Clinical trials

Septic shock is common complication in patients with critical illnesses, with higher incidence in low and medium income countries like ours. Disseminated intravascular coagulation (DIC) is also common in patients presenting to intensive care units. Further DIC is common coexisting condition seen in many patients presenting with sepsis and septic shock. Both DIC and septic shock individually are associated with very high mortality and morbidity and coexistence of both increase risk manifold. Organ dysfunction is a complication of both septic shock and DIC individually and in presence of coexistence risk further multiply. DIC scoring of every patient at risk as in patients presenting with septic shock help us to predict about patients having more chances to convert to overt DIC. Understanding effects of DIC on organ dysfunction in septic shock patients can help to prognosticate and guide towards early intervention. Also, there is paucity of literature on effect of DIC score changes on organ dysfunction in patients with septic shock.

Sarcoidosis is a multi-systemic granulomatous disease of unknown cause that is characterized by the formation of non-caseous epithelioid cell granulomas. Sarcoidosis involves the respiratory system in \> 90% of cases, usually the hilar and mediastinal nodes, and, less frequently, the lung tissue. Airway involvement, as judged by clinical features, physiologic testing, imaging techniques, bronchoscopy, and airway mucosal biopsy, has been observed in nearly two-thirds of patients with sarcoidosis. Although sarcoidosis involving thoracic lymph nodes and pulmonary parenchyma is familiar to most clinicians, airway involvement is often overlooked. The frequency of airway involvement increases as the parenchymal disease progresses, and\\airway involvement is associated with increased morbidity, respiratory symptoms, and mortality. The initial airway abnormality is the inflammation manifested by mucosal edema, erythema, and the formation of granulomas. As the airway disease progresses, the mucosa may demonstrate granularity, nodularity, cobble stoning, and friability. Sarcoid granulomas tend to develop along the bronchovascular bundle or in the vicinity of the airways. Overall quality of the endobronchial biopsy (EBB) will depend on the method by which it is obtained and cryo-EBB will most likely to provide better tissue for the diagnosis in comparison to forceps biopsy which has smaller sample as well as crush artifacts. Therefore, it is hypothesized that cryo-EBB will be better than forceps EBB and combined together it will increase the overall diagnostic yield of the sarcoidosis when combined with lymph node sampling by endobronchial ultrasound guided trans-bronchial needle aspiration (EBUS-TBNA). 1. Primary objective: To compare the diagnostic yield of cryo-EBB with forceps biopsy in patients undergoing routine EBUS-TBNA for suspected sarcoidosis. 2. Secondary Objective: To evaluate the overall diagnostic yield of combined endobronchial biopsy and EBUS-TBNA in patients undergoing routine EBUS-TBNA for suspected sarcoidosis. The relevance and the expected outcome of the proposed study 1. The study will provide insight to obtain an endobronchial biopsy either with cryo probe or forceps 2. The study will also provide information regarding overall increase in diagnostic yield if any when the endobronchial biopsies are combined with EBUS-TBNA.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition requiring respiratory support to maintain oxygenation. Very few biomarkers about ARDS have been identified but none of them has a sufficient specificity or sensitivity to characterize by itself the severity of lung condition. Investigators hypothesize that there is considerable change occurring in metabolic profiles in mild, moderate, and severe ARDS in comparison to healthy cohort, which can be detectable through serum analysis using NMR based metabolomics study. This research would help to understand metabolomics kinetics during the ARDS disease progression. Overall, NMR-based metabolomics study would provide an insight into the mediators involved in pathogenesis and progression of ARDS.

Prolonged circulatory shock is associated with marked disturbances in vascular supply to the brain, and endothelial dysfunction which can lead to disseminated intravascular coagulation and microvascular thrombosis. Pituitary dysfunction is documented following post-partum hemorrhage, traumatic brain injury and subarachnoid hemorrhage, which also affect blood flow to the pituitary. However, there are no studies assessing pituitary function in the aftermath of recovery from shock. This will be a prospective observational study of patients admitted in Critical Care Medicine (CCM) ICU who have recovered from prolonged septic shock (Lasting for a period of \> 24 hours). Blood samples of the participants will be estimated at the time of discharge from the ICU and at 6 months post discharge. Investigators will estimate fasting serum cortisol, TSH, Free T4, Testosterone (in males), Oestrogen (in females), LH, FSH, Prolactin, IGF-1 and plasma ACTH in all participants at both time points (at the time of ICU discharge and at 6-months follow-up). Participants who have borderline serum cortisol values (138-400 nmol/l) will be subjected to 250ug ACTH stimulation test. Expected outcome of the proposed study is to know proportion of patients having pituitary hormone axis dysfunction. Investigators will also look for pituitary dysfunction persist or revert, or there are new onset dysfunction at 6 month follow up. This would have major implications in the follow up and management of ICU survivors.

Cytomegalovirus (CMV) is a latent infection virus that is widespread in the population. CMV may reactivate under certain circumstances, and its hazardous nature has been proven, especially in immunosuppressed patients. However in recent years, some studies have found that CMV reactivation also exists in apparently immunocompetent patients during their critical illness. In these non-immunosuppressed patients, the presence of sepsis and its immunomodulatory effects may lead to reactivation of dormant viral infections. Studies found the incidence of CMV reactivation in up to one-fourth to half of these non-immunosuppressed patients during their critical illness. These studies also documented significantly higher length of ICU stay and mortality in critically ill patients with CMV reactivation. CMV reactivation has also been studied in specific critically ill cohorts, exhibiting there impact on mortality. David S Y Yong et al studied the effect of CMV reactivation on mortality in immunocompetent acute respiratory distress syndrome (ARDS) patients. In a recent study, it was found that among cohort of non-immunosuppressed patients with acute respiratory distress syndrome (ARDS), CMV reactivation occurred in 27 % of patients which was associated with overall increased ICU mortality. In another study among septic shock cohort (329 patients), herpesvirus reactivations were documented in 68% patients without prior immunodeficiency and concluded that reactivations could be independently associated with mortality. However currently, no study is available investigating the CMV reactivation and it's kinetics during critical illness in non immunocompetent patients requiring prolonged mechanical ventilation. In this planned observational study, we aim to find out the prevalence of Cytomegalovirus (CMV) reactivation, viral load and it's association with the severity of illness in non immunosuppressed ICU patients requiring prolong mechanical ventilation.

Septic shock is the most common form of circulatory shock encountered in patients admitted in intensive care unit. The initial management involves fluid resuscitation but if hypotension does not get resolved solely by it, then vasopressors become the mainstay of the management of shock to maintain adequate mean arterial pressure (MAP). Norepinephrine is recommended as the first line vasopressor in the management of septic shock as per Surviving Sepsis Campaign guidelines of 2021. It recommends addition of vasopressin to the regime if the target MAP is not achieved with just norepinephrine. However, in clinical practice various other vasopressors are being used in the management of septic shock, as per clinical condition. Different vasopressors have different modes of action and pharmacological effects on hemodynamics. Therefore, there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner. Thus, the concept of Norepinephrine Equivalence (NEE) came into existence. In the recent years, different studies were conducted in various parts of the world with different primary objectives. These authors have proposed different formulas for calculation Norepinephrine Equivalence (NEE) dose of the used vasopressors as an inference from their studies. All these formulas are based on assumptions and there lacks standardization. There are presently no studies available in the existing literature, where a prospective study is done to primarily determine the Norepinephrine equivalence dose (NEE) of other vasopressors in patients of septic shock. Hence, the investigators aim to find out equivalent dose of these different drugs, which are being used commonly in the management of septic shock, in a prospective planned study.