Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Electrical Impedance Tomography Monitoring of Bronchoalveolar Lavage in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: The impact of bronchoalveolar lavage on regional ventilation in mechanically ventilated patients with acute respiratory distress syndrome has rarely been described. Our objectives were use electrical impedance tomography to describe lung impedance variation post bronchoalveolar lavage and identify morphologic patterns according to respiratory failure severity. DESIGN: Monocenter physiologic study on mechanically ventilated patients. SETTING: University medical ICU. INTERVENTIONS: After a recruitment maneuver, tidal impedance variation distributions (a surrogate for impact of bronchoalveolar lavage on tidal volume distribution), end-expiratory lung impedance (correlated with end-expiratory lung volume and used to quantify postbronchoalveolar lavage derecruitment), respiratory mechanics, and blood gases were recorded before and over 6 hours post bronchoalveolar lavage with Pao2 to the Fio2 ratio. Patients were grouped according to their prebronchoalveolar lavage, that is, Pao2 to the Fio2 ratio less than 200 or greater than or equal to 200. RESULTS: Twenty-one patients (median [interquartile range] age 55 yr [50-58 yr]; 13 males), 13 with Pao2 to the Fio2 ratio less than 200, were included. Unlike that latter group, bronchoalveolar lavage significantly impacted tidal impedance variation distribution in patients with Pao2 to the Fio2 ratio greater than or equal to 200, with a ventilation shift to the contralateral lung (from 54% to 42% in the bronchoalveolar lavage side), which persisted up to 6 hours post bronchoalveolar lavage. Similarly, end-expiratory lung impedance was less distributed in the bronchoalveolar lavage side post procedure of patients with Pao2 to the Fio2 ratio greater than or equal to 200, but the difference did not reach statistical significance (p = 0.09). As reported for tidal impedance variation, end-expiratory lung impedance distribution in patients with severe or moderate acute respiratory distress syndrome did not change significantly during the 6 hours post bronchoalveolar lavage. Although bronchoalveolar lavage effects on gas exchanges were minor in all patients, static compliance in patients with Pao2 to the Fio2 ratio greater than or equal to 200 was significantly lower post bronchoalveolar lavage (p = 0.04). CONCLUSIONS: The negative impact of bronchoalveolar lavage on regional ventilation, which persisted at least 6 hours, appeared to be more profound in patients with normal lung function or mild acute respiratory distress syndrome. In contrast, regional ventilation, lung recruitment, respiratory mechanics, and gas exchanges were modestly impacted by the bronchoalveolar lavage in patients with severe or moderate acute respiratory distress syndrome. That finding is reassuring and supports not summarily proscribing bronchoalveolar lavage for the most severely ill with acute respiratory distress syndrome.

Microcirculation Evolution in Patients on Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock.

