Association between hospital onset of infection and outcomes in sepsis patients - A propensity score matched cohort study based on health claims data in Germany.

BACKGROUND: Hospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. OBJECTIVE: We aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. METHODS: This retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. RESULTS: We matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001). CONCLUSIONS: HAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control.

Psychometric properties of the Reintegration to Normal Living Index for sepsis survivors.

PURPOSE: Return to a normal state of living is a key patient-relevant outcome for sepsis survivors. The Reintegration to Normal Living Index (RNLI) assesses self-perceived participation in patients with chronic disease, but its psychometric properties have been analyzed neither for patients after sepsis nor in a German patient cohort. This study aims to analyze the psychometric properties of the German version of the RNLI in sepsis survivors. METHODS: In a prospective multicenter survey study, 287 sepsis survivors were interviewed 6 and 12 months after hospital discharge. Multiple-group categorical confirmatory factor analyses with three competing models were used to explore the factor structure of the RNLI. Concurrent validity was evaluated in relation to the EQ-5D-3L and the Barthel Index of Activities of Daily Living (ADL). RESULTS: Regarding structural validity, all models showed an acceptable model fit. Because of high correlation between the latent variables in the two-factor models (up to r = 0.969) and for reason of parsimony, we opted for the common factor model to analyze the concurrent validity. Our analyses showed moderate positive correlations between RNLI score and ADL score (r ≥ 0.630), EQ-5D-3L visual analogue scale (r ≥ 0.656) and EQ-5D-3L utility score (r ≥ 0.548). The reliability assessed by McDonald's Omega was 0.94. CONCLUSION: We found convincing evidence for good reliability, structural and concurrent validity of the RNLI in German sepsis survivors. We propose to use the RNLI in addition to generic health-related quality of life measures to assess the reintegration to normal living after sepsis.

Who gets the ventilator? A multicentre survey of intensivists' opinions of triage during the first wave of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused a shortage of intensive care resources. Intensivists' opinion of triage and ventilator allocation during the COVID-19 pandemic is not well described. METHODS: This was a survey concerning patient numbers, bed capacity, triage guidelines, and three virtual cases involving ventilator allocations. Physicians from 400 ICUs in a research network were invited to participate. Preferences were assessed with a five-point Likert scale. Additionally, age, gender, work experience, geography, and religion were recorded. RESULTS: Of 437 responders 31% were female. The mean age was 44.4 (SD 11.1) with a mean ICU experience of 13.7 (SD 10.5) years. Respondents were mostly European (88%). Sixty-six percent had triage guidelines available. Younger patients and caretakers of children were favoured for ventilator allocation although this was less clear if this involved withdrawal of the ventilator from another patient. Decisions did not differ with ICU experience, gender, religion, or guideline availability. Consultation of colleagues or an ethical committee decreased with age and male gender. CONCLUSION: Intensivists appeared to prioritise younger patients for ventilator allocation. The tendency to consult colleagues about triage decreased with age and male gender. Many found such tasks to be not purely medical and that authorities should assume responsibility for triage during resource scarcity.

Perceptions of Ethical Decision-Making Climate Among Clinicians Working in European and U.S. ICUs: Differences Between Nurses and Physicians.

