bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic-Directed Cardiopulmonary Resuscitation Improves Neurologic Outcomes and Mitochondrial Function in the Heart and Brain
Authors: Lautz Andrew J. , Morgan Ryan W. , Karlsson Michael , Mavroudis Constantine D. , Ko Tiffany S. , Licht Daniel J. , Nadkarni Vinay M. , Berg Robert A. , Sutton Robert M. , Kilbaugh Todd J. 
Published: January 2019

Objectives:
Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration—a potential neurotherapeutic target—remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation.

Design:
Randomized preclinical large animal trial.

Setting:
A large animal resuscitation laboratory at a large academic children’s hospital.

Subjects:
Twenty-eight 4-week-old female piglets (8–11 kg).

Interventions:
Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary resuscitation (n = 10; compression depth titrated to aortic systolic pressure of 90 mm Hg, vasopressors titrated to coronary perfusion pressure ≥ 20 mm Hg) or depth-guided cardiopulmonary resuscitation (n = 12; depth 1/3 chest diameter, epinephrine every 4 min). Six animals (sham group) underwent anesthesia and instrumentation without cardiac arrest. The primary outcomes were favorable neurologic outcome (swine Cerebral Performance Category ≤ 2) and mitochondrial maximal oxidative phosphorylation utilizing substrate for complex I and complex II (OXPHOSCI+CII) in the cerebral cortex and hippocampus.

Measurements and Main Results:
Favorable neurologic outcome was more likely with hemodynamic-directed cardiopulmonary resuscitation (7/10) than depth-guided cardiopulmonary resuscitation (1/12; p = 0.006). Hemodynamic-directed cardiopulmonary resuscitation resulted in higher intra-arrest coronary perfusion pressure, aortic pressures, and brain tissue oxygenation. Hemodynamic-directed cardiopulmonary resuscitation resulted in higher OXPHOSCI+CII (pmol oxygen/s × mg/citrate synthase) in the cortex (6.00 ± 0.28 vs 3.88 ± 0.43; p < 0.05) and hippocampus (6.26 ± 0.67 vs 3.55 ± 0.65; p < 0.05) and higher complex I respiration (pmol oxygen/s × mg) in the right (20.62 ± 1.06 vs 15.88 ± 0.81; p < 0.05) and left ventricles (20.14 ± 1.40 vs 14.17 ± 1.53; p < 0.05).

Conclusions:
In a model of asphyxia-associated pediatric cardiac arrest, hemodynamic-directed cardiopulmonary resuscitation increases rates of 24-hour survival with favorable neurologic outcome, intra-arrest hemodynamics, and cerebral and myocardial mitochondrial respiration.
A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury
Authors: Ortega Sterling B. , Pandiyan Poornima , Windsor Jana , Torres Vanessa O. , Selvaraj Uma M. , Lee Amy , Morriss Michael , Tian Fenghua , Raman Lakshmi , Stowe Ann M. 
Published: January 2019

Objectives:
Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

Design:
A single center prospective observational study.

Setting:
Pediatric and cardiac ICUs at a single tertiary care, academic center.

Patients:
Twenty pediatric extracorporeal membrane oxygenation patients (0–14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients

Interventions:
None.

Measurements and Main Results:
Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10–23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p < 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation.

Conclusions:
We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS.
Incidence, Risk Factors, and Outcomes of Intra-Abdominal Hypertension in Critically Ill Patients—A Prospective Multicenter Study (IROI Study)
Authors: Reintam Blaser Annika , Regli Adrian , De Keulenaer Bart , Kimball Edward J. , Starkopf Liis , Davis Wendy A. , Greiffenstein Patrick , Starkopf Joel 
Published: January 2019

Objectives:
To identify the prevalence, risk factors, and outcomes of intra-abdominal hypertension in a mixed multicenter ICU population.

Design:
Prospective observational study.

Setting:
Fifteen ICUs worldwide.

Patients:
Consecutive adult ICU patients with a bladder catheter.

Interventions:
None.

