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Arterial and central venous catheterizations and their use for continuous infusion of vasoactive drugs could lead to serious adverses events that could be life threatening. The incidence of human errors related patient adverses events could be decreased by the uses of algorithms and procedures. Concerning the continuous infusion of vasoactive drugs, the name of drug and its concentration should be clearly notified. The use of modern pump and noncompliant pipe could reduce the frequency bolus infusion and their related haemodynamic alterations. Reasonable procedure could reduce the arterial and central venous catheters related complications. Subclavian and radial sites should be preferred for central venous and arterial catheter insertion, respectively. The use of real time echographic guidance could facilitate the catheter insertion. These catheters should be removed when they are not indicated. Concerning the pulmonary artery catheter, the balloon tip should be inflated with visual control of the pulmonary artery pressure. Its removal is recommended within the first five days.

1. Increased aortic stiffness predisposes to myocardial ischaemia by increasing the systolic tension-time index and by decreasing aortic pressure throughout diastole. The tonometric subendocardial viability ratio (SEVR) is a non-invasive estimate of myocardial perfusion relative to cardiac workload. The hypothesis that SEVR is impaired in elderly hypertensives with high aortic pulse pressure (PP) was tested in the present study. 2. The SEVR was calculated by radial applanation tonometry in 203 subjects. In addition, diastolic time (DT), systolic time (ST) and mean diastolic and systolic aortic pressures (Pd and Ps, respectively) were calculated. First, 60 subjects matched for age and gender were analysed (20 controls, 20 hypertensives with pulse pressure (PP) < or = 60 mmHg, 20 hypertensives with PP > 60 mmHg; mean (+/-SD) age 64 +/- 9 years; 24 women, 36 men). The remaining 143 subjects, aged 53 +/- 10 years, were analysed subsequently. 3. The SEVR was similar in the three elderly groups (1.39 +/- 0.34, 1.39 +/- 0.28 and 1.35 +/- 0.25, in controls and hypertensive patients with PP < or = 60 and > 60 mmHg, respectively). The SEVR was positively related to DT/ST (r(2) = 0.89) and to DT (r(2) = 0.73) and was negatively related to heart rate (r(2) = 0.56; P < 0.001 each). However, SEVR was not related to ST, PP, mean Pd or mean Ps. At a given DT/ST, SEVR tended to be lower in hypertensives with PP > 60 mmHg than in hypertensives with normal PP. The positive linear relationship between SEVR and DT/ST was confirmed in the remaining 143 subjects (r(2) = 0.90), with no influence of aortic pressure. 4. The tonometric SEVR was not impaired in elderly hypertensive patients with increased aortic stiffness. In resting elderly and middle-aged individuals, the tonometric SEVR was mainly related to DT/ST ratio, not to aortic pressure.

Aims: Postsystolic wall thickening (PSWT) occurs after aortic valve closure. We investigated the influence of ischemia location and wall interactions on PSWT in normal and stunned myocardium., Methods and Results: Twenty-two dogs were studied. Seven chronically instrumented dogs (sonomicrometry) underwent 10-min coronary artery occlusion (CAO) of left circumflex artery ("LCX stunning") and seven other dogs underwent 10-min CAO of the anterior descending artery ("LAD stunning") followed by reperfusion. At baseline, there was no PSWT in the anterior wall whereas posterior wall started and finished to thicken after the anterior wall, demonstrating PSWT. With LCX stunning, PSWT was observed in the posterior wall without affecting the remote anterior wall. With LAD stunning, PSWT in the anterior wall was transient and of lower magnitude Vs. posterior wall; in the remote posterior wall, PSWT previously observed at baseline, almost vanished. Postsystolic to systolic wall thickening ratio identified (ROC analysis) normal, ischemic and stunned myocardium with different amplitudes between walls. Tissue Doppler Imaging demonstrated similar pattern in basal, mid and apical segments (additional n = 4 for both LCX and LAD stunning)., Conclusion: The present study demonstrates that location of ischemia and wall interactions produce discrepancies in PSWT between anterior and posterior walls in stunned myocardium.

Objective: Weaning-induced cardiogenic pulmonary oedema is a cause of weaning failure that is classically diagnosed by an increase in pulmonary artery occlusion pressure during a spontaneous breathing trial. During cardiogenic pulmonary oedema, a hypo-oncotic fluid is filtered toward the interstitial space. Thus, we tested whether the changes in plasma protein concentration during a weaning trial could diagnose weaning-induced pulmonary oedema., Design: Prospective study., Setting: The 24-bed medical intensive care unit of a university hospital., Patients: Forty-six patients who had failed two weaning trials., Intervention: Weaning-induced pulmonary oedema was diagnosed if a respiratory failure associated with an increase in pulmonary artery occlusion pressure above 18 mmHg occurred during a third weaning trial on a T-tube. The plasma protein concentration was measured before and at the end of the spontaneous breathing trial., Measurements and Results: During the weaning trial, pulmonary oedema was observed in 24 patients. In these patients, the plasma protein concentration increased by 11% (3-25%). The plasma protein concentration did not change significantly in patients who did not experience weaning-induced pulmonary oedema. An increase in the plasma protein concentration greater than 6% from baseline to the end of the weaning trial allowed detecting a weaning-induced pulmonary oedema with a sensitivity of 87% and a specificity of 95%., Conclusion: The acute changes in plasma protein concentration during a weaning trial represent an alternative method to right heart catheterisation for assessing weaning-induced pulmonary oedema.

