Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

Comparative effectiveness of alternative spontaneous breathing trial techniques: a systematic review and network meta-analysis of randomized trials.

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.

Mortality As a Measure of Treatment Effect in Clinical Trials Recruiting Critically Ill Patients.

OBJECTIVES: All-cause mortality is a common measure of treatment effect in ICU-based randomized clinical trials (RCTs). We sought to understand the performance characteristics of a mortality endpoint by evaluating its temporal course, responsiveness to differential treatment effects, and impact when used as an outcome measure in trials of acute illness. DATA SOURCES: We searched OVID Medline for RCTs published from 1990 to 2018. STUDY SELECTION: We reviewed RCTs that had randomized greater than or equal to 100 patients, were published in one of five high-impact general medical or eight critical care journals, and reported mortality at two or more distinct time points. We excluded trials recruiting pediatric or neonatal patients and cluster RCTs. DATA EXTRACTION: Mortality by randomization group was recorded from the article or estimated from survival curves. Trial impact was assessed by inclusion of results in clinical practice guidelines. DATA SYNTHESIS: From 2,592 potentially eligible trials, we included 343 RCTs (228,784 adult patients). While one third of all deaths by 180 days had occurred by day 7, the risk difference between study arms continued to increase until day 60 (p = 0.01) and possibly day 90 (p = 0.07) and remained stable thereafter. The number of deaths at ICU discharge approximated those at 28-30 days (95% [interquartile range [IQR], 86-106%]), and deaths at hospital discharge approximated those at 60 days (99% [IQR, 94-104%]). Only 13 of 43 interventions (30.2%) showing a mortality benefit have been adopted into widespread clinical practice. CONCLUSIONS: Our findings provide a conceptual framework for choosing a time horizon and interpreting mortality outcome in trials of acute illness. Differential mortality effects persist for 60 to 90 days following recruitment. Location-based measures approximate time-based measures for trials conducted outside the United States. The documentation of a mortality reduction has had a modest impact on practice.

Non-invasive ventilation versus invasive weaning in critically ill adults: a systematic review and meta-analysis.

BACKGROUND: Extubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data. RESULTS: We identified 28 trials, of moderate-to-good quality, involving 2066 patients, 44.6% with chronic obstructive pulmonary disease (COPD). Non-invasive weaning significantly reduced mortality (risk ratio (RR) 0.57, 95% CI 0.44 to 0.74; high quality), weaning failures (RR 0.59, 95% CI 0.43 to 0.81; high quality), pneumonia (RR 0.30, 95% CI 0.22 to 0.41; high quality), intensive care unit (ICU) (mean difference (MD) -4.62 days, 95% CI -5.91 to -3.34) and hospital stay (MD -6.29 days, 95% CI -8.90 to -3.68). Non-invasive weaning also significantly reduced the total duration of ventilation, duration of invasive ventilation and duration of ventilation related to weaning (MD -0.57, 95% CI -1.08 to -0.07) and tracheostomy rate. Mortality, pneumonia, reintubation and ICU stay were significantly lower in trials enrolling COPD (vs mixed) populations. CONCLUSION: Non-invasive weaning significantly reduced mortality, pneumonia and the duration of ventilation related to weaning, particularly in patients with COPD. Beneficial effects are less clear (or more careful patient selection is required) in non-COPD patients. PROSPERO REGISTRATION NUMBER: CRD42020201402.

Comparative Effectiveness of Protective Ventilation Strategies for Moderate and Severe Acute Respiratory Distress Syndrome. A Network Meta-Analysis.

