Search

When patients are unable to undergo diagnostics or treatments for various reasons, sedation can be applied. A psychological approach and/or non-pharmacological sedation is preferred. When this is not possible, pharmacological sedation may be considered. In principle, the level of sedation applied, will be no deeper than is necessary for the patient to undergo the treatment and for the practitioner to be able to perform the treatment. Sedation is aimed at reducing agitation, anxiety, and/or lowering consciousness. However, it is not a pain treatment. Pain treatment will therefore always require adequate local anaesthesia. This article highlights the different levels of sedation, areas of indication, and sedatives used in dentistry. The application of pharmacological sedation will always have to be considered for each individual situation, within a total treatment plan that is aimed at lastingly increasing treatability.Wanneer patiënten om uiteenlopende redenen niet in staat zijn om diagnostiek of behandelingen te ondergaan, kan sedatie worden toegepast. Een psychologische aanpak en/of niet-farmacologische sedatie heeft de voorkeur. Wanneer dit niet mogelijk is, kan farmacologische sedatie worden overwogen. In principe wordt daarbij geen dieper sedatieniveau toegepast dan voor de patiënt noodzakelijk is om de behandeling te kunnen ondergaan en voor de behandelaar om deze te kunnen uitvoeren. Sedatie is gericht op het verminderen van onrust, angst en/of bewustzijnsverlaging, maar niet op pijnbehandeling. Daarvoor zal altijd adequate lokale anesthesie nodig blijven. De verschillende sedatieniveaus, indicatiegebieden en toegepaste sedativa in de tandheelkunde zullen worden belicht. De toepassing van farmacologische sedatie zal altijd per individuele situatie moeten worden afgewogen, binnen een totaal behandelplan dat gericht is op het duurzaam vergroten van de behandelbaarheid.

Background This is the first Enhanced Recovery After Surgery (ERAS®) Society guideline for primary and secondary hospitals in low–middle-income countries (LMIC’s) for elective abdominal and gynecologic care. Methods The ERAS LMIC Guidelines group was established by the ERAS® Society in collaboration with different representatives of perioperative care from LMIC’s. The group consisted of seven members from the ERAS® Society and eight members from LMIC’s. An updated systematic literature search and evaluation of evidence from previous ERAS® guidelines was performed by the leading authors of the Colorectal (2018) and Gynecologic (2019) surgery guidelines (Gustafsson et al in World J Surg 43:6592–695, Nelson et al in Int J Gynecol Cancer 29(4):651–668). Meta-analyses randomized controlled trials (RCTs), prospective and retrospective cohort studies from both HIC’s and LMIC’s were considered for each perioperative item. The members in the LMIC group then applied the current evidence and adapted the recommendations for each intervention as well as identifying possible new items relevant to LMIC’s. The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE) methodology was used to determine the quality of the published evidence. The strength of the recommendations was based on importance of the problem, quality of evidence, balance between desirable and undesirable effects, acceptability to key stakeholders, cost of implementation and specifically the feasibility of implementing in LMIC’s and determined through discussions and consensus. Results In addition to previously described ERAS® Society interventions, the following items were included, revised or discussed: the Surgical Safety Checklist (SSC), preoperative routine human immunodeficiency virus (HIV) testing in countries with a high prevalence of HIV/AIDS (CD4 and viral load for those patients that are HIV positive), delirium screening and prevention, COVID 19 screening, VTE prophylaxis, immuno-nutrition, prehabilitation, minimally invasive surgery (MIS) and a standardized postoperative monitoring guideline. Conclusions These guidelines are seen as a starting point to address the urgent need to improve perioperative care and to effect data-driven, evidence-based care in LMIC’s.

