Outcomes of basic versus advanced prehospital life support in severe pediatric trauma.

OBJECTIVE: The role of basic life support (BLS) vs. advanced life support (ALS) in pediatric trauma is controversial. Although ALS is widely accepted as the gold standard, previous studies have found no advantage of ALS over BLS care in adult trauma. The objective of this study was to evaluate whether ALS transport confers a survival advantage over BLS among severely injured children. METHODS: A retrospective cohort study of data included in the Israeli National Trauma Registry from January 1, 2011, through December 31, 2020 was conducted. All the severely injured children (age < 18 years and injury severity score [ISS] ≥16) were included. Patient survival by mode of transport was analyzed using logistic regression. RESULTS: Of 3167 patients included in the study, 65.1% were transported by ALS and 34.9% by BLS. Significantly more patients transported by ALS had ISS ≥25 as well as abnormal vital signs at admission. The ALS and BLS cohorts were comparable in age, gender, mechanism of injury, and prehospital time. Children transported by ALS had higher in-hospital mortality (9.2% vs. 0.9%, p < 0.001). Following risk adjustment, patients transported by ALS teams were significantly more likely to die than patients transported by BLS (adjusted OR 2.27, 95% CI 1.05-5.41, p = 0.04). Patients with ISS ≥50 had comparable mortality rates in both groups (45.9% vs. 55.6%, p = 0.837) while patients with GCS <9 transported by ALS had higher mortality (25.9% vs. 11.5%, p = 0.019). Admission to a level II trauma center vs. a level I hospital was also associated with increased mortality (adjusted OR 2.78 (95% CI 1.75-4.55, p < 0.001). CONCLUSIONS: Among severely injured children, prehospital ALS care was not associated with lower mortality rates relative to BLS care. Because of potential confounding by severity in this retrospective analysis, further studies are warranted to validate these results.

Unassisted Return of Spontaneous Circulation Following Withdrawal of Life-Sustaining Therapy During Donation After Circulatory Determination of Death in a Child.

OBJECTIVES: To describe the unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child. DESIGN: Case report based on clinical observation and medical record review. SETTING: Community Children's Hospital. PATIENT: Two-year old child. INTERVENTIONS: Following hypoxic-ischemic brain injury, the child was taken to the operating room for withdrawal of life-sustaining treatment during controlled donation after circulatory determination of death. MEASUREMENTS AND MAIN RESULTS: In addition to direct observation by experienced pediatric critical care providers, the child was monitored with electrocardiography, pulse oximetry, and invasive blood pressure via femoral arterial catheter in addition to direct observation by experienced pediatric critical care providers. Unassisted return of spontaneous circulation occurred greater than 2 minutes following circulatory arrest and was accompanied by return of respiration. CONCLUSIONS: We provide the first report of unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child. In our case, return of spontaneous circulation occurred in the setting of controlled donation after circulatory determination of death and was accompanied by return of respiration. Return of spontaneous circulation greater than 2 minutes following circulatory arrest in our patient indicates that 2 minutes of observation is insufficient to ensure that cessation of circulation is permanent after withdrawal of life-sustaining treatment in a child.

Theoretical knowledge and skill retention 3 and 6 months after a European Newborn Life Support provider course.

INTRODUCTION: The European Resuscitation Council Newborn Life Support Course (ERC- NLS) aims at training healthcare professionals, involved in perinatal care, in order to intervene efficiently and promptly to assist transition or resuscitate neonates who require help at birth. However, limited data exists for the retention of the theoretical knowledge and practical skills provided by the course. This study aims to evaluate the degree of knowledge and skill retention 3 and 6 months after the ERC-NLS provider course. METHODS: This is a prospective study. Theoretical knowledge was evaluated using the ERC-approved NLS written test (50 True/False questions). Evaluation of technical skills included performance, on an Advanced Life Support neonatal maniquin (LAERDAL), of airway management, ventilation and support of circulation (21 detailed skills). The effect of certain factors on theoretical skill retention was also evaluated. RESULTS: One hundred and sixteen (n = 116) participants were initially recruited in the study (12 males and 104 females). Theoretical knowledge was evaluated in 113 participants (3 participants missed follow-up appointments) and technical skills in 80 participants. The mean score for theoretical knowledge was 86.24% ± 5.3, 80.88% ± 7.43 and 80.04% ± 7.04 at baseline, at 3 and 6 months, respectively. This difference was significant among the three time points (baseline vs 3 months: p < 0.001; baseline vs 6 months: p < 0.001; 3 month's vs 6 months: p = 0.034). Although gender did not have an effect, doctors and participants of higher education yielded higher score of success. Regarding technical skills, 9 skills showed a continuous decline of performance from baseline to 6 months, while no difference existed for 12 skills. CONCLUSIONS: Healthcare professionals after the NLS provider course retain satisfactory levels of theoretical knowledge and technical skills even at 6 months post-training, although, there is a decline compared to baseline. Further research is needed in order to establish the proper time and type of refreshment course in order to improve outcomes.

