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1.
Multidiscip Respir Med ; 16(1): 759, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-1810595

ABSTRACT

BACKGROUND: In COVID-19, higher than expected level of intrapulmonary shunt has been described, in association with a discrepancy between the initial relatively preserved lung mechanics and the hypoxia severity. This study aim was to measure the shunt fraction and variations of PaO2/FiO2 ratio and oxygen alveolar-arterial gradient (A-a O2) at different FiO2. METHODS: Shunt was measured by a non-invasive system during spontaneous breathing in 12 patients hospitalized at COVID-19 Semi-Intensive Care Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, between October 22 and November 23, 2020. RESULTS: Nine patients were men, mean age (±SD) 62±15 years, mean BMI 27.5±4.8 Kg/m2. Systemic hypertension, diabetes type 2 and previous myocardial infarction were referred in 33%, 17%, and 7%, respectively. Mean PaO2/FiO2 ratio was 234±66 and 11 patients presented a bilateral chest X-ray involvement. Mean shunt was 21±6%. Mainly in patients with a more severe respiratory failure, we found a progressive decrease of PaO2/FiO2 ratio with higher FiO2. Considering (A-a O2), we found a uniform tendency to increase with FiO2 increasing. Even in this case, the more severe were the patients, the higher was the slope, suggesting FiO2 insensitiveness due to a shunt effect, as strengthened by our measurements. CONCLUSION: Relying on a single evaluation of PaO2/FiO2 ratio, especially at high FiO2, could be misleading in COVID-19. We propose a two steps evaluation, the first at low SpO2 value (e.g., 92-94%) and the second one at high FiO2 (i.e., >0.7), allowing to characterize both the amendable (ventilation/perfusion mismatch), and the fixed (shunt) contribution quote of respiratory impairment, respectively.

2.
Med Clin (Engl Ed) ; 156(2): 55-60, 2021 Jan 22.
Article in English | MEDLINE | ID: covidwho-1804805

ABSTRACT

INTRODUCTION: The use of devices that provide continuous positive pressure in the airway has shown improvement in various pathologies that cause respiratory failure. In the COVID 19 pandemic episode the use of these devices has become widespread, but, due to the shortage of conventional CPAP devices, alternative devices have been manufactured. The objective of this study is to describe the use of these devices, as well as their efficacy. MATERIAL AND METHODS: Data are collected from patients admitted for Pneumonia due to COVID 19 at the IFEMA Field Hospital. Data are collected from 23 patients with respiratory failure and need for ventilatory support. RESULTS: Study carried out on a total of 23 patients, dated admission to IFEMA. Alternative CPAP was used in five patients (21.7%), while ventilatory support with a reservoir mask or Ventimask Venturi effect was used in the remaining 18 patients (78.3%). A progressive increase in saturation is observed in those patients in whom alternative CPAP was used (from 94% on average to 98% and 99% on average after 30 and 60 min with the mask, respectively), although this change was not significant (p = 0.058 and p = 0.122 respectively). No significant change in RF was observed at the beginning and end of the measurement in patients who used alternative CPAP (p = 0.423), but among those who did not use alternative CPAP (p = 0.001). A statistically significant improvement in the variable oxygen saturation / fraction inspired by oxygen is observed in patients who used alternative CPAP (p = 0.040). CONCLUSION: The use of these devices has helped the ventilatory work of several patients by improving their oxygenation parameters. To better observe the evolution of patients undergoing this therapy and compare them with patients with other types of ventilatory support, further studies are necessary.


INTRODUCCIÓN: El uso de dispositivos que aportan presión positiva continua en la vía aérea ha demostrado mejoría en diversas patologías que producen insuficiencia respiratoria. En el episodio de pandemia por COVID 19 el uso de estos dispositivos se ha generalizado, pero, debido a la escasez de dispositivos convencionales de CPAP, se han fabricado dispositivos alternativos. El objetivo de este estudio es describir el uso de estos dispositivos, así como su eficacia. MATERIAL Y MÉTODOS: Se recogen datos de pacientes ingresados por Neumonía por COVID 19 en el Hospital de campaña de IFEMA. Se recogen datos de pacientes con insuficiencia respiratoria y necesidad de soporte ventilatorio. RESULTADOS: Estudio realizado sobre un total de 23 pacientes, con fecha ingreso en IFEMA. Se empleó CPAP alternativa en cinco pacientes (21,7%), mientras que en los 18 pacientes restantes (78,3%) se usó soporte ventilatorio con mascarilla reservorio o Ventimask efecto Venturi. Se observa un aumento progresivo de la saturación en aquellos pacientes en los que se empleó CPAP alternativa (de 94% de promedio a 98% y 99% de promedio tras 30 y 60 minutos con la máscara, respectivamente), aunque este cambio no resultó significativo (p = 0,058 y p = 0,122 respectivamente). No se observó un cambio significativo de frecuencia respiratoria al inicio y final de la medición en pacientes que usaron CPAP alternativa (p = 0,423) pero si entre los que no la usaron (p = 0,001). Se observa una mejoría estadísticamente significativa en la variable Saturación de oxigeno / Fracción inspirado de oxígeno en los pacientes que usaron CPAP alternativa (p = 0,040). CONCLUSIÓN: El uso de estos dispositivos ha ayudado al trabajo ventilatorio de varios pacientes mejorando sus parámetros de oxigenación. Para observar mejor la evolución de los pacientes sometidos a esta terapia y compararlos con pacientes con otro tipo de soporte ventilatorio, son necesarios más estudios en los que se aleatorice su uso.

