Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16323
Revised: June 5, 2014
Accepted: July 24, 2014
Published online: November 21, 2014
AIM: To investigate the efficacy of lubiprostone compared to Senna on bowel symptoms and constipation in post-operative orthopedic patients treated with opioids.
METHODS: In this double blind, randomized, active comparator trial, adults who required opioids for analgesia following orthopedic procedures and who were admitted in inpatient rehabilitation were randomized following baseline assessments to lubiprostone (Amitza®), orally twice a day or Senna (generic) two capsules administered daily for six days. Subjects were assessed using the patient assessment of constipation (PAC)-symptoms (PAC-SYM) and the PAC-quality of life (PAC-QOL) scales measured at baseline and Day 7; Subjects were assessed daily for secondary measures included the Bristol stool scale bowel consistency, specific bowel symptom score (Nausea, cramping, straining, completeness, abdominal pain, time per lavatory attempt, assistance needed), adverse events and rescue medications required. Function was measured using the functional independence measure (FIM) at admission and discharge; length of stay (LOS) and missed treatments due to gastrointestinal symptoms were also assessed.
RESULTS: 64 adults were enrolled; 56 participants (28 in each group) had baseline and follow up measures and were included in the intention to treat (ITT) analyses. 43 participants completed the study, 21 in the active lubiprostone and 22 in the active Senna group. The mean age of the participants was 71.5 years (SD = 11.4 years, range: 28-96 years). In the ITT analyses, participants showed significant improvement in bowel symptoms as measured by the PAC-SYM (mean ± SD, -0.28 ± 0.60, range: -1-2.33) and PAC-QOL (mean ± SD, 0.33 ± 0.81, range: -1.5-2.0) over time, but there were no significant differences between the lubiprostone and Senna groups in mean change in the PAC-SYM (-0.20 ± 0.60 vs -0.36 ± 0.61, P = 0.61 respectively) or the PAC-QOL (0.29 ± 0.76 vs 0.37 ± 0.87, P = 0.61 respectively). The mean change in each bowel symptom also did not significantly differ between treatment groups on ITT analyses, except for completeness of bowel movement, with the Senna group showing greater negative mean change in bowel movement completeness (-0.56 ± 1.01 vs -2.00 ± 1.41, P = 0.03) and for reduction of abdominal pain, favoring Senna (-0.14 ± 0.73 vs -0.73 ± 1.08, P = 0.04). Fifteen (75%) participants in the lubiprostone and in the Senna group requested rescue treatments. Participants made significant functional improvement from admission to discharge over a median LOS of 12 d, with a mean FIM change of 29.13 ± 13.58 and no significant between group differences (27.0 ± 9.2 vs 31.5 ± 16.6, P = 0.27).
CONCLUSION: Both lubiprostone and Senna improved constipation-related symptoms and QOL in opioid-induced constipation, with no significant between-group differences.
Core tip: Constipation is frequent in postoperative orthopedic patients treated with opioids. Opioid side effects are associated with poorer pain control, and thus may limit the ability to mobilize patients immediately following orthopedic surgery. There is very limited information comparing the efficacy and safety of pharmacologic interventions for opioid-induced constipation. In this study we found that two medications, lubiprostone and Senna, were associated with improvement in bowel-related symptoms in opioid-induced constipation in post-operative orthopedic patients, with no differences found between the two medications. Rescue bowel medications were frequently required by participants in both groups, indicating that multiple laxative medications may be required for constipation symptom control in this setting.