A qualitative exploratory case series of patient and family experiences with ECPR for out-of-hospital cardiac arrest.

OBJECTIVE: There is currently no existing data examining the opinions of patients and families after treatment with extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). We sought to interview family members and patients to learn from their experiences and satisfaction with treatment. METHODS: We contacted family members and survivors for all cases treated with ECPR for refractory OHCA at St. Paul's Hospital between January 2014 and July 2018. We performed semi-structured interviews with participants, specifically within the topics of: information sharing (including impressions of an ECPR informational pamphlet), prognostication, organ donation, and perceived value of ECPR. Due to low participant enrolment, we described all interviews in a narrative approach. RESULTS: Within the study period, there were 23 OHCAs treated with ECPR; two survivors and three family members agreed to participate. Participants were satisfied with the treatment provided, including information sharing and prognostication. There were mixed opinions about the best method of information-sharing (verbal vs written), as well as the timing of organ donation conversations. All participants believed ECPR for OHCA to be of high value. CONCLUSION: Patient's conveyed satisfaction with ECPR treatment, with mixed views on the best information sharing strategy. Further study is needed to define the optimal methods and timing for discussions of organ donation, especially for treatments of with a relatively low likelihood success.

Success and complications of endotracheal intubation in critical care settings under COVID-19 protocols.

INTRODUCTION: The Covid-19 pandemic has required new protocols for endotracheal intubation mandating cumbersome personal protective equipment and modifications to prior intubation procedures. We assessed the success and complications of endotracheal intubation under such protocols. METHODS: We conducted a prospective study of endotracheal intubation in the emergency department, intensive care unit, or ward between September 11, 2018 and June 11, 2020 at two urban hospitals. Using a standardized form, we included basic demographics, intubation techniques, and success, and pre-specified complications, defined as critical (cardiac arrest or failure to intubate) or non-critical. At both sites, Covid-19 intubation protocols took effect on March 11, 2020, and we compared pre-post patients. The primary outcome was first-pass success without complications. Secondary outcomes included first-pass success and complications. We analysed by descriptive techniques. RESULTS: Overall, we collected 1534 patients before March 11, 2020 and 227 after; groups were similar in age and sex distribution. Staff endotracheal intubation increased from 37 to 63%. First pass success was 1262/1534 (82.3%) pre versus 195/227 (85.9%) post, for a difference of 3.6% (95% CI - 1.8-8.0%). First pass success without complications was 1116/1534 (72.8%) pre versus 168/227 (74.0%) post, for a difference of 1.3%, (95% CI - 5.2-7.0%). There were 226 complications pre (14.7%) versus 47 (20.7%) post, for a difference of 6.0%. (95% CI 0.6-12.1%). CONCLUSIONS: New pandemic endotracheal intubation protocols did not result in a decrease in first-pass success, or first-pass success without complications.

RéSUMé: INTRODUCTION: La Pandémie de Covid-19 a nécessité de nouveaux protocoles d'intubation endotrachéale exigeant un équipement de protection individuelle encombrant et des modifications aux procédures d'intubation antérieures. Nous avons évalué le succès et les complications de l'intubation endotrachéale dans le cadre de tels protocoles. MéTHODES: Nous avons mené une étude prospective de l'intubation endotrachéale dans le service des urgences, l'unité de soins intensifs ou dans un service de soins intensifs entre le 11 septembre 2018 et le 11 juin 2020 dans deux hôpitaux urbains. À l'aide d'un formulaire standardisé, nous avons inclus les données démographiques de base, les techniques et le succès d'intubation, ainsi que les complications pré-spécifiées, définies comme critiques (arrêt cardiaque ou échec d'intubation) ou non critiques. Sur les deux sites, les protocoles d'intubation Covid-19 sont entrés en vigueur le 11 mars 2020 et nous avons comparé les patients avant et après. Le principal résultat a été un premier passage réussi sans complications. Les résultats secondaires comprenaient le succès au premier passage et les complications. Nous avons analysé par des techniques descriptives. RéSULTATS: Dans l'ensemble, nous avons recueilli 1534 patients avant le 11 mars 2020 et 227 après; les groupes étaient similaires en termes de répartition par âge et par sexe. L'intubation endotrachéale par le personnel est passée de 37 % à 63 %. Le succès du premier passage était de 1262/1534 (82,3 %) avant contre 195/227 (85,9 %) après, soit une différence de 3,6 % (IC à 95 % ­1,8 à 8,0 %). Le succès du premier passage sans complications était de 1116/1534 (72,8 %) avant contre 168/227 (74,0 %) après, soit une différence de 1,3 %, (IC à 95 % -5,2 à 7,0 %). Il y avait 226 complications avant (14,7 %) contre 47 (20,7 %) après, pour une différence de 6,0 %. (IC à 95 % de 0,6 à 12,1 %). CONCLUSIONS: Les nouveaux protocoles d'intubation endotrachéale pandémique n'ont pas entraîné de diminution du succès du premier passage ou du succès du premier passage sans complications.

