Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Cytokine Storm and Immunomodulation in COVID-19.

COVID-19 has become a major pandemic in recent times. The exact pathophysiology and understanding of cytokine storm and immunomodulation are evolving. Various cytokines have been implicated in the pathophysiology of COVID-19. Immunosuppressant immunomodulators like steroids, canakinumab, anakinra, tocilizumab, sarilumab, baricitinib, ruxolitinib, bevacizumab, and itolizumab have been tried. Immunostimulant immunomodulators like interferons (IFNs) and Mycobacterium w (Mw) have also been repurposed. Considering the role of multiple cytokines implicated in COVID-19, molecules working on the majority of the targets, may hold a promising future prospect. HOW TO CITE THIS ARTICLE: Rangappa P. Cytokine Storm and Immunomodulation in COVID-19. Indian J Crit Care Med 2021;25(11):1288-1291.

Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19.

INTRODUCTION: There is strong evidence for the use of corticosteroid in the management of severe coronavirus disease-2019 (COVID-19). However, there is still uncertainty about the timing of corticosteroids. We undertook a modified Delphi study to develop expert consensus statements on the early identification of a subset of patients from non-severe COVID-19 who may benefit from using corticosteroids. METHODS: A modified Delphi was conducted with two anonymous surveys between April 30, 2021, and May 3, 2021. An expert panel of 35 experts was selected and invited to participate through e-mail. The consensus was defined as >70% votes in multiple-choice questions (MCQ) on Likert-scale type statements, while strong consensus as >90% votes in MCQ or >50% votes for "very important" on Likert-scale questions in the final round. RESULTS: Twenty experts completed two rounds of the survey. There was strong consensus for the increased work of breathing (95%), a positive six-minute walk test (90%), thorax computed tomography severity score of >14/25 (85%), new-onset organ dysfunction (using clinical or biochemical criteria) (80%), and C-reactive protein >5 times the upper limit of normal (70%) as the criteria for patients' selection. The experts recommended using oral or intravenous (IV) low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days and monitoring of oxygen saturation, body temperature, clinical scoring system, blood sugar, and inflammatory markers for any "red-flag" signs. CONCLUSION: The experts recommended against indiscriminate use of corticosteroids in mild to moderate COVID-19 without the signs of clinical worsening. Oral or IV low-dose corticosteroids (the equivalent of 6 mg/day dexamethasone) for 5-10 days are recommended for patients with features of disease progression based on clinical, biochemical, or radiological criteria after 5 days from symptom onset under close monitoring. HOW TO CITE THIS ARTICLE: How to cite this article: Nasa P, Chaudhry D, Govil D, Daga MK, Jain R, Chhallani AA, et al. Expert Consensus Statements on the Use of Corticosteroids in Non-severe COVID-19. Indian J Crit Care Med 2021;25(11):1280-1285.

Current Approaches to COVID-19: Therapy and Prevention.

The coronavirus disease-2019 (COVID-19) pandemic has affected millions of people worldwide. As our understanding of the disease is evolving, our approach to the patient management is also changing swiftly. Available new evidence is helping us take radical decisions in COVID-19 management. We searched for inclusion of the published literature on treatment of COVID-19 from around the globe. All relevant evidences available till the time of submission of this article were briefly discussed. Once advised as blanket therapy for all patients, recent reports of hydroxychloroquine with or without azithromycin indicated no potential benefit and use of such combination may increase the risk of arrhythmias. Clinical evidence with newer antivirals such as remdesivir and favipiravir is promising that can hasten the patient recovery and reduce the mortality. With steroids, evidence is much clear in that it should be used in low dose and for short period not extending beyond 7 days in moderate to severe hospitalized patients. Low-molecular-weight heparin should be initiated in all hospitalized COVID-19 patients and dose should be based on the coagulation profile and risk of thromboembolism. Immunomodulatory drugs such tocilizumab may be considered for severe and critically ill patients to improve the outcomes. Though ulinastatin can be a potential alternative immunomodulator, there is lack of clinical evidence on its usage in COVID-19. Convalescent plasma therapy can be potentially lifesaving in critically ill patients. However, there is need to generate further evidence with various such therapies. Though availability of a potent vaccine is awaited, current treatment of COVID-19 is based on available therapies, which is guided by the evidence. In this review, we discuss the potential treatments available around the globe with current evidence on each of such treatments. How to cite this article: Dixit SB, Zirpe KG, Kulkarni AP, Chaudhry D, Govil D, Mehta Y, et al. Current Approaches to COVID-19: Therapy and Prevention. Indian J Crit Care Med 2020;24(9):838-846.