Rationale: Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. Objectives: To compare the effects of low Vt, high Vt, high positive end-expiratory pressure (PEEP), prone ventilation, high-frequency oscillation, and venovenous extracorporeal membrane oxygenation (VV ECMO) on mortality in ARDS. Methods: We performed a network meta-analysis of randomized trials. We applied the Grading of Recommendations Assessment, Development and Evaluation methodology to discern the relative effect of interventions on mortality. Measurements and Main Results: We analyzed 34 trials including 9,085 adults with primarily moderate-to-severe ARDS (median baseline PaO2/FiO2, 118; interquartile range, 110-143). Prone positioning combined with low Vt was the best strategy (risk ratio [RR], 0.74 [95% confidence interval (CI), 0.60-0.92] vs. low Vt; high certainty). VV ECMO was also rated among the best (RR, 0.78 [95% CI, 0.58-1.05] vs. low Vt; RR, 0.66; [95% CI, 0.49-0.88] vs. high Vt) but was rated with lower certainty because VV ECMO was restricted to very severe ARDS (mean baseline PaO2/FiO2<75). High PEEP combined with low Vt was rated intermediately (RR, 0.91 [95% CI, 0.81-1.03] vs. low Vt; low certainty; RR, 0.77 [95% CI, 0.65-0.91] vs. high Vt; moderate certainty). High Vt was rated worst (RR, 1.19 [95% CI, 1.02-1.37] vs. low Vt; moderate certainty), and we found no support for high-frequency oscillation or high Vt with prone ventilation. Conclusions: These findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for critically ill adults with moderate-to-severe ARDS.

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients.

BACKGROUND: In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity. METHODS: Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering. RESULTS: Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0-50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering. CONCLUSION: Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

Compliance With Evidence-Based Processes of Care After Transitions Between Staff Intensivists.

OBJECTIVES: We sought to evaluate the impact of transitions of care among staff intensivists on the compliance with evidence-based processes of care. DESIGN: Cohort study using data from the Toronto Intensive Care Observational Registry. SETTING: Seven academic ICUs in Toronto, Ontario. PATIENTS: Critically ill mechanically ventilated adult patients. INTERVENTIONS: We explored the effects of the weekly transition of care among staff intensivists on compliance with three evidence-based processes of care (spontaneous breathing trials, lung-protective ventilation, and neuromuscular blocking agents). Two practices that are less guided by evidence (early discontinuation of antibiotics and extubation attempts) served as positive controls. We conducted the analysis using generalized estimating equations to account for clustering at the patient level. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 10,570 patients admitted between June 2014 and August 2018. Compliance varied for each practice (63.6%, 42.5%, and 21.1% for lung-protective ventilation, spontaneous breathing trials, and neuromuscular blockade, respectively). There was no effect of transitions of care on compliance with spontaneous breathing trials (odds ratio, 1.00; 95% CI, 0.95-1.07), lung-protective ventilation (odds ratio, 1.07, 95% CI, 0.90-1.26), or neuromuscular blockade use (odds ratio, 0.95; 95% CI, 0.75-1.20). However, early antibiotic discontinuation was more likely (odds ratio, 1.23; 95% CI, 1.06-1.42) and extubation attempts were less frequent (odds ratio, 0.77; 95% CI, 0.65-0.93) after a transition of care. CONCLUSIONS: We observed no significant impact of transitions of care between individual staff physicians on evidence-based processes of care for mechanically ventilated adult patients. However, transitions were associated with a lower likelihood of extubation and higher odds of earlier discontinuation of antibiotics.

