BACKGROUND:Central line-associated bloodstream infections (CLABSIs) cause preventable harm. We evaluated whether Chlorhexidine/Silver Sulfadiazine (CH/SSD)-impregnated CVCs reduce the CLABSI hazard compared with plain CVCs using time-to-event methodology. METHODS:A prospective cohort study was conducted in 6 hospitals in India, Malaysia, Papua New Guinea, and Turkey from 03/01/2023-10/31/2025. We included 1,294 plain-CVC patients and 456 CH/SSD-CVC patients. The primary endpoint was time to first CLABSI, estimated by Kaplan-Meier modeled with Cox proportional hazards regression. A prespecified landmark analysis assessed early risk at days 0-5. RESULTS:Within 30 days, 51 CLABSIs occurred in the plain-CVC group and 12 in the CH/SSD group. Kaplan-Meier cumulative incidence at 30 CVC-days showed statistically significant separation (log-rank X2 = 5.309; P = .021). In the primary Cox proportional hazards model, CH/SSD-CVCs were associated with a significantly lower hazard of CLABSI than plain-CVCs (hazard ratio = 0.297; 95%CI = 0.134-0.658; P = .003). In the prespecified early 0-5-day period, 13 CLABSIs occurred in the plain-CVC group and 0 in the CH/SSD-CVC group (log-rank X2 = 4.923; P = .026). ICU mortality was higher in the plain-CVC group (28.3% vs 18.4%; P < .001). CONCLUSIONS:CH/SSD-CVCs were associated with a significant reduction in the CLABSI hazard, supporting further study of their use as tools to prevent CLABSI.

Objective: To identify urinary catheter (UC)-associated urinary tract infection (CAUTI) incidence and risk factors. Design: A prospective cohort study. Setting: The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries. Participants: The study included 169,036 patients, hospitalized for 1,166,593 patient days. Methods: Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression. Results: Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower-middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001). Conclusions: CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities. Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

Background: Central line-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs) across Latin America exceed those in high-income countries significantly. Methods: We implemented the INICC multidimensional approach, incorporating an 11-component bundle, in 122 ICUs spanning nine Asian countries. We computed the CLABSI rate using the CDC/NSHN definition and criteria. The CLABSI rate per 1000 CL-days was calculated at baseline and throughout different phases of the intervention, including the 2nd month, 3rd month, 4-16 month, and 17-29 month periods. A two-sample t-test was employed to compare baseline CLABSI rates with intervention rates. Additionally, we utilized a generalized linear mixed model with a Poisson distribution to analyze the association between exposure and outcome. Results: A total of 124,946 patients were hospitalized over 717,270 patient-days, with 238,595 central line (CL)-days recorded. The rates of CLABSI per 1000 CL-days significantly decreased from 16.64 during the baseline period to 6.51 in the 2nd month (RR = 0.39; 95% CI = 0.36-0.42; p < 0.001), 3.71 in the 3rd month (RR = 0.22; 95% CI = 0.21-0.25; p < 0.001), 2.80 in the 4-16 month (RR = 0.17; 95% CI = 0.15-0.19; p < 0.001), and 2.18 in the 17-29 month (RR = 0.13; 95% CI = 0.11-0.15; p < 0.001) intervals. A multilevel Poisson regression model demonstrated a sustained, continuous, and statistically significant decrease in ratios of incidence rates, reaching 0.35 (p < 0.0001) during the 17-29 month period. Moreover, the all-cause in-ICU mortality rate significantly decreased from 13.23% to 10.96% (p = 0.0001) during the 17-29 month period. Conclusions: Our intervention led to an 87% reduction in CLABSI rates, with a 29-month follow-up.

