Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Postoperative anemia in cardiac surgery patients: a narrative review.

PURPOSE: Anemia reduces the blood's ability to carry and deliver oxygen. Following cardiac surgery, anemia is very common and affects up to 90% of patients. Nevertheless, there is a paucity of data examining the prognostic value of postoperative anemia. In this narrative review, we present findings from the relevant literature on postoperative anemia in cardiac surgery patients, focusing on the incidence, risk factors, and prognostic value of postoperative anemia. We also explore the potential utility of postoperative anemia as a therapeutic target to improve clinical outcomes. SOURCE: We conducted a targeted search of MEDLINE, Embase, and the Cochrane Database of Systematic Reviews up to September 2022, using a combination of search terms including postoperative (post-operative), perioperative (peri-operative), anemia (anaemia), and cardiac surgery. PRINCIPAL FINDINGS: The reported incidence of postoperative anemia varied from 29% to 94% across the studies, likely because of variations in patient inclusion criteria and classification of postoperative anemia. Nonetheless, the weight of the evidence suggests that postoperative anemia is common and is an independent risk factor for adverse postoperative outcomes such as acute kidney injury, stroke, mortality, and functional outcomes. CONCLUSIONS: In cardiac surgery patients, postoperative anemia is a common and prognostically important risk factor for postoperative morbidity and mortality. Nevertheless, there is a lack of data on whether active management of postoperative anemia is feasible or effective in improving patient outcomes.

RéSUMé: OBJECTIF: L'anémie réduit la capacité du sang à transporter et à fournir de l'oxygène. Suite à une chirurgie cardiaque, l'anémie est très fréquente et touche jusqu'à 90 % des patient·es. Néanmoins, il existe peu de données examinant la valeur pronostique de l'anémie postopératoire. Dans ce compte rendu narratif, nous présentons les résultats de la littérature pertinente sur l'anémie postopératoire chez les patient·es ayant bénéficié d'une chirurgie cardiaque, en mettant l'accent sur l'incidence, les facteurs de risque et la valeur pronostique de l'anémie postopératoire chez les personnes ayant bénéficié d'une chirurgie cardiaque. Nous explorons également l'utilité potentielle de l'anémie postopératoire en tant que cible thérapeutique pour améliorer les devenirs cliniques. SOURCES: Nous avons réalisé une recherche ciblée dans MEDLINE, Embase et la base de données des revues systématiques Cochrane jusqu'en septembre 2022, en utilisant une combinaison de termes de recherche, notamment postopératoire (postoperative/post-operative), périopératoire (perioperative/peri-operative), anémie (anemia/anaemia) et chirurgie cardiaque (cardiac surgery). CONSTATATIONS PRINCIPALES: L'incidence rapportée de l'anémie postopératoire variait de 29 % à 94 % d'une étude à l'autre, probablement en raison des variations dans les critères d'inclusion des patient·es et la classification de l'anémie postopératoire. Néanmoins, le poids de la preuve suggère que l'anémie postopératoire est courante et constitue un facteur de risque indépendant pour les devenirs postopératoires indésirables tels que l'insuffisance rénale aiguë, les accidents vasculaires cérébraux, la mortalité et les devenirs fonctionnels. CONCLUSION: Chez la patientèle en chirurgie cardiaque, l'anémie postopératoire est un facteur de risque commun et pronostiquement important de morbidité et de mortalité postopératoires. Néanmoins, il y a un manque de données sur la faisabilité ou l'efficacité de la prise en charge active de l'anémie postopératoire pour améliorer les devenirs des patient·es.

Cold-stored platelets for acute bleeding in cardiac surgical patients: a narrative review.

