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The role of matrix metalloproteinases (MMPs) in routine cardiac operations including cardiopulmonary bypass (CPB) is still poorly explored. The purpose of this systematic review was to thoroughly summarize and discuss the existing knowledge of the MMP profile in cardiac surgery. All studies meeting the inclusion criteria (i.e., those reporting detailed data about MMP release during and after CPB) were selected after screening the literature published between July 1975 and August 2022. Fifteen trials that enrolled a total of 431 participants were included. MMP levels were found to be significantly correlated with CPB in all included studies. The gelatinases MMP-2 and MMP-9 were highly released in cardiac surgery with CPB. MMP-9 levels were found to be increased after CPB start and during the duration of CPB. Particularly, it is overexpressed both in the myocardial tissue and circulating in the bloodstream. Also, MMP-2 levels increased after CPB both in plasma and in myocardial tissue. MMP-7, MMP-8, and MMP-13 levels increased after CPB start and remained elevated up to 6 h later. Increased levels of MMPs were associated with adverse post-operative outcomes. Conversely, TIMP-1 decreased with CPB. Mechanical and pharmacological strategies were applied in two studies to analyze their effect on the inflammatory response to cardiac surgery and CPB and on postoperative outcomes. New targeted MMP inhibitor therapies could protect against systemic inflammatory response syndrome after CPB and should be the subject of future large prospective multicenter randomized clinical trials.

To find out if there are any differences in biomarkers between severe isolated right ventricular (RV) dysfunction and severe isolated left ventricular (LV) dysfunction after cardiac surgery using cardiopulmonary bypass.Observational study.Teaching hospital.A total of 46 patients who had severe isolated RV or LV dysfunction after cardiac surgery.The authors collected perioperative clinical and biomarker data.Severe isolated RV dysfunction patients (n = 20) had higher postoperative direct bilirubin (p = 0.030), total bilirubin (p = 0.044), glucose (p = 0.011), and international normalized ratio (INR) (p = 0.050) by repeated measure analysis of variance when compared with patients with severe isolated LV dysfunction (n = 26). The RV group also showed lower preoperative alanine transferase (19.3 ± 1.5 v 32.7 ± 4.2, p = 0.001), higher 4-hour INR (1.5 ± 0.3 v 1.4 ± 0.2, p = 0.008), and higher 48-hour INR (1.8 ± 0.4 v 1.4 ± 0.1, p0.001). None in the LV group died, whereas 4 patients in the RV group died (all of them had preoperative atrial fibrillation and underwent double valve replacement surgery).The authors observed biomarkers differences between severe isolated RV dysfunction and severe isolated RV dysfunction.

Background: Postoperative bleeding after cardiac surgery is associated with increased morbidity and mortality. We tested the hypothesis that patients with a preoperatively estimated high risk of severe perioperative bleeding may have impaired early outcome after on-pump versus off-pump coronary artery bypass grafting (CABG). Method: Data from 7,352 consecutive patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicentre European Coronary Artery Bypass Grafting registry. The postoperative bleeding risk was estimated using the WILL-BLEED risk score. Of all included patients, 3,548 had an increased risk of severe perioperative bleeding (defined as a WILL-BLEED score ≥4) and were the subjects of this analysis. We compared the early outcomes between patients who underwent on-pump or off-pump CABG using a multivariate mixed model for risk-adjusted analysis. Results: Off-pump surgery was performed in 721 patients (20.3%). On-pump patients received more packed red blood cell units (on-pump: 1.41 [95% confidence interval {CI}, 0.99–1.86]; off-pump: 0.86 [95% CI, 0.64–1.08]; p

Background Pregnancy usually represents a risk factor for aortic dissection or thrombotic events, but therapeutic options are very scarce because the foetus limits the common approaches especially in the early stages of pregnancy. Case presentation We present a challenging case of a young woman in her 16th week of gestation with an history of multiple abortions associated with autoimmune thrombophilia. A strictly designed perioperative management protocol was required to remove a huge right endoventricular mass, due to her decision to not terminate the pregnancy. Conclusions Nowadays the mother, completely healthy, gived birth to her baby so it demonstrates how cardiac surgery, even in complicated circumstances, can be feasible during pregnancy through a multidisciplinary approach.

Summary: Acute kidney injury is a common complication after cardiac surgery that is associated with high postoperative morbidity and mortality. Levels of hemolysis are associated closely with the incidence and severity of kidney injury after cardiac surgery. Hemolysis is caused by prolonged surgical procedures and blood transfusions from cell-saver devices and is associated with the use of cardiopulmonary bypass. Plasma oxyhemoglobin is released into the circulation by damaged red blood cells that, via a dioxygenation reaction, depletes vascular nitric oxide (NO), a potent vasodilator molecule responsible for modulating organ perfusion and vascular homeostasis. Depleted plasma NO and increased levels of plasma oxyhemoglobin in the bloodstream lead to impairment of organ perfusion, inflammation, oxidative stress, and direct tubular injury, which, together, contribute to the development of renal injury after cardiac surgery. The administration of NO, a gas originally approved to treat pulmonary hypertension, maintains organ perfusion by preventing vascular NO depletion. In addition, this treatment improves cardiac output by reducing pulmonary vascular resistance and right heart workload. The clinical evidence of renal protection of NO gas therapy is supported by preclinical animal studies exploring the extrapulmonary protective effects of NO. Recent clinical trials showed a significant reduction of postoperative acute kidney injury when NO gas was administered during and after cardiac surgery.