Measurements and Main Results:
Four hundred ninety-one patients were included. Intra-abdominal pressure was measured a minimum of every 8 hours. Subjects with a mean intra-abdominal pressure equal to or greater than 12 mm Hg were defined as having intra-abdominal hypertension. Intra-abdominal hypertension was present in 34.0% of the patients on the day of ICU admission (159/467) and in 48.9% of the patients (240/491) during the observation period. The severity of intra-abdominal hypertension was as follows: grade I, 47.5%; grade II, 36.6%; grade III, 11.7%; and grade IV, 4.2%. The severity of intra-abdominal hypertension during the first 2 weeks of the ICU stay was identified as an independent predictor of 28- and 90-day mortality, whereas the presence of intra-abdominal hypertension on the day of ICU admission did not predict mortality. Body mass index, Acute Physiology and Chronic Health Evaluation II score greater than or equal to 18, presence of abdominal distension, absence of bowel sounds, and positive end-expiratory pressure greater than or equal to 7 cm H2O were independently associated with the development of intra-abdominal hypertension at any time during the observation period. In subjects without intra-abdominal hypertension on day 1, body mass index combined with daily positive fluid balance and positive end-expiratory pressure greater than or equal to 7 cm H2O (as documented on the day before intra-abdominal hypertension occurred) were associated with the development of intra-abdominal hypertension during the first week in the ICU.

Conclusions:
In our mixed ICU patient cohort, intra-abdominal hypertension occurred in almost half of all subjects and was twice as prevalent in mechanically ventilated patients as in spontaneously breathing patients. Presence and severity of intra-abdominal hypertension during the observation period significantly and independently increased 28- and 90-day mortality. Five admission day variables were independently associated with the presence or development of intra-abdominal hypertension. Positive fluid balance was associated with the development of intra-abdominal hypertension after day 1.
A Prognostic Enrichment Strategy for Selection of Patients With Acute Respiratory Distress Syndrome in Clinical Trials
Authors: Villar Jesús , Ambrós Alfonso , Mosteiro Fernando , Martínez Domingo , Fernández Lorena , Ferrando Carlos , Carriedo Demetrio , Soler Juan A. , Parrilla Dácil , Hernández Mónica , Andaluz-Ojeda David , Añón José M. , Vidal Anxela , González-Higueras Elena , Martín-Rodríguez Carmen , Díaz-Lamas Ana M. , Blanco Jesús , Belda Javier , Díaz-Domínguez Francisco J. , Rico-Feijoó Jesús , Martín-Delgado Carmen , Romera Miguel A. , González-Martín Jesús M. , Fernández Rosa L. , Kacmarek Robert M. 
Published: January 2019

Objectives:
Incomplete or ambiguous evidence for identifying high-risk patients with acute respiratory distress syndrome for enrollment into randomized controlled trials has come at the cost of an unreasonable number of negative trials. We examined a set of selected variables early in acute respiratory distress syndrome to determine accurate prognostic predictors for selecting high-risk patients for randomized controlled trials.

Design:
A training and testing study using a secondary analysis of data from four prospective, multicenter, observational studies.

Setting:
A network of multidisciplinary ICUs.

Patients:
We studied 1,200 patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation.

Interventions:
None.

Measurements and Main Results:
We evaluated different thresholds for patient’s age, Pao
2/Fio
2, plateau pressure, and number of extrapulmonary organ failures to predict ICU outcome at 24 hours of acute respiratory distress syndrome diagnosis. We generated 1,000 random scenarios as training (n = 900, 75% of population) and testing (n = 300, 25% of population) datasets and averaged the logistic coefficients for each scenario. Thresholds for age (< 50, 50–70, > 70 yr), Pao
2/Fio
2 (≤ 100, 101–150, > 150 mm Hg), plateau pressure (< 29, 29–30, > 30 cm H2O), and number of extrapulmonary organ failure (< 2, 2, > 2) stratified accurately acute respiratory distress syndrome patients into categories of risk. The model that included all four variables proved best to identify patients with the highest or lowest risk of death (area under the receiver operating characteristic curve, 0.86; 95% CI, 0.84–0.88). Decision tree analyses confirmed the accuracy and robustness of this enrichment model.

Conclusions:
Combined thresholds for patient’s age, Pao
2/Fio
2, plateau pressure, and extrapulmonary organ failure provides prognostic enrichment accuracy for stratifying and selecting acute respiratory distress syndrome patients for randomized controlled trials.
Six Hours of Manual Ventilation With a Bag-Valve-Mask Device Is Feasible and Clinically Consistent
Authors: Halpern Pinchas , Dang Tru , Epstein Yoram , Van Stijn–Bringas Dimitriades Diana , Koenig Kristi L. 
Published: January 2019

Objectives:
Manual ventilation of intubated patients is a common intervention. It requires skill as well as physical effort and is typically restricted to brief periods. Prolonged manual ventilation may be unavoidable in some scenarios, for example, extreme mass casualty incidents. The present study tested whether nurses are capable of appropriately manually ventilating patients for 6 hours.

