In-hospital cardiac arrests admitted alive in intensive care units: Insights from the CubRéa database.

BACKGROUND: In-hospital cardiac arrest(IHCA) has received little attention compared with out-of-hospital cardiac arrest. AIM: To address the paucity of data on IHCA patients, we examined key features, variations in mortality and predictors of death among patients admitted in French intensive care units(ICUs) from 1997 to 2015. METHODS: Using the database of the Collège des Utilisateurs de Bases de données en Réanimation(CUB-Réa) that prospectively collects data from ICUs in the greater Paris area, we determined temporal trends in the incidence of IHCA, patients' outcomes, crude and Simplified Acute Physiology Score(SAPS)-II Standardized mortality and predictors of in-ICU mortality. RESULTS: Of the 376,325 ICU admissions, 15,324(4.08%) had IHCA, with incidence increasing from 2.78% to 3.83%(p < 0.001). Over time, the patient age increased by 0.7 years(p = 0.04) and SAPS-II increased by 2.3%(p < 0.001). Crude in-ICU mortality decreased from 78% to 62.5% over the past 18 years(p < 0.001). The SAPS-II-standardized mortality also decreased over time from 78.4% to 68.3%(p < 0.001) representing a 10.1% relative decrease from 1997 to 2015. In multivariate analysis, admission in a more recent time-period was an independent correlate of decreased mortality(OR 0.40, 95%CI 0.35-0.46). CONCLUSION: Occurrence of IHCA increased over time but remains an uncommon reason for being admitted to ICU. From 1997 to 2015, we observed a change in patient profile, with older and more critically ill patients, despite which in-ICU mortality has substantially decreased in IHCA patients, likely resulting from a global improvement in the process of care and more widespread implementation of rapid response teams.

Epidemiology and Predictors of Long-Stays in Medical ICU: A Retrospective Cohort Study.

INTRODUCTION: Prolonged stays in ICU have been associated with overconsumption of resources but little is known about their epidemiology. We aimed to identify predictors and prognostic factors of extended stays, studying a long-stay population. METHODS: We present a retrospective cohort study between July 2000 and December 2013 comparing patients hospitalized in a medical ICU for ≥30 days (long-stay patients-LSP) with patients hospitalized for <30 days (short-stay patients-SSP). Admission characteristics were collected from the local database for every patient and evolution during the ICU stay was retrieved from LSP files. RESULTS: Among 8906 patients hospitalized in the ICU, 417 (4.7%) were LSP. At admission, male sex (adjusted odds-ratio (aOR) 1.4 [1.1; 1.7]), inpatient (aOR 2.0 [1.6; 2.4]) and in-ICU hospitalizations for respiratory (aOR 2.9 [1.6; 3.5]) or infectious diseases (aOR 1.6 [1.1; 2.5]) were all independently associated with a long stay in the ICU, while hospitalizations for metabolic (aOR 0.2 [0.1; 0.5]) or cardiovascular diseases (aOR 0.3 [0.2; 0.5]) were in favor of a short stay. In-ICU and in-hospital LSP mortality were 38.8% and 48.2%. Age (aOR 1.02 [1.00-1.04]), catecholamines (aOR 3.9 [1.9; 8.5]), renal replacement therapy (aOR 2.4 [1.3; 4.3]), primary disease-related complications (aOR 2.5 [1.4; 4.6]) and nosocomial infections (aOR 4.1 [1.8; 10.1]) were independently associated with mortality in LSP. CONCLUSION: LSP were highly comorbid patients mainly hospitalized for respiratory diseases. Their mortality was mostly related to nosocomial infections but the majority were discharged alive from the hospital.

How to strengthen the presence of patients in health technology assessments conducted by the health authorities.

The constant development of health technologies, combined with the increase in the cost of treatment, means that States must continually make choices about the introduction of new technologies into their healthcare system and how they are to be funded. In France, the systematic participation of patients in these processes is one of the targets to be met in terms of healthcare democracy. Although, on an international level, patient involvement in these assessments is constantly growing, it is difficult to define due to the presence of unstabilised elements in terms of both terminology and assessment methods. As a result, patient and public involvement in health technology assessments varies considerably from one country to the next, from one field to the next and even from one type of technology to the next. Several types of involvement exist, ranging from studies conducted to collect patient "insight" (experience, perception, needs, preferences, attitudes to treatment and health, etc.) to processes aimed at including patients in assessments (as individuals, as representatives of associations, etc.). Given the scope and complexity of the subject, and the difficulty involved in understanding all the different aspects of health technologies and innovations, the members of the Round Table chose to concentrate on health technology assessments (medicinal products and medical devices) to develop national recommendations on all possible types of patient involvement in the health technology assessment processes conducted by the health authorities in France.

