Immediate mobilization in post-anesthesia care unit does not increase overall postoperative physical activity after elective colorectal surgery: A randomized, double-blinded controlled trial within an enhanced recovery protocol.

BACKGROUND: The level of post-operative mobilization according to Enhanced Recovery After Surgery (ERAS) guidelines is not always achieved. We investigated whether immediate mobilization increases postoperative physical activity. The objective was to evaluate the effects of immediate postoperative mobilization in the post-anesthesia care unit (PACU) compared to standard care. METHODS: This randomized controlled trial, involved 144 patients, age ≥18 years, undergoing elective colorectal surgery. Patients were randomized to mobilization starting 30 min after arrival in the PACU, or to standard care. Standard care consisted of mobilization a few hours later at the ward according to ERAS guidelines. The primary outcome was physical activity, in terms of number of steps, measured with an accelerometer during postoperative days (PODs) 1-3. Secondary outcomes were physical capacity, functional mobility, time to readiness for discharge, complications, compliance with the ERAS protocol, and physical activity 1 month after surgery. RESULTS: With the intention-to-treat analysis of 144 participants (median age 71, 58% female) 47% underwent laparoscopic-or robotic-assisted surgery. No differences in physical activity during hospital stay were found between the participants in the intervention group compared to the standard care group (adjusted mean ratio 0.97 on POD 1 [95% CI, 0.75-1.27], p = 0.84; 0.89 on POD 2 [95% CI, 0.68-1.16], p = 0.39, and 0.90 on POD 3 [95% CI, 0.69-1.17], p = 0.44); no differences were found in any of the other outcome measures. CONCLUSIONS: Addition of the intervention of immediate mobilization to standard care did not make the patients more physically active during their hospital stay. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NTC 03357497.

An exploration of students' use of digital resources for self-study in anatomy: a survey study.

BACKGROUND: The development of technology has provided new ways for active engagement and for visualizing structures in anatomy education including digital resources that may be used outside of the classroom. To support students' learning, there is a need to better understand students' experiences of using digital resources. This study aimed to identify which resources students use, their preferences, the purpose of using them, and barriers to adopting tools for self-study of anatomy. METHODS: A mixed -methods approach combining qualitative and quantitative data was used to collect and analyse data. Two consecutive cohorts of first-semester medical students (n = 278) were invited to complete an anonymized survey. The survey consisted of itemized questions, free-text space for comments, and one open-ended question. Descriptive statistics were used for demographics and itemized answers. Comments and free-text answers were analysed qualitatively using abductive inference. RESULTS: One hundred and twenty-seven students completed the survey (response rate 45%). Most students (46%) reported that they spend more than 30 h/per week on self-study. They used a variety of digital resources for different purposes. Most students used digital resources to prepare for examinations, when they encountered difficulties and after going through a section. Students reported that they would use digital resources to a greater extent if they were offered an introduction, if resources were more accessible, and if they could interact with a tutor. The free-text responses revealed that digital resources helped students understand anatomy, allowed them to make active choices, provided tools for repetition and memorization, accelerated and simplified the learning process, and complemented other learning resources. CONCLUSIONS: Digital resources may support the understanding of anatomy by offering alternative modes of learning and providing a valuable complement to other learning resources. Educators should consider how digital resources are introduced and offer support and feedback.

Nurse anaesthetists' experiences of student nurse anaesthetist learning during clinical practice: a qualitative interview study.

BACKGROUND: The professional role of a nurse anaesthetist involves taking a pedagogical approach towards students, including supervision during clinical practice. Although supervisors are facilitators of student learning, they are offered little training in adult learning principles. The aim of this study was to describe supervisors' experience of student nurse anaesthetist learning during clinical practice in the operating room. METHOD: In this qualitative interview study, 12 semi-structured individual interviews were carried out with clinical supervising nurse anaesthetists. The data were analysed inductively using thematic analysis. RESULTS: The results are illustrated with one theme and five sub-themes. The clinical learning situation of student nurse anaesthetists is described as a reflection of different cultures coming together. The operating room environment is a new context to students, and students enter with different clinical background and experiences. There is tension in facilitating student learning due to demands for productivity; supervisors suggest the use of separate operating rooms with a special focus on learning in the future. CONCLUSION: Clinical practice facilitates student learning and is a parallel process to routine care. Thus, it requires the cultures of higher education and healthcare organizations to co-exist. This is illustrated with the theme "Contributing to students' future professional roles by bridging the hospital and university cultures". In the operating room, student learning is challenged by a new context and time pressure as shown by subthemes. To overcome challenges and support student learning in the operating room from a supervisors' perspective, interprofessional student teams are suggested as a future approach and need to be further investigated.