Objectives: The utilization of liver allografts could be optimized if nonacceptance is predicted. This study aimed to evaluate the prognostic ability of an updated Discard Risk Index in Eurotransplant.Materials and Methods: Potential deceased donors from January 2010 to December 2015 who had been reported to Eurotransplant were included in our analyses. Liver utilization was defined by transplant status as the primary outcome to evaluate the performance of the Eurotransplant-developed Discard Risk Index.Results: Of 11 670 potential livers, 9565 (81%) were actually transplanted. Donor sex, age, history of diabetes, drug abuse, use of vasopressors, body mass index category, serum sodium, cause of death, donor type, and levels of C-reactive protein, bilirubin, aspartate and alanine aminotransferases, international normalized ratio, and gamma-glutamyl transpeptidase were associated with discard and combined in the Eurotransplant-developed Discard Risk Index. Correlation between the two Discard Risk Indexes was high (r = 0.86), and both achieved high C statistics of 0.72 and 0.75 (P

Introduction The management of postoperative pain in anaesthesia is evolving with a deeper understanding of associating multiple modalities and analgesic medications. However, the motivations and barriers regarding the adoption of opioid-sparing analgesia are not well known. Methods We designed a modified Delphi survey to explore the perspectives and opinions of expert panellists with regard to opioid-sparing multimodal analgesia. 29 anaesthetists underwent an evolving three-round questionnaire to determine the level of agreement on certain aspects of multimodal analgesia, with the last round deciding if each statement was a priority. Results The results were aggregated and a consensus, defined as achievement of over 75% on the Likert scale, was reached for five out of eight statements. The panellists agreed there was a strong body of evidence supporting opioid-sparing multimodal analgesia. However, there existed multiple barriers to widespread adoption, foremost the lack of training and education, as well as the reluctance to change existing practices. Practical issues such as cost effectiveness, increased workload, or the lack of supply of anaesthetic agents were not perceived to be as critical in preventing adoption. Conclusion Thus, a focus on developing specific guidelines for multimodal analgesia and addressing gaps in education may improve the adoption of opioid-sparing analgesia.

Background Cardiac troponin T (cTnT) is a cornerstone biomarker for diagnosing myocardial infarction (MI). However, since the introduction of the high-sensitivity assays, cardiac troponins are also measured in pathologies with cardiac risk factors, such as end-stage renal disease (ESRD), making it more difficult for clinicians to diagnose MI. Previous studies of our group identified specific larger cTnT proteoforms for the acute phase of MI, while a study in serum of ESRD patients showed solely small cTnT fragments. However, others allocated the small cTnT fragments in serum of ESRD patients to a pre-analytic effect due to abundant thrombin generation in serum, as thrombin is known to cause fragmentation of cTnT. Purpose This study investigated the effect of multiple anticoagulation methods on cTnT proteoforms in vitro and in the blood of ESRD patients. Methods First, cTnT negative serum and lithium-heparinized (LH), ethylenediaminetetraacetic-acid (EDTA), and hirudin plasma tubes were spiked with human cTnT standard, incubated at 37°C till 48 hours, and analysed with Western Blotting using anti-cTnT Roche antibodies. Second, similar blood tubes were collected from ESRD patients (n=10) conform the Declaration of Helsinki, patient samples and spiked cTnT standards were separated using gel filtration chromatography (GFC) and cTnT was subsequently analysed using the Cobas 6000 analyser. Results After 48 hours of in vitro incubation of cTnT in hirudin plasma, no cTnT degradation was observed, while LH only showed minor degradation of 10% from intact 40 kDa cTnT to 29 kDa fragments (figure 1). Also, for both EDTA and serum, a time-dependent degradation from 40 kDa cTnT to 29 kDa fragments to 15–18 kDa fragments was observed. Moreover, in ESRD patients, GFC elution profiles of all blood tubes revealed that 85–98% of cTnT corresponded to small 15–18 kDa fragments (41–42 mL), while 2–15% were 29/40 kDa cTnT forms (27–28 mL). For comparison, standards of ternary T-I-C complex and intact cTnT eluted at 21 mL and 28 mL, respectively. Conclusions The extent of cTnT degradation in vitro is dependent on the anticoagulation method of the blood tubes, with absence of degradation exclusively in hirudin plasma. Since in ESRD patients for all blood tubes mainly small 15–18 kDa cTnT fragments were found, including hirudin plasma, cTnT degradation appears to occur in vivo. This observation supports the hypothesis that larger cTnT proteoforms might indeed be specific for the acute phase of MI, thereby supporting the opportunity for developing a more specific cTnT method. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMw Veni grant

