Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Dynamic tests of fluid responsiveness have been developed and investigated in clinical trials of goal-directed therapy. The impact of this approach on clinically relevant outcomes is unknown. We performed a systematic review and meta-analysis to evaluate whether fluid therapy guided by dynamic assessment of fluid responsiveness compared with standard care improves clinically relevant outcomes in adults admitted to the ICU. DATA SOURCES: Randomized controlled trials from MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov, and the International Clinical Trials Registry Platform from inception to December 2016, conference proceedings, and reference lists of relevant articles. STUDY SELECTION: Two reviewers independently identified randomized controlled trials comparing dynamic assessment of fluid responsiveness with standard care for acute volume resuscitation in adults admitted to the ICU. DATA EXTRACTION: Two reviewers independently abstracted trial-level data including population characteristics, interventions, clinical outcomes, and source of funding. Our primary outcome was mortality at longest duration of follow-up. Our secondary outcomes were ICU and hospital length of stay, duration of mechanical ventilation, and frequency of renal complications. The internal validity of trials was assessed in duplicate using the Cochrane Collaboration's Risk of Bias tool. DATA SYNTHESIS: We included 13 trials enrolling 1,652 patients. Methods used to assess fluid responsiveness included stroke volume variation (nine trials), pulse pressure variation (one trial), and stroke volume change with passive leg raise/fluid challenge (three trials). In 12 trials reporting mortality, the risk ratio for death associated with dynamic assessment of fluid responsiveness was 0.59 (95% CI, 0.42-0.83; I = 0%; n = 1,586). The absolute risk reduction in mortality associated with dynamic assessment of fluid responsiveness was -2.9% (95% CI, -5.6% to -0.2%). Dynamic assessment of fluid responsiveness was associated with reduced duration of ICU length of stay (weighted mean difference, -1.16 d [95% CI, -1.97 to -0.36]; I = 74%; n = 394, six trials) and mechanical ventilation (weighted mean difference, -2.98 hr [95% CI, -5.08 to -0.89]; I = 34%; n = 334, five trials). Three trials were adjudicated at unclear risk of bias; the remaining trials were at high risk of bias. CONCLUSIONS: In adult patients admitted to intensive care who required acute volume resuscitation, goal-directed therapy guided by assessment of fluid responsiveness appears to be associated with reduced mortality, ICU length of stay, and duration of mechanical ventilation. High-quality clinical trials in both medical and surgical ICU populations are warranted to inform routine care.

Extracorporeal Membrane Oxygenation, Pulmonary Embolectomy, and Right Ventricular Assist Device for Massive Pulmonary Embolism.

Consensus regarding the management of massive pulmonary embolism (PE) and persistent shock after thrombolysis is lacking. A 30-year-old man collapsed with massive PE 3 days after an exploratory laparotomy for penetrating trauma, and he remained hypoxic and hypotensive despite thrombolytic therapy. Extracorporeal membrane oxygenation (ECMO) was instituted as a bridge to surgical embolectomy, and placement of a right ventricular assist device (RVAD) was used to facilitate separation from cardiopulmonary bypass. After 48 hours, the RVAD was removed, and the patient survived to discharge. ECMO and temporary RVAD to support surgical embolectomy are lifesaving therapeutic considerations.

Current and Future Status of Extracorporeal Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest.

Numerous series, propensity-matched trials, and meta-analyses suggest that appropriate use of extracorporeal cardiopulmonary resuscitation (E-CPR) for in-hospital cardiac arrest (IHCA) can be lifesaving. Even with an antecedent cardiopulmonary resuscitation (CPR) duration in excess of 45 minutes, 30-day survival with favourable neurologic outcome using E-CPR is approximately 35%-45%. Survival may be related to age, duration of CPR, or etiology. Associated complications include sepsis, renal failure, limb and neurologic complications, hemorrhage, and thrombosis. However, methodological biases-including small sample size, selection bias, publication bias, and inability to control for confounders-in these series prevent definitive conclusions. As such, the 2015 American Heart Association Advanced Cardiac Life Support guidelines update recommended E-CPR as a Level of Evidence IIb recommendation in appropriate cases. The absence of high-quality evidence presents an opportunity for clinician/scientists to generate practice-defining data through collaborative investigation and prospective trials. A multidisciplinary dialogue is required to standardize the field and promote multicentre investigation of E-CPR with data sharing and the development of a foundation for high-quality trials. The objectives of this review are to (1) provide an overview of the strengths and limitations of currently available studies investigating the use of E-CPR in patients with IHCA and highlight knowledge gaps; (2) create a framework for the standardization of terminology, clinical practice, data collection, and investigation of E-CPR for patients with IHCA that will help ensure congruence in future work in this area; and (3) propose suggestions to guide future research by the cardiovascular community to advance this important field.

