Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock.

BACKGROUND: Left ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock. METHODS: A total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis. RESULTS: LVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality. CONCLUSIONS: MAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear. Trial registration NCT01747187 and NCT04695119.

Use of Aprotinin versus Tranexamic Acid in Cardiac Surgery Patients with High-Risk for Excessive Bleeding (APACHE) trial: a multicentre retrospective comparative non-randomized historical study.

OBJECTIVES: Following the reintroduction of aprotinin into the European market, the French Society of Cardiovascular and Thoracic Anaesthesiologists recommended its prophylactic use at half-dose for high-risk cardiac surgery patients. We examined whether the use of aprotinin instead of tranexamic acid could significantly reduce severe perioperative bleeding. METHODS: This multicentre, retrospective, historical study included cardiac surgery patients treated with aprotinin or tranexamic acid between December 2017 and September 2020. The primary efficacy end point was the severe or massive perioperative bleeding (class 3-4 of the universal definition of perioperative bleeding). The safety secondary end points included the occurrence of thromboembolic events and all-cause mortality within 30 days after surgery. RESULTS: Among the 693 patients included in the study, 347 received aprotinin and 346 took tranexamic acid. The percentage of patients with severe or massive bleeding was similar in the 2 groups (42.1% vs 43.6%, Adjusted odds ratio [ORadj] = 0.87, 95% confidence interval: 0.62-1.23, P = 0.44), as was the perioperative need for blood products (81.0% vs 83.2%, ORadj = 0.75, 95% confidence interval: 0.48-1.17, P = 0.20). However, the median (Interquartile range) 12 h postoperative blood loss was significantly lower in the aprotinin group (383 ml [241-625] vs 450 ml [290-730], P < 0.01). Compared to tranexamic acid, the intraoperative use of aprotinin was associated with increased risk for thromboembolic events (adjusted Hazard ratio 2.30 [95% Cl: 1.06-5.30]; P = 0.04). CONCLUSIONS: Given the modest reduction in blood loss at the expense of a significant increase in thromboembolic adverse events, aprotinin use in high-risk cardiac surgery patients should be based on a carefully considered benefit-risk assessment.

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

Epidemiology and outcome predictors in 450 patients with hanging-induced cardiac arrest: a retrospective study.

Background: Cardiac arrest is the most life-threatening complication of attempted suicide by hanging. However, data are scarce on its characteristics and outcome predictors. Methods: This retrospective observational multicentre study in 31 hospitals included consecutive adults admitted after cardiac arrest induced by suicidal hanging. Factors associated with in-hospital mortality were identified by multivariate logistic regression with multiple imputations for missing data and adjusted to the temporal trends over the study period. Results: Of 450 patients (350 men, median age, 43 [34-52] years), 305 (68%) had a psychiatric history, and 31 (6.9%) attempted hanging while hospitalized. The median time from unhanging to cardiopulmonary resuscitation was 0 [0-5] min, and the median time to return of spontaneous circulation (ROSC) was 20 [10-30] min. Seventy-nine (18%) patients survived to hospital discharge. Three variables were independently associated with higher in-hospital mortality: time from collapse or unhanging to ROSC>20 min (odds ratio [OR], 4.71; 95% confidence intervals [95%CIs], 2.02-10.96; p = 0.0004); glycaemia >1.4 g/L at admission (OR, 6.38; 95%CI, 2.60-15.66; p < 0.0001); and lactate >3.5 mmol/L at admission (OR, 6.08; 95%CI, 1.71-21.06; p = 0.005). A Glasgow Coma Scale (GCS) score of >5 at admission was associated with lower in-hospital mortality (OR, 0.009; 95%CI, 0.02-0.37; p = 0.0009). Conclusion: In patients with hanging-induced cardiac arrest, time from collapse or unhanging to return of spontaneous circulation, glycaemia, arterial lactate, and coma depth at admission were independently associated with survival to hospital discharge. Knowledge of these risk factors may help guide treatment decisions in these patients at high risk of hospital mortality.

Overview of the current use of levosimendan in France: a prospective observational cohort study.

BACKGROUND: Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. METHOD: The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. RESULTS: The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. CONCLUSIONS: We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.

Veno-arterial extracorporeal membrane oxygenation for circulatory failure in COVID-19 patients: insights from the ECMOSARS registry.

