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1.
Curr Opin Crit Care ; 28(6): 660-666, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2152245

ABSTRACT

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , Humans , COVID-19/therapy , Respiratory Insufficiency/therapy , Oxygen Inhalation Therapy , Hypoxia/therapy , Oxygen , Critical Care , Lung , Randomized Controlled Trials as Topic
2.
Am J Physiol Lung Cell Mol Physiol ; 323(3): L240-L250, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2138198

ABSTRACT

The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory epithelial cells, including epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator, and some transporters. These ion channels/transporters maintain the capacity of liquid layer on the surface of respiratory epithelial cells and provide an immune barrier for the respiratory system to clear off foreign pathogens. However, in some harmful external environments and/or pathological conditions, the respiratory epithelium is prone to hypoxia, which would destroy the ion transport function of the epithelium and unbalance the homeostasis of internal environment, triggering a series of pathological reactions. Many respiratory diseases associated with hypoxia manifest an increased expression of hypoxia-inducible factor-1, which mediates the integrity of the epithelial barrier and affects epithelial ion transport function. It is important to study the relationship between hypoxia and ion transport function, whereas the mechanism of hypoxia-induced ion transport dysfunction in respiratory diseases is not clear. This review focuses on the relationship between hypoxia and respiratory diseases, as well as dysfunction of ion transport and tight junctions in respiratory epithelial cells under hypoxia.


Subject(s)
Respiration Disorders , Sodium-Potassium-Exchanging ATPase , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Epithelial Sodium Channels/metabolism , Humans , Hypoxia/metabolism , Ion Transport , Respiration Disorders/metabolism , Respiratory Mucosa/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism
3.
J Neuropathol Exp Neurol ; 81(12): 988-995, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2135402

ABSTRACT

The brain of a 58-year-old woman was included as a civilian control in an ongoing autopsy study of military traumatic brain injury (TBI). The woman died due to a polysubstance drug overdose, with Coronavirus Disease 2019 (COVID-19) serving as a contributing factor. Immunohistochemical stains for ß-amyloid (Aß), routinely performed for the TBI study, revealed numerous, unusual neocortical Aß deposits. We investigated the autopsied brains of 10 additional young patients (<60 years old) who died of COVID-19, and found similar Aß deposits in all, using two different Aß antibodies across three different medical centers. The deposits failed to stain with Thioflavin-S. To investigate whether or not these deposits formed uniquely to COVID-19, we applied Aß immunostains to the autopsied brains of COVID-19-negative adults who died with acute respiratory distress syndrome and infants with severe cardiac anomalies, and also biopsy samples from patients with subacute cerebral infarcts. Cortical Aß deposits were also found in these cases, suggesting a link to hypoxia. The fate of these deposits and their effects on function are unknown, but it is possible that they contribute to the neurocognitive sequelae observed in some COVID-19 patients. Our findings may also have broader implications concerning hypoxia and its role in Aß deposition in the brain.


Subject(s)
Alzheimer Disease , Brain Injuries, Traumatic , COVID-19 , Neocortex , Humans , Adult , Female , Middle Aged , Neocortex/pathology , COVID-19/complications , Amyloid beta-Peptides/metabolism , Brain/pathology , Brain Injuries, Traumatic/pathology , Hypoxia/pathology , Alzheimer Disease/pathology
5.
Tokai J Exp Clin Med ; 47(4): 162-164, 2022 Dec 20.
Article in English | MEDLINE | ID: covidwho-2125176

ABSTRACT

We present the autopsy procedure and findings of severe coronavirus disease 2019 (COVID-19) pneumonia in an 85-year-old man. The patient required intubation immediately after admission for severe COVID-19 pneumonia. He had severe hypoxia that did not improve despite treatment with remdesivir, corticosteroids, and appropriate mechanical ventilation. On day 13, the patient developed sudden hypercapnia. His renal dysfunction subsequently worsened and became associated with hyperkalemia, and he passed away on day 15. An autopsy was performed to clarify the cause of the hypercapnic hypoxia. None of the medical personnel involved in the autopsy developed symptoms of COVID-19. Histologic examination showed various stages of diffuse alveolar damage throughout the lungs, with intra-alveolar hemorrhage in the upper zones. Microscopic examination of the kidneys revealed acute tubular necrosis. There was no significant systemic thrombosis. The autopsy findings were consistent with those typical of COVID-19.


