Association Between Post-COVID Pulmonary Dysfunction and New-Onset Anxiety and Depression and the Impact of Incentive Spirometer-Based Exercises.

Objective: To determine the rates of new-onset anxiety and depression in patients with restrictive or obstructive lung disease after COVID-19 infection and to assess the improvement in pulmonary functions and anxiety/depression scores after prescribing incentive spirometer-based breathing exercises.Methods: A 2-phase study with a cross-sectional and open-label randomized interventional design evaluated anxiety (Generalized Anxiety Disorder-7 [GAD-7] and Hamilton Anxiety Rating Scale [HARS]), depression (Patient Health Questionnaire-9 [PHQ-9]), and pulmonary function tests (PFTs) of 100 COVID-19 patients within 8 weeks of acute illness. Patients with pulmonary dysfunction were randomized (incentive spirometry vs controls), and anxiety/depression scores and lung function were reevaluated after 4 weeks.Results: The results revealed 35% (35/100) of mild-moderate COVID-19 patients had abnormal PFTs. Anxiety/depression was higher in patients with abnormal PFTs than in those with normal lung function (prevalence ratio: 1.8 [20% vs 11%]). The median HARS, GAD-7, and PHQ-9 scores decreased significantly with 4 weeks of incentive spirometry exercises (2 [0-5.5, P = .013], 2 [0-3.5, P = .006], and 2 [0-3.5, P = .006], respectively) compared to standard of care alone. More patients with incentive spirometry had normalization of pulmonary functions compared to controls (50% [8/16] vs 33% [6/18]). The mean age of patients with anxiety/depression was significantly higher than those without anxiety/depression (42 ± 11 vs 30 ± 7, P = .04).Conclusions: While the rates of new-onset anxiety/depression were higher in patients with pulmonary dysfunction, these rates were reduced with incentive spirometer-based exercises. Greater age may be a risk factor for abnormal pulmonary functions and greater anxiety or depression.Trials Registry: Clinical Trials Registry-India identifier: CTRI/2022/11/047183.Prim Care Companion CNS Disord 2023;25(5):23m03490. Author affiliations are listed at the end of this article.

Sequential Application and Post-Test Probability for Screening of Bladder Cancer Using Urinary Proteomic Biomarkers: A Review based Probabilistic Analysis.

BACKGROUND: Bladder cancer is one of the most common cancers in the world, with men being affected more than women. Diagnosis by cystoscopy, cytology and biopsy is invasive. Urine cytology, a non-invasive modality is not sensitive. This study is undertaken to evaluate whether non- invasive urinary proteomic profiling is more sensitive, specific for bladder cancer. OBJECTIVE: To evaluate the sensitivity and specificity of various urinary proteomic biomarkers as a screening tool for bladder cancer. METHODS: PubMed database was searched from 4th December 2011 to 30th November 2021 using Mesh terms and n = 10,364 articles were found. PRISMA guidelines were followed and Review articles, animal studies, Urinary tract infections, non-bladder cancer and other irrelevant articles were excluded. All studies who have reported mean/median (SD/IQR), sensitivity, specificity, cut off values (ROC analysis) were included (n=5). Post-test probability of various biomarkers was calculated using sequential approach. Pooled analysis was depicted using Forest plot. RESULTS: Analysis of diagnostic studies of bladder cancer showed the post-test probability of CYFRA21-1 was 36.6%. Using sequential approach, the panel of biomarkers CYFRA 21-1, CA-9, APE-1, COL13A1 has post-test probability of 95.10% to diagnose bladder cancer. Analysis of two observational studies with APOE (n= 447) showed non-significant increase of APO-E levels in bladder cancer cases (WMD: 66.41with 95% CI 52.70-185.51; p=0.27, I2 92.4%). CONCLUSION: In patients presenting with hematuria, a panel of CYFRA 21-1, CA-9, APE-1, COL13A1 markers can be considered for screening of bladder cancer.

Ultrasonography in cardiopulmonary emergencies.

