Binila Chacko

Background: Steroids have a role in the management of community-acquired pneumonia, COVID-19 related acute hypoxemic respiratory failure and refractory septic shock in adults. This study explored the role of steroids in severe scrub typhus infection. Methods: In this retrospective study spanning 3-years, patients fulfilling the case definition of scrub typhus infection and admitted to the intensive care unit (ICU) were included. Illness severity was assessed using the acute physiology and chronic health evaluation (APACHE-II) and sequential organ failure assessment (SOFA) scores. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ventilator-free days, vasopressor-free days, and ICU and hospital length of stay. Multivariable logistic regression was performed to assess whether steroids were independently associated with 28-day mortality. Results: The mean (SD) age of the study cohort (n = 114) was 45.7 (15.1) years; 67 received hydrocortisone. The median (interquartile range, IQR) APACHE-II score was 13 (9–18) and SOFA score was 9 (6–12). Patients receiving steroids were older (p = 0.04), had higher median [interquartile range, IQR] SOFA scores (11 [8-15] vs. 7 [5-10], p<0.001) and more organ systems involved (4 [3-5] vs. 3 [3-4], p<0.001), when compared with those who did not receive steroids. Ventilatory support was required in 88 patients (77.2%) and vasoactive support in 88 (77.2%); 71 patients (62.3%) required both. The 28-day mortality was 14.9%. On multivariable logistic regression, older age (OR, 1.08; 95% CI, 1.03–1.15) and higher respiratory SOFA score (OR, 2.02; 95% CI, 1.09–3.74) were independently associated with mortality, while cardiovascular SOFA (OR, 0.82; 95% CI, 0.51–1.32) and steroid use (OR, 9.34; 95% CI, 0.85–102.7) were not. Conclusions: In this retrospective cohort of critically ill scrub typhus patients, those with a higher cardiorespiratory disease severity preferentially received steroids. Steroids were not independently associated with 28-day mortality when adjusted for age and illness severity. The role of steroids in severe scrub typhus requires further study, particularly in the subset of patients with pneumonia and/or ARDS with low-dose vasopressor requirement.

Background: The neurotoxicity potential of polymyxin B is underrecognized. Results: Four critically ill patients treated with polymyxin B for suspected or confirmed nosocomial Gram‐negative infections developed acute hypercapnic respiratory failure temporally associated with polymyxin B administration. Respiratory support escalated from room air or low‐flow oxygen to noninvasive or invasive mechanical ventilation after one, two, five, and seven doses of polymyxin. No alternative explanation for the abrupt deterioration was identified after clinical evaluation. Following cessation of polymyxin ( n = 3) or dose reduction ( n = 1), all patients were liberated from ventilation within 60 h. Measured polymyxin concentrations were above the therapeutic range in all patients; however, the delayed timing of sampling, measured at variable intervals after the respiratory events, limits conclusions regarding causality and dose‐dependent toxicity. Conclusion: Polymyxin B should be considered as a potential cause of acute hypercapnic respiratory failure in critically ill patients when no alternative explanation is apparent. Both idiosyncratic susceptibility and drug accumulation may contribute, although the delayed timing of drug concentration measurements precludes firm conclusions regarding dose‐dependent toxicity. Further prospective studies are required to define the mechanisms and risk factors.

