A systematic review and meta-analysis of randomized controlled trials with trial sequence analysis of remdesivir for COVID-19 treatment.

Remdesivir is one of the proposed therapies for the corona virus disease 2019 (COVID-19). To assess the effect of remdesivir on mortality, need for invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation (ECMO), time to clinical improvement, and significant adverse effects. The study protocol was prospectively registered with The International Prospective Register of Systematic Reviews (Registration #CRD42021283221). Randomized controlled trials (RCTs) published in English detailing use of remdesivir in hospitalized patients with COVID-19 were included. Primary outcome was in hospital mortality among patients receiving remdesivir. Secondary outcomes were need for IMV and ECMO, time to clinical recovery, and significant adverse effects associated with remdesivir. Odds ratios (ORs) of worse outcome with 95% confidence interval (CI) in a forest plot were used to show the results of random effects meta-analysis. Remdesivir and placebo had similar in hospital mortality in the pooled analysis of five RCTs (OR: 0.93, 95% CI: 0.82-1.06). The remdesivir group needed less IMV/ECMO (OR: 0.59, 95% CI: 0.46-0.76) and recovered 1.06 days faster than placebo. Remdesivir did not affect transaminitis or renal damage. Trial sequence analysis showed that death has not reached the number of instances needed to predict futility. This meta-analysis shows that remdesivir therapy for COVID-19 is not associated with a mortality benefit. However, there is significant reduction in the need for IMV/ECMO.

Targeted Temperature Management in Unconscious Survivors of Postcardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Targeted temperature management (TTM) is a vital element of postresuscitation management after cardiac arrest. Though international guidelines recommend TTM, the supporting evidence is of low certainty. Aims and objectives: To estimate the effect of TTM strategy on mortality and neurological outcomes in postcardiac arrest survivors. Materials and methods: Randomized controlled trials (RCTs) published in English evaluating the use of TTM in adult comatose survivors of cardiac arrest were included. Studies were categorized into two groups, based on hypothermia vs normothermia. The main outcome was death due to any origin. The secondary outcome measures evaluated neurological outcome and complications associated with TTM. Outcomes were analyzed by calculating Odds Ratio (OR) of a worse outcome. ORs with 95% CIs in a forest plot were used to show the results of random-effects meta-analyses. Results: On pooled analysis of 11 RCTs, no difference was observed in death due to any origin rates in the hypothermia compared to the normothermia group (OR; 0.88, 95% CI: 0.39-1.16). Overall, no difference in poor neurological outcome was observed between the two groups (OR; 0.86, 95% CI: 0.66-1.12). Trial sequencing analysis for mortality and poor neurological outcome showed that number to achieve power to predict futility has been achieved in both the parameters. Conclusions: This meta-analysis showed that hypothermia compared to normothermia TTM strategies does not improve survival or neurologic outcomes. How to cite this article: Mishra SB, Patnaik R, Rath A, Samal S, Dash A, Nayak B. Targeted Temperature Management in Unconscious Survivors of Postcardiac Arrest: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2022;26(4):506-513.

The Impact of COVID-19 on the Clinical Practices, Working Environment, and Social Life of Intensivists in Non-COVID ICU.

Purpose: Enlightening the changes in the usual clinical practices, working environment, and social life of Intensivists working in noncoronavirus disease intensive care units (non-COVID ICU) during the COVID pandemic. Materials and methods: Observational cross-sectional study for Indian intensivists working in non-COVID ICUs conducted between July and September 2021. A 16-question online survey consisting of the work and social profile of the participating intensivists, changes in the usual clinical practices, working environment, and impact on their social life was administered. For the last three sections, intensivists were asked to compare pandemic times to prepandemic times (pre-mid-March 2020). Results: The number of invasive interventions performed by intensivists working in the private sector with lesser clinical experience (<12 years) were significantly less as compared to the government sector (p = 0.07) and clinically experienced (p = 0.07). Intensivists without comorbidities performed significantly lesser number of patient examinations (p = 0.03). The cooperation from healthcare workers (HCWs) decreased significantly with lesser experienced intensivists (p = 0.05). Leaves were significantly reduced in case of private sector intensivists (p = 0.06). Lesser experienced intensivists (p = 0.06) and intensivists working in the private sector (p = 0.06) spent significantly lesser time with family. Conclusion: Coronavirus disease-2019 (COVID-19) affected the non-COVID ICUs as well. Young and private sector intensivists were affected due to less leaves and family time. HCWs need proper training for better cooperation during the pandemic time. How to cite this article: Ghatak T, Singh RK, Kumar A, Patnaik R, Sanjeev OP, Verma A, et al. The Impact of COVID-19 on the Clinical Practices, Working Environment, and Social Life of Intensivists in Non-COVID ICU. Indian J Crit Care Med 2022;26(7):816-824.

