Publications by authors named "François Kerbaul"

68 Publications

Impact of the first Covid-19 outbreak on liver transplantation activity in France: A snapshot.

Clin Res Hepatol Gastroenterol 2020 Nov 8:101560. Epub 2020 Nov 8.

Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière Hospital, Paris, France. Electronic address:

Background: The global pandemic of Coronavirus Disease 2019 (COVID-19) has potentially affected liver transplantation (LT) programs worldwide. The aim of this study was to determine whether the COVID-19 outbreak affected organ donation and LT activity in France.

Methods: Data on the number of brain-dead donor procurements and adult liver transplantations were compared between two periods (1 January- 31 May 2019 vs. 1 January-31 May 2020).

Main Findings: There was a 28% decrease in the number of organ donations in 2020 (543 in 2020vs. 752 organ donations in 2019). A 22% decrease in the number of liver transplantations was also observed: 435 in 2020 vs. 556 LTs in 2019. Overall, the North East area which was the main COVID-19 cluster area, had > 25% decrease of the multiorgan procurement (-33% compared to 2019), and liver transplantation (-26% compared to 2019) activities in 2020 CONCLUSION: This analysis confirmed that during the COVID-19 outbreak there was a significant decrease in the number of organ donations and liver transplantations performed in France.
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http://dx.doi.org/10.1016/j.clinre.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649029PMC
November 2020

Impact of coronavirus disease 2019 on organ donation and transplantation in France.

Transpl Int 2021 01 10;34(1):204-206. Epub 2020 Nov 10.

Direction Prélèvement Greffe Organe - Tissus, Agence de la Biomédecine, La Plaine Saint-Denis, France.

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http://dx.doi.org/10.1111/tri.13769DOI Listing
January 2021

The impact of Coronavirus 19 disease on liver transplantation in France: The sickest first approach?

Clin Res Hepatol Gastroenterol 2020 09 22;44(4):e81-e83. Epub 2020 Jun 22.

AP-HP, Unité Médicale de Transplantation Hépatique Hôpital Pitié Salpêtrière, Boulevard de l'Hôpital 47-83, 75013 Paris, France; Sorbonne Université, inserm, Centre de recherche Saint-Antoine (CRSA), Paris, France; Sorbonne Université, inserm, Institute of Cardiometabolisme and Nutrition (ICAN), Paris, France.

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http://dx.doi.org/10.1016/j.clinre.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306706PMC
September 2020

Optimal Timing of Intervention in NSTE-ACS Without Pre-Treatment: The EARLY Randomized Trial.

JACC Cardiovasc Interv 2020 04;13(8):907-917

Aix-Marseille Université, Intensive Care Unit, Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France; Mediterranean Association for Research and Studies in Cardiology, Marseille, France; Centre for CardioVascular and Nutrition Research, INSERM 1263, INRA 1260, Marseille, France. Electronic address:

Objectives: The aim of this study was to compare a delayed and a very early invasive strategy in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) without pre-treatment.

Background: The optimal delay of the invasive strategy in patients with NSTE-ACS remains debated and has never been investigated in patients not pre-treated with P2Y-adenosine diphosphate receptor antagonists.

Methods: A prospective, open-label, randomized controlled trial was conducted. Altogether, 741 patients presenting with intermediate- or high-risk NSTE-ACS intended for an invasive strategy were included. The modified intention-to-treat analysis was composed of 709 patients after 32 withdrew consent. Patients were randomized 1:1 to the delayed invasive group (DG) (n = 363) with coronary angiography (CA) performed 12 to 72 h after randomization or the very early invasive group (EG) (n = 346) with CA within 2 h. No pre-treatment with a loading dose of a P2Y-adenosine diphosphate receptor antagonist was allowed before CA. The primary endpoint was the composite of cardiovascular death and recurrent ischemic events at 1 month, as determined by a blinded adjudication committee.

Results: Most patients had high-risk NSTE-ACS in both groups (93% in the EG vs. 92.5% in the DG). The median time between randomization and CA was 0 h (interquartile range [IQR]: 0 to 1 h) in the EG group and 18 h (IQR: 11 to 23 h) in the DG. The primary endpoint rate was significantly lower in the EG (4.4% vs. 21.3% in the DG; hazard ratio: 0.20; 95% confidence interval: 0.11 to 0.34; p < 0.001), driven by a reduction in recurrent ischemic events (19.8% vs. 2.9%; p < 0.001). No difference was observed for cardiovascular death.

Conclusions: Without pre-treatment, a very early invasive strategy was associated with a significant reduction in ischemic events at the time of percutaneous coronary intervention in patients with intermediate- and high-risk NSTE-ACS. (Early or Delayed Revascularization for Intermediate and High-Risk Non ST-Elevation Acute Coronary Syndromes; NCT02750579).
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http://dx.doi.org/10.1016/j.jcin.2020.01.231DOI Listing
April 2020

Correlation between field triage criteria and the injury severity score of trauma patients in a French inclusive regional trauma system.

Scand J Trauma Resusc Emerg Med 2019 Aug 5;27(1):71. Epub 2019 Aug 5.

Anesthesia and Intensive Care Department, Sainte-Anne Military Hospital, 83041, Toulon, France.

Background: In France, the pre-hospital field triage of trauma patients is currently based on the Vittel criteria algorithm. This algorithm was originally created in 2002 before the stratification of trauma centers and, at the national level, has not been revised since. This could be responsible for the overtriage of trauma patients in Level I Trauma Centers. The principal aim of this study was to evaluate the correlation between each Vittel field triage criterion and trauma patients' Injury Severity Score.

