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The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Purpose Postoperative pulmonary complications (PPCs) are a common cause of morbidity. Postoperative atelectasis is thought to be a significant risk factor in their development. Recent imaging studies suggest that patients’ extubation may result in similar postoperative atelectasis regardless of the intraoperative mechanical ventilation strategy used. In this pilot trial, we hypothesized that a study investigating the effects of an open lung extubation strategy compared with a conventional one on PPCs would be feasible. Methods We conducted a pilot, single-centre, double-blinded randomized controlled trial. Adult patients at moderate to high risk of PPCs and scheduled for elective surgery were eligible. Patients were randomized to an open lung extubation strategy (semirecumbent position, fraction of inspired oxygen [F I O 2 ] 50%, pressure support ventilation, unchanged positive end-expiratory pressure) or to a conventional extubation strategy (dorsal decubitus position, F I O 2 100%, manual bag ventilation). The primary feasibility outcome was global protocol adherence while the primary exploratory efficacy outcome was PPCs. Results We randomized 35 patients to the conventional extubation group and 34 to the open lung extubation group. We observed a global protocol adherence of 96% (95% confidence interval, 88 to 99), which was not different between groups. Eight PPCs occurred (two in the conventional extubation group vs six in the open lung extubation group). Less postoperative supplemental oxygen and better lung aeration were observed in the open lung extubation group. Conclusions In this single-centre pilot trial, we observed excellent feasibility. A multicentre pilot trial comparing the effect of an open lung extubation strategy with that of a conventional extubation strategy on the occurrence of PPCs is feasible. Study registration date ClinicalTrials.gov (NCT04993001); registered 6 August 2021.

Neonatal abstinence syndrome is increasingly prevalent, and may be related to opioid use disorders caused by postoperative prescriptions for pain control. We assessed the association of maternal prepregnancy surgery with risk of neonatal abstinence syndrome from opioid use disorders in future pregnancies. We conducted a longitudinal retrospective cohort study of 2 182 365 deliveries in Quebec, Canada, between 1989 and 2016. The main exposure was maternal prepregnancy surgery. The main outcome measure was neonatal abstinence syndrome in offspring. We adjusted associations for maternal comorbidity and pregnancy characteristics using log-binomial regression models. The prevalence of neonatal abstinence syndrome in the cohort was 10.7 per 10 000 births. Compared with no surgery, prepregnancy surgery was associated with a risk ratio (RR) of neonatal abstinence syndrome of 1.63 (95% confidence interval [CI] 1.49–1.78). Risk was greater for 3 or more prepregnancy surgeries (RR 2.34, 95% CI 2.07–2.63) and age < 15 years at first surgery (1 surgery: RR 2.08, 95% CI 1.71–2.54; 2 or more surgeries: RR 2.79, 95% CI 2.32–3.37). Nearly all surgical specialties increased the risk of neonatal abstinence syndrome, but associations were strongest for cardiothoracic surgery (RR 4.45, 95% CI 2.87–6.91), neurosurgery (RR 3.00, 95% CI 1.56–5.77) and urologic surgery (RR 3.03, 95% CI 2.16–4.26). Prepregnancy surgery is associated with the risk of neonatal abstinence syndrome in future pregnancies. Prescription opioids for postsurgical pain may result in opioid use disorders during future pregnancies, inadvertently increasing the risk of neonatal abstinence syndrome in offspring.

Attending anesthesiologists estimated IBL by adding the blood volume recovered in the cell saver canister (used for every transplantation), the regular suction canisters, and the sponges (by visual inspection), and then subtracted the irrigation fluid and heparin solution volumes used. Both measures may probably be used interchangeably at the population level to evaluate program performance, but probably not at the individual level. Tran, A; Heuser, J; Ramsay, T; McIsaac, DI; Martel, G. Techniques for blood loss estimation in major non-cardiac surgery: a systematic review and meta-analysis.

Purpose The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. Methods We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from “never” to “always”) and numerical or categorical answers. Results are presented as medians or proportions. Results We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48–64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. Conclusion Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

Purpose A consensus group recently proposed epidural analgesia as the optimal analgesic modality for patients with multiple traumatic rib fractures. However, its beneficial effects are not consistently recognized in the literature. We performed a systematic review and a meta-analysis of randomized controlled trials (RCT) of epidural analgesia in adult patients with traumatic rib fractures. Methods A systematic search strategy was applied to MEDLINE, EMBASE, the Cochrane Library and to the annual meeting of relevant societies (up to July 2008). All randomized controlled trials comparing epidural analgesia with other analgesic modalities in adult patients with traumatic rib fractures were included. Primary outcomes were mortality, ICU length of stay (LOS), hospital LOS and duration of mechanical ventilation. Results Eight studies (232 patients) met eligibility criteria. Epidural analgesia did not significantly affect mortality (odds ratio [OR] 1.6, 95% CI, 0.3, 9.3, 3 studies, n  = 89), ICU LOS (weighted mean difference [WMD] −3.7 days, 95% CI, −11.4, 4.0, 4 studies, n  = 135), hospital LOS (WMD −6.7, 95% CI, −19.8, 6.4, 4 studies, n  = 140) or duration of mechanical ventilation (WMD −7.5, 95% CI, −16.3, 1.2, 3 studies, n  = 101). Duration of mechanical ventilation was decreased when only studies using thoracic epidural analgesia with local anesthetics were evaluated (WMD −4.2, 95% CI, −5.5, −2.9, 2 studies, n  = 73). However, hypotension was significantly associated with the use of thoracic epidural analgesia with local anesthetics (OR 13.76, 95% CI, 2.89, 65.51, 3 studies, n  = 99). Conclusions No significant benefit of epidural analgesia on mortality, ICU and hospital LOS was observed compared to other analgesic modalities in adult patients with traumatic rib fractures. However, there may be a benefit on the duration of mechanical ventilation with the use of thoracic epidural analgesia with local anesthetics. Further research is required to evaluate the benefits and harms of epidural analgesia in this population before being considered as a standard of care therapy.

