Comparative Effect of High-Frequency Nasal Cannula and Noninvasive Ventilation on the Work of Breathing and Postoperative Pulmonary Complication after Pediatric Congenital Cardiac Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Various forms of commonly used noninvasive respiratory support strategies have considerable effect on diaphragmatic contractile function which can be evaluated using sonographic diaphragm activity parameters. OBJECTIVE: To compare the magnitude of respiratory workload decreased as assessed by thickening fraction of the diaphragm and longitudinal diaphragmatic strain while using high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) modes [nasal intermittent positive pressure ventilation (NIPPV) and bilevel positive airway pressure (BiPAP)] in pediatric patients after cardiothoracic surgery. METHODOLOGY: This prospective randomized controlled trial was performed at a tertiary care surgical intensive care unit in postcardiac surgery patients aged between 1 and 48 months, who were randomly allocated into three groups: 1) HFNC (with flows at 2 L/kg/min), 2) NIPPV via RAMS cannula in PSV mode (pressure support 8 cmH2O, PEEP 5 cmH2O), and 3) BiPAP in nCPAP mode (CPAP of 5 cmH2O). Measurements were recorded at baseline after extubation (R0) and subsequently every 12 hourly (R1, R2, R3, R4, R5) at 12, 24, 36, 48, and 60 hours respectively until therapy was discontinued. RESULTS: Sixty patients were included, with 20 patients each in the NIPPV group, HFNC group, and BiPAP group. Longitudinal strain at crura of diaphragm was lower in the BiPAP group as compared to HFNC group at R2-R4 [R2 (-4.27± -2.73 vs - 8.40± -6.40, P = 0.031), R3 (-5.32± -2.28 vs -8.44± -5.6, P = 0.015), and R4 (-3.8± -3.42 vs -12.4± -7.12, P = 0.040)]. PFR was higher in HFNC than NIPPV group at baseline and R1-R3[R0 (323 ± 114 vs 264 ± 80, P = 0.008), R1 (311 ± 114 vs 233 ± 66, P = 0.022), R2 (328 ± 116 vs 237 ± 4, P = 0.002), R3 (346 ± 112 vs 238 ± 54, P = 0.001)]. DTF and clinical parameters of increased work of breathing remain comparable between three groups. The rate of reintubation (within 48 hours of extubation or at ICU discharge) was 0.06% (1 in NIPPV, 1 in BiPAP, 2 in HFNC) and remain comparable between groups (P = 1.0). CONCLUSION: BiPAP may provide better decrease in work of breathing compared to HFNC as reflected by lower crural diaphragmatic strain pattern. HFNC may provide better oxygenation compared to NIPPV group, as reflected by higher PFR ratio. Failure rate and safety profile are similar among different methods used.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

Right Atrial Strain in Pediatric Pulmonary Hypertension-A Prospective Observational Study.

Right ventricular (RV) afterload due to elevated pulmonary arterial (PA) pressure in pulmonary hypertension (PH) causes long-term right atrial (RA) remodeling and dysfunction. RA function has been shown to correlate with PA pressures and outcome in both adult and pediatric patients with PH. We studied the role of RA strain in estimating PA pressures in congenital heart disease (CHD)-associated PH. Children below 12 years undergoing elective repair of CHD with left-to-right shunts and echocardiographic evidence of PH were included. RA reservoir, conduit and contractile strain along with conventional measures of RV function and PA pressure were measured using transthoracic echocardiography after induction of anaesthesia. Pre-and post-repair invasive PA pressures were measured after surgical exposure. 51 children with a median age of 24 months (range 4-144 months) were included, most of whom were undergoing VSD closure. Contractile RA strain showed good correlation with pre-repair systolic PA pressure in mmHg (r = 0.59, 95%CI 0.37-0.75) or expressed as a percentage of SBP (r = 0.67, 95%CI 0.49-0.80). It also predicted persistent postoperative PH as well as pre-repair pulmonary artery acceleration time and right ventricular systolic pressure measured from tricuspid regurgitation jet. The trends of correlation observed suggest a possible prognostic role of RA strain in ACHD with PH and potential utility in its echocardiographic assessment. The observed findings merit deeper evaluation in larger cohorts.

Evaluation of Quality of Recovery With Quality of Recovery-15 Score After Closed-Loop Anesthesia Delivery System-Guided Propofol Versus Desflurane General Anesthesia in Patients Undergoing Transabdominal Robotic Surgery: A Randomized Controlled Study.