Outcome of Patients Admitted to a Tertiary Referral Intensive Care Unit with Urosepsis Needing Source Control.

INTRODUCTION: Urosepsis is one of the common causes of admission to the Intensive Care Unit (ICU). It has traditionally been treated with antibiotics, but surgical management with Double J [DJ] ureteral stents is gaining popularity. This study compares patients with complicated urosepsis who underwent surgical source control by ureteral stenting with those managed medically. MATERIALS AND METHODS: The study enrolled patients admitted to a tertiary adult ICU with a diagnosis of urosepsis over a period of 2 years. The primary outcomes were renal replacement therapy (RRT) requirement and ICU mortality. The secondary outcomes were ICU and hospital length of stay, ventilator-free days, and inotrope free days. Patients were divided those with obstructive and nonobstructive urinary tract infection (UTI). RESULTS: A total of 58 patients met the criteria, of who 32 had obstructive UTI and were included in Group A, with the remaining 26 with nonobstructive UTI comprised Group B. In Group A, 27 patients underwent source control with ureteral DJ stenting, three patients recovered with medical management, and two who were advised source control did not consent to the procedure. Seventeen patients in Group A and seven patients in Group B required RRT (P = 0.044). There was no significant difference in ICU mortality, hospital mortality, and 28 days survival between the two groups. CONCLUSION: With early source control, obstructive UTI outcomes were comparable to nonobstructive UTI. However, despite undergoing ureteric stenting, more patients with obstructive UTI required RRT than those with nonobstructive UTI.

Cerebrospinal Fluid Lactate as a Prognostic Indicator in Postneurosurgical Bacterial Meningitis and Use of Intrathecal Colistin.

Postneurosurgical bacterial meningitis (PNBM) is an emergency and requires early diagnosis and treatment with appropriate antibiotics. The cornerstone of diagnosis is microbiological analysis of the cerebrospinal fluid (CSF) cytochemical characteristics such as leucocyte count, CSF glucose, and protein concentration and CSF: Serum glucose ratio. However, this is often misleading in PNBM. The role of CSF lactate assay for diagnosis and prognosis has been debated. This case report looks into the serial measurement of CSF lactates in PNBM. It also looks into the role of intrathecal colistin. CSF lactate showed a steady decrease corresponding to improvement in clinical condition. Hence, CSF lactate could have a better prognostic value than other conventional markers in PNBM. Intrathecal colistin, in conjunction with the standard antibiotics, can contribute to a quick resolution of the condition.

Practice Guidelines for Nutrition in Critically Ill Patients: A Relook for Indian Scenario.

BACKGROUND AND AIM: Intensive-care practices and settings may differ for India in comparison to other countries. While international guidelines are available to direct the use of enteral nutrition (EN), there are no recommendations specific to Indian settings. Advisory board meetings were arranged to develop the practice guidelines specific to Indian context, for the use of EN in critically ill patients and to overcome challenges in this field. METHODS: Various existing guidelines, meta-analyses, randomized controlled trials, controlled trials, and review articles were reviewed for their contextual relevance and strength. A systematic grading of practice guidelines by advisory board was done based on strength of the supporting evidence. Wherever Indian studies were not available, references were taken from the international guidelines. RESULTS: Based on the literature review, the recommendations for developing the practice guidelines were made as per the grading criteria agreed upon by the advisory board. The recommendations were to address challenges regarding EN versus parenteral nutrition; nutrition screening and assessment; nutrition in hemodynamically unstable; route of nutrition; tube feeding and challenges; tolerance; optimum calorie-protein requirements; selection of appropriate enteral feeding formula; micronutrients and immune-nutrients; standard nutrition in hepatic, renal, and respiratory diseases and documentation of nutrition practices. CONCLUSION: This paper summarizes the optimum nutrition practices for critically ill patients. The possible solutions to overcome the challenges in this field are presented as practice guidelines at the end of each section. These guidelines are expected to provide guidance in critical care settings regarding appropriate critical-care nutrition practices and to set up Intensive Care Unit nutrition protocols.

Pseudocholinesterase as a predictor of mortality and morbidity in organophosphorus poisoning.

