Liu, H.J., Gao, X.Z., Liu, X.M., Xia, M., Li, W.Y., & Jin, Y. (2014). Effect of intrathecal dexmedetomidine on spinal morphine analgesia in patients with refractory cancer pain. Journal of Palliative Medicine, 17, 837–840. 

To investigate the effects of intrathecal dexmedetomidine on analgesia receiving intrathecal morphine for refractory cancer-related pain

Patients were initially provided intrathecal morphine at 0.4 mg/ml at a continuous dose of 0.1 ml per hour, a bolus dose of 0.5 ml, and then pump parameters were adjusted if pain score were > 4 or more than eight bolus doses were needed on the previous day. An external catheter was connected to a computerized ambulatory delivery pump. Patients were monitored for seven days and then were crossed over to receive intrathecal morphine at the same initial dose plus dexmedetomidine at 1 mcg/ml in a continuous infusion for seven days. Daily average pain scores and other study measures were recorded at baseline and at the end of each seven-day study period.

• N = 24
• AGE = 58 years (SD = 14 years)
• MALES: 42%, FEMALES: 58%
• KEY DISEASE CHARACTERISTICS: Various tumor types; all had pain scores > 6 and systemic opioid use of more than 200 mg per day or dose-limiting side effects; the majority had nociceptive pain

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: China

• PHASE OF CARE: End of life care
• APPLICATIONS: Palliative care

Double-blinded, crossover, randomized trial

• Visual Analog Scale (VAS) for pain intensity 
• Number of bolus doses required
• Numeric Rating Scale (NRS) for sleep deprivation

Pain intensity and frequency declined significantly with intrathecal morphine (p < 0.05) and then declined more with the addition of dexmedetomidine (p < 0.05). Sleep deprivation was improved in the same pattern (p < 0.05). With morphine alone, daily morphine consumption was 7.9 mg (SD = 1.1) and bolus dose frequency was 6.9 (SD = 1.3). With the addition of dexmedetomidine, morphine consumption decreased to 5.3 mg (SD = 0.8), and the frequency of bolus doses decreased to 2.8 times (SD = 0.7). The most frequent side effects were nausea, vomiting, difficulty urinating, and somnolence. Constipation decreased from baseline.

The addition of intrathecal dexmedetomidine to morphine analgesia decreased morphine consumption and improved pain control in patients with refractory cancer-related pain.

• Small sample (< 100)

Dexmedetomidine is an alpha adrenergic receptor agonist that has sympatholytic, sedative, and analgesic effects. The findings of this study suggest that the addition of this medication to morphine analgesia administered intrathecally may improve pain control and reduce morphine consumption and the number of bolus doses needed for pain control. It also demonstrated sedative effects. Refractory pain can be very difficult to manage to achieve adequate pain control. The approach studied here may provide an option for the management of refractory pain. Additional studies are needed to fully establish the safety profile and efficacy of this treatment.