Barry A. Finegan

Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection?

Background: Two preconditioning stimuli should induce a more consistent overall cell protection. We hypothesized that remote ischemic preconditioning (RIPC, second preconditioning stimulus) applied during isoflurane inhalation (first preconditioning stimulus) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting. Methods: In this placebo-controlled randomized controlled study, patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping. Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance. The primary outcome was high-sensitivity cardiac troponin T release. Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide, high-sensitivity C-reactive protein, S100 protein, and short- and long-term clinical outcomes. Gene expression profiles were obtained from atrial tissue using microarrays. Results: RIPC (n = 27) did not reduce high-sensitivity cardiac troponin T release when compared with placebo (n = 28). Likewise, N-terminal pro-brain natriuretic peptide, a marker of myocardial dysfunction; high-sensitivity C-reactive protein, a marker of perioperative inflammatory response; and S100, a marker of cerebral injury, were not different between the groups. The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infarctions was higher in the RIPC group than the placebo group (14/27 vs. 6/28, P = 0.036). However, there was no difference in the 6-month cardiovascular outcome. N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism (P = 0.001) and DNA-damage signaling (P < 0.001), but not with RIPC-induced changes in gene expression. Conclusions: RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting.

Patient selection in ambulatory anesthesia — An evidence-based review: part II

PurposeTo identify and characterize the evidence supporting decisions made in the care of patients with selected medical conditions undergoing ambulatory anesthesia and surgery. Conditions highlighted in this review include: the elderly heart transplantation, hyper-reactive airway disease, coronary artery disease, and obstructive sleep apnea.SourceA structured search of MEDLINE ( 1966–2003) was performed using keywords for ambulatory surgery and patient condition. Selected articles were assigned a level of evidence using Centre for Evidence Based Medicine (CEBM) criteria. Recommendations were also graded using CEBM criteria.Principal findingsThe elderly may safely undergo ambulatory surgery but are at increased risk for hemodynamic variation in the operating room. The heart transplant recipient is at increased risk of coronary artery disease and renal insufficiency and should undergo careful preoperative evaluation. The patient with reactive airway disease is at increased risk of minor respiratory complications and should be encouraged to quit smoking. The patient with coronary artery disease and recent myocardial infarction may undergo ambulatory surgery without stress testing if functional capacity is adequate. The patient with obstructive sleep apnea is at increased risk of difficult tracheal intubation but the likelihood of airway obstruction and apnea following ambulatory surgery is unknown.ConclusionAmbulatory anesthesia is infrequently associated with adverse outcomes, however, knowledge regarding specific patient conditions is of generally low quality. Few prospective trials are available to guide management decisions.RésuméObjectifIdentifier et caractériser la preuve à l’appui des décisions prises sur les soins à donner aux patients qui présentent des pathologies médicales ciblées et qui subissent une anesthésie en chirurgie ambulatoire. Les situations sélectionnées dans cette revue comprennent : la vieillesse, la transplantation cardiaque, l’affection respiratoire hyper-réactionnelle, la coronaropathie et l’apnée obstructive du sommeil.SourceUne recherche structurée dans MEDLINE (1966–2003) a été réalisée selon les mots dés pour la chirurgie ambulatoire et l’état du patient. Les articles choisis ont été cotés selon le niveau de preuve des critères du Centre for Evidence Based Medicine (CEBM). Les recommandations ont aussi été graduées selon les critères du CEBM.Constatations principalesLes personnes âgées peuvent subir une opération ambulatoire en toute sécurité, mais sont plus à risque de variation hémodynamique en salle d’opération. Les greffés cardiaques sont plus à risque de coronaropathie et d’insuffisance rénale et doivent avoir une évaluation préopératoire minutieuse. Les cas d’affection respiratoire réactionnelle sont plus à risque de complications respiratoires mineures et doivent être encouragés à cesser de fumer. Le patient atteint de coronaropathie, victime récente d’infarctus myocardique, peut être vu en chirurgie ambulatoire sans épreuve d’effort si la capacité fonctionnelle est adéquate. En cas d’apnée obstructive du sommeil, il y a plus de risque de difficulté d’intubation trachéale, mais la possibilité d’obstruction des voies aériennes et d’apnée à la suite d’une opération ambulatoire n’est pas connue.ConclusionLanesthésie ambulatoire n’est pas souvent associée à des complications, même si la connaissance de pathologies spécifiques est peu développée en général. Il existe peu d’études prospectives permettant de guider les décisions thérapeutiques.

