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Opioid dosage for general anaesthesia and sedation relies on surrogate parameters such as heartrate and blood pressure. This implies the risk of both under- and overdosing. A promising tool to provide target-oriented opioid dosing is measuring the nociceptive flexion reflex threshold (NFRT). The aim of this study was to investigate the individual trajectories and to determine this methods' clinical practicability in the perioperative setting of cardiac surgery. NFRT was measured preoperatively (twice as baseline), immediately after surgery and later in the general ward (primary outcomes). No intraoperative measurements were performed since neuromuscular blockade hinders NFRT assessment. Administered analgesics and pain scores were also recorded (secondary outcomes). Data were collected from August 2019 to March 2020. 264 patients scheduled for cardiac surgery were screened for eligibility. 55 patients were included, 30 rendered datasets for analysis. Thresholds after conclusion of surgery [T ICU : median (IQR), 31.1 mA (21.5-50.0 mA)] were significantly higher than preoperatively [T pre : 9.2 mA (5.4-13.4 mA); P < 0.001]. In 11 patients (36.7%), no immediate postoperative reflex response was elicited. Later, all reflexes returned, but thresholds remained significantly higher than preoperatively [T post : 11.9 mA (9.2-16.6 mA); P = 0.043]. NFRT values after surgery were higher compared to baseline measurements. Subsequently they decreased but did not reach their baseline levels. There was no corresponding dose-dependency, suggesting multimodal effects on the nociceptive system. Unless measurements are not prevented by technical issues NFRT-assessment appears to be a future tool to target analgesics in patients not able to self-report pain. Trial registration Study registration: DRKS00021617. https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00021617 (registered retrospectively)., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: In many European countries and particularly in Germany, piritramide is the first choice opioid analgesic for the management of postoperative and posttraumatic pain., Objective: The aim of this study was to review the pharmacological properties of piritramide and to evaluate whether these result in any clinical advantages with respect to effectiveness, safety and side effect profile compared to other strong opioids., Material and Methods: A systematic literature search was conducted in PubMed and Google Scholar and 27 articles published between 1961 and 2015 were retrieved and included in this review., Results: Piritramide is a strong opioid that can only be administered parenterally. After intravenous injection it is effective after 17 min with pain relief lasting for up to 6 h. It is metabolized in the liver to inactive compounds, which is advantageous compared to morphine where active metabolites can accumulate in patients with renal failure. Piritramide is highly lipophilic resulting in a long context-sensitive half-life, making it unsuitable for continuous infusions. Studies further suggest that the side effect profile of piritramide is comparable to morphine., Conclusion: So far there is little evidence to support the widespread use of piritramide as first-line opioid analgesic for postoperative pain management in Germany. Especially lacking are in-depth studies about its mechanisms of action, receptor pharmacology, dose-response relationships and clinical dosing regimens. It is therefore questionable why piritramide is given priority.

Unlabelled: To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis., Implications: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.