PURPOSE: Cold-stored platelets (CSP) are an increasingly active topic of international research. They are maintained at 1-6 °C, in contrast to standard room-temperature platelets (RTP) kept at 20-24 °C. Recent evidence suggests that CSP have superior hemostatic properties compared with RTP. This narrative review explores the application of CSP in adult cardiac surgery, summarizes the preclinical and clinical evidence for their use, and highlights recent research. SOURCE: A targeted search of MEDLINE and other databases up to 24 February 2022 was conducted. Search terms combined concepts such as cardiac surgery, blood, platelet, and cold-stored. Searches of trial registries ClinicalTrials.gov and WHO International Clinical Trials Registry Platform were included. Articles were included if they described adult surgical patients as their population of interest and an association between CSP and clinical outcomes. References of included articles were hand searched. PRINCIPAL FINDINGS: When platelets are stored at 1-6 °C, their metabolic rate is slowed, preserving hemostatic function for increased storage duration. Cold-stored platelets have superior adhesion characteristics under physiologic shear conditions, and similar or superior aggregation responses to physiologic agonists. Cold-stored platelets undergo structural, metabolic, and molecular changes which appear to "prime" them for hemostatic activity. While preliminary, clinical evidence supports the conduct of trials comparing CSP with RTP for patients with platelet-related bleeding, such as those undergoing cardiac surgery. CONCLUSION: Cold-stored platelets may have several advantages over RTP, including increased hemostatic capacity, extended shelf-life, and reduced risk of bacterial contamination. Large clinical trials are needed to establish their potential role in the treatment of acutely bleeding patients.

RéSUMé: OBJECTIF: Les plaquettes conservées au froid (PCF) sont un sujet de recherche internationale de plus en plus populaire. Ces plaquettes sont maintenues à une température de 1-6 °C, contrairement aux plaquettes standard conservées à température ambiante (PTA), maintenues à 20­24 °C. Des données probantes récentes suggèrent que les PCF ont des propriétés hémostatiques supérieures aux PTA. Ce compte rendu narratif explore l'application de PCF en chirurgie cardiaque chez l'adulte, résume les données probantes précliniques et cliniques de leur utilisation, et met en évidence les recherches récentes. SOURCES: Une recherche ciblée dans MEDLINE et d'autres bases de données jusqu'au 24 février 2022 a été effectuée. Les termes de recherche combinaient des concepts en anglais tels que cardiac surgery, blood, platelet et cold-stored (soit chirurgie cardiaque, plaquette, et entreposage frigorifique). Des recherches dans les registres d'études ClinicalTrials.gov et le système d'enregistrement international des essais cliniques (ICTRP) de l'OMS ont été incluses. Les articles ont été inclus s'ils décrivaient des patient·es adultes de chirurgie en tant que population d'intérêt et une association entre les PCF et les issues cliniques. Les références des articles inclus ont fait l'objet d'une recherche manuelle. CONSTATATIONS PRINCIPALES: Lorsque les plaquettes sont conservées entre 1 et 6 °C, leur taux métabolique est ralenti, préservant la fonction hémostatique pour une durée d'entreposage accrue. Les plaquettes conservées au froid ont des caractéristiques d'adhésion supérieures dans des conditions de cisaillement physiologique et des réponses d'agrégation similaires ou supérieures aux agonistes physiologiques. Les plaquettes conservées au froid subissent des changements structurels, métaboliques et moléculaires qui semblent les « amorcer ¼ pour une activité hémostatique. Bien que préliminaires, les données probantes cliniques appuient la réalisation d'études comparant les PCF aux PTA chez la patientèle présentant des saignements liés aux plaquettes, tels que les personnes bénéficiant d'une chirurgie cardiaque. CONCLUSION: Les plaquettes conservées au froid peuvent présenter plusieurs avantages par rapport aux PTA, notamment une capacité hémostatique accrue, une durée de conservation prolongée et un risque réduit de contamination bactérienne. De grands essais cliniques sont nécessaires pour établir leur rôle potentiel dans le traitement de la patientèle en hémorragie aiguë.

What can ex vivo experiments contribute to clinical haemostasis management?

A recent ex vivo study found that post-cardiopulmonary bypass platelet defects can be restored with supplemental fibrinogen, but the clinical significance of this finding will require further study. We propose that the best management strategy for achieving haemostasis in bleeding surgical patients is to identify individualised coagulation defects and then use a targeted therapeutic approach that addresses each identified defect systematically.

Evaluation of the association of factor XIII at hospital arrival and outcomes in a cohort of severely injured patients.

