What evidence exists to no longer use docusate for bowel regimens in hospitalized patients?

Comment by InpharmD Researcher

Despite its widespread use, there is a lack of compelling evidence supporting the efficacy of docusate sodium. Clinical guidelines either do not mention docusate as a treatment option or recommend it with a low level of confidence. The results from clinical trials are heterogeneous, with possible benefits observed on those with spinal cord injuries, but not for patients in the postoperative setting. This has led to some authors advocating for removal of docusate from the hospital formulary.

Background

The American Society of Colon and Rectal Surgeons guideline on constipation does not include docusate sodium as one of the treatment options. Dietary modifications are recommended for symptomatic constipation as the first-line therapy. Recommended pharmacological interventions include osmotic laxatives (e.g., polyethylene glycol, lactulose), stimulant laxatives (e.g., bisacodyl – second line, short term only), and “newer agents” (e.g., lubiprostone, linaclotide) in refractory cases. In those with pelvic floor dyssynergia, biofeedback therapy is recommended as the first-line treatment. [1]

The World Gastroenterology Organization guideline states that stool softeners are a viable therapy option for constipation management. It rates evidence of recommendation for dioctyl sulfosuccinate (docusate) as Grade C and level of evidence as III; however, they do not provide descriptions of what these levels indicate. [2]

A position statement on constipation management by the American Gastroenterological Association also does not include docusate as a medical treatment option. Osmotic agents (e.g., milk of magnesia or polyethylene glycol) or stimulant laxatives (e.g., bisacodyl or glycerol suppositories) are recommended depending on stool consistency. [3]

The American College of Gastroenterology’s monograph on chronic idiopathic constipation (CIC) provides no statement on the use of docusate or stool softeners for the treatment of CIC. It lists fiber supplements, polyethylene glycol (PEG), lactulose, sodium picosulfate, bisacodyl, prucalopride, linaclotide, lubiprostone, and biofeedback (for CIC with pelvic floor dyssynergia) as effective treatment options. [4]

Per the European Society for Medical Oncology (ESMO) guidelines for management of constipation in advanced cancer, detergent/stool softeners (i.e., docusate) are generally not recommended in advanced disease as the use of docusate sodium in palliative care is based on inadequate experimental evidence. [5]

Data compiled in systematic reviews also suggest subpar evidence. According to a 2005 systematic review, the efficacy of docusate is modest at best, citing a small study suggesting no benefit with docusate treatment, and another study showing psyllium (5.1 grams twice daily) is superior to docusate (100 mg twice daily). Based on the available evidence, the reviewers rate the quality of evidence as poor (level III – insufficient because of a limited number of power of studies, flaws in their design or conduct), and classify the recommendation as Grade C (poor evidence to support a recommendation for or against the use of the modality). Another systematic review from 2014 on laxative use in functional constipation reports that docusate sodium is commonly used in practice, despite the lack of evidence compared to PEG. The review includes one study that meets its inclusion criteria, which compared docusate to psyllium and found improved efficacy with psyllium (Table 2). [6], [7]

A 2021 review determined that docusate did not show any benefits for constipation in older patients compared with placebo or psyllium or sennosides; psyllium and sennosides were observed to be more effective compared with docusate. This lackluster evidence of stool softeners for constipation in geriatrics was further reiterated in another 2021 review article. Soluble fibers that promote bulking, osmotic agents, and stimulants are generally recommended for initial or additional treatment. However, elderly patients may require treatment individualization based on medical history and potential adverse events. Overall, there appears to be a lack of data to support the use of docusate for constipation. As such, it is recommended that pharmacists and healthcare providers reassess and reconsider whether to use docusate and add additional medications to an already complex medication regimen in older populations. [8], [9]

Per the American Gastroenterological Association guidelines on the medical management of opioid-induced constipation (OIC), traditional laxatives, including docusate, are recommended as the first-line agents in treating OIC; however, the role of docusate or other laxatives in OIC prophylaxis is not explicitly discussed. A 2021 review evaluating the clinical evidence for docusate use in OIC management identified 13 guidelines or consensus recommendations (CR) and four primary literature studies. The authors noted consistent design limitations in the primary literature and a lack of primary evidence cited in the guidelines or CR to support their recommendations of using docusate for OIC prophylaxis or treatment. Finally, a review article on the management of OIC in palliative care patients does not discuss docusate salts as a laxative option in this population. It states that osmotic agents or stimulant laxatives (if no response in two days) can be considered in clinical practice; however, it notes there is a lack of evidence to guide safe and effective treatment of OIC in this group of patients. Even though docusate is widely prescribed for OIC, the evidence behind this recommendation is collectively weak across most of the guidelines and CR. Therefore, a close assessment of OIC protocols and/or algorithms among institutions and health care providers are warranted to incorporate evidence-based therapy and reduce unnecessary docusate use and associated costs. [10], [11], [12]

A 2015 Canadian study quantified the local pattern of laxative use and estimated some of the associated costs. Docusate was the most frequently prescribed laxative, accounting for over 165,000 doses, requiring an estimated 2,065 nursing hours for administration, with associated costs approaching $60,000 per year. The authors extrapolated their data to suggest that total healthcare spending in North America on docusate products likely exceeds $100,000,000 yearly. It was suggested that while inpatient laxative use is common and frequently persists following discharge, the routine use of docusate products in a constrained healthcare system may be wasteful. [13]

A single-center study attempted to design and apply a program for the comprehensive management of neurogenic bowel in 38 spinal cord injury patients. Docusate was used in 15 (44.1%) of patients, one of which was intolerant to its use (6.7%). Eight patients (53.3%) stopped medication by themselves due to poor results and two patients had the prescription ended due to poor results. By the end of the study, only four of the 15 patients (26.7%) were still on docusate at a mean dose of 150 mg/day (range, 100-200 mg/day). [14]

