Evaluation of Three Different Initial Doses of Intravenous Morphine
Aaron A. Tebbs, M.D., Craig Curry, M.D., Andreas Taenzer, M.D., Catharine La Vopa, R.N. Maine Medical Center, Portland, ME

Background: Although the use of intravenous (IV) morphine is common in the post-anesthesia care unit (PACU), there have been few studies evaluating the minimal effective dose (MED) required to reduce acute post-operative pain (1, 2). We conducted a prospective, randomized, double-blinded, clinical trial to evaluate the effect of three initial doses of morphine in patients with acute post-operative abdominal pain.
Methods: 70 adult patients, ASA class I or II, undergoing elective laparoscopic procedures (nissen fundoplication or cholecystecomy) with a post-operative numeric pain scale (NPS) score > 5 were randomized into three groups (2, 4, or 6 mg initial dose of morphine). All patients underwent general anesthesia with propofol, a volatile anesthetic, nitrous oxide, and muscle relaxant. In addition, each patient received fentanyl, toradol, ondansetron and local anesthetic wound infiltration. After the initial dose of morphine the NPS scores were recorded in 5 minute intervals and 25 mcg fentanyl boluses were given as needed.
Results: The 6 mg morphine group showed a significantly decreased NPS score after 5 minutes (P<0.01). Conversely, the 2 and 4 mg groups did not have a reduced NPS score until 20 and 15 minutes, respectively (P<0.01). When comparing the three groups, the 6 mg group dose-response curve was statistically different from the other two groups (See Figure 1) (P<0.01). Patients in all groups required a mean cumulative dose of at least 6 mg of morphine (or morphine equivalent) prior to experiencing a significant reduction in NPS scores. There was no respiratory depression in any group. Also of note, PONV rates and total time in PACU were lowest in the 6 mg study group (3).
Conclusion: The MED of IV morphine is 6 mg in this study population. This dose appears to
be in the range of MED in other studies of morphine in acute pain groups (1,2 4,5). The 6 mg study group demonstrated more rapid pain control when compared to the lower dose morphine groups with no observed increase in respiratory depression, PONV, or total time in PACU. When treating moderate-to-severe acute post-operative pain an initial loading dose of IV morphine should be considered.
References:

1. Beloeil H, Delage N, Negre I, Mazoit J, Benhamou D: The Median Effective Dose of Nefopam and Morphine Administered Intravenously for Postoperative Pain after Minor Surgery: A Prospective Randomized Double-blinded Isobolgraphic Study of their Analgesic Action. Anesth Analg. 2004; 98:395-400.
2. Levine J, Newton CG, Smith R, Fields HL: Analgesic Responses to Morphine and Placebo in Individuals with Postoperative Pain. Pain 1981; 10:379-389
3. Tebbs A, Curry C, Taenzer A, LaVopa C: Reduced Post Operative Nausea and Vomiting with 6 mg Initial Dose of IV Morphine. Presented at Maine Medical Center Research Forum, 2004
4. Aubrun F, Langeron O, Quesnel C, Coriat P, Riou B: Relationships Between Measurement of Pain Using Visual Analog Score and Morphine Requirements During Postoperative Intravenous Morphine Titration. Anesthesiol 2003; 98:1415-1421
5. Aubrun F, Monsel S, Langeron O, Coriat P, Riou B: Postoperative Titration of Intravenous Morphine. Euro Journal of Anes. 2001; 18:159-165

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