Feasibility of Prone Positioning for Brain-injured Patients with Severe Acute Respiratory Distress Syndrome: A Systematic Review and Pilot Study (ProBrain).

BACKGROUND: Prone position is a key component to treat hypoxemia in patients with severe acute respiratory distress syndrome. However, most studies evaluating it exclude patients with brain injuries without any medical evidence. METHODS: This study includes a systematic review to determine whether brain-injured patients were excluded in studies evaluating prone position on acute respiratory distress syndrome; a prospective study including consecutive brain-injured patients needing prone position. The primary endpoint was the evaluation of cerebral blood flow using transcranial Doppler after prone positioning. Secondary outcomes were intracranial pressure, cerebral perfusion pressure, and tissue oxygen pressure. RESULTS: From 8,183 citations retrieved, 120 studies were included in the systematic review. Among them, 90 studies excluded brain-injured patients (75%) without any justification, 16 included brain-injured patients (4 randomized, 7 nonrandomized studies, 5 retrospective), and 14 did not retrieve brain-injured data. Eleven patients were included in the authors' pilot study. No reduction of cerebral blood flow surrogates was observed during prone positioning, with diastolic speed values (mean ± SD) ranging from 37.7 ± 16.2 cm/s to 45.2 ± 19.3 cm/s for the right side (P = 0.897) and 39.6 ± 18.2 cm/s to 46.5 ± 21.3 cm/s for the left side (P = 0.569), and pulsatility index ranging from 1.14 ± 0.31 to 1.0 ± 0.32 for the right side (P = 0.145) and 1.14 ± 0.31 to 1.02 ± 0.2 for the left side (P = 0.564) before and during prone position. CONCLUSIONS: Brain-injured patients are largely excluded from studies evaluating prone position in acute respiratory distress syndrome. However, cerebral blood flow seems not to be altered considering increasing of mean arterial pressure during the session. Systematic exclusion of brain-injured patients appears to be unfounded, and prone position, while at risk in brain-injured patients, should be evaluated on these patients to review recommendations, considering close monitoring of neurologic and hemodynamic parameters.

Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases.

BACKGROUND: Precise data about ATTR-CM incidence rates at national level are scarce. Consequently, this study aimed to estimate the annual incidence and survival of transthyretin amyloid cardiomyopathy (ATTR-CM) in France between 2011 and 2019 using real world data. We used the French nationwide exhaustive data (SNDS database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis meglumine delivery) and a cardiovascular condition (identified by ICD-10 or medical procedure codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis or probable AA-form of amyloidosis were excluded. RESULTS: Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6 / 100,000 person-years in 2011 to 3.6 / 100,000 person-years in 2019 (p < 0.001), reaching 2377 new cases in 2019. Sex ratios (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). CONCLUSIONS: This is the first estimate of nationwide ATTR-CM incidence in France using comprehensive real-world databases. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.

Genetically determined thymic function affects strength and duration of immune response in COVID patients with pneumonia.

Thymic activation improves the outcome of COVID-19 patients with severe pneumonia. The rs2204985 genetic polymorphism within the TCRA-TCRD locus, which affects thymic output in healthy individuals, was found here to modify SARS-CoV-2-specific immunity and disease severity in COVID-19 patients with severe pneumonia. Forty patients with severe COVID-19 pneumonia were investigated. The GG genotype at the rs2204985 locus was associated, independently of age and sex, with stronger and long-lasting anti-SARS-CoV-2 helper and cytotoxic T cell responses 6 months after recovery. The GG genotype was also associated with less severe lung involvement, higher thymic production, and higher counts of blood naïve T lymphocytes, including recent thymic emigrants, and a larger population of activated stem cell memory CD4+ T cells. Overall, GG patients developed a more robust and sustained immunity to SARS-CoV-2. Polymorphism at rs2204985 locus should be considered as an additional predictive marker of anti-SARS-CoV-2 immune response.

