Control of Postoperative Hypotension Using a Closed-Loop System for Norepinephrine Infusion in Patients After Cardiac Surgery: A Randomized Trial.

BACKGROUND: Vasopressors are a cornerstone for the management of vasodilatory hypotension. Vasopressor infusions are currently adjusted manually to achieve a predefined arterial pressure target. We have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently during the perioperative period. We tested the hypothesis that patients managed using such a system postcardiac surgery would present less hypotension compared to patients receiving standard management. METHODS: A total of 40 patients admitted to the intensive care unit (ICU) after cardiac surgery were randomized into 2 groups for a 2-hour study period. In all patients, the objective was to maintain mean arterial pressure (MAP) between 65 and 75 mm Hg using norepinephrine. In the CLV group, the norepinephrine infusion was controlled via the CLV system; in the control group, it was adjusted manually by the ICU nurse. Fluid administration was standardized in both groups using an assisted fluid management system linked to an advanced hemodynamic monitoring system. The primary outcome was the percentage of time patients were hypotensive, defined as MAP <65 mm Hg, during the study period. RESULTS: Over the 2-hour study period, the percentage of time with hypotension was significantly lower in the CLV group than that in the control group (1.4% [0.9-2.3] vs 12.5% [9.9-24.3]; location difference, -9.8% [95% CI, -5.4 to -15.9]; P < .001). The percentage of time with MAP between 65 and 75 mm Hg was also greater in the CLV group (95% [89-96] vs 66% [59-77]; location difference, 27.6% [95% CI, 34.3-19.0]; P < .001). The percentage of time with an MAP >75 mm Hg (and norepinephrine still being infused) was also significantly lower in patients in the CLV group than that in the control group (3.2% [1.9-5.4] vs 20.6% [8.9-32.5]; location difference, -17% [95% CI, -10 to -24]; P < .001).The number of norepinephrine infusion rate modifications over the study period was greater in the CLV group than that in the control group (581 [548-597] vs 13 [11-14]; location difference, 568 [578-538]; P < .001). No adverse event occurred during the study period in both groups. CONCLUSIONS: Closed-loop control of norepinephrine infusion significantly decreases postoperative hypotension compared to manual control in patients admitted to the ICU after cardiac surgery.

Preload dependence indices to titrate volume expansion during septic shock: a randomized controlled trial.

INTRODUCTION: In septic shock, pulse pressure or cardiac output variation during passive leg raising are preload dependence indices reliable at predicting fluid responsiveness. Therefore, they may help to identify those patients who need intravascular volume expansion, while avoiding unnecessary fluid administration in the other patients. However, whether their use improves septic shock prognosis remains unknown. The aim of this study was to assess the clinical benefits of using preload dependence indices to titrate intravascular fluids during septic shock. METHODS: In a single-center randomized controlled trial, 60 septic shock patients were allocated to preload dependence indices-guided (preload dependence group) or central venous pressure-guided (control group) intravascular volume expansion with 30 patients in each group. The primary end point was time to shock resolution, defined by vasopressor weaning. RESULTS: There was no significant difference in time to shock resolution between groups (median (interquartile range) 2.0 (1.2 to 3.1) versus 2.3 (1.4 to 5.6) days in control and preload dependence groups, respectively). The daily amount of fluids administered for intravascular volume expansion was higher in the control than in the preload dependence group (917 (639 to 1,511) versus 383 (211 to 604) mL, P = 0.01), and the same held true for red cell transfusions (178 (82 to 304) versus 103 (0 to 183) mL, P = 0.04). Physiologic variable values did not change over time between groups, except for plasma lactate (time over group interaction, P <0.01). Mortality was not significantly different between groups (23% in the preload dependence group versus 47% in the control group, P = 0.10). Intravascular volume expansion was lower in the preload dependence group for patients with lower simplified acute physiology score II (SAPS II), and the opposite was found for patients in the upper two SAPS II quartiles. The amount of intravascular volume expansion did not change across the quartiles of severity in the control group, but steadily increased with severity in the preload dependence group. CONCLUSIONS: In patients with septic shock, titrating intravascular volume expansion with preload dependence indices did not change time to shock resolution, but resulted in less daily fluids intake, including red blood cells, without worsening patient outcome. TRIAL REGISTRATION: Clinicaltrials.gov NCT01972828. Registered 11 October 2013.

