Figure 6:

“Very high” remifentanil concentrations. A: After naloxone injection into the bilateral Parabrachial Nucleus/Kölliker-Fuse Complex, preBötzinger Complex including premotor neurons, and the Caudal Medullary Raphe, remifentanil was injected intravenously until apnea or to a maximal dose of 100 mcg. In 19 animals, the bolus caused a significant change in all parameters (Wilcoxon signed rank test, critical P<0.05). B: To determine whether the effect of “very high” remifentanil was due to insufficient antagonism of above brainstem regions, we plotted the difference between respiratory rate after the “very high” remifentanil bolus and baseline respiratory rate versus the difference from baseline for “analgesic” (black) and “apneic” (red) remifentanil concentrations at the end of the naloxone injection sequence. Values <0 indicate a decreased respiratory rate compared to baseline, i.e., −100% indicates apnea. Values >0 indicate an increased respiratory rate compared to baseline, which was not infrequently seen after naloxone injection into the raphe. Linear regression analysis showed little correlation between the “very high” remifentanil effect and level of reversal of “analgesic” and “apneic” remifentanil concentrations, suggesting that the naloxone injections correctly antagonized the study areas and that “very high” remifentanil concentrations depressed other areas of respiratory drive.