Table 3. Maximum decreases in minute ventilation after fentanyl bolus administration (%).
| Healthy volunteers | Opioid-tolerant patients | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0.2 ng/mL group | 0.5 ng/mL group | 1 ng/mL group | 2 ng/mL group | 5 ng/mL group | ||||||||||
| Placebo | BUP | Treatment Difference | Placebo | BUP | Treatment Difference | Placebo | BUP | Placebo | BUP | Placebo | BUP | Treatment Differenceb | ||
| Fentanyl Dose 1 a | N | 6 | 6 | 6 | 6 | 2 | 2 | 3 | 3 | 3 | 3 | |||
| LSM (95% CI) | -60.9 (-73.5, -48.2) | -53.1 (-65.8, -40.5) | 7.7 (-3.8, 19.3) | -51.3 (-64.3, -38.3) | -26.2 (-40.0, -12.5) | 25.1 (13.4, 36.8) | -82.3 (-105.2, -59.3) | -49.2 (-72.1, -26.3) | -44.3 (-63.0, -25.6) | -22.2 (-40.9, -3.5) | -62.5 (-81.2, -43.8) | -26.8 (-45.5, -8.1) | 29.9 (19.6, 40.3) | |
| p-value | 0.1590 | 0.001 | < .001 | |||||||||||
| Fentanyl Dose 2 a | N | 6 | 4 | 6 | 6 | 2 | 2 | 3 | 3 | 3 | 3 | |||
| LSM (95% CI) | -82.4 (-92.7, -72.0) | -70.3 (-82.8, -57.8) | 12.1 (-2.5, 26.7) | -79.0 (-89.4, -68.6) | -47.4 (-57.8, -37.0) | 31.6 (19.3, 43.8) | -93.5 (-122.3, -64.6) | -57.3 (-86.1, -28.4) | -68.4 (-91.9, -44.8) | -35.9 (-59.5, -12.4) | -87.5 (-111.0, -63.9) | -30.0 (-53.5, -6.5) | 42.8 (23.8, 61.8) | |
| p-value | 0.0916 | < .001 | 0.001 | |||||||||||
| Fentanyl Dose 3 a | N | 2 | 4 | 4 | 6 | 1 | 2 | 3 | 3 | 2 | 3 | |||
| LSM (95% CI) | -100.0 (-142.3, -57.7) | -83.2 (-113.2, -53.3) | 16.8 (-35.1, 68.7) | -93.6 (-123.6, -63.7) | -71.9 (-96.4, -47.5) | 21.7 (-16.9, 60.4) | -100.0 (-145.3, -54.7) | -71.8 (-103.8, -39.8) | -79.3 (-105.5, -53.2) | -46.1 (72.3, -20.0) | -88.1 (-120.1, -56.1) | -30.7 (-56.9, -4.6) | 39.4 (15.7, 63.1) | |
| p-value | 0.3788 | 0.1716 | 0.008 | |||||||||||
| Fentanyl Dose 4 a | N | 0 | 0 | 0 | 1 | 0 | 2 | 3 | 3 | 1 | 3 | |||
| LSM (95% CI) | NA | NA | NA | NA | NA | NA | NA | -68.7 (-140.2, 2.8) | -82.3 (-140.7, -23.9) | -33.7 (-92.1, 24.7) | -116.3 (-189.3, -42.2) | -50.5 (-108.9, 7.8) | 50.8 (27.7, 73.9) | |
| p-value | NA | NA | 0.006 | |||||||||||
BUP, buprenorphine; CI, confidence interval; LSM, least square mean; NA, not applicable. p<0.05 are presented in bold. Differences are LSM estimated treatment differences between buprenorphine and placebo.
aMaximum changes (%) in minute ventilation during first 10 minutes after each fentanyl administration compared to pre-fentanyl baseline.
b The three buprenorphine concentration level groups in patients were grouped for this analysis.