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1.
Indian J Crit Care Med ; 26(4): 416-418, 2022.
Article in English | MEDLINE | ID: covidwho-1954528

ABSTRACT

How to cite this article: Siddiqui SS, Patnaik R, Kulkarni AP. General Severity of Illness Scoring Systems and COVID-19 Mortality Predictions: Is "Old Still Gold?" Indian J Crit Care Med 2022;26(4):416-418.

2.
Sleep Science ; 15:4, 2022.
Article in English | EMBASE | ID: covidwho-1935307

ABSTRACT

Introduction: Sleep is the main determinant of human wellbeing, mental and physical health. Sleep effectiveness can be reported through its quality and depth. Based on this principle, individuals infected by the SARS - CoV-2 virus from the family of coronavirus viruses, develop tissue inflammation and cell damage, causing an increase in inflammatory cytokines in the organism of the infected. There are several common causes of sleep disorders in hospitalized patients, including medical conditions and underlying psychological problems. There are also several modifiable factors that promote sleep disturbances in critically ill patients, such as noise, light, interactions with patient care, medications, mechanical ventilation and very commonly pain. The lack of sleep, therefore, can negatively compromise immunity, increasing the chances of disease onset. There is also the influence of sleep on emotional processing, with a role in maintaining mood and emotional state. Sleep deprivation also has a strong negative impact on daily behavior and, consequently, on daily mental health. Objective: The aim of the present study was to evaluate the sleep characteristics of patients during hospitalization, with a confirmed diagnosis of COVID. Methods: This is a quantitative, descriptive study, carried out from July to September 2020 in patients with positive SARS-CoV-2 infection through the RT-PCR test of nasopharyngeal swabs, aged ≥ 18 years, of both sexes, admitted to the hospital's infirmary in the north of Rio Grande do Sul. The evaluation methods used were the sleep diary and a free application (Sleep As Android) available for smartphones. Results: Thirty patients were evaluated, the majority of whom were male (53%) and the average age was 52 years. Only 1 patient was previously healthy and the main associated comorbidities were hypertension and obesity. Less than 50% of individuals used sleeping pills. However, C-reactive protein levels were altered in most patients. As for the outcomes related to sleep characteristics, significant correlations were observed between increased nighttime awakenings and prolonged hospital stay. In addition, patients diagnosed with depression (23%) had a greater total sleep deficit in a hospital setting. Conclusion: Patients with COVID admitted to hospital nurse units destined for a pandemic have important changes in sleep which are directly related to their lower quality.

3.
Ann Med Surg (Lond) ; 80: 104201, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1936027

ABSTRACT

Critically ill COVID-19 patients have to undergo positive pressure ventilation, a non-physiological and invasive intervention that can be lifesaving in severe ARDS. Similar to any other intervention, it has its pros and cons. Despite following Lung Protective Ventilation (LPV), some of the complications are frequently reported in these critically ill patients and significantly impact overall mortality. The complications related to invasive mechanical ventilation (IMV) in critically ill COVID-19 patients can be broadly divided into pulmonary and non-pulmonary. Among pulmonary complications, the most frequent is ventilator-associated pneumonia. Others are barotrauma, including subcutaneous emphysema, pneumomediastinum, pneumothorax, bullous lesions, cardiopulmonary effects of right ventricular dysfunction, and pulmonary complications mimicking cardiac failure, including pulmonary edema. Tracheal complications, including full-thickness tracheal lesions (FTTLs) and tracheoesophageal fistulas (TEFs) are serious but rare complications. Non-Pulmonary complications include neurological, nephrological, ocular, and oral complications.

4.
Pakistan Journal of Medical and Health Sciences ; 16(6):395-400, 2022.
Article in English | EMBASE | ID: covidwho-1939797

