title: Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management.
abstract: BACKGROUND
  Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine in cancer pain therapy.
  
  
  METHODS
  After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4.
  
  
  RESULTS
  The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not.
  
  
  CONCLUSIONS
  Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may be of significant benefit in cancer pain management.
authors.affiliation: Department of Surgery, Orthopedics and Traumatology, Center for Pain Treatment, Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil. grlauret@fmrp.usp.br
authors.forename: G R
authors.initials: GR
authors.lastname: Lauretti
authors.forename: I C
authors.initials: IC
authors.lastname: Lima
authors.forename: M P
authors.initials: MP
authors.lastname: Reis
authors.forename: W A
authors.initials: WA
authors.lastname: Prado
authors.forename: N L
authors.initials: NL
authors.lastname: Pereira
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000009:adverse effects; D010148:Intractable Pain / Q000188:drug therapy*; D011446:Prospective Studies; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000701:Analgesics, Opioid; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D007649:Ketamine; D009020:Morphine; D005996:Nitroglycerin