The utilization of ultrasound has rapidly increased over the past few decades due to its ease of use, wider availability of portable machines, broad applicability, non-invasiveness, and real-time imaging. A varied spectrum of clinical conditions such as diverse lung pathologies and various etiologies of acute circulatory failure can be rapidly ascertained using bedside ultrasonography. It has been shown that lung ultrasonography has more sensitivity than chest x-ray in detecting pulmonary congestion in heart failure, subpleural lung consolidation in pneumonia, and characterizing and detecting even minimal pleural effusions. This review gives an overview of the application of ultrasonography in the evaluation of cardiopulmonary failure which is the most commonly encountered clinical entity in the emergency room (ER). The most feasible bedside tests to predict fluid responsiveness are described in this review. Lastly, essential ultrasonographic protocols that are useful for systematic examination of critically ill patients were presented.

Cefoperazone-induced Coagulopathy in Critically Ill Patients Admitted to Intensive Care Unit.

Background: N-methylthiotetrazole side chain (NMTT) of cefoperazone was attributed to inhibit the vitamin K epoxide enzyme. This mechanism is similar to warfarin; thus, vitamin K was suggested to antagonize the hematological effects of cefoperazone. The literature on critically ill patients receiving cefoperazone and its clinical significance on bleeding diathesis is sparse. Objectives: To assess the incidence of cefoperazone-induced coagulopathy (CIC), its clinical impact on bleeding episodes, and transfusion requirements. Predisposing factors and the role of prophylactic and therapeutic vitamin K were evaluated. Materials and methods: Prospective observational study of adult intensive care unit (ICU) patients (>18 years) receiving cefoperazone between December 2017 and December 2018. We excluded those on warfarin, those with preexisting elevated prothrombin time/international normalized ratio (PT/INR), and with bleeding manifestations. Relevant laboratory investigations and specific outcomes were noted for 6 days following therapy. Panel data regression was used to determine predictors of coagulopathy. Results: Among 65 patients, 17 (26%) had probable CIC. Hypoalbuminemia and vancomycin co-administration were risk factors for CIC. Hemoglobin drops and blood transfusions were not different between INR non-elevated and elevated groups (11 vs 8 gm/dL; p = 0.06 and 11 vs 8 units; p = 0.23, respectively). Prophylactic vitamin K did not offer any benefit toward preventing INR elevation. Therapeutic vitamin K significantly reduced INR when elevated [absolute risk reduction (ARR):57.5% and number needed to treat (NNT):1.7]. Conclusion: Results of this study revealed that CIC is not uncommon in ICUs. Based on the findings of the study, we suggest INR monitoring in patients receiving nephrotoxic agents and patients with hypoalbuminemia. We also recommend vitamin K administration in patients with elevated INR. How to cite this article: Gudivada KK, Krishna B, Sampath S. Cefoperazone-induced Coagulopathy in Critically Ill Patients Admitted to Intensive Care Unit. Indian J Crit Care Med 2023;27(3):183-189.

Outcomes of patients with thrombotic thrombocytopenic purpura treated in an intensive care unit.

Background Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by widespread microthrombosis that can predispose to multiple organ failure. The literature is sparse on the outcomes of critically ill patients with TTP managed in intensive care units (ICUs). We aimed to determine the mortality of ICU patients admitted with TTP and evaluate the predictors of survival. We also compared the incidence of nosocomial infection among those who did or did not receive plasma exchange (PE). Methods We conducted a retrospective study in a tertiary ICU. Two authors screened patients for eligibility from the hospital information system based on peripheral smear reports. Adult critically ill TTP patients managed in ICU were included. Patients with a diagnosis of haemolytic uraemic syndrome, autoimmune causes of haemolysis and pregnancy-related conditions, etc. were excluded. Two authors extracted data from medical charts. No imputation of missing variables was done. Non-parametric statistics were used to report data. Statistical analyses were performed using Stata version 16. Results Of the 535 records that were screened, 33 patients were deemed eligible. Mortality among TTP patients was 14 (42%). The women to men ratio was 7:3. At admission, greater degree of anaemia, thrombocytopenia, and higher lactate dehydrogenase levels were observed in non-survivors compared to survivors (5.4 g/dl [4.8-7.1] v. 7.6 g/dl [6.1-8.9], p=0.05; 17x103 µl v. 21x103 µl, p=0.63; and 2987 (1904-3614) U/L v. 2126 U/L (1941-3319), p=0.71; respectively]. Nineteen (57%) patients had acute kidney injury (AKI), of which 11 survived: 6 recovered completely from renal failure and 5 progressed to end-stage renal disease. Nosocomial infection rates were not different among those receiving and not receiving PE therapy (7 [33%] v. 3 [25%], respectively). Conclusion TTP is more common in women and has a high mortality. Older age, low haemoglobin and higher platelet transfusions are predictors of poor survival. Nosocomial infection rates were similar irrespective of receiving PE therapy.

