High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial.

OBJECTIVES: Sympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional practice. The trial objective was to compare the efficacy of high-dose and low-dose GTN in patients with SCAPE. METHODS: This was an open-label randomised control trial conducted in a tertiary care teaching hospital in India from 11 November 2021 to 30 November 2022. Consenting participants were randomised to high-dose GTN or conventional low-dose GTN. The primary outcome was symptom resolution at 6 hours and 12 hours. Secondary outcomes included intubation rates, admission rates, length of hospital stay, and any short-term adverse effects of GTN and major adverse cardiac events (MACE) at 30 days. RESULTS: Fifty-four participants were included (26 high-dose GTN, 26 low-dose GTN). At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the 'high-dose' group, compared with 3 (11.5%) in the 'low-dose' group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the 'high-dose' arm versus 19.5% in 'low-dose' arm . The low-dose group had longer median hospital stay (12 hours vs 72 hours), more frequent MACE (3.8% vs 26.9%, p=0.02) and a higher intubation rate (3.8% vs 19.2%, p=0.08). The only short-term adverse effect seen was a headache in both the groups. CONCLUSION: In SCAPE, patients receiving high-dose GTN (>100 mcg/min) had earlier symptom resolution compared with the conventional 'low dose' GTN without any significant adverse effects. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/11/037902).

Taming the Tiger: Ultra high dose nitroglycerin in managing sympathetic crashing acute pulmonary edema patient.

INTRODUCTION: Sympathetic Crashing Acute Pulmonary Edema (SCAPE) lies on the end of the acute heart failure syndrome spectrum with pulmonary edema in all lung zones. NTG at lower doses (10-20 µg/min) cause preload reduction, and at higher doses (> 100 µg/min) causes after-load reduction by arterial dilatation. The main aim is to decrease the afterload at the earliest to cut the vicious cycle caused by sudden sympathetic upsurge. To our knowledge, this is the highest nitroglycerin dose usage in the literature. CASE: A 60-year-old male with no known prior co-morbidities presented to our Emergency with complaints of acute onset severe shortness of breath, which was also associated with extreme diaphoresis, agitation, anxiety, and palpitations. On Examination, the patient was hypoxic and hypertensive with severe tachypnea and tachycardia. On Auscultation, diffuse bilateral crackles in all areas were heard. Point of care ultrasound showed bilateral B-profile in all lung zones, inferior vena cava was >50% collapsible. We managed the patient with non-invasive ventilation and ultrahigh dose nitroglycerin/ highest ever- 9 mg intravenous bolus with 76 mg infusion. The patient had improved within hours and did not require oxygen. The patient was discharged from the emergency after a few hours of observation. DISCUSSION: SCAPE occurs due to a vicious spiral involving increasing sympathetic outflow, excessive afterload, and worsening heart failure. The central, defining pathophysiological feature of SCAPE is pathologically elevated afterload due to systemic vasoconstriction and hypertension. SCAPE patients may be euvolemic, hypovolemic or hypervolemic. The problem is shift of fluid into the lungs rather than hypervolemia. The emphasis on treating pulmonary edema has shifted from diuretics to vasodilators, especially high-dose nitrates, combined with non-invasive positive pressure ventilation. CONCLUSION: This is the first report describing the safe and effective administration of ultra-high dose bolus/ highest dose ever and prolonged high-dose infusion for SCAPE, along with Non-invasive ventilation, which has prevented mechanical ventilation and mortality. High doses of intravenous NTG are extremely effective and safe for SCAPE patients.

Assessing the serum chymase level as an early predictor of dengue severity.

We conducted a prospective, observational study to assess the serum chymase level, a mast cell derived protease, as a predictor of dengue severity. NS1-positive non-severe dengue patients of age ≥14 years with duration of fever ≤4 days were included in the study. At the time of admission, the serum sample was taken for chymase estimation. Patients were followed up to four days after they became afebrile to find out the final diagnosis. Total of 338 non-severe dengue patients were recruited (mean age: 29.15 years; male: 66%). On follow-up, 26 patients (7.8%) developed severe dengue. Only chymase level (adjusted odds ratio [aOR]: 1.787; 95% confidence interval [CI]: 1.309-2.440) and platelet count at admission (aOR: 0.981; 95% CI: 0.968-0.993) were able to predict the severity after adjustment for all variables. But, for prediction of severe dengue, the area under receiver's operating curve of chymase was 0.835 (95% CI: 0.765-0.905), which was significantly higher than that of the platelet count at admission (0.760, 95% CI: 0.650-0.870) (p < .001). Patients who developed severe dengue in due course of illness had significantly higher serum chymase level at admission as compared with the rest of the patients. Similar findings were noted across all age-groups. At an optimum cut-off value of 1.35 ng/ml, chymase had a positive likelihood ratio (LR) of 3.5 and a negative LR of 0.15, for predicting severe dengue. This study demonstrated the potential ability of serum chymase levels at admission, as a biomarker for prediction of severe dengue in due course of illness.

