The effect of perioperative benzodiazepine administration on postoperative nausea and vomiting: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Despite recent systematic reviews suggesting their benefit for postoperative nausea, vomiting, or both (PONV) prevention, benzodiazepines have not been incorporated into guidelines for PONV prophylaxis because of concerns about possible adverse effects. We conducted an updated meta-analysis to inform future practice guidelines. METHODS: We included randomised controlled trials (RCTs) of all languages comparing benzodiazepines with non-benzodiazepine comparators in adults undergoing inpatient surgery. Our outcomes were postoperative nausea, vomiting, or both. We assessed risk of bias for RCTs using the Cochrane Risk of Bias tool. We pooled data using a random-effects model and assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We screened 31 413 abstracts and 950 full texts. We included 119 RCTs; 104 were included in quantitative synthesis. Based on moderate certainty evidence, we found that perioperative benzodiazepine administration reduced the incidence of PONV (52 studies, n=5086, relative risk [RR]: 0.77, 95% confidence interval [CI] 0.66-0.89; number needed to treat [NNT] 16; moderate certainty), postoperative nausea (55 studies, n=5916, RR: 0.72, 95% CI 0.62-0.83; NNT 21; moderate certainty), and postoperative vomiting (52 studies, n=5909, RR: 0.74, 95% CI 0.60-0.91; NNT 55; moderate certainty). CONCLUSIONS: Moderate quality evidence shows that perioperative benzodiazepine administration decreases the incidence of PONV. The results of this systematic review and meta-analysis will inform future clinical practice guidelines. SYSTEMATIC REVIEW PROTOCOL: The protocol for this systematic review was pre-registered with PROSPERO International Prospective Register of Systematic Reviews (CRD42022361088) and published in BMJ Open (PMID 31831540).

Clinician responses to disruptive intraoperative behaviour: patterns and norms identified from a multinational survey.

PURPOSE: Disruptive intraoperative behaviour can have detrimental consequences for clinicians, institutions, and patients. The way victims and witnesses respond to disruptive behaviour can ameliorate or exacerbate consequences. Nevertheless, previous research has neither described the responses of a multinational sample of clinicians nor developed tools to recognize and evaluate responses. METHODS: After obtaining ethics committee approval, 23 perioperative organizations distributed a survey evaluating clinician responses to disruptive behaviour. We grouped responses into four response strategies: passive, assertive, manipulative, and malicious. Thereafter, we derived norms (i.e., percentile distributions) for each response strategy using empirical distribution functions. Latent profile analysis identified groups of clinicians balancing their use of the four response strategies differently (i.e., response pattern groups). We used Chi square tests to examine associations between response pattern groups and respondent demographics. RESULTS: We analyzed 4,789 complete responses. In response to disruptive behaviour, 33.7% of clinicians altered medical care in ways that were unindicated, 54.6% avoided communication with team members, and 12.1% misled the offender. Profile analysis identified five response pattern groups: extreme passive-predominant (30.5% of clinicians), extreme assertive-predominant (20.5%), moderate passive-predominant (18.9%), moderate assertive-predominant (26.5%), and a disparate pattern (greater use of manipulative and malicious responses) (3.5%). Profession, sex, management responsibilities, and sexual orientation predicted the response pattern group (all, P < 0.001). DISCUSSION: The responses of thousands of clinicians involved passivity, manipulativeness, or maliciousness. We present norms and a response pattern classification to help organizations evaluate responses, recognize response patterns, and provide tailored support to victims and witnesses.

RéSUMé: OBJECTIF: Les comportements peropératoires perturbateurs ont des effets délétères tant sur l'équipe clinique que sur les institutions et la patientèle. La façon dont les victimes et les témoins réagissent à un comportement perturbateur peut en atténuer ou exacerber les conséquences. Néanmoins, les recherches antérieures n'ont pas décrit les réponses d'un échantillon multinational de clinicien·nes ni développé d'outils pour reconnaître et évaluer les réponses. MéTHODE: Après l'obtention de l'approbation du comité d'éthique, 23 organisations de soins périopératoires ont distribué un sondage évaluant les réponses des cliniciennes et cliniciens aux comportements perturbateurs. Nous avons regroupé les réponses en quatre stratégies de réponse : passive, assertive, manipulatrice et malveillante. Par la suite, nous avons dérivé des normes (c'est-à-dire des distributions centiles) pour chaque stratégie de réponse à l'aide de fonctions de distribution empiriques. L'analyse des profils latents a permis d'identifier des groupes de clinicien·nes équilibrant différemment leur utilisation des quatre stratégies de réponse (c.-à-d. des groupes de modèles de réponse). Nous avons utilisé des tests du chi carré pour examiner les associations entre les groupes de modèles de réponse et les données démographiques des répondant·es. RéSULTATS: Nous avons analysé 4789 réponses complètes. En réponse à un comportement perturbateur, 33,7 % des clinicien·nes ont modifié les soins médicaux d'une manière qui n'était pas indiquée, 54,6 % ont évité de communiquer avec les membres de l'équipe et 12,1 % ont induit la personne délinquante en erreur. L'analyse du profil a permis d'identifier cinq groupes de modèles de réponse : passif extrême-prédominant (30,5 % des clinicien·nes), affirmation de soi extrême-prédominante (20,5 %), passif modéré-prédominant (18,9 %), affirmation de soi modérée-prédominante (26,5 %) et attitudes disparates (utilisation accrue de réponses manipulatrices et malveillantes) (3,5 %). La profession, le sexe, les responsabilités de gestion et l'orientation sexuelle prédisaient le groupe de type de réponse (tous, P < 0,001). DISCUSSION: Les réponses de milliers de clinicien·nes impliquaient la passivité, la manipulation ou la malveillance. Nous présentons des normes et une classification des modèles d'intervention pour aider les organisations à évaluer les réponses, à reconnaître les modèles d'intervention et à fournir un soutien personnalisé aux victimes et aux témoins.

