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Crohn's disease (CD) is a painful inflammatory bowel disease with complex multigenic inheritance. Suggested on the basis of a few isolated reports CD patients require significantly higher post operative opioid doses than patients undergoing comparable severe abdominal surgery. Crohn's disease therefore may be a suitable model for the identification of novel pain susceptibility genes. In order to confirm this observation and to elucidate the underlying molecular mechanisms, we investigated if higher opioid needs of CD patients are due to a general change in pain sensitivity. Quantitative sensory testing (QST) was applied to a subgroup of patients and polymorphisms in the mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) were investigated. Significantly increased post operative opioid requirements in CD patients were confirmed and QST assessment demonstrates that CD patients do not display increased pain sensitivity in terms of lowered thresholds to thermal and mechanical stimuli. The data also suggest that common variants in OPRM1 and specific 'high pain sensitivity'COMT haplotypes may not be the cause of high opioid needs. The results indicate that a more complex pathway is involved in the greater post operative opioid demand in CD. Therefore the presence of other, as yet unknown, genes could modulate opioid requirements in CD patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Studies with rocuronium showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy (DMD). The objective of this study was to identify the pharmacokinetic and/or pharmacodynamic origin of these alterations.Methods: Twenty-five male patients (15 with DMD, 10 controls, aged 10-18 years) were studied. Patients were anaesthetized with propofol and sufentanil. Neuromuscular transmission was monitored by acceleromyography. Patients received a single intravenous dose of 0.3 mg kg(-1) rocuronium. In five patients of the DMD group, pharmacokinetic modelling was performed from arterial rocuronium concentrations. The time course of neuromuscular block was analysed with a sigmoid E(max) model including an effect compartment.Results: The pharmacokinetics of rocuronium in DMD patients were Vc 63 +/- 14 ml kg(-1), Cl 3.0 +/- 1.0 ml min(-1) kg(-1), half-lives 2.0 +/- 0.6, 20 +/- 10 and 129 +/- 98 min, SE. For both the DMD and the control group, the time course of neuromuscular block could be described by a sigmoid E(max) model using the estimated pharmacokinetic parameters of the DMD group. In patients with DMD, the equilibration between the central and effect compartment was significantly slower (T(1/2)ke0: 9.7 +/- 0.3 vs. 1.3 +/- 0.1 min) and the EC(50) was significantly smaller (512 +/- 20 vs. 1170 +/- 64 ng ml(-1)), whereas the ED(50) was 0.16 +/- 0.02 mg kg(-1) in both groups.Conclusion: The pharmacodynamics of rocuronium were significantly altered in patients with DMD, whereas the pharmacokinetics seemed to be similar to those in healthy adults. Patients with DMD were more sensitive with respect to effect site concentration but not with respect to dose. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders., Methods: International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process., Results: A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies., Conclusions: This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part II of the guidelines highlights postoperative management and special considerations., Methods: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations., Results: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items. No consensus could be reached regarding the preemptive use of fresh frozen plasma., Conclusion: The present ERAS recommendations for CRS ± HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS ± HIPEC and to prospectively evaluate recommendations in clinical practice., Competing Interests: Declaration of competing interest GN is Secretary of the ERAS® Society (no financial conflicts)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Enhanced recovery after surgery (ERAS) pathways have been shown to considerably reduce complications, length of stay and costs after most of surgical procedures by standardised application of best evidence-based perioperative care. The aim was to elaborate dedicated recommendations for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) in a two-part series of guidelines based on expert consensus. The present part I of the guidelines highlights preoperative and intraoperative management., Methods: The core group assembled a multidisciplinary panel of 24 experts involved in peritoneal surface malignancy surgery representing the fields of general surgery (n = 12), gynaecological surgery (n = 6), and anaesthesia (n = 6). Experts systematically reviewed and summarized the available evidence on 72 identified perioperative care items, following the GRADE (grading of recommendations, assessment, development, evaluation) system. Final consensus (defined as ≥50%, or ≥70% of weak/strong recommendations combined) was reached by a standardised 2-round Delphi process, regarding the strength of recommendations., Results: Response rates were 100% for both Delphi rounds. Quality of evidence was evaluated high, moderate low and very low, for 15 (21%), 26 (36%), 29 (40%) and 2 items, respectively. Consensus was reached for 71/72(98.6%) items. Strong recommendations were defined for 37 items, No consensus could be reached regarding the preemptive use of fresh frozen plasma., Conclusion: The present ERAS recommendations for CRS±HIPEC are based on a standardised expert consensus process providing clinicians with valuable guidance. There is an urgent need to produce high quality studies for CRS±HIPEC and to prospectively evaluate recommendations in clinical practice., Competing Interests: Declaration of competing interest All other authors declare to have no disclosures.This information has been provided by all authors individually in their attached author forms with date and signatures., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fine-meshed perioperative measurements are offering enormous potential for automatically investigating clinical complications during general anesthesia. In this study, we employed multiple machine learning methods to model perioperative hypoxia and compare their respective capabilities. After exporting and visualizing 620 series of perioperative vital signs, we had ten anesthesiologists annotate the subjective presence and severity of temporary post-intubation oxygen desaturation. We then applied specific clustering and prediction methods on the acquired annotations, and evaluated their performance in comparison to the inter-rater agreement between experts. When reproducing the expert annotations, the sensitivity and specificity of multi-layer neural networks substantially outperformed clustering and simpler threshold-based methods. The achieved performance of our best automated hypoxia models thereby approximately equaled the observed agreement between different medical experts. Furthermore, we deployed our classification methods for processing unlabeled inputs to estimate the incidence of hypoxic episodes in another sizeable patient cohort, which attests to the feasibility of using the approach on a larger scale. We interpret that our machine learning models could be instrumental for computerized observational studies of the clinical determinants of post-intubation oxygen deficiency. Future research might also investigate potential benefits of more advanced preprocessing approaches such as automated feature learning.

