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Papers by pascal vuilleumier

Trends in Anaesthesia and Critical Care, 2018

Direct oral anticoagulants are approved for use in the United States and Europe and are increasin... more Direct oral anticoagulants are approved for use in the United States and Europe and are increasingly used in chronic liver disease patients who have or are at risk of thrombotic events. While these drugs are clinically attractive because no monitoring is required, the risks and benefits in patients with hepatic or renal insufficiency who undergo surgery remain unclear. In this report, we describe the perioperative consequences, safety issues, and lessons learned from a patient undergoing an orthotopic liver transplant who was anticoagulated with rivaroxaban due to partial superior mesenteric vein thrombosis.

In 2007 the International Association for the Study of Pain (IASP) launched the campaign “Real Wo... more In 2007 the International Association for the Study of Pain (IASP) launched the campaign “Real Women, Real Pain”; 2007e2008 was declared as the “Global Year Against Pain” inWomen. By then it was recognized that 90% of women experience severe/unbearable labor pain, and that one very real consequence to labor pain was psychological: “Long-term emotional stress with potential adverse consequences on maternal mental health and family relationships” [1]. One year later Eisenach and his colleagues published their seminal data on the association between acute pain and postpartum depression [2]. Eisenach conducted a multicentre study across North America andWestern Europe, recruiting 1288 women after vaginal and cesarean delivery (CD). The reported combined incidence of acute pain 36 h after deliverywas 10.6%, and persistent pain at 8 weeks was 9.8%. Multivariable regression revealed a threefold increased risk of postpartum depression (PPD) in the presence of acute pain. Rates of persistent...

Purpose of review Because propofol is the sedative preferred by gastroenterologists, we focus thi... more Purpose of review Because propofol is the sedative preferred by gastroenterologists, we focus this review on gastroenterologist-directed propofol sedation, provide simulations of the respiratory depressant effect of different dosing protocols and give a perspective on future developments in computer-assisted sedation techniques. Recent findings Propofol use by nonanesthesiologists remains a contraindication in the package insert of propofol in most countries. Sedation guidelines produced by the American Society of Gastroenterology partially contradict those produced by the American Society of Anesthesiologists for sedation by nonanesthesiologists, whereas the German guidelines were developed with anesthesiologists involved. The use of fospropofol, recently approved by the US Food and Drug Administration for sedation, is considered an alternative to propofol by some gastroenterologists. Methodological errors in earlier pharmacological studies have to be solved before widespread use o...

Minerva Anestesiologica

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful con... more Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful conditions. Their peripheral anti-inflammatory effect due to inhibition of prostaglandin synthesis is well documented. In the late 1980's, animal data suggested for the first time that NSAIDs might have central effects as well. Since that time, central inflammatory and nociceptive pathways that are potential targets of NSAIDs have been extensively studied in both animal and human models. This review provides an overview of the relevant literature implicated in the central effects of NSAIDs. The role of different enzymes and mediators, as well as the central effects of NSAIDs are discussed. Literature search was performed by PubMed NCBI. A large body of evidence supports the central effects of NSAIDs in animal models of inflammatory pain conditions. Relevant mechanisms that underlie this central action involve spinal upregulation of the enzyme cyclooxygenase, increased spinal prostaglandin E2 production, modulation of inhibitory fast synaptic currents in lamina I and II of the dorsal horn, and glycine-dependent modulation of pain. Results from animal models are not yet sufficiently supported by human studies. This does not necessarily imply that the central effects of NSAIDs are irrelevant to human pain, but rather that methodological and regulatory barriers are the limiting step to translating findings from animal studies to human research protocols.