3.
Crit Care Explor ; 2(6): e0145, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795095

ABSTRACT

OBJECTIVE: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. DATA SOURCES: Retrospective chart review. STUDY SELECTION/DATA EXTRACTION: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2o and target plateau pressure 29 cm H2o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). DATA SYNTHESIS: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%-18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4-30 d). Following 48 hours of methylprednisolone, the A-a o2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). CONCLUSIONS: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.

4.
Crit Care Explor ; 2(9): e0207, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795073

ABSTRACT

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

5.
Crit Care Explor ; 2(10): e0266, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1795045

ABSTRACT

OBJECTIVES: There is accumulating evidence of a distinct coagulopathy in severe acute respiratory syndrome coronavirus 2 infection which is associated with poor prognosis in coronavirus disease 2019. Coagulation abnormalities in blood samples resemble systemic coagulopathies in other severe infections but demonstrate specific features such as a very high d-dimer. These clinical observations are consistent with histopathologic findings of locally disturbed pulmonary microvascular thrombosis and angiopathy in end-stage coronavirus disease 2019. However, exact underlying processes and the sequence of events are not fully understood. DATA SOURCES: CT perfusion may provide insight in the dynamic aspect of the vascularity in pulmonary lesions in coronavirus disease 2019 infection as, in contrast to dual energy CT, a multiphase perfusion pattern is displayed. STUDY SELECTION: In six patients with coronavirus disease 2019 pneumonia, findings on additional CT perfusion series were correlated with known histopathologic vascular patterns upon pulmonary autopsy of patients who had died of coronavirus disease 2019. DATA EXTRACTION: In this case series, we were able to show perfusion changes on CT scans in typical pulmonary lesions illustrating diverse patterns. DATA SYNTHESIS: We demonstrated hyperperfusion in areas with ground glass and a severely decreased perfusion pattern in more consolidated areas often seen later in the course of disease. A combination was also observed, illustrating temporal heterogeneity. CONCLUSIONS: These findings provide new insights into the pathophysiology of coronavirus disease 2019 pneumonia and further understanding of the mechanisms that lead to respiratory failure in these patients.

6.
Pediatr Emerg Care ; 38(1): e398-e403, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1767003

ABSTRACT

OBJECTIVES: Respiratory syncytial virus (RSV) in pediatric patients has been associated with low risk of concomitant bacterial infection. However, in children with severe disease, it occurs in 22% to 50% of patients. As viral testing becomes routine, bacterial codetections are increasingly identified in patients with non-RSV viruses. We hypothesized, among patients intubated for respiratory failure secondary to suspected infection, there are similar rates of codetection between RSV and non-RSV viral detections. METHODS: This retrospective chart review, conducted over a 5-year period, included all patients younger than 2 years who required intubation secondary to respiratory failure from an infectious etiology in a single pediatric emergency department. Patients intubated for noninfectious causes were excluded. RESULTS: We reviewed 274 patients, of which 181 had positive viral testing. Of these, 48% were RSV-positive and 52% were positive for viruses other than RSV. Codetection of bacteria was found in 76% (n = 65; 95% confidence interval [CI], 66%, 84%) of RSV-positive patients and 66% (n = 63, 95% CI: 57%, 76%) of patients positive with non-RSV viruses. Among patients with negative viral testing, 33% had bacterial growth on lower respiratory culture. Male sex was the only patient-related factor associated with increased odds of codetection (odds ratio [OR], 2.2; 95% CI, 1.08-4.38). The odds of codetection between RSV-positive patients and non-RSV viruses were not significantly different (OR, 1.3; 95% CI, 0.62-2.71). CONCLUSIONS: Bacterial codetection is common and not associated with anticipated patient-related factors or with a specific virus. These results suggest consideration of empiric antibiotics in infants with respiratory illness requiring intubation.


