Alan E. Jones

Association Between Arterial Hyperoxia Following Resuscitation From Cardiac Arrest and In-Hospital Mortality

CONTEXT Laboratory investigations suggest that exposure to hyperoxia after resuscitation from cardiac arrest may worsen anoxic brain injury; however, clinical data are lacking. OBJECTIVE To test the hypothesis that postresuscitation hyperoxia is associated with increased mortality. DESIGN, SETTING, AND PATIENTS Multicenter cohort study using the Project IMPACT critical care database of intensive care units (ICUs) at 120 US hospitals between 2001 and 2005. Patient inclusion criteria were age older than 17 years, nontraumatic cardiac arrest, cardiopulmonary resuscitation within 24 hours prior to ICU arrival, and arterial blood gas analysis performed within 24 hours following ICU arrival. Patients were divided into 3 groups defined a priori based on PaO(2) on the first arterial blood gas values obtained in the ICU. Hyperoxia was defined as PaO(2) of 300 mm Hg or greater; hypoxia, PaO(2) of less than 60 mm Hg (or ratio of PaO(2) to fraction of inspired oxygen <300); and normoxia, not classified as hyperoxia or hypoxia. MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Of 6326 patients, 1156 had hyperoxia (18%), 3999 had hypoxia (63%), and 1171 had normoxia (19%). The hyperoxia group had significantly higher in-hospital mortality (732/1156 [63%; 95% confidence interval {CI}, 60%-66%]) compared with the normoxia group (532/1171 [45%; 95% CI, 43%-48%]; proportion difference, 18% [95% CI, 14%-22%]) and the hypoxia group (2297/3999 [57%; 95% CI, 56%-59%]; proportion difference, 6% [95% CI, 3%-9%]). In a model controlling for potential confounders (eg, age, preadmission functional status, comorbid conditions, vital signs, and other physiological indices), hyperoxia exposure had an odds ratio for death of 1.8 (95% CI, 1.5-2.2). CONCLUSION Among patients admitted to the ICU following resuscitation from cardiac arrest, arterial hyperoxia was independently associated with increased in-hospital mortality compared with either hypoxia or normoxia.

Randomized, controlled trial of immediate versus delayed goal-directed ultrasound to identify the cause of nontraumatic hypotension in emergency department patients*

Objective:We examined a physician-performed, goal-directed ultrasound protocol for the emergency department management of nontraumatic, symptomatic, undifferentiated hypotension. Design:Randomized, controlled trial of immediate vs. delayed ultrasound. Setting:Urban, tertiary emergency department, census >100,000. Patients:Nontrauma emergency department patients, aged >17 yrs, and initial emergency department vital signs consistent with shock (systolic blood pressure <100 mm Hg or shock index >1.0), and agreement of two independent observers for at least one sign and symptom of inadequate tissue perfusion. Interventions:Group 1 (immediate ultrasound) received standard care plus goal-directed ultrasound at time 0. Group 2 (delayed ultrasound) received standard care for 15 mins and goal-directed ultrasound with standard care between 15 and 30 mins after time 0. Measurements and Main Results:Outcomes included the number of viable physician diagnoses at 15 mins and the rank of their likelihood of occurrence at both 15 and 30 mins. One hundred eighty-four patients were included. Group 1 (n = 88) had a smaller median number of viable diagnoses at 15 mins (median = 4) than did group 2 (n = 96, median = 9, Mann-Whitney U test, p < .0001). Physicians indicated the correct final diagnosis as most likely among their viable diagnosis list at 15 mins in 80% (95% confidence interval, 70–87%) of group 1 subjects vs. 50% (95% confidence interval, 40–60%) in group 2, difference of 30% (95% confidence interval, 16–42%). Conclusions:Incorporation of a goal-directed ultrasound protocol in the evaluation of nontraumatic, symptomatic, undifferentiated hypotension in adult patients results in fewer viable diagnostic etiologies and a more accurate physician impression of final diagnosis.

Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol.

Objective:We sought to determine the association between time to initial antibiotics and mortality of patients with septic shock treated with an emergency department-based early resuscitation protocol. Design:Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation. Setting:Three urban U.S. emergency departments. Patients:Adult patients with septic shock. Interventions:A quantitative resuscitation protocol in the emergency department targeting three physiological variables: central venous pressure, mean arterial pressure, and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all end points were achieved or a maximum of 6 hrs. Measurements and Main Results:Data on patients who received an initial dose of antibiotics after presentation to the emergency department were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was inhospital mortality. Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hrs after triage: 1 hr (odds ratio [OR], 1.2; 0.6–2.5), 2 hrs (OR, 0.71; 0.4–1.3), 3 hrs (OR, 0.59; 0.3–1.3). Mortality was significantly increased in patients who received initial antibiotics after shock recognition (n = 172 [59%]) compared with before shock recognition (OR, 2.4; 1.1–4.5); however, among patients who received antibiotics after shock recognition, mortality did not change with hourly delays in antibiotic administration. Conclusion:In this large, prospective study of emergency department patients with septic shock, we found no increase in mortality with each hour delay to administration of antibiotics after triage. However, delay in antibiotics until after shock recognition was associated with increased mortality.

Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest

Background— Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients. Methods and Results— This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO2) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO2 (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO2 was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO2 was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension. Conclusion— In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.

The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation

Objectives:Organ failure worsens outcome in sepsis. The Sequential Organ Failure Assessment (SOFA) score numerically quantifies the number and severity of failed organs. We examined the utility of the SOFA score for assessing outcome of patients with severe sepsis with evidence of hypoperfusion at the time of emergency department (ED) presentation. Design:Prospective observational study. Setting:Urban, tertiary ED with an annual census of >110,000. Patients:ED patients with severe sepsis with evidence of hypoperfusion. Inclusion criteria: suspected infection, two or more criteria of systemic inflammation, and either systolic blood pressure <90 mm Hg after a fluid bolus or lactate ≥4 mmol/L. Exclusion criteria: age <18 years or need for immediate surgery. Interventions:SOFA scores were calculated at ED recognition (T0) and 72 hours after intensive care unit admission (T72). The primary outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate the predictive ability of SOFA scores at each time point. The relationship between &Dgr; SOFA (change in SOFA from T0 to T72) was examined for linearity. Results:A total of 248 subjects aged 57 ± 16 years, 48% men, were enrolled over 2 years. All patients were treated with a standardized quantitative resuscitation protocol; the in-hospital mortality rate was 21%. The mean SOFA score at T0 was 7.1 ± 3.6 points and at T72 was 7.4 ± 4.9 points. The area under the receiver operating characteristic curve of SOFA for predicting in-hospital mortality at T0 was 0.75 (95% confidence interval 0.68–0.83) and at T72 was 0.84 (95% confidence interval 0.77–0.90). The &Dgr; SOFA was found to have a positive relationship with in-hospital mortality. Conclusions:The SOFA score provides potentially valuable prognostic information on in-hospital survival when applied to patients with severe sepsis with evidence of hypoperfusion at the time of ED presentation.

Multicenter Study of Central Venous Oxygen Saturation (ScvO2) as a Predictor of Mortality in Patients With Sepsis

STUDY OBJECTIVE Abnormal (both low and high) central venous saturation (ScvO(2)) is associated with increased mortality in emergency department (ED) patients with suspected sepsis. METHODS This was a secondary analysis of 4 prospectively collected registries of ED patients treated with early goal-directed therapy-based sepsis resuscitation protocols from 4 urban tertiary care hospitals. Inclusion criteria were sepsis, hypoperfusion defined by systolic blood pressure less than 90 mm Hg or lactate level greater than or equal to 4 mmol/L, and early goal-directed therapy treatment. ScvO(2) levels were stratified into 3 groups: hypoxia (ScvO(2) <70%); normoxia (ScvO(2) 71% to 89%); and hyperoxia (ScvO(2) 90% to 100%). The primary exposures were initial ScvO(2) and maximum ScvO(2) achieved, with the primary outcome as inhospital mortality. Multivariate analysis was performed. RESULTS There were 619 patients who met criteria and were included. For the maximum ScvO(2), compared with the mortality rate in the normoxia group of 96 of 465 (21%; 95% confidence interval [CI] 17% to 25%), both the hypoxia mortality rate, 25 of 62 (40%; 95% CI 29% to 53%) and hyperoxia mortality rate, 31 of 92 (34%; 95% CI 25% to 44%) were significantly higher, which remained significant in a multivariate modeling. When the initial ScvO(2) measurement was analyzed in a multivariate model, only hyperoxia was significantly higher. CONCLUSION The maximum ScvO(2) value achieved in the ED (both abnormally low and high) was associated with increased mortality. In multivariate analysis for initial ScvO(2), the hyperoxia group was associated with increased mortality, but not the hypoxia group. This study suggests that future research aimed at targeting methods to normalize high ScvO(2) values by therapies that improve microcirculatory flow or mitochondrial dysfunction may be warranted.

Incidence of Contrast-Induced Nephropathy after Contrast-Enhanced Computed Tomography in the Outpatient Setting

BACKGROUND AND OBJECTIVES No prospective study has reported the incidence of contrast-induced nephropathy (CIN) or the associated morbidity and mortality after contrast-enhanced computed tomography (CECT) in the outpatient setting. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We enrolled and followed a prospective, consecutive cohort (June 2007 through January 2009) of patients who received intravenous contrast for CECT in the emergency department of a large, academic, tertiary care center. Outcomes measured were as follows (1) CIN: An increase in serum creatinine > or =0.5 mg/dl or > or =25% 2 to 7 d after contrast administration; (2) severe renal failure: An increase in serum creatinine to > or =3.0 mg/dl or the need for dialysis at 45 d; and (3) renal failure as a contributing cause of death (consensus of three independent physicians) at 45 d. RESULTS The incidence of CIN was 11% (70 of 633) among the 633 patients enrolled. Fifteen (2%) patients died within 45 d, including six deaths after study-defined CIN. Seven (1%) patients developed severe renal failure, six of whom had study-defined CIN. Of the six patients with CIN and severe renal failure, four died, and adjudicators determined that renal failure significantly contributed to all four deaths. Thus, CIN was associated with an increased risk for severe renal failure and death from renal failure. CONCLUSIONS CIN occurs in >10% of patients who undergo CECT in the outpatient setting and is associated with a significant risk for severe renal failure and death.

The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis

Objective:Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on mortality from sepsis. Data Sources:We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy. Study Selection:We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality. Data Abstraction:Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I2 to assess for statistical heterogeneity (p < 0.10, I2 > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals. Results:The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43–0.96); however, there was statistically significant heterogeneity (p = 0.07, I2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I2 = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37–0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60–2.22). Conclusion:This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.

The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis

IntroductionPrevious reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.MethodsThis is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.ResultsA total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.ConclusionsMarkers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.

Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial

Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance.