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Background: Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk., Objectives: This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs., Design: The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans., Data Sources: Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.)., Eligibility Criteria: All studies that referred to the NMBA challenge were included without publication date limitations., Results: NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure., Conclusion: Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery., Aims: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery., Methods: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies., Results: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced., Conclusion: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Acute hypersensitivity reactions (AHRs) occurring in present-day anaesthesia can have severe, sometimes fatal, consequences and their incidence is increasing. The most frequent allergens responsible for AHR during anaesthesia are neuromuscular blocking agents (NMBAs) (70% of the cases) followed by antibiotics (18%), patent blue dye and methylene blue dye (5%), and latex (5%). Following an AHR, strategies for subsequent anaesthetic procedures (especially the choice of an NMBA) may be difficult to formulate due to inconclusive diagnostic analysis in up to 30% of AHRs. Current diagnosis of AHR relies on the detection of mast cell degranulation products and drug-specific type E immunoglobulins (IgE) in order to document an IgE-mediated anaphylaxis (IgE endotype). Nonetheless, other IgE-independent pathways can be involved in AHR, but their detection is not currently available in standard situations. The different mechanisms (endotypes) involved in peri-operative AHR may contribute to the inconclusive diagnostic work-up and this generates uncertainty concerning the culpable drug and strategy for subsequent anaesthetic procedures. This review provides details on the IgE endotype; an update on non-IgE related endotypes and the novel diagnostic tools that could characterise them. This detailed update is intended to provide explicit clinical reasoning tools to the anaesthesiologist faced with an incomplete AHR diagnostic work-up and to facilitate the decision-making process regarding anaesthetic procedures following an AHR to NMBAs., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

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)., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Acute hypersensitivity reactions to drugs occur infrequently during anaesthesia and the peri-operative period. When clinical presentation includes the classical triad, erythema, cardiovascular abnormalities and increased airway pressure, the diagnosis is evident and the challenge is to prescribe a therapeutic regimen according to guidelines and to manage refractory signs in a timely manner. In many situations, however, the initial clinical signs are isolated, such as increased airway pressure or arterial hypotension. Rendering a differential diagnosis with causes and mechanisms other than acute hypersensitivity reactions (AHRs) is difficult, delaying treatment with possible worsening of the clinical signs, and even death, in previously healthy individuals. In these difficult diagnostic situations, clinical reasoning is mandatory, and guidelines do not explicitly explain the elements on which clinical reasoning can be built. In this article, based on clinical evidence whenever available, experimental data and pathophysiology, we propose algorithms that have been evaluated by experts. The goal of these algorithms is to provide explicit elements on which the differential diagnosis of AHRs can be made, accelerating the implementation of adequate therapy., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

: Procedural sedation and analgesia (PSA) has become a widespread practice given the increasing demand to relieve anxiety, discomfort and pain during invasive diagnostic and therapeutic procedures. The role of, and credentialing required by, anaesthesiologists and practitioners performing PSA has been debated for years in different guidelines. For this reason, the European Society of Anaesthesiology (ESA) and the European Board of Anaesthesiology have created a taskforce of experts that has been assigned to create an evidence-based guideline and, whenever the evidence was weak, a consensus amongst experts on: the evaluation of adult patients undergoing PSA, the role and competences required for the clinicians to safely perform PSA, the commonly used drugs for PSA, the adverse events that PSA can lead to, the minimum monitoring requirements and post-procedure discharge criteria. A search of the literature from 2003 to 2016 was performed by a professional librarian and the retrieved articles were analysed to allow a critical appraisal according to the Grading of Recommendations Assessment, Development and Evaluation method. The Taskforce selected 2248 articles. Where there was insufficiently clear and concordant evidence on a topic, the Rand Appropriateness Method with three rounds of Delphi voting was used to obtain the highest level of consensus among the taskforce experts.These guidelines contain recommendations on PSA in the adult population. It does not address sedation performed in the ICU or in children and it does not aim to provide a legal statement on how PSA should be performed and by whom. The National Societies of Anaesthesiology and Ministries of Health should use this evidence-based document to help decision-making on how PSA should be performed in their countries. The final draft of the document was available to ESA members via the website for 4 weeks with the facility for them to upload their comments. Comments and suggestions of individual members and national Societies were considered and the guidelines were amended accordingly. The ESA guidelines Committee and ESA board finally approved and ratified it before publication.

These European Board of Anaesthesiology (EBA) recommendations for safe medication practice replace the first edition of the EBA recommendations published in 2011. They were updated because evidence from critical incident reporting systems continues to show that medication errors remain a major safety issue in anaesthesia, intensive care, emergency medicine and pain medicine, and there is an ongoing need for relevant up-to-date clinical guidance for practising anaesthesiologists. The recommendations are based on evidence wherever possible, with a focus on patient safety, and are primarily aimed at anaesthesiologists practising in Europe, although many will be applicable elsewhere. They emphasise the importance of correct labelling practice and the value of incident reporting so that lessons can be learned, risks reduced and a safety culture developed.