ABSTRACT

Because it has been well defined, bovine serum albumin (BSA) is highly suited to pharmacological effects, biotransformation, and bio-distribution of medicines initial research. Drug–protein interactions in the blood stream are known to have a significant impact on drug distribution, free concentration, and metabolism. Coronavirus disease 2019 (COVID-19) has spread globally as a severe pandemic. It is a serious threat to healthcare systems, economies, and is devastating to some populations, such as the elderly and those with comorbidities. Unfortunately, there is still no effective cure for COVID-19, especially the critically ill patients. The link between the mortality risk of patients hospitalized for COVID-19 and the function of blood albumin levels has been investigated. Because of albumin biological significance, the study goal conducted to apply spectroscopic methods to explore and comparing the kinetic and thermodynamic aspects of ceftriaxone's interaction with BSA, albumin isolated from healthy and covid-19 plasma. A pooled plasma from healthy and hospitalized covid-19 individuals (Karbala Province / Iraq) was used to purify albumin using HPLC technique. UV-vis spectrophotometric measurements of albumin-ceftriaxone complex formation recorded at different pH (7, 7.2, 7.4, 7.6 & 7.8) in phosphate buffer solution, and at six different temperatures (298, 301, 304, 307, 310 & 313) K. The equilibrium constant and the thermodynamic parameter such as ΔG, ΔH and ΔS were calculated. The drug-albumin (BSA, healthy and Covid-19 albumin) complexes are stable in 60 to 300 minutes, as evidenced by the steady absorbance studies. The reaction is from the first false order for drug-albumin (BSA, healthy and covid-19 plasma) complexes. Our finding suggesting the reaction is from the first false order. In the case of plasma albumin from individuals infected with - Covid-19, the values of (R2) are closer together. This is because the medication dominates the formation of a more stable complex with albumin. The stoichiometric ratio (coordination number) of complex between ceftriaxone and albumin at 298 k and pH=7.4 is 1:1. The Gibbs free energy for albumin-ceftriaxone is negative, indicating that the reaction is spontaneous. The positive enthalpy of contact indicates that the process is endothermic, requiring energy input. Positive enthalpy and entropy change also refer to the hydrophobic association and electrostatic contact that occurs between albumin molecules and ceftriaxone. It is worth noting that the complex formed between bovine albumin and the medication has less absorbency at pH = 7.4. That is, the complex is more stable, and it prefers natural helical shapes. Additionally, as the pH value shifts away from physiological (> 7.4 <), the intensity of complex absorption increases.

5.
Biomedicine (India) ; 42(3):539-542, 2022.
Article in English | EMBASE | ID: covidwho-1939774

ABSTRACT

Introduction and Aim: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly evolved into a pandemic infecting humans all over the world. Whether hematologic and immunologic responses play a crucial role in progression of COVID-19 is still not clear. Increasing scientific evidence has shown that abnormalities in routine hematological tests, have the potential to diagnose SARS-CoV-2 infection in an economical way. Major laboratory changes indicating systemic inflammation and multi-organ impairment including hematopoietic system leading to lymphocytopenia, neutrophilia, eosinopenia, mild thrombocytopenia and ratios derived from these hematological parameters indicated severe disease and/or fatal outcomes. The aim was to study the hematological profile of Covid-19 patients admitted at a tertiary care hospital at Ramanagar district. Materials and Methods: This retrospective study included 260 confirmed cases of Covid-19 diagnosed at a tertiary health care centre. Demographic, clinical, laboratory, treatment, and outcome data were extracted from the institutional electronic medical records after obtaining permission from the concerned authorities. From CBC test results obtained neutrophil lymphocyte ratio was derived. Results: The present study revealed that majority of Covid positive patients presented with lymphopenia. While a significant association was observed between N/L ratio and disease severity, no significant association was seen between platelet count and severity of the disease. Conclusion: Since the results of the present study features lymphopenia among large proportion of patients and elevated N/L ratio among critically ill patients these markers could be utilized as useful prognostic indicators during the initial assessment of disease severity and thus appropriate management can be planned for such patients before the condition of the patient deteriorates.

6.
International Journal of Pharma and Bio Sciences ; 13(7):2631-2637, 2022.
Article in English | EMBASE | ID: covidwho-1939434

ABSTRACT

Mycosis is an opportunistic infection that attacks patients who are immunocompromised. Our immune system is designed to defend us against fungus and bacteria. The fungus can expand, penetrate and kill tissue because it lacks immunity. It's everywhere, in soil and air and even in healthy people's noses and snot, says the researcher. “As we work to defend ourselves from COVID-19 and live with it, another hazard termed Mucormycosis has emerged. Mucormycosis, a fungal infection caused by Mucor with a 50% fatality rate, maybe provoked by the administration of steroids, a life-saving treatment for severe and critically ill Covid-19 patients. Stay safe from Mucormycosis, a fungus that has been discovered in Covid-19 patients.

7.
Journal of Hypertension ; 40:e171, 2022.
Article in English | EMBASE | ID: covidwho-1937715

ABSTRACT

Objective: 1. To evaluate the use of remote cardiac monitoring of critically ill COVID-19 patients. 2. To correlate DOZEE early warning score(DEWS) with severity and outcome Design and method: Ballistocardiography (BCG)Ballistocardiography is a noninvasive method based on the measurement of the body motion generated by the ejection of the blood at each cardiac cycle. It also contains motion arising from breathing, snoring and body movements. Dozee Early Warning System (DEWS): DEWS is an overall score for risk assessment of the physiological status of a person. It is a cumulative score of risk levels of physiological parameters like HR,RR and SPo2, which acts as an early predictor for possible physiological decline. Assessment of severity of of Acute-illness Detection of clinical deterioration Initiation of a timely and competent clinical response Total 39 subjects were observed where 24 of the subjects were Male and 15 Female and the average duration of stay at the hospital was 5 days. There were 20 patients who had comorbid conditions like HYPOTHYROID, NHL,ASTHMA etc. 19 patients did not present with any co morbidities. The outcome of 10 patients was death and 29 patients were discharged after recovery, as reported by the healthcare professionals at the ward. The vitals of the subjects were continuously monitored by Dozee, a contactless remote patient monitoring system enabled with Dozee Early Warning System (DEWS) which reflects the overall patient condition based on the Respiration, Heart Rate and Spo2 of the patients. Results: The data from the continuous monitoring of the respiration rate, heart rate and oxygen saturation of the 39 patients were analysed for their duration of stay at the hospital. The DEWS score of the patients were also analysed Conclusions: It was concluded that continuous vitals monitoring of the patients and the resulting Dews scores were an indicator of the improving or deteriorating condition of the patients. The discharged patients showed a decrease in the DEWS score, especially Breathing DEWS before they recovered. However, the expired patients showed steady increase or a stagnant high Breathing dews until time of death.