BACKGROUND: Severe traumatic bleeding depletes coagulation factor XIII (FXIII) and fibrinogen. However, the role of FXIII level in bleeding-related outcomes is unknown. OBJECTIVES: To evaluate the association between FXIII levels at hospital arrival and critical administration threshold (≥3 red blood cell units in 1 hour within the first 24 hours), bleeding-related outcomes, death, and baseline characteristics. METHODS: A retrospective cohort study was conducted in severely injured adult patients (Injury Severity Score of ≥22 or ≥2 red blood cell units transfused in 24 hours) admitted to a level 1 trauma center. Clinical and laboratory data were collected. Baseline FXIII antigen levels were measured in banked patient plasma. Multivariable logistic and linear regression models were used to estimate the association between FXIII levels, outcomes, and baseline characteristics. RESULTS: Three hundred sixty-four of 1730 subjects admitted during a 2-year period were analyzed. Median age was 44 years (IQR, 27-62 years), and median Injury Severity Score was 29 (IQR, 22-34). FXIII levels were not associated with critical administration threshold (odds ratio [OR], 1.06; 95% CI, 0.97-1.17) or death (OR, 0.98; 95% CI, 0.90-1.07). FXIII was associated with major bleeding (OR, 1.10; 95% CI, 1.02-1.2) and massive transfusion (OR, 1.25; 95% CI, 1.08-1.44). Lower baseline FXIII levels were associated with arrival from a referring hospital (FXIII level, -0.07 U/mL; 95% CI, -0.11 to -0.03), hemoglobin (FXIII level, -0.05 U/mL; 95% CI, -0.07 to -0.03), fibrinogen level (FXIII level, -0.05 U/mL; 95% CI, -0.08 to -0.02), and platelet count (FXIII level, -0.02 U/mL; 95% CI, -0.04 to -0.008). CONCLUSIONS: Baseline FXIII levels in severely injured patients were inconsistently associated with bleeding-related outcomes and mortality. However, their association with major bleeding warrants further investigation of the role of FXIII in massively transfused patients with trauma.

Impact of COVID-19 on electroconvulsive therapy practice across Canadian provinces during the first wave of the pandemic.

BACKGROUND: Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). METHODS: A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). RESULTS: Clinical operations of ECT programs were disrupted across all four regions - however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. CONCLUSIONS: The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians' activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.

Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients.

Importance: Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown. Objective: To determine cost-effectiveness of fibrinogen concentrate vs cryoprecipitate for managing active bleeding in adult patients who underwent cardiac surgery. Design, Setting, and Participants: A within-trial economic evaluation of the Fibrinogen Replenishment in Surgery (FIBERS) randomized clinical trial (February 2017 to November 2018) that took place at 4 hospitals based in Ontario, Canada, hospitals examined all in-hospital resource utilization costs and allogeneic blood product (ABP) transfusion costs incurred within 28 days of surgery. Participants included a subset of 495 adult patients from the FIBERS trial who underwent cardiac surgery and developed active bleeding and acquired hypofibrinogenemia requiring fibrinogen replacement. Interventions: Fibrinogen concentrate (4 g per dose) or cryoprecipitate (10 units per dose) randomized (1:1) up to 24 hours postcardiopulmonary bypass. Main Outcomes and Measures: Effectiveness outcomes included number of ABPs administered within 24 hours and 7 days of cardiopulmonary bypass. ABP transfusion (7-day) and in-hospital resource utilization (28-day) costs were evaluated and a multivariable net benefit regression model built for the full sample and predefined subgroups. Results: Patient level costs for 495 patients were evaluated (mean [SD] age 59.2 [15.4] years and 69.3% male.) Consistent with FIBERS, ABP transfusions and adverse events were similar in both treatment groups. Median (IQR) total 7-day ABP cost was CAD $2280 (US dollars [USD] $1697) (CAD $930 [USD $692]-CAD $4970 [USD $3701]) in the fibrinogen concentrate group and CAD $2770 (USD $1690) (IQR, CAD $1140 [USD $849]-CAD $5000 [USD $3723]) in the cryoprecipitate group. Median (interquartile range) total 28-day cost was CAD $38 180 (USD $28 431) $(IQR, CAD $26 350 [USD $19 622]-CAD $65 080 [USD $48 463]) in the fibrinogen concentrate group and CAD $38 790 (USD $28 886) (IQR, CAD $26 180 [USD $19 495]-CAD $70 380 [USD $52 409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2000 (USD $1489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness. Conclusions and Relevance: Fibrinogen concentrate is cost-effective when compared with cryoprecipitate in most bleeding adult patients who underwent cardiac surgery with acquired hypofibrinogenemia requiring fibrinogen replacement. The generalizability of these findings outside the Canadian health system needs to be verified.

Prevention and Management of Chronic Postsurgical Pain and Persistent Opioid Use Following Solid Organ Transplantation: Experiences From the Toronto General Hospital Transitional Pain Service.

BACKGROUND: With >700 transplant surgeries performed each year, Toronto General Hospital (TGH) is currently one of the largest adult transplant centers in North America. There is a lack of literature regarding both the identification and management of chronic postsurgical pain (CPSP) after organ transplantation. Since 2014, the TGH Transitional Pain Service (TPS) has helped manage patients who developed CPSP after solid organ transplantation (SOT), including heart, lung, liver, and renal transplants. METHODS: In this retrospective cohort study, we describe the association between opioid consumption, psychological characteristics of pain, and demographic characteristics of 140 SOT patients who participated in the multidisciplinary treatment at the TGH TPS, incorporating psychology and physiotherapy as key parts of our multimodal pain management regimen. RESULTS: Treatment by the multidisciplinary TPS team was associated with significant improvement in pain severity and a reduction in opioid consumption. CONCLUSIONS: Given the risk of CPSP after SOT, robust follow-up and management by a multidisciplinary team should be considered to prevent CPSP, help guide opioid weaning, and provide psychological support to these patients to improve their recovery trajectory and quality of life postoperatively.

Platelet preservation in cardiac surgery using minimally invasive extracorporeal circulation versus optimized cardiopulmonary bypass.

BACKGROUND: Minimally invasive extracorporeal circulation (MiECC) is employed as a strategy to attenuate the physiologic disturbance caused by cardiopulmonary bypass. The aim of this study was to compare the coagulation profile of MiECC to an optimized conventional extracorporeal circuit (OpECC) with regards to platelet function, rotational thromboelastometry and blood product usage. METHODS: A retrospective analysis of coronary artery bypass grafting operations using either MiECC or OpECC was performed at a single institution. RESULTS: A total of 112 patients were included, with 61 receiving MiECC and 51 OpECC patients. OpECC patients had a significantly larger BSA (1.95+/- 0.22m2 vs 1.88 +/- 0.18m2, p = 0.034), than those who received MiECC. No difference between groups was observed regarding red blood cell, plasma, and platelet transfusions. Functional platelet count during the warming phase of cardiopulmonary bypass was found to be higher in the MiECC group ((136 (102-171) x109/L vs 109 (94-136) x109/L), p = 0.027), as were functional platelets as a percent of total platelet count ((86 (77-91)% vs 76 (63-82)%), p = 0.003). There were no significant differences between other outcomes such as operative mortality, incidence of stroke, and intensive care unit length of stay. CONCLUSION: While we did not see a difference in blood transfusions, MiECC resulted in a statistically significant advantage over OpECC with regards to preservation of functional platelets.

Practice patterns of ABO-matching for cryoprecipitate and patient outcomes after ABO-compatible versus incompatible cryoprecipitate.

BACKGROUND AND OBJECTIVES: This sub-study of the FIBRES trial sought to examine the patterns of ABO-compatible cryoprecipitate administration and to identify adverse consequences of ABO-incompatible cryoprecipitate. MATERIALS AND METHODS: This was a post hoc analysis of data collected from the FIBRES randomized clinical trial comparing fibrinogen concentrate with cryoprecipitate in the treatment of bleeding related to hypofibrinogenemia after cardiac surgery. The primary outcome was the percentage of administered cryoprecipitate that was ABO-compatible. Secondary outcomes were adverse events at 28 days. A follow-up survey was distributed to the FIBRES participating sites to examine the rationale behind the identified cryoprecipitate ABO-matching practice patterns. RESULTS: A total of 363 patients were included: 53 (15%) received ABO-incompatible cryoprecipitate and 310 (85%) received ABO-compatible cryoprecipitate. There was an increased incidence of post-operative anaemia in the ABO-incompatible group (15; 28.3%) in comparison to the ABO-compatible (44; 14.2%) group (p = 0.01) at 28 days, which was unrelated to haemolysis, without a significant difference in transfusion requirement. In the multivariable logistic regression models accounting for clustering by site, there was no observed statistically significant association between the administration of ABO-incompatible cryoprecipitate and any other adverse outcomes. Nine out of 11 sites did not have a policy requiring ABO-matched cryoprecipitate. CONCLUSION: This sub-study demonstrated that most cryoprecipitate administered in practice is ABO-compatible, despite the absence of guidelines or blood bank policies to support this practice. A signal towards increased risk of post-operative anaemia may be explained by higher rates of urgent surgery (vs. elective) in the ABO-incompatible group. Future studies should prospectively examine the impact of ABO-compatible versus incompatible cryoprecipitate to conclusively establish if there is a meaningful clinical impact associated with the administration of ABO-incompatible cryoprecipitate.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Preoperative Antithrombin Supplementation in Patients at Risk for Antithrombin Deficiency After Cardiac Surgery.

