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Background: Pulse pressure variation (PPV) is not reliable in predicting preload responsiveness in patients receiving mechanical with spontaneous breathing (SB) activity. We hypothesised that an increase in PPV after a tidal volume (V T ) challenge (TVC) or a decrease in PPV during passive leg raising (PLR) can predict preload responsiveness in such cases., Methods: This prospective observational study was performed in two ICUs and included patients receiving mechanical ventilation with SB, for whom the treating physician decided to test preload responsiveness. Transthoracic echocardiography was used to measure the velocity-time integral (VTI) of the left ventricular outflow tract. Patients exhibiting an increase in VTI ≥12% during PLR were defined as PLR+ patients (or preload responders). Then, a TVC was performed by increasing V T by 2 ml kg -1 predicted body weight (PBW) for 1 min. PPV was recorded at each step., Results: Fifty-four patients (Simplified Acute Physiology Score II: 60 (25) ventilated with a V T of 6.5 (0.8) ml kg -1 PBW, were included. Twenty-two patients were PLR+. The absolute decrease in PPV during PLR and the absolute increase in PPV during TVC discriminated between PLR+ and PLR- patients with area under the receiver operating characteristic (AUROC) curve of 0.78 and 0.73, respectively, and cut-off values of -1% and +2%, respectively. Those AUROC curve values were similar but were significantly different from that of baseline PPV (0.61)., Conclusion: In patients undergoing mechanical ventilation with SB activity, PPV does not predict preload responsiveness. However, the decrease in PPV during PLR and the increase in PPV during a TVC help discriminate preload responders from non-responders with moderate accuracy., Clinical Trial Registration: NCT04369027 (ClinicalTrials.gov)., Competing Interests: Declarations of interest OH is a member of the medical advisory board of AMOMED. J-LT and XM are members of the medical advisory board of Pulsion/Getinge., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The end-expiratory occlusion (EEXPO) test detects preload responsiveness, but it is 15 s long and induces small changes in cardiac index (CI). It is doubtful whether the Starling bioreactance device, which averages CI over 24 s and refreshes the displayed value every 4 s (Starling-24.4), can detect the EEXPO-induced changes in CI (ΔCI). Our primary goal was to test whether this Starling device version detects preload responsiveness through EEXPO. We also tested whether shortening the averaging and refresh times to 8 s and one second, respectively, (Starling-8.1) improves the accuracy of the device in detecting preload responsiveness using EEXPO., Methods: In 42 mechanically ventilated patients, during a 15-s EEXPO, we measured ∆CI through calibrated pulse contour analysis (CI pulse , PiCCO2 device) and using the Starling device. For the latter, we considered both CI Starling-24.4 from the commercial version and CI Starling-8.1 derived from the raw data. For relative ∆CI Starling-24.4 and ∆CI Starling-8.1 during EEXPO, we calculated the area under the receiver operating characteristic curve (AUROC) to detect preload responsiveness, defined as an increase in CI pulse  ≥ 10% during passive leg raising (PLR). For both methods, the correlation coefficient vs. ∆CI pulse was calculated., Results: Twenty-six patients were preload responders and sixteen non preload-responders. The AUROC for ∆CI Starling-24.4 was significantly lower compared to ∆CI Starling-8.1 (0.680 ± 0.086 vs. 0.899 ± 0.049, respectively; p = 0.027). A significant correlation was observed between ∆CI Starling-8.1 and ∆CI pulse (r = 0.42; p = 0.009), but not between ∆CI Starling-24.4 and ∆CI pulse . During PLR, both ∆CI Starling-24.4 and ∆CI Starling-8.1 reliably detected preload responsiveness., Conclusions: Shortening the averaging and refresh times of the bioreactance signal to 8 s and one second, respectively, increases the reliability of the Starling device in detection of EEXPO-induced ∆CI., Trial Registration: No., Idrcb: 2018-A02825-50. Registered 13 December 2018., (© 2021. The Author(s).)

Background: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR)., Methods: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%., Results: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose., Conclusions: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock., (© 2021. The Author(s).)

Background: In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin., Methods: Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020., Results: Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14-21) vs. 15 (11-19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18-27) vs. 21 (15-24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70-109) vs. 100 (80-124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort., Conclusion: Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups., Trial Registration Number and Date of Registration: ClinicalTrials.gov (NCT04337983). Registered 30 March 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .

Objectives: To examine the effects of prone positioning on venous return and its determinants such as mean systemic pressure and venous return resistance in patients with acute respiratory distress syndrome., Design: Prospective monocentric study., Settings: A 25-bed medical ICU., Patients: About 22 patients with mild-to-severe acute respiratory distress syndrome in whom prone positioning was decided., Interventions: We obtained cardiac index, mean systemic pressure, and venous return resistance (the latter two estimated through the heart-lung interactions method) before and during prone positioning. Preload responsiveness was assessed at baseline using an end-expiratory occlusion test., Measurements and Main Results: Prone positioning significantly increased mean systemic pressure (from 24 mm Hg [19-34 mm Hg] to 35 mm Hg [32-46 mm Hg]). This was partly due to the trunk lowering performed before prone positioning. In seven patients, prone positioning increased cardiac index greater than or equal to 15%. All were preload responsive. In these patients, prone positioning increased mean systemic pressure by 82% (76-95%), central venous pressure by 33% (21-59%), (mean systemic pressure - central venous pressure) gradient by 144% (83-215)%, while it increased venous return resistance by 71% (60-154%). In 15 patients, prone positioning did not increase cardiac index greater than or equal to 15%. In these patients, prone positioning increased mean systemic pressure by 28% (18-56%) (p < 0.05 vs. patients with significant increase in cardiac index), central venous pressure by 21% (7-54%), (mean systemic pressure - central venous pressure) gradient by 28% (23-86%), and venous return resistance by 37% (17-77%). Eleven of these 15 patients were preload unresponsive., Conclusions: Prone positioning increased mean systemic pressure in all patients. The resulting change in cardiac index depended on the extent of increase in (mean systemic pressure - central venous pressure) gradient, of preload responsiveness, and of the increase in venous return resistance. Cardiac index increased only in preload-responsive patients if the increase in venous return resistance was lower than the increase in the (mean systemic pressure -central venous pressure) gradient., Competing Interests: Dr. Teboul received funding from Gettinge/Pulsion medical systems. Dr. Monnet received funding from Pulsion Medical Systems. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Importance: Little is known about long-term sequelae of COVID-19., Objective: To describe the consequences at 4 months in patients hospitalized for COVID-19., Design, Setting, and Participants: In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit., Exposures: Survival of hospitalization for COVID-19., Main Outcomes and Measures: Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography., Results: Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%)., Conclusions and Relevance: Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.