Various articles have advocated for the removal of docusate from hospital formulary due to lack of benefit. The addition of docusate increases patient polypharmacy and the multiple doses of large capsules or solutions are cited as a burden. A single center cost analysis in Canada found that over 165,000 doses of laxatives were administered, which accounts for an estimated 2000 nursing hours for administration. Such spending on docusate products was estimated to be in the hundreds of millions USD per year. Despite the strong opinions presented by authors, the articles lack documentation of successful removal of docusate from hospital formulary. [15], [16], [17]

References:

[1] Paquette IM, Varma M, Ternent C, Melton-Meaux G, Rafferty JF, Feingold D, Steele SR. The American Society of Colon and Rectal Surgeons' clinical practice guideline for the evaluation and management of constipation. Dis Colon Rectum. 2016;59(6):479-92.
[2] Lindberg G, Hamid S, Malfertheiner P, et al. Constipation: a global perspective. World Gastroenterology Organisation Global Guidelines. Milwaukee, WI: World Gastroenterology Organisation;2010.
[3] American Gastroenterological Association, Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-7.
[4] Ford AC, Moayyedi P, Lacy BE, et al; Task Force on the Management of Functional Bowel Disorders. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109 Suppl 1:S2-26;
[5] Larkin PJ, Cherny NI, La Carpia D, et al. Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(Suppl 4):iv111-iv125. doi:10.1093/annonc/mdy148
[6] Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol. 2005;100(4):936-71.
[7] Paré P, Fedorak RN. Systematic review of stimulant and nonstimulant laxatives for the treatment of functional constipation. Can J Gastroenterol Hepatol. 2014;28(10):549-57.
[8] Nguyen T. The Role of Docusate for Constipation in Older People. Sr Care Pharm. 2021;36(10):501-507. doi:10.4140/TCP.n.2021.501
[9] Lucak S, Lunsford TN, Harris LA. Evaluation and Treatment of Constipation in the Geriatric Population. Clin Geriatr Med. 2021;37(1):85-102. doi:10.1016/j.cger.2020.08.007
[10] Crockett SD, Greer KB, Heidelbaugh JJ, Falck-Ytter Y, Hanson BJ, Sultan S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Medical Management of Opioid-Induced Constipation. Gastroenterology. 2019 Jan;156(1):218-226. doi: 10.1053/j.gastro.2018.07.016. Epub 2018 Oct 16. PMID: 30340754.
[11] Engle AL, Winans ARM. Rethinking Docusate's Role in Opioid-Induced Constipation: A Critical Analysis of the Evidence. J Pain Palliat Care Pharmacother. 2021 Mar;35(1):63-72. doi: 10.1080/15360288.2020.1828529. Epub 2021 Feb 17. PMID: 33596159.
[12] Prichard D, Bharucha A. Management of opioid-induced constipation for people in palliative care. Int J Palliat Nurs. 2015;21(6):272, 274-80.
[13] Lee TC, McDonald EG, Bonnici A, Tamblyn R. Pattern of Inpatient Laxative Use: Waste Not, Want Not. JAMA Intern Med. 2016;176(8):1216-1217. doi:10.1001/jamainternmed.2016.2775
[14] Correa GI, Rotter KP. Clinical evaluation and management of neurogenic bowel after spinal cord injury. Spinal Cord. 2000;38(5):301-308. doi:10.1038/sj.sc.3100851
[15] McKee KY, Widera E. Habitual Prescribing of Laxatives-It's Time to Flush Outdated Protocols Down the Drain. JAMA Intern Med. 2016;176(8):1217-1219. doi:10.1001/jamainternmed.2016.2780
[16] MacMillan TE, Kamali R, Cavalcanti RB. Missed Opportunity to Deprescribe: Docusate for Constipation in Medical Inpatients. Am J Med. 2016;129(9):1001.e1-1001.e10017. doi:10.1016/j.amjmed.2016.04.008
[17] Fakheri RJ, Volpicelli FM. Things We Do for No Reason: Prescribing Docusate for Constipation in Hospitalized Adults. J Hosp Med. 2019;14(2):110-113. doi:10.12788/jhm.3124

Literature Review

A search of the published medical literature revealed 10 studies investigating the researchable question:

What evidence exists to no longer use docusate for bowel regimens in hospitalized patients?

Please see Tables 1-10 for your response.


 

Dioctyl sodium sulfosuccinate- an ineffective prophylactic laxative

Design

Randomized, single-center, open-label study

N=34

Objective

To evaluate if the routine use of dioctyl sodium sulfosuccinate (docusate sodium) 200 mg alters the incidence of constipation in a geriatric hospital setting

Study Groups

Docusate (n=17)

No laxative (n=17)

Inclusion Criteria

Patients admitted to a chronic medical service

Exclusion Criteria

Admitted with spinal cord injuries, acute myocardial infarction, or admitted for diarrhea

Methods

Patients who were consecutively admitted to a single center in California were randomized by a coin flip. Patients allocated to the docusate group received 100 mg BID (or 30 mL BID if they were unable to swallow). The control patients received no laxatives of any kind during the study period.

If patients randomized to docusate did not have a bowel movement after two days, they received a bisacodyl NF or glycerin suppositories on the evening of the third day. If this did not work, then patients would receive a sodium biphosphate and sodium phosphate enema. 