Use of direct oral anticoagulants in ICU patients. Part I - Applied pharmacology.

Direct oral anticoagulants (DOACs) have revolutionized the field of anticoagulation in the last decade, mainly due to their fixed dosing, rapid onset of anticoagulant effect, and non-inferiority to vitamin K antagonists for both efficacy and safety. Also, the availability of specific and non-specific reversal agents makes these drugs popular. However, in critically ill patients, significant alterations in drug pharmacokinetics and pharmacodynamics might occur due to various ongoing pathophysiological derangements like decreased gastrointestinal absorption, increased volume of distribution, and impaired renal and/or hepatic function. Insight into these changes is essential regarding the safe and effective use of DOACs in critically ill patients. The current article is a narrative review on the use of DOACs in intensive care unit patients, covering 'Applied pharmacology'; the second article in the series covers 'Clinical evidence'.

Use of direct oral anticoagulants in ICU patients. Part II - Clinical evidence.

During the last decade, utilization of direct oral anticoagulants (DOACs) has increased due to their pharmacokinetic profile and the fact that they are non-inferior to warfarin in the prevention of stroke in patients with atrial fibrillation, as well as for the treatment of venous thromboembolism. However, there are few studies about their use in critically ill patients. This article aims to review available evidence on the use of DOACs in the indicated conditions and anticoagulant management of medical or surgical patients receiving DOAC before intensive care unit (ICU) admission. The rapidly changing pathophysiology and heterogeneous nature of critically ill patients combined with limited evidence often leads to a high degree of individualization of DOAC regimens in ICU patients. This article is the second part of the narrative review series on the use of DOACs in ICU patients, focusing on current "Clinical evidence". "Applied pharma-cology" has been described in the first part.

Incorporating Lung Ultrasound in Clinical Pulmonary Infection Score as an Added Tool for Diagnosing Ventilator-associated Pneumonia: A Prospective Observational Study from a Tertiary Care Center.

Background: Clinical pulmonary infection score (CPIS) is an established diagnostic parameter for ventilator-associated pneumonia (VAP). Lung ultrasound (LUS) is an evolving tool for diagnosing VAP. Various scores have been proposed for the diagnosis of VAP, taking LUS as a parameter. We proposed whether replacing LUS with chest radiograph in CPIS criteria will add to the diagnosis of VAP. The current study was done to evaluate the diagnostic accuracy of LUS alone and in combination with clinical and microbiological criteria for VAP by replacing chest radiograph with LUS in CPIS. Materials and methods: We conducted a prospective single-center observational study including 110 patients with suspected VAP to investigate the diagnostic accuracy of LUS. Quantitative mini-bronchoalveolar lavage (mini-BAL) culture was considered the gold standard for diagnosis of VAP. Here, the authors have explored the combination of LUS, clinical, and microbiology parameters for diagnosing VAP. On replacing chest radiograph with LUS, sono-pulmonary infection score (SPIS) and modified SPIS (SPIS-mic, SPIS-cult) was formulated as a substitute for CPIS. Results: Overall LUS performance for VAP diagnosis was good with sensitivity, specificity, positive or negative predictive value, and positive or negative likelihood ratios of 91.3%, 70%, 89%, 75%, 3, and 0.1, respectively. Adding microbiology culture to LUS increased diagnostic accuracy. The areas under the curve for SPIS and modified SPIS were 0.808, 0.815, and 0.913, respectively. Conclusion: The diagnosis of VAP requires agreement between clinical, microbiological, and radiological criteria. Replacing chest radiograph with LUS in CPIS criteria (SPIS) increases diagnostic accuracy for VAP. Adding clinical and culture data to SPIS provided the highest diagnostic accuracy. Clinical parameters along with lung ultrasound increase diagnostic accuracy for VAP. How to cite this article: Samanta S, Patnaik R, Azim A, Gurjar M, Baronia AK, Poddar B, et al. Incorporating Lung Ultrasound in Clinical Pulmonary Infection Score as an Added Tool for Diagnosing Ventilator-associated Pneumonia: A Prospective Observational Study from a Tertiary Care Center. Indian J Crit Care Med 2021;25(3):284-291.

