Assessment of the interplay between blood and skin vascular abnormalities in adult purpura fulminans.

RATIONALE: Purpura fulminans in adults is a rare but devastating disease. Its pathophysiology is not well known. OBJECTIVES: To understand the pathophysiology of skin lesions in purpura fulminans, the interplay between circulating blood and vascular alterations was assessed. METHODS: Prospective multicenter study in four intensive care units. Patients with severe sepsis without skin lesions were recruited as control subjects. MEASUREMENTS AND MAIN RESULTS: Twenty patients with severe sepsis and purpura fulminans were recruited for blood sampling, and skin biopsy was performed in deceased patients. High severity of disease and mortality rates (80%) was observed. Skin biopsies in purpura fulminans lesions revealed thrombosis and extensive vascular damage: vascular congestion and dilation, endothelial necrosis, alteration of markers of endothelial integrity (CD31) and of the protein C pathway receptors (endothelial protein C receptor, thrombomodulin). Elevated plasminogen activating inhibitor-1 mRNA was also observed. Comparison with control patients showed that these lesions were specific to purpura fulminans. By contrast, no difference was observed for blood hemostasis parameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coagulation markers. Bacterial presence at the vascular wall was observed specifically in areas of vascular damage in eight of nine patients tested (including patients with Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, and Pseudomonas aeruginosa infection). CONCLUSIONS: Thrombi and extensive vascular damage with multifaceted prothrombotic local imbalance are characteristics of purpura fulminans. A "vascular wall infection" hypothesis, responsible for endothelial damage and subsequent skin lesions, can be put forward.

Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism.

We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone. The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock. 529 patients were included, 25 (4.7%, 95% CI 3.2-6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I-II to 8.4% in PESI class III-IV, and to 14.3% in PESI class V (p<0.001). In PESI class I-II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III-IV versus I-II, OR 3.1, 95% CI 1.2-8.3; class V versus I-II, OR 5.5, 95% CI 1.5-25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1-1.5) were independent predictors of an adverse outcome. In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI.

Initial resuscitation guided by the Surviving Sepsis Campaign recommendations and early echocardiographic assessment of hemodynamics in intensive care unit septic patients: a pilot study.

OBJECTIVE: To compare therapeutic interventions during initial resuscitation derived from echocardiographic assessment of hemodynamics and from the Surviving Sepsis Campaign guidelines in intensive care unit septic patients. DESIGN AND SETTING: Prospective, descriptive study in two intensive care units of teaching hospitals. METHODS: The number of ventilated patients with septic shock who were studied was 46. Transesophageal echocardiography was first performed (T1<3 hrs after intensive care unit admission) to adapt therapy according to the following predefined hemodynamic profiles: fluid loading (index of collapsibility of the superior vena cava≥36%), inotropic support (left ventricular fractional area change<45% without relevant index of collapsibility of the superior vena cava), or increased vasopressor support (right ventricular systolic dysfunction, unremarkable transesophageal echocardiography study consistent with sustained vasoplegia). Agreement for treatment decision between transesophageal echocardiography and Surviving Sepsis Campaign guidelines was evaluated. A second transesophageal echocardiography assessment (T2) was performed to validate therapeutic interventions. RESULTS: Although transesophageal echocardiography and Surviving Sepsis Campaign approaches were concordant to manage fluid loading in 32 of 46 patients (70%), echocardiography led to the absence of blood volume expansion in the remaining 14 patients who all had a central venous pressure<12 mm Hg. Accordingly, the agreement was weak between transesophageal echocardiography and Surviving Sepsis Campaign for the decision of fluid loading (κ: 0.37 [0.16;0.59]). With a cut-off value<8 mm Hg for central venous pressure, κ was 0.33 [-0.03;0.69]. Inotropes were prescribed based on transesophageal echocardiography assessment in 14 patients but would have been decided in only four patients according to Surviving Sepsis Campaign guidelines. As a result, the agreement between the two approaches for the decision of inotropic support was weak (κ: 0.23 [-0.04;0.50]). No right ventricular dysfunction was observed. No patient had anemia and only three patients with transesophageal echocardiography documented left ventricular systolic dysfunction had a central venous oxygen saturation<70%. CONCLUSIONS: A weak agreement was found in the prescription of fluid loading and inotropic support derived from early transesophageal echocardiography assessment of hemodynamics and Surviving Sepsis Campaign guidelines in patients presenting with septic shock.

Computed tomography for the detection of free-floating thrombi in the right heart in acute pulmonary embolism.

OBJECTIVES: The aim of this study was to assess the prevalence of free-floating thrombi in the right heart (FFT) and the accuracy of computed tomography (CT) for their detection in pulmonary embolism (PE). METHODS: We studied 340 consecutive patients presenting with PE. All patients underwent CT and echocardiography. RESULTS: The prevalence of FFT was 3.5% in the global population of PE and 22% in high-risk PE. Dyspnoea, cardiogenic shock, cardiac arrest and tachycardia were more frequently found in patients with FFT (p = 0.04, p < 0.0001, p = 0.0003 and p = 0.01, respectively). Sensitivity and specificity of CT for the detection of FFT were 100% (95% confidence interval: 74%-100%) and 97% (95%-99%), whereas positive and negative predictive values were 57% (34%-78%) and 100% (99%-100%). Among patients with FFT, right ventricular dilation was always detected by CT, whereas no right ventricular dilation was found among patients with a false diagnosis of FFT performed by CT (p < 0.0001). CONCLUSION: Prevalence of FFT is 3.5% and differs according to the clinical presentation. Detection of FFT by CT is feasible and should lead to echocardiography being promptly performed for the confirmation of FFT.

Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study.

RATIONALE: The short-term prognosis of pulmonary embolism (PE) depends on hemodynamic status and underlying disease. The prognostic value of right ventricular dysfunction and injury is less well established. OBJECTIVES: To evaluate prognostic factors of PE in a multicenter prospective cohort study. METHODS: Echocardiography, brain natriuretic peptide (BNP), N-terminal-proBNP and cardiac troponin I measurements were done on admission of 570 consecutive patients with an acute PE. A predictive model was based on independent predictors of 30-day adverse events defined as death, secondary cardiogenic shock, or recurrent venous thromboembolism. MEASUREMENTS AND MAIN RESULTS: At 30 days, 42 patients (7.4%; 95% confidence interval [CI], 5.5-9.8%) had adverse events. On multivariate analysis, altered mental state (odds ratio [OR] 6.8; 95% confidence interval [CI], 2.0-23.3), shock on admission (OR 2.8; 95% CI, 1.1-7.5), cancer (OR 2.9; 95% CI, 1.2-6.9), BNP (OR 1.3 for an increase of 250 ng/L; 95% CI, 1.1-1.6) and right to left ventricle diameter ratio (OR 1.2 for an increase of 0.1; 95% CI, 1.1-1.4) were associated with 30-days of adverse events. The predictive performance of the model was good (area under receiver operating characteristics curve 0.84 [95% CI, 0.78-0.90]), making it possible to develop a bedside prognostic score. CONCLUSIONS: BNP and echocardiography may be useful determinants of the short-term outcome for patients with PE, together with clinical findings. Patients with PE can be stratified according to the initial risk of adverse outcome, using a simple score based on clinical, echocardiographic, and biochemical variables.

Echocardiography: a help in the weaning process.

INTRODUCTION: To evaluate the ability of transthoracic echocardiography (TTE) to detect the effects of spontaneous breathing trial (SBT) on central hemodynamics and to identify indices predictive of cardiac-related weaning failure. METHODS: TTE was performed just before and at the end of a 30-min SBT in 117 patients fulfilling weaning criteria. Maximal velocities of mitral E and A waves, deceleration time of E wave (DTE), maximal velocity of E' wave (tissue Doppler at the lateral mitral annulus), and left ventricular (LV) stroke volume were measured. Values of TTE parameters were compared between baseline (pressure support ventilation) and SBT in all patients and according to LV ejection fraction (EF): >50% (n = 58), 35% to 50% (n = 30), and <35% (n = 29). Baseline TTE indices were also compared between patients who were weaned (n = 94) and those who failed (n = 23). RESULTS: Weaning failure was of cardiac origin in 20/23 patients (87%). SBT resulted in a significant increase in cardiac output and E/A, and a shortened DTE. At baseline, DTE was significantly shorter in patients with LVEF <35% when compared to other subgroups (median [25th-75th percentiles]: 119 ms [90-153]; vs. 187 ms [144-224] vs. 174 ms [152-193]; P < 0.01) and E/E' was greater (7.9 [5.4-9.1] vs. 6.0 [5.3-9.0] vs. 5.2 [4.7-6.0]; P < 0.01). When compared to patients who were successfully weaned, those patients who failed exhibited at baseline a significantly lower LVEF (36% [27-55] vs. 51% [43-55]: P = 0.04) and higher E/E' (7.0 [5.0-9.2] vs. 5.6 [5.2-6.3]: P = 0.04). CONCLUSIONS: TTE detects SBT-induced changes in central hemodynamics. When performed by an experienced operator prior to SBT, TTE helps in identifying patients at high risk of cardiac-related weaning failure when documenting a depressed LVEF, shortened DTE and increased E/E'. Further studies are needed to evaluate the impact of this screening strategy on the weaning process and patient outcome.

Noninvasive assessment of cardiac index in healthy volunteers: a comparison between thoracic impedance cardiography and Doppler echocardiography.

BACKGROUND: Thoracic bioimpedance cardiography (ICG) has been proposed as a noninvasive, continuous, operator-independent, and cost-effective method for cardiac output monitoring. In the present study, we compared cardiac index (CI) measurements with ICG (Niccomo device) and transthoracic Doppler echocardiography in resting healthy volunteers undergoing hemodynamic load challenge. METHODS: Twenty-five healthy volunteers (7 men and 18 women, mean age 36 +/- 6 yr, body surface area 1.75 +/- 0.17 m(2)) were investigated during three experimental conditions: baseline, positive end-expiratory pressure + 10 cm H(2)O and lower body positive pressure by means of medical antishock trousers inflated to 30 cm H(2)O in the abdominal compartment. RESULTS: ICG signal quality was >89% over all sets of measurements. A weak but significant relationship was observed between CI(TTE) and CI(ICG) (r = 0.36; P = 0.002). Agreement between both techniques was 0.94 L x min(-1) x m(-2) (95% CI: 0.77-1.11), limits of agreement were -0.47 to 2.35 L x min(-1) x m(-2), and percentage error was 53%. No statistically significant relationships were found between percent changes in CI(TTE) and CI(ICG) after applications of positive end-expiratory pressure + 10 cm H(2)O (r = 0.21; P = 0.31) and medical antishock trousers (r = 0.22; P = 0.30). CONCLUSIONS: Poor correlation and lack of agreement between absolute values of CI measured by ICG and transthoracic Doppler echocardiography were found in resting healthy volunteers. The Niccomo device was also unreliable for monitoring changes in CI during hemodynamic load challenge.

Actual incidence of global left ventricular hypokinesia in adult septic shock.

RATIONALE AND OBJECTIVE: To evaluate the actual incidence of global left ventricular hypokinesia in septic shock. METHOD: All mechanically ventilated patients treated for an episode of septic shock in our unit were studied by transesophageal echocardiography, at least once a day, during the first 3 days of hemodynamic support. In patients who recovered, echocardiography was repeated after weaning from vasoactive agents. Main measurements were obtained from the software of the apparatus. Global left ventricular hypokinesia was defined as a left ventricular ejection fraction of <45%. MEASUREMENTS AND MAIN RESULTS: During a 3-yr period (January 2004 through December 2006), 67 patients free from previous cardiac disease, and who survived for >48 hrs, were repeatedly studied. Global left ventricular hypokinesia was observed in 26 of these 67 patients at admission (primary hypokinesia) and in 14 after 24 or 48 hrs of hemodynamic support by norepinephrine (secondary hypokinesia), leading to an overall hypokinesia rate of 60%. Left ventricular hypokinesia was partially corrected by dobutamine, added to a reduced dosage of norepinephrine, or by epinephrine. This reversible acute left ventricular dysfunction was not associated with a worse prognosis. CONCLUSION: Global left ventricular hypokinesia is very frequent in adult septic shock and could be unmasked, in some patients, by norepinephrine treatment. Left ventricular hypokinesia is usually corrected by addition of an inotropic agent to the hemodynamic support.

Hemodynamic effects of passive leg raising: an echocardiographic study in patients with shock.