Electroencephalography-Guided Anesthesia and Delirium in Older Adults After Cardiac Surgery: The ENGAGES-Canada Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthesia decreases the incidence of delirium after cardiac surgery. Design, Setting, and Participants: Randomized, parallel-group clinical trial of 1140 adults 60 years or older undergoing cardiac surgery at 4 Canadian hospitals. Recruitment was from December 2016 to February 2022, with follow-up until February 2023. Interventions: Patients were randomized in a 1:1 ratio (stratified by hospital) to receive EEG-guided anesthesia (n = 567) or usual care (n = 573). Patients and those assessing outcomes were blinded to group assignment. Main Outcomes and Measures: The primary outcome was delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration and EEG suppression time. Secondary outcomes included intensive care and hospital length of stay. Serious adverse events included intraoperative awareness, medical complications, and 30-day mortality. Results: Of 1140 randomized patients (median [IQR] age, 70 [65-75] years; 282 [24.7%] women), 1131 (99.2%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 102 of 562 patients (18.15%) in the EEG-guided group and 103 of 569 patients (18.10%) in the usual care group (difference, 0.05% [95% CI, -4.57% to 4.67%]). In the EEG-guided group compared with the usual care group, the median volatile anesthetic minimum alveolar concentration was 0.14 (95% CI, 0.15 to 0.13) lower (0.66 vs 0.80) and there was a 7.7-minute (95% CI, 10.6 to 4.7) decrease in the median total time spent with EEG suppression (4.0 vs 11.7 min). There were no significant differences between groups in median length of intensive care unit (difference, 0 days [95% CI, -0.31 to 0.31]) or hospital stay (difference, 0 days [95% CI, -0.94 to 0.94]). No patients reported intraoperative awareness. Medical complications occurred in 64 of 567 patients (11.3%) in the EEG-guided group and 73 of 573 (12.7%) in the usual care group. Thirty-day mortality occurred in 8 of 567 patients (1.4%) in the EEG-guided group and 13 of 573 (2.3%) in the usual care group. Conclusions and Relevance: Among older adults undergoing cardiac surgery, EEG-guided anesthetic administration to minimize EEG suppression, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support EEG-guided anesthesia for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02692300.

Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.

Morbidity and mortality in patients managed with high compared with low blood pressure targets during on-pump cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Many believe that blood pressure management during cardiac surgery is associated with postoperative outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of high compared with low intraoperative blood pressure targets on postoperative morbidity and mortality in adults undergoing cardiac surgery on cardiopulmonary bypass (CPB). Our primary objective was to inform the design of a future large RCT. SOURCE: We searched MEDLINE, EMBASE, Web of Science, CINAHL, and CENTRAL for RCTs comparing high with low intraoperative blood pressure targets in adult patients undergoing any cardiac surgical procedure on CPB. We screened reference lists, grey literature, and conference proceedings. PRINCIPAL FINDINGS: We included eight RCTs (N =1,116 participants); all examined the effect of blood pressure management only during the CPB. Trial definitions of high compared with low blood pressure varied and, in some, there was a discrepancy between the target and achieved mean arterial pressure. We observed no difference in delirium, cognitive decline, stroke, acute kidney injury, or mortality between high and low blood pressure targets (very-low to low quality evidence). Higher blood pressure targets may have increased the risk of requiring a blood transfusion (three trials; n = 456 participants; relative risk, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.01; moderate quality evidence) but this finding was based on a small number of trials. CONCLUSION: Individual trial definitions of high and low blood pressure targets varied, limiting inferences. The effect of high (compared with low) blood pressure targets on other morbidity and mortality after cardiac surgery remains unclear because of limitations with the body of existing evidence. Research to determine the optimal management of blood pressure during cardiac surgery is required. STUDY REGISTRATION: PROSPERO (CRD42020177376); registered: 5 July 2020.

RéSUMé: OBJECTIF: Pour beaucoup, la prise en charge de la pression artérielle pendant la chirurgie cardiaque serait associée aux issues postopératoires. Nous avons réalisé une revue systématique et une méta-analyse d'études randomisées contrôlées (ERC) afin de déterminer l'impact de cibles peropératoires de pression artérielle élevées par rapport à des cibles basses sur la morbidité et la mortalité postopératoires d'adultes bénéficiant d'une chirurgie cardiaque sous circulation extracorporelle (CEC). Notre objectif principal était d'orienter la conception d'une future ERC d'envergure. SOURCES: Nous avons analysé les bases de données MEDLINE, EMBASE, Web of Science, CINAHL et CENTRAL afin d'en tirer les ERC comparant des cibles de pression artérielle peropératoire élevées à des cibles basses chez des patients adultes bénéficiant d'une intervention chirurgicale cardiaque sous CEC. Nous avons passé au crible les listes de références, la littérature grise et les travaux de congrès. CONSTATATIONS PRINCIPALES: Nous avons inclus huit ERC (N = 1116 participants); toutes les études ont examiné l'effet de la prise en charge de la pression artérielle uniquement pendant la CEC. Les définitions d'une pression artérielle élevée ou basse variaient d'une étude à l'autre et, dans certains cas, un écart a été noté entre la pression artérielle cible et la pression artérielle moyenne atteinte. Nous n'avons observé aucune différence dans les taux de delirium, de déclin cognitif, d'accident vasculaire cérébral, d'insuffisance rénale aiguë ou de mortalité entre les cibles de pression artérielle élevée et basse (données probantes de qualité très faible à faible). Des cibles de pression artérielle plus élevées pourraient avoir augmenté le risque de transfusion sanguine (trois études; n = 456 participants; risque relatif, 1,4; intervalle de confiance à 95 %, 1,1 à 1,9; P = 0,01; données probantes de qualité modérée), mais ce résultat se fondait sur un petit nombre d'études. CONCLUSION: Les définitions individuelles des cibles d'hypertension et d'hypotension artérielle variaient, ce qui a limité les inférences. L'effet de cibles de pression artérielle élevée (par rapport à une pression artérielle basse) sur d'autres mesures de la morbidité et de la mortalité après une chirurgie cardiaque demeure incertain en raison des limites de l'ensemble des données probantes existantes. Des recherches visant à déterminer la prise en charge optimale de la pression artérielle pendant la chirurgie cardiaque sont nécessaires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020177376); enregistrée le 5 juillet 2020.