Methods: Our Level I Trauma Center receives an average of 300 trauma patients per year. Demographic and physiological data, along with the entire trauma patient management process and Vittel field triage criteria, are recorded in a local trauma registry. The Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are calculated after a complete assessment of the trauma victim during their in-hospital management. Results were concerned with the presence of an ISS of greater than 15, which defined a major trauma patient; mortality within 30 days; and admission to the intensive care unit. This study is a registry analysis from January 2013 to September 2017.

Results: Of the 1373 patients in the registry, 1151 were included in the analysis with a mean age of 43 years (± 19) and a median ISS of 13 (IQR = 5-22), where 887 (77%) were male. Nine of the 24 Vittel criteria were associated with an ISS > 15. In a multivariate analysis, no criterion related to kinetic elements was significantly correlated with an ISS > 15, mortality within 30 days, or admission to intensive care. Three algorithm categories were predictive of a major trauma patient (ISS > 15): physiological variables, pre-hospital resuscitation, and physical injuries, while kinetic elements were not.

Conclusions: Criteria related to physiological variables, pre-hospital resuscitation, and physical injuries are the most relevant to predicting the severity of a trauma patient's condition. A revision of the VCA could potentially have beneficial effects on the over and undertriage phenomena, which constitute ongoing medical and financial concerns.
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http://dx.doi.org/10.1186/s13049-019-0652-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683531PMC
August 2019

Evaluation and Comparison of Different Prehospital Triage Scores of Trauma Patients on In-Hospital Mortality.

Prehosp Emerg Care 2019 Jul-Aug;23(4):543-550. Epub 2019 Jan 7.

Several prehospital major trauma patient triage scores have been developed, the triage revised trauma score (T-RTS), Vittel criteria, Mechanism/Glasgow Coma Scale/Age/Systolic blood pressure score (MGAP), and the new trauma score (NTS). These scoring schemes allow a rapid and accurate prognostic assessment of the severity of potential lesions. The aim of our study was to compare these scores with in-hospital mortality predictions in a cohort of consecutive trauma patients admitted in a Level 1 trauma center. Between 2013 and 2016, 1,112 patients were admitted to the "major trauma" spinneret of a Level 1 trauma center in the south of France. All prehospital data needed to calculate the T-RTS, Vittel criteria, the MGAP score, and the NTS were collected. The main evaluation criterion was in-hospital mortality at 30 days for all causes. The predictive performances of these scores were evaluated and compared with each other using the analysis of the receiver operating curves. A total of 1,001 patients were included in the analysis, 238 (24%) females, aged 43 ± 19 years with ISS 15 ± 13. The area under the curve was for each score: T-RTS, AUC = 0.84, [0.82-0.87]; Vittel criteria, AUC = 0.87 [0.85-0.89]; MGAP score, AUC = 0.91 [0.89-0.92] and NTS, AUC = 0.90 [0.88-0.92]. By comparing the ROC curves of these scores, the MGAP and NTS scores were statistically higher than the T-RTS. With the current thresholds, the sensitivity, specificity, positive and negative predictive values of these scores were 91%, 35%, 10%, 98% for T-RTS, 100%, 2%, 8%, 100% for Vittel criteria, 91%, 71%, 24%, 99% for MGAP score, 82%, 86%, 33%, 98% for NTS. Only Vittel's criteria allowed undertriage below 5% as recommended by the American College of Surgeons Committee on Trauma (ACSCOT). The comparison of these different triage scores concluded with a superiority of the MGAP and NTS scores compared with the T-RTS. Including the calculation of MGAP or NTS scores with the Vittel criteria would reduce the risk of overtriage in the Level 1 trauma centers by further directing patients at low risk of death to a lower-level trauma facility.
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http://dx.doi.org/10.1080/10903127.2018.1549627DOI Listing
January 2020

Corrigendum to "Stress Cardiomyopathy Managed with Extracorporeal Support after Self-Injection of Epinephrine".

Case Rep Crit Care 2018 9;2018:3121408. Epub 2018 Aug 9.

Réanimation des Urgences et Médicale, Assistance Publique Hôpitaux de Marseille, CHU la Timone 2, Aix-Marseille Université, Marseille, France.

[This corrects the article DOI: 10.1155/2017/3731069.].
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http://dx.doi.org/10.1155/2018/3121408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106969PMC
August 2018

Integrating extended focused assessment with sonography for trauma (eFAST) in the initial assessment of severe trauma: Impact on the management of 756 patients.

Injury 2018 Oct 8;49(10):1774-1780. Epub 2018 Jul 8.

Department of Anesthesiology and Critical Care, North university hospital, AP-HM, Marseille, France; Aix-Marseille University, Marseille, France; Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UMR 63, Marseille, France.

Background: Before total body computed tomography scan, an initial rapid imaging assessment should be conducted in the trauma bay. It generally includes a chest x-ray, pelvic x-ray, and an extended focused ultrasonography assessment for trauma. This initial imaging assessment has been poorly described since the increase in the use of ultrasound. Therefore, our study aimed to evaluate the diagnostic accuracy and therapeutic impact of this initial imaging work-up in severe trauma patients. A secondary aim was to assess the therapeutic impact of a chest x-ray according to the lung ultrasonography findings.

Methods: Patients with severe trauma who were admitted directly to our level 1 trauma center were consecutively included in this retrospective single center study. The diagnostic accuracy, therapeutic impact, and appropriate decision rate were calculated according to the initial assessment results of the whole body computed tomography scan and surgery reports.

Results: Among the 1315 trauma patients admitted, 756 were included in this research. Lung ultrasound showed a higher diagnostic accuracy for haemothorax and pneumothorax cases than the chest x-ray. Sensitivity and specificity of the abdominal ultrasound to detect intraperitoneal effusion were 70% and 96%, respectively. The initial assessment had a therapeutic impact in 76 (10%) of the patients, including 16 (2%) immediate laparotomies and 58 (7%) chest tube insertions. The pelvic x-ray had no therapeutic impact, and when the lung ultrasound was normal, the chest x-ray had a therapeutic impact of only 0.13%. Combining the chest x-ray and lung ultrasound allowed adequate management of all the pneumothorax and haemothorax cases. Only one of the 756 patients had initial management that was judged as inappropriate. This patient had a missed pelvic disjunction with active retroperitoneal bleeding, and underwent an inappropriate immediate laparotomy.