It is unclear if maternal and fetal outcomes of pregnant women admitted to the intensive care unit (ICU) with A/H1N1pdm and SARS-CoV-2 infection are different. This retrospective study (2007–2022) included pregnant women admitted to the ICU with real-time reverse transcription polymerase chain reaction-confirmed A/H1N1pdm or SARS-CoV-2 pneumonia; non-viral pneumonia and incomplete records were excluded. The primary outcome was maternal mortality. Secondary outcomes included need for organ support, duration of ventilation, hospital stay, and fetal outcome. Predictors of maternal mortality were explored using multivariate logistic regression. Fifty-six women (A/H1N1pdm = 42, SARS-CoV-2 = 14) were admitted to the ICU at a median (interquartile) gestational age of 32.3 (27.3–36) weeks. Gestational diabetes (p = 0.02), hypothyroidism (p = 0.04), hypertension (p = 0.09), and infertility treatment (p = 0.09) were more frequent among SARS-CoV-2 infected women. Time from symptom onset to ICU admission was 4 (3–5) days. Although APACHE-II scores were similar in both groups, a higher proportion of patients with A/H1N1pdm had tachycardia (87.8% vs 21.4%, p = 0.001), and their median oxygen saturation at admission was lower (89% vs 94%, p = 0.02). Ventilatory support (non-invasive and/or invasive support) was required in all A/H1N1pdm patients and 78.6% with SARS-CoV-2 (p = 0.013). Ventilation duration was 12 days (4–18) for SARS-CoV-2 and 4 days (2–7) for A/H1N1pdm (p < 0.001). The frequency of cardiac and renal dysfunction was similar in both groups. Maternal mortality was 21.4% in A/H1N1pdm and 28.6% in SARS-CoV-2; fetal loss was 16.7% and 26.3%, respectively. Four neonatal deaths occurred. Delayed hospital presentation independently predicted maternal mortality (OR: 1.8; 95% CI: 1.07–3.06). Respiratory failure due to A/H1N1pdm and SARS-CoV-2 infections in pregnancy is associated with high maternal mortality and fetal loss. Delayed presentation is independently associated with maternal death. Thomas VV, Nakkeeran G, Jacob KR, Chacko B, Moorthy M, Gowri M, et al. Maternal and Fetal Outcomes in Pregnant Women Admitted to the Intensive Care Unit with A/H1N1pdm or SARS-CoV-2 Infection: A Retrospective Study. Indian J Crit Care Med 2025;29(11):907–915.

Introduction: Recent studies have demonstrated a beneficial role of steroids in severe community-acquired pneumonia, severe COVID-19 infection and acute respiratory distress syndrome (ARDS) of diverse aetiology. This multicentre randomised controlled trial in severe scrub typhus pneumonitis and ARDS will compare the effects of 6 mg of dexamethasone once per day with placebo, in addition to standard treatment, on ventilator-free days (VFD), mortality and ventilatory requirement. Methods and analysis: The study, involving six sites, will recruit 440 patients with severe scrub typhus pneumonitis or ARDS to concealed, block-randomised, site-specific assignment of dexamethasone or placebo for 4–7 days. The primary outcome will be VFD, defined as days alive and free of ventilation at 28 days. Secondary outcomes will include 28-day mortality, need and duration of ventilation, and treatment failure, defined as death, or escalation of respiratory support from simple devices (nasal cannula, mask) to non-invasive or invasive ventilation, or the use of open-labelled steroids for worsening shock. The study will also ascertain if antinuclear antibody (ANA) expression during the acute phase of illness will predict steroid responsiveness. Subgroup analyses will be conducted a priori on ANA expression and the need for ventilation. All analyses will be conducted on an intention-to-treat basis. The trial, which commenced in April 2025, would clarify the role of corticosteroids in scrub typhus pneumonitis. Ethics and dissemination: The Institutional Review Board and Ethics Committee of the lead site, Christian Medical College, Vellore, India, has approved the study (IRB Min No 15920 (INTERVE) dated 22 November 2023). The remaining five sites have obtained approval from their respective ethics committees. Study results will be published in an international peer-reviewed journal. Trial registration number: CTRI/2024/12/077709. Registered 5 December 2024.

How to cite this article: Chacko B. Care Beyond Cure: Humanizing the Intensive Care Unit Journey. Indian J Crit Care Med 2024;28(10):901–902.

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.

