Biomarkers of coagulation, endothelial, platelet function, and fibrinolysis in patients with COVID-19: a prospective study.

Prospective and sequential evaluation of homeostatic changes leading to thrombosis across COVID 19 disease severity spectrum are limited. In this prospective observational study, haemostasis was evaluated in patients with mild, moderate-severe, and critical COVID-19 infection. Markers of endothelial activation [Soluble thrombomodulin (sTM), von Willebrand Factor (VWF)], platelet activation [Soluble P-selectin, beta-thromboglobulin (BTG)] and global haemostasis [Rotational thromboelastometry (ROTEM)] were evaluated on days 1 and 5 after admission. The study cohort comprised of 100 adult patients (mild = 20, moderate-severe = 22, critical = 58). Sixty-five patients received anticoagulation for 10 (7-14) days. Thrombotic events were seen in 9 patients. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in all subgroups, with levels in moderate-severe (sTM = 4.92 ng/ml, VWF = 295 U/dl) [reference-ranges: sTM = 2.26-4.55 ng/ml; Soluble P-selectin = 13.5-31.5 ng/ml; BTG = 0.034-1.99 ng/ml] and critical patients (sTM = 6.07 ng/ml, VWF = 294 U/dl) being significantly higher than in the mild group (sTM = 4.18 ng/ml, VWF = 206 U/dl). In contrast, platelet activation markers were elevated only in critically ill patients at baseline (Soluble P-selectin = 37.3 ng/ml, BTG = 2.51 ng/ml). The critical group had significantly lower fibrinolysis on days 1 and 5 when compared with the moderate-severe arm. COVID-19 infection was associated with graded endothelial activation and lower fibrinolysis that correlated with illness severity.

Approach to Intensive Care Costing and Provision of Cost-effective Care.

Intensive care unit (ICU) service is resource-intense, finite, and valuable. The outcome of critically ill patients has improved because of a better understanding of disease pathology, technological developments, and newer treatment modalities. These improvements have however come at a price, with ICUs contributing significantly to health budgets. Several costing tools are used to assess cost. Accurate assessment has been hampered by the lack of standardized methodology and the heterogeneity of ICUs. In a costing exercise, the level of disaggregation (micro-costing vs gross-costing) and the method of costing (top-down vs bottom-up) need to be considered. Intensive care unit costing also needs to be viewed from the perspective of stakeholders. While all stakeholders aim to provide quality health care, objectives may vary. For the public health care provider, the focus is on optimizing expenditure; for the private health care provider it is bottomline; for a patient, it is affordability; for an insurance service provider, it is minimizing payout; and for the regulator, it is ensuring quality standards and fair pricing. The field of health economics deals with the application of the principles of cost-minimization, cost-effectiveness, cost-utility, and cost-benefit to identify treatments that result in the best outcome at the lowest cost, without limiting resources to other competing interests. In the ICU setting, studies on the efficient use of available resources, and interventions that reduce cost and minimize avoidable cost, would not only translate to cost savings, lives saved, and quality-adjusted life years gained but also enable policymakers to better allocate health care resources. How to cite this article: Chacko B, Ramakrishnan N, Peter JV. Approach to Intensive Care Costing and Provision of Cost-effective Care. Indian J Crit Care Med 2023;27(12):876-887.

Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?