Wide Awake Local Anesthesia No Tourniquet (WALANT) technique improves the efficiency of distal nerve blocks for carpal tunnel release.

BACKGROUND: Axillary block is the standard for carpal tunnel release (CTR), providing effective anesthesia, and tolerance of tourniquet. Conversely, distal blocks are less used due to poor tolerance of tourniquet. Wide Awake Local Anesthesia No Tourniquet (WALANT), proposed for hand and wrist surgeries, avoids its use. This study assesses the benefits of the addition of WALANT to distal blocks during endoscopic CTR (eCTR). METHODS: This randomized, open-label, controlled trial prospectively enrolled 60 patients scheduled for eCTR. Patients were randomized to receive distal blocks at the wrist combined to either a high arm tourniquet (Distal block group) or a WALANT in the area of surgery (Distal + Walant group). The primary endpoint was the global pain score summing pain scores related to puncture, local anesthetic injection, pneumatic tourniquet, surgical procedure, tourniquet deflation, and residual sensitivity after surgery. RESULTS: Mean global pain score was significantly reduced in the Distal + Walant group (0.5 ± 1.4 vs. 2.2 ± 2.4; p < 0.001). No need for an additional anesthetic procedure was required in the Distal + Walant group. Even if the quality of visualization was high in both groups, it was better in the Distal block group (5 [5-5] vs. 4 [4-5]; p < 0.001). No rescue tourniquet was necessary for the Distal + Walant group. The rate of hematoma 15 days post-surgery was significantly reduced in the Distal + Walant group (20% vs. 57%; p < 0.01). CONCLUSIONS: The addition of WALANT to distal blocks is adapted for eCTR. This combined technique decreases perioperative pain scores, provides good surgery conditions, and reduces the risk of postoperative hematoma. CLINICAL TRIAL NUMBER AND REGISTRY URL: The trial was registered on ClinicalTrials.gov (NCT04494100) on July 31, 2020 https://clinicaltrials.gov/ct2/show/NCT04494100?term=CMC+ambroise+pare&cntry=FR&draw=4&rank=28.

Persistent diaphragm dysfunction after cardiac surgery is associated with adverse respiratory outcomes: a prospective observational ultrasound study.

BACKGROUND: Transient diaphragm dysfunction is common during the first week after cardiac surgery; however, the precise incidence, risk factors, and outcomes of persistent diaphragm dysfunction are not well described. METHODS: In a single-centre prospective cohort study, we included all consecutive patients over 18 yr who underwent elective cardiac surgery. Diaphragm function was evaluated with ultrasound (M-mode) by recording the excursion of both hemidiaphragms at two different time points: preoperatively and after the seventh postoperative day in patients breathing without assistance. Significant diaphragm dysfunction after the seventh day of the index cardiac surgery was defined as a decrease in diaphragm excursion below the lower limit of normal: at rest, < 9 mm for women and < 10 mm for men; after a sniff test, < 16 mm for women and < 18 mm for men. RESULTS: Overall, 122 patients were included in the analysis. The median [interquartile range (IQR)] age was 69 [59-74] years and 96/122 (79%) were men. Ten (8%) patients had diaphragm dysfunction after the seventh postoperative day. We did not identify risk factors for persistent diaphragm dysfunction. Persistent diaphragm dysfunction was associated with a longer median [IQR] duration of noninvasive (8 [0-34] vs 0 [0-0] hr; difference in medians, 8 hr; 95% confidence interval [CI], 0 to 22; P < 0.001) and invasive mechanical ventilation (5 [3-257] vs 3[2-4] hr; difference in medians, 2 hr; 95% CI, 0.5 to 41; P = 0.008); a higher reintubation rate (4/10, 40% vs 1/112, 0.9%; relative risk, 45; 95% CI, 7.1 to 278; P < 0.0001), a higher incidence of pneumonia (4/10 [40%] vs 7/112 [6%]; relative risk, 6; 95% CI, 2 to 16; P < 0.001), and longer median [IQR] length of stay in the intensive care unit (8 [5-29] vs 4 [2-6] days; difference in medians, 4 days; 95% CI, 2 to 12; P = 0.002). CONCLUSION: The incidence of persistent diaphragm dysfunction was 8% in patients undergoing elective cardiac surgery and was associated with adverse respiratory outcomes. STUDY REGISTRATION: ClinicalTrials.gov (NCT04276844); prospectively registered 19 February 2020.

