Enteral Naloxone Versus a Traditional Bowel Regimen for the Prevention of Opioid Induced Constipation in Trauma Patients

Analgesia Clinical Trial

Official title:

A Prospective, Randomized Trial of Enteral Naloxone Versus a Traditional Bowel Regimen in Prevention of Constipation and Decreased Gastric Motility in Critically Ill Trauma Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00799201
• Other study ID #: 07-01-1897
• Status: Terminated
• Phase: Phase 4
• First received: November 24, 2008
• Last updated: July 27, 2015
• Start date: August 2007
• Est. completion date: October 2012

Study information

• Verified date: July 2015
• Source: CAMC Health System
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if enteral naloxone is more effective than a traditional bowel regimen in the prevention and treatment of constipation and impaired gastric motility in critically ill trauma patients.

Description:

Impaired gastric motility and constipation are common issues among patients in the intensive care setting. Contributing factors include trauma, multiple surgical procedures, lack of ambulation, and the use of opiate analgesics to control pain. Common treatments for altered gastric motility and constipation include administration of pro-motility agents, stool softeners and bowel stimulants.

Enteral feeding is considered the safest and most effective way to provide nutrition to critically ill patients. Nutrition can be delayed and/or held when impaired gastric motility and constipation are present. Studies suggest that delays in the administration of nutrition can lead to prolonged ventilator time and increased length of stay in the intensive care setting as well as an increase in mortality.

Naloxone, a competitive opioid antagonist, is most commonly administered systemically to counteract the central and peripheral effects of opioids. When administered enterally naloxone has also been found to increase gastric emptying. Studies in patients receiving enteral feeds with multiple risk factors for altered gastric motility and constipation suggest that administration of enteral naloxone can reduce the incidence and extent of altered gastric motility and aid in defecation while not totally reversing the systemic effects of the opiate being administered. Due to these findings, it appears that enterally administered naloxone would provide a significant advantage over traditional gastrointestinal stimulants in preventing constipation in critically ill patients receiving continuous administration of opiate analgesics. In addition, the use of an enterally administered opiate antagonist may also alleviate the need for routine administration of pro-kinetic agents in order to promote adequate gastrointestinal motility and toleration of enterally administered nutrition. As a result, the comparison of enteral naloxone plus a stool softener versus a traditional bowel regimen containing a stimulant and stool softener will aid in assessing the effectiveness of opiate reversal locally in the gastrointestinal tract in prevention of decreased gastric motility and constipation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Males and non-pregnant females > 18 years of age and < 65 years of age

• MSICU admission to the trauma service at the General Hospital

• Scheduled for continuous infusion/administration of opiate analgesics for at least 24 hours

• Access for enteral administration of medications and tube feeds

• Initiation of tube feeds

Exclusion Criteria:

• NPO

• Pregnancy

• < 18 years of age or > 65 years of age

• Pancreatitis

• Ileus

• Large bowel obstruction present on plain X-ray or CT scan

• Recent intestinal anastomosis (within 2 weeks)

• Section of large bowel removed (within 2 weeks)

• Contraindications to metaclopramide (Reglan) such as parkinson's disease, tardive dyskinesia, etc.

• Traumatic brain injury with a glasgow coma score of at least 8

• Use of pharmacologic paralytics or neuromuscular blockade (NMB)

• Non-english speaking patients

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Analgesia
• Constipation

Intervention

Drug:
• Naloxone and Docusate
Naloxone 6mg (15 mL) every 6 hours plus docusate sodium liquid 10 mL (100mg) every 12 hours

Locations

Country	Name	City	State
United States	Charleston Area Medical Center, General Hospital	Charleston	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
CAMC Health System

Country where clinical trial is conducted

United States, 

References & Publications (11)

Artinian V, Krayem H, DiGiovine B. Effects of early enteral feeding on the outcome of critically ill mechanically ventilated medical patients. Chest. 2006 Apr;129(4):960-7. — View Citation

Ely EW, Truman B, Shintani A, Thomason JW, Wheeler AP, Gordon S, Francis J, Speroff T, Gautam S, Margolin R, Sessler CN, Dittus RS, Bernard GR. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003 Jun 11;289(22):2983-91. — View Citation

Hawryluck LA, Harvey WR, Lemieux-Charles L, Singer PA. Consensus guidelines on analgesia and sedation in dying intensive care unit patients. BMC Med Ethics. 2002 Aug 12;3:E3. — View Citation

Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD; Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002 Jan;30(1):119-41. Erratum in: Crit Care Med 2002 Mar;30(3):726. — View Citation

Liu M, Wittbrodt E. Low-dose oral naloxone reverses opioid-induced constipation and analgesia. J Pain Symptom Manage. 2002 Jan;23(1):48-53. — View Citation

Meissner W, Dohrn B, Reinhart K. Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia. Crit Care Med. 2003 Mar;31(3):776-80. — View Citation

Meissner W, Schmidt U, Hartmann M, Kath R, Reinhart K. Oral naloxone reverses opioid-associated constipation. Pain. 2000 Jan;84(1):105-9. — View Citation

Mixides G, Liebl MG, Bloom K. Enteral administration of naloxone for treatment of opioid-associated intragastric feeding intolerance. Pharmacotherapy. 2004 Feb;24(2):291-4. — View Citation

Mostafa SM, Bhandari S, Ritchie G, Gratton N, Wenstone R. Constipation and its implications in the critically ill patient. Br J Anaesth. 2003 Dec;91(6):815-9. — View Citation

Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, Tesoro EP, Elswick RK. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1338-44. — View Citation

Thomas MC, Erstad BL. Safety of enteral naloxone and i.v. neostigmine when used to relieve constipation. Am J Health Syst Pharm. 2003 Jun 15;60(12):1264-7. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of hours until first bowel movement		While the patient is receiving continuous or scheduled narcotics	Yes
Secondary	Residual volume/toleration of feeds		While the patient is receiving continuous or scheduled doses of narcotics	Yes
Secondary	Average number of bowel movements per day		While the patient is receiving continuous or scheduled narcotics	Yes
Secondary	Escalation of opioid dose due to impaired analgesia		While the patient is receiving study medications	Yes