Automated perioperative measurements such as cardiovascular monitoring data are commonly compared to established upper and lower thresholds, but could also allow for more complex interpretations. Analyzing such time series in extensive electronic medical records for research purposes may itself require customized automation, so we developed a set of algorithms for quantifying different aspects of temporal fluctuations. We implemented conventional measures of dispersion, summaries of absolute gradients between successive values, and Poincaré plots. We aggregated the severity and duration of hypotensive episodes by calculating the average area under different mean arterial pressure (MAP) thresholds. We applied these methods to 30,452 de-identified MAP series, and analyzed the similarity between alternative indices via hierarchical clustering. To explore the potential utility of these propositional metrics, we computed their statistical association with presumed complications due to cardiovascular instability. We observed that hierarchical clustering reliably segregated features that had been designed to quantify dissimilar aspects. Summaries of temporary hypotension turned out to be significantly increased among patient subgroups with subsequent signs of a complicated recovery. These associations were even stronger for measures that were specifically geared to capturing short-term MAP variability. These observations suggest the potential capability of our proposed algorithms for quantifying heterogeneous aspects of short-term MAP fluctuations. Future research might also target a wider selection of outcomes and other attributes that may be subject to intraoperative variability.

Purpose of Review: Orphan diseases certainly have a challenging impact on anesthesia practice. Low prevalence by definition leads to a profound lack of evidence-based medical knowledge, and anesthetists usually cannot rely on personal experience for handling this unique group of patients. Then again, more than 7000 known orphan diseases are estimated to affect 5% of the general population in total. Therefore, it is imperative to have a universally valid approach to anesthesia for orphan diseases., Recent Findings: Patients suffering from orphan diseases will be in need of anesthesia for disease-related diagnostic and therapeutic procedures as well as unrelated elective and emergency surgery and may present themselves on all levels of medical care. Instead of itemizing specifics for each disorder and procedure, we rather present a structured - checklist-like - approach to individually prepare for anesthesia and will highlight the most relevant anesthesiological problems and possible countermeasures. We will discuss a variety of sources of information to gain specific disease knowledge and procedural advice and will close this review by discussing the limitations of anesthesia for orphan diseases., Summary: Thanks to fast growing resources of knowledge, well tolerated and patient-oriented anesthesia is possible in spite of the inherent challenges of orphan diseases. We invite anesthetists to adapt, modify and improve our proposed structured approach to orphan anesthesia in the context of their daily practice.