8.
Biomedicines ; 10(7)2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1938688

ABSTRACT

(1) Background: COVID-19-associated pulmonary aspergillosis (CAPA) has worsened the prognosis of patients with pneumonia and acute respiratory distress syndrome admitted to the intensive care unit (ICU). The lack of specific diagnosis criteria is an obstacle to the timely initiation of appropriate antifungal therapy. Tracheal aspirate (TA) has been employed under special pandemic conditions. Galactomannan (GM) antigens are released during active fungal growth. (2) Methods: We proposed the term "CAPA in progress" (CAPA-IP) for diagnosis at an earlier stage by GM testing on TA in a specific population admitted to ICU presenting with clinical deterioration. A GM threshold ≥0.5 was set as the mycological inclusion criterion. This was followed by a pre-emptive short-course antifungal. (3) Results: We prospectively enrolled 200 ICU patients with COVID-19. Of these, 164 patients (82%) initially required invasive mechanical ventilation and GM was tested in TA in 93 patients. A subset of 19 patients (11.5%) fulfilled the CAPA-IP criteria at a median of 9 days after ICU admittance. The median GM value was 3.25 ± 2.82. CAPA-IP cases showed significantly higher ICU mortality [52.6% (10/19) vs. 34.5% (50/145), p = 0.036], as well as a much longer median ICU stay than those with a normal GM index [27 (7-64) vs. 11 (9-81) days, p = 0.008]. All cases were treated with a pre-emptive systemic antifungal for a median time of 19 (3-39) days. (4) Conclusions: CAPA-IP highlights a new real-life early approach in the field of fungal stewardship in ICU programs.

9.
Crit Care ; 26(1): 217, 2022 07 16.
Article in English | MEDLINE | ID: covidwho-1938337

ABSTRACT

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.


Subject(s)
COVID-19 , Cerebral Hemorrhage , Ischemic Stroke , Nervous System Diseases , Aged , COVID-19/complications , COVID-19/epidemiology , Cerebral Hemorrhage/virology , Critical Illness/epidemiology , Critical Illness/therapy , Female , Humans , Intensive Care Units , Ischemic Stroke/virology , Male , Middle Aged , Nervous System Diseases/virology , Pandemics , Prospective Studies , Registries , SARS-CoV-2
10.
J Acad Consult Liaison Psychiatry ; 2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1930918

ABSTRACT

BACKGROUND: COVID-19 has been a devastating pandemic with little known of its neuropsychiatric complications. Delirium is 1 of the most common neuropsychiatric syndromes among hospitalized cancer patients with incidence ranging from 25% to 40% and rates of up to 85% in the terminally ill. Data on the incidence, risk factors, duration, and outcomes of delirium in critically ill cancer patients with COVID-19 are lacking. OBJECTIVE: To report the incidence, riaks and outcomes of critically ill cancer patients who developed COVID-19. METHODS: This is a retrospective single-center study evaluating delirium frequency and outcomes in all critically ill cancer patients with COVID-19 admitted between March 1 and July 10, 2020. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit, performed twice daily by trained intensive care unit (ICU) nursing staff. Patients were considered to have a delirium-positive day if Confusion Assessment Method for Intensive Care Unit was positive at least once per day. RESULTS: A total of 70 patients were evaluated. Of those 70, 53 (75.7%) were found to be positive for delirium. Patients with delirium were significantly older than patients without delirium (median age 67.5 vs 60.3 y, P = 0.013). There were no significant differences in demographic characteristics, chronic medical conditions, neuropsychiatric history, cancer type, or application of prone positioning between the 2 groups. Delirium patients were less likely to receive cancer-directed therapies (58.5% vs 88.2%, P = 0.038) but more likely to receive antipsychotics (81.1% vs 41.2%, P = 0.004), dexmedetomidine (79.3% vs 11.8%, P < 0.001), steroids (84.9% vs 58.8%, P = 0.039), and vasopressors (90.6% vs 58.8%, P = 0.006). Delirium patients were more likely to be intubated (86.8% vs 41.2%, P < 0.001), and all tracheostomies (35.9%) occurred in patients with delirium. ICU length of stay (19 vs 8 d, P < 0.001) and hospital length of stay (37 vs 12 d, P < 0.001) were significantly longer in delirium patients, but there was no statistically significant difference in hospital mortality (43.4% vs 58.8%, P = 0.403) or ICU mortality (34.0% vs 58.8%, P = 0.090). CONCLUSIONS: Delirium in critically ill cancer patients with COVID-19 was associated with less cancer-directed therapies and increased hospital and ICU length of stay. However, the presence of delirium was not associated with an increase in hospital or ICU mortality.

