scholarly journals The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0251378
Author(s):  
Jovana Milic ◽  
Federico Banchelli ◽  
Marianna Meschiari ◽  
Erica Franceschini ◽  
Giacomo Ciusa ◽  
...  

Background The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. Methods In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Results Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab. Conclusion To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

Author(s):  
Jaclyn C. Omura ◽  
Maida Chen ◽  
Miriam Haviland ◽  
Susan Apkon

PURPOSE: Congenital myotonic dystrophy (CDM) results in hypotonia and acute respiratory distress at birth. Previous studies show that prolonged periods of intubation (>4 weeks) correlate with increased mortality rates. The objective is to describe the use and duration of respiratory support in newborns with CDM and how these relate to mortality. METHODS: A retrospective chart review was performed at a tertiary pediatric hospital among children with confirmed diagnosis of CDM. The main outcome measures were: mortality, duration of invasive mechanical ventilation (IMV) and non-invasive partial pressure ventilation (NIPPV), along with long-term use of respiratory support and equipment. RESULTS: A total of 18 subjects met inclusion criteria, 83%.f which had documented respiratory distress at birth, 39%.equired NIPPV, and 50%.equired intubation in the neonatal period. The earliest NIPPV was initiated at day one of life, and the latest extubation to NIPPV was at 17 days of life. CONCLUSION: This cohort required IMV for shorter periods with earlier transitions to NIPPV which suggests a possible change in practice and earlier transition to NIPPV recently. Further data are needed to determine if there is a possible correlation between the need for NIPPV/IMV and mortality rates.


Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 1035
Author(s):  
Rachel K. Marlow ◽  
Sydney Brouillette ◽  
Vannessa Williams ◽  
Ariann Lenihan ◽  
Nichole Nemec ◽  
...  

The American Academy of Pediatrics (AAP) recommends supportive care for the management of bronchiolitis. However, patients admitted to the intensive care unit with severe (critical) bronchiolitis define a unique group with varying needs for both non-invasive and invasive respiratory support. Currently, no guidance exists to help clinicians discern who will progress to invasive mechanical support. Here, we sought to identify key clinical features that distinguish pediatric patients with critical bronchiolitis requiring invasive mechanical ventilation from those that did not. We conducted a retrospective cohort study at a tertiary pediatric medical center. Children ≤2 years old admitted to the pediatric intensive care unit (PICU) from January 2015 to December 2019 with acute bronchiolitis were studied. Patients were divided into non-invasive respiratory support (NRS) and invasive mechanical ventilation (IMV) groups; the IMV group was further subdivided depending on timing of intubation relative to PICU admission. Of the 573 qualifying patients, 133 (23%) required invasive mechanical ventilation. Median age and weight were lower in the IMV group, while incidence of prematurity and pre-existing neurologic or genetic conditions were higher compared to the NRS group. Multi-microbial pneumonias were diagnosed more commonly in the IMV group, in turn associated with higher severity of illness scores, longer PICU lengths of stay, and more antibiotic usage. Within the IMV group, those intubated earlier had a shorter duration of mechanical ventilation and PICU length of stay, associated with lower pathogen load and, in turn, shorter antibiotic duration. Taken together, our data reveal that critically ill patients with bronchiolitis who require mechanical ventilation possess high risk features, including younger age, history of prematurity, neurologic or genetic co-morbidities, and a propensity for multi-microbial infections.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e030476 ◽  
Author(s):  
Jonathan Dale Casey ◽  
Erin R Vaughan ◽  
Bradley D Lloyd ◽  
Peter A Bilas ◽  
Eric J Hall ◽  
...  