Subject(s)
COVID-19 , Lung Diseases , Pneumonia , Male , Humans , Aged, 80 and over , Autopsy , Hospitals, Municipal , Lung Diseases/pathology , Hypoxia/complications
6.
Proc Natl Acad Sci U S A ; 119(46): e2120221119, 2022 11 16.
Article in English | MEDLINE | ID: covidwho-2106733

ABSTRACT

The COVID-19 pandemic has created a large population of patients who are slow to recover consciousness following mechanical ventilation and sedation in the intensive care unit. Few clinical scenarios are comparable. Possible exceptions are the rare patients in post-cardiac arrest coma with minimal to no structural brain injuries who recovered cognitive and motor functions after prolonged delays. A common electroencephalogram (EEG) signature seen in these patients is burst suppression [8]. Biophysical modeling has shown that burst suppression is likely a signature of a neurometabolic state that preserves basic cellular function "during states of lowered energy availability." These states likely act as a brain protective mechanism [9]. Similar EEG patterns are observed in the anoxia resistant painted turtle [24]. We present a conceptual analysis to interpret the brain state of COVID-19 patients suffering prolonged recovery of consciousness. We begin with the Ching model and integrate findings from other clinical scenarios and studies of the anoxia-tolerant physiology of the painted turtle. We postulate that prolonged recovery of consciousness in COVID-19 patients could reflect the effects of modest hypoxic injury to neurons and the unmasking of latent neuroprotective mechanisms in the human brain. This putative protective down-regulated state appears similar to that observed in the painted turtle and suggests new approaches to enhancing coma recovery [12].


Subject(s)
COVID-19 , Coma , Humans , Pandemics , Electroencephalography , Brain , Hypoxia
7.
Curr Drug Targets ; 23(13): 1277-1287, 2022.
Article in English | MEDLINE | ID: covidwho-2098966

ABSTRACT

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation of the renin-angiotensin system (RAS) may increase sympathetic discharge with dysautonomia development. Direct SARS-CoV-2 cytopathic effects and associated inflammatory reaction may lead to neuroinflammation, affecting different parts of the central nervous system (CNS), including the autonomic center in the hypothalamus, causing dysautonomia. High circulating AngII, hypoxia, oxidative stress, high pro-inflammatory cytokines, and emotional stress can also provoke autonomic deregulation and high sympathetic outflow with the development of the sympathetic storm. During SARS-CoV-2 infection with neuro-invasion, GABA-ergic neurons and nicotinic acetylcholine receptor (nAChR) are inhibited in the hypothalamic pre-sympathetic neurons leading to sympathetic storm and dysautonomia. Different therapeutic modalities are applied to treat SARS-CoV-2 infection, like antiviral and anti-inflammatory drugs. Ivermectin (IVM) is a robust repurposed drug widely used to prevent and manage mild-moderate Covid-19. IVM activates both GABA-ergic neurons and nAChRs to mitigate SARS-CoV-2 infection- induced dysautonomia. Therefore, in this brief report, we try to identify the potential role of IVM in managing Covid-19-induced dysautonomia.


Subject(s)
COVID-19 , Primary Dysautonomias , Humans , Animals , Bees , SARS-CoV-2 , Ivermectin , Hypoxia , gamma-Aminobutyric Acid
8.
PLoS One ; 17(11): e0276738, 2022.
Article in English | MEDLINE | ID: covidwho-2098753