11.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927930

ABSTRACT

RATIONALE The COVID-19 pandemic led to rapid changes in care-delivery for intensive care unit (ICU) patients, due to factors including high ICU strain, shifting team member roles, and changes in care locations. As these changes may have not only impacted patients with COVID-19 but also critically ill patients without COVID-19, we assessed changes in common ICU practices for mechanically ventilated patients without COVID before and after the start of the COVID-19 pandemic. METHODS We used the Premier Healthcare Database to identify mechanical ventilated ICU patients in the US from January 1, 2016 - December 31, 2020. Patients were excluded if they had an ICD-10 diagnosis of COVID-19 (U07.1) or if they were admitted to a hospital that did not contribute data for all five years. We assessed annual rates of common ICU imaging studies (chest CT scan, chest x-ray, lower extremity doppler ultrasound), bedside diagnostics (electrocardiogram, electroencephalogram), and bedside procedures (arterial line, central venous catheterization, bronchoscopy) and annual mortality rates. We used interrupted time series analysis, adjusted for seasonality and autocorrelation where present, to evaluate trends in ICU practices prior to the pandemic (March 2016 - February 2020), at the onset of the pandemic (April 2020) and as the pandemic progressed (April 2020 - December 2020). March 2020, as the US transitioned into the pandemic, was excluded from the analysis. RESULTS We identified 584,393 mechanically ventilated patients without COVID- 19 at 509 hospitals. Trends in ICU procedures and mortality are illustrated in Figure 1. At the onset of the pandemic, use of chest x-ray (-35.6% [-53.5 to -17.8%, p<0.001]), electrocardiogram (-14.8% [-21.9 to -7.6%, p<0.001]), and bronchoscopy (-1.2% [-1.8 to -0.6%, p<0.001]) decreased;rates of lower extremity doppler (-1.8% [-4.1 to -0.5%, p=0.12]), electroencephalogram (-0.8% [- 1.7 to 0.1%, p=0.09]), arterial lines (-0.09 [-1.0 to 0.9%, p=0.85]) and central venous catheters (+0.2 [-1.3 to 1.7%, p=0.77]) did not significantly change;use of chest CT increased 2.6% (0.9 to 4.3%, p=0.001). With the exception of chest CT, arterial lines, and central venous catheters, trends in all other measured procedures increased as the pandemic progressed, compared with pre-pandemic trends. There was no significant trend change in mortality at the onset of the pandemic or during the pandemic. CONCLUSIONS Multiple practice patterns changed among patients without COVID-19 early during the pandemic. However, no change in mortality was seen during this time. These findings warrant further investigation to determine their impact on patientcentered outcomes.

12.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927924

ABSTRACT

Rationale: The relationship between disability and outcomes after COVID-19 hospitalization remains largely unexplored. We hypothesized that patients with pre-COVID disability would have poorer hospital outcomes, and that COVID-19 hospitalization would be associated with increased disability at hospital discharge. Methods: Between August 2020 and July 2021, NHLBI PETAL Network hospitals prospectively enrolled patients hospitalized with symptomatic SARS-CoV2 infection (fever and/or respiratory signs or symptoms) confirmed by molecular testing. Patients or their surrogates reported pre-COVID ability to perform activities of daily living (ADL) and degree of frailty using standardized surveys at study entry (Katz's ADLs and Rockwood's Clinical Frailty Scale (CFS)). Study staff collected detailed clinical data throughout hospitalization. We examined bivariate and multivariable associations between pre-COVID disability and hospital outcomes and reported risk factors for increased disability at hospital discharge among patients surviving to hospital discharge. In analyses exploring factors associated with returning home to living independently or walking at discharge, we excluded patients not living independently or walking prior to COVID admission, respectively. Results: We enrolled 1369 patients across 44 US hospitals. Demographics are presented in the table, along with clinical management and outcomes. Most patients lived at home without help prior to hospitalization (n=1130, 84%), while 14% were dependent in 1-3 ADLs and 14% were dependent in 4 or more. Before hospitalization, 15% of patients were frail (CFS>4) and 15% were vulnerable (CFS=4). Most patients did not receive critical care (“acute illness”);389 patients (28%) were cared for in ICUs (“critical illness”), and 192 (14%) received mechanical ventilation. Overall, 100 (7%) patients died during their COVID-19 hospitalization. Median hospital length of stay was 6 days (IQR 4-8) for acutely ill patients, 14 days (IQR 9-24 days) for critically ill patients. Pre-COVID frailty was independently associated with hospital mortality (OR 3.5, 95% CI 1.9-6.5), adjusting for age and critical illness. Many patients experienced inability to walk and/or return home independently at hospital discharge, which were associated with baseline disability (OR 2.1, 95% CI 1.1-4.1 for inability to walk, OR 1.9, 95% 1.1-3.4 for inability to return home), adjusting for age and critical illness. Conclusion: Disability and frailty are common among patients hospitalized with SARS-CoV2 infection and associated with poorer outcomes. Additionally, COVID hospitalization is associated with increased disability and loss of independence, especially among critically ill patients. Improving recovery and patient centered outcomes after severe SARS-CoV2 hospitalization will likely require careful discharge planning, post-hospital follow-up, and additional research.