Prophylactic tranexamic acid use in non-cardiac surgeries at high risk for transfusion.

BACKGROUND: Tranexamic acid (TXA) reduces transfusion in a wide range of surgical populations, although its real-world use in non-cardiac surgeries has not been well described. The objective of this study was to describe prophylactic TXA use in non-cardiac surgeries at high risk for transfusion. METHODS: This is a retrospective cohort study of all adult patients undergoing major non-cardiac surgery at ≥5% risk of perioperative transfusion at five Canadian hospitals between January 2014 and December 2016. Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database were linked to transfusion and laboratory databases. TXA use was ascertained electronically from The Ottawa Hospital Data Warehouse and via manual chart review for Winnipeg hospitals. For each surgery, we evaluated the percentage of patients who received TXA as well as the specifics of TXA dosing and administration. RESULTS: TXA use was evaluable in 14 300 patients. Overall, 17% of surgeries received TXA, ranging from 0% to 68% among individual surgeries. TXA use was more common in orthopaedic (n = 2043/4942; 41%) and spine surgeries (n = 239/1322; 18%) compared to other surgical domains (n = 109/8036; 1%). TXA was commonly administered as a bolus (n = 2097/2391; 88%). The median TXA dose was 1000 mg (IQR 1000-1000 mg). CONCLUSION: TXA is predominantly used in orthopaedic and spine surgeries, with little uptake in other non-cardiac surgeries at high risk for red blood cell transfusion. Further studies are needed to evaluate the effectiveness and safety of TXA and to understand the barriers to TXA administration in a broad range of non-cardiac surgeries.

Impacts of elective surgical cancellations and postponements in Canada.

PURPOSE: Worldwide, patients experience difficulties accessing elective surgical care. This study examined the perceived health, social, and functional impacts of elective surgical cancellations and postponements in Canada. METHODS: We analyzed a subset of aggregate data from the Canadian Community Health Survey (CCHS) annual components from 2005 to 2014. Multivariable logistic regressions examined associations between past-year non-emergency surgical cancellations/postponements and perceived impacts of waiting for surgery (e.g., worry/stress/anxiety, pain, loss of work, loss of income, deterioration of health, relationships suffered). RESULTS: Among those who experienced a cancellation or postponement of a past-year non-emergency surgery (weighted n = 256,836; 11.8%), 23.5% (weighted n = 60,345) indicated their life was affected by waiting for surgery. After adjusting for type of surgery, year, and sociodemographics, those who experienced a surgical cancellation or postponement had increased odds of reporting their life was affected by waiting for surgery (adjusted odds ratio [aOR], 2.67; 99% confidence interval [CI], 1.41 to 5.1); in particular, they reported greater deterioration of their health (aOR, 3.47; 99% CI, 1.05 to 11.4) and increased dependence on relatives/friends (aOR, 2.53; 99% CI, 1.01 to 6.3) than those who did not have a cancellation or postponement. CONCLUSION: Results highlight the multifaceted perceived impacts of surgical cancellations/postponements. These findings suggest there is a need for improvements in reducing elective surgical cancellations and postponements. Results may also inform the development of targeted interventions to improve patients' health and quality of life while waiting for surgery.

RéSUMé: OBJECTIF: Partout dans le monde, les patients ont de la difficulté à accéder aux soins chirurgicaux non urgents. Cette étude a examiné les impacts de santé, sociaux et fonctionnels perçus des annulations et des reports de chirurgies non urgentes au Canada. MéTHODE: Nous avons analysé un sous-ensemble de données agrégées à partir des composantes annuelles de l'Enquête sur la santé dans les collectivités canadiennes (ESCC) colligées de 2005 à 2014. Des régressions logistiques multivariées ont examiné les associations entre les annulations / reports de chirurgies non urgentes de l'année précédente et les impacts perçus d'une attente pour une chirurgie (par ex., inquiétude/stress/anxiété, perte de travail, perte de revenus, détérioration de la santé, impact sur les relations interpersonnelles). RéSULTATS: Parmi les personnes ayant subi une annulation ou un report d'une chirurgie non urgente au cours de l'année précédente (n pondéré = 256 836; 11,8 %), 23,5 % (n pondéré = 60 345) ont indiqué que leur vie avait été affectée par l'attente d'une chirurgie. Après avoir ajusté les données pour tenir compte du type de chirurgie, de l'année et des données sociodémographiques, la probabilité que les personnes ayant vécu une annulation ou un report de chirurgie rapportent que leur vie avait été affectée par l'attente d'une chirurgie était plus élevée (rapport de cotes ajusté [RCA], 2,67; intervalle de confiance [IC] 99 %, 1,41 à 5,1); plus particulièrement, ces personnes rapportaient davantage de détérioration de leur santé (RCA, 3,47; IC 99 %, 1,05 à 11,4) et une dépendance accrue à l'aide de leurs amis/familles (RCA, 2,53; IC 99 %, 1,01 à 6,3) que les personnes n'ayant pas vécu d'annulation ou de retard. CONCLUSION: Ces résultats soulignent les facettes multiples des impacts perçus des annulations et reports de chirurgie. En outre, ils démontrent qu'il est nécessaire d'apporter des améliorations pour réduire les annulations et reports des chirurgies non urgentes. Ces résultats pourraient également aider à mettre au point des interventions ciblées pour améliorer la santé et la qualité de vie des patients en attente d'une chirurgie.

