Crit Care Med Research Articles

Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility?

How to cite this article: Angadi VM, Jindal A. Methylene Blue in Septic Shock-A Novel Weapon in Our Arsenal: Are Utility Studies Highlighting its Futility? Indian J Crit Care Med 2024;28(1):89.

Relationship of Endotracheal Tube Cuff Pressures with Changes in Body Positions of Critically Ill Patients on Mechanical Ventilation: An Observational Study.

Endotracheal tube cuff pressure (ETCP) is an important factor to determine the development of complications associated with invasive mechanical ventilation. To avoid preventable complications arising out of immobilization, frequent changes in body positioning are necessary. Such variations in body position can affect ETCP in critically ill patients who are on mechanical ventilation. So, our study aimed to assess the effect of changes in body position on ETCP in patients who are on mechanical ventilation. This prospective observational study included 31 critically ill intubated patients. Each study subject was first placed in a neutral starting position with a 30º head elevation. Then, they were subjected to a sequential change in body position based on the 16 most used positions as part of the critical care unit's (CCUs) daily routine. Endotracheal tube cuff pressure was measured after each position change. Data were analyzed using standard statistical tests. Statistically significant difference in ETCP was observed during anteflexion of neck, hyperextension of neck, left lateral flexion of neck, right lateral flexion of neck, left lateral rotation of neck, right lateral rotation of neck, 10o recumbent position, supine position, Trendelenburg position, and right lateral 30° and 45° positions. Maximum increase in ETCP was seen during anteflexion of neck (31 ± 4.5; 22-42 cm H2O). Our study demonstrates significant deviations in ETCP from the recommended range following changes in the body position of mechanically ventilated patients, highlighting the need for the measurement of ETCP after each position change and maintenance of the same within the target range. Roy O, Dasgupta S, Chandra A, Biswas P, Choudhury A, Ghosh S, et al. Relationship of Endotracheal Tube Cuff Pressures with Changes in Body Positions of Critically Ill Patients on Mechanical Ventilation: An Observational Study. Indian J Crit Care Med 2024;28(1):36-40.

Clinical Profile and Predictors of Intensive Care Admission in Neonicotinoid Poisoning in a Tertiary Care Hospital in South India.

Neonicotinoids are a newer class of pesticides that are believed to cause predominantly mild toxicity in humans. This study aimed to describe the clinical features of neonicotinoid poisoning and identify predictors of severe toxicity. This retrospective study included all patients with neonicotinoid poisoning admitted to a Tertiary Care Center in India over an 18-year period. Clinical and laboratory features were compared against outcomes to identify predictors of the need for intensive care admission. Twenty-eight patients were included in the study of which 28.6% had severe disease requiring ICU admission. A higher respiratory rate, blood lactate level, SOFA, and qSOFA scores as well as a lower Glasgow coma score at presentation predicted ICU admission. First-generation compounds and imidacloprid consumption were associated with longer ICU stays and a longer duration of invasive ventilation. Neonicotinoid compounds can cause significant toxicity with oral ingestion. Imidacloprid and other first-generation compounds were associated with more severe toxicity requiring intensive care. Simple clinical parameters assessed at presentation can be used to predict severe disease and the need for ICU care. Larger, prospective studies are required to confirm these findings. Sanga L, Jacob A, Jayakaran JAJ, Iyadurai R. Clinical Profile and Predictors of Intensive Care Admission in Neonicotinoid Poisoning in a Tertiary Care Hospital in South India. Indian J Crit Care Med 2024;28(1):66-69.

The Use of Sustained Low-efficiency Dialysis in the Treatment of Sepsis-associated Acute Kidney Injury in a Low-income Country: A Prospective Cohort Study.