BACKGROUND: Robotic technique of surgery allows surgeons to perform complex procedures in difficult-to-access areas of the abdominal/pelvic cavity (eg, radical prostatectomy and radical hysterectomy) with improved access and precision approach. At the same time, automated techniques efficiently deliver propofol total intravenous anesthesia (TIVA) with lower anesthetic consumption. As both above are likely to bring benefit to the patients, it is imperative to explore their effect on postanesthesia recovery. Quality of Recovery-15 (QoR-15) is a comprehensive patient-reported measure of the quality of postanesthesia recovery and assesses compendious patients' experiences (physical and mental well-being). This randomized study assessed the effect of automated propofol TIVA versus inhaled desflurane anesthesia on postoperative quality of recovery using the QoR-15 questionnaire in patients undergoing elective robotic surgery. METHODS: One hundred twenty patients undergoing robotic abdominal surgery under general anesthesia (GA) were randomly allocated to receive propofol TIVA administered by closed-loop anesthesia delivery system (CLADS) (CLADS group) or desflurane GA (desflurane group). Postoperative QoR-15 score on postoperative day 1 (POD-1) and postoperative day 2 (POD-2) (primary outcome variables), individual QoR-15 item scores (15 nos.), intraoperative hemodynamics (heart rate, mean blood pressure), anesthesia depth consistency, anesthesia delivery system performance, early recovery from anesthesia (time-to-eye-opening, and time to tracheal extubation), and postoperative adverse events (sedation, postoperative nausea and vomiting [PONV], pain, intraoperative awareness recall) (secondary outcome variables) were analyzed. RESULTS: On POD-1, the CLADS group scored significantly higher than the desflurane group in terms of "overall" QoR-15 score (QoR-15 score: 114.5 ± 13 vs 102.1 ± 20.4; P = .001) and 3 individual QoR-15 "items" scores ("feeling rested" 7.5 ± 1.9 vs 6.4 ± 2.2, P = .007; "good sleep" 7.8 ± 1.9 vs 6.6 ± 2.7, P = .027; and "feeling comfortable and in control" 8.1 ± 1.7 vs 6.9 ± 2.4, P = .006). On the POD-2, the CLADS group significantly outscored the desflurane group with respect to the "overall" QoR-15 score (126.0 ± 13.6 vs 116.3 ± 20.3; P = .011) and on "5" individual QoR-15 items ("feeling rested" 8.1 ± 1.4 vs 7.0 ± 2.0, P = .003; "able to return to work or usual home activities" 6.0 ± 2.2 vs 4.6 ± 2.6, P = .008; "feeling comfortable and in control" 8.6 ± 1.2 vs 7.7 ± 1.9, P = .004; "feeling of general well-being" 7.8 ± 1.6 vs 6.9 ± 2.0, P = .042; and "severe pain" 9.0 ± 1.9 vs 8.1 ± 2.5, P = .042). CONCLUSIONS: Automated propofol TIVA administered by CLADS is superior to desflurane inhalation GA with respect to early postoperative recovery as comprehensively assessed on the QoR-15 scoring system. The effect of combined automated precision anesthesia and surgery (robotics) techniques on postoperative recovery may be explored further.

Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Clinicoradiological Profile of COVID-19-Associated Rhino-Orbital Cerebral Mucormycosis with a Focus on Computed Tomography: A Clinical Case Series and Review.

COVID-19-associated rhino-orbital cerebral mucormycosis (ROCM) has a rapidly evolving course with high morbidity and mortality. We describe imaging features of COVID-19-associated ROCM based on noncontrast computed tomography (NCCT). This retrospective single-center observational study included 50 patients with COVID-19 from January 1, 2021 to June 30, 2021 who subsequently developed ROCM confirmed by fungal culture studies. All patients underwent NCCT of the paranasal sinuses as the diagnostic workup. The involvement of the nasal cavity, paranasal sinuses, orbits, and intracranial cavity was identified and graded. The ethmoid sinuses were most commonly involved [right (n = 46 of 50) > left (n = 45 of 50)], followed by the maxillary, sphenoid, and frontal sinuses. Thinning and erosions of the hard palate were noted in 18% of patients (n = 9), whereas 34% (n = 17) showed dehiscence of the lamina papyracea. Retromaxillary fat stranding was noted in 68% of patients (n = 34). Severe ethmoid sinusitis was associated significantly with ipsilateral pterygopalatine fossa involvement. The extraocular muscles were involved in 64% of patients (n = 32), with 84% (n = 42) showing orbital fat stranding. Proptosis of the affected eye was seen in 66% of patients, optic nerve involvement in 52%, and irregularity of globe contour in 12% (n = 6). The cavernous sinuses were affected in 10% of patients (n = 5), with three of them having temporal infarcts. COVID-19-associated ROCM is an acute, invasive fungal disease characterized by multisinus involvement, often with orbital and intracranial extension. Bilateral involvement with rapid progression should alert one to underlying COVID-19 disease.

Ultrasonic prediction of weaning failure in children undergoing cardiac surgery: A prospective observational study.

Background and Aim: To assess the utility of ultrasonic markers like B-line score (LUS), diaphragm thickness (DT), thickening fraction (DTF), and excursion (DE) as predictors of weaning outcomes in children on mechanical ventilation (MV) after cardiac surgery. Methods: This was a prospective observational study done in postcardiac surgical intensive care unit (ICU) of a tertiary care hospital. Children aged 1 month to 18 years, on MV after cardiac surgery from January to November 2017, were included. They were extubated after satisfying institutional weaning criteria. Ultrasound for LUS, DT, DTF, and DE was performed preoperatively, during pressure support ventilation (PSV) before extubation and 4 h after extubation. Results: Patients were divided into weaning failure and success groups based on reintubation within 48 h of extubation. Of the 50 evaluated patients, 43 (86%) were weaned successfully and 7 (14%) had weaning failure. The left DTF during PSV was lower in patients weaning failure (0.00%, interquartile range (IQR) 0.00-14.28 vs 16.67%, IQR 8.33-22.20, P = 0. 012). The left DTF≤ 14.64% during PSV (area under receiver's operating curve 0.795, P = 0.014), 85% sensitivity, and 57% specificity (positive likelihood ratio 1.97, negative likelihood ratio 0.25) could predict weaning failure. Conclusion: The left DTF during PSV is a good predictor of weaning failure in children on MV in postoperative ICU after congenital cardiac surgery. Take home message: In children on mechanical ventilation after cardiac surgery, left DTF during pressure support ventilation is a good predictor of weaning failure.

Automated Closed-Loop Propofol Anesthesia Versus Desflurane Inhalation Anesthesia in Obese Patients Undergoing Bariatric Surgery: A Comparative Randomized Analysis of Recovery Profile.

INTRODUCTION: Precision general anesthesia (GA) techniques that minimize the presence of residual anesthetic and facilitate recovery, are desirable in patients with morbid obesity. Automated administration of propofol total intravenous anesthesia (TIVA), which facilitates precision propofol delivery by factoring in continuous patient input variable (bispectral index) to establish a closed feedback loop system, may help mitigate concerns related to propofol's lipid solubility and adverse accumulation kinetics in patients with morbid obesity. This randomized study evaluated the recovery of patients with morbid obesity undergoing bariatric surgery under propofol TIVA automated by a closed-loop anesthesia delivery system (CLADS) versus desflurane GA. METHODS: Forty patients, randomly allocated to receive propofol TIVA (CLADS group) or desflurane GA (desflurane group), were evaluated for postoperative recovery (early and intermediate) (primary objective); they were evaluated for intraoperative hemodynamics, anesthesia depth consistency, anesthesia delivery performance characteristics, patient satisfaction, and incidence of adverse events (sedation, pain, postoperative nausea, and vomiting) (secondary objective). RESULTS: No difference was found for the time-to-eye-opening (CLADS group: 4.7 [3.0, 6.7] min vs. desflurane group: 5.6 [4.0, 6.9] min, P = 0.576), time-to-tracheal-extubation (CLADS group: 6.7 [4.7, 9.3] min vs. desflurane group: 7.0 [5.8, 9.2] min, P = 0.528), ability-to-shift score from operating room table to the transport bed (CLADS group: 3 [3.0, 3.5] vs. desflurane group: 3 [3.0, 4.0], P = 0.703), and time to achieve a modified Aldrete score 9/10 (CLADS group: 15 [15.0, 37.5] min vs. desflurane group: 15 [15.0, 43.7] min, P = 0.867). CONCLUSION: Automated propofol TIVA as administered by CLADS, which matched desflurane GA with respect to depth of anesthesia consistency and postanesthesia recovery profile, can be explored further as an alternative anesthesia technique in patients with morbid obesity.

Risk factors for clinically significant diffuse parenchymal lung abnormalities persisting after severe COVID-19 pneumonia.

