Harry B. van Wezel

Anesthesia's Effects on Plasma Glucose and Insulin and Cardiac Hexokinase at Similar Hemodynamics and Without Major Surgical Stress in Fed Rats

BACKGROUND:Recent evidence suggests that hexokinase mitochondria association attenuates cell death, and that plasma glucose and insulin concentrations can influence clinical outcome. In the present study, we examined how different anesthetics per se affect these variables of glucose metabolism, i.e., under similar hemodynamic conditions and in the absence of major surgical stress. METHODS:In fed rats, the effects of pentobarbital (PENTO), isoflurane (ISO), sevoflurane (SEVO), ketamine-medetomidine-atropine (KMA), and sufentanil-propofol-morphine (SPM) on the cardiac cellular localization of hexokinase (HK) and levels of plasma glucose and insulin were determined and compared with values obtained in nonanesthetized animals (control). The role of mitochondrial and sarcolemmal KATP-channels and α2-adrenergic receptor in ISO-induced hyperglycemia was also evaluated. RESULTS:Mean arterial blood pressure was similar among the different anesthetic strategies. PENTO (5.3 ± 0.2 mM) and SPM (5.1 ± 0.2 mM) had no significant effect on plasma glucose when compared with control (5.6 ± 0.1 mM). All other anesthetics induced hyperglycemia: 7.4 ± 0.2 mM (SEVO), 9.9 ± 0.3 mM (ISO), and 14.8 ± 1.0 mM (KMA). Insulin concentrations were increased with PENTO (2.13 ± 0.13 ng/mL) when compared with control (0.59 ± 0.22 ng/mL), but were unaffected by the other anesthetics. Inhibition of the mitochondrial KATP channel (5-hydroxydecanoate acid) or the α2-adrenergic receptor (yohimbine) did not prevent ISO-induced hyperglycemia. Only the nonspecific KATP channel inhibitor glibenclamide was able to prevent hyperglycemia by ISO. Cytoslic HK relative to total HK increased in the following sequence: control (35.5% ± 2.1%), SEVO (35.5% ± 2.7%), ISO (36.6% ± 1.7%), PENTO (41.2% ± 2.0%; P = 0.082 versus control), SPM (43.0% ± 1.8%; P = 0.039 versus control), and KMA (46.6 ± 2.3%; P = 0.002 versus control). CONCLUSIONS:Volatile anesthetics and KMA induce hyperglycemia, which can be explained, at least partly, by impaired glucose-induced insulin release. The data indicate that the inhibition of insulin release by ISO is mediated by sarcolemmal KATP channel activation. The use of PENTO and SPM is not associated with hyperglycemia. SPM and KMA reduce the antiapoptotic association of HK with mitochondria.

Prognostic Value of Biventricular Function in Hypotensive Patients After Cardiac Surgery as Assessed by Transesophageal Echocardiography

In patients after cardiac surgery, hypotension, defined as a mean arterial pressure less than 65 mmHg despite adequate filling pressures and positive inotropic medication, poses a problem. In addition, it is often difficult to determine whether these patients have suffered irreversible myocardial injury or if they are likely to recover. In this study, left and right ventricular function, as assessed by transesophageal echocardiography (TEE), was related to mortality both (1) quantitatively, using fractional area change (FAC), and (2) qualitatively, using a segmental wall motion analysis, which assigned a score to myocardial wall segments, in order to determine whether this technique can be used to predict survival. Mortality rate was very high in patients with biventricular and especially right ventricular failure (FAC less than 35%). Left and right ventricular wall motion abnormality indices were significantly better in survivors compared to nonsurvivors, but no distinct cut-off value could be determined. A wall motion index derived from only 6 segments at the mid-papillary muscle level was found to be as reliable as one based on 16 segments of the entire left ventricle. Thus, TEE provided information about the degree of left and right ventricular dysfunction by using a single cross-section at the papillary muscle level. It identified patients at high risk of death, ie, those with compromised right and biventricular function.

Transesophageal two-dimensional echocardiographic evaluation of biventricular dimension and function during positive end-expiratory pressure ventilation after coronary artery bypass grafting

Transesophageal 2-dimensional echocardiography was performed in 21 patients soon after uncomplicated coronary artery bypass grafting to determine the mechanism of positive end-expiratory pressure (PEEP) ventilation-induced decreased cardiac output. End-diastolic and end-systolic short-axis area and percent area reduction of right and left ventricles were determined during 5-cm H2O stepwise increments of PEEP ventilation. Simultaneously, cardiac output and right- and left-sided hemodynamic values were determined. Cardiac output, mean arterial pressure and end-diastolic area of both ventricles gradually decreased, and right and left atrial and pulmonary arterial pressures (mainstem and capillary wedge) increased. Left ventricular end-systolic area did not change, whereas right ventricular area decreased. Percent area reduction of both ventricles decreased (p less than 0.01). Thus, decrease in cardiac output during PEEP ventilation is primarily caused by decrease of preload rather than compromised contractility.