Subject(s)
Bacterial Infections , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Bacteria , Child , Humans , Infant , Male , Respiratory Syncytial Virus Infections/complications , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Retrospective Studies
7.
Disaster Med Public Health Prep ; 15(5): e33-e42, 2021 10.
Article in English | MEDLINE | ID: covidwho-1632365

ABSTRACT

OBJECTIVES: An unprecedented wave of patients with acute respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) hit emergency departments (EDs) in Lombardy, starting in the second half of February 2020. This study describes the direct and indirect impacts of the SARS-CoV-2 outbreak on an urban major-hospital ED. METHODS: Data regarding all patients diagnosed with COVID-19 presenting from February 1 to March 31, 2020, were prospectively collected, while data regarding non-COVID patients presenting within the same period in 2019 were retrospectively retrieved. RESULTS: ED attendance dropped by 37% in 2020. Two-thirds of this reduction occurred early after the identification of the first autochthonous COVID-19 case in Lombardy, before lockdown measures were enforced. Hospital admissions of non-COVID patients fell by 26%. During the peak of COVID-19 attendance, the ED faced an extraordinary increase in: patients needing oxygen (+239%) or noninvasive ventilation (+725%), transfers to the intensive care unit (+57%), and in-hospital mortality (+309%), compared with the same period in 2019. CONCLUSIONS: The COVID-19 outbreak determined an unprecedented upsurge in respiratory failure cases and mortality. Fear of contagion triggered a spontaneous, marked reduction of ED attendance, and, presumably, some as yet unknown quantity of missed or delayed diagnoses for conditions other than COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Communicable Disease Control , Emergency Service, Hospital , Fear , Humans , Retrospective Studies
8.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
9.
Front Immunol ; 12: 631233, 2021.
Article in English | MEDLINE | ID: covidwho-1575223

ABSTRACT

Coronavirus disease-19 caused by the novel RNA betacoronavirus SARS-CoV2 has first emerged in Wuhan, China in December 2019, and since then developed into a worldwide pandemic with >99 million people afflicted and >2.1 million fatal outcomes as of 24th January 2021. SARS-CoV2 targets the lower respiratory tract system leading to pneumonia with fever, cough, and dyspnea. Most patients develop only mild symptoms. However, a certain percentage develop severe symptoms with dyspnea, hypoxia, and lung involvement which can further progress to a critical stage where respiratory support due to respiratory failure is required. Most of the COVID-19 symptoms are related to hyperinflammation as seen in cytokine release syndrome and it is believed that fatalities are due to a COVID-19 related cytokine storm. Treatments with anti-inflammatory or anti-viral drugs are still in clinical trials or could not reduce mortality. This makes it necessary to develop novel anti-inflammatory therapies. Recently, the therapeutic potential of phytocannabinoids, the unique active compounds of the cannabis plant, has been discovered in the area of immunology. Phytocannabinoids are a group of terpenophenolic compounds which biological functions are conveyed by their interactions with the endocannabinoid system in humans. Here, we explore the anti-inflammatory function of cannabinoids in relation to inflammatory events that happen during severe COVID-19 disease, and how cannabinoids might help to prevent the progression from mild to severe disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Cannabinoids/therapeutic use , Cannabis/immunology , Cytokine Release Syndrome/therapy , Phytotherapy , SARS-CoV-2/physiology , Endocannabinoids/metabolism , Humans , Pandemics
10.
J Med Internet Res ; 23(2): e24246, 2021 02 10.
Article in English | MEDLINE | ID: covidwho-1573886

ABSTRACT

BACKGROUND: Predicting early respiratory failure due to COVID-19 can help triage patients to higher levels of care, allocate scarce resources, and reduce morbidity and mortality by appropriately monitoring and treating the patients at greatest risk for deterioration. Given the complexity of COVID-19, machine learning approaches may support clinical decision making for patients with this disease. OBJECTIVE: Our objective is to derive a machine learning model that predicts respiratory failure within 48 hours of admission based on data from the emergency department. METHODS: Data were collected from patients with COVID-19 who were admitted to Northwell Health acute care hospitals and were discharged, died, or spent a minimum of 48 hours in the hospital between March 1 and May 11, 2020. Of 11,525 patients, 933 (8.1%) were placed on invasive mechanical ventilation within 48 hours of admission. Variables used by the models included clinical and laboratory data commonly collected in the emergency department. We trained and validated three predictive models (two based on XGBoost and one that used logistic regression) using cross-hospital validation. We compared model performance among all three models as well as an established early warning score (Modified Early Warning Score) using receiver operating characteristic curves, precision-recall curves, and other metrics. RESULTS: The XGBoost model had the highest mean accuracy (0.919; area under the curve=0.77), outperforming the other two models as well as the Modified Early Warning Score. Important predictor variables included the type of oxygen delivery used in the emergency department, patient age, Emergency Severity Index level, respiratory rate, serum lactate, and demographic characteristics. CONCLUSIONS: The XGBoost model had high predictive accuracy, outperforming other early warning scores. The clinical plausibility and predictive ability of XGBoost suggest that the model could be used to predict 48-hour respiratory failure in admitted patients with COVID-19.