Conclusions: In our cohort, the initial imaging assessment allowed appropriate decisions in 755 of 756 patients, with a global therapeutic impact of 10%. The pelvic x-ray had a minimal therapeutic impact, and in the patients with normal lung ultrasounds, the chest x-ray marginally affected the management of our patients. The potential consequences of abandoning systematic chest and pelvic x-rays should be investigated in future randomized prospective studies.
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http://dx.doi.org/10.1016/j.injury.2018.07.002DOI Listing
October 2018

Adenosine Plasma Level and A2A Receptor Expression in Patients With Cardiogenic Shock.

Crit Care Med 2018 09;46(9):e874-e880

Department of Cardiology, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille, France.

Objectives: To investigate whether adenosine A2A receptors lead to vasodilation and positive inotropic function under stimulation and whether they play a role in the control of blood pressure in patients with cardiogenic shock.

Design: Prospective observational study.

Setting: Monocentric, Hopital Nord, Marseille, France.

Subjects: Patients with cardiogenic shock (n = 16), acute heart failure (n = 16), and acute myocardial infarction (n = 16).

Interventions: None.

Measurements And Main Results: Arterial adenosine plasma level and A2A receptor expression on peripheral blood mononuclear cells were evaluated by mass spectrometry and Western blot, respectively, at admission and after 24 hours. Hemodynamic parameters, including systemic vascular resistance, were also assessed. Mean adenosine plasma level at admission was significantly higher in patients with cardiogenic shock (2.74 ± 1.03 µM) versus acute heart failure (1.33 ± 0.27) or acute myocardial infarction (1.19 ± 0.27) (normal range, 0.4-0.8 µM) (p < 0.0001). No significant correlation was found between adenosine plasma level and systemic vascular resistance. Mean adenosine plasma level decreased significantly by 24 hours after admission in patients with cardiogenic shock (2.74 ± 1.03 to 1.53 ± 0.68; p < 0.001). Mean A2A receptor expression was significantly lower in patients with cardiogenic shock (1.18 ± 0.11) versus acute heart failure (1.18 ± 0.11 vs 1.39 ± 0.08) (p = 0.005).

Conclusions: We observed high adenosine plasma level and low A2A receptor expression at admission in patients with cardiogenic shock versus acute heart failure or acute myocardial infarction. This may contribute to the physiopathology of cardiogenic shock.
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http://dx.doi.org/10.1097/CCM.0000000000003252DOI Listing
September 2018

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

Eur J Anaesthesiol 2018 12;35(12):911-918

From the Department of Anaesthesia and Intensive Care Medicine (DL, LN, FK, NB, LV, CG), Department of Biochemistry (RG, EF), Department of Biostatistics (NR, RG), Department of Cardiac Surgery (AT, DG, VG), La Timone University Hospital, Aix-Marseille University, Marseille, France (FC).

Background: Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF).

Objective: We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF.

Design: A randomised controlled study.

Setting: Single University Hospital.

Patients: One hundred and ten patients scheduled for heart valve surgery with CPB.

Interventions: We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients.

Main Outcome Measures: The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay.

Results: The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005).

Conclusion: Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting.

Clinical Trial Registration: ClinicalTrials.gov, no.: NCT01999829.
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http://dx.doi.org/10.1097/EJA.0000000000000824DOI Listing
December 2018

Specific Pharmacological Profile of A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease.

J Am Heart Assoc 2018 04 13;7(8). Epub 2018 Apr 13.

UMR MD2, Aix-Marseille University, Marseille, France.

Background: The rapid and reliable exclusion of myocardial revascularization is a major unmet clinical need in patients with suspected coronary artery disease (CAD) and non-contributive electrocardiography and troponin. Non-invasive tests have high rates of false positives and negatives, and there is no biomarker to assess myocardial ischemia. The presence of spare adenosine A receptors (AR)-characterized by a high dissociation constant/half maximal effective concentration (K/EC) ratio-expressed on peripheral blood mononuclear cells (PBMC) has been associated with ischemia during exercise stress testing in patients with CAD. In this work, we investigated the diagnostic accuracy of spare AR versus fractional flow reserve (FFR) in patients with suspected CAD.

Methods And Results: Sixty patients with suspected CAD, but non-contributive electrocardiography and troponin, were consecutively enrolled in this prospective study. The binding (K), functional response (cyclic adenosine monophosphate [cAMP] production; EC) on PBMC AR were compared with FFR results. Patients were divided into 3 groups: 17 (group 1) with normal coronary angiography (n=13) or stenosis <20% (n=4); 21 with CAD and non-significant FFR (group 2); and 22 with CAD and significant FFR (group 3). Median K/EC was 6-fold higher in group 3 (4.20; interquartile range: 2.81-5.00) than group 2 (0.66; interquartile range: 0.47-1.25) and 7-fold higher than group 1 (0.60; interquartile range: 0.30-0.66).

Conclusions: In patients with suspected CAD and non-contributive electrocardiography and troponin, the absence of spare AR on PBMC may help to rule out myocardial ischemia.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.
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http://dx.doi.org/10.1161/JAHA.117.008290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015402PMC
April 2018

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

Clin Cardiol 2018 Jan 22;41(1):5-12. Epub 2018 Jan 22.

Aix-Marseille Université, AP-HM, Unité INSERM 1076, Unité de Soins Intensifs Cardiologiques, Department of Cardiology, Hôpital Nord, Marseille, France.