OBJECTIVES: To examine perceptions of nurses and physicians in regard to ethical decision-making climate in the ICU and to test the hypothesis that the worse the ethical decision-making climate, the greater the discordance between nurses' and physicians' rating of ethical decision-making climate with physicians hypothesized to rate the climate better than the nurses. DESIGN: Prospective observational study. SETTING: A total of 68 adult ICUs in 13 European countries and the United States. SUBJECTS: ICU physicians and nurses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Perceptions of ethical decision-making climate among clinicians were measured in April-May 2014, using a 35-items self-assessment questionnaire that evaluated seven factors (empowering leadership by physicians, interdisciplinary reflection, not avoiding end-of-life decisions, mutual respect within the interdisciplinary team, involvement of nurses in end-of-life care and decision-making, active decision-making by physicians, and ethical awareness). A total of 2,275 nurses and 717 physicians participated (response rate of 63%). Using cluster analysis, ICUs were categorized according to four ethical decision-making climates: good, average with nurses' involvement at end-of-life, average without nurses' involvement at end-of-life, and poor. Overall, physicians rated ethical decision-making climate more positively than nurses (p < 0.001 for all seven factors). Physicians had more positive perceptions of ethical decision-making climate than nurses in all 13 participating countries and in each individual participating ICU. Compared to ICUs with good or average ethical decision-making climates, ICUs with poor ethical decision-making climates had the greatest discordance between physicians and nurses. Although nurse/physician differences were found in all seven factors of ethical decision-making climate measurement, the factors with greatest discordance were regarding physician leadership, interdisciplinary reflection, and not avoiding end-of-life decisions. CONCLUSIONS: Physicians consistently perceived ICU ethical decision-making climate more positively than nurses. ICUs with poor ethical decision-making climates had the largest discrepancies.

Interprofessional Shared Decision-Making in the ICU: A Systematic Review and Recommendations From an Expert Panel.

OBJECTIVES: There is growing recognition that high-quality care for patients and families in the ICU requires exemplary interprofessional collaboration and communication. One important aspect is how the ICU team makes complex decisions. However, no recommendations have been published on interprofessional shared decision-making. The aim of this project is to use systematic review and normative analysis by experts to examine existing evidence regarding interprofessional shared decision-making, describe its principles and provide ICU clinicians with recommendations regarding its implementation. DATA SOURCES: We conducted a systematic review using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases and used normative analyses to formulate recommendations regarding interprofessional shared decision-making. STUDY SELECTION: Three authors screened titles and abstracts in duplicate. DATA SYNTHESIS: Four papers assessing the effect of interprofessional shared decision-making on quality of care were identified, suggesting that interprofessional shared decision-making is associated with improved processes and outcomes. Five recommendations, largely based on expert opinion, were developed: 1) interprofessional shared decision-making is a collaborative process among clinicians that allows for shared decisions regarding important treatment questions; 2) clinicians should consider engaging in interprofessional shared decision-making to promote the most appropriate and balanced decisions; 3) clinicians and hospitals should implement strategies to foster an ICU climate oriented toward interprofessional shared decision-making; 4) clinicians implementing interprofessional shared decision-making should consider incorporating a structured approach; and 5) further studies are needed to evaluate and improve the quality of interprofessional shared decision-making in ICUs. CONCLUSIONS: Clinicians should consider an interprofessional shared decision-making model that allows for the exchange of information, deliberation, and joint attainment of important treatment decisions.

What matters most to sepsis survivors: a qualitative analysis to identify specific health-related quality of life domains.

PURPOSE: It is unknown how sepsis survivors conceptualize health-related quality of life (HRQL). We aimed to identify important HRQL domains for this population. METHODS: A literature search was performed to inform an interview guide. Open-ended interviews were held with 15 purposefully sampled sepsis survivors. Interview transcripts were analyzed by interpretative phenomenological analysis to allow themes to develop organically. Resulting codes were reviewed by an independent expert. The preliminary list of domains was rated in a two-round Delphi consensus procedure with therapists and survivors. RESULTS: Eleven domains emerged as critically important: Psychological impairment, Fatigue, Physical impairment, Coping with daily life, Return to normal living, Ability to walk, Cognitive impairment, Self-perception, Control over one's life, Family support, and Delivery of health care. Sepsis survivors want a "normal life," to walk again, and to regain control without cognitive impairment. Family support is essential to overcome sepsis aftermaths. CONCLUSIONS: Survivors described many HRQL domains which are not captured by the QoL instruments that have traditionally been used to study ICU survivorship (i.e., SF-36 and EQ-5D). Future studies of QoL in ICU survivors should consider using both a traditional instrument so that results are comparable to previous research, as well as a more holistic QoL measurement instrument like the WHOQOL-BREF.