Background: In patients ventilated with tidal volume (Vt) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPV PLR ) or in IVCDV (ΔIVCDV PLR ) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDV Vt ) rather than changes in PPV (ΔPPV Vt )., Methods: In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness., Results: At baseline, IVCDV was not different between preload responders (n = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by - 38 ± 16% and - 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPV PLR , expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDV PLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPV Vt , expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDV Vt , but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3-18]%)., Conclusions: During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable., Trial Registration: Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.

Objectives: The end-expiratory occlusion test for assessing preload responsiveness consists in interrupting mechanical ventilation for 15 seconds at end-expiration and measuring the cardiac index changes. The perfusion index is the ratio between the pulsatile and the nonpulsatile portions of the plethysmography signal and is, in part, determined by stroke volume. We tested whether the end-expiratory occlusion-induced changes in perfusion index could detect a positive passive leg raising test, suggesting preload responsiveness., Design: Observational study., Setting: Medical ICU., Patients: Thirty-one ventilated patients without atrial fibrillation., Interventions: We measured perfusion index (Radical-7 device; Masimo Corp., Irvine, CA) and cardiac index (PiCCO2; Pulsion Medical Systems, Feldkirchen, Germany) before and during a passive leg raising test and a 15-second end-expiratory occlusion., Measurements and Main Results: In 19 patients with a positive passive leg raising test (increase in cardiac index ≥ 10%), compared to the baseline value and expressed as a relative change, passive leg raising increased cardiac index and perfusion index by 17% ± 7% and 49% ± 23%, respectively, In these patients, end-expiratory occlusion increased cardiac index and perfusion index by 6% ± 2% and 11% ± 8%, respectively. In the 12 patients with a negative passive leg raising test, perfusion index did not significantly change during passive leg raising and end-expiratory occlusion. Relative changes in perfusion index and cardiac index observed during all interventions were significantly correlated (r = 0.83). An end-expiratory occlusion-induced relative increase in perfusion index greater than or equal to 2.5% ([perfusion index during end-expiratory occlusion-perfusion index at baseline]/perfusion index at baseline × 100) detected a positive passive leg raising test with an area under the receiver operating characteristic curve of 0.95 ± 0.03. This threshold is larger than the least significant change observed for perfusion index (1.62% ± 0.80%)., Conclusions: Perfusion index could be used as a reliable surrogate of cardiac index for performing the end-expiratory occlusion test. Confirming previous results, the relative changes in perfusion index also reliably detected a positive passive leg raising test., Competing Interests: Dr. Teboul received funding from Getinge/Pulsion. Dr. Monnet received funding from Pulsion Medical Systems, and he received support for article research from Assistance publique-Hôpitaux de Paris. Drs. Teboul and Monnet are members of the Medical Advisory Board of Pulsion Medical Systems and have given lectures for Masimo Corp. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

A measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of the measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of scientific societies to establish the standards in their area of expertise. After adopting the same understandings and definitions (part 1), the different procedures for the validation of major quality criteria of measuring devices must be consensually established. In this metrologic review (part 2), we review the terms and definitions of validation, some basic processes leading to the display of an indication from a physiologic signal, and procedures for the validation of measuring instrument properties, with specific focus on perioperative and intensive care medicine including appropriate examples.

Any measurement is always afflicted with some degree of uncertainty. A correct understanding of the different types of uncertainty, their naming, and their definition is of crucial importance for an appropriate use of measuring instruments. However, in perioperative and intensive care medicine, the metrological requirements for measuring instruments are poorly defined and often used spuriously. The correct use of metrological terms is also of crucial importance in validation studies. The European Union published a new directive on medical devices, mentioning that in the case of devices with a measuring function, the notified body is involved in all aspects relating to the conformity of the device with the metrological requirements. It is therefore the task of the scientific societies to establish the standards in their area of expertise. Adopting the same understandings and definitions among clinicians and scientists is obviously the first step. In this metrologic review (part 1), we list and explain the most important terms defined by the International Bureau of Weights and Measures regarding quantities and units, properties of measurements, devices for measurement, properties of measuring devices, and measurement standards, with specific examples from perioperative and intensive care medicine.

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock., Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 14 questions focused on the profile of respondents, the triggering factors, first-line choice, dosing, timing, targets, additional treatment strategy, and suggested effect of inotropes. In addition, a group of 42 international ESICM experts was asked to formulate recommendations for the use of inotropes based on 11 questions., Results: A total of 839 physicians from 82 countries responded. Dobutamine was the first-line inotrope in critically ill patients with acute heart failure for 84% of respondents. Two-thirds of respondents (66%) stated to use inotropes when there were persistent clinical signs of hypoperfusion or persistent hyperlactatemia despite a supposed adequate use of fluids and vasopressors, with (44%) or without (22%) the context of low left ventricular ejection fraction. Nearly half (44%) of respondents stated an adequate cardiac output as target for inotropic treatment. The experts agreed on 11 strong recommendations, all of which were based on excellent (> 90%) or good (81-90%) agreement. Recommendations include the indications for inotropes (septic and cardiogenic shock), the choice of drugs (dobutamine, not dopamine), the triggers (low cardiac output and clinical signs of hypoperfusion) and targets (adequate cardiac output) and stopping criteria (adverse effects and clinical improvement)., Conclusion: Inotrope use in critically ill patients is quite heterogeneous as self-reported by individual caregivers. Eleven strong recommendations on the indications, choice, triggers and targets for the use of inotropes are given by international experts. Future studies should focus on consistent indications for inotrope use and implementation into a guideline for circulatory shock that encompasses individualized targets and outcomes.

