Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.

Importance: Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS). Objective: To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS. Design, Setting, and Participants: The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018. Interventions: Patients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours. Main Outcomes and Measures: The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours. Results: Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 µg/mL; difference, 7.94 µg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours. Conclusions and Relevance: In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT02106975.

An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests.

BACKGROUND: Interventions that lead to earlier liberation from mechanical ventilation can improve patient outcomes. This guideline, a collaborative effort between the American Thoracic Society and the American College of Chest Physicians, provides evidence-based recommendations to optimize liberation from mechanical ventilation in critically ill adults. METHODS: Two methodologists performed evidence syntheses to summarize available evidence relevant to key questions about liberation from mechanical ventilation. The methodologists appraised the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach and summarized the results in evidence profiles. The guideline panel then formulated recommendations after considering the balance of desirable consequences (benefits) versus undesirable consequences (burdens, adverse effects, and costs), the certainty in the evidence, and the feasibility and acceptability of various interventions. Recommendations were rated as strong or conditional. RESULTS: The guideline panel made four conditional recommendations related to rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. The recommendations were for acutely hospitalized adults mechanically ventilated for more than 24 hours to receive protocolized rehabilitation directed toward early mobilization, be managed with a ventilator liberation protocol, be assessed with a cuff leak test if they meet extubation criteria but are deemed high risk for postextubation stridor, and be administered systemic steroids for at least 4 hours before extubation if they fail the cuff leak test. CONCLUSIONS: The American Thoracic Society/American College of Chest Physicians recommendations are intended to support healthcare professionals in their decisions related to liberating critically ill adults from mechanical ventilation.

Official Executive Summary of an American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults.

BACKGROUND: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians. METHODS: A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention. RESULTS: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified after full-panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. CONCLUSIONS: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.

Rosuvastatin for sepsis-associated acute respiratory distress syndrome.

BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

Optimizing Respiratory Therapy Resources by De-Implementing Low-Value Care.

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs.

Biological Effects of Intravenous Vitamin C on Neutrophil Extracellular Traps and the Endothelial Glycocalyx in Patients with Sepsis-Induced ARDS.

(1) Background: The disease-modifying mechanisms of high-dose intravenous vitamin C (HDIVC) in sepsis induced acute respiratory distress syndrome (ARDS) is unclear. (2) Methods: We performed a post hoc study of plasma biomarkers from subjects enrolled in the randomized placebo-controlled trial CITRIS-ALI. We explored the effects of HDIVC on cell-free DNA (cfDNA) and syndecan-1, surrogates for neutrophil extracellular trap (NET) formation and degradation of the endothelial glycocalyx, respectively. (3) Results: In 167 study subjects, baseline cfDNA levels in HDIVC (84 subjects) and placebo (83 subjects) were 2.18 ng/µL (SD 4.20 ng/µL) and 2.65 ng/µL (SD 3.87 ng/µL), respectively, p = 0.45. At 48-h, the cfDNA reduction was 1.02 ng/µL greater in HDIVC than placebo, p = 0.05. Mean baseline syndecan-1 levels in HDIVC and placebo were 9.49 ng/mL (SD 5.57 ng/mL) and 10.83 ng/mL (SD 5.95 ng/mL), respectively, p = 0.14. At 48 h, placebo subjects exhibited a 1.53 ng/mL (95% CI, 0.96 to 2.11) increase in syndecan-1 vs. 0.75 ng/mL (95% CI, 0.21 to 1.29, p = 0.05), in HDIVC subjects. (4) Conclusions: HDIVC infusion attenuated cell-free DNA and syndecan-1, biomarkers associated with sepsis-induced ARDS. Improvement of these biomarkers suggests amelioration of NETosis and shedding of the vascular endothelial glycocalyx, respectively.

Acute kidney injury in patients with acute lung injury: impact of fluid accumulation on classification of acute kidney injury and associated outcomes.

OBJECTIVE: It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality. DESIGN: Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter. SETTING: Acute Respiratory Distress Syndrome Network hospitals. PATIENTS: One thousand patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The incidence of acute kidney injury, defined as an absolute rise in creatinine of ≥0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18). CONCLUSIONS: Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

Decrease in Positivity Rate of Influenza Tests Coinciding With Outbreak of SARS-CoV-2: Data From a Southeastern Wisconsin Laboratory.

BACKGROUND: The SARS-CoV-2 outbreak prompted public health interventions and changes in public behavior that may have affected the 2019-2020 influenza season. METHODS: Using data from a laboratory in southeastern Wisconsin, we compared the number of weekly influenza tests and their positivity rates during the 2019-2020 influenza season with the previous 4 seasons. RESULTS: The number of influenza tests per week at the outset of the SARS-CoV-2 outbreak was higher than the average the previous 4 years, and positivity rates declined to 0% earlier than any of the previous 4 seasons. CONCLUSION: The testing trajectory and positivity rate for influenza differed during the part of the 2019-2020 season coinciding with the SARS-CoV-2 outbreak as compared to similar periods during the previous 4 seasons.

A double-blind placebo-controlled study to evaluate the safety and efficacy of L-2-oxothiazolidine-4-carboxylic acid in the treatment of patients with acute respiratory distress syndrome.

OBJECTIVE: Acute respiratory distress syndrome is an abrupt inflammatory illness that involves damage from reactive oxygen species. We examined the efficacy and safety of oxothiazolidine-4-carboxylic acid (OTZ), a free radical scavenger, in treating acute respiratory distress syndrome. DESIGN: Double-blind, placebo-controlled trial. SETTING: Multicentered study. PATIENTS: Patients with a PaO2/FiO2 < or = 200 and bilateral infiltrates on chest radiograph, and requiring mechanical ventilation. INTERVENTIONS: We randomized 215 patients to receive OTZ, 210 mg/kg per day every 8 hrs for 14 days or placebo. MEASUREMENTS AND MAIN RESULTS: Ventilator-free days (the number of days alive and free from ventilator requirement) during the first 30 days of study were 8.3 vs. 13.5 days for the OTZ and placebo groups, respectively (p < .001). Mortality was 30/101 (29.7%) in the OTZ group and 18/114 (15.8%) in the placebo group during the 30-day study period (p = .014). This study was terminated prematurely for safety reasons after 215 of the planned 352 patients were enrolled. CONCLUSIONS: OTZ does not improve survival or reduce ventilator time in patients with acute respiratory distress syndrome and may worsen outcome, although mortality in the OTZ group was similar or lower than most similar trials. Alternatively, our results may be best explained by the unusually excellent outcome in the placebo group.

A replicable method for blood glucose control in critically Ill patients.

CONTEXT: To ensure interpretability and replicability of clinical experiments, methods must be adequately explicit and should elicit the same decision from different clinicians who comply with the study protocol. OBJECTIVE: The objective of this study was to determine whether clinician compliance with protocol recommendations exceeds 90%. DESIGN: We developed an adequately explicit computerized protocol (eProtocol-insulin) for managing critically ill adult patient blood glucose. We monitored clinician compliance with eProtocol-insulin recommendations in four intensive care units in four hospitals and compared blood glucose distributions with those of a simple clinical guideline at one hospital and a paper-based protocol at another. All protocols and the guideline used intravenous insulin and 80 to 110 mg/dL (4.4-6.1 mmol/L) blood glucose targets. SETTING: The setting for this study was four academic hospital intensive care units. PATIENTS: This study included critically ill adults requiring intravenous insulin. INTERVENTION: Intervention used in this study was a bedside computerized protocol for managing blood glucose. MAIN OUTCOME MEASURE: The main outcome measure was clinician compliance with eProtocol-insulin recommendations. RESULTS: The number of patients was 31 to 458 and the number of blood glucose measurements was 2,226 to 19,925 among the four intensive care units. Clinician compliance with eProtocol-insulin recommendations was 91% to 98%. Blood glucose distributions were similar in the four hospitals (generalized linear model p = .18). Compared with the simple guideline, eProtocol-insulin glucose measurements within target increased from 21% to 39%, and mean blood glucose decreased from 142 to 115 mg/dL (generalized linear model p < .001). Compared with the paper-based protocol, eProtocol-insulin glucose measurements within target increased from 28% to 42%, and mean blood glucose decreased from 134 to 116 mg/dL (generalized linear model p = .001). CONCLUSIONS: The 91% to 98% clinician compliance indicates eProtocol-insulin is an exportable instrument that can establish a replicable experimental method for clinical trials of blood glucose management in critically ill adults. Control of blood glucose was better with eProtocol-insulin than with a simple clinical guideline or a paper-based protocol.