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING: Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS: High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01458444.

Tissue hemoglobin monitoring is unable to follow variations of arterial hemoglobin during transitions from pulsatile to constant flow in cardiac surgery.

OBJECTIVE: To test whether the variations of tissue hemoglobin concentration (∆THb) measured by the FORE-SIGHT(TM) cerebral oximeter can accurately detect changes in arterial hemoglobin concentration (∆AHb) before, during, and after cardiopulmonary bypass. DESIGN: A prospective clinical study. SETTING: Cardiac surgery operating room. PARTICIPANTS: Thirty patients scheduled for cardiac surgery. INTERVENTIONS: Tissue hemoglobin concentration (THb) was recorded continuously via 2 sensors applied on the forehead and connected to the cerebral oximeter. Arterial hemoglobin concentration (AHb) was measured in a hematology analyzer laboratory. Hemodynamic and respiratory parameters as well as epidemiologic data also were noted. Data were collected at 3 perioperative times: After induction of anesthesia, 10 minutes after cardioplegia, and at the end of the surgery. MEASUREMENTS AND MAIN RESULTS: Ninety pairs of data were collected. The coefficient of linear regression between ∆THb and ∆AHb was 0.4 (p<0.001). After exclusion of Hb variations<5%, the trending ability of THb to predict ∆AHb was 87%. However, the Bland and Altman plot graph for THb and AHb showed major limits of agreement (2.4 times the standard deviation). Central venous pressure and carbon dioxide tension were linked independently and positively with THb (p = 0.03). CONCLUSIONS: Continuous monitoring of THb cannot accurately track variations of AHb during the transition from pulsatile to continuous flow and vice versa in cardiac surgery. Local hemodynamic factors such as PaCO2 and vasodilation significantly impact THb. In this setting, THb monitoring should not be used to guide eventual blood transfusion management.

Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial.

BACKGROUND: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING: French Ministry of Health, HiFIT trial.

Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial.

BACKGROUND: COVID-19-related acute respiratory distress syndrome (ARDS) is associated with a high mortality rate and longer mechanical ventilation. We aimed to assess the effectiveness of ventilation with ultra-low tidal volume (ULTV) compared with low tidal volume (LTV) in patients with COVID-19-related ARDS. METHODS: This study was a multicentre, open-label, parallel-group, randomised trial conducted in ten intensive care units in France. Eligible participants were aged 18 years or older, received invasive mechanical ventilation for COVID-19 (confirmed by RT-PCR), had ARDS according to the Berlin definition, a partial pressure of arterial oxygen to inspiratory oxygen fraction (PaO2/FiO2) ratio of 150 mm Hg or less, a tidal volume (VT) of 6·0 mL/kg predicted bodyweight or less, and received continuous intravenous sedation. Patients were randomly assigned (1:1) using randomisation blocks to receive ULTV (intervention group) aiming for VT of 4·0 mL/kg predicted bodyweight or LTV (control group) aiming for VT 6·0 mL/kg predicted bodyweight. Participants, investigators, and outcome assessors were not masked to group assignment. The primary outcome was a ranked composite score based on all-cause mortality at day 90 as the first criterion and ventilator-free days among patients alive at day 60 as the second criterion. Effect size was computed with the unmatched win ratio, on the basis of pairwise prioritised comparison of primary outcome components between every patient in the ULTV group and every patient in the LTV group. The unmatched win ratio was calculated as the ratio of the number of pairs with more favourable outcome in the ULTV group over the number of pairs with less favourable outcome in the ULTV group. Primary analysis was done in the modified intention-to-treat population, which included all participants who were randomly assigned and not lost to follow-up. This trial is registered with ClinicalTrials.gov, NCT04349618. FINDINGS: Between April 15, 2020, and April 13, 2021, 220 patients were included and five (2%) were excluded. 215 patients were randomly assigned (106 [49%] to the ULTV group and 109 [51%] to the LTV group). 58 (27%) patients were female and 157 (73%) were male. The median age was 68 years (IQR 60-74). 214 patients completed follow-up (one lost to follow-up in the ULTV group) and were included in the modified intention-to-treat analysis. The primary outcome was not significantly different between groups (unmatched win ratio in the ULTV group 0·85 [95% CI 0·60 to 1·19]; p=0·38). 46 (44%) of 105 patients in the ULTV group and 43 (39%) of 109 in the LTV group died by day 90 (absolute difference 4% [-9 to 18]; p=0·52). The rate of severe respiratory acidosis in the first 28 days was higher in the ULTV group than in the LTV group (35 [33%] vs 14 [13%]; absolute difference 20% [95% CI 9 to 31]; p=0·0004). INTERPRETATION: In patients with moderate-to-severe COVID-19-related ARDS, there was no significant difference with ULTV compared with LTV in the composite score based on mortality and ventilator-free days among patients alive at day 60. These findings do not support the systematic use of ULTV in patients with COVID-19-related ARDS. FUNDING: French Ministry of Solidarity and Health and Hospices Civils de Lyon.

Expiratory flow-volume loop profile and patient outcome in chronic obstructive pulmonary disease in acute respiratory failure: a prospective observational study in a single intensive care unit.

BACKGROUND: Expiratory flow-volume (EFV) loops are continuously displayed on the screen of intensive care unit (ICU) ventilators. OBJECTIVES: It was the aim of this study to investigate the relationships of EFV to chronic obstructive pulmonary disease (COPD) patient outcome. METHODS: This is a prospective study on COPD patients who received invasive mechanical ventilation for acute respiratory failure in the ICU. Within the 24-hour post-intubation period, the angle of the EFV slope during the last 50% of expiration was computed and patients were stratified into 4 quartiles. Resistance, compliance of the respiratory system and change in end-expiratory lung volume above relaxation volume were assessed. Patients were followed up to hospital discharge. The main outcome was hospital mortality. Secondary outcomes were ICU mortality, length of ICU stay, duration of invasive ventilation, number of intubations, oxygen and non-invasive ventilation. RESULTS: Thirty-eight patients were analysed. The first quartile comprised 9 patients (median angle 11°, interquartile range 8-12), the second 10 patients (median angle 26°, range 19-30), the third 10 patients (median angle 42°, range 39-46), and the fourth 9 patients (median angle 53°, range 49-64). Hospital and ICU mortality were not different between groups. Lengths of ICU and hospital stay and length of invasive ventilation were significantly different between groups, with the highest values observed in the first quartile. The rate of oxygen use and non-invasive ventilation in the ICU and at hospital discharge was significantly different between groups, with the highest rate observed in the first quartile. There was a significant negative correlation between angle and resistance, compliance of the respiratory system and change in end-expiratory lung volume above the relaxation volume. CONCLUSION: The slope of the angle during the last 50% of expired volume in the COPD patients was associated with worsened respiratory mechanics and higher morbidity.

Comparison of Alpha 200 and CoughAssist as intermittent positive pressure breathing devices: a bench study.

BACKGROUND: Intermittent positive pressure breathing (IPPB) is used in non-intubated patients to increase lung volume and to enhance coughing. Alpha 200 (Salvia Lifetec, Kronberg, Germany) is a specific IPPB device. CoughAssist (Respironics France, Carquefou, France) is a mechanical insufflator-exsufflator used to remove secretions in patients with inefficient cough. Both can also be used for intubated or tracheotomized patients. We assessed the impact of various artificial airways on the ability of the Alpha 200 and CoughAssist to generate insufflated volume. METHODS: We measured the insufflated volume and pressure at the airway opening in a lung model under 2 conditions of compliance (30 or 60 mL/cm H(2)O) at single resistance of 5 cm H(2)O/L/s. The devices were used at 2 set pressures: 30 and 40 cm H(2)O. The Alpha 200 was set at 2 inflation flows: 0.5 and 1 L/s, whereas CoughAssist was set at its highest value of 10 L/s. Measurements were done without (control) and with different size endotracheal tubes and tracheostomy cannulae. The relationships between insufflated volume and measured pressure were analyzed using linear regressions. RESULTS: The slopes and intercepts of the control relationship between insufflated volume and pressure were significantly greater with Alpha 200 at each set flow than with CoughAssist. As artificial airways were used, the insufflated volume did not differ from the control with CoughAssist, while with Alpha 200 it increased at each flow setting and for all mechanical conditions. The largest differences in insufflated volume between the 2 devices were observed for the largest endotracheal tubes and tracheostomy cannulas and for the lowest inflation flow setting in Alpha 200. These results can be explained in terms of how the devices function, as CoughAssist adapts by increasing flow, while Alpha 200 adapts by increasing inspiratory time. CONCLUSIONS: This bench study has shown that in the presence of artificial airways the value of the insufflated volume generated by the CoughAssist device was significantly lower than that generated by the Alpha 200 device.