BACKGROUND: During the second wave of the coronavirus disease 2019 (COVID-19) pandemic, a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction. AIM: To describe the clinical and laboratory characteristics, outcomes, and management of these patients, and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders. METHODS: This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital, between May and August 2021, who fulfilled clearly defined inclusion and exclusion criteria. Outcome was assessed by a change in PaO2/FiO2 ratio and levels of inflammatory markers before and after immunomodulation, duration of mechanical ventilation after starting treatment, and survival to discharge. RESULTS: Five patients developed delayed respiratory deterioration in the absence of new infection, fluid overload or extra-pulmonary organ dysfunction at a median interquartile range (IQR) duration of 32 (23-35) d after the onset of symptoms. These patients had elevated inflammatory markers, required mechanical ventilation for 13 (IQR 10-23) d, and responded to glucocorticoids and/or intravenous immunoglobulin. One patient died (20%). CONCLUSION: This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome - Adults by the paucity of extrapulmonary organ involvement. The diagnosis can be considered in patients presenting with delayed respiratory worsening, that is not attributable to cardiac dysfunction, fluid overload or ongoing infections, and associated with an increase in systemic inflammatory markers like C-reactive protein, inteleukin-6 and ferritin. A good response to immunomodulation can be expected. This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection.

Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study.

Introduction: The effectiveness of gastric lavage in organophosphorus (OP) poisoning has not been established. We assessed the ability of gastric lavage to remove OP insecticides as a preliminary stage in assessing effectiveness. Patients and methods: Organophosphorus poisoning patients presenting within 6 hours were included, irrespective of prior gastric lavage. A nasogastric tube was placed and gastric contents aspirated, followed by at least three cycles of gastric lavage with 200 mL of water. Samples from the initial aspirate and the first three lavage cycles were sent for identification and quantification of the OP compounds. Patients were monitored for complications of gastric lavage. Results: Around 42 patients underwent gastric lavage. Eight (19.0%) patients were excluded from the study because of a lack of analytical standards for ingested compounds. Insecticides were detectable in the lavage samples of 24 of 34 (70.6%) patients. Lipophilic OP compounds were detected in 23 of 24 patients, while no hydrophilic OP compounds could be detected in six patients with reported ingestion of hydrophilic compounds. For chlorpyrifos poisoning (n = 10), only 0.65 mg (SD 1.2) of the estimated ingested amount (n = 5) of 8,600 mg (SD 3,200) was recovered by gastric lavage. The mean proportion of the compound removed by initial gastric aspirate was 79.4% and subsequent three cycles removed 11.5, 6.6, and 2.7%. Conclusion: Lipophilic OP insecticides could be quantified in the stomach contents of OP poisoning patients with the first aspiration or lavage being most effective. The amount removed was very low; hence, routine use of gastric lavage for OP poisoning patients arriving within 6 hours is unlikely to be beneficial. How to cite this article: Mathansingh AJ, Jose A, Fleming JJ, Abhilash KPP, Chandiraseharan VK, Lenin A, et al. Quantification of Organophosphorus Insecticide Removed by Gastric Lavage in Acutely Poisoned Patients: An Observational Study. Indian J Crit Care Med 2023;27(6):397-402.

Retrospective study of comparison of clinical severity and outcome of hospitalised COVID-19 patients during the first and second waves of the pandemic in India.

OBJECTIVES: To compare the clinical severity and outcome of hospitalised patients during the two waves of the COVID-19 pandemic in India. SETTING: A tertiary care referral hospital in South India. PARTICIPANTS: Symptomatic SARS CoV-2 reverse transcriptase PCR positive patients presenting to the emergency department during the two waves were recruited. The first wave spanned between April and December 2020 and the second wave between April and May 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome of interest was mortality. Secondary outcomes included illness severity at presentation, need for oxygen therapy, non-invasive ventilation (NIV) and hospital or intensive care unit admission. RESULTS: The mean (SD) age of the 4971 hospitalised patients in the first wave was similar to the 2293 patients in the second wave (52.5±15.4 vs 52.1±15.1 years, p=0.37). When compared with the first wave, during the second wave, a higher proportion of patients presented with critical illness (11% vs 1.1%, p<0.001) and needed supplemental oxygen therapy (n=2092: 42.1% vs n=1459: 63.6%; p<0.001), NIV (n=643; 12.9% vs n=709; 30.9%; p<0.001) or inotropes/vasoactive drugs (n=108; 2.2% vs n=77: 3.4%; p=0.004). Mortality was higher during the second wave (19.2% vs 9.3%; p<0.001). On multivariable regression analysis, age >60 years (risk ratio, RR 2.80; 95% CI 2.12 to 3.70), D-dimer >1000 ng/mL (RR 1.34; 95% CI 1.15 to 1.55), treatment with supplemental oxygen (RR 14.6; 95% CI 8.98 to 23.6) and presentation during the second wave (RR 1.40; 95% CI 1.21 to 1.62) were independently associated with mortality. CONCLUSION: The second wave of the COVID-19 pandemic in India appeared to be associated with more severe presentation and higher mortality when compared with the first wave. Increasing age, elevated D-dimer levels and treatment with supplemental oxygen were independent predictors of mortality.