Student Nurse Anesthetists' and Supervisors' Perspectives of Learning in the Operating Room: An Integrative Review.

PURPOSE: The purpose of this review was to identify supporting and hindering factors for student nurse anesthetists' (SNAs') learning in the operating room during clinical practice, from students' and supervisors' perspectives. DESIGN: An integrative review. METHODS: Systematic searches were conducted in Medline, Cinahl, PsycInfo, and ERIC. Search terms were related to nurse anesthetist, education, operating room context, and clinical setting. Searches were performed at three points in time and in total 1,530 unique articles were identified. After screening using Covidence and using Joanna Briggs Institute appraisal tools, 34 articles remained. These were analyzed inductively using a constant comparison method. FINDINGS: Supporting factors include preparation before clinical practice, clearly stated expectations, a respectful relationship with the supervisor, daily planning and communication, and constructive feedback. Hindering factors include lack of time, disruptive behavior from supervisors or other team members, and environmental factors such as a high room temperature and noisy environment. CONCLUSIONS: SNAs' learning situation in the operating room resembles undergraduate nurses' learning during clinical practice. Educators and supervisors can take several actions to promote SNAs' learning. Further research is warranted on the effect of teamwork on SNAs' learning.

Entrustable professional activities (EPAs) for undergraduate medical education - development and exploration of social validity.

BACKGROUND: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders. AIM: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs. METHOD AND MATERIAL: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater's perception of the present graduates' required level of supervision when performing the activity. Free-text comments were also included and analyzed. RESULTS: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as "important" by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported "independent". The three themes of the free text comments were: 'relevant target areas and content'; 'definition of the activities'; and 'clinical practice and learning'. CONCLUSION: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.

Supervised Immediate Postoperative Mobilization After Elective Colorectal Surgery: A Feasibility Study.

BACKGROUND: Early mobilization is a significant part of the ERAS® Society guidelines, in which patients are recommended to spend 2 h out of bed on the day of surgery. However, it is not yet known how early patients can safely be mobilized after completion of colorectal surgery. The aim of this study was to evaluate the feasibility, and safety of providing almost immediate structured supervised mobilization starting 30 min post-surgery at the postoperative anesthesia care unit (PACU), and to describe reactions to this approach. METHODS: This feasibility study includes 42 patients aged ≥18 years who received elective colorectal surgery at Örebro University Hospital. They underwent a structured mobilization performed by a specialized physiotherapist using a modified Surgical ICU Optimal Mobilization Score (SOMS). SOMS determines the level of mobilization at four levels from no activity to ambulating. Mobilization was considered successful at SOMS ≥ 2, corresponding to sitting on the edge of the bed as a proxy of sitting in a chair due to lack of space. RESULTS: In all, 71% (n = 30) of the patients reached their highest level of mobilization between the second and third hour of arrival in the PACU. Before discharge to the ward, 43% (n = 18) could stand at the edge of the bed and 38% (n = 16) could ambulate. Symptoms that delayed advancement of mobilization were pain, somnolence, hypotension, nausea, and patient refusal. No serious adverse events occurred. CONCLUSIONS: Supervised mobilization is feasible and can safely be initiated in the immediate postoperative care after colorectal surgery. Trial registration Clinical trials.gov identifier: NTC03357497.

Three-dimensional visualisation of authentic cases in anatomy learning - An educational design study.