RéSUMé: CONTEXTE: Un dysfonctionnement transitoire du diaphragme est fréquent au cours de la première semaine après une chirurgie cardiaque. Toutefois, l'incidence précise, les facteurs de risque et les devenirs liés à un dysfonctionnement persistant du diaphragme ne sont pas bien décrits. MéTHODE: Dans une étude de cohorte prospective monocentrique, nous avons inclus tous les patients consécutifs de plus de 18 ans qui ont bénéficié d'une chirurgie cardiaque non urgente. La fonction du diaphragme a été évaluée à l'échographie (mode M) en enregistrant l'excursion des deux hémidiaphragmes à deux moments différents : avant l'opération et après le septième jour postopératoire chez les patients respirant sans assistance. Un dysfonctionnement significatif du diaphragme après le septième jour de la chirurgie cardiaque initiale a été défini comme une diminution de l'excursion diaphragmatique en dessous de la limite inférieure de la normale, soit : au repos, < 9 mm pour les femmes et < 10 mm pour les hommes; après un test de reniflement, < 16 mm pour les femmes et < 18 mm pour les hommes. RéSULTATS: Au total, 122 patients ont été inclus dans l'analyse. L'âge médian des patients (écart interquartile [ÉIQ]) était de 69 ans [59-74] ans et 96/122 (79 %) étaient des hommes. Dix (8 %) patients ont présenté un dysfonctionnement du diaphragme après le septième jour postopératoire. Nous n'avons pas identifié de facteurs de risque de dysfonctionnement persistant du diaphragme. Un dysfonctionnement persistant du diaphragme était associé à : une durée médiane [ÉIQ] de ventilation non invasive (8 [0­34] vs 0 [0­0] h; différence dans les médianes, 8 heures; intervalle de confiance [IC] à 95 %, 0 à 22; P < 0,001) et de ventilation mécanique invasive (5 [3­257] vs 3[2­4] h; différence dans les médianes, 2 heures; IC 95 %, 0,5 à 41; P = 0,008) plus longues, un taux de réintubation plus élevé (4/10, 40 % vs 1/112, 0,9 %; risque relatif, 45; IC 95 %, 7,1 à 278; P < 0,0001), une incidence plus élevée de pneumonie (4/10 [40 %] vs 7/112 [6 %]; risque relatif, 6; IC 95 %, de 2 à 16; P < 0,001), et une durée de séjour médiane [ÉIQ] plus longue à l'unité de soins intensifs (8 [5-29] vs 4 [2­6] jours; différence en médianes, 4 jours; IC 95 %, 2 à 12; P = 0,002). CONCLUSION: L'incidence de dysfonctionnement persistant du diaphragme était de 8 % chez les patients bénéficiant d'une chirurgie cardiaque non urgente et était associée à des issues respiratoires indésirables. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04276844); enregistrée prospectivement le 19 février 2020.

High-flow nasal oxygen for suspension laryngoscopy: a multicenter open-label study.

