Opioids and Immunomodulation - Intrathecal Morphine!

This issue of the Journal of Onco-Anaesthesiology and Perioperative Medicine reports an original article related to the use of intrathecal morphine for perioperative analgesia.[1] The use of intrathecal drugs, including opioids, has long been used as an adjuvant for increasing the duration of perioperative analgesia.[2] The intrathecal morphine has its concerns when administered intrathecally. Being a potent, long-acting, hydrophilic drug, it has the potential of not only immediate concerns but also delayed and long-term potential implications. It may lead to respiratory depression (both early onset, i.e. within 2–4 h of its administration, and delayed onset, i.e., after 6–24 h of its intrathecal administration), delayed sedation, cognitive effects, pruritis, nausea and vomiting, urinary retention, hypotension, bradycardia and even opioid-induced hyperalgesia and tolerance. Opioids have been implicated (although not conclusively proven) in the possibility of cancer recurrence and progression. The analgesic effects of opioids are primarily via μ-opioid receptors present in the central nervous system. However, the presence of these receptors on immune cells, such as dendritic cells, also influences the immune system. The response leads to immunomodulation/immunosuppression. Although the use of systemic morphine is mostly hypothesised for the tumor recurrence, evidence related to neuraxial opioids, particularly intrathecal morphine, is scarce. Neuraxial opioids, particularly intrathecal opioids, have their benefits with manageable associated adverse concerns, and appear to be acceptable for long-duration surgeries under general anaesthesia and requiring follow-up catheterisation. Its potential for immunomodulatory effects has not been explored much. Due to low doses and lesser systemic absorption, lower plasma levels are observed and thus appear to have minimal immunomodulatory impact.[3,4] However, the possibility of immunomodulation still exists due to the effects on spinal opioid receptors.[5,6] More promisingly, neuraxial opioids, more particularly intrathecal morphine, produce excellent analgesia and thus may reduce perioperative surgical stress, which in itself is beneficial for preventing the development of a milieu to promote tumour progression. By suppressing the sympathetic response and the inflammatory cytokine cascade, intrathecal morphine shall not influence tumor progression.[6–8] Pharmacogenetics influences the influence of opioids on the body’s response to opioids.[9] While systemic opioids, particularly morphine, have been implicated in cancer recurrence/progression via immunosuppression, the role of intrathecal morphine remains uncertain. Intrathecal morphine needs to be chosen based on its beneficial effects and weighed against its impact on the immune system remains a valuable tool in onco-anaesthesia for managing perioperative pain. Further research is needed to elucidate the relationship between intrathecal morphine and cancer outcomes. A multidisciplinary approach, particularly with the availability of various ultrasound-guided regional blocks like fascial plane blocks, needs to be followed in the perioperative period for cancer surgeries.