Five years ago, we described the skin-to-skin caesarean section, a procedure in which parental participation, slow delivery and direct skin-to-skin contact are important aspects. By multiple research, the skin-to-skin CS has been shown to have positive outcomes for the child and parents, as long as there is attention for neonatal thermal regulation. These outcomes should lead to cost reduction, versus the extra personnel costs for the nurse. However, a proper cost-effectiveness analysis has not yet been described. There are still many local differences in availability and performance of the skin-to-skin CS in the Netherlands, often caused by logistical challenges. In the meanwhile the protocol has been further optimized. In our opinion, the skin-to-skin caesarean section is better care for parents and their child, and should be available anywhere anytime, as long as the fetal and maternal condition permits this.

Introduction: The use of total intravenous anaesthesia (TIVA) has been well established as an anaesthetic technique over the last few decades. Significant variation in practice exists however, and volatile agents are still commonly used. This study aims to determine the motivations and barriers for using TIVA over the use of volatile agents by analysing the opinion of several international anaesthetists with specific expertise or interests. Methods and participants: The Delphi method was used to gain the opinions of expert panellists with a range of anaesthetic subspecialty expertise. Twenty-nine panellists were invited to complete three survey rounds containing statements regarding the use of TIVA. Anonymised data were captured through the software REDCap and analysed for consensus and prioritisation across statements. Starting with 12 statements, strong consensus was defined as ≥75% agreement. Stability was assessed between rounds. Results: Strong consensus was achieved for four statements regarding considerations for the use of TIVA. These statements addressed whether TIVA is useful in paediatric anaesthesia, the importance of TIVA in reducing the incidence of postoperative nausea and vomiting, its positive impact on the environment and effect on patient physiology, such as airway and haemodynamic control. Conclusions: Using the Delphi method, this international consensus showed that cost, lack of familiarity or training and the risk of delayed emergence are not considered obstacles to TIVA use. It appears, instead, that the primary motivations for its adoption are the impact of TIVA on patient experience, especially in paediatrics, and the benefit to the overall procedure outcome. The effect of TIVA on postoperative nausea and vomiting and patient physiology, as well as improving its availability in paediatrics were considered as priorities. We also identified areas where the debate remains open, generating new research questions on geographical variation and the potential impact of local availability of monitoring equipment.

Background and objectives: Sugammadex is an alternative pharmacological drug capable of reversing neuromuscular blockades without the limitations that are presented by anticholinesterase drugs. Coagulation disorders that are related to treatment with sugammadex were reported. The exact mechanism of the effects on coagulation are not fully understood. The objective of this research is to evaluate the effects of rocuronium, sugammadex and the rocuronium-sugammadex complex on coagulation in an experimental model in rats. Methods: This is an experimental randomized animal study. Wistar rats were randomly assigned into the following groups: the Control Group; the Ssal Group - 0.5 mL of intravenous saline; the Sugammadex Group - intravenous sugammadex (100 mg kg−1); and the Rocuronium-Sugammadex Group - intravenous solution with rocuronium (3.75 mg kg−1) and sugammadex (100 mg kg−1). Anesthesia was performed by using isoflurane with controlled ventilation. Coagulation factors were measured 10 minutes after the end of the preoperative preparation and 30 minutes after the administration of the drugs in accordance with the chosen groups. Results: Platelet counts, prothrombin times, and activated partial thromboplastin times were similar between the groups and between the moments within each group. There were reductions in the plasma fibrinogen levels between sample times 1 and 2 in the Rocuronium-Sugammadex group (p = 0.035). Conclusions: The rocuronium-sugammadex complex promoted reductions in plasma fibrinogen counts, although the levels were still within normal limits. Resumo Introdução e objetivos: O sugamadex é uma substância farmacológica alternativa capaz de reverter o bloqueio neuromuscular sem as limitações apresentadas pelos anticolinesterásicos. Entretanto, há relatos de transtornos de coagulação relacionados ao tratamento com sugamadex sem que mecanismos exatos de seus efeitos sobre a coagulação sejam totalmente compreendidos. O objetivo da presente pesquisa foi avaliar os efeitos do rocurônio, sugamadex e do complexo rocurônio-sugamadex sobre a coagulação em um modelo experimental com ratos. Métodos: Este é um estudo randomizado experimental animal. Ratos Wistar foram aleatoriamente designados aos seguintes grupos: grupo controle; Grupo Ssal - 0,5 mL de solução salina intravenosa; Grupo sugamadex - sugamadex intravenoso (100 mg.kg-1); e Grupo rocurônio-sugamadex - solução intravenosa com rocurônio (3,75 mg.kg-1) e sugamadex (100 mg.kg-1). A anestesia foi realizada utilizando-se isoflurano com ventilação controlada. Os fatores de coagulação foram medidos 10 minutos após o final do preparo pré-operatório e 30 minutos após a administração de drogas de acordo com os grupos escolhidos. Resultados: Contagem de plaquetas, tempo de protrombina e tempo de tromboplastina parcial ativada foram semelhantes entre os grupos e entre os momentos dentro de cada grupo. Houve redução nos níveis de fibrinogênio plasmático entre os tempos 1 e 2 no grupo rocurônio-sugamadex (p = 0,035). Conclusões: O complexo rocurônio-sugamadex promoveu reduções na contagem de fibrinogênio plasmático, apesar de os níveis continuarem dentro dos limites normais.