Outcome Measures

Bowel movements; quality of stool

Baseline Characteristics

 

Docusate (n=17)

No laxative (n=17)

 

Age, years

53.05 ± 4.42 59.68 ± 4.54  

Male

100% 100%  

Comatose

7 (41%) 6 (35%)  

Days followed

25.94 ± 4.32 25.58 ± 6.18  

Results

 

Docusate (n=17)

No laxative (n=17)

P-value

Bowel movements per patient

Stools per patient day

26.11 ± 5.82

0.8664 ± 0.1117

23.76 ± 6.28

0.8147 ± 0.1167

NS

Stool quality per patient

Watery liquid

Soft formed normal

Watery hard formed

Hard dry

Enema evacuated

 

3.60 ± 0.99

21.58 ± 5.52

0.64 ± 0.41

0.17 ± 0.05

0.47 ± 0.24 

 

9.64 ± 3.85

13.05 ± 3.32

0.05 ± 0.05

1.23 ± 1.45

0.11 ± 0.08

NS (for all)

NS=not significant

Adverse Events

None reported

Study Author Conclusions

No statistically significant difference was found in the objective variables of frequency or quality of stools. These results conclude that routine ‘prophylactic bowel medication’ (200 mg DDS) is not effective in altering the incidence of constipation in this hospital setting.

InpharmD Researcher Critique

While this study had a small sample size of elderly males, this patient group is particularly representative of the patients usually felt to be prone to impaction (elderly, debilitated, and bed-bound). The decision to not use a placebo was because the authors felt it would not have made a difference, as most patients were either comatose or disorientated and confused.

 

References:

Goodman J, Pang J, Bessman AN. Dioctyl sodium sulfosuccinate- an ineffective prophylactic laxative. J Chronic Dis. 1976;29(1):59-63. doi: 10.1016/0021-9681(76)90068-0

 

Psyllium is superior to docusate sodium for treatment of chronic constipation

Design

Multi‐site, randomized, double‐blind, double-dummy, parallel‐design study

N=170

Objective

To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium

Study Groups

Psyllium (n=88)

Docusate (n=82)

Inclusion criteria

A bowel movement frequency of <3/week during the baseline week just prior to treatment

Exclusion criteria

Obstructive or metabolic etiology for constipation, and subjects with a history of regular stimulant laxative use (>1 dose/week) or laxative abuse (greater than daily dosage recommended on the label for any laxative), pregnant or nursing female

Methods

A 2‐week baseline placebo phase preceded a 2‐week treatment phase. Subjects were randomized into one of two treatment groups: psyllium 5.1 g BID or docusate 100 mg BID.

Duration

2 weeks

Outcome Measures

Bowel movement frequency, stool weight, dry stool weight, total stool weight, stool water weight

Baseline Characteristics

 

Total population (N=170)

 

 

Age, years

37.2 ±0.83    

Women

156 (91.8%)    

White

109 (64.1%)    

Results

Endpoint

Psyllium (n=88)

Docusate (n=82)

P-value

Bowel Movement Frequency, BM/week

Baseline

Week 1

Week 2

 

3.08 ± 0.18

3.26 ± 0.19

3.51 ± 0.22

 

3.44 ± 0.20

3.07 ± 0.20

2.87 ± 0.22

 

 

0.247

0.021

Total Stool Weight, g/week

Baseline

Week 1

Week 2

 

260.94 ± 19.28

359.89 ± 22.88

354.34 ± 24.86

 

282.94 ± 21.41

271.91 ± 24.50

312.44 ± 24.93

 

 

0.005

0.118

Stool Water Content, %

Baseline

Week 1

Week 2

 

70.68 ± 0.66

73.01 ± 0.52

73.89 ± 0.58

 

71.05 ± 0.73

71.06 ± 0.60

71.58 ± 0.62

 

 

0.007

0.004

BM= bowel movement

Adverse Events

N/A

Study Author Conclusions

Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation. 

InpharmD Researcher Critique

The baseline characteristics where not separated into the two treatment groups. There is no way of determining if a group are predisposed to a higher likelihood of constipation. 

 

References:

McRorie JW, Daggy BP, Morel JG, Diersing PS, Miner PB, Robinson M. Psyllium is superior to docusate sodium for treatment of chronic constipation. Aliment Pharmacol Ther. 1998;12(5):491-7

 

Randomized, Double-Blind, Placebo-Controlled Trial of Oral Docusate in the Management of Constipation in Hospice Patients

Design

Prospective, randomized, double-blind, placebo-controlled trial

N=74

Objective

To assess the efficacy of docusate in hospice patients

Study Groups

Docusate and sennosides (n=35)

Placebo and sennosides (n=39)

Inclusion criteria

Age ≥ 18 years, able to take oral medications, no difficulty swallowing, nonmalignant or malignant diseases, on or off opioids, having a Palliative Performance Scale (PPS) score of 20% or more (able to tolerate sips or food, may or may not be bedbound, may or may not be confused), newly admitted to hospice

Exclusion criteria

Diagnosed with gastrointestinal stoma, contraindications to docusate, prescribed docusate "as needed", if docusate was prescribed in liquid or crushed form, or if docusate was discontinued or withheld before the patient was screened

Methods

Docusate was given as 200 mg BID, and sennoside tablets 8.6 mg were taken one to three times daily. In the docusate and placebo groups, 10 and 8 participants did not complete the 10-day study, respectively. 

