Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Surgery for primary hyperparathyroidism performed under local anaesthesia

Patients with primary hyperparathyroidism are often elderly with cardiovascular disease and in some an operation might be hazardous owing to anaesthetic complications. A technique for operation for primary hyperparathyroidism under local anaesthesia is described. The method uses a unilateral approach. Seventeen consecutive patients operated on under local anaesthesia were compared with a group of 15 patients undergoing surgery under general anaesthesia. Normocalcaemia was achieved in 14 patients in each group. There was no difference in the extent of pain or the overall well-being between the two groups as determined by a visual analogue scale. Patients receiving local anaesthesia, however, experienced significantly less nausea after operation (P < 0.01). There was more fluctuation in blood pressure and heart rate in the general anaesthesia group compared with the other group. Surgery for primary hyperparathyroidism can be performed safely under local anaesthesia, and could be offered to patients if general anaesthesia were not suitable or involved an increased perioperative risk. It should not be recommended for routine use in patients who are fit for general anaesthesia

Acupuncture for pain relief during childbirth

BACKGROUND: There are few studies on acupuncture in childbirth despite the generally established analgesic effect of acupuncture treatment. METHODS: The analgesic effect of acupuncture during childbirth was assessed by comparing the need for other pain treatments (epidural analgesia using bupivacaine, pudendal nerve block, intramuscular meperidine, nitrous oxide/oxygen, intracutaneous sterile water injections) in 90 women given acupuncture (acupuncture group) with that in 90 women not given acupuncture (control group). RESULTS: 52 women (58%) in the acupuncture group and 13 (14%) in the control group managed their deliveries without further pain treatment (p < 0.001). The groups were similar with respect to age, pariety, duration of delivery, use of oxytocine and incidence of Caesarean section. Acupuncture treatment was found to have no major side effects, and 85 women (94%) given acupuncture reported that they would reconsider acupuncture in future deliveries. CONCLUSION: Acupuncture reduces the need for other methods of analgesia in childbirth

Effects of nitrous oxide on human regional cerebral blood flow and isolated pial arteries

BACKGROUND: Results from previous studies on the effect of nitrous oxide (N2O) on the cerebral circulation are conflicting. Early reports claim N2O to have no effect whereas recent findings demonstrate a cerebral cortical vasodilatation during N2O inhalation, but the regional cerebral blood flow (CBF) in the subcortical structures is unknown. METHODS: Regional CBF was measured three-dimensionally with single photon emission computer-aided tomography after injection of xenon 133 in 8 spontaneously breathing men (mean age 29.6 yr) during normocapnia and hypocapnia with and without inhalation of 50% N2O. 8 isolated human pial arterial segments were mounted in organ baths. The segments were contracted with prostaglandin F2 alpha and subjected to 30% oxygen and 5.6% carbon dioxide in nitrogen or N2O. RESULTS: Normocapnic young men had a global CBF of 55 +/- 4 ml.100 g-1.min-1. Decreasing end-tidal CO2 tension by 1.3 kPa (9.3 mmHg) reduced CBF uniformly, with a decrease in global CBF to 45 +/- 2 ml.100 g-1.min-1 (P < 0.0001). During normocapnia, inhalation of 50% N2O increased mean CBF to 67 +/- 7 ml.100 g-1.min-1 (P < 0.0001). Inhalation of 50% N2O during hypocapnia increased mean CBF to 63 +/- 5 ml.100 g-1.min-1 (P < 0.0001). During N2O inhalation there was no significant difference in mean CBF between normo- and hypocapnia. However, during hypocapnia, but not during normocapnia, N2O inhalation significantly changed the distribution of regional CBF (P < 0.0001). Compared with hypocapnia without N2O, flow increased through the frontal (143%), parietal (140%) and temporal (133%) regions as well as through insula (151%), basal ganglia (145%) and thalamus (133%). In isolated human pial arteries, addition of N2O changed neither basal tension, nor the contraction elicited by prostaglandin F2 alpha. CONCLUSIONS: Inhalation of 50% N2O increased global CBF mainly by augmenting flow in frontal brain structures. In contrast, changes in carbon dioxide without N2O affected CBF uniformly in the brain. The uneven change in distribution of the CBF when N2O was added during hypocapnia, the reduced carbon dioxide response, and the lack of effect of N2O on isolated human pial arteries suggest that N2O may increase metabolism in selected brain areas

Side localization of parathyroid adenomas by simplified intraoperative venous sampling for parathyroid hormone

Side localization of parathyroid adenomas was performed by venous sampling for intact parathyroid hormone (PTH) in 20 consecutive patients with primary hyperparathyroidism (pHPT) after induction of anesthesia. The results were thus available during surgery. Nineteen of the patients had solitary parathyroid adenoma, and one had hyperplasia. There was no complication to the procedure. A lateralizing PTH gradient for a parathyroid adenoma was obtained in 13 patients. At surgery 12 of them (92%) were proved correct; that is, the adenoma was localized on the same side. Thus the technique correctly lateralized the adenoma in 12 of 19 patients (63%). We therefore conclude that the method of intraoperative venous sampling for intact PTH is safe, and the predictive value of a lateralizing gradient is high. It could therefore be used as an adjunct to surgical skill and noninvasive localization procedures in selected cases, for instance in patients with prior neck surgery and hypercalcemic crisis

International consensus recommendations for anesthetic and intensive care management of lung transplantation. An EACTAIC, SCA, ISHLT, ESOT, ESTS, and AST approved document

For patients with end-stage lung disease, LTx remains the only therapeutic option toward better chance of survival as well as improved quality of life. According to the International Society for Heart and Lung Transplantation (ISHLT) Transplant Registry, the number of LTx procedures has been rising despite limitations in available and suitable donor lungs and in the face of persistent donor shortages.1 The modern era of LTx is characterized by increasing complexity of recipient candidates including those receiving bridging extracorporeal support, a trend toward acceptance of suboptimal or extended criteria donors, and increasingly complicated surgical strategies.2 Despite these adverse conditions, contemporary survival figures for LTx continues to improve, especially considering the early period after LTx.1,2 While these achievements are remarkable and only possible by pushing the limits of what is conceivable, the procedure remains associated with high perioperative morbidity and mortality and the lowest long-term survival of all solid organ transplants. The leading cause of perioperative mortality, remains primary graft dysfunction (PGD).3-8 Registry data and recent randomized clinical trials conducted with the involvement of the leading transplant centers identify nearly 30% prevalence of severe allograft dysfunction with important influence on patient recovery, allograft quality, long term survival and quality of life.9 Beyond PGD, surgical complications account for approximately 10% of the perioperative mortality and infections are responsible for another 20%. Moreover, there is increasing evidence that in-hospital, extra-pulmonary complications comprising mainly of renal, cardiac, hepatic, and vascular adverse events are nearly ubiquitous and impact negatively on long-term outcomes