BACKGROUND:Our objective was to identify central line (CL)-associated bloodstream infections (CLABSI) rates and risk factors (RF) in Asia. METHODS:From 03/27/2004 to 02/11/2022, we conducted a multinational multicenter prospective cohort study in 281 ICUs of 95 hospitals in 44 cities in 9 Asian countries (China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam). For estimation of CLABSI rate we used CL-days as denominator and number of CLABSI as numerator. To estimate CLABSI RF for we analyzed the data using multiple logistic regression, and outcomes are shown as adjusted odds ratios (aOR). RESULTS:A total of 150,142 patients, hospitalized 853,604 days, acquired 1514 CLABSIs. Pooled CLABSI rate per 1000 CL-days was 5.08; per type of catheter were: femoral: 6.23; temporary hemodialysis: 4.08; jugular: 4.01; arterial: 3.14; PICC: 2.47; subclavian: 2.02. The highest rates were femoral, temporary for hemodialysis, and jugular, and the lowest PICC and subclavian. We analyzed following variables: Gender, age, length of stay (LOS) before CLABSI acquisition, CL-days before CLABSI acquisition, CL-device utilization ratio, CL-type, tracheostomy use, hospitalization type, ICU type, facility ownership and World Bank classifications by income level. Following were independently associated with CLABSI: LOS before CLABSI acquisition, rising risk 4% daily (aOR = 1.04; 95% CI = 1.03-1.04; p < 0.0001); number of CL-days before CLABSI acquisition, rising risk 5% per CL-day (aOR = 1.05; 95% CI 1.05-1.06; p < 0.0001); medical hospitalization (aOR = 1.21; 95% CI 1.04-1.39; p = 0.01); tracheostomy use (aOR = 2.02;95% CI 1.43-2.86; p < 0.0001); publicly-owned facility (aOR = 3.63; 95% CI 2.54-5.18; p < 0.0001); lower-middle-income country (aOR = 1.87; 95% CI 1.41-2.47; p < 0.0001). ICU with highest risk was pediatric (aOR = 2.86; 95% CI 1.71-4.82; p < 0.0001), followed by medical-surgical (aOR = 2.46; 95% CI 1.62-3.75; p < 0.0001). CL with the highest risk were internal-jugular (aOR = 3.32; 95% CI 2.84-3.88; p < 0.0001), and femoral (aOR = 3.13; 95% CI 2.48-3.95; p < 0.0001), and subclavian (aOR = 1.78; 95% CI 1.47-2.15; p < 0.0001) showed the lowest risk. CONCLUSIONS:The following CLABSI RFs are unlikely to change: country income level, facility-ownership, hospitalization type, and ICU type. Based on these findings it is suggested to focus on reducing LOS, CL-days, and tracheostomy; using subclavian or PICC instead of internal-jugular or femoral; and implementing evidence-based CLABSI prevention recommendations.

Abstract Objective: Rates of ventilator-associated pneumonia (VAP) in low- and middle-income countries (LMIC) are several times above those of high-income countries. The objective of this study was to identify risk factors (RFs) for VAP cases in ICUs of LMICs. Design: Prospective cohort study. Setting: This study was conducted across 743 ICUs of 282 hospitals in 144 cities in 42 Asian, African, European, Latin American, and Middle Eastern countries. Participants: The study included patients admitted to ICUs across 24 years. Results: In total, 289,643 patients were followed during 1,951,405 patient days and acquired 8,236 VAPs. We analyzed 10 independent variables. Multiple logistic regression identified the following independent VAP RFs: male sex (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.16–1.28; P < .0001); longer length of stay (LOS), which increased the risk 7% per day (aOR, 1.07; 95% CI, 1.07–1.08; P < .0001); mechanical ventilation (MV) utilization ratio (aOR, 1.27; 95% CI, 1.23–1.31; P < .0001); continuous positive airway pressure (CPAP), which was associated with the highest risk (aOR, 13.38; 95% CI, 11.57–15.48; P < .0001); tracheostomy connected to a MV, which was associated with the next-highest risk (aOR, 8.31; 95% CI, 7.21–9.58; P < .0001); endotracheal tube connected to a MV (aOR, 6.76; 95% CI, 6.34–7.21; P < .0001); surgical hospitalization (aOR, 1.23; 95% CI, 1.17–1.29; P < .0001); admission to a public hospital (aOR, 1.59; 95% CI, 1.35-1.86; P < .0001); middle-income country (aOR, 1.22; 95% CI, 15–1.29; P < .0001); admission to an adult-oncology ICU, which was associated with the highest risk (aOR, 4.05; 95% CI, 3.22–5.09; P < .0001), admission to a neurologic ICU, which was associated with the next-highest risk (aOR, 2.48; 95% CI, 1.78–3.45; P < .0001); and admission to a respiratory ICU (aOR, 2.35; 95% CI, 1.79–3.07; P < .0001). Admission to a coronary ICU showed the lowest risk (aOR, 0.63; 95% CI, 0.51–0.77; P < .0001). Conclusions: Some identified VAP RFs are unlikely to change: sex, hospitalization type, ICU type, facility ownership, and country income level. Based on our results, we recommend focusing on strategies to reduce LOS, to reduce the MV utilization ratio, to limit CPAP use and implementing a set of evidence-based VAP prevention recommendations.