BACKGROUND: Organophosphorus (OP) pesticide poisoning is a major clinical and public health problem in India. Mortality rate remains high at 15%-30%. AIMS: This prospective, observational study examines the relationship between pseudocholinesterase (PChE) activity and morbidity and mortality in OP poisoning. SETTING AND DESIGN: OP poisoning cases admitted to a tertiary care center Intensive Care Unit (ICU) over 5 years from 2010 to 2014 were studied. METHODS: Patients <16 years of age, those on steroids and those with neuromuscular weakness, were excluded from the study. Serum PChE level at admission was estimated and the severity of poisoning assessed accordingly. Primary outcome measures were ICU length of stay and ventilator-free days. Secondary outcome measures included vasopressor-free days, amount of atropine given, hospital length of stay, and ICU mortality. RESULTS: There were 37 patients included in the study, aged between 24 and 44 years, of which 65% were male. They were divided into two groups according to PChE levels. Group A with PChE levels more than 1000 IU/L had twenty patients and Group B with levels <1000 IU/L had 17 patients. Group B had longer ICU length of stay (P < 0.001) and fewer ventilator-free days (P < 0.001). They also had a fewer vasopressor-free days and a longer stay in hospital. CONCLUSIONS: PChE level at presentation is a reliable indicator of the severity of OP poisoning and a predictor of the need for mechanical ventilation and the duration of stay in the ICU.

Efficacy of conivaptan and hypertonic (3%) saline in treating hyponatremia due to syndrome of inappropriate antidiuretic hormone in a tertiary Intensive Care Unit.

BACKGROUND: Hyponatremia is one of the most common electrolyte abnormalities encountered in clinical practice and has a significant impact on morbidity and mortality in hospitalized patients. The optimal management of hyponatremia is still evolving. Over the last decade, vaptans have been increasingly used in clinical practice with promising results. MATERIALS AND METHODS: The study included eighty patients with symptomatic hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) admitted and treated in Intensive Care Unit (ICU) with either conivaptan or hypertonic (3%) saline. They were compared for time taken to achieve normal serum sodium, length of ICU and hospital stay, and adverse effects. RESULTS: The demographic data and serum sodium levels at admission were comparable between the two groups. After initiating correction, sodium levels at 6, 12, and 24 h were similar between the two groups. However, at 48 h, patients in the conivaptan group (Group C) had higher sodium levels (133.0 ± 3.8 mEq/L) as compared to hypertonic saline group (Group HS) (128.9 ± 2.6 mEq/L), which was statistically significant (P < 0.001). The length of ICU stay was less in the Group C (3.35 ± 0.89 days) when compared with the Group HS (4.61 ± 0.91 days) (P < 0.001). There was no significant difference in mortality between the two groups. CONCLUSION: In patients with symptomatic hyponatremia due to SIADH, conivaptan with its aquaresis property can achieve a significantly better sodium correction, resulting in reduced ICU and hospital stay with no significant adverse effects.

Postoperative nutrition practices in abdominal surgery patients in a tertiary referral hospital Intensive Care Unit: A prospective analysis.

BACKGROUND: Benefit of early enteral feeds in surgical patients admitted to Intensive Care Units (ICUs) has been emphasized by several studies. Apprehensions about anastomotic leaks in gastrointestinal surgical patients prevent initiation of early enteral nutrition (EN). The impact of these practices on outcome in Indian scenario is less studied. AIMS: This study compares the impact of early EN (within 48 h after surgery) with late EN (48 h postsurgery) on outcomes in abdominal surgical ICU patients. SETTINGS AND DESIGN: Postabdominal surgery patients admitted to a tertiary referral hospital ICU over a 2-year period were analyzed. METHODS: Only patients directly admitted to ICU after abdominal surgery were included in this study. ICU stay>3 days was considered as prolonged; with average ICU length of stay (LOS) for this ICU being 3 days. The primary outcome was in-patient mortality. ICU LOS, hospital LOS, infection rates, and ventilator days were secondary outcome measures. Acute Physiology and Chronic Health Evaluation II scores were calculated. SPSS and Microsoft Excel were used for analysis. RESULTS: Of 91 ICU patients included, 58 received early EN and 33 late EN. Hospital LOS and infection rates were less in early EN group. Use of parenteral nutrition (odds ratio [OR] 5.25, 95% confidence interval (CI); P = 0.003) and number of nil-per-oral days (OR 8.25, 95% CI; P ≤ 0.001) were other predictors of prolonged LOS. CONCLUSIONS: Early EN in postabdominal surgery ICU patients was associated with reduced hospital LOS and infection rates. ICU LOS, duration of mechanical ventilation and mortality rates did not vary.

Recurrent pleural effusions: an unusual presentation of chronic pancreatitis.

