Bernard Cholley

International expert statement on training standards for critical care ultrasonography

Training in ultrasound techniques for intensive care medicine physicians should aim at achieving competencies in three main areas: (1) general critical care ultrasound (GCCUS), (2) “basic” critical care echocardiography (CCE), and (3) advanced CCE. A group of 29 experts representing the European Society of Intensive Care Medicine (ESICM) and 11 other critical care societies worldwide worked on a potential framework for organizing training adapted to each area of competence. This framework is mainly aimed at defining minimal requirements but is by no means rigid or restrictive: each training organization can be adapted according to resources available. There was 100% agreement among the participants that general critical care ultrasound and “basic” critical care echocardiography should be mandatory in the curriculum of intensive care unit (ICU) physicians. It is the role of each critical care society to support the implementation of training in GCCUS and basic CCE in its own country.Training in ultrasound techniques for intensive care medicine physicians should aim at achieving competencies in three main areas: (1) general critical care ultrasound (GCCUS), (2) “basic” critical care echocardiography (CCE), and (3) advanced CCE. A group of 29 experts representing the European Society of Intensive Care Medicine (ESICM) and 11 other critical care societies worldwide worked on a potential framework for organizing training adapted to each area of competence. This framework is mainly aimed at defining minimal requirements but is by no means rigid or restrictive: each training organization can be adapted according to resources available. There was 100% agreement among the participants that general critical care ultrasound and “basic” critical care echocardiography should be mandatory in the curriculum of intensive care unit (ICU) physicians. It is the role of each critical care society to support the implementation of training in GCCUS and basic CCE in its own country.

Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report

AIMS Comparative studies suggest that stem cells committed to a cardiac lineage are more effective for improving heart function than those featuring an extra-cardiac phenotype. We have therefore developed a population of human embryonic stem cell (ESC)-derived cardiac progenitor cells. METHODS AND RESULTS Undifferentiated human ESCs (I6 line) were amplified and cardiac-committed by exposure to bone morphogenetic protein-2 and a fibroblast growth factor receptor inhibitor. Cells responding to these cardio-instructive cues express the cardiac transcription factor Isl-1 and the stage-specific embryonic antigen SSEA-1 which was then used to purify them by immunomagnetic sorting. The Isl-1(+) SSEA-1(+) cells were then embedded into a fibrin scaffold which was surgically delivered onto the infarct area in a 68-year-old patient suffering from severe heart failure [New York Heart Association [NYHA] functional Class III; left ventricular ejection fraction (LVEF): 26%]. A coronary artery bypass was performed concomitantly in a non-infarcted area. The implanted cells featured a high degree of purity (99% were SSEA-1(+)), had lost the expression of Sox-2 and Nanog, taken as markers for pluripotency, and strongly expressed Isl-1. The intraoperative delivery of the patch was expeditious. The post-operative course was uncomplicated either. After 3 months, the patient is symptomatically improved (NYHA functional Class I; LVEF: 36%) and a new-onset contractility is echocardiographically evident in the previously akinetic cell/patch-treated, non-revascularized area. There have been no complications such as arrhythmias, tumour formation, or immunosuppression-related adverse events. CONCLUSION This observation demonstrates the feasibility of generating a clinical-grade population of human ESC-derived cardiac progenitors and combining it within a tissue-engineered construct. While any conclusion pertaining to efficacy would be meaningless, the patients functional outcome yet provides an encouraging hint. Beyond this case, the platform that has been set could be useful for generating different ESC-derived lineage-specific progenies.

High incidence of myocardial ischemia during postpartum hemorrhage

BACKGROUND: Postpartum hemorrhage remains a major cause of global maternal morbidity and mortality, even in developed countries, despite the use of intensive care units. This study sought to (1) assess whether myocardial ischemia could be associated with and even aggravate hemorrhagic shock in young parturients admitted for postpartum hemorrhage, and (2) identify the independent risk factors for myocardial ischemia. METHODS: On their referral to the intensive care unit, a multidisciplinary team managed parturients with severe postpartum hemorrhage. Ventilation, transfusion, catecholamines, surgery, or angiography with uterine embolization were provided as clinically indicated. Plasma cardiac troponin I levels were used as a surrogate marker of acute myocardial injury and electrocardiograms of myocardial ischemia. RESULTS: A total of 55 parturients were referred with severe postpartum hemorrhage, all in hemorrhagic shock. Twenty-eight parturients (51%) had elevated serum levels of cardiac troponin I (9.4 microg/l [3.7-26.6 microg/l]), which were associated with electrocardiographic signs of ischemia and deteriorated myocardial contractility and correlated with the severity of hemorrhagic shock. Indeed, multivariate analysis identified low systolic and diastolic arterial blood pressure ( 115 beats/min) as independent predictors of myocardial injury. In addition, all patients who were given catecholamines also had elevated cardiac troponin I levels. CONCLUSIONS: These results suggest that treatment of postpartum hemorrhage-induced hemorrhagic shock should be coupled with concomitant prevention of myocardial ischemia, even in young parturients.

