title: Lubiprostone vs Senna in postoperative orthopedic surgery patients with opioid-induced constipation: a double-blind, active-comparator trial.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Both lubiprostone and Senna improved constipation-related symptoms and QOL in opioid-induced constipation, with no significant between-group differences.
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marciniak
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Santiago
authors.initials: S
authors.lastname: Toledo
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Jungwha
authors.initials: J
authors.lastname: Lee
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Jesselson
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Jillian
authors.initials: J
authors.lastname: Bateman
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Grover
authors.affiliation: Christina M Marciniak, Santiago Toledo, Department of Physical Medicine and Rehabilitation, School of Medicine, Northwestern University, Chicago, IL 60611, United States.
authors.forename: Joy
authors.initials: J
authors.lastname: Tierny
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000009:adverse effects*; D002400:Cathartics / Q000627:therapeutic use*; D002641:Chicago; D003248:Constipation / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068238:Lubiprostone; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000009:adverse effects*; D010149:Postoperative Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D011788:Quality of Life; D020127:Recovery of Function; D012676:Senna Extract / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D002400:Cathartics; D000068238:Lubiprostone; D012676:Senna Extract; D000527:Alprostadil
keywords: Constipation; Lubiprostone; Opioids; Orthopedics; Rehabilitation; Senna