Checklist for Early Recognition and Treatment of Acute Illness and Injury: An Exploratory Multicenter International Quality-Improvement Study in the ICUs With Variable Resources.

OBJECTIVES: To determine whether the "Checklist for Early Recognition and Treatment of Acute Illness and Injury" decision support tool during ICU admission and rounding is associated with improvements in nonadherence to evidence-based daily care processes and outcomes in variably resourced ICUs. DESIGN, SETTINGS, PATIENTS: This before-after study was performed in 34 ICUs (15 countries) from 2013 to 2017. Data were collected for 3 months before and 6 months after Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation. INTERVENTIONS: Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation using remote simulation training. MEASUREMENTS AND MAIN RESULTS: The coprimary outcomes, modified from the original protocol before data analysis, were nonadherence to 10 basic care processes and ICU and hospital length of stay. There were 1,447 patients in the preimplementation phase and 2,809 patients in the postimplementation phase. After adjusting for center effect, Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation was associated with reduced nonadherence to care processes (adjusted incidence rate ratio [95% CI]): deep vein thrombosis prophylaxis (0.74 [0.68-0.81), peptic ulcer prophylaxis (0.46 [0.38-0.57]), spontaneous breathing trial (0.81 [0.76-0.86]), family conferences (0.86 [0.81-0.92]), and daily assessment for the need of central venous catheters (0.85 [0.81-0.90]), urinary catheters (0.84 [0.80-0.88]), antimicrobials (0.66 [0.62-0.71]), and sedation (0.62 [0.57-0.67]). Analyses adjusted for baseline characteristics showed associations of Checklist for Early Recognition and Treatment of Acute Illness and Injury implementation with decreased ICU length of stay (adjusted ratio of geometric means [95% CI]) 0.86 [0.80-0.92]), hospital length of stay (0.92 [0.85-0.97]), and hospital mortality (adjusted odds ratio [95% CI], 0.81 (0.69-0.95). CONCLUSIONS: A quality-improvement intervention with remote simulation training to implement a decision support tool was associated with decreased nonadherence to daily care processes, shorter length of stay, and decreased mortality.

Critical Care Management of the Patient With Anaphylaxis: A Concise Definitive Review.

OBJECTIVES: Anaphylaxis is a rapidly progressive life-threatening syndrome manifesting as pruritus, urticaria, angioedema, bronchospasm and shock. The goal of this synthetic review is to provide a practical, updated approach to the evaluation and management of this disorder and associated complications. DATA SOURCES: A MEDLINE search was conducted with the MeSH of anaphylaxis, anaphylactic reaction, anaphylactic shock, refractory anaphylaxis and subheadings of diagnosis, classification, epidemiology, complications and pharmacology. The level of evidence supporting an intervention was evaluated based on the availability of randomized studies, expert opinion, case studies, reviews, practice parameters and other databases (including Cochrane). STUDY SELECTION: Selected publications describing anaphylaxis, clinical trials, diagnosis, mechanisms, risk factors and management were retrieved (reviews, guidelines, clinical trials, case series) and their bibliographies were also reviewed to identify relevant publications. DATA EXTRACTION: Data from the relevant publications were reviewed, summarized and the information synthesized. DATA SYNTHESIS: This is a synthetic review and the data obtained from a literature review was utilized to describe current trends in the diagnosis and management of the patient with anaphylaxis with a special emphasis on newer evolving concepts of anaphylaxis endotypes and phenotypes, management of refractory anaphylaxis in the ICU setting and review of therapeutic options for the elderly patient, or the complicated patient with severe cardiorespiratory complications. Most of the recommendations come from practice parameters, case studies or expert opinions, with a dearth of randomized trials to support specific interventions. CONCLUSION: Anaphylaxis is a rapidly progressive life-threatening disorder. The critical care physician needs to be familiar with the diagnosis, differential diagnosis, evaluation, and management of anaphylaxis. Skilled intervention in ICUs may be required for the patient with complicated, severe, or refractory anaphylaxis.

Outcomes After Extracorporeal Life Support Cannulation in Pediatric Patients With Trisomy 13 and Trisomy 18.

BACKGROUND: Indications for extracorporeal life support (ECLS) have evolved and expanded, yet its use in trisomy 13 (T13) and trisomy 18 (T18) patients remains controversial. We reviewed the experience of the Extracorporeal Life Support Organization with ECLS in these patients to inform practice at our institution. METHODS: The Extracorporeal Life Support Organization registry was queried for all patients younger than 18 y with an International Classification of Diseases, Ninth Edition/Tenth Edition code for T13 or T18 from 2000 to 2018. Basic demographics, ECLS details, and clinical outcomes were recorded. Descriptive statistics were performed. RESULTS: Twenty-eight patients were identified (15 with T13; 13 with T18), representing 0.06% (28 of 46,901) of pediatric ECLS cannulations. The median weight was 3.5 kg (range, 1.4-13), and age at cannulation was 52 d (range, 0 d-6.8 y). Time on ECLS ranged from 13 to 478 h (median, 114). Cardiac defects were diagnosed in 19 (68%) patients, of which 13 (46%) underwent surgical repair. Median oxygenation index pre-ECLS was 45. Venoarterial cannulations accounted for 82% of patients, whereas 14% underwent venovenous cannulation. Overall survival to hospital discharge was 46% with 86% of patients experiencing one or more complications. There were no survivors when cannulation continued past 12 d. CONCLUSIONS: Although complications are frequent, the mortality rate in patients with T13 and T18 remains within the reported range for the general pediatric population. T13 and T18 alone should not be viewed as absolute contraindications to ECLS within the pediatric population but rather considered during the evaluation of a patient's potential candidacy.

Withholding or withdrawing life-sustaining treatment in extremely low gestational age neonates.

OBJECTIVE: To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates. DESIGN: Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22-28 weeks gestation who died >12 hours through 120 days of age during 2011-2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST. RESULTS: Of 1168 deaths, 67.1% occurred following WWLST. Withdrawal of assisted ventilation (97.4%) was the primary modality. WWLST rates were inversely proportional to gestational age. Life-sustaining treatment was withheld or withdrawn more often for non-Hispanic white infants than for non-Hispanic black infants (72.7% vs 60.4%; 95% CI 1.00 to 1.92) or Hispanic infants (72.7% vs 67.2%; 95% CI 1.32 to 3.72). WWLST rates varied across centres (38.6-92.6%; p<0.001). The centre with the highest rate had adjusted odds 4.89 times greater than the average (95% CI 1.18 to 20.18). The adjusted odds of WWLST were higher for infants with necrotiing enterocolitis (OR 1.77, 95% CI 1.21 to 2.59) and severe brain injury (OR 1.98, 95% CI 1.44 to 2.74). CONCLUSIONS: Among infants who died, WWLST rates varied widely across centres and were associated with gestational age, race, ethnicity, necrotiing enterocolitis, and severe brain injury. Further exploration is needed into how race, centre, and approaches to care of infants with necrotiing enterocolitis and severe brain injury influence WWLST.

A randomised trial of the effectiveness of instructor versus automated manikin feedback for training junior doctors in life support skills.

