An Evaluation of Docusate Monotherapy and the Prevention of Opioid-Induced Constipation after Surgery.

Our purpose was to determine if docusate monotherapy is effective in preventing opioid-induced constipation in patients receiving opioids following orthopedic surgery. Our single-center, retrospective, cohort study evaluated 212 orthopedic patients who received opioids between May 1, 2018, and December 31, 2018. All patients were aged 18 years and older, hospitalized for more than 48 hours, and received docusate for primary prevention of constipation post-operatively. The primary outcome was the proportion of patients taking opioid medications who experienced docusate failure, defined as patients who did not have a bowel movement within 5 days of starting docusate after surgery or those patients who required the use of additional laxative agents to produce a bowel movement. After excluding patients which did not meet the inclusion criteria, 79.9% (n = 159/199) experienced docusate treatment failure. Of these patients, 42.8% (68/159) failed to have a bowel movement or had a bowel movement greater than 5 days post-surgery. The remaining 57.2% (91/159) of patients required an additional laxative to produce a bowel movement. Docusate monotherapy was not effective in preventing constipation in patients receiving opioids following elective orthopedic surgery. Based on these findings, we propose utilization of stimulant bowel products with proven efficacy as primary therapy after surgery to prevent constipation. Future multi-centered, randomized controlled trials are necessary to evaluate the differences in efficacy and safety between common bowel regimens in treating opioid-induced constipation in patients who undergo elective orthopedic surgery.

An Outbreak of Burkholderia cepacia Complex Infections Associated with Contaminated Liquid Docusate.

OBJECTIVE To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source. SETTING A 629-bed, tertiary-care, pediatric hospital in Houston, Texas. PATIENTS Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units. METHODS We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory. RESULTS Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2-148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation. CONCLUSIONS Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer. Infect Control Hosp Epidemiol 2017;38:567-573.

Polyethylene Glycol 3350 and Docusate Sodium Compared With Docusate Sodium Alone After Urogynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To compare time to first bowel movement and additional gastrointestinal outcomes between women receiving polyethylene glycol 3350 (PEG3350) and docusate sodium and docusate sodium alone after urogynecologic surgery. METHODS: Participants received twice-daily 100 mg docusate sodium and were randomized to daily 1) PEG3350 or 2) inert placebo for 5 days after urogynecologic surgery. They completed bowel diaries, Bristol stool scale, validated Patient Assessment of Constipation Symptom Questionnaire, and Patient Assessment of Constipation Quality-of-Life Questionnaire preoperatively and 1 week after surgery. Our primary outcome was time to first bowel movement after surgery. To detect a 1-day difference in time to first bowel movement (4 compared with 3 days), 63 participants were needed in each group. RESULTS: From September 2012 through March 2015, 145 women were randomized and 131 (90%) analyzed: 66 received PEG3350, and 65 received placebo. Polyethylene glycol 3350 did not significantly reduce time to first bowel movement after surgery compared with placebo (2.77 days [interquartile range 1.86-3.40] compared with 2.92 days [interquartile range 1.85-4.02] P=.25). Women in the PEG3350 group were less likely to take additional laxatives postoperatively, and the PEG3350 group was more adherent to the study drug regimen. Questionnaire scores, fecal incontinence, and urgency were similar between groups. CONCLUSION: In women taking routine docusate sodium after urogynecologic surgery, adding PEG3350 postoperatively did not reduce time to first bowel movement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01691742.

Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review.

UNLABELLED: Opioid-induced constipation (OIC) is a side effect of opioid therapy that can affect quality of life, adherence to treatment, and morbidity and possibly mortality. OBJECTIVES: To investigate whether docusate sodium, sennosides, and lactulose have equal efficacy and side effect profiles compared to PEG in the management of OIC in adults. METHODS: A systematic review was undertaken. Randomized controlled trials of adults taking opioids for cancer or non-cancer pain were considered if they met inclusion criteria. CONCLUSIONS: Statistical pooling was not possible as no studies met inclusion criteria. Large, well-powered, randomized controlled trials are feasible. Standard definitions of OIC would assist with the execution of these studies and contribute to their internal and external validity. Further research is strongly encouraged.

Magnetic resonance colonography without bowel cleansing using oral and rectal stool softeners (fecal cracking)--a feasibility study.

The aim of our study was to assess the effect of oral and rectal stool softeners on dark-lumen magnetic resonance (MR) colonography without bowel cleansing. Ten volunteers underwent MR colonography without colonic cleansing. A baseline examination was performed without oral or rectal administration of stool softeners. In a second set, volunteers ingested 60 ml of lactulose 24 h prior to MR examination. In a third examination, water as a rectal enema was replaced by a solution of 0.5%-docusate sodium (DS). A fourth MR examination was performed, in conjunction with both oral administration of lactulose and rectal application of DS. A T1-weighted data set was acquired at scanning times of 0, 5 and 10 min after colonic filling. A fourth data set was acquired 75 s after i.v. injection of contrast agent. Signal intensity of stool was calculated for all colonic segments. Without oral ingestion of lactulose or rectal enema with DS stool signal intensity was high and did not decrease over time. However, lactulose and DS caused a decrease in stool signal intensity. Both substances together led to a decreasing signal intensity of feces. Combination of lactulose and DS provided the lowest signal intensity of stool. Thus, feces could hardly be distinguished from dark rectal enema allowing for the assessment of the colonic wall.

Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.

BACKGROUND: The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort. OBJECTIVE: To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS. METHODS: Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain. RESULTS: Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were reported among 23 (72%) participants, resulting in a cold sore incidence rate of 19.8 per 100 person-months of observation. Online data were available for 32 outbreaks; the absence of a resolution date made it impossible to accurately calculate the duration of 12 (38%) outbreaks. Although the DSS treatment group had a shorter mean outbreak duration (6.6 vs 7.7 days, P =.2) and fewer mean days to crust formation (3.5 vs 4.9, P =.1), these differences did not reach statistical significance. The DSS group has statistically significant lower mean pain scores (3.1 vs 7.6, P =.04), but participants in this group also consumed more acetaminophen tablets than the placebo group (1.1 versus 0.5, P=.55). Adherence to medication was similar in both groups: 7 (50%) of the verum group reported using the cream as directed compared to 6 (46.2%) in the placebo group; (P =.8). CONCLUSIONS: We efficiently recruited participants and achieved high overall retention rates. However, participant adherence to the daily outbreak visit schedules was low and only 7 (50%) participants used the cream as directed. These limitations could be addressed in future Internet-based studies by using Personal Digital Assistants (PDAs), using reminder devices, and providing incentives. By enhancing participant adherence, clinical trials requiring frequent participant contact may be feasible over the Internet.

Bowel care for individuals with spinal cord injury: comparison of four approaches.

The efficacies of four bowel care regimens (bisacodyl suppositories, glycerin suppositories, mineral oil enemas and docusate sodium mini-enemas) were compared in seven subjects with traumatic spinal cord injury. Efficacy was assessed in terms of colonic transit time, bowel evacuation time and subjective responses to a questionnaire. Both docusate sodium mini-enemas and mineral oil enemas decreased total and left-sided colonic transit time. However, docusate sodium mini-enemas were superior to mineral oil enemas in terms of the decrease in bowel evacuation time and symptom reduction. Results in this small group of subjects suggest that docusate sodium mini-enemas may have advantages in the management of bowel evacuation in individuals with spinal cord injury.

The effects of four, commercial ceruminolytic agents on the middle ear.

Four, commercially available ceruminolytic agents and physiological saline were screened for ototoxic and inflammatory reactions on the middle ear mucosae of guinea pigs (n = 38) and dogs (n = 24). Each solution was injected transtympanically in anesthetized animals. The effects were assessed by brain stem auditory evoked response (BAER) tests to evaluate hearing function and by histological examination of the middle ear structures. Varying degrees of hearing loss and inflammation were observed in some guinea pigs and dogs treated with solutions A, C, and D, whereas no abnormal finding was associated with solution B or saline.

Phenolphthalein-induced toxic epidermal necrolysis.

OBJECTIVE: To report a case of phenolphthalein-induced toxic epidermal necrolysis (TEN) in a patient maintained on several other medications more commonly known to be associated with TEN. CASE SUMMARY: A 78-year-old white man presented with intractable lower back pain and constipation. On day 1 of admission, the patient exhibited a diffuse urticarial rash over his trunk and extremities. History revealed that the patient had taken a combination phenolphthalein/docusate sodium (Correctol) over-the-counter laxative 1 day prior to admission. He had a similar urticarial rash 1.5 years earlier with this product and was instructed not to use it. A biopsy was performed and evidence from light microscopic analysis of the tissue led to a diagnosis of TEN. Furosemide, spironolactone, allopurinol, and hydroxyurea were considered possible causes of the reaction and were discontinued. Despite this, the lesions worsened in severity. The patient subsequently responded well to intravenous antibiotics, intravenous corticosteroids, and local wound care. Furosemide, spironolactone, hydroxyurea, allopurinol, and docusate were all reintroduced without reactivation of the lesions. DISCUSSION: Phenolphthalein is the active ingredient in several over-the-counter laxative preparations and has only rarely been reported to cause TEN. (It is no longer contained in Correctol.) To our knowledge, this case report represents only the third description of laxative-induced TEN. Although this patient had been exposed to several other medications more commonly associated with TEN, his long-term tolerance of and uneventful rechallenge with these medications exclude them as potential catalysts to this drug reaction. The patient's previous rash and the temporal relation of this event and the ingestion of phenolphthalein, as well as the similarity of this case to other reports, point to phenolphthalein as the cause of TEN in this patient. CONCLUSIONS: TEN is a rare disorder that can be fatal in up to 30% of patients. Clinicians should include phenolphthalein in their list of possible causes of drug-induced TEN. A careful and complete medication history can help avoid unnecessary discontinuation of clinically important medications and inadvertent rechallenge with the causative agent.

