<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04437589</url>
  </required_header>
  <id_info>
    <org_study_id>OPIOIDANALGESIA1</org_study_id>
    <nct_id>NCT04437589</nct_id>
  </id_info>
  <brief_title>Opioid-Free Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Servei Central d' Anestesiologia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Servei Central d' Anestesiologia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cranio-cervical instability (CCI) has been well identified in diseases regarding connective&#xD;
      tissue, such as Ehlers-Danlos Syndrome/Hipermobility Type (EDS-HT). These patients frequently&#xD;
      suffer from severe widespread pain with very difficult management and control. Chronic&#xD;
      neuroinflamation, opioid-induced hyperalgesia, and central sensitization phenomena may&#xD;
      explain this complex painful condition. A retrospective, observational, consecutive case&#xD;
      series study is designed to determine if opioid-free anesthetic management shows a reduction&#xD;
      in postoperative pain and opioid rescues needs in comparison with opioid-based anesthesia&#xD;
      management for patients with EDS-HT undergoing crano-cervical fixation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cranio-cervical instability (CCI) has been well identified in diseases regarding connective&#xD;
      tissue, such as Ehlers-Danlos Syndrome/Hipermobility Type (EDS-HT). These patients frequently&#xD;
      suffer from severe widespread pain with very difficult management and control. Chronic&#xD;
      neuroinflamation, opioid-induced hyperalgesia, and central sensitization phenomena may&#xD;
      explain this complex painful condition. A retrospective, observational, consecutive case&#xD;
      series study is designed to determine if opioid-free anesthetic management shows a reduction&#xD;
      in postoperative pain and opioid rescues needs in comparison with opioid-based anesthesia&#xD;
      management for patients with EDS-HT undergoing craneo-cervical fixation.&#xD;
&#xD;
      Main Aim: To determine if the administration of opioid-free anesthesia with propofol,&#xD;
      lidocaine, ketamine, and dexmedetomidine shows reduction of postoperative pain, and&#xD;
      postoperative needs of opioids rescue in patients undergoing CCF.&#xD;
&#xD;
      Secondary Aims:&#xD;
&#xD;
        -  To determine if the administration of opioid-free anesthesia in patients undergoing CCF,&#xD;
           and postoperative Lidocaine, Ketamine, and Dexmedetomidine infusions can reduce the&#xD;
           preoperative needs of opioids treatment at discharge time.&#xD;
&#xD;
        -  To determine if the administration of opioid-free anesthesia in patients undergoing CCF&#xD;
           reduces the postoperative gastrointestinal complications.&#xD;
&#xD;
        -  To determine if the administration of postoperative Lidocaine, Ketamine, and&#xD;
           Dexmedetomidine infusions in patients underwent CCF can reduce the preoperative needs of&#xD;
           postoperative anxiolytic treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 6, 2018</start_date>
  <completion_date type="Actual">March 9, 2020</completion_date>
  <primary_completion_date type="Actual">March 9, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Age</measure>
    <time_frame>Baseline</time_frame>
    <description>Patient's age when the surgery was performed (in years)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sex</measure>
    <time_frame>Baseline</time_frame>
    <description>Patient sex classified in two groups: female (1) and male (2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PO Analgesia</measure>
    <time_frame>Baseline</time_frame>
    <description>Postoperative analgesia is a nominal variable which indicates the type of analgesia administered to the patient.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preoperative EVA</measure>
    <time_frame>Baseline</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Preoperative Opioids</measure>
    <time_frame>Baseline</time_frame>
    <description>The preoperative opioids is a categorical variable that indicates if the patient took opioids before the surgery.&#xD;
There are 4 options:&#xD;
No opioids or eventually taken as option 0&#xD;
Weak opioids (tramadol, codeine, trapentadol) as option 1&#xD;
Strong opioids (fentanile, oxicodone, morphine, buprenorphine) as option 2&#xD;
A combination of strong opioids as option 3</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative EVA 1</measure>
    <time_frame>1 day after surgery</time_frame>
    <description>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.&#xD;
The postoperative EVA 1 is measured 1 day after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative EVA 2</measure>
    <time_frame>2 days after surgery</time_frame>
