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  • Women in anaesthesia: a scoping review
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-23
    Laura Bosco; Gianni R. Lorello; Alana M. Flexman; Maya J. Hastie

    Despite an increase in the proportion of women anaesthesiologists over time, women remain under-represented in academic and leadership positions, honour awards, and academic promotion. Current literature has identified several reasons for the observed gender disparity in anaesthesiology leadership and faculty positions, including unsupportive work environments, lack of mentorship, personal choices, childcare responsibilities, and active discrimination against women. A scoping review design was selected to examine the nature and extent of available research. Our review provides an overview of the literature that explores gender issues in anaesthesiology, identifies gaps in the literature, and appraises effective strategies to improve gender equity in anaesthesiology. We searched PubMed, MEDLINE, and EMBASE up to July 2019, and included 30 studies for analysis. Most reports used retrospective or survey methodologies. The review shows that women anaesthesiologists face gender biases in the work environment, are under-represented in various positions of leadership or influence, and as authors. Work–life demands may impose a challenge. Motivation and interest in career advancement of women anaesthesiologists have not been well studied. Several strategies have been proposed, ranging from an individual to administrative level, which may help anaesthesiologists achieve equal representation of women in the field.

  • Gender effects in anaesthesia training in Australia and New Zealand
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-23
    Greta Pearce; Navdeep Sidhu; Alana Cavadino; Archana Shrivathsa; Richard Seglenieks

    Background Women face gender-based challenges in their medical education and career. Inequitable access to procedural training, a confidence gap, and professional identity deficit have been shown. We made a gender comparison of procedural case volume, confidence for independent practice, perceived gender and ethnic bias, and professional identity in Australasian anaesthesia trainees. Methods An online, voluntary, anonymous survey using SurveyMonkey® was delivered to Australasian anaesthesia trainees. Information collected included demographics, experience and confidence in 12 anaesthetic procedures, assessments relating to confidence and professional identity, and perceived gender and ethnic bias. Gender differences were evaluated. Results Three hundred and fifty-six trainees (22.2%) of the Australian and New Zealand College of Anaesthetists (ANZCA) responded. Male trainees reported a higher number (standard deviation) of procedures performed greater than 10 times (men 4.45 [2.55], women 3.78 [1.95]; P<0.001 adjusted for training level). Men were more likely to rate themselves at a training competency above their actual training level (men 18.6%, women 7.8%; P=0.004) and exaggerate procedural experience to supervisors (men 30.8%, women 11.8%; P<0.001). Final-year male trainees felt significantly more prepared for independent practice (P=0.021, trend across ordered responses). Women reported significantly higher levels of gender bias exhibited by patients (men 1.1%, women 84.5%; P<0.001) and in training overall (men 10.3%, women 55.3%; P<0.001), which was compounded in women with an ethnic minority background. Conclusions A discrepancy exists between the number of procedures performed by male and female anaesthesia trainees in Australia and New Zealand. Relative male overconfidence may be a major contributing factor to the gender confidence gap.

  • Women anaesthesiologists' attitudes and reported barriers to career advancement in anaesthesia: a survey of the European Society of Anaesthesiology
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-21
    Idit Matot; Stefan De Hert; Barak Cohen; Thea Koch

    Background Previous studies have confirmed gender imbalance in anaesthesia leadership. Whether women anaesthesiologists aspire to career advancement has not been reported. This European Society of Anaesthesiology (ESA) survey explored anaesthesiologists' motivation to advance their careers into leadership positions, and to identify reported barriers to advancement. Methods ESA members (n=10 033, 5245 men, 3759 women, 1029 undefined) were invited to complete a 25-item, Internet-based survey, and responses were analysed thematically. Results In total, 3048 ESA members (1706 women, 1342 men, 30% of all members) responded to the survey. The majority were specialists, married or with a partner, and have children; 47% of women and 48% of men wish to pursue a leadership career. Barriers to career promotion noted by women were primarily attributed to work–private time considerations (extra workload and less personal time [84%], responsibility for care of family [65%], lack of part-time work opportunities [67%]), and the shift away from clinical work [59%]). Men respondents indicated the same barriers although the proportions were significantly lower. Considerations related to the partner (lack of support, career development of partner) were last on the list of variables reported by women as barriers. Importantly, many women noted deficiencies in leadership (68%) and research education (55%), and women role models (41%) and self-confidence (44%). Conclusions This is the largest survey to date of women anaesthesiologists' view on career advancement. Despite the many barriers noted by women, they are as eager as men to assume leadership positions. The survey results help in identifying possible areas for intervention to assist in career development.

  • Gender distribution in United States anaesthesiology residency programme directors: trends and implications
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-21
    Laura S. Gonzalez; Brenda G. Fahy; Cynthia A. Lien

    The under-representation of women in academic leadership roles, including in anaesthesiology, is a well-documented phenomenon that has persisted for decades despite more women attending medical school, participating in anaesthesiology residencies, and joining academic faculties. The percentage of female anaesthesiologists who hold senior academic ranks or leadership roles, such as chair, lags behind the percentage of female anaesthesiologists overall. Trends towards increasing the numbers of women serving in educational leadership roles, specifically residency programme directors, suggest that there are areas in which academic anaesthesiology has been, and can continue, improving gender imbalance. Continued institutional efforts to recruit women into anaesthesiology, reduce gender bias, and promote interventions that foster gender equity in hiring and promotion will continue to benefit women, academic anaesthesiology departments, and the healthcare system overall.

  • Effect of combining peri-hamstring injection or anterior obturator nerve block on the analgesic efficacy of adductor canal block for anterior cruciate ligament reconstruction: a randomised controlled trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-21
    David F. Johnston; Rakesh V. Sondekoppam; Vishal Uppal; Robert Litchfield; Robert Giffin; Sugantha Ganapathy

    Background Pain after anterior cruciate ligament reconstruction (ACLR) with autologous hamstring graft can be attributed to both arthroscopic surgery and the graft donor site. This study investigated whether donor site pain control was superior with the addition of either peri-hamstring injection or anterior division obturator nerve block in comparison with adductor canal block (ACB) alone. Methods Patients scheduled to undergo knee arthroscopy with ACLR using a graft from the ipsilateral hamstring were randomised to one of three groups. All patients received ACB and multimodal analgesia. Subjects in Group H received peri-hamstring local anaesthetic injection while subjects in Group O received an anterior division of the obturator nerve block, and subjects in Group C served as a control group (ACB alone). Results In 105 subjects undergoing ACLR, there was no significant difference between groups H, O, and C for the primary outcome of pain on movement as assessed by numerical rating scale (NRS) on knee flexion at 2 h after operation (P=0.11). There was no difference in NRS at any time point in the first 48 h after operation, nor was there a difference in oxycodone consumption between the three groups at 24 h (P=0.2). Worst knee pain was initially at the graft donor site in all three groups, which transitioned to anterior knee pain after 12 h. Conclusions The addition of ultrasound-guided peri-hamstring injection or anterior division of obturator nerve block to ACB did not result in a significant reduction in pain or opioid consumption after ACLR with ipsilateral hamstring graft. Clinical trial registration NCT 01868282.

  • Sex differences in neurodevelopmental abnormalities caused by early-life anaesthesia exposure: a review
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-21
    Omar H. Cabrera; Thomas Gulvezan; Breanna Symmes; Nidia Quillinan; Vesna Jevtovic-Todorovic

    Exposure to anaesthetic drugs during the fetal or neonatal period induces widespread neuronal apoptosis in the brains of rodents and non-human primates. Hundreds of published preclinical studies and nearly 20 clinical studies have documented cognitive and behavioural deficits many months or years later, raising the spectre that early life anaesthesia exposure is a long-term, perhaps permanent, insult that might affect the quality of life of millions of humans. Although the phenomenon of anaesthesia-induced developmental neurotoxicity is well characterised, there are important and lingering questions pertaining to sex differences and neurodevelopmental sequelae that might occur differentially in females and males. We review the relevant literature on sex differences in the field of anaesthesia-induced developmental neurotoxicity, and present an emerging pattern of potential sex-dependent neurodevelopmental abnormalities in rodent models of human infant anaesthesia exposure.

  • Fostering belonging in academic anaesthesiology: faculty and department chair perspectives on supporting women anaesthesiologists
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-20
    Meghan B. Lane-Fall; Emily K.B. Gordon; Elizabeth A. Valentine; Stephanie A. Black; Patricia A. Kapur; Lee A. Fleisher

    An increasing number of global initiatives aim to address the disconnection between the increasing number of women entering medicine and the persistence of gender imbalance in the physician anaesthesiologist workforce. This commentary complements the global movement's efforts to increase women's representation in academic anaesthesiology by presenting considerations for fostering inclusion for women in academic anaesthesiology from both the faculty and departmental leadership perspectives in a US academic anaesthesiology department.

  • Women empowerment in anaesthesia research and clinical practice: meeting report from the British Journal of Anaesthesia Women in Anaesthesia Research symposium
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-20
    Christa Boer; S.Ramani Moonesinghe

    The Women in Anaesthesia Research Symposium (Prato, Italy; 4 June, 2019), supported by the British Journal of Anaesthesia in collaboration with Monash University, was organised to discuss challenges facing women in anaesthesia clinical practice and research. We provide an overview of institutional or departmental measures that were proposed during the symposium that may empower women in anaesthesia today.

  • The posterior femoral cutaneous nerve contributes significantly to sensory innervation of the lower leg: an anatomical investigation
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-20
    Georg C. Feigl; Mathias Schmid; Peter K. Zahn; Carla A. Avila González; Rainer J. Litz

    Background Incomplete peripheral nerve blocks distal to the popliteal region are commonly considered a sciatic and femoral/saphenous nerve block failure. The existence of a much more distal innervation area of the posterior femoral cutaneous nerve (PFCN) as described has not been assumed yet. We therefore investigated the distal termination of the PFCN in the lower leg. Methods In 83 human lower extremities embalmed with Theil's method, the course of the PFCN was investigated from the sub-gluteal fold to the most distal macroscopically dissectible branch. The topographic connection to other landmarks, such as the small saphenous vein or small arteries, was investigated. Results Popliteal ending of the PFCN was found in 9.7% of cases. The PFCN terminated at the proximal or distal lower leg in 45.7% and 44.6% of cases, respectively. The PFCN had a close connection to the Achilles tendon in 13.2% of cases and was found distally to the medial malleolus in one case. The small saphenous vein was close to the PFCN in 90.3% of cases and can therefore be used as a landmark to identify the nerve. In 40.9% of cases, the PFCN was accompanied by a small descending branch of the inferior gluteal artery. In two cases, an innervation of the fibula or calcaneus periosteum was found. Conclusions The PFCN has a much more distal termination in the lower leg than previously demonstrated. To ensure complete anaesthesia of the lower leg and foot, the PFCN must be included in combined peripheral nerve block procedures.