In this study, we aimed to assess the efficacy of high-flow nasal oxygen (HFNO) to maintain blood peripheral oxygen saturation (SpO2) in patients undergoing suspension laryngoscopy under general anesthesia. Adult patients were included in this bicenter study. After face-mask oxygenation, HFNO at a flow rate of 70 L min-1 and fraction of inspired oxygen 100% was initiated at loss of consciousness. At the end of HFNO, blood gas analysis was performed. Of the 29 included patients, five (17.2%; 95% confidence interval [CI]: 7.6-34.5) presented SpO2 <95% during the first 15 minutes of the procedure and eight patients (27.6%; 95% CI: 14.7-45.7) presented SpO2 <95% throughout the procedure. Six patients (20.7%; 95% CI: 9.8-38.4) required rescue jet ventilation. Median apnea time before SpO2 <95% was 13.5 (interquartile range [IQR]: 10-17.7) minutes. Arterial carbon dioxide tension at the end of the procedure or at the time of study discontinuation was 9.73 (IQR: 8.8-10.9) kPa and was higher than 8 kPa in 88.9% (95% CI: 71.9-96.1) of patients. HFNO was associated with a relatively high incidence of suboptimal oxygen saturation and hypercapnia during suspension laryngoscopy under general anesthesia and may not be considered the reference technique.

Transition matrices model as a way to better understand and predict intra-hospital pathways of covid-19 patients.

Since January 2020, the SARS-CoV-2 pandemic has severely affected hospital systems worldwide. In Europe, the first 3 epidemic waves (periods) have been the most severe in terms of number of infected and hospitalized patients. There are several descriptions of the demographic and clinical profiles of patients with COVID-19, but few studies of their hospital pathways. We used transition matrices, constructed from Markov chains, to illustrate the transition probabilities between different hospital wards for 90,834 patients between March 2020 and July 2021 managed in Paris area. We identified 3 epidemic periods (waves) during which the number of hospitalized patients was significantly high. Between the 3 periods, the main differences observed were: direct admission to ICU, from 14 to 18%, mortality from ICU, from 28 to 24%, length of stay (alive patients), from 9 to 7 days from CH and from 18 to 10 days from ICU. The proportion of patients transferred from CH to ICU remained stable. Understanding hospital pathways of patients is crucial to better monitor and anticipate the impact of SARS-CoV-2 pandemic on health system.

Personalized Reimbursement Model (PRM) program: A real-world data platform of cancer drugs use to improve and personalize drug pricing and reimbursement in France.

OBJECTIVE: This article describes the Personalized Reimbursement Model (PRM) program methodology, limitations, achievement and perspectives in using real-world data of cancer drugs use to improve and personalize drug pricing and reimbursement in France. MATERIALS AND METHODS: PRM platform aggregates Electronic Pharmacy Records (EPR) data from French medical centers (PRM centers) to build retrospective cohorts of patients treated with injectable cancer drugs in a hospital setting. Data extracted on January 1st, 2020, from breast cancer (BC) patients who received trastuzumab, trastuzumab emtansin or pertuzumab since January 1st, 2011, and from lung cancer (LC) patients who received bevacizumab or atezolizumab since January 1st, 2015, enabled recovering their injectable cancer drugs history from diagnosis date until December 30th, 2019, and served as dataset for assessment. RESULTS: 123 PRM centers provided data from 30,730 patients (25,660 BC and 5,070 LC patients respectively). Overall, 20,942 (82%) of BC and 4,716 (93%) of LC patients were analyzed. Completion rate was above 98% for patients characteristics, diagnostic and treatment related data. PRM centers cover 48% and 33% of BC and LC patients in-hospital therapeutic management in France, respectively. Distribution of BC and LC patients therapeutic management, by medical center category and geographic location, was similar in PRM centers to all French medical centers, ensuring the representativeness of the PRM platform. CONCLUSION: PRM Platform enabled building a national database generating on demand Real-World Evidence based on EPR. This enabled the first performance-based risk-sharing arrangements based on PRM data, between the CEPS and Roche, for atezolizumab cancer immunotherapy in metastatic non-small cell lung cancer indication.

Cerebrovascular Ischemic Events in Patients With Takayasu Arteritis.

BACKGROUND: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events. METHODS: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA. RESULTS: Among 320 patients with TA (median age at diagnosis, 36 [25-47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45-8.17]; P<0.0001), smoking (HR, 1.75 [1.01-3.02]; P=0.05), myocardial infarction history (HR, 0.21 [0.05-0.89]; P=0.039), thoracic aorta involvement (HR, 2.05 [1.30-3.75]; P=0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30-3.80]; P=0.005), and aspirin treatment (HR, 1.82 [1.04-3.19]; P=0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27-3.70]; P=0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91-8.99; P<0.0001), compared with those who had not. CONCLUSIONS: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.

Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.

Risk factors and complications associated with intra-operative or post-operative identification of a PFO in cardiac surgery patients: A cohort study.

Introduction: It is unknown whether patent foramen ovale (PFO) reopening in the peri-operative setting of cardiac surgery affects the risk for stroke and post-operative outcomes. Methods: We performed a single-center, retrospective study based on a prospectively collected database in a tertiary cardiac surgery center. Using logistic regression, we assessed risk factors of PFO finding around surgery and subsequent clinical complications. Results: Between January 2007 and July 2019, 11034 patients who underwent cardiac surgery in our center were included. A total of 233 patients (2.1%) presented a finding of PFO including 138 per-operative disclosures and 95 post-operative finding for hypoxemia. In the whole cohort, the mean age was 68.4 ± 11.5 years including 73.9% of men. Post-operative PFO finding was associated with more ischemic strokes compared with per-operative finding and control group [7(7.4%) vs. 3(2.2%) vs. 236(2.2), respectively; p = 0.003]. Moreover, patients with post-operative PFO reopening experienced a higher rate of pneumonia, reintubation, and longer length of stay in the ICU. Post-operative reopening of PFO, but not per-operative finding, was independently associated with ischemic strokes {adjusted odds-ratio = 3.5, 95% confidence interval (CI) [1.6-7.8]; p = 0.002}. Other variables associated with stroke incidence included age, mitral valve surgery, and ascending aorta surgery. Per- or post-operative PFO closure was associated with reduced adverse respiratory outcomes and a trend of the lower cerebral ischemic event. Conclusion: Patent foramen ovale finding incidence in peri-operative cardiac surgery care was rare (2%) but post-operative finding of PFO was associated with a increased risk of ischemic strokes, worsened respiratory outcomes, and prolonged hospitalization.

Takotsubo cardiomyopathy after cardiac surgery: A case-series and systematic review of literature.

Background: Takotsubo cardiomyopathy (TTC) is a rare entity after cardiac surgery. Aims: To describe patients' profile who developed postoperative TTC after cardiac surgery, management, and outcomes. Methods: We performed a systematic literature search to extract cases of TTC after adult cardiac surgery (from 1990 to 2021). Additionally, we extracted all cases of TTC in a prospective single-center cohort database of 10,000+ patients (from 2007 to 2019). We then combined all cases in a single cohort to describe its clinical features. Results: From 694 screened articles, we retained 71 individual cases published in 20 distinct articles (19 cases reports and 1 case-series). We combined these to 10 cases extracted from our cohort [among 10,682 patients (0.09%)]. Overall, we included 81 cases. Patients were aged 68 ± 10 years-old and 64/81 (79%) were women. Surgery procedures included mitral valve and/or tricuspid valve surgery in 70/81, 86%. TTC was diagnosed in the first days after surgery [median 4 (1-4) days]. Incidence of cardiogenic shock, defined as requirement of vasopressor and/or inotropic support was 24/29, 83% (data available on 29/81 patients). Refractory cardiogenic appeared in 5/81, 6% who required implantation of arterio-venous extra-corporeal membrane oxygenation, and 6/81, 7%, intra-aortic balloon pump. In-hospital mortality was 5/81, 6%. Conclusion: This systematic review, based on case reports and case series, showed that postoperative TTC appears as a rare complication after cardiac surgery and mainly occurred after mitral and/or tricuspid valve repair procedures. In this population, TTC is associated with high rate of cardiogenic shock.

Post-operative Right Ventricular Failure After Cardiac Surgery: A Cohort Study.