Duration

10 days

Outcome Measures

Stool frequency, volume, and consistency

Baseline Characteristics

 

Docusate (n=35)

Placebo (n=39)

Age, years

75.3 71.9

Women

15 (42.9%) 18 (46.2%)

Palliative Performance Scale score, %

42% 43.4% 

Mini-Mental State Exam score

24 26.5

Results

 

Docusate (n=25)

Placebo (n=31)

Average stool frequency per day

0.74 ± 0.47 0.69 ± 0.37

Most frequent Bristol Stool Form Scale type

Type 3 (sausage, cracks in surface)

Type 6 (mushy stool)

Type 4 (smooth and soft)

Type 5 (soft blobs)

Adverse Events

Not disclosed

Study Author Conclusions

There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate should be considered on an individual basis.

InpharmD Researcher Critique

Rapid decline of some patients, in particular, their inability to swallow medications, had an impact in the ability to continue in the study and could have skewed the final results. Baseline constipation/stool production values were not reported.

 

References:

Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. J Pain Symptom Manage. 2013;45(1):2-13.

 

Treatment of Constipation in Geriatric and Chronically Ill Patients: A Comparison

Design

Randomized, placebo-controlled, single-blinded

N=46

Objective

To compare the efficacy of daily Colace (docusate sodium) with twice-daily Colace and daily Surfak (docusate calcium)

Study Groups

Colace 100mg daily (n=13)

Colace 100mg twice daily (n=17)

Surfak 250mg daily (n=16)

Inclusion criteria

History of chronic functional constipation; dependent upon laxatives; had a bowel movement, naturally or with a Dulcolax suppository or enema, within 24 hours before entering the treatment phase of the study

Exclusion criteria

Unwilling or unable to cooperate with the study or give informed consent; patients with disorders of the gastrointestinal tract that would make it difficult to evaluate therapeutic response; patients treated during the preceding month with either of the test drugs

Methods

Patients were randomized to receive Colace 100 mg once daily in the morning, Colace 100 mg BID, or Surfack 240 mg once in the morning.

Duration

3 weeks

Outcome Measures

An increase in frequency of natural bowel movement 

Baseline Characteristics

 

Colace once daily

(n=13)

Colace BID

(n=17)

Surfak once daily 

(n=16)

Age, years (range)

83.4 (66-93) 82.2 (68-91) 80.8 (66-97)

Women

12 (92%) 15 (88%) 13 (81%)

White

13 17 16

Gastrointestinal disorder

3 5 4

Results

 

Colace once daily (n=13)

Colace BID (n=17)

Surfak once daily (n=16)

Increase in bowel movements

5 (38%) 8 (47%) 13 (81%)*

*p<0.02

Adverse Events

None reported.

Study Author Conclusions

Analysis of results showed 81% of the patients receiving Surfak (docusate calcium) improved, a significant result (p<0.02) when assessed by the sign test. By contrast, Colace 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 Surfak group increased approximately 62% over the placebo period, more than twice the 30% increase seen with DSS administered either BID or once daily

InpharmD Researcher Critique

Most of the study population included women and all of the study participants were Caucasian which may not represent the population of patients that experience constipation. This study also did not include severe constipation, as all patients were required to have at least one bowel movement before entry.

 

References:

Fain AM, Susat R, Herring M, Dorton K. Treatment of constipation in geriatric and chronically ill patients: a comparison. South Med J. 1978;71(6):677-80.

 

The Efficacy of Docusate Sodium and Senna Glycoside for the Treatment of Constipation After Rotator Cuff Repair: A Randomized Controlled Study

Design

Prospective, randomized controlled trial

N= 107

Objective

To determine the efficacy of docusate sodium and senna glycoside in the prevention and treatment of postoperative constipation

Study Groups

Docusate (n= 38)

Senna (n= 36)

Control (n= 33)

Inclusion Criteria

Age >18 years; scheduled to undergo arthroscopic rotator cuff repair (RCR)

Exclusion Criteria

History of previously diagnosed gastrointestinal syndromes; chronic pre-operative opioid use; previous surgery on the operative shoulder

Methods

Patients were randomized to receive either docusate sodium, senna glycoside, or no constipation medication starting in the postanesthesia care unit and continuing for at least 10 postoperative days. Additional medications were allowed if constipation was severe despite prescribed treatment. Bowel movements were recorded daily by the patient as well as opioid tablet consumption and laxative use.

Duration

10 days after operation

Outcome Measures

Primary: difference in the prevalence of postoperative constipation between the three treatment groups

Secondary: changes in postoperative constipation symptoms via the Patient Assessment of Constipation Symptoms (PAC-SYM); changes in quality of life via the Patient Assessment of Quality of Life (PAC-QOL); medication satisfaction via the Treatment Satisfaction Questionnaire for Medication (TSQM)

Baseline Characteristics

 

Docusate (n= 38)

Senna (n= 36)

Control (n= 33)  

Age, years

59.1 ± 8.9 59.2 ± 9.4 59.4 ± 7.8  

Male

52.6% 55.6% 63.6%  

White

86.8% 86.1% 84.7%  

Body mass index (BMI), kg/m2

30.7 ± 5.9 29.6 ± 6.1 29.5 ± 4.9  

Results

Endpoint

Docusate (n= 28)

Senna (n= 30)

Control (n= 28)

p-Value

Prevalence of constipation

71.4% 66.7% 64.3% 0.88

PAC-SYM

Preoperative

2 weeks postoperative

Change from preoperative

6 weeks postoperative

Change from 2 weeks postoperative

 

0.05 (0.00 to 0.18)

0.50 (0.09 to 1.43)

0.32 (0.00 to 0.80)

0.00 (0.00 to 0.39)

-0.27 (-0.80 to 0.00) 

 

0.09 (0.00 to 0.55)

0.55 (0.09 to 1.00)

0.14 (-0.09 to 0.91)

0.00 (0.00 to 0.27)

-0.27 (-0.09 to 0.27) 

 

0.00 (0.00 to 0.09)

0.36 (0.09 to 0.64)

0.18 (0.00 to 0.45)

0.00 (0.00 to 0.23

-0.09 (-0.63 to 0.00)

 

0.06

0.60

0.36

0.67

0.51 

PAC-QOL

Preoperative

2 weeks postoperative

Change from preoperative

6 weeks postoperative 

Change from 2 weeks postoperative

 

0.25 (0.14 to 0.32)

0.38 (0.20 to 0.97)

0.14 (0.04 to 0.50) 

0.29 (0.29 to 0.46)

0.00 (-0.45 to 0.07)

 

0.28 (0.14 to 0.52)

0.32 (0.18 to 0.91)

0.07 (-0.19 to 0.29)

0.32 (0.29 to 0.46)

0.00 (-0.46 to 0.14) 

 

0.29 (0.29 to 0.36)

0.29 (0.13 to 0.73)

-0.07 (-0.25 to 0.36)

0.29 (0.29 to 0.37)

0.04 (-0.43 to 0.25) 

 

0.15

0.32

0.06

0.40

0.55

TSQM

41.8 ± 11.1  42.8 ± 10.5 - 0.70

The results are based on 86 patients (80.4% of original enrollees) who completed the 10-day postoperative calendar log.

Study Author Conclusions

The use of docusate sodium or senna glycoside did not reduce the prevalence of constipation; improve constipation symptoms, or quality of life. Contrarily, the use of docusate sodium may worsen constipation symptoms and quality of life in patients who report constipation postoperatively. 

InpharmD Researcher Critique

Patients were not blinded to treatment and were predominately white, limiting the generalizability of study findings. 

 

References:

Weekes DG, Campbell RE, Giunta NJ, et al. The efficacy of docusate sodium and senna glycoside for the treatment of constipation after rotator cuff repair: A randomized controlled study. J Am Assoc Nurse Pract. 2021;34(1):62-69. Published 2021 Feb 18. doi:10.1097/JXX.0000000000000575

 

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

Design

Single-center, retrospective, cohort study

N= 199

Objective

To determine if docusate monotherapy is effective in preventing opioid-induced constipation (OIC) in patients receiving opioids following orthopedic surgery

Study Groups

Docusate sodium (n=199)

Inclusion Criteria

Age ≥ 18 years old, hospitalized for ≥48 hours, underwent elective surgery, and received docusate 

Exclusion Criteria

Not received docusate or opioids

Methods

Data was collected from a single 581-bed hospital servicing a rural community. Patients received docusate sodium 100 mg PO BID as defined by protocol following orthopedic surgery to prevent opioid-induced constipation. If constipation did not resolve with docusate therapy, patients could receive another laxative as decided upon by the provider. 

Duration

May 1, 2018 to December 31, 2018

Outcome Measures

Primary outcome: rate of docusate failure

Secondary outcome: rate of docusate failure in relation to each patient's morphine equivalent daily dose (MEDD)

Baseline Characteristics

 

Docusate (n= 199)

 

Age, years

70.0 ± 18.9  

Male

127 (63.82%)   

White

188 (94.47%)   

Length of hospitalization, hours

140.0 ± 67.5   

Orthopedic procedure type

Upper Extremity

Lower Extremity

Spinal

Incision and Drainage

 

8 (4.02%)

170 (85.43%)

11 (5.53%)

11 (5.53%)

 

Patients on multiple laxatives

70.4%

 

Results

Endpoint

Docusate (n= 199)

p-value

Rate of docusate failure

Number of bowel movements within 5 days

Additional laxatives 

159 (79.9%)

68 (32.2%)

91 (45.7%)

< 0.001

--

--

Rate of docusate failure

MEDD ≤ 50 mg/day

MEDD >50 mg/day

 

98 (76.0%)

59 (84.3%)

 

< 0.001

< 0.001

*The rate of docusate failure was measured as the proportion of patients who had no bowel movement within five days or used an additional laxative prior to their first bowel movement after starting an opioid.

Study Author Conclusions

Docusate monotherapy is not effective for the prevention of OIC following elective orthopedic procedures, regardless of a patient’s MEDD. To improve patient outcomes, other agents with proven efficacy should be utilized first-line. However, future head-to-head, prospective studies are needed to determine the optimal therapy for patients experiencing OIC.

InpharmD Researcher Critique

Retrospective studies are susceptible to inclusion bias and have limited generalizability. The majority of patients were white and underwent lower extremity surgery. Additional confounders that could influence the rate of docusate failure, but were not readily controlled, include diet, fluid intake, and concomitant medications.

 

References:

Yang A, Lam T, Jierjian E, Walden SG, Coulson EE. An Evaluation of Docusate Monotherapy and the Prevention of Opioid-Induced Constipation after Surgery. J Pain Palliat Care Pharmacother. 2022;36(1):18-23. doi:10.1080/15360288.2021.1884167

 

Summary of clinical review and trial characteristics of studies on taking docusate for opioid-induced constipation

Citation/design

Population

Intervention

Results

 Limitations

Ahmedzai et al.

2010

Systematic review

 

N=22

People prescribed opioids

 

Patients received Docusate 240 mg BID x 3 weeks compared to PL in a cross-over design.

  • No significant difference between docusate vs. placebo in stool frequency or consistency at 8 weeks after cross-over in 15/22 (68%) in those who completed the trial

  • Mean numbers of BM/week:  4.25 vs. 4.12 (not significant; p values not reported)

  • Percentage of soft and normal stools: 97% vs. 93% (not significant; p values not reported)
  • The opioid dose was unclear, sample size with even less completing the trial; results were presented without p values.