BACKGROUND: Many studies have investigated the value of three-dimensional (3D) images in learning anatomy. However, there is a lack of knowledge about students learning processes using technology and 3D images. To understand how to facilitate and support the learning of anatomy, there is a need to know more about the student perspectives on how they can use and benefit from 3D images. METHODS: This study used designed educational sessions informed by Educational Design Research to investigate the role of technology-enhanced 3D images in students' anatomy learning. Twenty-four students representing different health professions and multiple study levels, and one tutor, participated in the study. A visualisation table was used to display the images of real patient cases related to disorders associated with the abdomen and the brain. Students were asked to explore the images on their own and audio/video capture was used to record their words and actions. Directly following the session, students were interviewed about their perceptions and different ways of learning and studying anatomy. The tutor was interviewed about his reflections on the session and his role as a facilitator on two occasions. Content analysis was used in its manifest and latent form in the data analysis. RESULT: Two main categories describing the students' and tutor's accounts of learning using the visualisation table were identified: 1. Interpreting 3D images and 2. Educational sessions using visualisation tables. Each category had signifying themes representing interpretations of the latent meaning of the students' and tutor's accounts. These were: Realism and complexity; Processes of discernment; References to previous knowledge; Exploring on one's own is valuable; Context enhances learning experiences; Combinations of learning resources are needed and Working together affects the dynamics. CONCLUSIONS: This study identifies several important factors to be considered when designing effective and rewarding educational sessions using a visualization table and 3D images in anatomy education. Visualisation of authentic images has the potential to create interest and meaningfulness in studying anatomy. Students need time to actively explore images but also get tutor guidance to understand. Also, a combination of different resources comprises a more helpful whole than a single learning resource.

Bronchially instilled IgY-antibodies did not decrease pulmonary p. aeruginosa concentration in experimental porcine pneumonia.

BACKGROUND: P. aeruginosa possesses antibiotic resistance, making treatment difficult. Polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) have antibacterial effects, but have not been studied in large animal pneumonia. OBJECTIVES: To test if Pa-IgY decreases the concentration of P. aeruginosa in bronchoalveolar lavage in experimental porcine pneumonia over 27 hours. METHOD: Norwegian landrace pigs were anesthetized, mechanically ventilated, and subject to invasive monitoring. The animals were randomized to receive either P. aeruginosa (control, n = 12) or P aeruginosa + Pa-IgY antibodies with a repeated dose of Pa-IgY after 12 hours (intervention, n = 12) in the right lower pulmonary lobe. Bronchoalveolar lavage (BAL) cultures and physiological measurements were obtained repeatedly for 27 hours after which the pigs were sacrificed. RESULTS: BAL bacterial concentration increased in both groups and peaked at 107.28  ± 100.21  CFU/mL in the intervention group vs 107 .36  ± 100.50  CFU/mL in the control group (n.s.). BAL bacterial concentration decreased during the experiment to 105.35  ± 100 .39  CFU/mL in the intervention group vs 105.19  ± 100.37 in the control group (n.s.). The intervention group had lower heart rate (P < .001), lower cardiac index (P < .01), and lower arterial lactate (P < .001) compared to the control group. The core temperature was lower in the intervention group than in the control group (P < .001). CONCLUSION: The chosen dose of Pa-IgY did not decrease concentrations of P. aeruginosa in BAL over 27 hours. We conclude that it is unlikely that there is a large effect of this specific dose and route of administration of Pa-IgY in this type of model.

Get it together: Issues that facilitate collaboration in teams of learners in intensive care.

INTRODUCTION: The study describes issues that facilitate collaboration in teams of learners in an interprofessional education unit in intensive care. METHODS: A descriptive qualitative study design was applied using semi-structured interviews based on the critical incident technique and qualitative content analysis. Nineteen participants, eight learners in their specialist training, nine supervisors and two head supervisors in Sweden identified 47 incidents. RESULT: Teams of learners having control was the core issue. Motivation, time, experiences and reflection were central issues for facilitating collaboration. CONCLUSION: Efficiently training teams how to collaborate requires learners having control while acting on their common understanding and supervisors taking a facilitating role supporting teams to take control of their critical analysis.

Exploring teams of learners becoming "WE" in the Intensive Care Unit--a focused ethnographic study.

