Claudia Filippini

Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial.

CONTEXT Tracheotomy is used to replace endotracheal intubation in patients requiring prolonged ventilation; however, there is considerable variability in the time considered optimal for performing tracheotomy. This is of clinical importance because timing is a key criterion for performing a tracheotomy and patients who receive one require a large amount of health care resources. OBJECTIVE To determine the effectiveness of early tracheotomy (after 6-8 days of laryngeal intubation) compared with late tracheotomy (after 13-15 days of laryngeal intubation) in reducing the incidence of pneumonia and increasing the number of ventilator-free and intensive care unit (ICU)-free days. DESIGN, SETTING, AND PATIENTS Randomized controlled trial performed in 12 Italian ICUs from June 2004 to June 2008 of 600 adult patients enrolled without lung infection, who had been ventilated for 24 hours, had a Simplified Acute Physiology Score II between 35 and 65, and had a sequential organ failure assessment score of 5 or greater. INTERVENTION Patients who had worsening of respiratory conditions, unchanged or worse sequential organ failure assessment score, and no pneumonia 48 hours after inclusion were randomized to early tracheotomy (n = 209; 145 received tracheotomy) or late tracheotomy (n = 210; 119 received tracheotomy). MAIN OUTCOME MEASURES The primary endpoint was incidence of ventilator-associated pneumonia; secondary endpoints during the 28 days immediately following randomization were number of ventilator-free days, number of ICU-free days, and number of patients in each group who were still alive. RESULTS Ventilator-associated pneumonia was observed in 30 patients in the early tracheotomy group (14%; 95% confidence interval [CI], 10%-19%) and in 44 patients in the late tracheotomy group (21%; 95% CI, 15%-26%) (P = .07). During the 28 days immediately following randomization, the hazard ratio of developing ventilator-associated pneumonia was 0.66 (95% CI, 0.42-1.04), remaining connected to the ventilator was 0.70 (95% CI, 0.56-0.87), remaining in the ICU was 0.73 (95% CI, 0.55-0.97), and dying was 0.80 (95% CI, 0.56-1.15). CONCLUSION Among mechanically ventilated adult ICU patients, early tracheotomy compared with late tracheotomy did not result in statistically significant improvement in incidence of ventilator-associated pneumonia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00262431.

Effect of a Lung Protective Strategy for Organ Donors on Eligibility and Availability of Lungs for Transplantation A Randomized Controlled Trial

CONTEXT Many potential donor lungs deteriorate between the time of brain death and evaluation for transplantation suitability, possibly because of the ventilatory strategy used after brain death. OBJECTIVE To test whether a lung protective strategy increases the number of lungs available for transplantation. DESIGN, SETTING, AND PATIENTS Multicenter randomized controlled trial of patients with beating hearts who were potential organ donors conducted at 12 European intensive care units from September 2004 to May 2009 in the Protective Ventilatory Strategy in Potential Lung Donors Study. Interventions Potential donors were randomized to the conventional ventilatory strategy (with tidal volumes of 10-12 mL/kg of predicted body weight, positive end-expiratory pressure [PEEP] of 3-5 cm H(2)O, apnea tests performed by disconnecting the ventilator, and open circuit for airway suction) or the protective ventilatory strategy (with tidal volumes of 6-8 mL/kg of predicted body weight, PEEP of 8-10 cm H(2)O, apnea tests performed by using continuous positive airway pressure, and closed circuit for airway suction). MAIN OUTCOME MEASURES The number of organ donors meeting eligibility criteria for harvesting, number of lungs harvested, and 6-month survival of lung transplant recipients. RESULTS The trial was stopped after enrolling 118 patients (59 in the conventional ventilatory strategy and 59 in the protective ventilatory strategy) because of termination of funding. The number of patients who met lung donor eligibility criteria after the 6-hour observation period was 32 (54%) in the conventional strategy vs 56 (95%) in the protective strategy (difference of 41% [95% confidence interval {CI}, 26.5% to 54.8%]; P <.001). The number of patients in whom lungs were harvested was 16 (27%) in the conventional strategy vs 32 (54%) in the protective strategy (difference of 27% [95% CI, 10.0% to 44.5%]; P = .004). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (11/16 [69%] vs 24/32 [75%], respectively; difference of 6% [95% CI, -22% to 32%]). CONCLUSION Use of a lung protective strategy in potential organ donors with brain death increased the number of eligible and harvested lungs compared with a conventional strategy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00260676.

Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

Objectives:To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. Design:Matched cohort study with historical control. Setting:Two academic Italian ICUs. Patients:Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). Interventions:Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ⩽ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. Measurements and Main Results:Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07–0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5–31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6–57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. Conclusions:These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

The influence of gender on the epidemiology of and outcome from severe sepsis

IntroductionThe impact of gender on outcome in critically ill patients is unclear. Weinvestigated the influence of gender on the epidemiology of severe sepsis andassociated morbidity and mortality in a large cohort of ICU patients in the regionof Piedmont in Italy.MethodsThis was a post-hoc analysis of data from a prospective, multicenter,observational study in which all patients admitted to one of 24 participatingmedical and/or surgical ICUs between 3 April 2006 and 29 September 2006 wereincluded.ResultsOf the 3,902 patients included in the study, 63.5% were male. Female patients weresignificantly older than male patients (66 ± 16 years vs. 63 ± 16 years,P < 0.001). Female patients were less likely to have severe sepsisand septic shock on admission to the ICU and to develop these syndromes during theICU stay. ICU mortality was similar in men and women in the whole cohort (20.1%vs. 19.8%, P = 0.834), but in patients with severe sepsis wassignificantly greater in women than in men (63.5% vs. 46.4%, P = 0.007).In multivariate logistic regression analysis with ICU outcome as the dependentvariable, female gender was independently associated with a higher risk of ICUdeath in patients with severe sepsis (odds ratio = 2.33, 95% confidence interval =1.23 to 4.39, P = 0.009) but not in the whole cohort (odds ratio = 1.07,95% confidence interval = 0.87 to 1.34).ConclusionIn this large regional Italian cohort of ICU patients, there were more male thanfemale admissions. The prevalence of severe sepsis was lower in women than in men,but female gender was independently associated with a higher risk of death in theICU for patients with severe sepsis.

Medium Term Outcomes of Transapical Aortic Valve Implantation: Results From the Italian Registry of Trans-Apical Aortic Valve Implantation

BACKGROUND Transcatheter aortic valve implantation (TAVI) has been proposed as a therapeutic option for high-risk or inoperable patients with severe symptomatic aortic valve stenosis. The aim of this multicenter study was to assess early and medium term outcomes of transapical aortic valve implantation (TA-TAVI). METHODS From April 2008 through June 2012, a total of 774 patients were enrolled in the Italian Registry of Trans-Apical Aortic Valve Implantation (I-TA). Twenty-one centers were included in the I-TA registry. Outcomes were also analyzed according to the impact of the learning curve (first 50% cases versus second 50% cases of each center) and of the procedural volume (high-volume versus low-volume centers). RESULTS Mean age was 81.0±6.7 years, mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) I, EuroSCORE II, and The Society of Thoracic Surgeons risk score were 25.6%±16.3%, 9.4%±11.0%, and 10.6%±8.5%, respectively. Median follow-up was 12 months (range, 1 to 44). Thirty-day mortality was 9.9% (77 patients). Overall 1-, 2-, and 3-year survival was 81.7%±1.5%, 76.1%±1.9%, and 67.6%±3.2%, respectively. Thirty-day mortality of the first 50% patients of each center was higher when compared with the second half (p=0.04) but 3-year survival was not different (p=0.64). Conversely, 30-day mortality at low-volume centers versus high-volume centers was similar (p=0.22). At discharge, peak and mean transprosthetic gradients were 21.0±10.3 mm Hg and 10.2±4.1 mm Hg, respectively. These values remained stable 12 and 24 months after surgery. CONCLUSIONS Transapical TAVI provides good results in terms of early and midterm clinical and hemodynamic outcomes. Thus it appears to be a safe and effective alternative treatment for patients who are inoperable or have high surgical risk.

Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome.

Background:Guidelines suggest a plateau pressure (PPLAT) of 30 cm H2O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. Methods:Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a “reference standard.” Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics (“training set,” N = 30). Accuracy of these values was assessed in a second group of patients (“validation set,” N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; “physiological set,” N = 50). Results:Sensitivity and specificity of PPLAT of greater than 30 cm H2O were 0.06 (95% CI, 0.002–0.30) and 1.0 (95% CI, 0.87–1.00). PPLAT of greater than 25 cm H2O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35–0.97) and 0.75 (95% CI, 0.43–0.95) for PPLAT greater than 25 cm H2O versus 0.88 (95% CI, 0.47–1.00) and 0.50 (95% CI, 0.21–0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R2 = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R2 = 0.762). Conclusions:The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H2O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L.

Being overweight or obese is associated with decreased mortality in critically ill patients: A retrospective analysis of a large regional Italian multicenter cohort

PURPOSE To describe the epidemiology of obesity in a large cohort of intensive care unit (ICU) patients and study its impact on outcomes. METHODS All 3902 patients admitted to one of 24 ICUs in the Piedmont region of Italy from April 3 to September 29, 2006, were included in this retrospective analysis of data from a prospective, multicenter study. RESULTS Mean body mass index (BMI) was 26.0 ± 5.4 kg/m(2): 32.8% of patients had a normal BMI, 2.6% were underweight, 45.1% overweight, 16.5% obese, and 2.9% morbidly obese. ICU mortality was significantly (P < .05) lower in overweight (18.8%) and obese (17.5%) patients than in those of normal BMI (22%). In multivariate logistic regression analysis, being overweight (OR = 0.73; 95%CI: 0.58-0.91, P = .007) or obese (OR = 0.62; 95%CI: 50.45-0.85, P = .003) was associated with a reduced risk of ICU death. Being morbidly obese was independently associated with an increased risk of death in elective surgery patients whereas being underweight was independently associated with an increased risk of death in patients admitted for short-term monitoring and after elective surgery. CONCLUSIONS In this cohort, overweight and obese patients had a reduced risk of ICU death. Being underweight or morbidly obese was associated with an increased risk of death in some subgroups of patients.

Factors affecting pattern of care and survival in a population-based cohort of non-small-cell lung cancer incident cases

OBJECTIVE To analyze the role of sociodemographic factors as determinants of the initial pattern of care and survival in incident NSCLC cases. METHODS We linked 2298 incident NSCLC cases, identified by the Piedmont Cancer Registry of Turin (PCRT) with administrative health records to identify the initial pattern of care. Because stage of disease strongly influences pattern of care and prognosis of NSCLC, all the analyses were stratified according to stage (early and advanced). The association between the set of patients characteristics and the probability of accessing a specific pattern of care was analysed with a multivariable multinomial logistic regression model. Survival was analysed with the Cox proportional hazard model. RESULTS In the early stage group, presence of comorbidities, older age and low educational level were all associated with a lower probability of receiving surgery. These same factors, as well as being unmarried, were associated with higher probability of receiving other non-curative care only. The effects of comorbidities and low educational level as barriers to receiving more effective patterns of care were not relevant in the advanced stage group. When controlling for initial patterns of care, in the early stage group, an age older than 75 years and being unmarried were negative prognostic factors, while survival was completely independent from educational level. Among patients with an advanced stage of disease, only comorbidities had a negative impact on survival. CONCLUSION Appropriate lung cancer care is affected by sociodemographic factors. Greater attention to social and health programs is recommended to improve the timeliness of diagnosis, the staging of potentially resectable patients, and to implement more comprehensive multidisciplinary evaluations of those who may benefit from curative treatments.

