Noninvasive Ventilation in the Management of Respiratory Failure Due to COVID-19 Infection: Experience From a Resource-Limited Setting.

OBJECTIVE: To study the role of noninvasive ventilation (NIV) in Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV2) related acute respiratory failure (C-ARF). PATIENTS AND METHODS: Patients with C-ARF managed on NIV were categorized as NIV success or failure (death or intubation). Factors associated with failure were explored using regression analysis and expressed as odds ratio (OR) with 95% CI. RESULTS: Between April 1, 2020, and September 15, 2020, a total of 286 patients with a mean ± SD age of 53.1±11.6 years and Acute Physiology and Chronic Health Evaluation II score of 11.1±5.5 were initiated on NIV. Of the 182 patients (63.6%) successfully managed on NIV alone, 118 had moderate or severe acute respiratory distress syndrome. When compared with NIV success, NIV failure was associated with lower admission PaO2 to fraction of inspired oxygen ratio (P<.001) and higher respiratory rate (P<.001). On penalized logistic regression analysis, NIV failure was associated with higher Acute Physiology and Chronic Health Evaluation II score (OR, 1.12; 95% CI, 1.01 to 1.24), severe acute respiratory distress syndrome (OR, 3.99; 95% CI, 1.24 to 12.9), D-dimer level of 1000 ng/mL DDU (to convert to mg/L, divide by 1000) or greater (OR, 2.60; 95% CI, 1.16 to 5.87), need for inotropes or dialysis (OR, 12.7; 95% CI, 4.3 to 37.7), and nosocomial infections (OR, 13.6; 95% CI, 4.06 to 45.9). Overall mortality was 30.1% (86/286). In patients requiring intubation, time to intubation was longer in nonsurvivors than survivors (median, 5; interquartile range, 3-8 vs 3; interquartile range, 2-3 days; P<.001). CONCLUSION: Noninvasive ventilation can be used successfully in C-ARF. Illness severity and need for non-respiratory organ support predict NIV failure.

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity.

BACKGROUND: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. OBJECTIVES: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. METHODS: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. RESULTS: The 143 patients (104 males [80%], age 54 [42 - 65] years, median [inter-quartile range]) presented 4 (3-7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 - 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 - 165], p value < 0.001). CONCLUSIONS: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

Thromboelastograph:A prognostic marker in sepsis with organ dysfunction without overt bleeding.

BACKGROUND: Coagulation abnormalities are not infrequent in sepsis. It is unclear if abnormalities in thromboelastogram (TEG) are associated with mortality in patients with severe sepsis without overt bleeding. MATERIALS AND METHODS: In this prospective study, patients were categorised as those with normal coagulation, hypercoagulable or hypercoagulable state based on admission TEG parameters (R time, K time, Maximum amplitude (MA), α angle). Their association with mortality was explored using Fisher's exact and Mann-Whitney U test as appropriate. RESULTS: The study cohort (n = 87; 49 male) with median (IQR) age 51 (42-60) years and admission SOFA score 8 (6-11) included scrub typhus (24.1%), pneumonia (22.6%) and urosepsis (10.3%). Non-invasive and invasive ventilation and vasopressors were required in 28.1%, 68.9% and 74%, respectively. Mortality was 24.1%. Based on R time, K time and α angle, 3.5% to 9.3% had a hypercoagulable state and 26.7 to 29.9% were hypocoagulable. Prolonged R time (p = 0.04) and reduced alpha angle (p = 0.01) in patients with hypocoagulable state was associated with mortality. K time, α angle and MA were significantly different in patients requiring transfusion (p < 0.001). CONCLUSION: A subset of patients with severe sepsis without overt bleeding are hypocoagulable. Hypocoagulability is associated with mortality and need for transfusion.

Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis.