Epidemiology of intravenous immune globulin in septic shock: a retrospective cohort analysis of the Premier Healthcare Database.

PURPOSE: Intravenous immune globulin (IVIG) may improve survival in people with septic shock. Current utilization patterns of IVIG are unknown. We sought to characterize adult patients with septic shock requiring vasopressors who received IVIG, describes IVIG regimens, and evaluate determinants of IVIG use in patients with septic shock. METHODS: We conducted a retrospective database study of adult patients with septic shock admitted to US hospitals in the Premier Healthcare Database (from July 2010 to June 2013). We described the proportion of patients with septic shock receiving IVIG, examined IVIG regimens across sites and employed random-effects multivariable regression techniques to identify predictors of IVIG use. RESULTS: Intravenous immune globulin was administered to 0.3% (n = 685) of patients with septic shock; with a median [interquartile range (IQR)] dose of 1 [0.5-1.8] g·kg-1 for a median [IQR] of 1 [1-2] day. Receipt of IVIG was less likely for Black patients (odds ratio [OR], 0.54; 95% confidence interval [CI] 0.41 to 0.72) and patients without private insurance (Medicare OR, 0.73; 95% CI 0.59 to 0.90; Medicaid OR, 0.41; 95% CI 0.30 to 0.57) and more likely for patients with immunocompromise (OR, 6.83; 95% CI 5.47 to 8.53), necrotizing fasciitis (OR, 9.78; 95% CI 6.97 to 13.72), and toxic shock (OR, 56.9; 95% CI 38.7 to 83.7). CONCLUSIONS: Intravenous immune globulin is used infrequently across the US in patients with septic shock. Regimens of IVIG in septic shock may be less intensive than those associated with a survival benefit in meta-analyses. Observed infrequent use supports apparent clinical equipoise, perhaps secondary to limitations of the primary literature. A clinical trial evaluating the role of IVIG in septic shock is needed.

RéSUMé: OBJECTIF: L'immunoglobuline intraveineuse (IGIV) peut améliorer la survie chez les personnes atteintes de choc septique. Les pratiques actuelles d'utilisation de l'IGIV sont inconnues. Nous avons cherché à caractériser les patients adultes en état de choc septique et nécessitant des vasopresseurs qui ont reçu de l'IGIV, à décrire les dosages administrés d'IGIV, et à évaluer les causes déterminantes d'une utilisation d'IGIV chez ces patients. MéTHODE: Nous avons réalisé une étude rétrospective de base de données portant sur des patients adultes atteints de choc septique admis dans des hôpitaux américains et inclus dans la base de données Premier Healthcare (de juillet 2010 à juin 2013). Nous avons décrit la proportion de patients en choc septique recevant de l'IGIV, examiné les posologies utilisées d'IGIV à travers les sites et employé des techniques de régression multivariable à effets aléatoires pour identifier les prédicteurs de l'utilisation d'IGIV. RéSULTATS: L'IGIV a été administrée à 0,3 % (n = 685) des patients présentant un choc septique, avec une dose médiane [écart interquartile (ÉIQ)] de 1 [0,5­1,8] g·kg-1 pour une médiane [ÉIQ] de 1 [1­2] jour. L'administration d'IGIV était moins probable chez les patients noirs (rapport de cotes [RC], 0,54; intervalle de confiance [IC] à 95 %, 0,41 à 0,72) et les patients sans assurance privée (RC Medicare, 0,73; IC 95 %, 0,59 à 0,90; RC Medicaid, 0,41; IC 95 %, 0,30 à 0,57) et plus probable chez les patients immunodéprimés (RC, 6,83; IC 95 %, 5,47 à 8,53), atteints de fasciite nécrosante (RC, 9,78; IC 95 %, 6,97 à 13,72), et en choc toxique (RC, 56,9; IC 95 %, 38,7 à 83,7). CONCLUSION: L'IGIV est rarement utilisée aux États-Unis chez les patients en choc septique. Les dosages d'IGIV utilisés en cas de choc septique pourraient être moins intensifs que ceux associés à un effet bénéfique en matière de survie dans les méta-analyses. L'utilisation peu fréquente observée appuie une équivalence clinique apparente, peut-être secondaire aux limites de la littérature princeps. Une étude clinique évaluant le rôle de l'IGIV dans le choc septique est nécessaire.

Variation in prophylactic tranexamic acid administration among anesthesiologists and surgeons in orthopedic surgery: a retrospective cohort study.

PURPOSE: Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. METHODS: This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. RESULTS: In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000-1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. CONCLUSION: We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.