Background Ventilator associated pneumonia (VAP) rates in Asia are several times above those of US. The objective of this study is to identify VAP risk factors. Methods We conducted a prospective cohort study, between March 27, 2004 and November 2, 2022, in 279 ICUs of 95 hospitals in 44 cities in 9 Asian countries (China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, Vietnam). Results 153,717 patients, followed during 892,996 patient-days, acquired 3,369 VAPs. We analyzed 10 independent variables. Using multiple logistic regression we identified following independent VAP RFs= Age, rising VAP risk 1% per year (aOR=1.01; 95%CI=1.00-1.01, P<.0001); male gender (OR=1.17; 95%CI=1.08-1.26, P<.0001); length of stay, rising VAP risk 7% daily (aOR=1.07; 95%CI=1.06-1.07, P<.0001); mechanical ventilation (MV) device utilization (DU) ratio (OR=1.43; 95%CI=1.36-1.51; p<.0001); tracheostomy connected to a MV (OR=11.17; 95%CI=9.55-14.27; p<.0001); public (OR=1.84; 95%CI=1.49-2.26, P<.0001), and private (OR=1.57; 95%CI=1.29-1.91, P<.0001) compared with teaching hospitals; upper-middle income country (OR=1.86; 95%CI=1.63-2.14, P<.0001). Regarding ICUs, Medical-Surgical (OR=4.61; 95%CI=3.43-6.17; P<.0001), Neurologic (OR=3.76; 95%CI=2.43-5.82; P<.0001), Medical (OR=2.78; 95%CI=2.04-3.79; P<.0001), and Neuro-Surgical (OR=2.33; 95%CI=1.61-3.92; P<.0001) showed the highest risk. Conclusions Some identified VAP RFs are unlikely to change= age, gender, ICU type, facility ownership, country income level. Based on our results, we recommend limit use of tracheostomy, reducing LOS, reducing the MV/DU ratio, and implementing an evidence-based set of VAP prevention recommendations.