OBJECTIVES: To determine the effects of passive leg raising (PLR) on hemodynamics and on cardiac function according to the preload dependency defined by the superior vena cava collapsibility index (DeltaSVC). RESULTS: Forty patients with shock, sedated and mechanically ventilated, were included. Transesophageal echocardiography was performed. At baseline (T1), two groups were defined according to DeltaSVC. Eighteen patients presenting a DeltaSVC > 36%, an indicator of preload dependency, formed group 1, whereas 22 patients (group 2) exhibited a DeltaSVC < 30% (not preload-dependent). Measurements were then performed during PLR (T2), back to baseline (T3), and after volume expansion (T4) in group 1 only. At T1, DeltaSVC was significantly higher in group 1 than in group 2, 50 +/- 9% and 7 +/- 6%, respectively. In group 1, we found a decrease in DeltaSVC at T2 (24 +/- 9%) and T4 (17 +/- 7%), associated with increased systolic, diastolic and arterial pulse pressures. Cardiac index also increased, from 1.92 +/- 0.74 (T1) to 2.35 +/- 0.92 (T2) and 2.85 +/- 1.2 l/min/m(2) (T4) and left ventricular end-diastolic volume from 51 +/- 41 to 61 +/- 51 and 73 +/- 51 ml/m(2). None of these variations was found in group 2. No change in heart rate was observed. CONCLUSION: Hemodynamic changes related to PLR were only induced by increased cardiac preload.

Prone positioning unloads the right ventricle in severe ARDS.

BACKGROUND: Despite airway pressure limitation, acute cor pulmonale persists in a minority of ARDS patients. Insufficient airway pressure limitation, hypercapnia, or both may be responsible. Because prone positioning (PP) has been shown to be a safe way to reduce airway pressure and to improve alveolar ventilation, we decided to assess its effect on right ventricular (RV) pressure overload in ARDS patients. METHODS: Between January 1998 and December 2006, we studied 42 ARDS patients treated by PP to correct severe oxygenation impairment (Pao2/fraction of inspired oxygen ratio, <100 mm Hg). RV function was evaluated by bedside transesophageal echocardiography, before and after 18 h of prone-position ventilation. RV enlargement was measured by RV/left ventricular (LV) end-diastolic area ratio in the long axis. Septal dyskinesia was quantified by measuring short-axis systolic eccentricity of the LV. RESULTS: Before PP, 21 patients (50%) had acute cor pulmonale, defined by RV enlargement associated with septal dyskinesia (group 1), whereas 21 patients had a normal RV (group 2). PP was accompanied by a significant decrease in airway pressure and Paco2. In group 1, this produced a significant decrease in mean (+/-SD) RV enlargement (from 0.91+/-0.22 to 0.61+/-0.21) after 18 h of PP (p=0.000) and a significant reduction in mean septal dyskinesia (from 1.5+/-0.2 to 1.1+/-0.1) after 18 h of PP (p=0.000). CONCLUSION: In the most severe forms of ARDS, PP was an efficient means of controlling RV pressure overload.

Validation of a skills assessment scoring system for transesophageal echocardiographic monitoring of hemodynamics.

OBJECTIVE: Transesophageal echocardiography (TEE) is increasingly used in hemodynamic monitoring in the intensive care unit. This paper describes and validates a scoring system for assessing competence in TEE performed by intensivists for this indication. DESIGN: Prospective study over an 18-month period. SETTINGS: Two medical intensive care units. METHODS: The scoring system is used to assess four aspects of TEE: quality of the views (score out of 14); semiquantitative evaluation of respiratory variations in the superior vena cava, valve regurgitation, size of the right ventricle (score out of 10); accuracy of measurement of velocity-time integrals for pulmonary and aortic flow, peak velocity of the E and A waves of mitral flow, left ventricular fractional area change (score out of 8); summary and proposed treatment (score out of 8). The scoring system was validated by using it to assess intensivists after 1 month (M1), 3 months (M3) and 6 months (M6) of training. TEE was done on a mechanically ventilated, hypotensive patient and scored by comparing the intensivist's examination with that of the expert examiner. The intensivists were divided into two groups of theoretical expertise at the start of training. RESULTS: Nineteen intensivists were evaluated. The scores at M1 for level 0 (no experience in echocardiography) and level 1 (previous experience) were, respectively, 18.5 +/- 4 and 24.7 +/- 5. The scores at M1, M3, and M6 were, respectively, 20.4 +/- 5, 30.4 +/- 5 and 35.7 +/- 3. At M6, the intensivists had performed TEE 29 +/- 10 times. CONCLUSION: The scoring system was discriminatory and sensitive to change, and could be used as a tool to assess an intensivist's mastery of TEE.

Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation.

AIM OF THE STUDY: We investigated implementation and efficacy of mild therapeutic hypothermia in the treatment of out-of-hospital cardiac arrest due to ventricular fibrillation. MATERIALS AND METHODS: Two periods were compared, an historical one (36 patients) between 2000 and 2002 where therapeutic hypothermia was never used, and a recent period (32 patients) between 2003 and 2005 where therapeutic hypothermia (32-34 degrees C) was implemented prospectively in our unit. Cooling was obtained by simply using wet cloths and ice packs. Survival in the two groups and factors associated with survival were analysed, together with the neurological prognosis in discharged patients. RESULTS: Survival was significantly higher in the hypothermia group (56% versus 36%), whereas no significant difference was observed in severity between the two periods. Only age, time from return to spontaneous circulation <20min, and therapeutic hypothermia were independently associated with survival. Therapeutic hypothermia was well tolerated and was associated with a significant improvement in neurological outcome. Whereas only 23% of patients actually reached the target temperature in 2003, 100% did in 2005. CONCLUSION: Therapeutic hypothermia is efficient in significantly improving survival and neurological outcome of out-of-hospital cardiac arrest with ventricular fibrillation. By using a simple method, it can be implemented easily and quickly, without side effects.

Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients: A retrospective cohort study.

For vancomycin therapy of severe infections, the Infectious Diseases Society of America recommends high vancomycin trough levels, whose potential for inducing nephrotoxicity is controversial. We evaluated the incidence and risk factors of acute kidney injury (AKI) in critically ill patients given continuous intravenous vancomycin with target serum vancomycin levels of 20 to 30 mg/L.We retrospectively studied 107 continuous intravenous vancomycin treatments of ≥48 hours' duration with at least 2 serum vancomycin levels ≥20 mg/L in critically ill patients. Nephrotoxicity was defined according to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI (ie, serum creatinine elevation by ≥26.5 µmoL/L or to ≥1.5 times baseline). Risk factors for AKI were identified by univariate and multivariate analyses.AKI developed in 31 (29%) courses. Higher serum vancomycin levels were associated with AKI (P < 0.01). Factors independently associated with AKI were highest serum vancomycin ≥40 mg/L (odds ratio [OR], 3.75; 95% confidence interval [CI], 1.40-10.37; P < 0.01), higher cumulative number of organ failures (OR, 2.63 95%CI, 1.42-5.31; P < 0.01), and cirrhosis of the liver (OR, 5.58; 95%CI, 1.08-31.59; P = 0.04).In this study, 29% of critically ill patients had AKI develop during continuous intravenous vancomycin therapy targeting serum levels of 20 to 30 mg/L. Serum vancomycin level ≥40 mg/L was independently associated with AKI.

Oxygen uptake-to-delivery relationship: a way to assess adequate flow.

Invasive and noninvasive monitoring facilitates clinical evaluation when resuscitating patients with complex haemodynamic disorders. If the macrocirculation is to be stable, then it must adapt to blood flow or blood flow must be optimized. The objective of flow monitoring is to assist with matching observed oxygen consumption (VO2) to pathophysiological needs. If an adequate balance cannot be maintained then dysoxia occurs. In this review we propose a simple schema for global reasoning; we discuss the limitations of VO2 and arterial oxygen delivery (DaO2) assessment; and we address concerns about increasing DaO2 to supranormal values or targeting pre-established levels of DaO2, cardiac output, or mixed venous oxygen saturation. All of these haemodynamic variables are interrelated and limited by physiological and/or pathological processes. A unique global challenge, and one that is of great prognostic interest, is to achieve rapid matching between observed and needed VO2--no more and no less. However, measuring or calculating these two variables at the bedside remains difficult. In practice, we propose a distinction between three situations. Clinical and blood lactate clearance improvements can limit investigations in simple cases. Intermediate cases may be managed by continuous monitoring of VO2-related variables such as DaO2, cardiac output, or mixed venous oxygen saturation. In more complex cases, three methods can help to estimate the needed VO2 level: comparison with expected values from past physiological studies; analysis of the relationship between VO2 and oxygen delivery; and use of computer software to integrate the preceding two methods.