Limited data are available regarding the management and outcomes of patients with sepsis-associated acute kidney injury (SA-AKI) requiring dialysis in Sudan. Continuous renal replacement therapy (CRRT) is a highly favored treatment modality in such patients. However, it stays unavailable and expensive treatment in most low-income countries. We aimed to evaluate the use of sustained low-efficiency dialysis (SLED) in the treatment of hemodynamically unstable patients with SA-AKI admitted to the intensive care unit (ICU). A prospective cohort was conducted in Baraha Medical City, Khartoum, Sudan. Patients above 18 years of age, who were admitted to the ICU between January and September 2020 with SA-AKI, and required SLED or CRRT were enrolled. These were followed up till death or discharge from the ICU. They were observed regarding their dialysis tolerance, rate of renal recovery, ICU mortality, and cost of therapy. Data analysis was done using SPSS. Fifty-three adults were enrolled. Their mean age was 62 ± 11 years, and 56.6% were males. Thirty-one patients (58.5%) received SLED and 22 (41.5%) underwent CRRT. Patients in the two groups were age and sex matched and showed no significant differences in their comorbid conditions, source of sepsis, sequential organ failure assessment (SOFA) score, and their indications for dialysis (p > 0.05). Patients treated with SLED showed similar dialysis tolerance, rate of renal recovery, length of ICU admission, and risk of death compared to those treated with CRRT (p > 0.05). Moreover, SLED treatments were less expensive than CRRT, and the costs of ICU admission among the SLED group were significantly less (p < 0.001). Our study shows that SLED is safe and effective. It is readily available and can be routinely performed in the treatment of hemodynamically unstable patients with SA-AKI at a significantly lower cost. Taha AKA, Shigidi MMT, Abdulfatah NM, Alsayed RK. The Use of Sustained Low-efficiency Dialysis in the Treatment of Sepsis-associated Acute Kidney Injury in a Low-income Country: A Prospective Cohort Study. Indian J Crit Care Med 2024;28(1):30-35.

Medical treatment of pleural infection: antibiotic duration and corticosteroid usefulness.

Hassan M, et al. The Short versus Long Antibiotic Course for Pleural Infection Management (SLIM) randomised controlled open-label trial. ERJ Open Res 2023; 9: 00635-2022.Porcel JM, et al. Two vs. three weeks of treatment with amoxicillin-clavulanate for stabilized community-acquired complicated parapneumonic effusions. A preliminary non-inferiority, double-blind, randomized, controlled trial. Pleura Peritoneum 2020; 5: 20190027.Fitzgerald DB, et al. Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): a pilot randomized clinical trial. Am J Respir Crit Care Med 2022; 205: 1093-1101.

A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial.

The burden of sepsis is high in India and is associated with substantial morbidity and mortality. Vitamin C, an endogenous antioxidant, may improve patient outcomes. This was a parallel-group pilot feasibility randomized controlled trial conducted at 2 intensive care units in India. Adult patients (≥18 years) with proven or suspected infection as the main diagnosis and needing a continuous intravenous vasopressor infusion were randomized to intravenous vitamin C (50 mg/kg every 6 hours for a maximum of 16 doses) or matching placebo. Primary outcomes were related to protocol adherence and feasibility (enrollment per month). The key secondary outcome was the composite of mortality or persistent organ dysfunction (POD) at day 28 after randomization. 60 patients were screened, 51 were eligible, 32 were randomized, and 30 were included in the analysis (randomized/eligible ratio: 0.63). The overall rate of enrollment was 1.5 patients per month. The median (IQR) age was 63.5 (51.0, 70.0) and 70.0% of the patients were male. In both arms, all patients received ≥90% of scheduled doses of the study drug. No patient received open-label vitamin C and there were no deviations from the glucose monitoring protocol. The composite outcome of mortality or POD at day 28 occurred in 56.3% (9/16) in the vitamin C arm as compared to 42.9% (6/14) in the placebo arm [RR: 1.31 (95% CI: 0.62, 2.76), p = 0.47]. In this pilot feasibility randomized controlled trial of vitamin C for adult patients with sepsis, protocol adherence was excellent and feasibility endpoints were met. CTRI/2020/03/024371. Vijayaraghavan BKT, Venkataraman R, Ramanathan Y, Margabandhu S, Jayakumar D, Ramachandran P, et al. A Pilot Feasibility Randomized Controlled Trial of Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit: The Lessening Organ Dysfunction with Vitamin C-India (LOVIT-India) Trial. Indian J Crit Care Med 2023;27(12):910-916.

Author Response: Factors Requiring Improvement for Timely and Effective Treatment of Acute Stroke.

How to cite this article: Shah A, Diwan A. Author Response: Factors Requiring Improvement for Timely and Effective Treatment of Acute Stroke. Indian J Crit Care Med 2023;27(12):949-950.

Preemptive Intervention in Airflow Obstruction Status Prevents the Development of Bronchiolitis Obliterans Syndrome after Allogeneic Stem Cell Transplantation: Multicenter, Prospective Phase II Study (Chiba AFO-01)

Background: Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HCT) is recognized as pulmonary chronic graft-versus-host disease (GVHD), a progressive, irreversible, and sometimes fatal complication. Periodic pulmonary function testing (PFT) for early diagnosis and timely therapeutic intervention is essential. However, effective monitoring and adequate treatment strategy for BOS have not been established. The airflow obstruction (AFO) criteria (predicted FEV1 second decreased by 5% a year or more, and FEV1-second rate &amp;lt;80%) had proposed to detect of a precursor of BOS, and even at AFO status, it was confirmed that increasing the risk in mortality of 2.3-fold (95% CI, 1.6- 3.3; P &amp;lt; 0.001) (JW Chien et al. Am J Respir Crit Care Med. 2003). In our single-center retrospective analysis, 67.2% of AFO patients progressed to BOS, and similarly, the AFO was associated with poor survival (Nakao et al., in submission). Although immunosuppressive agents, especially steroids, are usually administered or augmented for new-onset BOS, sufficient response has not necessarily been obtained. The feasibility study with inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse had been reported, which was well tolerated; however, about one-third were a failure at 6 months, showed efficacy was extremely limited in advanced BOS. From these findings, we hypothesized that close monitoring and early intervention from the diagnosis of AFO using inhaled steroid long-acting β2-agonist budesonide/formoterol fumarate hydrate, clarithromycin, and montelukast (BCM) triplet therapy, could avert the progression to BOS. We conducted a multicenter, single-arm, open-label, prospective phase II study (Chiba AFO-01). This study was approved by the certified clinical research review board at Chiba University Hospital. (jRCTs031180338) Patients and Method: PFT was performed before and every 3 months after allo-HCT for 2 years, and from the time when the AFO criteria were met, BCM therapy was started and continued for 1 year. BOS and GVHD diagnoses were made according to the 2014 NIH Consensus Development Project on Criteria for Clinical Trials (BBMT 2015). The primary endpoint was the inhibition rate of BOS progression, and the secondary endpoints were AFO incidence rate, recurrence rate, survival rate, GVHD, intervention rate of systemic immunosuppressive therapy, and safety of BCM therapy. The statistical analysis plan considered it effective if the incidence of BOS with triple treatment was less than 65% with a two-sided P-value &amp;lt;0.10. Results: Between June 2016 and June 2018, 85 patients were enrolled, and 84 were included in the analysis. One was excluded from the analysis due to deviation. Fifteen of eighty-four (17.9%) met AFO criteria at the median of 178 days (63-728) after allo-HCT, and the 2-year cumulative incidence of AFO was 26.1%. Fourteen with AFO received the BCM treatment. Three patients developed BOS (0, 182, 420 days after onset of AFO). The BOS progression rate was 21.4% (95% CI: 4.7-50.8%), which was significantly below the threshold (65%) set by historical control, had demonstrated the inhibitory effect on BOS progression significantly ( P&amp;lt;0.001). No significant difference was observed in the relationship between AFO and primary disease, stem cell source, pretreatment, and chronic GVHD incidence compared to the non-AFO group. At the AFO diagnosis, 80% had not developed or concurrently diagnosed with chronic GVHD. During the study period, 80% had developed an active chronic GVHD in the AFO group and 54.2% in the non-AFO group. The BCM therapy was feasible, and 9 completed the treatment. Five were discontinued due to the development of IPS in 2, disease progression in 1, bacterial pneumonia in 1, and patient's preference in 1. No difference was observed between the two groups in 2-year OS (AFO 86.7% vs non-AFO 94.2%, Log-rank P=0.55) Conclusion: We revealed the target timeframe for PFT monitoring for early identifying patients at risk for subsequent BOS after allo-SCT. PFT monitoring and therapeutic intervention with BCM therapy for patients with AFO could improve outcomes. The therapeutic intervention from the BOS diagnosis is too late to improve prognosis, and early therapeutic intervention is essential when respiratory function decline is observed, regardless of the presence or absence of chronic GVHD.

Estimation of Postinfusion Resource Use and Total Costs of Care for Patients with R/R Follicular Lymphoma (FL) Receiving Lisocabtagene Maraleucel (liso-cel) in the TRANSCEND FL Study