According to recent literature, pretreatment with a P2Y ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y ADP receptor antagonist pretreatment.
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http://dx.doi.org/10.1002/clc.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490048PMC
January 2018

Mechanical Support in Cardiogenic Shock Complicating Acute Coronary Syndrome: Ready for Prime Time?

Curr Vasc Pharmacol 2018 ;16(5):418-426

Assistance Publique Hopitaux de Marseille, Department of Cardiology, Hopital Nord, Mediterranean Academic Association for Research and Studies in Cardiology (MARS Cardio), Aix-Marseille University, INSERM UMRS 1076, Marseille, France.

Cardiogenic Shock (CS) is a major challenge in current cardiology. Over the last decade, cardiogenic shock mortality has decreased somewhat, but it still remains high, particularly when associated with ischaemic heart disease. The challenges are numerous and include prevention, accurate diagnosis, prompt management and effective therapies to support a failing heart and prevent multi-organ failure. Despite improvements in the care of Acute Coronary Syndrome (ACS), it remains the most common cause of CS. In addition to existing medical therapy, mechanical circulatory support has been proposed for the management of ventricular failure. The intra-aortic balloon pump was amongst the first widely used percutaneous mechanical support devices, and more recently, systems providing a higher level of support have been developed. Although the evidence supporting their use is limited, they have the potential to significantly reduce CS-associated mortality. In this narrative review, we summarize the available evidence and discuss the future directions regarding percutaneous mechanical circulatory support in patients with left ventricular dysfunction and CS complicating ACS.
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http://dx.doi.org/10.2174/1570161116666180116165544DOI Listing
April 2019

Stress Cardiomyopathy Managed with Extracorporeal Support after Self-Injection of Epinephrine.

Case Rep Crit Care 2017 27;2017:3731069. Epub 2017 Aug 27.

Réanimation des Urgences et Médicale, Assistance Publique Hôpitaux de Marseille, CHU la Timone 2, Aix-Marseille Université, Marseille, France.

A 28-year-old man was admitted to the ICU for self-injection of Epinephrine. This injection resulted in the rapid development of a catecholamine-induced cardiomyopathy (inverted Takotsubo) with a severe cardiogenic shock. The importance of ventricular dysfunction required the implementation of a temporary arteriovenous circulatory support until the recovery of myocardial stunning. This case allows redefining the role of circulatory assistance during cardiotropic agents intoxication.
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http://dx.doi.org/10.1155/2017/3731069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592012PMC
August 2017

Timing of Coronary Invasive Strategy in Non-ST-Segment Elevation Acute Coronary Syndromes and Clinical Outcomes: An Updated Meta-Analysis.

JACC Cardiovasc Interv 2016 11;9(22):2267-2276

EA 3279-Public Health, Chronic Diseases and Quality of Life-Research Unit, Aix-Marseille University, Marseille, France.

Objectives: The aim of this study was to compare an early versus a delayed invasive strategy in non-ST-segment elevation acute coronary syndromes by performing a meta-analysis of all available randomized controlled clinical trials.

Background: An invasive approach is recommended to prevent death and myocardial infarction in non-ST-segment elevation acute coronary syndromes. However, the timing of angiography and the subsequent intervention, when required, remains controversial.

Methods: A previous meta-analysis of 7 randomized clinical trials comparing early and delayed invasive strategies in non-ST-segment elevation acute coronary syndromes with 3 new randomized clinical trials identified in a search of the published research (n = 10 trials, n = 6,397 patients) was updated.

Results: The median time between randomization and angiography ranged from 0.5 to 14.0 h in the early group and from 18.3 to 86.0 h in the delayed group. There was no difference in the primary endpoint of mortality (4% vs. 4.7%; random-effects odds ratio [OR]: 0.85; 95% confidence interval [CI]: 0.67 to 1.09; p = 0.20; I = 0%). The rate of myocardial infarction was also similar (6.7% vs. 7.7%; random-effects OR: 0.88; 95% CI: 0.53 to 1.45; p = 0.62; I = 77.5%). An early strategy was associated with a reduction in recurrent ischemia or refractory angina (3.8% vs. 5.8%; random-effects OR: 0.54; 95% CI: 0.40 to 0.74; p < 0.01; I = 28%) and a shorter in-hospital stay (median 112 h [interquartile range: 61 to 158 h] vs. 168 h [interquartile range: 90.3 to 192 h]; random-effects standardized mean difference -0.40; 95% CI: -0.59 to -0.21; p < 0.01; I = 79%). Major bleeding was similar in the 2 groups (3.9% vs. 4.2%; random-effects OR: 0.94; 95% CI: 0.73 to 1.22; p = 0.64; I = 0%).

Conclusions: An early invasive strategy does not reduce the risk for death or myocardial infarction compared with a delayed strategy. Recurrent ischemia and length of stay were significantly reduced with an early invasive strategy.
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http://dx.doi.org/10.1016/j.jcin.2016.09.017DOI Listing
November 2016

Prehospital and in-hospital course of care for patients with acute heart failure: Features and impact on prognosis in "real life".

Arch Cardiovasc Dis 2017 Feb 29;110(2):72-81. Epub 2016 Sep 29.

Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille (AP-HM), Unit of Heart Failure and Valvular Heart Disease, Department of Cardiology, Nord Hospital, 13915 Marseille cedex 20, France; Mediterranean Academic association for Research and Studies in Cardiology (MARS Cardio), Marseille, France. Electronic address:

Background: Acute heart failure (AHF) is a life-threatening medical emergency for which no new effective therapies have emerged in recent decades. No previous study has exhaustively described the entire course of care of AHF patients from first medical contact to hospital discharge or assessed its impact on prognosis.