AIM AND OBJECTIVE: Although studies have described the clinical profile of patients admitted to the intensive care unit (ICU) with tuberculosis, it is unclear if the type of tuberculosis (pulmonary, extrapulmonary, or disseminated) impacts outcome. MATRIALS AND METHODS: Demographic data, microbiology, treatment, and outcomes over 5 years (2012-16) were obtained from electronic records. Patients were categorized as pulmonary, extrapulmonary, or disseminated tuberculosis. Comparisons were done using t test and Fisher's exact test as appropriate. Predictors of outcome were explored using bivariate and multivariate logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Of the 428 ICU admissions with suspected tuberculosis, 212 (121 male) patients with mean (standard deviation) age of 41.9 (16.7) years and APACHE-II score of 20.8 (6.6) were diagnosed as pulmonary (n = 55) and extrapulmonary (n = 52) or disseminated tuberculosis (n = 105). In 50.5%, the diagnosis of tuberculosis was established during the current ICU admission when they presented with organ dysfunction. Overall, microbiological confirmation was possible in 75.5%; 14 (10.3%) isolates were Rifampicin resistant. ICU admission was required primarily for ventilation (n = 176; 83%) and hemodynamic instability (n = 67; 32%). Hospital mortality was 50%. Outcomes were similar in the three groups except for longer duration of stay (p value = 0.04) in disseminated tuberculosis. On multivariate logistic regression analysis, pulmonary tuberculosis (OR 2.83; 95% CI 1.15-6.95) and vasoactive treatment (OR 15.8; 95% CI 6.4-39.2) were independently associated with death; need for ventilation predicted mortality perfectly. CONCLUSION: In this cohort of patients admitted to ICU with tuberculosis, 50% were newly diagnosed during ICU admission. Pulmonary site of involvement and need for organ support are independent risk factors for death. HOW TO CITE THIS ARTICLE: Thomas L, Chacko B, Jupudi S, Mathuram A, George T, Gunasekaran K, et al. Clinical Profile and Outcome of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2021;25(1):21-28.

Tuberculous ARDS is associated with worse outcome when compared with non-tuberculous infectious ARDS.

BACKGROUND: Patients with tuberculosis (TB) developing acute respiratory distress syndrome (ARDS) may have a higher mortality when compared with ARDS of other infectious etiology. METHODOLOGY: In this single-centre retrospective cohort study spanning 5-years (2012 to 2016), TB-ARDS patients were age and gender matched (1:2) with non-TB infectious ARDS and followed up until death or hospital discharge. Clinical profile, treatment and outcomes were compared using t-test and Chi-square as appropriate. Mortality predictors were explored using Conditional Poisson regression analysis and expressed as relative risk (RR) with 95% confidence interval (CI). RESULTS: Of the 516 ARDS patients, 74 TB-ARDS and 148 non-TB infectious ARDS patients were included. Although admission APACHE-II (21.4 ± 7.1 vs. 17.6 ± 6.8, p < 0.001), incidence of shock (36.5% vs. 19.1%, p = 0.005) and mortality (59.5% vs. 29.7%, p < 0.001) were significantly higher in TB-ARDS than non-TB etiology, overall ICU length of stay and nosocomial infections were similar in both groups. On regression analysis, after adjusting for confounders, TB-ARDS (RR 1.82; 95% CI 1.13-2.92) and need for inotropes (RR 3.49; 95% CI 1.44-8.46) were independently associated with death. CONCLUSION: Patients with TB-ARDS presented sicker and had higher mortality when compared with ARDS due to non-TB infectious etiology.

Clinical spectrum, aetiology and predictors of acute febrile encephalopathy at a tertiary hospital in south India - A prospective observational study.

Acute febrile encephalopathy is a common syndrome in the tropics with high mortality encountered by emergency physicians. In order to study the aetiology of acute febrile encephalopathy and its mortality and functional outcome over one year, data on all patients >18 years of age with short duration of fever (<14 days) and altered mental status were collected and followed up until one month after discharge. Non-infectious aetiology, found in 29%, portends a poor outcome.

Acute infectious purpura fulminans: a case series from India.