Introduction: The use of volatile agents during cardiopulmonary bypass allows a “single drug anesthesia” and is associated with reduced peak postoperative troponin levels. Connecting the exhaust systems to the oxygenator’s gas outlet port is mandatory and allows to prevent operating room (but not atmospheric) pollution by volatile agents. The aim of this study was to create a prototype filter for volatile agents and to test its adsorption efficacy during an ex-vivo simulated conventional cardiopulmonary bypass test. Methods: We carried out bench tests to conceive a prototype filter that could prevent room and environment pollution without damaging membrane oxygenators. We performed the tests at the Engineering Center for Circulatory Assistance Laboratory, Dante Pazzanese Institute of Cardiology, São Paulo, Brazil. Bench tests included simulation of integral adsorption tests, filter dimensions and design, flow versus pressure curve, sizing, and tightness. Results: Calgon AT 410 was the best kind of activated charcoal granules for adsorption of sevoflurane, isoflurane, and desflurane. Filter dimension tests showed that a chamber of 30-cm width over 10-cm diameter filled with 200 g of the Calgon AT410 granules was the minimum required to fully adsorb sevoflurane for 90 min. Adsorption tests showed that the prototype filter fully adsorbed isoflurane in 100 ± 2.3 min, sevoflurane in 95 ± 3.4 min, and desflurane in 95 ± 4.3 min. Conclusion: The new version of our prototype filter adsorbed most of the volatile anesthetics agents during an ex-vivo simulated conventional cardiopulmonary bypass test.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Background Delirium after cardiac surgery is associated with adverse outcomes, including prolonged hospital stay, prolonged intensive care unit stay, and increased mortality. Effective preventive interventions and treatments still are largely unknown. Aim This systematic review aimed to gather and summarize the existing evidence from randomized trials concerning interventions studied in the prevention or treatment of delirium in adult patients undergoing cardiac surgery. Methods A systematic review of the literature using a key word strategy and Boolean operators was performed. PubMed and the Cochrane and Scopus databases were searched for pertinent studies until July 2018 (no inception limit). Results Of 2,556 articles identified, 56 studies met the inclusion criteria and were included in the review—39 addressed pharmacologic strategies and 17 nonpharmacologic interventions. Interestingly, 51 (91%) trials focused on delirium prevention and only 5 (9%) on delirium treatment. Most of the analyzed studies were recent double-blind, single-center trials conducted in Europe or North America, with a low risk of bias. Overall, 38 different interventions were identified: 15 (26%) interventions were performed before surgery, 20 (36%) in the operating room, and 21 (38%) after surgery. The most frequently analyzed strategies were the administration of dexmedetomidine, ketamine, antipsychotics, glucocorticoids, propofol, opioids, volatile anesthetics, local anesthetics, and remote ischemic preconditioning. The analyzed strategies were extremely heterogenous, and dexmedetomidine was the most promising measure able to prevent the development of postoperative delirium. Conclusions In the present systematic review of 56 randomized controlled trials that examined 38 interventions, the authors found that dexmedetomidine was the most frequently studied agent and that it might reduce the occurrence of delirium after cardiac surgery.

Aims: S100B has been proposed as a consolidated marker of brain damage in infants with congenital heart disease (CHD) undergoing cardiac surgery and cardiopulmonary bypass (CPB). The present study aimed to investigate whether S100B blood levels in the perioperative period differed in infants complicated or not by cyanotic CHD (CHDc) and correlated with oxygenation status (PaO2). Methods: We conducted a case-control study of 48 CHD infants without pre-existing neurological disorders undergoing surgical repair and CPB. 24 infants were CHDc and 24 were CHD controls. Blood samples for S100B assessment were collected at six monitoring time-points: before the surgical procedure (T0), after sternotomy but before CPB (T1), at the end of the cross-clamp CPB phase (T2), at the end of CPB (T3), at the end of the surgical procedure (T4), at 24 h postsurgery (T5). Results: In the CHDc group, S100B multiples of median (MoM) were significantly higher (p .05, for all) were found at T2, T3, T5. Linear regression analysis showed a positive correlation between S100B MoM at T3 and PaO2 (R = 0.84; p

Background: The intra-aortic balloon pump (IABP) is often used in high-risk patients undergoing cardiac surgery to improve coronary perfusion and decrease afterload. The effects of the IABP on cerebral hemodynamics are unknown. We therefore assessed the effect of the IABP on cerebral hemodynamics and on neurological complications in patients undergoing cardiac surgery who were randomized to receive or not receive preoperative IABP in the ‘Intra-aortic Balloon Counterpulsation in Patients Undergoing Cardiac Surgery’ (IABCS) trial. Methods: This is a prospectively planned analysis of the previously published IABCS trial. Patients undergoing elective coronary artery bypass surgery with ventricular ejection fraction ≤ 40% or EuroSCORE ≥ 6 received preoperative IABP (n = 90) or no IABP (n = 91). Cerebral blood flow velocity (CBFV) of the middle cerebral artery through transcranial Doppler and blood pressure through Finometer or intra-arterial line were recorded preoperatively (T1) and 24 h (T2) and 7 days after surgery (T3) in patients with preoperative IABP (n = 34) and without IABP (n = 33). Cerebral autoregulation was assessed by the autoregulation index that was estimated from the CBFV response to a step change in blood pressure derived by transfer function analysis. Delirium, stroke and cognitive decline 6 months after surgery were recorded. Results: There were no differences between the IABP and control patients in the autoregulation index (T1: 5.5 ± 1.9 vs. 5.7 ± 1.7; T2: 4.0 ± 1.9 vs. 4.1 ± 1.6; T3: 5.7 ± 2.0 vs. 5.7 ± 1.6, p = 0.97) or CBFV (T1: 57.3 ± 19.4 vs. 59.3 ± 11.8; T2: 74.0 ± 21.6 vs. 74.7 ± 17.5; T3: 71.1 ± 21.3 vs. 68.1 ± 15.1 cm/s; p = 0.952) at all time points. Groups were not different regarding postoperative rates of delirium (26.5% vs. 24.2%, p = 0.83), stroke (3.0% vs. 2.9%, p = 1.00) or cognitive decline through analysis of the Mini-Mental State Examination (16.7% vs. 40.7%; p = 0.07) and Montreal Cognitive Assessment (79.16% vs. 81.5%; p = 1.00). Conclusions: The preoperative use of the IABP in high-risk patients undergoing cardiac surgery did not affect cerebral hemodynamics and was not associated with a higher incidence of neurological complications. Trial registrationhttp://www.clinicaltrials.gov (NCT02143544)., SCOPUS: ar.j, info:eu-repo/semantics/published

