Effect of noninvasive ventilation on mortality and clinical outcomes among patients with severe hypoxemic COVID-19 pneumonia after high-flow nasal oxygen failure: a multicenter retrospective French cohort with propensity score analysis.

BACKGROUND: We assessed the effect of noninvasive ventilation (NIV) on mortality and length of stay after high flow nasal oxygenation (HFNO) failure among patients with severe hypoxemic COVID-19 pneumonia. METHODS: In this multicenter, retrospective study, we enrolled COVID-19 patients admitted in intensive care unit (ICU) for severe COVID-19 pneumonia with a HFNO failure from December 2020 to January 2022. The primary outcome was to compare the 90-day mortality between patients who required a straight intubation after HFNO failure and patients who received NIV after HFNO failure. Secondary outcomes included ICU and hospital length of stay. A propensity score analysis was performed to control for confounding factors between groups. Exploratory outcomes included a subgroup analysis for 90-day mortality. RESULTS: We included 461 patients with HFNO failure in the analysis, 233 patients in the straight intubation group and 228 in the NIV group. The 90-day mortality did not significantly differ between groups, 58/228 (25.4%) int the NIV group compared with 59/233 (25.3%) in the straight intubation group, with an adjusted hazard ratio (HR) after propensity score weighting of 0.82 [95%CI, 0.50-1.35] (p = 0.434). ICU length of stay was significantly shorter in the NIV group compared to the straight intubation group, 10.0 days [IQR, 7.0-19.8] versus 18.0 days [IQR,11.0-31.0] with a propensity score weighted HR of 1.77 [95%CI, 1.29-2.43] (p < 0.001). A subgroup analysis showed a significant increase in mortality rate for intubated patients in the NIV group with 56/122 (45.9%), compared to 59/233 (25.3%) for patients in the straight intubation group (p < 0.001). CONCLUSIONS: In severely hypoxemic COVID-19 patients, no significant differences were observed on 90-day mortality between patients receiving straight intubation and those receiving NIV after HFNO failure. NIV strategy was associated with a significant reduction in ICU length of stay, despite an increase in mortality in the subgroup of patients finally intubated.

Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia.

BACKGROUND: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined. METHODS: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO2/FiO2 ratio < 100 with FiO2 > 80% after a single awake prone positioning session. Patients with an increase in PaO2/FiO2 ratio > 20% were considered as responders. RESULTS: Overall, almitrine increased the PaO2/FiO2 ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders. CONCLUSIONS: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.

Impact of sex differences on cardiac injury in critically ill patients with COVID-19.

BACKGROUND: COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients' outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear. METHODS: In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated. RESULTS: We included 198 patients with a median age of 66 (56-73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40-0.80) vs. 0.80 (0.50-1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88-246) vs. 111 (62-192) mg/L, p = 0.03); D-Dimers (1293 (709-2523) vs. 900 (560-1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06-5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01-73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42-1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes. CONCLUSIONS: Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes. Clinical trial registration NCT04335162.

Use of high-flow nasal cannula oxygen and risk factors for high-flow nasal cannula oxygen failure in critically-ill patients with COVID-19.