Cost Trajectories at the End of Life: The Canadian Experience

A significant proportion of health care resources are consumed at end of life. As a result, decision and policy makers seek cost savings to enhance program planning. Most literature, however, combines the cost of all dying patients and, subsequently, fails to recognize the variation between trajectories of functional decline and utilization of health care services. In this article, we classified dying Albertans by categories of functional decline and assessed their utilization and costs. We used data from two years of health care utilization and costs for three annual cohorts of permanent residents of Alberta, Canada (April 1999 to March 2002). Literature, expert opinion, and cluster analysis were used to categorize the deceased according to sudden death, terminal illness, organ failure, frailty, and other causes of death. Expenditures were decomposed into constituent quantities and prices. We found that nearly 18,000 die per year in Alberta: sudden death (7.1%), terminal illness (29.8%), organ failure (30.5%), frailty (30.2%), and other causes (2.3%). Inpatient care remains the primary cost driver for all trajectories. Significant and predictable health care services are required by noncancer patients. Trajectories of costs are significantly different for the four categories of dying Albertans. Trajectories of dying are a useful classification for analyzing health care use and costs.

Inhibition of glycolysis and enhanced mechanical function of working rat hearts as a result of adenosine A1 receptor stimulation during reperfusion following ischaemia.

1 This study examined effects of adenosine and selective adenosine A1 and A2 receptor agonists on glucose metabolism in rat isolated working hearts perfused under aerobic conditions and during reperfusion after 35 min of global no‐flow ischaemia. 2 Hearts were perfused with a modified Krebs‐Henseleit buffer containing 1.25 mM Ca2+, 11 mM glucose, 1.2 mM palmitate and insulin (100 μu ml−1), and paced at 280 beats min−1. Rates of glycolysis and glucose oxidation were measured from the quantitative production of 3H2O and 14CO2, respectively, from [5‐3H/U‐14C]‐glucose. 3 Under aerobic conditions, adenosine (100 μm) and the adenosine A1 receptor agonist, N6‐cyclohexyladenosine (CHA, 0.05 μm), inhibited glycolysis but had no effect on either glucose oxidation or mechanical function (as assessed by heart rate systolic pressure product). The improved coupling of glycolysis to glucose oxidation reduced the calculated rate of proton production from glucose metabolism. The adenosine A1 receptor antagonist, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX 0.3 μm) did not alter glycolysis or glucose oxidation per se but completely antagonized the adenosine‐ and CHA‐induced inhibition of glycolysis and proton production. 4 During aerobic reperfusion following ischaemia, CHA (0.05 μm) again inhibited glycolysis and proton production from glucose metabolism and had no effect on glucose oxidation. CHA also significantly enhanced the recovery of mechanical function. In contrast, the selective adenosine A2a receptor agonist, CGS‐21680 (1.0 μm), exerted no metabolic or mechanical effects. Similar profiles of action were seen if these agonists were present during ischaemia and throughout reperfusion or when they were present only during reperfusion. 5 DPCPX (0.3 μm), added at reperfusion, antagonized the CHA‐induced improvement in mechanical function. It also significantly depressed the recovery of mechanical function per se during reperfusion. Both the metabolic and mechanical effects of adenosine (100 μm) were antagonized by the nonselective A1/A2 antagonist, 8‐sulphophenyltheophylline (100 μm). 6 These data demonstrate that inhibition of glycolysis and improved recovery of mechanical function during reperfusion of rat isolated hearts are mediated by an adenosine A1 receptor mechanism. Improved coupling of glycolysis and glucose oxidation during reperfusion may contribute to the enhanced recovery of mechanical function by decreasing proton production from glucose metabolism and the potential for intracellular Ca2+ accumulation, which if not corrected leads to mechanical dysfunction of the post‐ischaemic myocardium.