Purpose of Review: Predicting volume responsiveness in patients with spontaneous breathing activity is a difficult challenge in the emergency room as well as in the intensive care unit because heart-lung interactions indices cannot be reliably used as they can be in mechanically ventilated patients fully adapted to their ventilator. The aim of this review is to summarize the different tools that have been proposed to predict the hemodynamic response to fluid infusion in the presence of spontaneous breathing activity., Recent Findings: Clinical studies recently demonstrated that neither indicators of cardiac preload (filling pressures and end-diastolic ventricular dimensions) nor arterial pulse pressure respiratory variation was an accurate predictor of volume responsiveness in patients with spontaneous breathing activity with or without mechanical support. In contrast, performing a passive leg-raising test has been proved as valuable for this purpose., Summary: The passive leg-raising test is the only method that has been repeatedly shown to be reliable for predicting volume responsiveness in patients who experience spontaneous breathing. The appropriate utilization of this test requires a real-time assessment of its effects on systemic blood flow.

Objective: To assess whether the passive leg raising test can help in predicting fluid responsiveness., Design: Nonsystematic review of the literature., Results: Passive leg raising has been used as an endogenous fluid challenge and tested for predicting the hemodynamic response to fluid in patients with acute circulatory failure. This is now easy to perform at the bedside using methods that allow a real time measurement of systolic blood flow. A passive leg raising induced increase in descending aortic blood flow of at least 10% or in echocardiographic subaortic flow of at least 12% has been shown to predict fluid responsiveness. Importantly, this prediction remains very valuable in patients with cardiac arrhythmias or spontaneous breathing activity., Conclusions: Passive leg raising allows reliable prediction of fluid responsiveness even in patients with spontaneous breathing activity or arrhythmias. This test may come to be used increasingly at the bedside since it is easy to perform and effective, provided that its effects are assessed by a real-time measurement of cardiac output.

Objectives: To examine whether the agreement between pulse contour and transpulmonary thermodilution cardiac index (CI) measurements is altered by changes in vascular tone within an up to 6-hr calibration-free period., Design: Observational study., Setting: Medical intensive care unit of a university hospital., Patients: Fifty-nine critically ill patients., Interventions: None., Measurements and Main Results: Data from 59 critically ill patients equipped with a PiCCO device were retrospectively analyzed. The database contained the transpulmonary thermodilution CI (CI(T)) value obtained at each time point the device was calibrated and the pulse contour CI (CI(PC)) value recorded immediately before this time point. Seven subsets of CI pairs were defined according to intervals of time elapsed from the previous calibration (within the first 30 mins, between 30 mins and 1 hr, and every hour up to 6 hrs). In the whole set of 400 CI pairs, CI(PC) correlated with CI(T) (r2 = .68, p < .001). The bias +/- SD was 0.12 +/- 0.61 L/min/m2, and the percentage error was 35%. Among the seven time-interval subsets, the percentage error was <30% only in the two first ones (27% and 26%, respectively). When changes in systemic vascular resistance by >15% occurred (129 times), CI(PC) correlated with CI(T) (r2 = .64), the bias +/- SD was 0.12 +/- 0.62 L/min/m2, and the percentage error was 36%. In the subset of CI pairs recorded within the 1-hr calibration-free period while vascular resistance changed by >15% (n = 32), the bias +/- SD was 0.04 +/- 0.47 L/min/m and the percentage error was 29%., Conclusions: Our study in critically ill patients suggests that the agreement between pulse contour cardiac output and transpulmonary thermodilution cardiac output was not significantly influenced by changes in vascular tone. However, after a 1-hr calibration-free period, recalibration may be encouraged. Such a procedure provides helpful information drawn from other thermodilution-derived variables.

Background: Little is known about the most severe forms of Pneumocystis jiroveci pneumonia (PCP) in HIV-negative as compared with HIV-positive patients. Improved knowledge about the differential characteristics and management modalities could guide treatment based on HIV status., Methods: We retrospectively compared 72 patients (73 cases, 46 HIV-positive) admitted for PCP from 1993 to 2006 in the intensive care unit (ICU) of a university hospital., Results: The yearly incidence of ICU admissions for PCP in HIV-negative patients increased from 1993 (0%) to 2006 (6.5%). At admission, all but one non-HIV patient were receiving corticosteroids. Twenty-three (85%) HIV-negative patients were receiving an additional immunosuppressive treatment. At admission, HIV-negative patients were significantly older than HIV-positive patients (64 [18 to 82] versus 37 [28 to 56] years old) and had a significantly higher Simplified Acute Physiology Score (SAPS) II (38 [13 to 90] versus 27 [11 to 112]) but had a similar PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio (160 [61 to 322] versus 183 [38 to 380] mm Hg). Ventilatory support was required in a similar proportion of HIV-negative and HIV-positive cases (78% versus 61%), with a similar proportion of first-line non-invasive ventilation (NIV) (67% versus 54%). NIV failed in 71% of HIV-negative and in 13% of HIV-positive patients (p < 0.01). Mortality was significantly higher in HIV-negative than HIV-positive cases (48% versus 17%). The HIV-negative status (odds ratio 3.73, 95% confidence interval 1.10 to 12.60) and SAPS II (odds ratio 1.07, 95% confidence interval 1.02 to 1.12) were independently associated with mortality at multivariate analysis., Conclusion: The yearly incidence of ICU admissions for PCP in HIV-negative patients in our unit increased from 1993 to 2006. The course of the disease and the outcome were worse in HIV-negative patients. NIV often failed in HIV-negative cases, suggesting that NIV must be watched closely in this population.

Objective: Echocardiographic recording of the tricuspid annular plane systolic excursion (TAPSE) has been recommended for assessing right ventricular function in cardiac patients. The ability of TAPSE to reflect right ventricular function at baseline and to monitor acute changes in right ventricular function was tested in critically ill patients., Design: Prospective study., Setting: A 24-bed medical intensive care unit., Patients: Eighty-six patients admitted for acute respiratory failure, circulatory failure, or coma., Interventions: In 40 patients, the examination was repeated after volume expansion (n = 15), passive leg raising (n = 5), or dobutamine infusion (n = 20)., Measurements and Results: The right ventricular fractional area change, TAPSE, the left ventricular ejection fraction, and the ratio of right to left ventricular end-diastolic area were measured using Doppler echocardiography. In the overall population, TAPSE (19+/-5 mm) was positively related to left ventricular ejection fraction (r2 = 0.31, p < 0.001) and right ventricular fractional area change and was negatively related to age and to the ratio of right to left ventricular end-diastolic area. Multivariate analysis indicated that only left ventricular ejection fraction and age were independently related to TAPSE (multiple r2 = 0.36, p < 0.001). Following dynamic interventions, the changes in TAPSE were linearly related to changes in left ventricular ejection fraction (r2 = 0.65, p < 0.01) but notto changes in the right ventricular fractional area change., Conclusions: Unexpectedly, TAPSE was more strongly related to left ventricular ejection fraction than to indices of right ventricular function in critically ill patients. The potential interest of TAPSE as a dynamic marker of left ventricular systolic function deserves further study.

Objective: Peripheral arterial pulse pressure is increasingly used to assess hemodynamic status. Our aim was to test the respective influence of arterial stiffness, stroke volume, peripheral resistance, and various hemodynamic and demographic variables on peripheral pulse pressure in critically ill patients., Design: Prospective study., Setting: Medical intensive care unit of a university hospital., Interventions: None., Patients: 67 sinus rhythm patients (mean age 57+/-17 years) of whom 17 received vasoactive agents., Measurements and Results: The stroke volume was calculated by Doppler echocardiography. Radial pressures were calibrated from systolic and diastolic brachial cuff pressures. Central aortic pressure was estimated by radial applanation tonometry. The arterial compliance was estimated from the aortic pressure curve using the area method and the arterial stiffness was calculated as 1/compliance. The influences of age, body surface area, arterial stiffness, stroke volume, peripheral resistance, and time intervals on peripheral pulse pressure were tested using univariate and multivariate analyses. The mean arterial pressure ranged from 42 to 113 mmHg. Peripheral pulse pressure (59+/-17 mmHg) was higher than aortic pulse pressure (40+/-14 mmHg, p<0.001). In patients aged >or= 60 years whose mean arterial pressure was >or= 80 mmHg, peripheral pulse pressure was related to arterial stiffness (r2=0.41) and to stroke volume (multiple r2 =0.90). A similar but weaker relationship was observed in the overall population (multiple r2=0.52)., Conclusions: In critically ill patients, and especially in aged subjects with hemodynamic stability, peripheral pulse pressure mainly reflected the combined influences of arterial stiffness and stroke volume.

Purpose of Review: In the ICU only half of the patients are volume responsive - that is, they respond to fluid administration by increasing their cardiac output. We aim to summarize the methods available for predicting volume responsiveness, focusing on recent findings in patients with spontaneous breathing activity., Recent Findings: New information mainly comes from studies that have attempted to find accurate predictors of volume responsiveness in cases of spontaneous breathing activity when heart-lung interaction indices cannot be reliably used. Passive leg raising has emerged as a reliable test for this purpose. The hemodynamic response to this maneuver, which induces a transient increase in cardiac preload, has been shown to provide a robust prediction of volume responsiveness. Assessment of the effects of passive leg raising requires real-time measurement of cardiac output/stroke volume or their surrogates., Summary: Predicting the hemodynamic response to fluid administration in patients with acute circulatory failure is of major importance and numerous methods are now available. While the respiratory variations of stroke volume (or its surrogates) can be used in patients fully adapted to their ventilator, the passive leg-raising test has become a reliable predictive method in patients with spontaneous breathing activity.

Objective: In hemodynamically unstable patients with spontaneous breathing activity, predicting volume responsiveness is a difficult challenge since the respiratory variation in arterial pressure cannot be used. Our objective was to test whether volume responsiveness can be predicted by the response of stroke volume measured with transthoracic echocardiography to passive leg raising in patients with spontaneous breathing activity. We also examined whether common echocardiographic indices of cardiac filling status are valuable to predict volume responsiveness in this category of patients., Design and Setting: Prospective study in the medical intensive care unit of a university hospital., Patients: 24 patients with spontaneously breathing activity considered for volume expansion., Measurements: We measured the response of the echocardiographic stroke volume to passive leg raising and to saline infusion (500 ml over 15 min). The left ventricular end-diastolic area and the ratio of mitral inflow E wave velocity to early diastolic mitral annulus velocity (E/Ea) were also measured before and after saline infusion., Results: A passive leg raising induced increase in stroke volume of 12.5% or more predicted an increase in stroke volume of 15% or more after volume expansion with a sensitivity of 77% and a specificity of 100%. Neither left ventricular end-diastolic area nor E/Ea predicted volume responsiveness., Conclusions: In our critically ill patients with spontaneous breathing activity the response of echocardiographic stroke volume to passive leg raising was a good predictor of volume responsiveness. On the other hand, the common echocardiographic markers of cardiac filling status were not valuable for this purpose.

Aims: Post-systolic wall thickening (PSWT) occurs after aortic valve closure. This waste of thickening does not participate in ejection. PSWT increases with myocardial ischaemia and stunning but the effects of anti-anginal drugs on PSWT during myocardial dysfunction remain unknown. The effects of two heart rate reducing agents, i.e. the beta-blocker atenolol and the selective I(f) current inhibitor ivabradine, were compared on PSWT., Methods and Results: Coronary stenosis was calibrated in six conscious instrumented dogs to suppress increase in coronary blood flow during a 10 min treadmill exercise to induce myocardial stunning. After exercise completion, stenosis was relieved and saline, atenolol or ivabradine (both at 1 mg/kg iv) were administered. For similar heart rate reduction, ivabradine attenuated stunning, whereas atenolol further depressed systolic wall thickening. PSWT to total wall thickening ratio was significantly decreased by ivabradine vs. saline, whereas total wall thickening was similar. Thus, ivabradine devoted a greater part of thickening to systole by converting PSWT into ejectional thickening. In contrast, atenolol failed to reduce PSWT vs. saline. Atrial pacing abolished the effects of ivabradine but not those of atenolol., Conclusion: Selective heart rate reduction with ivabradine converts PSWT into ejectional thickening but not with atenolol secondary to its negative inotropism.