Background: Liso-cel, an autologous, CD19-directed, 4-1BB CAR T cell product administered at equal target doses of CD8 + and CD4 + CAR + T cells, has previously demonstrated clinically meaningful responses in patients with R/R FL in the global phase 2 TRANSCEND FL study (NCT04245839). Limited evidence is published on estimates of health care resource utilization (HCRU) and cost of postinfusion care among patients with large B-cell lymphoma (LBCL) treated with liso-cel (Palomba ML, et al. Leuk Lymphoma 2021), and no evidence is currently available for patients with R/R FL. This analysis evaluated postinfusion HCRU and estimated cost of care across a 6-month period among patients treated with liso-cel in the TRANSCEND FL study. Methods: In this retrospective analysis, patient-level HCRU data from the TRANSCEND FL study database, including hospitalizations and length of hospital stay (LOS) for the entire hospitalization period postinfusion (standard inpatient [IP] and ICU days), diagnostics (eg, laboratory work and imaging), procedures (eg, dialysis and intubation), and medications (eg, oncology supportive care, prophylactics, and other AE management), were analyzed from the day of liso-cel infusion through 6 months of follow-up. Postinfusion costs (not including the cost of liso-cel) were estimated using a microcosting methodology in which HCRU in the 6-month period was identified and unit costs sourced from public databases or literature (adjusted to 2023 US dollars [USD] using the Consumer Price Index) were applied to each HCRU. Facility costs were sourced from the Healthcare Cost and Utilization Project National Inpatient Sample (2020) databases (Dasta JF, et al. Crit Care Med 2005), and the US Centers for Medicare and Medicaid Services (CMS) Hospital Outpatient Prospective Payment System (OPPS; 2023). Diagnostic and procedure costs were obtained from the CMS OPPS (2023), clinical laboratory fee schedule (2023), physician fee schedule (2023), durable medical fee schedule (2023), and Dasta 2005. Medication cost data were obtained from IBM ® Micromedex ® RED BOOK ® (2023) using wholesale acquisition cost and were uniformly applied across sites of care. Average total cost by month after liso-cel infusion was calculated among patients with ongoing status in that month. Patients censored due to data cutoff were excluded. Results: A total of 130 patients were treated with liso-cel in the TRANSCEND FL study, primarily in the fourth-line setting (45.4%). These patients had a median (range) age of 60 (23‒80) years and were predominantly male (83/130 [63.8%]) and White (69/130 [53.1%]); 45 (34.6%) had unknown race. Among patients who received liso-cel infusions, the estimated mean 6-month postinfusion total cost of care was $89,516 (Figure 1). Most 6-month costs ($77,088 [86.1%]) were incurred in Month 1 after infusion and were primarily driven by facility costs ($66,683 [74.5%]), namely standard IP hospitalization and ICU stays. HCRU and LOS (including standard IP hospitalization and ICU days) are shown in Table 1. Almost all patients were hospitalized in the standard IP setting (128/130 [98.5%]). Few patients were admitted to the ICU (4/130 [3.1%]), and 3/130 (2.3%) had an emergency department visit. Median (range) hospitalization time was 14 (3‒45) days for standard IP and 5 (3‒7) days for ICU stays. Some patients received corticosteroids (30/130 [23.1%]) or tocilizumab (31/130 [23.8%]), and few required intravenous immunoglobulin (11/130 [8.5%]), vasopressors (4/130 [3.1%]), lumbar puncture (2/130 [1.5%]), or mechanical ventilation (1/130 [0.8%]). No patients received dialysis. Conclusions: The majority of costs in the 6-month period after liso-cel infusion among patients with R/R FL in the TRANSCEND FL study were incurred in Month 1 and were facility related (IP and ICU hospitalizations and LOS). These findings, consistent with those previously reported for patients with LBCL treated with liso-cel, support that a single infusion of liso-cel is associated with significantly less HCRU and costs after the initial treatment period in the first month.

The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study.

Sepsis is associated with wide variable coagulation abnormalities. Thromboelastography (TEG) effectively measures the viscoelastic properties of the clots. This study aims to illustrate the viscoelastic properties of clot quality and mass in sepsis and septic shock patients using TEG, as an effective tool over standard coagulation tests. A single-center, prospective observational study was conducted. 50 patients each meeting the criteria for sepsis and septic shock, and a healthy group of 30 patients was included in the study. Blood samples were obtained and analyzed for standard coagulation tests, platelet count, fibrinogen, and TEG study. A total of 130 patients were included. Septic shock patients had a higher sequential (sepsis-related) organ failure score. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were increased significantly as compared to the sepsis and control groups. TEG markers such as alpha angle, and maximum amplitude (MA) were significantly prolonged while reaction time (R time), was significantly shortened in the sepsis group as compared to the healthy group, suggestive of a hypercoagulable state in sepsis patients. While in septic shock patients, MA and Lysis Index 30 (LY 30) were significantly prolonged and, R time was significantly shortened compared to all other groups. Even though LY30 in sepsis patients was found to be within the normal range (p < 0.001), 18% of patients had prolonged LY30 indicating a hypercoagulable state with impaired fibrinolysis. Thromboelastography, as a point-of-care test combined with conventional coagulation tests can provide additional, clinically relevant information on coagulopathy, and outcome, and thus help guide treatment modality in sepsis and septic shock-induced coagulopathy. Mohapatra P, Kumar A, Singh RK, Gupta R, Hussain M, Singh S, et al. The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study. Indian J Crit Care Med 2023;27(9):625-634.

Stumbling Blocks to Stroke Thrombolysis: An Indian Perspective.