Antihypertensive and anti-ischemic effects of nicardipine and nitroprusside in patients undergoing coronary artery bypass grafting

The efficacy of nicardipine vs nitroprusside in controlling hypertension after sternotomy was compared in 120 patients undergoing coronary artery bypass grafting and anesthetized with fentanyl (100 micrograms/kg). All had good left ventricular function and had been receiving long term oral beta-blocking therapy. Patients were randomly allocated to 1 of 3 groups: group C, the control (n = 40), received no vasodilator; group N (n = 40) received intravenous nicardipine at an initial rate of 3 micrograms/kg/min; and group S (n = 40) received intravenous nitroprusside at an initial rate of 1 microgram/kg/min. Vasodilator infusion was begun before surgery and infusion rates were adjusted to maintain systolic blood pressure between 80 and 120% of postintubation (baseline) values. Additional measurements were obtained before incision and after sternotomy. In groups N and S, arterial blood pressure was effectively controlled in all patients. Before the incision, pulmonary artery pressure decreased in group S and systemic vascular resistance decreased in groups N and S. After sternotomy, mean arterial pressure, heart rate, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index and rate-pressure product increased in group C. At this time, pulmonary artery pressure returned to baseline values in group S. In groups N and S, heart rate, cardiac index and rate-pressure product increased, but, compared with baseline values, systemic vascular resistance remained low after sternotomy. Ischemic changes were seen in the electrocardiogram in 11 patients (28%) in group C, 10 patients (25%) in group S and 4 patients (10%) in group N. The concentration of creatine phosphokinase MB was not significantly different in the first 24 postoperative hours in any group.

How Soon Should Drainage Tubes Be Removed After Cardiac Operations

Pericardial effusion frequently occurs after cardiac operation. Despite its high incidence, the etiological process of postoperative pericardial effusion remains unclear. Residual blood or thrombus has often been suggested as a possible cause, implying that the occurrence of pericardial effusion could be related to the effectiveness of postoperative thoracic drainage. This possible relationship, however, has never been studied. We found that prolonging the duration of thoracic drainage by 24 hours often increases total chest tube output considerably but does not affect the incidence of postoperative pericardial effusion: approximately 55% of 100 patients in this study were shown by two-dimensional echocardiography to have pericardial effusion on the sixth postoperative day, regardless of the duration of postoperative drainage. Because of this, and because a long period of drainage causes discomfort for the patient, mechanical irritation to the heart and the pericardium, and an increased risk of infection, we recommend removing drains as soon as their efficacy has peaked, preferably on the first postoperative day.

A comparison of the effects of propofol and nitrous oxide on the electroencephalogram in epileptic patients during conscious sedation for dental procedures

The influence of sedative doses of propofol or nitrous oxide on the electroencephalogram was studied in 11 mentally handicapped patients with treated epilepsy undergoing dental procedures. At one session, propofol was titrated to achieve conscious sedation. The mean (+/- SD) dose requirements were 5.5 +/- 1.1 mg.kg-1.h-1. In six patients, the electroencephalogram was unchanged during propofol administration. In three patients, there was a decrease in epileptic activity, and in two patients, paroxysmal discharges disappeared. At another session, nitrous oxide was administered by nasal mask. The mean (+/- SD) concentration of nitrous oxide needed was 43.6% +/- 4.8%. The electroencephalogram did not change in nine patients, whereas in two patients epileptic activity decreased. There were no clinical epileptoid or other adverse manifestations during any treatment or up to 48 h thereafter. The results of the present study suggest that propofol or nitrous oxide can be administered in subanesthetic doses for conscious sedation in mentally handicapped patients with treated epilepsy.

The efficacy of nicardipine and nitroprusside in preventing poststernotomy hypertension

