Morbidity In Intensive Care Unit Research Articles

Protein Kinase C and Acute Respiratory Distress Syndrome

The acute respiratory distress syndrome (ARDS) is a major public health problem and a leading source of morbidity in intensive care units. Lung tissue in patients with ARDS is characterized by inflammation, with exuberant neutrophil infiltration, activation, and degranulation that is thought to initiate tissue injury through the release of proteases and oxygen radicals. Treatment of ARDS is supportive primarily because the underlying pathophysiology is poorly understood. This gap in knowledge must be addressed to identify urgently needed therapies. Recent research efforts in anti-inflammatory drug development have focused on identifying common control points in multiple signaling pathways. The protein kinase C (PKC) serine-threonine kinases are master regulators of proinflammatory signaling hubs, making them attractive therapeutic targets. Pharmacological inhibition of broad-spectrum PKC activity and, more importantly, of specific PKC isoforms (as well as deletion of PKCs in mice) exerts protective effects in various experimental models of lung injury. Furthermore, PKC isoforms have been implicated in inflammatory processes that may be involved in the pathophysiologic changes that result in ARDS, including activation of innate immune and endothelial cells, neutrophil trafficking to the lung, regulation of alveolar epithelial barrier functions, and control of neutrophil proinflammatory and prosurvival signaling. This review focuses on the mechanistic involvement of PKC isoforms in the pathogenesis of ARDS and highlights the potential of developing new therapeutic paradigms based on the selective inhibition (or activation) of specific PKC isoforms.

Nurse-Driven Quality Improvement Interventions to Reduce Hospital-Acquired Infection in the NICU

Hospital-acquired infections are a leading cause of morbidity and mortality in neonatal intensive care units. Central line-associated blood stream infection (CLABSI) and ventilator-associated pneumonia (VAP) are costly, preventable infections targeted for eradication by the Centers for Disease Control and Prevention. After evaluation of current practice and areas for improvement, neonatal-specific CLABSI and VAP bundles were developed and implemented on the basis of available best evidence. The overall goal was to reduce infection rates at or below benchmarks set by National Healthcare Safety Network. All neonates with central lines (umbilical or percutaneous) and/or patients who were endotracheally intubated were included. All patients were risk stratified on the basis of weight per National Healthcare Safety Network reporting requirements: less than 750 g, 751-1000 g, 1001-1500 g, 1501-2500 g, and greater than 2500 g. The research was conducted as a quality improvement study. Neonatal-specific educational modules were developed by neonatal nurse leaders for CLABSI and VAP. Bundle development entailed combining select interventions, mainly from the adult literature, that the nurse leaders believed would reduce infection rates. Nursing practice guidelines and supply carts were updated to ensure understanding, compliance, and convenience. A CLABSI checklist was initiated and used at the time of line insertion by the nurse to ensure standardized infection control practices. Compliance audits were performed by nurse leaders weekly on intubated patients to validate VAP bundle implementation. CLABSI and VAP bundle compliance was audited and infection rates were measured before and after both bundle implementations following strict National Healthcare Safety Network inclusion criteria for CLABSI and VAP determination. The reduction in CLABSI elicited 84 fewer hospital days, estimated cost savings of $348,000, a 92% reduction in CLABSI (preintervention to postintervention), and a reduction in central line days by 27%. The reduction in VAP resulted in 72 fewer hospital days, estimated cost savings of $300,000, 71% reduction in VAP (preintervention to postintervention), and a reduction in vent days by 31%. Nurses are central in hospital efforts to improve quality care. The bundled interventions provided the nurses with a structure to successfully implement a systematic process for improvement. Nursing leaders ensured that bundles were implemented strategically and provided consistent and specific feedback on intervention compliance with quarterly CLABSI and VAP rates. Real-time feedback assisted the registered nurses, neonatal nurse practitioners, and physicians appreciation of the effectiveness of the change in practice. Finally, empowering the bedside nurse to lead the bundle implementation increased personal ownership and compliance and ultimately improved practice and patient outcomes.