BACKGROUND: High-flow nasal oxygen therapy (HFNC) may be an attractive first-line ventilatory support in COVID-19 patients. However, HNFC use for the management of COVID-19 patients and risk factors for HFNC failure remain to be determined. METHODS: In this retrospective study, we included all consecutive COVID-19 patients admitted to our intensive care unit (ICU) in the first (Mars-May 2020) and second (August 2020- February 202) French pandemic waves. Patients with limitations for intubation were excluded. HFNC failure was defined as the need for intubation after ICU admission. The impact of HFNC use was analyzed in the whole cohort and after constructing a propensity score. Risk factors for HNFC failure were identified through a landmark time-dependent cause-specific Cox model. The ability of the 6-h ROX index to detect HFNC failure was assessed by generating receiver operating characteristic (ROC) curve. RESULTS: 200 patients were included: HFNC was used in 114(57%) patients, non-invasive ventilation in 25(12%) patients and 145(72%) patients were intubated with a median delay of 0 (0-2) days after ICU admission. Overall, 78(68%) patients had HFNC failure. Patients with HFNC failure had a higher ICU mortality rate (34 vs. 11%, p = 0.02) than those without. At landmark time of 48 and 72 h, SAPS-2 score, extent of CT-Scan abnormalities > 75% and HFNC duration (cause specific hazard ratio (CSH) = 0.11, 95% CI (0.04-0.28), per + 1 day, p < 0.001 at 48 h and CSH = 0.06, 95% CI (0.02-0.23), per + 1 day, p < 0.001 at 72 h) were associated with HFNC failure. The 6-h ROX index was lower in patients with HFNC failure but could not reliably predicted HFNC failure with an area under ROC curve of 0.65 (95% CI(0.52-0.78), p = 0.02). In the matched cohort, HFNC use was associated with a lower risk of intubation (CSH = 0.32, 95% CI (0.19-0.57), p < 0.001). CONCLUSIONS: In critically-ill COVID-19 patients, while HFNC use as first-line ventilatory support was associated with a lower risk of intubation, more than half of patients had HFNC failure. Risk factors for HFNC failure were SAPS-2 score and extent of CT-Scan abnormalities > 75%. The risk of HFNC failure could not be predicted by the 6-h ROX index but decreased after a 48-h HFNC duration.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.

Acute and fatal cephalosporin-induced autoimmune haemolytic anaemia.

We report the case of an 82-year old male patient admitted in our medical intensive care unit for diffuse skin lesions, 3 days after the onset of ceftriaxone for bilateral pneumonia without microbiological documentation. The patient concomitantly exhibited diffuse skin lesions compatible with livedo and neurological and haemodynamic failure. Biological analysis revealed acute haemolytic anaemia. Warming of patient, red blood-cells transfusion and high-doses corticosteroids were initiated and ceftriaxone was stopped. Despite these therapeutics, the patient exhibited multiple organ failure and died. The main suspected triggering factor of this acute and fatal haemolytic anaemia was ceftriaxone administration considering: (i) the delay between cephalosporin administration and symptoms; (ii) the worsening of livedo and acrocyanosis a few hours after meningeal ceftriaxone doses; and (iii) fatal evolution. Cephalosporin-induced autoimmune haemolytic anaemia is a rare and serious cause of livedo that should be suspected in patients exhibiting livedo and acute haemolytic anaemia within hours/days following cephalosporin administration.

Increase in Central Venous Pressure During Passive Leg Raising Cannot Detect Preload Unresponsiveness.

OBJECTIVE: By analogy with the classical central venous pressure rules to assess a fluid challenge, we hypothesized that an increase in central venous pressure greater than or equal to 5 cm H2O (i.e., 4 mm Hg) during passive leg raising can predict preload unresponsiveness diagnosed by the absence of increase in velocity-time integral of the left ventricular outflow tract greater than or equal to 10% during the test (negative passive leg raising test). DESIGN AND SETTINGS: Velocity-time integral was measured by transthoracic echocardiography. Central venous pressure and velocity-time integral were measured before and during passive leg raising. PATIENTS: Critically ill patients for whom the physician decided to test preload responsiveness by passive leg raising were prospectively included. MEASUREMENT AND MAIN RESULTS: Fifty-seven set of measurements were performed in 50 patients. Preload unresponsiveness (negative passive leg raising test) was observed in 32 cases. The changes in central venous pressure during passive leg raising did not differ between positive passive leg raising cases (positive passive leg raising test) and negative passive leg raising test cases (3 ± 2 vs 3 ± 2 mm Hg, respectively) and thus did not predict preload unresponsiveness (area under the receiver-operating characteristic curve of 0.59). An increase in central venous pressure greater than or equal to 4 mm Hg during passive leg raising was observed in 10 cases of positive passive leg raising test and in 11 cases of negative passive leg raising test. Taking an increase in central venous pressure greater than or equal to 3 or greater than or equal to 5 mm Hg rather than greater than or equal to 4 mm Hg during passive leg raising did not better allow one to identify negative passive leg raising test. CONCLUSIONS: Marked increase in central venous pressure during passive leg raising cannot identify negative passive leg raising test cases and thus preload unresponsiveness. Measurements of cardiac output (or its surrogates) during passive leg raising are, thus, mandatory to appropriately interpret this test.

Assessment of tissue oxygenation to personalize mean arterial pressure target in patients with septic shock.

OBJECTIVE: To investigate whether assessment of tissue oxygenation could help personalizing the mean arterial pressure (MAP) target in patients with septic shock. METHODS: We prospectively measured near-infrared spectroscopy variables in 22 patients with septic shock receiving norepinephrine with a MAP>75 mmHg within the first six hours of intensive care unit (ICU) stay for patients with community-acquired septic shock and within the first six hours of resuscitation for patients with ICU-acquired septic shock. All measurements were performed at MAP>75 mmHg ("high-MAP") and at MAP 65-70 mmHg ("low-MAP") after decreasing the norepinephrine dose. Relative changes in StO2 recovery slope (RS) >8% were considered clinically relevant. RESULTS: After decreasing the norepinephrine dose by 45 ± 24%, MAP significantly decreased from 81[78;84] to 68[67;69]mmHg, whereas cardiac index did not change. On average, the StO2-RS significantly decreased between high and low-MAP from 2.86[1.87;4.32] to 2.41[1.14;3.72]%/sec with a large interindividual variability: the StO2-RS decreased by >8% in 14 patients, increased by >8% in 4 patients and changes were < 8% in 4 patients. These changes in StO2-RS were correlated with the StO2-RS at low-MAP (r = 0.57,p = 0.006). At high-MAP, there was no difference between patients exhibiting a relevant decrease or increase in StO2-RS. CONCLUSIONS: A unique MAP target may not be suitable for all patients with septic shock as its impact on peripheral oxygenation may widely differ among patients. It could make sense to personalize MAP target through a multimodal assessment including peripheral oxygenation.

Concomitant systolic and diastolic alterations during chronic hypertension in pig.

The mechanical and cellular relationships between systole and diastole during left ventricular (LV) dysfunction remain to be established. LV contraction-relaxation coupling was examined during LV hypertrophy induced by chronic hypertension. Chronically instrumented pigs received angiotensin II infusion for4weeks to induce chronic hypertension (133 ±â€¯7 mmHg vs 98 ±â€¯5 mmHg for mean arterial pressure at Day 28 vs 0, respectively) and LV hypertrophy. LV function was investigated with the instrumentation and echocardiography for LV twist-untwist assessment before and after dobutamine infusion. The cellular mechanisms were investigated by exploring the intracellular Ca2+ handling. At Day 28, pigs exhibited LV hypertrophy with LV diastolic dysfunction (impaired LV isovolumic relaxation, increased LV end-diastolic pressure, decreased and delayed LV untwisting rate) and LV systolic dysfunction (impaired LV isovolumic contraction and twist) although LV ejection fraction was preserved. Isolated cardiomyocytes exhibited altered shortening and lengthening. Interestingly, contraction-relaxation coupling remained preserved both in vivo and in vitro during LV hypertrophy. LV systolic and diastolic dysfunctions were associated to post-translational remodeling and dysfunction of the type 2 cardiac ryanodine receptor/Ca2+ release channel (RyR2), i.e., PKA hyperphosphorylation of RyR2, depletion of calstabin 2 (FKBP12.6), RyR2 leak and hypersensitivity of RyR2 to cytosolic Ca2+ during both contraction and relaxation phases. In conclusion, LV contraction-relaxation coupling remained preserved during chronic hypertension despite LV systolic and diastolic dysfunctions. This implies that LV diastolic dysfunction is accompanied by LV systolic dysfunction. At the cellular level, this is linked to sarcoplasmic reticulum Ca2+ leak through PKA-mediated RyR2 hyperphosphorylation and depletion of its stabilizing partner.

Esophageal Doppler Can Predict Fluid Responsiveness Through End-Expiratory and End-Inspiratory Occlusion Tests.