Objective: To test whether assessing pulmonary permeability by transpulmonary thermodilution enables to differentiate increased permeability pulmonary edema (ALI/ARDS) from hydrostatic pulmonary edema., Design: Retrospective review of cases., Setting: A 24-bed medical intensive care unit of a university hospital., Patients: Forty-eight critically ill patients ventilated for acute respiratory failure with bilateral infiltrates on chest radiograph, a PaO(2)/FiO(2) ratio < 300 mmHg and extravascular lung water indexed for body weight >/= 12 ml/kg., Intervention: We assessed pulmonary permeability by two indexes obtained from transpulmonary thermodilution: extravascular lung water/pulmonary blood volume (PVPI) and the ratio of extravascular lung water index over global end-diastolic volume index. The cause of pulmonary edema was determined a posteriori by three experts, taking into account medical history, clinical features, echocardiographic left ventricular function, chest radiography findings, B-type natriuretic peptide serum concentration and the time-course of these findings with therapy. Experts were blind for pulmonary permeability indexes and for global end-diastolic volume., Measurements and Results: ALI/ARDS was diagnosed in 36 cases. The PVPI was 4.7+/-1.8 and 2.1+/-0.5 in patients with ALI/ARDS and hydrostatic pulmonary edema, respectively (p<0.05). The extravascular lung water index/global end-diastolic volume index ratio was 3.0 x 10(-2)+/-1.2 x 10(-2) and 1.4 x 10(-2)+/-0.4 x 10(-2) in patients with ALI/ARDS and with hydrostatic pulmonary edema, respectively (p<0.05). A PVPI >/= 3 and an extravascular lung water index/global end-diastolic index ratio >/= 1.8 x 10(-2) allowed the diagnosis of ALI/ARDS with a sensitivity of 85% and specificity of 100%., Conclusion: These results suggest that indexes of pulmonary permeability provided by transpulmonary thermodilution may be useful for determining the mechanism of pulmonary edema in the critically ill.

Background and Purpose: Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the beta-blocker atenolol and the selective inhibitor of If current, ivabradine., Experimental Approach: Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1 mg.kg-1) or ivabradine (1 mg.kg-1)., Key Results: Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35+/-0.07 vs 0.21+/-0.03 mm, respectively) and during exercise (0.30+/-0.04 vs 0.15+/-0.04 mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80+/-23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant tau and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing., Conclusion and Implications: For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection.

Unlabelled: The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bizé, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh., Objectives: Late preconditioning reduces contractile dysfunction during myocardial stunning. Mechanisms involving adaptation of calcium handling during excitation-contraction coupling to late preconditioning remain to be established. Thus, we investigated whether the late preconditioned myocardium is associated with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2) and its regulatory protein FKBP12.6., Methods: Chronically instrumented conscious dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10-min coronary artery occlusion followed by reperfusion. They were studied 24 h later in the late preconditioned state (day 1)., Results: Maximal velocity of wall thickening at day 1 was increased as compared to corresponding baseline at day 0 (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg) induced a dose-dependent decrease in wall thickening. In the late preconditioned state, this negative inotropic response was significantly reduced vs. control state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase after late preconditioning as compared to the control state. The amount of RyR2 and its phosphorylated state were similar and binding experiments did not reveal any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and phospholamban levels were not altered by late preconditioning., Conclusions: The late preconditioned myocardium is characterized by an adaptation of regional function associated with an increased expression of FKBP12.6. This demonstrates an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.

Objective: Fluid responsiveness requires the accurate measurement of cardiac output that can be approached by aortic blood flow (ABF) as measured by esophageal Doppler monitoring (EDM). EDM devices may either include an echo-determination of aortic diameter or estimate aortic diameter from nomograms and thus consider it as constant. However, it is unclear if measuring aortic diameter increases the accuracy of EDM to identify fluid responsiveness. Aortic diameter varies with arterial pressure such that its measure could be essential for assessing the changes in ABF during acute circulatory failure. We attempted to demonstrate that measuring aortic diameter improved the accuracy of EDM to assess fluid responsiveness., Design: Prospective study., Setting: University hospital intensive care unit., Patients: Seventy-six patients with acute circulatory failure in whom a fluid challenge was given., Interventions: Rapid volume expansion (500 mL of NaCl 0.9%)., Measurements and Main Results: We measured aortic velocity and area by EDM before and after fluid loading and evaluated the effects of fluid challenge on ABF, either measured after fluid infusion (measured ABFafter) or estimated assuming an unchanging aortic area (estimated ABFafter). If measured ABFafter was used for assessing fluid response, it was increased above 15% compared with ABF at baseline in 41 patients (responders). Conversely, estimated ABFafter increased above 15% from ABF at baseline in 27 patients only; that is, the effects of the challenge were underestimated in 14 patients. In these 14 patients, the relative change in mean arterial pressure during volume expansion was of greater magnitude than in patients who were classified as nonresponders by considering measured ABFafter., Conclusions: Monitoring the changes in aortic diameter improves the accuracy of EDM in assessing the hemodynamic effects of a fluid challenge, especially if it induces a large increase in arterial pressure. Estimating rather than measuring the aortic diameter may lead to underestimation of fluid responsiveness.

Purpose of Review: The purpose of this review was to summarize recent findings concerning the consequences of cardiopulmonary interactions in acute cardiogenic pulmonary edema, weaning from mechanical ventilation and fluid-responsiveness assessment by respiratory variations of stroke volume., Recent Findings: The efficacy of continuous or bilevel positive airway pressure in patients with acute cardiogenic pulmonary edema was strongly suggested by two recent meta-analyses. There is growing evidence to suggest that weaning-induced cardiac dysfunction and acute cardiogenic pulmonary edema could explain a large amount of liberation failure from mechanical ventilation. Despite a potential role for echocardiography and plasma measurements of B-type natriuretic peptide in demonstrating a cardiac origin to weaning failure, the demonstration of a significant increase in pulmonary-artery occlusion pressure during the weaning trial remains the gold standard for this purpose. In patients with heart failure there is no evidence for revisiting the reliability of the respiratory variation of stroke-volume surrogates to predict fluid responsiveness., Summary: For clinical practice, the knowledge of cardiopulmonary interactions is of paramount importance in understanding the crucial role of mechanical ventilation for treating patients with heart failure and, by contrast, the deleterious cardiovascular effects of weaning in patients with overt or hidden cardiac failure.

Objective: Values of central venous pressure of 8-12 mm Hg and of pulmonary artery occlusion pressure of 12-15 mm Hg have been proposed as volume resuscitation targets in recent international guidelines on management of severe sepsis. By analyzing a large number of volume challenges, our aim was to test the significance of the recommended target values in terms of prediction of volume responsiveness., Design: Retrospective study., Setting: A 24-bed medical intensive care unit., Patients: All consecutive septic patients monitored with a pulmonary artery catheter who underwent a volume challenge between 2001 and 2004., Intervention: None., Measurements and Main Results: A total of 150 volume challenges in 96 patients were reviewed. In 65 instances, the volume challenge resulted in an increase in cardiac index of > or =15% (responders). The pre-infusion central venous pressure was similar in responders and nonresponders (8 +/- 4 vs. 9 +/- 4 mm Hg). The pre-infusion pulmonary artery occlusion pressure was slightly lower in responders (10 +/- 4 vs. 11 +/- 4 mm Hg, p < .05). However, the significance of pulmonary artery occlusion pressure to predict fluid responsiveness was poor and similar to that of central venous pressure, as indicated by low values of areas under the receiver operating characteristic curves (0.58 and 0.63, respectively). A central venous pressure of <8 mm Hg and a pulmonary artery occlusion pressure of <12 mm Hg predicted volume responsiveness with a positive predictive value of only 47% and 54%, respectively. With the knowledge of a low stroke volume index (<30 mL.m), their positive predictive values were still unsatisfactory: 61% and 69%, respectively. When the combination of central venous pressure and pulmonary artery occlusion pressure was considered instead of either pressure alone, the degree of prediction of volume responsiveness was not improved., Conclusion: Our study demonstrates that cardiac filling pressures are poor predictors of fluid responsiveness in septic patients. Therefore, their use as targets for volume resuscitation must be discouraged, at least after the early phase of sepsis has concluded.

Brief coronary artery occlusion (CAO) and reperfusion induce myocardial stunning and late preconditioning. Postsystolic wall thickening (PSWT) also develops with CAO and reperfusion. However, the time course of PSWT during stunning and the regional function pattern of the preconditioned myocardium remain unknown. The goal of this study was to investigate the evolution of PSWT during myocardial stunning and its modifications during late preconditioning. Dogs were chronically instrumented to measure (sonomicrometry) systolic wall thickening (SWT), PSWT, total wall thickening (TWT = SWT + PSWT), and maximal rate of thickening (dWT/dt(max)). Two 10-min CAO (circumflex artery) were performed 24 h apart (day 0 and day 1, n = 7). At day 0, CAO decreased SWT and increased PSWT. During the first hours of the subsequent stunning, evolution of PSWT was symmetrical to that of SWT. At day 1, baseline SWT was similar to day 0, but PSWT was reduced (-66%), while dWT/dt(max) and SWT/TWT ratio increased (+48 and +14%, respectively). After CAO at day 1, stunning was reduced, indicating late preconditioning. Simultaneously vs. day 0, PSWT was significantly reduced, and dWT/dt(max) as well as SWT/TWT ratio were increased, i.e., a greater part of TWT was devoted to ejection. Similar decrease in PSWT was observed with a nonischemic preconditioning stimulus (rapid ventricular pacing, n = 4). In conclusion, a major contractile adaptation occurs during late preconditioning, i.e., the rate of wall thickening is enhanced and PWST is almost abolished. These phenotype adaptations represent potential approaches for characterizing stunning and late preconditioning with repetitive ischemia in humans.

Purpose of Review: Cardiac preload is frequently altered during hemodynamic failure and is a major focus of therapeutic management. The aim of this review was to summarize the invasive indicators of preload and the invasive predictors of preload responsiveness., Recent Findings: The static assessment of preload is based on the measurement of pulmonary artery occlusion pressure, which is still considered a gold standard. The reliability of the transpulmonary dilution method for bedside monitoring of cardiac volumes and preload has been clearly documented. Nonetheless, a number of recent studies have emphasized the poor value of static markers of preload for predicting a positive response to fluid therapy in comparison to 'dynamic' or 'functional' indices. Among them, the respiratory variation of arterial pulse pressure has been confirmed by numerous studies as an excellent indicator of volume responsiveness. The limitations for using these dynamic parameters have recently been emphasized so that alternative methods, such as passive leg raising or the respiratory systolic variation test, have been developed., Summary: The best prediction of the hemodynamic response to fluid therapy is afforded by functional evaluation of preload responsiveness rather than by static markers of preload.

The arterovenous difference in carbon dioxide tension (DeltaPCO2) can be calculated after simultaneous sampling of arterial blood (PaCO2) and of mixed venous blood from the distal of a pulmonary artery catheter (PvCO2). Under physiological conditions, DeltaPCO2 ranges from 2 to 5 mmHg. The DeltaPCO2 depends on carbon dioxide and cardiac output by a complex fashion. In this article, we detail the influence of these factors on DeltaPCO2 in normoxic conditions and in hypoxic conditions. We bring evidence that DeltaPCO2 cannot serve as a marker of tissue hypoxia contrary to what was initially thought. However, DeltaPCO2 can be considered as a marker of the adequacy of venous blood flow (i.e. cardiac output) to remove the total CO2 produced by the peripheral tissues. In this regard, the knowledge of DeltaPCO2 should help the clinicians for the decision of giving therapy aimed at increasing cardiac output.