PLOS ONE, May 9, 2018

Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy ... more Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy is well documented for neuropathic pain, the evidence is less clear in musculoskeletal pain conditions. The present study therefore evaluated the effect of the tricyclic antidepressant imipramine on chronic low-back pain in a randomized, double-blinded placebo-controlled design. To explore the mechanisms of action and the influence of drug metabolism, multimodal quantitative sensory tests (QST) and genotyping for cytochrome P450 2D6 (CYP2D6) were additionally performed. A single oral dose of imipramine 75 mg was compared to active placebo (tolterodine 1 mg) in 50 patients (32 females) with chronic non-specific low-back pain. Intensity of low-back pain was assessed on a 0-10 numeric rating scale at baseline and every 30 minutes after drug intake. Multimodal QST were performed at baseline and in hourly intervals for 2 hours. Pharmacogenetic influences of cytochrome P450 were addressed by CYP2D6 genotyping. No significant analgesic effect was detected neither on low-back pain nor on any of the sensory tests in the overall analyses. However, evidence for an interaction of the imipramine effect and CYP2D6 genotype was found for electrical and for pressure pain detection thresholds. Intermediate but not extensive metabolizers had a 1.20 times greater electrical pain threshold (95%-CI 1.10 to 1.31) and a 1.10 times greater pressure pain threshold (95%-CI 1.01 to 1.21) 60 minutes after imipramine than after placebo (p<0.001 and p = 0.034, respectively). The present study failed to demonstrate an immediate analgesic effect of imipramine on low-back pain. Anti-nociceptive effects as assessed by quantitative sensory tests may depend on CYP2D6 genotype, indicating that metabolizer status should be accounted for when future studies with tricyclic antidepressants are undertaken.

A & A Practice

Direct oral anticoagulants are approved for use in the United States and Europe and are increasin... more Direct oral anticoagulants are approved for use in the United States and Europe and are increasingly used in chronic liver disease patients who have or are at risk of thrombotic events. While these drugs are clinically attractive because no monitoring is required, the risks and benefits in patients with hepatic or renal insufficiency who undergo surgery remain unclear. In this report, we describe the perioperative consequences, safety issues, and lessons learned from a patient undergoing an orthotopic liver transplant who was anticoagulated with rivaroxaban due to partial superior mesenteric vein thrombosis.

Brain : a journal of neurology, 2018

See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory i... more See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory interneurons in the spinal cord use glycine and GABA for fast inhibitory neurotransmission. While there is abundant research on these inhibitory pain pathways in animal models, their relevance in humans remains unclear, largely due to the limited possibility to manipulate selectively these pathways in humans. Hyperekplexia is a rare human disease that is caused by loss-of-function mutations in genes encoding for glycine receptors and glycine transporters. In the present study, we tested whether hyperekplexia patients display altered pain perception or central pain modulation compared with healthy subjects. Seven patients with genetically and clinically confirmed hyperekplexia were compared to 14 healthy age- and sex-matched controls. The following quantitative sensory tests were performed: pressure pain detection threshold (primary outcome), ice water tolerance, single and repeated electr...

Scandinavian Journal of Pain

Introduction Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects ... more Introduction Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain. Methods In this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15 mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2 h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≤30% pain reduc...

Trends in Anaesthesia and Critical Care, 2015

Abstract Postpartum hemorrhage (PPH) remains a considerable burden on maternal morbidity and mort... more Abstract Postpartum hemorrhage (PPH) remains a considerable burden on maternal morbidity and mortality, accounting for 80% of severe maternal morbidity. Although a consensus on definitions on major obstetrical bleeding is lacking, postpartum blood losses greater than 500 ml after vaginal delivery and 1000 ml after cesarean section is considered as postpartum hemorrhage; a blood loss greater than 2500 ml is considered as severe postpartum hemorrhage. The definition of major obstetrical hemorrhage (MOH) is a broader term characterizing antenatal or postpartal bleeding. Approximately only 10% of MOH is predictable, as etiologies and risk factors leading to MOH are still poorly understood. This lack of predictability may result in delays for initiation of proper anesthesiologic management of MOH. The quantity of blood loss, combined to the rapidity in which blood loss happens in case of MOH remains an important challenge anesthesiologic teams otherwise usually face only in major vascular or trauma surgery. Preservation of maternal fertility is one of the major aims after maternal and neonatal resuscitation has been granted. Drugs used to increase uterine tone are reviewed in detail, as well as surgical measures available today. Fortunately lessons learned from trauma management have been implemented in major MOH protocols. Not only is maternal and neonatal well being the primary aim to keep in sight, preservation of fertility whenever possible is the next aim anesthesiologists are facing.