INTRODUCTION: Australian Standards require that clinicians undergo regular training in skills required to respond to the acute deterioration of a patient. Training focuses on the ability to appropriately respond to cardiac arrest, including delivering cardiac compressions, ventilation and appropriate defibrillation. Providing such training comes at a significant cost to the organisation and impacts on clinician time in direct patient care. If effective, the use of an automated manikin could significantly reduce costs and provide consistent training experiences. METHODS: Fifty-six resident medical officers were randomised to two groups to test two skills components of hospital life support training under two feedback conditions. The skills components were cardiac compressions and bag-valve-mask ventilation. The feedback conditions were automated feedback delivered by a simulation manikin and traditional feedback delivered by an instructor. All participants were exposed to both skills components and both feedback conditions in a counterbalanced block design. Participants completed surveys before and after training. RESULTS: The results demonstrated significantly better performance in cardiac compressions under the automated manikin feedback condition compared with the instructor feedback condition. This difference was not observed in bag-valve-mask ventilation. The majority of participants found the automated manikin feedback more useful than the instructor feedback. DISCUSSION: Automated manikin feedback was not inferior to instructor feedback for skill acquisition in cardiac compressions training. The automated feedback condition did not achieve the same level of significance in bag-valve-mask ventilation training. Results suggest training with automated feedback presents a cost-effective opportunity to lessen the training burden, whilst improving skill acquisition.

Application value of artificial liver support system in the treatment of cytokine storm in patients with COVID-19.

OBJECTIVE: To explore the application value of artificial liver support system in the clinical treatment of coronavirus disease 2019 (COVID-19) patients with cytokine storm. METHODS: Six cases of severe or critically severe COVID-19 patients treated in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 22 to February 4, 2020 were recruited, and all of them received artificial liver support treatment. Statistical analysis was carried out on the change of cytokines (TNF-α, IL-10, IL-6, IFN-γ, IL-2, IL-4), inflammation-related indicators (white blood cell, neutrophil, lymphocyte, C-reactive protein and procalcitonin), immune-related indicators (B lymphocyte percentage, natural killer cell percentage, CD3+CD4+CD8 T cell percentage), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 patients before and after treatment, and the proportions of patients with abnormal indicators were analyzed as well. In addition, computed tomography (CT) was used to observe the absorption of pulmonary lesions before and after the artificial liver support treatment. RESULTS: The levels of cytokines (IL-6 and IL-10) were effectively reduced in the 6 patients after treatment with the artificial liver support system. Meanwhile, the proportions of patients with abnormal TNF-α, IL-10, IL-6 and IFN-γ were all decreased (p < 0.05). The levels of inflammation-related indicators including white blood cell, C-reactive protein and procalcitonin, and the proportions of patients with these abnormal indicators were both significantly reduced (p < 0.05). The level of neutrophil was not effectively reduced before and after the treatment, but the proportion was significantly reduced (p < 0.05). However, the abnormality of lymphocyte in the patients was not improved. There was no significant difference in immune-related indicators, AST and ALT before and after the treatment (p > 0.05). CT imaging showed that the artificial liver support treatment contributed to absorption of pulmonary lesions. CONCLUSIONS: The artificial liver support system had a great clinical effect in the treatment of cytokine storm and inflammation in COVID-19 patients, and it could promote the absorption of infected lesions.

Challenges of a simplified opt-out consent process in a neonatal randomised controlled trial: qualitative study of parents' and health professionals' views and experiences.

BACKGROUND: More effective recruitment strategies like alternative approaches to consent are needed to facilitate adequately powered trials. Witholding Enteral feeds Around Transfusion was a multicentre, randomised, pilot trial that compared withholding and continuing feeds around transfusion. The primary clinical outcome was necrotising enterocolitis. The trial used simplified opt-out consent with concise parent information and no consent form. OBJECTIVE: To explore the views and experiences of parents and health professionals on the acceptability and feasibility of opt-out consent in randomised comparative effectiveness trials. METHODS: A qualitative, descriptive interview-based study nested within a randomised trial. Semistructured interview transcripts were analysed using inductive thematic analysis. SETTING: Eleven neonatal units in England. PARTICIPANTS: Eleven parents and ten health professionals with experience of simplified consent. RESULTS: Five themes emerged: 'opt-out consent operationalised as verbal opt-in consent', 'opt-out consent normalises participation while preserving parental choice', 'opt-out consent as an ongoing process of informed choice', 'consent without a consent form' and 'choosing to opt out of a comparative effectiveness trial', with two subthemes: 'wanting "normal care"' and 'a belief that feeding is better'. CONCLUSION: Introducing a novel form of consent proved challenging in practice. The principle of a simplified, opt-out approach to consent was generally considered feasible and acceptable by health professionals for a neonatal comparative effectiveness trial. The priority for parents was having the right to decide about trial participation, and they did not see opt-out consent as undermining this. Describing a study as 'opt-out' can help to normalise participation and emphasise that parents can withdraw consent.