Objective: Passive leg raising (PLR) represents a "self-volume challenge" that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. We hypothesized that the hemodynamic response to PLR predicts fluid responsiveness in mechanically ventilated patients., Design: Prospective study., Setting: Medical intensive care unit of a university hospital., Patients: We investigated 71 mechanically ventilated patients considered for volume expansion. Thirty-one patients had spontaneous breathing activity and/or arrhythmias., Interventions: We assessed hemodynamic status at baseline, after PLR, and after volume expansion (500 mL NaCl 0.9% infusion over 10 mins)., Measurements and Main Results: We recorded aortic blood flow using esophageal Doppler and arterial pulse pressure. We calculated the respiratory variation of pulse pressure in patients without arrhythmias. In 37 patients (responders), aortic blood flow increased by > or =15% after fluid infusion. A PLR increase of aortic blood flow > or =10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure > or =12% predicted volume responsiveness with significantly lower sensitivity (60%) and specificity (85%). In 30 patients without arrhythmias or spontaneous breathing, a respiratory variation in pulse pressure > or =12% was of similar predictive value as was PLR increases in aortic blood flow (sensitivity of 88% and specificity of 93%). In patients with spontaneous breathing activity, the specificity of respiratory variations in pulse pressure was poor (46%)., Conclusions: The changes in aortic blood flow induced by PLR predict preload responsiveness in ventilated patients, whereas with arrhythmias and spontaneous breathing activity, respiratory variations of arterial pulse pressure poorly predict preload responsiveness.

Objectives: Although the signalling pathways of late preconditioning have been extensively investigated, its consequence for myocardial metabolism remains unknown. Thus, myocardial oxygen consumption (MVO2) was evaluated before and under late preconditioning., Methods: In 7 chronically instrumented dogs, we measured MVO2 in vivo at baseline and during inotropic stimulation with dobutamine (10 and 20 microg/kg/min, i.v.) before (Day 0) and 24 h after (Day 1) a 10-min circumflex coronary artery occlusion., Results: At Day 0, dobutamine dose-dependently increased the triple product (heart ratexleft ventricular systolic pressurexleft ventricular maximum dP/dt), MVO2, coronary blood flow, and coronary sinus pO2. At Day 1, the triple product was similar at baseline and at each dose of dobutamine but MVO2 was significantly blunted as compared to Day 0 (-15+/-4%, -22+/-3% and -19+/-4% at baseline, dobutamine 10 and 20 microg/kg/min, respectively). Importantly, the relationship between MVO2 and triple product was significantly rightward shifted with late preconditioning, i.e., MVO2 was reduced for any level of triple product. At Day 1, the relationship between coronary blood flow and MVO2 was not altered as compared to Day 0 but coronary sinus pO2 was significantly increased vs. Day 0 for any level of coronary blood flow, suggesting that late preconditioning exerted no vasomotor effect but rather changed myocardial oxygen handling. These effects were abolished by administration of S-methyl-isothiourea (1.5 mg/kg, i.v.), a iNOS inhibitor., Conclusion: This study demonstrates that ischemic late preconditioning is characterized by a major reduction in MVO2, both at baseline and under inotropic stimulation. NO from iNOS contributes to this modification of metabolic phenotype.

Tachycardia with rapid ventricular pacing induces delayed preconditioning against arrhythmias secondary to coronary artery occlusion (CAO) and reperfusion (CAR) but its effects on myocardial stunning remains unknown. Accordingly, we investigated whether delayed preconditioning with ventricular pacing develops against myocardial stunning and whether this phenomenon is triggered by reactive oxygen species. Eight chronically instrumented conscious dogs underwent three experimental sequences in a random order a week apart: (a) 10-min CAO (coronary occluder) followed by CAR, i.e. "Control" sequence; (b) pacing (right ventricular electrodes, 240 beats/min during 40 min) performed 24 h before the 10-min CAO, i.e. "PC" sequence; and (c) N-(2-mercaptopropionyl)-glycine (MPG, 100 mg/kg per h) administered concomitantly to pacing and 10-min CAO performed 24 h later, i.e. "PC+MPG" sequence. During "Control", left ventricular (LV) wall thickening (%, sonomicrometry) was dramatically reduced during CAO (-96 +/- 5% from 2.9 +/- 0.4 mm) and remained depressed during CAR demonstrating myocardial stunning. During "PC", LV wall thickening was not altered by pacing per se and was similarly decreased during CAO vs. "Control". However, during CAR, LV wall thickening was improved vs. "Control" (e.g. -24 +/- 5% and -8 +/- 4% from corresponding baseline for "PC" and "Control", respectively at 2 h-CAR; P<0.05), demonstrating delayed preconditioning. Administration of MPG during pacing (n=5) abolished the beneficial effects of pacing. Myocardial lactate extraction and transmural distribution of regional myocardial blood flow (fluorescent microspheres) were not modified, by pacing. In conclusion, tachycardia with rapid ventricular pacing induces delayed cardioprotection against myocardial stunning. The production of reactive oxygen species independently from ischemia appears to be a major trigger for this phenomenon.