OBJECTIVES: To assess whether, in patients under mechanical ventilation, fluid responsiveness is predicted by the effects of short respiratory holds on cardiac index estimated by esophageal Doppler. DESIGN: Prospective, monocentric study. SETTING: Medical ICU. PATIENTS: Twenty-eight adult patients with acute circulatory failure and a decision of the clinicians in charge to administer fluids. INTERVENTIONS: Before and after infusing 500 mL of saline, we measured cardiac index estimated by esophageal Doppler before and during the last 5 seconds of successive 15-second end-inspiratory occlusion and end-expiratory occlusion, separated by 1 minute. Patients in whom volume expansion increased cardiac index measured by transpulmonary thermodilution greater than or equal to 15% were defined as "fluid responders." Cardiac index measured by the Pulse Contour Cardiac Output device (from pulse contour analysis or transpulmonary thermodilution) was used as the reference. MEASUREMENTS AND MAIN RESULTS: End-expiratory occlusion increased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (8% ± 2% vs 3% ± 1%, respectively; p < 0.0001) and end-inspiratory occlusion decreased cardiac index estimated by esophageal Doppler more in responders than in nonresponders (-8% ± 5% vs -4% ± 2%, respectively; p = 0.0002). Fluid responsiveness was predicted by the end-expiratory occlusion induced percent change in cardiac index estimated by esophageal Doppler with an area under the receiver operating characteristic curve of 1.00 (95% CI, 0.88-1.00) and a threshold value of 4% increase in cardiac index estimated by esophageal Doppler. It was predicted by the sum of absolute values of percent changes in cardiac index estimated by esophageal Doppler during both occlusions with a similar area under the receiver operating characteristic curve (0.99 [0.86-1.00]) and with a threshold of 9% change in cardiac index estimated by esophageal Doppler, which is compatible with the esophageal Doppler precision. CONCLUSIONS: If the absolute sum of the percent change in cardiac index estimated by esophageal Doppler induced by two successive end-inspiratory occlusion and end-expiratory occlusion maneuvers is greater than 9%, it is likely that a 500 mL fluid infusion will increase cardiac output. This diagnostic threshold is higher than if only end-expiratory occlusion induced percent changes in cardiac index estimated by esophageal Doppler are taken into account.

Validation and Critical Evaluation of the Effective Arterial Elastance in Critically Ill Patients.

OBJECTIVES: First, to validate bedside estimates of effective arterial elastance = end-systolic pressure/stroke volume in critically ill patients. Second, to document the added value of effective arterial elastance, which is increasingly used as an index of left ventricular afterload. DESIGN: Prospective study. SETTING: Medical ICU. PATIENTS: Fifty hemodynamically stable and spontaneously breathing patients equipped with a femoral (n = 21) or radial (n = 29) catheter were entered in a "comparison" study. Thirty ventilated patients with invasive hemodynamic monitoring (PiCCO-2; Pulsion Medical Systems, Feldkirchen, Germany), in whom fluid administration was planned were entered in a " dynamic" study. INTERVENTIONS: In the "dynamic" study, data were obtained before/after a 500 mL saline administration. MEASUREMENTS AND MAIN RESULTS: According to the "cardiocentric" view, end-systolic pressure was considered the classic index of left ventricular afterload. End-systolic pressure was calculated as 0.9 × systolic arterial pressure at the carotid, femoral, and radial artery level. In the "comparison" study, carotid tonometry allowed the calculation of the reference effective arterial elastance value (1.73 ± 0.62 mm Hg/mL). The femoral estimate of effective arterial elastance was more accurate and precise than the radial estimate. In the "dynamic" study, fluid administration increased stroke volume and end-systolic pressure, whereas effective arterial elastance (femoral estimate) and systemic vascular resistance did not change. Effective arterial elastance was related to systemic vascular resistance at baseline (r = 0.89) and fluid-induced changes in effective arterial elastance and systemic vascular resistance were correlated (r = 0.88). In the 15 fluid responders (cardiac index increases ≥ 15%), fluid administration increased end-systolic pressure and decreased effective arterial elastance and systemic vascular resistance (each p < 0.05). In the 15 fluid nonresponders, end-systolic pressure increased (p < 0.05), whereas effective arterial elastance and systemic vascular resistance remained unchanged. CONCLUSIONS: In critically ill patients, effective arterial elastance may be reliably estimated at bedside (0.9 × systolic femoral pressure/stroke volume). We support the use of this validated estimate of effective arterial elastance when coupled with an index of left ventricular contractility for studying the ventricular-arterial coupling. Conversely, effective arterial elastance should not be used in isolation as an index of left ventricular afterload.