Performance of the coughassist insufflation-exsufflation device in the presence of an endotracheal tube or tracheostomy tube: a bench study.

BACKGROUND: The CoughAssist is a mechanical insufflator-exsufflator designed to assist airway secretion clearance in patients with ineffective cough. The device may benefit intubated and tracheotomized patients. We assessed the impact of various artificial airways on peak expiratory flow (PEF) with the CoughAssist. METHODS: We measured PEF and pressure at the airway opening in a lung model during insufflation-exsufflation with the CoughAssist, at 3 set pressures: 30/-30, 40/-40, and 50/-50 cm H(2)O, first without (control), and then with different sizes (6.5 to 8.5 mm inner diameter) of endotracheal tube (ETT) and tracheostomy tube (6, 7, and 8 mm inner diameter), compliance settings of 30 and 60 mL/cm H(2)O, and resistance settings of 0 and 5 cm H(2)O/L/s). We analyzed the relationship between PEF and pressure with linear regression. RESULTS: With compliance of 30 mL/cm H(2)O and 0 resistance the slope of the control relationship between PEF and pressure was statistically significantly greater than during any conditions with ETT or tracheostomy tube. Therefore, in comparison to the control, the relationship of PEF to pressure significantly went in the direction from top to bottom as the ETT or tracheostomy tube became narrower. The findings were the same with compliance of 30 mL/cm H(2)O and resistance of 5 cm H(2)O/L/s. With compliance of 60 mL/cm H(2)O the highest set pressure values were not achieved and some relationships departed from linearity. The control slope of the relationship between PEF and pressure with compliance of 60 mL/cm H(2)O and 0 resistance did not significantly differ with any ETT or tracheostomy tube. CONCLUSIONS: The artificial airways significantly reduced PEF during insufflation-exsufflation with CoughAssist; the narrower the inner diameter of the artificial airway, the lower the PEF for a given expiratory pressure.

Management and long-term outcome of patients with chronic neuromuscular disease admitted to the intensive care unit for acute respiratory failure: a single-center retrospective study.

BACKGROUND: Patients with chronic neuromuscular disease represent less than 10% of those receiving mechanical ventilation in the intensive care unit (ICU). Little has been reported regarding either ICU management of acute respiratory failure (ARF) in the era of noninvasive mechanical ventilation (NIV) or long-term outcomes. OBJECTIVE: To describe the respiratory management of patients with chronic neuromuscular diseases admitted to our university hospital ICU for ARF, and the long-term outcomes. METHODS: We retrospectively analyzed patients with chronic neuromuscular diseases admitted to our ICU for a first episode of ARF between January 1, 1996, and February 27, 2007. We assessed severity of illness on ICU admission, respiratory management during ICU stay, and outcomes on June 15, 2008. RESULTS: During the study period, 87 patients (44 with hereditary and 43 with acquired neuromuscular diseases) had their first ARF episode that required ICU admission. In the hereditary-diseases group and the acquired-diseases group, respectively, the rates of NIV use during the ICU stay were 82% and 63% (P = .040), the intubation rates were 30% and 56% (P = .02), and the tracheotomy rates were 9% and 12% (difference not significant). At the final assessment (median 3 years) the mortality rate was 58%, and mortality was not significantly related to the type of neuromuscular disease. At final assessment, 46% of the patients were on NIV and 29% had tracheotomy. CONCLUSIONS: In our ICU, chronic neuromuscular disease is an uncommon cause of ARF, for which we often use NIV. These patients had a low probability of death in the ICU. Long-term outcome was independent of the type of neuromuscular disease.