Objective: To identify risk factors for mortality in intensive care units (ICUs) in Asia. Design: Prospective cohort study. Setting: The study included 317 ICUs of 96 hospitals in 44 cities in 9 countries of Asia: China, India, Malaysia, Mongolia, Nepal, Pakistan, Philippines, Sri Lanka, Thailand, and Vietnam. Participants: Patients aged >18 years admitted to ICUs. Results: In total, 157,667 patients were followed during 957,517 patient days, and 8,157 HAIs occurred. In multiple logistic regression, the following variables were associated with an increased mortality risk: central-line-associated bloodstream infection (CLABSI; aOR, 2.36; P < .0001), ventilator-associated event (VAE; aOR, 1.51; P < .0001), catheter-associated urinary tract infection (CAUTI; aOR, 1.04; P < .0001), and female sex (aOR, 1.06; P < .0001). Older age increased mortality risk by 1% per year (aOR, 1.01; P < .0001). Length of stay (LOS) increased mortality risk by 1% per bed day (aOR, 1.01; P < .0001). Central-line days increased mortality risk by 2% per central-line day (aOR, 1.02; P < .0001). Urinary catheter days increased mortality risk by 4% per urinary catheter day (aOR, 1.04; P < .0001). The highest mortality risks were associated with mechanical ventilation utilization ratio (aOR, 12.48; P < .0001), upper middle-income country (aOR, 1.09; P = .033), surgical hospitalization (aOR, 2.17; P < .0001), pediatric oncology ICU (aOR, 9.90; P < .0001), and adult oncology ICU (aOR, 4.52; P < .0001). Patients at university hospitals had the lowest mortality risk (aOR, 0.61; P < .0001). Conclusions: Some variables associated with an increased mortality risk are unlikely to change, such as age, sex, national economy, hospitalization type, and ICU type. Some other variables can be modified, such as LOS, central-line use, urinary catheter use, and mechanical ventilation as well as and acquisition of CLABSI, VAE, or CAUTI. To reduce mortality risk, we shall focus on strategies to reduce LOS; strategies to reduce central-line, urinary catheter, and mechanical ventilation use; and HAI prevention recommendations.

Background: The International Nosocomial Infection Control Consortium has found a high ICU mortality rate. Our aim was to identify all-cause mortality risk factors in ICU-patients. Methods: Multinational, multicenter, prospective cohort study at 786 ICUs of 312 hospitals in 147 cities in 37 Latin American, Asian, African, Middle Eastern, and European countries. Results: Between 07/01/1998 and 02/12/2022, 300,827 patients, followed during 2,167,397 patient-days, acquired 21,371 HAIs. Following mortality risk factors were identified in multiple logistic regression: Central line-associated bloodstream infection (aOR:1.84; P<.0001); ventilator-associated pneumonia (aOR:1.48; P<.0001); catheter-associated urinary tract infection (aOR:1.18;P<.0001); medical hospitalization (aOR:1.81; P<.0001); length of stay (LOS), risk rises 1% per day (aOR:1.01; P<.0001); female gender (aOR:1.09; P<.0001); age (aOR:1.012; P<.0001); central line-days, risk rises 2% per day (aOR:1.02; P<.0001); and mechanical venti-lator (MV)-utilization ratio (aOR:10.46; P<.0001). Coronary ICU showed the lowest risk for mortality (aOR: 0.34;P<.0001). Conclusion: Some identified risk factors are unlikely to change, such as country income-level, facility owner-ship, hospitalization type, gender, and age. Some can be modified; Central line-associated bloodstream infec-tion, ventilator-associated pneumonia, catheter-associated urinary tract infection, LOS, and MV-utilization. So, to lower the risk of death in ICUs, we recommend focusing on strategies to shorten the LOS, reduce MV -utilization, and use evidence-based recommendations to prevent HAIs. (c) 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

How to cite this article: Khilnani GC, Tiwari P, Zirpe KG, Chaudhary D, Govil D, Dixit S, et al. Guidelines for the Use of Procalcitonin for Rational Use of Antibiotics. Indian J Crit Care Med 2022;26(S2):S77-S94.

Background: Short-term peripheral venous catheter–associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter–associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available. Methods: Prospective, surveillance study on peripheral venous catheter–associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System. Results: We followed 83,295 intensive care unit patients for 369,371 bed-days and 376,492 peripheral venous catheter-days. We identified 999 peripheral venous catheter–associated bloodstream infections, amounting to a rate of 2.65/1000 peripheral venous catheter-days. Mortality in patients with peripheral venous catheter but without peripheral venous catheter–associated bloodstream infections was 4.53% and 12.21% in patients with peripheral venous catheter–associated bloodstream infections. The mean length of stay in patients with peripheral venous catheter but without peripheral venous catheter–associated bloodstream infections was 4.40 days and 7.11 days in patients with peripheral venous catheter and peripheral venous catheter–associated bloodstream infections. The microorganism profile showed 67.1% were Gram-negative bacteria: Escherichia coli (22.9%), Klebsiella spp (10.7%), Pseudomonas aeruginosa (5.3%), Enterobacter spp. (4.5%), and others (23.7%). The predominant Gram-positive bacteria were Staphylococcus aureus (11.4%). Conclusions: Infection prevention programs must be implemented to reduce the incidence of peripheral venous catheter–associated bloodstream infections.