OBJECTIVES: Despite the increasing use of venoarterial extracorporeal membrane oxygenation to treat severe cardiogenic shock patients, microcirculation data in this context are scarce. We evaluated the venoarterial extracorporeal membrane oxygenation impact on macrocirculatory hemodynamics and microcirculation in patients with refractory cardiogenic shock and compared the evolutions of those parameters between patients successfully weaned-off extracorporeal membrane oxygenation and those who died on extracorporeal membrane oxygenation. DESIGN: Prospective study. SETTING: Academic medical ICU. PATIENTS: Consecutive patients with refractory cardiogenic shock (cardiac arrest excluded) who required venoarterial extracorporeal membrane oxygenation and for whom sublingual microcirculation measurements before cannulation were possible. INTERVENTIONS: All patients were followed until death or venoarterial extracorporeal membrane oxygenation removal. Microcirculatory and macrocirculatory evaluations were made before, and 2, 4, 12, 24, and 48 hours after extracorporeal membrane oxygenation initiation, respectively. Patients weaned-off extracorporeal membrane oxygenation were also evaluated 6 hours before and after venoarterial extracorporeal membrane oxygenation removal. MEASUREMENTS AND MAIN RESULTS: Fourteen patients (median age, 58 yr [interquartile range, 56-62 yr]; Sequential Organ Failure Assessment score, 14 [12-18]) were included. Acute myocardial infarction (50%) was the main cause of cardiogenic shock. Six patients (33%) were successfully weaned-off extracorporeal membrane oxygenation. Profound microcirculation parameter changes found before venoarterial extracorporeal membrane oxygenation implantation regressed within 12 hours after extracorporeal membrane oxygenation onset. Pre-extracorporeal membrane oxygenation macrocirculation, echocardiography, arterial blood gases, and microcirculation parameters did not differ between patients who died on extracorporeal membrane oxygenation and those successfully weaned. However, perfused small-vessel density, small-vessel density, and percent perfused vessels were consistently higher and then stabilized 48 hours postcannulation for patients successfully weaned-off extracorporeal membrane oxygenation. CONCLUSIONS: Microcirculation is severely impaired in patients with refractory cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. Inability to rapidly restore microcirculation during the first 24 hours, despite normal global/macrocirculatory hemodynamics, was associated with death on extracorporeal membrane oxygenation. Further studies are now warranted to better determine the relevant microcirculation determinants during venoarterial extracorporeal membrane oxygenation support, before future routine use of this promising tool in clinical practice.

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.

Reporting of Organ Support Outcomes in Septic Shock Randomized Controlled Trials: A Methodologic Review-The Sepsis Organ Support Study.

OBJECTIVES: Many recent randomized controlled trials in the field of septic shock failed to demonstrate a benefit on mortality. Randomized controlled trials increasingly report organ support duration and organ support-free days as primary or secondary outcomes. We conducted a methodologic systematic review to assess how organ support outcomes were defined and reported in septic shock randomized controlled trials. DATA SOURCES: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. STUDY SELECTION: We included randomized controlled trials published between January 2004 and March 2018 that involved septic shock adults and assessed organ support duration and/or organ support-free days for hemodynamic support, respiratory support, or renal replacement therapy. DATA EXTRACTION: For each randomized controlled trial, we extracted the definitions of organ support duration and organ support-free days. We particularly evaluated how nonsurvivors were accounted for. Study authors were contacted to provide any missing information regarding these definitions. DATA SYNTHESIS: We included 28 randomized controlled trials. Organ support duration and organ support-free days outcomes were reported in 17 and 15 randomized controlled trials, respectively, for hemodynamic support, 15 and 15 for respiratory support, and five and nine for renal replacement therapy. Nonsurvivors were included in the organ support duration calculation in 13 of 14 randomized controlled trials (93%) for hemodynamic support and nine of 10 (90%) for respiratory support. The organ support-free days definition for hemodynamic support, respiratory support, and renal replacement therapy was reported in six of 15 randomized controlled trials (40%), eight of 15 randomized controlled trials (53%), and six of nine randomized controlled trials (67%) reporting an organ support-free days outcome, respectively. Of these, one half assigned "0" to nonsurvivors, and the other half attributed one point per day alive free of organ support up to a predefined time point. CONCLUSIONS: This study highlights the heterogeneity and infrequency of organ support duration/organ support-free days outcome reporting in septic shock trials. When reported, the definitions of these outcome measures and methods of calculation are also infrequently reported, in particular how nonsurvivors were accounted for, which may have an important impact on interpretation.

Transvenous Renal Biopsy of Critically Ill Patients: Safety and Diagnostic Yield.

