Francomano CA, Koby M, Tuchman K, Adcock J, Patel S. Cervical medullary syndrome secondary to craniocervical instability and ventral brainstem compression in hereditary hypermobility connective tissue disorders: 5-year follow-up after craniocervical reduction, fusion, and stabilization. Neurosurg Rev. 2019 Dec;42(4):915-936. doi: 10.1007/s10143-018-01070-4. Epub 2019 Jan 9.

  PMID: 30627832 BACKGROUND

• Scheper MC, de Vries JE, Verbunt J, Engelbert RH. Chronic pain in hypermobility syndrome and Ehlers-Danlos syndrome (hypermobility type): it is a challenge. J Pain Res. 2015 Aug 20;8:591-601. doi: 10.2147/JPR.S64251. eCollection 2015.

  PMID: 26316810 BACKGROUND

• Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011 Mar-Apr;14(2):145-61.

  PMID: 21412369 BACKGROUND

• Kim DJ, Bengali R, Anderson TA. Opioid-free anesthesia using continuous dexmedetomidine and lidocaine infusions in spine surgery. Korean J Anesthesiol. 2017 Dec;70(6):652-653. doi: 10.4097/kjae.2017.70.6.652. Epub 2017 Apr 21. No abstract available.

  PMID: 29225750 BACKGROUND

• Soffin EM, Wetmore DS, Beckman JD, Sheha ED, Vaishnav AS, Albert TJ, Gang CH, Qureshi SA. Opioid-free anesthesia within an enhanced recovery after surgery pathway for minimally invasive lumbar spine surgery: a retrospective matched cohort study. Neurosurg Focus. 2019 Apr 1;46(4):E8. doi: 10.3171/2019.1.FOCUS18645.

  PMID: 30933925 BACKGROUND

• Maheshwari K, Avitsian R, Sessler DI, Makarova N, Tanios M, Raza S, Traul D, Rajan S, Manlapaz M, Machado S, Krishnaney A, Machado A, Rosenquist R, Kurz A. Multimodal Analgesic Regimen for Spine Surgery: A Randomized Placebo-controlled Trial. Anesthesiology. 2020 May;132(5):992-1002. doi: 10.1097/ALN.0000000000003143.

  PMID: 32235144 BACKGROUND

• Dunn LK, Durieux ME, Nemergut EC. Non-opioid analgesics: Novel approaches to perioperative analgesia for major spine surgery. Best Pract Res Clin Anaesthesiol. 2016 Mar;30(1):79-89. doi: 10.1016/j.bpa.2015.11.002. Epub 2015 Nov 24.

  PMID: 27036605 BACKGROUND

• Frauenknecht J, Kirkham KR, Jacot-Guillarmod A, Albrecht E. Analgesic impact of intra-operative opioids vs. opioid-free anaesthesia: a systematic review and meta-analysis. Anaesthesia. 2019 May;74(5):651-662. doi: 10.1111/anae.14582. Epub 2019 Feb 25.

  PMID: 30802933 BACKGROUND

MeSH Terms

Conditions

Ehlers-Danlos Syndrome

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Carlos Rafael Ramirez Paesano, MD

  Servei d'Anestesiologia Centro Médico Teknon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 11, 2020
• First Posted: June 18, 2020
• Study Start: September 6, 2018
• Primary Completion: March 9, 2020
• Study Completion: March 9, 2020
• Last Updated: July 10, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)