The evolution of the British Journal of Anaesthesia: the first 100 years.

At this centenary of the British Journal of Anaesthesia (BJA) in 2023, six of its 12 editors/editors-in-chief detail developments over the decades that have led to the BJA becoming a high-impact international scientific journal. As a charity, the BJA supports academic research and training in anaesthesia, critical care, and pain medicine including funding of research grants and postgraduate education. Building on this foundation, the BJA continues to innovate as it aims to become fully electronic, expand into open access publishing, and increase the diversity of its editorial board.

Retesting the Hypothesis of a Clinical Randomized Controlled Trial in a Simulation Environment to Validate Anesthesia Simulation in Error Research (the VASER Study).

BACKGROUND: Simulation has been used to investigate clinical questions in anesthesia, surgery, and related disciplines, but there are few data demonstrating that results apply to clinical settings. We asked "would results of a simulation-based study justify the same principal conclusions as those of a larger clinical study?" METHODS: We compared results from a randomized controlled trial in a simulated environment involving 80 cases at three centers with those from a randomized controlled trial in a clinical environment involving 1,075 cases. In both studies, we compared conventional methods of anesthetic management with the use of a multimodal system (SAFERsleep; Safer Sleep LLC, Nashville, Tennessee) designed to reduce drug administration errors. Forty anesthesiologists each managed two simulated scenarios randomized to conventional methods or the new system. We compared the rate of error in drug administration or recording for the new system versus conventional methods in this simulated randomized controlled trial with that in the clinical randomized controlled trial (primary endpoint). Six experts were asked to indicate a clinically relevant effect size. RESULTS: In this simulated randomized controlled trial, mean (95% CI) rates of error per 100 administrations for the new system versus conventional groups were 6.0 (3.8 to 8.3) versus 11.6 (9.3 to 13.8; P = 0.001) compared with 9.1 (6.9 to 11.4) versus 11.6 (9.3 to 13.9) in the clinical randomized controlled trial (P = 0.045). A 10 to 30% change was considered clinically relevant. The mean (95% CI) difference in effect size was 27.0% (-7.6 to 61.6%). CONCLUSIONS: The results of our simulated randomized controlled trial justified the same primary conclusion as those of our larger clinical randomized controlled trial, but not a finding of equivalence in effect size.

Effects of subanesthetic dose of nitrous oxide on cerebral blood flow and metabolism: a multimodal magnetic resonance imaging study in healthy volunteers.

BACKGROUND: Nitrous oxide, in a concentration of 50% or more, is a known cerebral vasodilator. This study investigated whether a lower dose (30%) of nitrous oxide would also increase cerebral blood flow. In addition, the authors wished to study whether the increase in cerebral blood flow was accompanied by an increase in cerebral metabolism. METHODS: Multimodal Magnetic Resonance Imaging at 3T was performed, and data were obtained in 17 healthy volunteers during three inhalation conditions: medical air, oxygen-enriched medical air (40% oxygen), and 30% nitrous oxide with oxygen-enriched medical air (40% oxygen). Arterial spin labeling was used to derive the primary tissue specific hemodynamic outcomes: cerebral blood flow, arterial blood volume and arterial transit times. Magnetic Resonance Susceptometry and proton Magnetic Resonance Spectroscopy were used for secondary metabolic outcomes: venous oxygenation, oxygen extraction fraction, cerebral metabolic oxygen rate and prefrontal metabolites. RESULTS: Nitrous oxide in 40% oxygen, but not 40% oxygen alone, significantly increased gray matter cerebral blood flow (22%; P < 0.05) and arterial blood volume (41%; P < 0.05). Venous oxygenation increased in both oxygen and nitrous oxide conditions. Compared with medical air inhalation, nitrous oxide condition caused a significantly larger decrease in oxygen extraction fraction than 40% oxygen alone (mean [SD] 11.3 [5.6]% vs. 8.3 [5.9]% P < 0.05), while global cerebral metabolic rate and prefrontal metabolites remained unchanged. CONCLUSIONS: This study demonstrates that 30% nitrous oxide in oxygen-enriched air (40% oxygen) significantly increases cerebral perfusion, and reduces oxygen extraction fraction, reflecting a strong arterial vasodilatory effect without associated increases in metabolism.