Management of end-stage heart failure patients with or without ventricular assist device: an observational comparison of clinical and economic outcomes.

OBJECTIVES: Heart transplantation (HT) and ventricular assist devices (VAD) for the management of end-stage heart failure have not been directly compared. We compare the outcomes and use of resources with these 2 strategies in 2 European countries with different allocation systems. METHODS: We studied 83 patients managed by VAD as the first option in Bad Oeynhausen, Germany (Group I) and 141 managed with either HT or medical therapy, as the first option, in Paris, France (Group II). The primary end-point was 2-year survival. Kaplan-Meier analyses were performed after the application of propensity score weights to mitigate the effects of non-random group assignment. The secondary end-points were resource utilization and costs. Subgroup analyses were performed for patients undergoing HT and patients treated with inotropes at the enrolment time. RESULTS: The Group I patients were more severely ill and haemodynamically compromised, and 28% subsequently underwent HT vs 55% primary HT in Group II, P < 0.001. The adjusted probability of survival was 44% in Group I vs 70% in Group II, P <0.0001. The mean cumulated 2-year costs were €281 361 ± 156 223 in Group I and €47 638 ± 35 061 in Group II, P < 0.0001. Among patients who underwent HT, the adjusted probability of survival in Group I (n = 23) versus Group II (n = 78) was 76% versus 68%, respectively (0.09), though it differed in the inotrope-treated subgroups (77% in Group I vs 67% in Group II, P = 0.04). CONCLUSIONS: HT should remain the first option for end-stage heart failure patients, associated with improved outcomes and better cost-effectiveness profile. VAD devices represent an option when transplant is not possible or when patient presentation is not optimal.

Outcomes in elderly patients admitted to the intensive care unit with solid tumors.

BACKGROUND: As the population ages and cancer therapies improve, there is an increased call for elderly cancer patients to be admitted to the intensive care unit (ICU). This study aimed to assess short-term survival and prognostic factors in critically ill patients with solid tumors aged ≥65 years. METHODS: We conducted a retrospective study. The primary endpoint was ICU mortality. Resumption of anticancer therapy in patients who survived the ICU stay and 90-day mortality were secondary endpoints. All patients aged ≥65 years admitted to the ICU of Georges Pompidou Hospital (Paris, France) between 2009 and 2014 were eligible. RESULTS: Of 2327 eligible elderly patients (EP), 262 (75.0 ± 6.7 years) with solid tumors were analyzed. These patients were extremely critically ill (SAPS 2 61.9 ± 22.5), and 60.3% had metastatic disease. Gastrointestinal, lung and genitourinary cancers were the most common types of tumors. Mechanical ventilation was required in 51.5% of patients, inotropes in 48.1% and dialysis in 12.6%. Most patients (66.7%) were admitted for reasons unrelated to cancer, including sepsis (30.5%), acute respiratory failure (28.2%) and neurological problems (8.0%). ICU mortality in patients with cancer was 33.6 versus 32.6% among patients without cancer (p = 0.75). Among the cancer EP, the 90-day mortality was 51.9% (n = 136). In multivariate analysis, increased SAPS 2 score and primary tumor site were associated with 90-day death, whereas previous anticancer therapies and poor performance status were not. Among survivor patients from ICU with anti-tumoral treatment indication, 77 (52.7%) had resumption of anticancer treatment. CONCLUSIONS: Elderly solid tumor patients admitted to the ICU had a mortality rate similar to EP without cancer. Prognostic factors for 90-day mortality were more related to severity of clinical status at admission than the presence or stage of cancer, suggesting that early admission of EP with cancer to the ICU is appropriate.

Cardiogenic shock in intensive care units: evolution of prevalence, patient profile, management and outcomes, 1997-2012.