Design:
Volunteers performed ventilation on an electronic simulator for 6 hours while their own cardiorespiratory variables and the quality of the delivered ventilation were measured and recorded. The volunteers scored their perceived level of effort on a standard Borg Scale.

Setting:
Research laboratory at the Emergency Department, Tel Aviv Medical Center.

Subjects:
Ten nursing staff members of the Tel Aviv Sourasky Medical Center, 25–43 years old.

Interventions:
Volunteers ventilated manually a lung simulator for 6 hours.

Measurements and Main Results:
The subjects’ physiologic states, including blood pressure, heart rate, respiratory rate, and oxygen saturation, showed no significant changes over time. The quality of delivered ventilation was somewhat variable, but it was stable on the average: average tidal volume ranged between 524.8 and 607.0 mL (p = 0.33). There was a slight but significant increase (7.3–10.9 L/min [p = 0.048]) in minute volume throughout the test period, reaching values consistent with mild hyperventilation. The subjects scored their perceived working effort as very light to fairly light, with a nonsignificant gradual increase in the Borg score as the study progressed.

Conclusions:
Manual ventilation of intubated patients can be performed continuously for 6 hours without excessive physical effort on the part of the operator. The quality of delivered ventilation was clinically adequate for all of them. There was a mild but significant trend toward hyperventilation, albeit within safe clinical levels, which was due to an increasing ventilatory rate rather than an increase in tidal volume.
Transvenous Renal Biopsy of Critically Ill Patients: Safety and Diagnostic Yield
Authors: de Chambrun Marc Pineton , Cluzel Philippe , Brocheriou Isabelle , Bréchot Nicolas , Hékimian Guillaume , Turki Mohamed-Wafik , Franchineau Guillaume , Rouvier Philippe , Bourcier Simon , Bureau Côme , Nieszkowska Ania , Le Guennec Loïc , Mathian Alexis , Amoura Zahir , Schmidt Matthieu , Combes Alain , Luyt Charles-Edouard 
Published: January 2019

Objectives:
Transvenous renal biopsy is an alternative way to obtain kidney samples from patients with bleeding risk factors (e.g., antiplatelet therapy and anticoagulation or coagulation disorders). This study was undertaken to determine the safety and diagnostic yield of transvenous renal biopsy of critically ill patients.

Design:
Monocenter, retrospective, observational cohort study.

Setting:
A 26-bed French tertiary ICU.

Patients:
All patients undergoing in-ICU transvenous renal biopsy between January 2002 and February 2018.

Interventions:
None.

Measurements and Main Results:
Eighty patients (male/female sex ratio, 0.95; mean ± sd age, 47.3 ± 18.3 yr) were included. A histologic diagnosis was obtained for 77 patients (96.3%), with acute tubular necrosis being the most frequent: 23 (29.9%). A potentially treatable cause was found for 47 patients (58.7%). The numbers of patients with 0, 1, 2, or 3 factors (i.e., antiplatelet therapy, thrombopenia [< 150 G/L], and preventive or curative anticoagulation) at the time of the biopsy were, respectively: seven (8.8%), 37 (46.2%), 31 (38.7%), and five (6.3%). Four (5%) and two (2.5%) patients, respectively, had renal hematoma and macroscopic hematuria; none required any specific treatment. Six patients (7.5%) died in-ICU, and 90-day mortality was 8 of 80 (10%). No death was related to transvenous renal biopsy, and median biopsy-to-death interval was 38 days (interquartile range, 19.7–86 d).

Conclusions:
Based on this cohort of ICU patients with acute kidney injury, transvenous renal biopsy was safe and obtained a high diagnostic yield for these selected critically ill patients, even in the presence of multiple bleeding risk factors.
Continuous Electroencephalography After Moderate to Severe Traumatic Brain Injury
Authors: Lee Hyunjo , Mizrahi Moshe A. , Hartings Jed A. , Sharma Sameer , Pahren Laura , Ngwenya Laura B. , Moseley Brian D. , Privitera Michael , Tortella Frank C. , Foreman Brandon 
Published: January 2019

Objectives:
After traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.