ABSTRACT

Presently, coronavirus disease-19 (COVID-19) is spreading worldwide without an effective treatment method. For COVID-19, which is often asymptomatic, it is essential to adopt a method that does not cause aggravation, as well as a method to prevent infection. Whether aggravation can be predicted by analyzing the extent of lung damage on chest computed tomography (CT) scans was examined. The extent of lung damage on pre-intubation chest CT scans of 277 patients with COVID-19 was assessed. It was observed that aggravation occurred when the CT scan showed extensive damage associated with ground-glass opacification and/or consolidation (p < 0.0001). The extent of lung damage was similar across the upper, middle, and lower fields. Furthermore, upon comparing the extent of lung damage based on the number of days after onset, a significant difference was found between the severe pneumonia group (SPG) with intubation or those who died and non-severe pneumonia group (NSPG) ≥3 days after onset, with aggravation observed when ≥14.5% of the lungs exhibited damage at 3-5 days (sensitivity: 88.2%, specificity: 72.4%) and when ≥20.1% of the lungs exhibited damage at 6-8 days (sensitivity: 88.2%, specificity: 69.4%). Patients with aggravation suddenly developed hypoxemia after 7 days from the onset; however, chest CT scans obtained in the paucisymptomatic phase without hypoxemia indicated that subsequent aggravation could be predicted based on the degree of lung damage. Furthermore, in subjects aged ≥65 years, a significant difference between the SPG and NSPG was observed in the extent of lung damage early beginning from 3 days after onset, and it was found that the degree of lung damage could serve as a predictor of aggravation. Therefore, to predict and improve prognosis through rapid and appropriate management, evaluating patients with factors indicating poor prognosis using chest CT is essential.


Subject(s)
COVID-19 , Humans , COVID-19/diagnostic imaging , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Lung/diagnostic imaging , Hypoxia , Retrospective Studies
9.
Am J Case Rep ; 23: e937147, 2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2090898

ABSTRACT

BACKGROUND Inhaled nitric oxide (iNO) is used as a treatment for pulmonary arterial hypertension (PAH). Severe hypoxia with hypoxic vasoconstriction caused by severe acute respiratory distress syndrome (ARDS) can induce pulmonary hypertension with hemodynamic implications, mainly secondary to right ventricle (RV) systolic function impairment. We report the case of the use of iNO in a critically ill patient with bilateral SARS-CoV-2 pneumonia and severe ARDS and hypoxemia leading to acute severe PAH, causing a ventilation/perfusion mismatch, RV pressure overload, and RV systolic dysfunction. CASE REPORT A 36-year-old woman was admitted to the Intensive Care Unit with a severe ARDS associated with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Severe hypoxia and hypoxic vasoconstriction developed, leading to an acute increase in pulmonary vascular resistance, severe to moderate tricuspid regurgitation, RV pressure overload, RV systolic function impairment, and RV dilatation. Following 24 h of treatment with iNO at 15 ppm, significant oxygenation and hemodynamic improvement were noted, allowing vasopressors to be stopped. After 24 h of iNO treatment, echocardiography showed very mild tricuspid regurgitation, a non-dilated RV, no impairment of transverse free wall contractility, and no paradoxical septal motion. iNO was maintained for 7 days. The dose of iNO was progressively decreased with no adverse effects and maintaining an improvement of oxygenation and hemodynamic status, allowing respiratory weaning. CONCLUSIONS Sustained acute hypoxia in ARDS secondary to SARS-CoV-2 pneumonia can lead to PAH, causing a ventilation/perfusion mismatch and RV systolic impairment. iNO can be considered in patients with significant PAH causing hypoxemia and RV dysfunction.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Respiratory Distress Syndrome , Tricuspid Valve Insufficiency , Female , Humans , Adult , Nitric Oxide/therapeutic use , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , COVID-19/complications , Administration, Inhalation , SARS-CoV-2 , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Hypoxia/etiology
10.
Intern Med ; 61(8): 1219-1223, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-2089579

ABSTRACT

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.


Subject(s)
COVID-19 , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hypoxia/drug therapy , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Male
11.
Crit Care ; 26(1): 328, 2022 10 25.
Article in English | MEDLINE | ID: covidwho-2089224

ABSTRACT

BACKGROUND: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored. OBJECTIVE: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution. METHODS: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated. RESULTS: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04). CONCLUSIONS: The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. TRIAL REGISTRATION: Clinical Trials ID: NCT04316884, Registered March 13, 2020.


