Dexmedetomedine and Ketamine in Erector Spinae Block for Postoperative Analgesia Following Mastectomy.
Condition: Breast Cancer
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Persistent pain after breast cancer surgery is frequently observed in more than 60% of
      patients.The suboptimal management of perioperative pain can lead to the occurrence of
      persistent breast cancer pain syndrome and phantom breast pain. Dexmedetomidine, a novel
      α2-agonist with an eight-fold affinity for α2-adrenergic receptors (sedate and analgesic
      effects) as clonidine, while exerts much less α1-effects., has been found to significantly
      increase the duration of peripheral nerve blocks, with minimal systemic side effects.

      Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptors. It is
      used for sedation, premedication, induction, and maintenance of general anesthesia. Central,
      regional, and local anesthetic and analgesic properties have been reported for ketamine. Both
      can be used through Erector spinae plane block for postoperative pain control.
    

Detailed description: 
      Persistent pain after breast cancer surgery is frequently observed in more than 60% of
      patients.The suboptimal management of perioperative pain can lead to the occurrence of
      persistent breast cancer pain syndrome and phantom breast pain.

      A systematic review and meta-analysis of experimental studies showed that the provision of
      effective analgesia reduces both the number and incidence of metastases in experimental
      cancer models . Pain may influence body homeostasis and cancer progression by pain-related
      immune suppression.

      General anesthesia is the conventional, most frequently used anesthetic technique in breast
      cancer surgical interventions. Various regional anesthetic techniques have also been used;
      these include local wound infiltration, thoracic epidural anesthesia, paravertebral block
      (PVB), thoracic spinal anesthesia, and more recently, ultrasound-guided interfacial plane
      blocks such as pectoral nerve (PECS) blocks type 1 and 2 and the serratus plane block (SPB).
      Recently introduced erector spinae plane block (ESPB) requires less technical expertise
      (easy), and may be a safe alternative to PVB. ESP block is described for treating thoracic
      neuropathic pain with encouraging results. ESP is a potential space deep to erector spinae
      muscle (ES), where the injected local anaesthetic (LA) spreads cranio-caudally up to several
      levels as the ES fascia extends from nuchal fascia cranially to the sacrum caudally (C7-T2
      cranially and L2-L3 caudally), The block covers somatic and visceral pain during breast
      surgery blocks by blocking ventral rami, dorsal rami of spinal nerves, and rami communicans
      that transmit sympathetic fibers.

      There is another potentially beneficial effects of regional anaesthesia and analgesia on
      perioperative outcomes, these include decreased opioids consumption , lower rate of
      post-operative pulmonary complications, decreased post-operative nausea vomiting (PONV) and
      decreased duration of post-anaesthesia care unit stay. Regional anaesthesia has long-term
      oncological outcomes as it is considered protective for cancer recurrence by its indirect and
      direct antiproliferative effects.

      Over recent years, the addition of multiple types of additives to local anesthetics has been
      reported to improve analgesic effect of peripheral nerve block and regional blocks
      Dexmedetomidine, a novel α2-agonist with an eight-fold affinity for α2-adrenergic receptors
      (sedate and analgesic effects) as clonidine, while exerts much less α1-effects., has been
      found to significantly increase the duration of peripheral nerve blocks, with minimal
      systemic side effects.

      Ketamine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptors. It is
      used for sedation, premedication, induction, and maintenance of general anesthesia. Central,
      regional, and local anesthetic and analgesic properties have been reported for ketamine.
    

Intervention name(s): Bupivacaine Hydrochloride; Bupivacaine Hydrochloride and dexmedetomedine; Bupivacaine Hydrochloride and ketamine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): injection of Bupivacaine 0.25% in ESPB; injection of Bupivacaine 0.25% and dexmedetomedine in ESPB; injection of Bupivacaine 0.25% and ketamine in ESPB
Other intervention name(s): local anesthetic; local anesthetic and dexmedetomedine; local anesthetic and ketamine
Intervention MeSH terms: Ketamine; Bupivacaine; Anesthetics, Local; Anesthetics
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment