Midazolam versus dexmedetomidine: breakthrough use variations-the DREAMS trial secondary analysis

Patients in the terminal phase may require both regular medications and breakthrough medications for palliative symptom management. Breakthrough dosing can provide an objective measure of symptom management, but the relationships between symptom severity and breakthrough use in sedated patients in the terminal phase remain unclear. This study examined the relationship between symptom management and breakthrough medication use in dying patients receiving dexmedetomidine or midazolam as background sedative infusions.

This secondary analysis of the Dexmedetomidine for the Relief of End-of-life Agitation and optiMised Sedation trial included 52 palliative care inpatients randomised to subcutaneous infusion of dexmedetomidine (0.5 µg/kg/hour) or midazolam (0.25 mg/kg/day). Breakthrough medication use was correlated with Palliative Care Problem Severity Score (PCPSS) scores (0-3) using Spearman's coefficient. Primary analyses matched PCPSS-Pain with opioids, PCPSS-Psychological/Spiritual with sedatives and PCPSS-Other with other breakthrough medications, applying a Bonferroni correction (α=0.0083).

In total, 130 patient-days were analysed (71 dexmedetomidine, 59 midazolam). Symptom severity was mild and equivalent between arms (median PCPSS scores 0-1, all p>0.05). Total breakthrough doses were similar (2.5-3 daily). In the dexmedetomidine arm, PCPSS-Pain correlated with opioid use (r=0.46, p=0.001) and PCPSS-Psychological/Spiritual with sedative use (r=0.49, p=0.003), with a nonsignificant trend for PCPSS-Other (r=0.21, p=0.17). In the midazolam arm, correlations were absent or negative (r=-0.24 to 0.068, p>0.05).

Dexmedetomidine patients showed significant correlations between symptom severity and breakthrough opioid or sedative use, whereas midazolam patients did not. Despite similar mild symptom scores and breakthrough needs, only dexmedetomidine demonstrated expected symptom-medication relationships. This divergence warrants further research.