Subject(s)
COVID-19/physiopathology , Hospitalization , Intubation, Intratracheal/statistics & numerical data , Machine Learning , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/epidemiology , Aged , COVID-19/complications , Clinical Decision Rules , Early Warning Score , Emergency Service, Hospital , Female , Hospitals , Humans , Logistic Models , Male , Middle Aged , Patient Admission , ROC Curve , Respiratory Insufficiency/etiology , Retrospective Studies , SARS-CoV-2 , Triage
11.
Clin Infect Dis ; 73(11): e4039-e4046, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561704

ABSTRACT

BACKGROUND: Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K-dependent MGP (desphospho-uncarboxylated [dp-uc] MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography. RESULTS: dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores. CONCLUSIONS: dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.


Subject(s)
COVID-19 , Biomarkers , Humans , Risk Factors , SARS-CoV-2 , Vitamin K 1/analogs & derivatives
12.
Can J Anaesth ; 67(9): 1217-1248, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1536371

ABSTRACT

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.


RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l'Organisation mondiale de la santé pour guider l'utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d'aérosols, et de transmission associée d'éléments viraux (compte rendu 2). SOURCE: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d'études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d'insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d'études évaluant la dispersion de gouttelettes, la génération d'aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l'extraction des données et l'évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE. CONSTATATIONS PRINCIPALES: Aucune étude éligible n'incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l'intensification de l'oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d'insuffisance respiratoire. Les résultats n'ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l'unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d'aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l'effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n'aient rapporté aucune augmentation associée concernant la dispersion d'aérosols, l'une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d'aérosols élevée plus grandes. CONCLUSION: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l'escalade des traitements par rapport à l'oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d'insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.


Subject(s)
Coronavirus Infections/therapy , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Aerosols , COVID-19 , Cannula , Coronavirus Infections/complications , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Randomized Controlled Trials as Topic , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/virology
13.
Intern Med J ; 51(11): 1810-1815, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526370

ABSTRACT

BACKGROUND: COVID-19 long-term sequelae are ill-defined since only a few studies have explored the long-term consequences of this disease so far. AIMS: To evaluate the 6-month respiratory outcome and exercise capacity of COVID-19 acute respiratory failure (ARF) patients treated with continuous positive airway pressure (CPAP) during the first wave of the ongoing COVID-19 pandemic. METHODS: A retrospective observational study included COVID-19 patients with ARF. Interventions included CPAP during hospitalisation and 6-month follow up. Frailty assessment was carried out through frailty index (FI), pO2 /FiO2 during hospitalisation and at follow up, respiratory parameters, 6-min walking test (6MWT) and the modified British Medical Research Council (mMRC) and Borg scale at follow up. RESULTS: More than half of the patients had no dyspnoea according to the mMRC scale. Lower in-hospital pO2 /FiO2 correlated with higher Borg scale levels after 6MWT (ρ 0.27; P 0.04) at the follow-up visit. FI was positively correlated with length of hospitalisation (ρ 0.3; P 0.03) and negatively with the 6MWT distance walked (ρ -0.36; P 0.004). CONCLUSIONS: Robust and frail patients with COVID-19 ARF treated with CPAP outside the intensive care unit setting had good respiratory parameters and exercise capacity at 6-month follow up, although more severe patients had slightly poorer respiratory performance compared with patients with higher PaO2 /FiO2 and lower FI.


Subject(s)
COVID-19 , Respiratory Insufficiency , Continuous Positive Airway Pressure , Exercise Tolerance , Humans , Pandemics , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
15.
Crit Care Med ; 49(7): 1058-1067, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494030

ABSTRACT

OBJECTIVES: To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN: Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING: Critical care units at two large metropolitan hospitals in New York City. PATIENTS: Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS: Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS: Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS: In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.


