To Access Knowledge Regarding Organ Donation among Healthcare Workers and Their Willingness toward Organ Donation.

BACKGROUND: In India, critical shortage of organ donations, particularly deceased donations, has led to a dire situation in India, with thousands of patients waiting for transplants and a significant number of them succumbing. One of the reasons for the shortage of organs for transplantation is unawareness and prejudiced information about organ donation. Being direct or indirect stakeholders, the knowledge regarding organ donation among healthcare workers may play an important role in the donation process. AIM: To assess the knowledge regarding cadaver organ donation among healthcare workers and their willingness toward organ donation. MATERIALS AND METHODS: It is a cross-sectional offline self-administered questionnaire-based survey conducted among healthcare professionals at tertiary care teaching institutes. Survey was carried out between the months of August to December 2019. A structured questionnaire was used to assess knowledge and willingness toward organ donation. Statistical analyzed was done by using statistical package for social sciences (SPSS) 20.0. All p-values were considered significant at <0.05. RESULTS: A total of 1,039 healthcare professionals participated in the survey. Out of them, 362 (34.8%) were males and 675 (65%) were females. Average age of the healthcare workers participating in survey was 30.81 years, and age ranged from 18 to 60 years. Awareness regarding corneal donation after brain death was found to be maximum (89.7%) and was comparable to that of kidney (86.6%) and heart (83.7%). Participants were unlearned of donation of lungs, pancreas, hands and unaware of heart valve donation. About 45% respondents considered that age affected the donors. About 40% respondents considered younger patients as ideal recipients, while 18.7% respondents considered waiting list patients as ideal recipients. Doctors had highest willingness (78. 3%) for organ donation, followed by nurses (69.9%) and support staff (59.3%) (p < 0.001). Only 119 (11.5%) participants received organ donation cards as against 68.7% willingness toward organ donation (p < 0.01). CONCLUSION: We have observed fair awareness regarding overall cadaver organ donation concept among healthcare workers. There is a need to improve knowledge of extended age criteria and which organs can be retrieved from deceased donor. Authorities have to work hard on delivery of organ donation pledging card to promote donation program.

Metabolic management of accidental intoxication.

PURPOSE OF REVIEW: Unintentional intoxication comprises a major chunk of all intoxications. Most patients are in the pediatric age group with another set of patients being the elderly. Substances found to cause accidental intoxication vary from country to country and even within different regions of a country. Frequent reviews of current literature are needed to be abreast of trends. RECENT FINDINGS: Prescription drugs and household chemicals are major culprits when it comes to accidental intoxication. Acetaminophen, digoxin and metformin are some of the prominent prescription drugs frequently associated with unintentional intoxications. Increasingly alcohol based hand sanitizers are becoming an important etiology of these events, following their increased usage during the COVID-19 pandemic. Pattern recognition to identify class of intoxicant and supportive care including prevention of further absorption and increased excretion are cornerstones of therapy. Antidote when available should be used promptly. SUMMARY: Knowledge about current epidemiology of accidental intoxications, toxidrome pattern recognition and appropriate antidote usage beside adequate and timely supportive care help in successful management of the unfortunate victim of accidental intoxication.

Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study).

Background: Critically ill patients are frequently transported to various locations within the hospital for diagnostic and therapeutic purposes, which increases the risk of adverse events (AEs). This multicenter prospective observational study was undertaken to determine the incidence of AEs related to intrahospital transport, their severity, and their effects on patient outcomes. Patients and methods: We included consecutive unstable critically ill patients requiring intrahospital transport, across 15 Indian tertiary care centers over 5 months (October 11, 2022-February 20, 2023). Apart from the demographics and severity of illness, data related to transport itself, such as indications and destination, incidence of AEs, their category and treatment required, and patient outcomes, were recorded in a standard form. Results: Eight hundred and ninety-three patients were transported on 1065 occasions out of the intensive care unit (ICU). The mean (SD) acute physiology and chronic health evaluation II score of the patients was 15.38 (±7.35). One hundred and two AEs occurred, wherein cardiovascular instability was the most common occurrence (31, 30.4%). Two patients had cardiac arrest immediately after transport. Acute physiology and chronic health evaluation II [odds ratio (OR): 1.02, 95% confidence interval (CI) - 1.00-1.05, p = 0.04], emergent transport (OR: 5.11, 95% CI - 3.32-7.88, p = 0.00), and team composition (OR: 5.34, 95% CI - 1.63-17.5, p = 0.00) during transport were found to be independent predictors of AEs. Conclusion: We found a high incidence of AEs during intrahospital transport of critically ill patients. These events were more common during emergent transports and when the patients were transported by doctors. Transport by itself was not related to ICU mortality. We feel that stabilization of the patients before transport and adherence to a standardized protocol may help in minimizing the AEs, thereby enhancing patient safety. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Govil D, Dixit SB, Munjal M, et al. Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study). Indian J Crit Care Med 2023;27(9):635-641.