BACKGROUND: Research about collaboration within teams of learners in intensive care is sparse, as is research on how the learners in a group develop into a team. The aim of this study was to explore the collaboration in teams of learners during a rotation in an interprofessional education unit in intensive care from a sociocultural learning perspective. METHODS: Focused Ethnographic methods were used to collect data following eight teams of learners in 2009 and 2010. Each team consisted of one resident, one specialist nurse student and their supervisors (n = 28). The material consisted of 100 hours of observations, interviews, and four hours of sound recordings. A qualitative analysis explored changing patterns of interplay through a constant comparative approach. RESULTS: The learners' collaboration progressed along a pattern of participation common to all eight groups with a chronological starting point and an end point. The progress consisted of three main steps where the learners' groups developed into teams during a week's training. The supervisors' guided the progress by gradually stepping back to provide latitude for critical reflection and action. CONCLUSION: Our main conclusion in training teams of learners how to collaborate in the intensive care is the crucial understanding of how to guide them to act like a team, feel like a team and having the authority to act as a team.

How students discern anatomical structures using digital three-dimensional visualizations in anatomy education.

Learning anatomy holds specific challenges, like the appreciation of three-dimensional relationships between anatomical structures. So far, there is limited knowledge about how students construct their understanding of topographic anatomy. By understanding the processes by which students learn anatomical structures in 3D, educators will be better equipped to offer support and create successful learning situations. Using video analysis, this study investigates how students discern anatomical structures. Sixteen students at different levels of education and from different study programs were recorded audiovisually while exploring 3D digital images using a computerized visualization table. Eleven hours of recorded material were analyzed using interaction analysis and phenomenography. Seven categories were identified during data analysis, describing the qualitatively different patterns of actions that students use to make sense of anatomy: decoding the image; positioning the body in space; purposeful seeking, using knowledge and experience; making use of and creating variation; aimless exploration, and arriving at moments of understanding. The results suggest that anatomy instruction should be organized to let the students decide how and at what pace they examine visualized images. Particularly, the discovery process of decoding and positioning the body in space supports a deep learning approach for learning anatomy using visualizations. The students' activities should be facilitated and not directed.

Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.

Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell-associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH.

Epidural analgesia and mortality after colorectal cancer surgery: A retrospective cohort study.

BACKGROUND: Epidural analgesia (EA) has been the standard of care after major abdominal surgery for many years. This study aimed to correlate EA with postoperative complications, short- and long-term mortality in patients with and without EA after open surgery (OS) and minimally invasive surgery (MIS) for colorectal cancer. METHODS: Patient, clinical and outcome data were obtained from the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry. All adult patients diagnosed with colorectal cancer without metastases who underwent elective curative MIS or OS for colorectal cancer between January 2016 and December 2018 and who had data recorded in both registries, were included in the study. Data were analyzed for OS and MIS procedures separately. A Poisson regression model was used to investigate the association between EA and the outcomes of interest. RESULTS: Five thousand seven hundred sixty-two patients were included in the study, 2712 in the MIS and 3050 patients in the OS group. After adjusting for patient specific and clinically relevant variables in the regression model, no statistically significant difference in risk for complications; 30-day, 90-day, and up to 3-year mortality following either MIS or OS could be detected between the EA+ and EA-cohorts. CONCLUSIONS: In this large study cohort, EA as part of the comprehensive care provided was not associated with a reduction in postoperative complications risk or improved 30-day, 90-day, or 3-year survival after MIS or OS for colorectal cancer.

Authenticity made visible in medical students' experiences of feeling like a doctor.

OBJECTIVES: To interpret the phenomenon of authenticity made visible in medical students' experiences of feeling like a doctor, i.e., how authenticity took shape in narratives about feeling like a doctor in clinical situations where students were challenged to be independent and to a high degree make choices and clinical decisions. METHODS: The conducted research was positioned within phenomenological hermeneutic research tradition, interpreting participants' experiences in a life-world perspective using narrative inquiry. Fifteen medical students in their fifth year were interviewed focusing on clinical situations. An abductive analysis approach was used to discover patterns and to interpret data following a phenomenological hermeneutic research method for textual interpretation. RESULTS: The analysis resulted in a thematic structure of findings: Opportunity to experience authenticity through creating relationships; Opportunity to experience authenticity through responsibility; Opportunity to experience authenticity through independence, managing wholeness, and follow-up processes; Opportunity to experience authenticity through being able to reason and discern. Overarching the four themes was the perceived need for attachment, i.e. attachment to patients, to supervisors, to the workplace, to the situation and reasoning and knowledge. CONCLUSIONS: Essential for the experience of feeling like a doctor was authentic situations that resulted in the experienced members of a community of practice and the perceived development of a professional identity. These findings can advance the understanding of how clinical education should be organized to facilitate professional identity development.

