RESPIRATORY DEPRESSION FOLLOWING MORPHINE AND MORPHINE 6-GLUCURONIDE IN NORMAL SUBJECTS

1 Morphine 6-glucuronide (M6G) is a metabolite of morphine with analge sic 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 pa in test and other toxic effects were monitored. 2 Following morphine t here 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 p eriod (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 2 and 5.0 mg 70 kg(-1) This increased PCO2 follo wing morphine was associated with an increase in expired CO2 concentra tion (FECO(2)) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0. 002), compared with small but significant reductions in FECO(2) follow ing morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg(-1) P = 0.03 0, -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 significantl y 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). Vomiting o ccurred in 6 of 10 subjects after morphine but in none after any dose of M6G. All subjects were sedated after morphine but this effect was a bsent following M6G. 3 All treatments resulted in significant analgesi a compared with pre-treatment values (VAS pain score at 0.5 h post dos e, -67.7% for morphine (P < 0.0001), -47.9% for M6G 1.0 mg 70 kg(-1) ( P = 0.0008), -62.2% for M6G 3.3 mg 70 kg(-1) (P = 0.0002) and -71.4% f or M6G 5.0 mg 70 kg(-1) (P = 0.017). However, there were insufficient subjects to demonstrate a difference in analgesia between treatments a nd comparing all pain data across the study period by analysis of vari ance revealed no difference between treatments using either VAS (P = 0 .149), pain relief score (P = 0.103) or change in pain score (P = 0.14 8). 4 At the doses studied M6G produced little or no toxicity, whereas morphine caused significant respiratory depression, nausea and vomiti ng and sedation.