Introduction: Right ventricular failure (RVF) after cardiac surgery is an important risk factor for morbidity and mortality. Its diagnosis is challenging, and thus, its incidence and predictors are not well-established. We investigated the incidence, complications, and variables associated with clinically relevant post-operative RVF. Methods: We included all patients who underwent cardiac surgery with cardiopulmonary bypass between 2016 and 2019 in a cardiac surgery center with standardized diagnostic and therapeutic management of RVF. RVF was considered only if clinically relevant: associated with hemodynamic instability requiring catecholamine support and inhaled nitric oxide relayed by sildenafil. Results: Overall, 3,826 patients were included, of whom, 110 (2.9%) developed post-operative RVF. Mortality was not different among patients who developed post-operative RVF, compared with the rest of the cohort (1.8 vs. 0.7%, p = 0.17). Using a composite outcome that combined death, reintubation, stroke, and prolonged intensive care unit stay (more than 14 days) yielded an incidence of 6.6%, and RVF was associated with this composite outcome with an odds ratio of 3.6 (2.2-5.8), p < 0.001. In a multivariable model, pre-operative variables independently associated with post-operative RVF were pre-operative atrial fibrillation (AF) {adjusted odds ratio (adjOR) 3.22 [95% confidence interval (95%CI) = 1.94-5.36], p < 0.001}, left ventricle ejection fraction below 50% [adjOR = 2.55 (95%CI = 1.52-4.33), p < 0.001], systolic pulmonary artery pressure above 55 mmHg [adjOR = 8.64 (95%CI = 5.27-14.1); p < 0.001], mitral valve surgery [adjOR = 2.17 CI (95%CI = 1.28-3.66), p = 0.004], and tricuspid valve surgery [adjOR = 10.33 (95%CI = 6.14-17.4), p < 0.001]. In patients who developed post-operative RVF requiring treatment, 32 (29.1%) showed RV dysfunction before surgery. Conclusion: In this cohort study, 2.9% of patients developed clinically significant post-operative RVF. Moreover, RVF was associated with severe adverse outcomes, including death, strokes, reintubation, and prolonged intensive care unit stay.

Use of Almitrine and Inhaled Nitric Oxide in ARDS Due to COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by an acute respiratory distress syndrome (ARDS) with intense inflammation and endothelial dysfunction leading to particularly severe hypoxemia. We hypothesized that an impaired hypoxic pulmonary vasoconstriction aggravates hypoxemia. The objective of the study was to test the effect of two pulmonary vasoactive drugs on patient oxygenation. Methods: Observational, single-center, open-label study in one intensive care unit (ICU) of the Paris area, realized in April 2020. Eligible patients had coronavirus disease 2019 (COVID-19) and moderate to severe ARDS [arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <200 mmHg] despite conventional protective ventilation. Exclusion criteria included pulmonary artery hypertension defined by a pulmonary artery systolic pressure (PAPs) >45 mmHg. The assessment of oxygenation was based on PaO2/FiO2 at (1) baseline, then after (2) 30 min of inhaled nitric oxide (iNO) 10 ppm alone, then (3) 30 min combination of iNO + almitrine infusion 8 µg/kg/min, then (4) 30 min of almitrine infusion alone. Results: Among 20 patients requiring mechanical ventilation during the study period, 12 met the inclusion criteria. Baseline PaO2/FiO2 was 146 ± 48 mmHg. When iNO was combined with almitrine, PaO2/FiO2 rose to 255 ± 90 mmHg (+80 ± 49%, p = 0.005), also after almitrine alone: 238 ± 98 mmHg (+67 ± 75%, p = 0.02), but not after iNO alone: 185 ± 73 mmHg (+30 ± 5%, p = 0.49). No adverse events related to almitrine infusion or iNO was observed. Conclusion: Combining iNO and infused almitrine improved the short-term oxygenation in patients with COVID-19-related ARDS. This combination may be of interest when first-line therapies fail to restore adequate oxygenation. These findings argue for an impaired pulmonary hypoxic vasoconstriction in these patients.

The Ockham's razor for estimating the needs of ICU beds during a pandemic.