When a Bundle Is NOT Enough…The Value of Teamwork in Reducing Harm Associated with Ventilator Associated Pneumonia

According to the Centers for Disease Control, Ventilator-Associated Pneumonia (VAP) is a leading cause of morbidity and mortality in intensive care units. Both treatments and patient related-risk factors contribute to this condition. During 2011, our 25-bed intensive care unit (ICU) had 13 VAPS with 3487 days for a rate of 3.8/1000 vent days. VAP continued to be an issue despite nearly perfect bundle compliance. After defect analysis, identified contributing factors include the type of endotracheal tube and transportation of the patient out of the unit.

Bioenergetics, Mitochondrial Dysfunction, and Oxidative Stress in the Pathophysiology of Septic Encephalopathy

Sepsis is a major cause of mortality and morbidity in intensive care units. Acute and long-term brain dysfunctions have been demonstrated both in experimental models and septic patients. Sepsis-associated encephalopathy is an early and frequent manifestation but is underdiagnosed, because of the absence of specific biomarkers and of confounding factors such as sedatives used in the intensive care unit. Sepsis-associated encephalopathy may have acute and long-term consequences including development of autonomic dysfunction, delirium, and cognitive impairment. The mechanisms of sepsis-associated encephalopathy involve mitochondrial and vascular dysfunctions, oxidative stress, neurotransmission disturbances, inflammation, and cell death. Here we review specific evidence that links bioenergetics, mitochondrial dysfunction, and oxidative stress in the setting of brain dysfunctions associated to sepsis.

Treatment of Invasive Candida Infections in the Neonatal Intensive Care Unit

Invasive Candida infections are a leading cause of morbidity and mortality in the neonatal intensive care unit (NICU). Extremely preterm and very low birth weight infants are at the highest risk of infection. There are currently no antifungal agents that have FDA-labeling for the treatment of invasive candidiasis in the neonatal population. Based on the current IDSA guidelines, amphotericin and fluconazole are considered first-line options for neonatal candidiasis. The newer antifungal agents (i.e., echinocandins and voriconazole) are currently considered second-line or salvage therapy; however, evidence supporting their use is emerging. This review focuses on the supporting evidence for the selection of antifungal agents for treatment of invasive Candida infections in the NICU.

English

BACKGROUND: Hospital acquired bloodstream infections (BSI) are important cause of morbidity and mortality in Neonatal Intensive Care Unit (NICU) as well as of prolonged hospitalization and additional costs. AIM: The present study was performed to determine the incidence rate and incidence density of hospital acquired BSI in NICU along with their microbiological profile and sensitivity pattern. SETTINGS AND DESIGN: The study was conducted prospectively from 1 st May 2009 to 30 th June 2010, in the NICU at a tertiary care hospital in Gujarat. METHODS AND MATERIAL: Hospital acquired BSIs were identified according to National Nosocomial Infection Surveillance System (NNIS) definition. The incidence rate was calculated as BSIs per 100 admissions, and incidence density was calculated as BSIs per 1000 patient-days and 1000 central line-days. RESULTS: During the study period 626 neonates were admitted in NICU out of which 40 neonates were positive for hospital acquired BSI with incidence rate of 6.38 per 100 admissions and incidence density of 22.64 per 1000 patient-days. Central line-associated BSI (CLABSI) rate was 57.14 per 1000 central line- days. Klebsiella pneumoniae (67.5%) was the predominant isolate with all strains being ESBL producers. CONCLUSIONS: Hospital acquired BSIs in NICU was identified as a significant problem reflecting a need for strict implementation of preventive measures. Inadequate staffing has also been observed in the present study as a predisposing factor to the nosocomial BSIs. KEY-WORDS: Hospital acquired infections, Bloodstream Infections, Neonates, Intramural, Extramural, Central line. KEY MESSAGES: Surveillance data are crucial and should become an important component of hospital infection control program in NICU as it provides an overview of our infection control practices. INTRODUCTION: Patients treated in Neonatal Intensive Care Units (NICUs) are at highest risk for Hospital Acquired Infections (HAIs) 1 and bloodstream infections (BSIs) are most common in these settings. 2, 3 Surveillance of Hospital Acquired BSIs has proved to be an essential component in infection control and by determining the baseline HAI rates, changes in the rates can be detected and timely measures can be introduced thereby reducing HAI rates, mortality, morbidity and cost. 4 The purpose of this study was to determine the Hospital Acquired BSIs in