[Interprofessional simulation: an engaging and relevant technique for teamwork practice]. / Interprofessionell simulering är engagerande och relevant - Utbildningsstrategi som tränar samverkan över yrkesgränser, visar enkätstudie.

Stakeholders in healthcare and education find interprofessional teamwork to be crucial for today's complex healthcare. Consequently, the students need to prepare for future collaboration with other professions. Interprofessional simulation (IPS) is a technique in which several professions can engage together in clinical scenarios. Using a survey we studied the perceived relevance of two IPS settings in which last-year medical and nursing students participated in acute care scenarios. The findings showed that students perceive IPS as being highly relevant and that students from the other profession contributed to their learning. IPS holds promise as a pedagogical tool towards future interprofessional competence. However, pedagogical improvements can be made, and the professional perspectives can be better balanced. Furthermore, in order to equip students with broader interprofessional competence, scenarios should include several professions and a variety of clinical contexts.

Elevated ferritin and soluble CD25 in critically ill patients are associated with parameters of (hyper) inflammation and lymphocyte cytotoxicity.

BACKGROUND: Critically ill patients may develop a potentially fatal hyperinflammatory condition known as secondary (acquired) hemophagocytic lymphohistiocytosis (sHLH), the cause of which is unclear. We evaluated serum ferritin and soluble CD25 (sCD25) in critically ill patients, and their association with other parameters of inflammation and critical illness. Moreover, aiming to better understand the pathogenesis of sHLH, we also evaluated lymphocyte cytotoxicity parameters and correlations with the inflammatory markers ferritin and sCD25. METHODS: In a prospective observational study, 32 patients with ferritin ≥500 µg/L (24 with sepsis) were studied on admission to an intensive care unit (ICU) with regard to ferritin and corresponding clinical and laboratory features including sCD25, and detailed lymphocyte cytotoxicity and genetic analyses whenever possible. RESULTS: Critically ill patients had elevated, positively correlated levels of serum ferritin and sCD25 (rs=0.465, P=0.008); both associated with other risk factors of poor outcome in critically ill, such as thrombocytopenia (rs=-0.534, P=0.002 and rs=-0.421, P=0.018, respectively), and sCD25 with hypoalbuminemia (rs=-0.678, P<0.001) and life support treatments (rs=0.479, P=0.006). Interestingly, ferritin levels were inversely associated with natural killer (NK)-cell cytotoxicity (rs=-0.462, P=0.047) and degranulation (rs=-0.504, P=0.030). Moreover, of four patients with abnormally low cytotoxicity, three (75%) had <5% circulating NK-cells. CONCLUSIONS: Our study suggests that hyperferritinemia and sCD25 correlate with other laboratory parameters indicative of severe hyperinflammation and organ dysfunction in critically ill ICU-patients, indicating their value in identifying hyperinflammatory critically ill patients for early intervention. Furthermore, it suggests that hyperferritinemia and hyperinflammation may partly be associated with a low percentage circulating NK-cells, and hence, the associated low lymphocyte cytotoxicity.

Mixed endothelin receptor antagonism with tezosentan improves intestinal microcirculation in endotoxemic shock.