Subject(s)
COVID-19 , Papillomavirus Infections , Humans , COVID-19/drug therapy , Tomography, X-Ray Computed/methods , Lung , Hypoxia , Oxygen , Steroids , Edema
12.
PLoS One ; 17(10): e0273402, 2022.
Article in English | MEDLINE | ID: covidwho-2079731

ABSTRACT

BACKGROUND: The pathophysiology of COVID-19 remains poorly understood. We aimed to estimate the contribution of intrapulmonary shunting and ventilation-to-perfusion (VA/Q) mismatch using a mathematical model to construct oxygen-haemoglobin dissociation curves (ODCs). METHODS: ODCs were constructed using transcutaneous pulse oximetry at two different fractions of inspired oxygen (FiO2). 199 patients were included from two large district general hospitals in the South East of England from 1st to 14th January 2021. The study was supported by the National Institute of Health Research (NIHR) Clinical Research Network. RESULTS: Overall mortality was 29%. Mean age was 68.2 years (SEM 1·2) with 46% female. Median shunt on admission was 17% (IQR 8-24.5); VA/Q was 0.61 (IQR 0.52-0.73). Shunt was 37.5% higher in deaths (median 22%, IQR 9-29) compared to survivors (16%, 8-21; p = 0.0088) and was a predictor of mortality (OR 1.04; 95% CI 1.01-1.07). Admission oxygen saturations were more strongly predictive of mortality (OR 0.91, 95% CI 0.87-0.96). There was no difference in VA/Q mismatch between deaths (0.60; IQR 0.50-0.73) and survivors (0.61; IQR 0.52-0.73; p = 0.63) and it was not predictive of mortality (OR 0.68; 95% CI 0.18-2.52; p = 0.55). Shunt negatively correlated with admission oxygen saturation (R -0.533; p<0.0001) whereas VA/Q was not (R 0.1137; p = 0.12). INTERPRETATION: Shunt, not VA/Q mismatch, was associated with worsening hypoxia, though calculating shunt was not of prognostic value. This study adds to our understanding of the pathophysiology of hypoxaemia in COVID-19. Our inexpensive and reliable technique may provide further insights into the pathophysiology of hypoxia in other respiratory diseases.


Subject(s)
COVID-19 , Lung Diseases , Humans , Female , Aged , Male , Ventilation-Perfusion Ratio/physiology , Hypoxia , Oximetry/methods , Oxygen/physiology
13.
Int J Environ Res Public Health ; 19(19)2022 Oct 06.
Article in English | MEDLINE | ID: covidwho-2066063

ABSTRACT

BACKGROUND: Severe COVID-19 is associated with hypoxemia and acute respiratory distress syndrome (ARDS), which may predispose multiorgan failure and death. Inhaled nitric oxide (iNO) is a clinical vasodilator used in the management of acute respiratory distress syndrome (ARDS). This study evaluated the response rate to iNO in patients with COVID-19-ARDS. METHOD: We searched Medline and Embase databases in May 2022, and data on the use of iNO in the treatment of ARDS in COVID-19 patients were synthesized from studies that satisfied predefined inclusion criteria. A systematic synthesis of data was performed followed by meta-analysis. We performed the funnel plot and leave-one-out sensitivity test on the included studies to assess publication bias and possible exaggerated effect size. We compared the effect size of the studies from the Unites States with those from other countries and performed meta-regression to assess the effect of age, year of publication, and concomitant vasodilator use on the effect size. RESULTS: A total of 17 studies (including 712 COVID-19 patients) were included in this systematic review of which 8 studies (involving 265 COVID-19 patients) were subjected to meta-analysis. The overall response rate was 66% (95% CI, 47-84%) with significantly high between-studies heterogeneity (I2 = 94%, p < 0.001). The funnel plot showed publication bias, although the sensitivity test using leave-one-out analysis showed that removing any of the study does not remove the significance of the result. The response rate was higher in the Unites States, and meta-regression showed that age, year of publication, and use of concomitant vasodilators did not influence the response rate to iNO. CONCLUSION: iNO therapy is valuable in the treatment of hypoxemia in COVID-19 patients and may improve systemic oxygenation in patients with COVID-19-ARDS. Future studies should investigate the mechanism of the activity of iNO in COVID-19 patients to provide insight into the unexplored potential of iNO in general ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Administration, Inhalation , COVID-19/drug therapy , Humans , Hypoxia/drug therapy , Nitric Oxide/therapeutic use , Respiratory Distress Syndrome/drug therapy , Vasodilator Agents/adverse effects , Vasodilator Agents/therapeutic use
14.
Rev. latinoam. enferm. (Online) ; 29: e3397, 2021. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-2054525