Nosocomial infection surveillance in an Egyptian neonatal intensive care unit

Nosocomial infections (NIs) have become a matter of major concern and an important cause of morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study was to determine the incidence, anatomical sites and causative organisms of NI in an Egyptian NICU, and to assess the impact of NI on length of stay and mortality. This was a descriptive hospital-based study carried out for 12 months in the NICU of the Mansoura University Children's Hospital. NI rates were calculated using different denominators (overall nosocomial infection rate, nosocomial infection incidence density, device-specific infection rates and device-days infection rates). Of the 238 neonates evaluated, 49 developed 51 nosocomial infective episodes, equating to an incidence rate of 21.4% or 13.8 infections per 1000 bed-days. Pneumonia was the most frequently occurring infection (11.3%) followed by bloodstream infection (8.8%). The most frequently isolated organisms were Klebsiella spp. (33.3%) followed by Escherichia coli (21.6%). NIs were associated with prolonged hospital stay. NI is a significant problem in the Mansoura University Children's Hospital NICU. Gram-negative bacteria, especially Klebsiella spp., were the predominant causes of neonatal NI, as has been described in other studies from developing countries.

Nosocomial infections in neonatal intensive care units in developed and developing countries: how can we narrow the gap?

Nosocomial infections are one of the leading causes of mortality and morbidity in neonatal intensive care units (NICUs). Both the incidence and causes of infections vary widely among NICUs. However, the incidence of infection is higher in developing countries, where Gram-negative bacteria are usually reported to be the predominant pathogens. The report by Abdel-Wahab et al. in this issue of the Journal of Hospital Infection exemplifies these facts, and, as the authors note, is consistent with previous reports from Egypt. Factors such as climate and cultural practices have been suggested as explanations for the differences in infections between developing and developed countries. However, there is evidence that the pattern of nosocomial infection is directly related to healthcare resources. Tosson et al. reviewed twelve studies from eight Arabic countries including 2308 newborns with culture-proven sepsis and found that Gram-negative bacteria were the predominant pathogens in Libya, Egypt, Jordan, and Iraq (65e90% of all sepsis cases), whereas in

Endothelial NOS gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome

Respiratory Distress Syndrome (RDS) due to prematurity is one of the most important causes of morbidity and mortality in Neonatal Intensive Care Units. According to few studies in recent years, endothelial nitric oxide synthase (eNOS) gene polymorphisms are found to be partially responsible for liability to RDS. The purpose of this study was to determine the association between eNOS gene polymorphism and RDS in preterm neonates. The patient group consisted of 152 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 125 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. It was found that Glu/Glu, Glu/Asp, and Asp/Asp genotype frequencies of the eNOS gene polymorphism were 35.2%, 59.2%, and 5.6% of the control group, and 32.9%, 65.1%, and 2.0% of the patient group, respectively (P > 0.05). However, significant increases in Glu/Glu genotype and Glu allele frequencies were noted in the RDS groups when the preterm neonates were divided into two groups (24-30 weeks and 31-36 weeks) by gestational age. Additionally, Glu/Asp genotype and Asp allele were markedly less frequent among the RDS groups (P < 0.05). Asp allele frequency in boys and Glu allele frequency in girls were significantly high in RDS group (P < 0.05). These data suggest that there were significant gestational age-related differences between RDS and control groups in terms of Glu298Asp polymorphism. Therefore, RDS seems to develop with alterations in eNOS Glu298Asp genotype frequencies in the Turkish population.