Stroke is a leading cause of morbidity and mortality worldwide. Developing countries, however, still lag behind in providing timely thrombolytic therapy (TLT) to many eligible patients owing to various reasons. This study aims to identify such factors. This was a descriptive observational study undertaken over a period of 18 months at a tertiary care teaching hospital and included 252 acute ischemic stroke patients of which 200 were not thrombolyzed. The reasons for nonthrombolysis were recorded and analyzed. The study included 252 acute ischemic stroke patients of which only 20% were thrombolyzed. Of the 200 nonthrombolyzed patients, 55% arrived out of the window period while patient-related factors were the second biggest factor preventing thrombolysis. Hospital factors at 14% and financial constraints at 4.5% contributed significantly. Delayed consent emerged as an important factor making 6% of the delays. Stroke thrombolysis still faces various pre- and intrahospital barriers in India. There is an urgent need to improve infrastructure and organizational streamlining to enable eligible patients to receive prompt treatment. Shah A, Diwan A. Stumbling Blocks to Stroke Thrombolysis: An Indian Perspective. Indian J Crit Care Med 2023;27(9):616-619.

Utility of VCS Parameters as a Cost-effective and Early Marker of Sepsis: A Hospital-based Study.

Sepsis is a life-threatening condition. Nowadays, hospitals rely on laboratory parameters like CRP and procalcitonin to detect sepsis. There is a need to evaluate and validate more accurate and early predictors of sepsis in critically ill patients. We analyzed volume, conductivity, and scatter (VCS) parameters of leukocytes in sepsis patients and compared them with the control group with no illness. It was a prospective case-control study. A total of 80 patients were studied with 40 sepsis cases and 40 controls. Peripheral smear examination was done in all the cases. Other parameters, such as WBC count, neutrophil%, absolute neutrophil count (ANC), High-sensitive C-reactive protein (hs-CRP), procalcitonin, and blood cultures were analyzed. We took the data of the patients from medical records and correlated it with other tests. Complete blood picture reports were generated by the Beckman Coulter LH series (LH 750 and 780). VCS parameters for neutrophils, lymphocytes and monocytes were compared between both groups. The results were analyzed using SPSS software (16.0 version). The age group was 20-85 years with male predominance. The mean neutrophil volume (MNV) and mean monocyte volume (MMV) were higher in the sepsis group when compared with the control group. The mean neutrophil conductivity and scatter was lower in the sepsis group and comparatively higher in the control group, but it was insignificant. The mean neutrophil volume values were higher in the sepsis group even with low total leukocyte count (TLC) when the patient had sepsis. There is no change in the mean lymphocyte VCS parameter and mean monocyte conductivity, scatter in both the groups. The mean neutrophil volume and MMV are found to be good sensitive markers in the prediction of sepsis. Even when TLC is on the lower side in patients with sepsis, these parameters predict sepsis accurately. This helps clinicians to assess sepsis in patients at an early stage and has an important practical implication. Goyal H, Singhal A, Joseph M. Utility of VCS Parameters as a Cost-effective and Early Marker of Sepsis: A Hospital-based Study. Indian J Crit Care Med 2023;27(9):647-650.

Prevalence of Post-extubation Airway Penetration and Aspiration among Critically Ill Patients Assessed by an Eight-point Penetration-Aspiration Scale Using Flexible Endoscopy: A Cross-sectional Study.

Prolonged endotracheal intubation was found to be a risk factor for pulmonary aspiration following the extubation. In this study, we have tried to analyze the prevalence of airway penetration and aspiration among mechanically ventilated patient who received mechanical ventilation for a period of 48 hours or more. This cross-sectional study was done among non-neurologic critically ill patients who had an endotracheal tube for more than 48 hours and who got extubated subsequently. Such patients were taken for a fiberoptic endoscopic swallow study after the initial assessment by a speech pathologist. Airway penetration and aspiration was assessed by an eight-point penetration-aspiration scale after giving a test feed. Data of 99 patients were analyzed. Mean duration of intubation was 5.9 days. 1% of the patients had aspiration and 20% of the patients had varying degrees of penetration. Duration of endotracheal intubation, age, sex, comorbidities, admission diagnosis, and size of the endotracheal tube were found to have no association with penetration and aspiration. Prevalence of post-extubation aspiration was low among non-neurologic critically ill patients on short-term ventilation. Duration of endotracheal intubation, age, sex, comorbidities, and endotracheal tube size were not found to be significantly associated with the development of airway penetration. Contrary to previous studies, this study has shown that among non-neurologic critically ill patients who had an endotracheal tube for a shorter period before extubation, the prevalence of airway penetration and aspiration was low when assessed by an eight-point penetration-aspiration scale using flexible fiberoptic endoscopy. Hence, in such a cohort of patients, a routine swallowing evaluation by flexible endoscopy is not recommended. Vijayan D, Suresh Kumar VK, Harikrishnanan, Menon J, Ragitha, Jacob M, et al. Prevalence of Post-extubation Airway Penetration and Aspiration among Critically Ill Patients Assessed by an Eight-point Penetration-Aspiration Scale Using Flexible Endoscopy: A Cross-sectional Study. Indian J Crit Care Med 2023;27(9):651-654.