BMC Pharmacology and Toxicology, 2015

BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prol... more BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated. METHODS/DESIGN In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables. DISCUSSION Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients. TRIAL REGISTRATION Clinicaltrials.gov, NCT01179828.

Regional anesthesia and pain medicine, Jan 28, 2015

Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and... more Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and clinical practice, but information on reliability in patients with chronic pain is sparse. The aim of this study was to evaluate the reliability of different QST in patients with chronic low back pain. Eighty-nine patients with chronic low back pain participated in 2 identical experimental sessions, separated by at least 7 days. The following parameters were recorded: pressure pain detection and tolerance thresholds at the toe, electrical pain thresholds to single and repeated stimulation, heat pain detection and tolerance thresholds at the arm and leg, cold pain detection threshold at the arm and leg, and conditioned pain modulation using the cold pressor test.Reliability was analyzed using the coefficient of variation, the coefficient of repeatability, and the intraclass correlation coefficient. It was judged as acceptable or not based primarily on the analysis of the coefficient of r...

Trends in Anaesthesia and Critical Care, 2015

PAIN, 2015

Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA rec... more Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.

Current Anesthesiology Reports, 2013

In an attempt to provide some explanation for the observed differences in pain perception and ana... more In an attempt to provide some explanation for the observed differences in pain perception and analgesic requirements during labor and delivery between women, the idea that genetic variability is an important factor has emerged over the past decade. Bearing in mind the challenges posed when evaluating pain during childbirth as a phenotype, recent findings in the field of genetics and obstetric anesthesia are presented in this review; in particular those related to differences in labor analgesia requirements between women, the response to opioids after cesarean delivery, as well as theories on why post-cesarean pain may be different from other types of post-surgical pain.

The Clinical Journal of Pain, 2015

The intensity of post-egg retrieval pain is underestimated, with few studies examining postproced... more The intensity of post-egg retrieval pain is underestimated, with few studies examining postprocedural pain and predictors to identify women at risk for severe pain. We evaluated the influence of pre-procedural hormonal levels, ovarian factors, as well as mechanical temporal summation (mTS) as predictors for post-egg retrieval pain in women undergoing in vitro fertilization (IVF). Methods Eighteen women scheduled for ultrasound-guided egg retrieval under standardized anesthesia and post-procedural analgesia were enrolled. Pre-procedural mTS, questionnaires, clinical data related to anesthesia and the procedure itself, post-procedural pain scores and pain medication for breakthrough pain were recorded. Statistical analysis included Pearson product moment correlations, Mann-Whitney U tests and multiple linear regressions. Results Average peak post-egg retrieval pain during the first 24 hours was 5.0 ± 1.6 on an NRS scale (0=no pain, 10=worst pain imaginable). Peak post-egg retrieval pain was correlated with basal antimullerian hormone (AMH) (r=0.549, p=0.018), pre-procedural peak estradiol (r=0.582, p=0.011), total number of follicles (r=0.517, p=0.028) and number of retrieved eggs (r=0.510, p=0.031). Ovarian hyperstimulation syndrome (OHSS) (n=4) was associated with higher basal AMH (p=0.004), higher peak pain scores (p=0.049), but not with peak estradiol (p=0.13). The mTS did not correlate with peak post-procedural pain (r=0.266, p=0.286), or peak estradiol level (r=0.090, p=0.899).

Trends in Anaesthesia and Critical Care, 2018

Direct oral anticoagulants are approved for use in the United States and Europe and are increasin... more Direct oral anticoagulants are approved for use in the United States and Europe and are increasingly used in chronic liver disease patients who have or are at risk of thrombotic events. While these drugs are clinically attractive because no monitoring is required, the risks and benefits in patients with hepatic or renal insufficiency who undergo surgery remain unclear. In this report, we describe the perioperative consequences, safety issues, and lessons learned from a patient undergoing an orthotopic liver transplant who was anticoagulated with rivaroxaban due to partial superior mesenteric vein thrombosis.