Background The effect of nitric oxide (NO) on renal function is controversial in critical illness. We performed a systematic meta-analysis and trial sequential analysis to determine the effect of NO gas on renal function and other clinical outcomes in patients requiring cardiopulmonary bypass (CPB). The primary outcome was the relative risk (RR) of acute kidney injury (AKI), irrespective of the AKI stage. The secondary outcome was the mean difference (MD) in the length of ICU and hospital stay, the RR of postoperative hemorrhage, and the MD in levels of methemoglobin. Trial sequential analysis (TSA) was performed for the primary outcome. Results 54 trials were assessed for eligibility and 5 studies (579 patients) were eligible for meta-analysis. NO was associated with reduced risk of AKI (RR 0.76, 95% confidential interval [CI], 0.62 to 0.93, I2 = 0%). In the subgroup analysis by NO initiation timing, NO did not decrease the risk of AKI when started at the end of CPB (RR 1.20, 95% CI 0.52–2.78, I2 = 0%). However, NO did significantly reduce the risk of AKI when started from the beginning of CPB (RR 0.71, 95% CI 0.54–0.94, I2 = 10%). We conducted TSA based on three trials (400 patients) using KDIGO criteria and with low risk of bias. TSA indicated a CI of 0.50–1.02 and an optimal information size of 589 patients, suggesting a lack of definitive conclusion. Furthermore, NO does not affect the length of ICU and hospital stay or the risk of postoperative hemorrhage. NO slightly increased the level of methemoglobin at the end of CPB (MD 0.52%, 95% CI 0.27–0.78%, I2 = 90%), but it was clinically negligible. Conclusions NO appeared to reduce the risk of postoperative AKI in patients undergoing CPB. Additional studies are required to ascertain the finding and further determine the dosage, timing and duration of NO administration.

IntroductionPostoperative acute kidney injury (AKI) is a common complication in cardiac surgery. Levels of intravascular haemolysis are strongly associated with postoperative AKI and with prolonged (>90 min) use of cardiopulmonary bypass (CPB). Ferrous plasma haemoglobin released into the circulation acts as a scavenger of nitric oxide (NO) produced by endothelial cells. Consequently, the vascular bioavailability of NO is reduced, leading to vasoconstriction and impaired renal function. In patients with cardiovascular risk factors, the endothelium is dysfunctional and cannot replenish the NO deficit. A previous clinical study in young cardiac surgical patients with rheumatic fever, without evidence of endothelial dysfunction, showed that supplementation of NO gas decreases AKI by converting ferrous plasma haemoglobin to ferric methaemoglobin, thus preserving vascular NO. In this current trial, we hypothesised that 24 hours administration of NO gas will reduce AKI following CPB in patients with endothelial dysfunction.MethodsThis is a single-centre, randomised (1:1) controlled, parallel-arm superiority trial that includes patients with endothelial dysfunction, stable kidney function and who are undergoing cardiac surgery procedures with an expected CPB duration >90 min. After randomisation, 80 parts per million (ppm) NO (intervention group) or 80 ppm nitrogen (N2, control group) are added to the gas mixture. Test gases (N2or NO) are delivered during CPB and for 24 hours after surgery. The primary study outcome is the occurrence of AKI among study groups. Key secondary outcomes include AKI severity, occurrence of renal replacement therapy, major adverse kidney events at 6 weeks after surgery and mortality. We are recruiting 250 patients, allowing detection of a 35% AKI relative risk reduction, assuming a two-sided error of 0.05.Ethics and disseminationThe Partners Human Research Committee approved this trial. Recruitment began in February 2017. Dissemination plans include presentations at scientific conferences, scientific publications and advertising flyers and posters at Massachusetts General Hospital.Trial registration numberNCT02836899.

Objective To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. Design Randomized, placebo-controlled, pilot feasibility trial. Setting Cardiac surgery department of a tertiary hospital. Participants Forty patients undergoing combined valvular and coronary artery bypass surgery. Interventions Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. Measurements and Main Results The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). Conclusions A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

Background Endogenous nitric oxide (NO) may contribute to ischemic and anesthetic preconditioning while exogenous NO protects against ischemia-reperfusion (I/R) injury in the heart and other organs. Why those beneficial effects observed in animal models do not always translate into clinical effectiveness remains unclear. To mitigate reperfusion damage a source of NO is required. NO inhalation is known to increase tissue NO metabolites, but little information exists about the lifetime of these species. We therefore sought to investigate the fate of major NO metabolite classes following NO inhalation in mice in vivo. Methods C57BL/6J mice were exposed to 80 ppm NO for 1 h. NO metabolites were measured in blood (plasma and erythrocytes) and tissues (heart, liver, lung, kidney and brain) immediately after NO exposure and up to 48 h thereafter. Concentrations of S-nitrosothiols, N-nitrosamines and NO-heme products as well as nitrite and nitrate were quantified by gas-phase chemiluminescence and ion chromatography. In separate experiments, mice breathed 80 ppm NO for 1 h prior to cardiac I/R injury (induced by coronary arterial ligation for 1 h, followed by recovery). After sacrifice, the size of the myocardial infarction (MI) and the area at risk (AAR) were measured. Results After NO inhalation, elevated nitroso/nitrosyl levels returned to baseline over the next 24 h, with distinct multi-phasic decay profiles in each compartment. S/N-nitroso compounds and NO-hemoglobin in blood decreased exponentially, but remained above baseline for up to 30min, whereas nitrate was elevated for up to 3hrs after discontinuing NO breathing. Hepatic S/N-nitroso species concentrations remained steady for 30min before dropping exponentially. Nitrate only rose in blood, liver and kidney; nitrite tended to be lower in all organs immediately after NO inhalation but fluctuated considerably in concentration thereafter. NO inhalation before myocardial ischemia decreased the ratio of MI/AAR by 30% vs controls (p = 0.002); only cardiac S-nitrosothiols and NO-hemes were elevated at time of reperfusion onset. Conclusions Metabolites in blood do not reflect NO metabolite status of any organ. Although NO is rapidly inactivated by hemoglobin-mediated oxidation in the circulation, long-lived tissue metabolites may account for the myocardial preconditioning effects of inhaled NO. NO inhalation may afford similar protection in other organs., Highlights • Breathing 80 ppm NO for 1 h increases NO metabolite concentrations, except nitrite, in murine blood/tissues. • After NO inhalation, elevated NO metabolites return to baseline in a compartment-specific manner. • Cardiac S-nitrosothiol and NO-heme levels remain elevated for ∼1 h after discontinuation of NO treatment. • Breathing 80 ppm NO for 1 h just before cardiac ischemia reduces reperfusion injury in mice.