OBJECTIVES: The clinical profile and outcomes of patients with Coronavirus Disease 2019 (COVID-19) who require veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or veno-arterial-venous extracorporeal membrane oxygenation (VAV-ECMO) are poorly understood. We aimed to describe the characteristics and outcomes of these patients and to identify predictors of both favourable and unfavourable outcomes. METHODS: ECMOSARS is a multicentre, prospective, nationwide French registry enrolling patients who require veno-venous extracorporeal membrane oxygenation (ECMO)/VA-ECMO in the context of COVID-19 infection (652 patients at 41 centres). We focused on 47 patients supported with VA- or VAV-ECMO for refractory cardiogenic shock. RESULTS: The median age was 49. Fourteen percent of patients had a prior diagnosis of heart failure. The most common aetiologies of cardiogenic shock were acute pulmonary embolism (30%), myocarditis (28%) and acute coronary syndrome (4%). Extracorporeal cardiopulmonary resuscitation (E-CPR) occurred in 38%. In-hospital survival was 28% in the whole cohort, and 43% when E-CPR patients were excluded. ECMO cannulation was associated with significant improvements in pH and FiO2 on day 1, but non-survivors showed significantly more severe acidosis and higher FiO2 than survivors at this point (P = 0.030 and P = 0.006). Other factors associated with death were greater age (P = 0.02), higher body mass index (P = 0.03), E-CPR (P = 0.001), non-myocarditis aetiology (P = 0.02), higher serum lactates (P = 0.004), epinephrine (but not noradrenaline) use before initiation of ECMO (P = 0.003), haemorrhagic complications (P = 0.001), greater transfusion requirements (P = 0.001) and more severe Survival after Veno-Arterial ECMO (SAVE) and Sonographic Assessment of Intravascular Fluid Estimate (SAFE) scores (P = 0.01 and P = 0.03). CONCLUSIONS: We report the largest focused analysis of VA- and VAV-ECMO recipients in COVID-19. Although relatively rare, the need for temporary mechanical circulatory support in these patients is associated with poor prognosis. However, VA-ECMO remains a viable solution to rescue carefully selected patients. We identified factors associated with poor prognosis and suggest that E-CPR is not a reasonable indication for VA-ECMO in this population.

Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery patients: Rationale and design of the OPTIPAM randomized trial.

BACKGROUND: Postoperative morbidity and mortality after cardiac surgery with cardiopulmonary bypass (CPB) remain high despite recent advances in both anesthesia and perioperative management. Among modifiable risk factors for postoperative complications, optimal arterial pressure during and after surgery has been under debate for years. Recent data suggest that optimizing arterial pressure to the baseline of the patient may improve outcomes. We hypothesize that optimizing the mean arterial pressure (MAP) to the baseline MAP of the patient during cardiac surgery with CPB and during the first 24 hours postoperatively may improve outcomes. STUDY DESIGN: The OPTIPAM trial (NCT05403697) will be a multicenter, randomized, open-label controlled trial testing the superiority of optimized MAP management as compared with a MAP of 65 mm Hg or more during both the intraoperative and postoperative periods in 1,100 patients scheduled for cardiac surgery with CPB. The primary composite end point is the occurrence of acute kidney injury, neurological complications including stroke or postoperative delirium, and death. The secondary end points are hospital and intensive care unit lengths of stay, Day 7 and Day 90 mortality, postoperative cognitive dysfunction on Day 7 and Day 90, and quality of life at Day 7 and Day 90. Two interim analyses will assess the safety of the intervention. CONCLUSION: The OPTIPAM trial will assess the effectiveness of an individualized target of mean arterial pressure in cardiac surgery with CPB in reducing postoperative morbidity. CLINICAL TRIAL REGISTRATION: NCT05403697.

Gastric Cross-Sectional Area to Predict Gastric Intolerance in Critically Ill Patients: The Sono-ICU Prospective Observational Bicenter Study.