Resumo Introducao e objetivos O sugamadex e uma substância farmacologica alternativa capaz de reverter o bloqueio neuromuscular sem as limitacoes apresentadas pelos anticolinesterasicos. Entretanto, ha relatos de transtornos de coagulacao relacionados ao tratamento com sugamadex sem que mecanismos exatos de seus efeitos sobre a coagulacao sejam totalmente compreendidos. O objetivo da presente pesquisa foi avaliar os efeitos do rocuronio, sugamadex e do complexo rocuronio‐sugamadex sobre a coagulacao em um modelo experimental com ratos. Metodos Este e um estudo randomizado experimental animal. Ratos Wistar foram aleatoriamente designados aos seguintes grupos: grupo controle; Grupo Ssal – 0,5 mL de solucao salina intravenosa; Grupo sugamadex – sugamadex intravenoso (100 mg.kg‐1); e Grupo rocuronio‐sugamadex – solucao intravenosa com rocuronio (3,75 mg.kg‐1) e sugamadex (100 mg.kg‐1). A anestesia foi realizada utilizando‐se isoflurano com ventilacao controlada. Os fatores de coagulacao foram medidos 10 minutos apos o final do preparo pre‐operatorio e 30 minutos apos a administracao de drogas de acordo com os grupos escolhidos. Resultados Contagem de plaquetas, tempo de protrombina e tempo de tromboplastina parcial ativada foram semelhantes entre os grupos e entre os momentos dentro de cada grupo. Houve reducao nos niveis de fibrinogenio plasmatico entre os tempos 1 e 2 no grupo rocuronio‐sugamadex (p = 0,035). Conclusoes O complexo rocuronio‐sugamadex promoveu reducoes na contagem de fibrinogenio plasmatico, apesar de os niveis continuarem dentro dos limites normais.

Background There is increasing evidence for the use of lower insufflation pressures during laparoscopic surgery. Deep neuromuscular blockade allows for a safe reduction in intra-abdominal pressure without compromising the quality of the surgical field. While there is considerable evidence to support superior surgical conditions during deep neuromuscular blockade, there is only a limited amount of studies investigating patient outcomes. Moreover, results are not always consistent between studies and vary between different types of laparoscopic surgery. This study will investigate the effect of low-pressure pneumoperitoneum facilitated by deep NMB on quality of recovery after laparoscopic colorectal surgery. Methods The RECOVER study is a multicenter double-blinded randomized controlled trial consisting of 204 patients who will be randomized in a 1:1 fashion to group A, low-pressure pneumoperitoneum (8 mmHg) facilitated by deep neuromuscular blockade (post tetanic count of 1–2), or group B, normal-pressure pneumoperitoneum (12 mmHg) with moderate neuromuscular blockade (train-of-four response of 1–2). The primary outcome is quality of recovery on postoperative day 1, quantified by the Quality of Recovery-40 questionnaire. Discussion Few studies have investigated the effect of lower insufflation pressures facilitated by deep neuromuscular blockade on patient outcomes after laparoscopic colorectal procedures. This study will identify whether low pressure pneumoperitoneum and deep neuromuscular blockade will enhance recovery after colorectal laparoscopic surgery and, moreover, if this could be a valuable addition to the Enhanced Recovery After Surgery guidelines. Trial registration EudraCT 2018-001485-42. Registered on April 9, 2018. Clinicaltrials.govNCT03608436. Registered on July 30, 2018.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n = 24 000) to the finally relevant clinical studies ( n = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg -1 or rocuronium 0.9 to 1.2 mg kg -1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C). Sin financiación 4.183 JCR (2021) Q2, 12/34 Anesthesiology 0.979 SJR (2021) Q1, 19/128 Anesthesiology and Pain Medicine No data IDR 2021 UEV