OBJECTIVES Reports ranged from mixed to marginal tubing wear and spallation effects as a complication of roller pumps in cardiopulmonary bypass (CPB). Because the rollers constantly compress part of the tubing, we sought to determine whether circuit materials behave differently under a 3-h simulation of CPB. METHODS Two different tubing materials (silicone and Tygon) were tested with a customized experimental circuit, designed to allow in vitro simulation of CPB with priming volumes, pressures, revolutions per minute and temperatures equivalent to the clinical scenario. Samples were analysed with optical and field-emission scanning electron microscopy. We collected 200-ml fluid samples at 4 different times: before starting the CPB (T0), when the predicted revolutions per minute corresponded to about 2 min of CPB (T1), at 90 min (T2) and at 180 min (T3). At the end of CPB, we harvested 2 samples of tubing. Lastly, optical investigations and field-emission scanning electron microscopy observations were used for qualitative and quantitative analysis of circulating fragments. RESULTS T2 and T3 fluid samples showed more particles than T1 samples. Significant differences in terms of particle numbers were detected: silicone tubing released more fragments per millilitre than Tygon tubing, with both materials releasing particles from 5 to 500 µm. Silicone tubing was associated with a time-dependent increase in small particles released (P = 0.04), whereas this did not apply to large particles or to Tygon tubing. Yet, bootstrap estimates suggested that silicone tubing was associated with the release of more small particles whereas Tygon tubing released more large particles (both P CONCLUSIONS Silicone showed a worse spallation performance than Tygon, thus appearing less safe for more complex surgery of prolonged duration or for patients with a prior cerebral ischaemic event. Additional risk and cost-effectiveness comparisons to determine the potential benefits of one type of tubing material over the other are warranted to further expand our findings.

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. Measurements and Main Results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year.

Mycobacterium chimaera infections have mainly been associated with the heater-cooler unit (HCU) and, ultimately, linked to contaminated aerosols in the operation room. The contamination status of HCUs seems to be influenced by the maintenance, therefore, according to the manufacturer’s recommendations, peracetic acid (Puristeril) was introduced to increase HCU cleaning and disinfection protocol maintenance. Aerosol dispersion from Puristeril during maintenance can cause adverse effects to nearby workers. We aim to describe our technique to reduce the impact of Puristeril on operating room staff and to limit dispersion of its aerosol in the environment by performing the cleaning procedure through a closed circuit.

Background: Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers’ survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients. Methods: We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy. Results: Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment. Conclusions: A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications. Level of Evidence: V—therapeutic animal experiment.

Objectives Scanty data are available on 'second cross-clamping' following mitral valve repair in contemporary practice. The aim of this study was to evaluate the incidence, causes and outcomes of this event in patients referred for mitral repair for severe degenerative mitral regurgitation (MR). Methods The study population included 2318 patients with severe degenerative MR referred for mitral repair. A second cross-clamping was performed in 94 (4%) patients. Causes of the second cross-clamping, revising repair procedures, immediate echocardiographic outcomes and postoperative course were assessed and compared with the 'single cross-clamping cases' (2224 patients used as control). Clinical and echocardiographic follow-up information was available for 91 of the 94 second cross-clamping patients (97% complete) (median time 6 years, interquartile range 3-11). Results The most frequent causes of the second cross-clamping were residual MR >1+/4+ and systolic anterior motion. A residual prolapse was identified in 41 (43.5%) patients, systolic anterior motion in 22 (23.5%), untreated clefts in 14 (15%) and other mechanisms in 17 (18%). Second cardiopulmonary bypass and aortic cross-clamping times were 36 (range 28-50) and 23 (range 17-34) min, respectively. Hospital mortality was 0% in the second cross-clamping and 0.3% in the control group (P = 0.2). Postoperative complications and length of hospital stay were similar. At discharge, residual MR ≥2+/4+ was 2.1% in the second cross-clamping and 2.7% in the control group (P = 0.99). In the second cross-clamping, at 12 years, the cumulative incidence function of reoperation, recurrent MR ≥3+ and MR ≥2+ with death as competing risk were 5.7 ± 2.5% (95% confidence interval 2-12), 10.3 ± 4.3% (95% confidence interval 3.8-20) and 17 ± 5.2% (95% confidence interval 8-29), respectively. Conclusions In a large volume centre for mitral repair, a second cross-clamping is still performed in 3-5% of the patients. Because suboptimal immediate results are associated with impaired late outcomes of mitral reconstruction, a low threshold for a second cross-clamping seems to be justified. If the second repair is carried out with a relatively shorter additional cross-clamping time, mortality and morbidity are not increased and immediate and long-term results are very satisfactory.

Background There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications. Methods/design The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2–3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3–5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio

Background: Every year, over 1 million cardiac surgical procedures are performed all over the world. Reducing myocardial necrosis could have strong implications in postoperative clinical outcomes. Volatile anaesthetics have cardiac protective properties in the perioperative period of cardiac surgery. However, little data exists on the administration of volatile agents during cardiopulmonary bypass. The aim of this study was to assess if volatile anaesthetics administration during cardiopulmonary bypass reduces cardiac troponin release after cardiac surgery. Materials and methods: We retrospectively analysed data from 942 patients who underwent cardiac surgery in a teaching hospital. The only difference between the groups was the management of anaesthesia during CPB. The volatile group received sevoflurane or desflurane while the control group received a combination of propofol infusion and fentanyl boluses. Patients who received volatile anaesthetics during cardiopulmonary bypass (n=314) were propensity-matched 1:2 with patients who did not receive volatile anaesthetics during CPB (n=628). Results: We found a reduction in peak postoperative troponin I, from 7.8 ng/ml (4.8-13.1) in the non-volatile group to 6.8 ng/ml (3.7-11.8) in the volatile group (p=0.013), with no differences in mortality [2 (0.6%) in the volatile group and 2 (0.3%) in the non-volatile group (p=0.6)]. Conclusions: Adding volatile anaesthetics during cardiopulmonary bypass was associated with reduced peak postoperative troponin levels. Larger studies are required to confirm our data and to assess the effect of volatile agents on survival.