Novel events in the molecular regulation of muscle mass in critically ill patients.

Critically ill patients experience marked skeletal muscle atrophy, but the molecular mechanisms responsible for this are largely unresolved. Therefore, we investigated key genes and proteins, identified from cell and animal studies to control protein synthesis and breakdown, in vastus lateralis biopsy samples obtained from 10 patients and 10 age- and sex-matched healthy controls. Muscle cytokines IL-6 and TNF-α mRNA were higher in patients than in controls(6.5-fold; P < 0.001 and 2-fold; P < 0.01). From the perspective of muscle protein breakdown, muscle-specific E3-ligases (MAFbx and MuRF1) were higher in patients at mRNA (4.5-fold; P < 0.05 and 2.5-fold; P < 0.05) and protein (5-fold; P < 0.001 and 4.5-fold; P < 0.001) level. Furthermore, 20S proteasome mRNA and protein were higher in patients (5-fold; P < 0.001 and 2.5-fold; P < 0.01). Cathepsin-L mRNA was 2-fold higher (P < 0.01), whilst calpain-3 mRNA(2-fold; P < 0.01) and protein (4-fold; P < 0.01)were lower inpatients. Another novel observation was the 3-fold (P < 0.05) and 8.5-fold (P < 0.001) higher expression of myostatin mRNA and protein in patients. Widespread dephosphorylation (inactivation) of proteins regulating translation initiation factor activation and protein synthesis (Akt1, GSK3α,ß, mTOR, p70S6K and 4E-BP1) was observed in patients, which was paralleled by increases in their mRNAs. Finally, PDK4 mRNA and protein was 2-fold (P < 0.05) and 2.6-fold (P < 0.01), respectively, higher inpatients. In conclusion, we showed comprehensive alterations in molecular events thought to reduce muscle mass and carbohydrate (CHO) oxidation in critically ill patients. Nevertheless,these catabolic events were matched by a cellular programme of anabolic restoration at the transcriptional level. This shows a high molecular plasticity in the muscle of patients, and strategies to preserve muscle mass and metabolic function should focus on maintaining Akt phosphorylation and inhibiting myostatin expression.C

Anesthesia and patient safety: have we reached our limits?

PURPOSE OF REVIEW: To provide recent evidence of safety in anesthesia and appraise the role of established tools of safety improvement in anesthesia practice. RECENT FINDINGS: The current incidence of minor events or complications during anesthesia is estimated at 18-22%, for severe complications 0.45-1.4%, and for mortality of 1: 100 000. Evidence suggests that despite such low complication rates, further improvements can still be made by addressing systemic factors which are known to set up conditions for adverse events. In particular, improvements can be made in the areas of drug errors, and inadequate or lack of communication between different clinical teams during the process of handovers. In addition, the evidence is growing which highlights the importance of established tools such as critical incident reporting, quality management using plan-do-check-act cycles, use of checklists and use of simulation in training clinical staff in the areas of nontechnical skills. SUMMARY: Anesthesia is one of the safest clinical specialties and remains at the top among leaders of patient safety. This review provides evidence for the areas in which further progress can be made, and usefulness of certain tools, such as critical incident reporting, checklists, plan-do-check-act cycles and simulation, can be used for continued improvements.

Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome.

INTRODUCTION: Osteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain. METHODS AND ANALYSIS: This is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6 weeks of duloxetine (30 mg for 2 weeks, then 60 mg for 4 weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition. ETHICS AND DISSEMINATION: The study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: This trial is registered at ClinicalTrials.gov (NCT02208778).This work was supported by Arthritis Research UK (Grant 18769).

Frequent respiratory events in postoperative patients aged 60 years and above.