Effectiveness of a monitored home isolation program for COVID-19 infection during the second wave of the pandemic.

Background: The rapidity of spread of COVID-19 infection during the second wave of the pandemic placed tremendous stress on healthcare resources. This study evaluated the effectiveness of a monitored home isolation (HI) program. Methods: In this descriptive longitudinal study, symptomatic patients were screened in the HI clinic and eligible patients were followed up at home using tele-consultation, until recovery or hospitalization. HI failure was defined as need for hospitalization. Factors associated with HI failure were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). Results: During April and May 2021, 1957 RT-PCR confirmed patients (984 male) with mean (SD) age 40 (13.5) years were enrolled; 93.3% (n = 1825) were successfully managed at home. Of the 132 patients (6.7%) who failed HI, 57 (43.2%) required oxygen therapy and 23 needed intensive care admissions. Overall mortality was 0.4% (7/1957). On adjusted analysis, factors associated with HI failure were age ≥60 years (OR 2.24; 95%CI 1.26-3.99), male gender (OR 2.26; 95%CI 1.44-3.57), subjective reporting of breathing difficulty (OR 3.64; 95%CI 2.08-6.37), history of cough (OR 2.08; 95%CI 1.37-3.17), and higher heart rate (OR 1.04; 95%CI 1.02-1.05). Although patient status (non-healthcare workers), no prior vaccination and ≥2 comorbidities were associated with HI failure on unadjusted analysis, these were non-significant on adjusted analysis. Conclusion: Monitored HI program can be used successfully during a pandemic wave to judicially use scare hospital resources. Older male patients presenting with breathlessness or cough may warrant closer monitoring.

Good survival rate, moderate overall and good respirator quality of life, near normal pulmonary functions, and good return to work despite catastrophic economic costs 6 months following recovery from Acute Respiratory Distress Syndrome.

Introduction: Long-term quality of life, return to work, economic consequences following Acute Respiratory Distress Syndrome (ARDS) are not well described in India. This study was aimed to address the question. Methods: A prospective cohort study of 109 ARDS survivors were followed up for a minimum of 6 months following discharge. Quality of life was assessed using the SF-36 questionnaire. Respiratory quality was assessed using the St Georges Respiratory Questionnaire. Time to return to work was documented. Costs-direct medical, as well as indirect were documented up to 6 months. Results: At 6 months, 6/109 (5.5%) had expired. Low energy/vitality and general heath were noted in the SF-36 scores at 6 months; overall a moderate quality of life. Pulmonary function tests had mostly normalized. Six-min walk distance was 77% of predicted. Respiratory quality of life was good. It took at the median of 111 days to go back Interquartile range (55-193.5) to work with 88% of previously employed going back to work. There were no significant differences in the severity of ARDS and any of these outcomes at 6 months. The average total cost from the societal perspective was ₹ 231,450 (standard deviation 146,430-, 387,300). There was a significant difference between the 3-ARDS severity groups and costs (P < 0.01). There were no independent predictors of return to work. Conclusion: ARDS survivors have low 6-month mortality. Pulmonary physiology and exercise capacity was mostly normal. Overall, quality of life is average was moderate, while respiratory quality of life was good. Return to work was excellent, while cost of care falls under a catastrophic heath expense.

