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Background— In acute myocardial infarction, the relationship between volume and quality indicators (QIs) is poorly documented. Through a nationwide assessment of QIs at discharge repeated for 3 years, we aimed to quantify the relationship between volume and QIs in survivors after acute myocardial infarction. Methods and Results— Almost all healthcare centers in France participated. Medical records were randomly selected. Data collection was performed by an independent group. QIs for acute myocardial infarction were defined by an expert consensus group as appropriate prescription at discharge of aspirin, clopidogrel, β-blocker, statin, and an angiotensin-converting enzyme inhibitor in patients with left ventricular ejection fraction 300, a significantly lower rate of all QIs was observed in centers with the lowest volume. Odds ratios progressively decreased with increasing volume. Despite a significant increase in the composite QI over the 3 years, a significant relationship persisted between volume and quality of care. Conclusions— Analysis of QIs at discharge demonstrates the existence of a relationship between volume and appropriate prescriptions at discharge. Centers with the highest volume perform better on quality measures than centers with lower volumes. Temporal analysis over 3 consecutive years confirms this relationship and shows that it persists despite improvement in QIs between 2008 and 2010.

OBJECTIVE To investigate the role of metformin accumulation in the pathophysiology of metformin-associated lactic acidosis. RESEARCH DESIGN AND METHODS We used high-performance liquid chromatography to measure plasma metformin concentrations in 14 patients who experienced lactic acidosis (pH 5 mmol/l) while receiving chronic metformin treatment. Their treatment was generally based on alkalinization and dialysis therapy. RESULTS Clinical shock and/or evidence of tissue hypoxia was found in all patients with the exception of one who had a nonsteroidal anti-inflammatory drug-induced anuria. Ten patients had significant metformin accumulation (plasma metformin concentrations 4.1-84.9 mg/l, normal value 0.6 ± 0.5 mg/l before drug intake), generally because of failure to withdraw metformin despite intercurrent pathological conditions affecting its renal elimination (serum creatinine concentrations ranging from 269 to 1,091 μmol/l). There was no metformin accumulation (plasma metformin 0.03–0.7 mg/l) in the four other patients, who had less severe renal failure (serum creatinine 140–349 mumol/l). The severity of the patient's general condition did not predict early hospital mortality (death before discharge from the intensive care unit) even in patients in shock. Whereas it was high in those without metformin accumulation (only 1 of 4 patients recovered), early hospital mortality was low in the 10 patients with metformin accumulation and was not related to its extent (3 patients died with end-stage hepatic failure or cardiac failure). Correlation studies showed a positive correlation between serum creatinine and plasma metformin and between plasma metformin and arterial lactate but, for the latter correlation, only in patients with metformin accumulation. CONCLUSION Metformin-associated lactic acidosis is not necessarily due to metformin accumulation; true type B (aerobic) lactic acidosis, i.e., without an apparent associated hypoxic factor, seems exceptional. Neither the severity of the clinical picture nor the degree of metformin accumulation predicted survival; rather, the prognosis was dependent upon the severity of the associated pathological conditions.

Objective To determine the impact on hospital ranking of different aggregation methods when creating a composite score from a set of quality indicators relating to a single clinical condition. Design The analysis was based on 14966 medical records taken from all French hospitals that treated over 30 patients with acute myocardial infarction in 2008 (n=275). Five quality indicators measuring the quality of care delivered to patients with acute myocardial infarction at hospital discharge were aggregated by 5 methods issued from a variety of activity sectors (indicator average, all-or-none, budget allocation process, benefit of the doubt, and unobserved component model). Main outcome measures Each aggregation method was used to rank hospitals into 3 categories depending on the position of the 95% confidence interval of the composite score relative to the overall mean. Variations in rank according to method were estimated using weighted κ coefficients. Results Agreement between methods ranged from poor (κ=0.20) to almost perfect (κ=0.84). A change of method led to a change in rank for 71% (196 of 275) of hospitals. Only 14 of 121 hospitals which were ranked top and 20 of 118 which were ranked bottom, by at least 1 of the 5 methods, held their rank on a switch to the 4 other methods. Conclusion Hospital ranking varied widely according to 5 aggregation methods. If one method has to be chosen, for instance for reporting to governments, regulatory agencies, payers, health care professionals, and the public, it is necessary to provide its rationale and characteristics, and information on score uncertainty.

