Opioid-free anesthesia for patients with joint hypermobility syndrome undergoing craneo-cervical fixation: a case-series study focused on anti-hyperalgesic approach
Authors: Ramírez-Paesano Carlos , Juanola Galceran Albert , Rodiera Clarens Claudia , Gilete García Vicenҫ , Oliver Abadal Bartolomé , Vilchez Cobo Verónica , Ros Nebot Bibiana , Julián González Sara , Cao López Lucía , Santaliestra Fierro Jesús , Rodiera Olivé Josep 
Published: April 2021

Abstract
Background
Patients with Ehlers-Danlos Syndrome/Hypermobility Type (EDS-HT/JHS) and Craneo-Cervical Instability frequently suffer from severe widespread pain which is difficult to control. Chronic neuroinflammation, opioid-induced hyperalgesia, and central sensitization may explain this painful condition. The aim of this study was to determine if opioid-free anesthesia plus the postoperative administration of lidocaine, ketamine and dexmedetomidine can reduce postoperative pain and the need of methadone rescues in comparison with opioid-based management in these patients undergoing Craneo-Cervical Fixation (CCF). The secondary aim was to assess the needs of opioids at hospital-discharge, incidence of gastrointestinal complications and the requirement of anxiolytic.

Methods
A retrospective, consecutive case series study was designed. 42 patients with EDS-HT/JHS undergoing CCF were enrolled in two groups: an OFA-plus Group that received opioid-free anesthesia with propofol, lidocaine, ketamine and dexmedetomidine, and OP Group, opioid-based anesthesia-analgesia. The main variables: Preoperative Visual Analogue Score (VAS), postoperative VAS on the 1st, 2nd, 4th and 6th days, sufentanil or morphine requirements, need for methadone rescue, and VAS at hospital-discharge. Data was presented by mean ± SD, percentage, median or interquartile range. Chi-squared or Fisher’s test. 95% C.I and P values < 0.05.

Results
Nineteen patients in OFA-plus, and 23 patients in OP group. VAS was lower in OFA-plus on the postoperative days evaluated (p < 0.001).VAS at hospital-discharge was lower in OFA-plus: 4.96 (4.54–5.37) vs. OP 6.39 (6.07–6.71) (p < 0.001). Methadone requirement was lower in the OFA-plus (p < 0.001). 78% of patients in OFA-plus didn’t need methadone rescue. 95% in OP group needed methadone rescues at high doses(> 15 mg/day). No differences regarding equivalent doses of sufentanil or morphine consumption on the 2nd, 4th, and 6th postoperative days were found. OFA-plus decreased ileus, nausea and vomiting (p < 0.001). 60.9% in OFA-plus group decreased opioid requirements at hospital-discharge compared with preoperative values. A 77% reduction of anxiolytics requirements was shown.

Conclusion
OFA-plus management for patients undergoing CCF with EDS-HT/JHS shows significant reduction in postoperative pain and at hospital-discharge compared with opioid-based anesthesia. OFA-plus management decreases the total doses of methadone rescues, reduces anxiolytic requirements and gastrointestinal side-effects, except for constipation. OFA-plus management is a feasible option to improve postoperative pain control, reducing the opioids’ use and their postoperative side-effects in patients undergoing CCF with EDS-HT/JHS.