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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Ehlers-Danlos Syndrome, Craniocervical Syndrome

Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposure group<br>In this group the treatment applied for postoperative pain involves Free-opioid anesthesia (LKDi). | |
| Control group<br>In this group the treatment applied for postoperative pain involves an opioid-based anesthesia. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Craneocervical -instability, Craneocervical -fixation, Opioid induced hyperalgesia, Free-opioid-anesthesia, Ehlers-Danlos Syndrome, Joint Hipermobility syndrome, Central sensitization phenomena