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.

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.

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.

Acute respiratory distress syndrome: the heart side of the moon.

PURPOSE OF REVIEW: Circulatory failure is a frequent complication during acute respiratory distress syndrome (ARDS) and is associated with a poor outcome. This review aims at clarifying the mechanisms of circulatory failure during ARDS. RECENT FINDINGS: For the past decades, the right ventricle (RV) has gained a crucial interest since many authors confirmed the high incidence of acute cor pulmonale during ARDS and showed a potential role of the acute cor pulmonale in the poor outcome of ARDS patients. The most important recent progress demonstrated in ARDS ventilatory strategy is represented by the prone position, which has a huge beneficial effect on RV afterload. This review will focus on the mechanisms responsible for the RV dysfunction/failure during ARDS and on the strategy, which allows improving the right ventricular function. SUMMARY: The RV has a pivotal role in the circulatory failure of ARDS patients. The ventilatory strategy during ARDS has to pay a peculiar attention to the RV to rigorously control its afterload.

Assessment of the effects of inspiratory load on right ventricular function.

PURPOSE OF REVIEW: The right ventricle (RV) plays a pivotal role during respiratory failure because of its high sensitivity to small loading changes during inspiration. Both RVs, preload and afterload, are altered during inspiration, either in spontaneous breathing or during mechanical ventilation. Some clinical situations especially affect RV load during inspiration, for example acute asthma and acute respiratory distress syndrome. The aim of this review is to explain and to summarize the different mechanisms leading to RV failure in these situations. RECENT FINDINGS: Research has recently reemphasized the importance to well known physiology of the venous return which is a contributor of RV preload. Authors recently focused on the mean systemic filling pressure which is one of the determinants of venous return. Venous return may change in opposite direction according to the type of ventilation (spontaneous or assisted). Recent works have also demonstrated the crucial impact of lung inflation and driving pressure on RV afterload, and have confirmed the deleterious effect of severe RV failure, described as acute cor pulmonale. In most situations of RV overload induced by inspiration, significant pulse pressure variations are observed, either called 'pulsus paradoxus' in spontaneously breathing patients or 'reverse pulsus paradoxus' in mechanically ventilated patients. SUMMARY: RV is very sensitive to abnormal inspiration, which is always responsible for an increase in its afterload. Pulse pressure variations, central venous pressure and especially echocardiography may monitor RV function in abnormal clinical situations. The pulmonary artery catheter was also proposed although now less used.

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.

Value and determinants of the mean systemic filling pressure in critically ill patients.

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (ß = 2.67, P = 0.0004) and age (ß = -0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine.

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.

Doppler echocardiography in shocked patients.

PURPOSE OF REVIEW: To reiterate the necessity of integrating echocardiography in the management of shocked patients and to propose a step-by-step functional evaluation of hemodynamics proven to optimize hemodynamic monitoring and to adapt the treatment. RECENT FINDINGS: Echocardiography has become the cornerstone to hemodynamic monitoring. By providing real-time images, echocardiography has the advantage over 'blind' technologies of an excellent diagnostic performance and of quick provision of information about the pathophysiology of circulatory failure. Critical care echocardiography (CCE) has been defined as echocardiography performed and interpreted by intensivists themselves, 7/7 and 24/24, at the bedside. Basic CCE is mainly a diagnostic approach, allowing quick and focused examination of cardiac function. Advanced CCE is the core of functional hemodynamic monitoring. It is based not only on transthoracic echocardiography but also strongly on transesophageal echocardiography, a very useful approach in ventilated patients. However, this monitoring is discontinuous. A single-use 72-h indwelling transesophageal probe was recently tested, allowing functional hemodynamic monitoring more continuously. SUMMARY: Echocardiography has become a hemodynamic monitoring technique used worldwide. It allows to make a quick and simple diagnosis of typical hemodynamic situations, by means of basic CCE, and also to achieve real functional hemodynamic monitoring, through advanced CCE.

Evaluation of left ventricular systolic function revisited in septic shock.

The meta-analysis of Huang and coworkers failed to find any evidence for a protective effect of a decreased left ventricular (LV) ejection fraction (EF). These results have to be interpreted with caution since in most studies included in the meta-analysis patients with LV systolic dysfunction received inotropic drugs. We have some arguments suggesting that such a treatment may improve macrocirculation and microcirculation and finally prognosis. This paper allows us to clarify the meaning of LV function in septic shock patients. In all experimental models of septic shock using the load-independent parameter of LV systolic function, LV contractility impairment, called septic cardiomyopathy, has been reported to be constant. However, LVEF reflects the coupling between LV contractility and LV afterload. A normal LVEF may be observed when the arterial tone is severely depressed, as in septic shock, despite seriously impaired intrinsic LV contractility. LV systolic function, evaluated using an echocardiograph or another device, is then more a reflection of arterial tone (and its correction) than of intrinsic LV contractility. As a consequence, the incidence of LV systolic dysfunction greatly depends on the time of the evaluation, reflecting the fact that, during resuscitation and treatment, vasoplegia and then LV afterload are corrected, thus unmasking septic cardiomyopathy. With these points in mind, we can revisit the results of Margaret Parker's original study: it is not that the patients with a low EF survived better, but rather that the other patients had an increased mortality due to persistent profound vasoplegia.

Recombinant factor VIIa for uncontrollable bleeding in patients with extracorporeal membrane oxygenation: report on 15 cases and literature review.

INTRODUCTION: Bleeding is the most frequent complication in patients receiving venoarterial or venovenous extracorporeal membrane oxygenation (ECMO). Recombinant activated factor VII (rFVIIa) has been used in these patients with conflicting results. We describe our experience with rFVIIa for refractory bleeding in this setting and review the cases reported in the literature. METHODS: Clinical characteristics, demographics, bleeding, thrombotic complications, mortality, and rFVIIa administration were retrospectively collected for analysis from the electronic charts of the 15 patients in our intensive care unit who received rFVIIa while being given ECMO from January 2006 to March 2011. RESULTS: Fifteen patients received rFVIIa for persistent bleeding under venoarterial (n=11) or venovenous (n=4) ECMO. Bleeding dramatically decreased in 14 patients, without a major thrombotic event, except in one patient in whom a major stroke could not be ruled out. Two circuits were changed within the 48 hours after rFVIIa administration for clots in the membrane and decreased oxygenation but without massive clotting. The mortality rate was 60%. CONCLUSIONS: rFVIIa use for intractable hemorrhaging in patients receiving ECMO controlled bleeding, without major thrombotic events, and with 60% dying. Hence, its use warrants discussion, and clinicians should be aware of the possibility of potentially life-threatening systemic thrombosis, emboli, or circuit clotting. Whether rFVIIa can save the lives of such patients remains to be determined.

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.

PaCO2 and alveolar dead space are more relevant than PaO2/FiO2 ratio in monitoring the respiratory response to prone position in ARDS patients: a physiological study.

INTRODUCTION: Our aims in this study were to report changes in the ratio of alveolar dead space to tidal volume (VDalv/VT) in the prone position (PP) and to test whether changes in partial pressure of arterial CO2 (PaCO2) may be more relevant than changes in the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FiO2) in defining the respiratory response to PP. We also aimed to validate a recently proposed method of estimation of the physiological dead space (VDphysiol/VT) without measurement of expired CO2. METHODS: Thirteen patients with a PaO2/FiO2 ratio < 100 mmHg were included in the study. Plateau pressure (Pplat), positive end-expiratory pressure (PEEP), blood gas analysis and expiratory CO2 were recorded with patients in the supine position and after 3, 6, 9, 12 and 15 hours in the PP. Responders to PP were defined after 15 hours of PP either by an increase in PaO2/FiO2 ratio > 20 mmHg or by a decrease in PaCO2 > 2 mmHg. Estimated and measured VDphysiol/VT ratios were compared. RESULTS: PP induced a decrease in Pplat, PaCO2 and VDalv/VT ratio and increases in PaO2/FiO2 ratios and compliance of the respiratory system (Crs). Maximal changes were observed after six to nine hours. Changes in VDalv/VT were correlated with changes in Crs, but not with changes in PaO2/FiO2 ratios. When the response was defined by PaO2/FiO2 ratio, no significant differences in Pplat, PaCO2 or VDalv/VT alterations between responders (n = 7) and nonresponders (n = 6) were observed. When the response was defined by PaCO2, four patients were differently classified, and responders (n = 7) had a greater decrease in VDalv/VT ratio and in Pplat and a greater increase in PaO2/FiO2 ratio and in Crs than nonresponders (n = 6). Estimated VDphysiol/VT ratios significantly underestimated measured VDphysiol/VT ratios (concordance correlation coefficient 0.19 (interquartile ranges 0.091 to 0.28)), whereas changes during PP were more reliable (concordance correlation coefficient 0.51 (0.32 to 0.66)). CONCLUSIONS: PP induced a decrease in VDalv/VT ratio and an improvement in respiratory mechanics. The respiratory response to PP appeared more relevant when PaCO2 rather than the PaO2/FiO2 ratio was used. Estimated VDphysiol/VT ratios systematically underestimated measured VDphysiol/VT ratios.

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.

"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.