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1.
Acta anaesthesiologica Scandinavica ; 2023.
Article in English | EuropePMC | ID: covidwho-2213441

ABSTRACT

This Rapid Practice Guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19. This article is protected by copyright. All rights reserved.

2.
Crit Care Med ; 48(6): e440-e469, 2020 06.
Article in English | MEDLINE | ID: covidwho-2152192

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.


Subject(s)
Coronavirus Infections/therapy , Intensive Care Units/organization & administration , Pneumonia, Viral/therapy , Practice Guidelines as Topic/standards , Betacoronavirus , COVID-19 , Critical Illness , Diagnostic Techniques and Procedures/standards , Humans , Infection Control/methods , Infection Control/standards , Intensive Care Units/standards , Pandemics , Respiration, Artificial/methods , Respiration, Artificial/standards , SARS-CoV-2 , Shock/therapy
3.
BMJ : British Medical Journal (Online) ; 379, 2022.
Article in English | ProQuest Central | ID: covidwho-2152944

ABSTRACT

ObjectiveTo determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19.DesignSystematic review with frequentist and bayesian meta-analyses.Study eligibilityRandomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022.Data extraction and synthesisTwo reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes.Main outcome measuresThe primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events.Results17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94;high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07;high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval −0.5 to 3.4;low certainty), ICU length of stay (−2.1 days, −4.5 to 0.4;low certainty), hospital length of stay (−0.09 days, −0.69 to 0.51;moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44;low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97;posterior probability for relative risk <0.95=96%) but lower probability for mortality (0.90, 0.73 to 1.13;<0.95=68%).ConclusionsAwake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes.Systematic review registrationPROSPERO CRD42022314856.

4.
Sci Rep ; 12(1): 18186, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2096799

ABSTRACT

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon ß-1b), we evaluated the heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-ß1b and lopinavir-ritonavir and 38 received placebo. Interferon-ß1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-ß1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).


Subject(s)
Coronavirus Infections , Ritonavir , Animals , Humans , Antiviral Agents/therapeutic use , Cytokines/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use
6.
Curr Opin Crit Care ; 28(6): 638-644, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2063072

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease 2019 (COVID-19) pandemic has posed great challenges to intensive care units (ICUs) across the globe. The objective of this review is to provide an overview on how ICU surging was managed during COVID-19 pandemic, with a special focus on papers published in the last 18 months. RECENT FINDINGS: From the onset of the COVID-19 pandemic, it was apparent that the biggest challenge was the inequity of access to an adequately equipped and staffed ICU bed. The first wave was overwhelming; large surge of patients required critical care, resources were limited and non-COVID-19 care processes were severely compromised. Various approaches were used to address ICU staffing shortage and to expand the physical ICU space capacity. Because of restrictions to family visitations in most ICUs, the pandemic posed a threat to communication and family-centered ICU care. The pandemic, especially during the first wave, was accompanied by a high level of apprehension in the community, many uncertainties about clinical course and therapy and an influx of speculations and misinformation. SUMMARY: Although healthcare systems learned how to face some of the challenges with subsequent waves, the pandemic had persistent effects on healthcare systems.


Subject(s)
COVID-19 , Pandemics , Humans , COVID-19/epidemiology , SARS-CoV-2 , Intensive Care Units , Critical Care
7.
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
8.
N Engl J Med ; 386(25): 2387-2398, 2022 06 23.
Article in English | MEDLINE | ID: covidwho-1900733

ABSTRACT

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).


Subject(s)
Ascorbic Acid , Sepsis , Adult , Ascorbic Acid/adverse effects , Humans , Hypoglycemic Agents/therapeutic use , Intensive Care Units , Multiple Organ Failure , Quality of Life , Sepsis/drug therapy , Vasoconstrictor Agents/adverse effects , Vitamins/adverse effects
9.
JAMA ; 327(21): 2104-2113, 2022 06 07.
Article in English | MEDLINE | ID: covidwho-1898487

ABSTRACT

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.


Subject(s)
COVID-19 , Intubation, Intratracheal , Prone Position , Respiratory Insufficiency , Wakefulness , Adult , Aged , COVID-19/complications , COVID-19/therapy , Female , Humans , Hypoxia/etiology , Hypoxia/therapy , Intubation, Intratracheal/methods , Male , Middle Aged , Respiration, Artificial/methods , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
10.
J Infect Public Health ; 15(7): 826-834, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1895224

ABSTRACT

BACKGROUND: Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic. METHODS: This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses. RESULTS: There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio. CONCLUSION: DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.


Subject(s)
COVID-19 , Adult , Algorithms , Cohort Studies , Critical Illness , Decision Trees , Humans , Intensive Care Units , Machine Learning , Pandemics , Prospective Studies , Retrospective Studies , SARS-CoV-2
11.
JMIR Res Protoc ; 11(5): e36261, 2022 05 20.
Article in English | MEDLINE | ID: covidwho-1862513

ABSTRACT

BACKGROUND: The LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. OBJECTIVE: We aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. METHODS: The SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. RESULTS: The SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. CONCLUSIONS: We have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36261.

12.
Crit Care Clin ; 38(3): 601-621, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1850766

ABSTRACT

High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) via facemask or helmet have been increasingly used in managing acute hypoxemic respiratory failure (AHRF) owing to COVID-19 with the premise of reducing the need for invasive mechanical ventilation and possibly mortality. Their use carries the risk of delaying intubation and nosocomial infection transmission. To date, most studies on the effectiveness of these modalities are observational and suggest that HFNO and NIV have a role in the management of AHRF owing to COVID-19. Trials are ongoing and are evaluating different aspects of noninvasive respiratory support in patients with AHRF owing to COVID-19.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , COVID-19/therapy , Humans , Oxygen/therapeutic use , Oxygen Inhalation Therapy , Respiration, Artificial , Respiratory Insufficiency/therapy
13.
Intensive Care Med ; 47(9): 1024-1027, 2021 09.
Article in English | MEDLINE | ID: covidwho-1813638
14.
JAMA ; 327(13): 1247-1259, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1801957

ABSTRACT

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19 , Critical Illness , Platelet Aggregation Inhibitors , Venous Thromboembolism , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Aspirin/adverse effects , Aspirin/therapeutic use , Bayes Theorem , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Critical Illness/mortality , Critical Illness/therapy , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Respiration, Artificial , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
15.
JPEN J Parenter Enteral Nutr ; 45(S2): 79-84, 2021 11.
Article in English | MEDLINE | ID: covidwho-1767367

ABSTRACT

Despite a mounting evidentiary base, controversies surrounding critical care nutrition support persist. Anchored by a case of a 60-year-old male with esophageal cancer who develops acute hypoxemic respiratory failure and septic shock, five panelists from the American Society of Parenteral and Enteral Nutrition (ASPEN) 2021 Pre-Conference discuss key clinical dilemmas in critical care nutrition, including hierarchy of evidence, bedside evaluation of malnutrition, optimal protein dose, use of fiber, and therapies targeting gut function and gut microbiota .


Subject(s)
Critical Illness , Malnutrition , Critical Care , Critical Illness/therapy , Enteral Nutrition , Humans , Male , Malnutrition/complications , Malnutrition/diagnosis , Malnutrition/therapy , Middle Aged , Nutritional Support , Parenteral Nutrition
16.
Sci Rep ; 11(1): 22548, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1628380

ABSTRACT

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.


Subject(s)
Antibodies, Viral/immunology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Critical Illness/mortality , Middle East Respiratory Syndrome Coronavirus/immunology , Adult , Aged , Antibodies, Viral/blood , Antibody Formation , Cohort Studies , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Intensive Care Units , Kinetics , Male , Middle Aged , Organ Dysfunction Scores , Renal Replacement Therapy , Survival Analysis
17.
Am J Infect Control ; 50(9): 988-993, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1629725