The Turn Team: A Novel Strategy for Reducing Pressure Ulcers in the Surgical Intensive Care Unit

Pressure ulcers cause significant morbidity and mortality in the surgical intensive care unit (SICU). The purpose of this study was to determine if a dedicated team tasked with turning and repositioning all hemodynamically stable SICU patients could decrease the formation of pressure ulcers. A total of 507 patients in a 20-bed SICU in a university hospital were assessed for pressure ulcers using a point prevalence strategy, between December 2008 and September 2010, before and after implementation of a team tasked with turning and repositioning all hemodynamically stable patients every 2 hours around the clock. At baseline, when frequent turning was encouraged but not required, a total of 42 pressure ulcers were identified in 278 patients. After implementation of the turn team, a total of 12 pressure ulcers were identified in 229 patients (p < 0.0001). The preintervention group included 34 stage I and II ulcers and 8 higher stage ulcers. After implementation of the turn team, there were 7 stage I and II ulcers and 5 higher stage ulcers. The average Braden score was 16.5 in the preintervention group and 13.4 in the postintervention group (p = 0.04), suggesting that pressure ulcers were occurring in higher risk patients after implementation of the turn team. A team dedicated to turning SICU patients every 2 hours dramatically decreased the incidence of pressure ulcers. The majority of stage I and stage II ulcers appear to be preventable with an aggressive intervention aimed at pressure ulcer prevention.

Catheter related blood stream infections in the paediatric intensive care unit: A descriptive study

Context:Catheter related blood stream infections (CRBSI) contributes significantly to morbidity, mortality and costs in intensive care unit (ICU). The patient profile, infrastructure and resources in ICU are different in the developing world as compared to western countries. Studies regarding CRBSI from pediatric intensive care unit (PICU) are scanty in the Indian literature.Aims:To determine the frequency and risk factors of CRBSI in children admitted to PICU.Settings and Design:Descriptive study done in the PICU of a tertiary care teaching hospital over a period of four months.Materials and Methods:Study children were followed up from the time of catheterization till discharge. Their clinical and treatment details were recorded and blood culture was done every 72 h, starting at 48 h after catheterization. The adherence of doctors to Centre for Disease Control (CDC) guidelines for catheter insertion was assessed using a checklist.Statistical Analysis:Clinical parameters were compared between colonized and non-colonized subjects and between patients with and without CRBSI. Unpaired t-test and Chi-square test were used to test the significance of observed differences.Results:Out of the 41 children, 21 developed colonization of their central venous catheter (66.24/1000 catheter days), and two developed CRBSI (6.3/1000 catheter days). Infants had a higher risk for developing colonization (P = 0.01). There was 85% adherence to CDC guidelines for catheter insertion.Conclusions:The incidence of CRBSI and catheter colonization is high in our in spite of good catheter insertion practices. Hence further studies to establish the role of adherence to catheter maintenance practices in reducing risk of CRBSI is required. The role of a composite package of interventions including insertion and maintenance bundles specifically targeting infants needs to be studied to bring down the catheter colonization as well as CRBSI rates.

Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units (ICUs). In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution (Vd) and clearance (CL) of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs (increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis), therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations.

Impact of early enteral nutrition therapy on morbimortality reduction in a Pediatric Intensive Care Unit: A systematic review