BACKGROUND: It is possible to monitor an epidemic evolution by plotting the number of patients, or its log-transform, as a function of time. However, these representations do not allow quick identifications of significant changes in the outbreak; a key information for estimating the needs for hospital and ICU beds, for decision-making, and resource allocation. Moreover, an epidemic is characterised by a heterogeneous evolution that depends on many unpredictable factors, coming from the virus itself or from its ecosystem. Simulations are very complex and based on hypotheses that are impossible to certify a priori, since each outbreak is different and has specific characteristics. A validation phase is necessary that may delay the usefulness of these tools. We tested a simpler method for monitoring the epidemic and rapidly predicting the peak. RESULTS: We present here a simple and easy-to-draw figure by plotting the daily rate of change in the number of patients as a function of time. This allows: (1) to rapidly identify the changes in the infection growth, (2) to extrapolate the regression lines for predicting the peaks, and (3) to use simple statistical models for identifying the significant inflexions and deriving the uncertainties. This figure predicted confidently the peak epidemic of the three waves in France. CONCLUSION: Plotting the daily rate of change in the number of patients as a function of time is a simple tool for monitoring an epidemic growth, allowing to quickly identify significant changes and to help in predicting the peak of the infection, with its confidence interval.

Virtual reality vs. Kalinox® for management of pain in intensive care unit after cardiac surgery: a randomized study.

INTRODUCTION: The management of pain and anxiety remains a challenge in the intensive care unit. By distracting patients, virtual reality (VR) may have a role in painful procedures. We compared VR vs. an inhaled equimolar mixture of N2O and O2 (Kalinox®) for pain and anxiety management during the removal of chest drains after cardiac surgery. METHODS: Prospective, non-inferiority, open-label study. Patients were randomized, for Kalinox® or VR session during drain removal. The analgesia/nociception index (ANI) was monitored during the procedure for objective assessment of pain and anxiety. The primary endpoint was the ΔANI (ANImin - ANI0) during the procedure, based on ANIm (average on 4 min). We prespecified VR as non-inferior to Kalinox® with a margin of 3 points. Self-reported pain and anxiety were also analysed using numeric rate scale (NRS). RESULTS: 200 patients were included, 99 in the VR group and 101 in the Kalinox® group; 90 patients were analysed in both groups in per-protocol analysis. The median age was 68.0 years [60.0-74.8]. The ΔANI was - 15.1 ± 12.9 in the Kalinox® group and - 15.7 ± 11.6 in the VR group (NS). The mean difference was, therefore, - 0.6 [- 3.6 to 2.4], including the non-inferiority margin of 3. Patients in the VR group had a significantly higher pain NRS scale immediately after the drain removal, 5.0 [3.0-7.0] vs. 3.0 [2.0-6.0], p = 0.009, but no difference 10 min after. NRS of anxiety did not differ between the two groups. CONCLUSION: Based on the ANI, the current study showed that VR did not reach the statistical requirements for a proven non-inferiority vs. Kalinox® in managing pain and anxiety during chest drain removal. Moreover, VR was less effective based on NRS. More studies are needed to determine if VR might have a place in the overall approach to pain and anxiety in intensive care units. Trial registration NCT, NCT03956264. Registered 20 May 2019, https://clinicaltrials.gov/ct2/show/NCT03956264.

Efficacy of parasternal block to decrease intraoperative opioid use in coronary artery bypass surgery via sternotomy: a randomized controlled trial.