Background: Viral respiratory infections are the main causes of asthma exacerbation. The susceptibility of patients with asthma to develop an exacerbation when they present with severe pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is unknown. The objective of this study was to investigate the characteristics and outcomes of asthmatic patients with coronavirus disease 2019 (COVID-19) pneumonia who required hospitalisation during the spring 2020 outbreak in Paris, France., Methods: A prospective cohort follow-up was carried out from 15 March to 15 April 2020 in Bicêtre Hospital, University Paris-Saclay, France. All hospitalised patients with a SARS-CoV-2 infection who reported a history of asthma were included., Results: Among 768 hospitalised patients, 37 (4.8%) reported a history of asthma, which had been previously confirmed by a pulmonologist in 85% of cases. These asthmatic patients were mainly female (70%) and nonsmokers (85%), with a median age of 54 years (interquartile range (IQR) 42-67 years). None of them presented with an asthma exacerbation. 22 (59%) had major comorbidities and 31 (84%) had a body mass index ≥25 kg·m -2 . The most common comorbidities were obesity (36%), hypertension (27%) and diabetes (19%). All patients had a confirmed diagnosis of COVID-19 pneumonia on computed tomography of the chest. Eosinopenia was a typical biological feature with a median count of 0 cells·mm -3 (IQR 0-0 cells·mm -3 ). 11 patients (30%) were admitted into the intensive care unit, with three deaths (8.1%) occurring in the context of comorbidities., Conclusion: Asthma patients were not overrepresented among those with severe pneumonia due to SARS-CoV-2 infection who required hospitalisation. The worst outcomes were observed mainly in patients with major comorbidities., Competing Interests: Conflict of interest: A. Beurnier has nothing to disclose. Conflict of interest: E-M. Jutant has nothing to disclose. Conflict of interest: M. Jevnikar has nothing to disclose. Conflict of interest: A. Boucly has nothing to disclose. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: M. Preda has nothing to disclose. Conflict of interest: M. Frank has nothing to disclose. Conflict of interest: J. Laurent has nothing to disclose. Conflict of interest: C. Richard has nothing to disclose. Conflict of interest: X. Monnet has nothing to disclose. Conflict of interest: J. Duranteau has nothing to disclose. Conflict of interest: A. Harrois has nothing to disclose. Conflict of interest: M-C. Chaumais has nothing to disclose. Conflict of interest: M-F. Bellin has nothing to disclose. Conflict of interest: N. Noël has nothing to disclose. Conflict of interest: S. Bulifon has nothing to disclose. Conflict of interest: X. Jaïs has nothing to disclose. Conflict of interest: F. Parent has nothing to disclose. Conflict of interest: A. Seferian has nothing to disclose. Conflict of interest: L. Savale has nothing to disclose. Conflict of interest: O. Sitbon reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and MSD, personal fees from Acceleron Pharmaceuticals, Gossamer Bio and Ferrer, grants and personal fees from Bayer, grants from GlaxoSmithKline, outside the submitted work. Conflict of interest: D. Montani has nothing to disclose. Conflict of interest: M. Humbert reports grants, personal fees and non-financial support from GlaxoSmithKline, personal fees from AstraZeneca, Novartis, Roche, Sanofi and Teva, outside the submitted work., (Copyright ©ERS 2020.)

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 StO 2 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 StO 2 -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 StO 2 -RS decreased by >8% in 14 patients, increased by >8% in 4 patients and changes were < 8% in 4 patients. These changes in StO 2 -RS were correlated with the StO 2 -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 StO 2 -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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JLT and XM are members of the medical advisory board of Pulsion Medical Systems. The other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the preload dependence of femoral maximal change in pressure over time (dP/dtmax) during volume expansion in preload dependent and independent critically ill patients., Design: Retrospective database analysis., Setting: Two adult polyvalent ICUs., Patients: Twenty-five critically ill patients with acute circulatory failure., Interventions: Thirty-five fluid infusions of 500 mL normal saline., Measurements and Main Results: Changes in femoral dP/dtmax, systolic, diastolic, and pulse femoral arterial pressure were obtained from the pressure waveform analysis using the PiCCO2 system (Pulsion Medical Systems, Feldkirchen, Germany). Stroke volume index was obtained by transpulmonary thermodilution. Statistical analysis was performed comparing results before and after volume expansion and according to the presence or absence of preload dependence (increases in stroke volume index ≥ 15%). Femoral dP/dtmax increased by 46% after fluid infusion in preload-dependent cases (mean change = 510.6 mm Hg·s; p = 0.005) and remained stable in preload-independent ones (mean change = 49.2 mm Hg·s; p = 0.114). Fluid-induced changes in femoral dP/dtmax correlated with fluid-induced changes in stroke volume index in preload-dependent cases (r = 0.618; p = 0.032), but not in preload-independent ones. Femoral dP/dtmax strongly correlated with pulse and systolic arterial pressures and with total arterial stiffness, regardless of the preload dependence status (r > 0.9 and p < 0.001 in all cases)., Conclusions: Femoral dP/dtmax increased with volume expansion in case of preload dependence but not in case of preload independence and was strongly related to pulse pressure and total arterial stiffness regardless of preload dependence status. Therefore, femoral dP/dtmax is not a load-independent marker of left ventricular contractility and should be not used to track contractility in critically ill patients.

Rationale: Subclinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain, however, largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function. Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid. Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-1) enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e., >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate above 60 ml/min/1.73 m 2 at ICU admission. Measurements and Main Results: In total, 6.1% (122/2,004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8]; P  = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8]; P  < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1). Conclusions: Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.

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.

In patients with acute circulatory failure, the primary goal of volume expansion is to increase cardiac output. However, this expected effect is inconstant, so that in many instances, fluid administration does not result in any haemodynamic benefit. In such cases, fluid could only exert some deleterious effects. It is now well demonstrated that excessive fluid administration is harmful, especially during acute respiratory distress syndrome and in sepsis or septic shock. This is the reason why some tests and indices have been developed in order to assess "fluid responsiveness" before deciding to perform volume expansion. While preload markers have been used for many years for this purpose, they have been repeatedly shown to be unreliable, which is mainly related to physiological issues. As alternatives, "dynamic" indices have been introduced. These indices are based upon the changes in cardiac output or stroke volume resulting from various changes in preload conditions, induced by heart-lung interactions, postural manoeuvres or by the infusion of small amounts of fluids. The haemodynamic effects and the reliability of these "dynamic" indices of fluid responsiveness are now well described. From their respective advantages and limitations, it is also possible to describe their clinical interest and the clinical setting in which they are applicable., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-2020-hdm-18). The series “Hemodynamic monitoring in critically ill patients” was commissioned by the editorial office without any funding or sponsorship. XM and JLT report personal fees from Pulsion Medical Systems, during the conduct of the study. XM and JLT report personal fees from Getinge/Pulsion Medical System, outside the submitted work., (2020 Annals of Translational Medicine. All rights reserved.)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.220). The series “Hemodynamic Monitoring in Critically Ill Patients” was commissioned by the editorial office without any funding or sponsorship. XM and JLT are members of the Medical Advisory board (Pulsion Medical Systems). AB has no other conflicts of interest to declare.

