Albert Dahan

Leiden University Medical Centre | LUMC · Department of Anesthesiology

The widely prescribed opioid oxycodone may cause lethal respiratory depression. We compared the effects of oxycodone on breathing and antinociception in healthy young volunteers. After pharmacokinetic/pharmacodynamic modelling, we constructed utility functions to combine the wanted and unwanted endpoints into a single function. We hypothesized that...

Background: We determined the first prescribed opioid and the prescribers of opioids after knee and hip arthroplasty (KA/HA) between 2013 and 2018 in the Netherlands. We also evaluated whether the first prescribed opioid dose was associated with the total dispensed dose and long-term opioid use in the first postoperative year. Methods: The Dutch...

Background: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depre...

Background Opioids continue to be widely prescribed for chronic noncancer pain, despite the awareness that opioids provide only short-time pain relief, lead to dose accumulation, have numerous adverse effects, and are difficult to wean. As an alternative, we previously showed advantages of using pharmaceutical-grade cannabis in a population of chro...

In this pooled analysis of two randomized clinical trials, intraoperative opioid dosing based on the nociception level-index produced less pain compared to standard care with a difference in pain scores in the post-anesthesia care unit of 1.5 (95% CI 0.8–2.2) points on an 11-point scale. The proportion of patients with severe pain was lower by 70%....

Background Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI)...

Background To assess the prevalence, incidence, location, and behavior of chronic pre- and postoperative pain in bariatric surgery, and the use of analgesics. Methods A cross-sectional e-survey was conducted on 3928 post-bariatric patients and four-time points for pain assessment were evaluated: preoperative, on the ward, day 1 at home postoperati...

Background: Due the increasing need for storage of carbon dioxide (CO 2 ) more individuals are prone to be exposed to high concentrations of CO 2 accidentally released into atmosphere, with deleterious consequences. Methods: We tested the effect of increasing CO 2 concentrations in humans (6–12%) and rats (10–50%) at varying inhalation times (10–60...

Introduction In the past decades, the opioid crisis has heavily impacted parts of the US society and has been followed by an increase in the use of opioids worldwide. It is of paramount importance that we explore the origins of the US opioid epidemic to develop best practices to tackle the rising tide of opioid overdoses. Areas covered In this exp...

Ketamine is a versatile drug used for many indications and is administered via various routes. Here, we report on the pharmacodynamics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S-ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two 50 mg S-ketamine oral thin films...

Background: Animal data suggest that the antidepressant and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor modulator tianeptine is able to prevent opioid-induced respiratory depression. We hypothesize that oral or intravenous tianeptine can effectively prevent or counteract opioid-induced respiratory depression in humans. Methods:...

Background and purpose: Numbers on opioid prescriptions over time in arthroplasty patients are currently lacking. Therefore we determined the annual opioid prescribing rate in patients who received a hip/knee arthroplasty (HA/KA) between 2013 and 2018. Patients and methods: The Dutch Foundation for Pharmaceutical Statistics, which provides natio...

Ketamine is administered predominantly via the intravenous route for the various indications, including anesthesia, pain relief and treatment of depression. Here we report on the pharmacokinetics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of S -ketamine in a population of healthy male and female volunteers. Twenty v...

Background: Opioid overdoses are increasing in the Netherlands, and there may be other harms associated with prescription opioid use. We investigated the relationship between prescription opioid use and unplanned ICU admission and death. Methods: This is an analysis of linked government registries of the adult Dutch population (age ≥18 years) al...

Background: The optimal treatment strategy for postoperative pain following pancreatoduodenectomy remains unknown. The aim of this study was to investigate whether sublingual sufentanil tablet (SST) is a non-inferior analgesic compared to our standard-of-care (patient-controlled epidural analgesia [PCEA] or PCA morphine) in the treatment of pain f...

Study objective Quantitative neuromuscular monitoring is traditionally evaluated at the adductor pollicis muscle. By contrast, the TOF-Cuff compressomyograph evaluates neuromuscular block (NMB) at the upper arm. However, compressomyography has not been fully validated against other monitoring entities. This study evaluates the agreement between NMB...

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 possible reversal strategy is treatment of OIRD with the hypothalamic hormone and neuromodulator thyrotropin-releasing hormone (TRH). In this review, we perfor...

Introduction: Muscle relaxants are often given during general anesthesia to facilitate endotracheal intubation. However lingering effects after anesthesia-end may lead to respiratory compromise in the PACU. Strategies to reduce these adverse events include monitoring neuromuscular block, the use of short-acting agents and active pharmacological re...

