Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom.

PURPOSE: The trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions. METHODS: We included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget ( https://www.CovidUK.ICU ). RESULTS: Data for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO2/FiO2 on the day of death was 12.3(8.9-18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO2/FiO2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06-1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17-2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04-1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99-1.79]; P = 0.057) immediately prior to application of prone positioning were associated with lack of oxygenation response. Prone positioning was not applied to 76% of patients with moderate hypoxemia and 45% of those with severe hypoxemia and patients who died without receiving proning interventions had more missed opportunities for prone intervention [7 (3-15.5) versus 2 (0-6); P < 0.001]. Despite the severity of gas exchange deficit, most patients received lung-protective ventilation with tidal volumes less than 8 mL/kg and plateau pressures less than 30cmH2O. This was despite systematic errors in measurement of height and derived ideal body weight. CONCLUSIONS: Refractory hypoxaemia remains a major association with mortality, yet evidence based ARDS interventions, in particular prone positioning, were not implemented and had delayed application with an associated reduced responsiveness. Real-time service evaluation techniques offer opportunities to assess the delivery of care and improve protocolised implementation of evidence-based ARDS interventions, which might be associated with improvements in survival.

Procalcitonin accurately predicts lung transplant adults with low risk of pulmonary graft dysfunction and intensive care mortality.

PURPOSE: We evaluated the association of procalcitonin (PCT), IL-6-8-10 plasma levels during the first 72h after lung transplantation (LT) with ICU-mortality, oxygenation, primary graft dysfunction (PGD), and one-year graft function after LT. MATERIAL AND METHODS: Prospective, observational study. PCT and IL-6-8-10 plasma levels were measured at 24h, 48h and 72h after LT from 100 lung transplant recipients (LTr). Patients were followed until one year after LT. End-points were ICU survival, grade 3 PGD at 72h and one-year graft function. RESULTS: Higher PCT at 24h was associated with lower PaO2/FIO2 ratio and Grade 3 PGD over the first 72h after LT (p<0.05). PCT at 24h was higher in the 9 patients who died (2.90 vs 1.47ng/mL, p<0.05), with AUC=0.74 for predicting ICU-mortality. All patients with PCT<2ng/mL at 24h following LT, survived in the ICU (p<0.05). PCT and IL-10 at 48h were correlated with FEV1 (rho=-0.35) and FVC (rho=-0.29) one year after LT. (p<0.05). CONCLUSIONS: A breakpoint of PCT<2ng/mL within 24h has a high predictive value to exclude grade 3 PGD at 72h and for ICU survival. Moreover, both PCT and IL-10 within 48h were associated with significantly better graft function one year after surgery.

Pseudomonas aeruginosa ventilator-associated pneumonia management.

Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de-escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising.

Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia.

OBJECTIVE: To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. METHODS: A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. RESULTS: In the case of community acquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions. CONCLUSION: The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions.

Causas de la falta de adherencia a las guías terapéuticas para la neumonía grave / Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia

Objetivo: Valorar tasa de adherencia y causas de no adherencia a las guías terapéuticas internacionales para la prescripción antibiótica empírica en la neumonía grave en Latinoamérica. Métodos: Encuesta clínica realizada a 36 médicos de Latinoamérica donde se pedía indicar el tratamiento empírico en 2 casos clínicos ficticios de pacientes con infección respiratoria grave: neumonía adquirida en la comunidad y neumonía nosocomial. Resultados: En el caso de la neumonía comunitaria el tratamiento fue adecuado en el 30,6% de las prescripciones. Las causas de no adherencia fueron monoterapia (16,0%), cobertura no indicada para multirresistentes (4,0%) y empleo de antibióticos con espectro inadecuado (44,0%). En el caso de la neumonía nosocomial el cumplimiento de las guías terapéuticas Infectious Disease Society of America/American Thoracic Society fue del 2,8%. Las causas de falta de adherencia fueron monoterapia (14,3%) y la falta de doble tratamiento antibiótico frente a Pseudomonas aeruginosa (85,7%). En caso de considerar correcta la monoterapia con actividad frente a P. aeruginosa, el tratamiento sería adecuado en el 100% de los casos. Conclusión: En la neumonía comunitaria la adherencia a las guías terapéuticas Infectious Disease Society of America/American Thoracic Society fue del 30,6%; la causa más frecuente de incumplimiento fue el uso de monoterapia. La adherencia en el caso de la neumonía nosocomial fue del 2,8% y la causa más importante de incumplimiento fue la falta de doble tratamiento frente a P. aeruginosa, considerando adecuada monoterapia con actividad frente a P. aeruginosa la adherencia sería del 100%. .

Objective: To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. Methods: A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. Results: In the case of communityacquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions. Conclusion: The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions. .