Systematic review of contemporary outcomes of endovascular and open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: The purpose of the study was to provide a systematic review of the literature reporting the contemporary early outcomes after endovascular and open repair of thoracoabdominal aortic aneurysms (TAAAs). METHODS: MEDLINE and Embase were searched for studies from January 2006 to March 2018 that reported either endovascular (using branched or fenestrated endografts) or open repair of TAAA in at least 10 patients. Outcomes of interest included perioperative mortality, spinal cord injury (SCI), renal failure requiring dialysis, and stroke. Pooled proportions were determined using a random-effects model. RESULTS: The analysis included 71 studies, of which 24 and 47 reported outcomes after endovascular and open TAAA repair, respectively. Endovascular cohort patients were older and had higher rates of coronary artery disease, chronic obstructive pulmonary disease, and diabetes. Endovascular repair was associated with higher rates of SCI (13.5%; 95% confidence interval [CI], 10.5%-16.7%) compared with open repair (7.4%; 95% CI, 6.2%-8.7%; P < .01) but similar rates of permanent paralysis (5.2% [95% CI, 3.8%-6.7%] vs 4.4% [95% CI, 3.3%-5.6%]; P = .39), lower rates of postoperative dialysis (6.4% [95% CI, 3.2%-9.5%] vs 12.0% [95% CI, 8.2%-16.3%]; P = .03) but similar rates of being discharged on permanent dialysis (3.7% [95% CI, 2.0%-5.9%] vs 3.8% [95% CI, 2.9%-5.3%]; P = .93), a trend to lower stroke (2.7% [95% CI, 1.9%-3.6%] vs 3.9% [95% CI, 3.0%-4.9%]; P = .06), and similar perioperative mortality (7.4% [95% CI, 5.9%-9.1%] vs 8.9% [95% CI, 7.2%-10.9%]; P = .21). CONCLUSIONS: This systematic review summarizes the contemporary literature results of endovascular and open TAAA repair. Endovascular repair studies included patients with more comorbidities and were associated with higher rates of SCI but similar rates of permanent paraplegia, whereas open repair studies had higher rates of postoperative dialysis but similar rates of being discharged on permanent dialysis. Perioperative mortality rates were similar. Universally adopted reporting standards for patient characteristics, outcomes, and the conduct of contemporary comparative studies will allow better assessment and comparisons of the risks associated with the two surgical treatment options for TAAA.

Evidence Supporting Clinical Use of Proportional Assist Ventilation: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: While proportional assist ventilation (PAV), generates pressure in proportion to effort without a preselected target, proportional assist ventilation plus (PAV+) measures compliance and resistance, calculates work of breathing, and adjusts support to a preset assistance level. OBJECTIVE: To summarize randomized controlled trials (RCTs) comparing invasive or noninvasive PAV or PAV+ in critically ill patients. Data Sources: We searched multiple databases to April 2017 without language restrictions and conference proceedings from 5 meetings to identify randomized parallel-group and crossover RCTs that compared invasive or noninvasive PAV or PAV+ to another mode in critically ill adults or children and reported at least 1 clinically important outcome. RESULTS: We identified 14 RCTs (11 parallel group and 3 crossover) assessing PAV (n = 7) and PAV+ (n = 7) involving 931 adult patients. We found no effect of noninvasive PAV (vs noninvasive pressure support [PS]) on intubation (risk ratio 0.92 [0.59 to 1.43], I2 = 0%) or invasive PAV (vs invasive PS) on percentage rapid eye movement sleep (mean difference [MD] -2.93% [-14.20 to ±8.34], I2 = 43%). Compared to invasive PS, invasive PAV+ showed a nonsignificant increase in weaning time (MD +0.54 [-0.67 to +1.75] hours, I2 = 0%), but no effect on hospital mortality, reintubation, or tracheostomy. CONCLUSIONS: Current evidence does not support the use of invasive or noninvasive PAV or invasive PAV+ in critically ill adults. Amid low to moderate heterogeneity, we identified 3 promising areas for future research including assessing the role of noninvasive PAV as an initial support strategy in patients with acute respiratory failure, invasive PAV on sleep quality during invasive ventilation, and possibly invasive PAV+ for weaning.

When to transfuse your acute care patient? A narrative review of the risk of anemia and red blood cell transfusion based on clinical trial outcomes.

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l'anémie et de la transfusion d'érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l'impact de seuils spécifiques de transfusion d'hémoglobine est comparé. Dans ces études, les risques de l'anémie sont comparés aux risques de la transfusion d'érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l'anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l'interaction de plusieurs facteurs, notamment de l'équilibre entre le risque de l'anémie et le risque de la transfusion d'érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d'érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d'une hypoxie tissulaire induite par l'anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d'envergure, avec pour but l'amélioration de la survie sans complication des patients en état critique et périopératoires.

