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Journal: British journal of anaesthesia


The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders.


/st>Evidence is limited for the effectiveness of interventions for survivors of critical illness after hospital discharge. We explored the effect of an 8-week hospital-based exercise-training programme on physical fitness and quality-of-life.

Concepts: Clinical trial, Effectiveness, Exercise, Strength training


Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.


These guidelines provide a strategy to manage unanticipated difficulty with tracheal intubation. They are founded on published evidence. Where evidence is lacking, they have been directed by feedback from members of the Difficult Airway Society and based on expert opinion. These guidelines have been informed by advances in the understanding of crisis management; they emphasize the recognition and declaration of difficulty during airway management. A simplified, single algorithm now covers unanticipated difficulties in both routine intubation and rapid sequence induction. Planning for failed intubation should form part of the pre-induction briefing, particularly for urgent surgery. Emphasis is placed on assessment, preparation, positioning, preoxygenation, maintenance of oxygenation, and minimizing trauma from airway interventions. It is recommended that the number of airway interventions are limited, and blind techniques using a bougie or through supraglottic airway devices have been superseded by video- or fibre-optically guided intubation. If tracheal intubation fails, supraglottic airway devices are recommended to provide a route for oxygenation while reviewing how to proceed. Second-generation devices have advantages and are recommended. When both tracheal intubation and supraglottic airway device insertion have failed, waking the patient is the default option. If at this stage, face-mask oxygenation is impossible in the presence of muscle relaxation, cricothyroidotomy should follow immediately. Scalpel cricothyroidotomy is recommended as the preferred rescue technique and should be practised by all anaesthetists. The plans outlined are designed to be simple and easy to follow. They should be regularly rehearsed and made familiar to the whole theatre team.

Concepts: The Canon of Medicine, Surgery, Device, Management, Anesthesia, Endotracheal tube, Intubation, Emergency medical procedures


As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care.

Concepts: Surgery, Islamic Golden Age, Al-Andalus, Elective surgery


These guidelines describe a comprehensive strategy to optimize oxygenation, airway management, and tracheal intubation in critically ill patients, in all hospital locations. They are a direct response to the 4th National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society, which highlighted deficient management of these extremely vulnerable patients leading to major complications and avoidable deaths. They are founded on robust evidence where available, supplemented by expert consensus opinion where it is not. These guidelines recognize that improved outcomes of emergency airway management require closer attention to human factors, rather than simply introduction of new devices or improved technical proficiency. They stress the role of the airway team, a shared mental model, planning, and communication throughout airway management. The primacy of oxygenation including pre- and peroxygenation is emphasized. A modified rapid sequence approach is recommended. Optimal management is presented in an algorithm that combines Plans B and C, incorporating elements of the Vortex approach. To avoid delays and task fixation, the importance of limiting procedural attempts, promptly recognizing failure, and transitioning to the next algorithm step are emphasized. The guidelines recommend early use of a videolaryngoscope, with a screen visible to all, and second generation supraglottic airways for airway rescue. Recommendations for emergency front of neck airway are for a scalpel-bougie-tube technique while acknowledging the value of other techniques performed by trained experts. As most critical care airway catastrophes occur after intubation, from dislodged or blocked tubes, essential methods to avoid these complications are also emphasized.

Concepts: Critical thinking, The Canon of Medicine, Anesthesia, Endotracheal tube, Airway, Intubation, Consensus, Oropharyngeal airway


/st> Teaching trainees to become competent professionals who can keep the complex system of anaesthesia safe is important. From a safety point of view, non-technical skills such as smooth cooperation and good communication deserve as much attention as theoretical knowledge and practical skills, which by tradition have dominated training programmes in anaesthesiology. This study aimed to describe the way excellent anaesthetists act in the operating theatre, as seen by experienced anaesthesia nurses.