  • A randomised double-blind dose–response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal–epidural anaesthesia for Caesarean delivery
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-17
    Feng Fu; Fei Xiao; Wending Chen; Meijuan Yang; Yanhong Zhou; Warwick D. Ngan Kee; Xinzhong Chen

    Background Norepinephrine infusion has been suggested as an effective method for preventing hypotension during spinal anaesthesia for Caesarean delivery. However, optimal dosing regimens for norepinephrine have not been well established. This study aimed to determine the dose–response characteristics of a weight-adjusted fixed-rate infusion of norepinephrine to prevent hypotension during neuraxial anaesthesia for Caesarean delivery. Methods In a double-blind, randomised controlled trial, 80 parturients having elective Caesarean delivery received a prophylactic norepinephrine infusion at 0.025 μg kg−1 min−1 (Group N1), 0.05 μg kg−1 min−1 (Group N2), 0.075 μg kg−1 min−1 (Group N3), or 0.10 μg kg−1 min−1 (Group N4), starting immediately after induction of combined spinal–epidural anaesthesia. The primary outcome was non-occurrence of hypotension, defined as a decrease in systolic arterial pressure ≥20% below baseline value or to ≤90 mm Hg, before delivery. Values for 50% effective dose (ED50) and ED90 were calculated using probit regression. Results The incidence of hypotension was 11/20 (55%), 6/20 (30%), 2/20 (10%), and 1/20 (5%) in Groups N1, N2, N3, and N4, respectively (P<0.0001). The ED50 and ED90 (95% confidence interval) of norepinephrine infusions for preventing hypotension were 0.029 (–0.002 to 0.043) and 0.080 (0.065–0.116) μg kg−1 min−1, respectively. The incidence of reactive hypertension increased with increasing norepinephrine dose (P=0.002). Other adverse effects were similar among groups. Conclusions Under the conditions of this study, an infusion of norepinephrine 0.08 μg kg−1 min−1 was effective for preventing hypotension in 90% of patients. This information should provide a guide for initiating norepinephrine infusions. Clinical trial registration ChiCTR1900022322 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enindex.aspx).

  • Factors associated with persistent pain after childbirth: a narrative review
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-17
    Ryu Komatsu; Kazuo Ando; Pamela D. Flood

    A systematic literature search was performed to identify studies that reported risk factors for persistent pain after childbirth. Many studies have sought to identify risk factors for post-delivery pain in different populations, using different methodologies and different outcome variables. Studies of several different but interrelated post-partum pain syndromes have been conducted. Factors strongly and specifically associated with persistent incisional scar pain after Caesarean delivery include a coexisting persistent pain problem in another part of the body and severe acute postoperative pain. For persistent vaginal and perineal pain, operative vaginal delivery and the magnitude of perineal trauma have been consistently linked. History of pregnancy-related and pre-pregnancy back pain and heavier body weight are robust risk factors for persistent back pain after pregnancy. Unfortunately, limitations, particularly small samples and lack of a priori sample size calculation designed to detect specific effect sizes for risk of persistent pain outcomes, preclude definitive conclusions about many other predictors and the strength of outcome associations. In future studies, assessments of specific phenotypes using a rigorous analysis with appropriate predetermined sample sizes and validated instruments are needed to allow elucidation of stronger and reliable associations. Interventional studies targeting the most robustly associated, modifiable risk factors, such as acute post-partum pain, may lead to solutions for the prevention and treatment of these common problems that impact a large population.

  • Validating the inspired sinewave technique to measure the volume of the ‘baby lung’ in a porcine lung-injury model
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-14
    Douglas C. Crockett; Minh C. Tran; Federico Formenti; John N. Cronin; Göran Hedenstierna; Anders Larsson; Phi A. Phan; Andrew D. Farmery

    Background Bedside lung volume measurement could personalise ventilation and reduce driving pressure in patients with acute respiratory distress syndrome (ARDS). We investigated a modified gas-dilution method, the inspired sinewave technique (IST), to measure the effective lung volume (ELV) in pigs with uninjured lungs and in an ARDS model. Methods Anaesthetised mechanically ventilated pigs were studied before and after surfactant depletion by saline lavage. Changes in PEEP were used to change ELV. Paired measurements of absolute ELV were taken with IST (ELVIST) and compared with gold-standard measures (sulphur hexafluoride wash in/washout [ELVSF6] and computed tomography (CT) [ELVCT]). Measured volumes were used to calculate changes in ELV (ΔELV) between PEEP levels for each method (ΔELVIST, ΔELVSF6, and ΔELVCT). Results The coefficient of variation was <5% for repeated ELVIST measurements (n=13 pigs). There was a strong linear relationship between ELVIST and ELVSF6 in uninjured lungs (r2=0.97), and with both ELVSF6 and ELVCT in the ARDS model (r2=0.87 and 0.92, respectively). ELVIST had a mean bias of –12 to 13% (95% limits=±17 – 25%) compared with ELVSF6 and ELVCT. ΔELVIST was concordant with ΔELVSF6 and ΔELVCT in 98–100% of measurements, and had a mean bias of –73 to –77 ml (95% limits=±128 – 186 ml) compared with ΔELVSF6 and –1 ml (95% limits ±333 ml) compared with ΔELVCT. Conclusions IST provides a repeatable measure of absolute ELV and shows minimal bias when tracking PEEP-induced changes in lung volume compared with CT in a saline-lavage model of ARDS.

  • Higher age and obesity limit atelectasis formation during anaesthesia: an analysis of computed tomography data in 243 subjects
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-07
    Göran Hedenstierna; Leif Tokics; Henrik Reinius; Hans U. Rothen; Erland Östberg; John Öhrvik

    Background General anaesthesia is increasingly common in elderly and obese patients. Greater age and body mass index (BMI) worsen gas exchange. We assessed whether this is related to increasing atelectasis during general anaesthesia. Methods This primary analysis included pooled data from previously published studies of 243 subjects aged 18–78 yr, with BMI of 18–52 kg m−2. The subjects had no clinical signs of cardiopulmonary disease, and they underwent computed tomography (CT) awake and during anaesthesia before surgery after preoxygenation with an inspired oxygen fraction (FIO2) of >0.8, followed by mechanical ventilation with FIO2 of 0.3 or higher with no PEEP. Atelectasis was assessed by CT. Results Atelectasis area of up to 39 cm2 in a transverse scan near the diaphragm was seen in 90% of the subjects during anaesthesia. The log of atelectasis area was related to a quadratic function of (age+age2) with the most atelectasis at ∼50 yr (r2=0.08; P<0.001). Log atelectasis area was also related to a broken-line function of the BMI with the knee at 30 kg m−2 (r2=0.06; P<0.001). Greater atelectasis was seen in the subjects receiving FIO2 of 1.0 than FIO2 of 0.3–0.5 (12.8 vs 8.1 cm2; P<0.001). A multiple regression analysis, including a quadratic function of age, a broken-line function of the BMI, and dichotomised FIO2 (0.3–0.5/1.0) adjusting for ventilatory frequency, strengthened the association (r2=0.23; P<0.001). PaO2 decreased with both age and BMI. Conclusions Atelectasis during general anaesthesia increased with age up to 50 yr and decreased beyond that. Atelectasis increased with BMI in normal and overweight patients, but showed no further increase in obese subjects (BMI ≥30 kg m−2). Therefore, greater age and obesity appear to limit atelectasis formation during general anaesthesia. Clinical trial registration ▪.

  • Tracheal intubation in microgravity: a simulation study comparing direct laryngoscopy and videolaryngoscopy†
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-06
    Clément Starck; Séamus Thierry; Cécile Isabelle Bernard; Thierry Morineau; François Jaulin; Pascal Chapelain; Matthieu Komorowski

    Background The risk of severe medical and surgical events during long-duration spaceflight is significant. In space, many environmental and psychological factors may make tracheal intubation more difficult than on Earth. We hypothesised that, in microgravity, tracheal intubation may be facilitated by the use of a videolaryngoscope compared with direct laryngoscopy. Methods In a non-randomised, controlled, cross-over simulation study, we compared intubation performance of novice operators and experts, using either a direct laryngoscope or a videolaryngoscope, in weightlessness and in normogravity. The primary outcome was the success rate of tracheal intubation. Time to intubation and the confidence score into the success of tube placement were also recorded. Results When novices attempted to intubate the trachea in microgravity, the success rate of tracheal intubation using a videolaryngoscope was significantly higher (20/25 [80%]; 95% confidence interval [CI], 64.3–95.7 vs eight/20 [40%]; 95% CI, 18.5–61.5; P=0.006), and intubation time was shorter, compared with using a direct laryngoscope. In normogravity, the success rate of tracheal intubation by experts was significantly higher than that by novices (16/20 [80%]; 95% CI, 62.5–97.5 vs seven/25 [28%]; 95% CI, 10.4–45.6; P=0.001), but in microgravity, there was no significant difference between the experts and novices (19/20 [95%]; 95% CI, 85.4–100 vs 20/25 [80%]; 95% CI, 64.3–95.7; P=0.113). Higher confidence scores were achieved with videolaryngoscopy compared with direct laryngoscopy by both experts and novices in both microgravity and normogravity. Conclusions Videolaryngoscopy was associated with higher intubation success rate and speed, and higher confidence for correct tube placement by novice operators in microgravity, and as such may represent the best technique for advanced airway management during long-duration spaceflight.

