Need For Ventilation In Patients Research Articles

Azithromycin for COVID-19: Pharmacological Mechanisms, Challenges, and Prospects

The coronavirus disease (COVID)-19 pandemic led to a new challenge in the field of effective treatment methods for this disease. Antiviral and immunomodulatory agents were suggested as potential therapeutic methods in this field. Since the most severe clinical symptoms associated with COVID-19 disease appear to be acute respiratory syndrome, azithromycin has been proposed as a potentially effective drug in this context. We have updated the evidence and selected all relevant items to understand the mechanism of role of azithromycin, clinical efficacy, and their side effects in coronavirus disease-19 treatment on July 20th and updated on March 20th, 2020. A literature search of electronic databases including the Web of Science, PubMed, and Google Scholar was conducted by searching keywords such as "Azithromycin", "COVID-19", and "Combination therapy". The ultimate goal of this review was identifying eligible studies about the pharmacological activities, safety, and effectiveness of azithromycin in treating COVID-19 patients. Immunomodulatory properties of azithromycin include the ability to reduce cytokine production, maintain epithelial cell integrity, or prevent lung fibrosis. The use of azithromycin in some studies was associated with a decrease in mortality and need for ventilation in patients. These properties can be useful during the period of COVID-19 infection, especially in patients with underlying diseases. However, the evidence for the use of azithromycin is still scarce and the quality of the studies is low. In some retrospective studies, azithromycin was mainly evaluated in combination with hydroxychloroquine, which showed no particular advantage. The results of this review showed that azithromycin has appropriate and well-known safety characteristics in the treatment of patients with COVID-19. However, the most appropriate dosage in different stages of the disease and the effect of its combination with other drugs are important questions that should be considered in future clinical trials.

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock.

Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase that is released into circulation upon cell death. DPP3 is involved in the degradation of angiotensins, enkephalines, and endomorphines. It has been shown that circulating DPP3 (cDPP3) plasma concentration increases in cardiogenic shock (CS) patients and correlates with high mortality risk. Cardiogenic shock is a life-threatening syndrome associated with organ hypoperfusion. One of the common causes of CS is acute myocardial infarction (AMI). This study aimed to investigate if cDPP3 levels are associated with CS severity and the need for ventilation in patients suffering from CS. Fifteen patients with CS were included in this study. Six patients were invasively ventilated. The values of cDPP3 were higher in ventilated patients than in non-ventilated patients at admission, 3 h, and 24 h after admission in the intensive care unit. Patients with pulmonary hypertension at admission also showed high cDPP3 values at all time points. Furthermore, high cDPP3 levels were associated with reduced stroke volume. Our results suggest that cDPP3 could predict CS progression and guide therapy escalation.

Diaphragm Function Parameters in Patients with Severe COVID-19

The aim of the study was to investigate the feasibility of predicting the need for mechanical ventilation in patients with severe COVID-19 disease using ultrasound assessment of diaphragm function.Material and methods. An open prospective pilot study included 60 patients diagnosed with the novel coronavirus infection, who, at the time of admission to the intensive care unit (NEWS score > 6), underwent ultrasound assessment of diaphragm excursion, thickness and the diaphragm thickening fraction. Group 1 (n=30) included patients who did not require mechanical ventilation, and group 2 (n=30) consisted of patients who were subsequently transferred to mechanical ventilation.Results. Patients in group 2 had significantly lower diaphragm function parameters (left excursion value (P<0.001), right excursion value (P<0.001), diaphragm thickness on inspiration (P=0.043), and thickening fraction (P<0.001) than patients in group 1.Conclusion. Decreased diaphragm excursion of less than 17.1 mm on the right side is a predictor of initiation of mechanical ventilation in patients with the COVID-19 infection (sensitivity 93.3%, specificity 76.7%). Morphological examination in deceased patients of group 2 revealed pericellular and perivascular edema, venular thrombosis, endoneurial edema, and sludge in the lumen of arterioles.

Nonsteroidal anti-inflammatory drugs in acute viral respiratory tract infections: An updated systematic review.

In this systematic review, we aimed to assess the efficacy and safety of nonsteroidal anti‐inflammatory drugs (NSAIDs) in treating respiratory tract infections in adults and children. PubMed, Scopus, Web of Science, Cochrane, and Embase databases were searched. A total of 34 randomized clinical trials were included in this systematic review. We assessed the risk of bias of all included studies using the Cochrane tool for risk of bias assessment. The evidence on ibuprofen, naproxen, aspirin, diclofenac, and other NSAIDs were rated for degree of uncertainty for each of the study outcomes and summarized using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Our findings suggest that high‐quality evidence supports the use of NSAIDs to reduce fever in both adults and children. However, the evidence was uncertain for the use of NSAIDs to reduce cough. Most studies showed that NSAIDs significantly relieved sore throat. The evidence for mortality and oxygenation is limited. Regarding the adverse events, gastrointestinal discomfort was more frequently reported in children. For adults, our overall certainty in effect estimates was low and the increase in gastrointestinal adverse events was not clinically significant. In conclusion, NSAIDs seem to be beneficial in the outpatient management of fever and sore throat in adults and children. Although the evidence does not support their use to decrease mortality nor improve oxygenation in inpatient settings, the use of NSAIDs did not increase the rate of death or the need for ventilation in patients with respiratory tract infections. Further studies with a robust methodology and larger sample sizes are recommended.