Background & objectives: The risk factors for clinically significant diffuse parenchymal lung abnormalities (CS-DPLA) persisting after severe coronavirus disease 2019 (COVID-19) pneumonia remain unclear. The present study was conducted to assess whether COVID-19 severity and other parameters are associated with CS-DPLA. Methods: The study participants included patients who recovered after acute severe COVID-19 and presented with CS-DPLA at two or six month follow up and control group (without CS-DPLA). Adults volunteers without any acute illness, chronic respiratory illness and without a history of severe COVID-19 were included as healthy controls for the biomarker study. The CS-DPLA was identified as a multidimensional entity involving clinical, radiological and physiological pulmonary abnormalities. The primary exposure was the neutrophil-lymphocyte ratio (NLR). Recorded confounders included age, sex, peak lactate dehydrogenase (LDH), advanced respiratory support (ARS), length of hospital stay (LOS) and others; associations were analyzed using logistic regression. The baseline serum levels of surfactant protein D, cancer antigen 15-3 and transforming growth factor-ß (TGF-ß) were also compared among cases, controls and healthy volunteers. Results: We identified 91/160 (56.9%) and 42/144 (29.2%) participants with CS-DPLA at two and six months, respectively. Univariate analyses revealed associations of NLR, peak LDH, ARS and LOS with CS-DPLA at two months and of NLR and LOS at six months. The NLR was not independently associated with CS-DPLA at either visit. Only LOS independently predicted CS-DPLA at two months [adjusted odds ratios (aOR) (95% confidence interval [CI]), 1.16 (1.07-1.25); P<0.001] and six months [aOR (95% CI) and 1.07 (1.01-1.12); P=0.01]. Participants with CS-DPLA at six months had higher baseline serum TGF-ß levels than healthy volunteers. Interpretation and conclusions: Longer hospital stay was observed to be the only independent predictor of CS-DPLA six months after severe COVID-19. Serum TGF-ß should be evaluated further as a biomarker.

Utility of portal vein pulsatility fraction in patients undergoing corrective surgery for tetralogy of Fallot.

BACKGROUND: Right ventricle dysfunction is common after corrective surgery for tetralogy of Fallot and is associated with significant morbidity and mortality. We aimed to determine whether an increased portal vein pulsatility fraction (PVPF) was associated with worse clinical outcomes. METHODS: In a prospective, observational, single-centre study, PVPF and other commonly used parameters of right ventricle function were assessed in patients of all ages undergoing corrective surgery for tetralogy of Fallot intraoperatively, with transesophageal echocardiography, before and after bypass, and post-operatively, with transthoracic echocardiography, at days 1, 2, at extubation, and at ICU discharge. The correlation was tested between PVPF and mechanical ventilation duration, prolonged ICU stay, mortality, and right ventricle function. RESULTS: The study included 52 patients, and mortality was in 3 patients. PVPF measurement was feasible in 96% of the examinations. PVPF in the immediate post-operative period had sensitivity of 73.3% and a specificity of 74.3% in predicting the occurrence of the composite outcome of prolonged mechanical ventilation, ICU stay, or mortality. There was a moderate negative correlation of PVPF with right ventricle fractional area change and right ventricle global longitudinal strain (r = -0.577, p < 0.001 and r = 0.465, p < 0.001, respectively) and a strong positive correlation with abnormal hepatic vein waveform (rho = 0.749, p < 0.001). CONCLUSION: PVPF is an easily obtainable bedside parameter to assess right ventricular dysfunction and predict prolonged mechanical ventilation, prolonged ICU stay, and mortality.

Does Cricoid Pressure Increase the Laryngoscopy Force During Rapid Sequence Induction?-A Randomized Study.

OBJECTIVE: Cricoid pressure, a manoeuver used to prevent pulmonary aspiration during rapid sequence induction, can result in deterioration of laryngeal view and increased haemodynamic changes. Its effect on laryngoscopy force remains unevaluated. The study aimed to assess the impact of cricoid pressure on laryngoscopy force and intubation characteristics during rapid sequence induction. METHODS: Seventy American Society of Anaesthesiologists I/II patients, both sexes, aged 16-65, having non-obstetric emergency surgery were randomly assigned to the cricoid group, which received 30 N cricoid pressure during rapid sequence induction, and the sham group, which received 0 N pressure. Propofol, fentanyl, and succinylcholine were used to produce general anaesthesia. The primary outcome was the peak force of laryngoscopy. Secondary outcomes were the laryngoscopic view, time to execute endotracheal intubation, and intubation success rate. RESULTS: With the application of cricoid pressure, the peak forces of laryngoscopy increased significantly, with a mean difference (95% CI) of 15.5 (13.8-17.2) N. With and without CP, the mean peak forces were 40.758 (4.2) and 25.2 (2.6) N, respectively, P < .001. Without cricoid pressure, the intubation success rate was 100%, compared to 85.7% with cricoid pressure, P = .025. The proportions of CL1/2A/2B patients with and without cricoid pressure were 5/23/7 and 17/15/3, respectively, with P = .005. With cricoid pressure, there was a considerable increase in intubation duration, with a mean difference (95% CI) of 24.4 (2.2-19.9) seconds. CONCLUSION: Cricoid pressure increases peak forces during laryngoscopy, resulting in worse intubation characteristics. This demonstrates the need of exercising care while performing this manoeuver.