Antioxidant micronutrient supplements for adult critically ill patients: A bayesian multiple treatment comparisons meta-analysis.

BACKGROUND & AIMS: Antioxidant micronutrients (AxMs) have been administered to critically ill adults attempting to counteract the oxidative stress imposed during critical illness. However, results are conflicting and relative effectiveness of AxMs regimens is unknown. We conducted a Bayesian multi-treatment comparison (MTC) meta-analysis to identify the best AxM treatment regimen that will improve clinical outcomes. METHODS: PubMed, EMBASE, Web of Science and Cochrane databases were searched from the inception of databases through August 2020. Randomized controlled trials (RCT) comparing AxMs supplementations with placebo among critically ill adults were included. Two authors assessed trial quality using Cochrane risk of bias tool and assessed certainty of evidence (CoE). A random effect model, non-informative priors Bayesian MTC meta-analysis using gemtc package in R version 3.6.2 was performed. AxMs treatment effect on clinical outcomes (mortality, infection rates, intensive care unit (ICU) and hospital stays and ventilator days) were represented by absolute risk differences (ARD) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Prior to final analysis, we repeated the search through January 2021. RESULTS: 37 RCT (4905 patients) were included with 16 direct comparisons. With respect to mortality, the ARD for "vitamin E" compared with placebo was centred at -0.19 [95%CrI: -0.54,0.16; very low CoE] and was ranked the best treatment for mortality reduction as per surface under the cumulative ranking curve (SUCRA 0.71, 95%CrI: 0.07,1.00). A combination of "selenium, zinc and copper" was ranked the best for lowest ICU stay [-9.40, 95% CrI: -20.0,1.50; low CoE]. A combination of "selenium, zinc, copper and vitamin E" was ranked the best treatment for infection risk reduction [-0.22, 95% CrI: -0.61,0.17; very low CoE]. Ventilator days were least with a combination of "selenium, zinc and manganese" [2.80, 95% CrI: -6.30,0.89; low CoE]. Hospital stay was the lowest using a combination of "selenium, zinc and copper" [-13.00, 95% CrI: -38.00,13.00; very low CoE]. There is substantial uncertainty present in the rankings due to wide and overlapping 95% CrIs of SUCRA scores for the treatments. CONCLUSIONS: Studies on critically ill adult patients have suggested a possible beneficial effects of certain AxM supplementations over and above the recommended dietary allowance. However, evidence does not support their use in clinical practice due to the low confidence in the estimates. Current studies evaluating specific AxMs or their combinations are limited with small sample sizes. REGISTRATION: PROSPERO, CRD42020210199. TAKE-HOME MESSAGE: Evidence suggesting a potential benefit of AxMs use more than recommended doses in critically ill adults is weak, indicating that there is no justification for this practice.

Evaluation of Predictors, Kinetics of Renal Recovery and Outcomes of COVID-19 Patients with Acute Kidney Injury Admitted to Intensive Care Unit: An Observational Study.

