RESUMEN
PURPOSE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.
RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l'analgésie pour les patient·es gravement malades, mais l'exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l'hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d'effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l'égard de l'utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l'aide d'une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d'élaboration d'enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L'utilisation d'anti-inflammatoires non stéroïdiens a été décrite comme « rare ¼ (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l'acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l'utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n'ont pas mentionné l'utilisation courante d'AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.
RESUMEN
BACKGROUND: The spontaneous breathing trial (SBT) technique that best balance successful extubation with the risk for reintubation is unknown. We sought to determine the comparative efficacy and safety of alternative SBT techniques. METHODS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2023 for randomized or quasi-randomized trials comparing SBT techniques in critically ill adults and children and reported initial SBT success, successful extubation, reintubation (primary outcomes) and mortality (ICU, hospital, most protracted; secondary outcome) rates. Two reviewers screened, reviewed full-texts, and abstracted data. We performed frequentist random-effects network meta-analysis. RESULTS: We included 40 RCTs (6716 patients). Pressure Support (PS) versus T-piece SBTs was the most common comparison. Initial successful SBT rates were increased with PS [risk ratio (RR) 1.08, 95% confidence interval (CI) (1.05-1.11)], PS/automatic tube compensation (ATC) [1.12 (1.01 -1.25), high flow nasal cannulae (HFNC) [1.07 (1.00-1.13) (all moderate certainty), and ATC [RR 1.11, (1.03-1.20); low certainty] SBTs compared to T-piece SBTs. Similarly, initial successful SBT rates were increased with PS, ATC, and PS/ATC SBTs compared to continuous positive airway pressure (CPAP) SBTs. Successful extubation rates were increased with PS [RR 1.06, (1.03-1.09); high certainty], ATC [RR 1.13, (1.05-1.21); moderate certainty], and HFNC [RR 1.06, (1.02-1.11); high certainty] SBTs, compared to T-piece SBTs. There was little to no difference in reintubation rates with PS (vs. T-piece) SBTs [RR 1.05, (0.91-1.21); low certainty], but increased reintubation rates with PS [RR 2.84, (1.61-5.03); moderate certainty] and ATC [RR 2.95 (1.57-5.56); moderate certainty] SBTs compared to HFNC SBTs. CONCLUSIONS: SBTs conducted with pressure augmentation (PS, ATC, PS/ATC) versus without (T-piece, CPAP) increased initial successful SBT and successful extubation rates. Although SBTs conducted with PS or ATC versus HFNC increased reintubation rates, this was not the case for PS versus T-piece SBTs.
Asunto(s)
Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Extubación Traqueal/métodos , Extubación Traqueal/estadística & datos numéricos , Desconexión del Ventilador/métodos , Desconexión del Ventilador/estadística & datos numéricos , Desconexión del Ventilador/normasRESUMEN
Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the wild-type (WT) strain, with MotAB stators produced at an approximately 40-fold higher level than MotCD stators. However, utilization of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily utilized at low viscosities. Importantly, we find that cells with MotCD stators are ~10× more likely to have an active motor compared to cells uses the MotAB stators. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa, transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator utilization. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the "jamming transition" in active granular matter.IMPORTANCEIt is now known that there exist multifactorial influences on swarming motility for P. aeruginosa, but it is not clear precisely why stator selection in the flagellum motor is so important. We show differential production and utilization of the stators. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies: the fraction of flagellum-active cells in a population on average with MotCD is active ~10× more often than with MotAB. What emerges from this complex landscape of stator utilization and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility and how the stators potentially relate to surface sensing circuitry.