  • Open-label studies were included.

  • List of excluded studies not provided.

 

Ruston et al.

2013

Systematic review

Aged ≥18 years, constipation associated with chronic opioid use (for cancer and non-cancer pain or substance withdrawal), in- or out-patients, or palliative care

RCTs compared PEG to one of the following: lactulose, docusate, or sennosides

  • Management of constipation.
  • No studies met the inclusion criteria; hence, no conclusion can be drawn.

  • Insufficient evidence exists to determine the efficacy and side effect profiles of lactulose, docusate sodium, sennosides, and PEG in the treatment of OIC.

  • Inclusion criteria may have been too stringent.

  • Lack of clear definition for opioid-induced constipation.

  • List of excluded studies not provided but PRISMA diagram provided.

 

Tarumi et al.

2013

Prospective, multicenter, double-blind, placebo-controlled RCT (10-day trial)

N= 74

Aged ≥ 18 years; with cancer, newly admitted hospice residents, able to take oral meds, no gastrointestinal stoma, PPS score of ≥ 20%, Folstein MMSE score of > 23; expanded criteria to include patients with non-malignant disease and those not taking opioids

DS Group (n= 35): 2 x 100mg DS BID capsules plus, 1 to 3 S 8.6 mg tablets QD to TID

PL Group (n= 39): 2 x PL BID plus, 1 to 3 S 8.6 mg tablets QD to TID

  • Management of constipation.
  • BM mean difference: 0.05 (95% CI: -0.09 to 0.19)

    Responder Analysis:

  • BM on 50% or more days: DS 56% vs. PL71%

  • 1 BM every 3 consecutive days: DS 70.8% vs. PL 80.6%

  • Mean stool frequency: DS 1.0 ± 0.5 vs. PL 0.88 ± 0.30

  • No significant differences between stool volume in DS vs PL

  • Difficult BM: DS 32.5% vs. PL 25.0% (p= 0.57)

  • Sense of complete evacuation: DS 73.5% vs. PL 78.6 (p= 0.77)

  • Bowel care interventions: DS 68.6% vs. PL 74.4% (p= 0.77)

  • Allocation concealment and ITT not specified; (10 [40%] and 8 [21%] patients did not complete study in DS and PL groups, respectively).

 

  • Inclusion criteria expanded ~5 months after the start of the trial to include patients with non-malignant disease and those not taking opioids.

 

  • Randomization code could be broken at the request of the physician or patient; the occurrence of this is not specified.
 

Fosnes et al.

2011

Cross-sectional study

N= 197

Aged ≥ 60 years; nursing home residents; some mobile, some bedridden; using laxatives regularly or on-demand

Laxative Interventions:

  • Osmotic (lactulose, macrogol combinations)

  • Contact (bisacodyl, senna glycosides, sodium pico sulphate)

  • Bulk (ispaghula [psylla seeds])

  • Enemas (docusate sodium, laurilsulfate)

  • Softeners/Emollients (liquid paraffin)

Dosing Schedules:

 

  • On-demand
  • Regular use (standard dose) was the dosing schedule for docusate 

  • Regular use (high dose)

  • Management of constipation.
  • No results were explicitly provided for docusate sodium.

  • No conclusion could be reached as only five patients were reported to have used this treatment.

 
  • Inclusion of frail and mentally reduced participants; may reduce data quality for patients self-reported symptoms.

  • Differing sites may have alternate reporting methods, and the use of laxatives may have been imprecisely registered as they may not have been handled as accurately as other drugs.

  • Only a small number of patients used DS (n=5), and it was only one of many treatment regimens examined.

 

Hawley et al.

2008

Non-randomized, non-blinded, sequential cohort study

(Total of 488 days of observation)

N= 60

Hospitalized cancer patients (80% taking
opioids); 8.4 ± 2.5 days vs. 7.8 ± 2.7 days on bowel protocol in the
DS + S vs. S protocol, respectively

 

DS + S Protocol (n= 30)

Step 1: DS 200 mg po BID

Step 2: DS 200 mg po BID + S 17.2 mg po qhs

Step 3: DS 200 mg po TID + S 17.2 mg po BID (if no BM in past 48 hrs)

Step 4: DS 200 mg po TID + S 17.2 mg po TID (if no BM in next 24 hrs)

Step 5: DS 200mg po TID + S 25.8 mg po TID (if no BM after a further 24 hrs)

S-only Protocol (n=30)

Step 1: S 17.2 mg po qhs

Step 2: S 17.2 mg po BID (if no BM in past 48 hrs)

Step 3: S 17.2 mg po TID (if no BM in next 24 hrs)

Step 4: S 25.8 mg po TID (if no BM after a further 24 hrs)

Prevention and management of constipation.
 
Percent of days with at least 1 BM:
  • DS + S 49%
  • S 50% (p= 0.86)
 
BM at least 50% of days:
  • DS + S 43.3%
  • S 19 63.3% (p= 0.12)

BM at least 40% of days:

  • DS + S 60%
  • S 24 80% (p= 0.09)

Use of rescue medications:

  • DS + S 56.7%
  • S 40% (p= 0.19)

Subanalysis of patients admitted for symptom control or supportive care, DS+S (n= 19) and S (n= 24):

BM at least 50% of days:

  • DS + S 31.6%
  • S 62.5% (p= 0.04)

BM at least 40% of days:

  • DS + S 47.4%
  • S 79.2% (p= 0.09)

Subanalysis of patients admitted for symptom control or supportive care and on opioids, DS+S (n= 19) and S (n= 24):

BM at least 50% of days:

  • DS + S 31.3%
  • S 57.1% (p= 0.12)

BM at least 40% of days:

  • DS + S 50.0%
  • S 76.2% (p= 0.1)
  • No matching or adjustments for co-founders.

