Pierre Foëx

Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent

In a non-double-blind, prospective, randomized study, the intraoperative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beat-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication-Forty-four per cent of the untreated control patients and 61% of the patients pretreated with a beat-adrenergic blocking agent had normal preoperative electroca rdiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a betaadrenergic blocking agent (P < 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untereated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beat-adrenergic blocking agent, given with premedication, can significantly reduce that risk.

Myocardial protection by anesthetic agents against ischemia-reperfusion injury: An update for anesthesiologists

PurposeThe aim of this review of the literature was to evaluate the effectiveness of anesthetics in protecting the heart against myocardial ischemia-reperfusion injury.SourceArticles were obtained from the Medline database (1980-, search terms included heart, myocardium, coronary, ischemia, reperfusion injury, infarction, stunning, halothane, enflurane, desflurane, isoflurane, sevoflurane, opioid, morphine, fentanyl, alfentanil sufentanil, pentazocine, buprenorphine, barbiturate, thiopental, ketamine, propofol, preconditioning, neutrophil adhesion, free radical, antioxidant and calcium).Principal findingsProtection by volatile anesthetics, morphine and propofol is relatively well investigated. It is generally agreed that these agents reduce the myocardial damage caused by ischemia and reperfusion. Other anesthetics which are often used in clinical practice, such as fentanyl, ketamine, barbiturates and benzodiazepines have been much less studied, and their potential as cardioprotectors is currently unknown. There are some proposed mechanisms for protection by anesthetic agents: ischemic preconditioning-like effect, interference in the neutrophil/platelet-endothelium interaction, blockade of Ca2+ overload to the cytosolic space and antioxidant-like effect. Different anesthetics appear to have different mechanisms by which protection is exerted. Clinical applicability of anesthetic agent-induced protection has yet to be explored.ConclusionThere is increasing evidence of anesthetic agentinduced protection. At present, isoflurane, sevoflurane and morphine appear to be most promising as preconditioning-inducing agents. After the onset of ischemia, propofol could be selected to reduce ischemia-reperfusion injury. Future clinical application depends on the full elucidation of the underlying mechanisms and on clinical outcome trials.RésuméObjectifÉvaluer l’efficacité des anesthésiques dans la protection du cœur contre les lésions myocardiques d’ischémie-reperfusion.SourceDes articles ont été obtenus de la base de données Medline (1980-, les mots clefs étant heart, myocardium, coronary, ischemia, reperfusion injury, infarction, stunning, halothane, enflurane, desflurane, isoflurane, sevoflurane, opioid, morphine, fentanyl, alfentanil sufentanil, pentazocine, buprenorphine, barbiturate, thiopental, ketamine, propofol, preconditioning, neutrophil adhesion, free radical, antioxidant et calcium).Constatations principalesLa protection par des anesthésiques volatils, morphine et propofol, est relativement bien explorée. On s’accorde généralement pour dire que ces agents réduisent les lésions myocardiques causées par l’ischémie et la reperfusion. D’autres anesthésiques utilisés souvent en clinique, comme le fentanyl, la kétamine, les barbituriques et les benzodiazépines, ont été moins étudiés et leur potentiel cardioprotecteur est actuellement inconnu. On propose certains mécanismes de protection par les anesthésiques: un effet qui s’apparente à un préconditionnement, une interférence dans l’interaction entre polynucléaires neutrophiles/plaquettes-endothélium, un blocage de la surcharge de Ca2+ à l’espace cytosolique et un effet du genre antioxydant. Différents anesthésiques semblent présenter des mécanismes différents par lesquels la protection s’exerce. L’applicabilité de la protection induite par les agents anesthésiques est encore à étudier.ConclusionIl y a de plus en plus d’évidence de la protection induite par les anesthésiques. Présentement, l’isoflurane, le sévoflurane et la morphine semblent les agents inducteurs de préconditionnement les plus prometteurs. Après le début de l’ischémie, le propofol peut être choisi pour réduire les lésions d’ischémie-reperfusion. L’application clinique future repose sur la mise en lumière complète des mécanismes sous-jacents et sur des essais relatifs aux avantages cliniques.

Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.

Background:There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. Methods:The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Results:Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2–5.2), but there was substantial heterogeneity (I2 = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1–10.9, I2 = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4–2.3, I2 = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5–4.0, I2 = 4%). Conclusions:An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

Regional Ischemic Ventricular Dysfunction in Myocardium Supplied by a Narrowed Coronary Artery with Increasing Halothane Concentration in the Dog

The effects of increasing inspired halothane concentration (0.5, 1.0, 1.5, 2.0 per cent) upon left ventricular myocardium supplied by a critically narrowed coronary artery and a normal coronary artery were studied in 11 open-chested dogs. Regional ventricular function was measured by continuous recording of ventricular segment length using pairs of implanted miniature ultrasonic length detectors in the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LC) territories before and during critical stenosis of the LAD by a micrometer-controlled snare. Critical narrowing was documented by ischemic regional ventricular function (i.e., post-systolic shortening; systolic lengthening) limited to the LAD territory when FIO2 = 0 for 90 seconds. Hemodynamic variables (aortic, left atrial and left ventricular pressure, and heart rate) were measured, ECG lead II was recorded, and the first derivative of left ventricular pressure (LV dP/dt) and coronary perfusion pressure derived for each halothane concentration before and during LAD narrowing. Increasing halothane was associated with equivalent progressive depression of global ventricular function before and during LAD constriction. Prior to LAD constriction, no ischemic changes in regional function occurred. Regional ventricular function was normal during 0.5 percent halothane in the presence of LAD constriction. With increasing halothane during LAD constriction, ischemic regional ventricular function was observed in the LAD territory in eight of eleven hearts, whereas regional ventricular function remained normal in the LC territory. The epicardial ECG was recorded in three dogs and was insensitive as an indicator of ischemia, becoming abnormal only after severe ischemic changes were established. In these studies, in which heart rate remained constant, arterial blood pressure and LV dP/dt decreased, and left ventricular end-diastolic pressure increased, decrease in blood flow and oxygen delivery due to a lower perfusion pressure distal to the coronary artery narrowing appears to be primarily responsible for the observations. The authors hypothesize that clinically unapparent episodes of regional myocardial ischemia distal to narrowed coronary arteries may be an important cause of perioperative myocardial infarction.

Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels.

BACKGROUND Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels. METHODS Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. RESULTS Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control). CONCLUSION 5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.

Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications

Objective:To assess the incidence of major cardiac events in critically ill patients with a high risk of cardiac complications presenting with an elevated heart rate. Design and Setting:Observational, retrospective study in a 15-bed medical/surgical Intensive Care Unit (ICU) at a university hospital for a period of 12 months. Patients:We studied patients with a high risk of cardiac complications, according to the revised Goldman index, who were treated for at least 36 hrs in the ICU. Patients presenting with prolonged elevated heart rate, defined as a heart rate >95 beats/min for >12 hrs in at least one 24-hr period of their ICU stay, were investigated. Cardiac high-risk patients not developing this criterion served as controls. Major cardiac events, defined as nonfatal myocardial infarction, nonfatal cardiac arrest, and cardiac related death, were the primary outcome measures. Results:From a total of 791 patients, 69 patients were assessed as cardiac high-risk patients. Of 39 patients with prolonged elevated heart rates, 19 (49%) sustained major cardiac events, whereas in the control group of 30 patients, only four patients (13%) had a major cardiac event (p = .002; odds ratio, 6.2). Patients with elevated heart rate had to be treated 4.5 days longer in the ICU (p = .01), whereas the ICU and 30-day post-ICU discharge survival rates did not differ significantly. Conclusions:In this study, we provide evidence for an increased incidence of major cardiac events in critically ill, cardiac high-risk patients with a prolonged elevated heart rate during their ICU stay. In addition, elevated heart rate was associated with a significantly longer ICU stay.