Changes of Cardiac Function During Ultradistance Trail Running.

Previous studies have noted reversible cardiac dysfunction during marathon races, but few data are available concerning ultradistance trail running. The aim of this study was to assess echocardiographic parameters during ultradistance trail running. We performed an observational study in 66 participants to the 80-km Ecotrail of Paris Ile de France. All subjects had echocardiographic examinations before the race and on arrival, and 28 of them underwent serial echocardiographic examinations during the race (21 and 53 km). A single experienced physician performed all echocardiographic examinations, and the same protocol was always used (conventional 2-dimensional and Doppler left ventricular parameters and longitudinal strain). All echocardiographic parameters of left ventricular (LV) systolic function were significantly decreased on arrival (p ≤0.002). A significant reduction of LV systolic function was observed in 48% of study subjects on arrival. No significant modification was observed at 21 or at 53 km, and only global longitudinal strain was significantly decreased (p = 0.0008). At arrival, mitral E/A ratio and average mitral tissue Doppler imaging e' wave were significantly decreased (p = 0.0001 and p = 0.0004, respectively), but these changes were observed from 21 km. In conclusion, ultradistance trail running can lead to abnormalities of LV systolic and diastolic functions in amateur runners. Diastolic dysfunction arises earlier than systolic dysfunction. Left ventricular systolic dysfunction occurred in 48% of the study subjects and was detected early by assessment of longitudinal strain.

Histocompatibility leukocyte antigen-D related expression is specifically altered and predicts mortality in septic shock but not in other causes of shock.

Although the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR has been shown to be decreased during human sepsis, its level of expression in other nonseptic critical conditions is unclear. The aim of this study was to compare the level of HLA-DR expression on circulating monocytes among patients with septic, hemorrhagic, and cardiogenic shocks and severe sepsis without shock. At admission, HLA-DR expression was exclusively decreased in patients with septic shock (n = 30; P < 0.001), whereas the expression was similar between the other studied groups: cardiogenic shock (n = 16), hemorrhagic shock (n = 11), severe sepsis without shock (n = 18), and healthy volunteers (n = 8). HLA-DR expression was not predictive for overall mortality, but at day 1, an HLA-DR expression of less than 14 of mean fluorescence intensity (that corresponds to 40% labeled monocytes) was predictive of mortality exclusively in patients with septic shock (odds ratio, 11.4 and 95% confidence interval, 1.7; 78.4; P < 0.008). Catecholamine infusion, mechanical ventilation, positive blood culture, and number of units of blood or plasma transfused did not correlate with decreased HLA-DR expression. Thus, the decrease in HLA-DR expression is specific to septic shock and is associated, in septic shock patients, with increased mortality risk.

[Physiopathology of severe sepsis]. / Physiopathologie du sepsis sévère.

Regarding the definition. Severe sepsis associates an explosive inflammatory reaction and organ failure. It is secondary to bacterial, fungal or viral infection. It can be at the origin of acute circulatory failure (state of septic shock). Response of the organism to infection. The presence of certain components of the membrane of pathogenic agents induces the release of various mediators in cascade, notably cytokines. Toll-like receptors (10 cloned in humans) intervene in the detection of microbes and in the inherent and subsequently adaptive immune response. Immune paralysis. The release of pro-inflammatory mediators characterizes the initial phase of sepsis. Persistence of the latter provokes acquired immunodepression, related to an anti-inflammatory profile, and hence to a delayed decrease in hypersensitivity, an incapacity to cope with the infection and the onset of nosocomial infections. The role of the mediators. During sepsis, the cytokines are predominantly pro-inflammatory (TNF-alpha and notably IL-1beta) whereas others, produced concomitantly or subsequently, are predominantly anti-inflammatory (IL-10 in particular). In fact, the majority of the cytokines have multiple and intrinsic effects, they mediate immune defense but also pathological manifestations. Many other mediators intervene: coagulation or complement systems, contact system, breakdown products of the phospholipid membrane, arachidonic acid metabolites, free radicals and nitrous oxide. Endocrine and metabolic dysregulations. The concept of relative adrenal insufficiency and peripheral syndrome of resistance to glycocorticosteroids have led to hormone replacement therapy during septic shock. Acute insulin resistance has also been described. The role of the endothelium and coagulation. The endothelium plays a key part in the onset of vascular insufficiency during sepsis due to abnormalities in vasomotricity and thrombomodulation. The anticoagulant regulating system is perturbed; there is a decrease in protein C with inactivation of its active form, which has pro-fibrinolytic properties, and a decrease in antithrombin III. Regarding myocardial dysfunction During septic shock there is often severe left ventricular systolic dysfunction, sometimes also involving the right ventricle, largely under-diagnosed despite its severe prognosis, and associated with reduced or even collapsed heart rate.