Changing the admission process for elective surgery: an economic analysis

This study compared the costs of an inpatient elective surgical admission process with an outpatient based same day admission programme in patients undergoing laparoscopic cholecystectomy. The effect of this process change on annual surgical volume and case flow (number of procedures performed per surgical bed) in the year before the initiation of same-day method (1989/90) and subsequent to the widespread use of the process (1992/93), was abo assessed. Costs incurred by 53 patients who underwent preoperative anaesthetic and surgical assessment as outpatients and were admitted as an outpatient on the day of surgery (SD Group) were compared with those incurred by 11 patients who entered hospital on the day before surgery and underwent anaesthetic and other assessments as inpatients (IP Group). Nursing, radiology, laboratory, operating room, rehabilitation and clinic costs were obtained for each patient. The remaining costs were not amenable to individual attribution and were assigned to each group as a percentage of the allocated costs. The cost per case in the SD Group was

Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts.

360 less than in the IP Group, reflecting decreased nursing costs incurred by the SD Group. Between the period 1989/90 and 1992/93, the number of surgical beds declined 15.7%; however, surgical volume decreased by only 5.4%. Total case flow improved by 12.2%, that for elective and non-elective surgery increasing by 14.1% and 9.5%, respectively. Elective surgery, where same day admission was used, showed the greatest improvement in case flow. We conclude that a same day admission process reduces cost and serves to enhance hospital productivity.RésuméCette étude compare pour la cholécystectomie laparoscopique les coûts générés par la chirurgie réglée du patient hospitalisé avec ceux du patient ambulatoire. Elle évalue aussi les effets de ce changement de technique sur le volume chirurgical annuel et le débit chirurgical (nombre d’interventions par lit) pour l’année antérieure à l’initiation de la technique ambulatoire (1989–90) et celle qui a suivi sa propagation (1992–93). On a comparé les coûts générés par 53 patients dont l’évaluation pré-anesthésique et chinirgicale avait été réalisée dans le service de consultations externes et admis à l’hôpital le jour même de la chirurgie (groupe SD) avec les coûts générés par onze patients admis la vielle de l’intervention pour ces mêmes évaluations (groupe IP). Les coûts des soins infirmiers, de la radiologie, du laboratoire, des salles d’opérations, de la réhabilitation et des cliniques ont été obtenus pour chaque patient. Les autres coûts non imputables aux individus eux-mêmes, ont été assignés à chaque groupe en pourcentage des coûts alloués. Les coûts du groupe SD étaient de 360

The efficacy and resource utilization of remifentanil and fentanyl in fast-track coronary artery bypass graft surgery : A prospective randomized, double-blinded controlled, multi-center trial

inférieurs à ceux du groupe IP, ce qui reflète la baisse des coûts des soins infirmièrs encourus dans le groupe SD. Entre les périodes 1989–90 et 1992–93, le nombre des lits chirurgicaux a baissé de 15,7% alors que le volume chirurgical ne diminuait que de 5,4%. Le débit total s’est amélioré de 12,2%, alors que la chirurgie non urgente et la chirurgie urgente augmentaient respectivement de 14,1% et de 9,5%. Dans les cas d’admission de même jour, la plus grande augmentation du débit chirurgical a été pour la chirurgie non urgente. Nous concluons que l’admission le jour de la chirurgie réduit les coûts et augmente la productivité hospitalière.

Magnesium sulfate prophylaxis after cardiac operations

BackgroundAdenosine possesses marked cardioprotective properties, but the mechanisms for this beneficial effect are unclear. The objective of this study was to determine the effect of adenosine given before ischemia or at reperfusion on mechanical function, glucose oxidation, glycolysis, and metabolite levels in isolated, paced (280 beats per minute) working rat hearts. Methods and ResultsHearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 μU. mL-1 insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Adenosine (100, μM) pretreatment or adenosine (100 μM) at reperfusion markedly increased the recovery of mechanical function (from 44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia (coronary flow, 0.5 mL. min-1). Glucose oxidation (μmol. min-1. g dry wt-1) was inhibited during ischemia (from 0.44±0.04 to 0.12+0.01), and this was not altered by adenosine (100 μM). During reperfusion, glucose oxidation recovered (to 038±0.02) and adenosine (100, μM), given at reperfusion, further increased glucose oxidation (to 0.52+0.06). The rate of glycolysis (μmol. min-1. g dry wt-1), which was unaffected by ischemia per se, was inhibited by adenosine pretreatment (from 4.7±0.3 to 2.6±03). During reperfusion, glycolysis was also inhibited by adenosine relative to control (3.9±0.8) either when present during ischemia (2.6+0.6) or during reperfusion (1.4±0.4). These effects of adenosine on glucose metabolism reduced the calculated rate of H+ production attributable to glucose metabolism during the ischemic and reperfusion periods. Tissue lactate levels (μmol. g dry wt-1), which increased during ischemia (from 93±+1.1 to 87.4±10.3) and then declined during reperfusion (to 26.2±3.7), were depressed further by adenosine pretreatment (to 19.7±4.1) and by adenosine at reperfusion (to 13.6±2.1). ATP levels (μmol. g dry wt-1), which were depressed by ischemia (from 18.1 ± 1.1 to 10.6±+13) and tended to be further depressed during reperfusion (to 7.1±0.7), were increased by adenosine pretreatment (to 14.1±+1.2) and by adenosine at reperfusion (to 15.6+2.4). ConclusionsThe effects of adenosine on glucose metabolism that would tend to decrease cellular acidosis and hence, Ca2+ overload, may explain the beneficial effects of adenosine on mechanical function observed in these hearts during reperfusion after ischemia.