Impact of Fatigue on Emergency Physicians' Decision-making for Computed Tomographic Scan Requests and Inpatient Referrals: An Observational Study from a Tertiary Care Medical Center of the Sultanate of Oman.

Multiple factors contribute to decision fatigue experienced by emergency physicians (EPs). This study examines the association between decision fatigue and the frequency of computed tomographic (CT) scan requests and inpatient referrals among EPs. This retrospective database analysis was done for 3 months. Scans and inpatient referral requests were coded and analyzed to assess the impact of physician fatigue on decision-making. Subsequently, the outcomes were evaluated. The majority of patients (n = 481; 51.1%) had a CT brain request. Among these requests, the morning shift (8:00 a.m.-3:00 p.m.) accounted for the highest number (n = 400; 42.5%), followed by the evening shift (3:00-11:00 p.m.) (n = 345; 36.7%). Approximately one-third of the patients (n = 301; 31.9%) had positive CT scan findings. Statistical analysis comparing the first and the second halves of each shift did not reveal significant variations in the percentage of negative CT results (p-value: 0.093). Inpatient referral was necessary for over half of the patients (n = 1,048; 52.7%), and the majority of these referrals (n = 778; 74.2%) were deemed necessary for treatment under various surgical or medical specialties. There was a statistically significant difference in the proportion of negative inpatient referrals between the first and the second halves of the afternoon shift (p-value < 0.001). Fatigue among EPs was observed, leading to more frequent consultations without inpatient admission during the latter half of the afternoon shift. However, the study found no significant impact of decision fatigue on CT scan decision-making. Al-Arimi AH, Hazra D, Al-Alawi AKA. Impact of Fatigue on Emergency Physicians' Decision-making for Computed Tomographic Scan Requests and Inpatient Referrals: An Observational Study from a Tertiary Care Medical Center of the Sultanate of Oman. Indian J Crit Care Med 2023;27(9):620-624.

Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study).

Critically ill patients are frequently transported to various locations within the hospital for diagnostic and therapeutic purposes, which increases the risk of adverse events (AEs). This multicenter prospective observational study was undertaken to determine the incidence of AEs related to intrahospital transport, their severity, and their effects on patient outcomes. We included consecutive unstable critically ill patients requiring intrahospital transport, across 15 Indian tertiary care centers over 5 months (October 11, 2022-February 20, 2023). Apart from the demographics and severity of illness, data related to transport itself, such as indications and destination, incidence of AEs, their category and treatment required, and patient outcomes, were recorded in a standard form. Eight hundred and ninety-three patients were transported on 1065 occasions out of the intensive care unit (ICU). The mean (SD) acute physiology and chronic health evaluation II score of the patients was 15.38 (±7.35). One hundred and two AEs occurred, wherein cardiovascular instability was the most common occurrence (31, 30.4%). Two patients had cardiac arrest immediately after transport. Acute physiology and chronic health evaluation II [odds ratio (OR): 1.02, 95% confidence interval (CI) - 1.00-1.05, p = 0.04], emergent transport (OR: 5.11, 95% CI - 3.32-7.88, p = 0.00), and team composition (OR: 5.34, 95% CI - 1.63-17.5, p = 0.00) during transport were found to be independent predictors of AEs. We found a high incidence of AEs during intrahospital transport of critically ill patients. These events were more common during emergent transports and when the patients were transported by doctors. Transport by itself was not related to ICU mortality. We feel that stabilization of the patients before transport and adherence to a standardized protocol may help in minimizing the AEs, thereby enhancing patient safety. Zirpe KG, Tiwari AM, Kulkarni AP, Govil D, Dixit SB, Munjal M, et al. Adverse Events during Intrahospital Transport of Critically Ill Patients: A Multicenter, Prospective, Observational Study (I-TOUCH Study). Indian J Crit Care Med 2023;27(9):635-641.

An Observational Study from Northern India to Evaluate Catheter-associated Urinary Tract Infection in Medical Intensive Care Unit at a Tertiary Care Center.

