Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers

Anesthesiology, vol. 139, pp. 16–34

Abstract

BACKGROUND: Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities remain poorly understood. This study tested the hypothesis that IV morphine and hydromorphone differ in onset, magnitude, duration, and variability of analgesic and ventilatory effects. METHODS: The authors conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-h IV infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1 to 2 weeks apart. The authors measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discrete preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired carbon dioxide, and respiratory rate for 12 h after dosing. RESULTS: For morphine and hydromorphone, respectively, maximum miosis was less (3.9 [3.4 to 4.2] vs. 4.6 mm [4.0 to 5.0], P < 0.001; median and 25 to 75% quantiles) and occurred later (3.1 ± 0.9 vs. 2.3 ± 0.7 h after infusion start, P < 0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs. 50 ± 2°C, P < 0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P < 0.001); maximum end-expired CO2 was 47 (45 to 50) and 48 mmHg (46 to 51; P = 0.007) and occurred later (5.5 ± 2.8 vs. 3.0 ± 1.5 h after infusion start, P < 0.001); and respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P < 0.001), and occurred at similar times. The area under the temperature tolerance-time curve was less for morphine (1.8 [0.0 to 4.4]) than hydromorphone (5.4°C-h [1.6 to 12.1] P < 0.001). Interindividual variability in clinical effects did not differ between opioids. CONCLUSIONS: For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.

Authors 7

1. Konrad Meissner Aachen

   Leiden University · Washington University in St. Louis · Leiden University Medical Center · Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany; Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

   1Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany; Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

2. Albert Dahan Aachen Department of Anesthesiology, Leiden University Medical Center 2Department of Anesthesiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

   2Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

3. Erik Olofsen Aachen Department of Anesthesiology, Leiden University Medical Center 3Department of Anesthesiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

   3Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands

4. Christine Göpfert

   Washington University in St. Louis

   Affiliation as printed

   Chronic Pain Therapy, Kliniken Ostalb, Ellwangen, Germany; Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

   4Chronic Pain Therapy, Kliniken Ostalb, Ellwangen, Germany; Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

5. Jane Blood

   Washington University in St. Louis

   Affiliation as printed

   Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

   5Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri

6. Johannes Wieditz

   Universitätsmedizin Göttingen · University of Göttingen

   Affiliation as printed

   Anesthesiology Clinic, and Department of Medical Statistics, University of Medicine Göttingen, Göttingen, Germany

   6Anesthesiology Clinic, and Department of Medical Statistics, University of Medicine Göttingen, Göttingen, Germany

7. Evan D. Kharasch

   Duke University

   Affiliation as printed

   Department of Anesthesiology, Duke University, Durham, North Carolina

   7Department of Anesthesiology, Duke University, Durham, North Carolina