Acute infectious purpura fulminans is a serious, potentially fatal condition. We present a case series of 11 patients from March 2005 to March 2017, whose clinical symptoms were fever (100%), confusion (63.6%) and headache (55%), and whose common laboratory abnormalities were thrombocytopenia (100%), elevated alkaline phosphatase (70%) and anaemia (63.6%). Three patients (27%) developed gangrene and two presented in shock. Only one grew Neisseria meningitidis in cerebrospinal fluid (CSF) culture and another confirmed by latex agglutination and polymerase chain reaction in CSF. Five others had serology confirmed spotted fever rickettsioses (SFG). All received broad spectrum antibiotics; in 9/11 patients, this included doxycycline or azithromycin. The mean hospital stay was 10.2 days and overall mortality was 18.2%.

Trainee doctors in medicine prefer case-based learning compared to didactic teaching.

BACKGROUND: Sustaining interest and promoting deep learning is a challenge in any teaching method. The purpose of the study is to find the perception of trainee doctors in Internal Medicine and teaching faculty on the usefulness of case-based learning (CBL) and to compare assessment knowledge outcome with didactic seminars. METHODS AND MATERIALS: We developed and conducted a CBL teaching program on eight topics in infectious diseases. First group had CBL and second group had didactic seminars. In step 1, a clinical case was introduced in stages. Learning objectives were formulated and topics were divided among the trainees. At step 2, trainees shared what they had learnt from self-directed learning. Faculty summarized the case and learning points. In the seminar group, trainees made presentations on the given topics. Trainees who had CBL underwent a questionnaire survey. Multiple choice questions-based test was administered for both the groups. RESULTS: The trainee doctors and staff overwhelmingly found CBL to be more interesting, stimulating, and useful compared to didactic seminars. There was no statistical difference in the test scores. CONCLUSIONS: CBL is a useful and interesting method of learning and should be employed more often in teaching for trainee doctors.

Scrub Typhus-Associated Opsoclonus: Clinical Course and Longitudinal Outcomes in an Indian Cohort.

CONTEXT: Opsoclonus, a rare neurological manifestation in scrub typhus, causes significant distress and disability. There is a paucity of clinical data and outcomes in these patients. AIM: This study aims to describe the clinical and laboratory profile and longitudinal outcomes in a scrub typhus patient cohort with opsoclonus. SETTINGS AND DESIGN: This retrospective study was conducted in a 2700-bed teaching hospital in South India, in scrub typhus patients with opsoclonus over a 5-year period. PATIENTS AND METHODS: Clinical, laboratory, and radiological data and outcomes at discharge and 6- and 12-weeks postdischarge were documented. RESULTS: Of 1650 scrub typhus patients, 18 had opsoclonus. 17 had opsoclonus at presentation, while one patient developed opsoclonus on the 5th admission day, 1-day postdefervescence. Opsoclonus was first noted after a median interval of 11 (7-18) days from fever onset. It was associated with myoclonus in 94% (17/18), cerebellar dysfunction in 67% (12/18), extrapyramidal syndrome (EPS) in 33% (6/18), and aseptic meningitis in 17% (3/18) patients. Mean cerebrospinal fluid (CSF) white blood cell (WBC) count was 9 ± 2.7 cells/cumm, with mean CSF protein 118.5 ± 53.9 mg% and mean CSF glucose 97 ± 13 mg% in 1l/15 patients. Brain magnetic resonance imaging was unremarkable in 75% (9/12). Case-fatality rate was 5.5% (1/18). Complete resolution of the index neurological syndrome occurred at 12-week postdischarge. CONCLUSIONS: Opsoclonus is a rare neurological manifestation in scrub typhus, usually occurring in association with myoclonus, cerebellar dysfunction, or EPS. It appears to occur during the resolving febrile phase, with neurological deficits completely resolving at 12 weeks.

Outcomes and factors influencing outcomes of critically ill HIV-positive patients in a tertiary care center in South India.

