Benoit Vallet

Mortality after surgery in Europe: a 7 day cohort study

Summary Background Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe. Methods We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ2 and Fishers exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p<0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries. Findings We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19–1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland). Interpretation The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients. Funding European Society of Intensive Care Medicine, European Society of Anaesthesiology.

Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a "gray zone" approach.

Background:Respiratory arterial pulse pressure variations (PPV) are the best predictors of fluid responsiveness in mechanically ventilated patients during general anesthesia. However, previous studies were performed in a small number of patients and determined a single cutoff point to make clinical discrimination. The authors sought to test the predictive value of PPV in a large, multicenter study and to express it using a gray zone approach. Methods:The authors studied 413 patients during general anesthesia and mechanical ventilation in four centers. PPV, central venous pressure, and cardiac output were recorded before and after volume expansion (VE). Response to VE was defined as more than 15% increase in cardiac output after VE. The following approaches were used to determine the gray zones: resampled and two-graph receiver operator characteristic curves. The impact of changes in the benefit-risk balance of VE on the gray zone was also evaluated. Results:The authors observed 209 responders (51%) and 204 nonresponders (49%) to VE. The area under receiver operating characteristic curve was 0.89 (95% CI: 0.86–0.92) for PPV, compared with 0.57 (95% CI: 0.54–0.59) for central venous pressure (P < 10−5). The gray zone approach identified a range of PPV values (between 9% and 13%) for which fluid responsiveness could not be predicted reliably. These PPV values were seen in 98 (24%) patients. Changes in the cost ratio of VE moderately affected the gray zone limits. Conclusion:Despite a strong predictive value, PPV may be inconclusive (between 9% and 13%) in approximately 25% of patients during general anesthesia.

Clinical review: Update on hemodynamic monitoring - a consensus of 16

Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. With increased concerns about the use of invasive techniques, notably the pulmonary artery catheter, to measure cardiac output, recent years have seen an influx of new, less-invasive means of measuring hemodynamic variables, leaving the clinician somewhat bewildered as to which technique, if any, is best and which he/she should use. In this consensus paper, we try to provide some clarification, offering an objective review of the available monitoring systems, including their specific advantages and limitations, and highlighting some key principles underlying hemodynamic monitoring in critically ill patients.

High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

IntroductionOur purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss.MethodsThis was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures.ResultsA total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P = 0.03).ConclusionsThis study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH.Trial registrationControlled Trials ISRCTN09968140.

A balanced view of balanced solutions

The present review of fluid therapy studies using balanced solutions versus isotonic saline fluids (both crystalloids and colloids) aims to address recent controversy in this topic. The change to the acid-base equilibrium based on fluid selection is described. Key terms such as dilutional-hyperchloraemic acidosis (correctly used instead of dilutional acidosis or hyperchloraemic metabolic acidosis to account for both the Henderson-Hasselbalch and Stewart equations), isotonic saline and balanced solutions are defined. The review concludes that dilutional-hyperchloraemic acidosis is a side effect, mainly observed after the administration of large volumes of isotonic saline as a crystalloid. Its effect is moderate and relatively transient, and is minimised by limiting crystalloid administration through the use of colloids (in any carrier). Convincing evidence for clinically relevant adverse effects of dilutional-hyperchloraemic acidosis on renal function, coagulation, blood loss, the need for transfusion, gastrointestinal function or mortality cannot be found. In view of the long-term use of isotonic saline either as a crystalloid or as a colloid carrier, the paucity of data documenting detrimental effects of dilutional-hyperchloraemic acidosis and the limited published information on the effects of balanced solutions on outcome, we cannot currently recommend changing fluid therapy to the use of a balanced colloid preparation.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): Lessons from an International Sepsis Registry

Background:The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis.Materials and Methods:PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and ≥ 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board.Results:PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively.Conclusions:The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

Prognostic value of the dobutamine test in patients with sepsis syndrome and normal lactate values: a prospective, multicenter study.

To determine the oxygen supply (Vo2) and uptake (Vo2) responses to a 60-min dobutamine infusion in critically ill septic patients without circulatory shock and with normal blood lactate concentrations. Also, to determine whether these responses would predict outcome. Design:Prospective, cohort study. Setting:Five intensive care units in university-affiliated, city hospitals. Patients:Fifty critically ill patients with sepsis syndrome were studied from April 1990 to August 1991. Interventions:Pulmonary artery catheteriza-tion; fluid loading if pulmonary artery occlusion pressure was <10 mm Hg; and 10 μg/min/kg dobutamine infusion for 60 mins. Measurements and Main Results:Cardiac in-dex, Vo2, Vo2, and oxygen extraction ratio were determined immediately before and 1 hr after the onset of the dobutamine test. Using receiver operating characteristic curves, responders to the dobutamine infusion were identified by a >15% increase in Vo2 from the time immediately before to 1 hr after the onset of the dobutamine test. We identified 23 responders and 27 nonresponders. Groups differed significantly in age (responders 46 yrs vs. nonresponders 55 yrs) and associated chronic disease (responders one cancer vs. nonresponders six cancers). Significant changes in responders were: a) cardiac index increased 42.9%; b) systemic vascular resistance decreased 20.7%; and c) Vo2 increased 39.1% while Vo2 increased 40.8%, with no changes in oxygen extraction or blood lactate concentration. Significant changes in nonresponders were: a) cardiac index increased 14.2%; b) Vo2 increased 13.2%; and c) oxygen extraction decreased from 0.26 to 0.22. Lactate concentration increased significantly by 25.1% in nonresponders. The mortality rate in responders (8.7%) was significantly less than that rate in nonresponders (44.4%). Conclusions:Most of these septic patients without shock or hyperlactatemia responded to dobutamine infusion in one of two ways: with little increase in Vo2 and no increase in Vo2, or with significant increases in both Vo2 and Vo2 The latter response is typical of healthy volunteers given dobutamine. Because of the calorigenic effect of dobutamine, our results imply nothing about the presence or absence of oxygen supply limitation. Still, patients who had increases in Vo2 and Vo2 had a much higher survival rate than patients who did not. We speculate that the inability of some patients to respond to dobutamine and the associated higher mortality rate may be related to β-adrenoreceptor dysfunction. (Crit Care Med 1993; 21:1868–1875)