Objectives Prolonged cardiopulmonary bypass (CPB) is associated with hemolysis, resulting in increased plasma oxyhemoglobin and vascular nitric oxide depletion. The authors hypothesized that hemolysis associated with CPB would reduce nitric oxide bioavailability, resulting in high pulmonary and systemic vascular resistances that after CPB would normalize gradually over time, due to clearance of plasma oxyhemoglobin. The authors also investigated whether prolonged CPB (≥140 min) produced increased levels of hemolysis and greater pulmonary and systemic vasoconstriction. Design Prospective cohort study. Setting Single-center university hospital. Patients The study comprised 50 patients undergoing elective cardiac surgery requiring CPB. Interventions Plasma hemoglobin and plasma nitric oxide consumption were measured before surgery and after CPB. Pulmonary and systemic hemodynamics were measured after CPB. The effects of short (

Background Leaflet resection represents the reference standard for surgical treatment of mitral valve (MV) regurgitation. New approaches recently proposed place emphasis on respecting, rather than resecting, the leaflet tissue to avoid the drawbacks of the 'resection' approach. Objectives The lateral dislocation of mid portion of mitral posterior leaflet (P2) technique for MV repair is a nonresectional technique in which the prolapsed P2 segment is sutured to normal P1 segment. Our study evaluates the effectiveness of this technique. Patients and methods We performed the procedure on seven patients. Once ring annular sutures were placed, the prolapsed P2 segment was dislocated toward the normal P1 segment with a rotation of 90° and without any resection. If present, residual clefts between P2 and P3 segments were closed. Once the absence of residual mitral regurgitation is confirmed by saline pressure test, ring annuloplasty was completed. The valve was evaluated using transesophageal echocardiography in the operating room and by transthoracic echocardiography before discharge. Results At the last follow-up visit, transthoracic echocardiography revealed no mitral regurgitation and normal TRANSVALVULAR gradients. Conclusion The lateral dislocation of P2 is an easily fine-tuned technique for isolated P2 prolapse, with the advantage of short aortic cross-clamp and cardiopulmonary bypass times. We think it might be very favorable in older and frail patients. Long-term follow-up is necessary to assess the durability of this technique.

Inflammatory response and hemodilution are the main drawbacks of extracorporeal circulation. We hypothesize that the use of miniaturized extracorporeal circulation (MECC) might lower the systemic and myocardial inflammatory patterns compared with a standard system (SECC) and off-pump coronary artery bypass grafting (OPCABG). Sixty-one patients undergoing isolated coronary artery bypass graft were prospectively randomized to MECC (n = 19), SECC (n = 20), or OPCABG (n = 22). Blood samples were collected from radial artery and coronary sinus to analyze blood lactate, hemodilution, and markers for inflammation and endothelial activation such as tumor necrosis factor (TNF)-α, interleukin-6, monocyte chemotactic protein-1, and E-selectin. No differences were observed in early clinical outcome. Interleukin -6 levels increased in every group during and after cardiac surgery, whereas TNF-α values grew in the SECC group (p = 0.05). E-selectin systemic values decreased during and after operation (p = 0.001) in every group. Monocyte chemotactic protein-1 systemic and cardiac levels raised only in SECC group (p = 0.014). In conclusion, MECC is comparable to SECC and OPCABG in the clinical outcome of low-risk patients, and it might be extensively used with no additional intraoperative risk. The analysis of the inflammatory patterns of endothelial activation shows MECC as effective as OPCABG, suggesting further studies to clarify MECC recommendation in high-risk patients.

Objective Adequate maintenance of hypnosis during anesthesia throughout surgery using sevoflurane alone was investigated. In addition, sevoflurane pharmacokinetics during cardiopulmonary bypass were analyzed. Design This was a pilot pharmacokinetic study. Setting Tertiary care university hospital. Participants The study comprised 10 patients aged between 18 and 75 years who underwent elective mitral valve surgery. Interventions The end-tidal and sevoflurane plasma concentrations were measured throughout cardiac surgery procedures involving cardiopulmonary bypass. The sevoflurane plasma concentration was measured using gas chromatography. In addition, the ratio between sevoflurane alveolar concentration and inspired concentration over time (FA/FI) was analyzed to describe wash-in and wash-out curves. Measurements and Main Results Hypnosis was maintained adequately throughout surgery using sevoflurane alone. The bispectral index was maintained between 40 and 60 during cardiopulmonary bypass. The end-tidal sevoflurane was significantly different before and during cardiopulmonary bypass (1.86%±0.54% v 1.30%±0.58%, respectively; p

International audience; INTRODUCTION: This study was planned to investigate the impact of severe bleeding and blood transfusion on the development of stroke after coronary surgery.METHODS: This cohort study includes 2357 patients undergoing isolated CABG from the prospective European Coronary Artery Bypass Grafting (E-CABG) registry. Severity of bleeding was categorized according to the Universal Definition of Perioperative Bleeding (UDPB), E-CABG and PLATO definitions.RESULTS: Thirty patients (1.3%) suffered postoperative stroke. The amount of transfused red blood cell (RBC) (OR 1.10, 95%CI 1.03-1.18), preoperative use of unfractioned heparin (OR 4.49, 95%CI 1.91-10.60), emergency operation (OR 3.97, 95%CI 1.47-10.74), diseased ascending aorta (OR 4.62, 95%CI 1.37-15.65) and use of cardiopulmonary bypass (p = 0.043, OR 4.85, 95%CI 1.05-22.36) were independent predictors of postoperative stroke. Adjusted analysis showed that UDPB classes 3-4 (crude rate: 3.6% vs. 1.0%; adjusted OR 2.66, 95%CI 1.05-6.73), E-CABG bleeding grades 2-3 (crudes rate: 6.3% vs. 0.9%; adjusted OR 5.91, 95%CI 2.43-14.36), and PLATO life-threatening bleeding (crude rate: 2.5% vs. 0.6%, adjusted OR 3.70, 95%CI 1.59-8.64) were associated with an increased risk of stroke compared with no or moderate bleeding.CONCLUSIONS: Bleeding and blood transfusion are associated with an increased risk of stroke after CABG, which is highest in patients with severe bleeding.

Background: Cities around the world have underground or above-ground enclosed networks for pedestrian travel, representing unique environments for studying out-of-hospital cardiac arrest (OHCA) and resuscitation. The characteristics of OHCAs that occur in such networks are unknown. Objective: To determine whether cardiac arrests occurring in enclosed pedestrian networks are different from those in the encompassing city, using the PATH network in Toronto, the largest underground shopping complex in the world, as a model site. Methods: We identified all atraumatic, public-location OHCAs in Toronto from Apr. 2006 – Mar. 2015, and classified them according to location: Toronto, downtown, and PATH-accessible. PATH-accessible OHCAs are those that occur within the PATH network between the first underground and second above-ground floor. We collected demographic, prehospital intervention, and survival data for each OHCA. Statistical analysis was performed using t-tests and chi-squared tests. Results: We identified 2621 atraumatic public OHCAs, of which 521 were in downtown and 50 were PATH-accessible. Compared to Toronto overall, PATH-accessible OHCAs had significantly higher proportions of bystander witnessed interventions, initial shockable rhythm, and overall survival, with all differences being statistically significant. Similar significant differences were observed when comparing PATH-accessible to downtown OHCAs. There were no significant differences in demographics and survival among patients with initial shockable rhythm. Conclusion: This study suggests that OHCAs in enclosed pedestrian networks are uniquely different from other public settings. Bystander resuscitation efforts are significantly more frequent and survival rates are higher. Urban planners in similar networks worldwide should consider these findings when deciding on AED placement and how to cue bystander response.

Background. S100B protein, previously proposed as a consolidated marker of brain damage in congenital heart disease (CHD) newborns who underwent cardiac surgery and cardiopulmonary bypass (CPB), has been progressively abandoned due to S100B CNS extra-source such as adipose tissue. The present study investigated CHD newborns, if adipose tissue contributes significantly to S100B serum levels.Methods. We conducted a prospective study in 26 CHD infants, without preexisting neurological disorders, who underwent cardiac surgery and CPB in whom blood samples for S100B and adiponectin (ADN) measurement were drawn at five perioperative time-points.Results. S100B showed a significant increase from hospital admission up to 24 h after procedure reaching its maximum peak(P<0.01)during CPB and at the end of the surgical procedure. Moreover, ADN showed a flat pattern and no significant differences(P>0.05)have been found all along perioperative monitoring. ADN/S100B ratio pattern was identical to S100B alone with the higher peak at the end of CPB and remained higher up to 24 h from surgery.Conclusions. The present study provides evidence that, in CHD infants, S100B protein is not affected by an extra-source adipose tissue release as suggested by no changes in circulating ADN concentrations.

Objectives: Although antegrade selective cerebral perfusion (ASCP) provides good brain protection during aortic arch surgery, the issue of distal organ protection during circulatory arrest remains to be clarified. The aim of the study was to retrospectively evaluate the outcome of aortic arch surgery using ASCP at different temperatures, focusing on visceral functions (VFs). Methods: Three hundred and thirty-four patients underwent elective aortic arch surgery using ASCP from November 1996 to March 2011. Those patients without early postoperative low cardiac output syndrome were included. VFs were evaluated by comparing preoperative and postoperative creatinine, aspartate amino transferase, alanine amino transferase and bilirubin. Univariate and multivariate analysis were performed. Results: Three hundred and four patients represent the cohort of the study. Deeper systemic hypothermia (≤25°C) (Group A) was used in 194 patients (63.8%) and moderate hypothermia (>25°C) (Group B) in 110 patients (36.2%). The 30-day mortality rate was 3.6% in Group B and 5.2% in Group A (P = NS). Permanent neurological deficits occurred in 4 (3.6%) and in 14 patients (7.2%) of Group A and Group B, respectively (P = NS). Postoperative renal insufficiency requiring dialysis occurred in 6 patients (5.4%) in Group A and in 15 patients (7.7%) in Group B, the differences were not statistically significant. Biochemical markers of VFs increased in the postoperative period without differences between groups. At the multivariate analysis, cardiopulmonary bypass time >180 min (odds ratio (OR) = 2.16) was the only significant risk factor for renal dysfunction with or without liver dysfunction, while cardiopulmonary bypass time longer than 180min (OR = 2.28) and hypothermia higher than 25°C (OR = 0.54) were found to be independently related to liver dysfunction. Conclusions: Our results confirmed that ASCP with moderate hypothermia at 26°C is a safe method for brain protection. Moreover, during circulatory arrest, moderate hypothermia also offers good protection of visceral organs and it should be preferred for limited periods (

We report a case of a young man with hypoplastic right ventricle, who presented with recurrent untreatable arrhythmias after a Bjork Fontan procedure in infancy. He underwent one-and-a-half ventricle repair as an alternative surgery to Fontan revision. doi: 10.1111/jocs.12410 (J Card Surg 2014;29:832–835)

Introduction Use of extended criteria donors is one of the strategies to face the scarcity of donors for lung transplantation. Methods Between November 2002 and May 2009, we performed 52 LTs in 50 recipients, 10 of whom (group A) received lungs from donors aged 55 years or older (median, 58.5; range, 56–66 years) for comparison with 28 patients (group B) transplanted with lungs from donors younger than 55 years (median, 25.5; range, 15–54 years). We excluded 9 children and 3 recipients of combined liver plus lung transplantations from the study. Results Recipient age, gender, and indications for transplantation did not differ significantly between the 2 groups. Neither were there significant differences in PaO2/FiO2 ratios before lung retrieval, or length of the ischemic time The first PaO2/FiO2 on arrival to the intensive care unit (ICU) and the median length of ICU stay were similar. All patients, except 2 who died in the operating theatre, were extubated between 3 and 216 hours after the transplantation. Hospital mortality was similar in both groups: 3 patients in group A and 2 in group B (P = .1). The median portions of the predicted 1-second forced expiratory volume (FEV1) at 6 months after transplantation did not differ in the 2 groups: 62.4% in group A versus 70% in group B (P = .85). Conclusion Lung grafts from donors older than 55 years can be effectively used for transplantation, thus increasing the total organ pool.