Aim: To fully describe the course of care and analyze its influence on outcomes in patients hospitalized with an AHF syndrome in an academic university center.

Methods: One hundred and nineteen adults with AHF from three public academic university hospitals were consecutively enrolled in a multicenter prospective observational cohort study. All of the emergency departments, intensive care units, coronary care units, cardiology wards and other medical wards participated in the study.

Results: The composite primary outcome (6-month rate of cardiovascular death, readmission for acute heart failure, acute coronary syndrome or stroke) occurred in 59% of patients. This rate was high and similar regardless of first medical contact, type of transport, first medical department of admission and number of medical departments involved in the course of care. A cardiologist was involved in management in 80% of cases. The global median hospital stay was shorter with cardiology vs non-cardiology management (7 days [interquartile range 4-11] vs 10 days [interquartile range 7-18]; P=0.003). History of hypertension (P=0.004), need for non-invasive ventilation (P=0.023) and Lee prognostic score (P=0.028) were independently associated with the primary outcome.

Conclusions: Morbimortality and readmissions were high regardless of the course of care in patients admitted for AHF in real life. The reduction in hospital stay when cardiologists were involved in management encourages the creation of "mobile AHF cardiology teams".
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http://dx.doi.org/10.1016/j.acvd.2016.05.004DOI Listing
February 2017

Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness.

Medicine (Baltimore) 2016 Jun;95(26):e4060

aDepartment of Hyperbaric Medicine, Sainte-Anne Hospital, Toulon bDepartment of Hyperbaric Medicine, Sainte-Marguerite Hospital, Marseille cUMR MD2, Aix-Marseille University and Institute of Biological Research of the Army dLaboratory of Biochemistry, Timone University Hospital, Marseille eSchool of Biological Sciences, University of Reading, United Kingdom fInstitut des Sciences Biologiques, CNRS, France.

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder.Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013-June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia.We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined "BNP-cTnI" levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers.We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE.
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http://dx.doi.org/10.1097/MD.0000000000004060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937958PMC
June 2016

Platelet reactivity in patients receiving a maintenance dose of P2Y12-ADP receptor antagonists undergoing elective percutaneous coronary intervention.

Int J Cardiol 2016 Aug 1;216:190-3. Epub 2016 May 1.

Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France; MARS Cardio, Mediterranean Academic association for Research and Studies in Cardiology, Marseille, France.

Background: P2Y12-ADP receptor blockade during percutaneous coronary intervention (PCI) is critical to prevent thrombotic events. In patients under chronic P2Y12 blockers, the use of additional loading dose (LD) before an elective PCI is debated. We aimed to investigate the rate of high on-treatment platelet reactivity (HTPR) in patients undergoing elective PCI during chronic clopidogrel or ticagrelor therapy.

Methods And Results: We performed a sub-group analysis of a randomized trial comparing ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing PCI. Multi-vessel disease patients requiring a staged PCI one month after the ACS were included. The VASP (vasodilatatory phosphoprotein) index, which is a specific and reproducible platelet assay to measure P2Y12-ADP receptor activity, was used to assess the biological efficacy of the maintenance dose (MD) of ticagrelor and clopidogrel before PCI. Forty-one patients in each group of randomization required a staged PCI. They were similar regarding the baseline demographic, clinical and angiographic characteristics. The mean VASP index in the ticagrelor group was 20.7±8.8% compared to 51.8±17% in the clopidogrel group (p<0.001) before PCI. No patients had a VASP index ≥50% in the ticagrelor group compared to 56% in the clopidogrel group (p<0.001). Following PCI the rate of peri-procedural MI was higher in the clopidogrel group (p=0.02).

Conclusions: Unlike clopidogrel MD, ticagrelor MD achieves an optimal PR inhibition in all patients during a staged PCI.
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http://dx.doi.org/10.1016/j.ijcard.2016.04.165DOI Listing
August 2016

Myocardial inflammation in experimental acute right ventricular failure: Effects of prostacyclin therapy.

J Heart Lung Transplant 2015 Oct 16;34(10):1334-45. Epub 2015 May 16.

Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium. Electronic address:

Background: Acute transient pulmonary hypertension may induce a state of persistent right ventricular (RV) failure. We hypothesized that this could be related to an activation of inflammatory processes and reduced by prostacyclin therapy.

Methods: Sixteen dogs were assigned to a 90-minute pulmonary artery banding (n = 8), or to a sham operation (n = 8). Hemodynamic variables were measured 30 minutes after banding release. This was repeated in 7 dogs with pulmonary artery banding-induced RV failure, followed by a 60-minute epoprostenol infusion. After euthanasia of the animals, myocardial tissue was sampled.

Results: Persistent RV failure was associated with increased myocardial expression of interleukin (IL)-1β, IL-6, monocyte chemoattractant protein 1, pro-inflammatory IL-6/IL-10, and neutrophil and macrophage infiltration, whereas heme oxygenase 1 expression was decreased. These changes were observed in RV and to a lesser extent in the left ventricle (LV). In the RV only, expressions of prostacyclin synthase and anti-inflammatory IL-10 and IL-33 decreased and vascular cell adhesion molecule expression increased, whereas macrophage inflammatory protein-1α and intercellular adhesion molecule 1 expressions remained unchanged. After epoprostenol infusion, there was decreased expression of IL-1β, macrophage inflammatory protein-1α, and vascular cell adhesion molecule 1 and increased IL-10 expression in the RV and the LV, whereas monocyte chemoattractant protein-1 decreased in the RV only. Epoprostenol infusion resulted in decreased RV IL-6/IL-10 and pro-apoptotic Bax/Bcl-2, together with decreased RV neutrophil and RV and LV macrophage infiltration. The RV ratio of end systolic-to-pulmonary arterial elastances was inversely correlated to RV IL-6/IL-10, macrophage, and neutrophil infiltration, and to RV heme oxygenase-1 and IL-33 expression.

