Abstract：
BACKGROUND:Genetic variability contributes to variable clinical response to opioids. This study emerged from the observation of three Norwegian patients who showed no or extraordinary poor response to very high doses of opioids. We suspected a genetic defect and applied a 'most likely candidate gene' approach to investigate this possibility. METHODS:DNA sequencing was used to search for mutations in coding regions of the OPRM1 gene, encoding the μ opioid receptor (hMOR), in one patient. The remaining two patients, and two cohorts comprising 2158 European cancer pain patients and 600 Norwegian healthy volunteers, respectively, were genotyped using a custom-made TaqMan SNP allelic discrimination assay. RESULTS:DNA sequencing disclosed a homozygous, inactivating Arg181Cys mutation in hMOR in the patient who showed no effects from opioids. The two patients with poor effect from very high doses of opioids were both heterozygous for the mutation. Six heterozygous patients identified among the European cancer patients all used high doses of opioids and/or reported inferior effect on their pain. About one in every 100 Norwegians is heterozygous for the mutation. CONCLUSIONS:The Arg181Cys mutation occurs at clinically relevant frequencies and produces a signaling dead hMOR which may abolish or significantly reduce opioid effects in affected individuals. Anesthesiologists and practitioners in pain medicine should be aware of this mutation as a possible explanation for inefficiency of opioids and consider genotyping in relevant cases. Individuals homozygous for the mutation may need a highly personalized approach to pain therapy.
journal_name
Acta Anaesthesiol Scandjournal_title
Acta anaesthesiologica Scandinavicaauthors
Skorpen F,von Hofacker S,Bjørngaard M,Skogholt AH,Dale O,Kaasa S,Klepstad Pdoi
10.1111/aas.12739subject
Has Abstractpub_date
2016-09-01 00:00:00pages
1084-91issue
8eissn
0001-5172issn
1399-6576journal_volume
60pub_type
杂志文章abstract：:Aspiration pneumonitis is a severe complication of anesthesia. The objectives of this study were to determine if preoperative famotidine, a new histamine2-receptor antagonist, given by mouth either the evening before or the morning of elective surgery, reduced gastric residual volume and increased gastric pH in pediat...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1399-6576.1991.tb03328.x
更新日期：1991-07-01 00:00:00
abstract：BACKGROUND:Stress response to surgery is modulated by several factors, including magnitude of the injury, pain, type of procedure and choice of anaesthesia. Our purpose was to compare intra- and post-operative hormonal changes during total intravenous anaesthesia (TIVA) using propofol and remifentanil vs. sevoflurane a...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2008.01589.x
更新日期：2008-04-01 00:00:00
abstract：:This case illustrates the threading of an epidural catheter with electrical stimulation guidance from the lumbar epidural space to the thoracic space in a pediatric patient. A 17-year-old boy with Down syndrome, weighing 48 kg, was scheduled to undergo a laparotomy for duodenal obstruction and gastrostomy tube inserti...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.2005.00684.x
更新日期：2005-05-01 00:00:00
abstract：BACKGROUND:Epidural opioids are frequently combined with local anaesthetics for an additive antinociceptive effect. We investigated the efficacy of epidural fentanyl to 1.25 or 1.5 mg/ml ropivacaine for post-operative epidural analgesia in children. METHODS:One hundred and eight children undergoing hypospadias repair ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2009.02046.x
更新日期：2009-09-01 00:00:00
abstract：:The effects th groups the changes in CO and SV were due mainly to a reduced demand of oxygen transport and expected changes in sympatho-adrenergic tone rather than to myocardial depression. ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1981.tb01697.x
更新日期：1981-12-01 00:00:00
abstract：BACKGROUND:Intermittent pneumatic foot compression (IPC) is a useful technique for prophylaxis of peri-operative venous thromboembolism. The aim of this study was to determine the effect of IPC on blood coagulation/fibrinolysis and platelet function using a blood viscometer (Sonoclot) and a platelet aggregation monitor...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章
doi：10.1111/j.1399-6576.2005.00661.x
更新日期：2005-05-01 00:00:00
abstract：:The effects of hydralazine, clonidine, propranolol and methyldopa medications on the cardiovascular response to ketamine anaesthesia were studied in spontaneously hypertensive (SH) rats. Except in propranolol- and methyldopa-treated animals, blood pressure was increased by ketamine in all groups. The heart rate was in...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1978.tb01320.x
更新日期：1978-01-01 00:00:00
