Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock: An Indian perspective.

BACKGROUND: Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. AIM: To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. METHODS: We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. RESULTS: Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". CONCLUSION: This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

Knowledge, Attitudes, and Practices regarding Oral Fluid, Electrolyte, and Energy Management in Acute Nondiarrheal Illnesses among Physicians in India.

BACKGROUND: Fluid, electrolytes, and energy (FEE) management is important in the treatment of acute nondiarrheal illnesses. However, the use of FEE drinks in managing such illnesses is not well-documented. OBJECTIVE: This study aimed to understand physicians' knowledge, attitude, and practices (KAP) and perceived patient outcomes in treating FEE deficits in acute nondiarrheal illnesses using FEE drinks in India. MATERIALS AND METHODS: A cross-sectional respondent-blinded survey was designed and administered among practicing physicians across various specialties and prescribing statuses in India. KAP among groups of physicians was assessed, and the correlations between knowledge- attitudes, knowledge-practice, and knowledge-perceived outcomes were explored. RESULTS: A total of 494 physicians participated in the study from September to October 2021. Overall, knowledge scores were moderate. Prescribers had a higher average knowledge score and more proactive attitudes and practices as compared to nonprescribers. Most physicians agreed that FEE management recommendations could improve patients' recovery speed. There were significant positive correlations between knowledge scores and physicians' attitudes toward the importance of FEE management awareness, the importance of FEE management for patient recovery, and a physician's perception that FEE drinks improved patients' recovery time. There was no significant correlation between knowledge score and practices. CONCLUSION: There may be benefits from improving the knowledge of physicians in India in FEE management and developing guidelines for the use of FEE drinks in acute nondiarrheal illnesses. Further research exploring the knowledge-practice gap and evaluating the clinical benefit of FEE drinks in acute nondiarrheal illnesses should also be undertaken to develop such guidelines.

Extracorporeal blood purification strategies in sepsis and septic shock: An insight into recent advancements.

BACKGROUND: Despite various therapies to treat sepsis, it is one of the leading causes of mortality in the intensive care unit patients globally. Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies (ECT) which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators. AIM: To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes. METHODS: In this review, an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis. A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts. RESULTS: Results showed that ECT techniques such as high-volume hemofiltration, coupled plasma adsorption/filtration, resin or polymer adsorbers, and CytoSorb® are emerging as adjunct therapies to improve hemodynamic stability in sepsis. CytoSorb® has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores, lactate levels, total leucocyte count, platelet count, interleukin- IL-6, IL-10, and TNF levels. CONCLUSION: Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials. In addition to patient-tailored therapies, future research developments with therapies targeting the cellular level of the immune response are expected.

Comparing the Knowledge, Attitude, and Practices on Oral Fluids, Electrolytes, and Energy Management in Non-diarrheal Illnesses across Different Physician Specialties in India.