Background: The benefit of the sitting position for surgery of the posterior fossa and cervical spine is still a matter of controversy. In our study we analyzed the outcome after sitting position surgery at our institution. We compared the incidence of venous air embolism (VAE) as recognized with different monitoring techniques and the severity of complications., Methods: We retrospectively analyzed 600 patients, who underwent surgery for different posterior fossa and cervical spine pathologies, respectively, in the sitting position at our institution from 1995 to 2011. Intraoperative monitoring for VAE included endtidal CO2 level, Doppler ultrasound or intraoperative transesophageal echocardiography (TEE). We defined VAE as a decrease of the endtidal CO2 levels by more than 4 mm Hg, a characteristic sound in the thoracic Doppler, or any sign of air in the TEE., Results: We found an overall incidence of VAE in 19 % of all patients, whereas the rate of severe complications associated with VAE such as a decline of partial oxygen pressure (pO2) or a drop of blood pressure was only 3.3 % in all patients. Only three out of 600 operations had to be terminated because of non-controllable VAE (0.5 %). There was no mortality resulting from VAE in our series. We also found a difference in the incidence of VAE depending on the monitoring technique. The VAE rate as monitored with TEE was 25.6 % whereas the incidence of VAE in patients monitored with Doppler ultrasound was 9.4 %. The rate of a significant VAE was comparable in both methods 4.8 % vs. 1.2 %. All patients were preoperatively screened for persisting foramen ovale (PFO); 24 patients with clinically confirmed PFO were included in this series. There was no case of paradox air embolism., Conclusions: In our series, VAE was detected in 19 % of all patients in the sitting position. However, in only 0.5 % of cases a termination of the surgical procedure became necessary. In all other cases, the cause of air embolism could be found and eliminated during surgery. TEE was found to be the monitoring technique with the highest sensitivity. In our opinion, the sitting position is a safe positioning technique if TEE monitoring is used.

Neuromuscular disorders (NMDs) are a heterogeneous group of neurological and muscular diseases. Patients present with typical features such as wasting and weakness of skeletal muscles. However, despite these common clinical signs, underlying etiologies are nearly as multifaceted as the number of the diseases. For the anesthesiologist, it is very important to know the origin of a particular disease to select an appropriate anesthetic technique. Patients with NMDs are markedly sensitive to several anesthetics. Many reported anesthesia-related complications were caused by the administration of drugs like depolarizing and non-depolarizing muscle relaxants, volatile anesthetics, or respiratory and cardiovascular depressant agents.

Background: Studies with nondepolarizing neuromuscular blocking agents showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy. The objective of this study was to investigate if these alterations depend on disease progression., Methods: The authors studied 11 children (6-9 yr) with moderate Duchenne muscular dystrophy, 11 adolescents (12-16 yr) with advanced Duchenne muscular dystrophy, and 2 age-matched control groups of 8 patients each (5-9 and 10-17 yr). Anesthesia was performed with propofol and remifentanil. Patients received a single intravenous dose of 0.2 mg/kg mivacurium. Neuromuscular transmission was monitored by acceleromyography. The time course of neuromuscular blockade was characterized by the onset time and the times to different levels of recovery., Results: Onset and duration of neuromuscular blockade were significantly prolonged in adolescent Duchenne muscular dystrophy patients (onset time, 4.0 min; recovery index, 12.3 min; median), as compared with Duchenne muscular dystrophy children (onset time, 2.3 min; recovery index, 6.8 min), and also as compared with young controls (onset time, 2.0 min; recovery index, 4.4 min) and adolescent controls (onset time, 2.5 min; recovery index, 4.8 min). Within the Duchenne muscular dystrophy patients, onset time and recovery index increased significantly with age. In the control group, age had no effect., Conclusions: The neuromuscular blocking effects of mivacurium showed a significant age dependency in Duchenne muscular dystrophy patients, which was most probably caused by the progression of the disease.