  • Association between propofol dose and 1-year mortality in patients with and without a diagnosis of solid cancer
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-03
    Maximilian S. Schaefer; Dana Raub; Xinling Xu; Denys Shaydenfish; Bijan Teja; Khushi Chhangani; Stephanie D. Grabitz; Brian O'Gara; Peter Kienbaum; Timothy T. Houle; Giovanni Landoni; Matthias Eikermann

    Background Preclinical data suggest suppression of cancer proliferation by propofol, and retrospective studies suggest improved survival after cancer surgery with propofol-based anaesthesia. Methods To determine whether propofol dose administered for anaesthesia is associated with 1-yr mortality in patients with and without a diagnosis of solid cancer, we analysed adult patients undergoing monitored anaesthesia care or general anaesthesia at two academic medical centres in Boston, MA, USA. Logistic regression with interaction term analysis was applied with propofol dose (mg kg−1) as primary and diagnosis of solid cancer as co-primary exposure, and 1-yr mortality as the primary outcome. Results Of 280 081 patient cases, 10 744 (3.8%) died within 1 yr. Increasing propofol dose was associated with reduced odds of 1-yr mortality (adjusted odds ratio [aOR] 0.93 per 10 mg kg−1; 95% confidence interval [CI]: 0.89–0.98; absolute risk reduction fifth vs first quintile 0.5%; 95% CI: 0.2–0.7). This association was modified by a diagnosis of solid cancer (P<0.001 for interaction). Increasing propofol dose was associated with reduced odds of 1-yr mortality in patients without solid cancer (aOR: 0.78; 95% CI: 0.71–0.85), but not in patients with solid cancer (0.99; 0.94–1.04), a finding that was replicated when examining 5-yr mortality. Conclusions Increasing propofol dose is associated with lower 1-yr mortality in patients without, but not in patients with, a diagnosis of solid cancer. We found evidence for competing effects, modifying the association between propofol dose and mortality.

  • Preoperative intravenous iron before cardiac surgery: a prospective multicentre feasibility study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2020-01-03
    Andrew A. Klein; Marisa Chau; James A. Yeates; Timothy Collier; Caroline Evans; Seema Agarwal; Toby Richards

    Background Preoperative anaemia affects one third of patients undergoing cardiac surgery and is associated with increased mortality and morbidity. Although it is recommended that perioperative teams should identify and treat patients with preoperative anaemia before surgery, introducing new treatment protocols can be challenging in surgical pathways. The aim of this study was to assess the feasibility and effectiveness of introducing a preoperative intravenous iron service as a national initiative in cardiac surgery. Methods We performed a multicentre, stepped, observational study using the UK Association of Cardiothoracic Anaesthesia and Critical Care Research Network. The primary feasibility outcome was the ability to set up an anaemia and intravenous iron clinic at each site. The primary efficacy outcome was change in haemoglobin (Hb) concentration between intervention and operation. Secondary outcomes included blood transfusion and hospital stay. Patients with anaemia were compared with non-anaemic patients and with those who received intravenous iron as part of their routine treatment protocol. Results Seven out of 11 NHS hospitals successfully set up iron clinics over 2 yr, and 228 patients were recruited into this study. Patients with anaemia who received intravenous iron were at higher surgical risk, were more likely to have a known previous history of iron deficiency or anaemia, had a higher rate of chronic kidney disease, and were slightly more anaemic than the non-treated group. Intravenous iron was administered a median (inter-quartile range, IQR [range]) of 33 (15–53 [4–303]) days before surgery. Preoperative intravenous iron increased [Hb] from baseline to pre-surgery; mean (95% confidence interval) change was +8.4 (5.0–11.8) g L−1 (P<0.001). Overall, anaemic compared with non-anaemic patients were more likely to be transfused (49% [59/136] vs 27% (22/92), P=0.001) and stayed longer in hospital (median days [IQR], 9 [7–15] vs 8 [6–11]; P=0.014). The number of days alive and at home was lower in the anaemic group (median days [IQR], 20 [14–22] vs 21 [17–23]; P=0.033). Conclusion The development of an intravenous iron pathway is feasible but appears limited to selected high-risk cardiac patients in routine NHS practise. Although intravenous iron increased [Hb], there is a need for an appropriately powered clinical trial to assess the clinical effect of intravenous iron on patient-centred outcomes.

  • Cost-effectiveness of routine transoesophageal echocardiography during cardiac surgery: a discrete-event simulation study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-20
    Jan M. Dieleman; Paul S. Myles; Liliana Bulfone; Sandra Younie; Bas van Zaane; David McGiffin; Marj Moodie; Lan Gao

    Background The aim of this study was to simulate and compare the healthcare and economic outcomes associated with routine use of intraoperative transoesophageal echocardiography (TOE) in patients undergoing cardiac surgery with those associated with a scenario where TOE is not routinely used. Methods The impact of TOE on surgical decision-making was estimated through a systematic literature review. Individual short-term morbidity and mortality estimates were generated by application of the Society of Thoracic Surgeons risk calculator. Long-term event rates, unit costs, and utility weights were sourced from published literature and expert opinion. A discrete-event simulation model was then constructed to simulate both the in-hospital and post-discharge outcomes for patients undergoing cardiac surgery. Robustness of the base case results was examined through deterministic and probabilistic sensitivity analyses. An incremental cost–effectiveness ratio of €30 000 per quality-adjusted life-year gained was assumed to represent acceptable cost-effectiveness. Results Routine use of intraoperative TOE was associated with lower costs and higher benefits per patient, which indicates that use of TOE is a dominant strategy. The intervention resulted in the avoidance of 299 cardiac complications, 20 strokes, and 11 all-cause deaths per 10 000 patients. Routine intraoperative TOE was associated with an increased occurrence of bleeding owing to more valvular surgery and subsequent long-term anticoagulation. Conclusions Routine intraoperative TOE is a cost-effective procedure for patients undergoing cardiac surgery, leading to lower overall costs. It was associated with a decrease in long-term complications including stroke, cardiac complications, and death, although there was a slight increase in extracranial bleeding events.

  • Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-19
    Duminda N. Wijeysundera; W. Scott Beattie; Graham S. Hillis; Tom E.F. Abbott; Mark A. Shulman; Gareth L. Ackland; C. David Mazer; Paul S. Myles; Rupert M. Pearse; Brian H. Cuthbertson

    Background The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. Methods The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. Results The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96–0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92–0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00–1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01–1.05). Conclusions A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

  • Performance of modern syringe infusion pump assemblies at low infusion rates in the perioperative setting
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-19
    Martina Baeckert; Martin Batliner; Beate Grass; Philipp K. Buehler; Marianne Schmid Daners; Mirko Meboldt; Markus Weiss

    Background Syringe infusion pumps are used for the precise continuous administration of intravenous drugs. Their compliance and mechanical deficiencies have been found to cause considerable start-up delays, flow irregularities during vertical displacement, as well extensive delays of occlusion alarms at low infusion rates. The aim of this study was to evaluate the performance of several modern syringe infusion pumps at low infusion rates and the impact on drug concentration. Methods Seven currently marketed syringe infusion pump assemblies were assessed in an in vitro study during start-up, vertical displacement manoeuvres, and infusion line occlusion at a set flow rate of 1 ml h−1. The measured data were used as input for a pharmacokinetic simulation modelling plasma concentration during a standard neonatal continuous epinephrine infusion. Results The mean time from starting the infusion pump to steady-state flow varied from 89 to 1622 s. The zero-drug delivery time after lowering the pump ranged from 145 to 335 s. In all assemblies tested, occlusion alarm delays and measured flow irregularities during vertical displacement manoeuvres resulted in relevant deviations in plasma epinephrine concentration (>25%) as calculated by the pharmacokinetic simulation model. Conclusion Problems with the performance of syringe infusion pump assemblies can have considerable impact on plasma drug concentration when highly concentrated short-acting cardiovascular drugs are administered at low flow rates. The problems, which affected all assemblies tested, are mainly related to the functional principle of syringe infusion pumps and will only partially be solved by incremental improvements of existing equipment.

  • Socioeconomic deprivation and mortality after emergency laparotomy: an observational epidemiological study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-18
    Thomas E. Poulton; Ramani Moonesinghe; Rosalind Raine; Peter Martin

    Background Socioeconomic circumstances can influence access to healthcare, the standard of care provided, and a variety of outcomes. This study aimed to determine the association between crude and risk-adjusted 30-day mortality and socioeconomic group after emergency laparotomy, measure differences in meeting relevant perioperative standards of care, and investigate whether variation in hospital structure or process could explain any difference in mortality between socioeconomic groups. Methods This was an observational study of 58 790 patients, with data prospectively collected for the National Emergency Laparotomy Audit in 178 National Health Service hospitals in England between December 1, 2013 and November 31, 2016, linked with national administrative databases. The socioeconomic group was determined according to the Index of Multiple Deprivation quintile of each patient's usual place of residence. Results Overall, the crude 30-day mortality was 10.3%, with differences between the most-deprived (11.2%) and least-deprived (9.8%) quintiles (P<0.001). The more-deprived patients were more likely to have multiple comorbidities, were more acutely unwell at the time of surgery, and required a more-urgent surgery. After risk adjustment, the patients in the most-deprived quintile were at significantly higher risk of death compared with all other quintiles (adjusted odds ratio [95% confidence interval]: Q1 [most deprived]: reference; Q2: 0.83 [0.76–0.92]; Q3: 0.84 [0.76–0.92]; Q4: 0.87 [0.79–0.96]; Q5 [least deprived]: 0.77 [0.70–0.86]). We found no evidence that differences in hospital-level structure or patient-level performance in standards of care explained this association. Conclusions More-deprived patients have higher crude and risk-adjusted 30-day mortality after emergency laparotomy, but this is not explained by differences in the standards of care recorded within the National Emergency Laparotomy Audit.

  • Association between postoperative delirium and postoperative cerebral oxygen desaturation in older patients after cardiac surgery
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-18
    Ward Eertmans; Cathy De Deyne; Cornelia Genbrugge; Berend Marcus; Sofian Bouneb; Maud Beran; Tom Fret; Herbert Gutermann; Willem Boer; Margot Vander Laenen; René Heylen; Dieter Mesotten; Pascal Vanelderen; Frank Jans

    Background Near-infrared spectroscopy non-invasively measures regional cerebral oxygen saturation. Intraoperative cerebral desaturations have been associated with worse neurological outcomes. We investigated whether perioperative cerebral desaturations are associated with postoperative delirium in older patients after cardiac surgery. Methods Patients aged 70 yr and older scheduled for on-pump cardiac surgery were included between 2015 and 2017 in a single-centre, prospective, observational study. Baseline cerebral oxygen saturation was measured 1 day before surgery. Throughout surgery and after ICU admission, cerebral oxygen saturation was monitored continuously up to 72 h after operation. The presence of delirium was assessed using the confusion assessment method for the ICU. Association with delirium was evaluated with unadjusted analyses and multivariable logistic regression. Results Ninety-six of 103 patients were included, and 29 (30%) became delirious. Intraoperative cerebral oxygen saturation was not significantly associated with postoperative delirium. The lowest postoperative cerebral oxygen saturation was lower in patients who became delirious (P=0.001). The absolute and relative postoperative cerebral oxygen saturation decreases were more marked in patients with delirium (13 [6]% and 19 [9]%, respectively) compared with patients without delirium (9 [4]% and 14 [5]%; P=0.002 and P=0.001, respectively). These differences in cerebral oxygen saturation were no longer present after excluding cerebral oxygen saturation values after patients became delirious. Older age, previous stroke, higher EuroSCORE II, lower preoperative Mini-Mental Status Examination, and more substantial absolute postoperative cerebral oxygen saturation decreases were independently associated with postoperative delirium incidence. Conclusions Postoperative delirium in older patients undergoing cardiac surgery is associated with absolute decreases in postoperative cerebral oxygen saturation. These differences appear most detectable after the onset of delirium. Clinical trial registration NCT02532530.

