Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality.

BACKGROUND: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. METHODS: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. RESULTS: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. CONCLUSIONS: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. CLINICAL TRIAL REGISTRATION: NCT02141607.

Peri-operative massive pulmonary embolism management: is veno-arterial ECMO a therapeutic option?

Pulmonary embolism remains an important clinical problem with a high mortality rate. The potential for sudden and fatal hemodynamic deterioration highlights the need for a prompt diagnosis and appropriate intervention. The purpose of the present case report is to describe a successful peri-operative veno-arterial extra corporeal membrane oxygenation (VA-ECMO) implantation for assumed massive pulmonary embolism associated with high hemodynamic instability and severe hypoxemia. A 52-year-old female victim of a motorcycle accident had been operated on for unstable fractures that required optimal repair. Despite subcutaneous administration of 40 mg enoxaparin on day 0 and day 1, the patient developed a massive pulmonary embolism leading to peri-operative pulseless activity. As intravenous thrombolysis was strictly contraindicated, a VA-ECMO was successfully implanted and permitted to stabilize the patient's hemodynamics. The hemodynamic and respiratory status improved by day 3, and the ECMO was removed. A vena cava filter was implanted before successful and definitive stabilization of the femoral fracture and the L2 fracture on days 4 and 5. The patient was able to be mobilized 2 days after the surgery and was transferred to a rehabilitation ward on day 15. At that time, her cognitive functions had fully recovered. ECMO can provide lifesaving hemodynamic and respiratory support in patients with massive pulmonary embolism who are too unstable to tolerate other interventions, who have failed other therapies or for whom other therapies are contraindicated.

["Mobile" ECMO]. / Extracorporeal membrane oxygenation "mobile".

ECMO (extracorporeal membrane oxygenation) is a cardiac or respiratory support which uses the principle of extracorporeal circulation (ECC). It consists of a pump generating an output as well as a membrane oxygenating blood and removing CO2. Thanks to an ECMO mobile team, expert caregivers can now perform the circulatory support in primary centers and then transfer patients under assistance to the referral center. After a brief summary of the two different anatomical approaches (veno-arterial and veno-venous) as well as their indications, the authors will share their experience of two transferred patients under ECMO to Geneva. Referral center and ECMO mobile team concepts will then be detailed focusing on the present situation in Switzerland.

Performance of a new pulse contour method for continuous cardiac output monitoring: validation in critically ill patients.

BACKGROUND: A new calibrated pulse wave analysis method (VolumeView™/EV1000™, Edwards Lifesciences, Irvine, CA, USA) has been developed to continuously monitor cardiac output (CO). The aim of this study was to compare the performance of the VolumeView method, and of the PiCCO2™ pulse contour method (Pulsion Medical Systems, Munich, Germany), with reference transpulmonary thermodilution (TPTD) CO measurements. METHODS: This was a prospective, multicentre observational study performed in the surgical and interdisciplinary intensive care units of four tertiary hospitals. Seventy-two critically ill patients were monitored with a central venous catheter, and a thermistor-tipped femoral arterial VolumeView™ catheter connected to the EV1000™ monitor. After initial calibration by TPTD CO was continuously assessed using the VolumeView-CCO software (CCO(VolumeView)) during a 72 h period. TPTD was performed in order to obtain reference CO values (COREF). TPTD and arterial wave signals were transmitted to a PiCCO2™ monitor in order to obtain CCO(PiCCO) values. CCO(VolumeView) and CCO(PiCCO) were recorded over a 5 min interval before assessment of CO(TPTD). Bland-Altman analysis, %(errors), and concordance (trend analysis) were calculated. RESULTS: A total of 338 matched sets of data were available for comparison. Bias for CCO(VolumeView)-CO(REF) was -0.07 litre min(-1) and for CCO(PiCCO)-CO(REF) +0.03 litre min(-1). Corresponding limits of agreement were 2.00 and 2.48 litre min(-1) (P<0.01), %(errors) 29 and 37%, respectively. Trending capabilities were comparable for both techniques. CONCLUSIONS: The performance of the new VolumeView™-CCO method is as reliable as the PiCCO2™-CCO pulse wave analysis in critically ill patients. However, an improved precision was observed with the VolumeView™ technique. CLINICALTRIALS.GOV IDENTIFIER: NCT01405040.

Cardioplegia and ventricular late potentials in cardiac surgical patients.

BACKGROUND AND OBJECTIVE: Ventricular late potentials (LP) recording with signal-averaged electrocar- diogram allow identifying patients at risk of sudden death and ventricular tachycardia. Cardiac surgery with cardiopulmonary bypass (CPB) could predispose to the development of myocardial ischemia related to imperfect cardioplegia. To the best of our knowledge, no study investigated the protection of cardioplegia and CPB regarding the occurrence of LP in patients without previous myocardial infarction and undergoing cardiac surgery. METHODS: In 61 elective patients scheduled for cardiac surgery involving CPB, signal-averaged electrocar- diogram was performed the day before and 24-48 h after the surgery. The electrodes were positioned according to Frank's orthogonal derivations. Twenty five patients were excluded because of poor quality signals, leaving 36 patients (age, 64 ± 14) available for the analyses. An abnormal signal-averaged electrocardiogram was considered when ≥2 of the recorded indexes were present. McNemar's tests were performed on the dichotomized values to investigate differences in pre-post scores. RESULTS: The mean CPB duration was of 110 ± 57 min. Patients scheduled for cardiac surgery do not exhibited LP after CPB (no significant difference in pre-post CPB scores, P = NS). The probability of a patient with a negative score transitioning to a positive score was 0.23 (P = NS). CONCLUSIONS: The present study in cardiac surgical patients suggests that cardioplegia associated to CPB has no significant impact on the occurrence of LP, irrespective of surgery performed.

[Evaluation of skills required to practice advanced echocardiography in intensive care]. / Evaluation des compétences requises pour la pratique de l'échocardiographie à un niveau avancé aux soins intensifs.

In 2009, the Critical Care Network of the American College of Chest Physicians (ACCP) in partnership with La Sociéte de Reanimation de Langue Française selected a panel of experts to characterize competence in critical care ultrasonography. The task force developed a consensus and made recommendations concerning the qualifications in ultrasonography. Experts have identified specific skills that intensivit should acquire, by setting a minimum standard for the realisation and control of ultrasound. Last year, we published in the present journal the results of this consensus conference concerning the "basic echocardiography" for intensivit. This year, we summarize here the results of the consensus conference and its conclusions on the assessment of advanced level skills to practice echocardiography in intensive care.

[When the heart and/or the lung fails: the ECMO]. / Quand le coeur et/ou les poumons défaillent: oxygénation extracorporelle par "ECMO".

The Extra corporeal membrane oxygenation (ECMO) was initially proposed as a technique of respiratory support using an external membrane oxygenator. With time, it has also become a technique of cardiorespiratory support to ensure both gas exchange and organ perfusion until the restoration of organs function. This technical assistance can be central or peripheral and provides a partial or total circulatory support. The circuit includes a non occlusive centrifugal pump, an oxygenator for an enrichment of O2 and elimination of CO2 and cannulas for drainage and re-injection. Recently, the establishment of such assistance became possible percutaneously, allowing it to be initiated at the intensive care bedside or even before in-hospital admission.

Transthoracic echocardiography after heart surgery: could pleural view be of some help?

The pericardial effusion localized on the upper portion of the right atrium is a classical complication of the post-operative heart surgery setting. This issue is most likely not visualized by transthoracic echocardiography and needs the transoesophageal approach. The present case reports a situation where an associated bilateral pleural effusion permitted a new view of the heart which has been helpful to confirm the diagnosis of tamponade and to re-transfer the patient to the operative room.

[Physiopathologic aspects of microcirculation in intensive care]. / Aspects physiopathologiques de la microcirculation aux soins intensifs.

In critical care patients, microvascular alterations and perfusion heterogeneity play an important role in the persistence of cellular hypoxia despite a satisfactory functioning of the macrocirculation. Advance in the knowledge of microcirculatory pathophysiology, and its relation with the macrocirculation could be in the future a way to improve the outcome of critically ill patients. Moreover, the evolution of clinical practice towards microcirculation monitoring as a standard of care, with new therapeutic targets aimed to increase tissue perfusion, could be a revolution in critical care practice.

Characteristics of sepsis-induced cardiac dysfunction using speckle-tracking echocardiography: a feasibility study.

Septic cardiomyopathy is commonly encountered in patients with severe sepsis and septic shock. This study explores whether novel global and segmental echocardiographic markers of myocardial deformation, using two-dimensional speckle tracking, are associated with adverse sepsis outcomes. We conducted a retrospective observational feasibility study, at a tertiary care centre, of patients admitted to the ICU with a diagnosis of sepsis who underwent an echocardiogram within the first week of sepsis diagnosis. Data were collected on chamber dimensions, systolic and diastolic function, demographics, haemodynamics, and laboratory parameters. Global and segmental left ventricular longitudinal strain (LVLS) and tissue mitral annular displacement (TMAD) were assessed on 12 left ventricular segments and six mitral annulus segments in apical views, respectively. We explored associations of abnormal LVLS and TMAD with duration of mechanical ventilation, hospital length of stay, and mortality. Fifty-four patients were included. Global LVLS was not associated with any of the primary study endpoints. However, reduced systolic LVLS of the basal anterior segment was associated with in-hospital mortality. There was a suggestion that patients with a reduced global TMAD were associated with an increased risk of mortality and a short length of hospital stay but these associations were not statistically significant. Reduced global LVLS was associated with lower ejection fraction. Reduced global TMAD was associated with reduced global and segmental LVLS, reduced left ventricular ejection fraction, and increased left ventricular end-systolic and end-diastolic volumes. Speckle-tracking echocardiography can be performed feasibly in patients in sepsis. Global and segmental left ventricular deformation indices are associated with ejection fraction. Further studies need to evaluate the ability of these new indices to predict sepsis outcomes.

Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Validation of new positron emission tomography (PET) tracers or magnetic (MR) imaging contrast agents is based on isolated rodent heart preparations. The use of larger animals could provide a more direct validation using the devices used for humans. METHODS: An isolated pig heart preparation has been developed and adapted to the technical constraints of whole body PET and MR imaging. This preparation could be used either in the Langendorff or working mode after selective cannulation of both coronary arteries. RESULTS: The authors showed that quantification of regional kinetics of PET tracers was possible using this preparation by measuring fluorine-18-labeled deoxyglycose (18FDG) kinetics in remote and ischemic territories. Experiments using MR imaging contrast agents, for myocardial perfusion, demonstrated the ability of this preparation to accurately validate these contrast agents over a wide range of flow rates. CONCLUSIONS: An isolated pig heart preparation could be developed to fulfill the constraints of PET and MR imaging, and proved useful for the study of the distribution of different tracers or contrast media developed for functional cardiac imaging in humans.

Role of glycolysis in the energy production for the non-mechanical myocardial work in isolated pig hearts.

BACKGROUND: The dissociation of mechanical from non-mechanical energy utilisation can be studied using BDM (2,3-butanedione monoxime), which inhibits the actin-myosin interaction without inhibiting Ca2+ transport. The objective of the present study was to establish if increasing the non-mechanical energy demand of perfused isolated pig hearts by dobutamine stimulation requires glycolysis with increased exogenous glucose uptake. METHODS: Five isolated pig hearts (CTRL) were perfused for 90 min at constant flow (1 ml g(-1) min(-1)) with non-recirculating blood containing 30 mM BDM and 26 MBq/l of fluorine-18 2-fluoro-2-deoxyglucose (IFDG). This was compared with five hearts (DOBU) subjected to the same protocol for the first 30 min and then to dobutamine (1.5 microM) for the following 30 min and dobutamine (4 microM) for the last 30 min. Five other isolated hearts were perfused as for the DOBU group but without BDM (CTRLDOBU). Using a clinical PET scanner, glucose uptake was assessed by estimating 18FDG uptake using linear regression. The slope variations were compared using a global test of coincidence. RESULTS: Heart rate was at 100 +/- 2 b.p.m. in the CTRL group and at 180 +/- 7 b.p.m. in the DOBU group. 18FDG uptake was homogeneous within the whole myocardium and we observed a linear and regular increase in both the CTRL and DOBU groups (p, NS). In the CTRLDOBU group, 18FDG uptake was also homogeneous within the whole myocardium, but slopes of 18FDG uptake during dobutamine perfusion were higher than without dobutamine. CONCLUSION: In blood-perfused isolated pig hearts, exogenous glucose is not necessarily required when non-mechanical energy is increased by dobutamine stimulation. These findings suggest that ATP derived from glycolysis is not necessary to preserve myocardial Ca2+ transport during beta-adrenergic stimulation.

Slaughterhouse blood as a perfusate for studying myocardial function under ischemic conditions.

Metabolic studies using the in vitro non-recirculating blood-perfused isolated heart model require large volumes of blood. The present study was designed to determine whether heterologous pig blood collected from a slaughterhouse can be used as perfusate for isolated pig hearts perfused under aerobic and constant reduced flow conditions. Eight isolated working pig hearts perfused for 90 min at a constant flow of 1.5 ml g(-1) min(-1) with non-recirculated blood diluted with Krebs-Henseleit bicarbonate buffer at a hematocrit of 23% were compared to eight hearts subjected to the same protocol but perfused only with Krebs-Henseleit bicarbonate buffer solution. Hearts were paced at 100 bpm and subjected to aerobic perfusion at 38 degrees C. Hearts were weighed before perfusion and at the end of the experiment and the results are reported as percent weight gain (mean +/- SD). Comparisons between groups were performed by the Student t-test (P<0.05). After 90 min of perfusion with modified Krebs-Henseleit, perfused hearts presented a larger weight gain than blood-perfused hearts (39.34 +/- 9.27 vs 23.13 +/- 5.42%, P = 0.003). Left ventricular end-diastolic pressure was higher in the modified Krebs-Henseleit-perfused group than in the blood group (2.8 +/- 0.4 vs 2.3 +/- 0.3 mmHg, respectively, P = 0.01). We conclude that heterologous blood perfusion, by preserving a more physiological myocardial water content, is a better perfusion fluid than modified Krebs-Henseleit solution for quantitative studies of myocardial metabolism and heart function under ischemic conditions.