Evolution of Micron-Spaced Patterns within Precipitating Patterns of In Situ Synthesized Silver Nanoparticles in a Nanodot-Embedded PVA/PVP Film.

Periodic pattern formation beyond conventional precipitation reactions of electrolytes is of greater importance for gaining insights into the driving forces behind spontaneous spatiotemporal pattern formation in living matter. The Liesegang phenomenon is considered to be one of the important models for understanding well-defined periodic patterns. In this study, we have used biomolecule-derived photoluminescent carbon nanodots as reducing agents that were embedded in thin polymer films. The poor water content of polyvinyl alcohol/polyvinyl pyrrolidone films has been found to dictate the temporal scale of reaction-diffusion kinetics. Moreover, the precursors for the synthesis of nanodots have been varied to decipher the role of thiol groups present in glutathione in micron-spaced pattern formation of silver nanoparticles. A method to develop periodic patterns of plasmonic silver nanoparticles is of significant interest from technological aspects. Moreover, the formation of a micron-spaced pattern has been rationed by invoking a lowered nucleation threshold in terms of slow reaction-controlled aggregation. We expect that such an understanding of the chemical reaction-based pattern formation will help in resolving the formation of artistic spatiotemporal patterns in nature.

Impact of personal protective equipment on the effectiveness of chest compression - A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: To assess the impact of personal protective equipment (PPE) on different aspects of chest compression (CC) during cardiopulmonary resuscitation, we conducted this study. METHODS: This systematic review was performed according to the PRISMA. We searched PubMed, EMBASE and Web of Science from inception to June-6, 2020, limiting to the studies that reported the comparison of the effectiveness of CC in terms of CC rate, CC depth, the proportion of adequate CC rate, the proportion of adequate CC depth or proportion of adequate recoil; in study arms with or without PPE. Risk of bias was assessed by the ROB-2 and ROBINS-I tool. Quantitative data synthesis was done using the generic inverse variance method and the fixed-effects model. RESULTS: Five simulation-based studies were finally included. A Significant decrease in CC rate (SMD: -0.28, 95%CI: -0.47 to -0.10) and CC depth (SMD: -0.26, 95%CI: -0.44 to -0.07) were observed in the PPE arm as compared to the no-PPE arm. The difference in CC rate was more prominently seen in adult CPR than in paediatric CPR. Without PPE, the proportion of adequate CC rate delivered was 0.74, which reduced significantly to 0.60 after use of PPE (p - 0.035). Similarly, the proportion of adequate CC depth was significantly lesser (p - 0.001) in PPE arm (0.55), as compared to that of the no-PPE arm (0.78). CONCLUSION: The use of PPE compromises the quality of CC during CPR significantly, and newer ways to deliver chest compression has to be investigated. This study was prospectively registered in PROSPERO (CRD42020192031).

Lung sonographic findings in COVID-19 patients.

OBJECTIVE: The objective of this study was to describe the lung sonographic findings of COVID-19 patients prospectively and investigate its association with disease severity. METHODS: This study was conducted in an emergency department and included consecutively enrolled laboratory confirmed COVID-19 patients. Lung sonography findings were described in all the included patients and analysed with respect to the clinical severity of the patients. RESULTS: 106 patients were included in the study. Common sonographic findings in COVID-19 patients were pleural line irregularity or shredding (70% of patients), followed by B - profile (59%), pleural line thickening (33%), occasional B - lines (26%), sub-pleural consolidations (35%), deep consolidations (6%), spared areas (13%), confluent B - lines or waterfall sign (14%) and pleural effusion (9%). These findings tended to be present more bilaterally and in lower lung zones. Sonographic characteristics like bilateral lung involvement, B - profile, spared areas and confluent B - lines or waterfall sign were significantly associated (p < 0.01) with clinical severity (more frequent with increasing disease severity). CONCLUSION: The lung sonographic findings of COVID-19 were found more bilaterally and in lower lung zones, and specific findings like B - profile, pleural thickening, spared areas and confluent B - lines or waterfall sign were associated with severe COVID-19.

High-Dose Nitroglycerin Bolus for Sympathetic Crashing Acute Pulmonary Edema: A Prospective Observational Pilot Study.