In addition to fluid resuscitation, the vasopressor therapy is a fundamental treatment of septic shock-induced hypotension as it aims at correcting the vascular tone depression and then at improving organ perfusion pressure. Experts' recommendations currently position norepinephrine (NE) as the first-line vasopressor in septic shock. Vasopressin and its analogues are only second-line vasopressors as strong recent evidence suggests no benefit of their early administration in spite of promising preliminary data. Early administration of NE may allow achieving the initial mean arterial pressure (MAP) target faster and reducing the risk of fluid overload. The diastolic arterial pressure (DAP) as a marker of vascular tone, helps identifying the patients who need NE urgently. Available data suggest a MAP of 65 mmHg as the initial target but a more individualized approach is often required depending on several factors such as history of chronic hypertension or value of central venous pressure (CVP). In cases of refractory hypotension, increasing NE up to doses ≥1 µg/kg/min could be an option. However, current experts' guidelines suggest to combine NE with other vasopressors such as vasopressin, with the intent to rising the MAP to target or to decrease the NE dosage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.04.24). The series “Hemodynamic Monitoring in Critically Ill Patients” was commissioned by the editorial office without any funding or sponsorship. OH reports personal fees from Cheetah Medical, outside the submitted work. XM reports personal fees from Getinge/Pulsion and personal fees from Cheetah Medical, outside the submitted work. JLT reports personal fees from Getinge/Pulsion, outside the submitted work. The other authors have no other conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Purpose of Review: On the basis of recent literature, we summarized the new advances on the use of available dynamic indices of fluid responsiveness., Recent Findings: Reliability of passive leg raising to assess fluid responsiveness is well established provided that a real-time haemodynamic assessment is available. Recent studies have focused on totally noninvasive techniques to assess its haemodynamic effects with promising results. Presence of intra-abdominal hypertension is associated with false-negative cases of passive leg raising. Use of pulse pressure and stroke volume variations is limited and other heart-lung interaction tests have been developed. The tidal volume challenge may overcome the limitation of low tidal volume ventilation. Preliminary data suggest that changes in pulse pressure variation during this test well predict fluid responsiveness. Growing evidence confirms the good predictive performance of the end-expiratory occlusion test. All these dynamic tests allow selecting appropriate fluid responders and preventing excessive fluid administration. Performance of a mini-fluid challenge may help for the decision-making process of fluid management if other tests are not available., Summary: Several new dynamic variables and monitoring techniques to predict fluid responsiveness were investigated in the past years. Nevertheless, further research investigating their reliability and feasibility in larger cohorts is warranted. VIDEO ABSTRACT.

Background: We performed a systematic review and meta-analysis of studies assessing the end-expiratory occlusion test (EEXPO test)-induced changes in cardiac output (CO) measured by any haemodynamic monitoring device, as indicators of preload responsiveness., Methods: MEDLINE, EMBASE and Cochrane Database were screened for original articles. Bivariate random-effects meta-analysis determined the Area under the Summary Receiver Operating Characteristic (AUSROC) curve of EEXPO test-induced changes in CO to detect preload responsiveness, as well as pooled sensitivity and specificity and the best diagnostic threshold., Results: Thirteen studies (530 patients) were included. Nine studies were performed in the intensive care unit and four in the operating room. The pooled sensitivity and the pooled specificity for the EEXPO test-induced changes in CO were 0.85 [0.77-0.91] and 0.88 [0.83-0.91], respectively. The AUSROC curve was 0.91 [0.86-0.94] with the best threshold of CO increase at 5.1 ± 0.2%. The accuracy of the test was not different when changes in CO were monitored through pulse contour analysis compared to other methods (AUSROC: 0.93 [0.91-0.95] vs. 0.87 [0.82-0.96], respectively, p = 0.62). Also, it was not different in studies in which the tidal volume was ≤ 7 mL/kg compared to the remaining ones (AUSROC: 0.96 [0.92-0.97] vs. 0.89 [0.82-0.95] respectively, p = 0.44). Subgroup analyses identified one possible source of heterogeneity., Conclusions: EEXPO test-induced changes in CO reliably detect preload responsiveness. The diagnostic performance is not influenced by the method used to track the EEXPO test-induced changes in CO. Trial registration The study protocol was prospectively registered on PROSPERO: CRD42019138265.

Purpose: It has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (PEEP) may lead to an artefactual overestimation of extravascular lung water (EVLW) by transpulmonary thermodilution (TPTD)., Methods: In 60 ARDS patients, we measured EVLW (PiCCO2 device) at a PEEP level set to reach a plateau pressure of 30 cmH 2 O (HighPEEP start ) and 15 and 45 min after decreasing PEEP to 5 cmH 2 O (LowPEEP 15' and LowPEEP 45' , respectively). Then, we increased PEEP back to the baseline level (HighPEEP end ). Between HighPEEP start and LowPEEP 15' , we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (Crs) in the whole population, or by measuring the lung derecruited volume in 30 patients. We defined patients with a large derecruitment from the other ones as patients in whom the Crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population., Results: Reducing PEEP from HighPEEP start (14 ± 2 cmH 2 O) to LowPEEP 15' significantly decreased EVLW from 20 ± 4 to 18 ± 4 mL/kg, central venous pressure (CVP) from 15 ± 4 to 12 ± 4 mmHg, the arterial oxygen tension over inspired oxygen fraction (PaO 2 /FiO 2 ) ratio from 184 ± 76 to 150 ± 69 mmHg and lung volume by 144 [68-420] mL. The EVLW decrease was similar in "large derecruiters" and the other patients. When PEEP was re-increased to HighPEEP end , CVP, PaO 2 /FiO 2 and EVLW significantly re-increased. At linear mixed effect model, EVLW changes were significantly determined only by changes in PEEP and CVP (p < 0.001 and p = 0.03, respectively, n = 60). When the same analysis was performed by estimating recruitment according to lung volume changes (n = 30), CVP remained significantly associated to the changes in EVLW (p < 0.001)., Conclusions: In ARDS patients, changing the PEEP level induced parallel, small and reversible changes in EVLW. These changes were not due to an artefact of the TPTD technique and were likely due to the PEEP-induced changes in CVP, which is the backward pressure of the lung lymphatic drainage. Trial registration ID RCB: 2015-A01654-45. Registered 23 October 2015.