When does transapical aortic valve replacement become a futile procedure? An analysis from a national registry

OBJECTIVES Patient selection is crucial to achieve good outcomes and to avoid futile procedures in patients undergoing transcatheter aortic valve replacement. The aim of this multicenter retrospective study was to identify independent predictors of 1-year mortality in patients surviving after transapical transcatheter aortic valve replacement. METHODS We analyzed data from the Italian registry of transapical transcatheter aortic valve replacement that includes patients undergoing operation in 21 centers from 2007 to 2012. Futility was defined as mortality within 1 year after transapical transcatheter aortic valve replacement in patients surviving at 30 days. Thirty-day survivors were divided in 2 groups: futility (group F) and nonfutility (group NF). Cox proportional hazard regression analysis was performed to identify independent predictors of futility. RESULTS We analyzed data from 645 patients with survival of 30 days or more after transapical transcatheter aortic valve replacement. Groups F and NF included 60 patients (10.8%) and 585 patients (89.2%), respectively. Patients in group F were more likely to have insulin-dependent diabetes (15% vs 7.2%, P = .03), creatinine 2.0 mg/dL or greater or dialysis (18.3% vs 8.2%, P = .01), logistic European System for Cardiac Operative Risk Evaluation greater than 20% (66.7% vs 50.3%, P = .02), preoperative rhythm disorders (40% vs 25.3%, P = .03), critical preoperative state (8.3% vs 1.8%, P = .002), and left ventricular ejection fraction less than 30% (15% vs 2.9%, P < .001). The multivariate analysis identified the following as independent predictors of futility: insulin-dependent diabetes (odds ratio, 3.1; P = .003), creatinine 2.0 mg/dL or greater or dialysis (odds ratio, 2.52; P = .012), preoperative rhythm disorders (odds ratio, 1.88; P = .04), and left ventricular ejection fraction less than 30% (odds ratio, 4.34; P = .001). CONCLUSIONS According to our data, among patients undergoing transapical transcatheter aortic valve replacement, those with insulin-dependent diabetes, advanced chronic kidney disease, rhythm disorders, and low left ventricular ejection fraction have a higher risk to undergo futile procedures.

Ventilatory Management During Normothermic Ex Vivo Lung Perfusion: Effects on Clinical Outcomes.

Background During ex vivo lung perfusion (EVLP), fixed ventilator settings and monitoring of compliance are used to prevent ventilator-induced lung injury (VILI). Analysis of the airway pressure-time curve (stress index) has been proposed to assess the presence of VILI. We tested whether currently proposed ventilator settings expose lungs to VILI during EVLP and whether the stress index could identify VILI better than compliance. Methods Flow, volume, and airway opening pressure were collected continuously during EVLP. Durations of mechanical ventilation, intensive care unit (ICU) and hospital lengths of stay were recorded in lung recipients. Results Fourteen lungs underwent EVLP and were transplanted. In 5 lungs, 95 ± 2% of the stress index values were within the 0.95 to 1.05 range (protected); in the remaining nine lungs, 69 ± 1% of the values were greater than 1.05 and 15 ± 3% were less than 0.95 (nonprotected). There was a significant (P < 0.05) increase in cytokine concentrations after 4 hours of EVLP in the nonprotected lungs. Durations of mechanical ventilation, ICU, and hospital lengths of stay were shorter in recipients of protected than that of nonprotected lungs (P < 0.05). There was no correlation between compliance during EVLP and duration of mechanical ventilation or ICU and hospital lengths of stay in recipients, but the stress index during EVLP was significantly correlated with the duration of mechanical ventilation and with ICU and hospital lengths of stay (P < 0.05). Conclusions This small, preliminary study shows that ventilator settings currently proposed for EVLP may expose lungs to VILI. Use of the stress index to personalize ventilator settings needs to be tested in further clinical studies.