Comparison of Mechanical Insufflation-Exsufflation and Hypertonic Saline and Hyaluronic Acid With Conventional Open Catheter Suctioning in Intubated Patients.

BACKGROUND: Open respiratory secretion suctioning with a catheter causes pain and tracheobronchial mucosal injury in intubated patients. The goal of mechanical insufflation-exsufflation (MI-E) is to move secretions proximally and noninvasively by generating a high peak expiratory air flow. Nebulized hypertonic saline with hyaluronic acid (HS-HA) may facilitate suctioning by hydration. We assessed the safety and tolerance of a single session of airway clearance with MI-E and HS-HA in critically ill intubated patients. METHODS: Adults with a cuffed artificial airway were randomized to (1) open suctioning, (2) open suctioning after HS-HA, (3) MI-E, or (4) MI-E with HS-HA. Adverse events, pain and sedation/agitation scores, and respiratory and hemodynamic variables were collected before, during, and 5-min and 60-min post intervention. RESULTS: One-hundred twenty subjects were enrolled and completed the study. Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 22 (16-28); median (IQR) age was 69.0 (57.0-75.7) y, and 90 (75%) were male. Baseline respiratory and hemodynamic variables were comparable. Adverse events occurred in 30 subjects (25%), with no between-group differences. Behavioral pain equivalents and Richmond Agitation-Sedation Scale were higher during suctioning in groups 1 (P < .001) and 2 (P < .001). Independent predictive variables for higher pain and agitation/sedation scores were study groups 1 and 2 and simultaneous analgosedation, respectively. Noradrenaline infusion rates were lower at 60 min in groups 2 and 4. PaO2 /FIO2 had decreased at 5 min after open suctioning in group 1 and increased at 60 min in group 3. CONCLUSIONS: We observed no difference in adverse events. MI-E avoids pain and agitation.

The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial.

PURPOSE: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). MATERIALS AND METHODS: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). RESULTS: Eighty-three patients were randomized and received infusions (Cx611: n = 42]; placebo: n = 41]. The mean age was similar (Cx611: 61.1 [11.2] years; placebo: 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611: n = 9; placebo: n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611: 86.7%; placebo: 93.8%), mean number of ventilator-free days (Cx611: 12.2 [10.29] days; placebo: 15.4 [10.75] days), and overall survival (Cx611: 71.5%; placebo: 77.0%) did not differ between study arms. CONCLUSION: Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. TRIAL REGISTRATION: NCT03158727 (retrospectively registered: May 09, 2017). Full study protocol: https://clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf.

Long-term Outcomes and Recovery of Patients who Survived COVID-19: LUNG INJURY COVID-19 Study.

Background: LUNG INJURY COVID-19 (clinicaltrials.gov NCT 21/399-E) is a registry-based prospective observational cohort study to evaluate long-term outcomes and recovery 12 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection according to severity. Methods: Three hundred five coronavirus disease 2019 (COVID-19) survivors were included (moderate, 162; severe, 143). Twelve months after SARS-CoV-2 infection, there was resolution of respiratory symptoms (37.9% in severe vs 27.3% in moderate pneumonia; P = .089). Results: Exertional dyspnea was present (20% in severe vs 18.4% in moderate; P = .810). Abnormalities on chest radiology imaging were detected more often in severe COVID-19 infection vs moderate infection (29% vs 8.8%; P < .001). Pulmonary function testing (forced spirometry or diffusion) performed at 12 months of mean follow-up according to protocol detected anomalies in 31.4% of patients with severe COVID-19 courses and in 27.7% of moderate patients. Risk factors associated with diffusion impairment at 12 months were age (odds ratio [OR], 1.05; 95% CI, 1.01-1.10; P = .008), forced expiratory volume in 1 second predicted at follow-up (OR, 0.96; 95% CI, 0.93-0.99; P = .017), and dyspnea score at follow-up (OR, 3.16; 95% CI, 1.43-6.97; P = .004). Computed tomography (CT) scans performed at 12 months of mean follow-up showed evidence of fibrosis in almost half of patients with severe COVID-19 courses, who underwent CT according to protocol. Conclusions: At 12 months from infection onset, most patients refer to symptoms, particularly muscle weakness and dyspnea, and almost one-third of patients with severe COVID-19 pneumonia had impaired pulmonary diffusion and abnormalities on chest radiology imaging. These results emphasize the importance of systematic follow-up after severe COVID-19, with appropriate management of pulmonary sequelae.

