Respiratory depression following morphine and morphine-6-glucuronide in normal subjects.
1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic activity. A double-blind, randomised comparison of the effects of morphine and M6G on respiratory function was carried out in 10 normal subjects after i.v. morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was also assessed using an ischaemic pain test and other toxic effects were monitored. 2. Following morphine there was a significant increase in arterial PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P < 0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0.002), compared with small but significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/- 0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5 mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)
Thompson
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ICRF Department of Medical Oncology, St Bartholomew's and Homerton Hospitals, London, UK.
Joel
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John
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Wedzicha
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Maclean
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Slevin
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D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D003864:Depression, Chemical; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects* / Q000627:therapeutic use; D009022:Morphine Derivatives / Q000009:adverse effects* / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D010146:Pain / Q000188:drug therapy; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests; D014839:Vomiting / Q000139:chemically induced
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D002245:Carbon Dioxide; C035349:morphine-6-glucuronide; D009020:Morphine