Mitral valve prosthesis choice in patients <70 years: A systematic review and meta-analysis of 20 219 patients.

BACKGROUND: The optimal mitral prosthesis in young patients is unclear. This systematic review and meta-analysis were performed to compare outcomes between bileaflet mechanical mitral valve replacement (mMVR) and bioprosthesis mitral valve replacement (bioMVR) for MVR patients aged less than 70 years. METHODS: We searched MEDLINE and EMBASE databases from inception to July 2018 for studies comparing surgical outcomes of mMVR vs bioMVR. RESULTS: There were 14 observational studies with 20 219 patients (n = 14 658 mMVR and n = 5561 bioMVR). Patients receiving an mMVR were younger with fewer comorbidities including renal failure, dialysis, and less-infective endocarditis (P < .001). The estimated 10-year mortality ranged from 19% to 49% for mMVR and 22% to 58% for bioMVR among studies. Comparing matched or adjusted data, mMVR was associated with lower operative (risk ratio [RR]: 0.61; 95% confidence interval [CI]: 0.39, 0.94; P = .03) and long-term (HR: 0.81; 95% CI: 0.71, 0.92; P = .002) mortality at a median follow-up of 8 years (IQR: 6-10 years). Estimated 10-year risk for mitral valve reoperation ranged from 0% to 8% for mMVR and 8% to 22% for bioMVR among matched/adjusted studies. mMVR was associated with lower matched/adjusted risk of reoperation (HR: 0.35; 95% CI: 0.19, 0.65; P = .001) but with greater risk of bleeding (HR: 1.59; 95% CI: 1.19, 2.13; P = .002) and a trend to greater risk of stroke and embolism (HR: 1.70; 95% CI: 0.92, 3.15; P = .09). CONCLUSION: Mechanical MVR in patients aged less than 70 years is associated with a lower risk of operative mortality as well as a 20% lower risk of long-term death and 65% lower risk of mitral valve reoperation but 60% greater risk of bleeding compared with bioMVR in matched or adjusted data.

Clinical outcomes of mitral valve intervention in patients with mitral annular calcification: A systematic review and meta-analysis.

BACKGROUND: Mitral valve (MV) disease with mitral annular calcification (MAC) poses a surgical challenge and the clinical outcomes of MV surgery as well as transcatheter mitral valve replacement (TMVR) remain relatively unexplored. We performed a systematic review and meta-analysis to assess the effects of MAC on clinical outcomes following MV surgery and TMVR. METHODS: We searched MEDLINE and EMBASE databases until February 2019 for studies comparing clinical outcomes of MV surgery or TMVR in patients with and without MAC. Data were extracted by two independent investigators. Outcomes were perioperative and midterm complications and mortality. RESULTS: Seven observational studies enrolling 2902 patients were included. MAC patients were older, more likely to be female with greater chronic lung disease and kidney failure. Perioperative mortality was similar between patients with and without MAC undergoing MV surgery (risk ratio [RR], 1.15; 95% confidence interval [CI], 0.50-2.65; P = .74). MAC was associated with a higher risk of bleeding, permanent pacemaker implantation, and periprosthetic leak. Midterm mortality was greater in MAC patients undergoing MV surgery (incident rate ratio [IRR], 1.32; 95% CI, 1.05-1.67; P = .02). MAC patients undergoing TMVR had higher perioperative (RR, 4.65; 95% CI, 2.93-7.38; P < .01) and 1-year (RR, 5.44; 95% CI, 3.49-8.49; P < .01) mortality, decreased procedural success, greater left ventricular outflow tract obstruction and need for conversion to surgery when compared with patients undergoing TMVR for dysfunction of a bioprosthetic valve or annuloplasty ring. CONCLUSION: MV procedures in patients with MAC are associated with higher mortality and morbidity. This is largely driven by the high-risk patient profile associated with MAC. TMVR holds promise but has important limitations and should be reserved for select patients.