Background: In contrast to other types of shock, anaphylactic shock decreases cerebral blood flow more than would be expected from severe arterial hypotension, thus potentially affecting survival through brain ischaemia/hypoxia. We hypothesised that epinephrine (EPI) used as a first-line treatment of anaphylactic shock and arginine vasopressin (AVP) proposed in case of EPI refractoriness may have different effects on brain oxygenation., Objectives: To compare the effect of EPI and AVP on brain oxygenation under similar macro-haemodynamic target values in an anaphylactic shock model., Design: Prospective laboratory study., Setting: University laboratory., Animals: Male brown Norway rats (n = 27)., Interventions: Twenty-seven rats were sensitised with ovalbumin (OVA). Twenty rats had anaphylactic shock induced with OVA and were resuscitated with either 0.9% saline (OVA group), EPI (EPI group) or AVP (AVP group). Sensitised control rats received only 0.9% saline and no OVA (CON group)., Main Outcome Measures: Mean arterial pressure (MAP), carotid artery blood flow (CaBF), cerebral cortical blood flow (CBF) and hippocampal oxygen partial pressure (PtiO2) were recorded., Results: All rats in the OVA group died within 15 min. EPI and AVP restored comparable levels of MAP, carotid artery blood flow and CBF, and extended survival time. EPI was associated with biologically relevant and significantly (P < 0.05) higher PtiO2 values (nadir values at 20 min: 25.0 ± 2.2 mmHg) compared with the AVP group (14.9 ± 2.0 mmHg). The slopes of the correlations of MAP vs. PtiO2 and CBF were significantly steeper with AVP (more pressure dependence) compared with EPI. By the end of the experiment, hippocampal PtiO2 values between the EPI (24.1 ± 2.1 mmHg) and the AVP (20.8 ± 2.0 mmHg) groups were similar., Conclusion: At early, but not at late time points, resuscitation of anaphylactic shock with EPI or AVP to similar MAP and CBF endpoints resulted in hippocampal PtiO2 being significantly higher after EPI. In addition, the PtiO2 after EPI always remained above the threshold for brain hypoxia, whereas PtiO2 after AVP was below the hypoxic threshold most of the time. Because of this early brain hypoxia, AVP may not be the drug of first choice for resuscitation of anaphylactic shock.

Background: Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients., Objectives: We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms., Design: A single-centre, prospective observational study., Setting: Amiens University Hospital, France., Patients: All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed., Main Outcome Measures: Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1., Results: All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI)., Conclusion: These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

Background: Patients assess their own pain with a numerical rating scale (NRS). In the postanaesthesia care unit (PACU), NRS helps to determine and monitor analgesic administration, but is useless in patients who are unable to communicate. In non-PACU patients, acute pain increases pupillary diameter and pupillary light reflex amplitude (PLRA), the difference between pupillary diameter before and after light stimulation., Objectives: To study the association between postoperative pain (NRS) and pupillary diameter or PLRA in PACU patients after routine anaesthetic care., Design: Cross-sectional cohort study., Setting: Bichat-Claude Bernard Hospital, Paris., Patients: One hundred and forty-five patients undergoing planned surgery under general anaesthesia., Interventions: NRS, pupillary diameter and PLRA were measured on arrival in the PACU. When NRS was more than 4, intravenous morphine titration was started and a second measurement performed., Main Outcome Measures: Association between NRS and pupillary diameter or PLRA was assessed with Pearson correlation coefficient (r) as was association between changes in these variables after morphine titration., Results: Mean NRS was 4.7, and was more than 4 in 79 patients (55%). No statistically significant association was observed between NRS and pupillary diameter (r = 0.10, P = 0.54) or PLRA (r = 0.03, P = 0.72). Twenty-seven patients (19%) received morphine titration with significant decreases in NRS, pupillary diameter and PLRA afterwards. No association was observed between NRS changes and pupillary diameter or PLRA changes., Conclusion: Acute postoperative pain is not associated with pupillary diameter or PLRA. Further research is required to develop tools to assess pain in the PACU.

Background: Iron deficiency is the commonest cause of anaemia. It is apparent preoperatively in cardiac surgery patients and may influence transfusion requirements. In addition, iron deficiency per se is associated with fatigue., Objective: To determine the prevalence of preoperative iron deficiency and its association with perioperative anaemia, blood transfusions and fatigue in cardiac surgery patients., Setting: Academic hospital in Paris, France., Patients: One hundred consecutive patients without known iron disorder and scheduled for cardiac surgery were prospectively included in this observational study., Intervention: No intervention was performed., Measurements: A biological iron profile (transferrin saturation, ferritin, soluble transferrin receptor and C-reactive protein) was assessed on the day of surgery. Diagnosis of iron deficiency was defined using a previously published algorithm. Patient fatigue was assessed before surgery and 1 week afterwards (day 7) using the Multidimensional Fatigue Inventory (MFI-20) score that quotes five distinctive dimensions of fatigue., Results: Thirty-seven out of 100 patients were diagnosed with iron deficiency. These patients were younger [median (first-third quartile) 63 (43-70) vs. 70 (59-77) years (P = 0.004)], and more often female (51 vs. 21%, P = 0.003), than no iron deficiency patients. Preoperative iron deficiency was associated with lower preoperative haemoglobin levels (P = 0.006) and higher perioperative transfusion rates during the first week (62 vs. 35%, P = 0.019). Patients with iron deficiency but without anaemia (n = 25) received more packed red blood cells units than those without iron deficiency or anaemia (n = 50) [2 (0-2) vs. 0 (0-0) units, P < 0.05). Preoperative iron deficiency was associated with higher score of physical fatigue on day 7 (P = 0.01)., Conclusion: Preoperative iron deficiency is frequent among cardiac surgery patients and is associated with anaemia, higher transfusion requirements and postoperative fatigue.