BackgroundOver the past decades, opioid prescriptions have increased in the Netherlands. The Dutch general practitioners’ guideline on pain was recently updated and now aims to reduce opioid... Show moreBackgroundOver the past decades, opioid prescriptions have increased in the Netherlands. The Dutch general practitioners’ guideline on pain was recently updated and now aims to reduce opioid prescriptions and high-risk opioid use for non-cancer pain. The guideline, however, lacks practical measures for implementation.ObjectiveThis study aims to determine practical components for a tool that should assist Dutch primary care prescribers and implements the recently updated guideline to reduce opioid prescriptions and high-risk use.MethodsA modified Delphi approach was used. The practical components for the tool were identified based on systematic reviews, qualitative studies, and Dutch primary care guidelines. Suggested components were divided into Part A, containing components designed to reduce opioid initiation and stimulate short-term use, and Part B, containing components designed to reduce opioid use among patients on long-term opioid treatment. During three rounds, a multidisciplinary panel of 21 experts assessed the content, usability, and feasibility of these components by adding, deleting, and adapting components until consensus was reached on the outlines of an opioid reduction tool.ResultsThe resulting Part A consisted of six components, namely education, opioid decision tree, risk assessment, agreements on dosage and duration of use, guidance and follow-up, and interdisciplinary collaboration. The resulting Part B consisted of five components, namely education, patient identification, risk assessment, motivation, and tapering.ConclusionsIn this pragmatic Delphi study, components for an opioid reduction tool for Dutch primary care-givers are identified. These components need further development, and the final tool should be tested in an implementation study. Show less
Algera, M.H.; Cotten, J.F.; Velzen, M. van; Niesters, M.; Boon, M.; Shoham, D.S.; ... ; Dahan, A. 2022
Opioid-induced respiratory depression (OIRD) is a potentially life-threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a... Show moreOpioid-induced respiratory depression (OIRD) is a potentially life-threatening complication of opioid consumption. Apart from naloxone, an opioid antagonist that has various disadvantages, a possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin-releasing hormone (TRH). In this review, we performed a search in electronic databases and retrieved 52 papers on the effect of TRH and TRH-analogs on respiration and their efficacy in the reversal of OIRD in awake and anesthetized mammals, including humans. Animal studies show that TRH and its analog taltirelin stimulate breathing via an effect at the preBotzinger complex, an important respiratory rhythm generator within the brainstem respiratory network. An additional respiratory excitatory effect may be related to TRH's analeptic effect. In awake and anesthetized rodents, TRH and taltirelin improved morphine-and sufentanil-induced respiratory depression, by causing rapid shallow breathing. This pattern of breathing increases the work of breathing, dead space ventilation, atelectasis, and hypoxia. In awake and anesthetized humans, a continuous infusion of intravenous TRH with doses up to 8 mg, did not reverse sufentanil- or remifentanil-induced respiratory depression. This is related to poor penetration of TRH into the brain compartment but also other causes are discussed. No human data on taltirelin are available. In conclusion, data from animals and human indicate that TRH is not a viable reversal agent of OIRD in awake or anesthetized humans. Further human studies on the efficacy and safety of TRH's more potent and longer lasting analog taltirelin are needed as this agent seems to be a more promising reversal drug. Show less
Meijer, F.; Honing, M.; Roor, T.; Toet, S.; Calis, P.; Olofsen, E.; ... ; Dahan, A. 2021
Background: The majority of postoperative patients report moderate to severe pain, possibly related to opioid under-dosing or overdosing during surgery. Objective guidance of opioid dosing using... Show moreBackground: The majority of postoperative patients report moderate to severe pain, possibly related to opioid under-dosing or overdosing during surgery. Objective guidance of opioid dosing using the Nociception Level (NOL) index, a multiparameter artificial intelligence-driven index designed to monitor nociception during surgery, may lead to a more appropriate analgesic regimen, with effects beyond surgery. We tested whether NOL-guided opioid dosing during general anaesthesia results in less postoperative pain.Methods: In this two-centre RCT, 50 patients undergoing abdominal surgery under fentanyl/sevoflurane anaesthesia were randomised to NOL-guided fentanyl dosing or standard care in which fentanyl dosing was based on haemodynamics. The primary endpoint of the study was postoperative pain assessed in the PACU.Results: Median postoperative pain scores were 3.2 (inter-quartile range 1.3-4.3) and 4.8 (3.0-5.3) in NOL-guided and standard care groups, respectively (P=0.006). Postoperative morphine consumption (standard deviation) was 0.06 (0.07) mg kg(-1) (NOL-guided group) and 0.09 (0.09) mg kg(-1) (control group; P=0.204). During surgery, fentanyl dosing was not different between groups (NOL-guided group: 6.4 [4.2] mg kg(-1) vs standard care: 6.0 [2.2] mg kg(-1), P=0.749), although the variation between patients was greater in the NOL-guided group (% coefficient of variation 66% in the NOL-guided group vs 37% in the standard care group).Conclusions: Despite absence of differences in fentanyl and morphine consumption during and after surgery, a 1.6-point improvement in postoperative pain scores was observed in the NOL-guided group. We attribute this to NOL-driven rather than BP- and HR-driven fentanyl dosing during anaesthesia. Show less
Dahan, A.; Boon, M.; Velzen, M. van; Niesters, M. 2020
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