Outbreak of resistant Pseudomonas aeruginosa infections during a quarterly cycling antibiotic regimen.

BACKGROUND: Antibiotic cycling or rotation of antimicrobial agent classes has been proposed to combat antimicrobial resistance. METHODS: A prospective cohort study was conducted in a medical intensive care unit (ICU) of a university hospital between December 1, 2000, and September 30, 2002, as part of a three-center trial under the aegis of the U.S. Centers for Disease Control and Prevention. Patients admitted to the medical ICU for > 48 h were enrolled, and demographic and microbiological data were collected until discharge or death. Baseline data were collected for four months (12/1/00 to 3/31/01) and compared with data collected after institution of a quarterly cycling regimen (cycle order: Cefepime, ciprofloxacin, piperacillin-tazobactam, imipenem-cilastatin) for the empiric treatment of gram-negative infections (4/01/01 to 9/30/02). RESULTS: Of 1,074 consecutive admissions, 301 were enrolled, 59 during baseline and 242 during the cycling periods. An outbreak of multi-drug resistant Pseudomonas aeruginosa followed cycle 2 (cefepime), coinciding with cycles 3 and 4 (ciprofloxacin and piperacillin-tazobactam) (80.0 and 73.7 vs. 37.3 isolates/100 patients enrolled for cycles 3/4 and baseline, respectively; p = 0.04). Acinetobacter spp. were isolated less frequently during the cycling periods (15.3 vs. 1.2 isolates/100 patients for baseline and cycling periods, respectively; p > or = 0.01). The crude hospital mortality rate was similar (24/59 [41%] baseline vs. 73/242 [30%] cycling; p = 0.16) between periods. However, the percentage of patients admitted to the medical ICU who subsequently acquired an infection followed by in-hospital death was higher at baseline than during cycling: 15/59 (25.4%) vs. 33/242 (13.6%)(p = 0.04). CONCLUSIONS: In this study, the cycling strategy was not definitively associated with beneficial changes in unit epidemiology and in fact may have contributed to an outbreak of multi-drug resistant P. aeruginosa.

The purpose, composition, and function of an institutional review board: balancing priorities.

The institutional review board (IRB) is one part of the research enterprise designated to protect human subjects. At times the IRB can feel like an oppressive oversight body bound by regulations and designed to inhibit research. However, in reality the IRB was an attempt by the federal government to streamline a variety of processes to ensure the protection of human subjects. Growing out of a history of unethical scientific research, the principle goal of the IRB is to protect human subjects. At some institutions the IRB has an additional role, to take a second look at proposed scientific methods to ensure the highest quality research. The legal basis, purpose, composition, and function of an IRB, and potential challenges in human-subjects research are reviewed here.

Recent advances in understanding and treating acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a clinically and biologically heterogeneous disorder associated with many disease processes that injure the lung, culminating in increased non-hydrostatic extravascular lung water, reduced compliance, and severe hypoxemia. Despite enhanced understanding of molecular mechanisms, advances in ventilatory strategies, and general care of the critically ill patient, mortality remains unacceptably high. The Berlin definition of ARDS has now replaced the American-European Consensus Conference definition. The recently concluded Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) provided worldwide epidemiological data of ARDS including prevalence, geographic variability, mortality, and patterns of mechanical ventilation use. Failure of clinical therapeutic trials prompted the investigation and subsequent discovery of two distinct phenotypes of ARDS (hyper-inflammatory and hypo-inflammatory) that have different biomarker profiles and clinical courses and respond differently to the random application of positive end expiratory pressure (PEEP) and fluid management strategies. Low tidal volume ventilation remains the predominant mainstay of the ventilatory strategy in ARDS. High-frequency oscillatory ventilation, application of recruitment maneuvers, higher PEEP, extracorporeal membrane oxygenation, and alternate modes of mechanical ventilation have failed to show benefit. Similarly, most pharmacological therapies including keratinocyte growth factor, beta-2 agonists, and aspirin did not improve outcomes. Prone positioning and early neuromuscular blockade have demonstrated mortality benefit, and clinical guidelines now recommend their use. Current ongoing trials include the use of mesenchymal stem cells, vitamin C, re-evaluation of neuromuscular blockade, and extracorporeal carbon dioxide removal. In this article, we describe advances in the diagnosis, epidemiology, and treatment of ARDS over the past decade.

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

BACKGROUND: Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). OBJECTIVE: To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. DESIGN: Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. SETTING: 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. PATIENTS: 644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. MEASUREMENTS: Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. METHODS: We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. RESULTS: Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). LIMITATIONS: Sample size, lack of urine output data, and prehospitalization baseline creatinine. CONCLUSION: Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI.

CONTEXTE: L'insuffisance rénale aiguë (IRA) survient fréquemment chez les patients atteints d'une septicémie et du syndrome de détresse respiratoire aiguë (SDRA). OBJECTIF DE L'ÉTUDE: Déterminer si un traitement aux statines offre une protection contre l'IRA chez les patients atteints d'un SDRA associé à une septicémie. TYPE D'ÉTUDE: Il s'agit d'une analyse secondaire des données de l'étude SAILS (Statins for Acutely Injured Lungs in Sepsis), un essai contrôlé à répartition aléatoire qui se penchait sur l'effet d'un traitement à la rosuvastatine sur le taux de mortalité des patients atteints d'un SDRA associé à une septicémie. CADRE DE L'ÉTUDE: Les données proviennent de 44 centres hospitaliers du réseau National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. PATIENTS: Les 644 participants à l'essai SAILS (sur un total de 745) non dialysés à vie et pour qui on disposait de valeurs initiales de créatinine sérique. MESURES: La principale mesure observée était une atteinte d'IRA, définie selon les critères liés aux valeurs de la créatinine avancées par la fondation Kidney Disease : Improving Global Outcomes. Le facteur prédictif essentiel était la répartition aléatoire des sujets (traitement à la rosuvastatine ou par placébo). Les caractéristiques sociodémographiques des patients, l'étiologie du SDRA et la gravité de l'atteinte constituaient les covariables additionnelles colligées. MÉTHODOLOGIE: La survenue d'une IRA a été analysée par régression logistique multivariée chez deux sous-groupes : 511 patients qui ne présentaient initialement aucun signe clinique d'IRA et 93 patients initialement atteints d'IRA de stade 1. RÉSULTATS: Chez les sujets non atteints d'IRA au moment de la répartition, le traitement à la rosuvastatine n'a eu aucun effet sur le risque de survenue d'IRA (rapport de cotes corrigé : 0,99; IC 95 % : 0,67-1,44). Chez les sujets initialement atteints d'IRA de stade 1, le traitement à la rosuvastatine a été associé à un risque plus élevé d'aggravation de l'atteinte existante (rapport de cotes corrigé : 3,06; IC 95 % : 1,14-8,22). Cependant, chez ces mêmes sujets, lorsque la créatinine sérique a été ajustée selon le bilan hydrique cumulatif, l'effet néfaste de la rosuvastatine n'a plus été observé (rapport de cotes corrigé : 1,85; IC 95 % : 0,70-4,84). LIMITES: La taille de l'échantillon ainsi que l'absence de certaines données (concernant notamment la créatinine préhospitalisation et la diurèse) limitent les constats de notre étude. CONCLUSION: Un traitement par rosuvastatine n'a eu aucun effet protecteur contre le développement ou l'aggravation d'une IRA chez des patients atteints du SDRA associé à une septicémie.

Operating room efficiency and hospital capacity: factors affecting operating room use during maximum hospital census.

BACKGROUND: Academic medical centers are faced with increasing volumes, higher acuity, and, as a consequence, capacity issues. These affect operating room (OR) use and patient throughput, with negative impact on finances and patient and physician satisfaction. We evaluated our experiences in dealing with OR efficiency at a time of maximum hospital capacity and occupancy. STUDY DESIGN: Using a multidisciplinary approach, we put in place seven agreed-upon strategies: daily communication, improved bed planning, discharge by noon program, internal staffing pool, special assignments for a patient transition unit, incentives, and stepped up environmental services. RESULTS: After institution of these strategies, we were able to realize a gain in OR patient volume of 8% and a decrease in OR holds of 37%. This resulted in a decrease in canceled OR cases from 4.3% to 3.1%. CONCLUSIONS: Academic medical centers face occupancy issues that are not likely to go away and will have an impact on OR volume and productivity. To improve the situation in a short-term fashion, a multidisciplinary approach involving several strategies will be needed.