C-reactive protein as predictor of severe course of the new coronavirus infection in patients with chronic obstructive pulmonary disease in the intensive care unit

SummaryDespite a large number of observations, the role of chronic obstructive pulmonary disease (COPD) in the course and development of a new coronavirus infection is still unknown. The combination of these two process-es, which are characterized by the development of a sys-temic inflammatory reaction, leads to the development of a pronounced immune response, more severe com-plications and the formation of an atypical radiological pattern. In our work, 387 patients with a new coronavi-rus infection were examined in the intensive care unit. Among these 387 patients, 41 patients were diagnosed with COPD according to the GOLD criteria. The aim of the work is to determine the features of radiological manifes-tations and the course of a new coronavirus infection in patients with chronic obstructive pulmonary disease in the intensive care unit. Typical radiological manifesta-tions of a new coronavirus infections were detected in 90.5% of cases. 23 (56.1%) patients had a secondary infec-tion, 20 (48.8%) — sepsis, 10 (24.4%) — ARDS, 29 (70.7%) patients required mechanical ventilator, 24 (58.5%) pa-tients developed a fatal outcome. A 2-fold increase in the concentration of C-reactive protein was statistically significantly associated with an increase in the chances of more severe damage to lung tissue during primary CT examination (upon admission to hospital). A 2-fold increase in ferritin concentration was statistically signifi-cantly associated with an increase in the chances of more severe lung tissue damage (the maximum degree of lung tissue damage during the entire period of hospital stay). A comparative analysis revealed a tendency to a higher frequency of secondary infections in patients with pan-lobular emphysema and a higher frequency of the need for ventilation in patients with diffuse emphysema. Also, the presence of bullous emphysema was statistically sig-nificantly associated with a higher frequency of CT-3 de-grees of lung tissue damage upon admission. A compar-ative analysis revealed a statistically significantly higher concentration of C-reactive protein in a mixed COPD phe-notype compared with an emphysematous phenotype, a higher incidence of sepsis in patients with a mixed COPD phenotype compared with patients with an emphysema-tous and bronchitic phenotype.

Evaluation of potential anti-COVID-19 therapies

Evaluation of potential anti-COVID-19 therapies

Anakinra in COVID-19: important considerations for clinical trials

Anakinra in COVID-19: important considerations for clinical trials

Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis

BackgroundAcute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure.MethodsWe will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology.DiscussionThis study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure.Systematic review registrationPROSPERO CRD42019121755

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. Trial registration: ClinicalTrials.gov NCT02999815 Registration date: 21 December 2016

Influence of the serum levels of immunoglobulins on clinical outcomes in medical intensive-care patients

Endogenous immunoglobulins (Igs) are of fundamental importance in the host defense after microbial infections. However, the therapeutic administration of intravenous IgG (IVIgG) has not yet been shown to improve clinical outcomes in patients suffering from sepsis, and in the case of IgM-containing preparations (IVIgGMA) the positive evidence is only weak. Recently published studies implicate that Ig levels on admission could have an impact on the patient's response to IVIg treatment and on outcomes of critically ill patients. In this noninterventional study, the serum levels of IgG, IgM, and IgA were determined in 340 medical patients on ICU admission, and clinical outcomes were prospectively recorded (ICU mortality, need for renal replacement therapy (RRT), need for mechanical ventilation, substitution of coagulation factors, and amount of red cell transfusions). Patients were prospectively grouped according to their main reason for ICU admission (sepsis, respiratory failure, cardiovascular diseases, acute renal failure, postoperative condition, state after cardiopulmonal resuscitation, gastrointestinal diseases, and others). There was no correlation between the Ig levels on admission and ICU mortality neither in the total cohort of medical ICU patients nor in any prespecified subgroup. However, in a logistic regression model that was adjusted for APACHE II score on admission, an increase in serum IgG was associated with a reduced need for mechanical ventilation in patients suffering from cardiovascular disease. On the other hand, in patients suffering from sepsis, an increased level of IgM was linked to an increased administration of coagulation factors. Our data do not support the hypothesis that serum levels of immunoglobulins are linked to mortality in medical ICU patients.

Functional markers to predict the need for prolonged mechanical ventilation in patients with Guillain-Barré syndrome

Functional markers to predict the need for prolonged mechanical ventilation in patients with Guillain-Barré syndrome

Patients with congestive heart failure treated by physicians using intravenous nitroglycerin boluses in the emergency department have shorter hospital length of stay

Study objectives: Several studies have shown that high-dose nitroglycerin (NTG) is effective in decreasing the incidence of death, myocardial infarction, and need for mechanical ventilation in patients with congestive heart failure (CHF). We postulate that the use of intravenous NTG boluses in the emergency department (ED) would lead to decreased hospital length of stay for patients with CHF. Methods: This was a retrospective cohort in an urban nonteaching hospital with 43,000 annual ED visits. Consecutive patients treated by emergency physicians during a 20-month period who arrived between midnight and 8 am and were admitted for CHF exacerbation were included. We previously had shown that those arriving between midnight and 8 am were more likely to benefit from aggressive NTG therapy in the ED than those arriving at other times. To lessen the influence of outliers on the results, we a priori excluded patients with a length of stay greater than 10 days. On the basis of responses to a structured survey on the treatment of CHF in the ED, we divided emergency physicians into 2 groups: users and nonusers of intravenous bolus NTG. We then assigned CHF patients to 1 of the 2 groups according to their emergency physician categorization and calculated length of stay for each group of patients. We used Student's t test to compare means (α≤.05 taken as statistically significant). Results: The user and nonuser groups had 19 and 105 patients, respectively. The mean age (66±14 and 71±13 years, respectively) and the percentage of female patients (58% and 50%, respectively) was similar between the groups. The mean length of stay for the user and nonuser groups was 3.7±1.5 and 4.6±2.4 days, respectively. The difference of 0.9 days was statistically significant (95% confidence interval 0.0 to 1.7 days, P =.05). Conclusion: CHF patients who arrive between midnight and 8 am spend almost 1 day fewer in the hospital if they are treated by emergency physicians who use intravenous NTG boluses than if they are treated by those who do not.