Healthcare-associated infections are the leading cause of morbidity and mortality in hospitalized patients. Catheter-associated urinary tract infection (CAUTI) is a leading infection in ICU settings. This study aims to evaluate the patient and catheter-related factors contributing to the urinary tract infection as well as implementing the preventive measures ultimately curbing down the burden of healthcare-associated infections. This is a hospital-based observational study conducted in Department of Microbiology, from October 2020 to September 2021. A total of 150 patients admitted to Medical Intensive Care Unit (MICU) with the indwelling urinary catheter were included. Urine samples were collected with proper aseptic precautions and processed within 2 hours of collection. Identification and antimicrobial susceptibility testing of the isolated pathogens was done as per CLSI guidelines 2019. In this study, the CAUTI rate was 9.4 per 1000 urinary catheter days, while the overall magnitude was 14.67%. It was predominantly reported in 51-70-years age group (34%), and females (63.63%) outnumbered males (36.36%), with Escherichia coli being the commonest pathogen. The highest incidence was reported in the 3rd week of catheterization with diabetes being a predominant risk factor (17.24%). This study provides baseline data on CAUTI rate, pathogens isolated, and risk factors at our institute. The overall goal is to identify, educate, and implement best-practice measures for prevention and curbing down the incidence rates of catheter-associated urinary tract infections. Parihar S, Sharma R, Kinimi SV, Choudhary S. An Observational Study from Northern India to Evaluate Catheter-associated Urinary Tract Infection in Medical Intensive Care Unit at a Tertiary Care Center. Indian J Crit Care Med 2023;27(9):642-646.

Prophylactic Melatonin for Delirium in Intensive Care Unit: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.

Delirium, being a common disorder among critically ill patients, has a reported incidence ranging 45-83% in the intensive care unit (ICU) population. The prophylactic use of melatonin and melatonergics has been shown to have a positive effect in reducing the incidence of delirium in many clinical trials. Our study was thus proposed to find out the role of melatonin on the incidence and severity of ICU delirium, ICU and hospital length of stay (LOS), requirement, duration of mechanical ventilation, and ICU mortality. A systematic search of various databases was performed to find out the trials which compare melatonin with a placebo or standard therapy for delirium prevention with the results conveyed as mean differences (MDs) or risk ratios. The statistical software, Review Manager (RevMan, version 5.4), was used for data synthesis. Twelve studies were included in the meta-analysis. Prophylactic administration of melatonin or ramelteon was not associated with a statistically significant reduction in the incidence of delirium (odds ratio [OR] 0.63; confidence interval [CI]: 0.60, 1.32; p = 0.22), the severity of delirium (MD: 0.22; 95% CI: From -1.36 to 1.81; p = 0.78), ICU LOS (MD: 0.05; 95% CI: From -0.65 to 0.75; p = 0.89), hospital LOS (MD: -1.46; 95% CI: From -4.50 to -1.59; p = 0.35), need for mechanical ventilation (OR: 0.74, 95% CI: 0.38-1.44; p = 0.37), and ICU mortality (MD: 0.78; 95% CI: 0.56; 1.11; p = 0.62). However, a significant reduction in the duration of mechanical ventilation (MD: -0.85; 95% CI: From -1.64 to -0.06; p = 0.03) was found. Our meta-analysis suggests that melatonin when given prophylactically has no significant role in reducing the incidence and severity of delirium, ICU and hospital LOS, need for mechanical ventilation, duration of mechanical ventilation, and ICU mortality. Further studies are warranted. Mukundarajan R, Soni KD, Trikha A. Prophylactic Melatonin for Delirium in Intensive Care Unit: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2023;27(9):675-685.

Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study.

