Meissner, W., Schmidt, U., Hartmann, M., Kath, R., & Reinhart, K. (2000). Oral naloxone reverses opioid-associated constipation. Pain, 84, 105–109.

Study Purpose

To evaluate the use of oral naloxone for the management of opiate-associated constipation in patients with cancer.

Intervention Characteristics/Basic Study Process

Patients were observed for six days without intervention. Afterward, oral naloxone was titrated as follows: 3 mg TID (day 1), 6 mg TID (day 2), 9 mg TID (day 3), 12 mg TID (day 4; maximum). Titration was stopped with laxation or increased peristalsis.

Sample Characteristics

  • The study reported on a sample of 22 patients.
  • The final sample included 17 patients.

Setting

Hospital in Germany

Study Design

This was a controlled study with a control period, but not a control group.

Measurement Instruments/Methods

  • Himmelsbach Withdrawal Scale was used to monitor possible systemic withdrawal signs such as shivering or piloerection, yawning, perspiration, nausea or vomiting, tremor or restlessness, and lacrimation or rhinorrhea. Each sign was quantified as 0 (none), 1 (mild), 2 (moderate), or 3 (severe).
  • Laxation frequency
  • Pain intensity on an 11-step numerical rating scale
  • Laxatives received
  • Ratio of morphine dose to naloxone dose

Results

  • Nausea, restlessness, and sweating were the most common side effects.
  • Laxation increased in 14 of 17 patients, whereas laxative use decreased in 9 of 17 patients.
  • No difference existed in pain rating between study periods.
  • Other laxatives used were lactulose, paraffin, raglan, glycerol, castor oil, and sodium picosulfate.
  • Naloxone dose was based on opioid-tolerance level rather than morphine dose.

Conclusions

Starting with a low dose of naloxone and titrating up is recommended.

Limitations

  • Only six days were allocated for measurement periods.
  • A subjective Likert-type scale from 0 to 3 was used.
  • No control group existed for other laxative use (all participants were on at least one).
  • Overdosed patients (via medication error) were kept on the study.
  • The study did not control for diet, exercise, and fluid intake.
  • The p-value was not tested.