Background:We aimed to study organizational aspects, case mix, and practices in Indian intensive care units (ICUs) from 2018 to 2019, following the Indian Intensive Care Case Mix and Practice Patterns Study (INDICAPS) of 2010-2011. Methods:An observational, 4-day point prevalence study was performed between 2018 and 2019. ICU, patient characteristics, and interventions were recorded for 24 hours, and ICU outcomes till 30 days after the study day. Adherence to selected compliance measures was determined. Data were analyzed for 4,669 adult patients from 132 ICUs. Results:On the study day, mean age, acute physiology and chronic health evaluation (APACHE II), and sequential organ failure assessment (SOFA) scores were 56.9 ± 17.41 years, 16.7 ± 9.8, and 4.4 ± 3.6, respectively. Moreover, 24% and 22.2% of patients received mechanical ventilation (MV) and vasopressors or inotropes (VIs), respectively. On the study days, 1,195 patients (25.6%) were infected and 1,368 patients (29.3%) had sepsis during their ICU stay. ICU mortality was 1,092 out of 4,669 (23.4%), including 737 deaths and 355 terminal discharges (TDs) from ICU. Compliance for process measures related to MV ranged between 62.7 and 85.3%, 11.2 and 47.4% for monitoring delirium, sedation, and analgesia, and 7.7 and 25.3% for inappropriate transfusion of blood products. Only 34.8% of ICUs routinely used capnography. Large hospitals with ≥500 beds, closed ICUs, the APACHE II and SOFA scores, medical admissions, the presence of cancer or cirrhosis of the liver, the presence of infection on the study day, and the need for MV or VIs were independent predictors of mortality. Conclusions:Hospital size and closed ICUs are independently associated with worse outcomes. The proportion of TDs remains high. There is a scope for improvements in processes of care.Registered at clinicaltrials.gov (NCT03631927). How to cite this article:Divatia JV, Mehta Y, Govil D, Zirpe K, Amin PR, Ramakrishnan N, et al. Intensive Care in India in 2018-2019: The Second Indian Intensive Care Case Mix and Practice Patterns Study. Indian J Crit Care Med 2021;25(10):1093-1107.

Background: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. Methods: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. Results: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated uri-nary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeru-ginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. Conclusions: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them. (c) 2021 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc.

BACKGROUND:Short-term peripheral venous catheters-related bloodstream infections (PVCR-BSIs) rates have not been systematically studied in developing countries, and data on their incidence by number of device-days are not available. METHODS:Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013 to May 31, 2019 in 204 intensive care units (ICUs), members of the International Nosocomial Infection Control Consortium (INICC), from 57 hospitals in 19 cities of India. We applied US INICC definition criteria and reported methods using the INICC Surveillance Online System. RESULTS:We followed 7,513 ICU patients for 296,893 bed-days and 295,795 short term peripheral venous catheter (PVC)-days. We identified 863 PVCR-BSIs, amounting to a rate of 2.91/1,000 PVC-days. Mortality in patients with PVC but without PVCR-BSI was 4.14%, and 11.59% in patients with PVCR-BSI. The length of stay in patients with PVC but without PVCR-BSI was 4.13 days, and 5.9 days in patients with PVCR-BSI. The micro-organism profile showed 68% of gram negative bacteria: Escherichia coli (23%), Klebsiella spp (15%), Pseudomonas aeruginosa (5%), and others. The predominant gram-positive bacteria were Staphylococcus aureus (10%). CONCLUSIONS:PVCR-BSI rates found in our ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs.