Objective: Because recombinant human activated protein C (rhAPC) reduces NO production during sepsis, it could improve the vascular tone. We tested whether rhAPC reduces the dose of norepinephrine required to maintain mean arterial pressure (MAP) in septic shock patients., Design and Setting: Retrospective study in intensive care unit of two university hospitals., Patients: Twenty-two septic shock patients with at least two organ failures were retrospectively investigated for MAP and the required dose of norepinephrine before and 24 h after rhAPC administration. A control group of 22 septic shock patients with at least two organ failures who did not receive rhAPC was matched on age, SAPS II, MAP, and norepinephrine dose at the time of the theoretical start of rhAPC., Measurements and Results: The MAP remained stable and similar in the two groups (86+/-16 vs. 89+/-9 mmHg at 24 h). The required dose of norepinephrine increased in the control group (+38%, from -41% to +38%) but decreased in the treated group (-33%, from -74% to +11%)., Conclusions: rhAPC rapidly improved the vascular tone in septic shock patients as assessed by a decrease in the norepinephrine dose required to maintain arterial pressure.

The pulse oximetry plethysmographic signal resembles the peripheral arterial pressure waveform, and the degree of respiratory variation in the pulse oximetry wave is close to the degree of respiratory arterial pulse pressure variation. Thus, it is tempting to speculate that pulse oximetry can be used to assess preload responsiveness in mechanically ventilated patients. In this commentary we briefly review the complex meaning of the pulse oximetry plethysmographic signal and highlight the advantages, limitations and pitfalls of the pulse oximetry method. Future studies including volume challenge must be performed to test whether the pulse oximetry waveform can really serve as a nonivasive tool for the guidance of fluid therapy in patients receiving mechanical ventilation in intensive care units and in operating rooms.

Objective: To test whether fluid responsiveness can be predicted by the respiratory variation in aortic blood flow and/or the flow time corrected for heart rate monitored with esophageal Doppler., Design and Setting: Prospective study in a 24-bed medical intensive care unit of a university hospital., Patients: 38 mechanically ventilated patients with sinus rhythm and without spontaneous breathing activity in whom volume expansion was planned., Interventions: The aortic blood flow was measured using an esophageal Doppler monitoring device before and after fluid infusion (500 ml NaCl 0.9% over 10 min). The variation in aortic blood flow over a respiratory cycle between its minimal and maximal values was calculated. The flow time was also measured., Measurements and Results: Aortic blood flow increased by at least 15% after volume expansion in 20 patients (defined as responders). Before fluid infusion the respiratory variation in aortic flow was higher in responders than in nonresponders (28+/-12% vs. 12+/-5%). It significantly decreased after volume expansion (18+/-11%) in responders only. A respiratory variation in aortic flow before volume expansion of at least 18% predicted fluid responsiveness with a sensitivity of 90% and a specificity of 94%. Flow time increased with fluid infusion in responders and nonresponders. A flow time corrected for heart rate below 277 ms predicted fluid responsiveness with a sensitivity of 55% and a specificity of 94%. The area under the ROC curve generated for variation in aortic blood flow ABF was greater than that generated for flow time., Conclusions: The respiratory variation in aortic blood flow reliably predicts fluid responsiveness in patients with sinus rhythm and without breathing activity.

Corynebacterium ulcerans causes zoonotic infections, such as diphtheria and extrapharyngeal infections. We report here the first case of a diphtheria-like illness caused by C. ulcerans in France and transmitted likely by a dog to an immunocompromised woman.

Every increase in heart rate represents a poor prognostic factor in cardiology, and multiple arguments have now led to the belief that reducing heart rate is a major therapeutic challenge. A comparison of the pharmacological effects of If current inhibitors such as zatebradine, and more recently ivabradine (Procoralan) and beta-blockers, have demonstrated experimentally that reductions in heart rate and myocardial contractile force contribute equally to the reduction in myocardial oxygen consumption in the normal heart. Conversely, at a similar level of reduction in heart rate, the lack of a concomitant negative inotropic effect with ivabradine affords longer diastolic perfusion times than beta-blockers. In other words, a negative inotropic effect is deleterious when an increase in coronary blood flow is required. Hence, if the anti-ischaemic effects afforded by an If current inhibitor and a beta-blocker are roughly comparable, the former are clearly of higher benefit than beta-blockers in the treatment of myocardial dysfunction accompanying cardiac ischaemia-reperfusion, especially myocardial stunning.

Initially described more than 30 years ago, the Pulmonary Artery Catheter (PAC) technique was becoming more and more used in the following years. This hemodynamic monitoring device can be used according 2 different therapeutic attitudes. The first one strives to achieve supranormal hemodynamic values, particularly in terms of cardiac index and oxygen consumption. However, this attitude has been demonstrated to be deleterious in the intensive care setting and is, to date, strongly questioned in the perioperative period. Conversely, the use of PAC to optimize the hemodynamic status in an individualized manner appears more seductive, even if the impact of a therapeutic attitude guided by standardized protocols has never been investigated. Although the PAC affords a continuous monitoring of a large panel of hemodynamic data, including tissue oxygenation parameters and estimation of left cardiac filling pressures, some pitfalls may occur in the measurement as well as in the interpretation of the data. Furthermore, because it is an invasive procedure, the safety of the PAC has been seriously questioned for several years. However, the recent study of Richard and coworkers clearly demonstrated that the use of PAC was not responsible for increased mortality in severely ill patients with circulatory shock and/or acute respiratory distress syndrome. The development of educational programs would allow to improve the quality of the collection and interpretation of hemodynamic parameters with the hope to enhance the efficiency of the PAC for the management of critically ill patients.

Aims: The respective contributions of reduction in heart rate and inotropism in the beneficial effects of beta-blockade in ischaemic heart disease remains debated. The effects of selective heart rate reduction by ivabradine (If inhibitor) were compared to those of atenolol on exercise-induced ischaemia and stunning., Methods and Results: In seven instrumented dogs, coronary stenosis was calibrated to suppress increase in coronary blood flow during a 10-min treadmill exercise. When administered before exercise, atenolol and ivabradine similarly reduced heart rate versus saline at rest and during exercise (154+/-2 and 155+/-9 vs 217+/-13 beats/min, respectively). During exercise, left ventricular wall thickening (LVWth) was reduced to 2+/-1% from 23+/-4% under saline but ivabradine limited this effect (10+/-3%) and reduced the subsequent myocardial stunning vs saline. Atenolol also limited LVWth decrease during exercise (17+/-4%) but had no effect during recovery. When administered after exercise, ivabradine attenuated stunning and this effect disappeared when heart rate reduction was corrected by atrial pacing. Atenolol administered after exercise severely depressed LVWth vs saline., Conclusion: Selective heart rate reduction not only provides an anti-ischaemic effect but also per se improves contractility of the stunned myocardium. Additional negative inotropism is protective against ischaemia but deleterious during stunning.