Inflammatory cytokine response in patients with septic shock secondary to generalized peritonitis

Objectives: The aims of this study were the following: a) to assess the proinflammatory cytokine (tumor necrosis factor [TNF]‐α, interleukin [IL]‐1, and IL‐6) response in patients with septic shock secondary to generalized peritonitis; and b) to evaluate the influence of bacteremic status, type of peritonitis (acute perforation or postoperative), and peritoneal microbial status (mono‐ or polymicrobial) on cytokine expression and mortality. Design: Prospective study. Setting: Surgical intensive care unit of a university hospital. Patients: Fifty‐two consecutive patients with septic shock caused by generalized peritonitis. Interventions: Routine blood tests, blood cultures, and cytokine assays were performed during the first 3 days after onset of shock. Measurements and Main Results: Serum TNF‐α and IL‐6 concentrations were measured by using a radioimmunoassay, and IL‐1 concentrations were measured by using ELISA. Median serum concentrations on day 1 were: TNF‐α, 90 pg/mL; IL‐1, 7 pg/mL; and IL‐6, 5000 pg/mL. TNF‐α and IL‐6 concentrations decreased significantly between the first and third days of septic shock (p = .0001), whereas IL‐1 concentrations remained low. The decrease in IL‐6 tended to be more pronounced in the survivors group (p = .057). Median TNF‐α serum concentrations were higher in bacteremic compared with nonbacteremic patients (151 vs. 73 pg/mL, p = .003). TNF‐α, IL‐1, and IL‐6 serum concentrations and mortality were not different between acute perforation vs. postoperative peritonitis and mono‐ versus polymicrobial peritonitis. Conclusions: The systemic release of TNF‐α and IL‐6 during septic shock caused by generalized peritonitis was maximal on day 1 and decreased rapidly during the next days. No systemic release of IL‐1 was observed. IL‐6 serum concentrations remained higher in patients who subsequently died. Among the different features of peritonitis studied, only bacteremia influenced the systemic cytokine response (higher TNF‐α).

International consensus statement on training standards for advanced critical care echocardiography

Endorsed by the European Society of Intensive Care Medicine (ESICM), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), Société de Réanimation de Langue Française (SRLF), Asia Pacific Association of Critical Care Medicine, Canadian Critical Care Society, College of Intensive Care Medicine of Australia and New Zealand, Hong Kong College of Anaesthesiologists, Hong Kong Society of Critical Care Medicine. All authors certify that they endorse all parts of the published manuscript. The expert round table participants and the authors as a group are listed in the Appendix.

Noninvasive techniques for measurements of cardiac output.

Purpose of reviewMeasuring stroke volume or cardiac output is of paramount importance for the management of critically ill patients in the intensive care unit, or ‘high risk’ surgical patients in the operating room. The new noninvasive techniques are gaining acceptance among intensivists and anesthesiologists who have been trained almost exclusively in the pulmonary artery catheter and the thermodilution technique. Recent findingsThe present review focuses on the recent publications related to esophageal Doppler, Fick principle applied to carbon dioxide associated with partial rebreathing, and pulse contour analysis. Recent validation studies have confirmed the previous findings: all three methods provide reliable estimations of cardiac output and its variations. There is not a single method standing out and ruling out the others. Many investigators are now using one of the ‘noninvasive’ monitors to measure cardiac output in clinical or experimental studies. SummaryBy making cardiac output easily measurable in various settings, these techniques should all contribute to improve hemodynamic management in critically ill or high-risk surgical patients.

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

IntroductionThe risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.MethodsThis was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).ResultsFrequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.ConclusionsUnlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

Impaired plasma B-type natriuretic peptide clearance in human septic shock.

Introduction:High B-type natriuretic peptide (BNP) levels are reported in the context of septic shock. We hypothesized that high BNP levels might be related to an alteration in BNP clearance pathway, namely neutral endopeptidase (NEP) 24.11. NEP 24.11 activity was measured in septic shock and in cardiogenic shock patients. We further evaluated whether baseline plasma BNP can predict fluid responsiveness and whether BNP can still be released in plasma despite high initial BNP levels, in response to overloading. Material and Methods:Prospective observational study. Patients in severe sepsis (S) or in septic shock (SS) needing a fluid challenge were included. Stroke volume (SV) and BNP were measured before (SV1, BNP1) and 45 mins after (SV2, BNP2) a standardized fluid challenge. DeltaBNP was defined as the difference between BNP2 and BNP1. NEP 24.11 activity was determined by fluorometry in 12 SS and 4 S patients before fluid challenge and in 5 cardiogenic shock patients. Results:Twenty-three patients (61 ± 18 years old, Simplified Acute Physiology Score II: 54 ± 21; 19 SS, 4 S; BNP1: 1371 ± 1434 pg/mL) were studied. BNP1 concentrations were significantly higher in SS than in S (1643 ± 1437 vs. 80 ± 35 pg/mL; p = 0.002). There was no correlation between baseline BNP and fluid responsiveness. Nine of the 11 patients with BNP1 >1000 pg/mL were fluid responders. DeltaBNP was greater in fluid nonresponders than in fluid responders (22 ± 27% vs. 6 ± 11%, p = 0.028). Plasma BNP was higher in SS than in cardiogenic shock patients (1367 ± 1438 vs. 750 ± 346 respectively; p = 0.027). NEP 24.11 activity was lower in SS than in S patients (0.10 ± 0.06 nmole/mL/min vs. 0.50 ± 0.22 nmole/mL/min, p <0.0001) cardiogenic shock patients (0.10 ± 0.06 nmole/mL/min vs. 0.58 ± 0.19 nmole/mL/min; p = 0.002). Conclusion:High levels of BNP might be related to an alteration in BNP clearance. During sepsis, high BNP levels are not predictive of fluid nonresponsiveness. Nevertheless, in fluid nonresponders, acute ventricular stretching can result in further BNP release.

High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: A prospective study in 59 patients

BACKGROUND In several studies including patients with septic shock of various origins, high serum cytokine levels have been reported to correlate with poor outcome. The aim of this prospective study was to assess the prognostic value of cytokine serum levels in a group of patients with perioperative septic shock of digestive origin. METHODS From January 1992 to December 1994, 59 patients were evaluated (mean age, 68 +/- 15 years). From the first day of septic shock to day 7, blood was drawn every day to measure the conventional biologic parameters (white blood cell count, platelet count, hematocrit, blood urea nitrogen level, serum electrolytes level, pH, blood gases, serum lactate level, coagulation parameters, liver function tests) and tumor necrosis factor (TNF), interleukin-1, and interleukin-6. RESULTS No difference was observed between the 26 survivors and the 33 nonsurvivors with regard to age, gender, and cause of sepsis. On admission, mean platelet count was significantly higher in the survivors than in the nonsurvivors (260 +/- 142 versus 177 +/- 122 10(9)/L; p = 0.01). Mean blood urea nitrogen level was significantly lower in the survivors than in the nonsurvivors (9.6 +/- 9 versus 12 +/- 7 mmol/L; p = 0.04). No difference was observed between survivors and nonsurvivors for the other conventional biologic parameters and for serum interleukin-1 and interleukin-6 levels. Mean serum TNF level tended to be higher in survivors than in nonsurvivors (565 +/- 1325 versus 94 +/- 69 pg/ml; not significant). In the group survivor 9 (35%) of 26 patients had a serum TNF level greater than 200 pg/ml versus 2 (6%) of 33 patients in the nonsurvivor group (p < 0.02). Survival was noted in 6 (100%) of 6 patients who had both a serum TNF level greater than 200 pg/ml and a platelet count greater than 100.10(9)/L versus 1 (11%) of 9 in patients with neither of these criteria (p < 0.01). CONCLUSIONS In our patients with abdominal septic shock, high serum TNF levels were associated with increased survival. The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. Although this possibility must be further explored, a score combining the serum TNF level and platelet count could be helpful for the prognostic assessment of patients with abdominal septic shock.

Differential Effects of Chronic Oral Antihypertensive Therapies on Systemic Arterial Circulation and Ventricular Energetics in African-American Patients

BACKGROUND A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MVO2). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MVO2. METHODS AND RESULTS Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MVO2, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or ACL. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MVO2 per beat was reduced with these agents. Stress-time index, a measure of MVO2 per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol. CONCLUSIONS The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MVO2 in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MVO2 with each drug may provide a more physiological approach to the treatment of systemic hypertension in indivi