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In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units. Visual Abstract. COVID-19–Related Critical Illness In a large health system in the United States, investigators examined whether mortality, receipt of mechanical ventilation, and patient acuity changed over time among adult patients with COVID-19–related critical illness admitted to intensive care units., Background: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. Objective: To describe the epidemiology of COVID-19–related critical illness, including trends in outcomes and care delivery. Design: Single–health system, multihospital retrospective cohort study. Setting: 5 hospitals within the University of Pennsylvania Health System. Patients: Adults with COVID-19–related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. Measurements: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. Results: Among 468 patients with COVID-19–related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. Limitation: Single–health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. Conclusion: Among patients with COVID-19–related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. Primary Funding Source: Agency for Healthcare Research and Quality.

Neuromuscular blockade (NMB) with cisatracurium may improve outcomes in the acute respiratory distress syndrome (ARDS) population; however, optimal dosing strategy remains unknown. Factors affecting pharmacokinetics and pharmacodynamics of cisatracurium may impact the dose required to achieve adequate train-of-four (TOF) response. The aims of this study were to determine cisatracurium dose requirements in a critically ill ARDS population and to identify clinical factors that affect dosing. This was a single-center, retrospective cohort study of medical intensive care patients who received cisatracurium infusion for treatment of ARDS. “Stable dose” was defined as the infusion rate producing 2 consecutive TOFs of 1/4 to 2/4. Factors examined for association with dose were temperature, pH, age, and the presence of acute kidney injury (AKI). The analysis included 39 patients. The median stable dose of cisatracurium was 2.8 (2.0, 3.1) μg/kg/min. Multivariable linear regression model for weight-normalized dose identified AKI as a factor independently associated with steady-state dose requirements (% change −31.4, 95% confidence interval [CI]: −51.9, −2.3). Our study provides information on cisatracurium doses required in patients with ARDS to reduce time required to reach goal TOF. Further studies are needed to determine effect of AKI on cisatracurium dose requirements and clinical outcomes.

OBJECTIVE: Assess clinician perceptions of a machine learning-based early warning system to predict severe sepsis and septic shock (EWS 2.0) DESIGN: Prospective observational study SETTING: Tertiary teaching hospital in Philadelphia, PA PATIENTS: Non-ICU admissions November-December 2016 INTERVENTIONS: During a six-week study period conducted five months after EWS 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert’s helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours post-alert. MEASUREMENTS AND MAIN RESULTS: For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the First Survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed a Second Survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient’s risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. CONCLUSIONS: In general, clinical perceptions of EWS 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning-based sepsis alerts.

Objectives:Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes.Design:Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation.Setting:Tertiary teaching hospital

BACKGROUND: Staffing strategies used to meet the needs of respiratory care departments during the COVID-19 pandemic included the deployment of respiratory therapist extenders. The purpose of this study was to evaluate respiratory therapist extenders’ comfort level with critical care ventilators while caring for patients with COVID-19. To our knowledge, this is the first study to evaluate the deployment of certified registered nurse anesthetists (CRNAs) in a critical care setting. METHODS: A qualitative survey method was used to assess CRNA experience with critical care ventilators. Prior to deployment in the ICU, CRNAs were trained by clinical lead respiratory therapists. Education included respiratory clinical practices and ventilator management. Sixty-minute sessions were held with demonstration stations set up in ICUs for hands-on experience. RESULTS: Fifty-six CRNAs responded to our survey (63%). A mean ± SD of 9.48 ± 12.27 h was spent training prior to deployment in the ICU. CRNAs were at the bedside a mean ± SD of 73.0 ± 40.6 h during the pandemic. While CRNA comfort level with critical care ventilators increased significantly (P < .001) from the beginning to the end of their work experience, no statistically significant differences were found between CRNA comfort based on years of experience. Differences in comfort level were not found after training (chi-squared test 23.82, P = .09) or after ICU experience was completed (chi-squared test = 15.99, P = .45). Similarly, mean comfort level did not increase based on the number of hours spent working in the ICU (chi-squared test = 13.67, P = .55). CONCLUSIONS: Comfort level with mechanical ventilation increased for CRNAs working alongside respiratory therapists during the COVID-19 pandemic.

Objectives Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. Design Cohort study. Setting The medical and surgical ICUs at an academic medical center. Subjects We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. Interventions We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. Measurements and main results Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). Conclusions Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Background: Acid-base disturbances are frequent in critically ill patients. Arterial blood gas (ABG) is the gold standard in the diagnosis of these disturbances, but it is invasive with potential hazards. For patients with a central venous catheter, venous blood gas (VBG) sampling may be an alternative, less-invasive diagnostic tool. However, the accuracy of a central VBG-based acid-base disorder diagnosis compared to an ABG is unknown. The primary objective of this study was to assess the accuracy of a central VBG-based acid-base disorder diagnosis compared to the “gold standard” ABG in critically ill patients. Methods: This was a study of adult patients in a medical intensive care unit that had simultaneously drawn ABG and central VBG samples. Expert acid-base diagnosticians, all nephrologists, diagnosed the acid-base disorder(s) in each blood gas sample. The central VBG diagnostic accuracy was assessed with percent agreement, sensitivity, and specificity compared to the ABG-based diagnosis. Results: The study involved 23 participants. Overall, the central VBG had 100% sensitivity for metabolic acidosis, metabolic alkalosis, and respiratory acidosis, and lower sensitivity (71%) for respiratory alkalosis, and high percent agreement, ranging from 75 to 94%. VBG-based diagnoses in vasopressor-dependent patients (n = 13, 56.5%) performed similarly to the entire sample. Conclusions: In critically ill adult patients, central VBG may be used to detect and diagnose acid-base disturbances with reasonable diagnostic accuracy, even in shock states, compared to the ABG. This study supports the use of central VBG for diagnosis of acid-base disturbances in critically ill patients.

OBJECTIVES:. Prior studies have demonstrated suboptimal adherence to lung protective ventilation among patients with acute respiratory distress syndrome. A common barrier to providing this evidence-based practice is diagnostic uncertainty. We sought to test the hypothesis that patients with acute respiratory distress syndrome due to coronavirus disease 2019, in whom acute respiratory distress syndrome is easily recognized, would be more likely to receive low tidal volume ventilation than concurrently admitted acute respiratory distress syndrome patients without coronavirus disease 2019. DESIGN:. Retrospective cohort study. SETTING:. Five hospitals of a single health system. PATIENTS:. Mechanically ventilated patients with coronavirus disease 2019 or noncoronavirus disease 2019 acute respiratory distress syndrome as identified by an automated, electronic acute respiratory distress syndrome finder in clinical use at study hospitals. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among 333 coronavirus disease 2019 patients and 234 noncoronavirus disease 2019 acute respiratory distress syndrome patients, the average initial tidal volume was 6.4 cc/kg predicted body weight and 6.8 cc/kg predicted body weight, respectively. Patients had tidal volumes less than or equal to 6.5 cc/kg predicted body weight for a mean of 70% of the first 72 hours of mechanical ventilation in the coronavirus disease 2019 cohort, compared with 52% in the noncoronavirus disease 2019 cohort (unadjusted p < 0.001). After adjusting for height, gender, admitting hospital, and whether or not the patient was admitted to a medical specialty ICU, coronavirus disease 2019 diagnosis was associated with a 21% higher percentage of time receiving tidal volumes less than or equal to 6.5 cc/kg predicted body weight within the first 72 hours of mechanical ventilation (95% CI, 14–28%; p < 0.001). CONCLUSIONS:. Adherence to low tidal volume ventilation during the first 72 hours of mechanical ventilation is higher in patients with coronavirus disease 2019 than with acute respiratory distress syndrome without coronavirus disease 2019. This population may present an opportunity to understand facilitators of implementation of this life-saving evidence-based practice.

Hospital readmission is common after sepsis, yet the relationship between the index admission and readmission remains poorly understood. We sought to examine the relationship between infection during the index acute care hospitalization and readmission and to identify potentially modifiable factors during the index sepsis hospitalization associated with readmission.In a retrospective cohort study, we evaluated 444 sepsis survivors at risk of an unplanned hospital readmission in 2012. The primary outcome was 30-day unplanned hospital readmission.Three hospitals within an academic healthcare system.Four hundred forty-four sepsis survivors.Of 444 sepsis survivors, 23.4% (95% CI, 19.6-27.6%) experienced an unplanned 30-day readmission compared with 10.1% (95% CI, 9.6-10.7%) among 11,364 nonsepsis survivors over the same time period. The most common cause for readmission after sepsis was infection (69.2%, 72 of 104). Among infection-related readmissions, 51.4% were categorized as recurrent/unresolved. Patients with sepsis present on their index admission who also developed a hospital-acquired infection ("second hit") were nearly twice as likely to have an unplanned 30-day readmission compared with those who presented with sepsis at admission and did not develop a hospital-acquired infection or those who presented without infection and then developed hospital-acquired sepsis (38.6% vs 22.2% vs 20.0%, p = 0.04). Infection-related hospital readmissions, specifically, were more likely in patients with a "second hit" and patients receiving a longer duration of antibiotics. The use of total parenteral nutrition (p = 0.03), longer duration of antibiotics (p = 0.047), prior hospitalizations, and lower discharge hemoglobin (p = 0.04) were independently associated with hospital readmission.We confirmed that the majority of unplanned hospital readmissions after sepsis are due to an infection. We found that patients with sepsis at admission who developed a hospital-acquired infection, and those who received a longer duration of antibiotics, appear to be high-risk groups for unplanned, all-cause 30-day readmissions and infection-related 30-day readmissions.

BACKGROUND: Delayed mechanical ventilation monitoring may impede recognition of life-threatening acidemia. Coordination of multidisciplinary processes can be improved by using a checklist and time-out procedure. The study objective was to evaluate process-related outcomes after implementation of a post-intubation checklist and time out. METHODS: An observational study of a 24-bed medical ICU in Philadelphia, Pennsylvania, was conducted from January to December 2011. A random sample of mechanically ventilated adults was selected from the pre-intervention ( n = 80) and post-intervention ( n = 144) periods. The primary outcome was the proportion of subjects with an arterial blood gas (ABG) result within 60 min of mechanical ventilation initiation. Secondary outcomes included rates of respiratory acidosis, moderate-severe acidemia (pH

Sepsis remains a diagnostic challenge in the intensive care unit (ICU), and the use of biomarkers may help in differentiating bacterial sepsis from other causes of systemic inflammatory syndrome (SIRS). The goal of this study was to assess test characteristics of a number of biomarkers for identifying ICU patients with a very low likelihood of bacterial sepsis. A prospective cohort study was conducted in a medical ICU of a university hospital. Immunocompetent patients with presumed bacterial sepsis were consecutively enrolled from January 2012 to May 2013. Concentrations of nine biomarkers (α-2 macroglobulin, C-reactive protein [CRP], ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) were determined at baseline and at 24 h, 48 h, and 72 h after enrollment. Performance characteristics were calculated for various combinations of biomarkers for discrimination of bacterial sepsis from other causes of SIRS. Seventy patients were included during the study period; 31 (44%) had bacterial sepsis, and 39 (56%) had other causes of SIRS. PCT and CRP values were significantly higher at all measured time points in patients with bacterial sepsis. A number of combinations of PCT and CRP, using various cutoff values and measurement time points, demonstrated high negative predictive values (81.1% to 85.7%) and specificities (63.2% to 79.5%) for diagnosing bacterial sepsis. Combinations of PCT and CRP demonstrated a high ability to discriminate bacterial sepsis from other causes of SIRS in medical ICU patients. Future studies should focus on the use of these algorithms to improve antibiotic use in the ICU setting.

We implemented an electronic early warning and response system (EWRS) to improve detection of and response to severe sepsis. Sustainability of such a system requires stakeholder acceptance. We hypothesized that clinicians receiving such alerts perceive them to be useful and effective.To survey clinicians after EWRS notification about perceptions of the system.For a 6-week study period 1 month after EWRS implementation in a large tertiary referral medical center, bedside clinicians, including providers (physicians, advanced practice providers) and registered nurses (RNs), were surveyed confidentially within 2 hours of an alert.For the 247 alerts that triggered, 127 providers (51%) and 105 RNs (43%) completed the survey. Clinicians perceived most patients as stable before and after the alert. Approximately half (39% providers, 48% RNs) felt the alert provided new information, and about half (44% providers, 56% RNs) reported changes in management as a result of the alert, including closer monitoring and additional interventions. Over half (54% providers, 65% RNs) felt the alert was appropriately timed. Approximately one-third found the alert helpful (33% providers, 40% RNs) and fewer felt it improved patient care (24% providers, 35% RNs).A minority of responders perceived the EWRS to be useful, likely related to the perception that most patients identified were stable. However, management was altered half the time after an alert. These results suggest further improvements to the system are needed to enhance clinician perception of the system's utility.

Rationale: The epidemiology of post–acute care use and hospital readmission after sepsis remains largely unknown.Objectives: To examine the rate of post–acute care use and hospital readmission after sepsis and to examine risk factors and outcomes for hospital readmissions after sepsis.Methods: In an observational cohort study conducted in an academic health care system (2010–2012), we compared post–acute care use at discharge and hospital readmission after 3,620 sepsis hospitalizations with 108,958 nonsepsis hospitalizations. We used three validated, claims-based approaches to identify sepsis and severe sepsis.Measurements and Main Results: Post–acute care use at discharge was more likely after sepsis, driven by skilled care facility placement (35.4% after sepsis vs. 15.8%; P

Septic shock is associated with increased long-term morbidity and mortality. However, little is known about the use of hospital-based acute care in survivors after hospital discharge. The objectives of the study were to examine the frequency, timing, causes, and risk factors associated with emergency department visits and hospital readmissions within 30 days of discharge.Retrospective cohort study.Tertiary, academic hospital in the United States.Patients admitted with septic shock (serum lactate≥4 mmol/L or refractory hypotension) and discharged alive to a nonhospice setting between 2007 and 2010.None.The coprimary outcomes were all-cause hospital readmission and emergency department visits (treat-and-release encounters) within 30 days to any of the three health system hospitals. Of 269 at-risk survivors, 63 (23.4%; 95% CI, 18.2-28.5) were readmitted within 30 days of discharge and another 12 (4.5%; 95% CI, 2.3-7.7) returned to the emergency department for a treat-and-release visit. Readmissions occurred within 15 days of discharge in 75% of cases and were more likely in oncology patients (p=0.001) and patients with a longer hospital length of stay (p=0.04). Readmissions were frequently due to another life-threatening condition and resulted in death or discharge to hospice in 16% of cases. The reasons for readmission were deemed potentially related to the index septic shock hospitalization in 78% (49 of 63) of cases. The most common cause was infection related, accounting for 46% of all 30-day readmissions, followed by cardiovascular or thromboembolic events (18%).The use of hospital-based acute care appeared to be common in septic shock survivors. Encounters often led to readmission within 15 days of discharge, were frequently due to another acute condition, and appeared to result in substantial morbidity and mortality. Given the potential public health implications of these findings, validation studies are needed.

BACKGROUND Early recognition and timely intervention significantly reduce sepsis-related mortality. OBJECTIVE Describe the development, implementation, and impact of an early warning and response system (EWRS) for sepsis. DESIGN After tool derivation and validation, a preimplementation/postimplementation study with multivariable adjustment measured impact. SETTING Urban academic healthcare system. PATIENTS Adult non-ICU patients admitted to acute inpatient units from October 1, 2011 to October 31, 2011 for tool derivation, June 6, 2012 to July 5, 2012 for tool validation, and June 6, 2012 to September 4, 2012 and June 6, 2013 to September 4, 2013 for the preimplementation/postimplementation analysis. INTERVENTION An EWRS in our electronic health record monitored laboratory values and vital signs in real time. If a patient had ≥4 predefined abnormalities at any single time, the provider, nurse, and rapid response coordinator were notified and performed an immediate bedside patient evaluation. MEASUREMENTS Screen positive rates, test characteristics, predictive values, and likelihood ratios; system utilization; and resulting changes in processes and outcomes. RESULTS The tool's screen positive, sensitivity, specificity, and positive and negative predictive values and likelihood ratios for our composite of intensive care unit (ICU) transfer, rapid response team call, or death in the derivation cohort was 6%, 16%, 97%, 26%, 94%, 5.3, and 0.9, respectively. Validation values were similar. The EWRS resulted in a statistically significant increase in early sepsis care, ICU transfer, and sepsis documentation, and decreased sepsis mortality and increased discharge to home, although neither of these latter 2 findings reached statistical significance. CONCLUSIONS An automated prediction tool identified at-risk patients and prompted a bedside evaluation resulting in more timely sepsis care, improved documentation, and a suggestion of reduced mortality. Journal of Hospital Medicine 2015;10:26–31. © 2014 Society of Hospital Medicine

Background: Acute kidney injury is common in hospitalized patients, increases morbidity and mortality, and is under-recognized. To improve provider recognition, we previously developed an electronic alert system for acute kidney injury. To test the hypothesis that this electronic acute kidney injury alert could improve patient outcome, we designed a randomized controlled trial to test the effectiveness of this alert in hospitalized patients. The study design presented several methodologic, ethical, and statistical challenges. Purpose: To highlight the challenges faced and the solutions employed in the design and implementation of a clinical trial to determine whether the provision of an early electronic alert for acute kidney injury would improve outcomes in hospitalized patients. Challenges included how to randomize the delivery of the alert system and the ethical framework for waiving informed consent. Other methodologic challenges included the selection and statistical evaluation of our study outcome, a ranked-composite of a continuous covariate (creatinine) and two dichotomous outcomes (dialysis and death), and the use of the medical record as a source of trial data. Methods: We have designed a randomized trial to assess the effectiveness of an electronic alert system for acute kidney injury. With broad inclusion criteria, and a waiver of informed consent, we enroll and randomize virtually every patient with acute kidney injury in our hospital. Results: As of 31 March 2014, we have enrolled 2373 patients of 2400 targeted. Pre-alert data demonstrated a strong association between severity of acute kidney injury and inpatient mortality with a range of 6.4% in those with mild, stage 1 acute kidney injury, to 29% among those with stage 3 acute kidney injury (p < 0.001). We judged that informed consent would undermine the scientific validity of the study and present harms that are out of proportion to the very low risk intervention. Conclusion: Our study demonstrates the feasibility of designing an ethical randomized controlled trial of an early electronic alert for acute kidney injury without obtaining informed consent from individual participants. Our study outcome may serve as a model for other studies of acute kidney injury, insofar as our paradigm accounts for the effect that early death and dialysis have on assessment of acute kidney injury severity as defined by maximum achieved serum creatinine.

Supplemental Digital Content is available in the text., Objectives: Sedation minimization and ventilator liberation protocols improve outcomes but are challenging to implement. We sought to demonstrate proof-of-concept and impact of an electronic application promoting sedation minimization and ventilator liberation. Design: Multi-ICU proof-of-concept study and a single ICU before-after study. Setting: University hospital ICUs. Patients: Adult patients receiving mechanical ventilation. Interventions: An automated application consisting of 1) a web-based dashboard with real-time data on spontaneous breathing trial readiness, sedation depth, sedative infusions, and nudges to wean sedation and ventilatory support and 2) text-message alerts once patients met criteria for a spontaneous breathing trial and spontaneous awakening trial. Pre-intervention, sedation minimization, and ventilator liberation were reviewed daily during a multidisciplinary huddle. Post-intervention, the dashboard was used during the multidisciplinary huddle, throughout the day by respiratory therapists, and text alerts were sent to bedside providers. Measurements and Main Results: We enrolled 115 subjects in the proof-of-concept study. Spontaneous breathing trial alerts were accurate (98.3%), usually sent while patients were receiving mandatory ventilation (88.5%), and 61.9% of patients received concurrent spontaneous awakening trial alerts. We enrolled 457 subjects in the before-after study, 221 pre-intervention and 236 post-intervention. After implementation, patients were 28% more likely to be extubated (hazard ratio, 1.28; 95% CI, 1.01–1.63; p = 0.042) and 31% more likely to be discharged from the ICU (hazard ratio, 1.31; 95% CI, 1.03–1.67; p = 0.027) at any time point. After implementation, the median duration of mechanical ventilation was 2.20 days (95% CI, 0.09–4.31 d; p = 0.042) shorter and the median ICU length of stay was 2.65 days (95% CI, 0.13–5.16 d; p = 0.040) shorter, compared with the expected durations without the application. Conclusions: Implementation of an electronic dashboard and alert system promoting sedation minimization and ventilator liberation was associated with reductions in the duration of mechanical ventilation and ICU length of stay.

BACKGROUND A multidisciplinary team, including critical care nurses?and specialists, critical care intensivist physicians and infection?preventionists developed and implemented a new care leadership model to direct the assessment of central venous catheters?and central line bloodstream infection (CLABSI) risk in a medical intensive care unit (MICU) within an academic quaternary care hospital. METHODS The MICU unit based clinical leadership (UBCL) introduced weekly multidisciplinary central line rounding that incorportated assessments at the bedside from physicians, nurses, advanced practice providers and infection preventionists. Each discipline assessed each patient's central access from his or her professional perspective. This new practice widened the scope of assessments to include proper insertion practices, choice of line location and discussions about line removal. Additionally, this allowed a forum for direct feedback and discussion at the bedside and provided an opportunity for caregivers to learn from these experts. Technology supported the function of this team by introducing the use of mobile devices and?sophisticated research software providing a communication and?auditing arena. REDCap was implemented to structure the information efficiently. This allowed data to be securely accessed and completed at the bedside using a mobile phone or IPad. The team also used photographs to track their progress. “Before” and “after” photos of problematic lines visually depicted their success, and also provided education to staff in the unit newsletter, Central Line Rewind. RESULTS The MICU compared its CLABSI performance over a five month period in 2017 to 2018 (7/1 to 11/30). In 2017, the MICU incurred six (6) CLABSIs. In 2018, it incurred three (3). CONCLUSIONS The MICU reduced the number of CLABSIs by 50%. A consistent, comprehensive, interdisciplinary approach to assessing the central lines has allowed the MICU to more effectively assess the central lines. In addition, implementing a technological solution has enabled real-time peer review, including results from effective interventions.

Introduction Therapeutic hypothermia (TH) has been shown to improve outcomes in comatose Post-Cardiac Arrest Syndrome (PCAS) patients. It is unclear how long it takes these patients to regain neurologic responsiveness post-arrest. We sought to determine the duration to post-arrest awakening and factors associated with times to such responsiveness. Methods We performed a retrospective chart review of consecutive TH-treated PCAS patients at three hospitals participating in a US cardiac arrest registry from 2005 to 2011. We measured the time from arrest until first documentation of "awakening", defined as following commands purposefully. Results We included 194 consecutive TH-treated PCAS patients; mean age was 57±16 years; 59% were male; 40% had an initial shockable rhythm. Mean cooling duration was 24±8h and mean rewarming time was 14±13h. Survival to discharge was 44%, with 78% of these discharged with a good neurologic outcome. Of the 85 patients who awakened, median time to awakening was 3.2 days (IQR 2.2, 4.5) post-cardiac arrest. Median time to awakening for a patient discharged in good neurological condition was 2.8 days (IQR 2.0, 4.5) vs. 4.0 days (IQR 3.5, 7.6) for those who survived to discharge without a good neurological outcome ( p =0.035). There was no significant association between initial rhythm, renal insufficiency, paralytic use, post-arrest seizure, or location of arrest and time to awakening. Conclusion In TH-treated PCAS patients, time to awakening after resuscitation was highly variable and often longer than three days. Earlier awakening was associated with better neurologic status at hospital discharge.

Aims: Modification of the mortality risk associated with acute kidney injury (AKI) necessitates recognition of AKI when it occurs. We sought to determine whether formal documentation of AKI in the medical record, assessed by billing codes for AKI, would be associated with improved clinical outcomes. Methods: Retrospective cohort study conducted at three hospitals within a single university health system. Adults without severe underlying kidney disease who suffered in-hospital AKI as defined by a doubling of baseline creatinine (n = 5,438) were included. Those whose AKI was formally documented according to discharge billing codes were compared to those without such documentation in terms of 30-day mortality. Results: Formal documentation of AKI occurred in 2,325 patients (43%). Higher baseline creatinine, higher peak creatinine, medical admission status, and higher Sequential Organ Failure Assessment (SOFA) score were strongly associated with documentation of AKI. After adjustment for severity of disease, formal AKI documentation was associated with reduced 30-day mortality – OR 0.81 (0.68 – 0.96, p = 0.02). Patients with formal documentation were more likely to receive a nephrology consultation (31% vs. 6%, p

Objectives:Formal guidelines recommend that therapeutic hypothermia be considered after in-hospital cardiac arrest. The rate of therapeutic hypothermia use after in-hospital cardiac arrest and details about its implementation are unknown. We aimed to determine the use of therapeutic hypothermia for

BACKGROUND Clinical documentation is critical to health care quality and cost. The generally poor quality of such documentation has been well recognized, yet medical students, residents, and physicians receive little or no training in it. When clinical documentation quality (CDQ) training for residents and/or physicians is provided, it excludes key constructs of self-efficacy: vicarious learning (e.g., peer demonstration) and mastery (i.e., practice). CDQ training that incorporates these key self-efficacy constructs is more resource intensive. If such training could be shown to be more effective at enhancing clinician performance, it would support the investment of the additional resources required by health care systems and residency training programs. PURPOSES The aim of this study was to test the impact of CDQ training on clinician self-efficacy and performance and the relative efficacy of intervention designs employing two versus all four self-efficacy constructs. METHODOLOGY/APPROACH Ninety-one internal medicine residents at a major academic medical center in the northeastern United States were assigned to one of two self-efficacy-based training groups or a control group, with CDQ and clinical documentation self-efficacy measured before and after the interventions. A structural equation model (AMOS) allowed for testing the six hypotheses in the context of the whole study, and findings were cross-validated using traditional regression. FINDINGS Although both interventions increased CDQ, the training designed to include all four self-efficacy constructs had a significantly greater impact on improving CDQ. It also increased self-efficacy. PRACTICE IMPLICATIONS CDQ may be significantly improved and sustained by (a) training physicians in clinical documentation and (b) employing all four self-efficacy constructs in such training designs.

SummaryPulmonary embolism (PE) is a major cause of morbidity and mortality world-wide, and the use of thrombolytic therapy has been associated with favourable clinical outcomes in certain patient subsets. These potential benefits are counterbalanced by the risk of bleeding complications, the most devastating of which is intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from the 2003–2012 nationwide in-patient sample database (NIS) who received thrombolytics for PE. All patients with ICH during the PE hospitalisation were identified and a clinical risk score model was developed utilizing demographics and comorbidities. The dataset was divided 1:1 into derivation and validation cohorts. During 2003–2012, 176/9705 (1.8 %) patients with PE experienced ICH after thrombolytic use. Four independent prognostic factors were identified in a backward logistic regression model, and each was assigned a number of points proportional to its regression coefficient: pre-existing Peripheral vascular disease (1 point), age greater than 65 years (Elderly) (1 point), prior Cerebrovascular accident with residual deficit (5 points), and prior myocardial infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2 and ≥ 5 points were associated with ICH risks of 1.2 %, 1.9 %, 2.4 % and 17.8 %, respectively. Rates of ICH were similar in the validation cohort. The C-statistic for the risk score was 0.65 (0.61–0.70) in the derivation cohort and 0.66 (0.60–0.72) in the validation cohort. A novel risk score, derived from simple clinical historical elements was developed to predict ICH in PE patients treated with thrombolytics.Supplementary Material to this article is available online at www.thrombosis-online.com.

Transitions to outpatient care are crucial after critical illness, but the documentation practices in discharge documents after critical illness are unknown.To characterize the rates of documentation of various features of critical illness in discharge documents of patients diagnosed with acute respiratory distress syndrome (ARDS) during their hospital stay.We used natural language processing tools to build a keyword-based classifier that categorizes discharge documents by presence of terms from four groups of keywords related to critical illness. We used a multivariable modified Poisson regression model to infer patient- and hospital-level characteristics associated with documentation of relevant keywords. A manual chart review was used to validate the accuracy of the keyword-based classifier, and to assess for ARDS documentation during the hospital stay.Of 815 discharge documents, ARDS was identified in only 111 (13%). Mechanical ventilation was identified in 770 (92%) and intensive care unit (ICU) admission in 693 (83%) of discharge documents. Symptoms or recommendations related to post-intensive care syndrome were included in 306 (38%) of discharge documents. Patient age (older; relative risk [RR] = 0.97/yr, 95% confidence interval [CI] = 0.96-0.98) and higher PaO2:FiO2 (decreasing illness severity; RR = 0.96/10-unit increment, 95% CI = 0.93-0.98) were associated with decreased documentation of ARDS. Being discharged from a surgical (RR = 0.33, 95% CI = 0.22-0.50) compared with a medicine service was also associated with decreased rates of ARDS documentation. The manual chart review revealed 98% concordance between ARDS documentation in the discharge summary and during the hospital stay. Accuracy of the document classifier was 100% for ARDS and mechanical ventilation, 98% for ICU admission, and 95% for symptoms of post-intensive care syndrome.In the discharge documents of survivors of ARDS, ARDS itself is rarely mentioned, but mechanical ventilation and ICU stay frequently are. The low rates of documentation of ARDS appear to be concordant with low rates of documentation during the hospital stay, consistent with known underrecognition in the ICU. Natural language processing tools can be used to effectively analyze large numbers of discharge documents of patients with critical illness.

Background Lower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation. LRTI also occurs during mechanical ventilation, increasing the morbidity and mortality of intubated patients. We sought to understand the dynamics of respiratory tract microbiota following intubation and the relationship between microbial community structure and infection. Results We enrolled a cohort of 15 subjects with respiratory failure requiring intubation and mechanical ventilation from the medical intensive care unit at an academic medical center. Oropharyngeal (OP) and deep endotracheal (ET) secretions were sampled within 24 h of intubation and every 48–72 h thereafter. Bacterial community profiling was carried out by purifying DNA, PCR amplification of 16S ribosomal RNA (rRNA) gene sequences, deep sequencing, and bioinformatic community analysis. We compared enrolled subjects to a cohort of healthy subjects who had lower respiratory tract sampling by bronchoscopy. In contrast to the diverse upper respiratory tract and lower respiratory tract microbiota found in healthy controls, critically ill subjects had lower initial diversity at both sites. Diversity further diminished over time on the ventilator. In several subjects, the bacterial community was dominated by a single taxon over multiple time points. The clinical diagnosis of LRTI ascertained by chart review correlated with low community diversity and dominance of a single taxon. Dominant taxa matched clinical bacterial cultures where cultures were obtained and positive. In several cases, dominant taxa included bacteria not detected by culture, including Ureaplasma parvum and Enterococcus faecalis. Conclusions Longitudinal analysis of respiratory tract microbiota in critically ill patients provides insight into the pathogenesis and diagnosis of LRTI. 16S rRNA gene sequencing of endotracheal aspirate samples holds promise for expanded pathogen identification. Electronic supplementary material The online version of this article (doi:10.1186/s40168-016-0151-8) contains supplementary material, which is available to authorized users.

Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-α is important in the pathogenesis of IPS and that the TNF-α inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n=22) or CS plus etanercept from 2004 to 2007 (group 2, n=17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P=0.039). OS was significantly better for recipients of CS plus etanercept (P=0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17-56%) and 9.1% (95% CI 2-25%) for group 1 and 88.2% (95% CI 61-97%) and 18% (95% CI 4-38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS.

Rationale: Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for ALI. Objectives: To identify ALI risk variants after major trauma using a large-scale candidate gene approach. Methods: We performed a two-stage genetic association study. We derived findings in an African American cohort (n 5 222) using a cardiopulmonary disease‐centric 50K single nucleotide polymorphism (SNP) array. Genotype and haplotype distributions were compared between subjects with ALI and without ALI, with adjustment for clinical factors. Top performing SNPs (P , 1024) were tested in a multicenter European American trauma-associated ALI case-control population (n 5 600 ALI; n 5 2,266 population-based control subjects) for replication. The ALI-associated genomic region was sequenced, analyzed for in silico prediction of function, and plasma was assayed by ELISA and immunoblot. MeasurementsandMainResults:FiveSNPsdemonstratedasignificant association with ALI after adjustment for covariates in Stage I. Two SNPs in ANGPT2 (rs1868554 and rs2442598) replicated their significant association with ALI in Stage II. rs1868554 was robust to multiple comparison correction: odds ratio 1.22 (1.06‐1.40), P 5 0.0047. Resequencing identified predicted novel splice sites in linkage disequilibrium with rs1868554, and immunoblots showed higher proportion of variant angiopoietin-2 (ANG2) isoform associated with rs1868554T (0.81 vs. 0.48; P 5 0.038). Conclusions :A nANGPT2 region is associated with both ALI and variation in plasma angiopoietin-2 isoforms. Characterization of

Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients.Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance.The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006).Intubated patients in medical and surgical intensive care units.None.Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method.An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse intensive care units of a large academic medical center. Further studies are needed to evaluate the effect of automated prompts that such a system can initiate on the use of lung protective ventilation in patients with acute lung injury.

Objective: While the use of therapeutic hypothermia (TH) has improved outcomes after resuscitation from cardiac arrest, prognostication of survival and neurologic function remains difficult during the post-arrest time period. Bispectral index (BIS) monitoring, a non-invasive measurement of simplified electroencephalographic data, is increasingly being considered for post-arrest neurologic assessment and outcomes prediction, although data supporting the technique are limited. We hypothesized that BIS values within 24 h after resuscitation would correlate with neurologic outcomes at discharge. Methods: We prospectively collected BIS data in consecutive patients initially resuscitated from cardiac arrest and treated with TH in one academic medical center. We assessed BIS values in context of cerebral performance category (CPC) assessment on the day of discharge. Results: Data were collected in 62 post-arrest patients, of whom 26/62 (42%) survived to hospital discharge. Mean BIS values at 24 h post-resuscitation were significantly different in the survivors with CPC 1–2 (“good” outcome) vs those with CPC 3–5 (“poor” outcome) or death during hospitalization (49 ± 13 vs 30 ± 20; p < 0.001). Receiver operator characteristic analysis suggested that 24 h BIS was most predictive of CPC 1–2 outcome compared to the other timepoints; a BIS cutpoint of 45 exhibited a sensitivity of 63% and a specificity of 86%, with a positive likelihood ratio of 4.67. Sixteen patients exhibited a BIS of zero during at least one timepoint; all of these patients died during hospitalization. Conclusions: BIS monitoring values at 24 h post-resuscitation are correlated with neurologic outcomes in patients undergoing TH treatment. In 16/62 patients, a BIS of zero at any timepoint was observed, which was uniformly correlated with poor outcome after resuscitation from cardiac arrest; however, a non-zero BIS is insufficient as a sole predictor of good neurologic survival.

To prospectively evaluate outcomes associated with use of a triple-lumen (TL) peripherally inserted central catheter (PICC) in the intensive care unit (ICU) setting.Patients were prospectively enrolled in this HIPAA-compliant, institutional review board-approved study. Informed consent was obtained. All patients were in one hospital's ICUs and needed intermediate-term central venous access requiring three lumina. A 6-F tapered TL PICC was placed by a bedside nursing-based team with backup from the Interventional Radiology department. Placement complications, as well as long-term complications, were recorded. At catheter removal, ultrasonography (US) of the veins containing the TL PICC was performed to detect occult venous thrombosis. Regardless of indication for removal, catheters were sent for culture to detect colonization.The study was stopped prematurely after 50 of a planned 167 patients were enrolled when a scheduled interim analysis detected a venous thrombosis rate that was considered unacceptably high by the study oversight committee (thrombosis was symptomatic in 20% of patients [10 of 50]). Venous thrombosis (symptomatic or asymptomatic) was detected in 26 of 45 patients (58%; 95% confidence interval [CI]: 43%, 72%) examined with US. Documented catheter-related bloodstream infection did not occur (0%; 95% CI: 0%, 7%); colonization was detected in three of 29 catheter tips sent for culture (10%; 95% CI: 2%, 27%). Catheter malfunction and dislodgment occurred in one patient each.The TL PICC design used in this study resulted in unacceptably high venous thrombosis rates. Even when used in a high-risk setting for infection (ie, the ICU), rates of clinically evident infection and colonization were absent and low, respectively.

To systematically evaluate the effect of extracorporeal membrane oxygenation on survival in adults with acute respiratory failure and to help inform institutional decisions about implementing an extracorporeal membrane oxygenation program or transferring patients to experienced extracorporeal membrane oxygenation centers during the H1N1 influenza pandemic.National Guideline Clearinghouse, MEDLINE, EMBASE, Agency for Healthcare Research and Quality Evidence-based Practice reports, National Institute for Health and Clinical Excellence, Cochrane Library, International Network of Agencies for Health Technology Assessment, and citation review.Studies of extracorporeal membrane oxygenation in adult acute respiratory failure, reporting mortality rates for at least 10 patients in extracorporeal membrane oxygenation and nonextracorporeal membrane oxygenation groups.Mortality rates were abstracted for all patients and for patients with influenza. Risk ratios were meta-analyzed using random-effects methods and assessed for heterogeneity.There are no evidence-based clinical guidelines on the use of extracorporeal membrane oxygenation in patients with influenza. Three randomized controlled trials and three cohort studies evaluated extracorporeal membrane oxygenation in patients with acute respiratory failure; none reported specifically on patients with influenza. Meta-analysis of the randomized controlled trials revealed significant heterogeneity in risk of mortality. The summary risk ratio found by the meta-analysis was 0.93 (95% confidence interval, 0.71 to 1.22). The most recent trial found a reduction in mortality and severe disability at 6 months among patients in whom extracorporeal membrane oxygenation was considered. Observational studies suggest that extracorporeal membrane oxygenation for acute respiratory failure resulting from viral pneumonia is associated with improved mortality compared with other etiologies of acute respiratory failure.The best evidence to guide decisions regarding the use of extracorporeal membrane oxygenation for patients with influenza stems from trials of extracorporeal membrane oxygenation for acute respiratory failure of all etiologies, among which significant heterogeneity exists, and from case series describing outcomes of extracorporeal membrane oxygenation in patients with influenza. Thus, there is insufficient evidence to provide a recommendation for extracorporeal membrane oxygenation use among patients with respiratory failure resulting from influenza. However, clinicians should consider extracorporeal membrane oxygenation within the context of other salvage therapies for acute respiratory failure.

Objective: The authors designed an automated electronic system that incorporates data from multiple hospital information systems to screen for acute lung injury (ALI) in mechanically ventilated patients. The authors evaluated the accuracy of this system in diagnosing ALI in a cohort of patients with major trauma, but excluding patients with congestive heart failure (CHF). Design: Single-center validation study. Arterial blood gas (ABG) data and chest radiograph (CXR) reports for a cohort of intensive care unit (ICU) patients with major trauma but excluding patients with CHF were screened prospectively for ALI requiring intubation by an automated electronic system. The system was compared to a reference standard established through consensus of two blinded physician reviewers who independently screened the same population for ALI using all available ABG data and CXR images. The system's performance was evaluated (1) by measuring the sensitivity and overall accuracy, and (2) by measuring concordance with respect to the date of ALI identification (vs. reference standard). Measurements: One hundred ninety-nine trauma patients admitted to our level 1 trauma center with an initial injury severity score (ISS) 16 were evaluated for development of ALI in the first five days in an ICU after trauma. Main Results: The system demonstrated 87% sensitivity (95% confidence interval (CI) 82.3-91.7) and 89% specificity (95% CI 84.7-93.4). It identified ALI before or within the 24-hour period during which ALI was identified by the two reviewers in 87% of cases. Conclusions: An automated electronic system that screens intubated ICU trauma patients, excluding patients with CHF, for ALI based on CXR reports and results of ABGs is sufficiently accurate to identify many early cases of ALI.

Serum lactate is a potentially useful biomarker to risk-stratify patients with severe sepsis; however, it is plausible that elevated serum lactate is simply a manifestation of clinically apparent organ dysfunction and/or shock (i.e., refractory hypotension).To test whether the association between initial serum lactate level and mortality in patients presenting to the emergency department (ED) with severe sepsis is independent of organ dysfunction and shock.Single-center cohort study. The primary outcome was 28-day mortality and the risk factor variable was initial venous lactate (mmol/L), categorized as low (2), intermediate (2-3.9), or high (or = 4). Potential covariates included age, sex, race, acute and chronic organ dysfunction, severity of illness, and initiation of early goal-directed therapy. Multivariable logistic regression analyses were stratified on the presence or absence of shock.The ED of an academic tertiary care center from 2005 to 2007.Eight hundred thirty adults admitted with severe sepsis in the ED.None.Mortality at 28 days was 22.9% and median serum lactate was 2.9 mmol/L. Intermediate (odds ratio [OR] = 2.05, p = 0.024) and high serum lactate levels (OR = 4.87, p0.001) were associated with mortality in the nonshock subgroup. In the shock subgroup, intermediate (OR = 3.27, p = 0.022) and high serum lactate levels (OR = 4.87, p = 0.001) were also associated with mortality. After adjusting for potential confounders, intermediate and high serum lactate levels remained significantly associated with mortality within shock and nonshock strata.Initial serum lactate was associated with mortality independent of clinically apparent organ dysfunction and shock in patients admitted to the ED with severe sepsis. Both intermediate and high serum lactate levels were independently associated with mortality.

Comatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors.We examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6h of emergency department (ED) presentation.In May, 2005 we began prospectively identifying comatose (Glasgow Motor Score6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution.Between May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 degrees C) was 2.8h (range 0.8-23.2; SD=h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p=0.15).In patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.

Survival after out-of-hospital cardiac arrest (OHCA) remains unacceptably low. Therapeutic hypothermia (TH) is the most efficacious treatment option available for comatose survivors of cardiac arrest. However, clearly delineated instructions for how to induce, maintain, and conclude TH have not been published in a codified format.We assembled 11 clinicians from the University of Pennsylvania Schools of Medicine and Nursing for a day-long moderated discussion to review our institution's TH protocol and reach consensus on a step-by-step management plan of the comatose survivor of OHCA. We attempted to systematically work our way through the existing University of Pennsylvania TH protocol. The goal was to address critical decisions at each stage of care of the post-arrest patient, including whom to cool, how to cool, how long to cool, how to rewarm, neuroprognostication, and other fundamental aspects of patient management. We made every effort to include relevant scientific evidence with appropriate citations. However, given the paucity of data in certain areas, we have relied heavily on expert opinion.We present a step-by-step management plan for incorporation of TH in the care of the comatose survivor of OHCA, which can be adapted to a variety of clinical settings with diverse resources. This article is intended to supplement current care provided by health care providers and should be adopted in concert with current standards of post-arrest and intensive care unit care.

Acute lung injury (ALI) is a syndrome with significant morbidity and mortality, but its genetic susceptibility is not clearly understood. In the present study, we characterized functional promoter single nucleotide polymorphisms (SNPs) in the phase II antioxidant gene NQO1 (NAD(P)H:quinone oxidoreductase1) to evaluate its role in susceptibility to ALI. Three previously uncharacterized SNPs in the NQO1 promoter were selected for investigation. Luciferase assays were performed using constructs of each promoter polymorphism to evaluate function. Functional SNPs were genotyped in a prospective cohort of major trauma patients (N= 264) and assessed for association with development of ALI. The A/C SNP at −1221 decreased in vitro transcription of NQO1 at baseline and after exposure to hyperoxia and other oxidant stressors. Patients heterozygous for the −1221 C allele were at significantly lesser risk of ALI after major trauma compared with patients with wild‐type alleles, even after adjustment for APACHE III score, and mechanism of trauma [OR, 0.46 (95% CI 0.23, 0.90); P= 0.024]. This study demonstrated that the AC genotype at position −1221 in the NQO1 gene caused decreased transcription and was associated with a lower incidence of ALI following major trauma. These novel findings may have important implications in diseases with oxidant stress aetiologies.

BACKGROUND Single nucleotide polymorphisms in the myosin light chain kinase (MYLK) gene have been implicated in the risk of sepsis-related acute lung injury and asthma. MYLK encodes protein isoforms involved in multiple components of the inflammatory response, including apoptosis, vascular permeability, and leukocyte diapedesis. We tested the association of MYLK gene variation in the development of acute lung injury in major trauma patients. METHODS We conducted a prospective cohort study of 273 subjects with major trauma (injury severity score > or = 16). All x-rays and clinical data were reviewed by three clinicians for acute lung injury classification. A total of 17 tagging single nucleotide polymorphisms in MYLK were genotyped. Single nucleotide polymorphisms were individually assessed at the genotype level, and multiple logistic regression models were used to adjust for baseline variables. Haplotype analyses of sliding windows including 2-5 single nucleotide polymorphisms were conducted. RESULTS Ninety-one of the 273 subjects (33%) met criteria for acute lung injury within 5 days of traumatic insult. Three informative MYLK coding single nucleotide polymorphisms were individually associated with acute lung injury, with two informative risk-conferring genotypes His21Pro (CC genotype, odds ratio = 1.87, 95% confidence interval 1.06-3.33; p = 0.022) and Pro147Ser (TT, odds ratio = 2.13, 95% confidence interval 1.14-4.10; p = 0.011) more frequent than the noninformative Thr335Thr CC genotype (odds ratio = 0.42, 95% confidence interval 0.20-0.85; p = 0.010). Each of these genotypic associations was more pronounced in African Americans with trauma. Multivariate analyses demonstrated the association of each MYLK single nucleotide polymorphism with acute lung injury to be independent of age, injury severity score, Acute Physiology and Chronic Health Evaluation III, and the mechanism of trauma. Finally, haplotype analyses revealed strong acute lung injury associations with 2-4 single nucleotide polymorphism haplotypes, all involving His21Pro (p < 0.008). CONCLUSIONS Three MYLK coding single nucleotide polymorphisms previously associated with sepsis-induced acute lung injury and severe asthma in African Americans were associated with acute lung injury development after trauma in African Americans, although effect directions differed. These results confirm our prior studies implicating MYLK as a susceptibility gene in a distinct acute lung injury subset other than sepsis.

The Hospital of the University of Pennsylvania achieved a significant reduction in the time between prescription and administration of antibiotics by embedding a pharmacist in an MET to facilitate antibiotic delivery.

Extubation failure is associated with poor intensive care unit and hospital outcomes. Minute ventilation recovery time, an integrative measure of a patient's respiratory reserve, has been shown in a pilot study to predict extubation outcome; however, the methodology is subjective and impractical for routine use. The authors hypothesize that minute ventilation recovery time, measured using an objective and simpler method, would predict extubation outcome. A prospective cohort study was performed in adult medical and surgical intensive care unit patients intubated for >24 hours who were weaning from mechanical ventilation. Minute ventilation recovery time was measured using a new, simplified, and objective method following the final spontaneous breathing trial prior to extubation. The primary outcome was extubation failure, defined as reintubation within 7 days. The study cohort comprised 88 patients, of whom 22 (25%) failed extubation after a median of 3 days. Demographic data, weaning parameters, and the proportion of patients who passed an extubation screen were similar between groups ( P > .05). Minute ventilation recovery time was significantly longer in patients who failed extubation (15 [5-15] vs 2 [1-5] minutes, P < .001), consistent in both medical and surgical subgroups. Operating characteristics for a preliminary threshold (minute ventilation recovery time ≥5 minutes) for prediction of extubation failure were sensitivity = 0.78, specificity = 0.71, positive predictive value = 0.47, negative predictive value = 0.90, correctly classified = 0.72. Adjustment for significant covariates did not alter the relationship between minute ventilation recovery time ≥5 minutes and extubation failure (odds ratio = 4.9, 95% confidence interval 1.45-16.2, P < .02). C statistic was 0.79 ± 0.17. It was concluded that minute ventilation recovery time, measured using a feasible methodology, can predict extubation outcome in medical and surgical intensive care unit patients.

Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)-ie, daily interruption of sedatives-with spontaneous breathing trials (SBTs).In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630.One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14.7 days vs 11.6 days; mean difference 3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were discharged from intensive care (median time in intensive care 9.1 days vs 12.9 days; p=0.01) and the hospital earlier (median time in the hospital 14.9 days vs 19.2 days; p=0.04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6.0% difference, 95% CI 0.6% to 11.8%; p=0.03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1.2% difference, 95% CI -5.2% to 2.5%; p=0.47), as were total reintubation rates (13.8%vs 12.5%; 1.3% difference, 95% CI -8.6% to 6.1%; p=0.73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0.68, 95% CI 0.50 to 0.92; p=0.01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7.4, 95% CI 4.2 to 35.5).Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Title: Can a Computerized Sepsis Screening and Alert System Accurately Diagnose Sepsis in Hospitalized Floor Patients and Potentially Provide Opportunities for Early Intervention? A Pilot Study. Background: Sepsis Syndromes are major causes of morbidity and mortality for hospitalized patients. Several evidence-based interventions have been shown to improve outcomes but they must be instituted early to achieve better outcomes. However, early recognition of sepsis syndromes in hospitalized patients is challenging. Regrettably, SIRS is overly sensitive and not specific in the patient populations at greatest risk for developing sepsis. In addition, many hospitalized patients have baseline end-organ dysfunction, wherein subtle trends in laboratory abnormalities may escape detection. Electronic detection and alert systems offer a more focused and efficient methodology. This strategy has been deployed successfully in other aspects of critical care, e.g. in the early recognition of acute respiratory distress syndrome. We developed an electronic recognition and alert system to identify floor patients with sepsis syndromes. The objective of this study was to test the feasibility, accuracy, and potential value of a computerized sepsis screening and alert system in a large university hospital. Methods and findings: The sepsis alert used an abnormal white blood cell count coupled with a blood culture order to define sepsis. Cases were categorized as severe sepsis by meeting specified changes in laboratory tests for organ dysfunction in accordance with consensus conference criteria. Using a retrospective cohort study design, we evaluated 97 consecutive, non-intensive care unit patients who triggered a sepsis alert at a large, urban, academic medical center. The charts of the patients were reviewed and abstracted manually to determine whether sepsis was present. For confirmed sepsis cases, we determined adherence with sepsis care bundle measures, including the recognition of sepsis (using physician documentation as a proxy measure), measurement of serum lactate, administration of antibiotics, and intravenous fluid resuscitation for severe sepsis cases. Within the 97 patient cohort, 72 were confirmed to have sepsis or severe sepsis (positive predictive value of 74%). Sepsis or severe sepsis was not documented in 79%, serum lactate was not measured in 57%, antibiotics were not administered in 14% of patients with severe sepsis, and fluid boluses were not administered in 17% of patients with severe sepsis who had lactic acidosis, hypotension, and/or acute kidney injury. In patients with sepsis or severe sepsis, adherence to the complete sepsis bundle did not occur in 65%. Opportunities to improve sepsis care were more common when sepsis was not documented. Conclusion: A computerized sepsis screening and alert system designed to identify sepsis in hospitalized medical ward patients without the use of vital signs was feasible to implement and predictive for sepsis. This suggests that implementation of this system may improve the quality of sepsis care in hospitalized ward patients.

RBC transfusion has been associated with increased morbidity and mortality in a variety of clinical settings. We assessed the effect of RBC transfusion on in-hospital mortality in patients with acute lung injury (ALI).Cohort study of 248 consecutive patients with ALI. RBC transfusion was evaluated as both dichotomous and continuous variables, with outcome being in-hospital mortality adjusted for clinical confounders and length of total hospital stay.Overall in-hospital mortality rate was 39.5%. Of these patients, 207 of 248 patients (83.5%) receivedor = 1 U of packed RBCs. The transfusion of any packed RBCs was associated with an increased risk of death (adjusted odds ratio [OR], 3.12; 95% confidence interval [CI], 1.28 to 7.58; p0.001). The overall OR per unit was 1.06 (95% CI, 1.04 to 1.09; p0.001) in the complete multivariable model. Transfusion after ALI onset was associated with an adjusted OR of 1.13 (95% CI, 1.07 to 1.20; p0.001), while transfusion before ALI onset was not associated with higher risk. The adjusted OR per unit of nonleukoreduced RBC transfused was 1.14 (95% CI, 1.07 to 1.21; p0.001), while the adjusted OR for leukoreduced cells per unit transfused was 1.06 (95% CI, 1.03 to 1.09; p0.001).Transfusion of RBCs in patients with ALI was associated with increased in-hospital mortality. This risk occurred with RBC transfusion after the onset of ALI, and was greater for nonleukoreduced than for leukoreduced RBCs. Aggressive transfusion strategies in patients with established ALI should be questioned, pending further study.