Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders.

Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients' associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT.

Impact of the COVID-19 pandemic on liver transplant waitlist outcome in France.

The objective of this study was to investigate the impact of the COVID-19 pandemic on the outcome of patients on the liver transplantation (LT) waitlist in 2020 in France, in particular, the incidence of deaths and delisting for worsening condition, depending on the allocation score component. The 2020 cohort of patients on the waiting list was compared with the 2018/2019 cohorts. 2020 saw fewer LTs than in either 2019 or 2018 (1128, 1356, and 1325, respectively), together with fewer actual brain dead donors (1355, 1729, and 1743). In 2020, deaths or delisting for worsening condition increased significantly versus 2018/2019 (subdistribution hazard ratio 1.4, 95% confidence interval [CI] 1.2-1.7), after adjustment for age, place of care, diabetes, blood type, and score component, although COVID-19-related mortality was low. This increased risk mainly concerned patients with hepatocellular carcinoma (1.52, 95% CI 1.22-1.90), with 650 MELD exception points (2.19, 95% CI 1.08-4.43), and especially those without HCC and MELD scores from 25 to 30 (3.36 [95% CI 1.82-6.18]). In conclusion, by significantly decreasing LT activity in 2020, the COVID-19 pandemic increased the number of waitlist deaths and delisting for worsening condition, and significantly more for particular components of the score, including intermediate severity cirrhosis.

Long-term survival benefit from dual kidney transplantation using kidneys from donors with very extended criteria-a French cohort between 2002 and 2014.

BACKGROUND: This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). METHODS: Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. RESULTS: The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. CONCLUSIONS: In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.

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

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 P2Y12-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 P2Y12-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).

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

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.

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

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.

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

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.

Specific Pharmacological Profile of A2A Adenosine Receptor Predicts Reduced Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease.

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 A2A receptors (A2AR)-characterized by a high dissociation constant/half maximal effective concentration (KD/EC50) 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 A2AR 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 (KD), functional response (cyclic adenosine monophosphate [cAMP] production; EC50) on PBMC A2AR 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 KD/EC50 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 A2AR on PBMC may help to rule out myocardial ischemia. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03218007.

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

According to recent literature, pretreatment with a P2Y12 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 P2Y12 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 P2Y12 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 P2Y12 ADP receptor antagonist pretreatment.

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

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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Risk of reoperation for mitral bioprosthesis dysfunction.

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.