Evaluation of ventilator associated events in critically ill patients with invasive mechanical ventilation: A prospective cohort study at a resource limited setting in Northern India.

PURPOSE: The primary aim of this study was to identify the modifiable risk factors for acquiring ventilator associated events (VAE). Secondary aims were to investigate the intensive care unit (ICU) course and impact of VAE on patient outcome. METHODS: This prospective, observational single center cohort study included 247 patients on mechanical ventilation for 4 calendar days at a 20-bed ICU between January 2018-June 2019. RESULTS: VAE occurred in 59 episodes (rate 11.3 per 1000 ventilator-days). The Ventilator Utilization Ratio (VUR) was 0.57. The median time to onset of VAE was 6 days. Sepsis was the most common reason for initiating patients on invasive mechanical ventilation (IMV). Cumulative fluid balance ≥2 l (Odds Ratio 30.92; 95% CI 9.82-97.37) and greater number of days with vasopressor support (Odds Ratio 1.92; 95% CI 1.57-2.36) within 7 days of initiating IMV were significant risk factors for acquiring VAE (p < 0.001). VAE cases were ventilated for significantly more days (20 vs 14 days, p = 0.001, had longer days of ICU stay (29 vs 18 days; p = 0.002) and higher hospital mortality (p = 0.02). Klebsiella pneumoniae was the most common isolate (N = 28) and 32.1% were colistin resistant. CONCLUSIONS: Prospective intervention studies are needed to determine if targeting these risk factors can lower VAE rates in our setting.

Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review.

INTRODUCTION: Sepsis is a life-threatening organ dysfunction with increased incidence of morbidity and mortality. Early diagnosis and prompt therapeutic intervention is the cornerstone of sepsis care. Biomarkers play an important role in sepsis having both diagnostic and prognostic implications. Neutrophil CD64 (nCD64) is a useful candidate biomarker for sepsis. Neutrophil CD64 also known as Fc receptor 1 (FcR1), is a high-affinity receptor present on neutrophils for Fc part of immunoglobulin-G (IgG) heavy chain. Its expression gets strongly upregulated in response to proinflammatory cytokines of infection within 4-6 hours. Neutrophil CD64 integrates function involving both innate and adaptive immune responses. The aim of this review is to present literature about nCD64 as a diagnostic and prognostic marker in patients with sepsis/septic shock. BACKGROUND: The authors searched articles over 13 years, i.e., from 2006 to 2019. They included articles written in English only and further reviewed the reference list of selected articles to obtain potentially relevant articles. Reviews, letters, commentaries, correspondences, case reports, conference abstracts, expert opinions, editorials, and animal experiments were excluded. Articles involving pediatric patients (≤18 years) were also excluded. REVIEW RESULTS: Several studies have indicated that nCD64 is a highly sensitive and specific marker for the diagnosis of sepsis. Various combinations of biomarkers have been used with nCD64 for a better diagnostic value. Neutrophil CD64 as a prognostic marker in critically ill patients needs to be explored more. Most of the existing literatures have highlighted its prognostic utility based on single value at enrolment. There are limited literatures on prognostic implications of serial trend and kinetics of nCD64. CONCLUSION: Neutrophil CD64 is a useful diagnostic and prognostic marker of sepsis in critically ill patients. Additional studies are needed on nCD64 in sepsis based on sepsis-3 criteria. Further trials with large sample size are needed to establish prognostic implications of serial nCD64 trend. HOW TO CITE THIS ARTICLE: Patnaik R, Azim A, Agarwal V. Neutrophil CD64 a Diagnostic and Prognostic Marker of Sepsis in Adult Critically Ill Patients: A Brief Review. Indian J Crit Care Med 2020;24(12):1242-1250.