  • Many different healthcare providers were involved in patient care and were not all aware of their patient’s participation in the study.

  • Patients could take an enema, lactulose, or a suppository as required, therefore potentially confounding results.

  • More patients with GU cancer were enrolled in the second (S only) cohort, while GU was the least common cancer diagnosis in the first (DS + S) cohort.

 

SR, systematic review; RCT, randomized controlled trial; BM, bowel movement; D, docusate; OIC = opioid-induced constipation; PEG = polyethylene glycol; PL, placebo; MMSE, Mini-Mental Status Examination; PPS, Palliative Performance Scale, DS, docusate sodium; PL, placebo; S, sennosides; CI, confidence interval

 

References:

Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; June 26, 2014.

 

Bowel Care for Individuals with Spinal Cord Injury: Comparison of Four Approaches

Design

Prospective, open-label, crossover study

N= 7

Objective

To compare the efficacies of our commonly used bowel care preparations in hospitalized patients with clinically complete transection of the spinal cord who lacked spontaneous defecation

Study Groups

Bisacodyl suppositories (N= 7)

Glycerin suppositories (N= 7)

Mineral oil enema (N= 7)

Docusate sodium mini enema (N= 7)

Inclusion Criteria

Hospitalized patients with clinically complete traumatic transection of the spinal cord between C4 and T12; lacked spontaneous defecation; no bowel problems prior to spinal cord injury

Exclusion Criteria

History of diabetes mellitus, multiple sclerosis, inflammatory bowel disease, or hypothyroidism

Methods

Patients with spinal cord injury were given one week of therapy with one of four different modalities daily: two bisacodyl suppositories, two glycerin suppositories, one mineral oil enema (118 mL), or one docusate sodium mini enema (Theravac SB). After one week, the patient had a one-week washout before using another modality for an additional week. This was repeated for all four treatment modalities.

Digital stimulation (5-10 minutes) and abdominal massage supplemented each of these modalities in each individual. All patients were fed a regular diet in terms of fiber content. Bowel care was performed by the same caregiver for all patients and interventions.

After the one week of each regimen, total and segmental colonic transit times were determined using radiopaque markers for three days.

Duration

Treatment: 1 week

Washout: 1 week

Outcome Measures

Difficulty with evacuation score, bowel evacuation time, total colonic transit time

Baseline Characteristics

Subject #

Age, years

Level of injury

Duration of SCI, years

 

1

65 C6 35  

2

35 T12 8  

3

45 C4-5 15  

4

33 C5-7 2  

5

40 C6-7 20  

6

76 C4-5 30  

7

21 C5-7 2  

All subjects were male.

Results

 

Bisacodyl suppositories

Glycerin suppositories Mineral oil enema Docusate sodium mini-enema
Mean difficulty with evacuation score

6.57

7.71  5.81 4.71

Total colonic transit time, hours

47.6 48.0 34.5 32.0
Bowel evacuation time, minutes 63.5 57.6 46.5 31.5

There was no significant difference in total colonic transit time between docusate sodium or mineral oil enema (p > 0.05) but both produced significantly shorter transit times (p<0.05) than bisacodyl or glycerin suppositories.

Adverse Events

None reported

Study Author Conclusions

Docusate sodium mini-enemas may have advantages in the management of difficulty with evacuation in some individuals with spinal cord injury. However, given the heterogeneous nature of SCI (level and completeness of injury, interval since injury, GI baseline prior to injury), a larger study will be required before the role of docusate sodium mini-enemas in defecatory management after SCI is fully defined.

InpharmD Researcher Critique

Docusate sodium mini-enemas had the most effect on DWE times compared to the other regimens. Considering there were only 7 patients in the study, the data published here can be loosely referenced when making clinical decisions for this patient population. Definitions or evaluations of outcomes, such as the difficulty with evacuation score, were not clearly defined. Additionally, all patients were male, so these results may not be extrapolated to female patients.



References:

Amir I, Sharma R, Bauman WA, Korsten MA. Bowel care for individuals with spinal cord injury: comparison of four approaches. J Spinal Cord Med. 1998;21(1):21-24. doi:10.1080/10790268.1998.11719506

 

Pharmacologically Initiated Defecation for Persons With Spinal Cord Injury: Effectiveness of Three Agents

Design

Prospective, randomized, blinded, crossover study

N= 15

Objective

To compare the effectiveness of hydrogenated vegetable oil-based bisacodyl (HVB) suppositories, polyethylene glycol (PEG)-based bisacodyl (PGB) suppositories, and docusate sodium mini-enemas in subjects with spinal cord injuries

Study Groups

Vegetable oil-based bisacodyl (N= 15)

PEG-based bisacodyl (N= 15)

Docusate mini enema (n= 10)

Inclusion Criteria

At least 3 months since the SCI; spinal cord lesions above the 12th thoracic neurological level; lack of anal sensation; lack of voluntary anal sphincter contraction; stable bowel program with pharmacologically triggered bowel care; the absence of known gastrointestinal disease

Exclusion Criteria

None disclosed

Methods

Fifteen patients were randomized to a sequence of six suppositories (3 HVB and 3 PGB) for each of the six scheduled bowel care sessions. Additionally, 10 subjects were randomly selected to receive 3 docusate sodium mini-enemas. The hydrogenated vegetable oil-based and polyethylene-glycol-based bisacodyl suppositories contained 10 mg of bisacodyl. The docusate mini-enema (Theravac SB) was a 4 mL solution containing 238 mg of docusate sodium and 275 mg of glycerine.