AIM: To address the paucity of data on the characteristics, outcome and temporal trends in mortality of cardiogenic shock (CS) patients admitted to intensive care units (ICUs) we examined key features, variations in mortality from CS, and predictors of death in ICU patients over the past 15 years. METHODS AND RESULTS: From the 1997-2012 database of the Collège des Utilisateurs de Bases de données en Réanimation (CUB-Réa) that prospectively collects data from ICUs in the greater Paris area, we determined temporal trends in the incidence of CS, patient outcomes [Crude and Simplified Acute Physiology Score (SAPS)-II Standardized Mortality] and predictors of in-ICU mortality. Of the 316 905 ICU admissions, 19 416 (6.1%) exhibited CS, with incidence increasing from 4.1% to 7.7% (P < 0.001). Over time, the age of admitted patients decreased by 2.7 years [95% confidence interval (CI), -2.0 to -3.4] and SAPS-II increased by 5.8% (95% CI 4.8-6.8) from 58.7 ± 25.3 to 64.5 ± 23.3 (P < 0.001). Crude in-ICU mortality declined from 50% to 45% (-5.6%; 95% CI -7.7 to -3.5) as SAPS-II Standardized ICU mortality rates decreased from 56.5% to 44.2% (P < 0.001). A more recent time-period was an independent correlate of decreased mortality in multivariate analyses. The decrease in mortality rate was more marked in patients with decompensated heart failure, cardiac arrest, or acute myocardial infarction. CONCLUSIONS: Patients with CS represent a greater proportion of patients admitted to ICUs over the past 15 years, having become younger but more critically ill. Although their mortality has decreased, suggesting improved overall patient management, it remains particularly high, warranting further research specifically focused on this population.

Treatment intensity, age and outcome in medical ICU patients: results of a French administrative database.

BACKGROUND: Intensive care unit (ICU) patients are aging, and older age has been associated with higher mortality in ICU. As previous studies have reported that older age was also associated with less intensive treatment, we investigated the relationship between age, treatment intensity and mortality in medical ICU patients. METHODS: Data were extracted from the administrative database of 18 medical ICUs. Patients with a unique medical ICU stay and a Simplified Acute Physiology Score II (without age-related points) >15 were included. Treatment intensity was described with a novel indicator, which is a four-group classification based upon the most frequent ICU procedures. The relationship between age, treatment intensity and hospital mortality was analyzed with the estimation of standardized mortality ratio in the four groups of treatment intensity. RESULTS: A total of 23,578 patients, including 3203 patients aged ≥80 years, were analyzed. Hospital mortality increased from 13 % for the younger patients (age < 40 years) to 38 % for the older patients (age ≥ 80 years), while Simplified Acute Physiology Score II (without age-related points) increased only from 36 (age < 40 years) to 43 (age ≥ 80). Hospital mortality increased with age in the four groups of treatment intensity. Standardized mortality ratio increased with age among the patients with less intensive treatment but was not associated with age among the patients with the highest treatment intensity. CONCLUSION: Our results support the fact that the increase in mortality with age among ICU patients is not related to an increase in severity. Using a new tool to estimate ICU treatment intensity, our study suggests that mortality of ICU patients increases with age whatever the treatment intensity is. Further investigations are required to determinate whether this increase in mortality among older ICU patients is related to undertreatment or to a lower efficiency of organ support treatment.

Assessment of right ventricular dysfunction predictors before the implantation of a left ventricular assist device in end-stage heart failure patients using echocardiographic measures (ARVADE): Combination of left and right ventricular echocardiographic variables.

BACKGROUND: Right ventricular failure (RVF) is a major cause of morbidity and mortality in left ventricular assist device (LVAD) recipients. OBJECTIVES: To identify preoperative echocardiographic predictors of post-LVAD RVF. METHODS: Data were collected for 42 patients undergoing LVAD implantation in Germany. RVF was defined as the need for placement of a temporary right ventricular assist device or the use of inotropic agents for 14 days. Data for RVF patients were compared with those for patients without RVF. A score (ARVADE) was established with independent predictors of RVF by rounding the exponentiated regression model coefficients to the nearest 0.5. RESULTS: RVF occurred in 24 of 42 LVAD patients. Univariate analysis identified the following measurements as RVF risk factors: basal right ventricular end-diastolic diameter (RVEDD), minimal inferior vena cava diameter, pulsed Doppler transmitral E wave (Em), Em/tissue Doppler lateral systolic velocity (SLAT) ratio and Em/tissue Doppler septal systolic velocity (SSEPT) ratio. Em/SLAT≥18.5 (relative risk [RR] 2.78, 95% confidence interval [CI] 1.38-5.60; P=0.001), RVEDD≥50 mm (RR 1.97, 95% CI 1.21-3.20; P=0.008) and INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) level 1 (RR 1.74, 95% CI 1.04-2.91; P=0.04) were independent predictors of RVF. An ARVADE score>3 predicted the occurrence of post-implantation RVF with a sensitivity of 89% and a specificity of 74%. CONCLUSION: The ARVADE score, combining one clinical variable and three echocardiographic measurements, is potentially useful for selecting patients for the implantation of an assist device.

Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Biosimilars: from Technical to Pharmacoeconomic Considerations.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Methicillin-resistant Staphylococcus aureus bloodstream infections are associated with a higher energy deficit than other ICU-acquired bacteremia.