RéSUMé: OBJECTIF: L'acide tranexamique (ATX) réduit la transfusion d'érythrocytes dans diverses chirurgies orthopédiques. Cependant, les variations de pratique quant à son utilisation parmi les anesthésiologistes et les chirurgiens n'ont pas été décrites. Afin de cibler les stratégies futures de transfert des connaissances et de mise en œuvre, et pour mieux comprendre les déterminants de la variabilité dans l'utilisation prophylactique d'ATX, notre objectif principal était d'évaluer l'influence des membres de l'équipe chirurgicale sur la variabilité de l'administration prophylactique d'ATX. MéTHODE: Il s'agissait d'une étude de cohorte rétrospective de tous les patients adultes subissant une arthroplastie totale primaire de la hanche (ATH), une chirurgie de fracture de la hanche et une fusion intervertébrale ± vertébrectomie dans deux hôpitaux canadiens entre janvier 2014 et décembre 2016. Nous avons utilisé les codes de procédure de la Classification canadienne des interventions en santé dans la Base de données sur les congés des patients, que nous avons liée à la banque de données d'Ottawa. Nous avons décrit le pourcentage de patients qui ont reçu de l'ATX par chirurgie individuelle, les détails du dosage de l'ATX, et avons estimé l'effet des anesthésiologistes et des chirurgiens sur l'ATX prophylactique en réalisant des analyses de régression logistique multivariées à effets mixtes. RéSULTATS: Parmi les 3900 patients étudiés, l'ATX était le plus fréquemment utilisé lors d'une ATH primaire (85 %; n = 1344/1582), avec une utilisation plus faible lors de chirurgie de fracture de la hanche (23 %; n = 342/1506) et de chirurgie de fusion intervertébrale (23 %; n = 186/812). La dose totale médiane [écart interquartile] d'ATX était de 1000 mg [1000 à 1000], administrés dans 92 % des cas sous forme de bolus. Les anesthésiologistes et les chirurgiens ont ajouté une variabilité significative aux probabilités de recevoir de l'ATX lors d'une chirurgie de fracture de la hanche et de fusion, mais pas lors d'ATH primaire. La majeure partie de la variabilité dans l'utilisation d'ATX était attribuable aux facteurs liés au patient et à d'autres facteurs. CONCLUSION: Nous avons confirmé l'utilisation de routine de l'ATX dans l'ATH primaire, tout en observant une utilisation moins répandue et plus variable lors de chirurgie de fracture de la hanche et de fusion intervertébrale. Une étude plus approfondie est nécessaire pour comprendre les variations d'utilisation et les obstacles à la mise en œuvre de l'ATX dans une population plus étendue de patients de chirurgie orthopédique à haut risque de transfusion.

Prospective randomized trial of continuous femoral nerve block with posterior capsular injection versus periarticular injection for analgesia in primary total knee arthroplasty.

Background: Femoral nerve block (NB) and periarticular injection (PI) are 2 common options for pain control after total knee arthroplasty (TKA). We performed a prospective triple-blinded randomized trial comparing continuous femoral NB to PI, with follow-up to 1 year. Methods: Patients younger than 70 years of age who were scheduled to undergo elective primary TKA under spinal anesthesia between 2009 and 2010 were randomly allocated to receive either continuous femoral NB or PI. Patients in the NB group received ropivacaine through an NB catheter and a sham saline PI. The PI group received a PI of ropivacaine, morphine, ketorolac and epinephrine, and a sham saline infusion via an NB catheter. Both groups had standardized oral analgesia preoperatively, spinal anesthesia and sedation, and postoperative analgesia. Surgeons, anesthesiologists, patients and assessors were blinded to group assignment. Pain was measured twice daily on postoperative days 1 and 2, at rest and with motion, with a numeric rating scale. Patient satisfaction, pain (Oxford Knee Score) and range of motion were assessed at 1 year. Results: There were 39 participants in the NB group and 35 participants in the PI group. There were no statistically significant differences between the groups at baseline. Statistically but nonclinically significant reductions in pain scores on postoperative day 2 and in narcotic need on the day of surgery were found in the PI group. Patient-reported satisfaction did not differ at any time point. At 1 year, knee flexion was significantly greater in the NB group than in the PI group (mean range of motion 120° v. 110°, p = 0.03). Conclusion: There was no demonstrated improvement in pain control with the use of an NB versus PI when used with multimodal analgesia. Clinicians should opt for the modality that has the best efficiency for their surgical environment. ClinicalTrials.gov # NCT00869037

Contexte: Le bloc nerveux (BN) fémoral et l'infiltration périarticulaire (IP) sont 2 options d'usage courant pour maîtriser la douleur après l'arthroplastie totale du genou (ATG). Nous avons procédé à un essai prospectif randomisé à triple insu afin de comparer le BN fémoral et l'IP, avec un suivi allant jusqu'à 1 an. Méthodes: Les patients de moins de 70 ans qui devaient subir une ATG élective sous épidurale entre 2009 et 2010 ont été assignés aléatoirement à un BN fémoral continu ou à une IP. Les patients du groupe soumis au BN recevaient de la ropivacaïne par un cathéter de BN et une IF simulée (solution saline). Le groupe soumis à l'IP recevait de la ropivacaïne, de la morphine, du kétorolac et de l'épinéphrine et une perfusion simulée (solution saline) par un cathéter de BN. Les 2 groupes avaient reçu une analgésie orale standard avant l'intervention, une anesthésie rachidienne avec sédatifs et une analgésie postopératoire. Les chirurgiens, les anesthésiologistes, les patients et les évaluateurs ne connaissaient pas l'assignation des agents aux différents groupes. La douleur a été mesurée 2 fois par jour aux jours 1 et 2 postopératoires, au repos et à la mobilisation, au moyen d'une échelle numérique. La satisfaction des patients, la douleur (questionnaire d'Oxford pour le genou) et l'amplitude de mouvement ont toutes été évaluées après 1 an. Résultats: Le groupe soumis au BN comptait 39 participants et le groupe soumis à l'IP en comptait 35. Il n'y avait aucune différence statistiquement significative entre les groupes au départ. Des réductions statistiquement (et non cliniquement) significatives des scores de douleur au deuxième jour postopératoire et du recours aux narcotiques le jour de la chirurgie ont été notées dans le groupe soumis à l'IP. La satisfaction autodéclarée des patients n'a différé à aucun moment. Au bout de 1 an, la flexion du genou était significativement plus marquée dans le groupe soumis au BN que dans le groupe soumis à l'IP (amplitude de mouvement moyenne 120° c. 110°, p = 0,03) Conclusion: On n'a démontré aucune amélioration de la maîtrise de la douleur avec l'utilisation du BN c. IP avec analgésie multimodale. Les médecins devraient opter pour la modalité qui offre le meilleur degré d'efficience en fonction de leur environnement chirurgical. ClinicalTrials.gov # NCT00869037

Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis.

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (B-Free Pilot): a pilot, multicentre, randomised, cluster crossover trial.