The use of free online educational resources by Canadian emergency medicine residents and program directors.

UNLABELLED: Introduction Online educational resources (OERs) are increasingly available for emergency medicine (EM) education. This study describes and compares the use of free OERs by the Royal College of Physicians and Surgeons of Canada (RCPSC) EM residents and program directors (PDs) and investigates the relationship between the use of OERs and peer-reviewed literature. METHODS: A bilingual, online survey was distributed to RCPSC-EM residents and PDs using a modified Dillman method. The chi-square test and Fisher's exact test were used to compare the responses of residents and PDs. RESULTS: The survey was completed by 214/350 (61%) residents and 11/14 (79%) PDs. Free OERs were used by residents most frequently for general EM education (99.5%), procedural skills training (96%), and learning to interpret diagnostic tests (92%). OER modalities used most frequently included wikis (95%), file-sharing websites (95%), e-textbooks (94%), and podcasts (91%). Residents used wikis, podcasts, vodcasts, and file-sharing websites significantly more frequently than PDs. Relative to PDs, residents found entertainment value to be more important for choosing OERs (p<0.01). Some residents (23%) did not feel that literature references were important, whereas all PDs did. Both groups reported that OERs increased the amount of peer-reviewed literature (75% and 60%, respectively) that they read. CONCLUSIONS: EM residents make extensive use of OERs and differ from their PDs in the importance that they place on their entertainment value and incorporation of peer-reviewed references. OERs may increase the use of peer-reviewed literature in both groups. Given the prevalence of OER use for core educational goals among RCPSC-EM trainees, future efforts to facilitate critical appraisal and appropriate resource selection are warranted.

Extracorporeal membrane oxygenation for blastomycosis-related acute respiratory distress syndrome: a case series.

PURPOSE: Blastomyces dermatitidis is a dimorphic fungus endemic to North America capable of causing fatal respiratory failure. Acute respiratory distress syndrome (ARDS) complicates up to 10% of pulmonary blastomycosis in hospitalized patients and carries a mortality of 50-90%. This report describes the clinical course of four consecutive patients with blastomycosis-related ARDS treated with venovenous extracorporeal membrane oxygenation (ECMO) during 2009-2014. CLINICAL FEATURES: Four adults were referred from northwestern Ontario, Canada with progressive respiratory illnesses. All patients developed diffuse bilateral opacities on chest radiography and required mechanical ventilation within 6-72 hr. Patients satisfied Berlin criteria for severe ARDS with trough PaO2/F i O2 ratios of 44-61 on positive end-expiratory pressure of 12-24 cm H2O. Wet mount microscopy from respiratory samples showed broad-based yeast consistent with B.dermatitidis. Despite lung protective ventilation strategies with maximal F i O2 (patients A-D), neuromuscular blockade (patients A-D), inhaled nitric oxide (patients A and D), and prone positioning (patient D), progressive hypoxemia resulted in initiation of venovenous ECMO by hours 24-90 of mechanical ventilation with subsequent de-escalation of ventilatory support. In all four cases, ECMO decannulation was performed (7-23 days), mechanical ventilation was withdrawn (18-52 days), and the patients survived to hospital discharge (31-87 days). CONCLUSION: This report describes the successful application of ECMO as rescue therapy in aid of four patients with refractory blastomycosis-associated ARDS. In addition to early appropriate antimicrobial therapy, transfer to an institution experienced with ECMO should be considered when caring for patients from endemic areas with rapidly progressive respiratory failure.

Resuscitative extracorporeal membrane oxygenation for in hospital cardiac arrest: a Canadian observational experience.