In 2007 the International Association for the Study of Pain (IASP) launched the campaign “Real Wo... more In 2007 the International Association for the Study of Pain (IASP) launched the campaign “Real Women, Real Pain”; 2007e2008 was declared as the “Global Year Against Pain” inWomen. By then it was recognized that 90% of women experience severe/unbearable labor pain, and that one very real consequence to labor pain was psychological: “Long-term emotional stress with potential adverse consequences on maternal mental health and family relationships” [1]. One year later Eisenach and his colleagues published their seminal data on the association between acute pain and postpartum depression [2]. Eisenach conducted a multicentre study across North America andWestern Europe, recruiting 1288 women after vaginal and cesarean delivery (CD). The reported combined incidence of acute pain 36 h after deliverywas 10.6%, and persistent pain at 8 weeks was 9.8%. Multivariable regression revealed a threefold increased risk of postpartum depression (PPD) in the presence of acute pain. Rates of persistent...

Purpose of review Because propofol is the sedative preferred by gastroenterologists, we focus thi... more Purpose of review Because propofol is the sedative preferred by gastroenterologists, we focus this review on gastroenterologist-directed propofol sedation, provide simulations of the respiratory depressant effect of different dosing protocols and give a perspective on future developments in computer-assisted sedation techniques. Recent findings Propofol use by nonanesthesiologists remains a contraindication in the package insert of propofol in most countries. Sedation guidelines produced by the American Society of Gastroenterology partially contradict those produced by the American Society of Anesthesiologists for sedation by nonanesthesiologists, whereas the German guidelines were developed with anesthesiologists involved. The use of fospropofol, recently approved by the US Food and Drug Administration for sedation, is considered an alternative to propofol by some gastroenterologists. Methodological errors in earlier pharmacological studies have to be solved before widespread use o...

Minerva Anestesiologica

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful con... more Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for a variety of painful conditions. Their peripheral anti-inflammatory effect due to inhibition of prostaglandin synthesis is well documented. In the late 1980's, animal data suggested for the first time that NSAIDs might have central effects as well. Since that time, central inflammatory and nociceptive pathways that are potential targets of NSAIDs have been extensively studied in both animal and human models. This review provides an overview of the relevant literature implicated in the central effects of NSAIDs. The role of different enzymes and mediators, as well as the central effects of NSAIDs are discussed. Literature search was performed by PubMed NCBI. A large body of evidence supports the central effects of NSAIDs in animal models of inflammatory pain conditions. Relevant mechanisms that underlie this central action involve spinal upregulation of the enzyme cyclooxygenase, increased spinal prostaglandin E2 production, modulation of inhibitory fast synaptic currents in lamina I and II of the dorsal horn, and glycine-dependent modulation of pain. Results from animal models are not yet sufficiently supported by human studies. This does not necessarily imply that the central effects of NSAIDs are irrelevant to human pain, but rather that methodological and regulatory barriers are the limiting step to translating findings from animal studies to human research protocols.

