Effect of preoperative beta-blockade on perioperative mortality in coronary surgery.

BACKGROUND: Many preoperative factors can influence perioperative mortality in cardiac surgery. Because the perioperative use of beta-blocking agents may reduce perioperative cardiac complications in non-cardiac surgery, we considered the possibility that beta-blocking agents could improve survival in coronary surgery patients. METHODS: In a retrospective study on 1586 patients undergoing coronary bypass surgery, the relative risk of 30-day mortality was determined in relation to preoperative risk factors and medication. Factors included patient characteristics, pre-existing illness, specific cardiovascular risk factors, cardiac status and urgency of surgery. Treatment with beta-blocking agents, calcium antagonists, angiotensin-converting enzyme inhibitors, nitrates, anti-arrhythmic agents, diuretics and antithrombotic agents was taken into account. RESULTS: Sex, age, chronic obstructive pulmonary disease, urgency and the preoperative use of diuretics and chronic beta-blocking therapy were found to be linked to mortality (P<0.05). Backward stepwise regression testing identified age, urgency and beta-blocking therapy as independent factors that could predict mortality. CONCLUSIONS: Increasing age and urgency of surgery are associated with greater mortality, whereas preoperative beta-blocking therapy is associated with less mortality. The characteristics of patients who received chronic beta-blockade did not differ significantly from those of patients who did not. The results suggest that chronic preoperative beta-blocker therapy reduces 30-day mortality in coronary surgery.

Oxygen transport and myocardial function after the administration of albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% to rabbits.

BACKGROUND AND OBJECTIVE: The effects of administering albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% on oxygen transport and left ventricular function were prospectively investigated in different experimental conditions: baseline, fluid load, after 10 min of myocardial ischaemia and after reperfusion. METHODS: Twenty-seven rabbits received at random one of three colloids in escalating boluses over 10-15 min to achieve left ventricular end-diastolic pressures (LVEDP) between 8 and 10mmHg. A branch of the left anterior descending coronary artery was then temporarily occluded by a ligature and released after 10 min. Myocardial function was assessed using left ventricular pressure recordings and dimension data obtained from ultrasound crystals inserted onto the ventricular wall. Blood was sampled for the determination of oxygen delivery and consumption, the oxygen extraction ratio, acid-base status, and glucose and lactate concentrations. RESULTS: Administration of the colloids similarly increased oxygen delivery and improved left ventricular function in all groups. Peak rate of pressure development (dP/dt(max)) and oxygen delivery were reduced during ischaemia and reperfusion. The decrease in dP/dt(max) was more pronounced in the hydroxyethylstarch group. CONCLUSIONS: Administration of albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% had similar effects on oxygen delivery and myocardial function. After ischaemia and during reperfusion, the decrease in myocardial function was most pronounced with hydroxyethylstarch 6%.

Assessment of length-dependent regulation of myocardial function in coronary surgery patients using transmitral flow velocity patterns.

BACKGROUND: In a subset of coronary surgery patients, a transient increase in cardiac load by leg elevation resulted in a decrease in maximal rate of pressure development (dP/dtmax) and a major increase in end-diastolic pressure (EDP). This impairment of left ventricular (LV) function appeared to be related to a deficient length-dependent regulation of myocardial function. The present study investigated whether analysis of transmitral flow patterns with transesophageal echocardiography constituted a noninvasive method to identify these patients. METHODS: High-fidelity LV pressure tracings and transmitral flow signals were obtained in 50 coronary surgery patients during an increase in cardiac load by leg elevation. Using linear regression analysis, changes in transmitral E-wave velocity and deceleration time (DT) were related to changes in dP/dtmax and EDP. RESULTS: Changes in dP/dtmax with leg elevation were closely related to corresponding changes in E-wave velocity (r = 0.81; P < 0. 001) and to changes in DT (r = 0.78; P < 0.001). Similarly, changes in EDP were related to changes in E-wave velocity (r = 0.83; P < 0. 001) and to changes in DT (r = 0.84; P < 0.001). The decrease in dP/dtmax and the major increase in EDP in some patients was associated with an increase in E-wave velocity and a decrease in DT, indicating development of a restrictive LV filling pattern. CONCLUSIONS: Impairment of LV function with leg elevation was associated with the development of a restrictive transmitral filling pattern. Analysis of transmitral flow patterns by means of transesophageal echocardiography therefore allowed noninvasive identification of a subset of coronary surgery patients with impaired length-dependent regulation of LV function.

Role of the nitric oxide-cGMP pathway in the cardiovascular effects of anesthetic agents: a review.

Over the past 10 years, there has been an explosion of new information on the physiological and pathophysiological roles of nitric oxide (NO) within the cardiovascular system. With the increasing knowledge on the importance of NO in the regulation of cardiovascular function, possible involvement of the NO-cyclic guanosine-monmphosphate (cGMP) pathway in myocardial effects of anesthetics has attracted wide attention. This paper reviews the literature on the role of the nitric oxide-cGMP pathway in cardiovascular effects of volatile and intravenous anesthetics.

Postoperative analgesia with i.v. patient-controlled morphine: effect of adding ketamine.

We have studied the effect of adding ketamine to i.v. morphine patient-controlled analgesia (PCA) for the treatment of pain after laparotomy. Thirty patients were allocated randomly to receive PCA with saline or ketamine in a double-blind, randomized study. Analgesia was started in the recovery room when visual analogue scale (VAS) scores were > 4. A bolus dose of morphine 3 mg was given to all the patients followed by i.v. PCA. Simultaneously, an infusion of ketamine 2.5 micrograms kg-1 min-1 or saline was started. Pain scores, morphine consumption and side effects were noted for up to 48 h after the start of PCA. VAS scores decreased significantly with time (P = 0.0001) and were similar (P = 0.3083) in both groups. Cumulative morphine consumption at 48 h was significantly lower in the ketamine group (28 mg) than in the control group (54 mg) (P = 0.0003). Nausea was less frequent in the ketamine group (P = 0.03).

Sodium nitroprusside enhances in vivo left ventricular function in beta-adrenergically stimulated rabbit hearts.

OBJECTIVE: Sodium nitroprusside (SNP) is an activator of soluble guanylate cyclase, which depresses myocardial contractility. These exclusively negative inotropic effects of SNP were recently challenged by in vitro data.. In isolated rat ventricular myocytes, a moderate increase of cGMP improved the contractile response at baseline and in isoprenaline-stimulated conditions. The present study evaluated in vivo the inotropic effects of SNP at baseline and during administration of low dose dobutamine. METHODS: Anesthetized open-chest rabbits (n = 18) were instrumented with micromanometers, ultrasound crystals and atrial pacing wires. Measurements were obtained during caval occlusion with ventilation suspended at end-expiration. Systolic function was assessed with dP/dtmax and the slope Ees of the end-systolic pressure-volume relation. Diastolic function was assessed with the time constant tau and the stiffness constant Kc of the diastolic pressure-volume relation. SNP (0.02, 0.08, 0.32 microgram x kg-1) was administered at baseline and during low dose dobutamine. RESULTS: At baseline, SNP reduced dP/dtmax from 3750 +/- 88 to 3470+/- 88 mmHg/s (mean +/- s.e.m.) and Ees from 148 +/- 16 to 103 +/- 13 mmHg/ml (P < 0.01) . During dobutamine infusion, SNP increased dP/dtmax from 4340 +/- 125 to 4681 +/- 230 mmHg/s and Ees from 148 +/- 19 to 190 +/- 30 mmHg/ml (P < 0.01). Effects of SNP on dP/dtmax and Ees were different at baseline and during dobutamine (interaction P < 0.01). SNP did not alter Kc at baseline nor during dobutamine. CONCLUSIONS: SNP enhances in vivo systolic function in beta-adrenergically stimulated rabbits.

Continuous total intravenous anesthesia, using propofol and fentanyl in an open-thorax rabbit model: evaluation of cardiac contractile function and biochemical assessment.

Effects are reported of an anesthetic protocol involving use of predetermined intravenous (i.v.)-administered drug doses during acute experimental procedures in vagotomized, New Zealand White rabbits with open thorax (n = 20) in a nonsurvival study. After induction of anesthesia by intramuscular (i.m.) administration of ketamine hydrochloride (25 mg/kg of body weight) and xylazine hydrochloride (15 mg/kg), continuous total intravenous anesthesia (TIVA) with propofol (0.6 mg.kg-1.min-1), fentanyl (0.48 micrograms.kg-1.min-1) and the neuromuscular agent vecuronium bromide (0.003 mg.kg-1.min-1) was maintained. Oxygenation conditions, acid-base balance, biochemical and hemodynamic variables, and cardiac contractile function were assessed. Measurements were made and blood analysis was done at the moment of ear vein catheterization (P1); before (P2) and after (P3) sternotomy; after complete instrumentation (P4); and at the beginning (T1), in the middle (T2), and at the end (T3) of the experimental protocol. From T1 to T3, heart rate was kept constant by use of atrial pacing at a rate of 235 +/- 15 beats/min. During surgical preparation and instrumentation, hemoglobin (Hb) concentration decreased from 12.5 +/- 0.9 g/dl (mean +/- SEM) to 7.7 +/- 0.7 g/dl and remained stable thereafter. Blood gas analysis (PO2, PCO2, pH, HCO3-, base excess, measured SaO2) and measurement of plasma lactate concentration revealed constant, adequate oxygenation. Plasma electrolyte values (Na+, Cl-, K+, Ca2+) remained within physiologic ranges throughout. Blood glucose concentration increased from 229 +/- 30 mg/dl at P1 to 382 +/- 34 mg/dl at P3. At T1, glycemia had returned to normal values and remained stable. Heart rate, blood pressure, ventricular elastance (Ees), and diastolic stiffness constant (Kc) remained stable throughout. Other indices of ventricular function (dP/dtmax, thickening, ejection duration, and maximal left ventricular pressure) remained unaltered as well. Left ventricular relaxation (dP/dtmin, tau) did not change. After anesthesia induction by i.m. administration of ketamine and xylazine, TIVA with predetermined drug dosages of propofol and fentanyl provided stable cardiovascular function for open-thorax long-term experimental observations in a nonsurvival setting.