abstract：BACKGROUND:In this systematic review, we evaluated double-blind, randomized and controlled trials on the effect of wound infiltration with local anesthetics compared with the effect of placebo on post-operative pain after lumbar spine surgery. METHODS:Medline, the Cochrane Library and Google Scholar were searched for ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,meta分析,评审
doi：10.1111/j.1399-6576.2011.02629.x
更新日期：2012-03-01 00:00:00
abstract：BACKGROUND:Takotsubo syndrome (TS) is an acute cardiac condition with a substantial mortality for which no specific treatment is available. We have previously shown that isoflurane attenuates the development of left ventricular (LV) dysfunction in an experimental TS-model. We compared the effects of equi-anaesthetic do...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/aas.12857
更新日期：2017-03-01 00:00:00
abstract：BACKGROUND:Morbid obesity is associated with important differences in pharmacokinetics and pharmacodynamics. The aim of this study was to determine minimum alveolar concentration of sevoflurane for maintaining bispectral index (BIS) below 50 (MACBIS50 ) in morbidly obese patients undergoing bariatric surgery using the ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/aas.12038
更新日期：2013-04-01 00:00:00
abstract：BACKGROUND:Metohexital and propofol are short-acting induction agents, which have a tendency to prolong the QTc interval of the ECG. We studied whether this increase could be prevented by combining a beta-blocking agent, esmolol, with these drugs. Simultaneously, we studied the hemodynamic effects of these combinations...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2006.00911.x
更新日期：2006-02-01 00:00:00
abstract：BACKGROUND:Neostigmine, used for reversal of neuromuscular block, has been implicated in the development of postoperative nausea and vomiting (PONV). The use of mivacurium, which does not require neostigmine reversal due to its metabolism by plasma cholinesterase, has made it possible to study the effect of neostigmine...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1034/j.1399-6576.2001.045004495.x
更新日期：2001-04-01 00:00:00
abstract：:The majority of cancer patients develop pain before death. This pain has been shown to be underdiagnosed and undertreated. Opioid use has increased in the past 20 years in both developing and developed countries. The changing pattern in opioid use has resulted in the emergence of neurotoxicity as a major side effect o...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,评审
doi：10.1034/j.1399-6576.1999.430910.x
更新日期：1999-10-01 00:00:00
abstract：:Sixty children, aged 1-12 years, were investigated with regard to gastric pH and volume before general anaesthesia. Thirty children (group D) received diazepam 0.75 mg/kg b.w. rectally 1 h before anaesthesia. Thirty children (group L) received a "lytic cocktail" (pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1984.tb02139.x
更新日期：1984-12-01 00:00:00
abstract：:A standardized rat endotoxin shock model was used to assess the differential effects of four commonly used anesthetics upon hemodynamics before and during endotoxin shock. Forty-nine male Sprague-Dawley rats weighing 307 +/- 4 g were divided into five groups:freely-moving conscious, enflurane (2%), isoflurane (1.4%), ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1987.tb02619.x
更新日期：1987-08-01 00:00:00
abstract：:The effects of enflurane anaesthesia on central circulation, total oxygen uptake, splanchnic circulation and splanchnic oxygen uptake were studied in 10 artifically ventilated dogs, basally anaesthetized with thiopental and nitrous oxide. Hepatic arterial, superior mesenteric arterial and portal venous blood flows wer...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1979.tb01416.x
更新日期：1979-02-01 00:00:00
abstract：BACKGROUND:children undergoing ureteroneocystostomy suffer from post-operative pain due to the surgical incision and bladder spasm. A single-shot caudal block is a common technique for paediatric analgesia, but a disadvantage is the limitation of a short duration in spite of the additives co-administered. A few clinica...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2010.02354.x
更新日期：2011-01-01 00:00:00
abstract：:A 61-year-old woman (57 kg, 171 cm) underwent surgery under general anaesthesia with desflurane 5.8-6.1 vol. % end-tidal, remifentanil 0.2-0.4 μg/kg/min and rocuronium 35 mg (0.61 mg/kg). On return of the second twitch in the train-of-four (TOF) stimulation measured by acceleromyography, sugammadex 120 mg (2.1 mg/kg) ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/aas.12461
更新日期：2015-04-01 00:00:00
abstract：BACKGROUND:This study describes the design of a hypnosis closed-loop control system with propofol. The controller used a proportional-integral (PI) algorithm with the bispectral index (BIS) as the feedback signal. Our hypothesis was that a PI closed-loop control could be applied in clinical practice safely keeping the ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.2012.02738.x