PLOS ONE, May 9, 2018

Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy ... more Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy is well documented for neuropathic pain, the evidence is less clear in musculoskeletal pain conditions. The present study therefore evaluated the effect of the tricyclic antidepressant imipramine on chronic low-back pain in a randomized, double-blinded placebo-controlled design. To explore the mechanisms of action and the influence of drug metabolism, multimodal quantitative sensory tests (QST) and genotyping for cytochrome P450 2D6 (CYP2D6) were additionally performed. A single oral dose of imipramine 75 mg was compared to active placebo (tolterodine 1 mg) in 50 patients (32 females) with chronic non-specific low-back pain. Intensity of low-back pain was assessed on a 0-10 numeric rating scale at baseline and every 30 minutes after drug intake. Multimodal QST were performed at baseline and in hourly intervals for 2 hours. Pharmacogenetic influences of cytochrome P450 were addressed by CYP2D6 genotyping. No significant analgesic effect was detected neither on low-back pain nor on any of the sensory tests in the overall analyses. However, evidence for an interaction of the imipramine effect and CYP2D6 genotype was found for electrical and for pressure pain detection thresholds. Intermediate but not extensive metabolizers had a 1.20 times greater electrical pain threshold (95%-CI 1.10 to 1.31) and a 1.10 times greater pressure pain threshold (95%-CI 1.01 to 1.21) 60 minutes after imipramine than after placebo (p<0.001 and p = 0.034, respectively). The present study failed to demonstrate an immediate analgesic effect of imipramine on low-back pain. Anti-nociceptive effects as assessed by quantitative sensory tests may depend on CYP2D6 genotype, indicating that metabolizer status should be accounted for when future studies with tricyclic antidepressants are undertaken.

A & A Practice

Direct oral anticoagulants are approved for use in the United States and Europe and are increasin... more Direct oral anticoagulants are approved for use in the United States and Europe and are increasingly used in chronic liver disease patients who have or are at risk of thrombotic events. While these drugs are clinically attractive because no monitoring is required, the risks and benefits in patients with hepatic or renal insufficiency who undergo surgery remain unclear. In this report, we describe the perioperative consequences, safety issues, and lessons learned from a patient undergoing an orthotopic liver transplant who was anticoagulated with rivaroxaban due to partial superior mesenteric vein thrombosis.

Brain : a journal of neurology, 2018

See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory i... more See Dickenson (doi:10.1093/brain/awx334) for a scientific commentary on this article.Inhibitory interneurons in the spinal cord use glycine and GABA for fast inhibitory neurotransmission. While there is abundant research on these inhibitory pain pathways in animal models, their relevance in humans remains unclear, largely due to the limited possibility to manipulate selectively these pathways in humans. Hyperekplexia is a rare human disease that is caused by loss-of-function mutations in genes encoding for glycine receptors and glycine transporters. In the present study, we tested whether hyperekplexia patients display altered pain perception or central pain modulation compared with healthy subjects. Seven patients with genetically and clinically confirmed hyperekplexia were compared to 14 healthy age- and sex-matched controls. The following quantitative sensory tests were performed: pressure pain detection threshold (primary outcome), ice water tolerance, single and repeated electr...

Scandinavian Journal of Pain

Introduction Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects ... more Introduction Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain. Methods In this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15 mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2 h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≤30% pain reduc...

Trends in Anaesthesia and Critical Care, 2015

Abstract Postpartum hemorrhage (PPH) remains a considerable burden on maternal morbidity and mort... more Abstract Postpartum hemorrhage (PPH) remains a considerable burden on maternal morbidity and mortality, accounting for 80% of severe maternal morbidity. Although a consensus on definitions on major obstetrical bleeding is lacking, postpartum blood losses greater than 500 ml after vaginal delivery and 1000 ml after cesarean section is considered as postpartum hemorrhage; a blood loss greater than 2500 ml is considered as severe postpartum hemorrhage. The definition of major obstetrical hemorrhage (MOH) is a broader term characterizing antenatal or postpartal bleeding. Approximately only 10% of MOH is predictable, as etiologies and risk factors leading to MOH are still poorly understood. This lack of predictability may result in delays for initiation of proper anesthesiologic management of MOH. The quantity of blood loss, combined to the rapidity in which blood loss happens in case of MOH remains an important challenge anesthesiologic teams otherwise usually face only in major vascular or trauma surgery. Preservation of maternal fertility is one of the major aims after maternal and neonatal resuscitation has been granted. Drugs used to increase uterine tone are reviewed in detail, as well as surgical measures available today. Fortunately lessons learned from trauma management have been implemented in major MOH protocols. Not only is maternal and neonatal well being the primary aim to keep in sight, preservation of fertility whenever possible is the next aim anesthesiologists are facing.

