Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19.

INTRODUCTION: Given the current lack of an approved and effective treatment or vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), repositioning old drugs for use as an antiviral treatment is an interesting strategy because knowledge about these drugs' safety profile, posology, and drug interactions is already known. Chloroquine and hydroxychloroquine, widely used as antimalarial and autoimmune disease drugs, have recently been reported as a potential broad-spectrum antiviral drug. BACKGROUND: The in vitro antiviral activity of chloroquine has been identified since the late 1960s. However, antiviral mechanisms of chloroquine remain speculative. Several clinical trials have been conducted to test the efficacy and safety of chloroquine or hydroxychloroquine in the treatment of COVID-19-associated pneumonia. The quality of the studies and the outcomes are evaluated in this systematic review and meta-analysis. REVIEW RESULTS: Literature review revealed 23 clinical studies. Only 9 of 23 studies were randomized controlled trials. Of nine randomized controlled trials, only study by Skipper et al. was deemed to be at low risk of bias. All studies evaluated variedwith different outcomes. Mechanical ventilation and virological clearance were the only common outcomes evaluated in more than two studies. Virological clearance odds ratio (OR) was 1.25 (95% confidence interval [CI] of 0.57-2.73; Chi2 = 0.83; I2 = 0%). GRADE quality of evidence was downgraded by three levels to very low due to concerns about the risk of bias, inconsistency, and imprecision. For mechanical ventilation, OR was 1.09 (95% CI 0.80-1.50; Chi2 = 0; I2 = 0). GRADE quality of evidence was downgraded by two levels to low due to concerns about the risk of bias and imprecision. There was no statistically significant difference between the groups for these two outcomes. CONCLUSION: As per the available evidence, based on our review, we conclude that hydroxychloroquine/chloroquine has not shown to be beneficial when used for the treatment of patients with COVID-19 pneumonia. HOW TO CITE THIS ARTICLE: Shetty RM, Namachivayam A. Evidence for Chloroquine/Hydroxychloroquine in the Treatment of COVID-19. Indian J Crit Care Med 2021;25(4):441-452.

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.

R0 and Re of COVID-19: Can We Predict When the Pandemic Outbreak will be Contained?

R0 (R naught) is the basic reproduction number, also known as basic reproduction ratio or rate which is an epidemiological metric used to measure the transmissibility of infectious agents. R0 is a derivative of the following variables-the duration of infectivity after the patient gets infected, the likelihood of transmission of infection per contact between a susceptible person and an infectious individual, and the contact rate. R0 is usually estimated retrospectively from serial epidemiological data or using theoretical mathematical models. Epidemiologists can calculate R0 using contact-tracing data, the most common method is to use cumulative incidence data. When mathematical models are used, R0 values are estimated using ordinary differential equations. R0 of COVID-19 as initially estimated by the World Health Organization (WHO) was between 1.4 and 2.4. The forecast is of critical importance as it will help the governments to have an estimate as well as strategize quickly to avoid any unfavorable condition. HOW TO CITE THIS ARTICLE: Achaiah NC, Subbarajasetty SB, Shetty RM. R0 and Re of COVID-19: Can We Predict When the Pandemic Outbreak will be Contained? Indian J Crit Care Med 2020;24(11):1125-1127.

A Unique Case of Arterial Thrombosis and Recurrent CVA in ICU: Unfathomable Presentation of an Occult Malignancy.

INTRODUCTION: Critically ill patients may present with prothrombotic manifestations. Carcinoma cervix with prothrombotic manifestations are not common. Arterial thrombosis in such cases is very rare. We present a case of carcinoma cervix which posed a diagnostic dilemma and difficulty in localizing primary. This patient also had recurrent strokes and cardiac metastasis with metastatic arterial thrombosis. CASE DESCRIPTION: A 34-year-old lady presented with a history of acute lower limb ischemia and recurrent strokes. Transthoracic echocardiography showed valvular vegetations. Prothrombotic and infective endocarditis workup were negative. Histopathological examination (HPE) of clot showed metastatic squamous cells. Contrast CT of chest and abdomen only showed mediastinal lymphadenopathy. Endobronchial ultrasound (EBUS) with mediastinal lymph node biopsy showed metastatic squamous cells. As the patient gave a history of hysterectomy, Pap smear from the vault was sent, which was suggestive of high grade squamous intraepithelial neoplasia. Palliative chemotherapy was started. The patient made a good recovery and was discharged home in a stable condition. CONCLUSION: Arterial thrombosis is an uncommon manifestation of occult malignancy. Carcinoma cervix usually does not metastasize to heart, brain, and arteries, which was the case in our patient. A high index of suspicion and systematic evaluation can clinch the diagnosis even when rare complications of malignancy are presented by critically ill patients. CLINICAL SIGNIFICANCE: Any unprovoked thrombotic episodes should be extensively worked up for occult malignancies. We present a case demonstrating challenges faced by critical care physicians and benefits of methodical evaluation when confronted with unusual presentation of a malignancy. HOW TO CITE THIS ARTICLE: Rangappa R, Shetty RM, Denzil M, Haranahalli PE, Susmita S, Chaurasia S. A Unique Case of Arterial Thrombosis and Recurrent CVA in ICU: Unfathomable Presentation of an Occult Malignancy. Indian J Crit Care Med 2020;24(7):585-588.