Asunto(s)
Proteínas Bacterianas , Pseudomonas aeruginosa , Pseudomonas aeruginosa/genética , Biopelículas , Movimiento , Flagelos/genéticaRESUMEN
PURPOSE: Venous congestion is a pathophysiologic state that can result in organ dysfunction, particularly acute kidney injury (AKI). We sought to evaluate the feasibility of performing a definitive observational study to determine the impact of venous congestion quantified using point-of-care ultrasound (POCUS) in patients with septic shock. METHODS: We conducted a prospective observational feasibility study at two intensive care units (ICUs). We recruited adult patients with septic shock within 12 hr of ICU admission. Using the validated Venous Excess Ultrasound Score (VEXUS), we quantified venous congestion on day 1 and day 3 of ICU admission. The primary feasibility outcome was successful completion rate of the two VEXUS scores. We performed a survival analysis to quantify the hazard of renal replacement therapy (RRT). RESULTS: We enrolled 75 patients from January 2022 to January 2023. The success rate of completion for VEXUS scans was 94.5% (95% confidence interval [CI], 89.5 to 97.6). Severe venous congestion was present in 19% (14/75) of patients on ICU admission day 1 and in 16% (10/61) of patients on day 3. Venous congestion on ICU admission may be associated with a higher risk of requiring RRT (unadjusted hazard ratio, 3.35; 95% CI, 0.94 to 11.88; P = 0.06). CONCLUSIONS: It is feasible to conduct a definitive observational study exploring the association between venous congestion quantified with POCUS and clinical outcomes in patients with septic shock. We hypothesize that venous congestion may be associated with an increased hazard of receiving RRT.
RéSUMé: OBJECTIF: La congestion veineuse est un état physiopathologique qui peut entraîner un dysfonctionnement des organes, en particulier une insuffisance rénale aiguë (IRA). Nous avons cherché à évaluer la faisabilité de la réalisation d'une étude observationnelle définitive pour déterminer l'impact de la congestion veineuse quantifiée à l'aide de l'échographie ciblée (POCUS) chez des patient·es en choc septique. MéTHODE: Nous avons réalisé une étude de faisabilité observationnelle prospective dans deux unités de soins intensifs (USI). Nous avons recruté des patient·es adultes souffrant d'un choc septique dans les 12 heures suivant leur admission aux soins intensifs. À l'aide du score VEXUS (score d'échographie de l'excès veineux) validé, nous avons quantifié la congestion veineuse au jour 1 et au jour 3 de leur admission aux soins intensifs. Le principal critère de faisabilité était le taux de réussite des deux scores VEXUS. Nous avons réalisé une analyse de survie pour quantifier le risque de thérapie de substitution rénale (TSR). RéSULTATS: Nous avons recruté 75 patient·es de janvier 2022 à janvier 2023. Le taux de réussite des scores VEXUS était de 94,5 % (intervalle de confiance [IC] à 95 %, 89,5 à 97,6). Une congestion veineuse sévère était présente chez 19 % (14/75) des patient·es au jour 1 d'admission aux soins intensifs et chez 16 % (10/61) des patient·es au jour 3. La congestion veineuse lors de l'admission aux soins intensifs peut être associée à un risque plus élevé de nécessiter une TSR (rapport de risque non ajusté, 3,35; IC 95 %, 0,94 à 11,88; P = 0,06). CONCLUSION: Il est possible de mener une étude observationnelle définitive explorant l'association entre la congestion veineuse quantifiée par POCUS et les devenirs cliniques chez les patient·es en choc septique. Nous émettons l'hypothèse que la congestion veineuse peut être associée à un risque accru de recevoir une thérapie de substitution rénale.
Asunto(s)
Lesión Renal Aguda , Hiperemia , Choque Séptico , Adulto , Humanos , Choque Séptico/complicaciones , Choque Séptico/diagnóstico por imagen , Estudios Prospectivos , Hiperemia/diagnóstico por imagen , Hiperemia/complicaciones , Sistemas de Atención de Punto , Terapia de Reemplazo Renal , Unidades de Cuidados Intensivos , Lesión Renal Aguda/terapiaRESUMEN
OBJECTIVES: To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts patient-important outcomes. DATA SOURCES: A medical librarian searched Ovid MEDLINE, EMBASE, APA PsycInfo, and Wiley's Cochrane Library as well as clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2023. STUDY SELECTION: Independently and in duplicate, reviewers screened abstracts and titles for eligibility, then full text of qualifying studies. We included parallel-group randomized controlled trials (RCTs) that included critically ill adult patients with delirium. The intervention group was required to receive antipsychotic medications at any dose, whereas the control group received usual care or placebo. DATA EXTRACTION: Reviewers extracted data independently and in duplicate using a piloted abstraction form. Statistical analyses were conducted using RevMan software (version 5.4). DATA SYNTHESIS: Five RCTs ( n = 1750) met eligibility criteria. The use of antipsychotic medications compared with placebo did not increase the number of delirium- or coma-free days (mean difference 0.90 d; 95% CI, -0.32 to 2.12; moderate certainty), nor did it result in a difference in mortality, duration of mechanical ventilation, ICU, or hospital length of stay. The use of antipsychotics did not result in an increased risk of adverse events (risk ratio 1.27; 95% CI, 0.71-2.30; high certainty). Subgroup analysis of typical versus atypical antipsychotics did not identify any subgroup effect for any outcome. CONCLUSIONS: In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in delirium- or coma-free days when delirious critically ill adults are treated with antipsychotic medications. Further studies in the subset of patients with hyperactive delirium may be of benefit.
