Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

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.

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.

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.

Dexmedetomidine after Cardiac Surgery for Prevention of Delirium (EXACTUM) trial protocol: a multicentre randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Incidence of delirium after cardiac surgery remains high and delirium has a significant burden on short-term and long-term outcomes. Multiple causes can trigger delirium occurence, and it has been hypothesised that sleep disturbances can be one of them. Preserving the circadian rhythm with overnight infusion of low-dose dexmedetomidine has been shown to lower the occurrence of delirium in older patients after non-cardiac surgery. However, these results remain controversial. The aim of this study was to demonstrate the usefulness of sleep induction by overnight infusion of dexmedetomidine to prevent delirium after cardiac surgery. METHODS AND ANALYSIS: Dexmedetomidine after Cardiac Surgery for Prevention of Delirium is an investigator-initiated, randomised, placebo-controlled, parallel, multicentre, double-blinded trial. Nine centres in France will participate in the study. Patients aged 65 years or older and undergoing cardiac surgery will be enrolled in the study. The intervention starts on day 0 (the day of surgery) until intensive care unit (ICU) discharge; the treatment is administered from 20:00 to 08:00 on the next day. Infusion rate is modified by the treating nurse or the clinician with an objective of Richmond Agitation and Sedation Scale score from -1 to +1. The primary outcome is delirium occurrence evaluated with confusion assessment method for the ICU two times per day during 7 days following surgery. Secondary outcomes include incidence of agitation related events, self-evaluated quality of sleep, cognitive evaluation 3 months after surgery and quality of life 3 months after surgery. The sample size is 348. ETHICS AND DISSEMINATION: The study was approved for all participating centers by the French Central Ethics Committee (Comité de Protection des Personnes Ile de France VI, registration number 2018-000850-22). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03477344.

Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial.

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Impact of Sex in the Efficacy of Perioperative Desensitization Procedures in Heart Transplantation: A Retrospective Cohort Study.

Background: Sensitized patients, i.e. recipients with preformed donor-specific HLA antibodies (pfDSA), are at high-risk of developing antibody-mediated rejections (AMR) and dying after heart transplantation (HTx). Perioperative desensitization procedures are associated with better outcomes but can cause sensitization, which may influence their efficacy. Methods: In sensitized patients (pfDSA>1000 mean immunofluorescence (MFI) units), we assessed the effect of perioperative desensitization by comparing treated patients to a historical control cohort. Multivariable survival analyses were performed on the time to main outcome, a composite of death and biopsy-proven AMR with 5-year follow-up. Results: The study included 68 patients: 31 control and 37 treated patients. There was no difference in preoperative variables between the two groups, including cumulative pfDSA [4026 (1788;8725) vs 4560 (3162;13392) MFI units, p=0.28]. The cause of sensitization was pregnancy in 24/68, 35.3%, transfusion in 61/68, 89.7%, and previous HTx in 4/68, 5.9% patients. Multivariable analysis yielded significant protective association between desensitization and events (adjusted (adj.) hazard ratio (HR)=0.44 (95% confidence interval (95CI)=0.25-0.79), p=0.006) and deleterious association between cumulative pfDSA and events [per 1000-MFI increase, adj.HR=1.028 (1.002-1.053), p=0.031]. There was a sex-difference in the efficacy of desensitization: in men (n=35), the benefit was significant [unadj.HR=0.33 (95CI=0.14-0.78); p=0.01], but not in women (n=33) [unadj.HR=0.52 (0.23-1.17), p=0.11]. In terms of the number of patients treated, in men, 2.1 of patients that were treated prevented 1 event, while in women, 3.1 required treatment to prevent 1 event. Conclusion: Perioperative desensitization was associated with fewer AMR and deaths after HTx, and efficacy was more pronounced in men than women.

An international survey on aminoglycoside practices in critically ill patients: the AMINO III study.

