**3. Results**

Thirteen sheep were part of this study. One sheep of the thorax group was excluded as the TFP detached 18 h after placement. Data from this sheep were excluded from the study. All sheep recovered well after sedation.

### *3.1. Primary Outcome: Fentanyl Plasma Level*

Based on the selected TFP size, the overall average expected fentanyl administration rate was 2.08 μg/h/kg (range 2.01 to 2.16 μg/h/kg). The average expected fentanyl administration rate was 2.01 μg/h/kg (range 2.01 to 2.16 μg/h/kg) in the foreleg group and 2.07 μg/h/kg (range 2.01 to 2.1 μg/h/kg) in the thorax group.

In the foreleg group, five out of six sheep achieved a fentanyl plasma level threshold of >0.6 ng/mL after 3 h, and all sheep within 6 h. At least this level was maintained in all sheep for a minimum of 48 h and in four out of six sheep for a maximum of 72 h (Table 1, Figure 4). In the thorax group, only two sheep had fentanyl levels above 0.6 ng/mL after 3 h, four sheep after 6 h, five sheep after 9 h, and all six sheep after 12 h (Table 1, Figure 5). At 24 h, all six sheep still had a concentration above 0.6 ng/mL. However, thereafter it started to decline so that, by 36 h, the level of 0.6 ng/mL was achieved in only five sheep, at 72 h in three sheep, and by 96 h two sheep had level above 0.6 ng/mL. When comparing both groups, the fentanyl uptake was more consistent in terms of the onset of the desired plasma concentration as well as duration of e ffect (Figure 6), when applied to the foreleg than to the thorax. At 120 h, no sheep from either group were above the predefined threshold levels.

All sheep in the foreleg group were above 1.5 ng/mL at least once during the study, with 5/6 sheep reaching this level already after 3 h. In contrast, two out of six sheep of the thorax group never attained a fentanyl plasma level of 1.5 ng/mL and only one sheep reached this value after 3 h. A fentanyl plasma level > 1.5 ng/mL was achieved in all sheep of the foreleg group between 6 h and 18 h. In the thorax group, only four out of six sheep reached a plasma level of 1.5 ng/mL. These sheep achieved the predefined fentanyl plasma level between 9 h and 36 h. At 96 h, no sheep from either group was in the target plasma level range.

For the individual fentanyl plasma concentration peaks see Table 1.

In the foreleg group, one sheep displayed a striking drop in plasma levels after 24 h with values well above the 1.5 ng/mL threshold before (18 h) and after (36 h).


**Table 1.** Fentanyl plasma level of both groups (values marked in yellow are above 0.6 ng/mL; values marked with green are above 1.5 ng/mL; every column represents one sheep).

**Figure 4.** Foreleg—Fentanyl plasma level over time (the fentanyl level within the area marked in yellow, correspond to the minimal analgesic plasma level of 0.6–1.5 ng/mL described for humans; the area above marked in green represents values higher than 1.5 ng/mL).

**Figure 5.** Thorax—Fentanyl plasma level over time (the fentanyl level within the area marked in yellow, correspond to the minimal analgesic plasma level of 0.6–1.5 ng/mL described for humans; the area above marked in green represents values higher than 1.5 ng/mL).

**Figure 6.** Fentanyl plasma levels measured over time for TFP applied at the foreleg (**red**) and thorax (**black**) displayed in a box plot graph (the fentanyl level within the area marked in yellow, corresponds to the minimal analgesic plasma level of 0.6–1.5 ng/mL described for humans; the area above marked in green represents values higher than 1.5 ng/mL).