ABSTRACT

BACKGROUND: The higher risk of COVID-19 in health care workers (HCWs) is well-known. However, the risk within HCWs is not fully understood. The objective was to compare the COVID-19 risk in intensive care unit (ICU) vs non-ICU locations. METHODS: A prospective surveillance study was conducted among HCWs at a large tertiary care facility in Riyadh between March 1st to November 30th, 2020. HCWs included both clinical (provide direct patient care) and nonclinical positions (do not provide direct patient care). RESULTS: A total 1,594 HCWs with COVID-19 were included; 103 (6.5%) working in ICU and 1,491 (93.5%) working in non-ICU locations. Compared with non-ICU locations, ICU had more nurses (54.4% vs 22.1%, P < .001) and less support staff (2.9% vs 53.1%, P < .001). COVID-19 infection was similar in ICU and non-ICU locations (9.0% vs 9.8%, P = .374). However, it was significantly higher in ICU nurses (12.3% vs 6.5%, P < .001). Support staff had higher risk than other HCWs, irrespective of ICU working status (15.1% vs 7.2%, P < 0.001). The crude relative risk of COVID-19 in ICU vs non-ICU locations was 0.92, 95% confidence interval ( was 0.76-1.11 (P = .374). However, relative risk adjusted for professional category was significantly increased to 1.23, 95% confidence interval 1.01-1.50 (P = .036). CONCLUSIONS: ICU had a significantly higher risk of COVID-19 infection only after adjusting for the distribution and risk of different professional categories. The latter is probably determined by both exposure level and protection practices. The finding underscores the importance of strict implementation of preventive measures among all HCWs, including those performing nonclinical services.


Subject(s)
COVID-19 , COVID-19/epidemiology , Critical Care , Health Personnel , Humans , Prospective Studies
18.
Critical care clinics ; 2022.
Article in English | EuropePMC | ID: covidwho-1615015

ABSTRACT

High-flow nasal oxygen (HFNO) and non-invasive ventilation (NIV) via face-mask or helmet have been increasingly used in the management of acute hypoxemic respiratory failure (AHRF) due to COVID-19 with the premise of reducing the need for invasive mechanical ventilation and possibly mortality. However, their use carries the risk of delaying intubation and nosocomial infection transmission. To this date, most studies on the effectiveness of these modalities are observational and suggest that HFNO and NIV have a role in the management of AHRF due to COVID-19. A randomized controlled trial among patients with COVID-19 showed that helmet NIV versus HFNO led to a lower intubation rate but no difference in survival or the duration of respiratory support. The RECOVERY respiratory support trial demonstrated that CPAP, but not HFNO reduced a composite outcome of tracheal intubation or mortality within 30-days compared with conventional oxygen therapy. Additional trials are ongoing and are evaluating different aspects of noninvasive respiratory support in patients with AHRF due to COVID-19.

19.
Crit Care ; 25(1): 424, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1577182

ABSTRACT

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.


Subject(s)
Enteral Nutrition , Intensive Care Units , Critical Illness , Food, Formulated , Humans , Residual Volume
20.
Clin Immunol ; 234: 108911, 2022 01.
Article in English | MEDLINE | ID: covidwho-1588089

ABSTRACT

BACKGROUND: Natural killer (NK) cells play an essential role against viruses. NK cells express killer cell immunoglobulin-like receptors (KIRs) which regulate their activity and function. The polymorphisms in KIR haplotypes confer differential viral susceptibility and disease severity caused by infections. We investigated the association between KIR genes and COVID-19 disease severity. METHODS: 424 COVID-19 positive patients were divided according to their disease severity into mild, moderate and severe. KIR genes were genotyped using next generation sequencing (NGS). Association between KIR genes and COVID-19 disease severity was conducted and significant correlations were reported. RESULTS: In the COVID-19 patients, KIR Bx genotype was more common than AA genotype. The Bx genotype was found more frequently in patients with mild disease, while in severe disease the AA genotype was more common than the Bx genotype. The KIR2DS4 gene carried the highest risk for severe COVID-19 infection (OR 8.48, pc= 0.0084) followed by KIR3DL1 (OR 7.61, pc= 0.0192). CONCLUSIONS: Our findings suggest that KIR2DS4 and KIR3DL1 genes carry risk for severe COVID-19 disease.


Subject(s)
COVID-19/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic/genetics , Receptors, KIR/genetics , Adult , COVID-19/metabolism , Female , Gene Frequency/genetics , Genotype , Humans , Killer Cells, Natural/metabolism , Male , Middle Aged , SARS-CoV-2/pathogenicity
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