The efficacy of nicardipine and nitroprusside in preventing poststernotomy hypertension was compared in two groups of 45 patients undergoing coronary artery surgery. Patients were anesthetized with fentanyl, 100 micrograms/kg, and oxygen. Group N received nicardipine at an initial rate of 3 micrograms/kg/min. Group S received sodium nitroprusside at an initial rate of 1 microgram/kg/min. The vasodilators were started before surgery, and infusion rates were adjusted to maintain systolic blood pressure between 80% and 120% of postintubation (baseline) values. Additional measurements were obtained before incision and after sternotomy. In both groups, arterial blood pressure could be controlled effectively in all patients. In group S, pulmonary artery pressure (PAP) decreased before incision. At this time, systemic vascular resistance (SVR) decreased in both groups. After sternotomy, PAP returned to baseline values in group S. In both groups, heart rate, rate-pressure product, and cardiac index increased, while SVR remained decreased. In the period from induction of anesthesia to the start of cardiopulmonary bypass, the incidence of myocardial ischemia was greater (P less than 0.01) in group S (24%) than in group N (9%). Between the groups, the concentration of creatine phosphokinase MB was not significantly different in the first 24 hours postoperatively. In conclusion, it was shown that nicardipine may be a suitable alternative to nitroprusside for the prevention of poststernotomy hypertension and myocardial ischemia in patients undergoing coronary artery surgery.

Myocardial stunning, hibernation, and ischemic preconditioning

From the present review, it may be concluded that myocardial ischemia results in far more complicated syndromes than previously realized. Although not all aspects of the issues discussed in this review are currently a clinical reality in the daily practice of cardiovascular anesthesiologists, the understanding and application of these concepts are growing rapidly. Indications for revascularization procedures will be adjusted in patients with evidence of hibernating myocardium. In the future, postoperative myocardial dysfunction may be diminished by the prevention of myocardial stunning, for instance by altering the composition of the cardioplegic solution and other interventions. Finally, additional advances may involve reduction of the extent of perioperative myocardial infarctions by application of ischemic preconditioning.

Nicardipine for preservation of myocardial metabolism and function in patients undergoing coronary artery surgery

The present study was designed to evaluate the myocardial protective effect of nicardipine (NIC) in patients with normal left ventricular (LV) function (control vs. NIC treatment group) and impaired LV function (control vs. NIC treatment group) during extracorporeal circulation for coronary artery surgery. NIC infusions were begun approximately 12 min before aortic cross clamping (AoX) at an infusion rate of 5 micrograms.kg-1.min-1 and maintained for 10 min. Prior to AoX an additional bolus of NIC 5 mg was given. Coronary hemodynamics, myocardial metabolic parameters (continuous thermodilution), and regional LV function (two-dimensional transesophageal echocardiography) were measured. At 15 min after discontinuation of AoX, lactate production was found in the two control groups but not in the two NIC treatment groups. In the control groups, lactate production returned to extraction at sternal closure. At that time regional area ejection fraction (RAEF) had significantly improved in both groups with impaired LV function compared with postintubation (baseline) values. In NIC-treated patients with impaired LV function, however, the percentage improvement in RAEF was significantly greater than that in the control groups. Between the groups, there were no differences in the number of patients requiring inotropic support, pacing, and/or diuretics after bypass or postoperatively. There were no significant differences in postoperative creatine kinase myocardial band release or in the incidence of dysrhythmias, myocardial infarction, or mortality. The results of the present study suggest that NIC iv may be used to provide additional myocardial protection during extracorporeal circulation. In addition, in NIC-treated patients with compromised LV function, this may be associated with a more apparent improvement in RAEF than that seen in nontreated patients.

Myocardial metabolism and coronary sinus blood flow during coronary artery surgery: Effects of nitroprusside and nifedipine

The effects of nitroprusside and nifedipine on hemodynamics, coronary dynamics, and global myocardial metabolism were compared in two groups of patients undergoing elective coronary artery surgery, who were anesthetized with fentanyl, 100 micrograms/kg. After induction of anesthesia, either nitroprusside or nifedipine was started as follows: group S (n = 11) received nitroprusside at an initial rate of 1.3 micrograms/kg/min; group N (n = 9) received nifedipine at an initial rate of 0.7 micrograms/kg/min. Infusion rates were adjusted to maintain systolic blood pressure (SBP) between 80% and 120% of preinfusion (control) values. Control measurements were obtained 10 minutes after intubation. Then vasodilator infusion was started. Additional measurements were obtained 10 minutes after the start of infusion (before surgery) and after sternotomy. The mean (+/- SD) total dose requirements were: nitroprusside, 1.6 +/- 0.3 micrograms/kg/min; and nifedipine 1.1 +/- 0.7 micrograms/kg/min. The mean (+/- SD) total infusion time was: nitroprusside, 32 +/- 5 minutes; and nifedipine, 37 +/- 7 minutes. After 10 minutes of infusion there were decreases in SBP (p less than 0.001) and diastolic blood pressure (DBP; p less than 0.01) in group S. In group N only SBP decreased (p less than 0.01). At this time there were no significant changes in coronary sinus blood flow (CSBF) or myocardial oxygen consumption (MVO2) in either group. After stenotomy DBP remained decreased (p less than 0.05) in group S.(ABSTRACT TRUNCATED AT 250 WORDS)