BIS monitoring versus clinical assessment for sedation in mechanically ventilated adults in the intensive care unit and its impact on clinical outcomes and resource utilization.

BACKGROUND: Patients admitted to intensive care and on mechanical ventilation, are administered sedative and analgesic drugs to improve both their comfort and interaction with the ventilator. Optimizing sedation practice may reduce mortality, improve patient comfort and reduce cost. Current practice is to use scales or scores to assess depth of sedation based on clinical criteria such as consciousness, understanding and response to commands. However these are perceived as subjective assessment tools. Bispectral index (BIS) monitors, which are based on the processing of electroencephalographic signals, may overcome the restraints of the sedation scales and provide a more reliable and consistent guidance for the titration of sedation depth.The benefits of BIS monitoring of patients under general anaesthesia for surgical procedures have already been confirmed by another Cochrane review. By undertaking a well-conducted systematic review our aim was to find out if BIS monitoring improves outcomes in mechanically ventilated adult intensive care unit (ICU) patients. OBJECTIVES: To assess the effects of BIS monitoring compared with clinical sedation assessment on ICU length of stay (LOS), duration of mechanical ventilation, any cause mortality, risk of ventilator-associated pneumonia (VAP), risk of adverse events (e.g. self-extubation, unplanned disconnection of indwelling catheters), hospital LOS, amount of sedative agents used, cost, longer-term functional outcomes and quality of life as reported by authors for mechanically ventilated adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ProQuest, OpenGrey and SciSearch up to May 2017 and checked references citation searching and contacted study authors to identify additional studies. We searched trial registries, which included clinicaltrials.gov and controlled-trials.com. SELECTION CRITERIA: We included all randomized controlled trials comparing BIS versus clinical assessment (CA) for the management of sedation in mechanically ventilated critically ill adults. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. We undertook analysis using Revman 5.3 software. MAIN RESULTS: We identified 4245 possible studies from the initial search. Of those studies, four studies (256 participants) met the inclusion criteria. One more study is awaiting classification. Studies were, conducted in single-centre surgical and mixed medical-surgical ICUs. BIS monitor was used to assess the level of sedation in the intervention arm in all the studies. In the control arm, the sedation assessment tools for CA included the Sedation-Agitation Scale (SAS), Ramsay Sedation Scale (RSS) or subjective CA utilizing traditional clinical signs (heart rate, blood pressure, conscious level and pupillary size). Only one study was classified as low risk of bias, the other three studies were classified as high risk.There was no evidence of a difference in one study (N = 50) that measured ICU LOS (Median (Interquartile Range IQR) 8 (4 to 14) in the CA group; 12 (6 to 18) in the BIS group; low-quality evidence).There was little or no effect on the duration of mechanical ventilation (MD -0.02 days (95% CI -0.13 to 0.09; 2 studies; N = 155; I2 = 0%; low-quality evidence)). Adverse events were reported in one study (N = 105) and the effects on restlessness after suction, endotracheal tube resistance, pain tolerance during sedation or delirium after extubation were uncertain due to very low-quality evidence. Clinically relevant adverse events such as self-extubation were not reported in any study. Three studies reported the amount of sedative agents used. We could not measure combined difference in the amount of sedative agents used because of different sedation protocols and sedative agents used in the studies. GRADE quality of evidence was very low. No study reported other secondary outcomes of interest for the review. AUTHORS' CONCLUSIONS: We found insufficient evidence about the effects of BIS monitoring for sedation in critically ill mechanically ventilated adults on clinical outcomes or resource utilization. The findings are uncertain due to the low- and very low-quality evidence derived from a limited number of studies.