Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial.

PURPOSE: Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. MATERIALS AND METHODS: Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. RESULTS: We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference -1.8; 95% CI -8.4 to 4.9; P = .60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. CONCLUSIONS: Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. STUDY REGISTRATION NUMBER: NCT00994825 (ClinicalTrials.gov).

Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery.

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.). (AU)

Liberal transfusion strategy improves survival in perioperative but not in critically ill patients. A meta-analysis of randomised trials.

BACKGROUND: Guidelines support the use of a restrictive strategy in blood transfusion management in a variety of clinical settings. However, recent randomized controlled trials (RCTs) performed in the perioperative setting suggest a beneficial effect on survival of a liberal strategy. We aimed to assess the effect of liberal and restrictive blood transfusion strategies on mortality in perioperative and critically ill adult patients through a meta-analysis of RCTs. METHODS: We searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, Transfusion Evidence Library, and Google Scholar up to 27 March 2015, for RCTs performed in perioperative or critically ill adult patients, receiving a restrictive or liberal transfusion strategy, and reporting all-cause mortality. We used a fixed or random-effects model to calculate the odds ratio (OR) and 95% confidence interval (CI) for pooled data. We assessed heterogeneity using Cochrane's Q and I(2) tests. The primary outcome was all-cause mortality within 90-day follow-up. RESULTS: Patients in the perioperative period receiving a liberal transfusion strategy had lower all-cause mortality when compared with patients allocated to receive a restrictive transfusion strategy (OR 0.81; 95% CI 0.66‒1.00; P=0.05; I(2)=25%; Number needed to treat=97) with 7552 patients randomized in 17 trials. There was no difference in mortality among critically ill patients receiving a liberal transfusion strategy when compared with the restrictive transfusion strategy (OR 1.10; 95% CI 0.99‒1.23; P=0.07; I(2)=34%) with 3469 patients randomized in 10 trials. CONCLUSION: According to randomized published evidence, perioperative adult patients have an improved survival when receiving a liberal blood transfusion strategy.

Argatroban anticoagulation for heparin induced thrombocytopenia in patients with ventricular assist devices.

BACKGROUND: Patients receiving implantation of ventricular assist devices (VAD) suffer a high incidence of heparin induced thrombocytopenia (HIT); the occurrence of this condition is associated with increased complications and worse outcomes. We report our experience in the management of patients who were diagnosed with HIT either before (HITpre) or after (HITpost) implantation of VAD with argatroban, a direct thrombin inhibitor. METHODS: This retrospective analysis assessed data of VAD patients diagnosed with HIT at Deutsches Herzzentrum Berlin between November 2005 and April 2009. Argatroban dose requirements, anticoagulation efficacy and adverse events (death, thromboembolism, bleeding) were recorded. Procedural success (discharge from the hospital, heart transplantation, or recovery of the failing heart) was also assessed. RESULTS: Twenty-seven patients were identified (11 HITpre, 16 HITpost). Argatroban was effective in obtaining adequate anticoagulation with a reduced dose regimen (0.02-0.42 mcg/Kg/min starting dose; 0.02-1.5 mcg/Kg/min maintenance dose). We noted 5 thromboembolic complications (18%), 6 cases of major bleeding (22%) and 5 deaths (18%), all cause composite adverse end point occurring in 40% of patients. Procedural success was obtained in 81% of patients (92% HITpre, 69% HITpost). As compared to historical controls of patients treated with lepirudin in the period 2000-2005, results were significantly improved. CONCLUSION: Argatroban anticoagulation is feasible in patients with HIT after VAD implantation, without increasing bleeding risk. Its impact in terms of survival should be reviewed also in the light of the technological improvements of assist devices.

Bioline heparin-coated ECMO with bivalirudin anticoagulation in a patient with acute heparin-induced thrombocytopenia: the immune reaction appeared to continue unabated.

Heparin-induced thrombocytopenia (HIT) is a serious, antibody-mediated complication of heparin which significantly confers risks of thrombosis and devastating outcomes. Once diagnosed, it requires immediate cessation of heparin and therapy with an alternative anticoagulant. No data are available in the literature on the pathophysiology and clinical implications of performing prolonged extracorporeal membrane oxygenation with a heparin-coated system in a patient with acute HIT treated with bivalirudin.

Reduction of hemodilution in small adults undergoing open heart surgery: a prospective, randomized trial.

BACKGROUND: Given that there is an association between the degree of hemodilution during cardiopulmonary bypass (CPB) and postoperative complications, patients-outcome might be improved if the nadir hematocrit concentration is kept within an optimal range. Smaller patients are more likely to have a low hematocrit during CPB: this phenomenon may be related, at least partially, to the extreme hemodilution induced by a large fixed CPB priming volume. METHODS: Forty patients with a body surface area (BSA) < 1.7 m2 undergoing open heart operations were randomized to either standard CPB with full prime volume (control group) or reduced prime extracorporeal circuit and vacuum-assisted venous drainage (VAVD) (study group). RESULTS: There were no significant differences between the groups with respect to baseline characteristics, body surface area, hematologic profile and operative data. Clinical outcomes were similar. Nadir hematocrit and hemoglobin on bypass were significantly lower in the control group (22 +/- 2.3 vs. 24 +/- 2.5%, p < 0.02 and 7.4 +/- 0.7 vs. 8 +/- 0.9 g/dl, p < 0.04, respectively). Postoperative chest tube drainage was significantly higher in the control group (272 +/- 253 vs. 139 +/- 84 ml, p < 0.04). There was no difference in blood transfusion in the two groups (0.5 +/- 1.14 vs. 1.0 +/- 1.77 units of packed red blood cells (PRBC), p = 0.29). CONCLUSIONS: Lowering CPB priming volume by means of using a small oxygenator and vacuum-assisted venous drainage (VAVD) resulted in a significant decrease of intraoperative hemodilution. This technique should be strongly considered for patients with a small BSA (<1.7 m2) undergoing open heart surgery.

Anesthesiological management and outcome of 100 ''beating heart'' coronary artery bypass grafting.

AIM: The aim of this paper is to describe the anesthesiological management and the outcome of beating heart revascularization. METHODS: A prospective study has been performed in a tertiary teaching hospital on 100 consecutive patients undergoing off-pump coronary artery revascularization. The main features of anesthetic technique are the maintenance hemodynamic stability and atrial kick. RESULTS: Mechanical stabilisers shunts have improved the management of these patients. In hospital mortality was 1%, acute myocardial infarction 3%, low output syndrome 2%, atrial fibrillation 16%. Only 2% of patients had acute renal failure, but no patient needed renal replacement treatment. No neurologic event was noted. Only 19% of patients received blood transfusion. Ninety-seven % of patients were extubated within 12 h. CONCLUSIONS: The application of this anesthetic strategy combined with surgical skillful and new devices makes off-pump surgery safe also in high risk patients.

Multivessel off-pump coronary artery bypass grafting in a nonagenarian: anesthesiologic management.

A 90-year-old male admitted with history of angina (three-vessel disease) on medical therapy for hypertension and chronic renal failure was scheduled for elective coronary artery bypass grafting (CABG). After standard premedication and monitoring anesthesia was induced with propofol and maintained with isoflurane. Middle dose opioids and atracurium were also given. Multivessel revascularization was done through median sternotomy and anastomoses were performed with the aid of coronary stabilization and shunting. Cerebral and renal perfusion were maintained with high arterial pressure (140/70 mmHg) and continuous infusion of fenoldopam (0.05 microg kg(1) m(-1)). The perioperative period was uneventful. Elderly patients are at increased risk for mortality and morbidity after CABG. The procedure can be performed safely on elderly patients without using cardiopulmonary bypass and preventing cerebral and renal ipoperfusion.

Effects of cerestat and NBQX on functional and morphological outcomes in rat focal cerebral ischemia.

This study investigated the ability of NBQX, an AMPA receptor antagonist, and cerestat, a NMDA receptor antagonist, to counteract neurological deficits and morphological damage induced by permanent occlusion of the left middle cerebral artery (MCAO model) in the rat. NBQX (3, 10, and 30 mg/kg, ip) injected at 10, 60, and 120 min postocclusion did not reduce the volume of infarct in the MCAO model of cerebral ischemia and had marginal effects on sensory dysfunctions (vibrissae stimulation and body proprioception) and no effects on motor dysfunctions (forelimb flexion and footfault test). Conversely, cerestat (0.3, 1, and 3 mg/kg, sc) injected at 10 and 120 min postocclusion significantly reduced the ischemic volume at the dose of 1 mg/kg, and, at the same dose, significantly attenuated behavioural deficits in the body proprioception and in the forelimb flexion tests.