While there is limited patient-centred evidence (i.e., evidence that is important for patients and end-users) to inform the use of pharmacologic opioid minimization strategies (i.e., the use of opioid alternatives) for adult surgical patients requiring general anesthesia, such strategies are increasingly being adopted into practice. Our objectives were to describe anesthesiologists' beliefs regarding intraoperative opioid minimizing strategies use and utility, and to explore important clinical decision-making factors. We conducted a pan-Canadian web-based survey of anesthesiologists that was distributed using a modified Dillman technique. Our multidisciplinary team, including a patient partners panel, participated in the process of domains and items generation, items reduction, formatting, and composition. Our sampling frames were members of the Canadian Anesthesiologists' Society and members of the Association des Anesthésiologistes du Québec. We used the newsletters of each organization to distribute our survey, which was available in English and French and housed on the LimeSurvey (LimeSurvey GmbH, Hamburg, Germany) platform. From our eligible sampling frame, 18% completed the survey (356 respondents out of 2,008 eligible participants). Most of the respondents believed that using opioid minimization strategies during general anesthesia could improve postoperative clinical outcomes, including pain control (84% agree or strongly agree, n = 344/409). Reported use of pharmacologic opioid minimization strategies was variable; however, most respondents believed that nonsteroidal anti-inflammatory drugs, acetaminophen, N-methyl-D-aspartate receptor antagonists (ketamine), α -adrenoceptor agonists (dexmedetomidine), corticosteroids, and intravenous lidocaine improve prostoperative clinical outcomes. The primary factors guiding decision-making regarding the use of opioid minimization strategies were postoperative acute pain intensity, the impact of acute pain on functioning, patient well-being (i.e., quality of recovery) and patient satisfaction with care. A lack of evidence was the most important barrier limiting the use of opioid minimization strategies. In our survey of Canadian anesthesiologists, several opioid minimization strategies were believed to be effective complements to general anesthesia, although there was substantial variation in their reported use. Future randomized controlled trials and systematic reviews evaluating the effectiveness of opioid minimization strategies should prioritize patient-centred outcome measures assessment such as the quality of recovery or the impact of acute pain on functioning.

Background: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. Methods: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. Results: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 ([+ or -] standard deviation [SD] 10.5) and 21.4 ([+ or -] SD 11.3) in those receiving remdesivir and 14.2 ([+ or -] SD 11) and 19.5 ([+ or -] SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. Interpretation: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Purpose While there is limited patient-centred evidence (i.e., evidence that is important for patients and end-users) to inform the use of pharmacologic opioid minimization strategies (i.e., the use of opioid alternatives) for adult surgical patients requiring general anesthesia, such strategies are increasingly being adopted into practice. Our objectives were to describe anesthesiologists’ beliefs regarding intraoperative opioid minimizing strategies use and utility, and to explore important clinical decision-making factors. Methods We conducted a pan-Canadian web-based survey of anesthesiologists that was distributed using a modified Dillman technique. Our multidisciplinary team, including a patient partners panel, participated in the process of domains and items generation, items reduction, formatting, and composition. Our sampling frames were members of the Canadian Anesthesiologists’ Society and members of the Association des Anesthésiologistes du Québec. We used the newsletters of each organization to distribute our survey, which was available in English and French and housed on the LimeSurvey (LimeSurvey GmbH, Hamburg, Germany) platform. Results From our eligible sampling frame, 18% completed the survey (356 respondents out of 2,008 eligible participants). Most of the respondents believed that using opioid minimization strategies during general anesthesia could improve postoperative clinical outcomes, including pain control (84% agree or strongly agree, n  = 344/409). Reported use of pharmacologic opioid minimization strategies was variable; however, most respondents believed that nonsteroidal anti-inflammatory drugs, acetaminophen, N-methyl-D-aspartate receptor antagonists (ketamine), α 2 -adrenoceptor agonists (dexmedetomidine), corticosteroids, and intravenous lidocaine improve prostoperative clinical outcomes. The primary factors guiding decision-making regarding the use of opioid minimization strategies were postoperative acute pain intensity, the impact of acute pain on functioning, patient well-being (i.e., quality of recovery) and patient satisfaction with care. A lack of evidence was the most important barrier limiting the use of opioid minimization strategies. Conclusion In our survey of Canadian anesthesiologists, several opioid minimization strategies were believed to be effective complements to general anesthesia, although there was substantial variation in their reported use. Future randomized controlled trials and systematic reviews evaluating the effectiveness of opioid minimization strategies should prioritize patient-centred outcome measures assessment such as the quality of recovery or the impact of acute pain on functioning.