Effect of a quality improvement program on compliance to the sepsis bundle in non-ICU patients: a multicenter prospective before and after cohort study.

Objective: Sepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a "simplified 1-h bundle" (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU). Methods: Emergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort). Measurements and main results: The effect of QIP on bundle compliance and hospital mortality was evaluated in a before-after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the "simplified rapid (1 h) intervention bundle" (the Sepsis 6 bundle - S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p < 0.001). We then analyzed compliance with S6 and hospital mortality in the before- and after-QIP periods, stratifying the two patients' cohorts by admission characteristics. Adherence to the S6 bundle was increased in patients with severe sepsis in the absence of shock, in patients with serum lactate <4.0 mmol/L, and in patients with hypotension at the time of enrollment, regardless of the type of admission (from EDs or MWs). Subsequently, in an observational analysis, we also investigated the relation between bundle compliance and hospital mortality by logistic regression. In the after-QIP cohort, we observed a lower in-hospital mortality than that observed in the before-QIP cohort. This finding was reported in subgroups where a higher adherence to the S6 bundle in the after-QIP period was found. After adjustment for confounders, the QIP appeared to be independently associated with a significant improvement in hospital mortality. Among the single S6 procedures applied within the first hour of sepsis diagnosis, compliance with blood culture and antibiotic therapy appeared significantly associated with reduced in-hospital mortality. Conclusion: A multi-faceted QIP aimed at promoting an early simplified bundle of care for the management of septic patients out of the ICU was associated with improved compliance with sepsis bundles and lower in-hospital mortality.

The 3-T Model of Informed Consent for Nonstandard Risk Donors: A Proposal for Transplant Clinical Practice.

BACKGROUND: The risk of disease transmission from nonstandard risk donors (NSRDs) is low, and outcomes are similar or better relative to transplants performed with standard criteria donors. However, NSRDs have posed new ethical challenges to the informed consent (IC) process. Based on the shared decision-making model, coinciding with the 3 main timings of the IC process ([1] pretransplant assessments and waiting list registration, [2] time on the waiting list, and [3] time of the organ offer), we put forward a model (3-T Model) to summarize the knowledge on IC for NSRDs and to deliver conceptual and practical support to transplant providers on this emergent issue. METHODS: We searched PubMed and analyzed data from our area to provide evidence and ethical arguments to promote standardization of the timing of patient information, degree of patient participation, and disclosure of donor risk factors throughout the 3 stages of the time continuum leading to the potential acceptance of NSRDs. RESULTS: Each of the 3 timings carries special ethical significance and entails well-defined duties for transplant providers relative to patient involvement and information of the benefits and risks associated with NSRDs. Based on our framework, experience, and interpretation of the literature, we put forward a list of recommendations to combine standardization (ie, timing, content, and degree of patient participation) and individualization of IC. CONCLUSIONS: The 3-T Model may enable the prevention of physicians' arbitrariness and the promotion of patient-centered care. Future studies will assess the effectiveness of the 3-T Model in transplant clinical practice.

[Waiting time on dialysis for active access to renal transplantation: a multicenter cross-sectional study in Lombardy].

BACKGROUND: The amount of time spent in dialysis waiting for a renal transplantation significantly affects its outcome. Hence, the timely planning of patients' transplant evaluation is crucial. According to data from the Nord Italia Transplant program (NITp), the average waiting time between the beginning of dialysis and the admission to the regional transplant waiting list in Lombardy is 20.2 months. METHODS: A multicenter cross-sectional study was conducted in order to identify the causes of these delays and find solutions. Two questionnaires were administered to the directors of 47 Nephrology Units and to 106 patients undergoing dialysis in Lombardy respectively, during their first visit for admission to the transplant waiting list. RESULTS: The comparative analysis of the results revealed that both patients (52%) and directors (75%) consider the time required for registering to the waiting list too long. Patients judge information about the transplant to be insufficient, especially regarding the pre-emptive option (63% of patients declare that they had not been informed about this opportunity). Patients report a significantly longer time for the completion of pre-transplantation tests (more than 1 year in 23% of the cases) compared to that indicated by the directors. CONCLUSIONS: The study confirmed the necessity of providing better and more timely information to patients regarding the different kidney transplantation options and highlighted the importance of creating target-oriented and dedicated pathways in all hospitals.

"Why can't I give you my organs after my heart has stopped beating?" An overview of the main clinical, organisational, ethical and legal issues concerning organ donation after circulatory death in Italy.