Contains fulltext : 286720.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.

Background Magnesium sulphate is an important adjuvant drug in multimodal anaesthesia. In combination with rocuronium it can enhance neuromuscular blockade (NMB). Limited data exist concerning the effect of magnesium sulphate on the duration of deep or intense NMB and the period of no response. Objective(s) To determine the role of magnesium sulphate on the duration of rocuronium-induced deep and intense NMB, and the period of no response to nerve stimulation. Design A randomised controlled trial. Setting A public tertiary care hospital, Rio de Janeiro, Brazil, from February 2017 to March 2018. Patients All patients between 18 and 65 years of age scheduled to undergo elective otorhinolaryngological surgery, with a BMI between 18.5 and 24.9 kg m and an American Society of Anesthesiologists physical status classification of I or II. Intervention(s) Before induction of anaesthesia 60 patients were pretreated with an intravenous infusion of either 100 ml 0.9% saline (saline group), or 60 mg kg magnesium sulphate (magnesium group). After loss of consciousness, a bolus of rocuronium (0.6 mg kg) was administered. Neuromuscular function was measured by TOF-Watch SX monitor. Main outcome measures The primary and secondary outcomes were the duration of the period of no response to nerve stimulation and intense and deep NMB, respectively. An additional outcome was the NMB onset time. Results Median [IQR] durations of deep NMB were 20.3 [12.0 to 35.4] and 18.3 [11.2 to 26.3] min in the magnesium and saline groups, respectively (P = 0.18). Median durations of intense NMB were 21.7 [0.0 to 32.2] min and 0.0 [0.0 to 6.2] min (P = 0.001) in the magnesium and saline groups, respectively. Median durations of the period of no response were 40.8 [51.4 to 36.0] min and 28.0 [21.9 to 31.6] min (P = 0.0001) in the magnesium and saline groups, respectively. Conclusion Magnesium sulphate increased both the duration of intense NMB and the period of no response. The duration of deep NMB was similar in the magnesium sulphate group and saline group. Trial registration ClinicalTrials.gov identifier: NCT02989272.

Background This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. Methods We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. Results Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. Conclusions Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.

Background Lidocaine and magnesium sulfate have become increasingly utilized in general anesthesia. The present study evaluated the effects of these drugs, isolated or combined, on hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB). Methods At a university hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimuli were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation as follows: 3 mg.kg− 1 and 3 mg.kg− 1.h− 1 (lidocaine - L group), 40 mg.kg− 1 and 20 mg.kg− 1.h− 1 (magnesium - M group), equal doses of both drugs (magnesium plus lidocaine - ML group), and an equivalent volume of isotonic solution (control - C group). Hemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the train of four (TOF) ratio (TOFR > 0.9). Results The magnesium sulfate significantly prolonged all NMB recovery features, without changing the speed of onset of cisatracurium. The addition of lidocaine to Magnesium Sulfate did not influence the cisatracurium neuromuscular blockade. A similar finding was observed when this drug was used alone, with a significantly smaller fluctuation of mean arterial pressure (MAP) and heart rate (HR) measures during anesthesia induction and maintenance. Interestingly, the percentage of patients who achieved a TOFR of 90% without reaching T1–95% was higher in the M and ML groups. Than in the C and L groups. There were no adverse events reported in this study. Conclusion Intravenous lidocaine plays a significant role in the hemodynamic stability of patients under general anesthesia without exerting any additional impact on the NMB, even combined with magnesium sulfate. Aside from prolonging all NMB recovery characteristics without altering the onset speed, magnesium sulfate enhances the TOF recovery rate without T1 recovery. Our findings may aid clinical decisions involving the use of these drugs by encouraging their association in multimodal anesthesia or other therapeutic purposes. Trial registration NCT02483611 (registration date: 06-29-2015).

