Intravenous Levosimendan and Vasopressin in New-Onset Acute Pulmonary Hypertension After Weaning from Cardiopulmonary Bypass.

OBJECTIVE: A novel treatment with intravenous levosimendan and vasopressin for new-onset acute pulmonary hypertension after weaning from cardiopulmonary bypass is described. DESIGN: Retrospective analysis of a case series. SETTING: Single-center study. PARTICIPANTS: Nineteen patients undergoing cardiac surgery exhibited new-onset acute pulmonary hypertension with acute right ventricular dysfunction after cardiopulmonary bypass. INTERVENTION: Pulmonary hypertension with acute right heart dysfunction was treated with levosimendan as inodilator therapy and vasopressin combined with norepinephrine for systemic vasopressor therapy. MEASUREMENTS AND MAIN RESULTS: Mean pulmonary artery pressure decreased from 32 ± 9 to 26 ± 6 mmHg (p = 0.039) in the first 24 hours along with an increase in cardiac output (3.2 ± 1 to 4.2 ± 1.1 L/min; p = 0.012) and resolution of lactic acidosis. The ratio between mean pulmonary artery pressure and mean arterial pressure decreased from 1:2 to 1:3, and Wood units decreased from 3 ± 1 to 1.5 ± 2 (p = 0.042). At 30 days after intervention, 3 patients died. CONCLUSION: The combination of levosimendan for inotropic support of the right ventricle in conjunction with its vasodilatory effect on the pulmonary circulation, along with the combination of vasopressin and norepinephrine for systemic vasopressor therapy, may be an effective alternative for the treatment of acute new-onset pulmonary hypertension and acute right heart dysfunction after cardiopulmonary bypass. Although there are many confounding variables in this case series, these findings justify additional sufficiently powered trials.

Influence of pathogen and focus of infection on procalcitonin values in sepsis patients with bacteremia or candidemia.

BACKGROUND: This study aimed to evaluate the accuracy of procalcitonin (PCT) serum concentrations to diagnose Gram-negative bacteremia and the association of PCT serum concentrations with more specific pathogens and the focus of infection. METHODS: Secondary analysis of the prospectively collected patient-level dataset from a cluster randomized quality improvement trial was performed. The trial included sepsis patients with organ dysfunction treated in the participating intensive care units from 2011 to 2015. Test performance for the prediction of Gram-negative bacteremia was assessed by receiver operating curve analysis. Independent effects of specific pathogen groups and foci of infection on PCT concentrations were assessed by linear logistic regression models. RESULTS: Blood cultures (BC) and PCT concentrations had been taken in 4858 of 6561 documented patients. PCT was significantly higher in Gram-negative bacteremia compared to Gram-positive bacteremia or candidemia (p < 0.001). The area under the curve was 0.72 (95% confidence interval 0.71-0.74) for the prediction of Gram-negative bacteremia compared to all other blood culture results including negative blood cultures. The optimized cutoff value was 10 ng/ml (sensitivity 69%, specificity 35%). PCT differed significantly between specific groups of pathogens (p < 0.001) with highest concentrations in Escherichia coli, Streptococcus species and other Enterobacteriaceae. PCT was highest in urogenital followed by abdominal infection and lowest in respiratory infection (p < 0.001). In a linear regression model, Streptococci, E. coli and other Enterobacteriaceae detected from BC were associated with three times higher PCT values. Urogenital or abdominal foci of infection were associated with twofold increased PCT values independent of the pathogen. CONCLUSIONS: Serum PCT concentrations are higher in patients with Gram-negative bacteremia than in patients with Gram-positive bacteremia or candidemia. However, the discriminatory power of this difference is too low to guide therapeutic decisions. Variations in PCT serum concentrations are not determined solely by Gram-negative or Gram-positive bacteria but are also affected by distinct groups of pathogens and different foci of infection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01187134 . Registered on 23 August 2010.

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.

A multifaceted educational intervention improved anti-infectious measures but had no effect on mortality in patients with severe sepsis.

Sepsis is a major reason for preventable hospital deaths. A cluster-randomized controlled trial on an educational intervention did not show improvements of sepsis management or outcome. We now aimed to test an improved implementation strategy in a second intervention phase in which new intervention hospitals (former controls) received a multifaceted educational intervention, while controls (former intervention hospitals) only received feedback of quality indicators. Changes in outcomes from the first to the second intervention phase were compared between groups using hierarchical generalized linear models controlling for possible confounders. During the two phases, 19 control hospitals included 4050 patients with sepsis and 21 intervention hospitals included 2526 patients. 28-day mortality did not show significant changes between study phases in both groups. The proportion of patients receiving antimicrobial therapy within one hour increased in intervention hospitals, but not in control hospitals. Taking at least two sets of blood cultures increased significantly in both groups. During phase 2, intervention hospitals showed higher proportion of adequate initial antimicrobial therapy and de-escalation within 5 days. A survey among involved clinicians indicated lacking resources for quality improvement. Therefore, quality improvement programs should include all elements of sepsis guidelines and provide hospitals with sufficient resources for quality improvement.Trial registration: ClinicalTrials.gov, NCT01187134. Registered 23 August 2010, https://www.clinicaltrials.gov/ct2/show/study/NCT01187134 .

Pharmacologic Agents for the Treatment of Vasodilatory Shock.

Vasodilatory shock is a life-threatening syndrome in critically ill patients and is characterized by severe hypotension and resultant tissue hypoperfusion. This shock state requires the use of vasopressor agents to restore adequate vascular tone. Norepinephrine is still recommended as first-line vasopressor in the management of critically ill patients suffering from severe vasodilation. In the recent time, catecholaminergic vasopressor drugs have been associated with possible side effects at higher dosages. This so-called catecholamine toxicity has focused on alternative noncatecholaminergic vasopressors or the use of moderate doses of multiple vasopressors with complementary mechanisms of action. Besides vasopressin and terlipressin, angiotensin II may be a promising drug for the management of vasodilatory shock. In addition, adjunctive drugs, such as hydrocortisone, methylene blue or ascorbic acid can be added to conventional vasopressor therapy. The objective of this review is to give an overview of the current available vasopressor agents used in vasodilatory shock. A thorough search of PubMed was conducted in order to identify the majority of studies related to the subject. Data on the outcome of several drugs and future perspective of possible management strategies for the therapy of vasodilatory shock are discussed.

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial.

PURPOSE: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

Crossing the handover chasm: Clinicians' perceptions of barriers to the early detection and timely management of severe sepsis and septic shock.

PURPOSE: The purpose was to identify barriers to the early detection and timely management of severe sepsis throughout the emergency department (ED), general ward (GW), intermediate care unit (IMC), and the intensive care unit (ICU). MATERIALS AND METHODS: Five multicenter focus group discussions with 29 clinicians were conducted. Discussions were based on a moderation guide were recorded and transcribed. Qualitative analysis was performed according to the principles of the concept mapping method and the framework approach. RESULTS: The major causes of the delayed detection and treatment could be summarized in a framework of communication errors and handover difficulties throughout patients' course of treatment, which can be divided into 5 core areas: inadequate histories before hospital admission; poorly coordinated handovers between the ambulance service and the ED; delayed patient transfer between the ED and the GW as well as delays in patient transfers between the GW and the ICU by, for example, a lack of bed capacity and a shortage of staff. Generally, participants from all wards mentioned that the urgency with which septic patients needed to be treated was not communicated. CONCLUSIONS: Our study shows the need to improve intra- and interunit handover processes in hospital care, which would ensure a holistic treatment concept, thereby improving patient care.

Barriers and supportive conditions to improve quality of care for critically ill patients: A team approach to quality improvement.

PURPOSE: Despite the fact that Quality Improvement (QI) teams are widespread tools for improving performance in medical settings, little is known about what makes teams effective and successful. The goal of this study was to identify barriers and supportive conditions for QI teams to implement an effective and successful QI project to improve quality of care. MATERIALS AND METHODS: Multicenter expert interviews with 17 team leaders were conducted in a cluster randomized trial. Interviews were based on a semistructured interview guide and were recorded and transcribed. Qualitative analysis was performed according to the principles of grounded theory. RESULTS: The major findings of our study can be summarized in a framework of conditions that support the implementation of changes by QI teams. This framework can be divided into 5 core categories: the availability of external support, an interdisciplinary QI team, staff characteristics such as dedicated employees who are aware and experienced, and generally supportive structural circumstances. Furthermore, the interviewees reported that changes should be disseminated through, for example, repeating key elements or addressing employees directly. CONCLUSIONS: Using a grounded theory-based qualitative approach, we identified a framework of conditions supportive of QI-related change, which can help project initiators to create environments that are supportive of change.

Hyperlactatemia is an independent predictor of mortality and denotes distinct subtypes of severe sepsis and septic shock.

PURPOSE: Current guidelines and most trials do not consider elevated lactate (Lac) serum concentrations when grading sepsis severity. We therefore assessed the association of different types of circulatory dysfunction regarding presence of hyperlactatemia and need for vasopressor support with clinical presentation and outcome of sepsis. METHODS: In a secondary analysis of a prospective observational multicenter cohort study, 988 patients with severe sepsis were investigated regarding vasopressor support, Lac levels, and outcome. RESULTS: Twenty-eight-day mortality regarding shock or hyperlactatemia was as follows: hyperlactatemia more than 2.5 mmol/L and septic shock (tissue dysoxic shock): 451 patients with a mortality of 44.8%; hyperlactatemia without vasopressor need (cryptic shock): 72 patients, mortality 35.3%; no hyperlactatemia with vasopressor need (vasoplegic shock): 331 patients, mortality 27.7%; and absence of hyperlactemia or overt shock (severe sepsis): 134 patients, mortality 14.2% (P < .001). These groups showed differences in source and origin of infection. The influence of hyperlactatemia on 28-day mortality (P < .001) (odds ratio 3.0, 95% confidence interval 2.1-4.1 for Lac >4 mmol/L) was independent of vasopressor support (P < .001) (odds ratio 2.0, 95% confidence interval 1.3-3.0 for norepinephrine >0.1 µg/kg per minute) in logistic regression. CONCLUSIONS: Hyperlactatemia increases risk of death independent of vasopressor need resulting in different phenotypes within the classic categories of severe sepsis and septic shock.