Biochemical Predictors of Acute Kidney Injury in Critically Ill COVID-19 Patients.

It is estimated that 50% of patients with coronavirus disease 2019 (COVID-19) have varying degrees of renal involvement. In this clinical biomarker development research, we examined in a retrospective study design the temporal changes in biochemical laboratory parameters in relation to the development of acute kidney injury (AKI). In a sample of 399 patients admitted from May 2020 to May 2021 to a tertiary health care intensive care unit (ICU), the incidence of AKI was 27.3%, and the median time to AKI was on 7th day of ICU admission. Most common etiology of AKI was kidney hypoperfusion. Within 72 h of developmental of low blood pressure, 63.76% developed AKI. The likelihood of AKI was higher in those with elevated serum ferritin, aspartate transaminase, and thrombocytopenia (low platelet count). A cutoff value of 750.3 ng/mL [area under the ROC curve (AUC) = 0.777] for serum ferritin, and 40.05 U/L for alanine aminotransferase (AUC = 0.677) 1 day before development of AKI displayed, respectively, a sensitivity of 76.2% and 64.3%, whereas the specificity was 69.5% and 64.1%, respectively, for these two biochemical predictors. A cutoff value of platelets (152.50 × 109/L [AUC = 0.75]) measured 4 days before development of AKI, displayed 83.3% sensitivity and 16.4% specificity. Taken together, our study thoroughly examined the temporal association of various clinical and laboratory parameters with AKI and prediction models were developed as per results of the time series data. These observations in a tertiary health care setting contribute to ongoing efforts for biomarker discovery and development using routine biochemical tests so as to forecast AKI in patients with COVID-19.

Factors Associated With Non-invasive Oxygen Therapy Failure in COVID-19 Pneumonia: A Single Center, Retrospective Study in a Tertiary Hospital in North India.

BACKGROUND: Non-invasive oxygen therapy (NIT) consists of high-flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP). NIT is routinely being used for the management of acute respiratory failure secondary to coronavirus disease-2019 (COVID-19) with variable outcomes. However, previously published studies show that NIT failure might delay endotracheal intubation and invasive mechanical ventilation and results in worse outcomes in patients with hypoxemic respiratory failure. Early prediction of failure of NIT, will help in early decision-making in initiating invasive mechanical ventilation. We retrospectively studied the predictors for NIT failure in patients with moderate to severe COVID-19. METHODS: Adult patients (>18 years) admitted to the intensive care unit (ICU) with moderate to severe COVID-19 ARDS and received NIT [HFNO and CPAP non-invasive ventilation (NIV)] were included in this study. Baseline clinical and laboratory data were collected retrospectively from the electronic hospital information system. NIT failure was defined as the need for invasive mechanical ventilation after the initiation of NIT in the ICU. Univariate and multivariate logistic regression analyses were used to find out the possible predictors of NIT failure. RESULTS: Out of 254 patients admitted to ICU, 127 patients were initiated NIT at admission to ICU. During the course of the ICU stay, 33 (26%) patients subsequently required invasive mechanical ventilation (NIT failure). Respiratory rate-oxygenation index (ROX index) of <2.97 at two hours and <3.63 at six hours of ICU admission predicted NIT failure in our cohort of patients with a high positive predictive value. CONCLUSION: Patient selection is crucial for successful NIT in COVID-19. Application of ROX index measured in the first six hours of ICU admission helps in the identification of patients at risk of NIT failure with moderate to severe COVID-19 ARDS.

Effect of breathing intervention in patients with COVID and healthcare workers.

Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT). Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points. Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 µg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed. Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID. Trial registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.

