The esophageal sphincters constitute the anatomical protection against pulmonary aspiration. The aim of this thesis was to study the esophageal sphincters and how they are affected by different components of emergency anesthesia using high-resolution solid-state manometry. The effect of propofol (0.3 mg/kg) was studied in young and elderly volunteers. Propofol can be given as an anxiolytic agent for manometric studies of the lower esophageal sphincter (LES) without affecting the results. However, propofol is not recommended for studies of the upper esophageal sphincter (UES). The effects of cricoid pressure (CP) and peripheral pain were studied in awake volunteers, with and without remifentanil infusion (5 ng/ml). Pain did not affect pressure in the LES, but CP or remifentanil induced a significant decrease in LES pressure. However, neither CP nor remifentanil affected the barrier pressure (LES-intra gastric pressure). When CP was applied during ongoing remifentanil infusion, no further decrease in LES pressure was measured. CP induced high pressures in the area of the UES independent of remifentanil infusion, indicating that CP is effective in preventing gastroesophageal regurgitation. Barrier pressure was also studied in anesthetized patients after rocuronium (0.6 mg/kg) administration and no decrease was measured. In addition, alfentanil (20 μ/kg) added during anesthesia induction with propofol did not decrease the barrier pressure. In conclusion, CP seems to be effective in preventing regurgitation and does not affect barrier pressure. Muscle relaxation with rocuronium does not risk gastro-esophageal integrity. In addition, opioids can be integrated, even during emergency anethesia, without increasing the risk for pulmonary aspiration.

In the last decade, (non)prescription opioid abuse, opioid use disorder (OUD) diagnoses, and opioid-related overdoses have risen and represent a significant public health concern. One method of understanding OUD is as a disorder of choice that requires choosing opioid rewards at the expense of other nondrug rewards. The characterization of OUD as a disorder of choice is important as it implicates decision- making processes as therapeutic targets, such as the valuation of opioid rewards. However, reward-value measurement and interpretation are traditionally different in substance abuse research compared to related fields such as economics, animal behavior, and neuroeconomics and may be less effective for understanding how opioid rewards are valued. The present research therefore used choice procedures in line with behavioral/neuroeconomic studies to determine if drug-associated decision making could be predicted from economic choice theories. In Experiment 1, rats completed an isomorphic food-food probabilistic choice task with dynamic, unpredictable changes in reward probability that required constant updating of reward values. After initial training, the reward magnitude of one choice subsequently increased from one to two to three pellets. Additionally, rats were split between the Signaled and Unsignaled groups to understand how cues modulate reward value. After each choice, the Unsignaled group received distinct choice-dependent cues that were uninformative of the choice outcome. The Signaled group also received uninformative cues on one option, but the alternative choice produced reward-predictive cues that informed the trial outcome as a win or loss. Choice data were analyzed at a molar level using matching equations and molecular level using reinforcement learning (RL) models to determine how probability, reward magnitude, and reward-associated cues affected choice. Experiment 2 used an allomorphic drug versus food procedure where the food reward for one option was replaced by a self-administered remifentanil (REMI) infusion at doses of 1, 3 and 10 μg/kg. Finally, Experiment 3 assessed the potential for both REMI and food reward value to be commonly scaled within the brain by examining changes in nucleus accumbens (NAc) Oxygen (O2) dynamics. Results showed that increasing reward probability, magnitude, and the presence of reward-associated cues all independently increased the propensity of choosing the associated choice alternative, including REMI drug choices. Additionally, both molar matching and molecular RL models successfully parameterized rats’ decision dynamics. O2 dynamics were generally commensurate with the idea of a common value signal for REMI and food with changes in O2 signaling scaling with the reward magnitude of REMI rewards. Finally, RL model-derived reward prediction errors significantly correlated with peak O2 activity for reward delivery, suggesting a possible neurological mechanism of value updating. Results are discussed in terms of their implications for current conceptualizations of substance use disorders including a potential need to change the discourse surrounding how substance use disorders are modeled experimentally. Overall, the present research provides evidence that a choice model of substance use disorders may be a viable alternative to the disease model and could facilitate future treatment options centered around economic principles.

The thesis is focused on perioperative use of opioids during caesarean section. The general part is concerned with pharmacology of opioids due to their practical use during general and regional anaesthesia and postoperative analgesia with particular focus on remifentanil. Emphasis is put on the placental transfer of opioids into breast milk which has the possible influence on postnatal adaptation of the newborns and breastfeeding/lactation. The first part of the research describes current anaesthetic practice and opioid use in obstetrics in the Czech Republic according to the OBAAMA-CZ study in 2011. The second study on a unique group of 151 parturients showed that bolus application of remifentanil at a dose of 1 μg/kg at the time of 30 seconds before induction of general anaesthesia for caesarean section significantly stabilizes maternal hemodynamic parameters (blood pressure, heart rate) and reduces the stress response to tracheal intubation and skin incision. On the contrary, no influence on depth of anaesthesia (monitored by BIS) was found. But we demonstrated a slight effect of remifentanil on the assessment of postnatal adaptation of newborns at first minute after delivery. However, this attenuation was very short and in the fifth minute the results were already fully comparable to the control...

The thesis is focused on perioperative use of opioids during caesarean section. The general part is concerned with pharmacology of opioids due to their practical use during general and regional anaesthesia and postoperative analgesia with particular focus on remifentanil. Emphasis is put on the placental transfer of opioids into breast milk which has the possible influence on postnatal adaptation of the newborns and breastfeeding/lactation. The first part of the research describes current anaesthetic practice and opioid use in obstetrics in the Czech Republic according to the OBAAMA-CZ study in 2011. The second study on a unique group of 151 parturients showed that bolus application of remifentanil at a dose of 1 μg/kg at the time of 30 seconds before induction of general anaesthesia for caesarean section significantly stabilizes maternal hemodynamic parameters (blood pressure, heart rate) and reduces the stress response to tracheal intubation and skin incision. On the contrary, no influence on depth of anaesthesia (monitored by BIS) was found. But we demonstrated a slight effect of remifentanil on the assessment of postnatal adaptation of newborns at first minute after delivery. However, this attenuation was very short and in the fifth minute the results were already fully comparable to the control...