  • Hypnosis and communication reduce pain and anxiety in peripheral intravenous cannulation: Effect of Language and Confusion on Pain During Peripheral Intravenous Catheterization (KTHYPE), a multicentre randomised trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-18
    Nicolas Fusco; Franck Bernard; Fabienne Roelants; Christine Watremez; Hervé Musellec; Bruno Laviolle; Helene Beloeil

    Background Clinicians traditionally warn patients of pain before peripheral i.v. cannulation (PIVC). However, using words related to pain or undesirable experiences can result in greater pain and anxiety. The use of positive words can improve pain perception and subjective patient experience. We aimed to compare the effects of three types of communication, including hypnotic communication, on pain, comfort, and anxiety in patients during PIVC. Methods The Effect of Language and Confusion on Pain During Peripheral Intravenous Catheterization (KTHYPE) trial is a randomised, parallel, single-blind, multicentre study of patients undergoing PIVC on the dorsal face of the hand before surgery. Patients from three hospitals were randomly allocated to one of three groups: PIVC performed with a hypnosis technique (hypnosis group), negative connotation (nocebo group), and neutral connotation (neutral group). The primary outcome measure was the occurrence of pain measured with a 0–10 numerical rating scale just after PIVC. Results Of the 272 subjects analysed (hypnosis, n=89; nocebo, n=92; neutral, n=91), pain after PIVC was lower in the hypnosis group (mean [standard deviation]; range) (1.5 [1.9]; 0–5) compared with the neutral (3.5 [2.3]; 0–9; P<0.0001) and nocebo groups (3.8 [2.5]; 0–10; P<0.0001). Whilst anxiety was higher and comfort lower before PIVC in the hypnosis group, anxiety decreased and comfort perception increased after PIVC when hypnosis was used. Conclusions This is one of the first well-designed RCTs showing a significant benefit of a hypnosis technique during a routine procedure, such as PIVC. The results could facilitate implementation of hypnosis in daily clinical care. Clinical trial registration NCT02662322.

  • Acquired loss of cardiac vagal activity is associated with myocardial injury in patients undergoing noncardiac surgery: prospective observational mechanistic cohort study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-09-03
    Shaun M. May; Anna Reyes; Gladys Martir; Joseph Reynolds; Laura Gallego Paredes; Shamir Karmali; Robert C.M. Stephens; David Brealey; Gareth L. Ackland

    Background Myocardial injury is more frequent after noncardiac surgery in patients with preoperative cardiac vagal dysfunction, as quantified by delayed heart rate (HR) recovery after cessation of cardiopulmonary exercise testing. We hypothesised that serial and dynamic measures of cardiac vagal activity are also associated with myocardial injury after noncardiac surgery. Methods Serial autonomic measurements were made before and after surgery in patients undergoing elective noncardiac surgery. Cardiac vagal activity was quantified by HR variability and HR recovery after orthostatic challenge (supine to sitting). Revised cardiac risk index (RCRI) was calculated for each patient. The primary outcome was myocardial injury (high-sensitivity troponin ≥15 ng L−1) within 48 h of surgery, masked to investigators. The exposure of interest was cardiac vagal activity (high-frequency power spectral analysis [HFLn]) and HR recovery 90 s from peak HR after the orthostatic challenge. Results Myocardial injury occurred in 48/189 (25%) patients, in whom 41/48 (85%) RCRI was <2. In patients with myocardial injury, vagal activity (HFLn) declined from 5.15 (95% confidence interval [CI]: 4.58–5.72) before surgery to 4.33 (95% CI: 3.76–4.90; P<0.001) 24 h after surgery. In patients who remained free of myocardial injury, HFLn did not change (4.95 [95% CI: 4.64–5.26] before surgery vs 4.76 [95% CI: 4.44–5.08] after surgery). Before and after surgery, the orthostatic HR recovery was slower in patients with myocardial injury (5 beats min−1 [95% CI: 3–7]), compared with HR recovery in patients who remained free of myocardial injury (10 beats min−1 [95% CI: 7–12]; P=0.02). Conclusions Serial HR measures indicating loss of cardiac vagal activity are associated with perioperative myocardial injury in lower-risk patients undergoing noncardiac surgery.

  • Effect of goal-directed crystalloid- versus colloid-based fluid strategy on tissue oxygen tension: a randomised controlled trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-15
    Christian Reiterer; Barbara Kabon; Oliver Zotti; Mina Obradovic; Andrea Kurz; Edith Fleischmann

    Background Sufficient tissue oxygen tension may reduce the risk of postoperative wound infections. Supplemental administration of crystalloids increases subcutaneous oxygen tension (Psqo2). Colloids remain longer in the intravascular system and might therefore increase Psqo2 even more than crystalloids. Therefore, we tested the hypothesis that goal-directed colloid administration increases the perioperative Psqo2 more compared with crystalloid administration. Methods We randomly assigned 80 patients undergoing elective open abdominal surgery to receive fluid boluses of hydroxyethyl starch (HES) or lactated Ringer's (LR) solution guided by oesophageal Doppler. Intraoperative Psqo2 was measured in the upper arm. After operation, we measured the Psqo2 in the upper arm and in the surgical wound. Results Forty patients were enrolled in each group. Patients in the colloid group received HES solution 750 ml (500; 1000) and LR solution 1500 ml (1000; 2000). Patients in the crystalloid group received LR solution 2825 ml (2000; 3960). The goal-directed administration of colloids did not improve intraoperative Psqo2 in the arm compared with crystalloid administration (11.4 kPa [9.0; 16.6] vs 11.2 kPa [8.6; 15.1], respectively; P=0.58). Postoperative arm Psqo2 was 8.1 kPa (6.5; 9.6) in the colloid group and 7.3 kPa (5.7; 9.1) in the crystalloid group (P=0.11). Postoperative surgical wound Psqo2 was 10.7 kPa (8.6; 13.4) in the colloid group and 10.1 kPa (8.1; 12.7) in the crystalloid group (P=0.68). Conclusions Goal-directed colloid administration did not increase Psqo2 compared with goal-directed crystalloid administration in patients undergoing open abdominal surgery. Clinical trial registration NCT00517127.

  • Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-24
    Kun Wang; Mengge Wu; Jian Xu; Changshuai Wu; Baohui Zhang; Guonian Wang; Daqing Ma

    Background Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. Methods We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. Results Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. Conclusions DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.

  • Perioperative adverse events attributed to α2-adrenoceptor agonists in patients not at risk of cardiovascular events: systematic review and meta-analysis
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-14
    Migena Demiri; Tiago Antunes; Dominique Fletcher; Valeria Martinez

    Background Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. Methods We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. Results We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 μg kg−1 or with continuous administration alone. Conclusions Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. Protocol registration CRD42017071583.

  • Exposure to surgery under general anaesthesia and brain magnetic resonance imaging changes in older adults
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-03
    Juraj Sprung; S. Chandralekha Kruthiventi; David O. Warner; David S. Knopman; Ronald C. Petersen; Michelle M. Mielke; Clifford R. Jack; Jonathan Graff-Radford; David P. Martin; Andrew C. Hanson; Darrell R. Schroeder; Scott A. Przybelski; Phillip J. Schulte; Toby N. Weingarten; Prashanthi Vemuri

    Background Preclinical studies suggest that exposure to general anaesthesia (GA) could cause neurodegeneration consistent with Alzheimer's disease (AD) pathology. Brain magnetic resonance imaging (MRI) is useful to study structural brain changes. We tested the hypothesis that exposure to surgery with GA (surgery/GA) is associated with greater cortical thinning and increased frequency of white matter lesions. Methods This is a cross-sectional analysis of 70–91-yr-old participants enrolled in the Mayo Clinic Study of Aging who had baseline MRI. The thickness of selected cortical regions, the volume of white matter hyperintensities, and the frequency of cortical infarctions were compared in participants who were and were not exposed to surgery/GA within 20 yr before the first MRI obtained after enrolment. Results Of 1410 participants with MRI scans, 932 were exposed to surgery/GA before scanning. In adjusted analyses, cortical thickness in regions vulnerable to AD was significantly less in those exposed to surgery/GA in the prior 20 yr (difference −0.023 mm, [95% confidence interval (CI) −0.041 to −0.005], P=0.014). Those with surgery in the prior 20 yr were more likely to have ‘abnormal thickness’ compared with those without surgery (odds ratio=1.45, [95% CI 1.10–1.90], P=0.009). Exposure was not associated with white matter hyperintensities or the presence of brain infarcts. Conclusions This study suggests that exposure of older adults to surgical anaesthesia is associated with thinning in cortical regions implicated in AD. The pathogenesis and mechanisms driving these neurodegenerative changes, and the potential clinical significance of these findings, require further study.

  • Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-09-28
    Dongyi Tong; Christin M. Godale; Feni K. Kadakia; Zhiqing Gu; Cole S.K. Danzer; Alaa Alghamdi; Ping Zhao; Andreas W. Loepke; Steve C. Danzer

    Background Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be ‘injured’ and integrate abnormally into the brain. Methods The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later. Results The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37–1.5; P=0.010). Conclusions A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.

  • Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-14
    Jiandong Gao; Zhihua Sun; Zhaoyang Xiao; Qihang Du; Xinhuan Niu; Gongming Wang; Yu-Wen Chang; Yongtao Sun; Wei Sun; Amity Lin; Jacqueline C. Bresnahan; Mervyn Maze; Michael S. Beattie; Jonathan Z. Pan

    Background Spinal cord injury induces inflammatory responses that include the release of cytokines and the recruitment and activation of macrophages and microglia. Neuroinflammation at the lesion site contributes to secondary tissue injury and permanent locomotor dysfunction. Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is anti-inflammatory and neuroprotective in both preclinical and clinical trials. We investigated the effect of DEX on the microglial response, and histological and neurological outcomes in a rat model of cervical spinal cord injury. Methods Anaesthetised rats underwent unilateral (right) C5 spinal cord contusion (75 kdyne) using an impactor device. The locomotor function, injury size, and inflammatory responses were assessed. The effect of DEX was also studied in a microglial cell culture model. Results DEX significantly improved the ipsilateral upper-limb motor dysfunction (grooming and paw placement; P<0.0001 and P=0.0012), decreased the injury size (P<0.05), spared white matter (P<0.05), and reduced the number of activated macrophages (P<0.05) at the injury site 4 weeks post-SCI. In DEX-treated rats after injury, tissue RNA expression indicated a significant downregulation of pro-inflammatory markers (e.g. interleukin [IL]-1β, tumour necrosis factor-α, interleukin (IL)-6, and CD11b) and an upregulation of anti-inflammatory and pro-resolving M2 responses (e.g. IL-4, arginase-1, and CD206) (P<0.05). In lipopolysaccharide-stimulated cultured microglia, DEX produced a similar inflammation-modulatory effect as was seen in spinal cord injury. The benefits of DEX on these outcomes were mostly reversed by an α2-adrenergic receptor antagonist. Conclusions DEX significantly improves neurological outcomes and decreases tissue damage after spinal cord injury, which is associated with modulation of neuroinflammation and is partially mediated via α2-adrenergic receptor signaling.

  • Results of a phase 1 multicentre investigation of dexmedetomidine bolus and infusion in corrective infant cardiac surgery
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-14
    Athena F. Zuppa; Susan C. Nicolson; Nicole S. Wilder; Juan C. Ibla; Erin A. Gottlieb; Kristin M. Burns; Mario Stylianou; Felicia Trachtenberg; Hua Ni; Tera H. Skeen; Dean B. Andropoulos

    Background Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing. Methods We included 122 neonates and infants (0–180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200–300 pg ml−1), medium (400–500 pg ml−1), and high (600–700 pg ml−1) DEX plasma concentrations. Results Five of 122 subjects had adverse safety outcomes (4.1%; 95% confidence interval [CI], 1.8–9.2%). Two had junctional rhythm, two had second-/third-degree atrioventricular block, and one had hypotension. Clearance (CL) immediately postoperative and CL on CPB were reduced by approximately 50% and 95%, respectively, compared with pre-CPB CL. DEX clearance after CPB was 1240 ml min−1 70 kg−1. Age at 50% maximum clearance was approximately 2 days, and that at 90% maximum clearance was 18 days. Overall, 96.1% of measured DEX concentrations fell within the 5th–95th percentile prediction intervals in the PK model validation. Dosing strategies are recommended for steady-state DEX plasma levels ranging from 200 to 1000 pg ml−1. Conclusions When used with a careful dosing strategy, DEX results in low incidence and severity of adverse safety events in infants undergoing cardiac surgery with cardiopulmonary bypass. This validated PK model should assist clinicians in selecting appropriate dosing. The results of this phase 1 trial provide preliminary data for a phase 3 trial of DEX neuroprotection. Clinical trials registration NCT01915277.

  • Dopaminergic neurotransmission and genetic variation in chronification of post-surgical pain
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-09-23
    Roel R.I. van Reij; Elbert A.J. Joosten; Nynke J. van den Hoogen

    Chronic post-surgical pain (CPSP) is a debilitating condition affecting 10–50% of surgical patients. The current treatment strategy for CPSP is not optimal, and the identification of genetic variation in surgical patients might help to improve prediction and treatment of CPSP. The neurotransmitter dopamine (DA) has been associated with several chronic pain disorders. This narrative review focuses on DA neurotransmission as a potential target in the treatment of CPSP. The current knowledge on genetic variation within DA neurotransmission and its role in CPSP susceptibility are reviewed. Three genes involved in DA neurotransmission (COMT, GCH1, and DRD2) have been associated with variability in pain sensitivity, development of CPSP, and analgesic requirement. The direction of the effect of the association is sometimes inconclusive because of contradictory results, but ample evidence suggests a modulatory role of DA. Because of this modulatory role, DA is an excellent pharmacological target in the treatment of pain. Pharmacotherapy focused on DA neurotransmission has potential in both prevention (via D1-like receptors) and treatment (via D2-like receptors and DA reuptake inhibitors) of CPSP. The development of prediction models including genetic risk factors is necessary to better identify patients at risk.

  • Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-05
    Myoung H. Kim; Ju E. Oh; Seho. Park; Joo H. Kim; Ki Y. Lee; Sun J. Bai; Hyunjik Song; Hye J. Hwang; Dong W. Kim; Young C. Yoo

    Background There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. Methods Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. Results Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. Conclusions After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.

  • An automated machine learning-based model predicts postoperative mortality using readily-extractable preoperative electronic health record data
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-15
    Brian L. Hill; Robert Brown; Eilon Gabel; Nadav Rakocz; Christine Lee; Maxime Cannesson; Pierre Baldi; Loes Olde Loohuis; Ruth Johnson; Brandon Jew; Uri Maoz; Aman Mahajan; Sriram Sankararaman; Ira Hofer; Eran Halperin

    Background Rapid, preoperative identification of patients with the highest risk for medical complications is necessary to ensure that limited infrastructure and human resources are directed towards those most likely to benefit. Existing risk scores either lack specificity at the patient level or utilise the American Society of Anesthesiologists (ASA) physical status classification, which requires a clinician to review the chart. Methods We report on the use of machine learning algorithms, specifically random forests, to create a fully automated score that predicts postoperative in-hospital mortality based solely on structured data available at the time of surgery. Electronic health record data from 53 097 surgical patients (2.01% mortality rate) who underwent general anaesthesia between April 1, 2013 and December 10, 2018 in a large US academic medical centre were used to extract 58 preoperative features. Results Using a random forest classifier we found that automatically obtained preoperative features (area under the curve [AUC] of 0.932, 95% confidence interval [CI] 0.910–0.951) outperforms Preoperative Score to Predict Postoperative Mortality (POSPOM) scores (AUC of 0.660, 95% CI 0.598–0.722), Charlson comorbidity scores (AUC of 0.742, 95% CI 0.658–0.812), and ASA physical status (AUC of 0.866, 95% CI 0.829–0.897). Including the ASA physical status with the preoperative features achieves an AUC of 0.936 (95% CI 0.917–0.955). Conclusions This automated score outperforms the ASA physical status score, the Charlson comorbidity score, and the POSPOM score for predicting in-hospital mortality. Additionally, we integrate this score with a previously published postoperative score to demonstrate the extent to which patient risk changes during the perioperative period.

  • Humanistic medicine in anaesthesiology: development and assessment of a curriculum in humanism for postgraduate anaesthesiology trainees
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-05
    Cecilia Canales; Suzanne Strom; Cynthia T. Anderson; Michelle A. Fortier; Maxime Cannesson; Joseph B. Rinehart; Zeev N. Kain; Danielle Perret

    Background An unintended consequence of medical technologies is loss of personal interactions and humanism between patients and their healthcare providers, leading to depersonalisation of medicine. As humanism is not integrated as part of formal postgraduate anaesthesiology education curricula, our goal was to design, introduce, and evaluate a comprehensive humanism curriculum into anaesthesiology training. Methods Subject-matter experts developed and delivered the humanism curriculum, which included interactive workshops, simulation sessions, formal feedback, and patient immersion experience. The effectiveness of the programme was evaluated using pre- and post-curriculum assessments in first-year postgraduate trainee doctors (residents). Results The anaesthesiology residents reported high satisfaction scores. Pre-/post-Jefferson Scale of Patient Perceptions of Physician Empathy showed an increase in empathy ratings with a median improvement of 12 points (range; P=0.013). After training, patients rated the residents as more empathetic (31 [4] vs 22 [5]; P<0.001; 95% confidence interval [CI]: 7–12) and professional (47 [3] vs 35 [8]; P<0.001; 95% CI: 9–16). Patient overall satisfaction with their anaesthesia provider improved after training (51 [6] vs 37 [10]; P<0.001; 95% CI: 10–18). Patients rated their anxiety lower in the post-training period compared with pretraining (1.8 [2.3] vs 3.6 [1.6]; P=0.001; 95% CI: 0.8–2.9). Patient-reported pain scores decreased after training (2.3 [2.5] vs 3.8 [2.1]; P=0.010; 95% CI: 0.4–2.8). Conclusions Implementation of a humanism curriculum during postgraduate anaesthesiology training was well accepted, and can result in increased physician empathy and professionalism. This may improve patient pain, anxiety, and overall satisfaction with perioperative care.

  • Lung-protective ventilation for the surgical patient: international expert panel-based consensus recommendations
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-03
    Christopher C. Young; Erica M. Harris; Charles Vacchiano; Stephan Bodnar; Brooks Bukowy; R. Ryland D. Elliott; Jaclyn Migliarese; Chad Ragains; Brittany Trethewey; Amanda Woodward; Marcelo Gama de Abreu; Martin Girard; Emmanuel Futier; Jan P. Mulier; Paolo Pelosi; Juraj Sprung

    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.

  • Promoting anaesthetisia providers' non-technical skills through the Vital Anaesthesia Simulation Training (VAST) course in a low-resource setting
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-12
    Adam I. Mossenson; Eugene Tuyishime; David Rawson; Christian Mukwesi; Sara Whynot; Sean P. Mackinnon; Patricia Livingston

    Background Short educational programmes are important in building global anaesthesia workforce capacity. The Vital Anaesthesia Simulation Training (VAST) course is a 3-day immersive simulation-based programme concentrating on core clinical challenges and non-technical skills required by anaesthesia providers in low-resource settings. Methods This mixed methods study prospectively evaluated the impact of VAST in Rwanda. Anaesthetists' Non-Technical Skills (ANTS) scores were quantitatively assessed for 30 course participants at three time points (pre-, post-, and 4 months after VAST). Qualitative data were gathered during focus groups (4 months after VAST) to learn of participants' experiences implementing new knowledge into clinical practice. Results The ANTS total scores improved from pre- (11.0 [2.3]) (mean [standard deviation]) to post-test (14.0 [1.6]), and improvements were maintained at retention (14.2 [1.7]). A similar pattern was observed when data were analysed using the four ANTS categories (all P<0.001). The key theme that emerged during focus group discussions was that the use of cognitive aids and clinical algorithms, repeated and reinforced across simulated scenarios, encouraged a systematic approach to patient care. The participants attributed the systematic approach to improving their problem-solving skills and confidence, particularly during emergencies. They found value in well-functioning teams and shared decision-making. After VAST, the participants described empowerment to advocate for better patient care and system improvement. Conclusions VAST offers a simulation-based training to anaesthesia providers working in low-resource settings. Skills retention and self-reported application of learning into the workplace reflect the scope of impact of this training.