Background: Potent synthetic opioids, such as fentanyl, are increasingly abused, resulting in unprecedented numbers of fatalities from respiratory depression. Treatment with the high-affinity mu-opioid receptor partial agonist buprenorphine may prevent fatalities by reducing binding of potent opioids to the opioid receptor, limiting respiratory de...

Background Ketamine produces potent analgesia combined with psychedelic effects. It has been suggested that these two effects are associated and possibly that analgesia is generated by ketamine-induced dissociation. The authors performed a post hoc analysis of previously published data to quantify the pharmacodynamic properties of ketamine-induced...

Background Opioid-induced respiratory depression driven by ligand binding to mu-opioid receptors is a leading cause of opioid-related fatalities. Buprenorphine, a partial agonist, binds with high affinity to mu-opioid receptors but displays partial respiratory depression effects. The authors examined whether sustained buprenorphine plasma concentra...

Objective Many prescribed and over-the-counter medications, for example, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with upper gastrointestinal bleeding (UGIB). Recently, a decrease in prescribing of NSAIDs was observed in the Netherlands, but whether a similar decreasing trend could be observed in the incidence of severe UGIB (e...

Opioids may produce life-threatening respiratory depression and death from their actions at the opioid receptors within the brainstem respiratory neuronal network. Since there is an increasing number of conditions where the administration of the opioid receptor antagonist naloxone is inadequate or undesired, there is an increased interest in the de...

Study objective: To assess whether different intensities of intra-abdominal pressure and deep neuromuscular blockade influence the risk of intra-operative surgical complications during laparoscopic donor nephrectomy. Design: A pooled analysis of ten previously performed prospective randomized controlled trials. Setting: Laparoscopic donor neph...

Background Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block...

Although postoperative adverse respiratory events, defined by a decrease in respiratory rate (RR) and/or a drop in oxygen saturation (SpO2), occur frequently, many of such events are missed. The purpose of the current study was to assess whether continuous monitoring of the integrated pulmonary index (IPI), a composite index of SpO2, RR, end-tidal...

Background: Prescribing practice of pain medication is changing in the Netherlands; opioids are used more often instead of nonsteroidal anti-inflammatory drugs (NSAIDs), therefore we aimed to compare the use of pain medication with Slovenia which has stringent prescribing rules for strong opioids. Methods: We conducted a cohort study into national...

Background: Ketamine has cardiac excitatory side-effects. Currently, data on the effects of ketamine and metabolite concentrations on cardiac output are scarce. We therefore developed a pharmacodynamic model derived from data from a randomised clinical trial. The current study is part of a larger clinical study evaluating the potential mitigating...

Background: It is generally accepted that a neuraxial blockade strengthens the sedative effects of propofol. Deafferentation caused by neuraxial blockade is thought to play a key role. Objectives: The objective is to determine whether epidural blockade affects the bispectral index (BIS) of propofol and two other pharmacodynamic endpoints, mean a...

Purpose: Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during...

In humans, proof of long-term efficacy of ketamine treatment in neuropathic pain is lacking. To improve our understanding of ketamine behavior under various administration conditions, we performed a systematic review and meta-analyses of controlled studies on the efficacy of ketamine in mice and rats with a disease model of nerve injury on relief o...

Management of chronic pain is multidisciplinary, but pharmacotherapy is one of the mainstays of pain management. As applies in all medical therapies, clinicians must strive to achieve the best possible outcome for patients in terms of maximising benefit and minimizing risks, and ensure that this is conducted for each treatment and as an integral el...

General anesthesia is obtained by administration of potent hypnotics, analgesics and muscle relaxants. Apart from their intended effects (loss of consciousness, pain relief and muscle relaxation), these agents profoundly affect the control of breathing, in part by an effect within the peripheral chemoreflex loop that originates at the carotid bodie...

Introduction: Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice. Objectives: In the current study, we describe phenotypes of patients with CLBP based on the status of their endogenous pain modulatory system. Methods: Conditioned pain modulation (a measure of central pain inhibition), temporal summa...

Patient-controlled analgesia (PCA) is a popular and efficacious form of postoperative pain relief that, however, is not without complications. Here we describe a 73-year-old Somalian male patient that underwent abdominal surgery and received intravenous morphine PCA for postoperative pain relief. Due to his inability to speak the native language, h...

