title: The effect of transdermal nitroglycerin on spinal S(+)-ketamine antinociception following orthopedic surgery.
abstract: OBJECTIVE
  To determine whether combination of transdermal nitroglycerine (a nitric oxide generator) would enhance analgesia from epidural S(+)-ketamine (a N-methyl-D-aspartate antagonist) in patients undergoing orthopedic surgery with combined spinal anesthesia.
  
  
  METHODS
  Randomized, double-blind study.
  
  
  METHODS
  Orthopedic surgery unit of a teaching hospital.
  
  
  METHODS
  60 ASA physical status I and II patients scheduled for minor orthopedic knee surgery.
  
  
  METHODS
  Patients were randomized to one of five groups (n = 12) to receive combined epidural/intrathecal anesthesia. A 10-mL epidural injection was first administered to all patients (study drug or normal saline). Intrathecal anesthesia consisted of 15 mg bupivacaine. Twenty to 30 minutes after the spinal puncture, a transdermal patch of either nitroglycerin 5 mg or placebo was applied. The control group (CG) received epidural saline and transdermal placebo. The nitroglycerin group (NG) received epidural saline and transdermal nitroglycerine patch. The 0.1 mg/kg S(+)-ketamine epidural group (1 KG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal placebo. The 0.2 mg/kg S(+)-ketamine epidural group (2 KG) received 0.2 mg/kg epidural S(+)-ketamine and transdermal placebo. Finally, the nitroglycerin/0.1 mg/kg S(+)-ketamine epidural group (1 NKG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal nitroglycerin. Pain and adverse effects were evaluated using a 10-cm visual analog scale (VAS).
  
  
  RESULTS
  The groups were demographically the same. Sensory anesthetic level and VAS score for pain at the time of first rescue medication were similar among groups. The time to first rescue analgesic (min) was less in both the CG and the NG groups compared with the other groups (p < 0.05). Epidural S(+)-ketamine resulted in analgesia to both groups (1 KG < 2 KG; p < 0.05). The 1 NKG and the 2 KG displayed similar analgesia (p > 0.05). The CG required more rescue analgesics in 24 hours compared with the patients who received epidural S(+)-ketamine (p < 0.02).
  
  
  CONCLUSIONS
  Epidural S(+)-ketamine resulted in antinociception, which was enhanced by transdermal nitroglycerin.
authors.affiliation: Hospital das Clínicas, Department of Biomechanical and Medical Rehabilitation of the Locomotor Members, University of São Paulo, São Paulo, Brazil. grlauret@fmrp.usp.br
authors.forename: G R
authors.initials: GR
authors.lastname: Lauretti
authors.forename: A P
authors.initials: AP
authors.lastname: Oliveira
authors.forename: A M
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: C A
authors.initials: CA
authors.lastname: Paccola
mesh_terms: D000759:Adjuvants, Anesthesia / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000328:Adult; D015360:Analgesia, Epidural; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000767:Anesthesia, Epidural; D000775:Anesthesia, Spinal; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D007719:Knee Joint / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D020030:Nitric Oxide Donors / Q000008:administration & dosage* / Q000009:adverse effects; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000009:adverse effects; D019637:Orthopedic Procedures; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D000759:Adjuvants, Anesthesia; D000700:Analgesics; D020030:Nitric Oxide Donors; D016202:N-Methylaspartate; D007649:Ketamine; D005996:Nitroglycerin