Introduction: Over the last few years, near-infrared spectroscopy (NIRS) has been introduced to study cerebral haemodynamics and oxygenation. This paper points out how the use of an external source of CO2 effects on the absolute value of cerebral NIRS during cardiac surgery on cardiopulmonary bypass. Patients and methods: Between January 2010 and September 2011, 368 patients underwent congenital heart disease correction on cardiopulmonary bypass (CPB). Nineteen patients, with a mean age of 26 days (range 6-120 days), required an external source of CO2 to correct hypocarbia during cardiopulmonary bypass. Different parameters were monitored: NIRS value, oxygen saturation, oxygen partial pressure, CO2 partial pressure, haematocrit, mean arterial pressure and pH. They were analyzed during different phases of the surgical procedure: before, during and after CO2 infusion. Results: There were no deaths during the hospital stay. The NIRS value increased significantly (p2, from a starting value of 52.9 to a final value of 63.4. PaCO2 was found to increase too: from 31.3 mmHg to 40.6 mmHg. On the other hand, both values decreased when the CO2 was removed, to respective final values of 55.8 and 34.4 mmHg. Mean arterial pressure, haematocrit and PaO2 didn’t modify significantly during this period. Conclusions: Nowadays, NIRS is usually used in cardiac surgery to reduce possible risks of neurological damage. The importance of the role of pCO2 in the cerebral vascular resistance and in cerebral blood flow has already been proven. This research demonstrates a relationship between pCO2 and the NIRS value. This paper could introduce an important correcting tool when an inadequate NIRS value occurs although the level of oxygenation, haematocrit and mean arterial pressure are acceptable and the arterial line is accurately positioned.

Introduction: Non-invasive cerebral monitoring with the INVOS cerebral oximeter is an accepted good indicator of cerebral metabolism. In recent years, it has been used in the monitoring of patients who underwent cardiac surgery. Herein, we describe the INVOS trend during cardiopulmonary bypass (CPB) in a cohort of patients operated in our institution for congenital heart disease. Patients and methods: Between December 2009 and March 2010, 40 patients (mean age 8.4 years; range 11 days-60 years) underwent cardiac surgical procedures using CPB. Values of INVOS cerebral parameter, pH, oxygen saturation, and CO2 level were collected pre CPB, during cooling, re-warming and weaning, and post CPB. INVOS parameters were evaluated according to CPB priming, age and preoperative oxygen saturation. Results: Patients were divided according to CPB priming (haematic vs clear), age (≤1 vs >1 year of age) and oxygen saturation (≤92% vs >92%). During the operations, the trend demonstrated a reduction in INVOS value at the institution of CPB and a further reduction during the cooling phase in all groups.This has been correlated to the loss of pulsatile flow. However, the value recovered during re-warming, weaning and CPB discontinuation. Cyanotic patients presented a lower cerebral oximetry compared to acyanotic patients during the whole CPB period. Between age and priming groups, we noticed a statistical difference in cerebral oximetry, with a lower value in the younger patients and in the haematic priming group. This might be interrelated because all patients younger than 1 year old always received haematic CPB priming. Conclusions: We demonstrated that cerebral oximetry decreases with the loss of pulsatile flow regardless of the mean arterial pressure and, furthermore, is not directly related to the haematocrit value in patients with reduced pulmonary blood flow.

Context: Major surgery induces a catabolic state resulting in a net loss of body protein. Objectives: Our objective was to compare protein metabolism before and after surgery in nondiabetic patients with and without preoperative insulin resistance (IR). It was hypothesized that the anabolic response to feeding would be significantly impaired in those patients with preoperative insulin resistance. Design: A hyperinsulinemic-euglycemic clamp has been used to identify two groups of patients: IR and insulin sensitive (IS). A tracer kinetics technique has been used to evaluate the metabolic response to food intake in both groups. Setting: Patients undergoing cardiopulmonary bypass participated. Patients or Other Participants: Ten IS patients and 10 IR patients were enrolled in the study. Intervention: After an overnight fasting, a 3-h infusion of a solution composed of 20% glucose and of amino acids at a rate of 0.67 and 0.44 kcal/kg · h, respectively, was started in each group. Phenylalanine kinetics were studied at the end of fasting and feeding. Main Outcome Measure: Effect of feeding on protein balance before and after surgery was evaluated. Protein balance has been measured as the net difference of protein breakdown minus protein synthesis. Results: Protein balance increase after postoperative feeding was blunted only in the IR group. In contrast, in the IS group, the postoperative anabolic effect of feeding was the same as before surgery. Conclusions: These findings propose a link between insulin resistance and protein metabolism. When non-IR patients are fed, a significant anabolic effect in the postoperative period is demonstrated. In contrast, IR patients are less able to use feeding for synthetic purposes.