BACKGROUND: Among patients with reversible conditions who sustain cardiac arrest, extracorporeal membrane oxygenation (ECMO) may support end organ perfusion while bridging to definitive therapy. METHODS: A single center retrospective review (February 2008­September 2013) of adults receiving ECMO for cardiac arrest ≥15 min duration refractory to conventional management (E-CPR) or profound cardiogenic shock following IHCA (E-CS) was conducted. The primary outcome was 30-day survival with good neurologic function defined as a cerebral performance category (CPC) of 1­2. Secondary outcomes included intensive care unit (ICU) and hospital length of say, duration of mechanical ventilation, and univariate predictors of 30-day survival with favorable neurologic function. RESULTS: Thirty-two patients (55 ± 11 years, 66% male) were included of which 22 (69%) received E-CPR and 10 (31%) received E-CS following return of spontaneous circulation (ROSC). Cardiac arrest duration was 48.8 ± 21 min for those receiving E-CPR and 25 ± 23 min for the E-CS group. Patients received ECMO support for 70.7 ± 47.6 h. Death on ECMO support occurred in 7 (21.9%) patients, while 7 (21.9%) were bridged to another form of mechanical circulatory support, and 18 (56.3%) were successfully decannulated. ICU length of stay was 7.5 [3.3­14] days and ICU survival occurred in 16 (50%) of patients. 30-Day survival was 5 (50%) in the E-CS group, 10 (45.4%) in the E-CPR group, and 15 (47%) overall. All survivors had CPC 1­2 neurologic status. CONCLUSION: In this single center experience, the use of resuscitative ECMO was associated with neurologically favorable 30-day survival in 47% of patients with prolonged IHCA (H2012:172).

Characteristics of evidence-based medicine training in Royal College of Physicians and Surgeons of Canada emergency medicine residencies - a national survey of program directors.

BACKGROUND: Recent surveys suggest few emergency medicine (EM) training programs have formal evidence-based medicine (EBM) or journal club curricula. Our primary objective was to describe the methods of EBM training in Royal College of Physicians and Surgeons of Canada (RCPSC) EM residencies. Secondary objectives were to explore attitudes regarding current educational practices including e-learning, investigate barriers to journal club and EBM education, and assess the desire for national collaboration. METHODS: A 16-question survey containing binary, open-ended, and 5-pt Likert scale questions was distributed to the 14 RCPSC-EM program directors. Proportions of respondents (%), median, and IQR are reported. RESULTS: The response rate was 93% (13/14). Most programs (85%) had established EBM curricula. Curricula content was delivered most frequently via journal club, with 62% of programs having 10 or more sessions annually. Less than half of journal clubs (46%) were led consistently by EBM experts. Four programs did not use a critical appraisal tool in their sessions (31%). Additional teaching formats included didactic and small group sessions, self-directed e-learning, EBM workshops, and library tutorials. 54% of programs operated educational websites with EBM resources. Program directors attributed highest importance to two core goals in EBM training curricula: critical appraisal of medical literature, and application of literature to patient care (85% rating 5 - "most importance", respectively). Podcasts, blogs, and online journal clubs were valued for EBM teaching roles including creating exposure to literature (4, IQR 1.5) and linking literature to clinical practice experience (4, IQR 1.5) (1-no merit, 5-strong merit). Five of thirteen respondents rated lack of expert leadership and trained faculty educators as potential limitations to EBM education. The majority of respondents supported the creation of a national unified EBM educational resource (4, IQR 1) (1-no support, 5- strongly support). CONCLUSIONS: RCPSC-EM programs have established EBM teaching curricula and deliver content most frequently via journal club. A lack of EBM expert educators may limit content delivery at certain sites. Program directors supported the nationalization of EBM educational resources. A growing usage of electronic resources may represent an avenue to link national EBM educational expertise, facilitating future collaborative educational efforts.

Dissecting apoptosis and intrinsic death pathways in the heart.

The limited regenerative capacity of postnatal ventricular myocytes coupled with their meager ability for genetic manipulation has presented a major technical obstacle for deciphering apoptosis initiation and execution signals in the heart. In this report, we describe the technical approaches used to study the intrinsic death pathways in postnatal ventricular myocytes during acute hypoxic injury. Discussed are methods for hypoxia, recombinant adenovirus-mediated gene transfer, cellular viability assays using the vital dyes calcein acetomethoxyester and ethidium homodimer-1, analysis of nuclear morphology by use of Hoechst dye 33258, and assessment of the state of the mitochondrial permeability transition pore. Our work has established that hypoxia triggers perturbations to mitochondria consistent with loss of mitochondrial membrane potential, permeability transition pore opening, and apoptotic cell death by the intrinsic pathway.