ABSTRACT Clotting catastrophies are rarely encountered challenges in the Intensive Care Unit (ICU) and their presentation and progress maybe devastating and fulminant. Dramatic onset and involvement of multiple vascular beds should alert the clinician to look for these disorders. Outcomes may be improved with rapid diagnosis and prompt institution of specific therapies and interdisciplinary liaison holds the key to success. How to cite this article Sinha S, Todi SK. Clotting Catastrophies in the Intensive Care Unit. Indian J Crit Care Med 2019;23(Suppl 3):S197–S201.

Recent literature on the use of vitamin C in critically ill patient with sepsis has generated much interest. Analysing the scientific rationale for the increasing use of this molecule in the intensive care units (ICUs) around the world and differentiating it as a real hope for such patients from hype needs to proceed in a logical sequence of understanding the biological rationale, preclinical and clinical data including one published in this edition of IJA,[1] and applying rigors of evidence-based medicine as opposed to emotion-based medicine to decide on the current scope of its use. BIOLOGICAL RATIONALE Vitamin C (ascorbic acid) has a pleiotropic effect on various metabolic functions.[2] It is an antioxidant, improves endothelial function, improves microcirculation, decreases excessive endothelial permeability and acts as a cofactor in norepinephrine and vasopressin synthesis. It is not synthesised in the body and has to be replaced from external sources in deficiency states. The normal plasma vitamin C level is ≥23 μmol/L. In sepsis and other related conditions such as trauma and ischaemia/reperfusion injury, the serum levels (and presumably tissue levels) are decreased substantially. A recent study has shown that 88% of the septic patients have hypovitaminosis C (i.e., <23 μmol/L), whereas 38% have severe deficiency as seen in scurvy (i.e., <11 μmol/L). This deficiency is probably caused by reduced recycling of oxidised vitamin C. Low vitamin C level is associated with increased organ dysfunction and mortality, although this association does not imply causality; it may just reflect an epiphenomenon of critical illness similar to other physiological derangements such as hyperglycaemia, anaemia and hypovitaminosis, corrections of which do not convert into mortality benefit. In general, use of vitamin C both in replacement and pharmacological doses is safe, although precipitation of oxalate crystallopathy has been noted with high-dose vitamin C. Vitamin C can also interfere with glucose reading in point-of-care glucometer and can mask hypoglycaemia. Many of the clinical studies have used vitamin C with other antioxidants such as vitamin E and selenium. The rationale of its use with glucocorticoids is its facilitative property on steroid receptors by reversing their oxidation. Thiamine is used with high-dose vitamin C to prevent hyperoxaluria. Combination of deficiency state in septic patient with a reasonably safety profile has led to its use in critically ill patients. Preclinical data In animal model of traumatic shock, vitamin C was found to attenuate proinflammatory and procoagulant pathways.[3] In a cardiac arrest model, it was found to have a beneficial effect on neuronal and myocardial recovery when combined with hypothermia. In an ischaemia/reperfusion kidney model, vitamin C used in combination with vitamin E and hydrocortisone attenuated oxidative injury. CLINICAL DATA The current clinical data on the use of vitamin C on critically ill patient usually address improvement of surrogate markers like organ failure, length of stay, resuscitative fluid requirement, improved myocardial function and decrease in vasopressor requirement, in diverse patient populations with sepsis, trauma, burns, post angioplasty and so on, using large doses of vitamin C.[4] The renewed interest in this molecule came after the publication of a case–control, before–after study published in Chest by Marik et al. in 2017 on 80 patients (40 cases and 40 control) with septic shock. The study demonstrated not only significant improvement in surrogate markers but also a dramatic reduction in hospital mortality with treatment of a cocktail of vitamin C, thiamine and hydrocortisone (8.4%) compared with a propensity-matched historical control (40.4%).[4] In this issue of IJA, Marik et al.'s protocol was replicated in a small group of post cardiac surgery patients with septic shock, with reduction in vasopressor dose as the primary outcome, but they could not demonstrate any reduction in organ dysfunction or mortality.[1] The strength of the study was randomisation, but it was underpowered for mortality outcome. The results from this study need to be replicated in a larger trial. KNOWLEDGE GAP At present, there are substantial knowledge gaps in our understanding of vitamin C efficacy in critically ill patients. The following gaps in our understanding need to be studied before widespread use of Marik et al.'s cocktail is implemented in clinical practice: In most of the clinical studies, vitamin C has been used with hydrocortisone with reduction in vasopressor requirement as the primary endpoint. There is a strong evidence now of vasopressor-sparing effects of hydrocortisone alone, hence the additional benefit of vitamin C needs to be studied separately As we are entering an era of personalised medicine, vitamin C should be given to patients who have subnormal levels of the molecule and the dose should be targeted to achieve therapeutic levels rather than a fixed dose as practiced now The optimal timing and duration need to be addressed, probably depending on a marker of ongoing oxidative injury Additional role of thiamine needs to be studied. The specific patient subgroup of trauma, burn, surgical and medical patients in whom this therapy will be helpful need to be identified Pharmacokinetic/pharmacodynamic data which will address bolus versus continuous infusion of this molecule need to be determined Safety profile in patients with renal failure need to be studied. Around eight randomised clinical studies including a couple from India are underway to confirm the data by Marik et al. and to address the knowledge gaps in this area (CITRIS-ALI: NCT02106975) has been completed, hydrocortisone, vitamin C and thiamine for the Treatment of Sepsis and Septic Shock (HYVCTTSSS: (HYVCTTSSS)) is recruiting at present. Amrita institute in Kochi has undertaken a randomised study of Marik et al.'s protocol in septic shock patients in a medical/surgical ICU. The key question that is often asked by the practicing physician is “given the present data and pending future studies, whether vitamin C, thiamine and hydrocortisone should be used in critically ill patients?” It is natural that in conditions with high mortality like sepsis with only supportive therapy and infection control being the present treatment armamentarium, physicians will be inclined to use molecules with insufficient data but with no substantial harm and available at an affordable cost. Although this approach may not be scientifically desirable, it will be equally difficult to go against this trend. A compromise approach would be to document the use of this regimen in a standardised way along with patient specifics and have a big data bank for analysis, which might even be more informative than small randomised studies or meta-analyses. Finally, similar to Vanden Bergh's trial on glucose control and Rivers' study on early goal directed therapy, both of which were contradicted in subsequent trials, but were practice changing by increasing awareness of blood sugar control and early protocolised care in critically ill, studies on vitamin C use will increase awareness of vitamin deficiency states in these patients and some benefits can be expected by replacing it with simple inexpensive molecules.

