Association of intraoperative dexmedetomidine use with postoperative hypotension in unilateral hip and knee arthroplasties: a historical cohort study.

PURPOSE: Dexmedetomidine is frequently used as a sedative agent for orthopedic surgery patients undergoing total hip or knee arthroplasty. Although the benefits of dexmedetomidine are well described in the literature, there is also potential for harm, especially regarding the hemodynamic effects of dexmedetomidine in the postoperative setting. METHODS: This historical cohort study included all primary unilateral total hip or knee arthroplasties conducted from April 2017 to February 2020 in a single, university-affiliated, tertiary care centre (Jewish General Hospital, Montreal, QC, Canada). We used multivariable logistic regression to analyze the predictors for postoperative hypotension, defined as a systolic blood pressure < 90 mm Hg or any systolic blood pressure while on a vasopressor infusion in the postanesthesia care unit. Models were validated using calibration and discrimination with bootstrapping technique. RESULTS: One thousand five hundred and eighty-eight patients were included in this study. Postoperative hypotension occurred in 413 (26%) patients. Statistically significant predictors for postoperative hypotension included female sex (adjusted odds ratio [aOR], 3.24; 95% confidence interval [CI], 2.29 to 4.58), a history of transient ischemic attack or cerebrovascular accident (aOR, 1.97; 95% CI, 1.04 to 3.72), and intraoperative dexmedetomidine use (aOR, 2.61; 95% CI, 1.99 to 3.42). Moreover, the risk of postoperative hypotension was approximately two times higher than baseline, with a total intraoperative dexmedetomidine dose above 50 µg (relative risk, 1.99; 95% CI, 1.63 to 2.44; P < 0.001). A higher preoperative systolic blood pressure (aOR, 0.98; 95% CI, 0.97 to 0.99) was a protective factor for postoperative hypotension. CONCLUSION: In this historical cohort study, dexmedetomidine was a strong risk factor for postoperative hypotension in total hip or knee arthroplasty patients. Dexmedetomidine, and particularly at high cumulative doses above 50 µg, should be administered judiciously in high-risk surgical patients to minimize the risk of postoperative hypotension.

RéSUMé: OBJECTIF: La dexmédétomidine est fréquemment utilisée comme agent sédatif pour les patients en chirurgie orthopédique bénéficiant d'une arthroplastie totale de la hanche ou du genou. Bien que les avantages de la dexmédétomidine soient bien décrits dans la littérature, il existe également un potentiel de préjudice, en particulier en ce qui touche aux effets hémodynamiques de la dexmédétomidine dans un contexte postopératoire. MéTHODE: Cette étude de cohorte historique comprenait toutes les arthroplasties totales unilatérales primaires de la hanche ou du genou réalisées entre avril 2017 et février 2020 dans un seul centre de soins tertiaires universitaire (Hôpital général juif, Montréal, QC, Canada). Nous avons utilisé la régression logistique multivariable pour analyser les prédicteurs d'hypotension postopératoire, définie comme une tension artérielle systolique < 90 mmHg ou toute tension artérielle systolique pendant une perfusion de vasopresseurs en salle de réveil. Les modèles ont été validés à l'aide de l'étalonnage et de la discrimination avec une technique d'auto-amorçage. RéSULTATS: Mille cinq cent quatre-vingt-huit patients ont été inclus dans cette étude. Une hypotension postopératoire est survenue chez 413 (26 %) patients. Les prédicteurs statistiquement significatifs d'une hypotension postopératoire comprenaient le sexe féminin (rapport de cotes ajusté [RCA], 3,24; intervalle de confiance [IC] à 95 %, 2,29 à 4,58), des antécédents d'accident ischémique transitoire ou d'accident vasculaire cérébral (RCA, 1,97; IC 95 %, 1,04 à 3,72) et l'utilisation peropératoire de dexmédétomidine (RCA, 2,61; IC 95 %, 1,99 à 3,42). De plus, le risque d'hypotension postopératoire était environ deux fois plus élevé que la valeur initiale, avec une dose peropératoire totale de dexmédétomidine supérieure à 50 µg (risque relatif, 1,99; IC 95 %, 1,63 à 2,44; P < 0,001). Une tension artérielle systolique préopératoire plus élevée (RCA, 0,98; IC 95 %, 0,97 à 0,99) était un facteur protecteur contre l'hypotension postopératoire. CONCLUSION: Dans cette étude de cohorte historique, la dexmédétomidine était un facteur de risque important d'hypotension postopératoire chez les patients bénéficiant d'une arthroplastie totale de la hanche ou du genou. La dexmédétomidine, et en particulier à des doses cumulatives élevées supérieures à 50 µg, devrait être administrée judicieusement chez les patients chirurgicaux à haut risque afin de minimiser le risque d'hypotension postopératoire.