One-Year Outcomes in Caregivers of Critically Ill Patients.

BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

Frequency of Screening for Weaning From Mechanical Ventilation: Two Contemporaneous Proof-of-Principle Randomized Controlled Trials.

OBJECTIVES: It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. DESIGN: We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. SETTING: Ten and 11 ICUs in Canada, respectively. PATIENTS: Parallel trials of younger (RELEASE < 65 yr) and older (SENIOR ≥ 65 yr) critically ill adults invasively ventilated for at least 24 hours. INTERVENTIONS: Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. MEASUREMENTS AND MAIN RESULTS: In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. CONCLUSIONS: Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Aortic valve replacement with pulmonary hypertension: Meta-analysis of 70 676 patients.

BACKGROUND AND AIM OF THE STUDY: We compared early and late outcomes of surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) and pulmonary hypertension (PHT). METHODS: We searched MEDLINE and EMBASE databases until July 2018 for studies comparing patients with AS and none, mild-moderate, or severe PHT undergoing SAVR. Random-effects meta-analysis was performed. RESULTS: There were 12 observational studies with 70 676 patients with median follow-up 4.0 years (interquartile range, 2.6-4 years). Compared to patients with no PHT, patients with any PHT undergoing SAVR were older (mean difference [MD], 2.31 years; 95% confidence interval [CI], 1.38-3.23 years; P < .01), with greater comorbidities and reduced ejection fraction (MD, -4.36; 95%CI, -5.94 to -2.78; P < .01). Patients with any PHT had higher unadjusted (5.2% vs 2.4%; risk ratio [RR], 2.27; 95%CI, 2.04-2.53; P < .01) and adjusted (RR, 1.65; 95%CI, 1.28-2.14; P < .01) in-hospital mortality compared with no PHT. Severe (RR, 3.53; 95%CI, 1.46-8.54; P < .01) and mild-moderate PHT (RR, 2.13; 95%CI, 1.28-3.55; P < .01) were associated with higher unadjusted in-hospital mortality compared with no PHT. Any PHT was associated with a higher unadjusted risk of stroke (RR, 1.64; 95%CI, 1.42-1.90; P < .01), acute kidney injury (RR, 2.02; 95%CI, 1.50-2.72; P < .01), prolonged ventilation (RR, 1.62; 95%CI, 1.04-2.52; P = .03), and longer hospital stay (MD, 1.76 days; 95%CI, 0.57-2.95; P < .01). Severe (HR, 2.44; 95%CI, 1.60-3.72; P < .01) but not mild-moderate PHT (HR, 2.25; 95%CI, 0.91-5.59; P = .08) was associated with higher adjusted long-term mortality compared with no PHT. CONCLUSIONS: Patients with severe AS and severe PHT had a significant increase in operative mortality and more than double the risk of long-term mortality following SAVR compared with patients with no PHT. Such patients may benefit from a less invasive transcatheter aortic valve intervention.

Will This Patient Be Difficult to Intubate?: The Rational Clinical Examination Systematic Review.