BACKGROUND: Delirium is common after cardiac surgery and is associated with adverse outcomes. Perioperative benzodiazepine use is associated with delirium and is common during cardiac surgery, which may increase the risk of postoperative delirium. We undertook a pilot study to inform the feasibility of a large randomised cluster crossover trial examining whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared with liberal administration) would reduce delirium. METHODS: We conducted a two-centre, pilot, randomised cluster crossover trial with four 4 week crossover periods. Each centre was randomised to a policy of restricted or liberal use, and then alternated between the two policies during the remaining three periods. Our feasibility outcomes were adherence to each policy (goal ≥80%) and outcome assessment (one delirium assessment per day in the ICU in ≥90% of participants). We also evaluated the incidence of intraoperative awareness in one site using serial Brice questionnaires. RESULTS: Of 800 patients undergoing cardiac surgery during the trial period, 127/800 (15.9%) had delirium. Of these, 355/389 (91.3%) received benzodiazepines during the liberal benzodiazepine periods and 363/411 (88.3%) did not receive benzodiazepines during the restricted benzodiazepine periods. Amongst the 800 patients, 740 (92.5%) had ≥1 postoperative delirium assessment per day in the ICU. Of 521 patients screened for intraoperative awareness, one patient (0.2%), managed during the restricted benzodiazepine period (but who received benzodiazepine), experienced intraoperative awareness. CONCLUSIONS: This pilot study demonstrates the feasibility of a large, multicentre, randomised, cluster crossover trial examining whether an institutional policy of restricted vs liberal benzodiazepine use during cardiac surgery will reduce postoperative delirium. CLINICAL TRIAL REGISTRATION: NCT03053869.

Disruptive behaviour in the operating room is under-reported: an international survey.

PURPOSE: The purpose of this study was to investigate the reporting habits of clinicians who have been exposed to disruptive behaviour in the operating room (OR) and assess their satisfaction with management's responses to this issue. METHODS: Ethics committee approval was obtained. This was a pre-specified sub-study of a larger survey examining disruptive behaviour, which was distributed to OR clinicians in seven countries. Using Likert-style questions, this study ascertained the proportion of disruptive intraoperative behaviour that clinicians reported to management, as well as their degree of satisfaction with management's responses. Binomial logistic regression identified socio-demographic, exposure-related, and behavioural predictors that a clinician would never report disruptive behaviour. RESULTS: Four thousand, seven hundred and seventy-five respondents were part of the sub-study. Disruptive behaviour was under-reported by 96.5% (95% confidence interval [CI], 95.9 to 97.0) of respondents, and never reported by 30.9% (95% CI, 29.6 to 32.2) of respondents. Only 21.0% (95% CI, 19.8 to 22.2) of respondents expressed satisfaction with management's responses. Numerous socio-demographic, exposure-related, and behavioural predictors of reporting habits were identified. Socio-demographic groups who had higher odds of never reporting disruptive behaviour included younger clinicians, clinicians without management responsibilities, both anesthesiologists and surgeons (compared with nurses), biological females, and heterosexuals (all P < 0.05). CONCLUSIONS: Disruptive behaviour was under-reported by nearly all clinicians surveyed, and only one in five were satisfied with management's responses. For healthcare systems to meaningfully address the issue of disruptive behaviour, management must create reporting systems that clinicians will use. They must also respond in ways that clinicians can rely on to affect necessary change.

Abusive behaviour in Canadian and US operating rooms.

BACKGROUND: Disruptive intraoperative behaviour has detrimental effects on clinicians, institutions, and patients. Abusive behaviour is an egregious form of disruptive behaviour that has a particular risk of detrimental consequences. The prevalence of abusive behaviour in the operating room (OR) is uncertain. We therefore examined the prevalence and frequency of exposure to abusive behaviour in a cohort of Canadian and US OR clinicians. METHODS: This was a sub-study of an international survey examining disruptive behaviour in the OR. It included a cohort of clinicians from Canada and the United States who were recruited from six perioperative associations and two institutions. Clinicians were asked about their intraoperative exposure to three abusive behaviours: physical assault, verbal threats, and intimidating invasion of their personal space. From the responses, we derived the proportion of clinicians who experienced or witnessed abuse (i.e., prevalence) and the number of abusive events experienced by all respondents (i.e., frequency). RESULTS: Of the 7,465 clinicians who responded to the original international survey, 2,875 were part of this abuse sub-study (United States =1,010, Canada = 1,865). In the preceding year, 667 clinicians (23.2%; 95% confidence interval [CI], 21.6 to 24.8) personally experienced abuse, while 1,121 clinicians (39.0%; 95% CI, 37.2 to 40.8) witnessed colleagues being abused. In total, the group of respondents reported experiencing 14,237 abusive events in the preceding year. CONCLUSIONS: Both the number of clinicians who are exposed to abusive behaviour and the large number of reported events are concerning. Since these events can undermine team-work and affect patients, coworkers, and institutions, efforts are needed to further evaluate and manage the problem.