Changes in End-of-Life Practices in European Intensive Care Units From 1999 to 2016.

IMPORTANCE: End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time. OBJECTIVE: To determine the changes in end-of-life practices in European ICUs after 16 years. DESIGN, SETTING, AND PARTICIPANTS: Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision. EXPOSURES: Comparison between the 1999-2000 cohort vs 2015-2016 cohort. MAIN OUTCOMES AND MEASURES: End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists. RESULTS: Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75]; P < .001) and the proportion of female patients was similar (39.6% vs 38.7%; P = .58). Significantly more treatment limitations occurred in the 2015-2016 cohort compared with the 1999-2000 cohort (1601 [89.7%] vs 1918 [68.3%]; difference, 21.4% [95% CI, 19.2% to 23.6%]; P < .001), with more withholding of life-prolonging therapy (892 [50.0%] vs 1143 [40.7%]; difference, 9.3% [95% CI, 6.4% to 12.3%]; P < .001), more withdrawing of life-prolonging therapy (692 [38.8%] vs 695 [24.8%]; difference, 14.0% [95% CI, 11.2% to 16.8%]; P < .001), less failed CPR (110 [6.2%] vs 628 [22.4%]; difference, -16.2% [95% CI, -18.1% to -14.3%]; P < .001), less brain death (74 [4.1%] vs 261 [9.3%]; difference, -5.2% [95% CI, -6.6% to -3.8%]; P < .001) and less active shortening of the dying process (17 [1.0%] vs 80 [2.9%]; difference, -1.9% [95% CI, -2.7% to -1.1%]; P < .001). CONCLUSIONS AND RELEVANCE: Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.

[Non-beneficial therapy and emotional exhaustion in end-of-life care : Results of a survey among intensive care unit personnel]. / Übertherapie und emotionale Erschöpfung in der "end-of-life care" : Ergebnisse einer Mitarbeiterumfrage auf der Intensivstation.

BACKGROUND: End-of-life care (EOLC) in the intensive care unit (ICU) is becoming increasingly more common but ethical standards are compromised by growing economic pressure. It was previously found that perception of non-beneficial treatment (NBT) was independently associated with the core burnout dimension of emotional exhaustion. It is unknown whether factors of the work environment also play a role in the context of EOLC. OBJECTIVE: Is the working environment associated with perception of NBT or clinician burnout? MATERIAL AND METHODS: Physicians and nursing personnel from 11 German ICUs who took part in an international, longitudinal prospective observational study on EOLC in 2015-2016 were surveyed using validated instruments. Risk factors were obtained by multivariate multilevel analysis. RESULTS: The participation rate was 49.8% of personnel working in the ICU at the time of the survey. Overall, 325 nursing personnel, 91 residents and 26 consulting physicians participated. Nurses perceived NBT more frequently than physicians. Predictors for the perception of NBT were profession, collaboration in the EOLC context, excessively high workload (each p ≤ 0.001) and the numbers of weekend working days per month (p = 0.012). Protective factors against burnout included intensive care specialization (p = 0.001) and emotional support within the team (p ≤ 0.001), while emotional exhaustion through contact with relatives at the end of life and a high workload were both increased (each p ≤ 0.001). DISCUSSION: Using the example of EOLC, deficits in the work environment and stress factors were uncovered. Factors of the work environment are associated with perceived NBT. To reduce NBT and burnout, the quality of the work environment should be improved and intensive care specialization and emotional support within the team enhanced. Interprofessional decision-making among the ICU team and interprofessional collaboration should be improved by regular joint rounds and interprofessional case discussions. Mitigating stressful factors such as communication with relatives and high workload require allocation of respective resources.

Staff and family response to end-of-life care in the ICU.