  • Pathophysiological and clinical considerations in the perioperative care of patients with a previous ischaemic stroke: a multidisciplinary review
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-06
    Jatinder S. Minhas; William Rook; Ronney B. Panerai; Ryan L. Hoiland; Phil N. Ainslie; Jonathan P. Thompson; Amit K. Mistri; Thompson G. Robinson

    With an ageing population and increasing incidence of cerebrovascular disease, an increasing number of patients presenting for routine and emergency surgery have a prior history of stroke. This presents a challenge for pre-, intra-, and postoperative management as the neurological risk is considerably higher. Evidence is lacking around anaesthetic practice for patients with vascular neurological vulnerability. Through understanding the pathophysiological changes that occur after stroke, insight into the susceptibilities of the cerebral vasculature to intrinsic and extrinsic factors can be developed. Increasing understanding of post-stroke systemic and cerebral haemodynamics has provided improved outcomes from stroke and more robust secondary prevention, although this knowledge has yet to be applied to our delivery of anaesthesia in those with prior stroke. This review describes the key pathophysiological and clinical considerations that inform clinicians providing perioperative care for patients with a prior diagnosis of stroke.

  • Emergency front of neck access in children: a new learning approach in a rabbit model
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-04
    Francis Ulmer; Julian Lennertz; Robert Greif; Lukas Bütikofer; Lorenz Theiler; Thomas Riva

    Background Cannot-intubate cannot-ventilate situations in healthy children are uncommon but are often associated with poor outcome. Several airway management algorithms suggest emergency tracheal access. Little agreement exists on how to perform emergency front of the neck access (eFONA) in children <8 yr. We studied the learning curves of clinicians performing simulated paediatric eFONA. Methods After watching an instructional video, 50 physicians, from five medical specialties, performed 10 emergency tracheotomies on rabbit cadavers. We analysed their learning curves relative to performance time and concurring injuries. Results With an overall success rate of 94%, performance time decreased from 107 s (standard deviation [sd], 45) to 55 s (sd 17) over 10 attempts. The learning curve was steep between the first and the fourth attempts with an 11% decrease in performance time (95% confidence interval [CI], 9–13%; P<0.001) per attempt and then flattened to a 4% (95% CI, 3–5%; P<0.001) decrease per attempt between the fourth and the tenth attempt. Age, years of clinical experience, and sex showed a significant effect on the learning curve, whereas medical specialty and adult eFONA experience did not. The 58% (95% CI, 44–72%) probability for severe injury during the first attempt decreased to 14% (95% CI, 8–20%) at the second attempt. Men were more likely to cause minor injuries than women (P<0.001). Conclusions Irrespective of medical specialty, paediatric clinicians acquired the eFONA technique within four attempts and were on average able to establish an airway in <1 min when performing emergency tracheotomy on a paediatric airway simulator. Clinical trial registration NCT03576352.

  • Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-12-04
    Preet M. Singh; Narinder P. Singh; Matthew Reschke; Warwick D.Ngan Kee; Arvind Palanisamy; David T. Monks

    Background The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. Methods RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. Results We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. Conclusion Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.

  • Comparison of incidence of anaphylaxis between sugammadex and neostigmine: a retrospective multicentre observational study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-30
    Masaki Orihara; Tomonori Takazawa; Tatsuo Horiuchi; Shinya Sakamoto; Kazuhiro Nagumo; Yukinari Tomita; Akihiro Tomioka; Nagahide Yoshida; Akihiko Yokohama; Shigeru Saito

    Background Although cases of anaphylaxis caused by sugammadex have been reported, its incidence remains uncertain. Conversely, no studies have evaluated the incidence of anaphylaxis to neostigmine. Methods This was a retrospective multicentre observational study of patients who underwent surgery under general anaesthesia between 2012 and 2016 to compare the incidence of anaphylaxis with sugammadex with that of neostigmine at four tertiary hospitals in Japan. To ensure the quality of diagnosis, only cases with a clinical history suggestive of anaphylaxis, along with positive results from in vitro or in vivo testing, were assessed. Results From a total of 49 532 patients who received general anaesthesia included in this study, 18 cases of anaphylaxis were reported, of which six were attributable to sugammadex and none to neostigmine. There were no fatalities attributable to anaphylaxis. The incidence of anaphylaxis caused by all drugs or by sugammadex was calculated as 0.036% (95% confidence interval [CI]: 0.022–0.057%) and 0.02% (of the number of sugammadex cases) (95% CI: 0.007–0.044%), respectively. Conclusions The results suggest that neostigmine might be safer than sugammadex when assessing only the incidence of anaphylaxis. We believe that there is room for reconsideration of the choice of reversal agent for neuromuscular blocking agents by all anaesthetists. Clinical trial registration UMIN000022365; UMIN000033561.

  • Effect of reversal of deep neuromuscular block with sugammadex or moderate block by neostigmine on shoulder pain in elderly patients undergoing robotic prostatectomy
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-26
    Wendell H. Williams; Juan P. Cata; Javier D. Lasala; Neema Navai; Lei Feng; Vijaya Gottumukkala

    Background For some laparoscopic procedures, deep neuromuscular block has been shown to facilitate lower insufflation pressures and lower patient pain scores, and enhance postoperative recovery. We investigated the impact of deep neuromuscular block and its reversal on postoperative shoulder pain and outcomes after robotic prostate surgery. Methods Elderly men undergoing robotic prostatectomy were randomised to deep neuromuscular block (target post-tetanic twitch of 1–2 at the facial nerve) with sugammadex reversal or moderate neuromuscular block (target 1–2 train-of-four ratio) with neostigmine reversal. The primary endpoint was postoperative shoulder pain. The secondary endpoints included intraoperative insufflation pressure, surgical rating score, incidence of residual neuromuscular block, and postoperative recovery. Results A total of 50 subjects for each treatment arm were included in the analysis. The degree of neuromuscular block had no effect on the incidence of shoulder pain (deep block group 12% vs moderate block group 10%; P=1.0) or average insufflation pressure (median [inter-quartile range]) (13.3 [12.5–13.6] mm Hg vs 13.3 [11.7–14] mm Hg, P=0.86). After surgery, the deep block group had a higher normalised train-of-four ratio (0.98 [0.79–1.11] vs 0.85 [0.74–1.00]; P=0.008). The presence of postoperative shoulder pain was associated with higher BMI (31.8 [28–33.9] kg m−2 vs 28 [24.8–31.1] kg m−2; P=0.036) and longer insufflation time (186 [156–257] min vs 154 [126–198] min; P=0.028). Conclusions The use of deep neuromuscular block during surgery does not decrease postoperative shoulder pain or enhance recovery after robotic prostatectomy. Clinical trial registration NCT03210376.

  • Patterns in medication incidents: A 10-yr experience of a cross-national anaesthesia incident reporting system
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-25
    Yolanda Sanduende-Otero; Javier Villalón-Coca; Eva Romero-García; Óscar Díaz-Cambronero; Paul Barach; Daniel Arnal-Velasco

    Background Medication-related adverse events (MRE) in anaesthesia care are frequent and require a deeper understanding if we are to prevent medication harm. Methods We searched for reported MRE from the Spanish Anaesthesia Incident Reporting System (SENSAR) database over a 10-yr period. SENSAR is a cross-national, multicentre system focused on perioperative and critical care. A descriptive analysis of independent variables, phase of medication process, type of MRE, and medication group involved, and their relationships with morbidity was conducted. Results A total of 1970 MRE were identified from 7072 reported incidents. Patient harm was reported in 31% of the MRE. The administration phase was more frequent (42%) and showed the highest harm rate (44%) compared with other medication process phases. The most frequent types of MRE were wrong treatment regimen and wrong medication (55% of cases). The medication groups most commonly reported were those that alter haemostasis (18%), vasoconstrictor agents (13%), and opioids (10%). Vasoconstrictor agents, benzodiazepines, and neuromuscular blocking agents were the medication groups involved in patient harm four-fold more, and opioids three-fold more, than medications that alter haemostasis. The 1970 incidents were investigated and led to implementation of 4223 local corrective patient safety and quality improvement measures. Conclusions Patient harm in the perioperative setting from medications remains a major issue for patients, hospital leaders, and clinicians. We found patterns and specific causes that can be mitigated through proven systems solutions, and should be taken into consideration in designing sustainable solutions for safe perioperative care. Clinical trial registration NCT03615898.

  • Association between postoperative complications and lingering post-surgical pain: an observational cohort study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-23
    Mark Willingham; Govind Rangrass; Caitlin Curcuru; Arbi Ben Abdallah; Troy S. Wildes; Sherry McKinnon; Alex Kronzer; Anshuman Sharma; Dan Helsten; Bruce Hall; Michael S. Avidan; Simon Haroutounian

    Background Post-surgical pain that lingers beyond the initial few-week period of tissue healing is a major predictor of pain chronification, which leads to substantial disability and new persistent opioid analgesic use. We investigated whether postoperative medical complications increase the risk of lingering post-surgical pain. Methods The study population consisted of patients undergoing diverse elective surgical procedures in an academic referral centre in the USA, between September 2013 and May 2017. Multivariable logistic regression, adjusting for confounding variables and patient-specific risk factors, was used to test for an independent association between any major postoperative complication and functionally limiting lingering pain 1–3 months after surgery, as obtained from patient self-reports. Results The cohort included 11 986 adult surgical patients; 10 562 with complete data. At least one complication (cardiovascular, respiratory, renal/gastrointestinal, wound, thrombotic, or neural) was reported by 13.3% (95% confidence interval: 12.7–14.0) of patients, and 19.7% (19.0–20.5%) reported functionally limiting lingering post-surgical pain. After adjusting for known risk factors, the patients were twice as likely (odds ratio: 2.04; 1.78–2.35) to report lingering post-surgical pain if they also self-reported a postoperative complication. Experiencing a complication was also independently predictive of lingering post-surgical pain (odds ratio: 1.95; 1.26–3.04) when complication data were extracted from the National Surgical Quality Improvement Program registry, instead of being obtained from patient self-report. Conclusions Medical complications were associated with a two-fold increase in functionally limiting pain 1–3 months after surgery. Understanding the mechanisms that link complications to pathological persistence of pain could help develop future approaches to prevent persistent post-surgical pain.

  • Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-22
    Carlos Ferrando; César Aldecoa; Carmen Unzueta; F. Javier Belda; Julián Librero; Gerardo Tusman; Fernando Suárez-Sipmann; Salvador Peiró; Natividad Pozo; Andrea Brunelli; Ignacio Garutti; Clara Gallego; Aurelio Rodríguez; Jose Ignacio García; Oscar Díaz-Cambronero; Jaume Balust; Francisco J. Redondo; Manuel de la Matta; Sara Visiedo

    Background We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59–1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48–1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. Clinical trial registration NCT02776046.

