Energy expenditure in COVID-19 mechanically ventilated patients: A comparison of three methods of energy estimation.

BACKGROUND: Indirect calorimetry (IC) is the gold standard for measuring resting energy expenditure. Energy expenditure (EE) estimated by ventilator-derived carbon dioxide consumption (EEVCO2 ) has also been proposed. In the absence of IC, predictive weight-based equations have been recommended to estimate daily energy requirements. This study aims to compare simple predictive weight-based equations with those estimated by EEVCO2 and IC in mechanically ventilated patients of COVID-19. METHODS: Retrospective study of a cohort of critically ill adult patients with COVID-19 requiring mechanical ventilation and artificial nutrition to compare energy estimations by three methods through the calculation of bias and precision agreement, reliability, and accuracy rates. RESULTS: In 58 mechanically ventilated patients, a total of 117 paired measurements were obtained. The mean estimated energy derived from weight-based calculations was 2576 ± 469 kcal/24 h, as compared with 1507 ± 499 kcal/24 h when EE was estimated by IC, resulting in a significant bias of 1069 kcal/day (95% CI [-2158 to 18.7 kcal]; P < 0.001). Similarly, estimated mean EEVCO2 was 1388 ± 467 kcal/24 h when compared with estimation of EE from IC. A significant bias of only 118 kcal/day (95% CI [-187 to 422 kcal]; P < 0.001), compared by the Bland-Altman plot, was noted. CONCLUSION: The energy estimated with EEVCO2 correlated better with IC values than energy derived from weight-based calculations. Our data suggest that the use of simple predictive equations may potentially lead to overfeeding in mechanically ventilated patients with COVID-19.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS: This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION: This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

Smart secretion management to protect nurses from COVID19 and other infectious diseases.

BACKGROUND: COVID-19 has been linked to over 40 million infections and 1.1 million deaths in 210 countries as of October 19, 2020. This highly contagious communicable disease has put not only infected individuals but other patients and frontline workers like nurses at risk in hospitals, especially in Intensive Care units (ICUs). There is a need for minimizing patient contact, improving hand hygiene practices, and optimizing healthcare provider time, especially nurses. Globally it is estimated that nearly a million health care providers have been infected with COVID-19 as of the end of October 2020. METHODS: This retrospective service evaluation documents the experience of health care providers in a COVID-19 ICU in India that was used to implement new protocols for secretion management and oral hygiene. Patient chart information and staff feedback were utilized. INTERVENTION: This pilot study captures the practical benefits of using VAPCare, an automated, closed-loop system for oral secretion removal. RESULTS: Six patients were included in this small-scale study; three patients following the current standard of care for suctioning and oral hygiene and three receiving the new VAPCare and Lumen device protocol. With the new device protocol, the number of infected secretion interactions by a nurse was 50% lower, and nursing time spent on oral hygiene and secretion management 70% less than seen with the current standard of care. The number of disposable gloves used with VAPCare and Lumen was reduced by over 50%. All 10 nurses and six doctors gave positive feedback on device usage. The department recommended updating protocols to prioritize the use of the new secretion management system for patients with COVID19 and other highly contagious conditions. CONCLUSION: The findings are an early indication that using VAPCare for patients could help protect infected patients, other ICU patients, and health care workers.

Thromboelastography Profile of Patients with COVID-19 Admitted to Intensive Care Unit: A Single-center Retrospective Study from India.

Coronavirus disease (COVID-19) causes thromboinflammation resulting in a high incidence of venous thromboembolism (VTE) events, which occur in significant numbers despite giving standard thromboprophylaxis with low-molecular-weight heparins. Various markers and tests have been evaluated and found to have a strong association with the worse prognosis of the disease. Common coagulation markers like D-dimer and fibrinogen give more of a static picture of coagulation, whereas viscoelastic tests like thromboelastography (TEG) provide an understanding of the coagulation function and help in better interpretation. We conducted a retrospective analysis of TEG values of 32 patients with COVID-19 admitted to the intensive care unit (ICU). Hypercoagulation as defined by TEG-coagulation index (CI) higher than the upper limit of the normal reference range (NRR) is found in 62.5% of the patients. There is also a clear representation of hypercoagulability as reflected by TEG-R, TEG-K, and TEG-LY30 values lower than or toward the lower limit of NRR, and TEG-ANGLE, TEG-MA, and TEG-CI values higher than or toward the upper limit of NRR which is more pronounced in severe forms of the disease, both in comparison to NRRs and other non-COVID ICU patients. Findings are similar to that of earlier studies in patients with COVID-19 except for the LY30, which is retained in the majority of our patients. Thromboelastography can be a useful tool to understand and screen for COVID-19-related hypercoagulability and may help predict VTE events. The potential of TEG to determine the optimal anticoagulant therapy needs to be evaluated in larger prospective studies. How to cite this article: Saseedharan S, Talla VB, Chiluka A. Thromboelastography Profile of Patients with COVID-19 Admitted to Intensive Care Unit: A Single-center Retrospective Study from India. Indian J Crit Care Med 2020;24(12):1218-1222.

CT Scan Findings of Five Mildly Symptomatic COVID Patients from India.

The outbreak of the SARS-Cov-2 (Severe Acute Respiratory Syndrome - Coronavirus 2) viral pandemic which started at Wuhan China has spread to 200 countries and have resulted in a huge loss to mankind and the global economy. Computerised Tomographic (CT) scan may play an important role in the diagnosis and management of the COVID -19-the disease caused by the SARS-Cov-2. This modality might help in triaging this extremely contagious disease and thus help serve in reducing the outbreak. We present five cases that presented to the hospital with mild symptoms, where the CT scan findings were disproportionate to the symptoms thus leading to effective triage. This resulted in effective disposition in isolation ward and thus helped to protect the healthcare workers from contraction of the disease. This is especially important as the definitive diagnosis via RT-PCR (Reverse Transcriptase - Polymerase Chain Reaction) would take almost 24 hours in the present time in India. Key Words: CT scan, COVID- 19, Triage, SARS-Cov-2.