OBJECTIVES: Transvenous renal biopsy is an alternative way to obtain kidney samples from patients with bleeding risk factors (e.g., antiplatelet therapy and anticoagulation or coagulation disorders). This study was undertaken to determine the safety and diagnostic yield of transvenous renal biopsy of critically ill patients. DESIGN: Monocenter, retrospective, observational cohort study. SETTING: A 26-bed French tertiary ICU. PATIENTS: All patients undergoing in-ICU transvenous renal biopsy between January 2002 and February 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty patients (male/female sex ratio, 0.95; mean ± SD age, 47.3 ± 18.3 yr) were included. A histologic diagnosis was obtained for 77 patients (96.3%), with acute tubular necrosis being the most frequent: 23 (29.9%). A potentially treatable cause was found for 47 patients (58.7%). The numbers of patients with 0, 1, 2, or 3 factors (i.e., antiplatelet therapy, thrombopenia [< 150 G/L], and preventive or curative anticoagulation) at the time of the biopsy were, respectively: seven (8.8%), 37 (46.2%), 31 (38.7%), and five (6.3%). Four (5%) and two (2.5%) patients, respectively, had renal hematoma and macroscopic hematuria; none required any specific treatment. Six patients (7.5%) died in-ICU, and 90-day mortality was 8 of 80 (10%). No death was related to transvenous renal biopsy, and median biopsy-to-death interval was 38 days (interquartile range, 19.7-86 d). CONCLUSIONS: Based on this cohort of ICU patients with acute kidney injury, transvenous renal biopsy was safe and obtained a high diagnostic yield for these selected critically ill patients, even in the presence of multiple bleeding risk factors.

Exploring the microvascular impact of red blood cell transfusion in intensive care unit patients.

BACKGROUND: Red blood cell (RBC) transfusion is a common treatment for hospitalized patients. However, the effects of RBC transfusion on microvascular function remain controversial. METHODS: In a medical ICU in a tertiary teaching hospital, we prospectively included anemic patients requiring RBC transfusion. Skin microvascular reactivity was measured before and 30 min after RBC transfusion. Plasma was collected to analyze intravascular hemolysis and draw the lipidomic and cytokine profiles. RESULTS: In a cohort of 59 patients, the median age was 66 [55-81] years and SAPS II was 38 [24-48]. After RBC transfusion, endothelium-dependent microvascular reactivity improved in 35 (59%) patients, but worsened in 24 others (41%). Comparing clinical and biological markers revealed that baseline blood leucokyte counts distinguished improving from worsening patients (10.3 [5.7; 19.7] vs. 4.6 [2.1; 7.3] × 109/L; p = 0.001) and correlated with variations of microvascular reactivity (r = 0.36, p = 0.005). Blood platelet count was also higher in improving patients (200 [97; 280] vs 160 [40; 199] × 103/mL, p = 0.03) but did not correlate with variations of microvascular reactivity. We observed no intravascular hemolysis (HbCO, heme, bilirubin, LDH), but recorded a significant increase in RBC microparticle levels specific to improving patients after transfusion (292 [108; 531] vs. 53 [34; 99] MP/µL; p = 0.03). The improvement in microvascular dilation was positively correlated with RBC microparticle levels (R = 0.83, p < 0.001) and conversion of arachidonic acid into vasodilating eicosanoids. CONCLUSIONS: Patients displaying an improved microvascular reactivity after RBC transfusion had high blood leukocyte counts, increased RBC microparticle formation, and enhanced metabolism of arachidonic acid into vasodilating lipids. Our data suggested a contribution of recipient leukocytes to the vascular impact of RBC transfusion.

Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis.

OBJECTIVES: Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human. DESIGN: Prospective observational study. SETTING: Medical ICU in a tertiary teaching hospital. PATIENTS: To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01). CONCLUSIONS: We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.

Marked regional endothelial dysfunction in mottled skin area in patients with severe infections.

BACKGROUND: Mottling around the knee, reflecting a reduced skin blood flow, is predictive of mortality in patients with septic shock. However, the causative pathophysiology of mottling remains unknown. We hypothesized that the cutaneous hypoperfusion observed in the mottled area is related to regional endothelial dysfunction. METHODS: This was a prospective, observational study in a medical ICU in a tertiary teaching hospital. Consecutive adult patients with sepsis admitted to ICU were included. After resuscitation, endothelium-dependent vasodilation in the skin circulation was measured before and after iontophoresis of acetylcholine (Ach) in the forearm and the knee area. We analyzed the patterns of induced vasodilatation according to the presence or absence of mottling and vital status at 14 days. RESULTS: We evaluated 37 septic patients, including 11 without and 26 with septic shock. Overall 14-day mortality was 22%. Ten patients had mottling around the knee (10/37, 27%). In the knee area, the increased skin blood flow following iontophoresis of Ach was lower in patients with mottled skin as compared to patients without mottled skin (area under curve (AUC) 3280 (2643-6440) vs. 7980 (4233-19,707), both P < 0.05). In the forearm area, the increased skin blood flow following iontophoresis of Ach was similar in patients with and without mottled skin. Among patients with septic shock, the increased skin blood flow following iontophoresis of Ach in the knee area was significantly lower in non-survivors as compared to survivors at 14 days (AUC 3256 (2600-4426) vs. 7704 (4539-15,011), P < 0.01). In patients with septic shock, the increased skin blood flow in the forearm area following iontophoresis of Ach was similar in survivors and non-survivors at 14 days. CONCLUSION: Mottling is associated with regional endothelial dysfunction in patients with septic shock. Endothelial dysfunction in the knee skin area was more pronounced in non-survivors than in survivors.

Exploration of skin perfusion in cirrhotic patients with septic shock.

BACKGROUND & AIMS: Skin perfusion alterations are early and strong predictors of death in patients with septic shock. Cirrhosis is associated with systemic vasodilation and increases mortality from septic shock. We aimed at assessing whether the mottling score and tissue oxygen saturation (StO2) could be used as early predictors of death in cirrhotic patients with septic shock. METHODS: This observational study included cirrhotic patients with septic shock. Each 6 h during the first 24 h, we collected data reflecting macrocirculation (mean arterial pressure, heart rate, central venous pressure, and cardiac output) and organ perfusion (arterial lactate, urinary output, ScvO2, mottling score, thenar, and knee StO2). Data of 75 non-cirrhotic patients with previously reported septic shock were used as control. RESULTS: 42 cirrhotic patients were included. Mortality at day 14 was 71%. At H6, parameters reflecting macrocirculation were not associated with mortality, whereas higher arterial lactate and mottling score were associated with death. Mottling score was the strongest predictor of mortality (sensitivity=0.63, specificity=1, OR=42.4 (2.3-785.9)). At H6, knee StO2 decreased in non-survivors and predicted death (sensitivity=0.45, specificity=1). In comparison with control, mottling kinetic was different in cirrhotic patients (delayed mottling appearance in non-survivors, earlier mottling disappearance in survivors). Knee StO2 and skin perfusion, assessed by laser-Doppler, were higher in cirrhotic patients. CONCLUSIONS: Mottling score and knee StO2 at H6 were very specific predictors of death in patients with cirrhosis and septic shock. Their sensitivity was lower in cirrhotic patients due to delayed mottling appearance and higher knee StO2 related to higher skin perfusion.

Microcirculatory disorders during septic shock.

PURPOSE OF REVIEW: Despite the progress made over the past 20 years in the treatment of septic shock, mortality remains high. Microcirculatory disorders raise considerable interest aiming to improve the understanding of the physiopathology of septic shock and its management. RECENT FINDINGS: Numerous experimental and clinical studies have gradually focused on the analysis of microcirculatory blood flow and identified alterations in small vessels. These microcirculatory abnormalities appear early, are heterogeneous, and are directly linked to organ failure, as well as the patient's prognosis. These anomalies vary from one patient to the other, and their evolution during resuscitation cannot be predicted by the isolated analysis of global hemodynamic parameters such as blood pressure or heart rate. SUMMARY: Microcirculatory disorders appear at a central place of the physiopathology and are highly associated with the patient prognosis; it therefore seems important to develop and integrate parameters reflecting tissue perfusion in the management of septic shock.