Preference for Aggressive End-of-Life Care among Advanced Cancer Patients in Wuhan, China: A Cross-Sectional Study.

Life-sustaining treatments (LSTs) and end-of-life (EOL) care's goal for prolonging one's life are defined as aggressive EOL care among critically ill patients. They have limited effects and add unnecessary financial burden to advanced cancer patients. A questionnaire survey was conducted to collect information on demographics, disease conditions, preference for LSTs, and goal of EOL care among advanced cancer patients of comprehensive grade-A tertiary hospitals in Wuhan, mainland China. Most patients preferred to accept LSTs when they were in a critical condition, including cardiopulmonary resuscitation (89.9%), mechanical ventilation support (85.7%), nasogastric tube feeding (84.1%), blood transfusion (89.8%), general surgery (87.5%), and hemodialysis (85.8%). Most (88%) preferred prolonging life as the goal of EOL care. Logistic regression showed common influencing factors were participants who completed junior high/high school or below and were financially adequate had higher reference for aggressive EOL care. Patients whose physician had accurately disclosed prognosis; however, showed a decrease trend for aggressive EOL care. Most advanced cancer patients preferred to accept aggressive EOL care. Discussions about prognosis disclosure among physicians and patients should be improved. Education about LSTs' limitations and comfort-oriented care's benefits should be promoted among the advanced cancer patients in mainland China.

Experience of Basic Life Support among King Khalid University Health Profession Students, Southwestern Saudi Arabia.

BACKGROUND: Satisfactory experience about basic life support (BLS) is crucial to ensure rapid and efficient delivery of essential life-saving care during emergency situations. OBJECTIVES: To assess BLS experience among health profession students at King Khalid University (KKU), Southwestern Saudi Arabia. METHODS: A cross-sectional study was conducted on a representative sample of male and female health profession students, during the academic year 2019-2020. A self-reported questionnaire was utilized to collect data about BLS experiences, which included receiving BLS training, reasons for not having BLS training, suggestions to improve BLS training, encountering a situation that required the use of BLS, practicing BLS when needed and reasons for not practicing BLS when needed. RESULTS: Out of 1261 health profession students, 590 received formal BLS training with a prevalence rate of 46.8% (95% CI: 44.0-49.6), and 46.0% of them trained at the university. Important obstacles for non-attendance included busy academic schedule (54.7%) and high cost of the training course (18%). Overall, 84.1% supported integration of BLS training into their college curricula. Almost 26% encountered a situation that required BLS; however, only 32.4% responded. Through multivariate regression, the significant determinant of response was having formal BLS training (aOR = 4.24, 95% CI: 2.38-7.54). The frequent reasons for non-response were lack of adequate BLS knowledge (35.0%), nervousness (22.8%), and that the victim was of opposite sex (9.0%). CONCLUSION: It is recommended that more emphasis should be given to BLS training among undergraduates of health profession colleges in Southwestern Saudi Arabia. It is recommended that BLS training be integrated into health profession college curricula. Including BLS training as a graduation requirement for health profession students might motivate students to attain BLS training courses.

Teaching the Emergency Neurologic Life Support Course at Two Major Hospitals in Phnom Penh, Cambodia.