A comprehensive regional clinical and educational ECPR protocol decreases time to ECMO in patients with refractory out-of-hospital cardiac arrest.

OBJECTIVE: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival for refractory out-of-hospital cardiac arrest (OHCA). We developed a prehospital, emergency department (ED), and hospital-based clinical and educational protocol to improve the key variable of time-to-ECPR (TTE). METHODS: In a single urban health region we involved key prehospital, clinical, and administrative stakeholders over a 2-year period, to develop a regional ECPR program with destination to a single urban tertiary care hospital. We developed clear and reproducible inclusion criteria and processes, including measures of program efficiency. We conducted seminars and teaching modules to paramedics and hospital-based clinicians including monthly simulator sessions, and performed detailed reviews of each treated case in the form of report cards. In this before-and-after study we compared patients with ECPR attempted prior to, and after, protocol implementation. The primary outcome was TTE, defined as the time of initial professional CPR to establishment of extracorporeal circulation. We compared the median TTE for patients in the two groups using the Wilcoxon signed rank test. RESULTS: Four patients were identified prior to the protocol and managed in an ad hoc basis; for nine patients the protocol was utilized. Overall favourable neurological outcomes among ECPR-treated patients were 27%. The median TTE was 136 minutes (IQR 98 - 196) in the pre-protocol group, and 60 minutes (IQR 49 - 81) minutes in the protocol group (p=0.0165). CONCLUSION: An organized clinical and educational protocol to initiate ECPR for patients with OHCA is feasible and significantly reduces the key benchmark of time-to-ECPR flows.

Potential Candidates for a Structured Canadian ECPR Program for Out-of-Hospital Cardiac Arrest.

OBJECTIVE: Extracorporeal cardiopulmonary resuscitation (ECPR), while resource-intensive, may improve outcomes in selected patients with refractory out-of-hospital cardiac arrest (OHCA). We sought to identify patients who fulfilled a set of ECPR criteria in order to estimate: (1) the proportion of patients with refractory cardiac arrest who may have benefited from ECPR; and (2) the outcomes achieved with conventional resuscitation. METHODS: We performed a secondary analysis from a 52-month prospective registry of consecutive adult non-traumatic OHCA cases from a single urban Canadian health region serving one million patients. We developed a hypothetical ECPR-eligible cohort including adult patients <60 years of age with a witnessed OHCA, and either bystander CPR or EMS arrival within five minutes. The primary outcome was the proportion of ECPR-eligible patients who had refractory cardiac arrest, defined as termination of resuscitation pre-hospital or in the ED. The secondary outcome was the proportion of EPCR-eligible patients who survived to hospital discharge. RESULTS: Of 1,644 EMS-treated OHCA, 168 (10.2%) fulfilled our ECPR criteria. Overall, 54/1644 (3.3%; 95% CI 2.4%-4.1%) who were ECPR-eligible had refractory cardiac arrest. Of ECPR-eligible patients, 114/168 (68%, 95% CI 61%-75%) survived to hospital admission, and 70/168 (42%; 95% CI 34-49%) survived to hospital discharge. CONCLUSION: In our region, approximately 10% of EMS-treated cases of OHCA fulfilled our ECPR criteria, and approximately one-third of these (an average of 12 patients per year) were refractory to conventional resuscitation. The integration of an ECPR program into an existing high-performing system of care may have a small but clinically important effect on patient outcomes.

Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects.

OBJECTIVE: The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this. METHODS: This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 µg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum. RESULTS: Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response. CONCLUSION: Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling.

Limited echocardiography-guided therapy in subacute shock is associated with change in management and improved outcomes.

PURPOSE: The purpose of the study was to compare the effect of limited echocardiography (LE)-guided therapy to standard management on 28-day mortality, intravenous fluid prescription, and inotropic dosing following early resuscitation for shock. MATERIALS AND METHODS: Two hundred twenty critically ill patients with undifferentiated shock from a quaternary intensive care unit were included in the study. The LE group consisted of 110 consecutive patients prospectively studied over a 12-month period receiving LE-guided management. The standard management group consisted of 110 consecutive patients retrospectively studied with shock immediately prior to the LE intervention. RESULTS: In the LE group, fluid restriction was recommended in 71 (65%) patients and initiation of dobutamine in 27 (25%). Fluid prescription during the first 24 hours was significantly lower in LE patients (49 [33-74] vs 66 [42-100] mL/kg, P = .01), whereas 55% more LE patients received dobutamine (22% vs 12%, P = .01). The LE patients had improved 28-day survival (66% vs 56%, P = .04), a reduction in stage 3 acute kidney injury (20% vs 39%), and more days alive and free of renal support (28 [9.7-28] vs 25 [5-28], P = .04). CONCLUSIONS: Limited echocardiography-guided management following early resuscitation is associated with improved survival, less fluid, and increased inotropic prescription. A prospective randomized control trial is required to verify these results.