ABSTRACT

Objective: to describe scientific evidence regarding the use of prone positioning in the care provided to patients with acute respiratory failure caused by COVID-19. Method: this is a scoping review. PRISMA Extension for Scoping Reviews was used to support the writing of this study. The search was conducted in seven databases and resulted in 2,441 studies, 12 of which compose the sample. Descriptive statistics, such as relative and absolute frequencies, was used to analyze data. Results: prone positioning was mainly adopted in Intensive Care Units, lasted from a minimum of 12 up to 16 hours, and its prescription was based on specific criteria, such as PaO2/FiO2 ratio, oxygen saturation, and respiratory rate. The most prevalent complications were: accidental extubation, pressure ulcer, and facial edema. Decreased hypoxemia and mortality rates were the main outcomes reported. Conclusion: positive outcomes outweighed complications. Various cycles of prone positioning are needed, which may cause potential work overload for the health staff. Therefore, an appropriate number of trained workers is necessary, in addition to specific institutional protocols to ensure patient safety in this context.


Objetivo: descrever as evidências científicas acerca da utilização da posição prona na assistência ao paciente com insuficiência respiratória aguda provocada por COVID-19. Método: trata-se de uma scoping review. O instrumento PRISMA Extension for Scoping Reviews foi utilizado para a redação do estudo. As buscas foram realizadas em sete bases de dados, resultando em 2.441 estudos dos quais 12 compõem a amostra. Uma análise descritiva dos dados foi realizada empregando frequências relativas e absolutas. Resultados: a utilização da posição prona ocorreu principalmente em Unidades de Terapia Intensiva, com duração mínima de 12 a 16 horas, e teve como fundamentos de indicação critérios específicos, tais como a relação PaO2/FiO2, a saturação de oxigênio e a frequência respiratória. As complicações mais prevalentes da sua utilização foram: extubação acidental, lesão por pressão e edema facial. Identificou-se a redução da hipoxemia e da mortalidade como principais desfechos evidenciados na amostra. Conclusão: os desfechos positivos sobressaíram-se face às complicações. São necessários vários ciclos de pronação do paciente, fator causador de possível sobrecarga de trabalho da equipe de saúde. Portanto, são importantes um adequado dimensionamento dos profissionais, uma equipe treinada e protocolos institucionais específicos a fim de se garantir a segurança do paciente nesse contexto.


Objetivo: describir las evidencias científicas acerca de la utilización de la posición prona en la atención al paciente con insuficiencia respiratoria aguda provocada por COVID-19. Método: se trata de una revisión de escopo. El instrumento PRISMA Extension for Scoping Reviews fue utilizado para la redacción del estudio. Las búsquedas fueron realizadas en siete bases de datos, resultando en 2.441 estudios de los cuales 12 integran la muestra. Un análisis descriptivo de los datos fue desarrollado empleando frecuencias relativas y absolutas. Resultados: la utilización de la posición prona ocurrió principalmente en Unidades de Terapia Intensiva, con duración mínima de 12 a 16 horas, y tuvo como fundamentos de indicación criterios específicos, tales como la relación PaO2/FiO2, la saturación de oxígeno y la frecuencia respiratoria. Las complicaciones más frecuentes de su uso fueron: desintubación accidental, lesión por presión y edema facial. Se identificó la reducción de la hipoxemia y de la mortalidad como principales resultados evidenciados en la muestra. Conclusión: los resultados positivos se destacaran ante las complicaciones. Son necesarios varios ciclos de pronación del paciente, factor causante de una posible sobrecarga de trabajo del equipo de salud. Por lo tanto, son importantes un adecuado dimensionamiento de los profesionales, un equipo capacitado y protocolos institucionales específicos a fin de garantizar la seguridad del paciente en ese contexto.


