Unveiling Pathophysiological Insights: Serum Metabolic Dysregulation in Acute Respiratory Distress Syndrome Patients with Acute Kidney Injury.

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.

Diagnosis and management of invasive fungal diseases in non-neutropenic ICU patients, with focus on candidiasis and aspergillosis: a comprehensive review.

Invasive fungal diseases pose a significant threat to non-neutropenic ICU patients, with Candida and Aspergillus infections being the most common. However, diagnosing these infections in the ICU population remains challenging due to overlapping clinical features, poor sensitivity of blood cultures, and invasive sampling requirements. The classical host criteria for defining invasive fungal disease do not fully apply to ICU patients, leading to missed or delayed diagnoses. Recent advancements have improved our understanding of invasive fungal diseases, leading to revised definitions and diagnostic criteria. However, the diagnostic difficulties in ICU patients remain unresolved, highlighting the need for further research and evidence generation. Invasive candidiasis is the most prevalent form of invasive fungal disease in non-neutropenic ICU patients, presenting as candidemia and deep-seated candidiasis. Diagnosis relies on positive blood cultures or histopathology, while non-culture-based techniques such as beta-D-glucan assay and PCR-based tests show promise. Invasive aspergillosis predominantly manifests as invasive pulmonary aspergillosis in ICU patients, often associated with comorbidities and respiratory deterioration in viral pneumonia. Diagnosis remains challenging due to poor sensitivity of blood cultures and difficulties in performing lung biopsies. Various diagnostic criteria have been proposed, including mycological evidence, clinical/radiological factors and expanded list of host factors. Non-culture-based techniques such as galactomannan assay and PCR-based tests can aid in diagnosis. Antifungal management involves tailored therapy based on guidelines and individual patient factors. The complexity of diagnosing and managing invasive fungal diseases in ICU patients underscore the importance of ongoing research and the need for updated diagnostic criteria and treatment approaches. Invasive fungal disease, Invasive fungal infection, Invasive candidiasis, Invasive aspergillosis, Antifungal drugs.

Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study.

Background: Traumatic brain injury (TBI) is a major cause of mortality among young individuals, accounting for 65% of deaths in road traffic accidents. Paroxysmal sympathetic hyperactivity (PSH) is a common syndrome associated with TBI. This study represents the first prospective investigation aimed at assessing the impact of gabapentin on TBI patients, focusing on the prevention of secondary brain injury and brain edema while enhancing the Glasgow Coma Scale (GCS). Materials and methods: The study was conducted from September 2019 to July 2021 after receiving ethical committee approval. It included adult ICU patients (≥18 years) with moderate and severe GCS. Patients below 18 years, death within 48 hours, non-consenting, pregnant females, and individuals allergic to gabapentin were excluded from the study. Patients were randomly allocated in two groups: study group received 300 mg of gabapentin orally twice daily and control group received multivitamin tablets twice daily. The treatment period spanned 2 weeks. Follow-up occurred in the ICU and continued for up to 3 months post-discharge, including telephonic conversations. Results: About 60 patients were involved for analysis. Significant differences were found in GCS change from admission to discharge, Glasgow Outcome Scale (GOS) at 30 and 90 days, PSH episodes, and sedation bolus per day. Glasgow Coma Scale change was 53% in the study group compared with 25% in the control group (p = 0.009). Mortality was significantly lower in the study group. Glasgow Outcome Scale change between 30 and 90 days showed a 25% improvement in cases and no change in controls (p = 0.001). Conclusion: This pioneering study underscores the potential of gabapentin in managing traumatic brain injuries. How to cite this article: Singh R, Ambasta S, Bais PS, Azim A, Kumar S, Upreti B, et al. Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study. Indian J Crit Care Med 2024;28(2):120-125.

Quadriparesis with different diagnoses after COVID-19 vaccination: Case series and literature review.

