Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center.

BACKGROUND: Molecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects. METHODS: All intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy. RESULTS: We reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01). CONCLUSION: In this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.

Hydroxyethyl Starch for Fluid Management in Patients Undergoing Major Abdominal Surgery: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

BACKGROUND: In critically ill patients, warnings about a risk of death and acute kidney injury (AKI) with hydroxyethyl starch (HES) solutions have been raised. However, HES solutions may yet have a role to play in major abdominal surgery. This meta-analysis and trial sequential analysis (TSA) aimed to investigate the effect of HES intravascular volume replacement on the risk of AKI, intraoperative blood transfusion, and postoperative intra-abdominal complications compared to crystalloid intravascular volume replacement. METHODS: In this meta-analysis and TSA, we searched for randomized controlled trials (RCTs) comparing intraoperative HES intravascular volume replacement to crystalloid intravascular volume replacement in adult patients undergoing major abdominal surgery. Primary outcome was 30-day AKI, defined as a binary outcome according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, combining stages 1, 2, and 3 into an AKI category versus no AKI category (stage 0). Secondary outcomes included rates of intraoperative blood transfusion and postoperative intra-abdominal complications. We used random effects models to calculate summary estimates. We used relative risk (RR) as summary measure for dichotomous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome (P value <.05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P value <.01 was considered statistically significant). RESULTS: Seven RCTs including 2398 patients were included. HES intravascular volume replacement was not associated with an increased risk of 30-day AKI (RR = 1.22, 95% CI, 0.94-1.59; P = .13), when compared to crystalloid intravascular volume replacement. According to TSA, this analysis was underpowered. HES intravascular volume replacement was associated with higher rates of blood transfusion (RR = 1.57 99% CI, 1.10-2.25; P = .001), and similar rates of postoperative intra-abdominal complications (RR = 0.76 99% CI, 0.57-1.02; P = .02). CONCLUSIONS: In this meta-analysis to focus on HES intravascular volume replacement in major abdominal surgery, HES intravascular volume replacement was not associated with a higher risk of 30-day AKI when compared to crystalloid intravascular volume replacement. However, CI and TSA do not exclude harmful effects of HES intravascular volume replacement on the renal function.

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Rationale: Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. Objectives: To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness. To perform a comprehensive ultrasound-based characterization of histological and force production changes occurring in the diaphragm. Methods: Translational study using critically ill patients and mechanically ventilated piglets. Serial ultrasound examination of the diaphragm collecting thickness and SM was performed in both patients and piglets. Transdiaphragmatic pressure and diaphragmatic biopsies were collected in piglets. Measurements and Main Results: We enrolled 102 patients, 88 of whom were invasively mechanically ventilated. At baseline, SM was 14.3 ± 4.3 kPa and diaphragm end-expiratory thickness was 2.0 ± 0.5 mm. Decrease or increase by more than 10% from baseline was reported in 86% of the patients for thickness and in 92% of the patients for SM. An increase in diaphragmatic thickness during the stay was associated with a decrease in SM (ß = -9.34 ± 4.41; P = 0.03) after multivariable analysis. In the piglet sample, a decrease in SM over 3 days of mechanical ventilation was associated with loss of force production, slow and fast fiber atrophy, and increased lipid droplets accumulation. Conclusions: Increases in diaphragm thickness during critical illness is associated with decreased tissue stiffness as demonstrated by shear wave ultrasound elastography, consistent with the development of muscle injury and weakness. Clinical trial registered with www.clinicaltrials.gov (NCT03550222).

Pectoral Nerve Blocks for Breast Augmentation Surgery: A Randomized, Double-blind, Dual-centered Controlled Trial.