The incidence of (Human immune deficiency) HIV in India has fallen by 58% since the onset of the HIV epidemic. As of 2016 there are 2.1 million people living in India with HIV and only 49% of the adults with HIV are on ART (1). The HIV infected individuals may require intensive care due to various reasons. This study attempts to look at the outcomes of these patients admitted in the intensive care unit and the predictors of these outcomes. AIMS: 1. To assess the outcomes of critically ill HIV infected patients admitted in the medical intensive care unit. 2. Assessment of the factors that are likely to influence the outcome. MATERIALS AND METHODS: it is a retrospective medical review of all the patient records available on our electronic database. The study period was January 2008 - October 2013. RESULTS: in our study cohort the commonest reason for admission into the intensive care unit was sepsis associated with multi organ dysfunction (64%). A low CD 4 count, renal failure acute respiratory distress syndrome, and hypotension and multi organ dysfunction were predictive of a poor outcome in our study. CONCLUSION: The most common cause of admission of PLHIV in ours study cohort was Infections, ART associated side effects and low CD4 counts, presence of multi organ dysfunction, acute respiratory distress syndrome (ARDS), hypotension were associated with adverse outcomes.

Arterial thrombosis as primary presentation of endogenous Cushing's syndrome.

Cushing's syndrome is known to present with a characteristic set of clinical manifestations and complications, well described in literature. However, hypercoagulability remains an under recognised entity in Cushing's syndrome. A 31-year-old woman from Southern India presented with history of fever, left upper quadrant pain and progressive breathing difficulty for 3 weeks. Clinical examination revealed discriminatory features of Cushing's syndrome. Laboratory investigations showed biochemical features of endogenous ACTH-dependent Cushing's syndrome. Imaging of the abdomen revealed splenic collection, left-sided empyema and extensive arterial thrombosis. Gadolinium enhanced dynamic MRI of the pituitary gland revealed no evidence of an adenoma while a Ga-68 DOTATATE positron emission tomography CT scan ruled out an ectopic Cushing's. A diagnosis of endogenous Cushing's syndrome causing a prothrombotic state with extensive arterial thrombosis was made. She was initiated on oral anticoagulation and oral ketoconazole for medical adrenal suppression. She subsequently underwent bilateral adrenalectomy and was well at follow-up.

Cerebrovascular injury in cryptococcal meningitis.

Background Cryptococcal meningitis continues to be one of the common causes of chronic central nervous system infection worldwide. Individuals with cryptococcal meningitis can occasionally present with small vessel vasculitis causing infarcts primarily in the basal ganglia, internal capsule, and thalamus. Literature regarding patterns of cerebrovascular injury among patients with cryptococcal meningitis is scanty, and outcome following these vascular involvements is unknown. Aim To study the clinical profile, imaging findings, and details of vascular territory involved among patients admitted with cryptococcal meningitis and central nervous system infarct in a tertiary care center from India. And to compare the outcomes of patients of cryptococcal meningitis with or without central nervous system infarcts in terms of mortality and morbidity, Methodology A total of 151 patients with microbiologically proven cryptococcal meningitis over a time span of 11 years were retrospectively enrolled into the study. Of these, 66 patients met the inclusion criteria of having appropriate imaging of the brain. The presence of infarct in the imaging was analyzed by two independent radiologists. Patterns of central nervous system involvement and types of vascular injury were ascertained based on radiological parameters. Clinical parameters and outcomes of patients with and without infarcts were compared. Results Twenty (13%) of these patients had evidence of central nervous system infarcts on imaging. The mean age of patients with and without infarcts was 41 years and 38 years, respectively. Male predominance was present among both the groups. The presence of fever, neck stiffness, positive blood culture, and hydrocephalus in central nervous system imaging was similar among patients with or without infarct. Longer duration of illness, low sensorium at the time of presentation, low Glasgow Coma Scale score, presence of meningeal inflammation, cryptococcomas, and basal exudates in imaging were higher in patients with infarct. All the infarcts were of the lacunar type. Sixty percent of the cerebrovascular infarcts were acute in nature, 50% of these being multiple. Unilateral infarcts were seen in 70% of the patients. The most common site of infarct was the basal ganglia, others being distributed over the thalamus, frontal, temporal, parieto-occipital regions in the descending order. The presence of neurovascular involvement in the form of infarcts to the risk of morbidity and mortality had an odds ratio of 9.1 and 2.6, respectively. Conclusion Neurovascular involvement in chronic cryptococcal meningitis is a rare entity. These tend to present as multiple lacunar infarcts. Mortality and morbidity associated with these patients is higher when compared to patients who do not have infarcts. This result suggests that vascular injury plays a role in predicting outcome of patients with cryptococcal meningitis. Future studies are needed to understand the mechanism by which vascular events (infarcts) occur and result in poor outcome.