Subject(s)
Patient Care Team , Respiratory Distress Syndrome , Respiratory Insufficiency , Respiratory Tract Infections , Prone Position , Coronavirus Infections , Pressure Ulcer , Edema , Alkalies , Equipment and Supplies , Airway Extubation , Critical Care Nursing , Intensive Care Units , Hypoxia
15.
JAMA Netw Open ; 5(10): e2234425, 2022 10 03.
Article in English | MEDLINE | ID: covidwho-2047378

ABSTRACT

Importance: Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data. Objective: To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models. Design, Setting, and Participants: This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022. Exposures: Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia). Main Outcomes and Measures: The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark. Results: A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47). Conclusions and Relevance: These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , Aged , COVID-19/drug therapy , Clinical Trials as Topic , Female , Humans , Hypoxia , Male , Methylprednisolone/therapeutic use , Middle Aged , Multicenter Studies as Topic , Retrospective Studies
16.
JAMA ; 328(11): 1063-1072, 2022 09 20.
Article in English | MEDLINE | ID: covidwho-2047353

ABSTRACT

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.


Subject(s)
COVID-19 , Noninvasive Ventilation , Oxygen Inhalation Therapy , Respiratory Insufficiency , Acute Disease , Barotrauma/etiology , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Female , Humans , Hypoxia/etiology , Hypoxia/mortality , Hypoxia/therapy , Male , Middle Aged , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/methods , Oxygen/administration & dosage , Oxygen/adverse effects , Oxygen Inhalation Therapy/adverse effects , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Respiratory Insufficiency/therapy
17.
Int J Environ Res Public Health ; 19(18)2022 Sep 19.
Article in English | MEDLINE | ID: covidwho-2043699

ABSTRACT

Since the very beginning of the COVID-19 pandemic, numerous researchers have made an effort to determine the molecular composition of the SARS-CoV-2 virus, and the exact pathomechanism through which the virus exerts such a devastating effect on the host/infected organism. Recent scientific evidence highlights the affinity of the virus towards ACE2 receptors, which are widespread in multiple human systems, including the central nervous system (CNS) and cerebral vessels. Such an affinity may explain endothelial dysfunction and damage that is observed in COVID-positive patients in histopathological studies, with subsequent dysregulation of the cerebral circulation leading to transient or acute cerebrovascular accidents. In this paper, we aimed to evaluate the effects of COVID-related hypoxemia and direct viral invasion on the cerebral circulation, with special respect to the postulated pathomechanism, vulnerable groups of patients, clinical course and outcomes, as well as diagnostic imaging findings.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Angiotensin-Converting Enzyme 2 , COVID-19/complications , Humans , Hypoxia , Pandemics , SARS-CoV-2
18.
PLoS One ; 17(9): e0274485, 2022.
Article in English | MEDLINE | ID: covidwho-2043206