Lowering heart rate reduces myocardial oxygen consumption (MVO2) and produces potent anti-ischemic effects. The development of selective heart rate-reducing agents represents an alternative approach to the use of beta-blockers. Therefore, our goal was to establish the dose-response curve of the effects of ivabradine (If channel inhibitor) on MVO2 and diastolic time. Seven conscious and chronically instrumented dogs were investigated during exercise at spontaneous and paced heart rate (250 beats/min) after administration of increasing doses of ivabradine (0.25, 0.5, and 1 mg/kg i.v.). During exercise, ivabradine dose dependently and significantly reduced the exercise-induced tachycardia (-17, -21, and -32% at 0.25, 0.5, and 1 mg/kg, respectively, versus saline) without altering myocardial contractility nor mean ejection wall stress. A linear relationship between heart rate (HR) and MVO2 was demonstrated (MVO2 = 0.044 x HR - 1.4; r = 0.987). These effects of ivabradine on MVO2 were abolished by atrial pacing. Similarly, ivabradine dose dependently increased diastolic time without altering the inverse and non linear relationship between diastolic time and heart rate observed with saline. In conclusion, selective heart rate reduction with ivabradine dose dependently increases diastolic time and reduces MVO2 with a linear relationship between heart rate and MVO2. The lack of "on-off" pharmacological profile will predict the possibility of using a wide range of dose regimen.

The respective contributions of heart rate (HR) reduction and left ventricular (LV) negative inotropy to the effects of antianginal drugs are debated. Accordingly, eight instrumented dogs were investigated during exercise at spontaneous and paced HR (250 beats/min) after administration of either saline, atenolol, or ivabradine (selective pacemaker current channel blocker). During exercise, atenolol and ivabradine (both 1 mg/kg iv) similarly reduced HR (-30% from 222 +/- 5 beats/min), and LV mean ejection wall stress was not altered. LV dP/dt(max) was reduced by atenolol but not ivabradine. Diastolic time (DT) was increased by atenolol versus saline (195 +/- 6 vs. 123 +/- 4 ms, respectively) and to a greater extent by ivabradine (233 +/- 11 ms). Myocardial oxygen consumption (MVo(2)) was lower under ivabradine and atenolol versus saline (6.7 +/- 0.6 and 4.7 +/- 0.4 vs. 8.1 +/- 0.6 ml/min, respectively, P < 0.05). Under pacing, DT and MVo(2) were similar between ivabradine and saline but significantly reduced with atenolol. Thus HR reduction and negative inotropy equally contribute to the reduction in MVo(2) during exercise in the normal heart. The negative inotropy limits the increase in DT afforded by HR reduction.

Left ventricular (LV) relaxation is crucial for LV function, especially during exercise. We compared the effects of increasing doses of ivabradine, a selective inward hyperpolarization-activated current inhibitor, and atenolol on the rate and extent of LV relaxation (best fit method: time constant tau(BF), pressure asymptote P(BF)) at rest and during exercise. Eight dogs were chronically instrumented to measure LV pressure and LV wall stresses. During exercise under saline, heart rate increased from 108 +/- 5 to 220 +/- 6 beats/min and tau(BF) was significantly reduced from 22 +/- 1 to 14 +/- 2 ms. At rest, atenolol but not ivabradine increased tau(BF). For similar heart rate reductions during exercise, atenolol impeded the shortening of tau(BF) (23 +/- 2 ms) whereas ivabradine had no effect (15 +/- 2 ms). The extent of the relaxation process (P(BF)) at peak exercise was increased by ivabradine, and to a greater extent by atenolol, compared with saline. Thus, for a similar reduction in heart rate at rest and during exercise, ivabradine, in contrast with atenolol, does not exert any negative lusitropic effect.

We investigated the effects of the selective bradycardic agent ivabradine, an I(f) channel inhibitor, on exercise-induced ischemia and resulting myocardial stunning. Seven dogs were chronically instrumented to measure left ventricular (LV) wall thickening (Wth), aortic pressure and coronary blood flow (CBFv) (Doppler). Circumflex coronary artery stenosis was set up to suppress the increase in CBFv during a 10 min treadmill exercise. During exercise under saline, LVWth in the ischemic zone was depressed (-70 +/- 4%) and a prolonged myocardial stunning was subsequently observed. Infusion of ivabradine started before exercise significantly reduced heart rate (HR) at rest (-22 +/- 7%), during exercise (-33 +/- 4%) and throughout the recovery period (-21 +/- 2%). By reducing HR during exercise, ivabradine simultaneously improved LVWth compared with saline (14 +/- 1% versus 7 +/- 1%, respectively) and subendocardial perfusion (microspheres). This anti-ischemic effect was subsequently responsible for a strong decrease in the intensity and severity of myocardial stunning. All these beneficial effects were abolished when HR reduction during exercise was suppressed by atrial pacing. Interestingly, when ivabradine infusion was started after exercise, LVWth was still significantly enhanced and myocardial stunning strongly attenuated. This direct effect of ivabradine on the stunned myocardium disappeared when HR reduction was suppressed by atrial pacing at rest. In conclusion, this study demonstrates that ivabradine exerts an anti-ischemic effect that is responsible for subsequent protection against myocardial stunning. Furthermore, administration of ivabradine after the ischemic insult still improves LVWth of the stunned myocardium.