Background Intensive care unit (ICU) admission of adults with cystic fibrosis (CF) is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors. Methods Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality. Results Prior to ICU admission, all patients (mean age 28.1 ± 8 yr) had a severe lung disease (mean FEV1 28 ± 12% predicted; mean PaCO2 47 ± 9 mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60). At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV1 loss was associated with a poor outcome (HR = 1.47 [1.18–1.85], p = 0.001). SAPSII (HR = 1.08 [1.03–1.12], p < 0.001) and endotracheal intubation (HR = 16.60 [4.35–63.34], p < 0.001) were identified as strong independent predictors of mortality. Conclusion Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered.

Cerebellar syndromes and radiologic cerebellar atrophy after hyperpyrexia have occasionally been reported, mostly in neuroleptic malignant syndromes, but neuropathologic studies are extremely rare. We studied 3 patients (a 74-year-old woman, a 63-year-old man, and an 80-year-old man) who had heat stroke during heat waves in France. One patient had generalized seizures and died 28 hours after admission. The other patients survived one month and 2 months after admission; both had palatal myoclonus, and in one case, magnetic resonance imaging showed high signal intensity in the cerebral peduncles. The main neuropathology in the 3 cases was severe diffuse loss of Purkinje cells associated with heat shock protein 70 expression by Bergmann glia. In situ end labeling was negative in surviving Purkinje cells, suggesting that the mechanism of neuronal death was not apoptosis. Degeneration of Purkinje cells axons resulted in myelin pallor of the white matter of the folia and of the hilum of the dentate nuclei. DNA internucleosomal breakages were identified by in situ end labeling in the dentate nuclei and centromedian nuclei of the thalamus and were associated with degeneration of the cerebellar efferent pathways: superior cerebellar peduncles, decussation of the superior cerebellar peduncles (Wernekinck commissure), and dentatothalamic tract. These findings suggest that the mechanisms of neuronal death in the dentate nuclei and centromedian nuclei of the thalamus was different from that in Purkinje cells and more likely resulted from deafferentation. Ammon's horn and other areas susceptible to hypoxia were spared. These observations confirm the selective vulnerability of Purkinje cells to heat-induced injury and involvement of the cerebellar efferent pathways in palatal myoclonus.

Objective: The use of cardiopulmonary bypass (CPB) for lung transplantation (LTx) has been reported previously. This study reports the authors’ experience of planned and unplanned use of cardiopulmonary bypass for LTx. Design: Case series. Setting: A university teaching hospital. Participants: Patients undergoing LTx. Interventions: A retrospective analysis of the charts of all patients having undergone LTx over the last 10 years. Measurements and Main Results: Among 140 LTx, 23 (16%) were performed with the use of CPB. CPB was planned in 11 cases and unplanned in the 12 other cases. The use of CPB is associated with a longer period of postoperative mechanical ventilation, more pulmonary edema, more blood transfusion requirement, and an increase in postoperative mortality at 48 hours and 1 month. Surgical difficulties related to the dissection of the native left lung and acute right ventricular failure are the main reasons for unscheduled use of CPB. Conclusion: Scheduled and unscheduled CPB for LTx are associated with an increased mortality at 1 month and 1 year.