BACKGROUND: Antithrombin (AT) activity is reduced during cardiac operations with cardiopulmonary bypass (CPB), which is associated with adverse outcomes. Preoperative AT supplementation, to achieve >58% and <100% AT activity, may potentially reduce postoperative morbidity and mortality in cardiac operations with CPB. This prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of preoperative treatment with AT supplementation in patients at risk for low AT activity after undergoing cardiac surgery with CPB. METHODS: A total of 425 adult patients were randomized (1:1) to receive either a single dose of AT (n = 213) to achieve an absolute increase of 20% above pretreatment AT activity or placebo (n = 212) before surgery. The study duration was approximately 7 weeks. The primary efficacy end point was the percentage of patients with any component of a major morbidity composite (postoperative mortality, stroke, acute kidney injury [AKI], surgical reexploration, arterial or venous thromboembolic events, prolonged mechanical ventilation, and infection) in the 2 groups. Secondary end points included AT activity, blood loss, transfusion requirements, duration of intensive care unit (ICU), and hospital stays. Safety was also assessed. RESULTS: Overall, 399 patients (men, n = 300, 75.2%) with a mean (standard deviation [SD]) age of 66.1 (11.7) years, with the majority undergoing complex surgical procedures (n = 266, 67.9%), were analyzed. No differences in the percentage of patients experiencing morbidity composite outcomes between groups were observed (AT-treated 68/198 [34.3%] versus placebo 58/194 [29.9%]; P = .332; relative risk, 1.15). After AT infusion, AT activity was significantly higher in the AT group (108% [42-143]) versus placebo group (76% [40-110]), and lasted up to postoperative day 2. At ICU, the frequency of patients with AT activity ≥58% in the AT group (81.5%) was significantly higher ( P < .001) versus placebo group (43.2%). Secondary end point analysis did not show any advantage of AT over placebo group. There were significantly more patients with AKI ( P < .001) in the AT group (23/198; 11.6%) than in the placebo group (5/194, 2.6%). Safety results showed no differences in treatment-emergent adverse events nor bleeding events between groups. CONCLUSIONS: AT supplementation did not attenuate adverse postoperative outcomes in our cohort of patients undergoing cardiac surgery with CPB.

Titrated versus conventional anticoagulation management for thrombin generation in cardiac surgery: a randomized controlled trial.

PURPOSE: Optimal heparin titration during cardiopulmonary bypass (CPB) may reduce coagulation system activation and preserve hemostatic function post-CPB. Our objective was to assess if the Heparin Management System (HMS) Plus improves heparin titration, thereby leading to higher thrombin generation post-CPB compared with activated clotting time (ACT)-guided management. METHODS: We conducted a randomized controlled trial of 100 patients undergoing cardiac surgery with CPB at a single center. A total of 50 patients were randomized to conventional ACT-guided management, and 50 to the HMS Plus system. The primary outcome was change in thrombin generation post-CPB compared with baseline, as assessed by calibrated automated thrombography. Secondary outcomes included intraoperative blood loss, chest drain output up to 72 hr, and transfusions. In an exploratory analysis, we compared the quintile of patients with the highest average heparin concentration on CPB (≥ 4.0 mg⋅kg-1) with the rest of the cohort. RESULTS: A total of 100 patients were included in an intent-to-treat analysis. We observed no difference in post-CPB thrombin generation or secondary outcomes. However, patients in the HMS Plus group had higher average heparin concentrations while on CPB than patients in the conventional management group did (mean difference, -0.21; 95% confidence interval, -0.42 to -0.01). The quintile of patients with the highest average heparin concentration (4.0 mg⋅kg-1) had higher thrombin generation post-CPB than the rest of the cohort did. CONCLUSIONS: The HMS Plus system did not show significant benefits in thrombin generation, bleeding outcomes, or transfusion in patients undergoing cardiac surgery with CPB. Higher average heparin concentrations on CPB were associated with higher post-CPB thrombin generation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03347201); first submitted 12 October 2017.

