Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study).

BACKGROUND: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data. We aimed to compare the incidence of iGAS infection before and after the COVID-19 pandemic, describe iGAS patients' characteristics, and determine ICU mortality associated factors. METHODS: We performed a retrospective multicenter cohort study in 37 French ICUs, including all patients admitted for iGAS infections for two periods: two years before period (October 2018 to March 2019 and October 2019 to March 2020) and a one-year after period (October 2022 to March 2023) COVID-19 pandemic. iGAS infection was defined by Group A Streptococcus isolation from a normally sterile site. iGAS infections were identified using the International Classification of Diseases and confirmed with each center's microbiology laboratory databases. The incidence of iGAS infections was expressed in case rate. RESULTS: Two hundred and twenty-two patients were admitted to ICU for iGAS infections: 73 before and 149 after COVID-19 pandemic. Their case rate during the period before and after COVID-19 pandemic was 205 and 949/100,000 ICU admissions, respectively (p < 0.001), with more frequent STSS after the COVID-19 pandemic (61% vs. 45%, p = 0.015). iGAS patients (n = 222) had a median SOFA score of 8 (5-13), invasive mechanical ventilation and norepinephrine in 61% and 74% of patients. ICU mortality in iGAS patients was 19% (14% before and 22% after COVID-19 pandemic; p = 0.135). In multivariate analysis, invasive mechanical ventilation (OR = 6.08 (1.71-21.60), p = 0.005), STSS (OR = 5.75 (1.71-19.22), p = 0.005), acute kidney injury (OR = 4.85 (1.05-22.42), p = 0.043), immunosuppression (OR = 4.02 (1.03-15.59), p = 0.044), and diabetes (OR = 3.92 (1.42-10.79), p = 0.008) were significantly associated with ICU mortality. CONCLUSION: The incidence of iGAS infections requiring ICU admission increased by 4 to 5 after the COVID-19 pandemic. After the COVID-19 pandemic, the rate of STSS was higher, with no significant increase in ICU mortality rate.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

Venous return and mean systemic filling pressure: physiology and clinical applications.

Venous return is the flow of blood from the systemic venous network towards the right heart. At steady state, venous return equals cardiac output, as the venous and arterial systems operate in series. However, unlike the arterial one, the venous network is a capacitive system with a high compliance. It includes a part of unstressed blood, which is a reservoir that can be recruited via sympathetic endogenous or exogenous stimulation. Guyton's model describes the three determinants of venous return: the mean systemic filling pressure, the right atrial pressure and the resistance to venous return. Recently, new methods have been developed to explore such determinants at the bedside. In this narrative review, after a reminder about Guyton's model and current methods used to investigate it, we emphasize how Guyton's physiology helps understand the effects on cardiac output of common treatments used in critically ill patients.

Effects of Prone Positioning on Venous Return in Patients With Acute Respiratory Distress Syndrome.

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.

Thyroid Storm in the ICU: A Retrospective Multicenter Study.

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. CONCLUSIONS: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.

Diagnostic Accuracy of Respiratory Distress Observation Scales as Surrogates of Dyspnea Self-report in Intensive Care Unit Patients.

BACKGROUND: Dyspnea, like pain, can cause major suffering in intensive care unit (ICU) patients. Its evaluation relies on self-report; hence, the risk of being overlooked when verbal communication is impaired. Observation scales incorporating respiratory and behavioral signs (respiratory distress observation scales [RDOS]) can provide surrogates of dyspnea self-report in similar clinical contexts (palliative care). METHODS: The authors prospectively studied (single center, 16-bed ICU, large university hospital) 220 communicating ICU patients (derivation cohort, 120 patients; separate validation cohort, 100 patients). Dyspnea was assessed by dyspnea visual analog scale (D-VAS) and RDOS calculated from its eight components (heart rate, respiratory rate, nonpurposeful movements, neck muscle use during inspiration, abdominal paradox, end-expiratory grunting, nasal flaring, and facial expression of fear). An iterative principal component analysis and partial least square regression process aimed at identifying an optimized D-VAS correlate (intensive care RDOS [IC-RDOS]). RESULTS: In the derivation cohort, RDOS significantly correlated with D-VAS (r = 0.43; 95% CI, 0.29 to 0.58). A five-item IC-RDOS (heart rate, neck muscle use during inspiration, abdominal paradox, facial expression of fear, and supplemental oxygen) significantly better correlated with D-VAS (r = 0.61; 95% CI, 0.50 to 0.72). The median area under the receiver operating curve of IC-RDOS to predict D-VAS was 0.83 (interquartile range, 0.81 to 0.84). An IC-RDOS of 2.4 predicted D-VAS of 4 or greater with equal sensitivity and specificity (72%); an IC-RDOS of 6.3 predicted D-VAS of 4 or greater with 100% specificity. Similar results were found in the validation cohort. CONCLUSIONS: Combinations of observable signs correlate with dyspnea in communicating ICU patients. Future studies in noncommunicating patients will be needed to determine the responsiveness to therapeutic interventions and clinical usefulness.