Duration

None described

Outcome Measures

Time to flatus, flatus to stool flow, defecation period, time to off-of-toilet

Baseline Characteristics

 

All patients (N= 15)

   

Age, years (range)

45 (26-61)    

Time since injury, range

3 months to 45 years    

Complete spinal lesion

11 (73.3%)    
       
All patients had positive anal cutaneous reflex and bulbocavernosus reflex and normal to hyperreflexic lower extremity phasic stretch retlexes to tendon percussion.

Results

 

Vegetable oil-based bisacodyl (n= 15)

PEG-based bisacodyl (n= 15)

Docusate mini enema (n= 10)

Time to flatus, minutes

32 15 15

Flatus to stool flow, minutes

6.7 5.5 3.9

Defecations period, minutes 

36 20 17

Wait until transfer, minutes

10.9 10.7 7.4

Total bowel care time, minutes

74.5 43 37

There was a significant difference between total bowel care time between docusate and vegetable oil-based bisacodyl suppositories (p= 0.010), but not between PEG-based bisacodyl suppositories (p=0.458).

Adverse Events

No subjects reported GI symptoms or autonomic dysreflexia.

Study Author Conclusions

Bowel care in spinal cord injury patients took less time when initiated with polyethylene glycol-based bisacodyl suppositories or docusate mini-enema compared with hydrogenated vegetable oil-based bisacodyl suppositories.

InpharmD Researcher Critique

A strength of this study is the randomized, blinded design. Failure to routinely monitor and record whether the patients had stool in the rectal vaults prior to the start of the bowel care may have altered results. Additionally having multiple nurse staff complete the bowel care procedures might have introduced variation in technique and data collection. Additionally, the authors make no indications of which 10 patients were also allocated to receive the docusate mini-enema, potentially introducing selection bias.



References:

House JG, Stiens SA. Pharmacologically initiated defecation for persons with spinal cord injury: effectiveness of three agents. Arch Phys Med Rehabil. 1997;78(10):1062-1065. doi:10.1016/s0003-9993(97)90128-3

 

A Comparison of the Effectiveness of Therevac SB™ and Bisacodyl Suppositories in SCI Patients' Bowel Programs

Design

Prospective, nonrandomized, single-center, crossover trial

N= 14

Objective

To evaluate different bowel care products in patients with spinal cord injury (SCI) to give them the further assistance they needed to establish a successful bowel management program

Study Groups

All patients (N= 14)

Inclusion Criteria

Inpatients and outpatients treated at a single spinal cord injury center; experienced an evacuation delay of ≥45 minutes after bisacodyl suppository use; tried traditional interventions (e.g., timing, diet, techniques, and other medications) to improve bowel management without success; dissatisfied with his or her current bowel care regimen

Exclusion Criteria

None reported

Methods

Patients at a single California spinal cord injury center were evaluated for inclusion to use a non-formulary agent to improve their bowel management. No attempt was made to limit patients on the basis of injury level, completeness of injury, or time since injury. 

Therevac SB is a combination of liquid docusate sodium 283 mg and glycerine 275 mg in a liquid softsoap base (polyethylene glycol). The product is given as a single 4 mL "mini-enema." The main purpose of this investigation was to evaluate the effects of this product for formulary inclusion.

During the study, patients were instructed to continue their usual bowel management regimen and techniques, including diet and concomitant medications. They were asked to wear a watch or be in view of a clock when performing their bowel program so that they could record times accurately.

Each patient was instructed to continue using bisacodyl suppositories for five bowel programs so that baseline data could be gathered. They then used Therevac SB for five more bowel programs, recording the same type of data in the log. Finally, they were asked to record five additional bisacodyl suppositories to eliminate the effect of any change alone or a "drug rest" effect.

Duration

December 1992 to July 1993

Outcome Measures

Time to bowel movement

Baseline Characteristics

 

All patients (N= 14)

Mean age, years (range)

46 (27-67)

Male

13 (93%)

Years since injury (range)

19 (2-38)

Only 10 patients (71%) completed all 5 timings requested.

Results

The reduction in mean evacuation times with Therevac SB compared to the mean times with both bisacodyl interventions was found to be statistically significant (p< 0.01). Unfortunately, individual numbers were not reported.

There was no significant difference in evacuation time between the first and second bisacodyl interventions.

Of the four patients who dropped out, one appeared to have faster results with Therevac SB but chose not to complete the Therevac SB intervention and dropped out. Another patient reported that Therevac SB worked much more slowly than bisacodyl and had two bowel programs with this product with no results at all. The only female in the cohort reported Therevac SB worked more quickly but was "too strong" and gave a sensation of bowel cramping for several hours after use. The last patient dropped out because he felt Therevac SB did not work well for him.

Adverse Events

N/A

Study Author Conclusions

This study found a significant difference between bisacodyl and Therevac SB (docusate/glycerine enema) mean evacuation times for patients with spinal cord injury.

InpharmD Researcher Critique

This study is limited by the small sample size and lack of data reported. There was limited information regarding the baseline characteristics of the patients, and the results were only reported as a graph without individual numbers. Additionally, it was not possible to control all bowel care interventions by standardizing programs, as subjects already had established a combination of medications and techniques that seemed to work for them. Additionally, only one woman was included initially; since she did not complete the trial, these results may only be applicable to males.



References:

Dunn KL, Galka ML. A comparison of the effectiveness of Therevac SB and bisacodyl suppositories in SCI patients' bowel programs. Rehabil Nurs. 1994;19(6):334-338. doi:10.1002/j.2048-7940.1994.tb01336.x