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Objective While emphasized in clinical practice, the association between advanced airway insertion first-pass success (FPS) and patient outcomes is incompletely understood. We sought to determine the association of airway insertion FPS with adult out-of-hospital cardiac arrest (OHCA) outcomes in the Pragmatic Airway Resuscitation Trial (PART). Methods We performed a secondary analysis of PART, a multicenter clinical trial comparing LT and ETI upon adult OHCA outcomes. We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-h survival, hospital survival, and hospital survival with favorable neurologic status (Modified Rankin Scale ≤3). Using multivariable GEE (generalized estimating equations), we determined the association between FPS and OHCA outcomes, adjusting for age, sex, witnessed arrest, bystander CPR, initial rhythm, and initial airway type. Results Of 3004 patients enrolled in the trial, 1423 received LT, 1227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 86.2% and ETI 46.7%. FPS was associated with increased ROSC (aOR 1.23; 95%CI: 1.07–1.41)), but not 72-h survival (1.22; 0.94–1.58), hospital survival (0.90; 0.68–1.19) or hospital survival with favorable neurologic status (0.66; 0.37–1.19). Conclusion In adult OHCA, airway insertion FPS was associated with increased ROSC but not other OHCA outcomes. The influence of airway insertion FPS upon OHCA outcomes is unclear.

Purpose Oxygen delivery by high flow nasal cannula (HFNC) is effective in providing respiratory support. HFNC has utility in clearing the extra-thoracic dead space, making it potentially beneficial in the treatment of hypercapnic respiratory failure. This study compares high velocity nasal insufflation (HVNI), a form of HFNC, to non-invasive positive pressure ventilation (NIPPV) in their abilities to provide ventilatory support for patients with hypercapnic respiratory failure. Methods This is a pre-defined subgroup analysis from a larger randomized clinical trial of Emergency Department (ED) patients with respiratory failure requiring NIPPV support. Patients were randomized to HVNI or NIPPV. Subgroup selection was done for patients with discharge diagnoses of acute hypercapnic respiratory failure or acute exacerbation of chronic obstructive pulmonary disease. The primary outcomes were change in pCO2 and pH over time. Secondary outcomes were treatment failure and intubation rate. Results 65 patients with hypercapnic respiratory failure were compared. 34 were randomized to HVNI and 31 to NIPPV. The therapeutic impact on PCO2 and pH over time was similar in each group. The intubation rate was 5.9% in the HVNI group and 16.1% in the NIPPV group (p = 0.244). The rate of treatment failure was 23.5% in the HVNI group and 25.8% in the NIPPV group (p = 1.0). Conclusion HVNI may provide ventilatory support similar to NIPPV in patients presenting with acute hypercapnic respiratory failure, but further study is needed to corroborate these findings.

Introduction: While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling. Hypothesis: We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival. Methods: We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival. Results: In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p < 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p< 0.001). Conclusions: TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.

Introduction: After an out-of-hospital cardiac arrest (OHCA), the resulting hypoxic-ischemic injury (HII) to the brain remains the main cause of mortality. Standardized approaches for measuring the extent of injury and monitoring of changes are lacking and continue to be a critical barrier to progress in improving neurological survival. Objective: We sought to characterize the prevalence of HII detected on computerized tomography of the brain and its correlation to point-of-care optic nerve sheath diameter (ONSD) measurements as an alternative modality for detecting brain injury. Methods: Adult OHCA patients at an urban academic ED were included in this study on a convenience sample basis from 2018-2019. The patients were grouped by findings of hypoxic-ischemic injury (HII) on both initial and subsequent CT brain imaging performed after ROSC in respective groups. CT Brain findings were compared to ONSD measurements as performed with point-of-care ultrasound by fellowship-trained emergency physicians within one hour of hospital arrival and at 6 hours, after return of spontaneous circulation (ROSC) and to cerebral performance category (CPC) at hospital discharge. Results: 76 patients enrolled in the study had a median age was 59, 49% were female, and 37% survived to hospital discharge. 58 patients had CT head performed, 40 had ONSD measured within one hour, and 27 patients had both. Of that 27, 9 (33%) had evidence of HII on initial imaging and 15 (55%) had evidence of HII on subsequent imaging for a total of 20 unique patients. The average ONSD within 1 hour of ROSC for those with no HII on any imaging was 0.59 cm, and for those without HII on initial imaging but with HII on subsequent imaging was 0.67 cm, and this difference was statistically significant (p< 0.05). Of the 20 patients with HI, 14 (70%) patients died and 6 (30%) survived with a CPC of 4. The average time to first CT head was 4 hours and 45 mins and the average time to subsequent imaging was 97 hours and 45 mins. Conclusion: After an OHCA, early time point ONSD measurements can potentially indicate brain injury within 1 hour of ROSC even in those without initial evidence of HII on CT imaging.