Background: The management of non-diarrheal illnesses requires careful attention to maintaining the proper balance of fluids, electrolytes, and energy (FEE). Nevertheless, there is a limited amount of information accessible regarding the utilization of oral FEE formulations in the treatment of these conditions. Objective: The objective of this study was to assess and contrast the levels of knowledge, attitude, and practices (KAP) among various medical specialties in India when it comes to addressing FEE imbalances in non-diarrheal illnesses through the use of oral FEE formulations, as well as to examine how these approaches influence perceived patient outcomes. We also present a subgroup analysis of KAP in healthcare personnels (HCPs) whose practices include 25% or more diabetic or geriatric patients. Materials and methods: A cross-sectional online assessment was created and conducted among physicians (n = 494) representing different medical specialties in India, which include general practitioners (GPs) (n = 128), MD physicians (n = 121), gynecologists (n = 122), and pediatricians (n = 123). Results: A total of 494 physicians across specialties, including GPs, MDs (MD internal medicine physicians), obstetrics and gynecologists (OB-GYN), and pediatricians, participated in the online assessment from September to October 2021. Knowledge scores were moderate across specialties, and there was no significant difference in knowledge level across specialties. More pediatricians and GPs than other HCPs consider FEE deficit to have a high impact on recovery. Further, pediatrician prescribers consider FEE management to be of high importance compared to other specialties. A significantly higher percentage of pediatricians assess all their patients (100%) for hydration levels, and significantly more gynecologists spend >5 minutes providing hydration advice to their patients. Among all specialties, MD and gynecologist prescribers are more likely to recommend oral FEE for patient recovery. HCPs with diabetes practices agree slightly more than HCPs with geriatric practices that oral FEE management recommendations facilitate the speed of the recovery process from non-diarrheal illnesses in their patients. However, only approximately 30% of them recommend FEE to 70% of their eligible patients, of which approximately 70% of these HCPs give formal (written/electronic) prescriptions of ready-to-drink (RTD) fluids to their patients. Conclusion: Enhancing the understanding of physicians across diverse specialties in India regarding oral FEE management and formulating recommendations for the utilization of oral FEE formulations in non-diarrheal conditions could lead to better outcomes. While knowledge and awareness of oral FEE management are similar across specialties, their practice behaviors vary. Additional research into this disparity and the assessment of the clinical advantages of oral FEE formulations in non-diarrheal illnesses among various specialties should be conducted. How to cite this article: Sathe P, Chakravarty P, Tesado C, et al. Comparing the Knowledge, Attitude, and Practices on Oral Fluids, Electrolytes, and Energy Management in Non-diarrheal Illnesses across Different Physician Specialties in India. J Assoc Physicians India 2023;71(10):19-30.

A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients.

Background: From an epidemic outbreak, coronavirus disease-2019 (COVID-19) has quickly developed. Thymosin α1 (Tα1) has the ability to boost the T-cell numbers, support T-cell differentiation, maturation, and reduce cell apoptosis. In this study, we have investigated the efficacy and safety of Tα1 in moderate-to-severe COVID-19 patients. Patients and methods: In this double-blind, multicenter, two-arm, randomized, placebo-controlled, phase III clinical study, patients were randomized to receive either Tα1 or placebo in combination with standard of care (SOC). The data on all-cause mortality, clinical progression/deterioration, duration of hospital/intensive care unit (ICU) stay, and safety data were collected. The patients were telephonically followed up on Day 28. Results: A total of (n = 105) COVID-19 patients were included in the study, of which 40 and 65 were severe and moderate, respectively. Thymosin arm (11.1%) had a statistically lower death rate in comparison to the placebo arm (38.5%). A total of 67 adverse events were reported in 42 patients among 105 dosed patients during the study. Among them, 43 adverse events were of mild in nature, 16 adverse events were of moderate in nature, and 8 serious adverse events (death) occurred during the study. Conclusion: This study provides evidence that Tα1 can lower death rate in severe COVID-19 patients, reduce the load on hospitals by shortening the required number of days of hospitalization and help in abbreviating the requirement of oxygen support by positively impacting the recovery rate and time taken for recovery. How to cite this article: Shetty A, Chandrakant NS, Darnule RA, Manjunath BG, Sathe P. A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients. Indian J Crit Care Med 2022;26(8):913-919.

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.

Clinical outcomes of ceftazidime-avibactam versus meropenem in Indian patients with nosocomial pneumonia: Subset analysis from the REPROVE study.

The efficacy and safety of Ceftazidime-Avibactam (CAZ-AVI) as compared to meropenem for nosocomial pneumonia was established in a randomized, phase-III, non-inferiority trial REPROVE, which included Indian patients. We determined if the results for the Indian patients were in-line with the results of overall population. Descriptive analysis of efficacy and safety demonstrated ceftazidime-avibactam was comparable to meropenem in the management of nosocomial pneumonia in Indian patients and it may be a useful addition to the armamentarium of antibiotics for management of such infections with Enterobacterales and Pseudomonas.

Multicentered prospective investigator initiated study to evaluate the clinical outcomes with extracorporeal cytokine adsorption device (CytoSorb®) in patients with sepsis and septic shock.

