Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Use of subconscious and conscious suggestions combined with music as a relaxation technic

A radio experiment carried out over many years, added to previous clinical tests, has shown a sustained interest of the people for using preconscious (subliminal) suggestions combined with soothing music, as a relaxation technique. The purpose of this study was to compare systematically some combinations with their own components, i.e. the suggestions alone or the music alone. Moreover, drawing inspiration from the works of a Bulgarian psychiatrist, Georgi Lozanov, there were comparisons made of the efficacy of three types of combinations whether they included different kinds of suggestions: preconscious, close to the level of consciousness or conscious. Thirty-five (35) persons were subjected to tests in five experimental sessions, (music alone, three suggestion-music combinations, and suggestions alone), according to a latin-square design (5 x 5). Physiologic and psychologic measurements were used. The physiologic measurements did not show any significant difference between the various treatments. On the other hand, the psychologic measurements favoured the combinations rather than their components alone and specially the combination where suggestions were of an intensity close to the level of consciousness.     

Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase)

Essential fructosuria is one of the oldest known inborn errorsof metabolism. It is a benign condition which is believed toresult from deficiency of hepatic fructokinase (ketohexokinase,KHK, E.C.2.7.1.3). This enzyme catalyses the first step of metabolismof dietary fructose, conversion of fructose to fructose-1-phosphate.Despite the early recognition of this disorder, the primarystructure of human KHK and the molecular basis of essentialfructosuria have not been previously defined. In this report,the isolation and sequencing of full-length cDNA clones encodinghuman ketohexokinase are described. Alternative mRNA speciesand alternative KHK isozymes are produced by alternative polyadenylationand splicing of the KHK gene. The KHK proteins show a high levelof sequence conservation relative to rat KHK. Direct evidencethat mutation of the KHK structural gene is the cause of essentialfructosuria was also obtained. In a well-characterized family,in which three of eight siblings have fructosurla, all affectedindividuals are compound heterozygotes for two mutations Gly40Argand Ala43Thr. Both mutations result from G     

Adjuvant propofol enables better control of nausea and emesis secondary to chemotherapy for breast cancer

We investigated the prophylactic antiemetic effect of added lowdose infusion of propofol in patients exhibiting nausea and vomiting refractory to dexamethasone and serotonin antagonist during non-cisplatin chemotherapy for breast cancer. In a prospective open longitudinal study, 117 patients who had more than five episodes of nausea and vomiting in their first chemotherapy cycle during the first 24 hr completed the study. They received in addition to the usual prophylactic antiemetic regimen a continuous intravenous infusion of 1 mg · kg^?1 · hr^?1 propofol started four hours before chemotherapy and continued up to 24 hr for the two subsequent cycles. The number of vomiting / nausea episodes, level of sedation, patient activity, appetite and preference for future chemotherapy cycles were assessed. In the propofol supplemented cycles 90 and 80% of patients, during the 1st and 2nd propofol-assisted cycle respectively, were free of nausea and vomiting during the first 24 hr after chemotherapy. Patients were more frequently active and had more appetite during the propofol-assisted cycles. No propofol-associated side effects were observed. We conclude that the addition of a subhypnotic infusion of propofol enables better control of nausea and vomiting caused by non-cisplatin chemotherapy in the first 24 hr post-treatment.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.     

Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich,Switzerland

Background

The aim of this study was to investigate the impact of the introduction of a Patient Blood Management (PBM) programme in elective orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass loss, and transfusion.

Materials and methods

Orthopaedic operations (hip, n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were analysed. Period 1 (2008), was before the introduction of the PBM programme and period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative anaemia, RBC mass loss, and transfusion rates in the two periods were compared.

Results

In hip surgery, the percentage of patients with immediate pre-operative anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged, being 626±434 vs 635±450 mL (p=0.974). Transfusion rate was significantly reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre-operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss reduced from 573±355 to 476±365 mL (p<0.001). The transfusion rate dropped from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53±1.27 to 0.16±0.90 units (p<0.001). In spine surgery the prevalence of immediate pre-operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551±421 to 404±337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6% (p<0.001) and RBC transfusions decreased from 0.66±1.80 to 0.22±0.89 units (p=0.008).

Discussion

Detection and treatment of pre-operative anaemia, meticulous surgical technique, optimal surgical blood-saving techniques, and standardised transfusion triggers in the context of PBM programme resulted in a lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss, and a lower transfusion rate.