    <description>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.&#xD;
The postoperative EVA 2 is measured 2 day after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative EVA 4</measure>
    <time_frame>4 days after surgery</time_frame>
    <description>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.&#xD;
The postoperative EVA 4 is measured 4 day after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative EVA 6</measure>
    <time_frame>6 days after surgery</time_frame>
    <description>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.&#xD;
The postoperative EVA 6 is measured 6 day after surgery.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sufentanil doses 1</measure>
    <time_frame>From surgery release till first day of hospitalization</time_frame>
    <description>Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 1 day after surgery.&#xD;
Sufentanil doses 1 is a categorical variable with 4 levels:&#xD;
From 0 to 2 pills (equal or less than 30mcg/day) as level 1.&#xD;
From 2 to 4 pills (from 30mcg/day to 60mcg/day)&#xD;
From 5 to 10 pills (from 75mcg/day to 150 mcg/day)&#xD;
More than 10 pills (more than 150mcg/day)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sufentanil doses 2</measure>
    <time_frame>From first day of hospitalization till second day of hospitalization</time_frame>
    <description>Number of pills of sufentanil that the patient has token besides the main treatment. The variable is 2 days after surgery.&#xD;
Sufentanil doses 2 is a categorical variable with 4 levels:&#xD;
From 0 to 2 pills (equal or less than 30mcg/day) as level 1.&#xD;
From 2 to 4 pills (from 30mcg/day to 60mcg/day)&#xD;
From 5 to 10 pills (from 75mcg/day to 150 mcg/day)&#xD;
More than 10 pills (more than 150mcg/day)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sufentanil doses 4</measure>
    <time_frame>From second day of hospitalization till fourth day of hospitalization</time_frame>
    <description>Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 4 days after surgery.&#xD;
Sufentanil doses 4 is a categorical variable with 4 levels:&#xD;
From 0 to 2 pills (equal or less than 30mcg/day) as level 1.&#xD;
From 2 to 4 pills (from 30mcg/day to 60mcg/day)&#xD;
From 5 to 10 pills (from 75mcg/day to 150 mcg/day)&#xD;
More than 10 pills (more than 150mcg/day)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sufentanil doses 6</measure>
    <time_frame>From fourth day of hospitalization till sixth day of hospitalization</time_frame>
    <description>Number of pills of sufentanil that the patient has token besides the main treatment. The variable is gathered 6 days after surgery.&#xD;
Sufentanil doses 6 is a categorical variable with 4 levels:&#xD;
From 0 to 2 pills (equal or less than 30mcg/day) as level 1.&#xD;
From 2 to 4 pills (from 30mcg/day to 60mcg/day)&#xD;
From 5 to 10 pills (from 75mcg/day to 150 mcg/day)&#xD;
More than 10 pills (more than 150mcg/day)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rescue Methadone</measure>
    <time_frame>Baseline</time_frame>
    <description>Rescue Methadone is a categorical variable that indicates if the patient required the use of methadone as a secondary treatment besides the main one.&#xD;
The variable has 4 levels:&#xD;
No rescue as level 0&#xD;
5mg/day as level 1&#xD;
From 10mg/day to 15mg/day as level 2&#xD;
More than 15mg/day as level 3</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Morphine dosage 1</measure>
    <time_frame>From surgery release till first day of hospitalization</time_frame>
    <description>For those cases in which an infusion PCA morphine pump was placed, mean dose 1 day after surgery of the administered morphine.&#xD;
Daily morphine dosage is a categorical variable of 4 levels:&#xD;
Less than 30mg/day as level 1&#xD;
From 30mg/day to 60mg/day as level 2&#xD;
From 60mg/day to 150mg/day as level 3&#xD;
More than 150mg/day as level 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Morphine dosage 2</measure>
    <time_frame>From first day of hospitalization till second day of hospitalization</time_frame>
    <description>For those cases in which an infusion PCA morphine pump was placed, mean dose 2 days after surgery of the administered morphine.&#xD;
Daily morphine dosage is a categorical variable of 4 levels:&#xD;
Less than 30mg/day as level 1&#xD;
From 30mg/day to 60mg/day as level 2&#xD;
From 60mg/day to 150mg/day as level 3&#xD;
More than 150mg/day as level 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Morphine dosage 4</measure>
    <time_frame>From second day of hospitalization till fourth day of hospitalization</time_frame>
    <description>For those cases in which an infusion PCA morphine pump was placed, mean dose 4 days after surgery of the administered morphine.&#xD;
Daily morphine dosage is a categorical variable of 4 levels:&#xD;
Less than 30mg/day as level 1&#xD;
From 30mg/day to 60mg/day as level 2&#xD;