RéSUMé: OBJECTIF: Un titrage optimal de l'héparine pendant la circulation extracorporelle (CEC) peut réduire l'activation du système de coagulation et préserver la fonction hémostatique après la CEC. Notre objectif était d'évaluer si le système de gestion de l'héparine HMS Plus améliorait le titrage de l'héparine, entraînant ainsi une génération de thrombine plus élevée après la CEC par rapport à la gestion guidée par le temps de coagulation activé (ACT). MéTHODE: Nous avons réalisé une étude randomisée contrôlée de 100 patients bénéficiant d'une chirurgie cardiaque sous CEC dans un seul établissement. Au total, 50 patients ont été randomisés à une gestion conventionnelle guidée par l'ACT et 50 à une gestion guidée par le système HMS Plus. Le critère d'évaluation principal était la variation de la génération de thrombine post-CEC par rapport aux valeurs de base, telles qu'évaluées par thrombographie calibrée automatisée. Les critères secondaires comprenaient les pertes sanguines peropératoires, le drainage thoracique jusqu'à 72 heures et les transfusions. Dans une analyze exploratoire, nous avons comparé le quintile de patients ayant la concentration moyenne d'héparine la plus élevée sous CEC (≥ 4,0 mg⋅kg-1) au reste de la cohorte. RéSULTATS: Au total, 100 patients ont été inclus dans une analyze en intention de traiter. Nous n'avons observé aucune différence dans la génération de thrombine post-CEC ou dans nos critères d'évaluation secondaires. Cependant, les patients du groupe HMS Plus présentaient des concentrations moyennes d'héparine plus élevées sous CEC que les patients du groupe de gestion conventionnelle (différence moyenne, -0,21; intervalle de confiance à 95 %, -0,42 à -0,01). Le quintile de patients ayant la concentration moyenne d'héparine la plus élevée (4,0 mg⋅kg-1) avaient une génération de thrombine post-CEC plus élevée que le reste de la cohorte. CONCLUSION: Le système HMS Plus n'a pas montré d'avantages significatifs dans la génération de thrombine, les issues hémorragiques ou la transfusion chez les patients bénéficiant d'une chirurgie cardiaque sous CEC. Des concentrations moyennes d'héparine plus élevées sous CEC ont été associées à une génération de thrombine post-CEC plus élevée. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03347201); soumis pour la première fois le 12 octobre 2017.

Impact of cardiopulmonary bypass duration on efficacy of fibrinogen replacement with cryoprecipitate compared with fibrinogen concentrate: a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) randomised controlled trial.

BACKGROUND: Coagulopathy in cardiac surgery is frequently associated with acquired hypofibrinogenaemia, which can be treated with either purified fibrinogen concentrate (FC) or cryoprecipitate. Because the latter is not purified and therefore contains additional coagulation factors, it is thought to be more effective for treatment of coagulopathy that occurs after prolonged cardiopulmonary bypass (CPB). We examined the impact of CPB duration on the efficacy of the two therapies in cardiac surgery. METHODS: This was a post hoc analysis of the Fibrinogen Replenishment in Surgery (FIBRES) RCT comparing FC (4 g) to cryoprecipitate (10 U) in adult patients undergoing cardiac surgery and experiencing bleeding with acquired hypofibrinogenaemia (n=735). The primary outcome was allogeneic blood products transfused within 24 h after CPB. Subjects were stratified by CPB duration (≤120, 121-180, and >180 min). The interaction of treatment assignment with CPB duration was tested. RESULTS: Subjects with longer CPB duration experienced more bleeding and transfusion. With CPB time ≤120 min (FC, n=134; cryoprecipitate, n=146), the ratio of least-squares means between the FC and cryoprecipitate groups for total allogeneic blood products at 24 h was 0.90 (one-sided 97.5% confidence interval [CI]: 0.00-1.12); P=0.004. For subjects with CPB time 121-180 min, it was 1.00 ([one-sided 97.5% CI: 0.00-1.22]; P=0.03], and for CPB time >180 min it was 0.91 ([one-sided 97.5% CI: 0.00-1.12]; P=0.005). Results were similar for all secondary outcomes, with no interaction between treatment and CPB duration for all outcomes. CONCLUSIONS: The haemostatic efficacy of FC was non-inferior to cryoprecipitate irrespective of CPB duration in cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03037424.