Utility of Bedside Ultrasound Measurement of Optic Nerve Sheath Diameter as a Screening Tool for raised Intracranial Pressure in Neurocritical Care Prospective Observational Study.

Intracranial pressure (ICP) needs to be monitored in neurocritical patients. There is a need for portable bedside optic nerve ultrasound (ONUS) for early diagnosis to initiate the measures to reduce ICP Objective: To find the utility of bedside ONUS to diagnose raised ICP in neurocritical care. Materials and methods: After approval from the ethical committee, a prospective observational study was conducted. Optic nerve sheath diameter (ONSD) was measured in two groups: control group patients with neurological symptoms but computed tomography (CT)/magnetic resonance imaging (MRI) not suggestive of raised ICP, and second was study group patients with neurological symptoms and CT/MRI suggestive of elevated ICP Result: In patients with normal ICP, the mean ONSD in females was 4.47mm, and in males was 4.66mm. In patients with raised ICP, the mean ONSD in females was 6.45 ± 0.78 mm, and in males was 6.33 ± 0.70 mm. Regarding the correlation between Glasgow coma scale (GCS) and mean ONSD parameters, the coefficient of correlation (R) is 0.14; thus, there is a weak negative correlation. In our study, no difference was observed in raised mean ONSD in patients with different diagnoses. At a cut-off value of >4.8 mm, the sensitivity and specificity are 100% to diagnose raised ICP. Conclusion: Optic nerve sheath diameter (ONSD) is a reliable, rapid bedside screening tool in the Emergency Department/Critical Care/Operation Theatre to diagnose raised ICP. In order to keep a record of trends in ICP, we need to measure ONSD frequently. There was no correlation between GCS and ONSD measurement.

Ulinastatin Add-on to Standard of Care in Critically Ill COVID-19 Patients: A Multicenter, Retrospective Study.

AIM: To assess the impact on 30-day mortality with ulinastatin (ULI) used as add-on to standard of care (SOC) compared to SOC alone in coronavirus disease (COVID-19) patients requiring admission to the intensive care unit (ICU). MATERIALS AND METHODS: In this multicentric, retrospective study, we collected data on clinical, laboratory, and outcome parameters in patients with COVID-19. Thirty-day mortality outcome was compared among patients treated with SOC alone and ULI used as add-on to SOC. Odds ratio (OR) and 95% confidence intervals (CI) were determined to identify the predictors of 30-day mortality. RESULTS: Ninety-four patients were identified and enrolled in both groups with comparable baseline parameters. On univariate analysis, 30-day mortality was significantly lower in ULI plus SOC group than SOC alone group (36.2 vs 51.1%, OR 0.54, 95% CI 0.30-0.97, p = 0.040). The effect on mortality was more pronounced in patients who did not require intubation (10.9 vs 34.0%, OR 0.24, 95% CI 0.09-0.66, p = 0.006) and with early administration (within 72 hours of admission) of ULI (30.7 vs 57.9%, OR 0.32, 95% CI 0.11-0.91, p = 0.032). On multivariate analysis, only intubation predicted mortality (adjusted OR 10.13, 95% CI 3.77-27.25, p<0.0001) and the effect of ULI on survival was not significant (adjusted OR 0.58, 95% CI 0.22-1.52, p = 0.270). CONCLUSION: Given the limited options for COVID-19 patients treated in ICU, early administration of ULI may be helpful, especially in patients not requiring intubation to improve the outcomes. Further, a large, randomized study is warranted to confirm these findings.

