Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

Subclavian vein collapsibility as a predictor of fluid responsiveness in spontaneously breathing hypotensive patients.

INTRODUCTION: Volume replacement remains the cornerstone of resuscitation in critically ill patients. This study explored the ability of subclavian vein collapsibility index in predicting fluid responsiveness. MATERIAL AND METHODS: In this prospective observational study conducted in the Department of Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, hypotensive patients presenting to the emergency underwent sonographic evaluation of Inferior Vena Cava and right Subclavian vein at three time points. The study population was divided into two groups: Responders and non-responders, based on ≥ 15 % increase in stroke volume following fluid bolus. OBSERVATION AND RESULTS: Among 45 recruited patients, 33 patients were responders. The area under ROC curve for SCV CI at baseline to predict fluid responsiveness was 0.745 (95% confidence interval: 0.549 - 0.941; p = 0.014). An SCV-CI of 46 % predicts fluid responsiveness in a hypotensive patient in terms of change in stroke volume by 15% following fluid bolus with a sensitivity of 87.88 % (95 % confidence interval: 71.80% to 96.60%) and specificity of 66.67 % (95 % confidence interval: 34.89% to 90.08%). Spearman's correlation coefficient between IVC CI and SCV CI was 0.59 (p < 0.001, n = 135). CONCLUSION: The results of the study show that right subclavian vein respiratory variation has the ability to predict fluid responsiveness in a spontaneously breathing patient in circulatory shock and correlates with Inferior Vena Cava collapsibility index. Subclavian vein can be an alternative to Inferior Vena Cava in predicting fluid responsiveness in spontaneously breathing patients.

Atorvastatin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. TRIAL DESIGN: This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. PARTICIPANTS: The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. INTERVENTION AND COMPARATOR: In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute's COVID-19 treatment protocol and the treating physician's clinical judgment. MAIN OUTCOMES: All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. RANDOMISATION: The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). BLINDING (MASKING): The study will be an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. TRIAL STATUS: The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months TRIAL REGISTRATION: The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Colistin-induced acquired Bartter-like syndrome: an unusual cause of meltdown.

Colistin-induced nephrotoxicity is commonly associated with elevation of serum creatinine level or a reduction of urine output. Uncommonly, tubulopathy associated with colistin has been reported. Here we present a unique case of a 46-year-old man who developed polyuria, hypokalaemia, hypocalcaemia, hypomagnesemia and metabolic alkalosis after 3 days of therapy with intravenous colistimethate sodium. After ruling out other causes, a diagnosis of colistin-induced acquired Bartter syndrome was made. The patient required daily aggressive intravenous repletion of fluids and electrolytes. However, polyuria and metabolic abnormalities abated only after drug discontinuation.

Bedside sonography by medicine residents in critically Ill patients: A retrospective study from a teaching hospital in India.

CONTEXT: Ultrasonography has become the frontline diagnostic tool for emergency care because of its non-invasive nature and the feasibility to perform repeated quick assessments in sick patients. The effectiveness of this modality, when used by trainee doctors to take clinically important decisions in patients requiring emergency care, is not much explored. In this pilot study, we analyzed whether use of this technology by Medicine resident doctors can help in better decision making in acutely and critical ill patients. SETTING AND DESIGN: This is a retrospective study conducted in the Department of Medicine, All India Institute of Medical Sciences, New Delhi. METHODS AND MATERIALS: The study was conducted using patient data collected from acutely ill and critical care patients, who underwent bedside ultrasonography from August 2017 to August 2018. In all cases, resident doctor's finding had been assessed by an experienced operator before a treatment decision was made. STATISTICAL ANALYSIS USED: Continuous variables with normal distribution were computed using t test. Ordinal variables and variables following non-normal distribution were analyzed using the Wilcoxon rank-sum test. RESULTS: Thirty-two patients were recruited. There was agreement on 78% (25/32) ultrasound records between the trainee and the experienced operator. Among patients evaluated for shock, agreement reached 83% (15/18). Among patients who underwent transthoracic echocardiography, agreement was 66.7% (4/6). Among patients who underwent lung ultrasound, agreement was 70% (7/10). In both the patients in whom abdominal ultrasound was done, final inferences were consistent between the residents and experts. CONCLUSIONS: The results show that in majority of critically ill patients, Medicine residents made sonographic observations correctly and took clinically precise sonography guided decisions on par with expert sonologists even with minimal training and ultrasound exposure.

Binge alcohol consumption leading to hypokalemic rhabdomyolysis.

A 43-year-old man presented with acute onset rapidly progressive weakness in all four limbs (proximal greater than distal), following an episode of binge alcohol ingestion, and was admitted for evaluation and management. There was a history of decreased urine output since 2 days with dark-coloured urine. He was found to have severe hypokalemia and renal dysfunction. Serum creatine kinase was significantly high, and further investigation revealed significantly elevated serum and urine myoglobin levels suggestive of rhabdomyolysis, which was secondary to severe hypokalemia. Following supplementation with intravenous and oral potassium and supportive care, the weakness improved significantly, and he was subsequently discharged. This case describes severe hypokalemia, resulting in rhabdomyolysis and generalised lower motor neuron weakness, in a setting of binge alcohol ingestion, which is an entity rarely described in literature.