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

Ehlers-Danlos Syndrome Clinical Trial

Official title:

Opioid-Free Intravenous Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series Study Focused on Anti-hyperalgesic Approach

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04437589
• Other study ID #: OPIOIDANALGESIA1
• Status: Completed
• Start date: September 6, 2018
• Est. completion date: March 9, 2020

Study information

• Verified date: July 2020
• Source: Servei Central d' Anestesiologia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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 craneo-cervical fixation.

Main Aim: To determine if the administration of opioid-free anesthesia with propofol, lidocaine, ketamine, and dexmedetomidine shows reduction of postoperative pain, and postoperative needs of opioids rescue in patients undergoing CCF.

Secondary Aims:

• To determine if the administration of opioid-free anesthesia in patients undergoing CCF, and postoperative Lidocaine, Ketamine, and Dexmedetomidine infusions can reduce the preoperative needs of opioids treatment at discharge time.

• To determine if the administration of opioid-free anesthesia in patients undergoing CCF reduces the postoperative gastrointestinal complications.

• To determine if the administration of postoperative Lidocaine, Ketamine, and Dexmedetomidine infusions in patients underwent CCF can reduce the preoperative needs of postoperative anxiolytic treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• CCF to stabilized post-traumatic or oncologic CCI.

• Lidocaine allergy.

• Advances heart-block.

• Epilepsy or convulsive syndrome non-medicated.

Related Conditions & MeSH terms

• Craniocervical Syndrome
• Ehlers-Danlos Syndrome
• Joint Instability
• Syndrome

Locations

Country	Name	City	State
Spain	Centro Médico Teknon	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Servei Central d' Anestesiologia

Country where clinical trial is conducted

Spain, 

References & 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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Age	Patient's age when the surgery was performed (in years)	Baseline
Primary	Sex	Patient sex classified in two groups: female (1) and male (2)	Baseline
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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