Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:Blood lactate concentrations are frequently measured in critically ill patients and have important prognostic value. Here, we review some key questions related to their clinical use in sepsis. RECENT FINDINGS/RESULTS:Despite the metabolic hurdles, measuring lactate concentrations remains very informative in clinical practice. Although blood lactate levels change too slowly to represent the only guide to resuscitation, serial lactate levels can help to define the patient's trajectory and encourage a review of the therapeutic strategy if they remain stable or increase over time. SUMMARY/CONCLUSIONS:Lactate concentrations respond too slowly to be used to guide acute changes in therapy, but can help evaluate overall response. Hyperlactatemia should not be considered as a problem in itself, but as a warning of altered cell function.

PURPOSE OF REVIEW/OBJECTIVE:Current goals of resuscitation in septic shock are mainly a fixed volume of fluids and vasopressors to correct hypotension and improve tissue perfusion indicated by decreasing lactate levels. RECENT FINDINGS/RESULTS:Abnormal peripheral perfusion by objective and subjective parameters are associated with increased mortality in various phases of the treatment of critically ill patients including patients with septic shock. Ongoing resuscitation in septic shock patients with normal peripheral perfusion is not associated with improved outcome, rather with increased mortality. Mitigation of fluid resuscitation by using parameters of peripheral perfusion in septic shock seems to be safe. SUMMARY/CONCLUSIONS:Septic shock patients with normal peripheral perfusion represent a different clinical phenotype of patients that might benefit from limited resuscitation efforts. Parameters of peripheral perfusion could be used to guide the individualization of patients with septic shock.

•COVID-19 infection is associated with a prothrombotic state•Point of care ultrasound (POCUS) provides prompt bedside diagnosis of covid-19 complications such as clot in transit•Bedside TEE guidance of mechanical CPR arm placement improves the efficiency of chest compressions.

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Therapeutic treatment with two doses of topotecan (TPT), an FDA-approved TOP1 inhibitor, suppresses infection-induced inflammation in hamsters. TPT treatment as late as 4 days post-infection reduces morbidity and rescues mortality in a transgenic mouse model. These results support the potential of TOP1 inhibition as an effective host-directed therapy against severe SARS-CoV-2 infection. TPT and its derivatives are inexpensive clinical-grade inhibitors available in most countries. Clinical trials are needed to evaluate the efficacy of repurposing TOP1 inhibitors for severe coronavirus disease 2019 (COVID-19) in humans.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

BACKGROUND:Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS:) test (p < 0·05 was considered as unstable). RESULTS:Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION:Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION:The study was registered with Clinical trials.gov Identifier: NCT04534569.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

A measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of the measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of scientific societies to establish the standards in their area of expertise. After adopting the same understandings and definitions (part 1), the different procedures for the validation of major quality criteria of measuring devices must be consensually established. In this metrologic review (part 2), we review the terms and definitions of validation, some basic processes leading to the display of an indication from a physiologic signal, and procedures for the validation of measuring instrument properties, with specific focus on perioperative and intensive care medicine including appropriate examples.

Any measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of the scientific societies to establish the standards in their area of expertise. Adopting the same understandings and definitions among clinicians and scientists is obviously the first step. In this metrologic review (part 1), we list and explain the most important terms defined by the International Bureau of Weights and Measures regarding quantities and units, properties of measurements, devices for measurement, properties of measuring devices, and measurement standards, with specific examples from perioperative and intensive care medicine.

BACKGROUND:Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock. METHODS:From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions. RESULTS:A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement). CONCLUSION/CONCLUSIONS:Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.