At a recent pharmacy committee meeting, we discussed the potential use of enteral naloxone for ICU patients with opioid-induced constipation.
Opioids bind to mu receptors within the gastrointestinal tract. Activation of the bowel opioid receptors slow gastric transit time, decreases gastric secretions, and reduces intestinal muscle tone leading to enhanced fluid absorption and subsequently dry and hard stools.
Naloxone (Narcan®) solution for oral/enteral use
Mechanism of action:
Pure opioid antagonist that competes and displaces opioid at opioid receptor sites
As an antidote – pure opioid antagonist that competes and displaces opioids at opioid receptor sites
As an oral agent – Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability (if dosed properly) due to marked hepatic first-pass metabolism. As a result, oral naloxone only binds strong enough for a pharmacologic response at opioid receptors in the gastrointestinal tract without reducing the central effect of the opioid and precipitating systemic withdrawal.
Methylnaltrexone (Relistor®) SQ 12mg/0.6mL (much more expensive)
Rectal treatments: Bisacodyl (Dulcolax®), Enema
Oral constipation medications:
Polyethylene glycol (Miralax®)
Dose recommendations: 10 – 20 mcg/kg dose PO q8h (max dose: 400mcg) for 5 – 7 days, then re-evaluate therapy
Oral/enteral dose should be not administered intravenously to prevent systemic effect and withdrawal in patients
My take: Enteral naloxone (IV solution) may be helpful for opioid-induced constipation but caution is needed to assure it is administered enterally and at proper dose.
Some of the research studies:
Tofil N, Benner K, Faro S, Winkler M. The Use of Enteral Naloxone to Treat Opioid-Induced Constipation in a Pediatric Intensive Care Unit. Pediatr Crit Care Med. 2006;7(3):254-272.
Akkawi R, Eksborg S, Andersson A, et al. Effect of Oral Naloxone Hydrochloride on Gastrointestinal Transit in Premature Infants Treated with Morphine. Acta Paediatrica.2008;98:442-447
Liu M, Wittbrodt E. Low-Dose Oral Naloxone Reverses Opioid-Induced Constipation and Analgesia. J Pain Symptom Manage. 2002;23(1):48-53
Friedman J, Dello Buono F. Opioid antagonist in the Treatment of Opioid-Induced Constipation and Pruritus. Ann Pharmcother. 2001;35:85-91
Meissner W, Schmidt U, Hartmann M, et al. Oral Naloxone Reverses Opioid-Associated Constipation. Pain. 2000;84:105-109
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Key finding: 606 patients were randomized to treatment (placebo: n=202; lubiprostone: n=404). No statistically significant difference in overall SBM (spontaneous bowel movement) response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P=.2245).
My take: I agree with the authors that a simple plan like this has “the potential to become an important tool to be used in the care of children with functional constipation, improving both quality-of-care and clinical outcomes.”
This QR code provides 9 minute explanation of constipation and action plan:
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition
The overall prevalence of celiac disease in the entire cohort was 0.6%. Of those with functional constipation, 1 (0.5%) was diagnosed with celiac disease, and 3 (0.7%) of the control patients
The authors note that some prior publications (references 11 and 12) have found a slight increase risk of celiac disease in children with constipation.
My take: In children with functional constipation, the yield from testing for celiac disease is very low and probably not significantly greater than the general population. In children with irritable bowel syndrome (which is often confused with constipation), the yield is probably a bit higher.
“The highest proportion of participants – 68% – reported treatment satisfaction with kiwifruit while similar proportions of those receiving prunes and psyllium – 48% – reported satisfaction”
“The kiwi group had the lowest proportion of participants reporting treatment dissatisfaction at 7%….Participants receiving prunes and psyllium were more likely to report abdominal pain and bloating than those receiving kiwi”
Diagnosis of constipation is primarily based on history and physical exam –not abdominal xray (AXR). In a recent quality improvement study (G Moriel et al. J Pediatr 2020; 225: 109-116. Reducing Abdominal Radiographs to Diagnose Constipation in the Pediatric Emergency Department), ED physicians were trying to improve adherence to evidence-based guidelines for diagnosis of constipation in otherwise healthy children. In this article, the authors note evidence “has shown abdominal radiographs to be unreliable in establishing an association between clinical symptoms of constipation and fecal load on abdominal radiographs.”
As part of the study, the researchers provided two 20-minute presentations to the pediatric emergency department providers and sent emails to them and to resident housestaff. The email for ED provider’s included the provider’s baseline abdominal radiograph frequency. After study was initiated, a followup email was sent with similar information with key information on the project along with individualized data.
After the QI interventions, the total percentage of abdominal radiograph decreased to 18% (from 36% at baseline). This 18% decrease was significant ( P < .001) and sustained over a 12-month follow-up period.
The average length of stay was 1.07 hours longer for children who had an abdominal radiograph.
Clinically important return visits to the emergency department were uncommon during the postintervention phase (125/1830 [6.8%]), and not associated with whether or not an abdominal radiograph was performed at the initial visit.
While the study focused on healthy children, the authors noted that the overall population (6 mo-18 years) experienced a decline in AXR usage, regardless of exclusion criteria. At baseline the rate of AXR was 39.5% (1550/3926) which decreased to 20.7% (478/2311).
One interesting piece of data was showing that this intervention resulted in a sustained reduction for 12 months after the intervention observation period, which mitigates the potential influence of the Hawthorne effect.
My take: In my view, the keys to this intervention was providing individualized metrics as well as having leadership in establishing this project. The individualized metrics help physicians recognize when they are outliers and to motivate them to address this.
The images below show how much more prevalent problems with regurgitation, colic, functional diarrhea, dyschezia, and functional constipation in the first 3 months of life compared to later in the first year of life.