[Diagnosis of sepsis, severe sepsis and septic shock]. / Diagnostic du sepsis, du sepsis sévère et du choc septique.

Consensual and precise definitions. Sepsis is composed of a suspected or documented infection associated with at least 2 SIRS criteria (systemic inflammatory response syndrome). Severe sepsis is sepsis with arterial hypotension and failure of one or several organs following the reduction in tIssue perfusion. Septic shock is a severe sepsis, the hypotension of which is refractory to volemic expansion. From an epidemiological point of view. Over the past two decades, its incidence is on the increase. Mortality varies from 25 to 80% of cases and sepsis remains the first cause of death in intensive care. The elements of diagnosis. The initial clinical signs are those of an infection and the port of entry and microbiological proof must be systematically researched before the appearance of a drop in blood pressure with hemodynamic impact on the various organs and hence their possible failure. The biological abnormalities observed depend on the deficient organ(s); hyperlactatemia is a good marker of visceral hypoperfusion. The sepsis risk factors. Any situation enhancing immunodepression is a risk factor for sepsis. Factors of virulence of the micro-organisms also intervene and, in cases of fungal infection, inherent risk factors. Genetic susceptibility probably intervenes, genetic variability playing either a protective or a deleterious role (the interest of Toll-like receptors).

[Treatment of severe sepsis and septic shock]. / Traitement du sepsis sévère et du choc septique.

The 3 poles of treatment. These are the hemodynamic management, early antibiotherapy and more specific treatments, based on improved physiopathological knowledge. From a hemodynamic point of view The first stage must always be to detect and correct the hypovolemia. The administration of vasopressive amines (or vasoconstricting amines) is mandatory in the case of septic shock. The choice of the antibiotics In the absence of microbiological proof, it is based on the germs most often encountered in infections of the suspected site and community or nosocomial nature of the infection. The antibiotherapy must be set-up as early as possible once the bacteriological samples have been. Treatments based on the physiopathology The activated protein C possesses pro-fibrinolytic, anticoagulant and anti-inflammatory properties; it obtained marketing Authorization in Europe for patients with severe sepsis and at least 2 organ failures or hypotension. Low-dose corticosteroids should be prescribed in the case of septic shock with prolonged use of catecholamines, and if possible following a test with Synacthène(R) (relative adrenal insufficiency). Intensive insulin therapy is aimed at maintaining normal glycemia in the patients for as long as possible.

Hemodynamic effects of positive end-expiratory pressure during abdominal hyperpression: a preliminary study in healthy volunteers.

PURPOSE: An increase in abdominal pressure induces an increase in left ventricular afterload under clinical conditions. We tested the hypothesis that positive end-expiratory pressure (PEEP) could reverse the hemodynamic consequences of abdominal hyperpression by opposing the increase in left ventricular afterload. MATERIALS AND METHODS: Eight healthy volunteers were investigated during 3 experimental conditions: (1) baseline, (2) increase in abdominal pressure by means of medical antishock trousers (MAST) inflation, and (3) addition of PEEP +10 cm H(2)O. Heart loading conditions and left ventricular systolic and diastolic function were assessed by transthoracic echocardiography. RESULTS: The application of PEEP significantly reduced the prior increase in end-systolic wall stress: 45 ± 11 vs 55 ± 14 kdyn/cm(2), P < .05. Medical antishock trousers inflation significantly altered the deceleration time of mitral E wave: 199 ± 23 vs 156 ± 38 milliseconds, P < .05. Left ventricular preload and global systolic performance were unaffected by MAST and PEEP applications. CONCLUSIONS: The increase in left ventricular afterload induced by MAST inflation can be efficiently reduced by the use of a moderate PEEP. Potential clinical applications in the abdominal compartment syndrome or in the setting of laparoscopic surgery should be developed.