PURPOSE OF REVIEW: End-of-life (EOL) care can be stressful for clinicians as well as patients and their relatives. Decisions to withhold or withdraw life-sustaining therapy vary widely depending on culture, beliefs and organizational norms. The following review will describe the current understanding of the problem and give an overview over interventional studies. RECENT FINDINGS: EOL care is a risk factor for clinician burnout; poor work conditions contribute to emotional exhaustion and intent to leave. The impact of EOL care on families is part of the acute Family Intensive Care Unit Syndrome (FICUS) and the Post Intensive Care Syndrome-Family (PICS-F). Family-centered care (FCC) acknowledges the importance of relatives in the ICU. Several interventions have been evaluated, but evidence for their effectiveness is at best moderate. Some interventions even increased family stress. Interventional studies, which address clinician burnout are rare. SUMMARY: EOL care is associated with negative outcomes for ICU clinicians and relatives, but strength of evidence for interventions is weak because we lack understanding of associated factors like work conditions, organizational issues or individual attitudes. In order to develop complex interventions that can successfully mitigate stress related to EOL care, more research is necessary, which takes into account all potential determinants.

Perceived Nonbeneficial Treatment of Patients, Burnout, and Intention to Leave the Job Among ICU Nurses and Junior and Senior Physicians.

OBJECTIVES: Perceiving nonbeneficial treatment is stressful for ICU staff and may be associated with burnout. We aimed to investigate predictors and consequences of perceived nonbeneficial treatment and to compare nurses and junior and senior physicians. DESIGN: Cross-sectional, multicenter paper-pencil survey on personal and work-related characteristics, perceived nonbeneficial treatment, burnout, and intention to leave the job. SETTING: Convenience sample of 23 German ICUs. SUBJECTS: ICU nurses and physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 847 questionnaires were returned (51% response); 778 had complete data for final multivariate analyses. Nonbeneficial treatment was in median perceived "sometimes." Adjusted for covariates, it was perceived more often by nurses and junior physicians (both p ≤ 0.001 in comparison to senior physicians), while emotional exhaustion was highest in junior physicians (p ≤ 0.015 in comparison to senior physicians and nurses), who also had a higher intention to leave than nurses (p = 0.024). Nonbeneficial treatment was predicted by high workload and low quality collaboration with other departments (both p ≤ 0.001). Poor nurse-physician collaboration predicted perception of nonbeneficial treatment among junior physicians and nurses (both p ≤ 0.001) but not among senior physicians (p = 0.753). Nonbeneficial treatment was independently associated with the core burnout dimension emotional exhaustion (p ≤ 0.001), which significantly mediated the effect between nonbeneficial treatment and intention to leave (indirect effect: 0.11 [95% CI, 0.06-0.18]). CONCLUSIONS: Perceiving nonbeneficial treatment is related to burnout and may increase intention to leave. Efforts to reduce perception of nonbeneficial treatment should improve the work environment and should be tailored to the different experiences of nurses and junior and senior physicians.

Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU.

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting thresholds. No industry funding was associated with the guideline development. RESULTS: The scoping review yielded 683 qualitative studies; 228 were used for thematic analysis and Population, Intervention, Comparison, Outcome question development. The systematic review search yielded 4,158 reports after deduplication and 76 additional studies were added from alerts and hand searches; 238 studies met inclusion criteria. We made 23 recommendations from moderate, low, and very low level of evidence on the topics of: communication with family members, family presence, family support, consultations and ICU team members, and operational and environmental issues. We provide recommendations for future research and work-tools to support translation of the recommendations into practice. CONCLUSIONS: These guidelines identify the evidence base for best practices for family-centered care in the ICU. All recommendations were weak, highlighting the relative nascency of this field of research and the importance of future research to identify the most effective interventions to improve this important aspect of ICU care.

Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations.

RATIONALE: Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale. OBJECTIVES: To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies. METHODS: We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years. MEASUREMENTS AND MAIN RESULTS: The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215-386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98-226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334-571; τ = 0.38) for sepsis and 270 (95% CI, 176-412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually. CONCLUSIONS: Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.

End-of-life care in the intensive care unit: a patient-based questionnaire of intensive care unit staff perception and relatives' psychological response.

