BackgroundNociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which... Show moreBackgroundNociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies.MethodsWe conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli.ResultsThe average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45–49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9–11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies.ConclusionNociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions. Show less
Meijer, F.; Honing, M.; Roor, T.; Toet, S.; Calis, P.; Olofsen, E.; ... ; Dahan, A. 2021
Opioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and... Show moreOpioids are complex drugs that produce profit (most importantly analgesia) as well as a myriad of adverse effects including gastrointestinal motility disturbances, abuse and addiction, sedation and potentially lethal respiratory depression (RD). Consequently, opioid treatment requires careful evaluation in terms of benefit on the one hand and harm on the other. Considering benefit and harm from an economic perspective, opioid treatment should lead to profit maximization with decision theory defining utility as (profit - loss). We here focus on the most devastating opioid adverse effect, RD and define opioid utility U = P(benefit) - P(harm), where P(benefit) is the probability of opioid-induced analgesia and P(harm) the probability of opioid-induced RD. Other utility functions are also discussed including the utility U = P(benefit AND NOT harm), the most wanted opioid effect, i.e., analgesia without RD, and utility surfaces, which depict the continuum of probabilities of presence or absence of analgesia in combination with the presence or absence of RD. Utility functions are constructed from pharmacokinetic and pharmacodynamic data sets, although pragmatic utility functions may be constructed when pharmacokinetic data are not available. We here discuss utilities of several opioids including the partial mu-opioid-receptor agonist buprenorphine, the full opioid receptor agonists fentanyl and alfentanil, and the bifunctional opioid cebranopadol, which acts at mu-opioid and nociception/orphanin FQ-receptors. We argue that utility functions give clinicians the opportunity to make an informed decision when opioid analgesics are needed for pain relief, in which opioids with a positive utility function are preferred over opioids with negative functions. Furthermore, utility functions of subpopulations will give an extra insight as a utility functions measured in one subgroup (e.g., patients with postoperative pain, good opioid responders) may not be mirrored in other patient subgroups ( e.g., neuropathic pain patients, poor opioid responders). Show less
Oxytocin has been shown to increase trust, decrease anxiety, and affect learning as has been observed in conditioning paradigms. Trust, anxiety, and learning are important factors that influence... Show moreOxytocin has been shown to increase trust, decrease anxiety, and affect learning as has been observed in conditioning paradigms. Trust, anxiety, and learning are important factors that influence placebo effects. In this study, we investigated whether oxytocin can increase placebo analgesia, decrease nocebo hyperalgesia, and influence extinction processes of both. Eighty male volunteers were assigned to a 40 IU of oxytocin nasal spray group, or to a placebo control group. Placebo analgesia and nocebo hyperalgesia were induced by a conditioning procedure in combination with verbal suggestions. The results demonstrate that the conditioning procedure successfully elicited significant placebo analgesia and nocebo hyperalgesia responses (P < .001). Furthermore, extinction was observed (P < .001), although placebo and nocebo responses did not return to baseline and remained significant. Oxytocin did not influence placebo analgesia or nocebo hyperalgesia and had no effect on extinction. This study provides support against the placebo-boosting effects of oxytocin and was the first one to demonstrate that it also did not influence nocebo effects or extinction processes, however, these results pertain to only a male sample. As managing placebo and nocebo effects has widespread clinical implications, further research should investigate other neurobiological or behavioral pathways to boost placebo and decrease nocebo effects.Perspective: The present study demonstrated that placebo analgesia and nocebo hyperalgesia can be successfully induced by conditioning and verbal suggestions. We could not confirm the hypothesis that oxytocin affects either of these phenomena. Other pharmacological agents and behavioral manipulations for increasing placebo and decreasing nocebo effects should be investigated. (C) 2020 THE AUTHORS. Published by Elsevier Inc. on behalf of the U.S Association forthe Study of Pain. Show less
Sitsen, E.; Velzen, M. van; Rover, M. de; Dahan, A.; Niesters, M. 2020
Introduction: Spinal anesthesia induces short-term deafferentation and causes connectivity changes in brain areas involved in endogenous pain modulation. We determined whether spinal anesthesia... Show moreIntroduction: Spinal anesthesia induces short-term deafferentation and causes connectivity changes in brain areas involved in endogenous pain modulation. We determined whether spinal anesthesia alters pain sensitivity and offset analgesia. Offset analgesia is a manifestation of endogenous pain modulation and characterized by profound analgesia upon a small decrease in noxious stimulation.Methods: In this randomized controlled crossover trial, static thermal pain responses and offset analgesia were obtained in 22 healthy male volunteers during spinal anesthesia and control conditions (absence of spinal anesthesia). Pain responses and offset analgesia were measured on a remote skin area above the upper level of anesthesia (C8/Th1).Results: Following spinal injection of the local anesthetic, the average maximum anesthesia level was Th6. Static pain scores at C8/Th1 were higher during spinal anesthesia compared to control: 59.1 +/- 15.0 mm (spinal anesthesia) versus 51.7 +/- 19.7 mm (control; p = 0.03). Offset analgesia responses were decreased during spinal analgesia: pain score decrease 79 +/- 27% (spinal anesthesia) versus 90 +/- 17% (control; p = 0.016).Discussion: We confirmed that spinal anesthesia-induced deafferentation causes hyperalgesic responses to noxious thermal stimulation and reduced offset analgesia at dermatomes remote and above the level of deafferentation. While these data suggest that the reduction of offset analgesia has a central origin, related to alterations in brain areas involved in inhibitory pain control, we cannot exclude alternative (peripheral) mechanisms. Show less
Amerongen, G. van; Siebenga, P.S.; Gurrell, R.; Dua, P.; Whitlock, M.; Gorman, D.; ... ; Groeneveld, G.J. 2019