Candida parapsilosis is among the most frequent causes of candidiasis. Clinical isolates of this species show large variations in colony morphotype, ranging from round and smooth to a variety of non-smooth irregular colony shapes. A non-smooth appearance is related to increased formation of pseudohyphae, higher capacity to form biofilms on abiotic surfaces, and invading agar. Here, we present a comprehensive study of the cell wall proteome of C. parapsilosis reference strain CDC317 and seven clinical isolates under planktonic and sessile conditions. This analysis resulted in the identification of 40 wall proteins, most of them homologs of known Candida albicans cell wall proteins, such as Gas, Crh, Bgl2, Cht2, Ecm33, Sap, Sod, Plb, Pir, Pga30, Pga59, and adhesin family members. Comparative analysis of exponentially growing and stationary phase planktonic cultures of CDC317 at 30 °C and 37 °C revealed only minor variations. However, comparison of smooth isolates to non-smooth isolates with high biofilm formation capacity showed an increase in abundance and diversity of putative wall adhesins from Als, Iff/Hyr, and Hwp families in the latter. This difference depended more strongly on strain phenotype than on the growth conditions, as it was observed in planktonic as well as biofilm cells. Thus, in the set of isolates analyzed, the high biofilm formation capacity of non-smooth C. parapsilosis isolates with elongated cellular phenotypes correlates with the increased surface expression of putative wall adhesins in accordance with their proposed cellular function. This work was funded by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2013-47570-P and SAF2017-86188-P) and the regional government of Castilla-La Mancha (JCCM) (SBPLY/19/180501/000114), all co-financed by the EU (FEDER), to P.W.J.d.G. and E.E., the Consejería de Educación, Universidades e Investigación (GIC15/78 IT-990-16) of Gobierno Vasco-Eusko Jaurlaritza to E.E., and the FP7-PEOPLE-2013-ITN—Marie-Curie Action: “Initial Training Networks”: Molecular Mechanisms of Human Fungal Pathogen Host Interaction, ImResFun, MC-ITN-606786, to O.B.

Background Predicting survival of recipients after liver transplantation is regarded as one of the most important challenges in contemporary medicine. Hence, improving on current prediction models is of great interest.Nowadays, there is a strong discussion in the medical field about machine learning (ML) and whether it has greater potential than traditional regression models when dealing with complex data. Criticism to ML is related to unsuitable performance measures and lack of interpretability which is important for clinicians. Methods In this paper, ML techniques such as random forests and neural networks are applied to large data of 62294 patients from the United States with 97 predictors selected on clinical/statistical grounds, over more than 600, to predict survival from transplantation. Of particular interest is also the identification of potential risk factors. A comparison is performed between 3 different Cox models (with all variables, backward selection and LASSO) and 3 machine learning techniques: a random survival forest and 2 partial logistic artificial neural networks (PLANNs). For PLANNs, novel extensions to their original specification are tested. Emphasis is given on the advantages and pitfalls of each method and on the interpretability of the ML techniques. Results Well-established predictive measures are employed from the survival field (C-index, Brier score and Integrated Brier Score) and the strongest prognostic factors are identified for each model. Clinical endpoint is overall graft-survival defined as the time between transplantation and the date of graft-failure or death. The random survival forest shows slightly better predictive performance than Cox models based on the C-index. Neural networks show better performance than both Cox models and random survival forest based on the Integrated Brier Score at 10 years. Conclusion In this work, it is shown that machine learning techniques can be a useful tool for both prediction and interpretation in the survival context. From the ML techniques examined here, PLANN with 1 hidden layer predicts survival probabilities the most accurately, being as calibrated as the Cox model with all variables. Trial registration Retrospective data were provided by the Scientific Registry of Transplant Recipients under Data Use Agreement number 9477 for analysis of risk factors after liver transplantation.