Asunto(s)
Antipsicóticos , Enfermedad Crítica , Delirio , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Delirio/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Enfermedad Crítica/terapiaRESUMEN
Importance: Considerable controversy exists regarding the best spontaneous breathing trial (SBT) technique to use. Objective: To summarize trials comparing alternative SBTs. Data Sources: Several databases (MEDLINE [from inception to February 2023], the Cochrane Central Register of Controlled Trials [in February 2023], and Embase [from inception to February 2023] and 5 conference proceedings (from January 1990 to April 2023) were searched in this systematic review and meta-analysis. Study Selection: Randomized trials directly comparing SBT techniques in critically ill adults or children and reporting at least 1 clinical outcome were selected. Data Extraction and Synthesis: Paired reviewers independently screened citations, abstracted data, and assessed quality for the systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidelines). Data were pooled using random-effects models. Main Outcomes and Measures: Primary outcomes included SBT success, extubation success, and reintubation. Results: The systematic review and meta-analysis identified 40 trials that included 6716 patients. Low-quality evidence (14 trials [n = 4459]) suggested that patients were not more likely to pass a pressure support (PS) compared with a T-piece SBT (risk ratio [RR], 1.04; 95% CI, 0.97-1.11; P = .31; I2 = 73%), unless 1 outlier trial accounting for all heterogeneity was excluded (RR, 1.09; 95% CI, 1.06-1.12; P < .001; I2 = 0% [13 trials; n = 3939]; moderate-quality evidence), but were significantly more likely to be successfully extubated (RR, 1.07; 95% CI, 1.04-1.10; P < .001; I2 = 0%; 16 trials [n = 4462]; moderate-quality evidence). Limited data (5 trials [n = 502]) revealed that patients who underwent automatic tube compensation/continuous positive airway pressure compared with PS SBTs had a significantly higher successful extubation rate (RR, 1.10; 95% CI, 1.00-1.21; P = .04; I2 = 0% [low-quality evidence]). Compared with T-piece SBTs, high-flow oxygen SBTs (3 trials [n = 386]) had significantly higher successful extubation (RR, 1.06; 95% CI, 1.00-1.11; P = .04; I2 = 0%) and lower reintubation (RR, 0.37; 95% CI, 0.21-0.65; P = <.001; I2 = 0% [both low-quality evidence]) rates. Credible subgroup effects were not found. Conclusions and Relevance: In this systematic review and meta-analysis, the findings suggest that patients undergoing PS compared with T-piece SBTs were more likely to be extubated successfully and more likely to pass an SBT, after exclusion of an outlier trial. Pressure support SBTs were not associated with increased risk of reintubation. Future trials should compare SBT techniques that maximize differences in inspiratory support.
Asunto(s)
Enfermedad Crítica , Desconexión del Ventilador , Adulto , Niño , Humanos , Enfermedad Crítica/terapia , Desconexión del Ventilador/métodos , Oxígeno , Presión de las Vías Aéreas Positiva Contínua , Intubación IntratraquealRESUMEN
Conducting clinical research during a 2-year critical care fellowship is a challenging endeavor. Fellows are often met with multiple barriers when considering clinical research projects during fellowship, including time, mentorship, resources, and clinical support. This paper presents the perspective and experiences of a group of critical care fellows who conducted the DRIVE-SAFE (Driving Pressure in Assisted Ventilation as a Predictor for Successful Liberation from Invasive Mechanical Ventilation) feasibility study, which aimed to determine measurable physiological variables that could be associated with lung injury and affect duration of mechanical ventilation. This paper provides a guide for trainees on how to conduct prospective clinical research at the bedside. We describe three key steps, including formulating a research question, developing appropriate methodology, and establishing outcomes. We also present the challenges that trainees may encounter when conducting prospective studies and how to overcome these challenges with proper mentorship, training, and collaboration with key stakeholders. These perspectives may provide useful guidance for current and future trainees interested in conducting prospective clinical research at the bedside.
RESUMEN
INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.
Asunto(s)
Hiperemia , Sepsis , Choque Séptico , Adulto , Humanos , Estudios de Cohortes , Ensayos Clínicos Controlados Aleatorios como Asunto , Ultrasonografía Doppler , Estudios Multicéntricos como AsuntoRESUMEN
While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients. DATA SOURCES: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023. STUDY SELECTION: Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization. DATA EXTRACTION: In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8-31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis. CONCLUSIONS: In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.
RESUMEN
Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the WT strain, with MotAB stators produced â¼40-fold more than MotCD stators. However, recruitment of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily recruited at low viscosities. Importantly, we find that cells with MotCD stators are â¼10x more likely to have an active motor compared to cells without, so wild-type, WT, populations are intrinsically heterogeneous and not reducible to MotAB-dominant or MotCD-dominant behavior. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa , transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator recruitment. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the 'jamming transition' in active granular matter. Importance: After extensive study, it is now known that there exist multifactorial influences on swarming motility in P. aeruginosa , but it is not clear precisely why stator selection in the flagellum motor is so important or how this process is collectively initiated or arrested. Here, we show that for P. aeruginosa PA14, MotAB stators are produced â¼40-fold more than MotCD stators, but recruitment of MotCD over MotAB stators requires higher liquid viscosities. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies, the fraction of flagellum-active cells in a population on average, with MotCD active â¼10x more often than MotAB. What emerges from this complex landscape of stator recruitment and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility, and how they potentially relate to surface sensing circuitry.
RESUMEN
To evaluate the efficacy and cost-effectiveness of high-flow nasal cannula (HFNC) when compared with noninvasive positive pressure ventilation (NIPPV) in patients with acute hypoxic respiratory failure (AHRF). DATA SOURCES: We performed a comprehensive search of MEDLINE, Embase, CINAHL, the Cochrane library, and the international Health Technology Assessment database from inception to September 14, 2022. STUDY SELECTION: We included randomized control studies that compared HFNC to NIPPV in adult patients with AHRF. For clinical outcomes, we included only parallel group and crossover randomized control trials (RCTs). For economic outcomes, we included any study design that evaluated cost-effectiveness, cost-utility, or cost benefit analyses. DATA EXTRACTION: Clinical outcomes of interest included intubation, mortality, ICU and hospital length of stay (LOS), and patient-reported dyspnea. Economic outcomes of interest included costs, cost-effectiveness, and cost-utility. DATA SYNTHESIS: We included nine RCTs (n = 1,539 patients) and one cost-effectiveness study. Compared with NIPPV, HFNC may have no effect on the need for intubation (relative risk [RR], 0.93; 95% CI, 0.69-1.27; low certainty) and an uncertain effect on mortality (RR, 0.84; 95% CI, 0.59-1.21; very low certainty). In subgroup analysis, NIPPV delivered through the helmet interface-as opposed to the facemask interface-may reduce intubation compared with HFNC (p = 0.006; moderate credibility of subgroup effect). There was no difference in ICU or hospital LOS (both low certainty) and an uncertain effect on patient-reported dyspnea (very low certainty). We could make no conclusions regarding the cost-effectiveness of HFNC compared with NIPPV. CONCLUSIONS: HFNC and NIPPV may be similarly effective at reducing the need for intubation with an uncertain effect on mortality in hospitalized patients with hypoxemic respiratory failure. More research evaluating different interfaces in varying clinical contexts is needed to improve generalizability and precision of findings.