PURPOSE: Caloric insufficiency during the first week of intensive care unit (ICU) stay was reported to be associated with increased infection rates, especially ICU-acquired bloodstream infection (ICU-BSI). However, the predisposition to ICU-BSI by a given pathogen remains not well known. We aimed to determine the impact of early energy-calorie deficit on the pathogens responsible for ICU-BSI. DESIGN: Prospective, observational, cohort study in a 18-bed medical ICU of a tertiary care hospital. METHODS: Daily energy balance (energy-calorie intakes minus calculated energy-calorie expenditure) was compared according to the microbiological results of the blood cultures of 92 consecutive prolonged (at least 96 h) acute mechanically ventilated patients who developed a first episode of ICU-BSI. RESULTS: Among the 92 ICU-BSI, nine were due to methicillin-resistant Staphylococcus aureus (MRSA). The cumulated energy deficit of patients with MRSA ICU-BSI was greater than those with ICU-BSI caused by other pathogens (-1,348 ± 260 vs -1,000 ± 401 kcal/day from ICU admission to day of ICU-BSI, p = 0.008). ICU admission, risk factors for nosocomial infections, nutritional status, and conditions potentially limiting feeding did not differ significantly between the two groups. Patients with MRSA ICU-BSI had lower delivered energy and similar energy expenditure, causing higher energy deficits. More severe energy deficit and higher rate of MRSA blood cultures (p = 0.01 comparing quartiles) were observed. CONCLUSIONS: Early in-ICU energy deficit was associated with MRSA ICU-BSI in prolonged acute mechanically ventilated patients. Results suggest that limiting the early energy deficit could be a way to optimize MRSA ICU-BSI prevention.

Medico-economic evaluation of healthcare products. Methodology for defining a significant impact on French health insurance costs and selection of benchmarks for interpreting results.

Decree No. 2012-1116 of 2 October 2012 on medico-economic assignments of the French National Authority for Health (Haute autorité de santé, HAS) significantly alters the conditions for accessing the health products market in France. This paper presents a theoretical framework for interpreting the results of the economic evaluation of health technologies and summarises the facts available in France for developing benchmarks that will be used to interpret incremental cost-effectiveness ratios. This literature review shows that it is difficult to determine a threshold value but it is also difficult to interpret then incremental cost effectiveness ratio (ICER) results without a threshold value. In this context, round table participants favour a pragmatic approach based on "benchmarks" as opposed to a threshold value, based on an interpretative and normative perspective, i.e. benchmarks that can change over time based on feedback.

Impact of inodilator drugs on echocardiographic assessments of left ventricular filling pressure in patients with decompensated end-stage heart failure*.

OBJECTIVES: We investigated the impact of inodilators on the accuracy of E/e' ratio as a surrogate for pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure. SETTING: The ratio of early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity, E/e', and pulmonary artery occlusion pressure have been shown to be correlated. The validity of E/e' for predicting pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure was recently challenged, but the influence of inodilators was not taken into account, despite the reported influence of these drugs on left ventricular relaxation properties. PATIENTS AND INTERVENTION: Invasive hemodynamic monitoring and echocardiographic data were collected prospectively from 39 patients with decompensated end-stage systolic heart failure (92% male), aged 56 ± 13 years. These patients had dilated ventricles with a low cardiac index (1.9 ± 0.6 L/min/m) and high pulmonary artery occlusion pressure (22 ± 8 mm Hg), and 90% required inodilator support during hospitalization. MEASUREMENTS AND MAIN RESULTS: The correlation between septal E/e' and pulmonary artery occlusion pressure was good for examinations in the absence of inodilators (n = 21) (r = 0.7; p < 0.001), but no correlation was found when inodilators were used (n = 31). Lateral and mean E/e' were poorly correlated with pulmonary artery occlusion pressure, if at all, in both cases. CONCLUSIONS: By modifying ventricular relaxation properties and the influence of filling pressure on e', inodilator agents severely impair the correlation between E/e' and pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure.

Vancomycin pharmacokinetic and pharmacodynamic models for critically ill patients with post-sternotomy mediastinitis.