BMC Pharmacology and Toxicology, 2015

BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prol... more BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated. METHODS/DESIGN In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables. DISCUSSION Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients. TRIAL REGISTRATION Clinicaltrials.gov, NCT01179828.

Regional anesthesia and pain medicine, Jan 28, 2015

Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and... more Reliability is an essential condition for using quantitative sensory tests (QSTs) in research and clinical practice, but information on reliability in patients with chronic pain is sparse. The aim of this study was to evaluate the reliability of different QST in patients with chronic low back pain. Eighty-nine patients with chronic low back pain participated in 2 identical experimental sessions, separated by at least 7 days. The following parameters were recorded: pressure pain detection and tolerance thresholds at the toe, electrical pain thresholds to single and repeated stimulation, heat pain detection and tolerance thresholds at the arm and leg, cold pain detection threshold at the arm and leg, and conditioned pain modulation using the cold pressor test.Reliability was analyzed using the coefficient of variation, the coefficient of repeatability, and the intraclass correlation coefficient. It was judged as acceptable or not based primarily on the analysis of the coefficient of r...

Trends in Anaesthesia and Critical Care, 2015

PAIN, 2015

Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA rec... more Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain. Tolterodine (TLT) was used as an active placebo. The primary outcome parameter was a change in the area of cutaneous UVB irradiation-induced secondary hyperalgesia (ASH), which was monitored for 8 hours after drug application. Sedative effects were assessed in parallel to antihyperalgesia. Compared with TLT, recovery from hyperalgesia was significantly faster in the CBZ and CLN groups (P = 0.009). At the time point of maximum effect, the rate of recovery from hyperalgesia was accelerated by CBZ and CLN, relative to placebo by 15.7% (95% confidence interval [CI] 0.8-30.5), P = 0.040, and 28.6% (95% CI 4.5-52.6), P = 0.022, respectively. Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.

Current Anesthesiology Reports, 2013

In an attempt to provide some explanation for the observed differences in pain perception and ana... more In an attempt to provide some explanation for the observed differences in pain perception and analgesic requirements during labor and delivery between women, the idea that genetic variability is an important factor has emerged over the past decade. Bearing in mind the challenges posed when evaluating pain during childbirth as a phenotype, recent findings in the field of genetics and obstetric anesthesia are presented in this review; in particular those related to differences in labor analgesia requirements between women, the response to opioids after cesarean delivery, as well as theories on why post-cesarean pain may be different from other types of post-surgical pain.

The Clinical Journal of Pain, 2015

The intensity of post-egg retrieval pain is underestimated, with few studies examining postproced... more The intensity of post-egg retrieval pain is underestimated, with few studies examining postprocedural pain and predictors to identify women at risk for severe pain. We evaluated the influence of pre-procedural hormonal levels, ovarian factors, as well as mechanical temporal summation (mTS) as predictors for post-egg retrieval pain in women undergoing in vitro fertilization (IVF). Methods Eighteen women scheduled for ultrasound-guided egg retrieval under standardized anesthesia and post-procedural analgesia were enrolled. Pre-procedural mTS, questionnaires, clinical data related to anesthesia and the procedure itself, post-procedural pain scores and pain medication for breakthrough pain were recorded. Statistical analysis included Pearson product moment correlations, Mann-Whitney U tests and multiple linear regressions. Results Average peak post-egg retrieval pain during the first 24 hours was 5.0 ± 1.6 on an NRS scale (0=no pain, 10=worst pain imaginable). Peak post-egg retrieval pain was correlated with basal antimullerian hormone (AMH) (r=0.549, p=0.018), pre-procedural peak estradiol (r=0.582, p=0.011), total number of follicles (r=0.517, p=0.028) and number of retrieved eggs (r=0.510, p=0.031). Ovarian hyperstimulation syndrome (OHSS) (n=4) was associated with higher basal AMH (p=0.004), higher peak pain scores (p=0.049), but not with peak estradiol (p=0.13). The mTS did not correlate with peak post-procedural pain (r=0.266, p=0.286), or peak estradiol level (r=0.090, p=0.899).