Gastric capnometry with air-automated tonometry predicts outcome in critically ill patients

ContextContrary to tonometer gastric intramucosal pH, there is currently no validated threshold prognostic value for Pco2 gap (tonometer gastric mucosal Pco2 minus arterial Pco2) in the critically ill patient. ObjectiveTo demonstrate a relationship between Pco2 gap and mortality in mechanically ventilated patients. Design and SettingInception cohort study from a 9-month prospective survey of 95 consecutively ventilated critically ill patients in a teaching hospital. PatientsAll the ventilated patients of the intensive care unit were included at their admission. Measurements and Main ResultsGastric Pco2 using regional capnometry with air-automated tonometry, arterial gas, lactate, and organ system failure score were measured at admission and after 6, 12, 24, 48, 72, 96, and 120 hrs. For the entire population, the 28-day mortality was 44%. In multivariate analysis, independent predictors of death were organ system failure score (odds ratio, 2.12; 95% confidence interval, 1.02–3.14), 24-hr Pco2 gap (odds ratio, 1.57; 95% confidence interval, 1.10–2.24), and 24-hr lactate (odds ratio, 1.48; 95% confidence interval, 1.06–2.05). We found a threshold value of 20 mm Hg for Pco2 gap and 2.5 mmol/L for lactate, which was associated with a sensitivity of 0.70 and 0.72, respectively, and a specificity of 0.72 and 0.73, respectively. ConclusionThe Pco2 gap is a marker of mortality in ventilated patients in the intensive care unit.

Central venous O2 saturation and venous-to-arterial CO2 difference as complementary tools for goal-directed therapy during high-risk surgery

IntroductionCentral venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference (P(cv-a)CO2), a global index of tissue perfusion, could be used as a complementary tool to ScvO2 for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery.MethodsThis is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO2i), ScvO2, P(cv-a)CO2 and postoperative complications were recorded blindly for all patients.ResultsA total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO2 (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO2 (minScvO2) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO2i values. The optimal ScvO2 cut-off value was 70.6% and minScvO2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO2 was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10-6). In patients with complications and ScvO2 ≥71%, P(cv-a)CO2 was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO2 ≥71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value.ConclusionsScvO2 reflects important changes in O2 delivery in relation to O2 needs during the perioperative period. A P(cv-a)CO2 < 5 mmHg might serve as a complementary target to ScvO2 during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO2 ≥71% is achieved.Trial registrationClinicaltrials.gov Identifier: NCT00852449.

Endothelial cell dysfunction and coagulation.

Objectivesa) To review endothelial properties and to establish how these unperturbed properties contribute to the maintenance of endothelium anticoagulant activity; b) to better understand the relative contributions of endothelial cells and monocytes in sepsis-induced altered coagulation. Data SourcesA summary of published literature from MEDLINE search files and other original articles and reviews published on endothelial cell and monocyte functions and modifications owing to sepsis. Data Extraction and Synthesis Unperturbed endothelial cells provide anticoagulant properties; exposure to inflammatory and/or septic stimuli can rapidly lead to procoagulant behavior. Sepsis alters endothelial cell surface and induces tissue factor synthesis at the endothelial and subendothelial levels. During endotoxemia, endothelial cells generate adhesion molecules that bind leukocytes and monocytes, increasing local procoagulant reactions. Tissue factor expression is also increased at the level of the monocyte; the relative importance of endothelial injury and monocyte activation in coagulation disorders was recently assessed. Endothelium protection before induction of septic shock was not associated with any reduction in monocyte tissue factor expression, suggesting that altered coagulation was present despite normal endothelial cell function. On the other hand, decreased monocyte tissue factor expression was associated with a marked reduction in endothelial injury, increased endothelium-derived relaxation, and improved survival rate in treated animals. ConclusionsThis review suggests that monocyte activation and tissue factor expression may be of paramount importance in sepsis-associated injuries and that coagulation activation may contribute to the endothelial cell injury observed during sepsis. Endothelial injury, in turn, exacerbates sepsis-induced coagulation abnormalities.