Impact of prior vaccination with CovishieldTM and Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in South India during April and May 2021: a cohort study.

BACKGROUND: COVID-19 vaccines were authorised for emergency use to mitigate the impact of the pandemic. This study evaluated the effect of prior vaccination with either Oxford Astra Zeneca's Covishield™ or Bharath Biotech's Covaxin® on mortality among symptomatic COVID-19 patients during the second wave of the pandemic in India. METHODOLOGY: In this cohort study comprising of RT-PCR confirmed symptomatic COVID-19 patients presenting during April and May 2021, the effect of prior vaccination on mortality (primary outcome), need for hospitalization, oxygen therapy, non-invasive ventilation (NIV) and intensive care unit (ICU) admission were assessed and expressed as risk ratio (RR) with 95% confidence intervals (CI). RESULTS: The mean (SD) age of the cohort (n = 4183) was 46.3 (15.5) years; 17.9% (748/4183) had received at least one dose of Covishield™ and 4.8% (201/4183) had received Covaxin®. Mortality was 0.2% (95% CI: 0.2% - 0.7%), 3.5% (1.9-5.2%), 6.2% (0.3-12%) and 12.9% (11.8-14.1%) among fully vaccinated (>2 weeks after two doses), partially vaccinated (>2 weeks after one dose or <2 weeks after two doses), indeterminate (<2 weeks after one dose) and unvaccinated patients respectively. The difference in mortality among unvaccinated vs. fully vaccinated was 12.7% (95% CI: 11.4-13.9%), unvaccinated vs. partially vaccinated was 9.4% (7.4-11.4%) and unvaccinated vs. indeterminate vaccinated was 6.8% (0.8-12.7%). On adjusted analysis, as compared to unvaccinated patients, at least one dose of vaccine reduced the need for hospitalization (RR: 0.40; 95% CI: 0.35-0.47), oxygen (0.33; 0.27-0.40), NIV (0.23; 0.17-0.32), ICU admission (0.18; 0.12-0.27) and mortality (0.18; 0.11-0.29). CONCLUSION: Among symptomatic COVID-19 patients, prior vaccination with Covishield ™ or Covaxin® impacted the severity of illness and reduced mortality during a period of widespread delta variant circulation. Full vaccination conferred greater protection than partial vaccination.

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.

Clinical presentation of type 1 and type 2 pyrethroid poisoning in humans.

BACKGROUND: It is unclear if the clinical presentation of poisoning with type 1 and type 2 pyrethroid compounds is different. This study was undertaken to detail the clinical profile and outcome of patients presenting with pyrethroid poisoning and to quantify serum pyrethroid levels. PATIENTS AND METHODS: In this prospective study, patients were categorised as poisoning with type 1 pyrethroids or type 2 pyrethroids. Blood samples were sent for compound identification and quantification. Clinical features and outcomes were compared between the two groups. Factors associated with moderate and severe toxicity were explored using univariate logistic regression analysis and presented as odds ratio (OR) and 95% confidence intervals (CI). RESULTS: Type 1 pyrethroids were implicated in 16 patients and type 2 in 43 patients. The incidence of nausea and vomiting (81.2% vs. 81.3%) and tremor (37.5% vs. 32.6%) were similar in type 1 and type 2 poisoning; paraesthesia (6.2% vs. 32.6%, p = 0.04), hypersalivation (0% vs. 20.9%, p = 0.04), seizures (0% vs. 7%, p = 0.29) and depressed sensorium (0% vs. 18.6%, p = 0.03.) were observed more frequently in type 2 pyrethroid poisoning. Pyrethroids were detected in the serum samples of 24 patients; quantification was possible in 22 patients in whom serum levels ranged from 1.1 to 453 µg/ml. The compounds were undetectable in 35 patients. Two patients (lambda-cyhalothrin poisoning and cypermethrin poisoning) required intubation for low sensorium and respiratory distress. The median (interquartile range) duration of hospitalization was 12 (12-24) hours. All patients survived. Factors associated with moderate and severe toxicity included ingestion of a type 2 pyrethroid, lambda-cyhalothrin (OR 7.81, 95%CI 1.55-39.37, p = 0.01) and volume ingested (OR 1.01, 95%CI 1.00-1.02, p = 0.02). CONCLUSION: Patients with pyrethroid poisoning present predominantly with mild to moderate symptoms. Paraesthesia and hypersalivation are more frequent in type 2 poisoning. A favourable outcome can be expected.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