Multicentre study of ceftazidime/avibactam for Gram-negative bacteria infections in critically ill patients.

This study aimed to assess the efficacy of ceftazidime/avibactam (C/A) in the treatment of infections due to Gram-negative bacteria (GNB) in critically ill patients. A multicentre, retrospective, observational study was conducted in critically ill patients receiving C/A for GNB infections. We evaluated demographic data, localisation and severity of infection, clinical and microbiological outcomes, and mortality. A total of 68 patients received C/A for serious GNB infections. The main infections were respiratory (33.8%), intra-abdominal (22.1%) and urinary tract infections (10.3%); bacteraemia was found in 22 cases (32.4%). Most infections were complicated by septic shock (58.8%) or sepsis (36.8%) and most of them required life-supporting therapies. Enterobacterales (79.4%) and Pseudomonas aeruginosa (19.1%) were the most frequently isolated bacteria; 84.2% of isolates were carbapenem-resistant. Thirty-four patients (50.0%) received C/A in combination with other antimicrobials. Fifty patients (73.5%) presented a favourable clinical response. Microbiological eradication was documented in 25 cases (36.8%). No significant differences were found in clinical response between patients treated with monotherapy or combined therapy (79.4% vs. 67.6%; P = 0.27). Overall intensive care unit (ICU) mortality was 41.2%. Univariate analysis showed that 30-day all-cause mortality was significantly (P < 0.05) associated with bacteraemia, previous corticosteroid use and the need of life-supporting therapies. C/A appears to be an effective therapy for severe infections due to GNB, including carbapenem-resistant isolates, in critically ill patients. C/A combination therapy was not associated with a higher clinical response. Mortality correlated significantly with the presence of bacteraemia, previous corticosteroid use and the need for life-supporting therapies.

Multicenter study of ceftolozane/tazobactam for treatment of Pseudomonas aeruginosa infections in critically ill patients.

BACKGROUND: This study aimed to assess the efficacy of ceftolozane-tazobactam (C/T) for treating infections due to Pseudomonas aeruginosa (P. aeruginosa) in critically ill patients. PATIENTS AND METHODS: A multicenter, retrospective and observational study was conducted in critically ill patients receiving different C/T dosages and antibiotic combinations for P. aeruginosa infections. Demographic data, localisation and severity of infection, clinical and microbiological outcome, and mortality were evaluated. RESULTS: Ninety-five patients received C/T for P. aeruginosa serious infections. The main infections were nosocomial pneumonia (56.2%), intra-abdominal infection (10.5%), tracheobronchitis (8.4%), and urinary tract infection (6.3%). Most infections were complicated with sepsis (49.5%) or septic shock (45.3%), and bacteraemia (10.5%). Forty-six episodes were treated with high-dose C/T (3 g every 8 hours) and 38 episodes were treated with standard dosage (1.5 g every 8 hours). Almost half (44.2%) of the patients were treated with C/T monotherapy, and the remaining group received combination therapy with other antibiotics. Sixty-eight (71.6%) patients presented a favourable clinical response. Microbiological eradication was documented in 42.1% (40/95) of the episodes. The global ICU mortality was 36.5%. Univariate analysis showed that 30-day mortality was significantly associated (P < 0.05) with Charlson Index at ICU admission and the need of life-supporting therapies. CONCLUSIONS: C/T appeared to be an effective therapy for severe infections due to P. aeruginosa in critically ill patients. Mortality was mainly related to the severity of the infection. No benefit was observed with high-dose C/T or combination therapy with other antibiotics.

[Post mortem core needle biopsy of Covid-19 fatalities]. / Punción post mortem con aguja gruesa a cadáveres fallecidos por COVID-19.