Following vaccination with adenoviral vector-based ChAdOx1 nCoV-19, serious neurological adverse events have been reported. Here we report two cases who presented with quadriparesis following the adenoviral vector-based ChAdOx1 nCoV-19 vaccine. A 55-year-old male patient presented with quadriparesis after 8 days of the second dose of ChAdOx1 nCoV-19 vaccination. Imaging showed features of stroke with right basilar artery thrombosis; he was started on anticoagulation following which the patient's neurological status improved and he was discharged during the 7th week of hospital stay. A 19-year-old male patient presented with quadriparesis after 16 days of the first dose of ChAdOx1 nCoV-19 vaccination. Cerebral spinal fluid and nerve conduction study was suggestive of Guillain-Barre syndrome (GBS). Two doses of intravenous immunoglobulin were given, following which the patient's neurological status improved and he was discharged in the 11th week of his hospital stay. Awareness of neurological adverse effects and emphasis on the underlying mechanism of vaccine-induced thrombotic thrombocytopenia (VITT) and molecular mimicry in patients presenting with quadriparesis following ChAdOx1 nCoV-19 vaccination is important.

QTc Interval of Healthcare Workers from India: Baseline and Effect of Hydroxychloroquine Prophylaxis during the COVID-19 Pandemic.

Background: The aim of this study was to access the incidence of prolonged QTc interval and changes, if any, among Indian healthcare workers (HCWs) taking hydroxychloroquine (HCQ) prophylaxis while managing coronavirus disease 2019 (COVID-19) cases. Methods: At the beginning of the COVID-19 pandemic, as per the Indian Council of Medical Research (ICMR) policy, HCWs were advised to take HCQ as prophylaxis after getting an electrocardiogram (ECG) while being posted to look after COVID-19 patients. A follow-up ECG was repeated for those who took HCQ. The normal upper limit for QTc interval of 460 milliseconds (ms) for females and 450 ms for males was considered. Results: A baseline ECG was analyzed for 250 HCWs with a median age of 35 (30-43) years. The median QTc was 410 (395-421) ms with the prevalence of prolonged QTc of 1.8% in females and 0% in males. A follow-up ECG after HCQ intake for 43 HCWs was further analyzed. They had a median age of 35 (31-39) years and took an average dose of HCQ of 2372 ± 839 mg. Pre- and post-HCQ chemoprophylaxis QTc interval (ms) was as follows: 408 (386-419) and 405 (387-417), with P = 0.434, respectively. Conclusion: Among Indian HCWs, the prevalence of prolonged QTc is 1.8% and 0% in females and males, respectively. HCQ intake as chemoprophylaxis for COVID-19 did not affect their QTc interval.

Arterial cannulation in adult critical care patients: A comparative study between ultrasound guidance and palpation technique.

OBJECTIVE: To compare first attempt success rate for ultrasound-guided (USG) versus direct palpation (DP) for radial, femoral, and dorsalis pedis artery cannulations in adult intensive care unit (ICU) patients. DESIGN: Prospective randomized clinical trial. SETTING: Mixed adult ICU of a University Hospital. PARTICIPANTS: Adult patients (≥18 years) admitted to the ICU requiring invasive arterial pressure monitoring were included. Exclusion criteria were patients with a pre-existing arterial line and cannulated with other than a 20-gauge cannula for radial and dorsalis pedis artery. INTERVENTION: Comparison of arterial cannulation by USG versus palpation technique in radial, femoral and dorsalis pedis arteries. MAIN VARIABLES OF INTEREST: Primary outcome was first attempt success rate, secondary outcomes were assessing time for cannulations, number of attempts, overall success rate, complications, and comparison of two techniques on patients requiring vasopressor. RESULTS: 201 patients were enrolled in study, with 99 randomized to DP group and 102 to USG group. Arteries (radial, dorsalis pedis, femoral) cannulated in both groups were comparable (P = .193). Arterial line was placed on first attempt in 85 (83.3%) in USG group versus 55 (55.6%) in DP group (P = .02). Cannulation time in USG group was significantly shorter compared to DP group. CONCLUSIONS: In our study, USG arterial cannulation, compared to palpatory technique, had a higher success rate at first attempt and a shorter cannulation time. CLINICAL TRIAL REGISTRY OF INDIA NUMBER: CTRI/2020/01/022989.