Chronic pancreatitis is a rare cause of recurrent pleural effusion. Here is a case of recurrent massive left pleural effusions due to pancreaticopleural fistula (PPF) secondary to asymptomatic chronic pancreatitis. Pleural fluid analysis was inconclusive. Diagnosis was made by CT chest and abdomen and confirmed by MRCP and MRI. He required surgical intervention although medical management with pancreatic ductal stenting is the first line of treatment.

Haemophagocytic lymphohistiocytosis (HLH): case series in tertiary referral hospital over three years.

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease of normal but overactive histiocytes and lymphocytes that commonly appears in infancy, although it has been seen in all age groups. We are reporting a series of 5 cases of HLH in young adult and paediatric patients identified over three years.

India-discovered levonadifloxacin & alalevonadifloxacin: A review on susceptibility testing methods, CLSI quality control and breakpoints along with a brief account of their emerging therapeutic profile as a novel standard-of-care.

BACKGROUND: Levonadifloxacin (intravenous) and alalevonadifloxacin (oral prodrug) are novel antibiotics based on benzoquinolizine subclass of fluoroquinolone, licensed for clinical use in India in 2019. The active moiety, levonadifloxacin, is a broad-spectrum antibiotic with a high potency against methicillin-resistant Staphylococcus. aureus, multi-drug resistant pneumococci and anaerobes. OBJECTIVE: This review, for the first time, critically analyses the antimicrobial susceptibility testing methods, Clinical Laboratory & Standards Institute (CLSI)-quality control of susceptibility testing and breakpoints of levonadifloxacin. Further, the genesis, discovery and developmental aspects as well as therapeutic profile of levonadifloxacin and alalevonadifloxacin are briefly described. CONTENTS: In order to aid the scientific and clinician communities with a single comprehensive overview on all the key aspects of levonadifloxacin and alalevonadifloxacin, the present article covers the reference MIC and disk diffusion methods for levonadifloxacin susceptibility testing that were approved by CLSI and the reference ranges for quality control strains published in the CLSI M100 document. The breakpoints of levonadifloxacin were derived in concordance to US FDA, European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI approaches. Further, the article provides a brief account of challenges encountered during the discovery stages of levonadifloxacin and alalevonadifloxacin, activity spectrum and safety benefits accruing from structural novelty-linked mechanism of action. Further, the review also covers in vitro and in vivo activities, registrational clinical studies and patient-friendly features of levonadifloxacin/alalevonadifloxacin. Cumulatively, levonadifloxacin has a potential to offer a long awaited new standard-of-care treatment for the resistant Gram-positive bacterial infections.

Systemic thrombolytics as rescue therapy for COVID-19 patients with acute respiratory distress syndrome: A retrospective observational study.

Background: Coronavirus disease 2019 (COVID-19) pneumonia with severe acute respiratory distress syndrome (ARDS) is often associated with a progressive respiratory failure that is refractory to maximal ventilatory support and other ARDS strategies. Studies show evidence of a hypercoagulable state in COVID-19 patients, including capillary thrombosis and alveolar fibrin deposits which impede normal gas exchange. In this context, thrombolysis is considered as a salvage therapy to rescue critically hypoxemic patients. Methods: In this retrospective observational study, the efficacy of thrombolysis on outcome of COVID-19 ARDS with respiratory failure was analyzed. Patients with severe ARDS and d-dimer levels of 5 µg/ml or above were initiated on alteplase, as a 25 mg bolus followed by a 25 mg infusion over 22 h. Primary outcome was intensive care unit (ICU) mortality and secondary outcomes were change in PaO2/FiO2 24 h after thrombolysis, avoidance of intubation, ventilator free days (VFD), and ICU and hospital length-of-stay (LOS). Results: Thirteen out of 34 patients with severe COVID ARDS underwent thrombolysis. They had lower ICU mortality than non-thrombolysed patients (23.1% vs. 71.4%, P = 0.006), greater percentage improvement in PaO2/FiO2 (116% vs. 31.5%, P = 0.002), more VFDs (13 days vs. 0 day, P = 0.004), and lesser requirement for intubation (23.1% vs. 76.2%, P = 0.004). ICU and hospital LOS were similar. Conclusion: Thrombolysis can be considered as a rescue therapy for nonintubated COVID-19 ARDS patients with severe hypoxemic respiratory failure, who show evidence of a procoagulant state. Larger studies are needed before inclusion into the regular treatment protocol for COVID-19 patients.