The difficulties involved in performing autopsies of patients who had died due to COVID-19 required the use of alternative methods in order to obtain tissue samples of affected organs. We describe the technique of core needle aspiration, without ultrasonographic guidance, which we used in 19 cadavers and which produced a high yield in lungs, heart (>94%) and liver (>89%), thus enabling the study of the morphological changes produced by SARS-CoV-2.

Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit.

CONTEXT: Linezolid resistance is extremely uncommon in Staphylococcus aureus. OBJECTIVE: To report an outbreak with linezolid and methicillin-resistant S. aureus (LRSA) in an intensive care department and the effective control measures taken. DESIGN, SETTING, AND PATIENTS: Outbreak study of consecutive critically ill patients colonized and/or infected with LRSA at an intensive care department of a 1000-bed tertiary care university teaching hospital in Madrid, Spain. Patients were placed under strict contact isolation. Daily updates of outbreak data and recommendations for the use of linezolid were issued. Extensive environmental sampling and screening of the hands of health care workers were performed. MAIN OUTCOME MEASURES: Linezolid use and clinical and epidemiological characteristics and outcomes using minimal inhibitory concentrations, pulsed-field gel electrophoresis, and polymerase chain reaction of LRSA isolates. RESULTS: Between April 13 and June 26, 2008, 12 patients with LRSA were identified. In 6 patients, LRSA caused ventilator-associated pneumonia and in 3 patients it caused bacteremia. Isolates were susceptible to trimethoprim-sulfamethoxazole, glycopeptides, tigecycline, and daptomycin. Genotyping identified 1 predominant clone and 3 other types. Cfr-mediated linezolid resistance was demonstrated in all isolates. Potential hospital staff carriers and environmental samples were negative except for one. Six patients died, 5 of them in the intensive care unit, with 1 death attributed to LRSA infection. Linezolid use decreased from 202 defined daily doses in April 2008 to 25 defined daily doses in July 2008. Between July 2008 and April 2010, no new cases have been identified in the weekly surveillance cultures or diagnostic samples. CONCLUSIONS: The first clinical outbreak, to our knowledge, with LRSA mediated by the cfr gene developed at our center, was associated with nosocomial transmission and extensive usage of linezolid. Reduction of linezolid use and infection-control measures were associated with the termination of the outbreak.

Big data and machine learning in critical care: Opportunities for collaborative research.

The introduction of clinical information systems (CIS) in Intensive Care Units (ICUs) offers the possibility of storing a huge amount of machine-ready clinical data that can be used to improve patient outcomes and the allocation of resources, as well as suggest topics for randomized clinical trials. Clinicians, however, usually lack the necessary training for the analysis of large databases. In addition, there are issues referred to patient privacy and consent, and data quality. Multidisciplinary collaboration among clinicians, data engineers, machine-learning experts, statisticians, epidemiologists and other information scientists may overcome these problems. A multidisciplinary event (Critical Care Datathon) was held in Madrid (Spain) from 1 to 3 December 2017. Under the auspices of the Spanish Critical Care Society (SEMICYUC), the event was organized by the Massachusetts Institute of Technology (MIT) Critical Data Group (Cambridge, MA, USA), the Innovation Unit and Critical Care Department of San Carlos Clinic Hospital, and the Life Supporting Technologies group of Madrid Polytechnic University. After presentations referred to big data in the critical care environment, clinicians, data scientists and other health data science enthusiasts and lawyers worked in collaboration using an anonymized database (MIMIC III). Eight groups were formed to answer different clinical research questions elaborated prior to the meeting. The event produced analyses for the questions posed and outlined several future clinical research opportunities. Foundations were laid to enable future use of ICU databases in Spain, and a timeline was established for future meetings, as an example of how big data analysis tools have tremendous potential in our field.

Preliminary experience on the safety and tolerability of mechanical "insufflation-exsufflation" in subjects with artificial airway.