Donation after circulatory death (DCD) is a valuable option for the procurement of functioning organs for transplantation. Clinical results are promising and public acceptance is quite good in most western countries. Yet, although DCD is widespread in Europe, several problems still persist in Italy as well as in some other countries. This paper aims to describe the main clinical, organisational, ethical and legal issues at stake, bearing in mind the particular situation created by Italian legislation. Currently, as regards DCD, Italy is somewhat different from other countries. Therefore, every effort should be made for the safe and effective implementation of DCD programs: uncontrolled DCD programs should be promoted and encouraged, within the framework of shared and authoritative rules. At the same time, we need to tackle the question of controlled DCD, promoting debate among all involved subjects regarding the fundamental issues of end-of-life care within protocols that best integrate the highest standard of care for the dying and the legitimate interests of those awaiting a life-saving organ.

Incidence of carbapenem-resistant gram negatives in Italian transplant recipients: a nationwide surveillance study.

BACKGROUND: Bacterial infections remain a challenge to solid organ transplantation. Due to the alarming spread of carbapenem-resistant gram negative bacteria, these organisms have been frequently recognized as cause of severe infections in solid organ transplant recipients. METHODS AND FINDINGS: Between 15 May and 30 September 2012 we enrolled 887 solid organ transplant recipients in Italy with the aim to describe the epidemiology of gram negative bacteria spreading, to explore potential risk factors and to assess the effect of early isolation of gram negative bacteria on recipients' mortality during the first 90 days after transplantation. During the study period 185 clinical isolates of gram negative bacteria were reported, for an incidence of 2.39 per 1000 recipient-days. Positive cultures for gram negative bacteria occurred early after transplantation (median time 26 days; incidence rate 4.33, 1.67 and 1.14 per 1,000 recipient-days in the first, second and third month after SOT, respectively). Forty-nine of these clinical isolates were due to carbapenem-resistant gram negative bacteria (26.5%; incidence 0.63 per 1000 recipient-days). Carbapenems resistance was particularly frequent among Klebsiella spp. isolates (49.1%). Recipients with longer hospital stay and those who received either heart or lung graft were at the highest risk of testing positive for any gram negative bacteria. Moreover recipients with longer hospital stay, lung recipients and those admitted to hospital for more than 48h before transplantation had the highest probability to have culture(s) positive for carbapenem-resistant gram negative bacteria. Forty-four organ recipients died (0.57 per 1000 recipient-days) during the study period. Recipients with at least one positive culture for carbapenem-resistant gram negative bacteria had a 10.23-fold higher mortality rate than those who did not. CONCLUSION: The isolation of gram-negative bacteria is most frequent among recipient with hospital stays >48 hours prior to transplant and in those receiving either heart or lung transplants. Carbapenem-resistant gram negative isolates are associated with significant mortality.

Endotoxin activity level and septic shock: a possible role for specific anti-endotoxin therapy?

Endotoxin activity (EA) plays an essential role in sepsis syndrome pathogenesis. There has been considerable interest in measuring and removing EA to predict and improve the morbidity and mortality of patients with sepsis. We performed a prospective study to assess the prevalence of EA in critically ill patients and its association with organ dysfunction and outcome, as well as in septic shock. EA (EAA(TM)) was measured within 24 h from onset of refractory septic shock in an intensive care unit. Our study demonstrated that EA level is independent from the type or the source of infection, but reflects the severity of illness in critically ill septic shock patients. Extracorporeal EA removal (PMX-HP) was assessed following our ICU clinical practice. PMX-HP seems to have better outcome, but further studies are required to verify this hypothesis.

Endotoxin removal: how far from the evidence? The EUPHAS 2 Project.

Since 1994, a polystyrene fiber cartridge used for extracorporeal hemoperfusion, to which polymyxin B is bound and immobilized, has been used in septic patients in order to absorb and remove circulating lipopolysaccharide, thereby neutralizing the effects of this endotoxin. This therapy gradually gained acceptance as the amount of evidence increased from initial small clinical studies to a carefully conducted systematic review, and ultimately to the multicentered randomized clinical trial conducted in Italy, entitled the EUPHAS Study (Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock). While the conclusions of this initial randomized controlled trial were in agreement with previous studies, it possessed some important limitations, including a slow accrual rate, enrolling only 64 patients between 2004 and 2007, inability to blind treating physicians, and a premature study termination based on the results of the scheduled interim analysis. These limitations resulted in a modest patient sample size, which may have overestimated the true magnitude of the clinical effect. Apart from Japan, Italy is the current primary user of polymyxin B-hemoperfusion in the treatment of sepsis, with about 600 cartridges being used per year. However, no structured collection of data has been attempted, resulting in the an opportunity to understand the effects of polymyxin B-hemoperfusion on a large, diverse sample size. In response, Italian investigators and users of this treatment have designed a new prospective multicentered, collaborative data collection study, entitled EUPHAS 2. The aim of the EUPHAS 2 project is to collect a large database regarding polymyxin B-hemoperfusion treatments in order to better evaluate the efficacy and biological significance of endotoxin removal in clinical practice. Additionally, this study aims to verify the reproducibility of the data currently available in the literature, evaluate the patient population chosen for treatment and identify subpopulations of patients who may benefit from this treatment more than others.

Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury.

INTRODUCTION: The optimal dialysis dose for the treatment of acute kidney injury (AKI) is controversial. We sought to evaluate the relationship between renal replacement therapy (RRT) dose and outcome. METHODS: We performed a prospective multicentre observational study in 30 intensive care units (ICUs) in eight countries from June 2005 to December 2007. Delivered RRT dose was calculated in patients treated exclusively with either continuous RRT (CRRT) or intermittent RRT (IRRT) during their ICU stay. Dose was categorised into more-intensive (CRRT >or= 35 ml/kg/hour, IRRT >or= 6 sessions/week) or less-intensive (CRRT < 35 ml/kg/hour, IRRT < 6 sessions/week). The main outcome measures were ICU mortality, ICU length of stay and duration of mechanical ventilation. RESULTS: Of 15,200 critically ill patients admitted during the study period, 553 AKI patients were treated with RRT, including 338 who received CRRT only and 87 who received IRRT only. For CRRT, the median delivered dose was 27.1 ml/kg/hour (interquartile range (IQR) = 22.1 to 33.9). For IRRT, the median dose was 7 sessions/week (IQR = 5 to 7). Only 22% of CRRT patients and 64% of IRRT patients received a more-intensive dose. Crude ICU mortality among CRRT patients were 60.8% vs. 52.5% (more-intensive vs. less-intensive groups, respectively). In IRRT, this was 23.6 vs. 19.4%, respectively. On multivariable analysis, there was no significant association between RRT dose and ICU mortality (Odds ratio (OR) more-intensive vs. less-intensive: CRRT OR = 1.21, 95% confidence interval (CI) = 0.66 to 2.21; IRRT OR = 1.50, 95% CI = 0.48 to 4.67). Among survivors, shorter ICU stay and duration of mechanical ventilation were observed in the more-intensive RRT groups (more-intensive vs. less-intensive for all: CRRT (median): 15 (IQR = 8 to 26) vs. 19.5 (IQR = 12 to 33.5) ICU days, P = 0.063; 7 (IQR = 4 to 17) vs. 14 (IQR = 5 to 24) ventilation days, P = 0.031; IRRT: 8 (IQR = 5.5 to 14) vs. 18 (IQR = 13 to 35) ICU days, P = 0.008; 2.5 (IQR = 0 to 10) vs. 12 (IQR = 3 to 24) ventilation days, P = 0.026). CONCLUSIONS: After adjustment for multiple variables, these data provide no evidence for a survival benefit afforded by higher dose RRT. However, more-intensive RRT was associated with a favourable effect on ICU stay and duration of mechanical ventilation among survivors. This result warrants further exploration. TRIAL REGISTRATION: Cochrane Renal Group (CRG110600093).

[The model of the Niguarda Hospital Trauma Team in Milan]. / Il modello organizzativo del Trauma Team dell'Ospedale Niguarda di Milano.

The aim of this work was to describe the model and clinical results obtained by the Niguarda Trauma Team referral center for major trauma, in Milan. The Trauma Team is organized as a trauma service, where general surgeons, anesthesiologists, orthopedic surgeons and neurosurgeons work on a 24 hour rotation. When not in duty in the rotations, specialists work in their specific elective activities. The director of the Trauma Team has the responsibility for discussion and application of protocols, clinical assistance, quality assessment and training. The results of 1334 consecutive cases of major trauma during a 51 month period were reviewed using the trauma registry. 39% overtriage, which increased over the years, and 1.12% undertriage were recorded. Mortality of patients with injury severity scores > 15 was 21%, with a progressive decrease over the years. Blunt trauma accounted for 91.75% and were road-related in most cases. Skeletal injuries were the most frequent findings, but brain and thoraco-abdominal injuries were associated with a higher risk of death. 1476 surgical procedures (16.93% general surgery and 111 interventional angiographic studies) were performed. Quality assessment revealed a significant decrease in preventable deaths within the first 72 hours, after excluding patients admitted in extremis. The results presented in this study demonstrate the possibility of realising a model of organized trauma care in an emergency department in Italy, with patient outcomes comparable to those obtained in Trauma Center in other countries.

Rate of reintubation in mechanically ventilated neurosurgical and neurologic patients: evaluation of a systematic approach to weaning and extubation.

OBJECTIVE: To assess whether a systematic approach to weaning and extubation (intervention) is superior to the sole physician's judgment (control) in preventing reintubation secondary to extubation failure in patients with neurologic disorders. DESIGN: Randomized controlled trial. SETTING: Intensive care unit of a large teaching hospital. PATIENTS: Three hundred eighteen intubated patients who had been receiving mechanical ventilation for at least 12 hrs and were able to trigger the ventilator. INTERVENTIONS: Patients were randomized to the intervention (n = 165) or control group (n = 153). MEASUREMENTS: Rate of reintubation after extubation failure occurring within 48 hrs (primary end point). Duration of mechanical ventilation, length of intensive care unit stay, mortality, rate of tracheotomy (secondary end points). The perception of the research protocol by the intensive care unit staff was also assessed. MAIN RESULTS: The rate of reintubation was lower in the intervention (5%) than in the control (12.5%) group (p = 0.047). There was no difference in any of the other outcome variables (secondary end points). Simplified Acute Physiologic Score II (adjusted odds ratio 1.042 per unit; 95% confidence interval 1.006-1.080; p = 0.022) and inclusion in the control group (adjusted odds ratio 2.393; 95% confidence interval 1.000-5.726; p = 0.05) were the only two independent predictive factors for the risk of extubation failure. The protocol was felt by the staff to determine an improvement in patients' clinical outcome, but to increase intensive care unit workload; nurses and physiotherapists considered its impact on their professional role more positively than physicians. CONCLUSIONS: In patients with neurologic diseases, a systematic approach to weaning and extubation reduces the rate of reintubation secondary to extubation failure without affecting the duration of mechanical ventilation, and is overall positively perceived by intensive care unit professionals.

Giant intracranial aneurysms treated with deep hypothermia and circulatory arrest.

The use of deep hypothermic circulatory arrest (DHCA), using groin cannulation with the chest closed (CCDHCA), has improved the surgical treatment of large and giant cerebral aneurysms. Twelve consecutive ASA I-II patients (10 women and 2 men), with a mean age of 35 years (range 14 to 55 y) underwent DHCA for clipping or trapping of their aneurysm (giant, n=10; large, n=2; 42% posterior circulation), under balanced general anesthesia. Intraoperative standard monitors were completed with jugular oxygen saturation, pulmonary artery, pulmonary artery occlusion, central venous pressures, electroencephalography, evoked potentials, and cerebral (subdural), and core temperature. At the start of circulatory arrest, brain temperature was 15.1+/-1.1 degrees C (range 13.5 to 17.5), and core temperature 14.1+/-1.1 degrees C (range 12.7 to 17.0). Mean circulatory arrest time was 26.5+/-13.9 minutes (range 9 to 54) and anesthesia lasted 14+/-1 hours. Only one patient underwent DHCA with standard sternotomy, because of aortic insufficiency. Follow-up (up to 70 mo) revealed no deaths and Glasgow Outcome Scale at 6 months revealed good recovery in 9, moderate disability in 1, and severe disability in 2 patients. Selected patients with large/giant intracranial aneurysms, deemed unapproachable by conventional surgical techniques, were successfully treated using CCDHCA. Mortality rate was 0% and neurologic complications occurred in 25% of the patients.

Preventable trauma deaths: from panel review to population based-studies.

Preventable trauma deaths are defined as deaths which could be avoided if optimal care has been delivered. Studies on preventable trauma deaths have been accomplished initially with panel reviews of pre-hospital and hospital charts. However, several investigators questioned the reliability and validity of this method because of low reproducibility of implicit judgments when they are made by different experts. Nevertheless, number of studies were published all around the world and ultimately gained some credibility, particularly in regions where comparisons were made before and after trauma system implementation with a resultant fall in mortality. During the last decade of century the method of comparing observed survival with probability of survival calculated from large trauma registries has obtained popularity. Preventable trauma deaths were identified as deaths occurred notwithstanding a high calculated probability of survival. In recent years, preventable trauma deaths studies have been replaced by population-based studies, which use databases representative of overall population, therefore with high epidemiologic value. These databases contain readily available information which carry out the advantage of objectivity and large numbers. Nowadays, population-based researches provide the strongest evidence regarding the effectiveness of trauma systems and trauma centers on patient outcomes.

Study protocol: the DOse REsponse Multicentre International collaborative initiative (DO-RE-MI).

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.