RESUMEN
OBJECTIVE: To conduct a systematic review and meta-analysis to determine whether targeting a higher mean arterial pressure (MAP) compared with a lower MAP in adults with shock results in differences in patient important outcomes. DATA SOURCES: We searched MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov through May 2021. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify potentially eligible studies, then full text for final eligibility. We included parallel-group randomized controlled trials in adult patients with a diagnosis of shock requiring vasoactive medications. The higher MAP group was required to receive vasoactive medications to target a higher MAP as established by study authors, whereas the lower MAP group received vasoactive medications to target lower MAP. DATA EXTRACTION: In triplicate, reviewers independently extracted data using a prepiloted abstraction form. Statistical analyses were conducted using the RevMan software Version 5.3. DATA SYNTHESIS: Six randomized controlled trials (n = 3,690) met eligibility criteria. Targeting a higher MAP (75-85 mm Hg) compared with lower MAP of 65 mm Hg resulted in no difference in mortality (relative risk [RR], 1.06; 95% CI, 0.98-1.15; I2 = 0%; p = 0.12; moderate certainty. Targeting a higher MAP resulted in no difference in the risk of undergoing renal replacement therapy (RR, 0.96; 95% CI, 0.83-1.11; I2 = 24%; p = 0.57; moderate certainty); however, a subgroup analysis comparing patients with and without chronic hypertension demonstrated that a higher MAP may reduce the risk of undergoing renal replacement therapy (RR, 0.83; 95% CI, 0.71-0.98; I2 = 0%; p = 0.02). CONCLUSIONS: In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in mortality when a higher MAP is targeted in critically ill adult patients with shock. Further studies are needed to determine the impact of mean arterial pressure on need for renal replacement therapy in this population.
Asunto(s)
Presión Arterial , Enfermedad Crítica , Humanos , Adulto , Enfermedad Crítica/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Resultados Informados por el PacienteRESUMEN
Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN: Two-phase, single-center multistudy cohort. SETTING: University-affiliated ICU in Hamilton, ON, Canada. PATIENTS: Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS: Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.
RESUMEN
Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments.
RESUMEN
Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.
Asunto(s)
Delirio , Dexmedetomidina , Hipotensión , Adulto , Bradicardia/tratamiento farmacológico , Enfermedad Crítica/terapia , Delirio/tratamiento farmacológico , Delirio/epidemiología , Delirio/prevención & control , Dexmedetomidina/efectos adversos , Humanos , Hipnóticos y Sedantes/efectos adversos , Hipotensión/tratamiento farmacológico , Unidades de Cuidados Intensivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial/efectos adversosRESUMEN
BACKGROUND: As the Coronavirus Disease-2019 (COVID-19) pandemic continues, healthcare providers struggle to manage both COVID-19 and non-COVID patients while still providing high-quality care. We conducted a systematic review/meta-analysis to describe the effects of the COVID-19 pandemic on patients with non-COVID illness and on healthcare systems compared to non-pandemic epochs. METHODS: We searched Ovid MEDLINE/EMBASE/Cochrane Database of Systematic Reviews/CENTRAL/CINAHL (inception to December 31, 2020). All study types with COVID-pandemic time period (after December 31, 2019) with comparative non-pandemic time periods (prior to December 31, 2019). Data regarding study characteristics/case-mix/interventions/comparators/ outcomes (primary: mortality; secondary: morbidity/hospitalizations/disruptions-to-care. Paired reviewers conducted screening and abstraction, with conflicts resolved by discussion. Effect sizes for specific therapies were pooled using random-effects models. Risk of bias was assessed by Newcastle-Ottawa Scale, with evidence rating using GRADE methodology. RESULTS: Of 11,581 citations, 167 studies met eligibility. Our meta-analysis showed an increased mortality of 16% during the COVID pandemic for non-COVID illness compared with 11% mortality during the pre-pandemic period (RR 1.38, 95% CI: 1.28-1.50; absolute risk difference: 5% [95% CI: 4-6%], p<0.00001, very low certainty evidence). Twenty-eight studies (17%) reported significant changes in morbidity (where 93% reported increases), while 30 studies (18%) reported no significant change (very low certainty). Thirty-nine studies (23%) reported significant changes in hospitalizations (97% reporting decreases), while 111 studies (66%) reported no significant change (very low certainty). Sixty-two studies (37%) reported significant disruptions in standards-to-care (73% reporting increases), while 62 studies (37%) reported no significant change (very low certainty). CONCLUSIONS: There was a significant increase in mortality during the COVID pandemic compared to pre-pandemic times for non-COVID illnesses. When significant changes were reported, there was increased morbidity, decreased hospitalizations and increased disruptions in standards-of-care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020201256 (Sept 2, 2020).