Renal failure associated with laxative abuse.

Eating disorder patients often abuse laxatives in an attempt to purge excess food. Laxative abuse can cause hypokalemia and volume depletion. Hypokalemia, in turn, can lead to rhabdomyolysis. Laxative-induced hypokalemia and volume depletion have been previously reported to cause renal insufficiency, but not severe enough to require hemodialysis. A 27-year-old woman with a long history of laxative abuse presented with severe renal failure associated with hypokalemia and volume depletion. She required acute hemodialysis for worsening acidosis (pH 7.05) despite assisted ventilation. A prior episode of hypokalemic rhabdomyolysis at age 23 had resulted in only mild renal insufficiency. Her later episode of severe renal failure was linked to profound volume depletion (blood urea nitrogen 135 mg/dl). This patient calls attention to a potentially life-threatening complication of laxative abuse and indicates that volume depletion can exacerbate laxative-associated renal failure.

Non-medical prescribing.

Non-medical prescribing is increasingly being seen as a cost effective option by both the government and paramedical professional bodies. The use of potentially dangerous preparations in a wide range of clinical settings is not without danger, as illustrated by this case of facial palsy associated with the use of a proprietary brand of wax softener in an ear with a perforated ear drum.

Increased sensitivity to mechanical ventilation after surfactant inactivation in young rabbit lungs.

OBJECTIVES: To study the individual and combined effects of surfactant inactivation and mechanical ventilation on pulmonary microvascular permeability and lung compliance. DESIGN: Prospective, controlled trial. An isolated, perfused, lung model of surfactant inactivation and mechanical ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks) New Zealand white rabbits. SETTING: Laboratory of a university-affiliated medical school. MEASUREMENTS AND MAIN RESULTS: Isolated, perfused lungs were prepared for measurement of the capillary filtration coefficient before and after one of four interventions: instillation of dioctyl succinate, a surfactant inactivator, without ventilation (group 1); ventilation without dioctyl succinate at 15, 30, or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group 3); and control lungs without dioctyl succinate or ventilation (group 4). A significant increase in the capillary filtration coefficient was noted after dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and 45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced a significantly greater increase in the capillary filtration coefficient than ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. CONCLUSIONS: These data suggest that ventilation after surfactant inactivation is more injurious to the pulmonary microvasculature than ventilation alone, and that generalized lung overdistention is not the primary mechanism for microvascular injury in the diseased, noncompliant lung. The increases seen in the capillary filtration coefficient in postventilated surfactant inactivated lungs, even at low-ventilation pressures, suggest that low peak inspiratory pressures do not overdistend the dioctyl succinate-treated lung.

[Tienilic acid as a likely cause of "auto immune" active hepatitis (author's transl)]. / Hépatite active "auto-immune": responsabilité vraisemblable de l'acide tiénilique.

A 68 years old, non-alcoholic woman, with a history of viral hepatitis 40 years before, developed jaundice. Liver biopsy showed histological evidence of activity. HB virus markers were found to be lacking on two successive tests. Immunological investigations gave negative results, except for the presence of liver/kidney microsomal auto-antibodies. Systemic and portal blood eosinophilia suggested a drug-induced disease. The patient was being treated with sodium dioctyl-sulfosuccinate + dantrone and tienilic acid. Two months after these drugs were withdrawn her condition improved; she put on weight and serum transaminases, measured on two occasions, had returned to normal levels.

Amenorrhea and edema.

In a 22 year old woman extensive edema developed during evaluation for amenorrhea. It was learned then that she was consuming escessive amounts of a laxative daily. Balance studies were performed which demonstrated that she excreted large amounts of sodium in her liquid stools while taking the dose of laxative she had been using. The presence of increased plasma renin activity and increased urinary aldosterone suggest that in this patient the occurrence of the edema after she discontinued use of the laxative was due to secondary aldosteronism presumably caused by plasma volume depletion.

Treatment of constipation in geriatric and chronically ill patients: a comparison.

The difficulties of adequately managing constipation, particulary in patients with impaired or limited mobility as a result of surgery, cardiovascular or cerebral disease, or advanced age, led us to evaluate the use of stool softeners in a homogeneous group of institutionalized patients. Comparison was made between dioctyl sodium sulfosuccinate (DSS) (Colace), q.d. and b.i.d., and dioctyl calcium sulfosuccinate (DCS) (Surfak), q.d. Analysis of results showed 81% of the patients receiving DCS improved, a significant result (P is less than .02) when assessed by the sign test. By contrast, DSS caused no significant improvement over placebo, regardless of whether it was administered once or twice a day. The mean number of natural bowel movements among the DCS group increased approximately 62% over the placebo period, more than twice the 30% increase seen with DSS administered either b.i.d. or q.d. No adverse reactions were reported in any of the groups, and no significant study-induced changes occurred in laboratory measurements.