Mycobacterial blood culture as the only means of diagnosis of disseminated tuberculosis in advanced HIV infection.

The diagnosis of disseminated tuberculosis (TB) in advanced HIV infection is often delayed because of difficulty in obtaining suitable specimens for culture. A total of 32 such patients from South India with positive mycobacterial blood cultures were studied over ten years. Almost all (90%) had a febrile illness and the majority (68.7%) had clinical lung involvement, but only 27.3% had positive sputum smears. Liver biopsy yielded a positive diagnosis in only 1/7. Cytopenia was almost universal (96.9%). Bone marrow cultures were, however, positive in 54.8%, of whom one-quarter grew atypical mycobacteria. Mycobacterial blood culture is therefore a useful adjunct test to diagnose TB in advanced HIV.

Varicella Zoster Virus Infection of the Central Nervous System - 10 Year Experience from a Tertiary Hospital in South India.

INTRODUCTION: Varicella zoster virus is an exclusively human neurotrophic virus. The primary infection with the virus causes varicella. The virus remains latent in nervous tissue and upon secondary activation causes a variety of syndromes involving the central nervous system (CNS) including meningoencephalitis and cerebellitis. MATERIALS AND METHODS: In this study, we looked at the epidemiology, clinical and laboratory features, and outcomes of patients who were admitted with varicella zoster of the CNS from 2005 to 2014. RESULTS: There were 17 patients. Fever was present in 13 patients, seizures in 9 patients and headache and vomiting in 4 patients each. A generalized varicella rash was present in 8 out of 17 patients. A single dermatomal herpes zoster was present in seven patients. Two patients had no rash. Varicella zoster polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) was done in 5 patients of which 4 were positive and 1 was negative. Nine patients had diabetes with an average glycated hemoglobin of 8.6%. Total number of deaths was five. CONCLUSIONS: Patients with diabetes who develop varicella or herpes zoster may be at risk for CNS complications. The diagnosis of varicella encephalitis has to rest on a combination of clinical findings and CSF PCR, as neither the rash nor the PCR is sensitive enough to diagnose all the cases with varicella encephalitis.

A rare case report of Strychnos nux-vomica poisoning with bradycardia.

Strychnine poisoning is a rare method of deliberate self-harm in adults. Poisoning with strychnine leaves is a rare form of strychnine poisoning, as the usual plant parts used are nuts, bark, and seeds. Although the common cardiac manifestations of strychnine positioning include tachycardia and hypertension, we report a patient with mild strychnine poisoning with bradycardia.

Low-dose methotrexate-induced acute interstitial pneumonitis: Report of two cases from South India and review of literature.

Methotrexate (MTX) is an antimetabolite used as a disease-modifying agent for various rheumatological conditions. We report two patients who were treated with daily low-dose MTX and developed acute interstitial pneumonitis requiring hospital admission. MTX-induced pneumonitis is a rare life-threatening side effect, high index of clinical suspicion is required, treatment is mainly withdrawal of MTX, supportive therapy, and adjunctive steroids, outcome is good if condition is recognized early, and appropriate treatment is given.