Sample size calculations for randomized clinical trials published in anesthesiology journals: a comparison of 2010 versus 2016.

PURPOSE: Although every randomized clinical trial (RCT) needs participants, determining the ideal number of participants that balances limited resources and the ability to detect a real effect is difficult. Focussing on two-arm, parallel group, superiority RCTs published in six general anesthesiology journals, the objective of this study was to compare the quality of sample size calculations for RCTs published in 2010 vs 2016. METHODS: Each RCT's full text was searched for the presence of a sample size calculation, and the assumptions made by the investigators were compared with the actual values observed in the results. Analyses were only performed for sample size calculations that were amenable to replication, defined as using a clearly identified outcome that was continuous or binary in a standard sample size calculation procedure. RESULTS: The percentage of RCTs reporting all sample size calculation assumptions increased from 51% in 2010 to 84% in 2016. The difference between the values observed in the study and the expected values used for the sample size calculation for most RCTs was usually > 10% of the expected value, with negligible improvement from 2010 to 2016. CONCLUSION: While the reporting of sample size calculations improved from 2010 to 2016, the expected values in these sample size calculations often assumed effect sizes larger than those actually observed in the study. Since overly optimistic assumptions may systematically lead to underpowered RCTs, improvements in how to calculate and report sample sizes in anesthesiology research are needed.

The degree of adherence to CONSORT reporting guidelines for the abstracts of randomised clinical trials published in anaesthesia journals: A cross-sectional study of reporting adherence in 2010 and 2016.

BACKGROUND: Abstracts are intended to be concise summaries of the entire randomised clinical trial (RCT). Despite their importance, few studies have examined the reporting quality of abstracts in the anaesthesiology literature. OBJECTIVES: To examine the quality of RCT abstract reporting according to the CONSORT for Abstracts guidelines and determine whether recommended items omitted from the abstract were present in the body of the article. DESIGN: A cross-sectional study of RCTs. SETTING: This study was performed at the University of Western Ontario and University Hospital, London Health Sciences Centre. PARTICIPANTS: All RCTs meeting inclusion criteria that were published in 2010 or 2016 in six general anaesthesiology journals (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia and European Journal of Anaesthesiology). MAIN OUTCOME MEASURES: The 16 checklist items from the CONSORT for Abstracts statement were used to create a convenience score as a proxy for RCT abstract reporting quality, with each criterion measured as being reported in abstract, not reported in abstract but reported in full-text article, or not reported in abstract or full-text article. RESULTS: Of the 395 RCTs identified, 219 were published in 2010 and 176 were published in 2016. Out of the maximum possible score of 16, the median abstract score increased from 4 points [interquartile range (IQR): 3 to 5] in 2010 to 6 points [IQR: 5 to 8] in 2016. Although most checklist items showed improvement from 2010 to 2016, around 75% of RCTs in 2016 met fewer than half of the 16 items with no RCTs reporting all 16 items in the abstract. A majority of the RCTs had the information present in the full-text. In 2016, only 71 out of 176 (40%) of RCTs reported outcomes conforming to the CONSORT guidelines (with an effect size and a confidence interval around the effect size) in the Abstract. CONCLUSION: Abstracts for many anaesthesiology RCTs are incomplete selective summaries of the entire article.

PU.1 opposes IL-7-dependent proliferation of developing B cells with involvement of the direct target gene bruton tyrosine kinase.

Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 wk. However, little is known about the target genes that explain leukemogenesis in these mice. In this study we found that immature B cells were altered in frequency in the bone marrow of preleukemic CD19-CreΔPB mice. Enriched pro-B cells from CD19-CreΔPB mice induced disease upon transplantation, suggesting that these were leukemia-initiating cells. Bone marrow cells from preleukemic CD19-CreΔPB mice had increased responsiveness to IL-7 and could proliferate indefinitely in response to this cytokine. Bruton tyrosine kinase (BTK), a negative regulator of IL-7 signaling, was reduced in preleukemic and leukemic CD19-CreΔPB cells compared with controls. Induction of PU.1 expression in cultured CD19-CreΔPB pro-B cell lines induced Btk expression, followed by reduced STAT5 phosphorylation and early apoptosis. PU.1 and Spi-B regulated Btk directly as shown by chromatin immunoprecipitation analysis. Ectopic expression of BTK was sufficient to induce apoptosis in cultured pro-B cells. In summary, these results suggest that PU.1 and Spi-B activate Btk to oppose IL-7 responsiveness in developing B cells.