Longitudinal NMR Based Serum Metabolomics to Track the Potential Serum Biomarkers of Septic Shock.

Background: Septic shock, with a prolonged hospital stay, has the highest mortality rate worldwide. There is a need for better management of the disease, which requires time-dependent analysis of alteration occurring in the disease condition and subsequent planning of treatment strategies to curb mortality. Objective: The study aims to identify early metabolic signatures associated with septic shock before treatment and post-treatment. It also entails the progression of patients towards recovery, which clinicians could use to analyze treatment efficacy. Methods: The study was performed on 157 serum samples of patients with septic shock. We performed metabolomic, univariate, and multivariate statistics to identify the significant metabolite signature of patients prior to treatment and during treatment by collecting serum samples on the day I, day III, and day V of treatment. Results: We identified metabotypes of patients before treatment and post-treatment. The study showed time-dependent metabolite alteration in ketone bodies, amino acids, choline, and NAG in patients undergoing treatment. Conclusion: This study illustrates the metabolite's journey in septic shock and during treatment, which may be of prospective assistance to clinicians to monitor therapeutics.

Administration of 3% hypertonic saline via peripheral route: Is it really safe?

BACKGROUND: Administration of 3% sodiumchloride through a peripheral venous catheter is associated with risk of infusion-related adverse events (IRAE) due to its high osmolarity. Given this concern and the paucity of data regarding these events,many hospitals have policies that require central line administration of 3% sodiumchloride. OBJECTIVE: The objective of this analysis was to evaluate the incidence of IRAE associated with peripheral administration of 3% sodium chloride. METHODS: This analysis included patients who received 3% sodium chloride via a peripheral venous catheter between May 2017 and August 2019. The major endpoint of this analysiswas the overall incidence of IRAE, defined as the documentation of infiltration or phlebitis. Amultivariable logistic regression was performed to identify potential risk factors (e.g., age, infusion rate, infusion duration, peripheral venous catheter location, and needle gauge) for development of IRAE. RESULTS: A total of 706 administrations in 422 patientswere included. Seventy-four (10.5%) administrations were associated with a documented event. Based on the Infusion Nurses grading scale for infiltration or phlebitis, 48% of the events in this analysiswere grade 1 in severity. Duration of infusion of 3% sodiumchloride was found to be associated with an increased odds of an IRAE (OR per 1 h 1.02, 95% CI 1.01-1.02) in the multivariable analysis. Age, infusion rate, peripheral venous catheter location, and needle gauge were not independently associated with an increased risk of an IRAE. CONCLUSION: These data suggest that IRAE occurred more frequently when 3% sodium chloride was administered over a longer duration and themajority of events weremild with no permanent tissue injury. Itmay be reasonable to consider peripheral administration of 3% sodium chloride in the acute care setting for a short duration, although additional studies are needed to continue to evaluate its safety.

Metabolic fingerprint of patients showing responsiveness to treatment of septic shock in intensive care unit.

OBJECTIVE: An early metabolic signature associated with the responsiveness to treatment can be useful in the better management of septic shock patients. This would help clinicians in designing personalized treatment protocols for patients showing non-responsiveness to treatment. METHODS: We analyzed the serum on Day 1 (n = 60), Day 3 (n = 47), and Day 5 (n = 26) of patients with septic shock under treatment using NMR-based metabolomics. Partial least square discriminant analysis (PLS-DA) was performed to generate the list of metabolites that can be identified as potential disease biomarkers having statistical significance (that is, metabolites that had a VIP score > 1, and p value < 0.05, False discovery rate (FDR) < 0.05). RESULTS: Common significant metabolites amongst the three time points were obtained that distinguished the patients being responsive (R) and non-responsive (NR) to treatments, namely 3 hydroxybutyrate, lactate, and phenylalanine which were lower, whereas glutamate and choline higher in patients showing responsiveness. DISCUSSION: The study gave these metabolic signatures identifying patients' responsiveness to treatment. The results of the study will aid in the development of targeted therapy for ICU patients.

Association of hyperglycaemia at-admission & diabetes mellitus with 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection: A retrospective study.

Background & objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care. Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission. Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]. Interpretation & conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

New insights into development and mortality of COVID-19-associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real-world insights about the disease. METHODS: We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non-CAPA and deceased/survived CAPA patients using univariable and multivariable models. RESULTS: The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non-CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1-2.8]). Diabetes (odds ratio [OR] 1.92 [1.15-3.21]); persistent fever (2.54 [1.17-5.53]); hemoptysis (7.91 [4.45-14.06]); and lung lesions of cavitation (8.78 [2.27-34.03]), consolidation (9.06 [2.03-40.39]), and nodules (8.26 [2.39-28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09-6.55]), a high computed tomography score index (OR 1.18 [1.08-1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3-9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03-1.15] and mortality: 1.17 [1.08-1.28]) and lymphopenia (development: 0.68 [0.51-0.91] and mortality: 0.40 [0.20-0.83]) were associated with the development as well as mortality of CAPA. CONCLUSION: We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.

Analysis of Causes of Hepatic Dysfunction in Obstetric Patients in India: A Systematic Review.

BACKGROUND: Epidemiology of liver disease in obstetric patients shows geographical variation depending upon the prevalence of preeclampsia, viral hepatitis, and tropical vector-borne diseases like malaria, leptospirosis, etc. We undertook the current systematic review to analyze the causes of hepatic dysfunction in obstetric patients in India and identify the gaps in the literature and reporting. MATERIALS AND METHODS: We did a systematic review of studies reporting the causes of hepatic dysfunction in obstetric patients in India. A methodological quality assessment was done using a five-point questionnaire. RESULTS: A total of 21 studies qualified for evaluation. The rate of hepatic dysfunction among obstetric patients in India ranged from 0.15 to 3.3% with a mean and median rate of 1.49 and 0.93%, respectively. Preeclampsia/HELLP (mean = 36.0%, median = 31.4%, range: 3.6-83.8%) and viral hepatitis (mean = 34.1%, median = 35.5%, range: 5.1-61.8%) were the commonest causes of hepatic dysfunction. Other causes were intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, tropical fever (malaria, leptospirosis, dengue, scrub typhus), etc. Maternal mortality ranged from 1.4 to 40% (mean = 12.6%, median = 10.0%) and perinatal mortality was between 16.4 and 38.70% (mean = 31.75%, median = 35.5%). CONCLUSION: There is moderate quality evidence to show that preeclampsia/HELLP and viral hepatitis are the commonest causes of hepatic dysfunction in obstetric patients in India. HOW TO CITE THIS ARTICLE: Ahmed A, Saxena S, Pandey A, Mishra P, Azim A. Analysis of Causes of Hepatic Dysfunction in Obstetric Patients in India: A Systematic Review. Indian J Crit Care Med 2022;26(1):114-122.

The evolution of clot strength in critically ill COVID-19 patients: a prospective observational thromboelastography study.

The authors have done commendable work in exploring the utility of a comprehensive viscoelastic test for assessment of the coagulation cascade in Coronavirus disease 2019 (COVID-19) patients. This article published in your esteemed journal in November 2021 "The evolution of clot strength in critically-ill COVID-19 patients: a prospective observational thromboelastography study" found hypercoagulability in most of the patients at Intensive Care Unit (ICU) admission and also noted a persistently increased fibrin contribution to clot strength. However, we would like to comment upon a few points which may be of importance to the readers.

Arterial site selection for measurement of mean arterial pressure in septic shock patients on high-dose norepinephrine.

Background: The guidelines of the Surviving Sepsis Campaign suggest using invasive blood pressure (IBP) measurement in septic shock patients, without specifying for a preferred arterial site for accuracy in relation to the severity of septic shock. The objective of this study was to determine the mean arterial pressure (MAP) gradient between the femoral and radial artery sites in septic shock patients. Method: This prospective study was carried out at a 20-bed ICU in a university hospital. Simultaneous MAP measurements at femoral and radial arterial sites were obtained in septic shock patients receiving norepinephrine (≥0.1 µg/kg/min), with a pre-planned subgroup analysis for those receiving a high dose of norepinephrine (≥0.3 µg/kg/min). Results: The median norepinephrine dose across all 80 patients studied, including 59 patients on a high dose, was 0.4 (0.28-0.7) µg/kg/min. Overall, simultaneous measurement of MAP (mmHg) at the femoral and radial arterial sites produced mean (95% CI) MAP values of 81 (79-83) and 78 (76-80), respectively, with a mean difference of 3.3 (2.67-3.93), p < 0.001. In Bland-Altman analysis of MAP measurements, the detected effect sizes were 1.14 and 1.04 for the overall and high-dose cohorts, respectively, which indicates a significant difference between the measurements taken at each of the two arterial sites. The Pearson correlation coefficient indicated a weak but statistically significant correlation between MAP gradient and norepinephrine dose among patients receiving a high dose of norepinephrine (r = 0.289; p = 0.026; 95% CI 0.036-0.508). Conclusion: In septic shock patients, MAP readings were higher at the femoral site than at the radial site, particularly in those receiving a high dose of norepinephrine. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT03475667].

Etiology of Pregnancy-related Acute Kidney Injury among Obstetric Patients in India: A Systematic Review.

Background: Pregnancy-related acute kidney injury (PRAKI) is an important cause of fetomaternal mortality and morbidity in developing countries. We undertook a systematic review to identify the causes of PRAKI among obstetric patients in India. Materials and methods: We systematically searched PubMed, MEDLINE, Embase, and Google Scholar using appropriate search terminology between 1 January 2010 to 31 December 2021. Studies reporting the etiology of PRAKI among obstetric patients (pregnant and within 42 days postpartum) in India were included for evaluation. Studies done in any other geographical location besides India were excluded. We also excluded studies done in any one trimester or any specific subgroup of patients [e.g., postpartum acute kidney injury (AKI), postabortal AKI]. A five-point questionnaire was used to assess the risk of bias in included studies. The results were synthesized as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total number of 7 studies with 477 participants were included for analysis. All were single-center descriptive observational studies either done in tertiary care public or private hospitals. Sepsis (mean, 41.9%; median, 49.4%; and range, 6-56.1%) was the most common cause of PRAKI followed by hemorrhage (mean, 22.1%; median, 23.5%; and range, 8.3-38.5%) and pregnancy-induced hypertension (mean, 20.9%; median, 20.7; and range, 11.5-39%). Among these seven studies, five were of moderate quality, one was of high quality, and another one was of low quality. Our study is limited due to the lack of consensus definition of PRAKI in literature and heterogeneity in reporting methods. Our study highlights the need for a structured reporting format for PRAKI to understand the true disease burden and take control measures. Conclusion: There is a moderate quality of evidence to suggest that sepsis followed by hemorrhage and pregnancy-induced hypertension are the commonest causes of PRAKI in India. How to cite this article: Gautam M, Saxena S, Saran S, Ahmed A, Pandey A, Mishra P, et al. Etiology of Pregnancy-related Acute Kidney Injury among Obstetric Patients in India: A Systematic Review. Indian J Crit Care Med 2022;26(10):1141-1151.