Effect of intravenous acetaminophen on postoperative outcomes in hip fracture patients: a systematic review and narrative synthesis.

PURPOSE: Hip fractures are debilitating in older adults because of their impact on quality of life. Opioids are associated with adverse effects in this population, so oral acetaminophen is commonly prescribed to minimize opioid use. Intravenous (iv) acetaminophen has been reported to have superior efficacy and bioavailability than oral acetaminophen. Nevertheless, its effect on postoperative outcomes in emergency hip fractures is unclear. This systematic review assessed the effect of iv acetaminophen on postoperative outcomes in older hip fracture patients. SOURCE: We searched multiple databases from inception to June 2021 for studies on adults > 50 yr of age undergoing emergency hip fracture surgery who received iv acetaminophen (or paracetamol) and that reported postoperative outcomes. Relevant titles, abstracts, and full texts were screened based on the eligibility criteria. The Newcastle-Ottawa scale was used to assess the quality of the selected papers. PRINCIPAL FINDINGS: Of 3,510 initial studies, four met the inclusion criteria. One was a prospective cohort study and three were retrospective cohort studies. All four studies used historical control groups. Three studies reported a significantly lower mean opioid dose with iv acetaminophen than with oral acetaminophen. Three studies also reported a significantly shorter hospital stay. One study each reported a significant decrease in the number of missed physical therapy sessions, the need for one-to-one supervision, and episodes of delirium. CONCLUSION: There is very limited low-level evidence that iv acetaminophen improves preoperative and postoperative analgesia and shortens hospital stay in older hip fracture patients. Nevertheless, our results should be interpreted with caution since there are no prospective randomized trials investigating whether iv acetaminophen improves postoperative outcomes in this patient population. STUDY REGISTRATION: PROSPERO (CRD42021198174); registered 15 August 2021.

RéSUMé: OBJECTIF: Les fractures de la hanche sont débilitantes chez les personnes âgées en raison de leur impact sur leur qualité de vie. Les opioïdes sont associés à des effets indésirables chez cette population, de sorte que l'acétaminophène par voie orale est couramment prescrit pour minimiser la consommation d'opioïdes. L'acétaminophène par voie intraveineuse (IV) a une efficacité et une biodisponibilité supérieures à celles de l'acétaminophène par voie orale. Néanmoins, son effet sur les devenirs postopératoires dans les fractures d'urgence de la hanche n'est pas clair. Cette revue systématique a évalué l'effet de l'acétaminophène IV sur les devenirs postopératoires chez les patients âgés avec une fracture de la hanche. SOURCES: Nous avons effectué des recherches dans plusieurs bases de données de leur création à juin 2021 pour en tirer les études portant sur des adultes > 50 ans bénéficiant d'une chirurgie d'urgence pour une fracture de la hanche et ayant reçu de l'acétaminophène IV (ou paracétamol), et qui rapportait les devenirs postopératoires. Les titres, résumés et textes intégraux pertinents ont été sélectionnés en fonction des critères d'admissibilité. L'échelle de Newcastle-Ottawa a été utilisée pour évaluer la qualité des articles sélectionnés. CONSTATATIONS PRINCIPALES: Sur les 3510 études initiales, quatre ont répondu aux critères d'inclusion. L'une était une étude de cohorte prospective et trois étaient des études de cohorte rétrospectives. Les quatre études ont utilisé des groupes témoins historiques. Trois études ont rapporté une dose moyenne d'opioïdes significativement plus faible avec l'acétaminophène IV qu'avec de l'acétaminophène par voie orale. Trois études ont également rapporté un séjour à l'hôpital significativement plus court. Une diminution significative du nombre de séances de physiothérapie manquées a été rapporté dans une étude, une autre a rapporté une diminution significative de la nécessité de supervision individuelle, et une troisième une réduction des épisodes d'état confusionnel aigu. CONCLUSION: : Il n'existe que très peu de données probantes qui sont de faible qualité et selon lesquelles l'acétaminophène IV améliore l'analgésie préopératoire et postopératoire et réduit la durée de séjour à l'hôpital chez les patients âgés atteints d'une fracture de hanche. Néanmoins, nos résultats doivent être interprétés avec prudence car il n'existe pas d'étude randomisée prospective évaluant si l'acétaminophène IV améliore les issues postopératoires dans cette population de patients. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021198174); enregistrée le 15 août 2021.