Effect of Recruitment Maneuvers and PEEP on Respiratory Failure After Cardiothoracic Surgery in Obese Subjects: A Randomized Controlled Trial.

BACKGROUND: Obesity may increase the risk of respiratory failure after cardiothoracic surgery. A recruitment maneuver followed by PEEP might decrease the risk of respiratory failure in obese subjects. We hypothesized that the routine use after heart surgery of a recruitment maneuver followed by high or low PEEP level would decrease the frequency of respiratory failure in obese subjects. METHODS: In a pragmatic, randomized controlled trial, we assigned obese subjects (ie, with body mass index [BMI] ≥ 30 kg/m2) in the immediate postoperative period of cardiothoracic surgery to either volume control ventilation with 5 cm H2O of PEEP (control group) or a recruitment maneuver followed by 5 or 10 cm H2O of PEEP in the intervention arms (RM5 and RM10 groups, respectively). The primary outcome was the proportion of subjects with postextubation respiratory failure, defined as the need for re-intubation, bi-level positive airway pressure, or high-flow nasal cannula within the first 48 h. RESULTS: The study included 192 subjects: 65 in the control group (BMI 33.5 ± 3.2 kg/m2), 66 in the RM5 group (BMI 34.5 ± 3.2 kg/m2, and 61 in RM10 group (BMI 33.8 ± 4.8 kg/m2). Postextubation respiratory failure occurred in 14 subjects in the control group (21.5% [95% CI 13.3-35.3]), 21 subjects in the RM5 group (31.8% [95% CI 21.2-44.6]), and 9 subjects in the RM10 group (14.7% [95% CI 7.4-26.7]) (P = .07). The recruitment maneuver was stopped prematurely due to severe hypotension in 8 (12.1%) RM5 subjects and in 4 (6.6%) RM10 subjects (P = .28). There were no significant differences between the 3 groups for the frequencies of atelectasis, pneumonia, and death in the ICU. CONCLUSIONS: The routine use after heart surgery of a recruitment maneuver followed by 5 or 10 cm H2O of PEEP did not decrease the frequency of respiratory failure in obese subjects. A recruitment maneuver followed by 5 cm H2O of PEEP is inappropriate.

Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg-1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. METHODS: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg-1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg-1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. DISCUSSION: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.

Effect of cardiopulmonary bypass on activated partial thromboplastin time waveform analysis, serum procalcitonin and C-reactive protein concentrations.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is a frequent condition after cardiopulmonary bypass (CPB) and makes conventional biological tests fail to detect postoperative sepsis. Biphasic waveform (BPW) analysis is a new biological test derived from activated partial thromboplastin time that has recently been proposed for sepsis diagnosis. The aim of this study was to investigate the accuracy of BPW to detect sepsis after cardiac surgery under CPB. METHODS: We conducted a prospective study in American Society of Anesthesiologists' (ASA) physical status III and IV patients referred for cardiac surgery under CPB. Procalcitonin (PCT) and BPW were recorded before surgery and every day during the first week following surgery. Patients were then divided into three groups: patients presenting no SIRS, patients presenting with non-septic SIRS and patients presenting with sepsis. RESULTS: Thirty two patients were included. SIRS occurred in 16 patients (50%) including 5 sepsis (16%) and 11 (34%) non-septic SIRS. PCT and BPW were significantly increased in SIRS patients compared to no SIRS patients (0.9 [0.5-2.2] vs. 8.1 [2.0-21.3] ng/l for PCT and 0.10 [0.09-0.14] vs. 0.29 [0.16-0.56] %T/s for BPW; P < 0.05 for both). We observed no difference in peak PCT value between the sepsis group and the non-septic SIRS group (8.4 [7.5-32.2] vs. 7.8 [1.9-17.5] ng/l; P = 0.67). On the other hand, we found that BPW was significantly higher in the sepsis group compared to the non-septic SIRS group (0.57 [0.54-0.78] vs. 0.19 [0.14-0.29] %T/s; P < 0.01). We found that a BPW threshold value of 0.465%T/s was able to discriminate between sepsis and non-septic SIRS groups with a sensitivity of 100% and a specificity of 93% (area under the curve: 0.948 +/- 0.039; P < 0.01). Applying the previously published threshold of 0.25%T/s, we found a sensitivity of 100% and a specificity of 72% to discriminate between these two groups. Neither C-reactive protein (CRP) nor PCT had significant predictive value (area under the curve for CRP was 0.659 +/- 0.142; P = 0.26 and area under the curve for PCT was 0.704 +/- 0.133; P = 0.15). CONCLUSIONS: BPW has potential clinical applications for sepsis diagnosis in the postoperative period following cardiac surgery under CPB.