Background: The incidence of acute kidney injury (AKI) is greater than 50% among coronavirus disease-2019 (COVID-19) patients admitted to the intensive care unit (ICU). However, the literature on predictors and kinetics of renal recovery remains unclear. Patients and methods: This observational study was conducted in a 30-bedded mixed ICU of a tertiary care center from May 2020 to July 2021. A total of 200 consecutive adult COVID-19 patients who had AKI in ICU were included. Using logistic regression with the best subset selection, predictors of renal recovery were identified. Outcomes and kinetics of AKI recovery were determined. Results: Among 200 patients, 67 recovered from AKI, of which 38, 17, and 12 patients had transient AKI, persistent AKI, and acute kidney disease (AKD), respectively. A total of 25 patients had AKI relapse, primarily associated with hospital-acquired infections. Results of logistic regression showed that the combination of Acute Physiology and Chronic Health Evaluation (APACHE II) {odds ratio (OR) 1.1 [p < 0.001; 95% confidence interval (CI) 1.06-1.16]}, day onset of AKI [OR 1.6 (p = 0.001; 1.24-2.24)] and severity of AKI [OR 2.9 (p < 0.001; 2.03-4.36)] were the predictors associated with poor renal recovery. This model had sufficient discrimination with the area under the curve (AUC) of 0.86. Renal replacement therapy requirement and mortality among COVID-AKI patients were 68 and 84%, respectively. Conclusion: A higher APACHE II at admission, a longer time to onset of AKI, and the severity of AKI during ICU stay predicted poor renal recovery. Study results emphasize the need for stepping-up dialysis resources in the likely case of future waves of COVID-19. The relapse of AKI was associated with sepsis, and mortality rates were substantially high. How to cite this article: Gudivada KK, Narayan SK, Narasimha A, Krishna B, Muralidhara KD. Evaluation of Predictors, Kinetics of Renal Recovery and Outcomes of COVID-19 Patients with Acute Kidney Injury Admitted to Intensive Care Unit: An Observational Study. Indian J Crit Care Med 2022;26(12):1293-1299.

Antioxidant micronutrient supplementation in critically ill adults: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The role of antioxidant micronutrient (AxM) supplementation in the critically ill patients has been controversial, and recent trials have suggested a tendency to harm. Therefore, we performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCT) to examine the effect of AxM supplementation on clinical outcomes among critically ill adults. METHODS: PubMed, EMBASE, Cochrane, CINAHL, LILACS, DARE, SCOPUS, and Web of sciences databases were searched from inception to March 2019. RCTs that compared AxM supplements with placebo in adult critically ill patients and reporting mortality as an outcomes were included. Trial quality was assessed using updated cochrane risk of bias (RoB-II) tool. Primary outcome was all-cause mortality. Secondary outcomes were 28-day mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilator days and infection between the two groups. Outcomes were summarised using random-effects estimators. Quality of evidence (QOE) was rated using Grading of Recommendations, Assessment, Development and Evaluation. Prior to final analysis, we repeated the search through September 2019. R version 3.6.2 and STATA version 13 were used for all statistical analyses. RESULTS: Pooled analysis of 34 trials with 4678 patients revealed that AxM supplementation was associated with possible reduction in all-cause mortality (relative risk [RR], 0.89 [95%CI 0.79 to 0.99], TSA adjusted CI 0.77 to 1.03; Low QOE). Fragility index and number needed to treat were 1 and 41, respectively. Eight studies with low RoB (RR, 1.08; 95%CI 0.95 to 1.23; TSA CI, 0.64 to 1.82; moderate QOE) did not show mortality reduction with AxM supplementation. SECONDARY OUTCOMES: ICU LOS (weighted mean difference [WMD], -0.84; 95%CI -1.50 to -0.18; moderate QOE), hospitalization days (WMD, -2.83; 95%CI -3.91to -1.75; low QOE) and ventilator days (WMD, -1.87; 95%CI -3.60 to -0.14; very low QOE) showed a statistically significant benefit with AxM supplementation. In meta-regression analysis, neither the duration of AxM therapy nor the dosage of selenium, which was the most widely studied AxM, reported an association with mortality. CONCLUSION: Although AxM supplementation was associated with possible reduction in all-cause mortality, results from the TSA and studies with low RoB showing null effect suggest that the evidence of benefit is questionable. Secondary outcomes attained statistically significant benefit with AxM supplements, but the certainity of evidence was low. To summarize, current evidence does not justify administration of AxM in critically ill patients. REGISTRATION: PROSPERO, CRD42019125898.

Intensive insulin therapy and plasma exchange in hypertriglyceridaemic acute pancreatitis with multiple organ dysfunction.

