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INTRODUCTION: International data describes a changing pattern to trauma over the last decade, with an increasingly comorbid population presenting challenges to trauma management and resources. In Ireland, resource provision and management of trauma is being transformed to deliver a trauma network, in line with international best practice. Our hospital plays a crucial role within this network and is designated a Trauma Unit with Specialist Services (TUSS) to distinguish it from standard trauma units. METHODS: This study aims to describe the characteristics of patients and injuries and assess trends in mortality rates. It is a retrospective observational study of adult ICU trauma admissions from August 2010 to July 2021. Primary outcome was all-cause mortality at 30-days, 90-days, and 1 year. Secondary outcomes included length of stay, disposition, and complications. Patients were categorised by age, injury severity score (ISS), and mechanism of injury. RESULTS: In all, 709 patients were identified for final analysis. Annual admissions doubled since 2010/11, with a trough of 41 admissions, increasing to peak at 95 admissions in 2017/18. Blunt trauma accounted for 97.6% of cases. Falls <2 m (45.4%) and RTAs (29.2%) were the main mechanisms of injury. Polytrauma comprised 41.9% of admissions. Traumatic brain injury accounted for 30.2% of cases; 18.8% of these patients were transferred to a neurosurgical centre. The majority of patients, 58.1%, were severely injured (ISS ≥ 16). Patients ≥ 65 years of age accounted for 45.7% of admissions, with falls <2 m their primary mechanism of injury. The primary outcome of all-cause mortality reduced with an absolute risk reduction (ARR) of 8.0% (95% CI: -8.37%, 24.36%), 12.9% (95% CI: -4.19%, 29.94%) and 8.2% (95% CI: -9.64%, 26.09%) for 30-day, 90-day and 1-year respectively. Regression analysis demonstrated a significant reduction in mortality for 30-days and 90-days post presentation to hospital (P-values of 0.018, 0.033 and 0.152 for 30-day, 90-day and 1-year respectively). CONCLUSION: The burden of major trauma in our hospital is considerable and increasing over time. Substantial changes in demographics, injury mechanism and mortality were seen, with outcomes improving over time. This is consistent with international data where trauma systems have been adopted.
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Cuidados Críticos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Centros Traumatológicos , Heridas y Lesiones , Humanos , Masculino , Estudios Retrospectivos , Femenino , Centros Traumatológicos/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Anciano , Cuidados Críticos/estadística & datos numéricos , Irlanda/epidemiología , Tiempo de Internación/estadística & datos numéricos , Heridas y Lesiones/mortalidad , Heridas y Lesiones/terapia , Heridas y Lesiones/epidemiología , Mortalidad Hospitalaria , Traumatismo Múltiple/mortalidad , Traumatismo Múltiple/terapia , Traumatismo Múltiple/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Adulto JovenRESUMEN
Awake prone positioning (APP) of patients with acute hypoxaemic respiratory failure gained considerable attention during the early phases of the coronavirus disease 2019 (COVID-19) pandemic. Prior to the pandemic, reports of APP were limited to case series in patients with influenza and in immunocompromised patients, with encouraging results in terms of tolerance and oxygenation improvement. Prone positioning of awake patients with acute hypoxaemic respiratory failure appears to result in many of the same physiological changes improving oxygenation seen in invasively ventilated patients with moderate-severe acute respiratory distress syndrome. A number of randomised controlled studies published on patients with varying severity of COVID-19 have reported apparently contrasting outcomes. However, there is consistent evidence that more hypoxaemic patients requiring advanced respiratory support, who are managed in higher care environments and who can be prone for several hours, benefit most from APP use. We review the physiological basis by which prone positioning results in changes in lung mechanics and gas exchange and summarise the latest evidence base for APP primarily in COVID-19. We examine the key factors that influence the success of APP, the optimal target populations for APP and the key unknowns that will shape future research.