更新日期：2012-09-01 00:00:00
abstract：:The psychological reactions to hospitalization, anaesthesia, and operation in a group of 107 children from 1 to 12 years old, anaesthetized with ketamine or halothane after randomization were investigated through questionnaires, which the parents answered 1 month postoperatively. The percentage of replies was 96.3%. F...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1399-6576.1977.tb01258.x
更新日期：1977-01-01 00:00:00
abstract：BACKGROUND:Post-tonsillectomy pain can be severe. We investigated the analgesic effect from combinations of paracetamol, pregabalin and dexamethasone in adults undergoing tonsillectomy. METHODS:In this randomized double-blind study, 131 patients were assigned to either group A (paracetamol+placebo), group B (paracetam...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2010.02389.x
更新日期：2011-03-01 00:00:00
abstract：:In the developed world, an increasing number of patients receive therapy with vitamin K antagonists (VKA). This group of patients poses an additional challenge in the perioperative management of emergency surgery and trauma. The present review offers a detailed description of some treatment options for reversal of VKA...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,评审
doi：10.1111/j.1399-6576.2011.02414.x
更新日期：2011-05-01 00:00:00
abstract：BACKGROUND:propofol is an excellent sedative agent for use in patients undergoing bronchoscopy. The addition of an opioid to propofol can be advantageous because of the antitussive effect of the opioid and the possible improvement in sedation quality. However, it may increase the risk of hypoxaemia. To investigate the ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1399-6576.2010.02336.x
更新日期：2011-01-01 00:00:00
abstract：BACKGROUND:The relative potency of the steroid anaesthetic agent eltanolone has been compared with respect to induction of anaesthesia in ASA I and II young (18-40 years) and elderly (> 65 years) patients. METHOD:113 temazepam premedicated patients (60 elderly) were evaluated in an open randomised study. They were all...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1399-6576.1997.tb04862.x
更新日期：1997-10-01 00:00:00
abstract：BACKGROUND:Sugammadex is designed to be a reversal agent for steroidal muscle relaxants. The current trial was aimed to compare between sugammadex and neostigmine concerning the recovery time from neuromuscular blockade. We hypothesised that sugammadex might have shorter recovery time than neostigmine. METHODS:Sixty p...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章,随机对照试验
doi：10.1111/aas.12868
更新日期：2017-04-01 00:00:00
abstract：:In the presence of oxygen NO is oxidised to NO2, which is toxic in higher concentrations. In this technical investigation, we evaluated a dosage system, modified from Stenqvist et al. 1993 (1), regarding NO and NO2 levels. NO was administered before the ventilator and NO2 scavenged using a soda little absorber in the ...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1996.tb04437.x
更新日期：1996-03-01 00:00:00
abstract：:Differences have been found, which are usually 1% or less, between the left ventricular ejection time measured from the external carotid pulse tracing, and from the rate of change of thoracic impedance (dZ/dt) waveform, using either the second heart sound or the X-point of the dZ/dt tracing as the end-point. The Heath...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/j.1399-6576.1976.tb05044.x
更新日期：1976-01-01 00:00:00
abstract：:As the low blood solubility (blood gas partition coefficient 0.69) of sevoflurane suggests a rapid emergence from anaesthesia, recovery from sevoflurane anaesthesia was compared to isoflurane in outpatient gynaecological laparoscopy. Fifty ASA I or II, consenting women participated in a randomised, controlled and sing...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1399-6576.1995.tb04081.x
更新日期：1995-04-01 00:00:00
abstract：:Fifty patients with chronic resistant cervicobrachialgia were randomly divided into two groups. Twenty-five patients (group A) were treated with cervical epidural steroid/lidocaine injections and 17 patients (group B) were treated with steroid/lidocaine injections into the posterior neck muscles. Another eight patient...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1399-6576.1993.tb03765.x
更新日期：1993-08-01 00:00:00
abstract：BACKGROUND:Mechanical ventilation (MV) can result in inflammation and subsequent lung injury. Toll-like receptor (TLR)4 and NF-κB are proposed to play a crucial role in the MV-induced inflammatory response. Resveratrol (RVT) exhibits anti-inflammatory effects in vitro and in vivo supposedly by interfering with TLR4 sig...
journal_title：Acta anaesthesiologica Scandinavica
pub_type： 杂志文章
doi：10.1111/aas.12276
更新日期：2014-04-01 00:00:00