From 60mg/day to 150mg/day as level 3&#xD;
More than 150mg/day as level 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Morphine dosage 6</measure>
    <time_frame>From fourth day of hospitalization till sixth day of hospitalization</time_frame>
    <description>For those cases in which an infusion PCA morphine pump was placed, mean dose 6 days after surgery of the administered morphine.&#xD;
Daily morphine dosage is a categorical variable of 4 levels:&#xD;
Less than 30mg/day as level 1&#xD;
From 30mg/day to 60mg/day as level 2&#xD;
From 60mg/day to 150mg/day as level 3&#xD;
More than 150mg/day as level 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nausea and vomiting</measure>
    <time_frame>Baseline</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Intestinal ileus</measure>
    <time_frame>Baseline</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Constipation</measure>
    <time_frame>Baseline</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Anxiolytic rescue agent</measure>
    <time_frame>Baseline</time_frame>
    <description>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.&#xD;
The variable has 5 levels:&#xD;
Not required as level 0&#xD;
Eventually (1 time per day) as level 1&#xD;
Moderate (2 times per day) as level 2&#xD;
Frequent (3 times per day) as level 3&#xD;
Very Frequently (more than 3 times per day) as level 4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oral ketamine</measure>
    <time_frame>Baseline</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic opioid and hospital discharge</measure>
    <time_frame>Up to 6 days</time_frame>
    <description>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.&#xD;
The variable has 4 levels:&#xD;
No opioids as level 0&#xD;
Decrease when compared to preoperative (between 20% and 30%) as level 1&#xD;
Same dose when compared to preoperative as level 2&#xD;
More dose when compared to preoperative as level 3</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">42</enrollment>
  <condition>Ehlers-Danlos Syndrome</condition>
  <condition>Craniocervical Syndrome</condition>
  <arm_group>
    <arm_group_label>Exposure group</arm_group_label>
    <description>In this group the treatment applied for postoperative pain involves Free-opioid anesthesia (LKDi).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>In this group the treatment applied for postoperative pain involves an opioid-based anesthesia.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients between 18-60 years with diagnosis of Hypermobility Syndrome undergoing&#xD;
        Craneo-cervical fixation (CCF) between Sept, 2018 to March, 2020 to get stabilized&#xD;
        craneo-cervical instability (CCI), and performed under opioid-based total intravenous&#xD;
        anesthesia or opioid-free total intravenous anesthesia with lidocaine, ketamine and&#xD;
        dexmedetomidine (LKD).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of Hypermobility Syndrome undergoing Craneo-cervical&#xD;
             fixation (CCF)&#xD;
&#xD;
          -  Patients between 18-60 years.&#xD;
&#xD;
          -  Patients enrolled in CCF surgery between September 2018 to March 2020 to get&#xD;
             stabilized craneo-cervical instability (CCI).&#xD;
&#xD;
          -  Patients under opioid-based total intravenous anesthesia or opioid-free total&#xD;
             intravenous anesthesia with lidocaine, ketamine and dexmedetomidine (LKD).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  CCF to stabilized post-traumatic or oncologic CCI.&#xD;
&#xD;
          -  Lidocaine allergy.&#xD;
&#xD;
          -  Advances heart-block.&#xD;
&#xD;
          -  Epilepsy or convulsive syndrome non-medicated.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlos Rafael Ramirez Paesano, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Servei d'Anestesiologia Centro Médico Teknon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centro Médico Teknon</name>
      <address>
        <city>Barcelona</city>
        <zip>08022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>25655119</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>30627832</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>26316810</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>21412369</PMID>
  </reference>
  <reference>
    <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. No abstract available.</citation>
    <PMID>29225750</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>30933925</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>32235144</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>27036605</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>30802933</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Servei Central d' Anestesiologia</investigator_affiliation>
    <investigator_full_name>Carlos Ramirez Paesano</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Craneocervical -instability</keyword>