OBJECTIVE: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. DESIGN: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. SETTING: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. PARTICIPANTS: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. PRIMARY OUTCOME MEASURE: Factors associated with all-cause mortality at 28 days after enrolment. RESULTS: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO2/FiO2 ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death. CONCLUSION: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024775.

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.

Adrenaline is effective in reversing the inadequate heart rate response in atropine treated organophosphorus and carbamate poisoning.

BACKGROUND: In acute organophosphorus (OP) or carbamate poisoning, some patients require high dose atropine to counteract the effects on heart rate (HR) and blood pressure (BP). This study describes the factors associated with high dose atropine therapy and the use of adrenaline to reverse the inadequate HR response to atropine. METHODS: Consecutive patients admitted to the intensive care unit (ICU) were prospectively recruited. Demographic data, treatment and outcomes of patients who failed to achieve target HR (100/min) or systolic BP >90 mm Hg with either a cumulative atropine dose of 100-mg within 6-h following admission or an infusion of 30 mg/h for at least 3-h were compared with patients who achieved the targets. Factors associated with high dose atropine therapy were explored using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Of the 181 patients admitted with OP or carbamate poisoning, 155 patients fulfilled inclusion criteria. The mean (SD) age was 35.7 (15.8) years; admission APACHE-II score was 14.6 (7.5). Heart rate and/or BP target was not achieved in 13.6%. In these patients, target HR was achieved after adding adrenaline infusion at 2-4 µg/min. Ventilation duration (11.6 ± 6.3 vs. 8.4 ± 6.9 days, p = 0.05) and ICU stay (12.3 ± 5.8 vs. 8.9 ± 5.8 days, p = 0.01) were longer in patients requiring high dose atropine when compared with others. On multivariate logistic regression analysis, shorter time to presentation to hospital (p = 0.04) was associated with need for high dose atropine. Overall mortality was 9% and similar in both groups (p = 0.41). CONCLUSIONS: High dose atropine therapy is required in a subset of patients with OP and carbamate poisoning and was associated with longer ventilation duration and ICU stay. Adrenaline infusion improved hemodynamics in these patients.

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.

The impact of demonetisation on the utilisation of hospital services, patient outcomes and finances: a multicentre observational study from India.