Background: Continuous non-invasive cardiac output devices using digital photoplethysmography (PPG) are widely available for bedside use, but their interchangeability with reference methods has not yet been evaluated in a systematic review and patient data meta-analysis., Methods: A systematic review and meta-analysis of studies comparing non-invasive cardiac output monitoring using PPG with the invasive bolus thermodilution method was performed. With ethical approval, all published studies from the PUBMED, Embase, Scopus, Web of Science, and Google Scholar databases from January 1, 2010 to January 1, 2018 were included. From these analysed studies, individual patient data were interpreted using the interchangeability methods for both absolute values and changes in cardiac output measurements., Results: Ten studies comparing PPG and bolus thermodilution in the operating room and intensive care settings were included. The interchangeability rate (95% CI) was 37% (24-48) (n=1350 pairs of measurements). The interchangeability rate was poorer with the CNAP device (CNSystems, Graz, Austria) [18% (17-20)] than with the Clearsight (Edwards Lifesciences, Irvine, CA) device [33% (31-34), P<0.0001], for patients receiving norepinephrine [19% (17-20) vs. 33% (32-34), P<0.0001], and for patients with low mean arterial pressure (<65mmHg) [26% (23-29) vs. 30% (29-31), P<0.0001]. Among the 1009 comparisons of the changes in cardiac output between both methods, 561 (56%) were interpretable with a trend interchangeability rate at 24% (12-36)., Conclusions: Cardiac output measurements using PPG were not interchangeable with bolus thermodilution in regard to both absolute values and changes in cardiac output measurements, and should be used with caution in clinical practice., Trial Registration: PROSPERO ID CRD42018089513., (Copyright © 2019 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: The end-expiratory occlusion test predicts fluid responsiveness in ventilated intensive care patients; however, its utility in the operating room is questioned. We assessed end-expiratory occlusion test in laparotomic surgery for predicting volume expansion., Methods: Forty-six patients were included in this study: stage 1 (n = 26) with an end-expiratory occlusion test of 15 seconds, followed by volume expansion, which consisted of 250 mL of colloid over 5 minutes and stage 2 (n = 20) with an end-expiratory occlusion test of 25 seconds followed by volume expansion. The last 10 patients had transdiaphragmatic pressures probed. Patients with an increase in cardiac index >15% after volume expansion were responders. Pulse pressure variation, stroke volume (SV) index, and cardiac index were analyzed. Receiver operating characteristic curves were established for changes in SV and pulse pressure induced by end-expiratory occlusion test and pulse pressure variation using the responders status for volume expansion as outcome., Results: A total of 44 (38%) volume expansions were deemed responders. After end-expiratory occlusion test of 15 seconds, no hemodynamic variables were significantly increased. After end-expiratory occlusion test of 25 seconds, SV index increased in responders (37.1 ± 8.8 mL/m after end-expiratory occlusion test of 25 seconds versus 35.7 ± 8.6 before; P < .0001). End-expiratory occlusion test could not discriminate responders from nonresponders. Only pulse pressure variation had significantly different area under the curve from that expected by chance (0.7 [0.57-0.81]; P = .002 for end-expiratory occlusion test of 15 seconds; and 0.78 [0.64-0.89]; P = .0001 for end-expiratory occlusion test of 25 seconds). After laparotomy, gastric pressure decreased significantly (4 [2.75-5] vs 2 [2-4] cm H2O; P = .0417); no difference was noticed in the transdiaphragmatic gradient., Conclusions: End-expiratory occlusion test was not reliable to discriminate responders from nonresponders after volume expansion during laparotomic surgery.

Objectives: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin., Design: Prospective multicenter observational cohort study., Setting: Data from the French and euRopean Outcome reGistry in ICUs study., Patients: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included., Interventions: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality., Measurements and Main Results: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92)., Conclusions: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients.

Background: Volume expansion is aimed at increasing cardiac output (CO), but this variable is not always directly measured. We assessed the ability of changes in arterial pressure, pulse pressure variation (PPV) and heart rate (HR) or of a combination of them to detect a positive response of cardiac output (CO) to fluid administration., Methods: We retrospectively included 491 patients with circulatory failure. Before and after a 500-mL normal saline infusion, we measured CO (PiCCO device), HR, systolic (SAP), diastolic (DAP), mean (MAP) and pulse (PP) arterial pressure, PPV, shock index (HR/SAP) and the PP/HR ratio., Results: The fluid-induced changes in HR were not correlated with the fluid-induced changes in CO. The area under the receiver operating characteristic curve (AUROC) for changes in HR as detectors of a positive fluid response (CO increase ≥ 15%) was not different from 0.5. The fluid-induced changes in SAP, MAP, PP, PPV, shock index (HR/SAP) and the PP/HR ratio were correlated with the fluid-induced changes in CO, but with r < 0.4. The best detection was provided by increases in PP, but it was rough (AUROC = 0.719 ± 0.023, best threshold: increase ≥ 10%, sensitivity = 72 [66-77]%, specificity = 64 [57-70]%). Neither the decrease in shock index nor the changes in other indices combining changes in HR, shock index, PPV and PP provided a better detection of a positive fluid response than changes in PP., Conclusion: A positive response to fluid was roughly detected by changes in PP and not detected by changes in HR. Changes in combined indices including the shock index and the PP/HR ratio did not provide a better diagnostic accuracy.