ObjectiveTo assess the impact of early introduction of enteral nutrition therapy on morbidity and mortality reduction in a pediatric intensive care unit. MethodsA search was performed in the literature of the last 10 years in English, with the target population of individuals aged 1 month to 18 years admitted to pediatric intensive care units in the PubMed, Lilacs and Embase databases using the keywords: Critical Care, Nutritional Support and Nutrition Disorders or Malnutrition. ResultsDespite advances in the quality of clinical care, the prevalence of malnutrition in hospitalized children remains unchanged in the last 20 years (15-30%) and has implications for the time of admission, course of illness and morbidity. Malnutrition is common and is often poorly recognized and therefore, untreated. Nutritional therapy is an essential part in the treatment of severely ill pediatric patients who have hypercatabolic protein state, which can be minimized with an effective nutritional treatment plan. In this study, we reviewed publications which have shown that there is still a paucity of randomized and controlled studies with good statistical treatment in relation to enteral nutritional therapy with outcomes related to morbidity and mortality. The current guidelines for nutritional therapy in these patients are largely based on expert opinion and data extrapolated from adult studies and studies in healthy children. ConclusionThe scientific evidence on the use of enteral nutrition therapy in improving the development of critically ill pediatric patients is still scarce and further studies are needed focusing on it, and better guidelines must be formulated.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [3H]glucose and 2-deoxy[14C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Bedside peritoneal drainage:A primary treatment for perforated necrotizing enterocolitis

Background and purpose: Necrotizing enterocolitis is one of the leading causes of morbidity and mortality in neonatal intensive care units particularly in places without neonatal surgical facilities. The best treatment for perforated necrotizing enterocolitis is uncertain. Bedside peritoneal drainage has been used as primary treatment in the management of perforated necrotizing enterocolitis. This study aimed to compare outcomes of bedside peritoneal drainage done by general surgeons as a primary procedure for the treatment of preterm and/or low birth weight neonates with perforated necrotizing enterocolitis to outcomes of early laparotomy performed by pediatric surgeons as regards effectiveness of the procedure as a definitive treatment, the need for delayed laparotomy and mortality rate. Patients and methods: Fifty cases of preterm and/or low birth weight neonates with perforated necrotizing enterocolitis were randomly assigned to one of two groups. Group I was managed by bedside peritoneal drainage done by general surgeon while laparotomy was reserved for non responding cases. Group II was managed by early laparotomy done by pediatric surgeon. Data collected from all cases included birth weight (g), gestational age (weeks), gender, age at operation (bedside peritoneal drainage or early laparotomy). Delayed laparotomy was performed for infants who developed persistent fecal.fistula or suffered late intestinal stricture as well as for closure of enterostomy. Outcomes of bedside peritoneal drainage and early laparotomy were recorded and statistically compared regarding the effectiveness of procedure as a definitive treatment, need for delayed laparotomy and mortality. Results: 16 cases (64%) showed clinical improvement after bedside peritoneal drainage. Bedside peritoneal drainage in Group I and early laparotomy in Group II were effective as a definitive treatment in 10 cases (40%) and 15 cases (60%) respectively. Delayed laparotomy was indicated in 7 cases(28%) in Group I and 8 cases (32%) in Group II.Mortality was recorded in 8 patients (32%) in BPD group and in 9 patients (36%) in laparotomy group. Conclusion: According to this study, outcomes of bedside peritoneal drainage as a primary treatment for low birth weight and/or preterm neonates with perforated necrotizing enterocolitis showed no significant statistical difference as regards the need for delayed laparotomy and mortality rate when compared to the outcomes of early laparotomy as a primary treatment for the same conditions. Bedside peritoneal drainage provides a useful primary procedure for the management of preterm and low birth weight neonates with perforated necrotizing enterocolitis particularly in healthcare facilities without neonatal surgery capacity.

1335 Efficacy of Prophylactic Fluconazole in Reducing Candidemia in High Risk NICU And PICU Patients

BackgroundCandidal infection is a common cause of morbidity and mortality in neonatal intensive care unit (NICU) and pediatric intensive care unit(PICU) pateints, especially those with risk factors.ObjectivesTo determine the prevalence...

1163 Epidemiology of Proven Nosocomial Sepsis in Low Birth Weight Infants Admitted in the Level 3 Neonatal Intensive Care Unit

BackgroundNosocomial infections remains a leading cause of morbidity and mortality in Neonatal Intensive Care Unit(NICU).AimTo assess incidence, etiology and outcome of culture-proven nosocomial sepsis in low birth weight(LBW) infants.MethodsRetrospective study...