BackgroundLidocaine and magnesium sulfate have become increasingly utilisedin general anaesthesia. The present study evaluated the effects of these drugs, isolated or combined on the hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB).MethodsAt a University hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimulus, were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation respectively: 3 mg.kg-1 and 3 mg.kg-1.h-1 (Lidocaine -L group), 40 mg.kg-1 and 20 mg.kg-1.h-1 (Magnesium - M group), equal doses of both drugs (Magnesium plus lidocaine - MLgroup) and, a equivalent volume of isotonic solution (Control - C group). Haemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the Traino of Four ratio (TOF=0.9).ResultsThe Lidocaine group presented a highly significant small hemodynamic fluctuation during the anesthesia induction and maintenance period (p

The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of MYC/BCL2/BCL6 as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in MYD88/CD79B. We investigated whether MYD88/CD79B mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, MYD88/CD79B mutations were identified by allele-specific polymerase chain reaction or next-generationsequencing, MYC/BCL2/BCL6 rearrangements were analyzed by fluorescence in situ hybridization, and EBV was studied by EBV-encoded RNA in situ hybridization. Associations of molecular features with clinicopathologic characteristics, outcome, and prognosis according to the International Prognostic Index (IPI) were investigated. MYD88 and CD79B mutations were identified in 29.6% and 12.3%, MYC, BCL2, and BCL6 rearrangements in 10.6%, 13.6%, and 20.3%, and EBV in 11.7% of DLBCL, respectively. Prominent mutual exclusivity between EBV positivity, rearrangements, and MYD88/CD79B mutations established the value of molecular markers for the recognition of biologically distinct DLBCL subtypes. MYD88-mutated DLBCL had a significantly inferior 5-year overall survival than wild-type MYD88 DLBCL (log-rank; P=0.019). DLBCL without any of the studied aberrations had superior overall survival compared to cases carrying .1 aberrancy (log-rank; P=0.010). MYD88 mutations retained their adverse prognostic impact upon adjustment for other genetic and clinical variables by multivariable analysis and improved the prognostic performance of the IPI. This study demonstrates the clinical utility of defining MYD88-mutated DLBCL as a distinct molecular subtype with adverse prognosis. Our data call for sequence analysis of MYD88 in routine diagnostics of DLBCL to optimize classification and prognostication, and to guide the development of improved treatment strategies.

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies. © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

In the past 40 years, the knowledge and management of acute postoperative pain have been improved significantly. In ERAS pathways adequate postoperative pain relief is an important component in order to improve the quality of perioperative care and to reduce postoperative morbidity and length of hospital stay. Adequate management of postoperative pain leads to attenuating surgical stress and maintaining postoperative physiological functions. Furthermore, opioid-sparing analgesic strategies—including regional analgesia techniques as part of multimodel, evidence-based, and procedure-specific multimodal pain management—should be implemented as a standard of care.

In 1839, Carl Friedrich Gauss published his famous article on the modeling of the terrestrial magnetic field. Benefiting from the previous scientific knowledge about the gravitational theory, Gauss assumed that the Earth was surrounded by a magnetic potential which obeys the Laplace equation. And Gauss solved this equation in spherical coordinates. Gauss assumed a trial solution of the form \( \frac{1}{r^n}U\left(\theta, \phi \right) \) where he generated a solution as a series of associated Legendre polynomials. In order to compute the coefficients in the spherical harmonic expression for the potential, Gauss selected 189 equations involving 24 unknown coefficients that he then found by the method of least squares. Indeed, Gauss assumed that the magnetic potential V goes to zero as the radius r goes to infinity. Unfortunately, the magnetic potential is unknown at the Earth surface, and only the three components of the earth magnetic field are accessible. Therefore, Gauss needed data from terrestrial magnetic observatories. We shall give a brief historical survey of magnetic observations, followed by comments on the gravitational theories, mainly from the works of Lagrange, Laplace and Legendre on potential theory. Finally we shall examine the validity of Gauss’ approach and his results.