How to approach and treat VAP in ICU patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most frequent clinical problems in ICU with an elevated morbidity and costs associated with it, in addition to prolonged MV, ICU-length of stay (LOS) and hospital-length of stay. Current challenges in VAP management include the absence of a diagnostic gold standard; the lack of evidence regarding contamination vs. airway colonization vs. infection; and the increasing antibiotic resistance. We performed a Pubmed search of articles addressing the management of ventilator-associated pneumonia (VAP). Immunocompromised patients, children and VAP due to multi-drug resistant pathogens were excluded from the analysis. When facing a patient with VAP, it's important to address a few key questions for the patient's optimal management: when should antibiotics be started?; what microorganisms should be covered?; is there risk for multirresistant microorganisms?; how to choose the initial agent?; how microbiological tests determine antibiotic changes?; and lastly, which dose and for how long?. It's important not to delay adequate treatment, since outcomes improve when empirical treatment is early and effective. We recommend short course of broad-spectrum antibiotics, followed by de-escalation when susceptibilities are available. Individualization of treatment is the key to optimal management.

Management of Pseudomonas aeruginosa pneumonia: one size does not fit all.

In view of the mortality associated with Pseudomonas aeruginosa (PSA) ventilator-associated pneumonia (VAP) and the frequency of inadequate initial empiric therapy, recent findings underscore the need for a different management paradigm with effective anti-pseudomonal vaccines for prophylaxis of patients at risk. The association of virulence factors is a variable that splits PSA in two phenotypes, with the possibility of adjunctive immunomodulatory therapy for management of virulent strains. We comment on recent advances in and the state of the art of PSA-VAP management and discuss a new paradigm for tailored and optimal management.

Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013).

OBJECTIVE: The objective of the present study was to compare antibiotic prescribing practices and survival in the ICU for patients with pneumococcal severe community-acquired pneumonia (SCAP) between 2000 and 2013. METHODS: This was a matched case-control study of two prospectively recorded cohorts in Europe. Eighty patients from the Community-Acquired Pneumonia en la Unidad de Cuidados Intensivos (CAPUCI) II study (case group) were matched with 80 patients from CAPUCI I (control group) based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age. RESULTS: Demographic data were comparable in the two groups. Combined antibiotic therapy increased from 66.2% to 87.5% (P < .01), and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0% (P < .01). ICU mortality was significantly lower (OR, 0.82; 95% CI, 0.68-0.98) in cases, both in the whole population and in the subgroups of patients with shock (OR, 0.67; 95% CI, 0.50-0.89) or receiving mechanical ventilation (OR, 0.73; 95% CI, 0.55-0.96). In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation (OR, 5.23; 95% CI, 1.60-17.17) and decreased in patients receiving early antibiotic treatment (OR, 0.36; 95% CI, 0.15-0.87) and combined therapy (OR, 0.19; 95% CI, 0.07-0.51). CONCLUSIONS: In pneumococcal SCAP, early antibiotic prescription and use of combination therapy increased. Both were associated with improved survival.

Elevation of creatine kinase is associated with worse outcomes in 2009 pH1N1 influenza A infection.

BACKGROUND: Current medical knowledge lacks specific information regarding creatine kinase (CK) elevation in influenza A pH1N1 (2009) infection. OBJECTIVES: Primary endpoints were correlation between CK at intensive care unit (ICU) admission and ICU mortality. Secondary endpoints were ICU length of stay (LOS), mechanical ventilation (MV), and requirement of renal replacement techniques (RRT). MATERIALS AND METHODS: A prospective multicenter register included all adults admitted for severe acute respiratory insufficiency (SARI) with confirmed pH1N1 in 148 ICUs. Clinical data including demographics, comorbidities, laboratory information, organ involvement, and prognostic data were registered. Post hoc classification of subjects was determined according to CK level. Data are expressed as median (interquartile range). RESULTS: Five hundred and five (505) patients were evaluable. Global ICU mortality was 17.8 % without documented differences between breakpoints. CK ≥500 UI/L was documented in 23.8 % of ICU admissions, being associated with greater renal dysfunction: acute kidney injury (AKI) was more frequent (26.1 versus 17.1 %, p < 0.05) and twofold requirement of RRT [11 versus 5.6 %, p < 0.05; odds ratio (OR) = 2.09 (95 % confidence interval [CI] 1.01-4.32)]. Increase of CK ≥1,000 UI/L was associated with two or more quadrant involvement on chest X-ray (63.2 versus 40.2 %, p < 0.01) and increased intubation risk (73.9 versus 56.7 %, p = 0.07) and duration of mechanical ventilation (median 15 days versus 11 days, p < 0.01). As a result, CK ≥1,000 UI/L was associated with 5 extra days of ICU and hospital LOS. CONCLUSIONS: CK is a biomarker of severity in pH1N1 infection. Elevation of CK was associated with more complications and increased ICU LOS and healthcare resources.