BACKGROUND: Microcirculatory dysfunction is a common feature of sepsis. The potent vasoconstrictor endothelin (ET) is released in sepsis and endotoxemia, potentially contributing to sepsis-induced microcirculatory failure. In this study we tested the hypothesis that mixed ET receptor antagonism with tezosentan would improve splanchnic microcirculatory blood flow in acute porcine endotoxemia. MATERIALS AND METHODS: Sixteen anesthetized and mechanically ventilated pigs received an infusion of endotoxin for 300 min. After 120 min eight pigs received a bolus dose of tezosentan 1 mg/kg followed by an infusion of tezosentan of 1 mg/kg/h throughout the experiment. Eight pigs served as endotoxin controls. Laser Doppler flowmetry was used to measure microcirculatory blood flow in the liver and in the ileal and colon mucosa. PCO(2) in the ileal mucosa was measured by air tonometry and portal vein flow by an ultrasonic flow probe. RESULTS: Endotoxin administration induced a state of shock with impaired splanchnic microcirculatory blood flow. Microcirculation in the mucosa of the colon and ileum and mucosal-arterial PCO(2) gap were improved by tezosentan. Portal vein flow was increased, but hepatic microcirculatory blood flow was not significantly improved. Tezosentan preserved cardiac index and decreased pulmonary capillary wedge pressure compared to controls, without causing any differences in the heart rate or mean arterial blood pressure response. Tezosentan also distinctly improved pH and arterial lactate values. CONCLUSIONS: The findings of this study indicate that ET is involved in the microcirculatory dysfunction seen in the ileal and colon mucosa in early endotoxemia. Moreover, this detrimental effect was counteracted by i.v. administration of the mixed ET receptor antagonist tezosentan.

Early- versus late-onset shock in European intensive care units.

We investigated the possible differences in epidemiology, clinical course, management, and outcome between early and late occurrence of shock using data from the Sepsis Occurrence in Acutely Ill Patients Study, a large European multicenter study, which prospectively collected data from all adult intensive care unit (ICU) patients admitted to a participating center within a 2-week period in 2002. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor agents. Early and late shock were defined as onset of shock within the first 2 days in the ICU or later, respectively. Of 3,147 patients, 1,058 (33.6%) had shock at any time, of whom 462 (43.7%) had septic shock. Patients with late shock had a higher incidence of respiratory (87.4 vs. 69.7%, P < 0.001) and hepatic (15.5 vs. 8.7%, P < 0.05) failure, and more often received dopamine (44.7% vs. 34.5%, P < 0.05) and albumin (31.1% vs. 20.3%, P < 0.001) than patients who developed shock early. Intensive care unit and hospital mortality rates were greater in patients who developed shock late, rather than early (52.4% vs. 36.8% and 55.3% vs. 43%, respectively, P < 0.02). In a multivariable analysis, late shock was associated with an independent risk of higher ICU mortality in shock patients (odds ratio, 2.6; 95% confidence interval, 1.6-4.3, P < 0.001). These observations have important implications in establishing individual prognosis as well as in the design and interpretation of clinical trials.

Cerebral influences of sodium and angiotensin II on cardiovascular function in hypotensive hemorrhage.

During progressive blood loss several mechanisms act in concert to compensate for the reduced intravascular volume with the overall aim to provide sufficient blood supply to vital organs. The hemodynamic responses in this situation follow a characteristic course of events in conscious individuals with an initial phase of largely maintained blood pressure and tachycardia followed by an abrupt fall in pressure, accompanied by bradycardia and widespread inhibition of sympathetic nervous activity when 20-30% of the blood volume is lost. Our research has focussed on Na+ and angiotensin II effects on the brain for the cardiovascular compensatory mechanisms in response to hypotensive hemorrhage in sheep. We have found that intracerebroventricular infusion of hypertonic NaCl solution improves the tolerance to blood loss, i.e., increases the amount of blood loss needed to induce hypotension. Inhalation anesthesia abolished this effect of the infusion. Similarly, corresponding infusions of angiotensin II also increased the resistance to blood loss in conscious animals only, although accompanied by different hemodynamic compensatory mechanisms. The effects of intracerebroventricular hypertonic NaCl infusion on cardiovascular compensation during hemorrhage are similar to those achieved with treatment of hemorrhagic shock with intravenous infusions of small volumes of hypertonic NaCl solutions. We therefore suggest that a substantial part of the beneficial effect of that treatment is mediated via direct effects of the hypernatremia on the brain. These observations also illustrate the need for further elucidation of more possible influences on autonomic functions by increased Na+ concentration which, together with hypovolemia, is a hallmark of dehydration.