  • Predicting acute postoperative pain by the Qnox score at the end of surgery: a prospective observational study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-21
    Thomas Ledowski; Isabel Schmitz-Rode

    Background The QNox score (Quantium Medical S.L., distributed by Fresenius Kabi) has recently been introduced as a tool to quantify intraoperative analgesia. Being based on the analysis of electroencephalographic data, QNox is distinctly different to other methods of nociception monitoring that rely almost entirely on the assessment of sympathetic activity. However, there are currently no published data to validate use of QNox in a clinical setting. We investigated the value of pre-arousal QNox data at the end of surgery for prediction of acute postoperative pain in the PACU. Methods A total of 150 patients scheduled for non-emergency surgery under sevoflurane-opioid general anaesthesia were included in the study. At the end of surgery but before patient arousal, QNox was measured minutely for 5 min. After admission to the recovery room, pain scores (numeric rating scale [NRS], 0–10) were obtained 5 minutely for 15 min. Results Data from 144 patients were analysed. QNox before arousal showed no correlation (ρ=0.057) with acute postoperative pain in the PACU. Furthermore, the score was found to have no value for the prediction of acute postoperative pain (area under the receiver operating curve, 0.501; 95% confidence interval, 0.406–0.597). Conclusion QNox at the end of surgery before arousal showed no association with and allowed no prediction of acute pain in the PACU. Clinical trial registration ACTRN12618001662257.

  • Effects of positive end-expiratory pressure/recruitment manoeuvres compared with zero end-expiratory pressure on atelectasis during open gynaecological surgery as assessed by ultrasonography: a randomised controlled trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-14
    Vincent Généreux; Michaël Chassé; François Girard; Nathalie Massicotte; Carl Chartrand-Lefebvre; Martin Girard

    Background During general anaesthesia, most patients develop atelectasis, which promotes postoperative pulmonary complications. RCTs that investigated perioperative lung protection have failed to reduce postoperative pulmonary complications consistently. Ultrasound imaging could help confirm the effects of different protective ventilatory strategies, but this has not been tested in trials. The objective of this study was to use ultrasonography to evaluate whether lung-protective ventilation measures reduce perioperative atelectasis. Methods We conducted a prospective, randomised patient- and assessor-blinded controlled trial in women undergoing open gynaecological surgery. Subjects were randomised to either lung protection or zero end-expiratory pressure (ZEEP; with no recruitment manoeuvres [RMs]). Lung protection entailed PEEP (7 cm H2O) and RMs every 30 min. Lung ultrasonography was undertaken at five predefined time points. The primary outcome was the difference in lung ultrasonography score (LUS) between groups before emergence; a lower LUS indicates better lung aeration. Results We recruited 45 women (34–85 yr old). Women randomised to lung protection had lower mean (standard deviation) LUS before emergence (6.1 [3.7]), compared with women randomised to ZEEP (11.7 [3.9]; 95% confidence interval for the difference between group means [–7.9 to –3.2]; P<0.0001). This difference did not persist after extubation, with similar mean LUSs in women who had received intraoperative lung protection (7.0 [4.1]), compared with women randomised to receive ZEEP (7.7 [3.1]). Conclusions As assessed by lung ultrasonography, intraoperative PEEP/RMs decreased aeration loss during general anaesthesia. However, similar degrees of aeration loss were observed after tracheal extubation regardless of intraoperative ventilatory strategy. Clinical trial registration NCT02055807.

  • Effect of intravenous dexamethasone on the anaesthetic characteristics of peripheral nerve block: a double-blind, randomised controlled, dose–response volunteer study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-11-09
    Anthony Short; Kariem El-Boghdadly; Hance Clarke; Tomomi Komaba; Rongyu Jin; Ki Jinn Chin; Vincent Chan

    Background Intravenous dexamethasone is thought to prolong the duration of peripheral nerve block, but the dose–response relationship remains unclear. The aim of this volunteer study was to evaluate the dose–response effect of i.v. dexamethasone on the prolongation of median nerve block. Methods In a double-blind, randomised controlled study, 18 volunteer subjects received two median nerve blocks separated by a washout period. One block was conducted alongside an infusion of saline and the other alongside i.v. dexamethasone 2, 4, or 8 mg. The primary outcome was time to return of normal pinprick sensation. Secondary outcomes included thermal quantitative sensory testing (QST) for the time to return of cold detection threshold (CDT), warm detection threshold (WDT), cold pain threshold (CPT), heat pain threshold (HPT), area under QST curves, grip strength, and the incidence of adverse effects. Results The primary outcome, time to recovery of pinprick sensation, was similar between volunteers receiving saline or i.v. dexamethasone, regardless of dose (P=0.99). The time to recovery of QST milestones was similar between groups, although area under QST curves indicated prolongation of CDT (0 vs 8 mg, P=0.002) and WDT (0 vs 2 mg, P=0.008; 0 vs 4 mg, P=0.001; 0 vs 8 mg, P<0.001). There was no difference in motor recovery or adverse effects. Conclusions Intravenous dexamethasone failed to significantly prolong the duration of pinprick anaesthesia regardless of dose. However, area under QST curve analysis indicated a dose-independent prolongation of CDT and WDT, the clinical significance of which is unclear. Clinical trial registration NCT02864602 (clinicaltrials.gov).

  • Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-24
    Julian Rössler; Felix Schoenrath; Burkhardt Seifert; Alexander Kaserer; Gabriela H. Spahn; Volkmar Falk; Donat R. Spahn

    Background Iron deficiency is frequent in patients undergoing cardiac surgery. The relevance of iron deficiency, however, is ill defined. Therefore, our study aimed to investigate the impact of iron deficiency (ferritin <100 μg L−1) with or without concomitant anaemia on clinical outcome after cardiac surgery. Methods In this prospective observational study, 730 patients undergoing elective cardiac surgery were assigned into four groups according to their iron status and anaemia. Mortality, serious adverse events (SAEs), major cardiac and cerebrovascular events (MACCEs), allogenic blood transfusion requirements, and length of hospital stay were assessed during a 90-day follow-up period. The effect of iron deficiency on these outcomes was first calculated in models adjusting for anaemia only, followed by two multivariate models adjusting for anaemia and either the EuroSCORE II or any possible confounders. Results The presence of iron deficiency (ferritin <100 μg L−1) was associated with an increase in 90-day mortality from 2% to 5% in patients without anaemia, and from 4% to 14% in patients with anaemia. Logistic regression resulted in an odds ratio of 3.5 (95% confidence interval: 1.5–8.4); P=0.004. The effect persisted in both multivariate models. Moreover, iron deficiency was associated with an increased incidence of SAEs, MACCEs, transfusion, and prolonged hospital stay. Conclusions Preoperative iron deficiency (ferritin <100 μg L−1) was independently associated with increased mortality, more SAEs, and prolonged hospital stay after cardiac surgery. These findings underline the importance of preoperative iron deficiency screening in the context of a comprehensive patient blood management programme, and highlight its importance as a research topic in cardiac surgery. Clinical trial registration NCT02031289.

  • The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-22
    Brian A. Baldo; Michael A. Rose

    Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT2A but not 5-HT1A receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.

  • Use of a train-of-four ratio of 0.95 versus 0.9 for tracheal extubation: an exploratory analysis of POPULAR data
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-10
    Manfred Blobner; Jennifer M. Hunter; Claude Meistelman; Andreas Hoeft; Markus W. Hollmann; Eva Kirmeier; Heidrun Lewald; Kurt Ulm

    Background The prospective observational European multicentre cohort study (POPULAR) of postoperative pulmonary complications (NCT01865513) did not demonstrate that adherence to the recommended train-of-four ratio (TOFR) of 0.9 before extubation was associated with better pulmonary outcomes from the first postoperative day up to hospital discharge. We re-analysed the POPULAR data as to whether there existed a better threshold for TOFR recovery before extubation to reduce postoperative pulmonary complications in patients who had quantitative neuromuscular monitoring (87% acceleromyography). Methods To identify the optimal TOFR, the complete case cohort of patients with quantitative neuromuscular monitoring (n=3150) was split into several pairs of sub-cohorts related to TOFR values from 0.86 to 0.96; values of 0.97 and higher could not be used as the sub-cohorts were too small. The optimal TOFR was considered to have the lowest P-value from multivariate logistic regression calculated for each of the TOFR values. Data are presented as adjusted absolute risk reduction or median difference with 95% confidence interval. Results Extubating patients with TOFR >0.95 rather than >0.9 reduced the adjusted risk of postoperative pulmonary complications by 3.5% (0.7–6.0%) from that reported in POPULAR (11.3%). Increasing the recommended TOFR from 0.9 to 0.95 reduced the adjusted risk by 4.9% (1.2–8.5%). Sub-cohorts resulting from 1:1 propensity score matching revealed that sugammadex had been given in higher doses by 0.30 (0.13–0.48) mg kg−1 in the sub-cohort with TOFR > 0.95. Conclusions A post hoc analysis of patients receiving quantitative monitoring of neuromuscular function suggests that postoperative pulmonary complications are reduced for TOFR > 0.95 before tracheal extubation compared with TOFR > 0.9. Trial registration number NCT01865513.

  • Tranexamic acid in open aortic aneurysm surgery: a randomised clinical trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-10
    Fabrizio Monaco; Pasquale Nardelli; Laura Pasin; Gaia Barucco; Cristina Mattioli; Nora Di Tomasso; Giuseppe Dalessandro; Giuseppe Giardina; Giovanni Landoni; Roberto Chiesa; Alberto Zangrillo

    Background Bleeding and transfusions affect mortality in aortic surgery. Although tranexamic acid significantly reduced bleeding in multiple settings, its role in major vascular surgery was never studied. The aim of this study was to determine if tranexamic acid reduces blood loss in open abdominal aortic aneurysm (AAA) surgery. Methods A total of 100 patients undergoing elective open AAA repair were randomised to receive tranexamic acid (a loading dose of 500 mg and a continuous infusion of 250 mg h−1) or placebo. The primary outcome was intraoperative blood loss, and the secondary outcomes were the number of patients receiving red blood cells, occurrence of thromboembolic events, and mortality. Data were analysed using the intention-to-treat principle. Results Fifty patients were randomised into each group. Median (inter-quartile range) intraoperative blood loss was 400 (300–1050) ml in the tranexamic acid group vs 500 (360–1000) ml in the placebo group (P=0.44). Transfusion rate was seven/50 (14%) in the tranexamic group vs 12/50 (24%) in the placebo group (P=0.20). No thrombosis was recorded. In a post hoc analysis, postoperative blood loss was reduced in the tranexamic group both at 4 h (60 [40–80] ml vs 100 [60–140] ml, P<0.001) and 24 h (180 [120–275] vs 275 [190–395] ml, P=0.003) after surgery. At 1 yr, three patients were dead, all in the placebo group (P=0.24) and all after 28 days. Conclusions Tranexamic acid did not reduce intraoperative blood loss or blood transfusions in open AAA repair, although it may reduce postoperative blood loss without increasing adverse effects. Clinical trial registration NCT02335359.

  • Comparison of the effects of perineural or intravenous dexamethasone on low volume interscalene brachial plexus block: a randomised equivalence trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2019-10-05
    Paul G. McHardy; Oskar Singer; Imad T. Awad; Ben Safa; Patrick D.G. Henry; Alex Kiss; Shelly K. Au; Lilia Kaustov; Stephen Choi

    Background Efforts to prolong interscalene block (ISB) analgesia include the use of local anaesthetic adjuvants such as dexamethasone. Previous work showing prolonged block duration suggests that both perineural and intravenous (i.v.) routes can both prolong analgesia. The superiority of either route is controversial given the design of previous studies. As perineural dexamethasone is an off-label use, anaesthesiologists should be fully informed of the clinical differences, if any, on block duration. This study was designed to test whether perineural vs i.v. dexamethasone administration are equivalent. Methods We randomised 182 eligible patients scheduled for arthroscopic shoulder surgery to receive low-dose ISB (0.5% ropivacaine 5 ml) with perineural or i.v. dexamethasone 4 mg. Subjects, anaesthesiologists, and research personnel were blinded. All subjects also received a standardised general anaesthetic and multimodal analgesia. The primary outcome was duration of analgesia analysed as an equivalence outcome (2 h equivalency margin) using the two one-sided test (TOST) method. Results For the primary outcome, duration of analgesia, and perineural and i.v. administration of dexamethasone were not equivalent. The upper and lower bounds of the 90% confidence interval were 1 h (P=0.12) and –2.5 h (P=0.01), respectively. The observed difference in mean block duration was not clinically relevant (0.75 h longer for i.v. dexamethasone). There were no other clinically significant differences between groups. Conclusion In the context of low-volume ISB with ropivacaine, perineural and i.v. dexamethasone were not equivalent in terms of their effects on block duration. However, there were no clinically significant differences in outcomes, and there is no advantage of perineural over intravenous dexamethasone. www.clinicaltrials.gov registration NCT02322242.

  • High intraoperative inspiratory oxygen fraction and risk of major respiratory complications
    Br. J. Anaesth. (IF 6.199) Pub Date : 2018-01-09
    Staehr-Rye A, Meyhoff C, Scheffenbichler F, et al.

    British Journal of Anaesthesia, 2017; 119(1): 140–9, DOI 10.1093/bja/aex128

  • Acute traumatic coagulopathy: pathophysiology and resuscitation
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-08-09

    British Journal of Anaesthesia, 2016; 117(S3): iii31–iii43, DOI 10.1093/bja/aew328

  • Systematic review to determine which validated measurement tools can be used to assess risk of problematic analgesic use in patients with chronic pain
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-09-14
    Lawrence R, Mogford D, Colvin L, et al.

    Background. Misuse of prescription opioids, and other drugs prescribed for chronic pain, has increased, with major concerns about harm. This review was undertaken to identify validated measurement tools for risk assessment and monitoring of chronic non-cancer pain patients being considered for, or currently prescribed, analgesic drugs with abuse potential.Methods. Selected databases (Embase, Medline, Cochrane library/CENTRAL, PsycINFO, PubMed, CINAHL) were systematically searched for studies evaluating tools for risk of analgesic misuse, either before, or during, analgesic therapy for chronic pain, using predetermined inclusion/exclusion criteria. Two independent reviewers assessed abstracts, selected full texts, extracted data and assessed quality.Results. 30 studies from 1844 met inclusion criteria, including three systematic reviews, with an additional four studies from bibliography review. The studies covered 14 tools pertaining to opioid use, with none for non-opioid analgesics.Although there is no single, clear factor identifying opioid misuse, previous substance misuse appears important. Deception, including lying to clinicians, and using drugs belonging to others are common features. Smoking history may be relevant.Conclusions. For predicting prescription opioid misuse, the pain medication questionnaire (PMQ) and the screener and opioid assessment for patients with pain (SOAPP) had the best evidence; both developed and validated in five separate studies (four each of acceptable quality). The current opioid misuse measure (COMM) performed best screening for current misuse, developed and validated in three studies of acceptable quality. A small number of tools may accurately predict, or identify, opioid misuse. There are none for non-opioid analgesics, where there is a potential need.

  • Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-09-27
    Hocking K, Alvis B, Baudenbacher F, et al.

    BackgroundThe assessment of intravascular volume status remains a challenge for clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the peripheral venous waveform that has been used to monitor volume status. We present a proof-of-concept study for evaluating the efficacy of PIVA in detecting changes in fluid volume. MethodsWe enrolled 37 hospitalized patients undergoing haemodialysis (HD) as a controlled model for intravascular volume loss. Respiratory rate (F0) and pulse rate (F1) frequencies were measured. PIVA signal was obtained by fast Fourier analysis of the venous waveform followed by weighing the magnitude of the amplitude of the pulse rate frequency. PIVA was compared with peripheral venous pressure and standard monitoring of vital signs. ResultsRegression analysis showed a linear correlation between volume loss and change in the PIVA signal (R2=0.77). Receiver operator curves demonstrated that the PIVA signal showed an area under the curve of 0.89 for detection of 20 ml kg−1 change in volume. There was no correlation between volume loss and peripheral venous pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory rate were consistent with similar numbers derived from the bio-impedance and electrical signals from the electrocardiogram. ConclusionsPIVA is a minimally invasive, novel modality for detecting changes in fluid volume status, respiratory rate and pulse rate in spontaneously breathing patients with peripheral i.v. cannulas.

  • Intraoperative naloxone reduces remifentanil-induced postoperative hyperalgesia but not pain: a randomized controlled trial
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-10-03
    Koo C, Yoon S, Kim B, et al.

    BackgroundIntraoperative use of a high-dose remifentanil may induce postoperative hyperalgesia. Low-dose naloxone can selectively reverse some adverse effects of opioids without compromising analgesia. We thus hypothesized that the intraoperative use of a high-dose remifentanil combined with a low-dose naloxone infusion reduces postoperative hyperalgesia compared with the use of remifentanil alone. MethodsPatients undergoing elective thyroid surgery were randomly assigned into one of three groups, depending on the intraoperative effect-site concentration of remifentanil, with or without a continuous infusion of naloxone: 4 ng ml−1 remifentanil with 0.05 μg kg−1 h−1 naloxone in the high-remifentanil with naloxone group, and 4 or 1 ng ml−1 remifentanil with a placebo in the high- or low-remifentanil groups, respectively. We measured the pain thresholds (primary outcome) to mechanical stimuli using von Frey filaments and incidence of hyperalgesia on the peri-incisional area 24 h after surgery. We also measured pain intensity, analgesic consumptions and adverse events up to 48 h after surgery. ResultsThe pain threshold presented as von Frey numbers [median (interquartile range)] was significantly lower in the high-remifentanil group (n=31) than in the high-remifentanil with naloxone (n=30) and the low-remifentanil (n=30) groups [3.63 (3.22–3.84) vs 3.84 (3.76–4.00) vs 3.80 (3.69–4.08), P=0.011]. The incidence of hyperalgesia was also higher in the high-remifentanil group than in the other groups [21/31 vs 10/30 vs 9/30, P=0.005]. Postoperative pain intensity, analgesic consumptions and adverse events were similar between groups. ConclusionsThe intraoperative use of low-dose naloxone combined with high-dose remifentanil reduced postoperative hyperalgesia but not pain. Clinical trial registrationNCT02856087.

  • Assessment of changes in lactate concentration with intravascular microdialysis during high-risk cardiac surgery using the trend interchangeability method
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-10-03
    Gouëzel C, Lorne E, Bonnet V, et al.

    Background. Blood lactate is a strong predictor of mortality, and repeated blood lactate assays are recommended during surgery in high-risk patients. We hypothesized that the use of intravascular microdialysis incorporated in a central venous catheter would be interchangeable with the reference blood gas technique to monitor changes in blood lactate.Methods. Microdialysis and central venous blood lactate measurements were recorded simultaneously in high-risk cardiac surgical patients. The correlation between absolute values was determined by linear regression, and the Bland–Altman test for repeated measurements was used to compare bias, precision, and limits of agreement. Changes in lactate measurements were evaluated with a four-quadrant plot and trend interchangeability method (TIM).Results. In the 23 patients analysed, the central venous catheter was used as part of standard care, with no complications. The correlation coefficient for absolute values (n=104) was 0.96 (P<0.0001). The bias, precision, and limits of agreement were −0.19, 0.51, and −1.20 to 0.82 mmol litre−1, respectively. The concordance rate for changes in blood lactate measurements (n=80) was 94% with the four-quadrant plot. In contrast, the TIM showed that 23 (29) changes in lactate measurements were not interpretable, and among the remaining 57 (71) interpretable changes, 18 (32) were interchangeable, 8 (14) were in the grey zone, and 31 (54) were not interchangeable.Conclusions. Microdialysis with a central venous catheter appears to provide reliable absolute blood lactate values. Although changes in blood lactate measurements showed an excellent concordance rate, changes between the two methods were poorly interchangeable with the TIM.Clinical trial registration. NCT02296593.

  • Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-10-04
    Piegeler T, Clausen N, Weiss M, et al.

    Background. Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions.Methods. Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord.Results. Overall, the ‘body’ turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8–50.9) to 117.4% (93.6–141.2). This difference was diminished when the ‘cord’ turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of ‘body’ rotation to the tip.Conclusions. ‘Cord’ turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope ‘body’ only. Straightening the fibrescope cord and combined ‘body’ and ‘cord’ turning are recommended.

  • An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers
    Br. J. Anaesth. (IF 6.199) Pub Date : 2017-10-04
    van der Schrier R, Jonkman K, van Velzen M, et al.

    BackgroundThere is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg. MethodsFifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake. ResultsAll three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference −5.0 L min−1, 95% confidence interval: −7.1 to −2.9 L min−1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05). ConclusionsIn this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

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上海纽约大学William Glover