The concept of balanced general anesthesia, which consists of unconsciousness, analgesia, and relaxation, the components of the “triad of anesthesia,” was first described by Cecil Gray in 1946 and was a big step forward in anesthesia and perioperative care. General anesthesia was performed using high doses of hypnotics or inhalation gases, which resulted in hemodynamic suppression and dangerous deep levels of anesthesia with concomitant morbidity and mortality. However, even with these high doses of anesthetic drugs, suppression of noxious or nociceptive stimuli was difficult. Therefore, the introduction of balanced anesthesia using different drugs to reach each desired goal was the first step in the development of multimodal analgesic and general anesthesia techniques that are applied in enhanced recovery after surgery (ERAS) pathways.

Resumo O transplante cardiaco e um procedimento frequente no tratamento da disfuncao cardiaca em estagio final. Portanto, essa populacao de pacientes tambem sera exposta com mais frequencia a outros procedimentos cirurgicos mais comuns apos o transplante. Em sua avaliacao, o anestesiologista deve ter em mente algumas questoes especificas relacionadas a historia de transplante cardiaco desses pacientes, tais como a reversao do bloqueio neuromuscular. Varios estudos relataram que os inibidores da colinesterase, como a neostigmina, podem produzir uma bradicardia dose‐dependente que ameaca a vida em receptores de transplante cardiaco, enquanto um estudo relatou o uso seguro de neostigmina. A reversao do bloqueio neuromuscular com sugamadex e outra possibilidade, mas os dados na literatura sao escassos. Descrevemos cinco casos nos quais a reversao bem‐sucedida do bloqueio neuromuscular foi realizada com sugamadex em receptores pediatricos de transplante cardiaco sem deixar sequelas e discutimos a reversao do bloqueio neuromuscular nessa populacao de pacientes.

Purpose of Review The purpose of this chapter is to provide a brief review of the literature on the recent developments in neuromuscular blockade and reversal agents. Recent Findings Novel drug development resulted in pharmacological advancements in neuromuscular management and led to a new series of compounds, chlorofumarates, such as gantacurium, CW002, and CW011. These drugs have a fast onset and rapid to intermediate duration of action and can be rapidly reversed by l-cysteine adduction without side effects that are commonly observed with anticholinesterase reversal drugs. Another new advancement is the development of a new class of reversal drugs, the calabadions. These drugs are able to reverse both steroidal and non-steroidal non-depolarizing neuromuscular blocking drugs rapidly. Summary Recent advancements in neuromuscular blocking agents and reversal drugs have shown promise in improving safety of management of neuromuscular blockade. Preclinical and clinical studies are discussed. However, to date these new drugs are not yet available for clinical use.

Background After reversal of a rocuronium-induced neuromuscular blockade with sugammadex, the recovery of train-of-four ratio to 0.9 is faster than recovery of first twitch of the train-of-four to 90% in adults. These findings after reversal of neuromuscular blockade with sugammadex have not yet been investigated in pediatric patients. Aims The aim of this retrospective analysis was to investigate the relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio after reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric patients. Methods Patients ASA I-III, aged 2-11 years, and who underwent abdominal and/or perineal surgery were included in the analysis. After extracting the necessary data from the hospital database, the patients were divided into 2 groups based on the dose of sugammadex received: group A: 2 mg.kg-1 for reversal of moderate neuromuscular blockade and group B: 4 mg.kg-1 for reversal of deep neuromuscular blockade. The relationship of the recovery of first twitch of the train-of-four height and train-of-four ratio in these 2 groups were analyzed. Results Data from 43 pediatric patients aged 2-11 years could be analyzed. The first twitch of the train-of-four height at the recovery of train-of-four ratio to 0.9 in group B was statistically significantly lower compared with group A. This height 3 and 5 minutes after the train-of-four ratio reached 0.9 showed no statistically significant differences between groups. Conclusion The results were in line with the results found in adults and showed that the train-of-four ratio recovered to 0.9 was faster than first twitch of the train-of-four height recovered to the same level.