The effect of graft ischemic time on early graft function and long-term survival of patients who underwent lung transplantation remains controversial. Consequently, graft ischemic time has not been incorporated in the decision-making process at the time of graft acceptance.To investigate the relationship between graft ischemic time and (1) early graft function and (2) long-term survival after lung transplantation.The data from 752 patients who underwent single lung transplantation (n = 258), bilateral lung transplantation (n = 247), and heart-lung transplantation (n = 247) in seven French transplantation centers during a 12-year period were reviewed. Independent data quality control was done to ensure the quality of the collected variables. Mean graft ischemic time was 245.8 +/- 96.4 minutes (range 50-660). After adjustment on 11 potential confounders, graft ischemic time was associated with the recipient Pa(O2)/FI(O2) ratio recorded within the first 6 hours and with long-term survival in patients undergoing single or double lung transplantation but not in patients undergoing heart-lung transplantation. The relationship between graft ischemic time and survival appears to be of cubic form with a cutoff value of 330 minutes. These results were unaffected by the preservation fluid employed.The results of this large cohort of patients suggest a close relationship between graft ischemic time and both early gas exchange and long-term survival after single and double lung transplantation. Such relationship was not found in patients undergoing heart-lung transplantation. The expected graft ischemic time should be incorporated in the decision-making process at the time of graft acceptance.

International audience; Background: The liberalization of lung-donor criteria and the use of marginal donors have been advocated to face the current shortage of donors in lung transplantation. However, the impact of donor characteristics on the outcome of lung transplantation is still largely unknown. We aimed to determine, on a large cohort of patients, the effect of donors characteristics on short- and long-term outcome of lung transplantation. Methods: Between 1988 and 1998, a total of 785 adult patients underwent single-lung transplantation (n 270), bilateral-lung transplantation (n = 251), and heart-lung transplantation (n = 264) in 7 centers in France. We constructed several multivariate models to assess the relationship between donor characteristics and early gas exchange, duration of mechanical ventilation, and long-term survival after lung transplantation. Results: Among donor characteristics, donor gas exchange before harvest was found to be significantly associated with recipient early gas exchange, duration of mechanical ventilation, and long-term survival after adjustment for potential confounding variables. Moreover, nonlinear modeling showed a steep increase in the relative risk of death when donor Pao(2)/Fio(2) before harvest was below 350 (hazard ratio 1.43; 95% confidence interval 1.10 - 1.85; p = 0.01). Donor and recipient sex mismatch were also found to be significantly associated with long-term survival. Conclusions: Although liberalization of lung-donor criteria may be considered to overcome the shortage of lung donors, our data suggest that the violation of the gas-exchange criterion should be avoided.

To assess incidence, outcome, and early predictors of mortality for patients with primary graft failure (PGF) following lung transplantation (LTx), and to develop an injury severity score able to accurately predict ICU mortality for these patients.Retrospective cohort analysis.Two LTx centers in Paris.Two hundred fifty-nine patients who underwent LTx over a 12-year period.One hundred thirty-one patients (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days following LTx associated with gas exchange impairment (PaO(2)/fraction of inspired oxygen ratio300 mm Hg). This syndrome was associated with an increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days, mean +/- SD; p0.001) and ICU mortality (29% vs 10.9%; p0.01). The patients with PGF were randomly assigned to developmental (n = 85) and validation (n = 46) samples. Using logistic regression analysis, four variables were found associated with ICU mortality in these patients: age, degree of gas exchange impairment, graft ischemic time, and severe early hemodynamic failure. An ischemia/reperfusion injury severity score was derived using these four variables. Model calibration was good in the developmental and validation samples, as was model discrimination (area under receiver operating characteristic curves, 0.93 and 0.85, respectively).PGF following LTx is a frequent event, with significant ICU morbidity and mortality. We demonstrate that four simple factors allow prediction of ICU mortality with good accuracy.