BACKGROUND: While aminoglycosides (AG) have been used for decades, debate remains on their optimal dosing strategy. We investigated the international practices of AG usage specifically regarding dosing and therapeutic drug monitoring (TDM) in critically ill patients. We conducted a prospective, multicentre, observational, cohort study in 59 intensive-care units (ICUs) in 5 countries enrolling all ICU patients receiving AG therapy for septic shock. RESULTS: We enrolled 931 septic ICU patients [mean ± standard deviation, age 63 ± 15 years, female 364 (39%), median (IQR) SAPS II 51 (38-65)] receiving AG as part of empirical (761, 84%) or directed (147, 16%) therapy. The AG used was amikacin in 614 (66%), gentamicin in 303 (33%), and tobramycin in 14 (1%) patients. The median (IQR) duration of therapy was 2 (1-3) days, the number of doses was 2 (1-2), the median dose was 25 ± 6, 6 ± 2, and 6 ± 2 mg/kg for amikacin, gentamicin, and tobramycin respectively, and the median dosing interval was 26 (23.5-43.5) h. TDM of Cmax and Cmin was performed in 437 (47%) and 501 (57%) patients, respectively, after the first dose with 295 (68%) patients achieving a Cmax/MIC > 8 and 353 (71%) having concentrations above Cmin recommended thresholds. The ICU mortality rate was 27% with multivariable analysis showing no correlation between AG dosing or pharmacokinetic/pharmacodynamic target attainment and clinical outcomes. CONCLUSION: Short courses of high AG doses are mainly used in ICU patients with septic shock, although wide variability in AG usage is reported. We could show no correlation between PK/PD target attainment and clinical outcome. Efforts to optimize the first AG dose remain necessary. Trial registration Clinical Trials, NCT02850029, registered on 29th July 2016, retrospectively registered, https://www.clinicaltrials.gov.

SARS-CoV-2 Fulminant Myocarditis.

An 18-year-old male without prior medical history developed fulminant myocarditis concomitant to severe COVID-19 pneumonia, which was confirmed using serial cardiac magnetic resonance. This may have important diagnostic, monitoring, and pathogenic implications. (Level of Difficulty: Intermediate.).

A single-center long-term experience with marginal donor utilization for heart transplantation.

BACKGROUND: To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). METHODS: Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age >55 years, high-dose inotropic support, left ventricular ejection fraction <45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio <0.86, ischemic time >4 hours. RESULTS: A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%; P < .001), less acute renal failure (23% vs 34%; P < .001), and higher survival rates (90.2% vs 81.8% at 30 days, 79.5% vs 71.1% at 1 year, 51.8% vs 45.4% at 12 years; P = .01) than recipients who received an organ from a MD. There was no statistically significant difference in 30-day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12 years; P = .43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. CONCLUSIONS: Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30-day survival.

Risk Factors for Developing Severe Acute Kidney Injury in Adult Patients With Refractory Postcardiotomy Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: Postcardiotomy cardiogenic shock occurs in 2-6% of patients undergoing cardiac surgery, and 1% of cardiac surgery patients will require mechanical circulatory support using venoarterial extracorporeal membrane oxygenation. Acute kidney injury is a frequent complication in this population and negatively impacts the survival. We aimed to determine whether the timing of extracorporeal membrane oxygenation implantation influences the renal prognosis of these patients. DESIGN: Retrospective observational cohort study between January 2013 and December 2016. SETTING: An 18-bed surgical ICU in a university hospital. PATIENTS: A total of 4,796 consecutive adult patients who underwent cardiac surgery were included in the study, and 347 (7.2%) were assisted with venoarterial extracorporeal membrane oxygenation for refractory postcardiotomy cardiogenic shock. The patients who died during the first 48 hours after venoarterial extracorporeal membrane oxygenation implantation were excluded. The complete-case analysis included 257 patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence, within 10 days following the venoarterial extracorporeal membrane oxygenation implantation, of a stage 3 acute kidney injury defined by the Kidney Disease: Improving Global Outcomes group. One hundred sixty-nine patients (65.7%) presented with a Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury; 14 patients (5.4%) died before the end of the follow-up period, without developing the primary outcome. Ninety-two percent of patients with Kidney Disease: Improving Global Outcomes 3 acute kidney injury received renal replacement therapy, for a median duration of 7 days (3-16 d). Late implantation of venoarterial extracorporeal membrane oxygenation was independently associated with an increased risk of Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury (odds ratio, 2.81 [95% CI, 1.31-6.07]; p = 0.008). The other factors associated with Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury were preoperative left ventricular ejection fraction (odds ratio, 1.03 [95% CI, 1.01-1.05]; p = 0.007), intraoperative plasma transfusion (odds ratio, 1.13 [95% CI, 1.02-1.26]; p = 0.022), increased bilirubinemia level (odds ratio, 1.013 [95% CI, 1.001-1.026]; p = 0.032), and increased creatinine levels (odds ratio, 1.012 [95% CI, 1.006-1.018]; p < 0.001) on the day of implantation. CONCLUSIONS: Significant kidney dysfunction is particularly frequent in patients with refractory postcardiotomy cardiogenic shock assisted with venoarterial extracorporeal membrane oxygenation. Early implantation of extracorporeal membrane oxygenation may help prevent acute kidney injury.

Guidelines: Anaesthesia in the context of COVID-19 pandemic.

OBJECTIVES: The world is currently facing an unprecedented healthcare crisis caused by the COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. METHODS: The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) protection of staff and patients; (2) benefit/risk and patient information; (3) preoperative assessment and decision on intervention; (4) modalities of the preanaesthesia consultation; (5) specificity of anaesthesia and analgesia; (6) dedicated circuits and (7) containment exit type of interventions. RESULTS: The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. CONCLUSION: We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context.

Timing of ß-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study.

BACKGROUND: For cardiac surgery patients under chronic ß-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of ß-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation. METHODS: This multicenter prospective French cohort study included patients on ß-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of ß-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of ß-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed). RESULTS: Of 663 patients, ß-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of ß-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h. CONCLUSIONS: ß-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) ß-blocker reintroduction after cardiac surgery.

Predictive risk factors for postoperative pneumonia after heart transplantation.

BACKGROUND: Pneumonia is a frequent complication in patients undergoing heart transplantation (HTx) that increases morbidity and mortality in this population. Nevertheless, the risk factors for postoperative pneumonia (POP) are still unknown. The aim of this study was to investigate the predictive risk factors for POP in HTx recipients. METHODS: In this retrospective study, all patients undergoing HTx between January 2014 and December 2015 were included. All cases of POP occurring until hospital discharge were investigated. The study aimed to determine risk factors using univariate and multivariate Cox regression models. Data are expressed in Odds Ratio [95% CI]. P < 0.05 was necessary to reject the null hypothesis. RESULTS: A total of 175 patients were included without any patients being lost to follow-up, and 89 instances of POP were diagnosed in 59 (34%) patients. Enterobacteriaceae and Pseudomonas aeruginosa were the most common pathogens. In the multivariate analysis, the risk factors were preoperative mechanical ventilation (OR 1.42 [1.12-1.80], P < 0.01) and perioperative blood transfusion (OR 1.42 [95% CI: 1.20-1.70], P < 0.01). POP significantly impacted mortality at 30 days (OR: 4 [1.3-12.4], P = 0.01) and 1 year (OR: 6.8 [2.5-8.4], P < 0.01) and was associated with a longer duration of mechanical ventilation, time to weaning from venoarterial extracorporeal membrane oxygenation and stay in an intensive care unit. Plasma exchanges and intravenous administration of immunoglobulins did not increase the risk of POP. CONCLUSION: After HTx, preoperative mechanical ventilation and blood transfusion were risk factors for POP and were associated with increased mortality. Enterobacteriaceae and Pseudomonas aeruginosa are the most common pathogens of POP.

Mechanical circulatory support with the Impella 5.0 and the Impella Left Direct pumps for postcardiotomy cardiogenic shock at La Pitié-Salpêtrière Hospital.