BACKGROUND: Pectoral nerve blocks have been proposed for analgesia during and after breast cancer surgery, but data are conflicted in aesthetic breast surgery. This trial tested the primary hypothesis that adding a preincisional pectoral nerve block is superior to systemic multimodal analgesic regimen alone for pain control after breast augmentation surgery. A second hypothesis is that rescue opioid consumption would be decreased with a long-lasting effect for both outcomes during the following days. METHODS: Seventy-three adult female patients undergoing aesthetic breast augmentation surgery under general anesthesia were randomly allocated to receive a pectoral nerve block versus no block. Both groups received standard care with protocolized multimodal analgesia alone including systematic acetaminophen and nonsteroidal anti-inflammatory drugs. The primary outcome measure was the maximal numerical rating scale in the first 6 h after extubation. Secondary outcomes included intraoperative remifentanil consumption and from extubation to day 5: maximal numerical rating scale, postoperative cumulative opioid consumption and postoperative opioid side effects, and patient satisfaction recorded at day 5. RESULTS: The maximal numerical rating scale score in the first 6 h was lower in the pectoral nerve block group compared with the control group (3.9 ± 2.5 vs. 5.2 ± 2.2; difference: -1.2 [95% CI, -2.3 to -0.1]; P = 0.036). The pectoral nerve block group had a lower maximal numerical rating scale between days 1 and 5 (2.2 ± 1.9 vs. 3.2 ± 1.7; P = 0.032). The cumulative amount of overall opioids consumption (oral morphine equivalent) was lower for the pectoral nerve block group from hour 6 to day 1 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 31.5] mg, P = 0.006) and from days 1 to 5 (0.0 [0.0 to 21.0] vs. 21.0 [0.0 to 51] mg, P = 0.002). CONCLUSIONS: Pectoral nerve block in conjunction with multimodal analgesia provides effective perioperative pain relief after aesthetic breast surgery and is associated with reduced opioid consumption over the first 5 postoperative days.

Posterior Quadratus Lumborum Block in Total Hip Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Pain management is important for ensuring early mobilization after hip arthroplasty; however, the optimal components remain controversial. Recently, the quadratus lumborum block has been proposed as an analgesic option. The current study tested the hypothesis that the posterior quadratus lumborum block combined with multimodal analgesia decreases morphine consumption after hip arthroplasty. METHODS: This study was a prospective, randomized, double-blind, placebo-controlled trial. Before general anesthesia, 100 participating patients scheduled for elective total hip arthroplasty were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.33% ropivacaine (n = 50) or normal saline (n = 50). For all patients, multimodal analgesia included systematic administration of acetaminophen, ketoprofen, and a morphine intravenous patient-controlled analgesia. The primary outcome was total intravenous morphine consumption in the first 24 h. Secondary outcomes recorded intraoperative sufentanil consumption; morphine consumption in the postanesthesia care unit; pain scores at extubation and at 2, 6, 12, and 24 h; motor blockade; time to first standing and ambulation; hospital length of stay; and adverse events. RESULTS: There was no significant difference in the 24-h total morphine consumption (ropivacaine group, median [interquartile range], 13 [7 to 21] versus saline group, 16 [9 to 21] mg; median difference, -1.5; 95% CI, -5 to 2; P = 0.337). Pain scores were not different between the groups (ß = -0.4; 95% CI, -0.9 to 0.2; P = 0.199). There was no statistical difference between the two groups in intraoperative sufentanil consumption, morphine consumption in the postanesthesia care unit, motor blockade, times to first standing (median difference, 0.83 h; 95% CI, -1.7 to 3.4; P = 0.690) and ambulation (median difference, -1.85 h; 95% CI, -4.5 to 0.8; P = 0.173), hospital length of stay, and adverse events. CONCLUSIONS: After elective hip arthroplasty, neither morphine consumption nor pain scores were reduced by the addition of a posterior quadratus lumborum block to a multimodal analgesia regimen.

Reversibility of Acute Kidney Injury in Medical ICU Patients: Predictability Performance of Urinary Tissue Inhibitor of Metalloproteinase-2 x Insulin-Like Growth Factor-Binding Protein 7 and Renal Resistive Index.

