David Osman

Passive leg raising predicts fluid responsiveness in the critically ill.

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 ≥15% after fluid infusion. A PLR increase of aortic blood flow ≥10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure ≥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 ≥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.

Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge.

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 ≥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−2), 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.

Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients

Objective:During mechanical ventilation, inspiration cyclically decreases the left cardiac preload. Thus, an end-expiratory occlusion may prevent the cyclic impediment in left cardiac preload and may act like a fluid challenge. We tested whether this could serve as a functional test for fluid responsiveness in patients with circulatory failure. Design:Prospective study. Setting:Medical intensive care unit. Patients:Thirty-four mechanically ventilated patients with shock in whom volume expansion was planned. Intervention:A 15-second end-expiratory occlusion followed by a 500 mL saline infusion. Measurements:Arterial pressure and pulse contour-derived cardiac index (PiCCOplus) at baseline, during passive leg raising (PLR), during the 5-last seconds of the end-expiratory occlusion, and after volume expansion. Main Results:Volume expansion increased cardiac index by >15% (2.4 ± 1.0 to 3.3 ± 1.2 L/min/m2, p < 0.05) in 23 patients (“responders”). Before volume expansion, the end-expiratory occlusion significantly increased arterial pulse pressure by 15% ± 15% and cardiac index by 12% ± 11% in responders whereas arterial pulse pressure and cardiac index did not change significantly in nonresponders. Fluid responsiveness was predicted by an increase in pulse pressure ≥5% during the end-expiratory occlusion with a sensitivity and a specificity of 87% and 100%, respectively, and by an increase in cardiac index ≥5% during the end-expiratory occlusion with a sensitivity and a specificity of 91% and 100%, respectively. The response of pulse pressure and cardiac index to the end-expiratory occlusion predicted fluid responsiveness with an accuracy that was similar to the response of cardiac index to PLR and that was significantly better than the response of pulse pressure to PLR (receiver operating characteristic curves area 0.957 [95% confidence interval {CI:} 0.825–0.994], 0.972 [95% CI: 0.849–0.995], 0.937 [95% CI: 0.797–0.990], and 0.675 [95% CI: 0.497–0.829], respectively). Conclusions:The hemodynamic response to an end-expiratory occlusion can predict volume responsiveness in mechanically ventilated patients.

Effects of changes in vascular tone on the agreement between pulse contour and transpulmonary thermodilution cardiac output measurements within an up to 6-hour calibration-free period*

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 (CIT) value obtained at each time point the device was calibrated and the pulse contour CI (CIPC) 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, CIPC correlated with CIT (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), CIPC correlated with CIT (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/m2 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.

Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome.

Objective:Acute respiratory distress syndrome might be associated with an increase in extravascular lung water index and pulmonary vascular permeability index, which can be measured by transpulmonary thermodilution. We tested whether extravascular lung water index and pulmonary vascular permeability index are independent prognostic factors in patients with acute respiratory distress syndrome. Design:Retrospective study. Setting:Medical intensive care unit. Patients:Two hundred consecutive acute respiratory distress syndrome patients (age = 57 ± 17, Simplified Acute Physiology Score II = 57 ± 20, overall day-28 mortality = 54%). Measurements:Extravascular lung water index and pulmonary vascular permeability index were collected (PiCCO device, Pulsion Medical Systems) at each day of the acute respiratory distress syndrome episode. Main Results:The maximum values of extravascular lung water index and pulmonary vascular permeability index recorded during the acute respiratory distress syndrome episode (maximum value of extravascular lung water index and maximum value of pulmonary vascular permeability index, respectively) were significantly higher in nonsurvivors than in survivors at day-28 (mean ± SD: 24 ± 10 mL/kg vs. 19 ± 7 mL/kg of predicted body weight, p < 0.001 [t-test] for maximum value of extravascular lung water index and median [interquartile range]: 4.4 [3.3–6.1] vs. 3.5 [2.8–4.4], p = 0.001 for maximum value of pulmonary vascular permeability index, Wilcoxon’s test). In multivariate analyses, maximum value of extravascular lung water index or maximum value of pulmonary vascular permeability index, Simplified Acute Physiology Score II, maximum blood lactate, mean positive end-expiratory pressure, mean cumulative fluid balance, and the minimal ratio of arterial oxygen pressure over the inspired oxygen fraction were all independently associated with day-28 mortality. A maximum value of extravascular lung water index >21 mL/kg predicted day-28 mortality with a sensitivity of (mean [95% confidence interval]) 54% (44–63)% and a specificity of 73% (63–82)%. The mortality rate was 70% in patients with a maximum value of extravascular lung water index >21 mL/kg and 43% in the remaining patients (p = 0.0003). A maximum value of pulmonary vascular permeability index >3.8 predicted day-28 mortality with a sensitivity of (mean [95% confidence interval]) 67% (57–76)% and a specificity of 65% (54–75)%. The mortality rate was 69% in patients with a maximum value of pulmonary vascular permeability index >3.8 and 37% in the group with a maximum value of pulmonary vascular permeability index ⩽3.8 (p < 0.0001). Conclusions:Extravascular lung water index and pulmonary vascular permeability index measured by transpulmonary thermodilution are independent risk factors of day-28 mortality in patients with acute respiratory distress syndrome.