Asunto(s)
COVID-19 , Coronavirus , COVID-19/epidemiología , Personal de Salud , Hospitalización , Humanos , PandemiasRESUMEN
Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.
Asunto(s)
COVID-19 , Intubación Intratraqueal , Posición Prona , Insuficiencia Respiratoria , Vigilia , Adulto , Anciano , COVID-19/complicaciones , COVID-19/terapia , Femenino , Humanos , Hipoxia/etiología , Hipoxia/terapia , Intubación Intratraqueal/métodos , Masculino , Persona de Mediana Edad , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/terapiaRESUMEN
PURPOSE: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICMRPG) was to formulate evidencebased guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). METHODS: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and webbased discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. RESULTS: The ICMRPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". CONCLUSION: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.
Asunto(s)
Anestesia , Dexmedetomidina , Adulto , Dexmedetomidina/uso terapéutico , Humanos , Hipnóticos y Sedantes/uso terapéutico , Unidades de Cuidados Intensivos , Respiración Artificial/métodosRESUMEN
The downregulation of Pseudomonas aeruginosa flagellar motility is a key event in biofilm formation, host colonization, and the formation of microbial communities, but the external factors that repress motility are not well understood. Here, we report that on soft agar, swarming motility can be repressed by cells that are nonmotile due to the absence of a flagellum or flagellar rotation. Mutants that lack either flagellum biosynthesis or rotation, when present at as little as 5% of the total population, suppressed swarming of wild-type cells. Non-swarming cells required functional type IV pili and the ability to produce Pel exopolysaccharide to suppress swarming by the flagellated wild type. Flagellated cells required only type IV pili, but not Pel production, for their swarming to be repressed by non-flagellated cells. We hypothesize that interactions between motile and nonmotile cells may enhance the formation of sessile communities, including those involving multiple genotypes, phenotypically diverse cells, and perhaps other species. IMPORTANCE Our study shows that, under the conditions tested, a small population of non-swarming cells can impact the motility behavior of a larger population. The interactions that lead to the suppression of swarming motility require type IV pili and a secreted polysaccharide, two factors with known roles in biofilm formation. These data suggest that interactions between motile and nonmotile cells may enhance the transition to sessile growth in populations and promote interactions between cells with different genotypes.
Asunto(s)
Regulación Bacteriana de la Expresión Génica , Pseudomonas aeruginosa , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Flagelos/metabolismo , Pseudomonas aeruginosa/metabolismoRESUMEN
Background and aim: With the Coronavirus Disease 2019 (COVID-19) pandemic continuing to impact healthcare systems around the world, healthcare providers are attempting to balance resources devoted to COVID-19 patients while minimizing excess mortality overall (both COVID-19 and non-COVID-19 patients). To this end, we conducted a systematic review (SR) to describe the effect of the COVID-19 pandemic on all-cause excess mortality (COVID-19 and non-COVID-19) during the pandemic timeframe compared to non-pandemic times. Methods: We searched EMBASE, Cochrane Database of SRs, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Controlled Trials Register (CENTRAL), from inception (1948) to December 31, 2020. We used a two-stage review process to screen/extract data. We assessed risk of bias using Newcastle-Ottawa Scale (NOS). We used Critical Appraisal and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Of 11,581 citations, 194 studies met eligibility. Of these studies, 31 had mortality comparisons (n = 433,196,345 participants). Compared to pre-pandemic times, during the COVID-19 pandemic, our meta-analysis demonstrated that COVID-19 mortality had an increased risk difference (RD) of 0.06% (95% CI: 0.06-0.06% p < 0.00001). All-cause mortality also increased [relative risk (RR): 1.53, 95% confidence interval (CI): 1.38-1.70, p < 0.00001] alongside non-COVID-19 mortality (RR: 1.18, 1.07-1.30, p < 0.00001). There was "very low" certainty of evidence through GRADE assessment for all outcomes studied, demonstrating the evidence as uncertain. Interpretation: The COVID-19 pandemic may have caused significant increases in all-cause excess mortality, greater than those accounted for by increases due to COVID-19 mortality alone, although the evidence is uncertain. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42020201256].