Objectives: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge., Design: Ancillary investigation of a prospective observational study., Setting: Twenty-one ICUs with 1-year follow-up., Patients: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included., Interventions: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors., Measurements and Main Results: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease)., Conclusions: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Objectives: To compare the passive leg raising test ability to predict fluid responsiveness in patients with and without intra-abdominal hypertension., Design: Observational study., Setting: Medical ICU., Patients: Mechanically ventilated patients monitored with a PiCCO2 device (Pulsion Medical Systems, Feldkirchen, Germany) in whom fluid expansion was planned, with (intra-abdominal hypertension+) and without (intra-abdominal hypertension-) intra-abdominal hypertension, defined by an intra-abdominal pressure greater than or equal to 12 mm Hg (bladder pressure)., Interventions: We measured the changes in cardiac index during passive leg raising and after volume expansion. The passive leg raising test was defined as positive if it increased cardiac index greater than or equal to 10%. Fluid responsiveness was defined by a fluid-induced increase in cardiac index greater than or equal to 15%., Measurements and Main Results: We included 60 patients, 30 without intra-abdominal hypertension (15 fluid responders and 15 fluid nonresponders) and 30 with intra-abdominal hypertension (21 fluid responders and nine fluid nonresponders). The intra-abdominal pressure at baseline was 4 ± 3 mm Hg in intra-abdominal hypertension- and 20 ± 6 mm Hg in intra-abdominal hypertension+ patients (p < 0.01). In intra-abdominal hypertension- patients with fluid responsiveness, cardiac index increased by 25% ± 19% during passive leg raising and by 35% ± 14% after volume expansion. The passive leg raising test was positive in 14 patients. The passive leg raising test was negative in all intra-abdominal hypertension- patients without fluid responsiveness. In intra-abdominal hypertension+ patients with fluid responsiveness, cardiac index increased by 10% ± 14% during passive leg raising (p = 0.01 vs intra-abdominal hypertension- patients) and by 32% ± 18% during volume expansion (p = 0.72 vs intra-abdominal hypertension- patients). Among these patients, the passive leg raising test was negative in 15 patients (false negatives) and positive in six patients (true positives). Among the nine intra-abdominal hypertension+ patients without fluid responsiveness, the passive leg raising test was negative in all but one patient. The area under the receiver operating characteristic curve of the passive leg raising test for detecting fluid responsiveness was 0.98 ± 0.02 (p < 0.001 vs 0.5) in intra-abdominal hypertension- patients and 0.60 ± 0.11 in intra-abdominal hypertension+ patients (p = 0.37 vs 0.5)., Conclusions: Intra-abdominal hypertension is responsible for some false negatives to the passive leg raising test.

Assessing the adequacy of oxygen delivery with oxygen requirements is one of the key-goal of haemodynamic resuscitation. Clinical examination, lactate and central or mixed venous oxygen saturation (S v O 2 and S cv O 2 , respectively) all have their limitations. Many of them may be overcome by the use of the carbon dioxide (CO 2 )-derived variables. The venoarterial difference in CO 2 tension ("ΔPCO 2 " or "PCO 2 gap") is not an indicator of anaerobic metabolism since it is influenced by the oxygen consumption. By contrast, it reliably indicates whether blood flow is sufficient to carry CO 2 from the peripheral tissue to the lungs in view of its clearance: it, thus, reflects the adequacy of cardiac output with the metabolic condition. The ratio of the PCO 2 gap with the arteriovenous difference of oxygen content (PCO 2 gap/C a-v O 2 ) might be a marker of anaerobiosis. Conversely to S v O 2 and S cv O 2 , it remains interpretable if the oxygen extraction is impaired as it is in case of sepsis. Compared to lactate, it has the main advantage to change without delay and to provide a real-time monitoring of tissue hypoxia., Competing Interests: Conflicts of Interest: JL Teboul and X Monnet are members of the Medical Advisory Board of Pulsion Medical Systems, Getinge. F Gavelli has no conflicts of interest to declare.

Purpose of Review: Transpulmonary thermodilution (TPTD) devices invasively measure not only cardiac output but also several other haemodynamic variables estimating cardiac preload, cardiac preload, systolic function, the lung oedema and systolic function, the lung oedema and the pulmonary permeability. In light of the recent literature, we describe how different indices are measured, emphasize their clinical interest and list potential limits and side-effects of the technique., Recent Findings: Estimation of cardiac output measurement with TPTD is now well established, at least when compared with the pulmonary artery catheter. The advantage of calibrating the pulse contour analysis, as it is allowed by TPTD indices, is clearly established over uncalibrated devices. The greatest advantage of TPTD is to measure extravascular lung water and pulmonary permeability, which may be useful to diagnose acute respiratory distress syndrome and manage fluid therapy in various critical diseases. It also allows a rapid detection of left ventricular systolic failure. The information it provides must be considered complementary to that provided by echocardiography., Summary: TPTD provides several indices that may help in making decisions during the therapeutic management of haemodynamically unstable patients. It should be used for the most critically ill patients, whose management requires a reliable, precise and holistic view of the cardiopulmonary condition.

Background: Femoral dP/dt max (maximum rate of the arterial pressure increase during systole) measured by pulse contour analysis has been proposed as a surrogate of left ventricular (LV) dP/dt max and as an estimator of LV systolic function. However, femoral dP/dt max may be influenced by LV loading conditions. In this study, we evaluated the impact of variations of LV systolic function, preload and afterload on femoral dP/dt max in critically ill patients with cardiovascular failure to ascertain its reliability as a marker of LV systolic function., Results: We performed a prospective observational study to evaluate changes in femoral dP/dt max , thermodilution-derived variables (PiCCO2-Pulsion Medical Systems, Feldkirchen, Germany) and LV ejection fraction (LVEF) measured by transthoracic echocardiography during variations in dobutamine and norepinephrine doses and during volume expansion (VE) and passive leg raising (PLR). Correlations with arterial pulse and systolic pressure, effective arterial elastance, total arterial compliance and LVEF were also evaluated. In absolute values, femoral dP/dt max deviated from baseline by 21% (201 ± 297 mmHg/s; p = 0.013) following variations in dobutamine dose (n = 17) and by 15% (177 ± 135 mmHg/s; p < 0.001) following norepinephrine dose changes (n = 29). Femoral dP/dt max remained unchanged after VE and PLR (n = 24). Changes in femoral dP/dt max were strongly correlated with changes in pulse pressure and systolic arterial pressure during dobutamine dose changes (R = 0.942 and 0.897, respectively), norepinephrine changes (R = 0.977 and 0.941, respectively) and VE or PLR (R = 0.924 and 0.897, respectively) (p < 0.05 in all cases). Changes in femoral dP/dt max were correlated with changes in LVEF (R = 0.527) during dobutamine dose variations but also with effective arterial elastance and total arterial compliance in the norepinephrine group (R = 0.638 and R = - 0.689) (p < 0.05 in all cases)., Conclusions: Pulse contour analysis-derived femoral dP/dt max was not only influenced by LV systolic function but also and prominently by LV afterload and arterial waveform characteristics in patients with acute cardiovascular failure. These results suggest that femoral dP/dt max calculated by pulse contour analysis is an unreliable estimate of LV systolic function during changes in LV afterload and arterial load by norepinephrine and directly linked to arterial waveform determinants.

