Correlation of the Dose of Midazolam for Symptom Control with Administration Periods

Abstract

Although tolerance to midazolam is sometimes described in the palliative care literature, no studies have systemically examined the possibility. To explore the association between midazolam dose for symptom palliation and the administration period, a retrospective study was performed on 62 terminally ill cancer patients who required parenteral midazolam in the final three days of life. The mean maximum dose and administration period of midazolam were 38 +/- 45 mg/day (median = 24) and 10 +/- 19 days (median = 2.5), respectively. Thirteen patients (21%) received midazolam at a dose of 60 mg/day or more, and 13 patients (21%) received it for 14 days or longer. The maximum doses were significantly correlated with patient age (rho = -0.32, P = 0.012) and the administration period (rho = 0.47, P < 0.01); and were significantly higher in patients who received midazolam for 14 days or longer (74 +/- 63 mg/day vs. 28 +/- 34 mg/day, P < 0.01). Multivariate analyses revealed that younger age (< or =70) and longer administration periods (> or =14 days) were independent determinants for a midazolam requirement of 60 mg/day or more (odds ratios [95% C.I.] = 0.091 [0.009 - 0.92], P = 0.042; 11 [2.3 - 54], P < 0.01; respectively). The significant correlation of midazolam doses with administration period suggests that the longer use of midazolam can result in the development of tolerance. This finding suggests that midazolam should be reserved for patients with limited prognoses.

The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice

“…It is frequently used in palliative care as a sedative or anticonvulsant (Morita et al, 2003). It is supposed to be used over short periods of time with the longest time of use reported being 35 days.…”

Palliative sedation in pediatric oncology

“…Midazolam ist ein Benzodiazepin mit kurzer Wirkdauer, ist dadurch gut steuerbar und antagonisierbar und gilt als Medikament der ersten Wahl bei Erwachsenen mit den Nachteilen der Tachyphylaxie nach h€ aufiger Anwendung [5].…”

“…Kinder haben, Neugeborene und junge S€ auglinge ausgenommen, auf das K€ orpergewicht bezogen eine viel h€ ohere Fremdstoffclearance als Erwachsene [8]. Wir wissen allerdings nicht, ob die Tachyphylaxie und oft paradoxe Reaktion auf erh€ ohte Clearance oder auf ein weiter fortgeschrittenes Stadium der Erkrankung und damit mehr € Angste des Kindes zur€ uckzuf€ uhren ist, dazu w€ aren Spiegelmessungen notwendig [5].…”

Treatment with midazolam for nocturnal sedation of terminal cancer patients in a hospice setting

“…In the field of palliative medicine, midazolam has been administered by continuous infusion intravenously or subcutaneously to ease terminal uncontrollable symptoms such as delirium, nausea and vomiting, dyspnea, and fatigue [10][11][12].…”

“…Midazolam appears to be suitable for administration by continuous infusion for nocturnal sedation, because it has be characterized by relatively rapid onset of action and short recovery time. While it is possible that tolerance may develop during continuous long-term use of midazolam [4,[10][11][12], it has not been reported, as far as we know, whether tolerance develops during repeated intermittent short-term infusion for insomnia. In the present study, patients with terminal cancer treated with midazolam infusion were retrospectively surveyed to assess the optimal infusion rates of midazolam needed to maintain appropriate sleep without oversedation and with clear arousal on the following morning.…”