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.

Comparative evaluation of three interfaces for non-invasive ventilation: a randomized cross-over design physiologic study on healthy volunteers.

INTRODUCTION: Interface choice is crucial for non-invasive ventilation (NIV) success. We compared a new interface, the helmet next (HN), with the facial mask (FM) and the standard helmet (HS) in twelve healthy volunteers. METHODS: In this study, five NIV trials were randomly applied, preceded and followed by a trial of unassisted spontaneous breathing (SB). Baseline settings, for example, 5 cmH2O of both inspiratory pressure support (PS) and positive end-expiratory pressure (PEEP), were applied through FM, HS and HN, while increased settings (PS and PEEP of 8 cmH2O) were only applied through HS and HN. We measured flow, airway, esophageal and gastric pressures, and calculated inspiratory effort indexes and trigger delays. Comfort was assessed with a visual-analog-scale. RESULTS: We found that FM, HS and HN at baseline settings were not significantly different with respect to inspiratory effort indexes and comfort. Inspiratory trigger delay and time of synchrony (TI,synchrony) were significantly improved by FM compared to both helmets, whereas expiratory trigger delay was shorter with FM, as opposed to HS only. HN at increased settings performed better than FM in decreasing inspiratory effort measured by pressure-time product of transdiaphragmatic pressure (PTPdi)/breath (10.7 ± 9.9 versus 17.0 ± 11.0 cmH2Os), and PTPdi/min (128 ± 96 versus 204 ± 81 cmH2Os/min), and PTPdi/L (12.6 ± 9.9 versus 30.2 ± 16.8 cmH2Os/L). TI, synchrony was inferior between HN and HS at increased settings and FM. CONCLUSIONS: HN might hold some advantages with respect to interaction and synchrony between subject and ventilator, but studies on patients are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01610960.

Assessing pain in paralyzed critically ill patients receiving neuromuscular blocking agents: A monocenter prospective cohort.

INTRODUCTION: Given the absence of established recommendations for pain assessment in pharmacologically paralyzed Intensive-Care-Units (ICU) patients under Neuro-Muscular-Blocking Agents (NMBA), this study assessed the validity of various parameters for evaluating pain in this specific population. PATIENTS AND METHODS: Four electrophysiological parameters (instant-Analgesia-Nociception-Index (ANI), Bispectral index (BIS), Heart Rate (HR) and Mean Arterial Blood Pressure (ABP)) and one clinical parameter (Behavioural-Pain-Scale (BPS)) were recorded during tracheal-suctioning in all consecutive ICU patients who required a continuous infusion of cisatracurium, before and just after paralysis recovery measured by Train-of-Four ratio. The validity of the five pain-related parameters was assessed by comparing the values recorded during different situations (before/during/after the nociceptive procedure) (discriminant-validity, primary outcome), and the effect of paralysis was assessed by comparing values obtained during and after paralysis (reliability, secondary outcome). RESULTS: Twenty patients were analyzed. ANI, BIS, and HR significantly changed during the nociceptive procedure in both paralysis and recovery, while BPS changed only post-recovery. ANI and HR were unaffected by paralysis, unlike BIS and BPS (mixed-effect model). ANI exhibited the highest discriminant-validity, with values (min 0/max 100) decreasing from 71 [48-89] at rest to 41 [25-72] during tracheal suctioning in paralyzed patients, and from 71 [53-85] at rest to 40 [31-52] in non-paralyzed patients. CONCLUSIONS: ANI proves the most discriminant parameter for pain detection in both paralyzed and non-paralyzed sedated ICU patients. Its significant and clinically relevant decrease during tracheal suctioning remains unaltered by NMBA use. Pending further studies on analgesia protocols based on ANI, it could be used to assess pain during nociceptive procedures in ICU patients receiving NMBA.

Improving the ability of image sensors to detect faint stars and moving objects using image deconvolution techniques.

In this paper we show how the techniques of image deconvolution can increase the ability of image sensors as, for example, CCD imagers, to detect faint stars or faint orbital objects (small satellites and space debris). In the case of faint stars, we show that this benefit is equivalent to double the quantum efficiency of the used image sensor or to increase the effective telescope aperture by more than 30% without decreasing the astrometric precision or introducing artificial bias. In the case of orbital objects, the deconvolution technique can double the signal-to-noise ratio of the image, which helps to discover and control dangerous objects as space debris or lost satellites. The benefits obtained using CCD detectors can be extrapolated to any kind of image sensors.