Natural regulatory T cells limit angiotensin II-induced aneurysm formation and rupture in mice.

OBJECTIVE: Abdominal aortic aneurysm is an inflammatory disease leading to destructive vascular remodeling and ultimately to lethal aortic rupture. Despite its frequent association with atherosclerosis, compelling studies have shown striking differences and potentially opposite roles of T-cell helper responses in aneurysm as compared with atherosclerosis, casting doubt on the relevance and suitability of T-cell-targeted therapies in this context. APPROACH AND RESULTS: Here, we show that selective depletion of T regulatory (Treg) cells using a CD25-specific monoclonal antibody significantly enhances the susceptibility of C57Bl/6 mice to angiotensin II-induced abdominal aortic aneurysm and promotes aortic rupture (n=25-44 mice/group). Similar results are observed in angiotensin II-treated Cd80(-/-)/Cd86(-/-) or Cd28(-/-) mice with impaired Treg cell homeostasis (n=18-23 mice/group). Treg cell depletion is associated with increased immune cell activation and a blunted interleukin (IL)-10 anti-inflammatory response, suggesting an immunoinflammatory imbalance. Interestingly, Il-10(-/-) mice (n=20 mice/group) show increased susceptibility to angiotensin II-induced abdominal aortic aneurysm and aortic rupture and are insensitive to Treg cell depletion. Finally, reconstitution of Cd28(-/-) Treg-deficient mice with Treg cells (n=22 mice/group) restores a balance in the immunoinflammatory response, rescues the animals from increased susceptibility to aneurysm, and prevents aortic dissection. CONCLUSIONS: These results identify a critical role for Treg cells and IL-10 in the control of aneurysm formation and its progression to rupture and suggest that therapies targeting Treg responses may be most suited to treat aneurysmal disease.

Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock.

Shock is a common reason for medical intensive care unit admission, with septic and cardiogenic accounting for most of the etiologies. However, the potential severity of adverse side effects of drugs indicates that any medication should be carefully scrutinized for potential pharmacokinetic and pharmacodynamic interactions that may result. We herein report the case of a life-threatening shock mimicking successively anaphylactic, cardiogenic, and septic shock, which was finally related to disulfiram ethanol reaction. Indeed, disulfiram ethanol reaction is known to provoke unpleasant symptoms through vasodilatation in various organs. However, extreme manifestations of vasodilatory shock may lead to circulatory failure and lactic acidosis. Because of large prevalence of alcoholism and disulfiram medication, emergency physicians and medical specialists should be aware of this life-threatening condition, with its misleading presentation.

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.

Extracorporeal cardiopulmonary resuscitation for refractory in-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a rescue therapy for refractory cardiac arrest, but its high mortality has raised questions about patient selection. No selection criteria have been proposed for patients experiencing in-hospital cardiac arrest. We aimed to identify selection criteria available at the time ECPR was considered for patients with in-hospital cardiac arrest. We analyzed data of in-hospital cardiac arrest patients undergoing ECPR in our extracorporeal membrane oxygenation (ECMO) center (March 2007 to March 2019). Intensive care unit (ICU) and 1-year survival post-hospital discharge were assessed. Factors associated with ICU survival before ECPR were investigated. An external validation cohort from a previous multicenter study was used to validate our results. RESULTS: Among the 137 patients (67.9% men; median [IQR] age, 54 [43-62] years; low-flow duration, 45 [30-70] min) requiring ECPR, 32.1% were weaned-off ECMO. Their respective ICU- and 1-year survival rates were 21.9% and 19%. Most 1-year survivors had favorable neurological outcomes (cerebral performance category score 1 or 2). ICU survivors compared to nonsurvivors, respectively, were more likely to have a shockable initial rhythm (53.3% versus 24.3%; P < 0.01), a shorter median (IQR) low-flow time (30 (25-53) versus 50 (35-80) min, P < 0.01) and they more frequently underwent a subsequent intervention (63.3% versus 26.2%, P < 0.01). The algorithm obtained by combining age, initial rhythm and low-flow duration discriminated between patient groups with very different survival probabilities in the derivation and validation cohorts. CONCLUSION: Survival of ECPR-managed in-hospital cardiac arrest patients in this cohort was poor but hospital survivors' 1-year neurological outcomes were favorable. When deciding whether or not to use ECPR, the combination of age, initial rhythm and low-flow duration can improve patient selection.

A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) is a challenging diagnosis and is associated with extremely high mortality in critically ill patients, particularly due to delayed diagnosis and when complicated by intestinal necrosis. Plasma citrulline and intestinal-fatty acid binding protein (I-FABP) have been proposed as potential biomarkers, but have never been studied prospectively in this setting. We aimed to investigate diagnostic features, the accuracy of plasma citrulline and I-FABP to diagnose NOMI and intestinal necrosis as well as prognosis. METHODS: We conducted a prospective observational study in 3 tertiary ICU centers in consecutive patients with NOMI suspicion defined by at least two inclusion criteria among: new-onset or worsening circulatory failure, gastrointestinal dysfunction, biological signs and CT-scan signs of mesenteric ischemia. Diagnosis features and outcomes were compared according to NOMI, intestinal necrosis or ruled out diagnosis using stringent classification criteria. RESULTS: Diagnosis of NOMI was suspected in 61 patients and confirmed for 33 patients, with intestinal necrosis occurring in 27 patients. Clinical digestive signs, routine laboratory results and CT signs of mesenteric ischemia did not discriminate intestinal necrosis from ischemia without necrosis. Plasma I-FABP was significantly increased in presence of intestinal necrosis (AUC 0.83 [0.70-0.96]). A threshold of 3114 pg/mL showed a sensitivity of 70% [50-86], specificity of 85% [55-98], a negative predictive value of 58% [36-93] and a positive predictive value 90% [67-96] for intestinal necrosis diagnosis. When intestinal necrosis was present, surgical resection was significantly associated with ICU survival (38.5%), whereas no patient survived without necrosis resection (HR = 0.31 [0.12-0.75], p = 0.01). CONCLUSION: In critically ill patients with NOMI, intestinal necrosis was associated with extremely high mortality, and increased survival when necrosis resection was performed. Elevated plasma I-FABP was associated with the diagnosis of intestinal necrosis. Further studies are needed to investigate plasma I-FABP and citrulline performance in less severe forms of NOMI.

Non-occlusive mesenteric ischemia: Diagnostic challenges and perspectives in the era of artificial intelligence.

Acute mesenteric ischemia (AMI) is a severe condition associated with poor prognosis, ultimately leading to death due to multiorgan failure. Several mechanisms may lead to AMI, and non-occlusive mesenteric ischemia (NOMI) represents a particular form of AMI. NOMI is prevalent in intensive care units in critically ill patients. In NOMI management, promptness and accuracy of diagnosis are paramount to achieve decisive treatment, but the last decades have been marked by failure to improve NOMI prognosis, due to lack of tools to detect this condition. While real-life diagnostic management relies on a combination of physical examination, several biomarkers, imaging, and endoscopy to detect the possibility of several grades of NOMI, research studies only focus on a few elements at a time. In the era of artificial intelligence (AI), which can aggregate thousands of variables in complex longitudinal models, the prospect of achieving accurate diagnosis through machine-learning-based algorithms may be sought. In the following work, we bring you a state-of-the-art literature review regarding NOMI, its presentation, its mechanics, and the pitfalls of routine work-up diagnostic exams including biomarkers, imaging, and endoscopy, we raise the perspectives of new biomarker exams, and finally we discuss what AI may add to the field, after summarizing what this technique encompasses.