To evaluate the correlation between gastric cross-sectional area (GCSA) and the occurrence of gastric intolerance in critically ill patients within 24 hours of the measurement. DESIGN: Two-center prospective observational study. SETTING: Two academic ICUs in France between June 2020 and August 2021. PATIENTS: All surgical intubated ICU patients greater than or equal to 18 years old receiving enteral feeding for greater than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-four patients were included, 11 (25%) of whom presented digestive intolerance. Primary outcome was assessment of the association between GCSA and the occurrence of gastric intolerance within 24 hours of the measurement. GCSA value was significantly higher in patients with upper digestive intolerance compared to those without (553 mm2 [interquartile range (IQR), 500-649 mm2] vs 970 mm2 [IQR, 777-1,047]; p < 0.001, respectively). The optimal threshold for predicting upper digestive intolerance was 720 mm2 (area under the receiver operating characteristic curve 0.86; positive predictive value 62.5%; negative predictive value 96.4%; sensibility 0.91; and specificity 0.81). Multivariate analysis (weighted by propensity score), including known risk factors, showed that GCSA above the 720 mm2 threshold was independently associated with the occurrence of upper digestive intolerance (odds ratio, 1.85; 1.37-2.49; p < 0.0002). Measurement quality was "good" (i.e., liver, aorta, superior mesenteric vein, and pancreas were all visualized) in 81% of cases. CONCLUSIONS: Measurement of GCSA by ultrasound would allow prediction of gastric intolerance in critically ill patients. This should be confirmed by a prospective score validation and interventional trials.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

Pain Assessment Using Virtual Reality Facemask During Bone Marrow Aspiration: Prospective Study Including Propensity-Matched Analysis.

BACKGROUND: Bone marrow aspiration (BMA) is a medical procedure necessary to the diagnosis and monitoring of patients with hematological or nonhematological disorders. This procedure is considered painful, and patients are generally anxious before and during BMA. OBJECTIVE: This study assesses the effect of immersive virtual reality on pain during BMA. METHODS: This observational prospective and monocentric study enrolled 105 consecutive patients who underwent sternal BMA with lidocaine anesthesia. The study was carried on during 2 periods. First, virtual reality facemask (VRF) was proposed to all patients in the absence of exclusion criteria. During the second period, BMA was performed without the VRF. For all patients, pain intensity after the procedure was assessed using a 10-point numerical pain rating scale (NPRS). All analyses were performed on propensity score-matched cohort (with or without VRF) to evaluate efficacy on NRPS levels. RESULTS: The final matched cohort included 12 patients in the VRF group and 24 in the control group. No difference in anxiety level before BMA evaluated by the patient and by the operator was observed between groups (P=.71 and .42 respectively). No difference of NPRS was observed using VRF when compared to control group (median NPRS 3.8, IQR 2.0-6.3 vs 3.0, IQR 1.9-3.0, respectively; P=.09). CONCLUSIONS: Our study did not prove the efficacy of VRF to reduce pain during BMA.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

BACKGROUND: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality. METHODS: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551). Association between red blood cells transfusion administered in intensive care unit and 1-year mortality in critical care survivors was analyzed using an augmented inverse probability of treatment weighting-augmented inverse probability of censoring weighting method to control confounders. RESULTS: Among the 1551 ICU-survivors, 42% received at least one unit of red blood cells while in intensive care unit. Patients in the transfusion group had greater severity scores than those in the no-transfusion group. According to unweighted analysis, 1-year post-critical care mortality was greater in the transfusion group compared to the no-transfusion group (hazard ratio (HR) 1.78, 95% CI 1.45-2.16). Weighted analyses including 40 confounders, showed that transfusion remained associated with a higher risk of long-term mortality (HR 1.21, 95% CI 1.06-1.46). CONCLUSIONS: Our results suggest a high incidence of in-ICU RBC transfusion and that in-ICU transfusion is associated with a higher 1-year mortality among in-ICU survivors. Trial registration ( NCT01367093 ; Registered 6 June 2011).

Prophylactic levosimendan in patients with low ejection fraction undergoing coronary artery bypass grafting: A pooled analysis of two multicentre randomised controlled trials.

OBJECTIVES: To assess the effect of preoperative levosimendan on mortality at day 90 in patients with left ventricular ejection fraction (LVEF) ≤ 40%, and to investigate a possible differential effect between patients undergoing isolated coronary artery bypass grafting (CABG) versus CABG combined with valve replacement surgery. DESIGN: Pooled analysis of two multicentre randomised controlled trials (RCT) investigating prophylactic levosimendan versus placebo prior to CABG surgery on mortality at day 90 in patients with LVEF ≤ 40%. A meta-analysis of all RCT investigating the same issue was also conducted. RESULTS: A cohort of 1084 patients (809 isolated CABG, and 275 combined surgery) resulted from the merging of LEVO-CTS and LICORN databases. Seventy-two patients were dead at day 90. The mortality at day 90 was not different between levosimendan and placebo (Hazard Ratio (HR): 0.73, 95% CI: 0.41-1.28, p = 0.27). However, there was a significant interaction between the type of surgery and the study drug (p = 0.004). We observed a decrease in mortality at day 90 in the isolated CABG subgroup (HR: 0.39, 95% CI: 0.19-0.82, p = 0.013), but not in the combined surgery subgroup (HR: 1.73, 95% CI: 0.77-3.92, p = 0.19). The meta-analysis of 6 RCT involving 1441 patients confirmed the differential effect on mortality at day 30 between the 2 subgroups. CONCLUSIONS: Preoperative levosimendan did not reduce mortality in a mixed surgical population with LV dysfunction. However, the subgroup of patients undergoing isolated CABG had a reduction in mortality at day 90, whereas there was no significant effect in combined surgery patients. This finding requires confirmation with a specific prospective trial.

Guidelines on enhanced recovery after cardiac surgery under cardiopulmonary bypass or off-pump.

OBJECTIVE: To provide recommendations for enhanced recovery after cardiac surgery (ERACS) based on a multimodal perioperative medicine approach in adult cardiac surgery patients with the aim of improving patient satisfaction, reducing postoperative mortality and morbidity, and reducing the length of hospital stay. DESIGN: A consensus committee of 20 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Société française de chirurgie thoracique et cardio-vasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide the assessment of the quality of evidence. METHODS: Six fields were defined: (1) selection of the patient pathway and its information; (2) preoperative management and rehabilitation; (3) anaesthesia and analgesia for cardiac surgery; (4) surgical strategy for cardiac surgery and bypass management; (5) patient blood management; and (6) postoperative enhanced recovery. For each field, the objective of the recommendations was to answer questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). Based on these questions, an extensive bibliographic search was carried out and analyses were performed using the GRADE approach. The recommendations were formulated according to the GRADE methodology and then voted on by all the experts according to the GRADE grid method. RESULTS: The SFAR/SFCTCV guideline panel provided 33 recommendations on the management of patients undergoing cardiac surgery under cardiopulmonary bypass or off-pump. After three rounds of voting and several amendments, a strong agreement was reached for the 33 recommendations. Of these recommendations, 10 have a high level of evidence (7 GRADE 1+ and 3 GRADE 1-); 19 have a moderate level of evidence (15 GRADE 2+ and 4 GRADE 2-); and 4 are expert opinions. Finally, no recommendations were provided for 3 questions. CONCLUSIONS: Strong agreement existed among the experts to provide recommendations to optimise the complete perioperative management of patients undergoing cardiac surgery.

Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

PURPOSE: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP). METHODS: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days. RESULTS: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. CONCLUSIONS: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

Perioperative outcomes of pheochromocytoma/paraganglioma surgery preceded by Takotsubo-like cardiomyopathy.

BACKGROUND: Pheochromocytomas and paragangliomas can induce severe cardiovascular manifestations such as Takotsubo-like cardiomyopathy. What the perioperative outcomes are of patients presenting with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy remains an unresolved question. METHODS: From 2006 to 2019, all patients who underwent surgery for pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy were included from 3 high-volume centers, with specific attention to perioperative hemodynamic instability and postoperative outcomes. RESULTS: Overall, 37 patients were included, with a median age of 45 years. Patients were operated on 2 months (1-4) after a Takotsubo-like cardiomyopathy episode; 33 (89%) had a laparoscopic approach. All those who underwent surgery presented in a hemodynamically stable situation. All except 1 of the pheochromocytomas/paragangliomas patients had at least 1 antihypertensive treatment at the time of surgery. The median preoperative systolic blood pressure in the Takotsubo-like cardiomyopathy group was 120 mm Hg (95-132). Overall, 27/34 (79%) of patients required vasoactive drugs during surgery with nicardipine (n = 22), esmolol (n = 12), and/or norepinephrine (n = 8). No patient presented a catecholamine-induced life-threatening complication such as hypertensive crisis, cardiac arrhythmias, pulmonary edema, cardiac ischemia, or Takotsubo-like cardiomyopathy in the perioperative period. Severe morbi-mortality was nil. The systematic review identified 5 studies including 38 pheochromocytomas/paragangliomas patients with at least 1 episode of acute heart failure considered as Takotsubo-like cardiomyopathy before surgery, of which 28 patients had delayed surgery with 1 postoperative death. CONCLUSION: Hemodynamically stabilized patients with pheochromocytomas/paragangliomas preceded by Takotsubo-like cardiomyopathy can be safely scheduled for an elective pheochromocytomas/paragangliomas surgery, with similar intra and postoperative outcomes as those without Takotsubo-like cardiomyopathy.