Effects of naloxegol on whole gut transit in opioid-naïve healthy subjects receiving codeine: A randomized, controlled trial.

BACKGROUND: Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu-opiate opioid receptor antagonist. AIM: To compare the effects on pan-gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers. METHODS: We conducted a randomized, double-blind, placebo-controlled, single-center, parallel-group study in 72 healthy opioid-naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2 , colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2 . KEY RESULTS: Participants were 59.7% women, median BMI 25.0 kg/m2 , and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2 . There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min [IQR 110.5-238.6]) and naloxegol (95.5 min [89.1-135.4]). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% [0.0-45.0]) and naloxegol (51% [18.8-76.2]). However, no significant differences were found between codeine-treated participants concomitantly receiving placebo or naloxegol. CONCLUSIONS AND INFERENCES: Short-term administration of naloxegol (25 mg) in healthy, opioid-naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid-naïve subjects.

Rectal gas volume: Defining cut-offs for screening for evacuation disorders in patients with constipation.

BACKGROUND: Diagnosis of rectal evacuation disorders (RED) is currently based on anorectal manometry (ARM) and evacuation tests in specialized laboratories; we recently showed higher rectal gas volume (RGV) and maximum rectal gas transaxial area (MRGTA) measured on abdominal and pelvic computed tomography (CT) in patients with documented RED.The aim of this study was to obtain cut-off values of RGV, MRGTA, and rectal area on scout film (RASF) to differentiate constipated patients with RED from those without RED, based on ARM, balloon expulsion test (BET), and colon transit test. METHODS: We identified 118 constipated patients (65 with RED) with prior record of CT. Using standard CT software, we used a variable region of interest (ROI) program to measure RGV, MRTGA, and RASF, as previously described. We constructed receiver operating characteristics curves based on different values, and we estimated AUC, specificity, and positive predictive value (PPV) to detect RED in patients with constipation. KEY RESULTS: Receiver operating characteristics of the models to predict RED showed AUC 0.751 for RGV and 0.737 for MRGTA (both P<.001), and 0.623 for RASF (P=.029). At specificity of 90%, RGV of 30 mL had a PPV 77.3%, MRGTA of 10 cm2 had a PPV 75.0%, and RFAS of 9 cm2 had a PPV of 68.8% for identifying constipated patients with RED. CONCLUSIONS & INFERENCES: Rectal gas measurements on abdominal imaging may indicate RED in patients with constipation. At ~90% specificity for RED, RGV of 20 or 30 mL or MRGTA of 10 cm2 on CT has PPV ~75%, and RASF of >9 cm2 has PPV of ~69%.

Opioid analgesic use among patients presenting with acute abdominal pain and factors associated with surgical diagnoses.

BACKGROUND: The prevalence of chronic opioid use among non-cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non-cancer patients presenting with AAP to an emergency department (ED). METHODS: We performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP. We used electronic medical records, and focused on 2352 adults with AAP who underwent abdominal CT scan within 24 hours of presentation. We determined odds ratios of association with constipation and features predicting conditions that may require surgery (surgical diagnosis). KEY RESULTS: There were 2352 eligible patients; 18.8% were opioid users. Constipation was more frequent in opioid (35.1%) compared to non-opioid users [OR 2.88 (95% CI 2.28, 3.62)]. Prevalence of surgical diagnosis in the opioid and non-opioid users was 35.3% and 41.7% respectively (P=.019). By univariate analysis, age and neutrophil count independently predicted increased risk, and chronic opioid use decreased risk of surgical diagnosis. Internal validation of logistic models using a randomly selected validation subset (25% of entire cohort, 587/2352) showed receiver operating characteristic (ROC) curves for the validation and full cohorts were similar. CONCLUSIONS AND INFERENCES: Approximately 19% of adults presenting with AAP were opioid users; constipation is almost three times as likely in opioid users compared to non-opioid users presenting with AAP. Factors significantly associated with altered risk of surgical diagnoses were age, opioid use, and neutrophil count.