13.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927923

ABSTRACT

Rationale: LAU-7b is developed as a broadly effective oral COVID-19 therapeutic targeting membrane lipids to exert dual antiviral and inflammation-controlling activity. SARS-CoV-2 reprograms host cellular lipid metabolism to favor entry and replication, a mechanism shared by all lipid-enveloped viruses. LAU-7b decreases host cell membrane lipids fluidity, inhibits de-novo cell lipogenesis, and modulates phospholipid signaling promoting resolution of inflammation. Due to its host-directed mutation-agnostic mechanism, LAU-7b utility could span across future variants, as demonstrated in-vitro against multiple SARS-CoV-2 strains and MERS-CoV. RESOLUTION, a large Phase 2/3 study evaluating LAU-7b in hospitalized COVID-19 patients, is ongoing in the US and Canada, and preliminary Phase 2 results are presented. Methods: RESOLUTION is a placebocontrolled study of oral LAU-7b, once-a-day for 14 days on top of standard of care, in hospitalized COVID-19 patients at risk of developing pulmonary complications. The Phase 2 portion of the study randomized 148 patients with moderate-to-severe COVID-19 and 84 patients in critical condition, but not on invasive ventilation. Key endpoints included proportion of patients alive and free of respiratory failure at Day 29, rates of progression to mechanical ventilation and all-causes death by Day 60, time to recovery and length of hospitalization. Results: Both study arms were highly comparable in terms of mean age, number of comorbidities and concomitant medications. LAU-7b demonstrated a 100% reduction in the risk of progressing to mechanical ventilation or death by Day 60 in moderate-to-severe COVID-19 patients. None of the 76 patients on LAU-7b required mechanical ventilation and none died, while 5 out of 72 patients on placebo progressed to mechanical ventilation (6.9% difference, p=0.025), and 4 patients died (5.6% difference, p=0.053). LAU-7b group also showed an increase of 6.9% (p=0.055) in the proportion of patients alive and free of respiratory failure at Day 29, versus placebo. Patients on LAU-7b tended to recover more rapidly and leave hospital faster. LAU-7b was well-tolerated, with safety comparable to placebo. Critically ill patients treated with LAU-7b did not show improvement over placebo, suggesting that COVID-19 patients in respiratory failure at baseline are too severely affected to benefit. Conclusion: LAU-7b showed positive results in the trial's Phase 2 portion on both survival and avoidance of mechanical ventilation in moderate-to-severe COVID-19. The confirmatory Phase 3 portion was triggered and received approval from the FDA and Health Canada, focusing on moderate-to-severe COVID-19 and using the “Proportion of patients requiring mechanical ventilation and/or death by Day 60” as primary efficacy endpoint.

14.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927884

ABSTRACT

RATIONALE Immune dysregulation and endothelial injury are implicated in the pathobiology of acute respiratory distress syndrome (ARDS) due to COVID-19. Circulating biomarkers of immune and endothelial dysfunction are variably associated with outcomes in COVID-19 ARDS, with most studies conducted before routine use of systemic corticosteroids. We therefore evaluated the association of baseline inflammatory and endothelial biomarkers with mortality in a recent cohort of critically ill COVID-19 patients. METHODS We prospectively enrolled an observational cohort of COVID-19 ARDS patients from the intensive care unit (ICU) of an urban, academic hospital in Boston, Massachusetts from January 1 to March 1, 2021 (N=100). Patients were aged ≥ 18 years, had confirmed COVID-19 by polymerase chain reaction, and had a diagnosis of ARDS adjudicated by board-certified pulmonary and critical care physicians. Plasma samples were collected on day 1 of ICU admission. Clinical course was followed for 60 days post-enrollment or until discharge. Recorded clinical data included demographics, comorbidities, modified sequential organ failure assessment (mSOFA) score, hospital and ICU length of stay (LOS), and ventilator days. Eleven plasma analytes were measured using a Luminex Discovery Assay (R and D Systems) and Creactive protein (CRP) was measured by the hospital core laboratory. RESULTS Of 100 ICU patients with severe COVID-19 with acute respiratory failure, 74 were intubated and 68 had a plasma sample from day 1 of their ICU admission. Of those intubated (n=74), all met ARDS criteria, mean age (± standard deviation) was 64 ± 15 years, 39 (40%) were female, mean BMI was 30 ± 8, median mSOFA was 6 (IQR 4-8), median PaO2 was 105 mmHg (IQR 83-131 mmHg), and median PaO2/FiO2 was 174 (IQR 132- 235). Seventy patients (95%) received systemic corticosteroids. Median ventilator days was 15 (IQR 8-21), median ICU LOS was 17 days (IQR 10-27), and median hospital LOS was 22 days (IQR 16-32). At 30 days, 29 (40%) patients died, and at 60 days, 33 (45%) patients died. A total of 12 prespecified analytes were profiled (Figure). Only the endothelial biomarker von Willebrand factor (vWF) was associated with mortality at day 30 (∗P=0.003) and day 60 (P=0.002) using logistic regression adjusted for age, mSOFA, and multiple comparisons (P<0.004 significant by Bonferroni). CONCLUSION In a cohort of patients with ARDS due to COVID-19 receiving systemic corticosteroids, there was no association between inflammatory markers and mortality. However, the endothelial protein vWF remained associated with mortality suggesting endothelial injury is incompletely mitigated by systemic corticosteroids.

15.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927881

ABSTRACT

Introduction: COVID-19 is a well-known cause of severe ARDS (acute respiratory distress syndrome), however recent data suggests that COVID-19 could represent a unique form of lung injury that places patients at increased risk of various uncommon complications such as pneumothorax, pneumomediastinum and subcutaneous emphysema. Studies so far have reported an increased incidence of barotrauma in intubated COVID-19 patients with unclear predictors. Our study aims to identify the different variables associated with development of pneumothorax, pneumomediastinum and subcutaneous emphysema in critically ill COVID-19 patients. Methods: We examined patients admitted to the intensive care unit from March 2020 to Feb 2021 at a large tertiary care center in Detroit, Michigan. We identified a total of 25 patients with COVID-19 ARDS requiring mechanical ventilation who developed pneumothorax, 12 who developed pneumomediastinum and 7 with subcutaneous emphysema. We compared those to 66 patients admitted with COVID-19 ARDS also requiring mechanical ventilation who did not develop any of these complications. The mean age of patients in our subject group was 61.81 years compared to a mean of 69.05 years in the control group. Male patients accounted for 58.33% of the subject group and 60.61% in the control group. Results: we detected a statistically significant difference in the modified Sequential Organ Failure Assessment Score (mSOFA) between the patients who developed these complications compared to those who did not (p<0.0001), with score being surprisingly lower in the group who developed the complication as opposed to those who did not (median mSOFA in subjects 3.5, n=32 vs median mSOFA in controls 11, n=66). Analysis of the subgroups of the mSOFA score revealed no statistically significant difference in the PF ratio (p=0.1995), platelet counts (p=0.065) and total bilirubin (p=0.4403). However, MAP was noted to be significantly lower in the control group than in the subject group accounting for a higher mSOFA score (p=0.0031). Similarly, creatinine was noted to be higher in the control group (p<0.0001) compared to the subject group. Discussion: In viewing our baseline patient characteristics we found a statistically significant difference (p<0.0001) in the rate of baseline chronic kidney disease between our subjects and control patients, with control patients having 100% baseline CKD and subjects having 19.4% baseline CKD. This could account for the higher mSOFA scores in controls. Conclusion: mSOFA did not predict the development of pneumothorax, pneumomediastinum or subcutaneous emphysema in patients admitted with COVID-19 ARDS requiring mechanical ventilation.

16.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927862

ABSTRACT

Rationale: The COVID-19 pandemic has renewed interest in the use of inhaled anesthetics for sedation of ventilated critically ill patients. Compared to intravenous sedatives, inhaled anesthetics reduce lung inflammation, time to extubation, and ICU length of stay. However, their impact on cognitive and psychiatric outcomes is less clear. In this systematic review we summarize the impact of inhaled sedatives on cognitive and psychiatric outcomes in ventilated critically ill patients. Methods: We searched MEDLINE, EMBASE, and PsychINFO for studies from 1970 - 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anesthetics. We included case series, observational, cohort, and randomized controlled trials. Outcome(s) of interest included cognition, anxiety, depression, hallucinations, psychomotor recovery, and PTSD, as well as instruments for assessing these outcomes. Results: We identified a total of twelve studies that examined at least one of our outcomes of interest (16 total outcomes). Four studies were in post cardiac arrest survivors, three in post-operative (non-cardiac) patients, two in post-operative cardiac patients, and three more in mixed medical-surgical patients. Seven studies reported incidence of delirium, two assessed neurologic recovery post cardiac-arrest, and two examined ICU memories. One study reported on each of anxiety, depression, hallucinations, PTSD, psychomotor recovery, and long-term cognitive dysfunction more than 3 months following ICU discharge. Of the seven studies reporting on delirium, only one reported an increase in delirium for those sedated with intravenous sedation compared to volatile. The remaining studies did not report any difference in delirium incidence between modes of sedation. Similarly, no difference between sedation methods were observed for neurologic recovery following cardiac arrest, anxiety, depression, hallucinations, PTSD, psychomotor recovery, or long-term cognitive dysfunction. The most commonly used tool used was the CAM-ICU tool (delirium outcome;3 studies). Five studies used subjective chart review to assess their outcome of interest, or did not report their method of assessment. Conclusions: Few studies examined cognitive and psychiatric outcomes in critically ill adults sedated with volatile anesthetics. As volatile anesthetics offer a promising alternative mode of sedation in the ICU, future studies should incorporate assessment of these important patientcentered outcomes using validated objective tools during and following hospital stay.

17.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927829

ABSTRACT

Introduction: Neutrophil extracellular traps (NETs) are extrusions of intracellular DNA and granular material released by neutrophils as part of the host immune response. While intended as a defense mechanism, excessive production of NETs may play a role in the pathogenesis of ARDS. Fostamatinib appears to limit NET formation. A phase 2 study of fostamatinib for COVID-19 associated acute lung injury found fostamatinib to be associated with improved clinical outcomes. No patients in the clinical trial were on extracorporeal membrane oxygenator (ECMO) support. In this we report our experience with two critically ill patients on veno-venous (VV) ECMO treated with fostamatinib. Case 1: A 46-year-old male with no significant PMH was admitted with COVID-19 associated ARDS (CARDS). He required intubation on hospital day (HD) 10. Due to refractory hypoxemia, he was cannulated for VV ECMO that same day. By day 19, he had improved and was decannulated from ECMO. Following decannulation, he continued to struggle. He developed a pneumothorax which was addressed with a chest tube. Despite this he had refractory hypoxemia requiring neuromuscular blockade (NMB). Broad spectrum antibiotics were initiated. No superinfection was identified. He was again cannulated for VV ECMO on HD 30. On HD 36, fostamatinib was initiated at a dose of 150 mg bid for 14 days. The patient demonstrated fairly rapid improvement by HD 39, allowing for minimization of ECMO support. He was decannulated from VV ECMO on HD 46. He currently resides at home and has no need for oxygen. Case 2: A 53- year-old male with a PMH of psoriasis on etanercept was admitted with CARDS. He was intubated HD 1, but continued to require substantial support including prone positioning and NMB. On HD 5 he was cannulated for VV ECMO. He had early improvement and was decannulated on HD 10;however, he developed Staph aureus pneumonia resulting in marked clinical decline. On HD 12 he was placed back on VV ECMO support. He was also initiated on fostamatanib 150 mg twice daily for 14 days. He demonstrated fairly rapid improvement in oxygenation but required prolonged ECMO support for CO2 clearance. He was successfully decannulated from VV ECMO on HD 45. He is currently living at home. Conclusion: Fostamatinib appears safe to administer to COVID patients on ECMO. While it is speculative to make inferences with regards to efficacy, it is noteworthy that both critically ill COVID-19 patients treated with fostamatinib survived.

18.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927826

ABSTRACT

Introduction: Encephalopathy in a transplant recipient is a challenging clinical presentation that requires a broad differential (both infectious and noninfectious) and consideration of exposures. West Nile Virus (WNV) encephalitis is a rare etiology of encephalopathy in a transplant recipient with controversial management. Case: A man in his seventies presented due to encephalopathy in September 2021. Medical history was significant for deceased donor kidney transplant in September 2020 and myasthenia gravis. Immunosuppression consisted of tacrolimus, mycophenolic acid, and prednisone 10 mg daily. He was on fluconazole for coccidioidomycosis prophylaxis. Symptoms consisted of worsening weakness over five days and headaches for two days. On admission, he was febrile to 38.1° C and had altered mental status. He was started on empiric meningitis treatment with ampicillin, vancomycin, cefepime, and acyclovir, and was given doxycycline for atypical coverage. He developed worsening encephalopathy and was intubated for airway protection. CSF profile revealed 255/mm3 WBC (77% neutrophils, 20% lymphocytes, 3% monocytes), 45/mm3 RBC, 61 glucose mg/dL (serum 126 mg/dL), and 96.1 mg/dL protein. Exposure history was significant for visiting family in central Arizona several weeks prior to presentation where he was exposed to mosquitos and two cats. He ate at a fast-food restaurant two days prior to presentation. He received three doses of COVID-19 vaccine. He was born and raised in Arizona and has remote travel to Mexico. Extensive studies (considering the risk factors above) identified the etiology of his encephalopathy as WNV encephalitis with positive serum PCR, elevated serum and CSF IgM with normal IgG. Unfortunately, the patient expired despite aggressive therapy. Discussion: This case represents three interesting challenges that we feel will be of interest to the conference attendees. The first is encephalopathy in a transplant recipient within one year of transplant requires a broad differential including donor-derived infections, opportunistic organisms that can cause meningoencephalitis, as well as knowledge of local and seasonal pathogens on the rise. With the monsoon season in 2021, Arizona rose to become one of the top ten states in the country with WNV cases. The second is management of a critically ill patient with meningitis and myasthenia gravis, since multiple agents for empiric therapy have been associated with worsening of or precipitating myasthenic crisis. Finally, supportive care is the mainstay of the management of WNV encephalitis and IVIG and adjustments in immunosuppression is controversial.

