Pressure control plus spontaneous ventilation versus volume assist-control ventilation in acute respiratory distress syndrome. A randomised clinical trial.

PURPOSE: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS). METHODS: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO2/FiO2 < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60. RESULTS: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups. CONCLUSIONS: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels.

Modes of administration of nitric oxide devices and ventilators flow-by impact the delivery of pre-determined concentrations.

BACKGROUND: Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators' flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. METHODS: We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. RESULTS: We identified three iNO-device generations based on the way they deliver NO flow: "Continuous", "Sequential to inspiratory phase" (I-Sequential) and "Proportional to inspiratory and expiratory ventilator flow" (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. CONCLUSION: We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations' accuracy. Ventilator's flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

Hematological features and alternate diagnoses in critically ill thrombotic antiphospholipid syndrome patients.

OBJECTIVES: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome. METHODS: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied. RESULTS: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients. CONCLUSION: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated.

A new physiological manikin to test and compare ventilation devices during cardiopulmonary resuscitation.

Background: There is a lack of bench systems permitting to evaluate ventilation devices in the specific context of cardiac arrest. Objectives: The objective of the study is to assess if a new physiological manikin may permit to evaluate the performances of medical devices dedicated to ventilation during cardiopulmonary resuscitation (CPR). Methods: Specific CPR-related features required to reproduce realistic ventilation were implemented into the SAM (Sarthe Anjou Mayenne) manikin. In the first place, the manikin ability to mimic ventilation during CPR was assessed and compared to real-life tracings of airway pressure, flow and capnogram from three out of hospital cardiac arrest (OHCA) patients. In addition, to illustrate the interest of this manikin, ventilation was evaluated during mechanical continuous chest compressions with two devices dedicated to CPR: the Boussignac cardiac arrest device (B-card - Vygon; Ecouen France) and the Impedance Threshold Device (ITD - Zoll; Chelmsford, MA). Results: The SAM manikin enabled precise replication of ventilation tracings as observed in three OHCA patients during CPR, and it allowed for comparison between two distinct ventilation devices. B-card generated a mean, maximum and minimum intrathoracic pressure of 6.3 (±0.1) cmH2O, 18.9 (±1.1) cmH2O and -0.3 (±0.2) cmH2O respectively; while ITD generated a mean, maximum and minimum intrathoracic pressure of -1.6 (±0.0) cmH2O, 5.7 (±0.1) cmH2O and -4.8 (±0.1) cmH2O respectively during CPR. B-card allowed to increase passive ventilation compared to the ITD which resulted in a dramatic limitation of passive ventilation. Conclusion: The SAM manikin is an innovative model integrating specific physiological features that permit to accurately evaluate and compare ventilation devices during CPR.

Oesophageal pressure monitoring in intubated patients by intensive care units' nurses: An educational study.

Trained ICU nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. We thus conducted a prospective educational study aiming to assess the ability of ICU nurses to perform reliable oesophageal pressure measurements after a short dedicated training program. All the 11 nurses who completed the program succeeded their practical evaluation (nine (82%) at the first evaluation and two (18%) at their second attempt). These results show that this training program is feasible and that trained ICU nurses can perform accurate oesophageal pressure measurements in mechanically ventilated patients.

Bedside personalized methods based on electrical impedance tomography or respiratory mechanics to set PEEP in ARDS and recruitment-to-inflation ratio: a physiologic study.

BACKGROUND: Various Positive End-Expiratory Pressure (PEEP) titration strategies have been proposed to optimize ventilation in patients with acute respiratory distress syndrome (ARDS). We aimed to compare PEEP titration strategies based on electrical impedance tomography (EIT) to methods derived from respiratory system mechanics with or without esophageal pressure measurements, in terms of PEEP levels and association with recruitability. METHODS: Nineteen patients with ARDS were enrolled. Recruitability was assessed by the estimated Recruitment-to-Inflation ratio (R/Iest) between PEEP 15 and 5 cmH2O. Then, a decremental PEEP trial from PEEP 20 to 5 cmH2O was performed. PEEP levels determined by the following strategies were studied: (1) plateau pressure 28-30 cmH2O (Express), (2) minimal positive expiratory transpulmonary pressure (Positive PLe), (3) center of ventilation closest to 0.5 (CoV) and (4) intersection of the EIT-based overdistension and lung collapse curves (Crossing Point). In addition, the PEEP levels determined by the Crossing Point strategy were assessed using different PEEP ranges during the decremental PEEP trial. RESULTS: Express and CoV strategies led to higher PEEP levels than the Positive PLe and Crossing Point ones (17 [14-17], 20 [17-20], 8 [5-11], 10 [8-11] respectively, p < 0.001). For each strategy, there was no significant association between the optimal PEEP level and R/Iest (Crossing Point: r2 = 0.073, p = 0.263; CoV: r2 < 0.001, p = 0.941; Express: r2 < 0.001, p = 0.920; Positive PLe: r2 = 0.037, p = 0.461). The PEEP level obtained with the Crossing Point strategy was impacted by the PEEP range used during the decremental PEEP trial. CONCLUSIONS: CoV and Express strategies led to higher PEEP levels than the Crossing Point and Positive PLe strategies. Optimal PEEP levels proposed by these four methods were not associated with recruitability. Recruitability should be specifically assessed in ARDS patients to optimize PEEP titration.

3-Methylmethcathinone Intoxication: Discrepancies Between Blood Concentrations and Clinical Outcomes-A Short Communication.

BACKGROUND: The absence of a correlation between the blood concentration of 3-methylmethcathinone (3-MMC) and clinical outcomes in intoxication cases has been attributed to stability issues. Indeed, a loss of more than 50%, 70%, and even 95% of 3-MMC in whole blood after 2 weeks of storage at 20°C, 4°C, and room temperature, respectively, has been reported in the past. Here, the authors report the case of a 43-year-old man who was hospitalized with generalized convulsive status epilepticus related to 3-MMC use with a plasma concentration of 9600 ng/mL (delay between sampling and analysis <72 hours). The stability of 3-MMC was evaluated in several biological specimens. METHODS: Three quality control samples (human plasma, whole blood, and postmortem blood) spiked with 3-MMC were stored at -20°C and 4°C for 14 days. The initial analysis was performed on day 1 to establish the initial concentration of 3-MMC in each specimen type, and the samples were divided into 2 aliquots for storage under both conditions. Further analyses were performed on days 7 and 14 for each specimen, and the results were compared with those obtained on day 1. RESULTS: 3-MMC appeared relatively stable in whole and postmortem blood when stored at -20°C for 1 week, with losses of <3% in both matrices (0% and 2.5%, respectively). At +4°C, 3-MMC losses ranged from 25% to 53%. CONCLUSIONS: These results differ from others reported in the literature. Hence, it may be hypothesized that other elements should be considered to explain the discrepancy between the concentration and toxicity pointed out by the Toxicology community, especially the development of tolerance.

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).