BACKGROUND: Communication is a hallmark of end-of-life care in the intensive care unit. It may influence the impact of end-of-life care on patients' relatives. We aimed to assess end-of-life care and communication from the perspective of intensive care unit staff and relate it to relatives' psychological symptoms. DESIGN: Prospective observational study based on consecutive patients with severe sepsis receiving end-of-life care; trial registration NCT01247792. SETTING/PARTICIPANTS: Four interdisciplinary intensive care units of a German University hospital. Responsible health personnel (attendings, residents and nurses) were questioned on the day of the first end-of-life decision (to withdraw or withhold life-supporting therapies) and after patients had died or were discharged. Relatives were interviewed by phone after 90 days. RESULTS: Overall, 145 patients, 610 caregiver responses (92% response) and 84 relative interviews (70% response) were analysed. Most (86%) end-of-life decisions were initiated by attendings and only 2% by nurses; 41% of nurses did not know enough about end-of-life decisions to communicate with relatives. Discomfort with end-of-life decisions was low. Relatives reported high satisfaction with decision-making and care, 87% thought their degree of involvement had been just right. However, 51%, 48% or 33% of relatives had symptoms of post-traumatic stress disorder, anxiety or depression, respectively. Predictors for depression and post-traumatic stress disorder were patient age and relatives' gender. Relatives' satisfaction with medical care and communication predicted less anxiety (p = 0.025). CONCLUSION: Communication should be improved within the intensive care unit caregiver team to strengthen the involvement of nurses in end-of-life care. Improved communication between caregivers and the family might lessen relatives' long-term anxiety.

Seeking worldwide professional consensus on the principles of end-of-life care for the critically ill. The Consensus for Worldwide End-of-Life Practice for Patients in Intensive Care Units (WELPICUS) study.

Great differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. Country coordinators were identified and draft statements were developed for major end-of-life issues and translated into six languages. Multidisciplinary responses using a web-based survey assessed agreement or disagreement with definitions and statements linked to anonymous demographic information. Consensus was prospectively defined as >80% agreement. Definitions and statements not obtaining consensus were revised based on comments of respondents, and then translated and redistributed. Of the initial 1,283 responses from 32 countries, consensus was found for 66 (81%) of the 81 definitions and statements; 26 (32%) had >90% agreement. With 83 additional responses to the original questionnaire (1,366 total) and 604 responses to the revised statements, consensus could be obtained for another 11 of the 15 statements. Consensus was obtained for informed consent, withholding and withdrawing life-sustaining treatment, legal requirements, intensive care unit therapies, cardiopulmonary resuscitation, shared decision making, medical and nursing consensus, brain death, and palliative care. Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.

New approaches to sepsis: molecular diagnostics and biomarkers.

Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies.

Perioperative fluid therapy with tetrastarch and gelatin in cardiac surgery--a prospective sequential analysis*.

OBJECTIVES: To determine clinical outcomes of synthetic colloids, tetrastarch, and gelatin, used before and after cardiac surgery. DESIGN: Prospective observational cohort study. SETTING: Fifty-bed cardiac ICU. PATIENTS: Six thousand four hundred seventy-eight consecutive patients with cardiopulmonary bypass surgery. INTERVENTIONS: Fluid therapy in the operating room and on the ICU directed at preset hemodynamic goals: 1) hydroxyethyl starch (predominantly 6% hydroxyethyl starch 130/0.4) in 2004-2006, n = 2,137; 2) 4% gelatin in 2006-2008, n = 2,324; and 3) only crystalloids in 2008-2010, n = 2,017. MEASUREMENTS AND MAIN RESULTS: Renal replacement therapy was more common during periods when patients received synthetic colloids compared to only crystalloids. Risk of renal replacement therapy was greater after hydroxyethyl starch (odds ratio, 2.29; 95% CI, 1.47-3.60) and gelatin (odds ratio, 2.75; 95% CI, 1.84-4.16; both p < 0.001) compared to crystalloid. Propensity score stratification confirmed greater use of renal replacement therapy in the hydroxyethyl starch and gelatin periods compared to the crystalloid period (odds ratio, 1.46 [1.08, 1.97]; p = 0.013 and odds ratio, 1.72 [1.33, 2.24]; p < 0.001, respectively). Time to vasopressor cessation, normalization of serum lactate, and mean arterial pressure did not differ among groups. Total fluid requirement was 163 mL/kg in the hydroxyethyl starch period, 207 mL/kg in the gelatin period, and 224 mL/kg in the crystalloid period. Fluid intake was higher in the crystalloid group only during the first 20 hours. CONCLUSIONS: In cardiac surgery patients, fluid therapy with perioperative administration of synthetic colloids carries a high risk of renal replacement therapy and is not more effective than treating with only crystalloids.