Design:
Post hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID2566 study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as “ictal-interictal continuum”; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures.

Setting:
Twenty U.S. level I trauma centers.

Patients:
Patients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4–12 were included.

Interventions:
None.

Measurements and Main Results:
Among 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30–9.09), absence of N2 sleep transients (3.69; 1.69–8.20), predominant delta activity (2.82; 1.32–6.10), and discontinuous background (5.33; 2.28–12.96) within the first 72 hours of monitoring.

Conclusions:
Severe ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.
Evolution and Impact of Thrombocytopenia in Septic Shock: A Retrospective Cohort Study
Authors: Menard Chantalle E. , Kumar Anand , Houston Donald S. , Turgeon Alexis F. , Rimmer Emily , Houston Brett L. , Doucette Steven , Zarychanski Ryan 
Published: January 2019

Objectives:
To characterize the prevalence, incidence, and temporal evolution of thrombocytopenia (platelets < 100 × 109/L) in septic shock and to investigate the independent association of thrombocytopenia on clinical outcomes.

Design:
Retrospective, propensity-matched, cohort study.

Setting:
Two academic ICUs in Winnipeg, Canada.

Patients:
Nine-hundred eighty adult patients diagnosed with septic shock between 2007 and 2012.

Interventions:
Propensity-matched cohort analysis and Cox proportional hazard model evaluating thrombocytopenia over time.

Measurements and Main Results:
Of 980 adults, 165 patients (16.8%) had thrombocytopenia at ICU admission (prevalent), whereas 271 (27.7%) developed thrombocytopenia during ICU admission (incident). Among patients with incident thrombocytopenia, the median time from ICU admission to thrombocytopenia was 2 days (interquartile range, 1–3 d). Among survivors, the median time from incident thrombocytopenia to platelet recovery was 6 days (interquartile range, 4–8 d). The median time from liberation of vasopressors to recovery of platelets concentration (≥ 100 × 109/L) was 2 days (interquartile range, 0–4 d). In a propensity-matched analysis, thrombocytopenia was associated with increased durations of ICU length of stay (9 vs 6 d; p < 0.01), mechanical ventilation (7 vs 4 d; p < 0.01), and vasopressor use (4 vs 3 d; p < 0.01), as well as increased major bleeding events (41% vs 18%; p < 0.01). In an adjusted Cox proportional hazards model, thrombocytopenia was significantly associated with both increased ICU mortality (hazard ratio, 1.99; 95% CI, 1.51–2.63) and hospital mortality (hazard ratio, 1.93; 95% CI, 1.48–2.51).

Conclusions:
Both the prevalence and incidence of thrombocytopenia are high in septic shock. Incident thrombocytopenia occurs early in septic shock, and platelet recovery lags behind clinical recovery. In septic shock, thrombocytopenia is associated with increased length of stay, longer duration of organ support, major bleeding events, and mortality.
A Fate Worse Than Death: Prognostication of Devastating Brain Injury
Authors: Pratt Alexandra K. , Chang Jason J. , Sederstrom Nneka O. 
Published: January 2019

Objectives:To describe the sources of uncertainty in prognosticating devastating brain injury, the role of the intensivist in prognostication, and ethical considerations in prognosticating devastating brain injury in the ICU.Data Sources:A PubMed literature review was performed.Study Selection:Articles relevant to prognosis in intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and postcardiac arrest anoxic encephalopathy were selected.Data Extraction:Data regarding definition and prognosis of devastating brain injury were extracted. Themes related to how clinicians perform prognostication and their accuracy were reviewed and extracted.Data Synthesis:Although there are differences in pathophysiology and therefore prognosis in the various etiologies of devastating brain injury, some common themes emerge. Physicians tend to have fairly good prognostic accuracy, especially in severe cases with poor prognosis. Full supportive care is recommended for at least 72 hours from initial presentation to maximize the potential for recovery and minimize secondary injury. However, physician approaches to the timing of and recommendations for withdrawal of life-sustaining therapy have a significant impact on mortality from devastating brain injury.Conclusions:Intensivists should consider the modern literature describing prognosis for devastating brain injury and provide appropriate time for patient recovery and for discussions with the patient’s surrogates. Surrogates wish to have a prognosis enumerated even when uncertainty exists. These discussions must be handled with care and include admission of uncertainty when it exists. Respect for patient autonomy remains paramount, although physicians are not required to provide inappropriate medical therapies.