IMPORTANCE: Recognizing patients in whom endotracheal intubation is likely to be difficult can help alert physicians to the need for assistance from a clinician with airway training and having advanced airway management equipment available. OBJECTIVE: To identify risk factors and physical findings that predict difficult intubation. DATA SOURCES: The databases of MEDLINE and EMBASE were searched from 1946 to June 2018 and from 1947 to June 2018, respectively, and the reference lists from the retrieved articles and previous reviews were searched for additional studies. STUDY SELECTION: Sixty-two studies with high (level 1-3) methodological quality that evaluated the accuracy of clinical findings for identifying difficult intubation were reviewed. DATA EXTRACTION AND SYNTHESIS: Two authors independently abstracted data. Bivariate random-effects meta-analyses were used to calculate summary positive likelihood ratios across studies or univariate random-effects models when bivariate models failed to converge. RESULTS: Among the 62 high-quality studies involving 33 559 patients, 10% (95% CI, 8.2%-12%) of patients were difficult to intubate. The physical examination findings that best predicted a difficult intubation included a grade of class 3 on the upper lip bite test (lower incisors cannot extend to reach the upper lip; positive likelihood ratio, 14 [95% CI, 8.9-22]; specificity, 0.96 [95% CI, 0.93-0.97]), shorter hyomental distance (range of <3-5.5 cm; positive likelihood ratio, 6.4 [95% CI, 4.1-10]; specificity, 0.97 [95% CI, 0.94-0.98]), retrognathia (mandible measuring <9 cm from the angle of the jaw to the tip of the chin or subjectively short; positive likelihood ratio, 6.0 [95% CI, 3.1-11]; specificity, 0.98 [95% CI, 0.90-1.0]), and a combination of physical findings based on the Wilson score (positive likelihood ratio, 9.1 [95% CI, 5.1-16]; specificity, 0.95 [95% CI, 0.90-0.98]). The widely used modified Mallampati score (≥3) had a positive likelihood ratio of 4.1 (95% CI, 3.0-5.6; specificity, 0.87 [95% CI, 0.81-0.91]). CONCLUSIONS AND RELEVANCE: Although several simple clinical findings are useful for predicting a higher likelihood of difficult endotracheal intubation, no clinical finding reliably excludes a difficult intubation. An abnormal upper lip bite test, which is easily assessed by clinicians, raises the probability of difficult intubation from 10% to greater than 60% for the average-risk patient.

A systematic review and meta-analysis of early outcomes after endovascular versus open repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: The objective of this study was to compare the early results of endovascular vs open thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: MEDLINE and Embase were searched for studies from January 2006 to March 2018 that compared endovascular vs open repair of TAAA using branched or fenestrated endografts. Data were subjected to a meta-analysis using a random-effects model. The outcomes of interest included early mortality, spinal cord injury, renal failure requiring dialysis, stroke, and hospital length of stay. RESULTS: Eight comparative studies met inclusion criteria. There were two retrospective propensity-matched studies, two unadjusted single-center retrospective studies, and four unadjusted national population-based studies. Mortality in the matched studies was equivalent in both groups. Pooled analysis of all unmatched observational studies revealed a survival benefit for endovascular over open repair (relative risk [RR], 0.63; 95% confidence interval [CI],0.45-0.87); P < .01, I2 = 47%). Endovascular repair was also associated with lower incidence of spinal cord injury (RR, 0.65; 95% CI, 0.42-1.01; P = .05; I2 = 28%). For unmatched studies, pooled RR of renal failure requiring dialysis significantly favored endovascular repair (RR, 0.44; 95% CI, 0.23-0.85; P = .01; I2 = 0%), although in the adjusted cohort, risk of dialysis was not different (RR, 1.00; 95% CI, 0.06-15.65; P = 1.00). Postoperative stroke rate was reported in three unadjusted studies and was not different between groups (RR, 0.81; 95% CI, 0.28-2.40; P = .71; I2 = 77%). Hospital length of stay was reported in four studies and was shorter in the endovascular group (mean difference, -4.4 days; 95% CI, -6.6 to -1.7; P < .01; I2 = 73%). CONCLUSIONS: There are few reports comparing endovascular vs open repair of TAAAs. Short-term outcomes may be improved in patients undergoing endovascular treatment of TAAA on the basis of a limited number of studies with high risk of bias. These findings highlight the need for larger comparative studies with standardization of reporting.

Transcatheter valve-in-valve versus redo surgical aortic valve replacement for the treatment of degenerated bioprosthetic aortic valve: A systematic review and meta-analysis.