Does the Pleth variability index indicate the respiratory-induced variation in the plethysmogram and arterial pressure waveforms?

BACKGROUND: Respiratory variations in the pulse oximeter plethysmographic waveform amplitude (deltaPOP) are sensitive to changes in preload and can predict fluid responsiveness in mechanically ventilated patients. However, they cannot be easily calculated from a bedside monitor. Pleth variability index (PVI, Masimo Corp., Irvine, CA) is a new algorithm that automatically calculates deltaPOP. The aim of our study was to test the ability of this new device to automatically and continuously monitor deltaPOP. METHODS: Twenty-five patients were studied after induction of general anesthesia. PVI automatically and continuously calculates the respiratory variations in the plethysmography waveform amplitude (perfusion index). Data (mean arterial blood pressure, central venous pressure, respiratory variations in arterial pulse pressure, deltaPOP, and PVI) were recorded at baseline in anti-Trendelenburg position and, finally, in Trendelenburg position. RESULTS: There was a significant relationship between PVI and deltaPOP (r = 0.92; P < 0.05). Over the 75 measurements, 42 (56%) presented a deltaPOP value > 13%. A PVI threshold value of 11.5% was able to discriminate between deltaPOP >13% and deltaPOP < or = 13% with a sensitivity of 93% and a specificity of 97%. Area under the curve for PVI to predict deltaPOP > 13% was 0.990 +/- 0.07. CONCLUSION: This study is the first to demonstrate the ability of PVI, an index automatically derived from the pulse oximeter waveform analysis, to automatically and continuously monitor deltaPOP. This new index has potential clinical applications for noninvasive fluid responsiveness monitoring.

Applicability of Pulse Pressure Variation during Unstable Hemodynamic Events in the Intensive Care Unit: A Five-Day Prospective Multicenter Study.

Pulse pressure variation can predict fluid responsiveness in strict applicability conditions. The purpose of this study was to describe the clinical applicability of pulse pressure variation during episodes of patient hemodynamic instability in the intensive care unit. We conducted a five-day, seven-center prospective study that included patients presenting with an unstable hemodynamic event. The six predefined inclusion criteria for pulse pressure variation applicability were as follows: mechanical ventilation, tidal volume >7 mL/kg, sinus rhythm, no spontaneous breath, heart rate/respiratory rate ratio >3.6, absence of right ventricular dysfunction, or severe valvulopathy. Seventy-three patients presented at least one unstable hemodynamic event, with a total of 163 unstable hemodynamic events. The six predefined criteria for the applicability of pulse pressure variation were completely present in only 7% of these. This data indicates that PPV should only be used alongside a strong understanding of the relevant physiology and applicability criteria. Although these exclusion criteria appear to be profound, they likely represent an absolute contraindication of use for only a minority of critical care patients.

Total percutaneous femoral vessels cannulation for minimally invasive mitral valve surgery.

BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) has experienced several technological changes in the last two decades. Our aim was to describe one of the most recent improvements, the utilization of a total percutaneous femoral vessels cannulation technique during MIMVS. METHODS: We performed a retrospective observational analysis of this technique among 300 consecutive MIMVS patients, with particular focus on cannulation aspects of MIMVS, its success rate and potential complications. RESULTS: From October 2008 to December 2012, 300 patients (60% males) were operated on. Mean age was 62.9±16.4 years. Indications for operation included mitral valve repair (93%) and mitral valve replacement (7%). Two femoral arterial catheterizations failed and required conversion to sternotomy. The complications on the arterial side were: 5 (1.6%) cases of bleeding during the introduction of Prostar leading to a preoperative surgical hemostasis; 2 (0.6%) retroperitoneal bleeds during cardiopulmonary bypass requiring difficult surgical control but with an uneventful follow-up; 6 (2%) bleeding episodes after removal of the arterial cannula easily controlled by direct surgical revision; 1 (0.3%) arterio-venous fistula requiring a surgical correction on postoperative day 32; 1 (0.3%) patient had a transitory claudication due to a superficial femoral artery thrombosis progressively compensated by the collateral circulation. There were no postoperative bleeding complications. There were no other complications linked to the femoral cannulations or to the groin occurred during the follow-up. The percentage of uneventful arterial cannulations was 80% among the first 50 patients (N=10 out of 50) and 98.8% thereafter (N=3 out of 250). CONCLUSIONS: Total percutaneous femoral vessels cannulation technique is particularly suitable for MIMVS with a high success rate and few complications after a short learning curve. With the advent of the percutaneous approach, the traditional complications of the groin incision have completely disappeared in modern operations with no groin infection, hematoma or lymphocele.

Evaluation of recruited lung volume at inspiratory plateau pressure with PEEP using bedside digital chest X-ray in patients with acute lung injury/ARDS.

BACKGROUND: We wanted to assess whether there was a significant relationship between recruited lung volume (V(rec)) and change in density on digital processed chest x-ray measured at 2 different levels of inspiratory plateau pressure corresponding to 2 PEEP levels in patients with acute lung injury or ARDS. METHODS: In 14 subjects, PEEP 5 cm H2O and 15 cm H2O were prospectively applied in a random order for 10 min. At the end of each period, chest x-ray was taken using a digital portable device, and a pressure-volume curve of the respiratory system was performed. We also assessed P(aO2), and the static and the dynamic (C(dyn,rs)) compliance of the respiratory system. Change in end-expiratory lung volume between tidal breath and relaxation volume of the respiratory system was determined. Radiological attenuation was measured on chest x-rays in 4 regions of interest in the right lung, and in 3 regions of interest in the left lung, drawn in posterior intercostal spaces from top to bottom, by using dedicated software. The ratio of lung density in each region between PEEP 15 and PEEP 5 (rP15/P5) and their arithmetic mean (µP15/P5) were computed. V(rec) was determined from the pressure-volume curves. RESULTS: The median value of rP15/P5 in the 98 lung levels was 0.91 (0.80-1.01), which was significantly different from 1 (P < .001). The values of rP15/P5 were not significantly different between the lung levels. The median values of V(rec) and µP15/P5 were 288 (173-402) mL and 0.90 (0.80-0.97), respectively. There was a significant negative correlation between V(rec) and µP15/P5 (R = -0.77, P = .01). The reduction in µP15/P5 tended to correlate with the increase in C(dyn,rs) (R = -0.49, P = .077) or in P(aO2) (R = -0.53, P = .05) between PEEP 15 cm H2O and PEEP 5 cm H2O. CONCLUSIONS: Digital chest x-ray done at the bedside in acute lung injury/ARDS subjects was able to detect a reduction in density between PEEP 5 cm H2O and PEEP 15 cm H2O, which correlated with V(rec).

Efficacy and safety of recruitment maneuvers in acute respiratory distress syndrome.

Recruitment maneuvers (RM) consist of a ventilatory strategy that increases the transpulmonary pressure transiently to reopen the recruitable lung units in acute respiratory distress syndrome (ARDS). The rationales to use RM in ARDS are that there is a massive loss of aerated lung and that once the end-inspiratory pressure surpasses the regional critical opening pressure of the lung units, those units are likely to reopen. There are different methods to perform RM when using the conventional ICU ventilator. The three RM methods that are mostly used and investigated are sighs, sustained inflation, and extended sigh. There is no standardization of any of the above RM. Meta-analysis recommended not to use RM in routine in stable ARDS patients but to run them in case of life-threatening hypoxemia. There are some concerns regarding the safety of RM in terms of hemodynamics preservation and lung injury as well. The rapid rising in pressure can be a factor that explains the potential harmful effects of the RM. In this review, we describe the balance between the beneficial effects and the harmful consequences of RM. Recent animal studies are discussed.