Conclusions: Acute afterload-induced persistent RV failure is associated with an activation of inflammatory processes, which are limited by epoprostenol.
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http://dx.doi.org/10.1016/j.healun.2015.05.004DOI Listing
October 2015

Epidemiology of unintentional drowning in a metropolis of the French Mediterranean coast: a retrospective analysis (2000-2011).

Int J Inj Contr Saf Promot 2016 Sep 17;23(3):317-22. Epub 2015 Jun 17.

a SAMU13, Pôle RUSH, CHU La Timone, AP-HM, Marseille, France.

Drowning affects more than 500,000 people worldwide and is responsible for at least 350,000 deaths each year. In France, 1235 drowning resulting in 496 deaths were recorded in the summer 2012. This retrospective study has investigated the epidemiology of drowning in the city of Marseille (South of France) between 2000 and 2011. We identified 449 cases of unintentional drowning. The highest incidence was found among males with a median age of 36 years. The incidence was 5.3 victims per 10,000 inhabitants with a mortality rate of 1.2 per 10,000. These accidents occurred mainly at sea (89%) and during the summer season. A majority of drowning victims (69%) were admitted in a hospital. This is the only study in France to analyse data on drowning throughout the year and over a long period. Drowning is a serious condition burdened by 22% of victims who die.
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http://dx.doi.org/10.1080/17457300.2015.1047862DOI Listing
September 2016

Comparison of Ticagrelor Versus Prasugrel to Prevent Periprocedural Myonecrosis in Acute Coronary Syndromes.

Am J Cardiol 2015 Aug 9;116(3):339-43. Epub 2015 May 9.

UMR MD2, Aix-Marseille Université, Marseille, France; Pole RUSH, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Guidelines recommend a ticagrelor loading dose (LD) before PCI or a prasugrel LD at the time of percutaneous coronary intervention (PCI) in intermediate and high-risk non-ST-elevation acute coronary syndrome (NSTE-ACS). However, achieving an optimal PR inhibition at the time of PCI is critical to prevent adverse events and depends on the timing of LD intake in relation to PCI. We aimed to compare the rate of myonecrosis related to PCI in patients with NSTE-ACS receiving ticagrelor pretreatment versus prasugrel at the time of intervention. We prospectively randomized 213 patients with NSTE-ACS to a 180 mg of ticagrelor LD given as soon as possible after admission and before PCI or to a 60 mg LD of prasugrel given at the time of PCI. The primary end point was the rate of periprocedural myonecrosis as defined by an increase of >5 times the ninety-ninth percentiles in troponin-negative patients or a 20% increase in troponin-positive patients. The 2 groups were similar regarding baseline characteristics including clinical setting (p = 0.2). Procedural characteristics were also identical including the number of treated vessels and stenting procedures. Patients in the prasugrel group more often required emergent PCI (p = 0.001). Patients in the ticagrelor group had less periprocedural myonecrosis compared with those in the prasugrel group (19.8% vs 38.3%; p = 0.03). The rate of major adverse cardiovascular events and Bleeding Academic Research Consortium ≥2 at 1-month follow-up was low and similar between the 2 groups. In conclusion, a ticagrelor LD as soon as possible before PCI is superior to prasugrel at the time of PCI to prevent periprocedural myonecrosis in NSTE-ACS.
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http://dx.doi.org/10.1016/j.amjcard.2015.04.050DOI Listing
August 2015

Ticagrelor increases endothelial progenitor cell level compared to clopidogrel in acute coronary syndromes: A prospective randomized study.

Int J Cardiol 2015 31;187:502-7. Epub 2015 Mar 31.

Vascular Research Center of Marseille, INSERM UMR-S 1076, Aix-Marseille Université, Marseille, France; Laboratoire d'Hématologie et de Biologie Vasculaire, Assistance-Publique Hôpitaux de Marseille, Centre hospitalo-universitaire de la Conception, Marseille, France.

Background: The clinical benefit of ticagrelor compared to clopidogrel in ACS patients suggested off-target property. Such pleiotropic effect could be mediated by circulating endothelial progenitor cells (EPC) which are critical for vascular healing. We aimed to investigate the impact of ticagrelor on EPC in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Methods: We prospectively randomized 106 ACS patients to ticagrelor or clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were analyzed by flow cytometry allowing one to determine the levels of CD34+ PC, CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission and at 1 month. Changes in PC level were calculated as the difference between 1 month and baseline value.

Results: The 2 groups were similar regarding baseline characteristics including PC numbers on admission. The 2 groups had similar change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that patients treated by ticagrelor had a significantly higher increase in levels of these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs 0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02). Changes in the level of CD34+CD133+ PC correlated with platelet activity measured by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity.

Conclusions: Ticagrelor increases the number of EPC in ACS patients suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug.
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http://dx.doi.org/10.1016/j.ijcard.2015.03.414DOI Listing
March 2016

[Reverse Takotsubo cardiomyopathy after iatrogenic epinephrine injection requiring percutaneous extracorporeal membrane oxygenation].

Can J Anaesth 2014 Dec 4;61(12):1093-7. Epub 2014 Sep 4.

Unité de réanimation de chirurgie cardiaque, service d'anesthésie réanimation 2, CHU La Timone adultes, Marseille, France,

Purpose: Takotsubo cardiomyopathy is characterized by the sudden onset of reversible left ventricular dysfunction. Associated refractory cardiogenic shock is a rare occurrence and may require extracorporeal membrane oxygenation (ECMO). We report a case of a patient who, following the inadvertent injection of 1 mg of epinephrine, presented with reverse Takotsubo cardiomyopathy and refractory cardiogenic shock that required the implementation of a percutaneous ECMO.