Refractory shock, which fails to respond to conventional vasopressor therapy, is a common complication of sepsis. Methylene blue has emerged as a potential adjunctive treatment option for reversing refractory shock in sepsis. The aim of this study was to evaluate the impact of intravenous methylene blue infusion on hemodynamic improvement and mortality in patients with refractory shock. This was an observational prospective study for the duration of six months conducted at intensive care a medical college and teaching hospital including 76 patients with a diagnosis of septic shock requiring vasopressor therapy. Intravenous (IV) methylene blue was infused as a bolus dose with 2 mg/kg dose in 20 minutes and its response to mean arterial blood pressure, decrease in vasopressor therapy, lactate level, and urine output was recorded in next 2 hours. Patients with improvement in mean arterial pressure (MAP) by 10% or decrease in vasopressor therapy in the next 2 hours were leveled as responder. The length of intensive care unit (ICU) stay, duration of mechanical ventilation, incidence of acute kidney injury (AKI), and mortality were compared between responder and non-responder. A total of 76 patients with refractory shock were included in the study. With the use of IV methylene blue, 41 (53.9%) patients showed significant improvement in MAP within 2 hours (70.17 ± 8.30 vs 64.28 ± 11.84, p = 0.005). Responders were 4.019 times more likely to have vasopressor-free time within 24 hours (18.4% vs 5.3%, p = 0.020, odds ratio 4.019, 95% confidence interval, 1.180-13.682). However, there was no significant difference in terms of mortality, length of ICU stay, ventilator free days, and incidence of AKI. In the responder group, there was a significant increase in the MAP and decrease in vasopressor requirement pre- and post-infusion of methylene blue (p < 0.05). Responder had shorter vasopressor-free days as compared with non-responder (5.34 vs 6.79, p = 0.008) while the mean survival time was longer with responders (21.97 vs 15.93 days, p = 0.024). The use of IV methylene blue in refractory shock as an adjuvant therapy significantly improved the mean arterial blood pressure and decreased the requirement of vasopressor therapy as well as improvement in the survival time. However, there was no change in the mortality, length of ICU stay, ventilator-free days, or incidence of AKI in the patients. Rajbanshi LK, Bajracharya A, Arjyal B, Devkota D. Can Use of Intravenous Methylene Blue Improve the Hemodynamics and Outcome of the Patients with Refractory Septic Shock? An Observational Study. Indian J Crit Care Med 2023;27(9):669-674.

Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae.

Rapid molecular diagnostics to predict carbapenem resistance well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of Carbapenem-resistant Enterobacteriaceae (CRE). A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on gram-negative bacteria (GNB) flagged blood culture samples, in an Indian intensive care unit between January 2015 and November 2018. We analyzed the performance of Xpert Carba-R in comparison with routine DST. A total of 164 GNBs were isolated from 160 patients. Klebsiella pneumoniae and Escherichia coli were the predominant isolates. Carba-R was positive in 35.36% of samples and 45.34% were carbapenem-resistant (CR) on routine DST. The distribution of the CR gene was: Oxacillinase (OXA) (50%), NDM (32.7%) followed by OXA and NDM co-expression (15.51%). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of Carba-R were 90.74, 93.15, 13.25, 0.10, 83.58 and 96.31% for Enterobacteriaceae. The median time to obtain the Carba-R report was 30 hours 34 minutes vs 74 hours and 20 minutes for routine DST. Based on the Carba-R report, 9.72% of patients had escalation and 27.08% had de-escalation of antibiotics. Xpert Carba-R serves as a rapid diagnostic tool for predicting carbapenem resistance in intensive care unit patients with bacteremia caused by Enterobacteriaceae. Rajendran S, Gopalakrishnan R, Tarigopula A, Kumar DS, Nambi PS, Sethuraman N, et al. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae. Indian J Crit Care Med 2023;27(9):655-662.

Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant AcinetobacterBaumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India.

In the Indian setting, antimicrobial resistance in A. baumannii is a considerable problem, especially in intensive care units (ICUs). Due to the limited data, clinicians are left with very few choices except polymyxins for treating serious infections caused by A. baumannii. There is sparse data regarding the local mechanisms of resistance. Given the current therapeutic challenges, it is critical to know the local enzymatic patterns and antibiograms. A retrospective analysis of 50 episodes of bacteremia caused by CRAB. We analyzed the enzyme patterns and the susceptibility rates to various antibiotics. The resistance rates for amikacin, tigecycline, minocycline, and fluoroquinolones were 88, 82, 50, and 88% respectively. OXA-23 was the most commonly isolated enzyme (86% of the isolates produced OXA-23) followed by OXA-51 and NDM. The overall mortality was high (58%). On univariate analysis, pneumonia, and higher Pitt's bacteremia score were significantly associated with mortality (p = 0.04 and p = 0.001 respectively). Of the total patients who received combination therapy, a majority (58%) received polymyxin plus meropenem. Combination therapy using polymyxins as a backbone was not associated with reduced mortality (p = 0.1). A. baumannii is associated with significant morbidity and mortality, as shown in our study. The rates of resistance for aminoglycosides were very high, and minocycline showed better susceptibility rates in comparison with tigecycline. In our study, OXA-23 and NDM remained the most important enzymes. The routine use of the combination of polymyxin and meropenem may not offer a significant advantage over monotherapy. Prayag PS, Patwardhan SA, Joshi RS, Panchakshari SP, Rane T, Prayag AP. Enzyme Patterns and Factors Associated with Mortality among Patients with Carbapenem Resistant Acinetobacter Baumannii (CRAB) Bacteremia: Real World Evidence from a Tertiary Center in India. Indian J Crit Care Med 2023;27(9):663-668.