Background: The aim of this study was to investigate the effect and safety of pyridostigmine for the reversal of a neuromuscular block (NMB) in patients with Duchenne muscular dystrophy (DMD). In patients with DMD recovery from a rocuronium-induced NMB is markedly delayed., Methods: Fourteen DMD patients (aged between 11 and 19 years) scheduled for elective scoliosis repair were studied. Following tracheal intubation without muscle relaxant, all patients received a single dose of rocuronium 0.6 mg.kg(-1). NMB was monitored by acceleromyography at the adductor pollicis muscle. When the first twitch height (T1) of the train-of-four (TOF) had recovered to 25% seven patients received either pyridostigmine 0.1 mg.kg(-1) (the anticholinergic drug with a long duration of action) or saline in a blinded manner. The times to attain TOF ratio of 0.9 were recorded. For comparison the Mann-Whitney U-test was used., Results: Recovery to TOF ratio of 0.9 was significantly (P < 0.05) accelerated by pyridostigmine [84 (median), 57-141(range)] compared with controls (148, 84-243 min). The recovery time (time between T1 of 25% and TOF of 90%) was also significantly (P < 0.01) shortened by pyridostigmine (15, 8-49 vs 76, 43-144 min, respectively). Time to recovery of T(1) to 90% was not different between the groups (108, 63-134 vs 169. 61-208 min, respectively)., Conclusions: Pyridostigmine 0.1 mg.kg(-1) effectively reversed a rocuronium-induced NMB in DMD patients.

Background: In patients with Duchenne's muscular dystrophy (DMD) recovery from neuromuscular block is delayed. It has been assumed that this is because of a higher potency of muscle relaxants in this patient cohort. We determined the peak effect, and the time course of action of rocuronium 0.3 mg x kg(-1) (ED(95)) in DMD patients., Methods: Twenty-four patients (12 with DMD and 12 controls; aged 10-18 years) were studied. All patients were anesthetized with propofol and fentanyl/remifentanil. Neuromuscular transmission was monitored by acceleromyography. After induction all patients received a single dose of rocuronium 0.3 mg x kg(-1). The complete time course of action as onset, peak effect and spontaneous recovery was recorded., Results: The onset time (s) to maximum block was significantly (P < 0.01) prolonged in DMD patients (median: 315; range: 120-465) compared with controls (195, 75-270). The peak effect (% twitch depression relative to baseline) was not different between the groups (DMD: 59-100; controls: 28-100). In the DMD group, recovery was significantly (P < 0.01) delayed compared with controls at all recorded time points. The clinical duration (min) was 40.3 (22-89) in the DMD group vs 9.8 (6-17) in the control group (P < 0.01)., Conclusions: The similar peak effect in both groups does not confirm the thesis of rocuronium having a higher potency in DMD patients. The documented very long recovery after the ED(95) of rocuronium emphasizes the need for careful assessment of neuromuscular function in DMD patients.

Purpose: Priming is a known technique to accelerate onset of neuromuscular blockade (NMB). Its effect on NMB of the larynx has not been studied yet., Methods: We compared a priming technique with a bolus application of rocuronium on the onset of NMB at the laryngeal adductor and the adductor pollicis muscles (AP). In 30 female patients, after induction of anesthesia a tube with a surface electrode was placed into the trachea prior to the administration of any neuromuscular blocking agent to monitor electromyography (EMG) of the laryngeal adductor muscles. Neuromuscular monitoring consisted of EMG of the laryngeal adductor muscles and the left AP. Patients were randomized into two groups. After transcutaneous stimulation of the recurrent laryngeal nerve and ulnar nerve, a bolus of rocuronium 0.6 mg x kg(-1) (Bolus group) or a priming dose of rocuronium 0.06 mg x kg(-1) followed by rocuronium 0.54 mg x kg(-1) three minutes later (Priming group) were injected. Lag time, onset 90%, onset time and peak effect of NMB were recorded and compared; a P < 0.05 was considered significant., Results: The onset 90% and onset time measured at the laryngeal adductor muscles (onset: 44.7 +/- 7.4 vs 74.0 +/- 23.8 sec) and at the AP (onset: 105.4 +/- 29.9 vs 139.2 +/- 51.5 sec) were significantly shorter in the Priming group than in the Bolus group. Within groups, the onset times were significantly shorter at the laryngeal muscles in comparison to AP., Conclusion: Our results indicate that a priming technique with rocuronium significantly accelerates the onset of NMB at the laryngeal adductor muscles. Our results further support the use of rocuronium as an alternative to succinylcholine for rapid sequence induction.