IntroductionFollowing extubation from invasive mechanical ventilation, nearly one in seven critically ill adults requires reintubation. Reintubation is independently associated with increased mortality. Postextubation respiratory support (non-invasive ventilation or high-flow nasal cannula applied at the time of extubation) has been reported in small-to-moderate-sized trials to reduce reintubation rates among hypercapnic patients, high-risk patients without hypercapnia and low-risk patients without hypercapnia. It is unknown whether protocolised provision of postextubation respiratory support to every patient undergoing extubation would reduce the overall reintubation rate, compared with usual care.Methods and analysisThe Protocolized Post-Extubation Respiratory Support (PROPER) trial is a pragmatic, cluster cross-over trial being conducted between 1 October 2017 and 31 March 2019 in the medical intensive care unit of Vanderbilt University Medical Center. PROPER compares usual care versus protocolized post-extubation respiratory support (a respiratory therapist-driven protocol that advises the provision of non-invasive ventilation or high-flow nasal cannula based on patient characteristics). For the duration of the trial, the unit is divided into two clusters. One cluster receives protocolised support and the other receives usual care. Each cluster crosses over between treatment group assignments every 3 months. All adults undergoing extubation from invasive mechanical ventilation are enrolled except those who received less than 12 hours of mechanical ventilation, have ‘Do Not Intubate’ orders, or have been previously reintubated during the hospitalisation. The anticipated enrolment is approximately 630 patients. The primary outcome is reintubation within 96 hours of extubation.Ethics and disseminationThe trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.Trial registration numberNCT03288311.


2021 ◽  
Author(s):  
Michael Hultström ◽  
Ola Hellkvist ◽  
Lucian Covaciu ◽  
Filip Fredén ◽  
Robert Frithiof ◽  
...  

Abstract Introduction The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC. Methods This was a sub-study of a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden for critical COVID-19. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV). Results A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio (up to 48 mmHg, from HFNC to MV). Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mm Hg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible. Conclusion HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio precludes using ARDS grade as a measure of pulmonary damage during HFNC.


Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3302
Author(s):  
Michał Czapla ◽  
Raúl Juárez-Vela ◽  
Vicente Gea-Caballero ◽  
Stanisław Zieliński ◽  
Marzena Zielińska

Background: Coronavirus disease 2019 (COVID-19) has become one of the leading causes of death worldwide. The impact of poor nutritional status on increased mortality and prolonged ICU (intensive care unit) stay in critically ill patients is well-documented. This study aims to assess how nutritional status and BMI (body mass index) affected in-hospital mortality in critically ill COVID-19 patients Methods: We conducted a retrospective study and analysed medical records of 286 COVID-19 patients admitted to the intensive care unit of the University Clinical Hospital in Wroclaw (Poland). Results: A total of 286 patients were analysed. In the sample group, 8% of patients who died had a BMI within the normal range, 46% were overweight, and 46% were obese. There was a statistically significantly higher death rate in men (73%) and those with BMIs between 25.0–29.9 (p = 0.011). Nonsurvivors had a statistically significantly higher HF (Heart Failure) rate (p = 0.037) and HT (hypertension) rate (p < 0.001). Furthermore, nonsurvivors were statistically significantly older (p < 0.001). The risk of death was higher in overweight patients (HR = 2.13; p = 0.038). Mortality was influenced by higher scores in parameters such as age (HR = 1.03; p = 0.001), NRS2002 (nutritional risk score, HR = 1.18; p = 0.019), PCT (procalcitonin, HR = 1.10; p < 0.001) and potassium level (HR = 1.40; p = 0.023). Conclusions: Being overweight in critically ill COVID-19 patients requiring invasive mechanical ventilation increases their risk of death significantly. Additional factors indicating a higher risk of death include the patient’s age, high PCT, potassium levels, and NRS ≥ 3 measured at the time of admission to the ICU.


2020 ◽  
Vol 15 ◽  
Author(s):  
Valentina Di Lecce ◽  
Giovanna Elisiana Carpagnano ◽  
Paola Pierucci ◽  
Vitaliano Nicola Quaranta ◽  
Federica Barratta ◽  
...  