‘Matching Michigan’: a 2-year stepped interventional programme to minimise central venous catheter-blood stream infections in intensive care units in England

BackgroundBloodstream infections from central venous catheters (CVC-BSIs) increase morbidity and costs in intensive care units (ICUs). Substantial reductions in CVC-BSI rates have been reported using a combination of technical and...

Improving body antioxidant capacity with antioxidant therapies improves pulmonary outcome in COPD patients

Background Chronic obstructive pulmonary disease (COPD) is one of the important causes of morbidity and mortality in the intensive care unit (ICU). Many studies have proven that free radicals cause damage to the pulmonary system. Antioxidants are compounds that can stop free radical-induced oxidative damage. There are two important types of antioxidants with different modes of action: enzymatic and nonenzymatic. Methods Our study was carried out on 60 COPD patients admitted to the ICU for respiratory causes. Patients were divided into three groups of 20 each. Group I (control group) received no antioxidant supplementation, group II received nonenzymatic antioxidant in the form of vitamins A, E, and C, group III received in addition to vitamins A, E, and C, enzymatic antioxidants in the form of selenium and zinc. Antioxidant treatment was administered for 30 days from the day of admission to the ICU. Acute physiology and chronic health evaluation II score was measured on the day of admission and after 7 days; total antioxidant capacity (TAC) was also measured on admission and on the seventh day; in addition, incidence and time of mechanical ventilation, time spent in the ICU as well as time until discharge, and, finally, mortality incidence during a 30-day period were all recorded and statistically analyzed. Results TAC level increased in both groups of antioxidant supplementation after 7 days of supplementation. In addition, there were decreases in the time spent by the patients on mechanical ventilation as well as the time of ICU stay and hospital stay. There was no statistical change in the incidence of mechanical ventilation, mortality rate, or acute physiology and chronic health evaluation score after 7 days of antioxidant supplementation. Conclusion We found from our study that supplementing COPD patients in the ICU with antioxidants, either nonenzymatic (vitamins A, E, and C) or a combination of nonenzymatic and enzymatic (selenium and zinc), led to an increase in the TAC level and an improvement in the clinical condition, evidenced by a decrease in the time spent on mechanical ventilation and in the ICU, with faster discharge from the hospital but with no effect on the incidence of mechanical ventilation or the mortality rate.

Effect of Tight Glucose Control with Insulin on the Thyroid Axis of Critically Ill Children and Its Relation with Outcome

Tight glucose control (TGC) to normal-for-age fasting blood glucose levels reduced morbidity and mortality in surgical adult and pediatric intensive care unit (ICU) patients. In adults, TGC did not affect the illness-induced alterations in thyroid hormones. With better feeding in children than in adult patients, we hypothesized that TGC in pediatric ICU patients reactivates the thyroid axis. The aim of this study was to assess the impact of TGC on the thyroid axis in pediatric ICU patients and to investigate how these changes affect the TGC outcome benefit. We conducted a preplanned analysis of all patients not treated with thyroid hormone, dopamine, or corticosteroids who were included in a randomized controlled trial on TGC (n=700). Serum TSH, T4, T3, and rT3 were measured upon admission and on ICU day 3 or the last ICU day for patients discharged earlier. Changes from baseline were compared for the TGC and usual care groups. The impact on the outcome benefit of TGC was assessed with multivariable Cox proportional hazard analysis, correcting for baseline risk factors. TGC further lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were unaltered. With TGC, the likelihood of earlier live discharge from the ICU was 19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010-1.407; P=0.03). This benefit was statistically explained by the further reduction of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a lower likelihood for earlier live discharge (hazard ratio per unit increase, 0.863; 95% confidence interval, 0.806-0.927; P<0.0001). TGC further accentuated the peripheral inactivation of thyroid hormone. This effect, mimicking a fasting response, statistically explained part of the clinical outcome benefit of TGC.