Low-flow ECCO2R conjoined with renal replacement therapy platform to manage pulmonary vascular dysfunction with refractory hypercapnia in ARDS.

Background: Hypercapnia worsens lung vascular dysfunction during acute respiratory distress syndrome (ARDS). We tested whether an extracorporeal carbon dioxide removal (ECCO2R) device based on a renal replacement therapy platform (Prismalung®) may reduce PaCO2 and alleviate lung vascular dysfunction in ARDS patients with refractory hypercapnia. Methods: We planned to prospectively include 20 patients with moderate-to-severe ARDS, pulmonary vascular dysfunction on echocardiography, and PaCO2 ≥ 48 mmHg despite instrumental dead space reduction and the increase in respiratory rate. Hemodynamics, echocardiography, respiratory mechanics, and arterial blood gases were recorded at 2 (H2), 6 (H6) and 24 (H24) hours as ECCO2R treatment was continued for at least 24 h. Results: Only eight patients were included, and the study was stopped due to worldwide shortage of ECCO2R membranes and the pandemic. Only one patient fulfilled the primary endpoint criterion (decrease in PaCO2 of more than 20 %) at H2, but this objective was achieved in half of patients (n = 4) at H6. The percentage of patients with a PaCO2 value < 48 mmHg increased with time, from 0/8 (0 %) at H0, to 3/8 (37.5 %) at H2 and 4/8 (50 %) at H6 (p = 0.04). There was no major change in hemodynamic and echocardiographic variables with ECCO2R, except for a significant decrease in heart rate. ECCO2R was prematurely discontinued before H24 in five (62.5 %) patients, due to membrane clotting in all cases. Conclusions: This pilot study testing showed a narrow efficacy and high rate of membrane thrombosis with the first version of the system. Improved versions should be tested in future trials. Trial registration: Registered at clinicaltrials.gov, identifier: NCT03303807, Registered: October 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03303807.

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.

Right ventricular failure in septic shock: characterization, incidence and impact on fluid responsiveness.

OBJECTIVE: Incidence of right ventricular (RV) failure in septic shock patients is not well known, and tricuspid annular plane systolic excursion (TAPSE) could be of limited value. We report the incidence of RV failure in patients with septic shock, its potential impact on the response to fluids, as well as TAPSE values. DESIGN: Ancillary study of the HEMOPRED prospective multicenter study includes patients under mechanical ventilation with circulatory failure. SETTING: This is a multicenter intensive care unit study PATIENTS: Two hundred and eighty-two patients with septic shock were analyzed. Patients were classified in three groups based on central venous pressure (CVP) and RV size (RV/LV end-diastolic area, EDA). In group 1, patients had no RV dilatation (RV/LVEDA < 0.6). In group 2, patients had RV dilatation (RV/LVEDA ≥ 0.6) with a CVP < 8 mmHg (no venous congestion). RV failure was defined in group 3 by RV dilatation and a CVP ≥ 8 mmHg. Pulse pressure variation (PPV) was systematically recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 41% of patients were in group 1, 17% in group 2 and 42% in group 3. A correlation between RV size and CVP was only observed in group 3. Higher RV size was associated with a lower response to passive leg raising for a given PPV. A large overlap of TAPSE values was observed between the 3 groups. 63.5% of patients with RV failure had a normal TAPSE. CONCLUSIONS: RV failure, defined by critical care echocardiography (RV dilatation) and a surrogate of venous congestion (CVP ≥ 8 mmHg), was frequently observed in septic shock patients and negatively associated with response to a fluid challenge despite significant PPV. TAPSE was unable to discriminate patients with or without RV failure.

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.

"You helped me keep my head above water"-experience of bereavement research after loss of a loved one in the ICU: insights from the ARREVE study.

PURPOSE: Bereavement research has helped to improve end-of-life practices in the ICU. However, few studies have explored bereaved relatives experience of research participation in this context. We aimed to explore the experience of bereaved relatives' participation in the ARREVE study which included three telephone follow-up calls to complete several quantitative tools. METHODS: Volunteer relatives who participated in the 12-month follow-up call completed a questionnaire about research participation that included ten open-ended questions so that respondents could use their own words and thoughts. These open-ended questions were analyzed using qualitative analysis that examines themes within the data. RESULTS: 175/311 relatives completed the questionnaire. Three themes were derived from the thematic analysis: (1) struggling: reactivation of emotional distress associated with the ICU experience and the loss is frequent, specifically during the 1st follow-up call. (2) Resilience: as time goes by, research participation becomes increasingly positive. The calls are a help both in giving meaning to the relatives' experience and in accepting the loss. (3) Recognition: research calls can compensate for the absence of support during bereavement. CONCLUSION: Although some emotional difficulties must be acknowledged, bereavement research is overall associated with benefits, by facilitating emotional adjustments, meaning-making and resilience. Lack of support and social isolation during bereavement are frequent experiences, revealing that support strategies for bereaved relatives should be developed after the loss of a loved one in the ICU.