BACKGROUND: Sympathetic crashing acute pulmonary edema (SCAPE) is a severe form of hypertensive acute heart failure with a dramatic presentation. Rapid identification and management in the emergency department (ED) is key to saving these patients and preventing morbidity associated with endotracheal intubation and intensive care treatment. Use of high-dose nitroglycerin (NTG) and noninvasive ventilation (NIV) has been advocated in management of such patients. OBJECTIVE: To study the feasibility and safety of high-dose NTG combined with NIV in SCAPE. METHODS: This was a prospective observational pilot study done in the ED of a tertiary care hospital. All patients were treated with high-dose NTG and NIV. The primary objective was to study the feasibility and safety of the SCAPE management protocol in terms of the outcome of the patient. Resolution of symptoms in 6 h and need for intubation were recorded as endpoints. Any complications associated with high-dose NTG were also recorded. RESULTS: A total of 25 patients were recruited. The mean bolus dose of NTG given was 872 µg, and mean cumulative dose, 35 mg. There was no incidence of hypotension after the bolus dose of nitroglycerin. Eleven patients had resolution of symptoms at 3 h of therapy. Twenty-four patients were discharged from the ED itself after a brief period of observation, and one patient was intubated and shifted to the intensive care unit. CONCLUSION: Use of our specific SCAPE treatment algorithm, which included high-dose NTG and NIV, was safe and provided rapid resolution of symptoms.

Prognostic Value of Serum Procalcitonin Levels in Patients With Febrile Neutropenia Presenting to the Emergency Department.

BACKGROUND: Various risk-stratification scores have been developed to identify low-risk febrile neutropenia (FN). The Multinational Association of Supportive Care in Cancer (MASCC) score is a commonly used validated scoring system, although its performance varies due to its subjectivity. Biomarkers like procalcitonin (PCT) are being used in patients with FN to detect bacteremia and additional complications. OBJECTIVE: Our objective was to compare the performance of MASCC score with PCT in predicting adverse outcomes in patients with FN. METHODS: This was a prospective observational study that included chemotherapy-induced FN in hematologic or solid malignancy. The MASCC score, PCT levels, and blood cultures were taken at the first point of contact, and patient treatment was managed according to routine institutional protocol. The primary outcome was mortality at 30 days. RESULTS: A total of 100 patients were recruited, of which 92 had hematologic malignancy and 8 had solid malignancy. Forty-six patients were classified as low risk by MASCC score (≥21). The PCT threshold, 1.42 ng/mL, was taken as a cutoff value, with area under the receiver operating characteristic curve (AUROC) of 0.664 (95% confidence interval [CI] -0.55 to 0.77) for predicting mortality. AUROC for MASCC was 0.586 (95% CI 0.462 to 0.711). CONCLUSIONS: PCT is a useful marker with better prognostic efficacy than MASCC score in patients with FN and can be used as an adjunct to the score in risk-stratifying patients with FN.

COVID-19 in health care workers - A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: It is essential to know the proportion of health care workers (HCW) who are COVID 19 positive, as well as the severity and mortality among them. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic review and meta-analysis. Databases including PubMed, EMBASE and Web of Science were searched from December-31, 2019 to April-23, 2020. The search was limited to the studies that reported the data on the number of COVID-19 positive healthcare workers, among the COVID-19 positive patients. Case reports, duplicate publications, reviews, and family-based studies were excluded. The methodological quality of studies was assessed by the Appraisal tool for Cross-Sectional Studies (AXIS) tool. RESULTS: In this systematic review and meta-analysis, we pooled eleven studies to investigate the above factors. The overall proportion of HCW who were SARS-CoV-2 positive among all COVID-19 patients was 10.1% (95%CI: 5.3-14.9). This proportion varied according to the country of study i.e. China (7 studies) - 4.2%, 95%CI:2.4-6.0; United States (3 studies) - 17.8%, 95%CI:7.5-28.0; and Italy (1 study) - 9.0%, 95%CI:8.6-9.4. The incidence of severe or critical disease in HCW (9.9%, 95%CI:0.8-18.9) was significantly lower (p < 0.001) than the incidence of severe or critical disease in all COVID-19 positive patients (29.4%, 95%CI:18.6-40.2). Similarly, the mortality among HCW (0.3%, 95%CI:0.2-0.4) was also significantly lower (p < 0.001) as compared to that of all patients (2.3%, 95%CI:2.2-2.4). CONCLUSION: Health care workers who are COVID-19 positive constituted a significant proportion of all COVID-19 patients; but the severity and mortality were lower among them.

Endotracheal Tube Placement Confirmation by Ultrasonography: A Systematic Review and Meta-Analysis of more than 2500 Patients.