The recent Coronavirus disease 19 (COVID-19) pandemic, first in China and then also in Italy, brought to the attention the problem of the saturation of Intensive Care Units (ICUs). Almost all previous reports showed that in ICU less than half of patients were treated with invasive mechanical ventilation (IMV) and the rest of them with non-invasive respiratory support. This highlighted the role of respiratory intensive care units (RICUs), where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support, avoiding ICU admission. In this report, we describe baseline characteristics and clinical outcomes of 97 patients with moderate to severe respiratory failure due to COVID-19 admitted to the RICU of the Policlinico of Bari from March 11th to May 31st 2020. In our population, most of the subjects were male (72%), non-smokers (76%), with a mean age of 69.65±14 years. Ninety-one percent of patients presented at least one comorbidity and 60% had more than two comorbidities. At admission, 40% of patients showed PaO2/FiO2 ratio between 100 and 200 and 17% showed Pa02/FiO2 ratio <100. Mean Pa02/FiO2 ratio at admission was 186.4±80. These patients were treated with non-invasive respiratory support 40% with CPAP, 38% with BPAP, 3% with HFNC, 11% with standard oxygen therapy or with IMV through tracheostomy (patients in step down from ICU, 8%). Patients discharged to general ward (GW) were 51%, 30% was transferred to ICU and 19% died. To the best of our knowledge, this is one of the few described experiences of patients with respiratory failure due to COVID-19 treated outside the ICU, in a RICU. Outcomes of our patients, characterized by several risk factors for disease progression, were satisfactory compared with other experiences regarding patients treated with non-invasive respiratory support in ICU. The strategical allocation of our RICU, between ED and ICU, might have positively influenced clinical outcomes of our patients.


2020 ◽  
Author(s):  
Gustavo Fernandez Romero ◽  
Eduardo Dominguez-Castillo ◽  
Matthew Zheng ◽  
Ibraheem Yousef ◽  
Melinda Darnell ◽  
...  

Abstract Background: Determine the impact of tobacco smoking status on patients hospitalized with COVID-19 pneumonia in the need for ICU care, mechanical ventilation and mortality. Methods: We performed a retrospective cohort study, that involved chart review. All adults 18 years or older with a diagnosis of COVID-19 pneumonia hospitalized from March 15th, 2020 to May 06th, 2020 with a positive reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab for COVID-19. We used chi-squared test for categorical variables and student t-tests or Wilcoxon rank sum tests for continuous variables. We further used adjusted and unadjusted logistic regression to assess risk factors for mortality and intubation.Results: Among 577 patients hospitalized with COVID-19 pneumonia, 268 (46.4%) had a history of smoking including 187 former and 81 active smokers. The former smokers when compared with non-smokers were predominantly older with more comorbidities. Also, when compared with never smokers D Dimer levels were elevated in active (p=0.05) and former smokers (p<0.01). The former smokers versus non-smokers required increased need for advanced non-invasive respiratory support on admission (p<0.05), ICU care (p<0.05) and had higher mortality [1.99 (CI 95% 1.03-3.85, p<0.05)]. Active smokers versus non-smokers received more mechanical ventilation [OR 2.11 (CI 95% 1.06-4.19, p<0.05)].Conclusions: In our cohort of hospitalized patients with COVID-19 pneumonia, former smokers had higher need for non-invasive respiratory support on admission, ICU care, and mortality compared to non-smokers. Also, active smokers versus non-smokers needed more mechanical ventilation.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Seyhan Pala Cifci ◽  
Yasemin Urcan Tapan ◽  
Bengu Turemis Erkul ◽  
Yusuf Savran ◽  
Bilgin Comert

Objective. Oxygen therapy is one of the most common treatment modalities for hypoxemic patients, but target goals for normoxemia are not clearly defined. Therefore, iatrogenic hyperoxia is a very common situation. The results from the recent clinical researches about hyperoxia indicate that hyperoxia can be related to worse outcomes than expected in some critically ill patients. According to our literature knowledge, there are not any reports researching the effect of hyperoxia on clinical course of patients who are not treated with invasive mechanical ventilation. In this study, we aimed to determine the effect of hyperoxia on mortality, and length of stay and also possible side effects of hyperoxia on the patients who are treated with oxygen by noninvasive devices. Materials and Methods. One hundred and eighty-seven patients who met inclusion criteria, treated in Dokuz Eylul University Medical Intensive Care Unit between January 1, 2016, and October 31, 2018, were examined retrospectively. These patients’ demographic data, oxygen saturation (SpO2) values for the first 24 hours, APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, whether they needed intubation, if they did how many days they got ventilated, length of stay in intensive care unit and hospital, maximum PaO2 values of the first day, oxygen treatment method of the first 24 hours, and the rates of mortality were recorded. Results. Hyperoxemia was determined in 62 of 187 patients who were not treated with invasive mechanic ventilation in the first 24 hours of admission. Upon further investigation of the relation between comorbid situations and hyperoxia, hyperoxia frequency in patients with COPD was detected to be statistically low (16% vs. 35%, p<0.008). Hospital mortality was significantly high (51.6% vs. 35.2%, p<0.04) in patients with hyperoxia. When the types of oxygen support therapies were investigated, hyperoxia frequency was found higher in patients treated with supplemental oxygen (nasal cannula, oronasal mask, high flow oxygen therapy) than patients treated with NIMV (44.2% vs. 25.5%, p<0.008). After exclusion of 56 patients who were intubated and treated with invasive mechanical ventilation after the first 24 hours, hyperoxemia was determined in 46 of 131 patients. Mortality in patients with hyperoxemia who were not treated with invasive mechanical ventilation during hospital stay was statistically higher when compared to normoxemic patients (41.3% vs 15.3%, p<0.001). Conclusion. We report that hyperoxemia increases the hospital mortality in patients treated with noninvasive respiratory support. At the same time, we determined that hyperoxemia frequency was lower in COPD patients and the ones treated with NIMV. Conservative oxygen therapy strategy can be suggested to decrease the hyperoxia prevalence and mortality rates.


