title: Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy.
abstract: OBJECTIVE
  To examine analgesia and adverse effects of combination epidural pain therapy consisting of administration of morphine with either low dose of ketamine, neostigmine, or midazolam in terminal cancer pain patients.
  
  
  METHODS
  Randomized double-blind study.
  
  
  METHODS
  Teaching hospital.
  
  
  METHODS
  48 terminal cancer patients suffering from chronic pain.
  
  
  METHODS
  Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a 10-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. Pain was initially treated with epidural morphine 2 mg twice daily (12-hr intervals) to maintain the VAS below 4/10. Afterwards, VAS scores > or = 4/10 at any time were treated by adding the epidural study drug (2 ml), which was administered each morning, just after the 2-mg epidural morphine administration. The control group (CG) received 2 mg of epidural morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ketamine (2 ml). The neostigmine group (NG) received 100 micrograms epidural neostigmine (2 ml). The midazolam group (MG) received 500 micrograms epidural midazolam (2 ml). Patients received the study drugs on a daily basis.
  
  
  RESULTS
  Duration of effective analgesia was measured as time from the study drug administration to the first patient's VAS score > or = 4/10 recorded in days. The groups were demographically the same. The VAS pain scores prior to the treatment were also similar 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 administration until patient complaint of pain VAS > or = 4/10 was 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).
  
  
  CONCLUSIONS
  The association of either low-dose epidural ketamine or neostigmine (but not midazolam) to epidural morphine increased the duration of analgesia in the population studied (gt;20 days) compared to the CG and MG (8 to 10 days) when administered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects.
authors.affiliation: Department of Surgery, Orthopedics and Traumatology, Hospital das Clinicas, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil.
authors.forename: G R
authors.initials: GR
authors.lastname: Lauretti
authors.forename: J M
authors.initials: JM
authors.lastname: Gomes
authors.forename: M P
authors.initials: MP
authors.lastname: Reis
authors.forename: N L
authors.initials: NL
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D015360:Analgesia, Epidural; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D009388:Neostigmine / Q000627:therapeutic use*; D010148:Intractable Pain / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D009388:Neostigmine; D007649:Ketamine; D009020:Morphine; D008874:Midazolam