BACKGROUND: The integration of point-of-care ultrasound in endotracheal tube placement confirmation has been focus of many recent studies. OBJECTIVES: We sought to determine the diagnostic accuracy of ultrasonography in confirmation of endotracheal intubation compared with standard confirmatory methods. METHODS: We completed an extensive search of PubMed, EMBASE, Cochrane Central, Web of Science, and bibliographies of the selected articles from inception to October 2019. The search was limited to prospective studies conducted in human adults that compared the accuracy of ultrasonography in confirming the endotracheal tube position with a reference standard. The methodologic quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate random-effects model summarized diagnostic accuracy statistics. Subgroup analyses by ultrasonographic signs, study location, the operator's specialty, types of transducer, the technique of ultrasound confirmation, and clinical setting (cardiac arrest vs. non-cardiac arrest) were performed. RESULTS: Thirty studies involving 2534 patients were selected for this meta-analysis. The estimated pooled sensitivity and specificity for ultrasonography were 0.982 (95% confidence interval [CI] 0.971-0.988) and 0.957 (95% CI 0.901-0.982), respectively. Subgroup analyses did not reveal significant difference by ultrasonographic sign used, location, the sonographer's specialty, transducer type, or ultrasound technique used. Ultrasound was also found to be a useful adjunct in confirming endotracheal tube position in the subgroup of patients with cardiac arrest, with sensitivity of 0.99 (95% CI 0.98-1.00) and specificity of 0.84 (95% CI 0.67-1.00), respectively. CONCLUSIONS: Ultrasonography is a valuable and reliable adjunct for endotracheal tube confirmation, including during cardiac arrest resuscitation.

"Six-dial Strategy"-Mechanical Ventilation during Cardiopulmonary Resuscitation.

As per current guidelines, whenever an advanced airway is in place during cardiopulmonary resuscitation, positive pressure ventilation should be provided without pausing for chest compression. Positive pressure ventilation can be provided through bag-valve resuscitator (BV) or mechanical ventilator (MV), which was found to be equally efficacious. In a busy emergency department, with less trained personnel use of MV is advantageous over BV in terms of reducing human errors and relieving the airway manager to focus on other resuscitation tasks. Currently, there are no guidelines specific to MV settings in cardiac arrest. We present a concept of "six-dial ventilator strategy during CPR" that encompasses the evidence-based settings appropriate during chest compression. We suggest use of volume control ventilation with the following settings: (1) positive end-expiratory pressure of 0 cm of water (to allow venous return), (2) tidal volume of 8 mL/kg with fraction of inspired oxygen at 100% (for adequate oxygenation), (3) respiratory rate of 10 per minute (for adequate ventilation), (4) maximum peak inspiratory pressure or P max alarm of 60 cm of water (to allow tidal volume delivery during chest compression), (5) switching OFF trigger (to avoid trigger by chest recoil), and (6) inspiratory to expiratory time ratio of 1:5 (to provide adequate inspiratory time of 1 second). How to cite this article: Sahu AK, Timilsina G, Mathew R, Jamshed N, Aggarwal P. "Six-dial Strategy"-Mechanical Ventilation during Cardiopulmonary Resuscitation. Indian J Crit Care Med 2020;24(6):487-489.

Transradial approach for collateral embolisation.

Significant aortopulmonary collaterals in cyanotic CHD patients require closure immediately before definitive intracardiac repair. Traditionally, the transfemoral access has been used for this purpose; however in a few cases, selective and stable hooking of collaterals may be extremely difficult. We describe a case in which we used a new approach for collateral embolisation in a difficult situation.

Mycobacterium tuberculosis H37Ra: a surrogate for the expression of conserved, multimeric proteins of M.tb H37Rv.

BACKGROUND: Obtaining sufficient quantities of recombinant M.tb proteins using traditional approaches is often unsuccessful. Several enzymes of the glycolytic cycle are known to be multifunctional, however relatively few enzymes from M.tb H37Rv have been characterized in the context of their enzymatic and pleiotropic roles. One of the primary reasons is the difficulty in obtaining sufficient amounts of functionally active protein. RESULTS: In the current study, using M.tb glyceraldehyde-3-phosphate dehydrogenase (GAPDH) we demonstrate that expression in E. coli or M. smegmatis results in insolubility and improper subcellular localization. In addition, expression of such conserved multisubunit proteins poses the problem of heteromerization with host homologues. Importantly the expression host dramatically affected the yield and functionality of GAPDH in terms of both enzymatic activity and moonlighting function (transferrin binding). The applicability of this system was further confirmed using two additional enzymes i.e. M.tb Pyruvate kinase and Enolase. CONCLUSIONS: Our studies establish that the attenuated strain M.tb H37Ra is a suitable host for the expression of highly hydrophobic, conserved, multimeric proteins of M.tb H37Rv. Significantly, this expression host overcomes the limitations of E. coli and M. smegmatis expression and yields recombinant protein that is qualitatively superior to that obtained by traditional methods. The current study highlights the fact that protein functionality (which is an an essential requirement for all in vitro assays and drug development) may be altered by the choice of expression host.