The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris between 1988 and 1999, the preservation technique applied to the donor lung was single-flush perfusion of the pulmonary artery with one of several solutions of intracellular (Euro-Collins, n = 61; University of Wisconsin, n = 24) or extracellular composition (Cambridge, n = 64; Celsior, n = 21). The early postoperative outcome of these patients was reviewed. Reimplantation edema occurred in 48% of all patients, and the overall 1-mo survival rate was 84%. No significant difference in the incidence of edema, duration of mechanical ventilation, and 1-mo survival rate was observed between the four groups or between intra- and extracellular groups. After adjustment for graft ischemic time by means of multivariate analysis, the use of extracellular preservation fluid was associated with a lower incidence of reimplantation edema without effect on 1-mo mortality. Graft ischemic time was associated with both edema occurrence and 1-mo survival rate (p = 0.02 and p = 0.01, respectively). We conclude that extracellular-type solutions are associated with better lung preservation than intracellular-type solutions in clinical transplantation.

Objectives To assess the efficacy of the Simplified Acute Physiology Score (SAPS II) in intermediate care units. A number of patients hospitalized in the intensive care unit (ICU) could be hospitalized in alternative structures, intermediate care units, which are equipped to handle their monitoring needs and able to provide adequate treatment at a lower cost. Characterization of the patients relies on the assessment of their severity of illness by severity scores. The efficiency of severity scores has been established in ICU patients, but not in the setting of intermediate care units. Design Prospective study. Setting Intermediate care unit of a multidisciplinary hospital. Patients Four hundred thirty-three patients admitted to the intermediate care unit. Interventions None. Measurements and Main Results Of 561 consecutive patients admitted to the intermediate care unit during a 12-mo period, 433 patients could be included in the analysis. Patients were admitted from the emergency ward (60.9%). Of the study patients, 60.9% were admitted from the emergency ward for mostly (96%) medical reasons. Average length of stay was 3.1 +/- 2.3 (SD) days. Death rate in the intermediate care unit was 2.7% (n = 11). Average SAPS II was 22.3 +/- 12.0 (range 6 to 73). Hospital death rate was 8.1%, whereas the expected mortality rate derived from SAPS II was 8.7%. To assess the performance of the system, a formal goodness-of-fit test was performed to evaluate calibration. Calibration was accurate using the C coefficient of Hosmer-Lemeshow statistics (C = 2.4; p > 0.5). The discriminant power of SAPS II, measured by the area under the receiver operating characteristic curve was excellent (0.85 +/- 0.04). Conclusions The SAPS II assessment of severity of illness in patients admitted to an intermediate care unit is reliable. These results will need to be confirmed, using different patient samplings from intermediate care units. (Crit Care Med 1998; 26:1368-1371)

Bilateral lung transplantation (BLT) is a recently described procedure based on two sequential single-lung transplantations (SLT), which are performed by a transverse sternobithoracotomy. It does not require either cardiac arrest or routine use of cardiopulmonary bypass (CPB). The intraoperative management of 10 patients suffering from end-stage pulmonary disease is reported. Implantation of the first graft is quite similar to a SLT. Problems encountered during this procedure (ie, hypoxemia, hypercapnia, or low cardiac output) were due to restricted pulmonary and cardiac reserve. Preoperative and intraoperative assessment of the recipient's respiratory and cardiac status was, therefore, of prime importance. Mild preoperative pulmonary hypertension, well-preserved right ventricular function, and removal of the less well-perfused lung limited these difficulties; no patient required partial CPB at this stage. During the second lung implantation, gas exchange was provided by the first grafted lung. Measurements of pulmonary vascular resistance (PVR), venous admixture (Qva/Qt), and dead space (VD/VT) assessed with the arterial-to-end-tidal CO2 difference were used to confirm the adequacy of perfusion and V/Q matching. In one patient, partial CPB was instituted because of surgical difficulty related to inadequate size matching of the lungs. In the other patients, first graft function was satisfactory and the second graft was implanted without CPB. With chest closure, PVR returned to nearly normal values (range, 57-293, mean 167 dynes.s.cm-5) and Qva/Qt increased (range, 3 to 36, mean 20%). This limited series demonstrates that CPB is optional during this procedure. Good selection of recipients and donors, good lung preservation methods, and a short duration of cold ischemia are essential to success.

The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.