BACKGROUND: Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade that will lead to an auto amplifying cytokine production: The cytokine storm. Hemoadsorption by CytoSorb® therapy is a new technology that helps to address the cytokine storm and to regain control over various inflammatory conditions. AIM: To evaluate prospectively CytoSorb® therapy used as an adjunctive therapy along with standard of care in septic patients admitted to intensive care unit (ICU). METHODS: This was a prospective, real time, investigator initiated, observational multicenter study conducted in patients admitted to the ICU with sepsis and septic shock. The improvement of mean arterial pressure and reduction of vasopressor needs were evaluated as primary outcome. The change in laboratory parameters, sepsis scores [acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA)] and vital parameters were considered as secondary outcome. The outcomes were also evaluated in the survivor and non-survivor group. Descriptive statistics were used; a P value < 0.05 was considered to be statistically significant. RESULTS: Overall, 45 patients aged ≥ 18 and ≤ 80 years were included; the majority were men (n = 31; 69.0%), with mean age 47.16 ± 14.11 years. Post CytoSorb® therapy, 26 patients survived and 3 patients were lost to follow-up. In the survivor group, the percentage dose reduction in vasopressor was norepinephrine (51.4%), epinephrine (69.4%) and vasopressin (13.9%). A reduction in interleukin-6 levels (52.3%) was observed in the survivor group. Platelet count improved to 30.1% (P = 0.2938), and total lung capacity count significantly reduced by 33% (P < 0.0001). Serum creatinine and serum lactate were reduced by 33.3% (P = 0.0190) and 39.4% (P = 0.0120), respectively. The mean APACHE II score was 25.46 ± 2.91 and SOFA scores was 12.90 ± 4.02 before initiation of CytoSorb® therapy, and they were reduced significantly post therapy (APACHE II 20.1 ± 2.47; P < 0.0001 and SOFA 9.04 ± 3.00; P = 0.0003) in the survivor group. The predicted mortality in our patient population before CytoSorb® therapy was 56.5%, and it was reduced to 48.8% (actual mortality) after CytoSorb® therapy. We reported 75% survival rate in patients given treatment in < 24 h of ICU admission and 68% survival rates in patients given treatment within 24-48 h of ICU admission. In the survivor group, the average number of days spent in the ICU was 4.44 ± 1.66 d; while in the non-survivor group, the average number of days spent in ICU was 8.5 ± 15.9 d. CytoSorb® therapy was safe and well tolerated with no adverse events reported. CONCLUSION: CytoSorb® might be an effective adjuvant therapy in stabilizing sepsis and septic shock patients. However, it is advisable to start the therapy at an early stage (preferably within 24 h after onset of septic shock).

Management of ventilator associated pneumonia with a new antibiotic adjuvant entity (ceftriaxone+sulbactam+disodium edetate) - A novel approach to spare carbapenems.

BACKGROUND: Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii). METHOD: This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed. RESULTS: Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin. CONCLUSIONS: Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases.

Intensive Care in India: The Indian Intensive Care Case Mix and Practice Patterns Study.

AIMS: To obtain information on organizational aspects, case mix and practices in Indian Intensive Care Units (ICUs). PATIENTS AND METHODS: An observational, 4-day point prevalence study was performed between 2010 and 2011 in 4209 patients from 124 ICUs. ICU and patient characteristics, and interventions were recorded for 24 h of the study day, and outcomes till 30 days after the study day. Data were analyzed for 4038 adult patients from 120 ICUs. RESULTS: On the study day, mean age, Acute Physiology and Chronic Health Evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores were 54.1 ± 17.1 years, 17.4 ± 9.2 and 3.8 ± 3.6, respectively. About 46.4% patients had ≥1 organ failure. Nearly, 37% and 22.2% patients received mechanical ventilation (MV) and vasopressors or inotropes, respectively. Nearly, 12.2% patients developed an infection in the ICU. About 28.3% patients had severe sepsis or septic shock (SvSpSS) during their ICU stay. About 60.7% patients without infection received antibiotics. There were 546 deaths and 183 terminal discharges (TDs) from ICU (including left against medical advice or discharged on request), with ICU mortality 729/4038 (18.1%). In 1627 patients admitted within 24 h of the study day, the standardized mortality ratio was 0.67. The APACHE II and SOFA scores, public hospital ICUs, medical ICUs, inadequately equipped ICUs, medical admission, self-paying patient, presence of SvSpSS, acute respiratory failure or cancer, need for a fluid bolus, and MV were independent predictors of mortality. CONCLUSIONS: The high proportion of TDs and the association of public hospitals, self-paying patients, and inadequately equipped hospitals with mortality has important implications for critical care in India.