2020 ◽  
pp. 204887262091994
Author(s):  
Thomas Metkus ◽  
P Elliott Miller ◽  
Carlos L Alviar ◽  
Jacob C Jentzer ◽  
Sean van Diepen ◽  
...  

Background The incidences of invasive mechanical ventilation and non-invasive ventilation among patients with non-ST segment elevation myocardial infarction and associated prognosis are not well characterized. Methods We conducted a retrospective cohort study of patients with admission diagnosis of non-ST segment elevation myocardial infarction using the US National Inpatient Sample database between 2002–2014. The exposure variable was invasive mechanical ventilation or non-invasive ventilation within 24 h of admission, compared to no respiratory support. The primary outcome was in-hospital mortality. We determined the association between respiratory support and mortality using Cox proportional hazard models. Results A total of 4,152,421 non-ST segment elevation myocardial infarction hospitalizations were identified, among whom 1.3% required non-invasive ventilation and 1.9% required invasive mechanical ventilation. Non-invasive ventilation use increased over time (0.4% in 2002 to 2.4% in 2014, p<0.001) while there was no definite trend in invasive mechanical ventilation use. Revascularization was lower for non-ST segment elevation myocardial infarction hospitalizations including invasive mechanical ventilation (23.9%) and non-invasive ventilation (14.5%) compared to 36.5% of those without respiratory support ( p<0.001). In-hospital mortality was 3.1% for non-ST segment elevation myocardial infarction without respiratory support compared to 9.2% with non-invasive ventilation (adjusted hazard ratio 1.86, 95% confidence interval 1.74–1.98) and 37.2% with invasive mechanical ventilation (adjusted hazard ratio 3.03, 95% confidence interval 2.88–3.19). Mortality for non-ST segment elevation myocardial infarction-non-invasive ventilation is improving over time while mortality for non-ST segment elevation myocardial infarction-invasive mechanical ventilation is increasing over time. Conclusion Mechanical respiratory support in non-ST segment elevation myocardial infarction is used in an important minority of cases, is increasing and is independently associated with mortality. Studies of the optimal management of acute coronary syndrome complicated by respiratory failure are needed to improve outcomes.


Author(s):  
Audrey F Pennington ◽  
Lyudmyla Kompaniyets ◽  
April D Summers ◽  
Melissa L Danielson ◽  
Alyson B Goodman ◽  
...  

Abstract Background Older adults and people from certain racial and ethnic groups are disproportionately represented in COVID-19 hospitalizations and deaths. Methods Using data from the Premier Healthcare Database on 181,813 hospitalized adults diagnosed with COVID-19 during March–September 2020 we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death); and determine whether the impact of age on clinical severity differs by race/ethnicity. Results Overall, 84,497 (47%) patients were admitted to the ICU, 29,078 (16%) received IMV, and 27,864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio [95% CI]: 0.96 [0.92, 0.99]), and higher among Hispanic/Latino patients (RR [95% CI]: 1.15 [1.09, 1.20]), non-Hispanic Asian patients (RR [95% CI]: 1.16 [1.09, 1.23]), and patients of other racial and ethnic groups (RR [95% CI]: 1.13 [1.06, 1.21]). Risk of ICU admission and IMV was elevated among some racial and ethnic groups. Conclusions These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce SARS-CoV-2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.


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