Effects of passive leg raising and volume expansion on mean systemic pressure and venous return in shock in humans.

INTRODUCTION: The aim of this study was to assess how mean systemic pressure (Psm) and resistance to venous return (Rvr) behave during passive leg raising (PLR) in cases of fluid responsiveness and fluid unresponsiveness. METHOD: In 30 patients with an acute circulatory failure, in order to estimate the venous return curve, we constructed the regression line between pairs of cardiac index (CI) and central venous pressure (CVP). Values were measured during end-inspiratory and end-expiratory ventilatory occlusions performed at two levels of positive end-expiratory pressure. The x-axis intercept was used to estimate Psm and the inverse of the slope to quantify Rvr. These measurements were obtained at baseline, during PLR and after fluid infusion. Patients in whom fluid infusion increased CI by more than 15 % were defined as "fluid-responders". RESULTS: In fluid-responders (n = 15), CVP and Psm significantly increased (from 7 ± 3 to 9 ± 4 mmHg and from 25 ± 13 to 31 ± 13 mmHg, respectively) during PLR. The Psm-CVP gradient significantly increased by 20 ± 30 % while Rvr did not change significantly during PLR. In fluid-nonresponders, CVP and Psm increased significantly but the Psm-CVP gradient did not change significantly during PLR. PLR did not change the intra-abdominal pressure in the whole population (14 ± 6 mmHg before vs. 13 ± 5 mmHg during PLR, p = 0.26) and in patients with intra-abdominal hypertension at baseline (17 ± 4 mmHg before vs. 16 ± 4 mmHg during PLR, p = 0.14). In the latter group, PLR increased Psm from 22 ± 11 to 27 ± 10 mmHg (p <0.01) and did not change Rvr (5.1 ± 2.6 to 5.2 ± 3 mmHg/min/m(2)/mL, p = 0.71). In fluid-responders, Psm, CVP and the Psm-CVP gradient significantly increased during fluid infusion while the Rvr did not change. In fluid-nonresponders, CVP and Psm increased significantly during fluid infusion while the Psm-CVP gradient and Rvr did not change. CONCLUSION: PLR significantly increased Psm without modifying Rvr. This was also the case in patients with intra-abdominal hypertension. In case of fluid responsiveness, PLR increased venous return by increasing Psm to a larger extent than CVP. In patients with fluid unresponsiveness, PLR increased Psm but did not change the Psm-CVP gradient. Fluid infusion induced similar effects on Psm and Rvr.

Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction.

INTRODUCTION: The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction. METHODS: PSV, NAVA, and PAV were set to obtain a tidal volume (VT) of 6 to 8 ml/kg (PSV100, NAVA100, and PAV100) in 16 intubated patients. Assistance was further decreased by 50% (PSV50, NAVA50, and PAV50) and then increased by 50% (PSV150, NAVA150, and PAV150) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. VT, peak EAdi, coefficient of variation of VT and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated. RESULTS: PAV and NAVA prevented the increase of VT with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV150 and NAVA150 versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV150, P <0.05). EAdi was higher with PAV than with PSV at level100 and level150. The coefficient of variation of VT was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA100 and PAV100 versus 13 (IQR 11 to 18)% with PSV100, P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV (P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV (P <0.05). CONCLUSIONS: PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCT02056093 . Registered 18 December 2013.

Beneficial hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome.

RATIONALE: The effects of prone positioning during acute respiratory distress syndrome on all the components of cardiac function have not been investigated under protective ventilation and maximal alveolar recruitment. OBJECTIVES: To investigate the hemodynamic effects of prone positioning. METHODS: We included 18 patients with acute respiratory distress syndrome ventilated with protective ventilation and an end-expiratory positive pressure titrated to a plateau pressure of 28-30 cm H2O. Before and within 20 minutes of starting prone positioning, hemodynamic, respiratory, intraabdominal pressure, and echocardiographic data were collected. Before prone positioning, preload reserve was assessed by a passive leg raising test. MEASUREMENTS AND MAIN RESULTS: In all patients, prone positioning increased the ratio of arterial oxygen partial pressure over inspired oxygen fraction, the intraabdominal pressure, and the right and left cardiac preload. The pulmonary vascular resistance decreased along with the ratio of the right/left ventricular end-diastolic areas suggesting a decrease of the right ventricular afterload. In the nine patients with preload reserve, prone positioning significantly increased cardiac index (3.0 [2.3-3.5] to 3.6 [3.2-4.4] L/min/m(2)). In the remaining patients, cardiac index did not change despite a significant decrease in the pulmonary vascular resistance. CONCLUSIONS: In patients with acute respiratory distress syndrome under protective ventilation and maximal alveolar recruitment, prone positioning increased the cardiac index only in patients with preload reserve, emphasizing the important role of preload in the hemodynamic effects of prone positioning.

Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.

INTRODUCTION: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. METHODS: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. RESULTS: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? CONCLUSION: These recommendations should optimize the use of oxygen during ARF.

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

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

End-expiratory occlusion test predicts preload responsiveness independently of positive end-expiratory pressure during acute respiratory distress syndrome.

OBJECTIVE: A 15-second end-expiratory occlusion increases cardiac preload and allows detection of preload dependence. We tested whether the reliability of this test depends upon positive end-expiratory pressure. DESIGN: : Prospective study. SETTING: Medical ICU. PATIENTS: Thirty-four patients presenting with acute circulatory failure and acute respiratory distress syndrome ventilated with a tidal volume of 6.7 mL/kg (interquartile range, 6.3-7.1). MEASUREMENTS: At positive end-expiratory pressure = 5 cm H2O, we measured the changes in cardiac index induced by end-expiratory occlusion and a passive leg raising test. Preload dependence was defined by a passive leg raising-induced increase in cardiac index greater than or equal to 10%. Positive end-expiratory pressure was increased to a plateau pressure of 30 cm H2O, and end-expiratory occlusion and passive leg raising were performed again. MAIN RESULTS: At positive end-expiratory pressure = 5 cm H2O, 29% of patients were passive leg raising responders. An end-expiratory occlusion-induced increase in cardiac index greater than or equal to 5% detected a passive leg raising-induced increase in cardiac index greater than or equal to 10% with a sensitivity of 90% (95% CI, 56-100) and a specificity of 88% (95% CI, 68-97). At higher positive end-expiratory pressure (15 cm H2O [interquartile range, 13-15]), the plateau pressure - positive end-expiratory pressure difference did not change (15 mm Hg [14-17] vs 15 mm Hg [13-18] before the positive end-expiratory pressure increase). Increasing positive end-expiratory pressure significantly reduced cardiac index in passive leg raising responders (-27% [interquartile range, -6 to -56]) but not in other patients. At high positive end-expiratory pressure, passive leg raising increased cardiac index to a larger extent than at positive end-expiratory pressure = 5 cm H2O (19% [interquartile range, 15-34] vs 16% [interquartile range, 13-23], respectively). The proportion of passive leg raising responders significantly increased (34 vs 29%, respectively), meaning preload dependence had increased. At higher positive end-expiratory pressure, an end-expiratory occlusion-induced increase in cardiac index greater than or equal to 6% detected a passive leg raising-induced increase in cardiac index greater than or equal to 10% with a sensitivity of 100% (95% CI, 75-100) and a specificity of 90% (95% CI, 70-99). CONCLUSIONS: The end-expiratory occlusion test is reliable for detecting preload dependence whatever the positive end-expiratory pressure during acute respiratory distress syndrome.

Lactate and venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio, but not central venous oxygen saturation, predict increase in oxygen consumption in fluid responders.

OBJECTIVES: During circulatory failure, the ultimate goal of treatments that increase cardiac output is to reduce tissue hypoxia. This can only occur if oxygen consumption depends on oxygen delivery. We compared the ability of central venous oxygen saturation and markers of anaerobic metabolism to predict whether a fluid-induced increase in oxygen delivery results in an increase in oxygen consumption. DESIGN: Prospective study. SETTING: ICU. PATIENTS: Fifty-one patients with an acute circulatory failure (78% of septic origin). MEASUREMENTS: Before and after a volume expansion (500 mL of saline), we measured cardiac index, o2- and Co2-derived variables and lactate. MAIN RESULTS: Volume expansion increased cardiac index ≥ 15% in 49% of patients ("volume-responders"). Oxygen delivery significantly increased in these 25 patients (+32% ± 16%, p < 0.0001). An increase in oxygen consumption ≥ 15% concomitantly occurred in 56% of these 25 volume-responders (+38% ± 28%). Compared with the volume-responders in whom oxygen consumption did not increase, the volume-responders in whom oxygen consumption increased ≥ 15% were characterized by a higher lactate (2.3 ± 1.1 mmol/L vs. 5.5 ± 4.0 mmol/L, respectively) and a higher ratio of the veno-arterial carbon dioxide tension difference (P(v - a)Co2) over the arteriovenous oxygen content difference (C(a - v)o2). A fluid-induced increase in oxygen consumption greater than or equal to 15% was not predicted by baseline central venous oxygen saturation but by high baseline lactate and (P(v - a)Co2/C(a - v)o2 ratio (areas under the receiving operating characteristics curves: 0.68 ± 0.11, 0.94 ± 0.05, and 0.91 ± 0.06). In volume-nonresponders, volume expansion did not significantly change cardiac index, but the oxygen delivery decreased due to a hemodilution-induced decrease in hematocrit. CONCLUSIONS: In volume-responders, unlike markers of anaerobic metabolism, central venous oxygen saturation did not allow the prediction of whether a fluid-induced increase in oxygen delivery would result in an increase in oxygen consumption. This suggests that along with indicators of volume-responsiveness, the indicators of anaerobic metabolism should be considered instead of central venous oxygen saturation for starting hemodynamic resuscitation.

Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA-ECMO flows in a cardiogenic shock population and determine the risk factors of 'high-ECMO flow'. METHODS AND RESULTS: A 7 year database of patients supported with VA-ECMO was used. Based on the median flow during the first 48 h of the VA-ECMO run, patients were classified as 'high-flow' or 'low-flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator-associated pneumonia, ECMO-related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in-hospital and 60 day mortality. Risk factors of high-ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA-ECMO, median age was 51 (40-59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end-stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high-flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26-58) vs. 56 (42-74), P < 0.001], higher lactate [3.6 (2.2-5.8) mmol/L vs. 5.2 (3-9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41-375) U/L vs. 309 (85-939) U/L, P < 0.001], among others. The 'low-flow' group had less ventilator-associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5-7.5) vs. 6 (3-12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high-flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1-7.1] and pre-ECMO lactate (OR 1.1, 95% CI 1.0-1.2). CONCLUSIONS: In patients with refractory cardiogenic shock supported with VA-ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator-associated pneumonia but similar survival compared with patients with lower flows.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study.

BACKGROUND: Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. METHODS: We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. RESULTS: Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75-24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47-84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27-18.6)] as being independently associated with in-ICU mortality. CONCLUSIONS: SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Effects of norepinephrine on mean systemic pressure and venous return in human septic shock.

OBJECTIVES: Norepinephrine exerts venoconstriction that could increase both the mean systemic pressure and the resistance to venous return, but this has not yet been investigated in human septic shock. We examined the relative importance of both effects and the resulting effect on venous return when decreasing the dose of norepinephrine. SETTING: Intensive care unit. PATIENTS: Sixteen septic shock patients. MEASUREMENTS: For estimating the venous return curve, we constructed the regression line between the pairs of cardiac index (pulse contour analysis) and central venous pressure values. These values were measured during 15-sec end-inspiratory and end-expiratory ventilatory occlusions performed at two levels of positive end-expiratory pressure, in view of widening the range of cardiac index:central venous pressure measurements and increasing the accuracy of the regression line. The x-axis intercept of the regression line was used to estimate the mean systemic pressure and the inverse of the slope of the regression line to quantify resistance to venous return. These measurements were obtained before and after decreasing the dose of norepinephrine. Passive leg raising was performed before and after decreasing the dose of norepinephrine. MAIN RESULTS: Decreasing the dose of norepinephrine from 0.30 (0.10-1.40) to 0.19 (0.08-1.15) µg/kg/min decreased the mean systemic pressure from 33 ± 12 mm Hg to 26 ± 10 mm Hg (p = .0003). The slope of the multipoint cardiac index:central venous pressure relationship increased (p = .02). The resistance to venous return decreased, i.e., 1/slope decreased. Simultaneously, cardiac index decreased from 3.47 ± 0.86 L/min/m2 to 3.28 ± 0.76 L/min/m (p = .04), indicating a decrease in venous return. Passive leg raising increased cardiac index to a larger extent after (8% ± 4%) than before (1% ± 4%) decreasing norepinephrine (p = .001), suggesting an increase in unstressed blood volume at the lowest dose of norepinephrine. CONCLUSIONS: In septic shock patients, decreasing the dose of norepinephrine decreased the mean systemic pressure and, to a lesser extent, the resistance to venous return. As a result, venous return decreased.

Prognostic Value of the Intensive Care Respiratory Distress Observation Scale on ICU Admission.