OBJECTIVE: This study aims to assess the effect of a preoperative parasternal plane block (PSB) on opioid consumption required to maintain hemodynamic stability during sternotomy for coronary artery bypass graft surgery. METHODS: This double-blind, randomized, placebo-controlled trial prospectively enrolled 35 patients scheduled for coronary artery bypass graft surgery under general anesthesia with propofol and remifentanil. Patients were randomized to receive preoperative PSB using either ropivacaine (PSB group) or saline solution (placebo group) (1:1 ratio). The primary endpoint was the maximal effect-site concentration of remifentanil required to maintain heart rate and blood pressure within the recommended ranges during sternotomy. RESULTS: Median maximum concentration of remifentanil necessary to maintain adequate hemodynamic status during sternotomy was significantly reduced in PSB group (4.2 (2.5-6.0) ng/mL) compared with placebo group (7.0 (5.2-8.0) ng/mL) (p=0.02). Mean maximum concentration of propofol used to control depth of anesthesia was also reduced (3.9±1.1 µg/mL vs 5.0±1.5 µg/mL, PSB vs placebo, respectively; p=0.02). This reduction in propofol consumption during sternotomy enabled a more adequate level of sedation to be maintained in patients (minimum patient state index was 11.7±8.7 in placebo group and 18.3±6.8 in PSB group; p=0.02). PSB reduced postoperative inflammatory response by limiting concentrations of proinflammatory cytokines IL-8, IL-18, IL-23, IL-33 and MCP-1 measured in the first 7-day after surgery (p<0.05). CONCLUSIONS: Preoperative PSB reduced the maximum concentrations of remifentanil and propofol required to maintain hemodynamic stability and depth of anesthesia during sternotomy. TRIAL REGISTRATION NUMBER: NCT03734159.Sébastien Bloc, M.D.1,2; Brieuc P. Pérot, Ph.D.3; Hadrien Gibert, M.D.1; Jean-Dominique Law Koune, M.D.1; Yannick Burg, M.D.1; Didier Leclerc, M.D.1; Anne-Sophie Vuitton, M.D.1; Christophe De La Jonquière, M.D.1; Marine Luka, L.S.3; Thierry Waldmann, M.D.4; Nicolas Vistarini, M.D.4; Stéphane Aubert, M.D.4; Mickaël M. Ménager, Ph.D.3; Messaouda Merzoug, Ph.D.2; Cécile Naudin, Ph.D.2; Pierre Squara, M.D.2,5.

Diaphragm Dysfunction After Cardiac Surgery: Reappraisal.

OBJECTIVES: The aim of this study was to re-investigate the incidence, risk factors, and outcomes of postoperative diaphragmatic dysfunction (DD) with actual cardiac surgery procedures. DESIGN: Single-center, retrospective, observational study based on a prospectively collected database. SETTING: Tertiary care cardiac surgery center. PARTICIPANTS: Patients who underwent cardiac surgery between January 2016 and September 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The DD group included patients with clinically perceptible diaphragmatic paralysis, which was confirmed by chest ultrasound (amplitude of the diaphragm movement in time-motion mode at rest, after a sniff test). The primary endpoint was the incidence of DD. Among 3,577 patients included, the authors found 272 cases of DD (7.6%). Individuals with DD had more arterial hypertension (64.3% v 52.6%; p < 0.0001), higher body mass index (BMI) (28 [25-30] kg/m2v 26 [24-29] kg/m2; p < 0.0002), and higher incidence of coronary bypass grafting (CABG) (58.8% v 46.6%; p = 0.0001). DD was associated with more postoperative pneumonia (23.9% v 8.7%; p < 0.0001), reintubation (8.8% v 2.9%; p < 0.0001), tracheotomy (3.3% v 0.3%; p < 0.0001), noninvasive ventilation (45.6% v 5.4%; p < 0.0001), duration of mechanical ventilation (five [four-11] hours v four [three-six] hours; p < 0.0001), and intensive care unit and hospital stays (14 [11-17] days v 13 [11-16] days; p < 0.0001). In multivariate analysis, DD was associated with CABG (odds ratio [OR] 1.9 [1.5-2.6]; p = 0.0001), arterial hypertension (OR 1.4 [1.1-1.9]; p = 0.008), and BMI (OR per point 1.04 [1.01-1.07] kg/m2; p = 0.003). CONCLUSIONS: The incidence of symptomatic DD after cardiac surgery was 7.6%, leading to respiratory complications and increased ICU stay. CABG was the principal factor associated with DD.