BACKGROUND AND AIMS:Sepsis is a major worldwide cause of morbidity and mortality. Most sepsis epidemiologic data are from the Western literature. Sparse data from India describe the epidemiology of infection rather than sepsis which is a host response to infection. This study describes the epidemiology of sepsis in the Intensive Care Unit (ICU) of an Indian tertiary care hospital.SUBJECTS AND METHODS:A prospective study conducted between June 2006 and May 2011. All consecutively admitted patients during the 5 year study >=18 years of age were included and data obtained from hospital in-patient records. Variables measured were the incidence of severe sepsis, ICU, hospital, and 28-day mortality, the median length of ICU stay, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score, infection site, and microbial profile.RESULTS:There were 4711 admissions during the study with 282 (6.2%, 95% confidence interval 2.3, 13.1) admissions with severe sepsis. ICU mortality, hospital mortality, and 28-day mortality were 56%, 63.6%, and 62.8%, respectively. Predominant infection site was respiratory tract. The most common organisms were Gram-negative microbes. The most common microbe was Acinetobacter baumanni. Median APACHE II score on admission was 22 (interquartile range 16-28) and median length of ICU stay was 8 days. Severe sepsis attributable mortality was 85%.CONCLUSION:Severe sepsis is common in Indian ICUs and is mainly due to Gram-negative organisms. ICU mortality is high in this group and care is resource intensive due to increased length of stay.