Subject(s)
COVID-19/therapy , Respiration, Artificial , Tracheostomy/methods , Aged , Cohort Studies , Critical Care , Dilatation/methods , Female , Humans , Male , Middle Aged , New York City/epidemiology , SARS-CoV-2 , Time Factors
16.
Crit Care Med ; 49(10): e1001-e1014, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1475867

ABSTRACT

OBJECTIVES: Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019-related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes. DESIGN AND SETTING: We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020. SUBJECTS AND INTERVENTION: Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included. MEASUREMENTS AND MAIN RESULTS: Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25-54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14-25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3-6%). Respiratory rate decreased post prone positioning (mean difference, -3.2 breaths/min; 95% CI, -4.6 to -1.9). Intubation and mortality rates were 24% (95% CI, 17-32%) and 13% (95% CI, 6-19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them. CONCLUSIONS: Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Prone Position/physiology , COVID-19/mortality , Humans , Patient Positioning , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology
17.
Clin Respir J ; 14(3): 214-221, 2020 Mar.
Article in English | MEDLINE | ID: covidwho-1455532

ABSTRACT

BACKGROUND: Patients with neuromuscular disorders (NMDs) are likely to develop respiratory failure which requires noninvasive ventilation (NIV). Ventilation via a mouthpiece (MPV) is an option to offer daytime NIV. OBJECTIVES: To determine the preferred equipment for MPV by patients with NMDs. METHODS: Two MPV equipment sets were compared in 20 patients with NMDs. Set 1, consisted of a non-dedicated ventilator for MPV (PB560, Covidien) with a plastic angled mouthpiece. Set 2, consisted of a dedicated MPV ventilator (Trilogy 100, Philips Respironics) without backup rate and kiss trigger combined with a silicone straw mouthpiece. The Borg dyspnea score, ventilator free time, transcutaneous oxygen saturation (SpO2) and carbon dioxide tension (TcCO2 ) were recorded with and without MPV. Patient perception was assessed by a 17-items list. RESULTS: Carbon dioxide tension measurements and total perception score were not different between the two MPV sets. Dyspnea score was lower with the non-dedicated versus dedicated equipment, 1 (0.5) versus 3 (1-6), P < 0.01. All patients with a ventilator free time lower than 6 hours preferred a set backup rate rather than a kiss trigger. Sixty five percent of patients preferred the commercial arm support and 55% preferred the plastic angled mouthpiece. CONCLUSIONS: Dedicated and non-dedicated MPV equipment are deemed effective and comfortable. Individualization of arm support and mouthpiece is advised to ensure success of MPV. A ventilator free time lower than 6 hours seems to be a useful indicator to a priori set a backup rate rather than a rate at zero associated to the kiss trigger.


Subject(s)
Neuromuscular Diseases/complications , Noninvasive Ventilation/instrumentation , Respiratory Insufficiency/therapy , Ventilators, Mechanical/statistics & numerical data , Adolescent , Adult , Blood Gas Monitoring, Transcutaneous/methods , Carbon Dioxide/metabolism , Case-Control Studies , Cross-Over Studies , Dyspnea/diagnosis , Equipment Design , Female , Humans , Male , Perception , Time Factors , Ventilators, Mechanical/trends , Young Adult
18.
Am J Emerg Med ; 38(7): 1488-1493, 2020 07.
Article in English | MEDLINE | ID: covidwho-1450042

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Drug Therapy, Combination , Emergency Service, Hospital , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/antagonists & inhibitors , Pandemics , Pyrazines/therapeutic use , Randomized Controlled Trials as Topic , SARS-CoV-2
19.
Lancet Respir Med ; 9(8): 933-936, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413072

ABSTRACT

The 2012 Berlin definition of acute respiratory distress syndrome (ARDS) provided validated support for three levels of initial arterial hypoxaemia that correlated with mortality in patients receiving ventilatory support. Since 2015, high-flow nasal oxygen (HFNO) has become widely used as an effective therapeutic support for acute respiratory failure, most recently in patients with severe COVID-19. We propose that the Berlin definition of ARDS be broadened to include patients treated with HFNO of at least 30 L/min who fulfil the other criteria for the Berlin definition of ARDS. An expanded definition would make the diagnosis of ARDS more widely applicable, allowing patients at an earlier stage of the syndrome to be recognised, independent of the need for endotracheal intubation or positive-pressure ventilation, with benefits for the testing of early interventions and the study of factors associated with the course of ARDS. We identify key questions that could be addressed in refining an expanded definition of ARDS, the implementation of which could lead to improvements in clinical practice and clinical outcomes for patients.


Subject(s)
COVID-19 , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Early Diagnosis , Humans , Patient Selection , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Time-to-Treatment/standards
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