RéSUMé: CONTEXTE: Les comportements peropératoires perturbateurs ont des effets délétères tant sur les cliniciens que sur les institutions et les patients. Un comportement dit abusif est une forme flagrante de comportement perturbateur qui comporte un risque particulier de conséquences délétères. La prévalence des comportements abusifs en salle d'opération (SOP) est inconnue. Nous avons donc examiné la prévalence et la fréquence d'exposition à des comportements abusifs d'une cohorte de cliniciens de SOP canadiens et américains. MéTHODE: Il s'agit d'une sous-étude d'un sondage international examinant les comportements perturbateurs en SOP. Notre étude a inclus une cohorte de cliniciens du Canada et des États-Unis recrutés dans six associations périopératoires et deux institutions. On a interrogé les cliniciens à propos de leur exposition peropératoire à trois comportements abusifs : les agressions physiques, les menaces verbales et l'invasion intimidante de leur espace personnel. À partir de leurs réponses, nous avons dérivé la proportion de cliniciens ayant été victimes ou témoins d'abus (soit la prévalence) et le nombre d'événements abusifs subis par tous les répondants (soit la fréquence). RéSULTATS: Parmi les 7465 cliniciens ayant répondu au sondage international original, 2875 ont pris part à cette sous-étude sur les abus (États-Unis =1010, Canada = 1865). Au cours de l'année précédant le sondage, 667 cliniciens (23,2 %; intervalle de confiance [IC] 95 %, 21,6 à 24,8) ont personnellement subi des abus, alors que 1121 cliniciens (39,0 %; IC 95 %, 37,2 à 40,8) ont été témoins d'abus à l'égard de collègues. Au total, le groupe de répondants a été exposé à 14 237 événements abusifs au cours de l'année précédente. CONCLUSION: Tant le nombre de cliniciens exposés à des comportements abusifs que le nombre important d'événements rapportés sont inquiétants. Étant donné que ces événements peuvent nuire au travail d'équipe et affecter les patients, les collègues et les institutions, des efforts sont nécessaires afin d'évaluer ce problème et de le régler.

Post-traumatic stress in the postoperative period: current status and future directions.

PURPOSE: This narrative review summarizes the current literature on postoperative traumatic stress, namely post-traumatic stress disorder (PTSD), including defining features, epidemiology, identification of patient and perioperative risk factors, assessment tools, intervention recommendations, and future directions. PRINCIPAL FINDINGS: Postoperative traumatic stress occurs in approximately 20% of patients following surgery, with additionally elevated rates in specific surgical groups. Potential risk factors include the perceived uncontrollable nature of high-risk surgery, psychiatric history, intraoperative awareness, dissociation, surgical complications, medication administration, delirium, and pain. PTSD after surgery may manifest in ways that are distinct from traditional conceptualizations of PTSD. Identification of perioperative risk factors and stress symptoms in the early postoperative period may provide opportunities for intervention. CONCLUSION: Research on postoperative traumatic stress, including PTSD, is in its infancy. Current evidence shows elevated incidence rates of postoperative traumatic stress, which can worsen overall physical and mental health outcomes. Future research on assessment, prevention, and treatment is warranted.

Prevalence and predictors of exposure to disruptive behaviour in the operating room.

PURPOSE: Disruptive intraoperative behaviour ranges from incivility to abuse. This behaviour can have deleterious effects on clinicians, students, institutions, and patients. Previous investigations of this behaviour used underdeveloped tools or small sampling frames. We therefore examined the prevalence and predictors of perceived exposure to disruptive behaviour in a multinational sample of operating room clinicians. METHODS: A total of 134 perioperative associations in seven countries were asked to distribute a survey examining five types of exposure to disruptive behaviour: personal, directed toward patients, directed toward colleagues, directed toward others, or undirected. To compare the average amount of exposure with each type, we used a Friedman's test with select post hoc Wilcoxon tests. A negative binomial regression model identified socio-demographic predictors of personal exposure. RESULTS: Of the 134 organizations approached, 23 (17%) complied. The total response rate was estimated to be 7.6% (7465/101,624). Almost all (97.0%; 95% confidence interval [CI], 96.6 to 97.4) of the respondents reported exposure to disruptive behaviour in the past year, with the average respondent experiencing 61 incidents per year (95% CI, 57 to 65). Groups reporting higher personal exposure included clinicians who were young, inexperienced, female, non-heterosexual, working as nurses, or working in clinics with private funding (all P < 0.05). CONCLUSION: Perceived exposure to disruptive behaviour was prevalent and frequent, with the most common behaviours involving speaking ill of clinicians and patients. These perceptions, whether accurate or not, can result in detrimental consequences. Greater efforts are required to eliminate disruptive intraoperative behaviour, with recognition that specific groups are more likely to report experiencing such behaviours.

RéSUMé: OBJECTIF: Les comportements perturbateurs en salle d'opération vont de l'incivilité à l'abus. Ce type de comportement peut avoir des effets délétères sur les cliniciens, les étudiants, les institutions et les patients. Les études précédentes de ce type de comportement se sont servies d'outils sous-développés ou de cadres d'échantillonnage restreints. Nous avons donc examiné la prévalence et les prédicteurs d'une exposition perçue à un comportement perturbateur dans un échantillon multinational de cliniciens de salle d'opération. MéTHODE: Au total, on a demandé à 134 associations périopératoires issues de sept pays de distribuer un sondage examinant cinq types d'exposition à des comportements perturbateurs : personnel, dirigé vers les patients, dirigé vers des collègues, dirigé vers les autres, ou non dirigé. Afin de comparer le nombre moyen d'expositions à chacun de ces types de comportement, nous avons utilisé un test de Friedman accompagné d'une sélection de tests de Wilcoxon réalisés post-hoc. Un modèle de régression binomiale négative a identifié les prédicteurs sociodémographiques d'exposition personnelle. RéSULTATS: Parmi les 134 organismes contactés, 23 (17 %) ont accepté de distribuer le sondage. Le taux de réponse total était estimé à 7,6 % (7465/101 624). Presque tous (97,0 %; intervalle de confiance [IC] 95 %, 96,6 à 97,4) les répondants ont rapporté avoir été exposés à des comportements perturbateurs au cours de l'année précédente, un répondant moyen subissant 61 incidents par année (IC 95 %, 57 à 65). Parmi les groupes rapportant une exposition personnelle plus élevée, les jeunes cliniciens, ceux avec peu d'expérience, les femmes, les non-hétérosexuels, le personnel infirmier ou les personnes travaillant dans des cliniques privées (tous P < 0,05) ont été identifiés. CONCLUSION: L'exposition perçue à des comportements perturbateurs était élevée et fréquente, les comportements les plus souvent rapportés étant la médisance à l'égard des cliniciens ou des patients. Ces perceptions, qu'elles soient vraies ou non, peuvent entraîner des conséquences délétères. Des efforts plus importants sont nécessaires afin d'éliminer les comportements perturbateurs en salle d'opération, en reconnaissant que certains groupes vulnérables sont plus à risque de rapporter avoir subi de tels comportements.

