Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.
OBJECTIVE
To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively.


METHODS
In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144). Average Pain Intensity at Rest over days 1-3 (0- to 10-point numerical rating scale [NRS]) was the primary efficacy endpoint. Secondary endpoints included Average Pain Intensity upon Sitting, Standing, and Walking over days 1-3 (0- to 10-point NRS) as well as Average Total Daily Dose of Morphine over days 1-3.


BACKGROUND
This trial is registered on www.clinicaltrials.gov (NCT00788710).


RESULTS
The least squares (LS) means (95% CI) for the primary endpoint were 3.26 (2.96, 3.55); 2.46 (2.16, 2.76); and 2.40 (2.11, 2.69) for placebo, etoricoxib 90 mg, and etoricoxib 120 mg, respectively, significantly different for both etoricoxib doses versus placebo (p < 0.001). Patients on etoricoxib 90 mg and 120 mg required ~30% less morphine per day than those on placebo (p < 0.001), which led to more rapid bowel recovery in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain ≤3/10.


CONCLUSIONS
A key limitation for this study was that movement-evoked pain measurements were not designated as primary endpoints.


CONCLUSIONS
In patients undergoing total abdominal hysterectomy, etoricoxib 90 mg and 120 mg dosed preoperatively and then continued postoperatively significantly reduces both resting and movement-related pain, as well as reduced opioid (morphine) consumption that led to more rapid bowel recovery.
Department of Anesthesiology, Thomas Jefferson University, Philadelphia, PA 19107, USA. Eugene.Viscusi@jefferson.edu
Eugene R
ER
Viscusi
Tara L
TL
Frenkl
Craig T
CT
Hartrick
Narinder
N
Rawal
Henrik
H
Kehlet
Dimitris
D
Papanicolaou
Arnold
A
Gammaitoni
Amy T
AT
Ko
Leslie M
LM
Morgan
Anish
A
Mehta
Sean P
SP
Curtis
Paul M
PM
Peloso
D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects / Q000379:methods; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D019990:Perioperative Care / Q000379:methods; D010919:Placebos; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000700:Analgesics; D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D010919:Placebos; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib