Journal Cover
Critical Care Medicine
Journal Prestige (SJR): 3.116
Citation Impact (citeScore): 3
Number of Followers: 288  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0090-3493
Published by LWW Wolters Kluwer Homepage  [305 journals]
  • The Effect of Goal-Directed Therapy on Patient Morbidity and Mortality
           After Traumatic Brain Injury: Results From the Progesterone for the
           Treatment of Traumatic Brain Injury III Clinical Trial*
    • Authors: Merck; Lisa H.; Yeatts, Sharon D.; Silbergleit, Robert; Manley, Geoffrey T.; Pauls, Qi; Palesch, Yuko; Conwit, Robin; Le Roux, Peter; Miller, Joseph; Frankel, Michael; Wright, David W.
      Abstract: imageObjectives: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial.Design: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial.Setting: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network.Patients: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4–12.Measurements and Main Results: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a “transgression.” Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either: 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model.Results: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002).Conclusions: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Immune Checkpoint Inhibition in Sepsis: A Phase 1b Randomized,
           Placebo-Controlled, Single Ascending Dose Study of Antiprogrammed Cell
           Death-Ligand 1 Antibody (BMS-936559)*
    • Authors: Hotchkiss; Richard S.; Colston, Elizabeth; Yende, Sachin; Angus, Derek C.; Moldawer, Lyle L.; Crouser, Elliott D.; Martin, Greg S.; Coopersmith, Craig M.; Brakenridge, Scott; Mayr, Florian B.; Park, Pauline K.; Ye, June; Catlett, Ian M.; Girgis, Ihab G.; Grasela, Dennis M.
      Abstract: imageObjectives: To assess for the first time the safety and pharmacokinetics of an antiprogrammed cell death-ligand 1 immune checkpoint inhibitor (BMS-936559; Bristol-Myers Squibb, Princeton, NJ) and its effect on immune biomarkers in participants with sepsis-associated immunosuppression.Design: Randomized, placebo-controlled, dose-escalation.Setting: Seven U.S. hospital ICUs.Study Population: Twenty-four participants with sepsis, organ dysfunction (hypotension, acute respiratory failure, and/or acute renal injury), and absolute lymphocyte count less than or equal to 1,100 cells/μL.Interventions: Participants received single-dose BMS-936559 (10–900 mg; n = 20) or placebo (n = 4) infusions. Primary endpoints were death and adverse events; key secondary endpoints included receptor occupancy and monocyte human leukocyte antigen-DR levels.Measurements and Main Results: The treated group was older (median 62 yr treated pooled vs 46 yr placebo), and a greater percentage had more than 2 organ dysfunctions (55% treated pooled vs 25% placebo); other baseline characteristics were comparable. Overall mortality was 25% (10 mg dose: 2/4; 30 mg: 2/4; 100 mg: 1/4; 300 mg: 1/4; 900 mg: 0/4; placebo: 0/4). All participants had adverse events (75% grade 1–2). Seventeen percent had a serious adverse event (3/20 treated pooled, 1/4 placebo), with none deemed drug-related. Adverse events that were potentially immune-related occurred in 54% of participants; most were grade 1–2, none required corticosteroids, and none were deemed drug-related. No significant changes in cytokine levels were observed. Full receptor occupancy was achieved for 28 days after BMS-936559 (900 mg). At the two highest doses, an apparent increase in monocyte human leukocyte antigen-DR expression (> 5,000 monoclonal antibodies/cell) was observed and persisted beyond 28 days.Conclusions: In this first clinical evaluation of programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition in sepsis, BMS-936559 was well tolerated, with no evidence of drug-induced hypercytokinemia or cytokine storm, and at higher doses, some indication of restored immune status over 28 days. Further randomized trials on programmed cell death protein-1/programmed cell death-ligand 1 pathway inhibition are needed to evaluate its clinical safety and efficacy in patients with sepsis.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Does Obesity Protect Against Death in Sepsis' A Retrospective Cohort
           Study of 55,038 Adult Patients*
    • Authors: Pepper; Dominique J.; Demirkale, Cumhur Y.; Sun, Junfeng; Rhee, Chanu; Fram, David; Eichacker, Peter; Klompas, Michael; Suffredini, Anthony F.; Kadri, Sameer S.
      Abstract: imageObjectives: Observational studies suggest obesity is associated with sepsis survival, but these studies are small, fail to adjust for key confounders, measure body mass index at inconsistent time points, and/or use administrative data to define sepsis. To estimate the relationship between body mass index and sepsis mortality using detailed clinical data for case detection and risk adjustment.Design: Retrospective cohort analysis of a large clinical data repository.Setting: One-hundred thirty-nine hospitals in the United States.Patients: Adult inpatients with sepsis meeting Sepsis-3 criteria.Exposure: Body mass index in six categories: underweight (body mass index < 18.5 kg/m2), normal weight (body mass index = 18.5–24.9 kg/m2), overweight (body mass index = 25.0–29.9 kg/m2), obese class I (body mass index = 30.0–34.9 kg/m2), obese class II (body mass index = 35.0–39.9 kg/m2), and obese class III (body mass index ≥ 40 kg/m2).Measurements: Multivariate logistic regression with generalized estimating equations to estimate the effect of body mass index category on short-term mortality (in-hospital death or discharge to hospice) adjusting for patient, infection, and hospital-level factors. Sensitivity analyses were conducted in subgroups of age, gender, Elixhauser comorbidity index, Sequential Organ Failure Assessment quartiles, bacteremic sepsis, and ICU admission.Main Results: From 2009 to 2015, we identified 55,038 adults with sepsis and assessable body mass index measurements: 6% underweight, 33% normal weight, 28% overweight, and 33% obese. Crude mortality was inversely proportional to body mass index category: underweight (31%), normal weight (24%), overweight (19%), obese class I (16%), obese class II (16%), and obese class III (14%). Compared with normal weight, the adjusted odds ratio (95% CI) of mortality was 1.62 (1.50–1.74) for underweight, 0.73 (0.70–0.77) for overweight, 0.61 (0.57–0.66) for obese class I, 0.61 (0.55–0.67) for obese class II, and 0.65 (0.59–0.71) for obese class III. Results were consistent in sensitivity analyses.Conclusions: In adults with clinically defined sepsis, we demonstrate lower short-term mortality in patients with higher body mass indices compared with those with normal body mass indices (both unadjusted and adjusted analyses) and higher short-term mortality in those with low body mass indices. Understanding how obesity improves survival in sepsis would inform prognostic and therapeutic strategies.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Peripheral Blood Mononuclear Cells Demonstrate Mitochondrial Damage
           Clearance During Sepsis
    • Authors: Kraft; Bryan D.; Chen, Lingye; Suliman, Hagir B.; Piantadosi, Claude A.; Welty-Wolf, Karen E.
      Abstract: imageObjectives: Metabolic derangements in sepsis stem from mitochondrial injury and contribute significantly to organ failure and mortality; however, little is known about mitochondrial recovery in human sepsis. We sought to test markers of mitochondrial injury and recovery (mitochondrial biogenesis) noninvasively in peripheral blood mononuclear cells from patients with sepsis and correlate serial measurements with clinical outcomes.Design: Prospective case-control study.Setting: Academic Medical Center and Veterans Affairs Hospital.Patients: Uninfected control patients (n = 20) and septic ICU patients (n = 37).Interventions: Blood samples were collected once from control patients and serially with clinical data on days 1, 3, and 5 from septic patients. Gene products for HMOX1, NRF1, PPARGC1A, and TFAM, and mitochondrial DNA ND1 and D-loop were measured by quantitative reverse transcriptase-polymerase chain reaction. Proinflammatory cytokines were measured in plasma and neutrophil lysates.Measurements and Main Results: Median (interquartile range) Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 21 (8) and 10 (4), respectively, and 90-day mortality was 19%. Transcript levels of all four genes in peripheral blood mononuclear cells were significantly reduced in septic patients on day 1 (p < 0.05), whereas mitochondrial DNA copy number fell and plasma D-loop increased (both p < 0.05), indicative of mitochondrial damage. D-loop content was directly proportional to tumor necrosis factor-α and high-mobility group protein B1 cytokine expression. By day 5, we observed transcriptional activation of mitochondrial biogenesis and restoration of mitochondrial DNA copy number (p < 0.05). Patients with early activation of mitochondrial biogenesis were ICU-free by 1 week.Conclusions: Our findings support data that sepsis-induced mitochondrial damage is reversed by activation of mitochondrial biogenesis and that gene transcripts measured noninvasively in peripheral blood mononuclear cells can serve as novel biomarkers of sepsis recovery.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Central Venous Access Capability and Critical Care Telemedicine Decreases
           Inter-Hospital Transfer Among Severe Sepsis Patients: A Mixed Methods
           Design
    • Authors: Ilko; Steven A.; Vakkalanka, J. Priyanka; Ahmed, Azeemuddin; Harland, Karisa K.; Mohr, Nicholas M.
      Abstract: imageObjectives: Severe sepsis is a complex, resource intensive, and potentially lethal condition and rural patients have worse outcomes than urban patients. Early identification and treatment are important to improving outcomes. The objective of this study was to identify hospital-specific factors associated with inter-hospital transfer.Design: Mixed method study integrating data from a telephone survey and retrospective cohort study of state administrative claims.Setting and Subjects: Survey of Iowa emergency department administrators between May 2017 and June 2017 and cohort of adults seen in Iowa emergency departments for severe sepsis and septic shock between January 2005 and December 2013.Interventions: None.Measurements and Main Results: Multivariable logistic regression was used to identify independent predictors of inter-hospital transfer. We included 114 institutions that provided data (response rate = 99%), and responses were linked to a total of 150,845 visits for severe sepsis/septic shock. In our adjusted model, having the capability to place central venous catheters or having a subscription to a tele-ICU service was independently associated with lower odds of inter-hospital transfer (adjusted odds ratio, 0.69; 95% CI, 0.54–0.86 and adjusted odds ratio, 0.69; 95% CI, 0.54–0.88, respectively). A facility’s participation in a sepsis-specific quality improvement initiative was associated with 62% higher odds of transfer (adjusted odds ratio, 1.62; 95% CI, 1.10–2.39).Conclusions: The insertion of central venous catheters and access to a critical care physician during sepsis treatment are important capabilities in hospitals that transfer fewer sepsis patients. In the future, hospital-specific capabilities may be used to identify institutions as regional sepsis centers.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Neutropenic Enterocolitis in Critically Ill Patients: Spectrum of the
           Disease and Risk of Invasive Fungal Disease
    • Authors: Duceau; Baptiste; Picard, Muriel; Pirracchio, Romain; Wanquet, Anne; Pène, Frédéric; Merceron, Sybille; Mokart, Djamel; Moreau, Anne-Sophie; Lengliné, Etienne; Canet, Emmanuel; Lemiale, Virginie; Mariotte, Eric; Azoulay, Elie; Zafrani, Lara
      Abstract: imageObjectives: Neutropenic enterocolitis occurs in about 5.3% of patients hospitalized for hematologic malignancies receiving chemotherapy. Data from critically ill patients with neutropenic enterocolitis are scarce. Our objectives were to describe the population of patients with neutropenic enterocolitis admitted to an ICU and to investigate the risk factors of invasive fungal disease.Design: A multicentric retrospective cohort study between January 2010 and August 2017.Setting: Six French ICUs members of the Groupe de Recherche Respiratoire en Onco-Hématologie research network.Patients: Adult neutropenic patients hospitalized in the ICU with a diagnosis of enteritis and/or colitis. Patients with differential diagnosis (Clostridium difficile colitis, viral colitis, inflammatory enterocolitis, mesenteric ischemia, radiation-induced gastrointestinal toxicity, and Graft vs Host Disease) were excluded.Interventions: None.Measurement and Main Results: We included 134 patients (median Sequential Organ Failure Assessment 10 [8–12]), with 38.8% hospital mortality and 32.1% ICU mortality rates. The main underlying malignancies were acute leukemia (n = 65, 48.5%), lymphoma (n = 49, 36.6%), solid tumor (n = 14, 10.4%), and myeloma (n = 4, 3.0%). Patients were neutropenic during a median of 14 days (9–22 d). Infection was documented in 81 patients (60.4%), including an isolated bacterial infection in 64 patients (47.8%), an isolated fungal infection in nine patients (6.7%), and a coinfection with both pathogens in eight patients (5.0%). Radiologically assessed enteritis (odds ratio, 2.60; 95% CI, 1.32–7.56; p = 0.015) and HIV infection (odds ratio, 2.03; 95% CI, 1.21–3.31; p = 0.016) were independently associated with invasive fungal disease.Conclusions: The rate of invasive fungal disease reaches 20% in patients with neutropenic enterocolitis when enteritis is considered. To avoid treatment delay, antifungal therapy might be systematically discussed in ICU patients admitted for neutropenic enterocolitis with radiologically assessed enteritis.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • ICU Utilization for Patients With Acute Exacerbation of Chronic
           Obstructive Pulmonary Disease Receiving Noninvasive Ventilation
    • Authors: Myers; Laura C.; Faridi, Mohammad Kamal; Currier, Paul; Camargo, Carlos A. Jr
      Abstract: imageObjectives: We investigated whether patients with chronic obstructive pulmonary disease could safely receive noninvasive ventilation outside of the ICU.Design: Retrospective cohort study.Setting: Twelve states with ICU utilization flag from the State Inpatient Database from 2014.Patients: Patients greater than or equal to 18 years old with primary diagnosis of acute exacerbation of chronic obstructive pulmonary disease and secondary diagnosis of respiratory failure who received noninvasive ventilation.Interventions: None.Measurements and Main Results: Multilevel logistic regression models were used to obtain hospital-level ICU utilization rates. We risk-adjusted using both patient/hospital characteristics. The primary outcome was in-hospital mortality; secondary outcomes were invasive monitoring (arterial/central catheters), hospital length of stay, and cost. We examined 5,081 hospitalizations from 424 hospitals with ICU utilization ranging from 0.05 to 0.98. The overall median in-hospital mortality was 2.62% (interquartile range, 1.72–3.88%). ICU utilization was not significantly associated with in-hospital mortality (β = 0.01; p = 0.05) or length of stay (β = 0.18; p = 0.41), which was confirmed by Spearman correlation (ρ = 0.06; p = 0.20 and ρ = 0.02; p = 0.64, respectively). However, lower ICU utilization was associated with lower rates of invasive monitor placement by linear regression (β = 0.05; p < 0.001) and Spearman correlation (ρ = 0.28; p < 0.001). Lower ICU utilization was also associated with significantly lower cost by linear regression (β = 14.91; p = 0.02) but not by Spearman correlation (ρ = 0.09; p = 0.07).Conclusions: There is wide variability in the rate of ICU utilization for noninvasive ventilation across hospitals. Chronic obstructive pulmonary disease patients receiving noninvasive ventilation had similar in-hospital mortality across the ICU utilization spectrum but a lower rate of receiving invasive monitors and probably lower cost when treated in lower ICU-utilizing hospitals. Although the results suggest that noninvasive ventilation can be delivered safely outside of the ICU, we advocate for hospital-specific risk assessment if a hospital were considering changing its noninvasive ventilation delivery policy.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The Effect of Mechanical Ventilation on Peripheral Perfusion Index and Its
           Association With the Prognosis of Critically Ill Patients
    • Authors: Su; Longxiang; Zhang, Ruiming; Zhang, Qing; Xu, Qun; Zhou, Xiang; Cui, Na; Wang, Hao; Wang, Xiaoting; Chai, Wenzhao; Rui, Xi; Liu, Dawei; Long, Yun
      Abstract: imageObjectives: This study aimed to explore the relationship between the variables of mechanical ventilation and circulatory perfusion and its association with ICU mortality during the first day of mechanical ventilation.Design: Retrospective cohort study.Setting: The Department of Critical Care Medicine, Peking Union Medical College Hospital.Patients: Patients who have undergone mechanical ventilation.Interventions: None.Measurements and Main Results: This study used the main clinical data obtained from the real-time bedside messaging systems of mechanically ventilated patients during their first day in the ICU from May 2013 to May 2016, including data on the variables of mechanical ventilation and circulatory perfusion. An analysis was then performed on the association of the above data with the patient’s in-ICU mortality. There were 5,103 patients who received mechanical ventilation during this period, and of these, 309 patients died during their ICU treatment. Peak airway pressure, mean airway pressure, respiratory rate, heart rate, mean arterial pressure, FIO2, blood oxygen saturation, PO2, peripheral perfusion index, and lactate level were correlated with patient outcomes. A Cox logistic regression analysis suggested that mean airway pressure and perfusion index were the most independent risk and protective factors, respectively, for patient ICU mortality. The areas under the curve for a poor prognosis for mean airway pressure and perfusion index were 0.799 (95% CI, 0.77–0.829) and 0.759 (95% CI, 0.729–0.789), respectively. Further, mean airway pressure and perfusion index exhibited a causal interaction. The relative excess risk due to interaction was 2.061 (–0.691 to 4.814), the attributable proportion due to interaction was 0.210 (–0.027 to 0.447), and the synergy index was 1.306 (0.930–1.833).Conclusions: A higher mean airway pressure and lower perfusion index provided a worse prognosis in mechanically ventilated patients, and it appears that these two variables have a casual interaction.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Impact of Body Temperature Abnormalities on the Implementation of Sepsis
           Bundles and Outcomes in Patients With Severe Sepsis: A Retrospective
           Sub-Analysis of the Focused Outcome Research on Emergency Care for Acute
           Respiratory Distress Syndrome, Sepsis and Trauma Study
    • Authors: Kushimoto; Shigeki; Abe, Toshikazu; Ogura, Hiroshi; Shiraishi, Atsushi; Saitoh, Daizoh; Fujishima, Seitaro; Mayumi, Toshihiko; Hifumi, Toru; Shiino, Yasukazu; Nakada, Taka-aki; Tarui, Takehiko; Otomo, Yasuhiro; Okamoto, Kohji; Umemura, Yutaka; Kotani, Joji; Sakamoto, Yuichiro; Sasaki, Junichi; Shiraishi, Shin-ichiro; Takuma, Kiyotsugu; Tsuruta, Ryosuke; Hagiwara, Akiyoshi; Yamakawa, Kazuma; Masuno, Tomohiko; Takeyama, Naoshi; Yamashita, Norio; Ikeda, Hiroto; Ueyama, Masashi; Fujimi, Satoshi; Gando, Satoshi; on behalf of JAAM Focused Outcome Research on Emergency Care for Acute respiratory distress syndrome, Sepsis Trauma (FORECAST Group
      Abstract: imageObjectives: To investigate the impact of body temperature on disease severity, implementation of sepsis bundles, and outcomes in severe sepsis patients.Design: Retrospective sub-analysis.Setting: Fifty-nine ICUs in Japan, from January 2016 to March 2017.Patients: Adult patients with severe sepsis based on Sepsis-2 were enrolled and divided into three categories (body temperature < 36°C, 36–38°C,> 38°C), using the core body temperature at ICU admission.Interventions: None.Measurements and Main Results: Compliance with the bundles proposed in the Surviving Sepsis Campaign Guidelines 2012, in-hospital mortality, disposition after discharge, and the number of ICU and ventilator-free days were evaluated. Of 1,143 enrolled patients, 127, 565, and 451 were categorized as having body temperature less than 36°C, 36–38°C, and greater than 38°C, respectively. Hypothermia—body temperature less than 36°C—was observed in 11.1% of patients. Patients with hypothermia were significantly older than those with a body temperature of 36–38°C or greater than 38°C and had a lower body mass index and higher prevalence of septic shock than those with body temperature greater than 38°C. Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on the day of enrollment were also significantly higher in hypothermia patients. Implementation rates of the entire 3-hour bundle and administration of broad-spectrum antibiotics significantly differed across categories; implementation rates were significantly lower in patients with body temperature less than 36°C than in those with body temperature greater than 38°C. Implementation rate of the entire 3-hour resuscitation bundle + vasopressor use + remeasured lactate significantly differed across categories, as did the in-hospital and 28-day mortality. The odds ratio for in-hospital mortality relative to the reference range of body temperature greater than 38°C was 1.760 (95% CI, 1.134–2.732) in the group with hypothermia. The proportions of ICU-free and ventilator-free days also significantly differed between categories and were significantly smaller in patients with hypothermia.Conclusions: Hypothermia was associated with a significantly higher disease severity, mortality risk, and lower implementation of sepsis bundles.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Moderate-Intensity Insulin Therapy Is Associated With Reduced Length of
           Stay in Critically Ill Patients With Diabetic Ketoacidosis and
           Hyperosmolar Hyperglycemic State
    • Authors: Firestone; Rachelle L.; Parker, Patricia L.; Pandya, Komal A.; Wilson, Machelle D.; Duby, Jeremiah J.
      Abstract: imageObjectives: Insulin infusion therapy is commonly used in the hospital setting to manage diabetic ketoacidosis and hyperosmolar hyperglycemic state. Clinical evidence suggests both hypoglycemia and glycemic variability negatively impact patient outcomes. The hypothesis of this study was that moderate-intensity insulin therapy decreases hospital length of stay and prevalence of hypoglycemia in patients with diabetic ketoacidosis and hyperosmolar hyperglycemic state.Design: Pre-post study.Setting: Large academic medical center in the United States.Patients: Two-hundred one consecutive, nonpregnant, adult patients admitted for diabetic ketoacidosis and hyperosmolar hyperglycemic state between October 2010 and December 2014.Interventions: High-intensity insulin therapy versus moderate-intensity insulin therapy. High-intensity insulin therapy was designed to rapidly normalize blood glucose levels with bolus doses of insulin and rapid insulin titration. Moderate-intensity insulin therapy was designed to mitigate glycemic variability and hypoglycemia through avoidance of bolus dosing, a liberalized blood glucose target, and gradual insulin titration.Measurements and Main Results: Hospital and ICU length of stay were reduced by 23.6% and 38%, respectively. The relative risk of remaining in the hospital at day 7 (0.51; p = 0.022) and day 14 (0.28; p = 0.044) were significantly reduced by the moderate-intensity insulin therapy strategy. The relative risk of remaining in the ICU at 48 hours was significantly lower in the moderate-intensity insulin therapy cohort (0.34; p = 0.0048). The prevalence (35% vs 1%; p = 0.0003) and relative risk (0.028; p = 0.0004) of hypoglycemia were significantly lower in the moderate-intensity insulin therapy cohort. Glycemic variability decreased by 28.6% (p < 0.0001). There was no difference in the time to anion gap closure (p = 0.123).Conclusions: Moderate-intensity insulin therapy for diabetic ketoacidosis and hyperosmolar hyperglycemic state resulted in improvements in hospital and ICU length of stay, which appeared to be associated with decreased glycemic variability.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill
           Children
    • Authors: Faustino; Edward Vincent S.; Hirshberg, Eliotte L.; Asaro, Lisa A.; Biagas, Katherine V.; Pinto, Neethi; Srinivasan, Vijay; Bagdure, Dayanand N.; Steil, Garry M.; Coughlin-Wells, Kerry; Wypij, David; Nadkarni, Vinay M.; Agus, Michael S. D.; Mourani, Peter M.; Chima, Ranjit; Thomas, Neal J.; Li, Simon; Pinto, Alan; Newth, Christopher; Hassinger, Amanda; Bysani, Kris; Rehder, Kyle J.; Kandil, Sarah; Wintergerst, Kupper; Schwarz, Adam; Marsillio, Lauren; Cvijanovich, Natalie; Pham, Nga; Quasney, Michael; Flori, Heidi; Federman, Myke; Nett, Sholeen; Viteri, Shirley; Schneider, James; Medar, Shivanand; Sapru, Anil; McQuillen, Patrick; Babbitt, Christopher; Lin, John C.; Jouvet, Philippe; Yanay, Ofer; Allen, Christine; for the Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT Study InvestigatorsHeart And Lung Failure-Pediatric INsulin Titration (HALF-PIN Faustino, Edward Vincent S.; Hirshberg, Eliotte L.; Asaro, Lisa A.; Biagas, Katherine V.; Pinto, Neethi; Srinivasan, Vijay; Bagdure, Dayanand N.; Steil, Garry M.; Coughlin-Wells, Kerry; Wypij, David; Nadkarni, Vinay M.; Agus, Michael S. D.; Mourani, Peter M.; Chima, Ranjit; Thomas, Neal J.; Li, Simon; Pinto, Alan; Newth, Christopher; Hassinger, Amanda; Bysani, Kris; Rehder, Kyle J.; Kandil, Sarah; Wintergerst, Kupper; Schwarz, Adam; Marsillio, Lauren; Cvijanovich, Natalie; Pham, Nga; Quasney, Michael; Flori, Heidi; Federman, Myke; Nett, Sholeen; Viteri, Shirley; Schneider, James; Medar, Shivanand; Sapru, Anil; McQuillen, Patrick; Babbitt, Christopher; Lin, John C.; Jouvet, Philippe; Yanay, Ofer; Allen, Christine; for the Heart And Lung Failure-Pediatric INsulin Titration (HALF-PINT Study InvestigatorsHeart And Lung Failure-Pediatric INsulin Titration (HALF-PIN
      Abstract: imageObjectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children.Design: Nested case-control study.Setting: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia.Patients: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness.Interventions: None.Measurements and Main Results: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia.Conclusions: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Renal Replacement Therapy in the ICU
    • Authors: Rachoin; Jean-Sebastien; Weisberg, Lawrence S.
      Abstract: Objectives: The incidence of acute kidney injury in critically ill patients is increasing steeply. Acute kidney injury in this setting is associated with high morbidity and mortality. There is no doubt that renal replacement therapy for the most severe forms of acute kidney injury can be life saving, but there are a number of uncertainties about the optimal application of renal replacement therapy for patients with acute kidney injury. The objective of this synthetic review is to present current evidence supporting best practices in renal replacement therapy for critically ill patients with acute kidney injury.Data Sources: We reviewed literature regarding timing of initiation of renal replacement therapy, optimal vascular access for renal replacement therapy in acute kidney injury, modality selection and dose or intensity of renal replacement therapy, and anticoagulation during renal replacement therapy, using the following databases: MEDLINE and PubMed. We also reviewed bibliographic citations of retrieved articles.Study Selection: We reviewed only English language articles.Conclusions: Current evidence sheds light on many areas of controversy regarding renal replacement therapy in acute kidney injury, providing a foundation for best practices. Nonetheless, important questions remain to be answered by ongoing and future investigation.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Impact of the Advanced Practice Provider in Adult Critical Care: A
           Systematic Review and Meta-Analysis*
    • Authors: Kreeftenberg; Herman G.; Pouwels, Sjaak; Bindels, Alexander J. G. H.; de Bie, Ashley; van der Voort, Peter H. J.
      Abstract: imageObjectives: To evaluate the effects on quality and efficiency of implementation of the advanced practice provider in critical care.Data Sources: PubMed, Embase, The Cochrane Library, and CINAHL were used to extract articles regarding advanced practice providers in critical care.Study Selection: Articles were selected when reporting a comparison between advanced practice providers and physician resident/fellows regarding the outcome measures of mortality, length of stay, or specific tasks. Descriptive studies without comparison were excluded. The methodological quality of the included studies was rated using the Newcastle-Ottawa scale. The agreement between the reviewers was assessed with Cohen’s kappa. A meta-analysis was constructed on mortality and length of stay.Data Extraction and Synthesis: One-hundred fifty-six studies were assessed by full text. Thirty comparative cohort studies were selected and analyzed. These compared advanced practice providers with physician resident/fellows. All studies comprised adult intensive care. Most of the included studies showed a moderate to good quality. Over time, the study designs advanced from retrospective designs to include prospective and comparative designs.Data Synthesis: Four random effects meta-analyses on length of stay and mortality were constructed from the available studies. These meta-analyses showed no significant difference between performance of advanced practice providers on the ICU and physician residents/fellows on the ICU, suggesting the quality of care of both groups was equal. Mean difference for length of stay on the ICU was 0.34 (95% CI, –0.31 to 1.00; I2 = 99%) and for in hospital length of stay 0.02 (95% CI, –0.85 to 0.89; I2 = 91%); whereas the odds ratio for ICU mortality was 0.98 (95% CI, 0.81–1.19; I2 = 37.3%) and for hospital mortality 0.92 (95% CI, 0.79–1.07; I2 = 28%).Conclusions: This review and meta-analysis shows no differences between acute care given by advanced practice providers compared with physician resident/fellows measured as length of stay or mortality. However, advanced practice providers might add value to care in several other ways, but this needs further study.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Where There Is No Law, There Is No Transgression: Goal-Directed Therapy
           for Traumatic Brain Injury*
    • Authors: Koenig; Matthew A.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Saved From Sepsis: Can Immunotherapy Improve Acute and Postacute
           Outcomes'*
    • Authors: Cawcutt; Kelly A.; Kalil, Andre C.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • What Is the Skinny on Obesity During Sepsis'*
    • Authors: Crouser; Elliott D.; Caldwell, Charles C.; Hotchkiss, Richard S.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Integrating Advanced Practice Providers Into the Multiprofessional
           Critical Care Team*
    • Authors: Meissen; Heather H.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Sepsis Epidemiology From Administrative Data: Going, Going…*
    • Authors: Simpson; Steven Q.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • A Novel Approach for the Targeted Inhibition of Platelet
           Activation—Separating the Good From the Bad*
    • Authors: Rossaint; Jan; Zarbock, Alexander
      Abstract: imageNo abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Effect of Antihypertensive Medications on Sepsis-Related Outcomes: A
           Population-Based Cohort Study*
    • Authors: Kim; Joohae; Kim, Young Ae; Hwangbo, Bin; Kim, Min Jeong; Cho, Hyunsoon; Hwangbo, Yul; Lee, Eun Sook
      Abstract: imageObjectives: Although the effect of antihypertensive agents on sepsis has been studied, evidence for survival benefit was limited in the literature. We investigated differences in sepsis-related outcomes depending on the antihypertensive drugs given prior to sepsis in patients with hypertension.Design: Population-based cohort study.Setting: Sample cohort Database of the National Health Insurance Service from 2003 to 2013 in South Korea.Patients: Patients over 30 years old who were diagnosed with sepsis after receiving hypertension treatment.Interventions: None.Measurements and Main Results: Primary outcomes, 30-day and 90-day mortality rates, were analyzed for differences among three representative antihypertensive medications: angiotensin- converting enzyme inhibitors or angiotensin II receptor blockers, calcium channel blockers, and thiazides. In total, 4,549 patients diagnosed with hypertension prior to hospitalization for sepsis were identified. The 30-day mortality was significantly higher among patients who did not receive any medications within 1 month before sepsis (36.8%) than among patients who did (32.0%; p < 0.001). The risk for 90-days mortality was significantly lower in prior angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker users (reference) than in other drug users (odds ratio, 1.27; 95% CI, 1.07–1.52). There was no difference in the risk for 30-day and 90-day mortality depending on whether calcium channel blockers or thiazides were used. Use of calcium channel blockers was associated with a decreased risk for inotropic agent administration, compared with those of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio, 1.23; 95% CI, 1.05–1.44) and thiazides (odds ratio, 1.33; 95% CI, 1.12–1.58).Conclusions: In patients with sepsis, lower mortality rate was associated with prior use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers not with use of calcium channel blockers or thiazides. The requirement of inotropic agents was significantly lower in prior use of calcium channel blockers, although the survival benefits were not prominent.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Enhanced Performance of Next-Generation Sequencing Diagnostics Compared
           With Standard of Care Microbiological Diagnostics in Patients Suffering
           From Septic Shock
    • Authors: Grumaz; Silke; Grumaz, Christian; Vainshtein, Yevhen; Stevens, Philip; Glanz, Karolina; Decker, Sebastian O.; Hofer, Stefan; Weigand, Markus A.; Brenner, Thorsten; Sohn, Kai
      Abstract: imageObjectives: Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Within the presented investigation, higher performance of next-generation sequencing-based diagnostics was validated by comparison to matched blood cultures.Design: A secondary analysis of a prospective, observational, single-center study.Setting: Surgical ICU of a university hospital and research laboratory.Patients: Fifty patients with septic shock, 20 uninfected patients with elective surgery as control cohort.Interventions: None.Measurements and Main Results: From 256 plasma samples of 48 septic patients at up to seven consecutive time points within the 28-day observation period, cell-free DNA was isolated and analyzed by next-generation sequencing and relevance scoring. In parallel, results from culture-based diagnostics (e.g., blood culture) were obtained. Plausibility of blood culture and next-generation sequencing results as well as adequacy of antibiotic therapy was evaluated by an independent expert panel. In contrast to blood culture with a positivity rate of 33% at sepsis onset, the positivity rate for next-generation sequencing-based pathogen identification was 72%. Over the whole study period, blood culture positivity was 11%, and next-generation sequencing positivity was 71%. Ninety-six percent of positive next-generation sequencing results for acute sepsis time points were plausible and would have led to a change to a more adequate therapy in 53% of cases as assessed by the expert evaluation.Conclusions: Our results show that next-generation sequencing-based analyses of bloodstream infections provide a valuable diagnostic platform for the identification of clinically relevant pathogens with higher sensitivity and specificity than blood culture, indicating that patients might benefit from a more appropriate therapy based on next-generation sequencing-based diagnosis.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Detection of Intestinal Tissue Perfusion by Real-Time Breath Methane
           Analysis in Rat and Pig Models of Mesenteric Circulatory Distress
    • Authors: Szucs; Szilárd; Bari, Gábor; Ugocsai, Melinda; Lashkarivand, Reza Ali; Lajkó, Norbert; Mohácsi, Árpád; Szabó, Anna; Kaszaki, József; Boros, Mihály; Érces, Dániel; Varga, Gabriella
      Abstract: imageObjectives: Methane (CH4) breath test is an established diagnostic method for gastrointestinal functional disorders. Our aim was to explore the possible link between splanchnic circulatory changes and exhaled CH4 in an attempt to recognize intestinal perfusion failure.Design: Randomized, controlled in vivo animal study.Setting: University research laboratory.Subjects: Anesthetized, ventilated Sprague-Dawley rats (280 ± 30 g) and Vietnamese minipigs (31 ± 7 kg).Interventions: In the first series, CH4 was administered intraluminally into the ileum before 45 minutes mesenteric ischemia or before reperfusion in non-CH4 producer rats to test the appearance of the gas in the exhaled air. In the porcine experiments, the superior mesenteric artery was gradually obstructed during consecutive, 30-minute flow reductions and 30-minute reperfusions achieving complete occlusion after four cycles (n = 6), or nonocclusive mesenteric ischemia was induced by pericardial tamponade (n = 12), which decreased superior mesenteric artery flow from 351 ± 55 to 182 ± 67 mL/min and mean arterial pressure from 96.7 ± 18.2 to 41.5 ± 4.6 mm Hg for 60 minutes.Measurements and Main Results: Macrohemodynamics were monitored continuously; RBC velocity of the ileal serosa or mucosa was recorded by intravital videomicroscopy. The concentration of exhaled CH4 was measured online simultaneously with high-sensitivity photoacoustic spectroscopy. The intestinal flow changes during the occlusion-reperfusion phases were accompanied by parallel changes in breath CH4 output. Also in cardiac tamponade-induced nonocclusive intestinal ischemia, the superior mesenteric artery flow and RBC velocity correlated significantly with parallel changes in CH4 concentration in the exhaled air (Pearson’s r = 0.669 or r = 0.632, respectively).Conclusions: we report a combination of in vivo experimental data on a close association of an exhaled endogenous gas with acute mesenteric macro- and microvascular flow changes. Breath CH4 analysis may offer a noninvasive approach to follow the status of the splanchnic circulation.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Circulating Secretoneurin Concentrations After Cardiac Surgery: Data From
           the FINNish Acute Kidney Injury Heart Study
    • Authors: Brynildsen; Jon; Petäjä, Liisa; Myhre, Peder L.; Lyngbakken, Magnus N.; Nygård, Ståle; Stridsberg, Mats; Christensen, Geir; Ottesen, Anett H.; Pettilä, Ville; Omland, Torbjørn; Røsjø, Helge
      Abstract: imageObjectives: Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known.Design: Prospective, observational, single-center sub-study of a multicenter study.Setting: Prospective observational study of survival in patients undergoing cardiac surgery.Patients: A total of 619 patients undergoing cardiac surgery.Interventions: Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery.Measurements and Main Results: We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow-up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1–3, 147–206 pmol/L] vs 160 pmol/L [131–193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129–217 pmol/L] vs 143 pmol/L [111–173 pmol/L]; p < 0.001). Secretoneurin concentrations decreased from preoperative to postoperative measurements in survivors, whereas we observed no significant decrease in secretoneurin concentrations among nonsurvivors. Secretoneurin concentrations were weakly correlated with established risk indices. Patients with the highest postoperative secretoneurin concentrations had worse outcome compared with patients with lower secretoneurin concentrations (p < 0.001 by the log-rank test) and postoperative secretoneurin concentrations were associated with time to death in multivariate Cox regression analysis: hazard ratio lnsecretoneurin 2.96 (95% CI, 1.46–5.99; p = 0.003). Adding postoperative secretoneurin concentrations to European System for Cardiac Operative Risk Evaluation II improved patient risk stratification, as assessed by the integrated discrimination index: 0.023 (95% CI, 0.0043–0.041; p = 0.016).Conclusions: Circulating postoperative secretoneurin concentrations provide incremental prognostic information to established risk indices in patients undergoing cardiac surgery.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Targeting CD39 Toward Activated Platelets Reduces Systemic Inflammation
           and Improves Survival in Sepsis: A Preclinical Pilot Study*
    • Authors: Granja; Tiago; Körner, Andreas; Glück, Christian; Hohmann, Jan David; Wang, Xiaowei; Köhler, David; Streißenberger, Ariane; Nandurkar, Harshal H.; Mirakaj, Valbona; Rosenberger, Peter; Peter, Karlheinz; Straub, Andreas
      Abstract: imageObjectives: Sepsis is associated with a systemic inflammatory reaction, which can result in a life-endangering organ dysfunction. Pro-inflammatory responses during sepsis are characterized by increased activation of leukocytes and platelets, formation of platelet-neutrophil aggregates, and cytokine production. Sequestration of platelet-neutrophil aggregates in the microvasculature contributes to tissue damage during sepsis. At present no effective therapeutic strategy to ameliorate these events is available. In this preclinical pilot study, a novel anti-inflammatory approach was evaluated, which targets nucleoside triphosphate hydrolase activity toward activated platelets via a recombinant fusion protein combining a single-chain antibody against activated glycoprotein IIb/IIIa and the extracellular domain of CD39 (targ-CD39).Design: Experimental animal study and cell culture study.Setting: University-based experimental laboratory.Subjects: Human dermal microvascular endothelial cells 1, human platelets and neutrophils, and C57BL/6NCrl mice.Interventions: Platelet-leukocyte-endothelium interactions were evaluated under inflammatory conditions in vitro and in a murine lipopolysaccharide-induced sepsis model in vivo. The outcome of polymicrobial sepsis was evaluated in a murine cecal ligation and puncture model. To evaluate the anti-inflammatory potential of activated platelet targeted nucleoside triphosphate hydrolase activity, we employed a potato apyrase in vitro and in vivo, as well as targ-CD39 and as a control, nontarg-CD39 in vivo.Measurements and Main Results: Under conditions of sepsis, agents with nucleoside triphosphate hydrolase activity decreased platelet-leukocyte-endothelium interaction, transcription of pro-inflammatory cytokines, microvascular platelet-neutrophil aggregate sequestration, activation marker expression on platelets and neutrophils contained in these aggregates, leukocyte extravasation, and organ damage. Targ-CD39 had the strongest effect on these variables and retained hemostasis in contrast to nontarg-CD39 and potato apyrase. Most importantly, targ-CD39 improved survival in the cecal ligation and puncture model to a stronger extent then nontarg-CD39 and potato apyrase.Conclusions: Targeting nucleoside triphosphate hydrolase activity (CD39) toward activated platelets is a promising new treatment concept to decrease systemic inflammation and mortality of sepsis. This innovative therapeutic approach warrants further development toward clinical application.
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Medicine and Intensive Care Training: The Search for the Holy Grail of
           Diversity Within Harmonization
    • Authors: Roux; Damien; Azoulay, Elie; Schwebel, Carole; Terzi, Nicolas; Combes, Alain; Ehrmann, Stephan
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The authors reply
    • Authors: Tisherman; Samuel A.; Spevetz, Antionette; Blosser, Sandralee A.; Brown, Daniel; Chang, Cherylee; Efron, Philip A.; O’Connor, Michael; Sevransky, Jonathan E.; Wessman, Brian T.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Preventing Mental Health Symptoms in Post ICU Patients and Their Family
           Members
    • Authors: Tripathy; Swagata; Kar, Nilamadhab
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The authors reply
    • Authors: Kredentser; Maia S.; Olafson, Kendiss; Sareen, Jitender; Bienvenu, O. Joseph
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • On the Right Track, Finally'
    • Authors: Petitjeans; Fabrice; Leroy, Sandrine; Geloen, Alain; Pichot, Cyrille; Ghignone, Marco; Quintin, Luc
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The authors reply
    • Authors: Morelli; Andrea; Sanfilippo, Filippo; Rehberg, Sebastian; Ertmer, Cristian
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Really Early Enteral Nutrition Reduces Mortality in Patients With Major
           Burn Injury
    • Authors: Feng; Xia; Leng, Baolang
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The author replies
    • Authors: Doig; Gordon S.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Thiamine and Difficulties in Differentiating Type A From B Lactic Acidosis
    • Authors: Patel; Jayshil J.; Bergl, Paul
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • The authors reply
    • Authors: Woolum; Jordan A.; Flannery, Alexander H.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
  • Angiotensin II: Time to Study Starting a Stopped Heart
    • Authors: McCurdy; Michael T.; Khanna, Ashish K.; Busse, Laurence W.
      Abstract: No abstract available
      PubDate: Wed, 01 May 2019 00:00:00 GMT-
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
Home (Search)
Subjects A-Z
Publishers A-Z
Customise
APIs
Your IP address: 18.215.159.156
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-