BACKGROUND: Catheter suctioning of respiratory secretions in intubated subjects is limited to the proximal airway and associated with traumatic lesions to the mucosa and poor tolerance. "Mechanical insufflation-exsufflation" exerts positive pressure, followed by an abrupt drop to negative pressure. Potential advantages of this technique are aspiration of distal airway secretions, avoiding trauma, and improving tolerance. METHODS: We applied insufflation of 50 cmH2O for 3 s and exsufflation of - 45 cmH2O for 4 s in patients with an endotracheal tube or tracheostomy cannula requiring secretion suctioning. Cycles of 10 to 12 insufflations-exsufflations were performed and repeated if secretions were aspirated and visible in the proximal artificial airway. Clinical and laboratory parameters were collected before and 5 and 60 min after the procedure. Subjects were followed during their ICU stay until discharge or death. RESULTS: Mechanical insufflation-exsufflation was applied 26 times to 7 male and 6 female subjects requiring suctioning. Mean age was 62.6 ± 20 years and mean Apache II score 23.3 ± 7.4 points. At each session, a median of 2 (IQR 1; 2) cycles on median day of intubation 11.5 (IQR 6.25; 25.75) were performed. Mean insufflation tidal volume was 1043.6 ± 649.9 ml. No statistically significant differences were identified between baseline and post-procedure time points. Barotrauma, desaturation, atelectasis, hemoptysis, or other airway complication and hemodynamic complications were not detected. All, except one, of the mechanical insufflation-exsufflation sessions were productive, showing secretions in the proximal artificial airway, and were well tolerated. CONCLUSIONS: Our preliminary data suggest that mechanical insufflation-exsufflation may be safe and effective in patients with artificial airway. Safety and efficacy need to be confirmed in larger studies with different patient populations. TRIAL REGISTRATION: EudraCT 2017-005201-13 (EU Clinical Trials Register).

Diabetic ketoacidosis inducing myocardial infarction secondary to treatment with dapagliflozin: a case report.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are able to provoke diabetic ketoacidosis (DKA) with absence or low levels of ketone bodies in urine and slightly elevated blood glucose levels, which could delay the diagnosis; however, the presence of high urine output, due to the excretion of glucose, can help to identify the true cause.

Direct hemoperfusion with polymyxin B-immobilized cartridge in severe sepsis due to intestinal perforation: hemodynamic findings and clinical considerations in anticoagulation therapy.

BACKGROUND: High levels of endotoxin have been reported as a risk factor for mortality in critical patients. Toraymyxin® is a column designed to remove circulating blood endotoxin by direct hemoperfusion widely used in Japan. OBJECTIVES: To evaluate the effect of direct hemoperfusion with Toraymyxin® (DHP-PMX) as an adjuvant treatment in patients with severe sepsis due to intestinal perforation in terms of hemodynamic function and coagulation abnormalities. METHODS: Prospective cohort study with a historical control group. Cohort 1: prospective cohort undergoing two sessions of DHP-PMX (n=14). Cohort 2: retrospective historical cohort (n=7). The anticoagulation regime was used according to the protocol of each centre and to the special conditions of each patient. RESULTS: Mean norepinephrine dose was significantly reduced (0.9 ± 0.5 µg/kg/min pre-first DHP-PMX vs 0.3 ± 0.4 µg/kg/min post-second DHP-PMX treatment, p<0.05). Central venous pressure (CVP) and stroke volume variation (SVV) remained without significant changes during the study, as well as cardiac index (CI) in patients with initial CI ≥ 2.5 L/min/m2. CI significantly increased in patients with initial CI<2.5 L/min/m2 (2.1 ± 0.4 pre-first DHP-PMX vs 3.4 ± 0.4 pre-second DHP-PMX session, p=0.01). Mean platelet count pre-first and post-second DHP-PMX decreased significantly (213.9 x 10(3) ± 138.5 x 10(3) platelets/mm3 vs 91.0 x 10(3) ± 53.5 x 10(3) platelets/mm3, p=0.03), without significant changes during each DHP-PMX treatment. Patients did not experience bleeding nor complications derived from DHP-PMX treatments. Survival rates at 28 and 56 days did not differ significantly between cohort 1 and 2 (21.4% vs 42.9%; 42.9% vs 57.1%; respectively). CONCLUSIONS: Performing two sessions of DHP-PMX treatment in a cohort of patients with abdominal sepsis is a feasible adjuvant therapeutic approach, safe in terms of coagulation abnormalities, can be done with different anticoagulation protocols, improves hemodynamic status and may impact on survival.