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COVID-19 , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Humanos , Vigilia , Posición Prona/fisiología , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/terapia , Pulmón , Posicionamiento del Paciente/métodosRESUMEN
BACKGROUND: COVID-19 pneumonia is associated with the development of acute respiratory distress syndrome (ARDS) displaying some typical histological features. These include diffuse alveolar damage with extensive pulmonary coagulation activation. This results in fibrin deposition in the microvasculature, leading to the formation of hyaline membranes in the air sacs. Well-conducted clinical trials have found that nebulised heparin limits pulmonary fibrin deposition, attenuates progression of ARDS, hastens recovery and is safe in non-COVID ARDS. Unfractionated heparin also inactivates the SARS-CoV-2 virus and prevents entry into mammalian cells. Nebulisation of heparin may therefore limit fibrin-mediated lung injury and inhibit pulmonary infection by SARS-CoV-2. Based on these findings, we designed the CHARTER-Ireland Study, a phase 1b/2a randomised controlled study of nebulised heparin in patients requiring advanced respiratory support for COVID-19 pneumonia. METHODS: This is a multi-centre, phase 1b/IIa, randomised, parallel-group, open-label study. The study will randomise 40 SARs-CoV-2-positive patients receiving advanced respiratory support in a critical care area. Randomisation will be via 1:1 allocation to usual care plus nebulised unfractionated heparin 6 hourly to day 10 while receiving advanced respiratory support or usual care only. The study aims to evaluate whether unfractionated heparin will decrease the procoagulant response associated with ARDS up to day 10. The study will also assess safety and tolerability of nebulised heparin as defined by number of severe adverse events; oxygen index and respiratory oxygenation index of intubated and unintubated, respectively; ventilatory ratio; and plasma concentration of interleukin (IL)-1ß, IL6, IL-8, IL-10 and soluble tumour necrosis factor receptor 1, C-reactive protein, procalcitonin, ferritin, fibrinogen and lactate dehydrogenase as well as the ratios of IL-1ß/IL-10 and IL-6/IL-10. These parameters will be assessed on days 1, 3, 5 and 10; time to separation from advanced respiratory support, time to discharge from the intensive care unit and number tracheostomised to day 28; and survival to days 28 and 60 and to hospital discharge, censored at day 60. Some clinical outcome data from our study will be included in the international meta-trials, CHARTER and INHALE-HEP. DISCUSSION: This trial aims to provide evidence of potential therapeutic benefit while establishing safety of nebulised heparin in the management of ARDS associated with SARs-CoV-2 infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04511923 . Registered on 13 August 2020. Protocol version 8, 22/12/2021 Protocol identifier: NUIG-2020-003 EudraCT registration number: 2020-003349-12 9 October 2020.
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Lesión Pulmonar Aguda , COVID-19 , Síndrome de Dificultad Respiratoria , Lesión Pulmonar Aguda/diagnóstico , Lesión Pulmonar Aguda/etiología , Animales , Fibrina , Heparina/efectos adversos , Humanos , Interleucina-10 , Irlanda , Mamíferos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , SARS-CoV-2RESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed the disproportionate effects of pandemics on frontline workers and the ethical imperative to provide effective prophylaxis. We present a model for a pragmatic randomised controlled trial (RCT) that utilises Bayesian methods to rapidly determine the efficacy or futility of a prophylactic agent. METHODS: We initially planned to undertake a multicentre, phase III, parallel-group, open-label RCT, to determine if hydroxychloroquine (HCQ) taken once a week was effective in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in healthcare workers (HCW) aged ≥ 18 years in New Zealand (NZ) and Ireland. Participants were to be randomised 2:1 to either HCQ (800 mg stat then 400 mg weekly) or no prophylaxis. The primary endpoint was time to Nucleic Acid Amplification Test-proven SARS-CoV-2 infection. Secondary outcome variables included mortality, hospitalisation, intensive care unit admissions and length of mechanical ventilation. The trial had no fixed sample size or duration of intervention. Bayesian adaptive analyses were planned to occur fortnightly, commencing with a weakly informative prior for the no prophylaxis group hazard rate and a moderately informative prior on the intervention log hazard ratio centred on 'no effect'. Stopping for expected success would be executed if the intervention had a greater than 0.975 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Final success would be declared if, after completion of 8 weeks of follow-up (reflecting the long half-life of HCQ), the prophylaxis had at least a 0.95 posterior probability of reducing the risk of SARS-CoV-2 infection by more than 10%. Futility would be declared if HCQ was shown to have less than a 0.10 posterior probability of reducing acquisition of SARS-CoV-2 infection by more than 20%. DISCUSSION: This study did not begin recruitment due to the marked reduction in COVID-19 cases in NZ and concerns regarding the efficacy and risks of HCQ treatment in COVID-19. Nonetheless, the model presented can be easily adapted for other potential prophylactic agents and pathogens, and pre-established collaborative models like this should be shared and incorporated into future pandemic preparedness planning. TRIAL REGISTRATION: The decision not to proceed with the study was made before trial registration occurred.
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COVID-19 , Pandemias , COVID-19/prevención & control , Personal de Salud , Humanos , Hidroxicloroquina/efectos adversos , Pandemias/prevención & control , SARS-CoV-2RESUMEN
There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.
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Tratamiento Farmacológico de COVID-19 , Ventilación no Invasiva , Insuficiencia Respiratoria , Extubación Traqueal , Heparina , Humanos , Pulmón , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Respiratoria/inducido químicamente , SARS-CoV-2 , Resultado del TratamientoRESUMEN
BACKGROUND: Awake prone positioning (APP) has been advocated to improve oxygenation and prevent intubation of patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). This paper aims to synthesize the available evidence on the efficacy of APP. METHODS: We performed a systematic review of proportional outcomes from observational studies to compare intubation rate in patients treated with APP or with standard care. RESULTS: A total of 46 published and 4 unpublished observational studies that included 2,994 subjects were included, of which 921 were managed with APP and 870 were managed with usual care. APP was associated with significant improvement of oxygenation parameters in 381 cases of 19 studies that reported this outcome. Among the 41 studies assessing intubation rates (870 subjects treated with APP and 852 subjects treated with usual care), the intubation rate was 27% (95% CI 19-37%) as compared to 30% (95% CI 20-42%) (P = .71), even when duration of application, use of adjunctive respiratory assist device (high-flow nasal cannula or noninvasive ventilation), and severity of oxygenation deficit were taken into account. There appeared to be a trend toward improved mortality when APP was compared with usual care (11% vs 22%), which was not statistically significant. CONCLUSIONS: APP was associated with improvement of oxygenation but did not reduce the intubation rate in subjects with acute respiratory failure due to COVID-19. This finding is limited by the high heterogeneity and the observational nature of included studies. Randomized controlled clinical studies are needed to definitively assess whether APP could improve key outcome such as intubation rate and mortality in these patients.
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COVID-19 , Ventilación no Invasiva , Insuficiencia Respiratoria , Humanos , COVID-19/complicaciones , COVID-19/terapia , Vigilia , Posición Prona , Hipoxia/etiología , Hipoxia/terapia , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/complicacionesRESUMEN
BACKGROUND: Awake prone positioning has been reported to improve oxygenation for patients with COVID-19 in retrospective and observational studies, but whether it improves patient-centred outcomes is unknown. We aimed to evaluate the efficacy of awake prone positioning to prevent intubation or death in patients with severe COVID-19 in a large-scale randomised trial. METHODS: In this prospective, a priori set up and defined, collaborative meta-trial of six randomised controlled open-label superiority trials, adults who required respiratory support with high-flow nasal cannula for acute hypoxaemic respiratory failure due to COVID-19 were randomly assigned to awake prone positioning or standard care. Hospitals from six countries were involved: Canada, France, Ireland, Mexico, USA, Spain. Patients or their care providers were not masked to allocated treatment. The primary composite outcome was treatment failure, defined as the proportion of patients intubated or dying within 28 days of enrolment. The six trials are registered with ClinicalTrials.gov, NCT04325906, NCT04347941, NCT04358939, NCT04395144, NCT04391140, and NCT04477655. FINDINGS: Between April 2, 2020 and Jan 26, 2021, 1126 patients were enrolled and randomly assigned to awake prone positioning (n=567) or standard care (n=559). 1121 patients (excluding five who withdrew from the study) were included in the intention-to-treat analysis. Treatment failure occurred in 223 (40%) of 564 patients assigned to awake prone positioning and in 257 (46%) of 557 patients assigned to standard care (relative risk 0·86 [95% CI 0·75-0·98]). The hazard ratio (HR) for intubation was 0·75 (0·62-0·91), and the HR for mortality was 0·87 (0·68-1·11) with awake prone positioning compared with standard care within 28 days of enrolment. The incidence of prespecified adverse events was low and similar in both groups. INTERPRETATION: Awake prone positioning of patients with hypoxaemic respiratory failure due to COVID-19 reduces the incidence of treatment failure and the need for intubation without any signal of harm. These results support routine awake prone positioning of patients with COVID-19 who require support with high-flow nasal cannula. FUNDING: Open AI inc, Rice Foundation, Projet Hospitalier de Recherche Clinique Interrégional, Appel d'Offre 2020, Groupement Interrégional de Recherche Clinique et d'Innovation Grand Ouest, Association pour la Promotion à Tours de la Réanimation Médicale, Fond de dotation du CHRU de Tours, Fisher & Paykel Healthcare Ltd.