Neuraxial block, death and serious cardiovascular morbidity in the POISE trial

BACKGROUND This post hoc analysis aimed to determine whether neuraxial block was associated with a composite of cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal cardiac arrest within 30 days of randomization in POISE trial patients. METHODS A total of 8351 non-cardiac surgical patients at high risk of cardiovascular complications were randomized to β-blocker or placebo. Neuraxial block was defined as spinal, lumbar or thoracic epidural anaesthesia. Logistic regression, with weighting using estimated propensity scores, was used to determine the association between neuraxial block and primary and secondary outcomes. RESULTS Neuraxial block was associated with an increased risk of the primary outcome [287 (7.3%) vs 229 (5.7%); odds ratio (OR), 1.24; 95% confidence interval (CI), 1.02-1.49; P=0.03] and MI [230 (5.9%) vs 177 (4.4%); OR, 1.32; 95% CI, 1.07-1.64; P=0.009] but not stroke [23 (0.6%) vs 32 (0.8%); OR, 0.76; 95% CI, 0.44-1.33; P=0.34], death [96 (2.5%) vs 111 (2.8%); OR, 0.87; 95% CI, 0.65-1.17; P=0.37] or clinically significant hypotension [522 (13.4%) vs 484 (12.1%); OR, 1.13; 95% CI, 0.99-1.30; P=0.08]. Thoracic epidural with general anaesthesia was associated with a worse primary outcome than general anaesthesia alone [86 (12.1%) vs 119 (5.4%); OR, 2.95; 95% CI, 2.00-4.35; P<0.001]. CONCLUSIONS In patients at high risk of cardiovascular morbidity, neuraxial block was associated with an increased risk of adverse cardiovascular outcomes, which could be causal or because of residual confounding.

A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning

Background: The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open‐chested dogs.

Isoflurane causes regional myocardial dysfunction in dogs with critical coronary artery stenoses

The effects of Isoflurane-induced hypotension to mean aortic pressures of 70 and 55 mmHg on global and regional right and left ventricular performance (ultrasonic dimension technique) and on coronary hemodynamics (electromagnetic flow probes) were studied in 12 open-chest dogs (anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium) with critical coronary artery stenoses (micrometer-controlled snares) of the right and left anterior descending coronary arteries. The stenoses reduced resting coronary blood flow by approximately 10% without affecting global or regional myocardial performance. During subsequent isoflurane administration, coronary blood flow fell markedly. In the areas supplied by the stenosed coronary arteries, segment length shortening decreased by 70% (P < 0.01), and regional akinesis, paradoxical motion, or postsystolic shortening developed in 9 of 12 animals. In contrast, in the areas supplied by normal coronary arteries, myocardial segment length shortening decreased significantly less and did not show signs of dysfunction. In these non-ischemic areas at both concentrations of isoflurane, end diastolic and systolic dimensions were greater in the right than in the left ventricle, probably related to differences in right (unchanged) and left (reduced) ventricular afterloads. The data indicate that in the presence of coronary artery stenoses, isoflurane-induced hypotension may cause regional myocardial dysfunction suggestive of ischemia.

Effects of Halothane on Left Ventricular Relaxation and Early Diastolic Coronary Blood Flow in the Dog

The effects of graded concentrations of halothane on left ventricular relaxation and phasic coronary blood flow (CBF) were studied in six open-chest, anesthetized dogs. Global and regional left ventricular function were measured. Besides the expected dose-dependent depression of contractility, regional shortening, and cardiac output, halothane caused significant increases in the time constant of relaxation (Trelax), and decreased and delayed the nadir of peak negative left ventricular dP/dt. Dose-dependent reductions of CBF were noted. Percentage CBF during isovolumic relaxation was significantly reduced and showed a strong inverse correlation with Trelax. Halothane appears to interfere with the inactivation process of the heart; this in turn may impede the early rise in CBF during isovolumic relaxation.