Background There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first international consensus conference on this topic. Methods The consensus was a continuous international internet-based process with a final meeting on June 28th 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting and ranking. Results Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, the use of preoperative intra-aortic balloon counterpulsation and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. Conclusion This international consensus conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

In designing the anaesthetic plan for patients undergoing surgery, the choice of anaesthetic agent may often appear irrelevant and the best results obtained by the use of a technique or a drug with which the anaesthesia care provider is familiar. Nevertheless, in those surgical procedures (cardiopulmonary bypass, carotid surgery and cerebral aneurysm surgery) and clinical situations (subarachnoid haemorrhage, stroke, brain trauma and postcardiac arrest resuscitation) where protecting the CNS is a priority, the choice of anaesthetic drug assumes a fundamental role. Treating patients with a neuroprotective agent may be a consideration in improving overall neurological outcome. Therefore, a clear understanding of the relative degree of protection provided by various agents becomes essential in deciding on the most appropriate anaesthetic treatment geared to these objectives. This article surveys the current literature on the effects of the most commonly used anaesthetic drugs (volatile and gaseous inhalation, and intravenous agents) with regard to their role in neuroprotection. A systematic search was performed in the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL) and Cochrane Library databases using the following keywords: ‘brain’ (with the limits ‘newborn’ or ‘infant’ or ‘child’ or ‘neonate’ or ‘neonatal’ or ‘animals’) AND ‘neurodegeneration’ or ‘apoptosis’ or ‘toxicity’ or ‘neuroprotection’ in combination with individual drug names (‘halothane’, ‘isoflurane’, ‘desflurane’, ‘sevoflurane’, ‘nitrous oxide’, ‘xenon’, ‘barbiturates’, ‘thiopental’, ‘propofol’, ‘ketamine’). Over 600 abstracts for articles published from January 1980 to April 2010, including studies in animals, humans and in vitro, were examined, but just over 100 of them were considered and reviewed for quality. Taken as a whole, the available data appear to indicate that anaesthetic drugs such as barbiturates, propofol, xenon and most volatile anaesthetics (halothane, isoflurane, desflurane, sevoflurane) show neuroprotective effects that protect cerebral tissue from adverse events – such as apoptosis, degeneration, inflammation and energy failure – caused by chronic neurodegenerative diseases, ischaemia, stroke or nervous system trauma. Nevertheless, in several studies, the administration of gaseous, volatile and intravenous anaesthetics (especially isoflurane and ketamine) was also associated with dosedependent and exposure time-dependent neurodegenerative effects in the developing animal brain. At present, available experimental data do not Approval for publication Signed Date Number of amended pages returned LEADING ARTICLE CNS Drugs 2010; 24 (11): 1-15 1172-7047/10/0011-0001/$49.95/0 ª 2010 Adis Data Information BV. All rights reserved. AUTHOR PROOF support the selection of any one anaesthetic agent over the others. Furthermore, the relative benefit of one anaesthetic versus another, with regard to neuroprotective potential, is unlikely to form a rational basis for choice. Each drug has some undesirable adverse effects that, together with the patient’s medical and surgical history, appear to be decisive in choosing the most suitable anaesthetic agent for a specific situation. Moreover, it is important to highlight that many of the studies in the literature have been conducted in animals or in vitro; hence, results and conclusions of most of them may not be directly applied to the clinical setting. For these reasons, and given the serious implications for public health, we believe that further investigation – geared mainly to clarifying the complex interactions between anaesthetic drug actions and specific mechanisms involved in brain injury, within a setting as close as possible to the clinical situation – is imperative.

Pharmacokinetics is a discipline aimed at predicting the best dosage and dosing regimen for each single drug in order to ensure and maintain therapeutically effective concentrations at the action sites. In cardiac critical care patients, various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs. Gastrointestinal drug absorption may be erratic and unpredictable in the early postoperative period, and so patients may be unresponsive to oral therapy; thus the intravenous route should be preferred for life-saving drugs whenever feasible. Variations in the extracellular fluid content as a response to the trauma of surgery and the fluid load or significant drug loss through thoracic drainages may significantly lower plasma concentrations of extracellularly distributed hydrophilic antimicrobials (β-lactams, aminoglycosides and glycopeptides). Drug metabolism may be altered by the systemic inflammatory response and/or multiple organ failure and/or drug-drug pharmacokinetic interactions that can potentially occur during polytherapy, especially in immunosuppressed cardiac transplant patients. Instability of renal function may promote significant changes in body fluid concentrations of renally eliminated drugs, even in a brief period of hours. Finally, the application of extracorporeal circulation by means of cardiopulmonary bypass may significantly alter the disposition of several drugs during the operation because of acute haemodilution, hypoalbuminaemia, hypothermia and/or adsorption to the bypass equipment. Accordingly, to avoid either overexposure and the consequent increased risk of toxicity or underexposure and the consequent risk of therapeutic failure in critically ill cardiac patients, the dosing regimens of several drugs are expected to be significantly different from those suggested for clinically stable patients. Additionally, therapeutic drug monitoring may be helpful in the management of drug therapy and should be routinely used to guide individualized dose adjustments for (i) immunosuppressants whenever cytochrome P450 3A4 isoenzyme inhibitors (e.g. macrolide antibacterials, azole antifungals) or inducers (e.g. rifampicin [rifampin]) are added to or withdrawn from the regimen; and (ii) glycopeptide and aminoglycoside antibacterials whenever haemodynamically active agents (such as dopamine, dobutamine and furosemide [frusemide]) are added to or withdrawn from the regimen, and also whenever significant changes of haemodynamics and/or of renal function occur. © 2008 Adis Data Information BV. All rights reserved.

A modified polyethersulphone graft membrane was loaded with antiproteases, with the aim of reducing the active protease blood concentration during hemodialysis in acute catabolic renal failure or cardiopulmonary bypass. As protease/antiprotease system, elastase and α 1 -antitrypsin were used. The concentration of active elastase in aqueous solutions decreased as function of contact time with the membrane, approaching saturation. A 40% loss of elastase activity was obtained at pH 7.4, which was not due to autolysis, which accounted for 5% of the loss. The highest reduction was achieved at pH 9.0 (25% higher than at pH 7.4). The saturation level of elastase decrease, calculated by means of the Einstein equation, was reached after more than 47 minutes. We speculate that a time reduction might be achieved either increasing the concentration of immobilized antiproteases, or increasing the rate of elastase movement across the membranes by hydraulic, osmotic, or temperature gradients. This technology can be applied to hemodialysis, and in extracorporeal blood circulation to promote elastase release.