D Dimer in acute care.

Pulmonary embolism, Deep Vein Thrombosis (DVT) and Disseminated intravascular coagulation (DIC) are important sources of mortality and morbidity in intensive care unit (ICU). And every time D-dimer remains the the commonest investigation. Many times D-dimer is erroneously considered as a diagnostic test in above mentioned conditions. Its interpretation requires cautions. To circumvent this source of error it is necessary to understand D-dimer test and its significance in various disorder. This article review some basic details of D-dimer, condition associated with its increased level and some prognostic value in intracranial hemorrhage and gastrointestinal (GI) bleed.

Assessment of performance and utility of mortality prediction models in a single Indian mixed tertiary intensive care unit.

OBJECTIVES: To assess the performance and utility of two mortality prediction models viz. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) in a single Indian mixed tertiary intensive care unit (ICU). Secondary objectives were bench-marking and setting a base line for research. MATERIALS AND METHODS: In this observational cohort, data needed for calculation of both scores were prospectively collected for all consecutive admissions to 28-bedded ICU in the year 2011. After excluding readmissions, discharges within 24 h and age <18 years, the records of 1543 patients were analyzed using appropriate statistical methods. RESULTS: Both models overpredicted mortality in this cohort [standardized mortality ratio (SMR) 0.88 ± 0.05 and 0.95 ± 0.06 using APACHE II and SAPS II respectively]. Patterns of predicted mortality had strong association with true mortality (R (2) = 0.98 for APACHE II and R (2) = 0.99 for SAPS II). Both models performed poorly in formal Hosmer-Lemeshow goodness-of-fit testing (Chi-square = 12.8 (P = 0.03) for APACHE II, Chi-square = 26.6 (P = 0.001) for SAPS II) but showed good discrimination (area under receiver operating characteristic curve 0.86 ± 0.013 SE (P < 0.001) and 0.83 ± 0.013 SE (P < 0.001) for APACHE II and SAPS II, respectively). There were wide variations in SMRs calculated for subgroups based on International Classification of Disease, 10(th) edition (standard deviation ± 0.27 for APACHE II and 0.30 for SAPS II). INTERPRETATION AND CONCLUSION: Lack of fit of data to the models and wide variation in SMRs in subgroups put a limitation on utility of these models as tools for assessing quality of care and comparing performances of different units without customization. Considering comparable performance and simplicity of use, efforts should be made to adapt SAPS II.

Mucormycosis of mandible with unfavorable outcome.

Mucormycosis is a fulminant fungal infection that occurs most often in diabetic and immunocompromised individuals. Our patient, with uncontrolled diabetes mellitus and multiple systemic disorders, developed postextraction mucormycosis of mandible, an extremely rare complication. An initial clinical and radiographic diagnosis of mandibular osteomyelitis was made and the lesion was treated medically and surgically with curettage and saucerisation. The specimen was sent for histopathological evaluation, which showed necrotic area containing broad aseptate fungal hyphae with right angle branching consistent with mucormycosis. The patient succumbed to multipleorgan failure secondary to septicemia. The disease is usually fatal with a poor survival rate; there is still paucity of literature on the definitive management of this disease involving the mandible. This paper emphasizes the need for correction of underlying immunodeficiency and early diagnosis with aggressive multimodality treatment approach to offer the best chance of survival.