Matrix Metalloproteinase-7 and ADAM-12 (a Disintegrin and Metalloproteinase-12) Define a Signaling Axis in Agonist-Induced Hypertension and Cardiac Hypertrophy

We compared (a) the perioperative complications; (b) times to eligibility for, and actual time of the following: extubation, less intense monitoring, intensive care unit (ICU), and hospital discharge; and (c) resource utilization of nursing ratio for patients receiving either a typical fentanyl/isoflurane/propofol regimen or a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in 304 adults by using a prospective randomized, double-blinded, double-dummy trial. There were no differences in demographic data, or perioperative mortality and morbidity between the two study groups. The mini-mental status examination at postoperative Days 1 to 3 were similar between the two groups. The eligible and actual times for extubation, less intense monitoring, ICU discharge, and hospital discharge were not significantly different. Further analyses revealed no differences in times for extubation and resource utilization after stratification by preoperative risk scores, age, and country. The nurse/patient ratio was similar between the remifentanil/isoflurane/propofol and fentanyl/isoflu-rane/propofol groups during the initial ICU phase and less intense monitoring phase. Increasing preoperative risk scores and older age (>70 yr) were associated with longer times until extubation (eligible), ICU discharge (eligible and actual), and hospital discharge (eligible and actual). Times until extubation (eligible and actual) and less intense monitoring (eligible) were significantly shorter in Canadian patients than United States’ patients. However, there was no difference in hospital length of stay in Canadian and United States’ patients. We conclude that both anesthesia techniques permit early and similar times until tracheal extubation, less intense monitoring, ICU and hospital discharge, and reduced resource utilization after coronary artery bypass graft surgery.

Selective ordering of preoperative investigations by anesthesiologists reduces the number and cost of tests

One hundred patients undergoing elective cardiac operations were randomized into placebo (n = 54) and magnesium (n = 46) groups. The magnesium group received six doses of 2.4 g (19.2 mEq) magnesium sulfate intravenously in the first 24 hours after the cardiac operation. The magnesium group had higher serum magnesium concentrations postoperatively (1.09 +/- 0.20 versus 0.75 +/- 0.13 mmol/L; p < 0.0001), postoperative day 1 (1.49 +/- 0.34 versus 0.70 +/- 0.12 mmol/L; p < 0.0001) and postoperative day 2 (0.96 +/- 0.19 versus 0.76 +/- 0.07 mmol/L; p < 0.0001). Patients in the magnesium group had a lower incidence of ventricular tachyarrythmias (VTs) (17.3% versus 51.9%; p = 0.0006), less need for treatment (6.5% versus 20.3%; p < 0.0001), fewer VT episodes/patient (0.3 +/- 0.8 versus 1.39 +/- 1.9; p < 0.0001), and a reduction in the severity of VTs as measured by the modified Lown grade (p = 0.0002). No differences were demonstrated with respect to supraventricular tachyarrythmias. The magnesium group had reduced absolute creatine kinase-MB levels (5.3 +/- 4.2 versus 28.4 +/- 28 IU/L; p = 0.001) as well as creatine kinase-MB fraction (0.01 +/- 0.02 versus 0.05 +/- 0.04; p = 0.001) on postoperative day 1. Serum magnesium concentrations were lower during VTs than during periods of sinus rhythm (0.75 +/- 0.75 versus 1.02 +/- 0.35 mmol/L; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)