OBJECTIVETo report the International Nosocomial Infection Control Consortium surveillance data from 40 hospitals (20 cities) in India 2004–2013.METHODSSurveillance using US National Healthcare Safety Network’s criteria and definitions, and International Nosocomial Infection Control Consortium methodology.RESULTSWe collected data from 236,700 ICU patients for 970,713 bed-daysPooled device-associated healthcare-associated infection rates for adult and pediatric ICUs were 5.1 central line–associated bloodstream infections (CLABSIs)/1,000 central line–days, 9.4 cases of ventilator-associated pneumonia (VAPs)/1,000 mechanical ventilator–days, and 2.1 catheter-associated urinary tract infections/1,000 urinary catheter–daysIn neonatal ICUs (NICUs) pooled rates were 36.2 CLABSIs/1,000 central line–days and 1.9 VAPs/1,000 mechanical ventilator–daysExtra length of stay in adult and pediatric ICUs was 9.5 for CLABSI, 9.1 for VAP, and 10.0 for catheter-associated urinary tract infections. Extra length of stay in NICUs was 14.7 for CLABSI and 38.7 for VAPCrude extra mortality was 16.3% for CLABSI, 22.7% for VAP, and 6.6% for catheter-associated urinary tract infections in adult and pediatric ICUs, and 1.2% for CLABSI and 8.3% for VAP in NICUsPooled device use ratios were 0.21 for mechanical ventilator, 0.39 for central line, and 0.53 for urinary catheter in adult and pediatric ICUs; and 0.07 for mechanical ventilator and 0.06 for central line in NICUs.CONCLUSIONSDespite a lower device use ratio in our ICUs, our device-associated healthcare-associated infection rates are higher than National Healthcare Safety Network, but lower than International Nosocomial Infection Control Consortium Report.Infect. Control Hosp. Epidemiol. 2016;37(2):172–181

Objective: To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach on central line-associated bloodstream infection (CLABSI) rates in eight cities of India.Methods: This was a prospective, before-and-after cohort study of 35 650 patients hospitalized in 16 adult intensive care units of 11 hospitals. During the baseline period, outcome surveillance of CLABSI was performed, applying the definitions of the CDC/NHSN (US Centers for Disease Control and Prevention/National Healthcare Safety Network). During the intervention, the INICC approach was implemented, which included a bundle of interventions, education, outcome surveillance, process surveillance, feedback on CLABSI rates and consequences, and performance feedback. Random effects Poisson regression was used for clustering of CLABSI rates across time periods.Results: During the baseline period, 9472 central line (CL)-days and 61 CLABSIs were recorded; during the intervention period, 80 898 CL-days and 404 CLABSIs were recorded. The baseline rate was 6.4 CLABSIs per 1000 CL-days, which was reduced to 3.9 CLABSIs per 1000 CL-days in the second year and maintained for 36 months of follow-up, accounting for a 53% CLABSI rate reduction (incidence rate ratio 0.47, 95% confidence interval 0.31-0.70; p = 0.0001).Conclusions: Implementing the six components of the INICC approach simultaneously was associated with a significant reduction in the CLABSI rate in India, which remained stable during 36 months of follow-up. (C) 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

SUMMARYVentilator-associated pneumonias (VAPs) are a worldwide problem that significantly increases patient morbidity, mortality, and length of stay (LoS), and their effects should be estimated to account for the timing of infection. The purpose of the study was to estimate extra LoS and mortality in an intensive-care unit (ICU) due to a VAP in a cohort of 69 248 admissions followed for 283 069 days in ICUs from 10 countries. Data were arranged according to the multi-state format. Extra LoS and increased risk of death were estimated independently in each country, and their results were combined using a random-effects meta-analysis. VAP prolonged LoS by an average of 2·03 days (95% CI 1·52–2·54 days), and increased the risk of death by 14% (95% CI 2–27). The increased risk of death due to VAP was explained by confounding with patient morbidity.