Return to work after sepsis-a German population-based health claims study.

Background: Long-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis. Methods: This retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement. Results: Among 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days). Conclusion: One out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.

The Effects of Postacute Rehabilitation on Mortality, Chronic Care Dependency, Health Care Use, and Costs in Sepsis Survivors.

Rationale: Sepsis often leads to long-term functional deficits and increased mortality in survivors. Postacute rehabilitation can decrease long-term sepsis mortality, but its impact on nursing care dependency, health care use, and costs is insufficiently understood. Objectives: To assess the short-term (7-12 months postdischarge) and long-term (13-36 months postdischarge) effect of inpatient rehabilitation within 6 months after hospitalization on mortality, nursing care dependency, health care use, and costs. Methods: An observational cohort study used health claims data from the health insurer AOK (Allgemeine Ortskrankenkasse). Among 23.0 million AOK beneficiaries, adult beneficiaries hospitalized with sepsis in 2013-2014 were identified by explicit codes from the International Classification of Diseases, Tenth Revision. The study included patients who were nonemployed presepsis, for whom rehabilitation is reimbursed by the AOK and thus included in the dataset, and who survived at least 6 months postdischarge. The effect of rehabilitation was estimated by statistical comparisons of patients with rehabilitation (treatment group) and those without (reference group). Possible differential effects were investigated for the subgroup of ICU-treated sepsis survivors. The study used inverse probability of treatment weighting based on propensity scores to adjust for differences in relevant covariates. Costs for rehabilitation in the 6 months postsepsis were not included in the cost analysis. Results: Among 41,918 6-month sepsis survivors, 17.2% (n = 7,224) received rehabilitation. There was no significant difference in short-term survival between survivors with and without rehabilitation. Long-term survival rates were significantly higher in the rehabilitation group (90.4% vs. 88.7%; odds ratio [OR] = 1.2; 95% confidence interval [95% CI] = 1.1-1.3; P = 0.003). Survivors with rehabilitation had a higher mean number of hospital readmissions (7-12 months after sepsis: 0.82 vs. 0.76; P = 0.014) and were more frequently dependent on nursing care (7-12 months after sepsis: 47.8% vs. 42.3%; OR = 1.2; 95% CI = 1.2-1.3; P < 0.001; 13-36 months after sepsis: 52.5% vs. 47.5%; OR = 1.2; 95% CI = 1.1-1.3; P < 0.001) compared with those without rehabilitation, whereas total health care costs at 7-36 months after sepsis did not differ between groups. ICU-treated sepsis patients with rehabilitation had higher short- and long-term survival rates (short-term: 93.5% vs. 90.9%; OR = 1.5; 95% CI = 1.2-1.7; P < 0.001; long-term: 89.1% vs. 86.3%; OR = 1.3; 95% CI = 1.1-1.5; P < 0.001) than ICU-treated sepsis patients without rehabilitation. Conclusions: Rehabilitation within the first 6 months after ICU- and non-ICU-treated sepsis is associated with increased long-term survival within 3 years after sepsis without added total health care costs. Future work should aim to confirm and explain these exploratory findings.