Acute pancreatitis (AP) is a common emergency in gastroenterology. After gallstone disease and alcoholism, hypertriglyceridaemia (HTG) is the next common cause for AP. The role of intensive insulin therapy (IIT) and plasma exchange (PE) in hypertriglyceridaemic acute pancreatitis (HTG-AP) is still debatable. We report a 56-year-old farmer with HTG-AP who presented with a recurrence of AP. On admission, his plasma triglycerides were 4773 mg/dl with a wide range of laboratory abnormalities. Over the course of his illness, he developed multiple organ failure. He received early IIT initially, and PE once haemodynamic stability was achieved. This approach improved the functioning of the organs. In haemodynamically unstable patients with HTG-AP, we suggest early initiation of IIT, followed by adjuvant PE after the resolution of shock, to ameliorate organ dysfunction and improve overall outcome.

Comparison of ease of intubation in sniffing position and further neck flexion.

BACKGROUND AND AIMS: Optimization of patient's head and neck position for the best laryngeal view is the most important step before laryngoscopy and intubation. The objective of this prospective crossover study was to determine the differences, if any, between the gold standard sniffing position (SP) and the further head elevation (HE) (neck flexion) with regard to the incidence of difficult laryngoscopy, intubation difficulty, and variables of the I ntubation Difficulty Scale (IDS) in adult patients undergoing elective surgery under general anesthesia. MATERIAL AND METHODS: In the "SP" the neck must be flexed on the chest by elevating the head with a cushion under the occiput and extending the head at the atlanto-occipital joint. Our study was carried out to evaluate the glottic view in SP compared to further HE by 1.5 inches during direct laryngoscopy in elective surgeries. Patients were randomly assigned to either Group A ("SP" during first laryngoscopy and "HE" during second laryngoscopy) or vice versa in Group B. The effect of patient position on ease of intubation was assessed using a quantitative scale - The intubation difficulty scale (IDS). RESULTS: There were significant differences with regard to glottic visualization (P = 0.00), number of operators (P = 0.001), laryngeal pressure (P = 0.00), and lifting force (P = 0.00) required for intubation and IDS (P = 0.00), thus favoring further HE position. CONCLUSION: We conclude that the HE position is superior to standard SP with regard to ease of intubation as assessed by IDS.

Evaluation of Quality Indicators in an Indian Intensive Care Unit Using "CHITRA" Database.

BACKGROUND: Quality indicators (QIs) are essential for maintaining quality of care in the critically ill. The Indian Society of Critical Care Medicine proposed benchmarks and enabled Indian Intensive Care Units (ICUs) to capture data in an electronic database: Customized Health in Intensive Care Trainable Research and Analysis (CHITRA) tool. The purpose of this study is to report QIs in an Indian ICU using this database. MATERIALS AND METHODS: Data from patients admitted to ICU between October 2015 and January 2017 were entered into CHITRA. The following QIs were analyzed: standardized mortality ratio (SMR), length of ICU stay (LOS-ICU), pressure ulcer (PU) rate, patient fall rate (FR), ICU readmission rate, reintubation rate, ventilator-associated condition (VAC), central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), and iatrogenic pneumothorax rate. RESULTS: A total of 2642 patient's information was suitable for analysis. Median age of ICU admission was 53 years (interquartile range [IQR]: 36-65), with a mean APACHE score of 18 (SD 7.7). Median LOS-ICU was 3 days (IQR 2-6) and SMR was 1.1 (95% confidence interval 1.05-1.38). Pneumothorax rate, PU rate, and FR were 2.6, 4.1, and 0.3 per 1000 respectively, whereas readmission rate was 0.7% and reintubation rate was 3.5%. VAC, CLABSI, and CAUTI were 8.5, 23, 3.1 per 1000 ventilator and catheter days, respectively. CONCLUSION: This study has successfully evaluated a range of QIs in a mixed ICU of a tertiary hospital utilizing CHITRA database.

Differential cyanosis and undiagnosed eisenmenger's syndrome: The importance of pulse oximetry.

Eisenmenger's physiology has significant anesthetic implications. The symptamology, in the early course of disease can be subtle at times and missed on regular PAC. Pulse oximetry, in our patient detected differential saturations. The possibility of underlying congenital cardiac illness was assumed, rescheduling of case was debated and finally the abnormal cardiac lesions were identified in ECHO in immediate postoperative period.