Retrospective Cohort Observational Study to compare the Effect of Mycobacterium w along with Standard of Care vs Standard of Care alone in critically ill COVID-19 Patients.

BACKGROUND: COVID-19 has created enormous health crisis in India due to limited available treatments. Majority of the physicians use sepsis as a prototype to understand the pathophysiology of COVID-19 as there are similarities. Heat-killed Mycobacterium w (Mw) (Inj. Mw®) is a known immunomodulator, which is approved for the treatment of gram-negative sepsis. This observational study was aimed to evaluate the role of Mw along with standard of care (SOC) in critically ill COVID-19 patients. METHODS: Total 448 patients' data (intervention group: 298 in Mw plus SOC vs 150 in SOC alone) with reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed critically ill COVID-19 patients who were admitted at five tertiary care centers were evaluated. They were observed for changes in laboratory [C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), and interleukin-6 (IL-6)] parameters, hospital stay, intensive care unit (ICU) stay, and discharge status after giving 0.3 mL intradermal Mw for 3 consecutive days along with SOC during hospitalization. Standard of care included injectable steroids, remdesivir, and heparin. Data were analyzed using STATA 14.2 (StataCorp., College Station, Texas, USA). RESULTS: In baseline characteristics, Mw plus SOC arm had more critically ill patients as seen by higher high-resolution computed tomography (HRCT) score, higher lab values [CRP, ferritin, D-dimer, LDH, creatinine, alanine aminotransferase (ALT)], and more oxygen requirement as compared to SOC alone. Mycobacterium w arm had significantly higher mortality rate in ICU and hospital. Both hospital stay and ICU stay were longer in Mw arm. However, subgroup analysis found that early initiation of Mw (<3 days vs >3 days) was associated with significantly lesser odds of mortality and lesser odds of intubation requirement. Early initiation of Mw (<3 days vs >3 days) also resulted in significantly lesser duration of stay in the ICU along with reduction of CRP, D-dimer, and LDH. Moreover, further analysis of early initiation of Mw (<3 days vs control) resulted in significant reduction in lab values (procalcitonin, CRP, ferritin, LDH, and D-dimer). CONCLUSION: Mw when added to SOC was found to associate with significantly increased risk of mortality and increased length of hospital stay. However, time since admission to administration of Mw was a significant predictor of in-ICU deaths in multivariate analysis. Early initiation of Mw (<3 days) was observed to be a protective factor against ICU deaths from the multivariate logistic regression model. However, large randomized controlled trials are required to support the same.

Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia.

PURPOSE: We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. METHODS: We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. RESULTS: We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). CONCLUSION: Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.

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.

Noninvasive Respiratory Assist Devices in the Management of COVID-19-related Hypoxic Respiratory Failure: Pune ISCCM COVID-19 ARDS Study Consortium (PICASo).

Objective: To determine whether high-flow nasal oxygen (HFNO) or noninvasive ventilator (NIV) can avoid invasive mechanical ventilation (IMV) in COVID-19-related acute respiratory distress syndrome (ADRS), and the outcome predictors of these modalities. Design: Multicenter retrospective study conducted in 12 ICUs in Pune, India. Patients: Patients with COVID-19 pneumonia who had PaO2/FiO2 ratio <150 and were treated with HFNO and/or NIV. Intervention: HFNO and/or NIV. Measurements: The primary outcome was to assess the need of IMV. Secondary outcomes were death at Day 28 and mortality rates in different treatment groups. Main results: Among 1,201 patients who met the inclusion criteria, 35.9% (431/1,201) were treated successfully with HFNO and/or NIV and did not require IMV. About 59.5% (714/1,201) patients needed IMV for the failure of HFNO and/or NIV. About 48.3, 61.6, and 63.6% of patients who were treated with HFNO, NIV, or both, respectively, needed IMV. The need of IMV was significantly lower in the HFNO group (p <0.001). The 28-day mortality was 44.9, 59.9, and 59.6% in the patients treated with HFNO, NIV, or both, respectively (p <0.001). On multivariate regression analysis, presence of any comorbidity, SpO2 <90%, and presence of nonrespiratory organ dysfunction were independent and significant determinants of mortality (p <0.05). Conclusions: During COVID-19 pandemic surge, HFNO and/or NIV could successfully avoid IMV in 35.5% individuals with PO2/FiO2 ratio <150. Those who needed IMV due to failure of HFNO or NIV had high (87.5%) mortality. How to cite this article: Jog S, Zirpe K, Dixit S, Godavarthy P, Shahane M, Kadapatti K, et al. Noninvasive Respiratory Assist Devices in the Management of COVID-19-related Hypoxic Respiratory Failure: Pune ISCCM COVID-19 ARDS Study Consortium (PICASo). Indian J Crit Care Med 2022;26(7):791-797.

ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy.

Acute kidney injury (AKI) is a complex syndrome with a high incidence and considerable morbidity in critically ill patients. Renal replacement therapy (RRT) remains the mainstay of treatment for AKI. There are at present multiple disparities in uniform definition, diagnosis, and prevention of AKI and timing of initiation, mode, optimal dose, and discontinuation of RRT that need to be addressed. The Indian Society of Critical Care Medicine (ISCCM) AKI and RRT guidelines aim to address the clinical issues pertaining to AKI and practices to be followed for RRT, which will aid the clinicians in their day-to-day management of ICU patients with AKI. How to cite this article: Mishra RC, Sodhi K, Prakash KC, Tyagi N, Chanchalani G, Annigeri RA, et al. ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy. Indian J Crit Care Med 2022;26(S2):S13-S42.

Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation.

How to cite this article: Srinivasan S, Kumar PG, Govil D, Gupta S, Kumar V, Pichamuthu K, et al. Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S7-S12.

Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics.

How to cite this article: Khilnani GC, Tiwari P, Zirpe KG, Chaudhary D, Govil D, Dixit S, et al. Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics. Indian J Crit Care Med 2022;26(S2):S77-S94.

Recommendations for Evaluation and Selection of Deceased Organ Donor: Position Statement of ISCCM.

There is a wide gap between patients who need transplants and the organs that are available in India. Extending the standard donation criterion is certainly important to address the scarcity of organs for transplantation. Intensivists play a major role in the success of deceased donor organ transplants. Recommendations for deceased donor organ evaluation are not discussed in most intensive care guidelines. The purpose of this position statement is to establish current evidence-based recommendations for multiprofessional critical care staff in the evaluation, assessment, and selection of potential organ donors. These recommendations will give "real-world" criteria that are acceptable in the Indian context. The aim of this set of recommendations is to both increase the number and enhance the quality of transplantable organs. How to cite this article: Zirpe KG, Tiwari AM, Pandit RA, Govil D, Mishra RC, Samavedam S, et al. Recommendations for Evaluation and Selection of Deceased Organ Donor: Position Statement of ISCCM. Indian J Crit Care Med 2022;26(S2):S43-S50.

Indian Society of Critical Care Medicine Consensus Statement for Prevention of Venous Thromboembolism in the Critical Care Unit.

