The Addition of Intrathecal Clonidine to Reduce Medication-Related Side-Effects in Cancer Pain: A Retrospective Cohort Study

Evgeny Bulat,1 Rahul Chaturvedi,2 Peyton Johnson,2 Neal Rakesh,3 Amitabh Gulati3 1Pain Treatment Specialists, VIP Medical Group, New York, NY, USA; 2Department of Anesthesiology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY, USA; 3Department of Anesthesiology & Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Neal Rakesh, Department of Anesthesiology & Critical Care Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, M 308, New York, NY, 10065, Email [email protected]: Compared to conventional medical management, targeted drug delivery provides superior cancer pain management with fewer side-effects and potentially improved survival. Intrathecal (IT) clonidine has been used off-label to improve analgesia in patients with cancer pain, but evidence regarding safe dosing in this patient population is limited. This study evaluates the impact of adding IT clonidine on pain, opioid consumption, and the prevalence of medication-related side-effects. It also provides initial dosing recommendations for cancer pain.Materials and Methods: This was a retrospective chart review conducted at a single academic cancer center. Medical records between 2012 and 2022 were queried for patients who had an intrathecal pump (ITP). Patients’ charts were reviewed prior to starting IT clonidine, at the IT clonidine start date, at 1– 3 months follow-up, and at over three months follow-up. Primary outcomes included the visual analog scale (VAS) score and daily systemic morphine milligram equivalents (MME). Secondary outcomes included IT or systemic medication side-effects and the daily doses of concurrent IT opioids and local anesthetic (LA).Results: Eighteen patients were included. No significant change in VAS or systemic MME was observed at follow-up after starting IT clonidine. Median daily IT bupivacaine and opioids with or without patient-controlled boluses significantly rose by the first follow-up; by the second follow-up, only IT opioids were elevated. There was a trend towards a lower prevalence of medication-related side-effects across follow-up periods. On post-hoc logistic regression analysis, IT clonidine dosing was the sole significant predictor of side-effect prevalence. Higher IT clonidine dosing was associated with a lower likelihood of side-effects. Initial IT clonidine doses of 40– 60 mcg/day were associated with a 50– 75% reduced probability of side-effects.Conclusion: While its role in reducing pain and systemic opioids is complex, IT clonidine may have a beneficial role in mitigating medication-related side-effects from systemic opioids, IT opioids, or LA for cancer pain. IT clonidine may be safely initiated at doses of 40– 60 mcg/day for this indication.Keywords: intrathecal pump, intrathecal clonidine, morphine milligram equivalent, MME, visual analog scale, VAS, cancer pain