Abstract

BackgroundPatients 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.MethodsA 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.ResultsNineteen 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.ConclusionOFA-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.

Highlights

  • Cranio-cervical instability (CCI) has been well identified in diseases with connective tissue disorders like EhlersDanlos Syndrome-Hypermobility Type/Joint Hypermobility Syndrome (EDS-HT/JHS)

  • Ramírez‐Paesano et al Orphanet J Rare Dis (2021) 16:172 decreases the total doses of methadone rescues, reduces anxiolytic requirements and gastrointestinal side-effects, except for constipation

  • The reduction of Visual Analogue Score (VAS) was more important on the 1stpostoperative dayin the opioid-free anesthetic techniques (OFA)-plus group 5.35 (4.83–5.86) vs. Opioid-based anesthesia and analgesia management (OP) group 7.89 (7.56–8.23) (p < 0.001), meaning a decrease up to 32% of VAS in OFA-plus group

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Summary

Introduction

Cranio-cervical instability (CCI) has been well identified in diseases with connective tissue disorders like EhlersDanlos Syndrome-Hypermobility Type/Joint Hypermobility Syndrome (EDS-HT/JHS). Generalized joint hypermobility can exhibit laxity of the ligaments of the spine and a propensity to have severe symptoms due to CCI and Cervical Medullary Syndrome (CMS) that may be involved in the development of severe proprioceptive disturbances causing soft tissue microtrauma and generalized musculoskeletal pain [1, 2]. CMS may be explained by the traumatic deformation of axons that induces abnormal sodium influx through mechanically sensitive ­Na+ channels. This subsequently triggers an increase in intra-axonal calcium via the opening of the voltage-gated calcium channel, up-regulation of glutaminergic pathway,chronic neuro-inflammation and apoptosis. Patients with Ehlers-Danlos Syndrome/Hypermobility Type (EDS-HT/JHS) and Craneo-Cervical Instabil‐ ity frequently suffer from severe widespread pain which is difficult to control. The secondary aim was to assess the needs of opioids at hospital-discharge, incidence of gastrointestinal complications and the requirement of anxiolytic

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