BACKGROUND: The association between dyspnea and mortality has not been demonstrated in the ICU setting. We tested the hypothesis that dyspnea (self-reported respiratory discomfort) or its observational correlates (5-item intensive care Respiratory Distress Observation Scale [IC-RDOS]) assessed on ICU admission would be associated with ICU mortality. METHODS: Ancillary analysis of single-center data prospectively collected from 220 communicative ICU subjects allocated to a derivation cohort of 120 subjects and a separate validation cohort of 100 subjects. Dyspnea was assessed dichotomously (yes/no), with a dyspnea visual analog scale (measured in mm), and IC-RDOS was calculated. Multivariate logistic regression was used to identify factors associated with ICU and hospital mortality. RESULTS: Dyspnea was reported by 69 (58%; median 45 [interquartile range [IQR] 32-60] mm) and 47 (47%; 38 [IQR 26-48] mm) subjects in the derivation and validation cohorts, respectively. IC-RDOS was 2.3 (1.2-3.1) and 2.4 (1.3-2.8), respectively. IC-RDOS values were higher in subjects with dyspnea than in subjects without dyspnea in both the derivation cohort (2.6 [2.2-4.6] vs 1.4 [0.9-2.4], P < .001) and the validation cohort (2.6 [2.3-4.4] vs 2.2 [1.0-2.8], P < .001). On multivariate analysis of the derivation cohort, admission for hemorrhagic shock (odds ratio 13.98), IC-RDOS (odds ratio 1.77), and Simplified Acute Physiology Score II (odds ratio 1.10) was associated with ICU mortality. Areas under the receiving operating characteristic curve of IC-RDOS to predict ICU mortality were 0.785 and 0.794 in the derivation and validation cohorts, respectively. CONCLUSIONS: IC-RDOS, an observational correlate of dyspnea, but not dyspnea itself, was associated with higher mortality in ICU subjects.

Precision of the transpulmonary thermodilution measurements.

INTRODUCTION: We wanted to determine the number of cold bolus injections that are necessary for achieving an acceptable level of precision for measuring cardiac index (CI), indexed global end-diastolic volume (GEDVi) and indexed extravascular lung water (EVLWi) by transpulmonary thermodilution. METHODS: We included 91 hemodynamically stable patients (age 59 (25% to 75% interquartile range: 39 to 79) years, simplified acute physiologic score (SAPS)II 59 (53 to 65), 56% under norepinephrine) who were monitored by a PiCCO2 device. We performed five successive cold saline (15 mL, 6 °C) injections and recorded the measurements of CI, GEDVi and EVLWi. RESULTS: Considering five boluses, the coefficient of variation (CV, calculated as standard deviation divided by the mean of the five measurements) was 7 (5 to 11)%, 7 (5 to 12)% and 7 (6 to 12)% for CI, GEDVi and EVLWi, respectively. If the results of two bolus injections were averaged, the precision (2 × CV/√ number of boluses) was 10 (7 to 15)%, 10 (7 to 17)% and 8 (7 to 14)% for CI, GEDVi and EVLWi, respectively. If the results of three bolus injections were averaged, the precision dropped below 10%, that is, the cut-off that is generally considered as acceptable (8 (6 to 12)%, 8 (6 to 14)% and 8 (7 to 14)% for CI, GEDVi and EVLWi, respectively). If two injections were performed, the least significant change, that is, the minimal change in value that could be trusted to be significant, was 14 (10 to 21)%, 14 (10 to 24)% and 14 (11 to 23)% for CI, GEDVi and EVLWi, respectively. If three injections were performed, the least significant change was 12 (8 to 17)%, 12 (8 to 19)% and 12 (9 to 19)% for CI, GEDVi and EVLWi, respectively, that is, below the 15% cut-off that is usually considered as clinically relevant. CONCLUSIONS: These results support the injection of at least three cold boluses for obtaining an acceptable precision when transpulmonary thermodilution is used for measuring CI, GEDVi and EVLWi.

Management of myocardial dysfunction in severe sepsis.

Sepsis-induced cardiac dysfunction is a frequent and severe complication of septic shock. The mechanisms responsible for its development are complex and intricate. Echocardiography is the best method to make the diagnosis of cardiac dysfunction. Biomarkers (B-type natriuretic peptides and cardiac troponins) can alert clinicians of the possibility of cardiac dysfunction. Low plasma levels can serve to rule out a severe cardiac dysfunction. By contrast, high levels should prompt the performance of an echocardiographic examination. The transpulmonary thermodilution monitor and the pulmonary artery catheter can also be used to alert clinicians or to monitor the effects of inotropic therapy. Dobutamine is the first-line therapy. Its administration remains a matter of debate and should be carefully monitored in terms of efficacy and tolerance.