5-Fluorouracil rechallenge after 5-fluorouracil-induced hyperammonemic encephalopathy.

For several decades, 5-Fluorouracil (5-FU) has been the backbone of many chemotherapy regimens for various tumor types. Its most common side effects are gastrointestinal disorders, mucositis, myelosuppression, hand-foot syndrome, and rarely cardiac toxicity. More rarely, 5-FU infusion can induce hyperammonemic encephalopathy. 5-FU toxicities can be worsened by complete or partial genetic and/or phenotypic dihydropyrimidine dehydrogenase deficiency. Here, we report the case of a patient who initially developed a 5-FU-induced hyperammonemic encephalopathy after receiving FOLFIRINOX (oxaliplatin, irinotecan, folinic acid, and 5-FU) chemotherapy with bevacizumab to treat a metastatic gastrointestinal cancer of unknown primary. Thereafter, the patient was rechallenged successfully by the same chemotherapy regimen (FOLFIRINOX) for more than 6 months with a protocol consisting in a free protein diet, and administration of ammonium chelators, and Krebs and urea cycle intermediates, to prevent further hyperammonemia. We also present a review of the literature on 5-FU rechallenge after 5-FU-induced hyperammonemic encephalopathy.

What is the lowest change in cardiac output that transthoracic echocardiography can detect?

BACKGROUND: In critically ill patients, changes in the velocity-time integral (VTI) of the left ventricular outflow tract, measured by transthoracic echocardiography (TTE), are often used to non-invasively assess the response to fluid administration or for performing tests assessing fluid responsiveness. However, the precision of TTE measurements has not yet been investigated in such patients. First, we aimed at assessing how many measurements should be averaged within one TTE examination to reach a sufficient precision for various variables. Second, we aimed at identifying the least significant change (LSC) of these variables between successive TTE examinations. METHODS: We prospectively included 100 haemodynamically stable patients in whom TTE examination was planned. Three TTE examinations were performed, the first and the third by one operator and the second by another one. We calculated the precision and LSC (1) within one examination depending on the number of averaged measurements and (2) between measurements performed in two successive examinations. RESULTS: In patients in sinus rhythm, averaging three measurements within an examination was enough for obtaining an acceptable precision (interquartile range highest value < 10%) for VTI. In patients with atrial fibrillation, averaging five measurements was necessary. The precision of some other common TTE variables depending on the number of measurements is provided. Between two successive examinations performed by the same operator, the LSC was 11 [5-18]% for VTI. If two operators performed the examinations, the LSC for VTI significantly increased to 14 [8-26]%. The LSC between two examinations for other TTE variables is also provided. CONCLUSIONS: Averaging three measurements within one TTE examination is enough for obtaining precise measurements for VTI in patients in sinus rhythm but not in patients with atrial fibrillation. Between two TTE examinations performed by the same operator, the LSC of VTI is compatible with the assessment of the effects of a 500-mL fluid infusion but is not precise enough for assessing the effects of some tests predicting preload responsiveness.

Less or more hemodynamic monitoring in critically ill patients.

PURPOSE OF REVIEW: Hemodynamic investigations are required in patients with shock to identify the type of shock, to select the most appropriate treatments and to assess the patient's response to the selected therapy. We discuss how to select the most appropriate hemodynamic monitoring techniques in patients with shock as well as the future of hemodynamic monitoring. RECENT FINDINGS: Over the last decades, the hemodynamic monitoring techniques have evolved from intermittent toward continuous and real-time measurements and from invasive toward less-invasive approaches. In patients with shock, current guidelines recommend the echocardiography as the preferred modality for the initial hemodynamic evaluation. In patients with shock nonresponsive to initial therapy and/or in the most complex patients, it is recommended to monitor the cardiac output and to use advanced hemodynamic monitoring techniques. They also provide other useful variables that are useful for managing the most complex cases. Uncalibrated and noninvasive cardiac output monitors are not reliable enough in the intensive care setting. SUMMARY: The use of echocardiography should be initially encouraged in patients with shock to identify the type of shock and to select the most appropriate therapy. The use of more invasive hemodynamic monitoring techniques should be discussed on an individualized basis.

Pressure Waveform Analysis.

Monitoring cardiac output is of special interest for detecting early hemodynamic impairment and for guiding its treatment. Among the techniques that are available to monitor cardiac output, pressure waveform analysis estimates cardiac output from the shape of the arterial pressure curve. It is based on the general principle that the amplitude of the systolic part of the arterial curve is proportional to cardiac output and arterial compliance. Such an estimation of cardiac output has the advantage of being continuous and in real time. With "calibrated" devices, the initial estimation of cardiac output by pressure waveform analysis is calibrated by measurements of cardiac output made by transpulmonary thermal or lithium dilution. Later, at each time transpulmonary dilution is performed, the estimation by pressure waveform analysis, which may drift over time, is calibrated again. By contrast, uncalibrated devices do not use any independent measurement of cardiac output. Unlike calibrated devices, they can be plugged to any arterial catheter. Nevertheless, uncalibrated devices are not reliable in cases of significant short-term changes in arterial resistance, as for instance in patients undergoing liver surgery or those with vasodilatory shock receiving vasopressors. Perioperative hemodynamic monitoring is recommended for high-risk surgical patients since it reduces the number of complications in these patients. The pressure waveform analysis monitoring, especially with uncalibrated devices, is suitable for this purpose. In the intensive care setting, hemodynamic monitoring is recommended for patients with acute circulatory failure, who do not respond to initial therapy. Since these patients often experience large changes in arterial resistance, either spontaneously or due to vasoactive drugs, calibrated devices are more suitable in this context. Not only are they more reliable than uncalibrated devices but also they provide a comprehensive hemodynamic assessment through measurements of a variety of transpulmonary thermodilution-related variables. In this review, we summarize the characteristics of the monitoring devices using the pressure waveform analysis and discuss the appropriate use of different devices in the perioperative and intensive care unit settings.

Predicting Fluid Responsiveness in Critically Ill Patients by Using Combined End-Expiratory and End-Inspiratory Occlusions With Echocardiography.

OBJECTIVES: First, we aimed at assessing whether fluid responsiveness is predicted by the effects of an end-expiratory occlusion on the velocity-time integral of the left ventricular outflow tract. Second, we investigated whether adding the effects of an end-inspiratory occlusion and of an end-expiratory occlusion on velocity-time integral can predict fluid responsiveness with similar reliability than end-expiratory occlusion alone but with a higher threshold, which might be more compatible with the precision of echocardiography. DESIGN: Diagnostic study. SETTING: Medical ICU. PATIENTS: Thirty mechanically ventilated patients in whom fluid administration was planned. INTERVENTIONS: A 15-second end-expiratory occlusion and end-inspiratory occlusion, separated by 1 minute, followed by a 500-mL saline administration. MEASUREMENTS AND MAIN RESULTS: Pulse contour analysis-derived cardiac index and velocity-time integral were measured during the last 5 seconds of 15-second end-inspiratory occlusion and end-expiratory occlusion and after fluid administration. End-expiratory occlusion increased velocity-time integral more in responders than in nonresponders to fluid administration (11% ± 5% vs 3% ± 1%, respectively; p < 0.0001), and end-inspiratory occlusion decreased velocity-time integral more in responders than in nonresponders (12% ± 5% vs 5% ± 2%, respectively; p = 0.0002). When adding the absolute values of changes in velocity-time integral observed during both occlusions, velocity-time integral changed by 23% ± 9% in responders and by 8% ± 3% in nonresponders. Fluid responsiveness was predicted by the end-expiratory occlusion-induced change in velocity-time integral with an area under the receiver operating characteristic curve of 0.938 (0.785-0.989) and a threshold value of 5%. Fluid responsiveness was predicted by the sum of absolute values of changes in velocity-time integral during both occlusions with a similar reliability (area under the receiver operating characteristic curve = 0.973 [0.838-1.000]) but with a threshold of 13%. Both sensitivity and specificity were 93% (68-100%). CONCLUSIONS: If consecutive end-inspiratory occlusion and end-expiratory occlusion change velocity-time integral is greater than or equal to 13% in total, fluid responsiveness is accurately predicted. This threshold is more compatible with the precision of echocardiography than that obtained by end-expiratory occlusion alone.

Improvement of left ventricular filling by ivabradine during chronic hypertension: involvement of contraction-relaxation coupling.

Chronic hypertension is associated with left ventricular (LV) hypertrophy and LV diastolic dysfunction with impaired isovolumic relaxation and abnormal LV filling. Increased heart rate (HR) worsens these alterations. We investigated whether the I f channel blocker ivabradine exerts beneficial effects on LV filling dynamic. In this setting, we also evaluated the relationship between LV filling and isovolumic contraction as a consequence of contraction-relaxation coupling. Therefore, hypertension was induced by a continuous infusion of angiotensin II during 28 days in 10 chronically instrumented pigs. LV function was investigated after stopping angiotensin II infusion to offset the changes in loading conditions. In the normal heart, LV relaxation filling, LV early filling, LV peak early filling rate were positively correlated to HR. In contrast, these parameters were significantly reduced at day 28 vs. day 0 (18, 42, and 26 %, respectively) despite the increase in HR (108 ± 6 beats/min vs. 73 ± 2 beats/min, respectively). These abnormalities were corrected by acute administration of ivabradine (1 mg/kg, iv). Ivabradine still exerted these effects when HR was controlled at 150 beats/min by atrial pacing. Interestingly, LV relaxation filling, LV early filling and LV peak early filling were strongly correlated with both isovolumic contraction and relaxation. In conclusion, ivabradine improves LV filling during chronic hypertension. The mechanism involves LV contraction-relaxation coupling through normalization of isovolumic contraction and relaxation as well as HR-independent mechanisms.

Optimizing the circulation in the prone patient.

PURPOSE OF REVIEW: Prone positioning is recommended as a rescue therapy to improve arterial oxygenation in patients with severe acute respiratory distress syndrome (ARDS). In this review, we summarize the macro and the microcirculatory effects of prone positioning and emphasize which hemodynamic variables can be monitored when this therapy is applied. RECENT FINDINGS: Early and prolonged prone positioning sessions significantly decrease the mortality of patients with severe ARDS. Prone positioning increases cardiac preload and decreases right ventricular afterload in patients with ARDS under protective ventilation and maximal lung recruitment. This results in an increase in cardiac output only in patients with preload reserve, emphasizing the important role of preload in the hemodynamic effects of prone positioning. Prone positioning might also exert some effects on regional and/or local blood flows, which mainly result from the increase in intra-abdominal pressure. Because prone positioning does not produce a significant increase in intra-abdominal pressure, it does not exert deleterious effects on the microcirculation of intra-abdominal organs. SUMMARY: Prone positioning generally exerts beneficial macrocirculatory effects, which can result in increased cardiac output in patients with preload reserve without negatively altering regional circulations.

Monitoring: from cardiac output monitoring to echocardiography.

PURPOSE OF REVIEW: Hemodynamic exploration is mandatory in patients with shock to identify the type of shock, to select the best therapeutic strategy, and to assess the efficacy of the selected therapy. In this review, we summarize the characteristics of the main available hemodynamic monitoring systems and emphasize on how to select the most appropriate ones in patients with circulatory shock. RECENT FINDINGS: Over the past decade, hemodynamic monitoring techniques have progressively evolved from intermittent toward real-time measurements and from invasive toward less invasive approaches. Nowadays, echocardiography is recommended as the first-line modality of hemodynamic evaluation in patients with shock. Current guidelines recommend reserving advanced hemodynamic monitoring systems for patients not responding to the initial therapy and/or for complex conditions such as combination of shock with acute respiratory distress syndrome. Invasive and noninvasive uncalibrated cardiac output monitors, as well as esophageal Doppler, could find their place in the perioperative context rather than in patients with shock. SUMMARY: The use of echocardiography should be encouraged at the initial period of shock to identify main involved mechanisms and to select the appropriate therapy. The use of more invasive monitoring systems should be discussed on an individualized basis.

Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study.

INTRODUCTION: Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. METHODS: Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. RESULTS: One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. CONCLUSIONS: We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.