Clinical Features: A 49-yr-old female patient presented with reverse Takotsubo cardiomyopathy in the operating room after an inadvertent injection of epinephrine. The development of refractory cardiogenic shock required emergent use of a mobile percutaneous ECMO system. It was possible to wean this support after four days, and the patient was later discharged without cardiac or neurological sequelae. The investigations performed confirmed the iatrogenic nature of this reverse Takotsubo cardiomyopathy.

Conclusion: Takotsubo cardiomyopathy following an injection of epinephrine remains a rare but increasingly described occurrence. The severity of the symptoms appears to be patient dependent, but refractory cardiogenic shock may occur and require significant circulatory support. If this situation occurs in a hospital where this necessary equipment is lacking, a mobile ECMO unit appears to be a viable solution to optimize the patient's chances of survival.
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http://dx.doi.org/10.1007/s12630-014-0230-xDOI Listing
December 2014

Purinergic profile of fainting divers is different from patients with vasovagal syncope.

Int J Cardiol 2014 Jul 24;174(3):741-3. Epub 2014 Apr 24.

UMR MD2, AMU, Faculty of Medicine, Marseille, France; IRBA, France; Laboratory of Biochemistry, Timone University Hospital, AP-HM, France. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.04.090DOI Listing
July 2014

Prehospital ultrasound thoracic examination to improve decision making, triage, and care in blunt trauma.

Am J Emerg Med 2014 Jul 7;32(7):817.e1-2. Epub 2014 Jan 7.

Department of Emergency Medicine and Intensive Care, Timone University Hospital, Marseille, France.

Prehospital acute blunt thoracic trauma care remains difficult. Among then, diagnosis of atelectasis with ultrasound remains rare and unusual. We report the case of a worker who had a sharp chest pain currently after using a jackhammer. First clinical examination suspected a left tension pneumothorax but ruled out by sliding sign in left hemithorax ultrasound (US) examination. The right upper thoracic scan showed a well-defined lung point, a "hepatization" appearance with static air bronchograms, a diaphragm elevation and a dextrocardia in B mode, and a pseudobarcode with no lung pulse in Time Motion (TM) mode. A "rip's organ absent sign" excluded the hypothesis of an acute diaphragmatic rupture. An atelectasis was at once suspected and confirmed at hospital by tomodensitometry. Diaphragmatic injury can be suspected when "rip's absent organ sign," diaphragm poor movement or elevation, liver sliding sign, subphrenic effusion, or spleen or liver intrathoracic presence. Unusually, these signs can put diagnosis in a wrong track as described in our case report. Lung pulse, absent sliding sign, or hemidiaphragm standstill is highly suspect of atelectasis but cannot be established formally. However, in patients with alveolar consolidation displaying air bronchograms, the dynamic air bronchograms indicated lung contusion, distinguishing it from atelectasis. Static air bronchograms were seen in most atelectases and one-third of cases of contusion or pneumonia. Fast scan can be useful to evoke atelectasis in blunt trauma. Differential diagnoses such as diaphragmatic rupture or consolidation could be discarded. Ultrasound examination could justify a precise semiological description.
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http://dx.doi.org/10.1016/j.ajem.2013.12.063DOI Listing
July 2014

Heme oxygenase-1 and inflammation in experimental right ventricular failure on prolonged overcirculation-induced pulmonary hypertension.

PLoS One 2013 25;8(7):e69470. Epub 2013 Jul 25.

Laboratory of Physiology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.

Heme oxygenase (HO)-1 is a stress response enzyme which presents with cardiovascular protective and anti-inflammatory properties. Six-month chronic overcirculation-induced pulmonary arterial hypertension (PAH) in piglets has been previously reported as a model of right ventricular (RV) failure related to the RV activation of apoptotic and inflammatory processes. We hypothesized that altered HO-1 signalling could be involved in both pulmonary vascular and RV changes. Fifteen growing piglets were assigned to a sham operation (n = 8) or to an anastomosis of the left innominate artery to the pulmonary arterial trunk (n = 7). Six months later, hemodynamics was evaluated after closure of the shunt. After euthanasia of the animals, pulmonary and myocardial tissue was sampled for pathobiological evaluation. Prolonged shunting was associated with a tendency to decreased pulmonary gene and protein expressions of HO-1, while pulmonary gene expressions of interleukin (IL)-33, IL-19, intercellular adhesion molecule (ICAM)-1 and -2 were increased. Pulmonary expressions of constitutive HO-2 and pro-inflammatory tumor necrosis factor (TNF)-α remained unchanged. Pulmonary vascular resistance (evaluated by pressure/flow plots) was inversely correlated to pulmonary HO-1 protein and IL-19 gene expressions, and correlated to pulmonary ICAM-1 gene expression. Pulmonary arteriolar medial thickness and PVR were inversely correlated to pulmonary IL-19 expression. RV expression of HO-1 was decreased, while RV gene expressions TNF-α and ICAM-2 were increased. There was a correlation between RV ratio of end-systolic to pulmonary arterial elastances and RV HO-1 expression. These results suggest that downregulation of HO-1 is associated to PAH and RV failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0069470PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723896PMC
March 2014

Ischemia-modified albumin and adenosine plasma concentrations are associated with severe systemic inflammatory response syndrome after cardiopulmonary bypass.

J Crit Care 2013 Oct 29;28(5):747-55. Epub 2013 Apr 29.

Pôle d'Anesthésie-Réanimation, Groupe Hospitalier de La Timone, Marseille, Cedex 05, France; UMR MD2, Aix-Marseille University (AMU), Marseille, France.