Deep vein thrombosis (DVT) is a preventable complication of critical illness, and this guideline aims to convey a pragmatic approach to the problem. Guidelines have multiplied over the last decade, and their utility has become increasingly conflicted as the reader interprets all suggestions or recommendations as something that must be followed. The nuances of grade of recommendation vs level of evidence are often ignored, and the difference between a "we suggest" vs a "we recommend" is overlooked. There is a general unease among clinicians that failure to follow the guidelines translates to poor medical practice and legal culpability. We attempt to overcome these limitations by highlighting ambiguity when it occurs and refraining from dogmatic recommendations in the absence of robust evidence. Readers and practitioners may find the lack of specific recommendations unsatisfactory, but we believe that true ambiguity is better than inaccurate certainty. We have attempted to comply with the guidelines on how to create guidelines.1 And to overcome the poor compliance with these guidelines.2 Some observers have expressed concern that DVT prophylaxis guidelines may cause more harm than good.3 We have placed greater emphasis on large randomized controlled trials (RCTs) with clinical end point and de-emphasized RCTs with surrogate end points and also de-emphasized hypothesis generating studies (observational studies, small RCTs, and meta-analysis of these studies). We have de-emphasized RCTs in non-intensive care unit populations like postoperative patients or those with cancer and stroke. We have also considered resource limitation settings and have avoided recommending costly and poorly proven therapeutic options. How to cite this article: Jagiasi BG, Chhallani AA, Dixit SB, Kumar R, Pandit RA, Govil D, et al. Indian Society of Critical Care Medicine Consensus Statement for Prevention of Venous Thromboembolism in the Critical Care Unit. Indian J Crit Care Med 2022;26(S2):S51-S65.

Intensive Care in India in 2018-2019: The Second Indian Intensive Care Case Mix and Practice Patterns Study.

BACKGROUND: We aimed to study organizational aspects, case mix, and practices in Indian intensive care units (ICUs) from 2018 to 2019, following the Indian Intensive Care Case Mix and Practice Patterns Study (INDICAPS) of 2010-2011. METHODS: An observational, 4-day point prevalence study was performed between 2018 and 2019. ICU, patient characteristics, and interventions were recorded for 24 hours, and ICU outcomes till 30 days after the study day. Adherence to selected compliance measures was determined. Data were analyzed for 4,669 adult patients from 132 ICUs. RESULTS: On the study day, mean age, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were 56.9 ± 17.41 years, 16.7 ± 9.8, and 4.4 ± 3.6, respectively. Moreover, 24% and 22.2% of patients received mechanical ventilation (MV) and vasopressors or inotropes (VIs), respectively. On the study days, 1,195 patients (25.6%) were infected and 1,368 patients (29.3%) had sepsis during their ICU stay. ICU mortality was 1,092 out of 4,669 (23.4%), including 737 deaths and 355 terminal discharges (TDs) from ICU. Compliance for process measures related to MV ranged between 62.7 and 85.3%, 11.2 and 47.4% for monitoring delirium, sedation, and analgesia, and 7.7 and 25.3% for inappropriate transfusion of blood products. Only 34.8% of ICUs routinely used capnography. Large hospitals with ≥500 beds, closed ICUs, the APACHE II and SOFA scores, medical admissions, the presence of cancer or cirrhosis of the liver, the presence of infection on the study day, and the need for MV or VIs were independent predictors of mortality. CONCLUSIONS: Hospital size and closed ICUs are independently associated with worse outcomes. The proportion of TDs remains high. There is a scope for improvements in processes of care.Registered at clinicaltrials.gov (NCT03631927). HOW TO CITE THIS ARTICLE: Divatia JV, Mehta Y, Govil D, Zirpe K, Amin PR, Ramakrishnan N, et al. Intensive Care in India in 2018-2019: The Second Indian Intensive Care Case Mix and Practice Patterns Study. Indian J Crit Care Med 2021;25(10):1093-1107.

Therapeutic Approaches in Modulating the Inflammatory and Immunological Response in Patients With Sepsis, Acute Respiratory Distress Syndrome, and Pancreatitis: An Expert Opinion Review.

Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.

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.

How Have Nutrition Practices in the ICU Changed in the Last Decade (2011-2020): A Scoping Review.

Malnutrition is more prevalent in the critically ill than ambulatory patients due to a variety of factors. Strategies employed in the optimization of nutrition practices rely largely on the review of published literature and guidelines. While the last decade was marked by some landmark large randomized controlled trials taking place and some high-quality systematic reviews, it still has left us with many unanswered questions. The evidence generated by these trials can, to a good extent, extrapolate to the developed countries. However, its implementation in developing and third-world countries needs further elaboration and logistical considerations. With this scoping review, we attempt to provide insights into the landmark developments in the decade 2011-2020. Solutions to employ and implement the results of these developments and ways for their corroboration into a larger population are also discussed.

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.

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.