Concepts: Scientific method, Psychology, Surgery, Skill, Anesthesia, Training, Learning, Knowledge


Postoperative pulmonary complications (PPCs) occur frequently and are associated with substantial morbidity and mortality. Evidence suggests that reduction of PPCs can be accomplished by using lung-protective ventilation strategies intraoperatively, but a consensus on perioperative management has not been established. We sought to determine recommendations for lung protection for the surgical patient at an international consensus development conference. Seven experts produced 24 questions concerning preoperative assessment and intraoperative mechanical ventilation for patients at risk of developing PPCs. Six researchers assessed the literature using questions as a framework for their review. The modified Delphi method was utilised by a team of experts to produce recommendations and statements from study questions. An expert consensus was reached for 22 recommendations and four statements. The following are the highlights: (i) a dedicated score should be used for preoperative pulmonary risk evaluation; and (ii) an individualised mechanical ventilation may improve the mechanics of breathing and respiratory function, and prevent PPCs. The ventilator should initially be set to a tidal volume of 6-8 ml kg-1 predicted body weight and positive end-expiratory pressure (PEEP) 5 cm H2O. PEEP should be individualised thereafter. When recruitment manoeuvres are performed, the lowest effective pressure and shortest effective time or fewest number of breaths should be used.


BACKGROUND: /st>Neuromuscular blocking drugs (NMBDs) are the most common cause of intraoperative anaphylaxis in Western Australia. Differences in the rates of anaphylaxis between individual agents have been surmised in the past, but not proven, and are an important consideration if agents are otherwise equivalent. METHODS: /st>We estimated a rate of anaphylaxis to NMBDs by analysing cases of NMBD anaphylaxis referred to the only specialized diagnostic centre in Western Australia over a 10 yr period. Exposure was approximated by analysing a 5 yr period of NMBD ampoule sales data. Agents were also ranked according to the prevalence of cross-reactivity in patients with previous NMBD anaphylaxis. RESULTS: /st>Rocuronium was responsible for 56% of cases of NMBD anaphylaxis, succinylcholine 21%, and vecuronium 11%. There was no difference in the severity of reactions for different NMBDs. Rocuronium had a higher rate of IgE-mediated anaphylaxis compared with vecuronium (8.0 vs 2.8 per 100 000 exposures; P=0.0013). The prevalence of cross-reactivity after NMBD anaphylaxis suggested that succinylcholine also has a high risk of triggering anaphylaxis. Cisatracurium had the lowest prevalence of cross-reactivity in patients with known anaphylaxis to rocuronium or vecuronium. CONCLUSIONS: /st>Rocuronium has a higher rate of IgE-mediated anaphylaxis compared with vecuronium, a result that is statistically significant and clinically important. Cisatracurium had the lowest rate of cross-reactivity in patients who had previously suffered anaphylaxis to rocuronium or vecuronium.

Concepts: Statistics, Statistical significance, Incidence, Difference, Differences, Muscle relaxants, Quaternary ammonium compounds, Cisatracurium


Management of life-threatening acute severe asthma in children and adults may require anaesthetic and intensive care. The inhaled route for drug delivery is not appropriate when only small respiratory gas volumes are shifted; the i.v. route may be associated with greater side-effects. Magnesium sulphate i.v. has a place in acute asthma management because it is a mild bronchodilator, and has a stabilizing effect on the atria which may attenuate tachycardia occurring after inhaled and i.v. salbutamol. If intubation and ventilation are required, a reduction in bronchoconstriction by any means before and during these procedures should reduce morbidity. This narrative review aims to show strengths and weakness of the evidence, present controversies, and forward opinions of the author. The review contains a practical guide to the setting up, use and efficiency of nebulizers, metered dose inhalers, and spacers (chambers). It also presents a commonsense approach to the management of severe asthmatics in whom delay in bronchodilatation would cause clinical deterioration. When self-inhaled agents have had no effect, i.v. drugs may help avoid intubation and ventilation. The review includes suggestions for the use of inhaled anaesthetics, anaesthetic induction, and brief notes on subsequent ventilation of the lungs.

Concepts: Asthma, Lung, Magnesium, Magnesium sulfate, Allergy, Epinephrine, Nebulizer, Bronchoconstriction