Predictors of the Outcomes Following the Tocilizumab Treatment for Severe COVID-19.

BACKGROUND:  Tocilizumab is used in severe COVID-19 yet has significant rates of treatment failure. OBJECTIVES:  This retrospective study aimed to identify early predictors of the response to tocilizumab therapy. METHODS:  Biochemical and clinical characteristics of adult patients who received tocilizumab for severe COVID-19 pneumonia were retrospectively examined. A multivariable logistic regression model was constructed to identify factors that could predict the failure of tocilizumab therapy. A predictive nomogram was also created using the selected model. RESULTS:  Out of 101 eligible patients, 30 had treatment failure, and 71 survived on a 28-day follow-up. The partial pressure of oxygen to fraction of inspired oxygen ratio (PFR) on the day of tocilizumab administration (100 vs 80.5), lactate dehydrogenase (LDH; 668 vs 507 U/L), neutrophil-to-lymphocyte ratio (NL ratio; 24.7 vs 10), and creatine kinase myocardial band (CKMB; 30.9 vs 22.7 U/L) were significantly different among the non-survivors and survivors, respectively. A logistic regression model was created, identifying LDH, NL ratio, pro-brain natriuretic peptide (ProBNP), and PFR on the day of tocilizumab administration as best predictors of mortality with an optimism-corrected area under the receiver operator characteristics (ROC) curve of 0.82. The model-implied odds ratios for mortality were 1.89 (95% CI 1.13-3.15) for every 100 U/L rise in serum LDH, 2.29 (95% CI 2.2-4.39) for every 10 unit rise in NL ratio, 1.23 (95% CI 0.95-1.58) for every 100 pg/ml increase in ProBNP, and 0.36 (95% CI 0.13-0.95) for every mmHg rise in PFR at intervention. CONCLUSION:  This study identified NL ratio, LDH, CKMB, and PFR at intervention as important markers of risk of treatment failure following the tocilizumab therapy. A multivariable logistic regression model including LDH, NL ratio, ProBNP, and PFR at intervention best predicted the risk of mortality in patients with severe COVID-19 pneumonia treated with tocilizumab.

How We Do It: Whole Lung Lavage.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disorder characterized by the accumulation of surfactant in the alveolar spaces resulting in hypoxemic respiratory failure. Whole lung lavage (WLL), the preferred treatment for PAP, physically removes the lipoproteinaceous material from the alveolar spaces. Since its initial description in 1963, the WLL procedure has undergone various modifications. However, the procedure has not been standardized yet. After securing a double lumen endotracheal tube, we perform WLL under general anesthesia. One lung is ventilated, while the other is lavaged using one-liter aliquots of pre-warmed saline. We use gravity-assisted drainage of the lavaged lung after each cycle till the milky white and opaque fluid becomes clear (usually 15-20 cycles). Herein, we describe the step-by-step procedure, precautions, and monitoring of WLL. We also provide videos demonstrating one-lung ventilation and bronchoscopic confirmation of lung isolation.

Development of a cost-effective ex vivo lung perfusion system for lung transplantation in India.

Background & objectives: Standard donor lung preservation with cold flush and storage allows up to six hours between retrieval of lungs from the donor and transplantation in the recipient. Ex vivo lung perfusion (EVLP) systems mimic physiological ventilation and perfusion in the donor lungs with potential for prolonged lung preservation and donor lung reconditioning. In this study, it was aimed to perform EVLP on discarded donor lungs using a locally developed EVLP system. Methods: Equipment that are routinely used for cardiac surgeries were collected and a functional EVLP system was assembled. This system was used on five pairs of lungs retrieved from brain-dead organ donors. The lungs were ventilated and pulmonary circulation was continuously perfused with a solution containing oxygen and nutrients for four hours. The system was tested without red blood cells (RBCs) added to the solution (acellular group; n=3; A1, A2 and A3) and also with RBCs added to the solution (cellular group; n=2; C1 and C2). Results: The EVLP system was successfully used in four (A1, A2, A3 and C2) of the five lung pairs. Mechanical and gas exchange functions of the lungs were preserved in these lung pairs. One lung pair (C1) worsened and developed pulmonary oedema. Histopathological examination of all five lung pairs was satisfactory at the end of the procedure. Major challenges faced were leakage of solution from the system and obstruction to drainage of RBCs containing solution from the lungs. Interpretation & conclusions: The results of the present study suggest that, it is possible to maintain the lungs retrieved for transplantation in a physiological condition using a locally prepared EVLP system and a solution without RBCs.