Managing respiratory failure (RF) secondary to acute decompensated heart failure (ADHF) with non-invasive positive-pressure ventilation (NIPPV) has been shown to significantly improve morbidity and mortality in patients presenting to the emergency department (ED). This subgroup analysis compares high-velocity nasal insufflation (HVNI), a form of high-flow nasal cannula, with NIPPV in the treatment of RF secondary to ADHF with respect to therapy failure, as indicated by the requirement for intubation or all-cause arm failure including subjective crossover to the alternate therapy.The subgroup analysis is from a larger randomized control trial of adults presenting to the ED with RF requiring NIPPV support. Patients were randomly selected to therapy, and subgroup selection was established a priori in the original study as a discharge diagnosis. The primary outcome was therapy failure at 72 h after enrolment.Subgroup analysis included a total of 22 HVNI and 20 NIPPV patients which fit discharge diagnosis ADHF. Baseline patient characteristics were not statistically significant. Primary outcomes were not statistically significant: intubation rate (p = 1.000), therapy success (p = 1.000). Repeated measures (vitals, dyspnea, blood gases) showed comparable differences over initial 4 h. Physicians scored HVNI superior on patient comfort/tolerance (p 0.001), ease of use (p = 0.004), and monitoring (p = 0.036). Limitations were technical inability to blind the clinician team and lack of power of the subgroup analysis.In conclusion, this subgroup analysis suggests HVNI may be non-inferior to NIPPV in patients with respiratory failure secondary to ADHF that do not need emergent intubation.

Targeted temperature management (TTM) is recommended postcardiac arrest. The cooling method with the highest safety and efficacy is unknown. The COOL-ARREST pilot trial aimed to evaluate the safety and efficacy of the most contemporary ZOLL Thermogard XP Intravascular Temperature Management (IVTM) system for providing mild TTM postcardiac arrest. This multicenter, prospective, single-arm, observational pilot trial enrolled patients at eight U.S. hospitals between July 28, 2014, and July 24, 2015. Adult (≥18 years old), out-of-hospital cardiac arrest subjects of presumed cardiac etiology who achieved return of spontaneous circulation (ROSC) were considered for inclusion. Patients were excluded if (1) awake or consistently following commands after ROSC, (2) significant prearrest neurological dysfunction, (3) terminal illness or advanced directives precluding aggressive care, and (4) severe hemodynamic instability or shock. Patient temperature was maintained at 33.0°C ± 0.3°C for a total of 24 hours followed by controlled rewarming (0.1-0.2°C/h). Logistic regressions were used to assess association of good functional outcome (modified Rankin Scale ≤3) measured at the time of hospital discharge with shockable rhythm (yes/no), age, gender, race/ethnicity, lay-rescuer cardiopulmonary resuscitation, time to basic life support (minutes), time to ROSC (minutes), lactate (mg/dL), and pH on admission. The ZOLL IVTM system was effective at inducing TTM (median time to target temperature from initiation, 89 minutes [interquartile range 42-155]). Adverse events most often included electrolyte abnormalities and dysrhythmias. Of patients surviving to hospital discharge, 16/20 patients had a good functional outcome. A total of 18 patients survived through 90-day follow-up, at which time 94% (17/18) of patients had good functional outcome. The COOL-ARREST pilot trial demonstrates high safety and efficacy of the ZOLL Thermogard XP IVTM system in the application of mild TTM postcardiac arrest. This observational trial also revealed noteworthy variability in the management of postcardiac arrest patients, particularly with the use of early withdrawal of life-sustaining therapy.

Background: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation. Study design: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed. Results: Fifteen patients from a large Level I trauma center met the criteria. The median PaO2/FiO2 ratio was 53.0 (IQR, 27.0–76.0), median injury severity score was 34.0 (IQR, 27.0–43.0), and the median duration of ECMO support was 11 days (IQR, 7.5–20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%). Conclusions: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

Introduction: Coronavirus disease 2019 (COVID-19) was first reported in the Houston city area in the first week of March 2020. Soon hospitals in the city were overrun with COVID-19 patients. By October, COVID-19 had resulted in 216,025 deaths in the US1. Older patients and Hispanic, American Indian/Alaskan Natives, Black, and Asian patients have experienced the highest excessive deaths1. The aim of our research was to study the factors associated with mortality among COVID-19 patients. Methods: The study was conducted on patients at a large university-affiliated multi-hospital system. The study used data from electronic medical records with an inpatient admission from March-October 2020 and a confirmed diagnosis of COVID-19. The data included demographic information, prescreening information, length of stay, discharge disposition, diagnoses and comorbidity, respiratory support, medications, and laboratory test results. The dependent variable in all analyses was defined as a discharge disposition of in-hospital death or hospice. Unadjusted logistic regression analyses were carried out on all variables, and a multivariable logistic regression model was built using variables that lowered the Akaike information criterion. Laboratory values missing at random were imputed by multiple imputations using chained equations. Results: There were 8,341 inpatients admissions, of whom 1,139 died or received hospice. The median age was 72 years among dead/hospice patients and 55 years among patients discharged alive (p

Introduction: Out-of-Hospital cardiac arrest (OHCA) is the leading cause of death with an overall survival rate of less than 10%. Organ failure and metabolic impairment are two critical elements of post-CA syndrome. Taurine and glutamate are amino acids that are expressed primarily in heart and brain. The compensatory release during osmotic stress, as seen in CA, amplifies reperfusion injury, heart stunning and brain edema. Thus, taurine and glutamate concentrations in blood likely reflects the extent of injury in the heart and brain following CA. Hypothesis: Plasma taurine and glutamate concentration correlates with CA outcomes. Methods: Adult OHCA patients (n=37) at an urban academic ED were enrolled from 2018-2019. Among them, 14 were survivors (S) and 23 were nonsurvivors (NS). Blood samples were collected at various time points including the time at hospital arrival, 6, 24, 48, 72 hours after arrival (T0, 6, 24, 48 and 72 h, respectively), and measured. T-test and GEE were used for mean comparison and longitudinal trend analysis, respectively. p < 0.05 was considered as statistically significant. Results: Plasma taurine and glutamate concentrations were compared between S and NS at T0 and across all time points. Both concentrations were significantly higher in NS vs S group at T0 (for taurine: 77.7 ± 40.0 in NS vs. 60.0 ± 31.9 μM in S, p =0.014; for glutamate: 176.4 ± 98.7 in NS vs. 162.8 ± 111.1 μM in S, p =0.0496), and showed a decreasing trend over time. In the first 6 h, taurine and glutamate level decreased more in S group than NS group (over 30% drop in S compared to Conclusions: Blood taurine and glutamate may serve as early biomarkers in predicting OHCA outcomes. Monitoring their change over time can help physicians tailor treatment decisions and patient management.

Introduction: Neurologically guided resuscitation after out-of-hospital cardiac arrest (OHCA) to improve survival has been limited due to knowledge gaps in cerebral edema changes. Point-of-care ultrasound (POCUS) for the assessment of optic nerve sheath diameter (ONSD) is an established modality to characterize the extent of cerebral edema. We aimed to describe ONSD differences by sex, rhythm type, neurological outcome using cerebral performance category (CPC), and overall survival status. Methods: We studied adult OHCA treated at an urban academic ED with return of spontaneous circulation (ROSC) from May 2018 to May 2020. After ROSC, trained emergency physicians obtained bilateral ONSD measurements at 1, 6, 24, 48, and 72 hours, in the transverse, oblique, and sagittal planes for each eye. All the ONSD measurements were averaged for each time point and comparisons were made between each predictor’s categories. To compare the mean at each time point between groups, t-test or ANOVA was used. The trend comparison was done using generalized estimating equations. Statistical analysis was performed using SAS 9.4 under the significance level of 0.05. Results: Out of 62 eligible patients, 35 (56%) were male and 27 (44%) were female, 33 (59%) had a shockable rhythm and 23 (41%) had non-shockable rhythm. At 72 hr, 6 (10%) had a CPC of 1-2 and 57 (90%) had CPC of 3-5. Overall, there were 37 (61%) survivors and 24 (39%) non-survivors. There was a notable sex difference in the mean ONSD across all time points between males and females (p = 0.031), with males showing higher ONSD, and between shockable and non-shockable (p= 0.035), with the shockable group having relatively lower ONSD. There is a statistically significant difference of mean ONSD between CPC 1-2 and CPC 3-5 groups at 6hr, 48hr, and at 72hr, with higher means in the CPC 3-5 group. Across all times, the trend line was statistically significant between non-survivors and survivors (p= 0.015), with non-survivors having higher ONSD. Conclusion: Males, patients with non-shockable rhythm, CPC 3-5 at 72 hr, and non-survivors had higher ONSD. Understanding cerebral edema dynamics during resuscitation will allow for future work to potentially tailor interventions to individual patient cerebral injury patterns.

Background Transfusion of red blood cells (RBC) is common, can have adverse effects, and is a costly and limited resource. Interventions that reduce iatrogenic blood losses could reduce transfusions. The objectives of this pilot trial were to assess the feasibility (acceptability of the intervention and suitability of eligibility criteria) and potential effectiveness of pediatric size phlebotomy tubes in adult critically ill patients. Methods We conducted a pilot, randomized controlled trial in the medical intensive care unit (ICU) of a university-affiliated, tertiary care referral hospital from November 2017 to September 2018. A total of 200 patients with hemoglobin of at least 7 g/dL and without bleeding were randomized to pediatric or adult size phlebotomy tubes. Stratification was according to baseline hemoglobin (7–9.49 g/dL, 9.5–11.99 g/dL, and 12 g/dL or greater). Acceptability was measured via the number of blood test recollections and the number of patients that discontinued the use of pediatric tubes. The suitability of patient eligibility criteria was determined by identifying baseline characteristics associated with RBC transfusions. Potential effectiveness was estimated from the time to RBC transfusion or to hemoglobin level below 7 g/dL. Results The use of pediatric tubes was acceptable as patients experienced a low number of tests recollections (on average 1 every 57 days), and none of the participants discontinued their use. The baseline hemoglobin category was the only factor that appeared to be independently associated with RBC transfusions. A total of 6 patients (6%) in the pediatric tube group and 11 patients (11%) in the adult tube group (hazard ratio, 0.69; 95% CI, 0.25 to 1.9) received an RBC transfusion or reached hemoglobin below 7 g/dL. Almost all of these patients (16 of 17 participants) had baseline hemoglobin of 7–9.49 g/dL. Conclusions This pilot study suggests that pediatric phlebotomy tubes are acceptable to patients and can therefore be used in adult ICU patients. A future study should focus on patients with hemoglobin levels below 9.5 g/dL, as these patients have a high risk of transfusions. This intervention has the potential of being successful in selected patients. A definitive trial is warranted. Trial registration ClinicalTrials.gov, NCT03286465. Retrospectively registered on September 18, 2017.

Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock. Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock. Design, Setting, and Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019. Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102). Main Outcomes and Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses. Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively). Conclusions and Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock. Trial Registration: ClinicalTrials.gov Identifier: NCT03389555.

Introduction: The multicenter Pragmatic Airway Resuscitation Trial (PART) demonstrated better adult out-of-hospital cardiac arrest (OHCA) outcomes with initial laryngeal tube (LT) insertion than endotracheal intubation (ETI) airway management. While emphasized in clinical practice, the effect of advanced airway insertion first-pass success (FPS) upon outcomes after OHCA is unknown. We sought to determine the direct and indirect mediating effects of LT and ETI FPS upon adult OHCA in a secondary analysis of PART. HYPOTHESES: 1) FPS associated with adult OHCA outcomes. 2) FPS mediates (explains) the association between airway type (LT vs. ETI) and adult OHCA outcomes. Methods: We defined FPS as successful LT insertion or ETI on the first attempt as reported by EMS personnel. We examined the outcomes return of spontaneous circulation (ROSC), 72-hour survival, hospital survival, and hospital survival with favorable neurologic function (MRS ≤3). Using multivariable GEE, we determined the association between FPS and outcomes after OHCA, adjusting for age, sex, witnessed arrest status, bystander CPR, initial rhythm, and trial randomization. Using the method of Baron and Kenny, we used mediation analysis to explain the contribution of FPS towards differences in OHCA outcomes between LT and ETI. Results: Of 3,004 patients enrolled in the trial, 1,423 received LT, 1,227 received ETI, 354 received bag-valve-mask ventilation only. FPS was: LT 90.3% and ETI 51.5%. FPS was associated with increased ROSC (adjusted OR 1.36, 95% CI 1.04-1.78) and 72h survival (1.45; 1.20-1.74) but not hospital survival (0.94; 0.67-1.31) or hospital survival with favorable neurologic function (0.70; 0.40-1.23). FPS had a strong mediating effect on the OHCA outcome differences between LT and ETI; 72h survival (74% mediated); ROSC (53% mediated); hospital survival (52% mediated); hospital survival with favorable neurologic status (35% mediated). Conclusion: In adult with OHCA, airway insertion FPS is associated with increased ROSC and 72h survival. Differences in OHCA outcomes between LT and ETI are largely explained by differences in FPS. EMS personnel should emphasize FPS in the advanced airway management of OHCA.

Twiddler’s syndrome refers to a rare condition in which a pacemaker or automatic implantable cardioverter-defibrillator (AICD) malfunctions due to coiling of the device in the skin pocket and resultant lead displacement. This image is the chest radiograph (CXR) of a 54-year-old male who presented to the emergency department with chest pain five months after his AICD was placed. The CXR shows AICD leads coiled around the device and the absence of leads in the ventricle consistent with Twiddler’s syndrome. Patients with twiddler’s syndrome should be admitted for operative intervention.

Out-of-hospital cardiac arrest (OHCA) is associated with high mortality. Current methods for predicting mortality post-arrest require data unavailable at the time of initial medical contact. We created and validated a risk prediction model for patients experiencing OHCA who achieved return of spontaneous circulation (ROSC) which relies only on objective information routinely obtained at first medical contact.We performed a retrospective evaluation of 14,892 OHCA patients in a large metropolitan cardiac arrest registry, of which 3952 patients had usable data. This population was divided into a derivation cohort (n = 2,635) and a verification cohort (n = 1,317) in a 2:1 ratio. Backward stepwise logistic regression was used to identify baseline factors independently associated with death after sustained ROSC in the derivation cohort. The cardiac arrest survival score (CASS) was created from the model and its association with in-hospital mortality was examined in both the derivation and verification cohorts.Baseline characteristics of the derivation and verification cohorts were not different. The final CASS model included age75 years (odds ratio [OR] = 1.61, confidence interval [CI][1.30-1.99], p 0.001), unwitnessed arrest (OR = 1.95, CI[1.58-2.40], p 0.001), home arrest (OR = 1.28, CI[1.07-1.53], p = 0.008), absence of bystander CPR (OR = 1.35, CI[1.12-1.64], p = 0.003), and non-shockable initial rhythm (OR = 3.81, CI[3.19-4.56], p 0.001). The area under the curve for the model derivation and model verification cohorts were 0.7172 and 0.7081, respectively.CASS accurately predicts mortality in OHCA patients. The model uses only binary, objective clinical data routinely obtained at first medical contact. Early risk stratification may allow identification of more patients in whom timely and aggressive invasive management may improve outcomes.

The combination of thiamine, ascorbic acid, and hydrocortisone has recently emerged as a potential adjunctive therapy to antibiotics, infectious source control, and supportive care for patients with sepsis and septic shock. In the present manuscript, we provide a comprehensive review of the pathophysiologic basis and supporting research for each element of the thiamine, ascorbic acid, and hydrocortisone drug combination in sepsis. In addition, we describe potential areas of synergy between these therapies and discuss the strengths/weaknesses of the two studies to date which have evaluated the drug combination in patients with severe infection. Finally, we describe the current state of current clinical practice as it relates to the thiamine, ascorbic acid, and hydrocortisone combination and present an overview of the randomized, placebo-controlled, multi-center Ascorbic acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial and other planned/ongoing randomized clinical trials.

Introduction: The purpose of this study was to assess safety and efficacy of thrombolysis in the setting of aggressive blood pressure (BP) control as it compares to standard BP control or no BP control prior to thrombolysis. Methods: We performed a retrospective review of patients treated with tissue plasminogen activator (tPA) for acute ischemic stroke (AIS) between 2004-2011. We compared the outcomes of patients treated with tPA for AIS who required aggressive BP control prior to thrombolysis to those requiring standard or no BP control prior to thrombolysis. The primary outcome of interest was safety, defined by all grades of hemorrhagic transformation and neurologic deterioration. The secondary outcome was efficacy, determined by functional status at discharge, and in-hospital deaths. Results: Of 427 patients included in the analysis, 89 received aggressive BP control prior to thrombolysis, 65 received standard BP control, and 273 required no BP control prior to thrombolysis. Patients requiring BP control had more severe strokes, with median arrival National Institutes of Health Stroke Scale of 10 (IQR [6-17]) in patients not requiring BP control versus 11 (IQR [5-16]) and 13 (IQR [7-20]) in patients requiring standard and aggressive BP lowering therapies, respectively (p=0.048). In a multiple logistic regression model adjusting for baseline differences, there were no statistically significant differences in adverse events between the three groups (P>0.10). Conclusion: We observed no association between BP control and adverse outcomes in ischemic stroke patients undergoing thrombolysis. However, additional study is necessary to confirm or refute the safety of aggressive BP control prior to thrombolysis.

Author(s): Okafor, Nnaemeka G.; Doshi, Pratik B.; Miller, Sara K.; McCarthy, James J.; Hoot, Nathan R.; Darger, Bryan F.; Benitez, Roberto C.; Chathampally, Yashwant G. | Abstract: Introduction: Medical errors are frequently under-reported, yet their appropriate analysis, coupled with remediation, is essential for continuous quality improvement. The emergency department (ED) is recognized as a complex and chaotic environment prone to errors. In this paper, we describe the design and implementation of a web-based ED-specific incident reporting system using an iterative process.Methods: A web-based, password-protected tool was developed by members of a quality assurance committee for ED providers to report incidents that they believe could impact patient safety.Results: The utilization of this system in one residency program with two academic sites resulted in an increase from 81 reported incidents in 2009, the first year of use, to 561 reported incidents in 2012. This is an increase in rate of reported events from 0.07% of all ED visits to 0.44% of all ED visits. In 2012, faculty reported 60% of all incidents, while residents and midlevel providers reported 24% and 16% respectively. The most commonly reported incidents were delays in care and management concerns. Conclusion: Error reporting frequency can be dramatically improved by using a web-based, user-friendly, voluntary, and non-punitive reporting system.

Objectives Diagnostic errors are common in the emergency department (ED), but few studies have comprehensively evaluated their types and origins. We analysed incidents reported by ED physicians to determine disease conditions, contributory factors and patient harm associated with ED-related diagnostic errors. Methods Between 1 March 2009 and 31 December 2013, ED physicians reported 509 incidents using a department-specific voluntary incident-reporting system that we implemented at two large academic hospital-affiliated EDs. For this study, we analysed 209 incidents related to diagnosis. A quality assurance team led by an ED physician champion reviewed each incident and interviewed physicians when necessary to confirm the presence/absence of diagnostic error and to determine the contributory factors. We generated descriptive statistics quantifying disease conditions involved, contributory factors and patient harm from errors. Results Among the 209 incidents, we identified 214 diagnostic errors associated with 65 unique diseases/conditions, including sepsis (9.6%), acute coronary syndrome (9.1%), fractures (8.6%) and vascular injuries (8.6%). Contributory factors included cognitive (n=317), system related (n=192) and non-remedial (n=106). Cognitive factors included faulty information verification (41.3%) and faulty information processing (30.6%) whereas system factors included high workload (34.4%) and inefficient ED processes (40.1%). Non-remediable factors included atypical presentation (31.3%) and the patients’ inability to provide a history (31.3%). Most errors (75%) involved multiple factors. Major harm was associated with 34/209 (16.3%) of reported incidents. Conclusions Most diagnostic errors in ED appeared to relate to common disease conditions. While sustaining diagnostic error reporting programmes might be challenging, our analysis reveals the potential value of such systems in identifying targets for improving patient safety in the ED.

BACKGROUND The effect of red blood cell (RBC) storage on oxygenation in critically ill patients is still unknown. The objective of this study was to determine the association of RBC storage with oxygenation, long-term neurologic recovery, and death after traumatic brain injury. METHODS We used data from a 2 × 2 factorial randomized controlled trial of administration of erythropoietin or placebo and of assignment to transfusion threshold of less than 7g/dL or less than 10 g/dL in neurosurgical intensive care units in two US Level 1 trauma centers. Patients had severe traumatic brain injury with closed head injury, were unable to follow commands, and were enrolled within 6 hours of injury. Blood oxygenation 1 hour after the transfusion as measured by jugular venous oxygen saturation (n = 59) was the primary outcome. Secondary outcomes were brain tissue oxygenation (n = 77), 6-month Glasgow Outcome Scale (GOS) score (n = 122) collected using a structured interview and dichotomized into favorable (good recovery or moderate disability) or unfavorable outcome (severe disability, vegetative state, or dead), and mortality (n = 125). RBC age was defined as the maximum age of RBCs over all units in one transfusion per patient. For long-term outcomes, RBC age was defined as the mean age over all units given. RESULTS We failed to detect an association of RBC age with jugular venous oxygen saturation (linear regression β = 1.59; 95% confidence interval [CI], -2.99 to 6.18; p = 0.49), brain tissue oxygenation (linear regression β = 0.20; 95% CI, -0.23 to 0.63; p = 0.36), GOS score (odds ratio, 1.37; 95% CI, 0.53-3.57; p = 0.52), and mortality (hazard ratio, 1.35; 95% CI, 0.61-2.98; p = 0.46). CONCLUSION Limitations of this study include the fact that the RBC ages were not randomized, although this was a prospective study. We conclude that older blood does not seem to have adverse effects in severe traumatic brain injury. LEVEL OF EVIDENCE Prognostic study, level III.

Objectives The objective was to assess relative incidence of clinical adverse effects between patients receiving, and not receiving, iodinated contrast prior to thrombolysis. Methods This was a retrospective registry review of patients presenting to the emergency department treated with recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke between 2004 and 2012. The authors compared the occurrence of all grades of intracranial hemorrhage (ICH), symptomatic intracranial hemorrhage (sICH), and in-hospital deaths between patients undergoing computed tomographic angiography (CTA) prior to thrombolysis and those who did not. Results A total of 1,014 patients were available for analysis meeting inclusion criteria. A total of 473 patients underwent CTA prior to rt-PA administration. Baseline characteristics were generally similar across groups, excepting fewer signs of acute infarct and old stroke in the CTA group (28.8% vs. 8.5% and 9.9% vs. 3.7%, respectively) and creatinine. Adverse event outcomes were not consistently distributed across the groups. Patients in the CTA group had a similar incidence of any ICH (11.0% vs. 8.1%, p = 0.120), but fewer type II parenchymal hemorrhages (2.1% vs. 4.6%, p = 0.025) and fewer in-hospital deaths (7.2% vs. 12.6%, p = 0.005). Conclusions No consistent harms were observed in association with intravenous iodinated contrast prior to rt-PA administration. It is reasonable to continue CTA prior to thrombolysis as clinically indicated.

Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. NCT00313716 registered 4/2006

The incidence of adult respiratory distress syndrome (ARDS) in severe traumatic brain injury (TBI) is poorly reported. Recently, a new definition for ARDS was proposed, the Berlin definition. The percentage of patients represented by TBI in the Berlin criteria study is limited. This study describes the incidence and associated mortality of ARDS in TBI patients.The study was an analysis of the safety of erythropoietin administration and transfusion threshold on the incidence of ARDS in severe TBI patients. Three reviewers independently assessed all patients enrolled in the study for acute lung injury/ARDS using the Berlin and the American-European Consensus Conference (AECC) definitions. A Cox proportional hazards model was used to assess the relationship between ARDS and mortality and 6-month Glasgow Outcome Scale (GOS) score.Two hundred patients were enrolled in the study. Of the patients, 21% (41 of 200) and 26% (52 of 200) developed ARDS using the AECC and Berlin definitions, respectively, with a median time of 3 days (interquartile range, 3) after injury. ARDS by either definition was associated with increased mortality (p = 0.04) but not with differences in functional outcome as measured by the GOS score at 6 months. Adjusted analysis using the Berlin criteria showed an increased mortality associated with ADS (p = 0.01).Severe TBI is associated with an incidence of ARDS ranging from 20% to 25%. The incidence is comparable between the Berlin and AECC definitions. ARDS is associated with increased mortality in severe TBI patients, but further studies are needed to validate these findings.Epidemiologic study, level II.

Monitoring oxygen saturation of blood drawn from a catheter placed within the superior vena cava (ScvO2) has recently been promoted as a substitute for evaluating oxygen saturation of mixed venous blood drawn from the pulmonary artery (Sv̄O2). The Sv̄O2 reflects the balance between oxygen delivery and oxygen consumption throughout the body and, among critically ill patients, may be helpful for assessing resuscitation, cardiac function, or oxygen homeostasis end points. Use of ScvO2 instead has been promoted because of its easier access and recent use during resuscitation of patients with severe infections. Although data from healthy subjects and critically ill patients are available, no study has been done among organ donors to evaluate customary values for either ScvO2 or Sv̄O2 or how well the values correspond. After loss of oxygen consumption in the brain following brain death, the customary values for these variables may be different from values in other groups of patients. Therefore, until donor-specific normative values for these important parameters are identified, we do not recommend that ScvO2 be used to evaluate the balance between donor oxygen consumption and delivery or as a variable to guide treatment.

Study objective We compare high-velocity nasal insufflation, a form of high-flow nasal cannula, with noninvasive positive-pressure ventilation in the treatment of undifferentiated respiratory failure with respect to therapy failure, as indicated by requirement for endotracheal intubation or cross over to the alternative therapy. Methods This was a multicenter, randomized trial of adults presenting to the emergency department (ED) with respiratory failure requiring noninvasive positive-pressure ventilation. Patients were randomly assigned to high-velocity nasal insufflation (initial flow 35 L/min; temperature 35°C (95°F) to 37°C (98.6°F); FiO 2 1.0) or noninvasive positive-pressure ventilation using an oronasal mask (inspiratory positive airway pressure 10 cm H 2 O; expiratory positive airway pressure 5 cm H 2 O). The primary outcome was therapy failure at 72 hours after enrollment. A subjective outcome of crossover was allowed as a risk mitigation to support deferment of informed consent. Noninferiority margins were set at 15 and 20 percentage points, respectively. Results A total of 204 patients were enrolled and included in the analysis, randomized to high-velocity nasal insufflation (104) and noninvasive positive-pressure ventilation (100). The intubation rate (high-velocity nasal insufflation=7%; noninvasive positive-pressure ventilation=13%; risk difference=–6%; 95% confidence interval –14% to 2%) and any failure of the assigned arm (high-velocity nasal insufflation=26%; noninvasive positive-pressure ventilation=17%; risk difference 9%; confidence interval –2% to 20%) at 72 hours met noninferiority. The effect on PCO 2 over time was similar in the entire study population and in patients with baseline hypercapnia. Vital signs and blood gas analyses improved similarly over time. The primary limitation was the technical inability to blind the clinical team. Conclusion High-velocity nasal insufflation is noninferior to noninvasive positive-pressure ventilation for the treatment of undifferentiated respiratory failure in adult patients presenting to the ED.

Objectives Therapeutic hypothermia has been shown to improve neurologic outcome and survival in out-of-hospital cardiac arrest (OHCA) following return of spontaneous circulation (ROSC), and current guidelines recommend therapeutic hypothermia for all comatose survivors of OHCA. However, recommendations for nonshockable rhythms are not as strongly supported. Our study aims to provide further evidence on the use of therapeutic hypothermia in nonshockable rhythms. Methods A multivariate analysis with propensity score matching was performed using a cardiac arrest registry maintained by the Houston Fire Department. The analysis was limited to adult patients achieving ROSC following OHCA secondary to nonshockable rhythm in Houston from 2007 to 2012 with definitive information regarding the implementation of therapeutic hypothermia. The primary outcome was survival to hospital discharge. Results Of 9,479 records identified for analysis, 7,839 had an initial nonshockable rhythm. Of these, 2,609 (33.3%) had sustained ROSC and 1,768 (22.6%) were admitted to the hospital. Data on therapeutic hypothermia use were available for 696 patients, with 335 (48.1%) receiving therapeutic hypothermia. Propensity score matching yielded 260 case/control pairs. The odds of survival to hospital discharge was an odds ratio of 1.07 (95% confidence interval = 0.71 to 1.60) for those in the therapeutic hypothermia group versus the nontherapeutic hypothermia group (p = 0.79). Conclusions Based on this retrospective study, therapeutic hypothermia is not associated with improved survival in patients with OHCA secondary to nonshockable rhythms. Given the limitations of our study, further prospective trials to assess the effect of therapeutic hypothermia for OHCA with nonshockable rhythms are warranted.

Cerebral dysfunction caused by traumatic brain injury may adversely affect cerebral hemodynamics and oxygenation leading to worse outcomes if oxygen capacity is decreased due to anemia. In a randomized clinical trial of 200 patients comparing transfusion thresholds

Cardiac arrest (CA) is associated with high mortality. Currently, no validated method for predicting mortality post CA exists. A prognostication tool may improve medical decisions and resource allocation. We created and validated a novel scoring system (Cardiac Arrest Survival Score) for predicting

Introduction: The incidence of out of hospital cardiac arrest (OHCA) in the U.S. is approximately 400,000 patients per year. Despite quality improvement efforts, overall survival after cardiac arrest remains poor, suggesting that there are other factors at play. One such variable is total ischemic time. This analysis was performed to determine the role of total ischemic time in hospital survival after OHCA. Methods: The OHCA records were queried from the cardiac arrest registry maintained by Houston Fire department from 2007-2012.Association between outcome and predictor variables was assessed using logistic regression. The outcome variable is defined as survival and discharge from the hospital. Our predictor variable of interest was Estimated Total Ischemic Time, which was calculated as the difference between time of Return of Spontaneous Circulation (ROSC) and Fire Rescue Dispatch time. The Hosmer-Lemeshow Goodness of Fit test grouped by ten showed that the null (the model) should not be rejected (p = 0.8678). The final model includes Estimated Total Ischemic Time, age divided into categories by decade, presence of a shockable rhythm, and presence of a witness to the cardiac arrest. Results: The database consisted of 9,074 OHCA cases, of which 446 were included in the final analysis. According to our model, the data suggests there is a decrease in probability of survival as estimated total ischemic time increases. The odds of survival and discharge from the hospital of an OHCA patient with an estimated total ischemic time of 2 minutes is 0.956 (95%CI 0.936 - 0.977) times the odds of a patient whose estimated total ischemic time was 1 minute. Conclusion: Estimated Total Ischemic Time is a significant contributor to the probability of survival, however it is not the only one. This model exemplifies just one example of the importance of adjusting for both prehospital and hospital care in clinical decision-making and healthcare quality improvement.

Aim of the study The decision to accept or decline cardiopulmonary resuscitation (CPR) by surrogate decision makers on behalf of a family member is a common and important component of end-of-life decision-making in the ICU. While many determinants influence this decision, surrogates’ understanding of CPR may be a major guiding factor. However, little is known about surrogates’ knowledge and perceptions of CPR during the periods of time when their family member is critically ill. We conducted this study to explore surrogates’ understanding of some basic concepts of CPR. Methods This is a descriptive, survey-based exploratory study of understanding of CPR concepts and outcomes conducted in a single-center medical ICU at a tertiary academic hospital in the United States. Study subjects were surrogate decision-makers of critically ill ICU patients who participated in an interview-format survey within 24 h of the patient's ICU admission. Results Of 97 eligible subjects (surrogates), 50 were enrolled in this study and represented a wide spectrum of demographics. All subjects had heard of CPR. The main source of information about CPR was a course. While 46% identified cardiac arrest as a main indication for CPR, only 8% identified at least 2 of the 3 main components of CPR. The majority (72%) believed survival after CPR was ≥75%. Forty-two percent of surrogates had spoken to the patient about CPR prior to coming to the hospital, and 57% had spoken to the physician during this hospitalization. Twenty-six percent changed their decision on CPR during the ICU stay. Conclusion There is a wide variation in surrogates’ understanding and knowledge of CPR concepts and outcomes.

OBJECTIVE To determine the effect of early enteral feeding on the outcome of critically ill medical patients whose hemodynamic condition is unstable. METHODS Prospectively collected data in a multi-institutional medical intensive care unit database were analyzed retrospectively. A total of 1174 patients were identified who required mechanical ventilation for more than 2 days and were treated with vasopressor agents to support blood pressure. The patients were divided into 2 groups: those who received enteral nutrition (n = 707) within 48 hours of the start of mechanical ventilation, termed the early enteral nutrition group, and those who did not (n = 467), termed the late enteral nutrition group. The primary end points were overall intensive care unit and hospital mortality. Subgroup analyses were used to evaluate potential confounding variables. The data were also analyzed after adjustments for confounding by matching for propensity score. RESULTS Intensive care unit and hospital mortality were lower in the early enteral nutrition group than in the late enteral group: 22.5% vs 28.3%; P = 03; and 34.0% vs 44.0%; P < .001, respectively. The beneficial effect of early feeding was more evident in the sickest patients, that is, those treated with multiple vasopressors (odds ratio, 0.36; 95% confidence interval, 0.15-0.85) and those without early improvement (odds ratio, 0.59; 95% confidence interval, 0.39-0.90). When adjustments were made for confounding by matching for propensity score, early feeding was associated with decreased hospital mortality. CONCLUSION Early enteral nutrition may be associated with reduced intensive care unit and hospital mortality in patients whose hemodynamic condition is unstable.

Importance There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. Objective To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. Design, Setting, and Participants Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. Interventions Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. Main Outcomes and Measures Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. Results There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). Conclusions and Relevance In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. Trial Registration clinicaltrials.gov Identifier:NCT00313716

Objectives The objective was to determine the efficacy of coadministration of subcutaneous (SQ) insulin glargine in combination with intravenous (IV) insulin for treating diabetic ketoacidosis (DKA). Methods This was a prospective, randomized, controlled trial comparing coadministration of insulin glargine and IV insulin (experimental) with IV insulin (standard care control). The setting was emergency departments (EDs) in two hospitals in Houston, Texas. Patients presenting with blood sugar ≥ 200 mg/dL, pH ≤ 7.3, bicarbonate (HCO3) ≤ 18 mg/dL, ketonemia or ketonuria, and anion gap ≥ 16 between November 2012 and April 2013 were enrolled. All patients received IV insulin. Additionally, the experimental group was given SQ insulin glargine within 2 hours of diagnosis. Upon closure of anion gap, patients in the control group were subsequently transitioned to long-acting insulin. In the study group, IV insulin was discontinued and long-acting SQ insulin was reinstituted 24 hours after initial introduction. The primary outcome of time to closure of anion gap (TCAG) was compared between groups using a general linear model (GLM), adjusting for initial anion gap, etiology, and presence of comorbidities. Similarly, the secondary outcome hospital length of stay (LOS) was adjusted for age, etiology, and hospital site in the GLM. Rate of hypoglycemia and intensive care unit (ICU) admission was compared using Fisher's exact test while ICU LOS was compared using Wilcoxon's two-sample test. Results A total of 40 patients were enrolled in this pilot trial. The estimated mean TCAG was 10.2 hours (SE ± 6.8 hours) in the experimental group and 11.6 hours (SE ± 6.4 hours) in the control group (p = 0.63). The estimated mean hospital LOS was 3.9 days (SE ± 3.4 days) in the experimental group and 4.8 days (SE ± 3.6 days) in the control group (p = 0.66). Incidents of hypoglycemia, rates of ICU admission, and ICU LOS were similar between the groups. Conclusions Coadministration of glargine in combination with an insulin infusion in the acute management of DKA is feasible. Further study is needed to determine the true efficacy in terms of TCAG and hospital LOS.