Background: Delirium is common among patients in intensive care units. Antipsychotics have been shown to reduce the incidence of delirium in post-operative patients. We set out to compare the efficacy of risperidone to placebo in preventing delirium in critically ill patients admitted to a medical ICU. Methods: This double-blind, randomised controlled trial compared prophylactic low-dose risperidone to placebo in critically ill patients. Patients were screened daily for delirium using a validated screening tool (CAM-ICU), and the incidence of delirium was compared between groups. Results: Forty-five patients were recruited. Baseline demographic characteristics, diagnosis and severity of illness were not statistically significantly different between groups. There was no significant difference in the incidence of delirium, adverse events or complications. Conclusion: In this study, low-dose risperidone did not prevent the incidence of delirium. As delirium is a heterogeneous syndrome, a single intervention may not be effective across subtypes and aetiologies (ISRCTN17375500) Key Message: Prophylactic risperidone did not reduce the incidence of delirium in ICU patients in this small study. As delirium is a heterogeneous syndrome, a single intervention may not be effective across subtypes and aetiologies.

Background: In critically ill patients with low albumin, dose individualization of phenytoin is a challenge. The currently used Sheiner-Tozer equation does not accurately predict the free phenytoin concentration in serum and can result in incorrect dose modifications. The best measure to advocate in these patients is the direct measurement of free phenytoin concentration. Aims and objectives: Phenytoin exhibits complex pharmacokinetics, requiring careful therapeutic drug monitoring. This study aimed to compare the accuracy of the established Sheiner-Tozer calculation method against the direct measurement of free phenytoin concentration in serum by high performance liquid chromatography in critically ill patients with low albumin. Materials and methods: Blood specimens for direct measurement of both total and free phenytoin concentration were obtained from 57 patients with hypoalbuminemia monitored in the intensive care unit. Results: The median [inter-quartile range (IQR)] for Sheiner-Tozer equation calculated total phenytoin concentration and direct-measured total was 17.14 (10.63-24.53) and 9.82 (6.02-13.85) mu g mL(-1), respectively. Approximately 53 and 5% of patients were found to be subtherapeutic and supratherapeutic for direct-measured total phenytoin concentrations, respectively. In contrast, on applying the Sheiner-Tozer calculation, 23 and 40% had subtherapeutic and supratherapeutic concentrations, respectively, for total phenytoin concentration. The median (IQR) for direct-measured routine and Sheiner-Tozer equation calculated free phenytoin concentration were 1.92 (1.06-2.76), 0.98 (0.60-1.39), and 1.71 (1.06-2.45) mu g mL(-1), respectively. Only 45.7% of patients were in agreement with respect to the therapeutic category when direct-measured free was compared against routine calculation free. Conclusion: In patients with low albumin, free phenytoin concentration based on the Sheiner-Tozer corrected equation accurately classified patients based on their therapeutic category of free phenytoin in 73.7% of patients. Hence, for individualization of phenytoin dosage in critically ill patients with low albumin, we recommend direct measurement of free phenytoin concentration.

Introduction: COVID-19 infection is associated with haemostatic changes often leading to thrombosis. Such changes have not been serially and comprehensively evaluated. Methods: Haemostasis was comprehensively evaluated in patients with mild, moderate-severe and critical COVID-19 infection including 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)] on days 1 and 5 after hospital admission. All patients with d-dimer >1000ng/ml received therapeutic doses of anticoagulation. Results: 100 adult patients (mild =20, moderate-severe =22, critical =58), mean age 54.4±14.1 years were recruited. Compared to mild COVID-19 disease, critically ill patients were older (p=0.02) and required ventilatory support for 7.5 (6–14) (median, IQR) days. Sixty-five patients received anticoagulation for 10 (7–14) (median, IQR) days. Thrombotic events were seen in 9 patients. No major bleeding occurred in any patient despite majority receiving therapeutic anticoagulation. In-hospital mortality was 21%. Endothelial activation markers were elevated at baseline in the three severity groups with levels in moderate-severe (sTM=4.92 ng/ml, VWF=295U/dl) and critical patients (sTM=6.07 ng/ml, VWF=294U/dl) being significantly higher than in the mild group (sTM=4.18 ng/ml, VWF=206 U/dl; p < 0.05). In contrast, increased platelet activation was evident only in the critically ill (Soluble P-selectin=37.3ng/ml, BTG=2.51ng/ml; p <0.0001). Higher d-dimer values and lower fibrinolysis were also associated with increasing COVID-19 severity. Increased D-dimer and Factor VIII levels on day 5 [p