Purpose: Severe systemic inflammatory response syndrome (SIRS) occurring after cardiopulmonary bypass (CPB) is a common cause of mortality during cardiac surgery. These syndromes are characterized by vasoplegia and ischemia-reperfusion phenomenom. Adenosine is a strong endogenous vasodilating agent, which may be involved in blood pressure failure during CPB induced by severe SIRS. Ischemia-modified albumin (IMA) is considered as a sensitive marker of tissue ischemia. We examined whether the IMA or adenosine plasma concentrations (APCs) change during a severe SIRS-induced blood pressure failure during CPB.

Materials And Methods: Plasma concentration and IMA (median [range]) were measured before, during, and after surgery in 86 patients who underwent coronary revascularization under CBP and were correlated to postoperative clinical course.

Results: Preoperative APC values (1.45 [0.52-2.11] μmol L(-1) vs 0.36 [0.12-0.66] μmol L(-1)) and IMA (144 [91-198] IU mL(-1) vs 109 [61-183] U mL(-1)) were significantly increased in patients presenting postoperative severe SIRS. Mean durations of mechanical ventilation, stay in the intensive care unit, and requirement of vasoactive drugs were significantly higher in patients with higher APC and IMA, but APC was the best predictive marker a postoperative severe.

Conclusions: Adenosine plasma concentration and IMA concentration are associated with postoperative severe SIRS after CPB.
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http://dx.doi.org/10.1016/j.jcrc.2013.02.014DOI Listing
October 2013

Is there any benefit to adding intravenous ketamine to patient-controlled epidural analgesia after thoracic surgery? A randomized double-blind study.

Eur J Cardiothorac Surg 2012 Oct 12;42(4):e58-65. Epub 2012 Jul 12.

Intensive Care and Anesthesiology Unit 2, Timone/Sainte-Marguerite Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France.

Objectives: Thoracic surgery is associated with severe acute postoperative pain, leading to pulmonary complications and hyperalgesia-induced chronic pain. Thoracic patient-controlled epidural analgesia is also considered as the gold-standard postoperative analgesia. As previously described in major digestive surgery, combination with low-dose intravenous (i.v.) ketamine could potentiate epidural analgesia and facilitate pulmonary function recovery following thoracotomy.

Methods: In a randomized, double-blind trial, 60 patients scheduled to undergo thoracotomy were included. All patients received a thoracic epidural catheter placed before surgery, and standardized general anaesthesia. They were allocated to two groups to receive either an i.v. bolus of ketamine at induction, followed by a continuous infusion during surgery and the first 48 h postoperatively, or an i.v. placebo (a saline solution under the same infusion modalities). Cumulative epidural ropivacaine consumption, postoperative pain scores (patient self-rated numeric pain intensity scale), analgesic rescue consumption, residual pain, haemodynamics and respiratory recovery function were recorded from 12 h to 3 months. Data were expressed as mean ± standard deviation or median ± interquartile range (25-75%). The comparisons between ketamine and placebo groups were performed using χ(2) or Fisher's exact tests for frequencies, and Mann-Whitney tests for quantitative variables.

Results: Epidural ropivacaine consumption was similar between groups during the first 48 postoperative hours. Postoperative pain scores and spirometric parameters were not significantly different between groups. But the incidence of postoperative nausea was significantly increased in patients owning to the ketamine group. Finally, the incidence of residual pain was similar between groups at 1 and 3 months following thoracotomy.

Conclusions: Adding i.v. ketamine did not potentiate epidural analgesia neither to reduce acute and chronic postoperative pain nor to improve pulmonary dysfunction following thoracic surgery. Pain scores were low in both groups, mainly because of an optimized analgesia provided by the patient-controlled epidural mode, and might explain this lack of benefit in adding i.v. ketamine.
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http://dx.doi.org/10.1093/ejcts/ezs398DOI Listing
October 2012

Risk of reoperation for mitral bioprosthesis dysfunction.

J Heart Valve Dis 2012 Jan;21(1):56-60

Service de Chirurgie Cardiaque, Hôpital de la Timone, Marseille, France.

Background And Aim Of The Study: Today, when a mitral valve replacement is required, more patients and surgeons choose a bioprosthesis. Yet, the rationale of this choice is unclear in patients in whom age represents a predicting factor for reoperation. The study aim was to define the risk factors for reoperation after mitral bioprosthesis failure.

Methods: A total of 282 consecutive patients (202 women, 80 men; mean age at surgery 61 years; range: 28-88 years) who underwent reoperation for mitral bioprosthesis failure between 1990 and 2006 was reviewed. Surgery was undertaken because of bioprosthesis degeneration (91%), prosthetic valve infective endocarditis (6%), paravalvular leak (2%), or other causes (1%). Emergency procedures were performed in 7% of cases. Associated procedures included tricuspid valve surgery in 16% of patients (tricuspid valve repair in 11%, tricuspid valve replacement in 5%) and coronary artery bypass graft in 5%. Almost one-fifth of patients (18%) had undergone more than one previous mitral valve replacement.

Results: The overall operative mortality was 7.4% (n = 21). Factors identified (by multivariate analysis) as predictors of operative death included: presence of diabetes mellitus (odds ratio (OR) = 8.69, 95% CI 2.55-29.61; p = 0.001), chronic obstructive pulmonary disease (OR = 9.01, 95% CI 1.72-47.18; p = 0.009), NYHA class III/IV (OR 5.46, 95% CI 1.41-21.16; p = 0.01), and pulmonary artery pressure > 60 mmHg (OR = 3.13, 95% CI 1.10-8.94; p = 0.03). Associated procedures were not significant risk factors for mortality. New prostheses were mechanical in 68% of cases, and bioprostheses in 32%.

Conclusion: One reoperation for mitral bioprosthesis dysfunction is acceptable if the patient can be expected to survive to reoperation while free from comorbidities and the severe effects of mitral disease. The application of strict selective criteria to recipients at the first valve replacement, combined with a close follow up, may allow this goal to be achieved.
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January 2012