Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy

Study Objective: To examine analgesia and adverse effects of combination ep idural pain therapy consisting of administration of morphine with either lo w dose of ketamine, neostigmine, or midazolam in terminal cancer pain patie nts. Design: Randomized double-blind study. Setting: Teaching hospital. Patients: 48 terminal cancer patients suffering from chronic pain. Interventions: Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a IO-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. All patients were taking oral amitriptyline 50 mg at bedtime. P ain was initially treated with epidural morphine 2 mg twice daily (12-hr in tervals) to maintain the VAS below 4/10. Afterwards, VAS scores greater tha n or equal to 4/10 at any time were treated by adding the epidural study dr ug (2 ml), which runs administered each morning, just after the 2-mg epidur al morphine administration. The control group, (CG) received 2 mg of epidur al morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ket amine (2 ml). The neostigmine group (NG) received 100 mu g epidural, neosti gmine (2 ml). The midazolam group (MG) received 500 mu g epidural midazolam (2 ml). Patients received the study drugs on a daily basis. Measurements and Main Results: Duration of effective analgesia was measured as time from the study drug administration to the first patient's VAS scor e greater than or equal to 4/10 recorded in days. The groups were demograph ically the same. The VAS pain scores prior to the treatment were also simil ar among groups. Only the patients in the KG demonstrated lower VAS scores compared to the MG (p = 0.018). Time since the epidural study drug administ ration until patient complaint of pain VAS greater than or equal to 4/10 wa s higher for both the KG and NG compared to the CG (KG > CG, p = 0.049; NG > CG; p = 0.0163). Only the KG used less epidural morphine compared to the CG during the period of study (25 days) (p = 0.003). Conclusion: The association of either low-dose epidural ketamine or neostig mine (but not midazolam) to epidural morphine increased the duration of ana lgesia in the population studied (gt; 20 days) compared to the CG and MG (8 to 10 days) when administrered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects. (C) 2000 by Elsevier Science Inc.