OBJECTIVES: Postcardiotomy cardiogenic shock (PCCS) is associated with high mortality rates of 50-80%. Although veno-arterial extracorporeal membrane oxygenation has been used as mechanical circulatory support in patients with PCCS, it is associated with a high rate of complications and poor quality of life. The Impella 5.0 and Impella Left Direct (LD) (Impella 5.0/LD) are minimally invasive left ventricular assist devices that provide effective haemodynamic support resulting in left ventricular unloading and systemic perfusion. Our goal was to describe the outcome of patients with PCCS supported with the Impella 5.0/LD at La Pitié-Salpêtrière Hospital. METHODS: We retrospectively reviewed consecutive patients supported with the Impella 5.0/LD for PCCS between December 2010 and June 2015. Survival outcome and in-hospital complications were assessed. RESULTS: A total of 29 patients (63 ± 14 years, 17% women) with PCCS were supported with the Impella 5.0/LD. At baseline, 69% experienced chronic heart failure, 66% had dilated cardiomyopathy and 57% had valvular disease. The mean EuroSCORE II was 22 ± 17 and the ejection fraction was 28 ± 11%. Most of the patients underwent isolated valve surgery (45%) or isolated coronary artery bypass grafting (38%). The mean duration of Impella support was 9 ± 7 days. Weaning from the Impella was successful in 72.4%, and 58.6% survived to discharge. Recovery of native heart function was observed in 100% of discharged patients. Survival to 30 days and to 1 year from Impella implant was 58.6% and 51.7%, respectively. CONCLUSIONS: The Impella 5.0 and the Impella LD represent an excellent treatment option for critically ill patients with PCCS and are associated with favourable survival outcome and native heart recovery.

Levosimendan in the light of the results of the recent randomized controlled trials: an expert opinion paper.

Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

Colour Doppler ultrasound after major cardiac surgery improves diagnostic accuracy of the pulmonary infection score in acute respiratory failure: A prospective observational study.

BACKGROUND: Postoperative pneumonia is a frequent complication after cardiac surgery, and its diagnosis is difficult. Little is known about the diagnostic accuracy of lung ultrasound (LUS) in the detection of pneumonia in cardiac surgical patients. The substitution of chest radiography by colour Doppler LUS (LUS-sCPIS) in the simplified clinical pulmonary infection score (sCPIS) could improve the diagnosis of pneumonia following cardiac surgery. OBJECTIVE: The aim of this study was to compare the diagnostic accuracy of LUS-sCPIS and of sCPIS alone in the detection of postoperative pneumonia after cardiac surgery. DESIGN: A prospective study of diagnostic accuracy. SETTING: A Surgical Intensive Care Unit of a French University Hospital. PATIENTS: Fifty-one patients with acute respiratory failure within 72 h after cardiac surgery were enrolled between January and May 2015. MAIN OUTCOME MEASURE: The two index tests, LUS-sCPIS and sCPIS, were calculated for all patients at the onset of acute respiratory failure. The reference standard for the diagnosis of pneumonia was based on the consensus of three physicians, blind to the sCPIS and LUS-sCPIS data, based on a posthoc review of all the clinical, radiological and microbiological evidence. The diagnostic accuracy of LUS-sCPIS was compared with that of sCPIS in the detection of postoperative pneumonia. RESULTS: Pneumonia was diagnosed in 26 out of 51 patients. The LUS-sCPIS detected the presence of pneumonia with a sensitivity of 92% (95% CI 0.85 to 0.99) and a specificity of 68% (95% CI 0.55 to 0.81). The sCPIS detected the presence of pneumonia with a sensitivity of 35% (95% CI 0.22 to 0.48) and a specificity of 84% (95% CI 0.74 to 0.94). The area under the curve (AUC) of LUS-sCPIS at 0.80 (95% CI 0.69 to 0.91) was higher than the AUC of sCPIS at 0.59 (95% CI 0.47 to 0.71; P = 0.0008). CONCLUSION: Compared with sCPIS, LUS-sCPIS improved diagnostic accuracy in the detection of postoperative pneumonia in patients with acute respiratory failure after cardiac surgery. It could be a useful bedside tool to guide pneumonia management. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03279887.