One-Year Mental and Physical Health Assessment in Survivors after Extracorporeal Membrane Oxygenation for COVID-19-related Acute Respiratory Distress Syndrome.

Rationale: Long-term outcomes of patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome treated with extracorporeal membrane oxygenation (ECMO) are unknown. Objectives: To assess physical examination, pulmonary function tests, anxiety, depression, post-traumatic stress disorder and quality of life at 6 and 12 months after ECMO onset. Methods: Multicenter, prospective study in patients who received ECMO for COVID-19 acute respiratory distress syndrome from March to June 2020 and survived hospital discharge. Measurements and Main Results: Of 80 eligible patients, 62 were enrolled in seven French ICUs. ECMO and invasive mechanical ventilation duration were 18 (11-25) and 36 (27-62) days, respectively. All were alive, but only 19/50 (38%) returned to work and 13/42 (31%) had recovered a normal sex drive at 1 year. Pulmonary function tests were almost normal at 6 months, except for DlCO, which was still impaired at 12 months. Mental health, role-emotional, and role-physical were the most impaired domain compared with patients receiving ECMO who did not have COVID-19. One year after ICU admission, 19/43 (44%) patients had significant anxiety, 18/43 (42%) had depression symptoms, and 21/50 (42%) were at risk for post-traumatic stress disorders. Conclusions: Despite the partial recovery of the lung function tests at 1 year, the physical and psychological function of this population remains impaired. Based on the comparison with long-term follow-up of patients receiving ECMO who did not have COVID-19, poor mental and physical health may be more related to COVID-19 than to ECMO in itself, although this needs confirmation.

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. METHODS: In this multicenter, randomized trial, we assigned patients with ARDS to receive either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The same mechanical-ventilation strategies were used in both groups. The primary outcome was death from any cause at 28 days. RESULTS: After the enrollment of 205 patients, the trial was prematurely stopped by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups in the primary outcome. Four patients who did not meet the eligibility criteria were excluded. At day 28, a total of 34 of 99 patients (34.3%) in the conservative-oxygen group and 27 of 102 patients (26.5%) in the liberal-oxygen group had died (difference, 7.8 percentage points; 95% confidence interval [CI], -4.8 to 20.6). At day 90, 44.4% of the patients in the conservative-oxygen group and 30.4% of the patients in the liberal-oxygen group had died (difference, 14.0 percentage points; 95% CI, 0.7 to 27.2). Five mesenteric ischemic events occurred in the conservative-oxygen group. CONCLUSIONS: Among patients with ARDS, early exposure to a conservative-oxygenation strategy with a Pao2 between 55 and 70 mm Hg did not increase survival at 28 days. (Funded by the French Ministry of Health; LOCO2 ClinicalTrials.gov number, NCT02713451.).

Prone Positioning During Extracorporeal Membrane Oxygenation in Patients With Severe ARDS: The PRONECMO Randomized Clinical Trial.

Importance: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. Objective: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. Design, Setting, and Participants: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. Interventions: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). Main Outcomes and Measures: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation-free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. Results: Among 170 randomized patients (median age, 51 [IQR, 43-59] years; n = 60 women [35%]), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19-related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% [95% CI, -14.9% to 15.2%]; subdistribution hazard ratio, 1.11 [95% CI, 0.71-1.75]; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, -4.9 [95% CI, -11.2 to 1.5] days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 2.4% [95% CI, -13.9% to 18.6%]; P = .62). No serious adverse events were reported during the prone position procedure. Conclusions and Relevance: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. Trial Registration: ClinicalTrials.gov Identifier: NCT04607551.

Optimizing PO2 during peripheral veno-arterial ECMO: a narrative review.

During refractory cardiogenic shock and cardiac arrest, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to restore a circulatory output. However, it also impacts significantly arterial oxygenation. Recent guidelines of the Extracorporeal Life Support Organization (ELSO) recommend targeting postoxygenator partial pressure of oxygen (PPOSTO2) around 150 mmHg. In this narrative review, we intend to summarize the rationale and evidence for this PPOSTO2 target recommendation. Because this is the most used configuration, we focus on peripheral VA-ECMO. To date, clinicians do not know how to set the sweep gas oxygen fraction (FSO2). Because of the oxygenator's performance, arterial hyperoxemia is common during VA-ECMO support. Interpretation of oxygenation is complex in this setting because of the dual circulation phenomenon, depending on both the native cardiac output and the VA-ECMO blood flow. Such dual circulation results in dual oxygenation, with heterogeneous oxygen partial pressure (PO2) along the aorta, and heterogeneous oxygenation between organs, depending on the mixing zone location. Data regarding oxygenation during VA-ECMO are scarce, but several observational studies have reported an association between hyperoxemia and mortality, especially after refractory cardiac arrest. While hyperoxemia should be avoided, there are also more and more studies in non-ECMO patients suggesting the harm of a too restrictive oxygenation strategy. Finally, setting FSO2 to target strict normoxemia is challenging because continuous monitoring of postoxygenator oxygen saturation is not widely available. The threshold of PPOSTO2 around 150 mmHg is supported by limited evidence but aims at respecting a safe margin, avoiding both hypoxemia and severe hyperoxemia.

Evaluating the Risk of Irreversible Intestinal Necrosis Among Critically Ill Patients With Nonocclusive Mesenteric Ischemia.

INTRODUCTION: To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS: All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS: We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate <40%. These factors were included in a new NOMI-ITN score, with 1 point attributed for each variable. ITN was observed in 6%, 38%, 65%, 88%, and 100% of patients with NOMI-ITN score ranging from 0 to 4, respectively. The NOMI-ITN score outperformed the Clichy score for the prediction of ITN (area under the receiver operating characteristics curve 0.882 [95% confidence interval 0.826-0.938] vs 0.674 [95% confidence interval 0.582-0.766], respectively, P < 0.001). DISCUSSION: We propose a new 4-point score aimed at stratifying risk of ITN in patients with NOMI. The Clichy score should be applied to patients with occlusive acute mesenteric ischemia only.

Diagnostic performance of CT for the detection of transmural bowel necrosis in non-occlusive mesenteric ischemia.

OBJECTIVES: To evaluate the diagnostic performance of CT for transmural necrosis (TN) in non-occlusive mesenteric ischemia (NOMI) according to the bowel segment involved. METHODS: From January 2009 to December 2019, all patients admitted to the intensive care unit (ICU) and requiring laparotomy for NOMI were retrospectively studied. CT had to have been performed within 24 h prior to laparotomy and were reviewed by two abdominal radiologists, with a consensus reading in case of disagreement. A set of CT features of mesenteric ischemia were assessed, separating the stomach, jejunum, ileum, and right (RC) and left colon (LC). Univariate and multivariate analyses were performed to identify features associated with TN. Its influence on overall survival (OS) was assessed. RESULTS: Among 145 patients, 95 (66%) had ≥ 1 bowel segment with TN, including 7 (5%), 31 (21%), 43 (29%), 45 (31%), and 52 (35%) in the stomach, jejunum, ileum, RC, and LC, respectively. Overall inter-reader agreement of CT features was significantly lower in the colon than in the small bowel (0.59 [0.52-0.65] vs 0.74 [0.70-0.77] respectively). The absence of bowel wall enhancement was the only CT feature associated with TN by multivariate analysis, whatever the bowel segment involved. Proximal TN was associated with poorer OS (p < 0.001). CONCLUSIONS: The absence of bowel wall enhancement remains the most consistent CT feature of transmural necrosis, whatever the bowel segment involved in NOMI. Inter-reader agreement of CT features is lower in the colon than in the small bowel. Proximal TN seems to be associated with poorer OS. KEY POINTS: • The absence of bowel wall enhancement is the most consistent CT feature associated with transmural necrosis in NOMI, whatever is the bowel segment involved. • Inter-reader agreement is lower in the colon than in the small bowel in NOMI. • In NOMI, the more proximal the bowel necrosis, the worse the prognosis.

Semi-elemental versus polymeric formula for enteral nutrition in brain-injured critically ill patients: a randomized trial.