Ex vivo binding of flibanserin to serotonin 5-HT1A and 5-HT2A receptors.

Flibanserin has been reported to be an agonist at 5-HT1A-receptors and an antagonist at 5-HT2A receptors, with higher affinity for 5-HT1A receptors. Despite the fact that less receptor occupation is required by full agonists than by antagonists to exert their effects, flibanserin was shown to exert 5-HT2A antagonism at doses (4-5 mg kg-1) that are lower or equal to those required to stimulate 5-HT1A receptors. In order to understand this phenomenon, the interaction of flibanserin with 5-HT1A and 5-HT2A receptors was evaluated in ex vivo binding studies. This interaction was evaluated in the prefrontal cortex, hippocampus and midbrain by using [3H]8-OH-DPAT and [3H]ketanserin to label 5-HT1A and 5-HT2A receptors, respectively. Flibanserin was given at 1, 10 and 30 mg kg-1 intraperitoneally. The dose of 1 mg kg-1 displaced both radioligands preferentially in the frontal cortex. The doses of 10 and 30 mg kg-1 reduced the binding of both radioligands in all the three brain regions non-selectively by about 50% and 70%, respectively. The displacement was maximal after 0.5 h and was reduced or not evident after 3 h. We conclude that 5-HT2 antagonism brought about by low doses of flibanserin may reflect functional mechanisms more than receptor-mediated effects.

[Interposed abdominal compression in mechanical cardiopulmonary resuscitation. Description of a clinical case]. / IAC mCPR. Descrizione di un caso clinico.

Among the different techniques proposed to integrate the standard cardiopulmonary resuscitation (sCPR) protocol, mechanical CPR (mCPR) and interposed abdominal compression (IAC) were found to be particularly effective for the simplicity of the procedure and the significant results obtained. A case of a 54-year old male with cardiogenic shock following viral infection, in which prolonged mechanical cardiopulmonary resuscitation with interposed abdominal compression was performed, is presented. Five hours after admission in the ICU, the patient's condition worsened with subsequent cardiac arrest with pulseless electrical activity (PEA). Mechanical CPR was promptly started, subsequently associated with IAC and prolonged for 1 hour and 20 minutes. Although the patient survived for only eight hours following cardiac arrest, prolonged IAC-mCPR allowed to start extra corporeal circulation (CPP). The patient was then transferred to the cardiosurgical operating theatre for ventricular assistance by centrifugal pump (VAP). Cardiovascular data obtained from patients monitoring did not shown any cardiac lesions or adverse effects as observed by autoptic examination and suggest the reliability of this mechanical method, which allows a better performance when compared to standard CPR. In prolonged resuscitations a few contraindications to both mCPR and IAC suggest the application of the associated techniques at all times in cardiac arrest, combining the benefits of both procedures.

Characterization of a reversed-phase high-performance liquid chromatographic system for the determination of blood amino acids.

High-performance liquid chromatography was used to separate physiological amino acids in perchloric acid supernatants of blood samples. Precolumn derivatization with phenyl isothiocyanate was carried out, starting with 20 microliters of supernatant; 2-10 microliters were injected into a 30-cm Pico Tag column, which was eluted with a gradient of two eluents in 64 min. Stock amino acid solutions prepared in water, hydrochloric acid or perchloric acid showed comparable recoveries on serial dilution (parallelism test). The recovery of crystalline amino acids added to blood in amounts ranging from normal to six times normal was generally satisfactory. The within-assay relative standard deviations were less than 5% for many amino acids. The performance of the system was less than satisfactory for cysteine and methionine. Glutamine and asparagine are interconverted into glutamate and aspartate, respectively, in a time-dependent fashion; a separate measurement of one member of the pair is therefore required in order to assay the other starting from the sum of both chromatographic peaks. The method is suitable for the relatively rapid, sensitive and accurate measurement of blood amino acids in perchloric acid supernatants (in which other relevant metabolites are customarily assayed) over a wide range of physiological concentrations, on very small amounts of sample.