  <keyword>Craneocervical -fixation</keyword>
  <keyword>Opioid induced hyperalgesia</keyword>
  <keyword>Free-opioid-anesthesia</keyword>
  <keyword>Ehlers-Danlos Syndrome</keyword>
  <keyword>Joint Hipermobility syndrome</keyword>
  <keyword>Central sensitization phenomena</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Instability</mesh_term>
    <mesh_term>Ehlers-Danlos Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04437589
org study id: OPIOIDANALGESIA1
nct id: NCT04437589
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Cohort
time perspective: Retrospective
measure: Age
time frame: Baseline
description: Patient's age when the surgery was performed (in years)
measure: Sex
time frame: Baseline
description: Patient sex classified in two groups: female (1) and male (2)
measure: PO Analgesia
time frame: Baseline
description: 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.
measure: Preoperative EVA
time frame: Baseline
description: 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.
measure: Preoperative Opioids
time frame: Baseline
description: 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
measure: Postoperative EVA 1
time frame: 1 day after surgery
description: 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.
measure: Postoperative EVA 2
time frame: 2 days after surgery
description: 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.
measure: Postoperative EVA 4
time frame: 4 days after surgery
description: 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.
measure: Postoperative EVA 6
time frame: 6 days after surgery
description: 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.
measure: Sufentanil doses 1
time frame: From surgery release till first day of hospitalization
description: 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)
measure: Sufentanil doses 2
time frame: From first day of hospitalization till second day of hospitalization
description: 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)
measure: Sufentanil doses 4
time frame: From second day of hospitalization till fourth day of hospitalization
description: 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)
measure: Sufentanil doses 6
time frame: From fourth day of hospitalization till sixth day of hospitalization
description: 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)
measure: Rescue Methadone
time frame: Baseline
description: 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
measure: Morphine dosage 1
time frame: From surgery release till first day of hospitalization
description: 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
measure: Morphine dosage 2
time frame: From first day of hospitalization till second day of hospitalization
description: 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
measure: Morphine dosage 4
time frame: From second day of hospitalization till fourth day of hospitalization
description: 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
measure: Morphine dosage 6
time frame: From fourth day of hospitalization till sixth day of hospitalization
description: 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
measure: Nausea and vomiting
time frame: Baseline
description: 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).
measure: Intestinal ileus
time frame: Baseline
description: 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).
measure: Constipation
time frame: Baseline
description: 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).
measure: Anxiolytic rescue agent
time frame: Baseline
description: 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
measure: Oral ketamine
time frame: Baseline
description: 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).
measure: Chronic opioid and hospital discharge
time frame: Up to 6 days
description: 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
arm group label: Exposure group
description: In this group the treatment applied for postoperative pain involves Free-opioid anesthesia (LKDi).
arm group label: Control group
description: In this group the treatment applied for postoperative pain involves an opioid-based anesthesia.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Carlos Rafael Ramirez Paesano, MD
role: Principal Investigator
affiliation: Servei d'Anestesiologia Centro Médico Teknon
facility: 
country: Spain
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PMID: 29225750
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PMID: 30933925
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PMID: 30802933
responsible party type: Principal Investigator
investigator affiliation: Servei Central d' Anestesiologia
investigator full name: Carlos Ramirez Paesano
investigator title: Principal Investigator
mesh term: Joint Instability
mesh term: Ehlers-Danlos Syndrome
mesh term: Syndrome
sharing ipd: No