There is limited information on the occurrence of respiratory events in postoperative patients after discharge from the postanesthesia care unit. We studied the respiratory rate (RR) of 68 patients aged 60 years and above during the first 6 hours following elective surgery under general anesthesia to assess the frequency of respiratory events in the care unit and on the ward. RR was derived from the continuous RR counter RespiR8, measuring RR by quantifying the humidity of exhaled air. One-minute-averaged RRs were collected and analyzed to assess the frequency of postoperative bradypnea (RR 1-6 breaths/minute) and apnea (cessation of inspiratory flow ≥60 seconds). Values were median (interquartile range) or mean (SD). The median RR was 13 (10-15) breaths/minute. In the 6-hour postoperative period, 78% and 57% of patients experienced at least one bradypnea or apnea event, respectively. A median of ten (3.5-24) bradypnea and three (1-11) apnea events were detected per patient. The occurrence of respiratory events in the postanesthesia care unit (PACU) was a predictor of events on the ward (bradypnea, r2=0.4, P<0.001; apnea, r2=0.2, P<0.001). Morphine consumption correlated weakly with respiratory events in the PACU, but not on the ward. Patients with apnea had significantly larger neck circumference than patients without (39.6 [0.7] versus 37.4 [0.8] cm, P<0.05). Bradypneic or apneic respiratory events are frequent in postoperative elderly patients and even occur relatively late after surgery. Continuous respiratory monitoring on the ward, especially in patients with risk factors, such as early occurrence of events, opioid use, and larger neck circumference, is likely warranted.

Sex differences in metabolic and adipose tissue responses to juvenile-onset obesity in sheep.

Sex is a major factor determining adipose tissue distribution and the subsequent adverse effects of obesity-related disease including type 2 diabetes. The role of gender on juvenile obesity and the accompanying metabolic and inflammatory responses is not well established. Using an ovine model of juvenile onset obesity induced by reduced physical activity, we examined the effect of gender on metabolic, circulatory, and related inflammatory and energy-sensing profiles of the major adipose tissue depots. Despite a similar increase in fat mass with obesity between genders, males demonstrated a higher storage capacity of lipids within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast, obese females became hypercortisolemic, a response that was positively correlated with central fat mass. Analysis of gene expression in perirenal-abdominal adipose tissue demonstrated the stimulation of inflammatory markers in males, but not females, with obesity. Obese females displayed increased expression of genes involved in the glucocorticoid axis and energy sensing in perirenal-abdominal, but not omental, adipose tissue, indicating a depot-specific mechanism that may be protective from the adverse effects of metabolic dysfunction and inflammation. In conclusion, young males are at a greater risk than females to the onset of comorbidities associated with juvenile-onset obesity. These sex-specific differences in cortisol and adipose tissue could explain the earlier onset of the metabolic-related diseases in males compared with females after obesity.

The influence of sex on early stage markers of kidney dysfunction in response to juvenile obesity.

Changes within the kidney in response to obesity are critical in determining the magnitude of later dysfunction. However, the cause of this process in response to juvenile onset obesity and how it can be determined by sex is poorly understood. We therefore examined the effect of juvenile obesity induced by exposure to a restricted activity environment from weaning until early adulthood on the molecular responses within the kidney together with glomerular area and nucleated cell number. This was stratified by sex and was undertaken in a sheep model of early obesity. Despite a similar magnitude of increase in fat mass with obesity onset between sexes, adverse effects on glomerular area and cell number together with raised gene expression within the kidney only occurred in males. Irrespective of obesity, gene expression of C-C motif receptor 2 was higher, and interleukin-6 lower, in male kidneys compared with female kidneys. The effects of sex on molecular differences within the kidney were amplified with obesity, which had no effect on any gene studied in females but had an enhanced response in males. Obese males therefore showed increased gene expression of a range of markers relating to the glucocorticoid axis, inflammation, and lipid sensing. In conclusion, young females were protected from adverse renal effects of obesity, which results in very little inflammatory or related responses. Our findings emphasize the critical importance of sex specificity in disease pathogenesis. An increased understanding of the specific mechanisms will have important implications for therapeutic strategies aimed at preventing adverse consequences of obesity.

The WHO surgical checklist.

Following the overwhelming evidence of adverse events in hospital practice, the World Health Organization (WHO)'s World Alliance for Patient Safety has launched the 'Safe Surgery Saves Lives' campaign, which has developed a surgical safety checklist aimed to improve patient safety. The implementation of this checklist has met with mixed reactions in different institutions. Many countries have still not adopted its use. In this article, a brief review is presented regarding the role of the WHO checklist, barriers to its implementation and strategies for successful adoption.