OBJECTIVE: To determine the effect of offering a subset of the Emergency Neurological Life Support (ENLS) course modules on provider knowledge and self-reported confidence in acute management of neurocritically ill patients in a low-middle income country (LMIC). METHODS: Eight ENLS modules were provided by in-person lecture using English to Khmer translated slides and a medical translator to physicians and nurses of 2 hospitals in Phnom Penh, Cambodia in May 2019. Providers included emergency, neurology, neurologic surgery, and general intensive care. Demographics, pre- and postcourse knowledge of ENLS content areas, and pre- and postcourse confidence in managing neurocritically ill patients were assessed. Data were pooled across both hospitals for analysis. RESULTS: A total of 57 health care providers were approached for participation: 52 (25 physicians, 27 nurses) participated; 45 completed all study instruments. Pre- and postcourse knowledge scores showed no significant differences between providers. Postcourse, 37/45 (82.2%) participants reported that the content had prepared them for acute management of neurocritically ill patients. Satisfaction with module content ranged from 77.8%-80.0% per module. For the 8 modules, a majority of participants agreed that course material had provided them with knowledge and skills to provide acute care for patients' neurologic emergencies (68.4%-88.6%). CONCLUSIONS: Provision of ENLS course module content increased LMIC provider self-reported knowledge and confidence in acute management of neurocritically ill patients immediately postcourse. Tailoring ENLS course presentation to a particular LMIC setting warrants additional investigation, as does the effect of ENLS course training on neurocritically ill patient outcomes in the LMIC setting.

End-of-life care in a pediatric intensive care unit: the impact of the development of a palliative care unit.

BACKGROUND: The purpose of this paper is to describe how end-of-life care is managed when life-support limitation is decided in a Pediatric Intensive Care Unit and to analyze the influence of the further development of the Palliative Care Unit. METHODS: A 15-year retrospective study of children who died after life-support limitation was initiated in a pediatric intensive care unit. Patients were divided into two groups, pre- and post-palliative care unit development. Epidemiological and clinical data, the decision-making process, and the approach were analyzed. Data was obtained from patient medical records. RESULTS: One hundred seventy-five patients were included. The main reason for admission was respiratory failure (86/175). A previous pathology was present in 152 patients (61/152 were neurological issues). The medical team and family participated together in the decision-making in 145 cases (82.8%). The family made the request in 10 cases (9 vs. 1, p = 0.019). Withdrawal was the main life-support limitation (113/175), followed by withholding life-sustaining treatments (37/175). Withdrawal was more frequent in the post-palliative group (57.4% vs. 74.3%, p = 0.031). In absolute numbers, respiratory support was the main type of support withdrawn. CONCLUSIONS: The main cause of life-support limitation was the unfavourable evolution of the underlying pathology. Families were involved in the decision-making process in a high percentage of the cases. The development of the Palliative Care Unit changed life-support limitation in our unit, with differences detected in the type of patient and in the strategy used. Increased confidence among intensivists when providing end-of-life care, and the availability of a Palliative Care Unit may contribute to improvements in the quality of end-of-life care.

Successful use of an artificial placenta-based life support system to treat extremely preterm ovine fetuses compromised by intrauterine inflammation.