[Cardiovascular manifestations of systemic elastorrhexis]. / Manifestations cardiovasculaires de l'élastorrhéxie systématisée.

INTRODUCTION: Systemic elastorrhexis or Grönblad-Strandberg-Touraine syndrome is a rare inherited disease characterized by a generalized elastic tissue dysplasia and polymorphic clinical features, with the main tissues affected being cutaneous, ocular and arterial. CURRENT KNOWLEDGE AND KEY POINTS: Usual cardiovascular complications of this entity include ischemic heart disease, renovascular hypertension and atherosclerotic peripheral vascular disease. Some cases of restrictive cardiomyopathies and valvular disease have been reported. Coronary artery disease, often with early onset, is seen in approximately 20% of cases. FUTURE PROSPECTS AND PROJECTS: This review of the literature concerning a rare cause of cardiopathy underlines the need to search for underlying elastorrhexis in the clinical setting of early onset and severe coronary artery disease or arteriopathy, especially in the absence of vascular risk factors. This hereditary disease has been traced to chromosome 16p13.1 and may in the future be easily diagnosed, bypassing the need for cutaneous biopsy.

[Mid-term prognostic value of plasma heavy-chain myosin in thrombolysed myocardial infarction]. / Valeur pronostique à moyen terme du dosage des chaines lourdes de la myosine plasmatique dans l'infarctus du myocarde thrombolysé.

Plasma myosin heavy chain assay, which can be easily performed during the acute phase of myocardial infarction, is a recent method allowing quantitative assessment of the extent of infarction. However, to our knowledge, its prognostic value has not been studied in contrast with serum myosin light chain assay. We monitored the state of health of 40 patients (including 37 men with a mean age of 56 years) for two years after a first myocardial infarction, thrombolized during the acute phase. Their survival (mortality) and the development of "cardiac events" (MI, angina, sudden death, etc.) were evaluated at 2 years. The results observed at 2 years were correlated with the initial plasma myosin assay results and other direct and indirect methods of assessment of the extent of infarction, performed during the acute phase of myocardial infarction (cardiac enzymes, contrast angiography). The main result of this study is the demonstration that an unusual plasma myosin release kinetic (complex appearance) is predictive for the medium-term development of heart failure (p = 0.04) and/or destabilization of coronary insufficiency (p = 0.02). These results need to be emphasized, as with only 5 serum myosin assays performed over a 10-day period, it seems possible to identify a group of patients at high risk of medium-term complications, who possess a complex release kinetic during the acute phase of myocardial infarction and a value for area under the curve greater than 10.470 microliters U/L (cut-off value, p = 0.043).

[Anuric renal insufficiency caused by bilateral ureteral lithiasis]. / Insuffisance rénale anurique par lithiase urétérale bilatérale.

A 73-year-old man was admitted to the ICU for anuria. He reported no history of urinary disease. The abdominal roentgenography and two echographies showed an empty urinary bladder, a right ureteral calculus without dilatation of the urinary tract. Computed tomography demonstrated the presence of a left ureteral stone. Bilateral retrograde ureteroscopy and drainage allowed a rapid recovery. When the abdominal roentgenography and echography cannot explain the occurrence of anuria, the computed tomography, or better the helical CT, can demonstrate the presence of otherwise unrecognized calculi.

[Acute dissection of the ascending thoracic aorta complicated by myocardial infarct: an unavoidable diagnostic pitfall?]. / Dissection aiguë de l'aorte thoracique ascendante compliquée d'infarctus du myocarde: un piège diagnostique inévitable?

BACKGROUND: Acute dissection of the aorta during myocardial infarction is exceptional. In such cases, fibrinolysis can be fatal. CASE REPORTS: A 63-year-old woman with a history of hypertension was referred to our intensive care unit with the diagnosis of early stage inferior myocardial infarction. Thrombolysis was instituted and the patient rapidly developed cardiovascular collapse with global heart failure. Coronarography was attempted to revascularize the occluded coronary artery but the coronary arteries could not be catheterized. An aortography was performed and gave the diagnosis of De Bakey type I dissection of the aorta. The patient died from cardiac arrest after a phase of low cardiac output. DISCUSSION: This case illustrates how myocardial infarction can complicate or mask acute dissection of the aorta. It also raises the question of transthoracic echocardiography prior to institution of fibrinolysis.