Should serial monitoring of procalcitonin be done routinely in critically ill patients of ICU: A systematic review and meta-analysis.

Sepsis is a life-threatening condition with dysregulated host response to infection. It is a major determinant of mortality in the intensive care unit (ICU). Procalcitonin (PCT) is widely investigated for prognosis in patients with sepsis. Most of the studies have cited that elevated PCT concentrations and PCT non-clearance are associated with poor outcomes in patients with sepsis and some studies have cited as having no additional benefit. Most of the studies have evaluated single PCT measurement and correlated with prognosis and outcome in septic patients. Limited literature is there about serial PCT levels and its impact on the outcome of patients with sepsis. We searched literature through PubMed, Embase, Web of Knowledge, and the Cochrane Library from 2007 to 2017 and present a systematic review and meta-analysis of studies evaluating the utility of serial measurement of PCT for prognosis in critically ill patients. Articles that assessed PCT non-clearance as a marker of mortality data were included. The primary objective of this meta-analysis was to pool the results of all the available studies on serial PCT non-clearance as a mortality predictor and formulate overall area under receiver operating curve (AUROC). To find out the overall proportion of mortality in PCT non-clearance was our secondary objective. To detect the mortality using PCT non-clearance, ROC curve analysis was done. Area under curve (AUC) of the studies was varying between 0.52 and 0.86. Overall AUC was observed 0.711 (95% confidence interval (CI): 0.662-0.760) under fixed effect model and 0.708 (95% CI: 0.648-0.769) under random effect model. There was moderate variation among the studies, i.e., I2 50.80% (95% CI: 0.00-80.42%). The overall proportion of mortality was 37.54% with much heterogeneity (I2 88.24%) among the studies. PCT non-clearance is a fair predictor of mortality. Further studies are needed to define optimal cut off point for PCT non-clearance in ICU patients with sepsis.

Comparison of Paravertebral Block by Anatomic Landmark Technique to Ultrasound-Guided Paravertebral Block for Breast Surgery Anesthesia: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Paravertebral block (PVB) is an established technique for providing anesthesia for breast surgery. The primary objective was to compare anatomical landmark technique (ALT) to the ultrasound-guided (USG) PVB block for providing surgical anesthesia. Secondary objectives included comparison of perioperative analgesia and complications. METHODS: This randomized, controlled, observer-blinded study included 72 females, aged 18 to 65 years, American Society of Anesthesiologists physical status I or II, undergoing elective unilateral breast surgery. Study participants were randomized to the ALT group or USG group. Ipsilateral PVB was performed with the respective technique from T1 to T6. Five milliliters of local anesthetic mixture (0.5% ropivacaine, 5 µg/mL adrenaline, 1 µg/kg clonidine) was administered at each level. Paravertebral catheter was inserted at T4/T3 level. After confirming sensory loss, patients were taken up for surgery with propofol sedation (20-50 µg/kg per minute). RESULTS: More patients in the USG group (34/36 [94.44%]) had a successful block as compared with the ALT group (26/36 [72.22%]) (P = 0.024). Difference in proportion was 18.1 (95% confidence interval, 0.15-36.0) (P = 0.024) after adjustment for age. More dermatomes were blocked in the USG group (P = 0.0018) with less sparing of upper T2 and T3 dermatomes (P = 0.003, P = 0.006, respectively). Median time to first postoperative analgesic requirement was 502.5 minutes (range, 195-1440 minutes) in the USG group versus 377.5 minutes (range, 215-1440 minutes) in the ALT group. Pain at rest and movement 2 and 4 hours postoperatively and number of catheter top-ups in 24 hours postoperatively were lesser in the USG group (P = 0.012). Complications were comparable. CONCLUSIONS: Ultrasound-guided PVB provided better anesthesia and perioperative analgesia than the landmark technique for breast surgery. CLINICAL TRIAL REGISTRATION: The trial was registered retrospectively at the Clinical Trial Registry of India, CTRI/2015/05/005774.