BACKGROUND: The properties of semi-elemental enteral nutrition might theoretically improve gastrointestinal tolerance in brain-injured patients, known to suffer gastroparesis. The purpose of this study was to compare the efficacy and tolerance of a semi-elemental versus a polymeric formula for enteral nutrition (EN) in brain-injured critically ill patients. METHODS: Prospective, randomized study including brain-injured adult patients [Glasgow Coma Scale (GCS) ≤ 8] with an expected duration of mechanical ventilation > 48 h. INTERVENTION: an enteral semi-elemental (SE group) or polymeric (P group) formula. EN was started within 36 h after admission to the intensive care unit and was delivered according to a standardized nurse-driven protocol. The primary endpoint was the percentage of patients who received both 60% of the daily energy goal at 3 days and 100% of the daily energy goal at 5 days after inclusion. Tolerance of EN was assessed by the rate of gastroparesis, vomiting and diarrhea. RESULTS: Respectively, 100 and 95 patients were analyzed in the SE and P groups: Age (57[44-65] versus 55[40-65] years) and GCS (6[3-7] versus 5[3-7]) did not differ between groups. The percentage of patients achieving the primary endpoint was similar (46% and 48%, respectively; relative risk (RR) [95% confidence interval (CI)] = 1.05 (0.78-1.42); p = 0.73). The mean daily energy intake was, respectively, 20.2 ± 6.3 versus 21.0 ± 6.5 kcal/kg/day (p = 0.42). Protein intakes were 1.3 ± 0.4 versus 1.1 ± 0.3 g/kg/day (p < 0.0001). Respectively, 18% versus 12% patients presented gastroparesis (p = 0.21), and 16% versus 8% patients suffered from diarrhea (p = 0.11). No patient presented vomiting in either group. CONCLUSION: Semi-elemental compared to polymeric formula did not improve daily energy intake or gastrointestinal tolerance of enteral nutrition. TRIAL REGISTRATION: EudraCT/ID-RCB 2012-A00078-35 (registered January 17, 2012).

Malposition of the Extracorporeal Membrane Oxygenation Venous Cannula in an Accessory Hepatic Vein.

We report a case of a refractory cardiogenic shock secondary to myocardial infarction in a 70-year-old patient requiring femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO). At initial transesophageal echocardiography, the venous cannula tip was seen in the inferior vena cava (IVC), but not in right atrium. On day 8, ultrasonic examination identified that the end of the venous cannula was in the hepatic vein (HV). Despite such malposition, no disturbance in extracorporeal membrane oxygenation (ECMO) venous return was observed. Moving or replacing the cannula was considered a high-risk maneuver potentially resulting in hepatic laceration with hemoperitoneum. Because of adequate venous drainage, allowing sufficient blood flow, venous cannula repositioning was delayed until day 10, when a ventricular defect was repaired and ECMO was weaned off. At the time of VA-ECMO implantation, the venous cannula has to be positioned in the right atrium using real time echo monitoring. Visualization of the guide wire in the IVC but not in the right atrium is insufficient to ensure appropriate venous cannula positioning. Indeed, either accidental catheterization or cannula migration into the HV is possible during ECMO. Health care professionals dealing with ECMO have to be aware of this possible malposition, to correct it and prevent insufficient venous drainage or traumatic complications.

Should we perform decompressive laparotomy during severe acute pancreatitis with intra-abdominal hypertension below 25 mmHg: Only the gut knows.

We suggest that during severe acute pancreatitis (SAP) with intra-abdominal hypertension, practitioners should consider decompressive laparotomy, even with intra-abdominal pressure (IAP) below 25 mmHg. Indeed, in this setting, non-occlusive mesenteric ischemia (NOMI) may occur even with IAP below this cutoff and lead to transmural necrosis if abdominal perfusion pressure is not promptly restored. We report our experience of 18 critically ill patients with SAP having undergone decompressive laparotomy of which one third had NOMI while IAP was mostly below 25 mmHg.

Plasma citrulline concentration and plasma LPS detection among critically ill patients a prospective observational study.

PURPOSE: Gut can be a source of sepsis but sepsis itself can induce gut dysfunction. We aimed to study whether plasma citrulline, a marker of enterocyte mass, was correlated with plasma lipopolysaccharide, a potential marker of bacterial translocation among critically ill patients. MATERIALS AND METHODS: Critically ill patients admitted to the ICU. Plasma citrulline and plasma LPS concentration and activity were measured at ICU admission. Patients were compared according to the presence of sepsis at ICU admission. RESULTS: 109 critically ill patients, with SOFA score 8 [6-12], were prospectively included. Sixty six patients (61%) had sepsis at ICU admission. There was no correlation between plasma citrulline concentration and plasma LPS concentration or activity. However, sepsis at ICU admission was associated with a lower plasma citrulline concentration (13.4 µmol.L-1 vs 21.3 µmol.L-1, p = 0.02). Plasma LPS activity was significantly higher among patients with abdominal sepsis compared to patients with extra-abdominal sepsis (1.04 EU/mL vs 0.63, p = 0.01). CONCLUSIONS: Plasma citrulline is not associated with the level of plasma LPS but is strongly decreased among septic patients. Detection of LPS is ubiquitous among critically ill patients but abdominal sepsis is associated with increased plasma LPS activity compared to extra-abdominal sepsis.

Oxygenation management during veno-arterial ECMO support for cardiogenic shock: a multicentric retrospective cohort study.

BACKGOUND: Hyperoxemia is common and associated with poor outcome during veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. However, little is known about practical daily management of oxygenation. Then, we aim to describe sweep gas oxygen fraction (FSO2), postoxygenator oxygen partial pressure (PPOSTO2), inspired oxygen fraction (FIO2), and right radial arterial oxygen partial pressure (PaO2) between day 1 and day 7 of peripheral VA ECMO support. We also aim to evaluate the association between oxygenation parameters and outcome. In this retrospective multicentric study, each participating center had to report data on the last 10 eligible patients for whom the ICU stay was terminated. Patients with extracorporeal cardiopulmonary resuscitation were excluded. Primary endpoint was individual mean FSO2 during the seven first days of ECMO support (FSO2 mean (day 1-7)). RESULTS: Between August 2019 and March 2022, 139 patients were enrolled in 14 ECMO centers in France, and one in Switzerland. Among them, the median value for FSO2 mean (day 1-7) was 70 [57; 79] % but varied according to center case volume. Compared to high volume centers, centers with less than 30 VA-ECMO runs per year were more likely to maintain FSO2 ≥ 70% (OR 5.04, CI 95% [1.39; 20.4], p = 0.017). Median value for right radial PaO2 mean (day 1-7) was 114 [92; 145] mmHg, and decreased from 125 [86; 207] mmHg at day 1, to 97 [81; 133] mmHg at day 3 (p < 0.01). Severe hyperoxemia (i.e. right radial PaO2 ≥ 300 mmHg) occurred in 16 patients (12%). PPOSTO2, a surrogate of the lower body oxygenation, was measured in only 39 patients (28%) among four centers. The median value of PPOSTO2 mean (day 1-7) value was 198 [169; 231] mmHg. By multivariate analysis, age (OR 1.07, CI95% [1.03-1.11], p < 0.001), FSO2 mean (day 1-3)(OR 1.03 [1.00-1.06], p = 0.039), and right radial PaO2 mean (day 1-3) (OR 1.03, CI95% [1.00-1.02], p = 0.023) were associated with in-ICU mortality. CONCLUSION: In a multicentric cohort of cardiogenic shock supported by VA ECMO, the median value for FSO2 mean (day 1-7) was 70 [57; 79] %. PPOSTO2 monitoring was infrequent and revealed significant hyperoxemia. Higher FSO2 mean (day 1-3) and right radial PaO2 mean (day 1-3) were independently associated with in-ICU mortality.

Coma With Hyperammonemia in a Patient With Kwashiorkor.

We describe a case of coma-related hyperammonemia in a woman presenting with severe edematous malnutrition (Kwashiorkor-like), without underlying hepatic disease. Our main hypothesis is that the patient developed a functional urea cycle disorder, due to the inability to synthesize N-acetylglutamate which is the activator of the first enzymes (carbamoyl phosphate synthetase) of urea cycle, in a context of severe deficiency of essential amino acids and of acetyl-CoA. Severe hyperammonemia is a medical emergency exposing to the risk of cerebral edema. Urgent treatment should interrupt protein intake, stimulate protein anabolism, and remove ammonia from the blood using renal replacement therapy and ammonia scavengers. Hyperammonemia should be searched in case of unexplained coma, even among patients without hepatic disorder, in particular among young patients. Hyperammonemia should also be searched among patients with severe protein-calorie malnutrition.