19.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927824

ABSTRACT

Introduction: Naso-(NGT) and oro-gastric tubes play an integral role in the nutritional support of patients who are not able to meet dietary needs through independent oral consumption. Although uncommon, serious pulmonary complications may arise from this mostly blindly performed procedure (0.2-2%). We report a case of an elderly female who developed a right-sided tension pneumothorax (PTX). necessitating tube thoracostomy following NGT misplacement. Case: Our patient is a 79-year-old elderly female woman with no known past medical history who was admitted for altered mentation and hypoxemia due to COVID-19. Although her initial course was complicated by progressive respiratory failure requiring ICU admission and initiation of high-flow nasal cannula, she was quickly weaned to nasal cannula and transferred to a regular floor. Due to poor mentation and inconsistent food intake, enteral access was attempted using a weighted-tip 10 FR NGT. The patient had mild cough and discomfort during the procedure. There was no resistance during insertion. After advancement to 55 CM the patient ceased coughing and the procedure was completed. Chest X-ray (CXR) obtained as part of routine post-procedural evaluation revealed an intra-pleural NGT abutting the R hemi-diaphragm (Figure) and small PTX. Follow-up CXR revealed enlarging PTX with mediastinal shift to the left for which emergent thoracostomy utilizing a 14FR pig-tail catheter was performed. There was complete resolution of the pneumothorax with removal of the chest tube three days later. The patient was discharged home shortly after. Discussion: NGT placement is commonly performed by healthcare providers of varying degrees of expertise and experience. Risk factors associated with complications include multiple attempts, insertion at night, presence of artificial airway and altered mentation, among others. In case of trans-pulmonary placement, withdrawal of intra-pleural NGTs is associated with high risk of pneumothorax and requires close observation. To decrease the likelihood of malposition, a two-step radiograph, gradual progression technique can be deployed if fluoroscopic placement is not available. This should be strongly considered in patients at high risk for adverse events. Conclusions: Blind insertion of NGT using traditional techniques may be of limited safety and put patients at risk of complications. This is particularly true in those who are critically ill, frail or experiencing altered mentation. Institutional protocols to identify patients at high risk on whom blind placement should not be attempted are warranted. Post-withdrawal CXR to rule-out the presence of tension physiology is highly recommended.

20.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927769

ABSTRACT

RATIONALE During this unprecedented COVID-19 pandemic intensive care units (ICU) need efficient ways to deliver patient care. As hospital workload increases, so does the risk for medical error and delays in care. A systematic initial approach and timely documentation is important to provide an efficient and thorough assessment and to facilitate communication within the interprofessional team. We aimed to evaluate documentation of key assessment elements at ICU admission. METHODS The Checklist for Early Recognition and Treatment of Acute Illness and Injury (CERTAIN) is a validated tool that reduces errors in the initial assessment and ongoing care of critically ill patients. With Mayo IRB approval, electronic medical records (EMR) of a convenience sample of ICU patients admitted to medical, surgical and mixed ICUs at our institution during October 2021 were reviewed to assess documentation of the CERTAIN primary survey, including assessment of airway, breathing, cardiac, disability, and exposure (ABCDE);vital signs;intravenous access;point of care labs and ultrasound (POCUS);differential diagnosis;and plan by systems including code status and goals of care. Patients admitted for post-operative monitoring and those who declined the use of their medical records for research were excluded. RESULTS Forty patient EMRs were reviewed. Median age was 65 years, 47.5% were female, and respiratory failure was the most common reason for ICU admission. Documented frequency of airway assessment was 32.5%, breathing 92.5%, cardiac 70%, disability 42.5%, and exposure 85%. Thorough vital sign review including temperature was documented in 47.5% of ICU admissions. A comment or plan for intravenous or intraosseous access was documented in 75% of patients. Completion or review of same day point of care labs was documented in 55%. Cardiac POCUS was documented in 9 of 40 ICU admissions. No patients had documented lung or abdominal POCUS. 80% had a differential diagnosis documented as part of their initial assessment. All patients had a complete plan by systems. 85% of patients had a documented code status, although it was unclear if it had been actively re-addressed on ICU admission. CONCLUSION EMR documentation of key findings at the time of ICU admission leaves significant opportunities for improvement, with particularly large gaps in primary survey and POCUS assessment. The results of this study, combined with ongoing direct observation of ICU admissions using the CERTAIN checklist, will inform future recommendations to improve the performance and documentation of key assessment elements during the “golden first hour” of ICU admission.

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