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COVID-19 , Posicionamiento del Paciente , Posición Prona , Insuficiencia Respiratoria , Adulto , COVID-19/terapia , Canadá , Francia , Humanos , Irlanda , México , Estudios Prospectivos , Insuficiencia Respiratoria/terapia , SARS-CoV-2 , España , Resultado del Tratamiento , Estados Unidos , VigiliaRESUMEN
Introduction: The first case of COVID-19 in Ireland was diagnosed on 29 February 2020. Within the same week, our Department of Anaesthesia and Critical Care at University Hospital Galway began to tackle the educational challenge by developing an â¯in situ interprofessional simulation programme to prepare staff for the impending outbreak. Principles and approaches used for simulation-based training: We describe principles applied to identify core educational and system engineering objectives to prepare healthcare workers (HCWs) for infection control, personal and psychological safety, technical and crisis resource management skills. We discuss application of educational theories, rationale for simulation modes and debriefing techniques. Development of the simulation programme: 3 anaesthesia (general, obstetric, paediatric) and 1 critical care silo were created. 13 simulated scenarios were developed for teaching as well as for testing workflows specific to the outbreak. To support HCWs and ensure safety, management guidelines, cognitive aids and checklists were developed using simulation. The cumulative number of HCWs trained in simulation was 750 over a 4-week period. Challenges and future directions: Due to the protracted nature of the pandemic, simulation educators should address questions related to sustainability, infection control while delivering simulation, establishment of hybrid programmes and support for psychological preparedness.
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AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.
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COVID-19 , Heparina , Adulto , Teorema de Bayes , Humanos , Estudios Prospectivos , SARS-CoV-2 , Resultado del TratamientoRESUMEN
INTRODUCTION: Prone positioning (PP) is an effective first-line intervention to treat patients with moderate to severe acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation, as it improves gas exchanges and reduces mortality. The use of PP in awake spontaneous breathing patients with ARDS secondary to COVID-19 was reported to improve oxygenation in few retrospective trials with small sample size. High-level evidence of awake PP for hypoxaemic patients with COVID-19 patients is still lacking. METHODS AND ANALYSIS: The protocol of this meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled open label superiority trials. This design is particularly adapted to a rapid scientific response in the pandemic setting. It will take place in multiple sites, among others in USA, Canada, Ireland, France and Spain. Patients will be followed up for 28 days. Patients will be randomised to receive whether awake PP and nasal high flow therapy or standard medical treatment and nasal high flow therapy. Primary outcome is defined as the occurrence rate of tracheal intubation or death up to day 28. An interim analysis plan has been set up on aggregated data from the participating research groups. ETHICS AND DISSEMINATION: Ethics approvals were obtained in all participating countries. Results of the meta-trial will be submitted for publication in a peer-reviewed journal. Each randomised controlled trial was registered individually, as follows: NCT04325906, NCT04347941, NCT04358939, NCT04395144 and NCT04391140.
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Infecciones por Coronavirus/terapia , Hipoxia/terapia , Terapia por Inhalación de Oxígeno/métodos , Posicionamiento del Paciente/métodos , Neumonía Viral/terapia , Posición Prona , Betacoronavirus , COVID-19 , Cánula , Estudios de Equivalencia como Asunto , Humanos , Metaanálisis como Asunto , Pandemias , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2 , VigiliaAsunto(s)
Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Posición Prona , Insuficiencia Respiratoria/terapia , COVID-19 , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/complicaciones , Humanos , Pandemias , Posicionamiento del Paciente , Neumonía Viral/complicaciones , Respiración Artificial , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/etiologíaRESUMEN
BACKGROUND: Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. METHODS/DESIGN: 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. DISCUSSION: The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.