OBJECTIVE: To determine the safety and efficacy of valve-in-valve transcatheter aortic valve replacement (ViV) versus redo surgical aortic valve replacement (SAVR) for the treatment of previously failed aortic bioprostheses. BACKGROUND: Valve-in-valve has emerged as a treatment option for patients with a failed aortic bioprosthesis. Evidence for safety and efficacy remains limited to small studies. METHODS: Medline and Embase were searched to 2017 for studies that directly compared ViV to redo SAVR. A random effects meta-analysis was performed. RESULTS: Four unadjusted (n = 298) and two propensity-matched (n = 200) observational studies were included. Valve-in-valve patients were 2.85-years older (P = 0.03) and were 23% higher in predicted mortality risk (ratio of means: 1.23, 95% confidence interval (95%CI): 1.02-1.48). There was no difference in peri-operative mortality (4.4% vs. 5.7%, P = 0.83;I2 = 0%) or late mortality, reported at median one year follow-up (incident rate ratio (IRR) 0.93, 95%CI: 0.74-1.16, P = 0.51, I2 = 0%) between ViV and redo SAVR. The incidence of permanent pacemaker implantation (8.3% vs 14.6%; P = 0.05;I2 = 0%) and dialysis (3.2% vs. 10.3%; P = 0.03; I2 = 0%) were lower in ViV. There was a reduction in the incidence of severe patient-prosthesis mismatch (3.3% vs 13.5%; P = 0.03; I2 = 0%) and mild or greater paravalvular leak (5.5% vs 21.1%; P = 0.03; I2 = 37%) in the redo SAVR group compared to ViV. CONCLUSIONS: Despite higher predicted surgical risk of ViV patients, there was no difference in mortality but less permanent pacemaker implantation and dialysis compared to redo SAVR. Choice of treatment must be individualized for both anatomical and patient risk factors; in high risk patients with favorable previous prosthesis size, valve-in-valve may be preferred.

Effect of High-Flow Nasal Cannula Oxygen Therapy Versus Conventional Oxygen Therapy and Noninvasive Ventilation on Reintubation Rate in Adult Patients After Extubation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of high-flow nasal cannula (HFNC) on reintubation in adult patients. PROCEDURES: Ovid Medline, Embase, and Cochrane Database of Systematic Reviews were searched up to November 1, 2016, for RCTs comparing HFNC versus conventional oxygen therapy (COT) or noninvasive ventilation (NIV) in adult patients after extubation. The primary outcome was reintubation rate, and the secondary outcomes included complications, tolerance and comfort, time to reintubation, length of stay, and mortality. Dichotomous outcomes were presented as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as weighted mean difference and 95% CIs. The random effects model was used for data pooling. FINDINGS: Seven RCTs involving 2781 patients were included in the analysis. The HFNC had a similar reintubation rate compared to either COT (RR, 0.58; 95% CI, 0.21-1.60; P = .29; 5 RCTs, n = 1347) or NIV (RR, 1.11; 95% CI, 0.88-1.40; P = .37; 2 RCTs, n = 1434). In subgroup of critically ill patients, the HFNC group had a significantly lower reintubation rate compared to the COT group (RR, 0.35; 95% CI, 0.19-0.64; P = .0007; 2 RCTs, n = 632; interaction P = .07 compared to postoperative subgroup). Qualitative analysis suggested that HFNC might be associated with less complications and improved patient's tolerance and comfort. The HFNC might not delay reintubation. Trial sequential analysis on the primary outcome showed that required information size was not reached. CONCLUSION: The evidence suggests that COT may still be the first-line therapy in postoperative patients without acute respiratory failure. However, in critically ill patients, HFNC may be a potential alternative respiratory support to COT and NIV, with the latter often associating with patient intolerance and requiring a monitored setting. Because required information size was not reached, further high-quality studies are required to confirm these results.