ABSTRACT

BACKGROUND: COVID-19 is known to be associated to potentially fatal neurological complications; therefore, it is essential to understand the risk factors for its development and the impact they have on the outcome of COVID-19 patients. AIMS: To determine the risk factors for developing fatal neurological complications and their outcome in hospitalized COVID-19 patients. MATERIAL AND METHODS: Case control study based on hospitalized patients was conducted from July 15th 2021 to December 15th 2021. Cases and controls were COVID-19 confirmed patients with and without severe neurological manifestations. Age, comorbid conditions, vaccination status, Blood Sugar Random (BSR), D-dimers levels, anticoagulation type and dosage were taken as predictors (exposure variables) for developing neurological complications. In the case-only (subgroup) analysis, 28-day mortality were analyzed using the same predictors including admission hypoxemia. Chi square test and regression model were built to calculate OR with 95%CI. RESULTS: Among 383 patients (median age, 56 years [IQR, 24-110]; 49.9% men); 95 had neurological complications (cases) and 288 did not (controls). Development of neurological complications among COVID-19 related hospitalizations was significantly associated with old age >71 yrs. (cases, 23.2%; controls, 13.5%; OR, 3.31; 95% CI, 1.28-8.55), presence of diabetes mellitus (37.9% vs. 24%; OR, 1.9; 95% CI, 1.2-3.1), admission hyperglycemia (BSR 351-600 mg/dl), (29.5% vs. 7.6%; OR, 3.11; 95%CI, 1.54-6.33), raised D-dimer levels 5000-10,000 ng/ml (41% vs. 11.8%; OR, 5.2; 95% CI, 3.02-8.9), prophylactic dose anticoagulation (43.2% vs. 28.1%; OR, 1.9; 95%CI, 1.2-3.1), and unvaccinated status of COVID-19 patients (90.5% vs. 75.6%; OR, 3.01; 95% CI, 1.44-6.25). Neurological complications with COVID-19 were associated with increased likelihood of death or invasive mechanical ventilation by day 28 (86.3% vs. 45.1%; OR, 7.66; 95% CI, 4.08-14.4). In case-only analysis (median age, 56 years [IQR, 27,110]; 50.5% women), 67 (70.5%) had CVE, 21 (22.1%) had Encephalitis, and 7 (7.4%) had GBS as neurological manifestations. 28-day mortality among these patients was strongly associated with a lower likelihood of vaccination. (6.1% cases vs. 30.8% controls; OR, .146; 95%CI, .033- .64), being younger 17-45 yrs. (12.2% vs. 46.2%; OR, .162; 95%CI, .045-.58), having no comorbid condition (19.5% vs. 61.5%; OR, .151; 95%CI, .044- .525), having cerebrovascular events and GBS as type of neurological manifestation (76.8% vs.30.8%; OR, 7.46; 95%CI, 2.06-26.96), (2.4% vs. 38.4%; OR, .04; 95%CI, .007- 0.24) respectively, and presence of hypoxemia at admission (91.5% vs. 15.4%; OR, 58.92; 95%CI, 10.83-320.67). CONCLUSION: Old age, presence of Diabetes Mellitus, unvaccinated status of patients, high BSR at admission, high D-dimers, and prophylactic dose anticoagulation were identifies as increased risk factors for developing serious neurological complications among COVID-19 patients. Neurological problems in COVID-19 patients raised death risk 7.6-fold. The most common neurological complication was cerebrovascular events, followed by encephalitis and GBS. Unvaccinated status, cerebrovascular events, and admission hypoxemia are associated with an increased likelihood of 28-day mortality among these patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Encephalitis , Nervous System Diseases , Aged , Anticoagulants , Blood Glucose , COVID-19/complications , Case-Control Studies , Diabetes Mellitus/epidemiology , Female , Hospitalization , Humans , Hypoxia , Male , Middle Aged , Nervous System Diseases/epidemiology , Nervous System Diseases/etiology , Retrospective Studies , SARS-CoV-2
20.
PLoS One ; 17(9): e0274910, 2022.
Article in English | MEDLINE | ID: covidwho-2039433

ABSTRACT

It is well known that the presence of comorbidities and age-related health issues may hide biochemical and metabolic features triggered by SARS-CoV-2 infection and other diseases associated to hypoxia, as they are by themselves chronic inflammatory conditions that may potentially disturb metabolic homeostasis and thereby negatively impact on COVID-19 progression. To unveil the metabolic abnormalities inherent to hypoxemia caused by COVID-19, we here applied gas chromatography coupled to mass spectrometry to analyze the main metabolic changes exhibited by a population of male patients less than 50 years of age with mild/moderate and severe COVID-19 without pre-existing comorbidities known to predispose to life-threatening complications from this infection. Several differences in serum levels of particular metabolites between normal controls and patients with COVID-19 as well as between mild/moderate and severe COVID-19 were identified. These included increased glutamic acid and reduced glutamine, cystine, threonic acid, and proline levels. In particular, using the entire metabolomic fingerprint obtained, we observed that glutamine/glutamate metabolism was associated with disease severity as patients in the severe COVID-19 group presented the lowest and higher serum levels of these amino acids, respectively. These data highlight the hypoxia-derived metabolic alterations provoked by SARS-CoV-2 infection in the absence of pre-existing co-morbidities as well as the value of amino acid metabolism in determining reactive oxygen species recycling pathways, which when impaired may lead to increased oxidation of proteins and cell damage. They also provide insights on new supportive therapies for COVID-19 and other disorders that involve altered redox homeostasis and lower oxygen levels that may lead to better outcomes of disease severity.


Subject(s)
COVID-19 , Glutamic Acid , Amino Acids/metabolism , Cystine/metabolism , Gas Chromatography-Mass Spectrometry , Glutamic Acid/metabolism , Glutamine/metabolism , Homeostasis , Humans , Hypoxia , Male , Oxidation-Reduction , Oxygen , Proline/metabolism , Reactive Oxygen Species , SARS-CoV-2
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