Rationale: Detecting weaning-induced pulmonary oedema (WIPO) is important because its treatment might prompt extubation. For this purpose, lung ultrasound might be an attractive tool, since it demonstrates pulmonary oedema through the appearance of B-lines., Objectives: To test the ideal profile (increase in the number of B-lines) for diagnosing WIPO., Methods: Before and at the end of 62 spontaneous breathing trials (SBT) performed in 42 patients, we prospectively assessed lung ultrasound on four anterior chest wall points. B-lines were counted before and at the end of SBT. We looked for the threshold of B-line increase (Delta-B-lines) that provided the best diagnostic accuracy, compared to the reference diagnosis of WIPO established by experts blinded to lung ultrasound., Results: SBT failed in 33 cases. WIPO occurred in 17 cases and all failed. The best diagnostic accuracy was reached with a Delta-B-lines ≥ 6. Among WIPO, the number of B-lines increased by ≥ 6 in 15 cases (including 13 cases with an increase of ≥ 8 B-lines). Among the 16 cases with SBT failure but without WIPO, the Delta-B-lines was ≥ 6 in two cases. Among the 33 cases with SBT failure, this profile diagnosed WIPO with a sensitivity of 88% (64-98) and a specificity of 88% (62-98) [area under the receiver operating characteristic curve 0.91 (0.75-0.98)]. Among the 29 cases with SBT success, a Delta-B-lines ≥ 6 occurred in two cases., Conclusions: This study suggests that a Delta-B-lines ≥  6 on four anterior points allows the diagnosis of WIPO with the best accuracy. This should be confirmed in larger populations.

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.

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.

Objective: To compare cardiac index (CI) between Proaqt/PulsioFlex ® and oesophageal Doppler (OD) and the ability of the PulsioFlex ® to track CI changes induced by fluid challenge and secondly to assess the impact of the time interval between two auto-calibrations of PulsioFlex ® on the accuracy of the measured CI., Methods: In a single hospital, 49 intermediate-risk oncologic abdominal surgery patients were included in an observational study. We measured the cardiac Index (CI) provided by OD and by the Proaqt/PulsioFlex ® before and after internal calibration, which were performed randomly at specific intervals after the initial one (30, 60, 90 and 120min). The ability to track fluid responsiveness was evaluated by measuring stroke volume variation, pulse pressure variation (PPV) and CI before and after a 250ml fluid challenge and assessed by a receiver operating characteristic curve analysis., Results: The percentages of error before calibration were 51, 58, 82, 81% for 30, 60, 90 and 120min, they were 39, 57, 65, and 54% after calibration. Trending ability is assumed by a 93% concordance rate after applying a 15% exclusion zone. The trend interchangeability rate was 13.75%. The area under the curve for fluid responsiveness measured by PPV and SVV PulsioFlex were respectively 0.67 [0.57-0.77], P<0.01 and 0.75 [0.47-0.66], which was not clinically relevant., Conclusions: The Proaqt/Pulsioflex ® system is not equivalent to OD for haemodynamic monitoring during non-vascular abdominal surgery in intermediate-risk patients. More studies are required to define the effect of the auto-calibration on the system., (Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

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.

Background: Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use., Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14)., Results: A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60-65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg., Conclusion: Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

Background: A passive leg raising (PLR) test is positive if the cardiac index (CI) increased by > 10%, but it requires a direct measurement of CI. On the oxygen saturation plethysmographic signal, the perfusion index (PI) is the ratio between the pulsatile and the non-pulsatile portions. We hypothesised that the changes in PI could predict a positive PLR test and thus preload responsiveness in a totally non-invasive way., Methods: In patients with acute circulatory failure, we measured PI (Radical-7) and CI (PiCCO2) before and during a PLR test and, if decided, before and after volume expansion (500-mL saline)., Results: Three patients were excluded because the plethysmography signal was absent and 3 other ones because it was unstable. Eventually, 72 patients were analysed. In 34 patients with a positive PLR test (increase in CI ≥ 10%), CI and PI increased during PLR by 21 ± 10% and 54 ± 53%, respectively. In the 38 patients with a negative PLR test, PI did not significantly change during PLR. In 26 patients in whom volume expansion was performed, CI and PI increased by 28 ± 14% and 53 ± 63%, respectively. The correlation between the PI and CI changes for all interventions was significant (r = 0.64, p < 0.001). During the PLR test, if PI increased by > 9%, a positive response of CI (≥ 10%) was diagnosed with a sensitivity of 91 (76-98%) and a specificity of 79 (63-90%) (area under the receiver operating characteristics curve 0.89 (0.80-0.95), p < 0.0001)., Conclusion: An increase in PI during PLR by 9% accurately detects a positive response of the PLR test., Trial Registration: ID RCB 2016-A00959-42. Registered 27 June 2016.

Fluid administration leads to a significant increase in cardiac output in only half of ICU patients. This has led to the concept of assessing fluid responsiveness before infusing fluid. Pulse pressure variation (PPV), which quantifies the changes in arterial pulse pressure during mechanical ventilation, is one of the dynamic variables that can predict fluid responsiveness. The underlying hypothesis is that large respiratory changes in left ventricular stroke volume, and thus pulse pressure, occur in cases of biventricular preload responsiveness. Several studies showed that PPV accurately predicts fluid responsiveness when patients are under controlled mechanical ventilation. Nevertheless, in many conditions encountered in the ICU, the interpretation of PPV is unreliable (spontaneous breathing, cardiac arrhythmias) or doubtful (low Vt). To overcome some of these limitations, researchers have proposed using simple tests such as the Vt challenge to evaluate the dynamic response of PPV. The applicability of PPV is higher in the operating room setting, where fluid strategies made on the basis of PPV improve postoperative outcomes. In medical critically ill patients, although no randomized controlled trial has compared PPV-based fluid management with standard care, the Surviving Sepsis Campaign guidelines recommend using fluid responsiveness indices, including PPV, whenever applicable. In conclusion, PPV is useful for managing fluid therapy under specific conditions where it is reliable. The kinetics of PPV during diagnostic or therapeutic tests is also helpful for fluid management.

Background: The accuracy of respiratory variation of the inferior vena cava (rvIVC) in predicting fluid responsiveness, particularly in spontaneously breathing patients is unclear., Objectives: To consider the evidence to support the accuracy of rvIVC in identifying patients who are unlikely to benefit from fluid administration., Design: Systematic review and meta-analysis., Data Source: We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILCAS and WHO Clinical Trial Registry from inception to June 2017., Eligibility Criteria: Case-control or cohort studies that evaluated the accuracy of rvIVC in living adult humans were included. A study was included in the meta-analysis if data enabling construction of 2 × 2 tables were reported, calculated or could be obtained from authors and met the above cited criteria., Result: A total of 23 studies including 1574 patients were included in qualitative analysis. The meta-analysis involved 20 studies and 761 patients. Pooled sensitivity and specificity of rvIVC in 330 spontaneously breathing patients were 0.80 [95% confidence interval (CI) 0.68 to 0.89] and 0.79 (95% CI 0.60 to 0.90). Pooled sensitivity and specificity of rvIVC in 431 mechanically ventilated patients were 0.79 (95% CI 0.67 to 0.86) and 0.70 (95% CI 0.63 to 0.76)., Conclusion: Decreased inferior vena caval respiratory variation is moderately accurate in predicting fluid unresponsiveness both in spontaneous and mechanically ventilated patients. The findings of this review should be used in the appropriate clinical context and in conjunction with other clinical assessments of fluid status., Identifier: CRD 42017068028.

Background: Rapid detection of changes in cardiac index (CI) in real time using minimally invasive monitors may be of clinical benefit. We tested whether the Starling-SV bioreactance device, which averages CI over a short 8 s period, could assess the effects of passive leg raising (PLR), a clinical test that is recommended to assess fluid responsiveness during septic shock., Methods: In 32 critically ill patients, we measured CI by transpulmonary thermodilution (PiCCO2, CI td ), pulse contour analysis (PiCCO2, CI Pulse ), and the Starling-SV device (CI Starling ) at baseline. CI Pulse and CI Starling were measured again at the end of a PLR test. In the 13 patients with a positive PLR test, CI td , CI Pulse , and CI Starling were measured before and after a 500 ml saline infusion. The primary outcome was relative changes from baseline measurements in CI td , CI Pulse , and CI Starling . Secondary outcomes compared absolute values measured by each method., Results: Relative changes in CI Pulse and CI td were significantly correlated (r=0.82; n=45; P<0.001), with an 89% concordance rate (n=45 paired measurements). Relative changes in CI Starling and CI td were also significantly correlated (r=0.59; n=45; P<0.001) with a 78% concordance rate. For absolute measures of CI (n=77 paired measurements), the bias between CI Pulse and CI td was 0.01 L min -1  m -2 (limits of agreement, -0.49 and 0.51 L min -1  m -2 ; 15% percentage error). Bias between CI Starling and CI td was 0.03 L min -1  m -2 (limits of agreement, -1.61 and 1.67 L min -1  m -2 ; 48% percentage error)., Conclusions: In critically ill patients, a non-invasive bioreactance device with a shorter averaging period assessed a passive leg raising test with reasonable accuracy., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Fluid administration is the first-line therapy in patients with acute circulatory failure. The main goal of fluid administration is to increase the cardiac output and ultimately the oxygen delivery. Nevertheless, the decision to administer fluids or not should be carefully considered, since half of critically ill patients are fluid unresponsive, and the deleterious effects of fluid overload clearly documented. Thus, except at the initial phase of hypovolemic or septic shock, where hypovolemia is constant and most of the patients responsive to the initial fluid resuscitation, it is of importance to test fluid responsiveness before administering fluids in critically ill patients. The static markers of cardiac preload cannot reliably predict fluid responsiveness, although they have been used for decades. To address this issue, some dynamic tests have been developed over the past years. All these tests consist in measuring the changes in cardiac output in response to the transient changes in cardiac preload that they induced. Most of these tests are based on the heart-lung interactions. The pulse pressure or stroke volume respiratory variations were first described, following by the respiratory variations of the vena cava diameter or of the internal jugular vein diameter. Nevertheless, all these tests are reliable only under strict conditions limiting their use in many clinical situations. Other tests such as passive leg raising or end-expiratory occlusion act as an internal volume challenge. To reliably predict fluid responsiveness, physicians must choose among these different dynamic tests, depending on their respective limitations and on the cardiac output monitoring technique which is used. In this review, we will summarize the most recent findings regarding the prediction of fluid responsiveness in ventilated patients., Competing Interests: Conflicts of Interest: X Monnet and JL Teboul are members of Medical Advisory board of Pulsion/Getinge. M Jozwiak has no conflicts of interest to declare.

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.

The prognosis of septic shock is tightly linked to the earliness of both appropriate antibiotic therapy and early hemodynamic resuscitation. This latter is essentially based on fluid and vasopressors administration. The step-by-step strategy, called "early goal-directed therapy" (EGDT) developed in 2001 and endorsed by the Surviving Sepsis Campaign (SSC) between 2004 and 2016 is no longer recommended. Indeed, recent multicenter randomized clinical trials showed no reduction in all-cause mortality, duration of organ support and in-hospital length of stay with EGDT in comparison with standard care. The most recent SCC guidelines have dropped the original EGDT by deleting the central venous pressure and the central venous oxygen saturation from the recommendations. Dynamic variables of fluid responsiveness are now recommended to be used after an initial fluid infusion of a fixed volume (30 mL/kg) during the first three hours of resuscitation. However, this approach is also questionable due to the lack of individualization at the early and crucial phase of resuscitation. In this review, we propose a more personalized approach for the early and later phases of fluid resuscitation during sepsis.