Conjugated linoleic acid (CLA): is it time to supplement asthma therapy?

The limitations and side effects of existing asthma therapies prompt interest in complementary and alternative therapies. Conjugated linoleic acids (CLA) are a family of natural fatty acids found primarily in beef and dairy products. These molecules have a variety of biological properties which suggest potential benefit in asthma, including effects on energy regulation, lipid metabolism, inflammation and immune function. Here we review the evidence for these effects from pre-clinical and clinical studies, their significance in the context of human asthma, and discuss the potential role for CLA supplementation in asthma management.

Community-acquired pneumonia in older patients: does age influence systemic cytokine levels in community-acquired pneumonia?

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a major cause of death in the elderly. The age-related increase in comorbid illnesses plays a part but the effect of aging on the immune response may be equally important. We aimed to evaluate patients with CAP for evidence of a muted response to infection in elderly patients admitted to hospital compared with a younger patient group. METHODS: Patients with CAP admitted through the Emergency Department were recruited for this prospective observational study. Clinical data were collected at presentation. Severity of pneumonia was assessed using the British Thoracic Society confusion, urea nitrogen, respiratory rate, blood pressure (CURB) score, the Pneumonia Severity Index (PSI) and the systemic inflammatory response syndrome (SIRS) definition. IL-6 and IL-10 levels were measured within 24 h of admission. RESULTS: Eighty patients were included in the study, of whom 38 (48%) were female. The median age was 74 years (range 18-95). Patients greater than 65 years of age had a lower incidence of chest pain and a higher incidence of altered mental status on presentation. CURB score and PSI were higher in the older patients. SIRS showed similar frequencies in both groups. IL-6 and IL-10 levels were similar in young (< 65 years), older (> 65 years) and very elderly (> 80 years) patients. This finding was not altered by severity of pneumonia. CONCLUSIONS: Age does not diminish the severity of illness scores in patients with CAP. There was no blunting of the systemic cytokine response with advanced age in this study.

Interleukin-9 and -13 inhibit spontaneous and corticosteroid induced apoptosis of normal airway epithelial cells.

The airway epithelium is the target of physical and allergic insults. The resulting inflammatory signals from Th2 cytokines including interleukin (IL)-9 and IL-13 have pleiotropic activities and have been implicated in airway remodeling in asthmatics. The objective of this study was to determine the role of IL-9 and IL-13 in the regulation of normal airway epithelial cell death and epithelial repair. In a cell culture model, a normal human airway epithelial cell line and primary airway epithelial cells were treated with IL-9 or IL-13 alone and in combination. Apoptosis was determined by multiple techniques, including enrichment of nucleosomes released into the cytoplasm, mitochondrial membrane polarity perturbation, cytosolic cytochrome c released and the detection of cleaved p85-poly(ADP-ribose)polymerase (PARP). Proliferation was quantified by BrdU incorporation. IL-9 and IL-13 treatment, alone and in combination, resulted in a significant reduction in spontaneous airway epithelial cell apoptosis when compared to controls. The cytoprotective effect of IL-9 was associated with up-regulation of the antiapoptotic molecule Bcl-2. IL-13 also demonstrated coordinate pro-proliferative activity .Dexamethasone induces apoptosis in airway epithelial cells. Coincubation with IL-9 or IL-13 was protective against this corticosteroid-induced apoptosis by up-regulation of Bcl-2. These data demonstrate that IL-9 and IL-13 may be critical to normal cellular homeostasis in the setting of airway epithelial injury. A dysregulated response to these cytokines may contribute to airway remodeling in asthma.

Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol and cigarette smoke.

The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium. Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations. We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged. Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression. We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease. Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts. Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein. The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS. Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect. The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression. Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.

Respiratory epithelial cells require Toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide.

BACKGROUND: The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human beta-defensin 2 (HBD2) represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced HBD2 expression by human A549 epithelial cells. METHODS: Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. RESULTS: We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. CONCLUSION: This data defines an additional role for TLR4 in the host defense in the lung.