Conflictos de intereses en revistas médicas / Conflicts of interest in medical journals

Las revistas médicas son una fuente de información de gran importancia para los profesionales en medicina, para los pacientes y para los encargados de diseñar las políticas. Por lo tanto, es crucial que toda información y publicaciones en dichas revistas sean confiables y fidedignas. Está claro que los conflictos de intereses (CDI) pueden lastimar la credibilidad de una publicación y/o de una revista y tener consecuencias de largo alcance, socavando la confianza de los lectores de dichas publicaciones médicas. Este editorial pretende abordar algunos temas importantes relacionados con el CDI en revistas médicas. Específicamente se hará referencia a la definición y tipos de CDI, así como a las prácticas recomendadas para resolver tales conflictos.

The effects of propofol or sevoflurane on the estimated cerebral perfusion pressure and zero flow pressure.

The zero flow pressure (ZFP) is the pressure at which blood flow ceases through a vascular bed. Using transcranial Doppler ultrasonography, we investigated the effects of propofol or sevoflurane on the estimated cerebral perfusion pressure (eCPP) and ZFP in the cerebral circulation. Twenty-three healthy patients undergoing nonneurosurgical procedures under general anesthesia were studied. After induction of anesthesia using propofol, the anesthesia was maintained with either propofol infusion (n = 13) or sevoflurane (n = 10). Middle cerebral artery flow velocity, noninvasive arterial blood pressure, and end-tidal carbon dioxide partial pressure were recorded awake as a baseline, and during steady-state anesthesia at normocapnia (baseline end-tidal carbon dioxide partial pressure) and hypocapnia (1 kPa below baseline). The eCPP and ZFP were calculated using an established formula. The mean arterial blood pressure decreased in both groups. The eCPP decreased significantly in the propofol group (median, from 58 to 41 mm Hg) but not in the sevoflurane group (from 60 to 62 mm Hg). Correspondingly, ZFP increased significantly in the propofol group (from 25 to 33 mm Hg) and it decreased significantly in the sevoflurane group (from 27 to 7 mm Hg). Hypocapnia did not change eCPP or ZFP in the propofol group, but it significantly decreased eCPP and increased ZFP in the sevoflurane group.

Noninvasive estimation of cerebral perfusion pressure and zero flow pressure in healthy volunteers: the effects of changes in end-tidal carbon dioxide.

UNLABELLED: Zero flow pressure (ZFP) in the cerebral circulation is defined as the arterial pressure at which flow ceases. Noninvasive methods of estimating cerebral perfusion pressure (CPP) and ZFP using transcranial Doppler ultrasonography have been described. There is a paucity of normal physiological data related to changes in estimated CPP (eCPP) and ZFP induced by changes in carbon dioxide (CO(2)). We studied the effects of CO(2) on eCPP and ZFP in 17 healthy volunteers. After baseline measurements of middle cerebral artery blood-flow velocity and blood pressure, subjects voluntarily hyperventilated to decrease their end-tidal CO(2) (PE'CO(2)) by approximately 7.5 mm Hg, and then they increased their PE'CO(2) by approximately 7.5 mm Hg by breathing through a Mapleson D circuit. Blood-flow velocity and blood pressure were recorded at each stage. The eCPP and ZFP were calculated by using established formulas, and the results were analyzed with analysis of variance. With increasing PE'CO(2), eCPP increased from 50.67 mm Hg (8.33 mm Hg) (mean [SD]) to 60.87 mm Hg (9.28 mm Hg) (20% increase; P < 0.001), with a corresponding decrease in ZFP (P = 0.017); hypocapnia resulted in the opposite effects on eCPP and ZFP. These results indicate physiological changes in eCPP and ZFP that can be expected from changes in CO(2) in subjects without any neurological disorder. IMPLICATIONS: Increasing end-tidal CO(2) increases the estimated cerebral perfusion pressure and vice versa. These results are opposite to those expected from the known effects of CO(2) on intracranial pressure. Thus, we support the suggestion that, in the absence of intracranial hypertension, vascular tone remains a major determinant of effective downstream pressure and cerebral perfusion.