Background Deep neuromuscular block is associated with improved working conditions during laparoscopic surgery when propofol is used as a general anaesthetic. However, whether deep neuromuscular block yields similar beneficial effects when anaesthesia is maintained using volatile inhalation anaesthesia has not been systematically investigated. Vola...

Over the past decade opioid use has risen globally. The causes and consequences of this increase, especially in Europe, are poorly understood. We conducted a population-based cohort study using national statistics on analgesics prescriptions, opioid poisoning hospital admissions and deaths in the Netherlands from 2013 to 2017. Pain prevalence and s...

Background: The majority of postoperative patients report moderate to severe pain, possibly related to opioid underdosing 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...

Background Recent studies show activity of ketamine metabolites, such as hydroxynorketamine, in producing rapid relief of depression-related symptoms and analgesia. To improve our understanding of the pharmacokinetics of ketamine and metabolites norketamine, dehydronorketamine, and hydroxynorketamine, we developed a population pharmacokinetic model...

Introduction: 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 upo...

Chronic opioid consumption is associated with addiction, physical dependence and tolerance. Tolerance results in dose escalation to maintain the desired opioid effect. Intake of high‐dose or potent opioids may cause life‐threatening respiratory depression, an effect that may be reduced by tolerance. We performed a pharmacokinetic‐pharmacodynamic an...

Background: To improve understanding of the respiratory behavior of oliceridine, a μ-opioid receptor agonist that selectively engages the G-protein-coupled signaling pathway with reduced activation of the β-arrestin pathway, the authors compared its utility function with that of morphine. It was hypothesized that at equianalgesia, oliceridine will...

Background: Opioids are potent painkillers but come with serious adverse effects ranging from addiction to potentially lethal respiratory depression. A variety of drugs with separate mechanisms of action are available to prevent or reverse opioid-induced respiratory depression (OIRD). Methods: The authors reviewed human studies on reversal of OI...

Background The use of epidural analgesia (EA) in pancreatic surgery remains under debate. This study compares patients treated with EA versus non-EA after open pancreatectomy in a tertiary referral center. Methods All patients undergoing open pancreatectomy from 2013 to 2017 were retrospectively reviewed. (Non-)EA was terminated on postoperative d...

What we already know about this topic: The nociception level index (Medasense Biometrics Ltd., Ramat Gan, Israel), is a reliable measure of moderate to intense noxious stimulation during anesthesia and surgery WHAT THIS ARTICLE TELLS US THAT IS NEW: In a randomized trial in patients having major abdominal surgery, compared to standard practice, no...

Introduction Surgical rating scales (SRSs) enable the surgeon to uniformly quantify surgical working conditions. They are increasingly used as a primary outcome in studies evaluating the effect of anaesthesia or surgery-related interventions on the quality of the surgical work field. SRSs are especially used in laparoscopic surgery due to a renewed...

In this experimental randomized placebo-controlled 4-way crossover trial, we explored the analgesic effects of inhaled pharmaceutical-grade cannabis in 20 chronic pain patients with fibromyalgia. We tested 4 different cannabis varieties with exact knowledge on their [INCREMENT]-tetrahydrocannabinol (THC) and cannabidiol (CBD) content: Bedrocan (22....

It is not straightforward to simultaneously evaluate the beneficial and harmful effects of pain management, since different drugs may possess different analgesia and adverse effect profiles. Utility functions, derived from the pharmacokinetics and pharmacodynamics of individual outcome parameters, have been constructed to address this problem. Here...

Objective To compare the costs of a strategy of patient controlled remifentanil versus epidural analgesia for pain relief in labour. Design We performed a multicentre randomised controlled trial in 15 hospitals in the Netherlands, the RAVEL trial. Costs were analysed from a health care perspective alongside the RAVEL trial. Population Pregnant wo...

CONSORT checklist of information to include when reporting a randomised trial. (DOC)

Patient information and informed consent form. (DOC)

Full study protocol. (DOC)

Maternal and neonatal outcome. (DOC)

Reasons for neonatal admission. (DOCX)

Object In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief. We evaluated the predictive value of a block on the outcome of surgery. Methods In total, three blocks were performed at two we...

Background: The clinical relevance of the suggested hyperalgesic effects of remifentanil is still unclear, especially in the long term. Objective: The current study evaluated the impact of remifentanil on thermal thresholds 3 days and 12 months after surgery, measured with Quantitative Sensory Testing. Design: A prospective, single-blind, rand...