OBJECTIVES: Urinary biomarkers and renal Doppler sonography remain considered as promising tools to distinguish transient from persistent acute kidney injury. The performance of the urinary biomarker, tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 and of renal resistive index to predict persistent acute kidney injury showed contradictory results. Our aim was to evaluate the performance of tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 and renal resistive index in predicting reversibility of acute kidney injury in critically ill patients. DESIGN: Prospective observational study. SETTING: Twenty-bed medical ICU in an university hospital. PATIENTS: Consecutive patients with acute kidney injury. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Renal resistive index was measured within 12 hours after admission, and urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 was measured at H0, H6, H12, and H24. Renal dysfunction reversibility was evaluated at day 3. Receiver operating characteristic curves were plotted to evaluate diagnostic performance of renal resistive index and tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 to predict a persistent acute kidney injury. Overall, 100 patients were included in whom 50 with persistent acute kidney injury. Renal resistive index was higher in persistent acute kidney injury group. Urinary tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was not significantly different at each time between both groups. The performance of tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was poor with respectively an area under the receiver operating characteristic curves of 0.57 (95% CI, 0.45-0.68), 0.58 (95% CI, 0.47-0.69), 0.61 (95% CI, 0.50-0.72), and 0.57 (95% CI, 0.46-0.68) at H0, H6, H12, and H24. The area under the receiver operating characteristic curve for renal resistive index was 0.93 (95% CI, 0.89-0.98). A renal resistive index greater than or equal to 0.685 predicting persistent acute kidney injury with 78% (95% CI, 64-88%) sensitivity and 90% (95% CI, 78-97%) specificity. CONCLUSIONS: Renal resistive index had a good performance for predicting the reversibility of acute kidney injury in critically ill patients. Urinary tissue inhibitor of metalloproteinase-2 x insulin-like growth factor-binding protein 7 was unable to differentiate transient from persistent acute kidney injury.

Correction to: Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients.

In the publication of this article [1], there was an error in the Family Name of one of the authors. This has now been updated in the original article.

Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients.

BACKGROUND: Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated. METHODS: Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency. RESULTS: We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50-0.94]), the biceps brachii (ICC 0.88 [0.67-0.96]) and the rectus femoris (ICC 0.76 [0.34-0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71-0.98], 0.93 [0.82-0.98] and 0.92 [0.81-0.98] for the diaphragm; 0.96 [0.86-0.99], 0.98 [0.94-0.99] and 0.99 [0.96-1] for the biceps brachii and 0.91 [0.51-0.98], 0.97 [0.93-0.99] and 0.99 [0.97-1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively. CONCLUSIONS: SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients. TRIAL REGISTRATION: The study was registered (ClinicalTrial NCT03550222).

Management and outcomes of COVID-19 patients admitted in a newly created ICU and an expert ICU, a retrospective observational study.

BACKGROUND: The COVID-19 pandemic abruptly increased the inflow of patients requiring intensive care units (ICU). French health institutions responded by a twofold capacity increase with temporary upgraded beds, supplemental beds in pre-existing ICUs, or newly created units (New-ICU). We aimed to compare outcomes according to admission in expert pre-existing ICUs or in New-ICU. METHODS: This multicenter retrospective observational study was conducted in two 20-bed expert ICUs of a University Hospital (Expert-ICU) and in one 16-bed New-ICU in a private clinic managed respectively by 3 and 2 physicians during daytime and by one physician during the night shift. All consecutive adult patients with COVID-19-related acute hypoxemic respiratory failure admitted after centralized regional management by a dedicated crisis cell were included. The primary outcome was 180-day mortality. Propensity score matching and restricted cubic spline for predicted mortality over time were performed. RESULTS: During the study period, 165 and 176 patients were enrolled in Expert-ICU and New-ICU respectively, 162 (98%) and 157 (89%) patients were analyzed. The unadjusted 180-day mortality was 30.8% in Expert-ICU and 28.7% in New-ICU, (log-rank test, p = 0.7). After propensity score matching, 123 pairs (76 and 78%) of patients were matched, with no significant difference in mortality (32% vs. 32%, OR 1.00 [0.89; 1.12], p = 1). Adjusted predicted mortality decreased over time (p < 0.01) in both Expert-ICU and New-ICU. CONCLUSIONS: In COVID-19 patients with acute hypoxemic respiratory failure, hospitalization in a new ICU was not associated with mortality at day 180.

Which spontaneous breathing trial to predict effort to breathe after extubation according to five critical illnesses: the cross-over GLOBAL WEAN study protocol.

INTRODUCTION: Readiness to be freed from ventilatory support can be evaluated by spontaneous breathing trial (SBT) assessing the patient's ability to sustain respiratory effort after extubation. Current SBT practices are heterogenous and there are few physiological studies on the topic. The objective of this study is to assess which SBT best reproduces inspiratory effort to breathe after extubation depending on the patient's illness. METHODS AND ANALYSIS: This will be a multicentre randomised cross-over physiological study, in a large population, in the era of modern intensive care units using last generation modern ventilators. Each included patient will perform three 15-minute SBTs in a random order: pressure support ventilation (PSV) level of 7 cmH2O with positive end expiratory pressure (PEEP) level of 0 cmH2O, PSV 0 cmH2O with PEEP 0 cmH2O and T-piece trial. A rest period of baseline state ventilation will be observed between the SBTs (10 min) and before extubation (30 min). Primary outcome will be the inspiratory muscle effort, reflected by pressure time product per minute (PTPmin). This will be calculated from oesophageal pressure measurements at baseline state, before and after each SBT and 20 min after extubation. Secondary outcomes will be PTPmin at 24 hours and 48 hours after extubation, changes in physiological variables and respiratory parameters at each step, postextubation respiratory management and the rate of successful extubation. One hundred patients with at least 24 hours of invasive mechanical ventilation will be analysed, divided into five categories of critical illness: abdominal surgery, brain injury, chest trauma, chronic obstructive pulmonary disease and miscellaneous (pneumonia, sepsis, heart disease). ETHICS AND DISSEMINATION: The study project was approved by the appropriate ethics committee (2019-A01063-54, Comité de Protection des Personnes TOURS - Région Centre - Ouest 1, France). Informed consent is required, for all patients or surrogate in case of inability to give consent. TRIAL REGISTRATION NUMBER: NCT04222569.

Outcomes and time trends of acute respiratory distress syndrome patients with and without liver cirrhosis: an observational cohort.

BACKGROUND: In studies prior to lung-protective ventilation, liver cirrhosis in acute respiratory distress syndrome (ARDS) was associated with high mortality rates. Since patients with cirrhosis have been excluded from many trials on ARDS, their outcome when treated with lung-protective ventilation is unclear. The objectives were to assess whether cirrhosis is associated with mortality in ARDS and trends over time in mortality and severity. METHODS: We conducted a retrospective analysis of a prospective observational cohort conducted in a 20-bed tertiary ICU from October 2003 to December 2021. All consecutive adult critically ill patients with ARDS were included. ARDS was defined by the Berlin criteria. The primary outcome was 90 day mortality, assessed with Kaplan-Meier curves and multivariate Cox analysis. Time trends were assessed on 90 day mortality, Sequential Organ-Function Assessment score (SOFA) and non-hepatic SOFA. Ventilation settings were compared between patients with and without cirrhosis. RESULTS: Of the 7155 patients screened, 863 had a diagnosis of ARDS. Among these ARDS patients, 157(18%) had cirrhosis. The overall 90 day mortality was of 43% (378/863), 57% (90/157) in patients with cirrhosis and 41% (288/706) in patients without cirrhosis (p < 0.001). On survival curves, cirrhosis was associated with 90 day mortality (p < 0.001). Cirrhosis was independently associated with 90 day mortality in multivariate analysis (hazard ratio = 1.56, 95% confidence interval 1.20-2.02). There was no change in mortality over time in ARDS patients with and without cirrhosis. SOFA (p = 0.04) and non-hepatic SOFA (p = 0.02) increased over time in ARDS patients without cirrhosis, and remained stable in ARDS patients with cirrhosis. Tidal volume, positive end-expiratory pressure, plateau pressure and driving pressure were not different between ARDS patients with and without cirrhosis. CONCLUSIONS: Although ARDS management improved over the last decades, the 90 day mortality remained high and stable over time for both ARDS patients with (57%) and without cirrhosis (41%). Nevertheless, the severity of patients without cirrhosis has increased over time, while the severity of patients with cirrhosis has remained stable.