The 2014 updated version of the Confusion Assessment Method for the Intensive Care Unit compared to the 5th version of the Diagnostic and Statistical Manual of Mental Disorders and other current methods used by intensivists.

BACKGROUND: One third of patients admitted to an intensive care unit (ICU) will develop delirium. However, delirium is under-recognized by bedside clinicians without the use of delirium screening tools, such as the Intensive Care Delirium Screening Checklist (ICDSC) or the Confusion Assessment Method for the ICU (CAM-ICU). The CAM-ICU was updated in 2014 to improve its use by clinicians throughout the world. It has never been validated compared to the new reference standard, the Diagnostic and Statistical Manual of Mental Disorders 5th version (DSM-5). METHODS: We made a prospective psychometric study in a 16-bed medical-surgical ICU of a French academic hospital, to measure the diagnostic performance of the 2014 updated CAM-ICU compared to the DSM-5 as the reference standard. We included consecutive adult patients with a Richmond Agitation Sedation Scale (RASS) ≥ -3, without preexisting cognitive disorders, psychosis or cerebral injury. Delirium was independently assessed by neuropsychological experts using an operationalized approach to DSM-5, by investigators using the CAM-ICU and the ICDSC, by bedside clinicians and by ICU patients. The sensitivity, specificity, positive and negative predictive values were calculated considering neuropsychologist DSM-5 assessments as the reference standard (primary endpoint). CAM-ICU inter-observer agreement, as well as that between delirium diagnosis methods and the reference standard, was summarized using κ coefficients, which were subsequently compared using the Z-test. RESULTS: Delirium was diagnosed by experts in 38% of the 108 patients included for analysis. The CAM-ICU had a sensitivity of 83%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 91%. Compared to the reference standard, the CAM-ICU had a significantly (p < 0.05) higher agreement (κ = 0.86 ± 0.05) than the physicians,' residents' and nurses' diagnoses (κ = 0.65 ± 0.09; 0.63 ± 0.09; 0.61 ± 0.09, respectively), as well as the patient's own impression of feeling delirious (κ = 0.02 ± 0.11). Differences between the ICDSC (κ = 0.69 ± 0.07) and CAM-ICU were not significant (p = 0.054). The CAM-ICU demonstrated a high reliability for inter-observer agreement (κ = 0.87 ± 0.06). CONCLUSIONS: The 2014 updated version of the CAM-ICU is valid according to DSM-5 criteria and reliable regarding inter-observer agreement in a research setting. Delirium remains under-recognized by bedside clinicians.

Immediate interruption of sedation compared with usual sedation care in critically ill postoperative patients (SOS-Ventilation): a randomised, parallel-group clinical trial.

BACKGROUND: Avoidance of excessive sedation and subsequent prolonged mechanical ventilation in intensive care units (ICUs) is recommended, but no data are available for critically ill postoperative patients. We hypothesised that in such patients stopping sedation immediately after admission to the ICU could reduce unnecessary sedation and improve patient outcomes. METHODS: We did a randomised, parallel-group, clinical trial at three ICUs in France. Stratified randomisation with minimisation (1:1 via a restricted web platform) was used to assign eligible patients (aged ≥18 years, admitted to an ICU after abdominal surgery, and expected to require at least 12 h of mechanical ventilation because of a critical illness defined by a Sequential Organ Failure Assessment score >1 for any organ, but without severe acute respiratory distress syndrome or brain injury) to usual sedation care provided according to recommended practices (control group) or to immediate interruption of sedation (intervention group). The primary outcome was the time to successful extubation (defined as the time from randomisation to the time of extubation [or tracheotomy mask] for at least 48 h). All patients who underwent randomisation (except for those who were excluded after randomisation) were included in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT01486121. FINDINGS: Between Dec 2, 2011, and Feb 27, 2014, 137 patients were randomly assigned to the control (n=68) or intervention groups (n=69). In the intention-to-treat analysis, time to successful extubation was significantly lower in the intervention group than in the control group (median 8 h [IQR 4-36] vs 50 h [29-93], group difference -33·6 h [95% CI -44·9 to -22·4]; p<0·0001). The adjusted hazard ratio was 5·2 (95% CI 3·1-8·8, p<0·0001). INTERPRETATION: Immediate interruption of sedation in critically ill postoperative patients with organ dysfunction who were admitted to the ICU after abdominal surgery improved outcomes compared with usual sedation care. These findings support interruption of sedation in these patients following transfer from the operating room. FUNDING: Délégation à la Recherche Clinique et à l'Innovation du Groupement de Coopération Sanitaire de la Mission d'Enseignement, de Recherche, de Référence et d'Innovation (DRCI-GCS-MERRI) de Montpellier-Nîmes.

Diaphragmatic dysfunction in patients with ICU-acquired weakness and its impact on extubation failure.

PURPOSE: Diaphragm function is rarely studied in intensive care patients with unit-acquired weakness (ICUAW) in whom weaning from mechanical ventilation is challenging. The aim of the present study was to evaluate the diaphragm function and the outcome using a multimodal approach in ICUAW patients. METHODS: Patients were eligible if they were diagnosed for ICUAW [Medical Research Council (MRC) Score <48], mechanically ventilated for at least 48 h and were undergoing a spontaneous breathing trial. Diaphragm function was assessed using magnetic stimulation of the phrenic nerves (change in endotracheal tube pressure), maximal inspiratory pressure and ultrasonographically (thickening fraction). Diaphragmatic dysfunction was defined by a change in endotracheal tube pressure below 11 cmH2O. The endpoints were to describe the correlation between diaphragm function and ICUAW and its impact on extubation. RESULTS: Among 185 consecutive patients ventilated for more than 48 h, 40 (22 %) with a MRC score of 31 [20-36] were included. Diaphragm dysfunction was observed with ICUAW in 32 patients (80 %). Change in endotracheal tube pressure and MRC score were not correlated. Maximal inspiratory pressure was correlated with change in endotracheal tube pressure after magnetic stimulation of the phrenic nerves (r = 0.43; p = 0.005) and MRC score (r = 0.34; p = 0.02). Thickening fraction was less than 20 % in 70 % of the patients and was statistically correlated with change in endotracheal tube pressure (r = 0.4; p = 0.02) but not with MRC score. Half of the patients could be extubated without needing reintubation within 72 h. CONCLUSION: Diaphragm dysfunction is frequent in patients with ICU-acquired weakness (80 %) but poorly correlated with the ICU-acquired weakness MRC score. Half of the patients with ICU-acquired weakness were successfully extubated. Half of the patients who failed the weaning process died during the ICU stay.

Feasibility and effectiveness of prone position in morbidly obese patients with ARDS: a case-control clinical study.

BACKGROUND: Obese patients are at risk for developing atelectasis and ARDS. Prone position (PP) may reduce atelectasis, and it improves oxygenation and outcome in severe hypoxemic patients with ARDS, but little is known about its effect in obese patients with ARDS. METHODS: Morbidly obese patients (BMI ≥ 35 kg/m²) with ARDS (Pao2/FIo2 ratio ≤ 200 mm Hg) were matched to nonobese (BMI < 30 kg/m²) patients with ARDS in a case-control clinical study. The primary end points were safety and complications of PP; the secondary end points were the effect on oxygenation (Pao2/FIo2 ratio at the end of PP), length of mechanical ventilation and ICU stay, nosocomial infections, and mortality. RESULTS: Between January 2005 and December 2009, 149 patients were admitted for ARDS. Thirty-three obese patients were matched with 33 nonobese patients. Median (25th-75th percentile) PP duration was 9 h (6-11 h) in obese patients and 8 h (7-12 h) in nonobese patients (P = .28). We collected 51 complications: 25 in obese and 26 in nonobese patients. The number of patients with at least one complication was similar across groups (n = 10, 30%). Pao2/FIo2 ratio increased significantly more in obese patients (from 118 ± 43 mm Hg to 222 ± 84 mm Hg) than in nonobese patients (from 113 ± 43 mm Hg to 174 ± 80 mm Hg; P = .03). Length of mechanical ventilation, ICU stay, and nosocomial infections did not differ significantly, but mortality at 90 days was significantly lower in obese patients (27% vs 48%, P < .05). CONCLUSIONS: PP seems safe in obese patients and may improve oxygenation more than in nonobese patients. Obese patients could be a subgroup of patients with ARDS who may benefit the most of PP.