Albumin use for fluid resuscitation in cardiac surgical patients: a survey of Canadian perioperative care providers.

PURPOSE: To evaluate the perceptions and practices of Canadian cardiovascular anesthesiologists and intensivists towards intravenous albumin as a resuscitation fluid in patients undergoing cardiac surgery. METHODS: We conducted a cross-sectional survey of cardiac anesthesiologists and intensivists involved in the care of cardiac surgical patients. The 22-item survey included seven open-ended questions and assessed practice patterns and attitudes towards albumin. Descriptive statistics were analyzed using counts and proportions. Qualitative data were analyzed to identify themes describing albumin use patterns in Canada. RESULTS: A total of 133 respondents from seven provinces participated, with 83 (62%) using albumin perioperatively. The majority of respondents (77%) felt a low fluid balance in cardiac surgical patients was important, and that supplementing crystalloids with albumin was helpful for this objective (67%). There was poor agreement among survey respondents regarding the role of albumin for faster vasopressor weaning or intensive care discharge, and ≥ 90% did not feel albumin reduced mortality, renal injury, or coagulopathy. Nevertheless, cardiac surgical patients were identified as a distinct population where albumin may help to minimize fluid balance. There was an acknowledged paucity of formal evidence supporting possible benefits. Fewer than 10% of respondents could identify institutional or national guidelines for albumin use. A lack of evidence supporting albumin use in cardiac surgical patients, especially those at highest risk of complications, was a frequently identified concern. CONCLUSIONS: The majority of Canadian anesthesiologists and intensivists (62%) use albumin in cardiac surgical patients. There is clinical equipoise regarding its utility, and an acknowledged need for higher quality evidence to guide practice.

RéSUMé: OBJECTIF: Évaluer les perceptions et les pratiques des anesthésiologistes et intensivistes cardiovasculaires canadiens à l'égard de l'albumine intraveineuse comme liquide de réanimation pour les patients bénéficiant d'une chirurgie cardiaque. MéTHODE: Nous avons mené un sondage transversal auprès d'anesthésiologistes et d'intensivistes cardiaques impliqués dans les soins aux patients de chirurgie cardiaque. Le sondage en 22 éléments comprenait sept questions ouvertes et évaluait les habitudes de pratique et les attitudes des praticiens à l'égard de l'albumine. Les statistiques descriptives ont été analysées à l'aide de dénombrements et de proportions. Des données qualitatives ont été analysées pour identifier des thèmes décrivant les tendances d'utilisation de l'albumine au Canada. RéSULTATS: Au total, 133 répondants de sept provinces ont participé, et 83 (62 %) utilisent l'albumine en périopératoire. La majorité des répondants (77 %) estimaient qu'un bilan liquidien négatif était important chez les patients en chirurgie cardiaque et que la supplémentation en cristalloïdes par de l'albumine était utile pour atteindre cet objectif (67 %). Il y avait un faible accord parmi les répondants concernant le rôle de l'albumine pour accélérer le sevrage des vasopresseurs ou la sortie de soins intensifs, et ≥ 90 % ne pensaient pas que l'albumine réduisait la mortalité, les lésions rénales ou la coagulopathie. Néanmoins, les patients en chirurgie cardiaque ont été identifiés comme une population distincte pour laquelle l'albumine pourrait contribuer à minimiser le bilan liquidien. Il y avait un manque reconnu de données probantes formelles à l'appui des avantages possibles. Moins de 10 % des répondants ont pu trouver des lignes directrices institutionnelles ou nationales portant sur l'utilisation de l'albumine. Le manque de données probantes à l'appui de l'utilisation de l'albumine chez les patients en chirurgie cardiaque, en particulier chez ceux présentant le risque le plus élevé de complications, était une préoccupation fréquemment identifiée. CONCLUSION: La majorité des anesthésiologistes et intensivistes canadiens (62 %) utilisent l'albumine chez les patients en chirurgie cardiaque. Il existe un équilibre clinique quant à son utilité et un besoin reconnu de données probantes de meilleure qualité pour guider la pratique.