Effect of Electroencephalography-Guided Anesthetic Administration on Postoperative Delirium Among Older Adults Undergoing Major Surgery: The ENGAGES Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, often suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthetic administration decreases the incidence of postoperative delirium. Design, Setting, and Participants: Randomized clinical trial of 1232 adults aged 60 years and older undergoing major surgery and receiving general anesthesia at Barnes-Jewish Hospital in St Louis. Recruitment was from January 2015 to May 2018, with follow-up until July 2018. Interventions: Patients were randomized 1:1 (stratified by cardiac vs noncardiac surgery and positive vs negative recent fall history) to receive EEG-guided anesthetic administration (n = 614) or usual anesthetic care (n = 618). Main Outcomes and Measures: The primary outcome was incident delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration, EEG suppression, and hypotension. Adverse events included undesirable intraoperative movement, intraoperative awareness with recall, postoperative nausea and vomiting, medical complications, and death. Results: Of the 1232 randomized patients (median age, 69 years [range, 60 to 95]; 563 women [45.7%]), 1213 (98.5%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 157 of 604 patients (26.0%) in the guided group and 140 of 609 patients (23.0%) in the usual care group (difference, 3.0% [95% CI, -2.0% to 8.0%]; P = .22). Median end-tidal volatile anesthetic concentration was significantly lower in the guided group than the usual care group (0.69 vs 0.80 minimum alveolar concentration; difference, -0.11 [95% CI, -0.13 to -0.10), and median cumulative time with EEG suppression was significantly less (7 vs 13 minutes; difference, -6.0 [95% CI, -9.9 to -2.1]). There was no significant difference between groups in the median cumulative time with mean arterial pressure below 60 mm Hg (7 vs 7 minutes; difference, 0.0 [95% CI, -1.7 to 1.7]). Undesirable movement occurred in 137 patients (22.3%) in the guided and 95 (15.4%) in the usual care group. No patients reported intraoperative awareness. Postoperative nausea and vomiting was reported in 48 patients (7.8%) in the guided and 55 patients (8.9%) in the usual care group. Serious adverse events were reported in 124 patients (20.2%) in the guided and 130 (21.0%) in the usual care group. Within 30 days of surgery, 4 patients (0.65%) in the guided group and 19 (3.07%) in the usual care group died. Conclusions and Relevance: Among older adults undergoing major surgery, EEG-guided anesthetic administration, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support the use of EEG-guided anesthetic administration for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02241655.

Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

BACKGROUND: Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. METHODS: The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. FINDINGS: Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI -6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. INTERPRETATION: A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. FUNDING: National Institutes of Health and Cancer Center Support.

Achieving Milestones as a Prerequisite for Proceeding With a Clinical Trial.

BACKGROUND: Although the National Institutes of Health (NIH) invests $30 billion in research annually, many funded studies fail to generate results that can inform practice. The National Institutes of Health introduced a phased funding mechanism as one potential solution. Study-specific milestones are established for an initial pilot phase. We assess the utility of this phased approach through the ongoing Electroencephalography (EEG) Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) pragmatic clinical trial. The hypothesis of the trial is that EEG guidance of general anesthesia, through prevention of EEG suppression, can decrease postoperative delirium and its downstream negative sequelae. METHODS: In collaboration with study stakeholders, we identified critical milestones for the ENGAGES study, with themes common to many clinical trials. These themes include: regulatory tasks; enrollment targets; feasibility and impact of study intervention; primary outcome incidence; measurement reliability of primary outcome; and follow-up. Progress in achieving the milestones was assessed at regular intervals during the pilot phase by ENGAGES investigators, a National Institute on Aging program officer, and a nonpartisan research organization (Westat). RESULTS: Regulatory tasks, including institutional review board approval, infrastructure establishment, and trial registration, were completed on schedule. A total of 117 patients were randomized, exceeding the target by 51. The EEG-guided protocol was successfully implemented, and a relevant effect on anesthetic practice was demonstrated (decrease in median age-adjusted minimum alveolar anesthetic concentration from 0.93 to 0.78 [P < .001] and increase in median proportion of zero EEG suppression time from 87% to 94% [P < .01]). Nearly all patients (115 of 117, 98.3%) were assessed for delirium using the Confusion Assessment Method, and the delirium incidence was similar (28.1%; 95% CI, 20%-37%) to the estimate (25%) used for the sample size calculation. Good interrater reliability of delirium assessment was demonstrated (κ = 0.94 [95% CI, 0.86-1]). Finally, 1-month follow-up vital status data were obtained for 96.9% of patients, with 85.7% of patients completing at least 1 survey. CONCLUSIONS: With the ENGAGES trial, we demonstrated that key milestones can be identified and progressively assessed during a pilot phase. Success in attaining appropriate milestones hypothetically predicts meaningful completion of a study, and can provide justification for proceeding beyond a pilot phase. The impact of this phased approach on return on investment and scientific yield requires additional study.

The role of randomized cluster crossover trials for comparative effectiveness testing in anesthesia: design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial.

Increasingly, clinicians and researchers recognize that studies of interventions need to evaluate not only their therapeutic efficacy (i.e., the effect on an outcome in ideal, controlled settings) but also their real-world effectiveness in broad, unselected patient groups. Effectiveness trials inform clinical practice by comparing variations in therapeutic approaches that fall within the standard of care. In this article, we discuss the need for studies of comparative effectiveness in anesthesia and the limitations of individual patient randomized-controlled trials in determining comparative effectiveness. We introduce the concept of randomized cluster crossover trials as a means of answering questions of comparative effectiveness in anesthesia, using the design of the Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial (Clinicaltrials.gov identifier NCT03053869).