Critical care management and outcome of severe Pneumocystis pneumonia in patients with and without HIV infection

BackgroundLittle 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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.

Echocardiographic diagnosis of pulmonary artery occlusion pressure elevation during weaning from mechanical ventilation

Objective:Weaning-induced pulmonary edema is a cause of weaning failure in high-risk patients. The diagnosis may require pulmonary artery catheterization to demonstrate increased pulmonary artery occlusion pressure (PAOP) during weaning. Transthoracic echocardiography can estimate left ventricular filling pressures using early (E) and late (A) peak diastolic velocities measured with Doppler transmitral flow, and tissue Doppler imaging of mitral annulus velocities including early (Ea) peak diastolic velocity. We tested the hypothesis that E/A and E/Ea could be used to detect weaning-induced PAOP elevation defined by a PAOP ≥18 mm Hg during a spontaneous breathing trial (SBT). Measurements and Main Results:We included 39 patients who previously failed two consecutive SBTs. A third SBT was performed over a maximum 1-hour period using a T-piece. The PAOP, E/A, and E/Ea were measured before and during this SBT. Receiver operating characteristic curves were constructed to determine the optimal sensitivity and specificity values of E/A and E/Ea obtained at the end of the SBT for predicting a weaning-induced PAOP elevation. Weaning-induced PAOP elevation occurred in 17 patients. A value of E/A >0.95 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 88% and a specificity of 68%. A value of E/Ea >8.5 at the end of the SBT predicted weaning-induced PAOP elevation with a sensitivity of 94% and a specificity of 73%. The combination of E/A >0.95 and E/Ea >8.5 predicted a weaning-induced PAOP elevation with a sensitivity of 82% and a specificity of 91%. Conclusion:At the end of an SBT, the combination of E/A >0.95 and E/Ea >8.5 measured with transthoracic echocardiography allowed an accurate noninvasive detection of weaning-induced PAOP elevation.

Hemodynamic impact of a positive end-expiratory pressure setting in acute respiratory distress syndrome: importance of the volume status.

Objective:The hemodynamic impact of positive end-expiratory pressure in acute respiratory distress syndrome and the underlying mechanisms have not been extensively investigated during low stretch ventilation. Our aim was to evaluate the hemodynamic effect of increasing positive end-expiratory pressure when tidal volume and the plateau pressure are limited and to explore the underlying mechanisms. Design:Prospective study. Setting:Medical intensive care unit. Patients:Twenty-one acute respiratory distress syndrome patients ventilated with a tidal volume of 6.0 ± 0.5 mL/kg of predicted body weight. Intervention:Positive end-expiratory pressure was significantly increased from 5 ± 1 cm H2O to 13 ± 4 cm H2O for reaching a plateau pressure of 30 ± 1 cm H2O. At high positive end-expiratory pressure, passive leg raising was performed for increasing the central blood volume. Measurements:We performed echocardiography and pulmonary artery catheterization during positive end-expiratory pressure increase and during passive leg raising at high positive end-expiratory pressure. Main Results:With positive end-expiratory pressure elevation, the cardiac index decreased by 13% ± 9%. The right ventricular end-diastolic area, right atrial pressure, and pulmonary vascular resistance increased by 13% ± 20%, 34% ± 24% and 32% ± 31%, respectively (p < .01; p = .04; and p < .01 vs. baseline, respectively). The transpulmonary pressure difference (mean pulmonary artery pressure – pulmonary artery occlusion pressure) increased (p < .05). Both at low and high positive end-expiratory pressure, an acute cor pulmonale was observed in the same three (14%) patients. At high positive end-expiratory pressure, the passive leg raising significantly increased the right and left ventricular end-diastolic areas and right atrial pressure. Passive leg raising also decreased the transpulmonary pressure difference (p < .05), increased the cardiac index by 14% ± 10%, and decreased the pulmonary vascular resistance by 21% ± 20% (both p < .01 vs. baseline). Conclusions:In acute respiratory distress syndrome patients, a positive end-expiratory pressure increase with limited tidal volume and plateau pressure reduced cardiac output by increasing the right ventricular afterload. Passive leg raising restored cardiac output by reducing the transpulmonary pressure difference and the pulmonary vascular resistance. This suggests that some pulmonary microvessels were collapsed by positive end-expiratory pressure elevation and were recruited by increasing the central blood volume.

Arterial pressure allows monitoring the changes in cardiac output induced by volume expansion but not by norepinephrine.

Objective: To evaluate to which extent the systemic arterial pulse pressure could be used as a surrogate of cardiac output for assessing the effects of a fluid challenge and of norepinephrine. Design: Observational study. Setting: Medical intensive care unit. Patients: Patients with an acute circulatory failure who received a fluid challenge (228 patients, group 1) or in whom norepinephrine was introduced or increased (145 patients, group 2). Interventions: We measured the systolic, diastolic, and mean arterial pressure, pulse pressure, and the transpulmonary thermodilution cardiac output before and after the therapeutic interventions. Main Results: In group 1, the fluid challenge significantly increased cardiac output by 24% ± 25%. It significantly increased cardiac output by ≥15% (+35% ± 27%) in 142 patients (“responders”). The fluid-induced changes in cardiac output were correlated with the changes in pulse pressure (r = .56, p < .0001), systolic arterial pressure (r = .55, p < .0001), diastolic arterial pressure (r = .37, p < .0001), and mean arterial pressure (r = .52, p < .0001). At multivariate analysis, changes in pulse pressure were significantly related to changes in stroke volume (multiple r = .52) and to age (r = .12). A fluid-induced increase in pulse pressure of ≥17% allowed detecting a fluid-induced increase in cardiac output of ≥15% with a sensitivity of 65[56–72]% and a specificity of 85[76–92]%. The area under the receiver operating characteristic curves for the fluid-induced changes in mean arterial pressure and in diastolic arterial pressure was significantly lower than for pulse pressure. In group 2, the introduction/increase of norepinephrine significantly increased cardiac output by 14% ± 18%. The changes in cardiac output induced by the introduction/increase in the dose of norepinephrine were correlated with the changes in pulse pressure and systolic arterial pressure (r = .21 and .29, respectively, p = .001) but to a significantly lesser extent than in group 1. Conclusions: Pulse pressure and systolic arterial pressure could be used for detecting the fluid-induced changes in cardiac output, in spite of a significant proportion of false-negative cases. By contrast, the changes in pulse pressure and systolic arterial pressure were unable to detect the changes in cardiac output induced by norepinephrine.

Measuring aortic diameter improves accuracy of esophageal Doppler in assessing fluid responsiveness.

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.