BACKGROUND: Ex vivo uterine environment therapy is an experimental intensive care strategy for extremely preterm infants born between 21 and 24 weeks of gestation. Gas exchange is performed by membranous oxygenators connected by catheters to the umbilical vessels. The fetus is submerged in a bath of synthetic amniotic fluid. The lungs remain fluid filled, and pulmonary respiration does not occur. Intrauterine inflammation is strongly associated with extremely preterm birth and fetal injury. At present, there are no data that we are aware of to show that artificial placenta-based systems can be used to support extremely preterm fetuses compromised by exposure to intrauterine inflammation. OBJECTIVE: To evaluate the ability of our ex vivo uterine environment therapy platform to support extremely preterm ovine fetuses (95-day gestational age; approximately equivalent to 24 weeks of human gestation) exposed to intrauterine inflammation for a period of 120 hours, the following primary endpoints were chosen: (1) maintenance of key physiological variables within normal ranges, (2) absence of infection and inflammation, (3) absence of brain injury, and (4) gross fetal growth and cardiovascular function matching that of age-matched in utero controls. STUDY DESIGN: Ten ewes with singleton pregnancies were each given a single intraamniotic injection of 10-mg Escherichia coli lipopolysaccharides under ultrasound guidance 48 hours before undergoing surgical delivery for adaptation to ex vivo uterine environment therapy at 95-day gestation (term=150 days). Fetuses were adapted to ex vivo uterine environment therapy and maintained for 120 hours with constant monitoring of key vital parameters (ex vivo uterine environment group) before being killed at 100-day equivalent gestational age. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, biochemical parameters, inflammatory markers, and microbial load to exclude infection. Ultrasound was conducted at 48 hours after intraamniotic lipopolysaccharides (before surgery) to confirm fetal viability and at the conclusion of the experiments (before euthanasia) to evaluate cardiac function. Brain injury was evaluated by gross anatomic and histopathologic investigations. Eight singleton pregnant control animals were similarly exposed to intraamniotic lipopolysaccharides at 93-day gestation and were killed at 100-day gestation to allow comparative postmortem analyses (control group). Biobanked samples from age-matched saline-treated animals served as an additional comparison group. Successful instillation of lipopolysaccharides into the amniotic fluid exposure was confirmed by amniotic fluid analysis at the time of administration and by analyzing cytokine levels in fetal plasma and amniotic fluid. Data were tested for mean differences using analysis of variance. RESULTS: Six of 8 lipopolysaccharide control group (75%) and 8 of 10 ex vivo uterine environment group fetuses (80%) successfully completed their protocols. Six of 8 ex vivo uterine environment group fetuses required dexamethasone phosphate treatment to manage profound refractory hypotension. Weight and crown-rump length were reduced in ex vivo uterine environment group fetuses at euthanasia than those in lipopolysaccharide control group fetuses (P<.05). There were no biologically significant differences in cardiac ultrasound measurement, differential leukocyte counts (P>.05), plasma tumor necrosis factor α, monocyte chemoattractant protein-1 concentrations (P>.05), or liver function tests between groups. Daily blood cultures were negative for aerobic and anaerobic growth in all ex vivo uterine environment group animals. No cases of intraventricular hemorrhage were observed. White matter injury was identified in 3 of 6 lipopolysaccharide control group fetuses and 3 of 8 vivo uterine environment group fetuses. CONCLUSION: We report the use of an artificial placenta-based system to support extremely preterm lambs compromised by exposure to intrauterine inflammation. Our data highlight key challenges (refractory hypotension, growth restriction, and white matter injury) to be overcome in the development and use of artificial placenta technology for extremely preterm infants. As such challenges seem largely absent from studies based on healthy pregnancies, additional experiments of this nature using clinically relevant model systems are essential for further development of this technology and its eventual clinical application.

Framework to Support the Process of Decision-Making on Life-Sustaining Treatments in the ICU: Results of a Delphi Study.

OBJECTIVES: To develop a consensus framework that can guide the process of decision-making on continuing or limiting life-sustaining treatments in ICU patients, using evidence-based items, supported by caregivers, patients, and surrogate decision makers from multiple countries. DESIGN: A three-round web-based international Delphi consensus study with a priori consensus definition was conducted with experts from 13 countries. Participants reviewed items of the decision-making process on a seven-point Likert scale or with open-ended questions. Questions concerned terminology, content, and timing of decision-making steps. The summarized results (including mean scores) and expert suggestions were presented in the subsequent round for review. SETTING: Web-based surveys of international participants representing ICU physicians, nurses, former ICU patients, and surrogate decision makers. PATIENTS: Not applicable. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: In three rounds, respectively, 28, 28, and 27 (of 33 invited) physicians together with 12, 10, and seven (of 19 invited) nurses participated. Patients and surrogates were involved in round one and 12 of 27 responded. Caregivers were mostly working in university affiliated hospitals in Northern Europe. During the Delphi process, most items were modified in order to reach consensus. Seven items lacked consensus after three rounds. The final consensus framework comprises the content and timing of four elements; three elements focused on caregiver-surrogate communication (admission meeting, follow-up meeting, goals-of-care meeting); and one element (weekly time-out meeting) focused on assessing preferences, prognosis, and proportionality of ICU treatment among professionals. CONCLUSIONS: Physicians, nurses, patients, and surrogates generated a consensus-based framework to guide the process of decision-making on continuing or limiting life-sustaining treatments in the ICU. Early, frequent, and scheduled family meetings combined with a repeated multidisciplinary time-out meeting may support decisions in relation to patient preferences, prognosis, and proportionality.