Cardiovascular clusters in septic shock combining clinical and echocardiographic parameters: a post hoc analysis.

PURPOSE: Mechanisms of circulatory failure are complex and frequently intricate in septic shock. Better characterization could help to optimize hemodynamic support. METHODS: Two published prospective databases from 12 different ICUs including echocardiographic monitoring performed by a transesophageal route at the initial phase of septic shock were merged for post hoc analysis. Hierarchical clustering in a principal components approach was used to define cardiovascular phenotypes using clinical and echocardiographic parameters. Missing data were imputed. FINDINGS: A total of 360 patients (median age 64 [55; 74]) were included in the analysis. Five different clusters were defined: patients well resuscitated (cluster 1, n = 61, 16.9%) without left ventricular (LV) systolic dysfunction, right ventricular (RV) failure or fluid responsiveness, patients with LV systolic dysfunction (cluster 2, n = 64, 17.7%), patients with hyperkinetic profile (cluster 3, n = 84, 23.3%), patients with RV failure (cluster 4, n = 81, 22.5%) and patients with persistent hypovolemia (cluster 5, n = 70, 19.4%). Day 7 mortality was 9.8%, 32.8%, 8.3%, 27.2%, and 23.2%, while ICU mortality was 21.3%, 50.0%, 23.8%, 42.0%, and 38.6% in clusters 1, 2, 3, 4, and 5, respectively (p < 0.001 for both). CONCLUSION: Our clustering approach on a large population of septic shock patients, based on clinical and echocardiographic parameters, was able to characterize five different cardiovascular phenotypes. How this could help physicians to optimize hemodynamic support should be evaluated in the future.

Value of measuring esophageal pressure to evaluate heart-lung interactions-applications for invasive hemodynamic monitoring.

Evaluation of intrathoracic pressure is the cornerstone of the understanding of heart-lung interactions, but is not easily feasible at the bedside. Esophageal pressure (Pes) has been shown to be a good surrogate for intrathoracic pressure and can be more easily measured using a small esophageal catheter, but is not routinely employed. It can provide crucial information for the study of heart-lung interactions in both controlled and spontaneous ventilation. This review presents the physiological basis, the technical aspects and the value in clinical practice of the measurement of Pes.

Limited value of end-expiratory inferior vena cava diameter to predict fluid responsiveness impact of intra-abdominal pressure.

PURPOSE: We sought to determine the diagnostic ability of the end-expiratory inferior vena cava diameter (IVCEE) to predict fluid responsiveness (FR) and the potential confounding effect of intra-abdominal pressure (IAP). METHODS: In this multicenter study, 540 consecutive ventilated patients with shock of various origins underwent an echocardiographic assessment by experts. The IVCEE, velocity time integral (VTI) of the left ventricular outflow tract (LVOT) and intra-abdominal pressure (IAP) were measured. Passive leg raising (PLR) was then systematically used to perform a reversible central blood volume expansion. FR was defined by an increase in LVOT VTI ≥ 10% after 1 min of PLR. RESULTS: Since IVCEE was not obtained in 117 patients (22%), 423 were studied (septic shock: 56%), 129 of them (30%) having elevated IAP (≥ 12 mmHg) and 172 of them (41%) exhibiting FR. IVCEE ≤ 13 mm predicted FR with a specificity of at least 80% in 62 patients (15%), while IVCEE ≥ 25 mm predicted the absence of FR with a specificity of at least 80% in 61 patients (14%). In the remaining 300 patients (71%), the intermediate value of IVCEE did not allow predicting FR. An adjusted relationship between IVCEE and FR was observed while this relationship was less pronounced in patients with IAP ≥ 12 mmHg. CONCLUSIONS: Measurement of IVCEE in ventilated patients is moderately feasible and poorly predicts FR, with IAP acting as a confounding factor. IVCEE might add some value to guide fluid therapy but should not be used alone for fluid prediction purposes.

Correction to: Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

Correction to: Intensive Care Med (2017) DOI 10.1007/s00134-017-4891-0.

Terminal weaning or immediate extubation for withdrawing mechanical ventilation in critically ill patients (the ARREVE observational study).

PURPOSE: The relative merits of immediate extubation versus terminal weaning for mechanical ventilation withdrawal are controversial, particularly regarding the experience of patients and relatives. METHODS: This prospective observational multicentre study (ARREVE) was done in 43 French ICUs to compare terminal weaning and immediate extubation, as chosen by the ICU team. Terminal weaning was a gradual decrease in the amount of ventilatory assistance and immediate extubation was extubation without any previous decrease in ventilatory assistance. The primary outcome was posttraumatic stress symptoms (Impact of Event Scale Revised, IES-R) in relatives 3 months after the death. Secondary outcomes were complicated grief, anxiety, and depression symptoms in relatives; comfort of patients during the dying process; and job strain in staff. RESULTS: We enrolled 212 (85.5%) relatives of 248 patients with terminal weaning and 190 relatives (90.5%) of 210 patients with immediate extubation. Immediate extubation was associated with airway obstruction and a higher mean Behavioural Pain Scale score compared to terminal weaning. In relatives, IES-R scores after 3 months were not significantly different between groups (31.9 ± 18.1 versus 30.5 ± 16.2, respectively; adjusted difference, -1.9; 95% confidence interval, -5.9 to 2.1; p = 0.36); neither were there any differences in complicated grief, anxiety, or depression scores. Assistant nurses had lower job strain scores in the immediate extubation group. CONCLUSIONS: Compared to terminal weaning, immediate extubation was not associated with differences in psychological welfare of relatives when each method constituted standard practice in the ICU where it was applied. Patients had more airway obstruction and gasps with immediate extubation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01818895.

Right heart function during acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is burdened with significant mortality, mainly in connection with circulatory failure. The right ventricle (RV) is the weak link of hemodynamic stability among ARDS patients and its failure, also named "severe" acute cor pulmonale (ACP), is responsible for excess mortality. Driving pressure ≥18 cmH2O, PaCO2 ≥48 mmHg and PaO2/FiO2 <150 mmHg are three preventable factors recently identified as independently associated with ACP, on which ventilator strategy designed to protect the RV has to focus. This is largely achieved by the use of early and extended sessions of prone positioning (PP) and by daily monitoring of the RV by echocardiography.

Epidemiology of extended-spectrum beta-lactamase-producing Enterobacteriaceae in an intensive care unit with no single rooms.

BACKGROUND: The transmission of extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBL) is prevented by additional contact precautions, mainly relying on isolation in a single room and hand hygiene. Contact isolation cannot be achieved in our 12-bed ICU, which has only double rooms. We report the epidemiology of ESBL imported, acquired and transmitted in an ICU with no single rooms. METHODS: We prospectively conducted an observational and non-interventional study in a French 12-bed ICU. Inclusion criteria were patients >18 years of age treated by at least two successive nursing teams. Patient characteristics at admission and clinical data during hospital stay were collected prospectively. ESBL carriage was monitored using rectal swabs collected at admission and once weekly during the ICU stay. Potential cross-transmission was studied (1) by identifying index patients defined as possible ESBL sources for transmission, (2) by classifying each ESBL strain according to the cefotaximase München (CTXM) 1 and 9 groups and (3) by gene sequencing for remaining cases of possible transmission. RESULTS: From June 2014 to April 2015, of 550 patients admitted to the ICU, 470 met the inclusion criteria and 221 had at least two rectal swabs. The rate of ESBL colonization, mainly by Escherichia coli, at admission was 13.2%. The incidence of ESBL acquisition, mainly with E. coli too, was 4.1%. Mortality did not differ between ESBL carriers and non-carriers. In univariate analysis, ESBL acquisition was associated with male gender, SAPS II, SOFA, chronic kidney disease at admission, duration of mechanical ventilation, need for catecholamine and the ICU LOS. In multivariate analysis, SAPS II at admission was the only risk factor for ESBL acquisition. We confirmed cross-transmission, emanating from the same index patient, in two of the nine patients with ESBL acquisition (0.8%, 2/221). No case of cross-transmission in the same double room was observed. DISCUSSION AND CONCLUSION: Prevalence of ESBL colonization in our ICU was 13.2%. Despite the absence single rooms, the incidence of ESBL acquisition was 4.1% and cross-transmission was proven in only two cases, resulting from the same index patient who was not hospitalized in the same double room.

Impact of positive pressure ventilation on mean systemic filling pressure in critically ill patients after death.

Mean systemic filling pressure (Pms) defines the pressure measured in the venous-arterial system when the cardiac output is nil. Its estimation has been proposed in patients with beating hearts by building the venous return curve, using different pairs of right atrial pressure/cardiac output during mechanical ventilation. We raised the hypothesis according to which the Pms is altered by tidal ventilation and positive end-expiratory pressure (PEEP), which would challenge this extrapolation method based on cardiopulmonary interactions. We conducted a two-center, noninterventional, observational, and prospective study, using an arterial and a venous catheter to measure the pressure in the circulatory system at the time of death in critically ill, mechanically ventilated patients with a PEEP. Arterial (Part) and venous pressures (Pra) were recorded in five conditions: at end expiration and end inspiration with and without PEEP and finally once the ventilator was disconnected. Part and Pra did not differ in any experimental conditions. Tidal ventilation increased Pra and Part by 2.4 and 1.9 mmHg, respectively, whereas PEEP increased both values by 1.2 and 1 mmHg, respectively. After disconnection of the ventilator, Pra and Part were 10.0 ± 4.2 and 9.9 ± 4.2 mmHg, respectively. Pms increases during mechanical ventilation, with an effect of tidal ventilation and PEEP. This calls into question the validity of its evaluation in heart-beating patients using cardiopulmonary interactions during mechanical ventilation.NEW & NOTEWORTHY The physiology of the mean systemic filling pressure (Pms) is not well understood in human beings. This study is the first report of a tidal ventilation- and positive end-expiratory pressure-related increase in Pms in critically ill patients. The results challenge the utility and the value estimating Pms in heart-beating patients by reconstruction of the venous return curve using varying inflation pressures.

Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients.

RATIONALE: Assessment of fluid responsiveness relies on dynamic echocardiographic parameters that have not yet been compared in large cohorts. OBJECTIVES: To determine the diagnostic accuracy of dynamic parameters used to predict fluid responsiveness in ventilated patients with a circulatory failure of any cause. METHODS: In this multicenter prospective study, respiratory variations of superior vena cava diameter (∆SVC) measured using transesophageal echocardiography, of inferior vena cava diameter (∆IVC) measured using transthoracic echocardiography, of the maximal Doppler velocity in left ventricular outflow tract (∆VmaxAo) measured using either approach, and pulse pressure variations (∆PP) were recorded with the patient in the semirecumbent position. In each patient, a passive leg raise was performed and an increase of aortic velocity time integral greater than or equal to 10% defined fluid responsiveness. MEASUREMENTS AND MAIN RESULTS: Among 540 patients (379 men; age, 65 ± 13 yr; Simplified Acute Physiological Score II, 59 ± 18; Sequential Organ Failure Assessment, 10 ± 3), 229 exhibited fluid responsiveness (42%). ∆PP, ∆VmaxAo, ∆SVC, and ∆IVC could be measured in 78.5%, 78.0%, 99.6%, and 78.1% of cases, respectively. ∆SVC greater than or equal to 21%, ∆VmaxAo greater than or equal to 10%, and ∆IVC greater than or equal to 8% had a sensitivity of 61% (95% confidence interval, 57-66%), 79% (75-83%), and 55% (50-59%), respectively, and a specificity of 84% (81-87%), 64% (59-69%), and 70% (66-75%), respectively. The area under the receiver operating characteristic curve of ∆SVC was significantly greater than that of ∆IVC (P = 0.02) and ∆PP (P = 0.01). CONCLUSIONS: ∆VmaxAo had the best sensitivity and ∆SVC the best specificity in predicting fluid responsiveness. ∆SVC had a greater diagnostic accuracy than ∆IVC and ∆PP, but its measurement requires transesophageal echocardiography.

On the complexity of scoring acute respiratory distress syndrome: do not forget hemodynamics!

Acute respiratory distress syndrome (ARDS) remains associated with a poor outcome despite recent major therapeutic advances. Forecasting the outcome of patients suffering from such a syndrome is of a crucial interest and many scores have been proposed, all suffering from limits responsible for important discrepancies. Authors try to elaborate simple, routine and reliable scores but most of them do not consider hemodynamics yet acknowledged as a major determinant of outcome. This article aims at reminding the approach of scoring in ARDS and at deeply describing the most recently published one in order to highlight their main pitfall, which is to forget the hemodynamics.

Critical care ultrasonography in acute respiratory failure.

Acute respiratory failure (ARF) is a leading indication for performing critical care ultrasonography (CCUS) which, in these patients, combines critical care echocardiography (CCE) and chest ultrasonography. CCE is ideally suited to guide the diagnostic work-up in patients presenting with ARF since it allows the assessment of left ventricular filling pressure and pulmonary artery pressure, and the identification of a potential underlying cardiopathy. In addition, CCE precisely depicts the consequences of pulmonary vascular lesions on right ventricular function and helps in adjusting the ventilator settings in patients sustaining moderate-to-severe acute respiratory distress syndrome. Similarly, CCE helps in identifying patients at high risk of ventilator weaning failure, depicts the mechanisms of weaning pulmonary edema in those patients who fail a spontaneous breathing trial, and guides tailored therapeutic strategy. In all these clinical settings, CCE provides unparalleled information on both the efficacy and tolerance of therapeutic changes. Chest ultrasonography provides further insights into pleural and lung abnormalities associated with ARF, irrespective of its origin. It also allows the assessment of the effects of treatment on lung aeration or pleural effusions. The major limitation of lung ultrasonography is that it is currently based on a qualitative approach in the absence of standardized quantification parameters. CCE combined with chest ultrasonography rapidly provides highly relevant information in patients sustaining ARF. A pragmatic strategy based on the serial use of CCUS for the management of patients presenting with ARF of various origins is detailed in the present manuscript.