BACKGROUND: This study assessed trends in healthcare utilisation in relation to the implementation of an economic policy in India wherein 500 and 1000 rupee notes were demonetised. METHODS: In this ambidirectional observational study of private not-for-profit hospitals, data on hospital outpatient and inpatient numbers, surgeries, emergency department (ED) visits, obstetric admissions and mortality were obtained for pre-demonetisation (September/October 2016), early (November/December 2016) and late demonetisation (January/February 2017), and post-demonetisation periods (March/April 2017) and compared with the control period (2015-2016) from 11 centres (three tertiary hospitals; eight secondary). A Bayesian regression analysis was performed to adjust for seasonal (winter) effect. Monthly financial data, including the proportion of cash versus non-cash transactions, were collected. FINDINGS: Overall, at the pooled all-hospital level, Bayesian analysis showed non-significant increase in outpatients (535.4, 95% CI -7097 to 8116) and decrease in deaths (-6.3 per 1000 inpatients, 95% CI -15.45 to 2.75) and a significant decrease in inpatients (-145.6, 95% CI -286.4 to -10.63) during demonetisation. Analysis at the level of secondary and tertiary hospitals showed a variable effect. For individual hospitals, after adjusting for the seasonal effect, some hospitals observed a significant reduction in outpatient (n=2) and inpatient (n=3) numbers, ED visits (n=4) and mortality (n=2) during demonetisation, while others reported significantly increased outpatient numbers (n=3) and ED visits (n=2). Deliveries remained unchanged during demonetisation in the hospitals that provided the service. There was no significant reduction in hospital incomes during demonetisation. In tertiary hospitals, there was a significant increase in non-cash component of transactions from 35% to 60% (p=0.02) that persisted beyond the demonetisation period. CONCLUSIONS: The effect of demonetisation on healthcare utilisation was variable. Some hospitals witnessed a significant reduction in utilisation in some areas, while others reported increased utilisation. There was an increase in non-cash transactions that persisted beyond the period of demonetisation.

Levonadifloxacin, a recently approved benzoquinolizine fluoroquinolone, exhibits potent in vitro activity against contemporary Staphylococcus aureus isolates and Bengal Bay clone isolates collected from a large Indian tertiary care hospital.

OBJECTIVES: Levonadifloxacin (WCK 771; IV) and its prodrug alalevonadifloxacin (WCK 2349; oral) are benzoquinolizine fluoroquinolones, recently approved in India for the treatment of acute bacterial skin and skin structure infections with concurrent bacteraemia and diabetic foot infections. Ahead of its market launch, the present study aimed to assess the in vitro activity of levonadifloxacin against contemporary Staphylococcus aureus isolates collected from a large tertiary care hospital in India. Additionally, levonadifloxacin activity was tested against hVISA and Bengal Bay clone MRSA isolates. METHODS: Non-duplicate S. aureus (n = 793) isolates collected at Christian Medical College hospital, Vellore, India during 2013-19 were included in the study. MRSA isolates were identified using a cefoxitin disc diffusion assay. MICs of levonadifloxacin and comparator antibiotics were determined using the broth microdilution method. Mutations in QRDRs were identified for selected levofloxacin-non-susceptible isolates. MLST profiling was undertaken to detect the Bengal Bay clone. RESULTS: Among the 793 isolates, 441 (55.6%) were MRSA and 626 (78.9%) were non-susceptible to levofloxacin. Levonadifloxacin showed MIC50 and MIC90 values of 0.25 and 0.5 mg/L, respectively, for all S. aureus, which included hVISA and Bengal Bay clone MRSA. The potency of levonadifloxacin was 16 times superior compared with levofloxacin. CONCLUSIONS: The present study demonstrated potent activity of levonadifloxacin against contemporary S. aureus isolates, which included MRSA isolates, hVISA isolates, Bengal Bay clone isolates and a high proportion of quinolone-non-susceptible isolates. The potent activity of levonadifloxacin observed in this study supports its clinical use for the treatment of S. aureus infections.

An observational study on the practice of noninvasive ventilation at a tertiary level Australian intensive care unit.

BACKGROUND: Failure of Non-Invasive Ventilation (NIV) is associated with increased morbidity and mortality among critically ill patients. Although there is evidence of association between disease related factors and NIV failure, it is unclear whether factors related to NIV application contribute to NIV failure. OBJECTIVES: To evaluate NIV failure rate and factors associated with NIV failure. DESIGN, SETTINGS AND OUTCOMES: Prospective, observational, pilot study conducted in a 23-bed, tertiary care Intensive Care Unit (ICU). NIV failure was defined as application of NIV resulting in intubation or death in ICU. RESULTS: Amongst 238 patients admitted with respiratory failure, NIV was administered to 60 patients (34 males, 26 females) for a total of 70 application episodes. The etiology of respiratory failure included acute pulmonary edema (28.6%), acute lung injury (22.9%) and pneumonia (15.7%). The mean (SD) age was 62 (17.6) years, BMI 32.0 (8.5) kg/m2 and median APACHE-II score 17.5 (14.0-23.8). NIV failure occurred in 22 out of 70 applications (31.4% [95%CI 20.0-43.0]). NIV failure assessed by simple logistic regression analysis, was associated with admission diagnosis (OR 6.0, 95%CI: 1.3-28.7, p = 0.03), use of bi-level NIV-PS (OR 5.00, 95%CI: 1.04-24.1, p = 0.04), presence of nasogastric tube (OR 6.20, 95%CI: 1.9-19.8, p < 0.01) and with short NIV breaks in the 2nd 24-hours (OR 0.96, 95%CI: 0.91-0.99, p = 0.04). CONCLUSION: NIV failure was observed in 31.4%. Factors associated with NIV failure were etiology of respiratory illness, type of NIV support and short NIV breaks, presumably reflecting illness severity or progress of disease. The presence of a nasogastric tube during application of NIV may adversely impact NIV application.

Reversal of Anticoagulants in Critical Care.

There has seen an increase in anticoagulant consumption worldwide over the past few decades. With this widespread utilization of anticoagulants, clinicians are increasingly likely to encounter situations where anticoagulants would need to be withheld. This includes emergency and elective procedures or surgeries as well as major or minor bleeding as a direct result of over anticoagulation or consequent to other intercurrent illnesses such as sepsis or trauma with multiorgan failure, where the anticoagulant may contribute to coagulation abnormalities. Clinicians are required to have a thorough understanding of the indications for anticoagulant prescription, drug interactions and monitoring, indications and options of reversal of anticoagulation and management of bleeding in the situations described above. Once the acute process is managed, the ongoing need and timing of reinitiation of anticoagulation is also crucial. This article provides an overview on the indications for reversal of anticoagulation, the agents used for reversal and the timing of reinitiation of anticoagulants. HOW TO CITE THIS ARTICLE: Chacko B, Peter JV, Subramani K. Reversal of Anticoagulants in Critical Care. Indian J Crit Care Med 2019;23(Suppl 3):S221-S225.

Impact of an antimicrobial stewardship intervention in India: Evaluation of post-prescription review and feedback as a method of promoting optimal antimicrobial use in the intensive care units of a tertiary-care hospital.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are effective in developed countries. In this study, we assessed the effectiveness of an infectious disease (ID) physician-driven post-prescription review and feedback as an ASP strategy in India, a low middle-income country (LMIC). DESIGN AND SETTING: This prospective cohort study was carried out for 18 months in 2 intensive care units of a tertiary-care hospital, consisting of 3 phases: baseline, intervention, and follow up. Each phase spanned 6 months. PARTICIPANTS: Patients aged ≥15 years receiving 48 hours of study antibiotics were recruited for the study. METHODS: During the intervention phase, an ID physician reviewed the included cases and gave alternate recommendations if the antibiotic use was inappropriate. Acceptance of the recommendations was measured after 48 hours. The primary outcome of the study was days of therapy (DOT) per 1,000 study patient days (PD). RESULTS: Overall, 401 patients were recruited in the baseline phase, 381 patients were recruited in the intervention phase, and 379 patients were recruited in the follow-up phase. Antimicrobial use decreased from 831.5 during the baseline phase to 717 DOT per 1,000 PD in the intervention phase (P < .0001). The effect was sustained in the follow-up phase (713.6 DOT per 1,000 PD). De-escalation according to culture susceptibility improved significantly in the intervention phase versus the baseline phase (42.7% vs 23.6%; P < .0001). Overall, 73.3% of antibiotic prescriptions were inappropriate. Recommendations by the ID team were accepted in 60.7% of the cases. CONCLUSION: The ID physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute-care setting in India.