BACKGROUND AND OBJECTIVE: Vancomycin is commonly used to treat serious methicillin-resistant staphylococcal infections, especially post-sternotomy mediastinitis (PSM). However, information on pharmacokinetics and pharmacodynamics in intensive care unit (ICU) patients remains scarce. We conducted vancomycin pharmacokinetic-pharmacodynamic modeling for ICU patients with PSM. METHODS: This cohort study included 30 consecutive patients who received multiple vancomycin doses during primary closed drainage of PSM with Redon catheters, targeting serum drug trough concentrations of 25-35 mg/L, and generating 359 serum vancomycin concentration-time values for analysis. Population pharmacodynamics served to describe the withdrawal of Redon catheters, i.e., the probability of in-ICU cure. RESULTS: Vancomycin pharmacokinetics corresponded to a two-compartment open model with first-order elimination kinetics. Mean [between-subject variability] population estimates were 1.91 (men)/1.25 (women) [0.28] L/h for vancomycin elimination, with intercompartmental clearance of 5.71 [1.01] L/h, and respective central and peripheral distribution volumes of 21.9 and 68 [0.53] L. Vancomycin clearance increased with body weight and declined with severity at ICU admission and serum creatinine (SCr), thereby allowing the prediction of the vancomycin plateau. Intercompartmental clearance decreased with diabetes mellitus (-70 %). The probability of withdrawing all Redon catheters (patient cured) was dependent only on the area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) exposures ratio in plasma. Neither preoperative factors, antistaphylococcal co-treatments, nor the initial number of Redon catheters significantly influenced this probability. The AUC/MIC exposures ratio had no significant effect on SCr levels. CONCLUSION: These modeling analysis results identified five clinically relevant covariates that influenced vancomycin pharmacokinetics and might achieve better individualization of vancomycin dosing for methicillin-resistant staphylococcal PSM in ICU patients.

Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due to Pseudomonas aeruginosa.

OBJECTIVE: To estimate the prevalence of ventilator-associated pneumonia caused by Pseudomonas aeruginosa in patients at risk for ventilator-associated pneumonia and to describe risk factors for P. aeruginosa ventilator-associated pneumonia. DESIGN: Prospective, observational study. SETTING: ICUs at 56 sites in 11 countries across four regions: the United States (n = 502 patients), Europe (n = 495), Latin America (n = 500), and Asia Pacific (n = 376). PATIENTS: Adults intubated and mechanically ventilated for 48 hours to 7 days, inclusive. INTERVENTIONS: None (local standard of care). MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia prevalence as defined by local investigators were 15.6% (293/1,873) globally, 13.5% in the United States, 19.4% in Europe, 13.8% in Latin America, and 16.0% in Asia Pacific (p = 0.04). Corresponding P. aeruginosa ventilator-associated pneumonia prevalences were 4.1%, 3.4%, 4.8%, 4.6%, and 3.2% (p = 0.49). Of 50 patients with P. aeruginosa ventilator-associated pneumonia who underwent surveillance testing, 19 (38%) had prior P. aeruginosa colonization and 31 (62%) did not (odds ratio, 7.99; 95% CI, 4.31-14.71). Of predefined risk factors for multidrug resistance (hereafter, risk factors), the most frequent in all patients were antimicrobial therapy within 90 days (51.9% of enrolled patients) and current hospitalization of more than or equal to 5 days (45.3%). None of these risk factors were significantly associated with P. aeruginosa ventilator-associated pneumonia by multivariate logistic regression. Risk factors associated with prior P. aeruginosa colonization were antimicrobial therapy within 90 days (odds ratio, 0.46; 95% CI, 0.29-0.73) and high proportion of antibiotic resistance in the community or hospital unit (odds ratio, 1.79; 95% CI, 1.14-2.82). CONCLUSIONS: Our findings suggest that ventilator-associated pneumonia remains a common ICU infection and that P. aeruginosa is one of the most common causative pathogens. The odds of developing P. aeruginosa ventilator-associated pneumonia were eight times higher in patients with prior P. aeruginosa colonization than in uncolonized patients, which in turn was associated with local resistance.

Severe excessive dynamic airway collapse in a patient with primary Sjögren's syndrome.

Airway and cystic lung diseases can be observed in patients with Sjögren's syndrome. We report a case of such a patient suffering from respiratory failure due to recurrent episodes of right pneumothorax, requiring invasive mechanical ventilation. Despite thoracic drainage and adequate pneumothorax management, the patient could not be weaned from the ventilator. Fiberoptic bronchoscopy revealed severe central excessive dynamic airway collapse of the lower part of the trachea and proximal bronchi. The severity of airway collapse was maximal at the intermediate bronchus level, with a near-complete obstruction during expiration. Inspiratory and expiratory computed tomography studies confirmed the fiberoptic findings and suggested a possible expiratory posterior compression of the intermediate bronchus by parenchymal lung cysts. Stenting was considered, but the patient died from ventilator-associated pneumonia before the procedure could be performed. This case is the first description of severe central excessive dynamic airway collapse in a patient with primary Sjögren's syndrome complicated by diffuse airway and cystic lung disease.