Dose dependent effect of aprotinin on rate of clot formation.

Forty-eight patients scheduled for elective cardiac surgery were randomly assigned to receive aprotinin in the following doses: 0.2 mg kg-1 (group A), 0.7 mg kg-1 (group B), 1 mg kg-1 (group C) and 1.4 mg kg-1 (group D). Clot formation was analysed by thromboelastography immediately after induction of anaesthesia and again 30 min after administration of aprotinin. Rate of clot formation was assessed using R (reaction time = rate of initial fibrin formation), K (clot formation time = rate of fibrin build-up and cross linking) and angle of clot formation (denoting speed at which solid clot forms). Strength of the clot was assessed by maximal amplitude of clot formation (MA) and % lysis after 30 and 60 min. Significant reduction of R and K times and increase in angle of clot formation was observed in groups A and B. This effect was not apparent in the other groups. In group D, an increase in R time was noted. These findings indicate a dose-dependent effect of aprotinin on rate of clot formation with an earlier clot formation at low doses.

Onset of segmental relaxation dysfunction with decreased myocardial tissue perfusion: modulation by propofol.

OBJECTIVES: To estimate myocardial oxygen needs by studying the effects of reduced coronary blood flow on segmental myocardial function. To study the tolerance of limited oxygen supply to a myocardial segment during propofol administration. DESIGN: A prospective experimental study. SETTING: An experimental animal laboratory in a university. PARTICIPANTS: Eighteen adult dogs, weighing 20 to 35 kg. INTERVENTIONS: Open thorax open pericardium experiments were performed under standard anesthetic conditions. Segment length gauges were placed subendocardially in an anteroapical and in a basal segment. Flow to the anteroapical segment was reduced by tightening a micrometer-controlled snare placed around the second diagonal coronary artery. Left ventricular pressure-length signals allowed for identification of onset of relaxation dysfunction. Myocardial tissue flow at onset of relaxation dysfunction was defined as critical flow. Tracer microspheres were used to measure subepicardial, midwall, and subendocardial flow at critical flow. MEASUREMENTS AND MAIN RESULTS: Stability of the model and reproducibility of critical flow were studied in a first series of six dogs with the hearts paced at 110 beats/min. Hemodynamics, left ventricular, and segmental myocardial function during critical flow were stable. Subendocardial critical flow was identical with each flow reduction (45% +/- 5, 44% +/- 8, and 43% +/- 5 of baseline myocardial tissue flow). In a second series of six dogs, critical flow was measured at pacing rates 100 beats/min, 150 beats/min, and 100 beats/min with propranolol, 0.1 mg/kg, pretreatment. Critical flows were 38% +/- 5, 55% +/- 6, and 17% +/- 2 of baseline, respectively (p < 0.05). In a third series of six dogs, critical flow was measured during sufentanil, 0.6 microgram/kg/min, and increasing doses of propofol (P0: 0.0 mg/kg/h, P4: 4.0 mg/kg/h and P8: 8.0 mg/kg/h). Heart rate was kept constant at 110 beats/min. When compared with P0, hemodynamic and left ventricular contraction parameters were stable at P4 but were decreased at P8. At P0, critical flow was: 0.63 +/- 0.14, at P4: 0.34 +/- 0.09, and at P8: 0.25 +/- 0.07 mL/min/g (p < 0.05). CONCLUSION: Critical myocardial tissue flow was reproducible and sensitive for altered myocardial oxygen needs. The negative inotropic properties of P decreased myocardial oxygen needs during unchanged hemodynamic and left ventricular contraction parameters. A higher P dose depressed left ventricular function.

Myocardial metabolism during anaesthesia with propofol--low dose fentanyl for coronary artery bypass surgery.

We have studied the haemodynamic and myocardial effects of propofol-fentanyl anaesthesia in 12 patients undergoing coronary artery bypass surgery during the pre-bypass period. The induction dose of propofol was 1.5 mg kg-1 and mean infusion rate during maintenance was 4.48 mg kg-1 h-1 (range 1.87-7.24 mg kg-1 h-1). The total dose of fentanyl was 30 micrograms kg-1. The haemodynamic changes indicated myocardial depression and peripheral vasodilatation. Coronary sinus flow and indicators of global myocardial perfusion (myocardial oxygen consumption, myocardial lactate extraction) did not change. Although not excluding regional myocardial ischaemia, these results show that propofol-fentanyl anaesthesia has no major adverse effects on cardiac function.

Influence of thiopental, etomidate, and propofol on regional myocardial function in the normal and acute ischemic heart segment in dogs.

The effects of 30-min infusions of thiopental (20, 30, 40, 50, 60, and 70 mg.kg-1.h-1), etomidate (2.4, 3.6, 7.2, 9.6, 12, and 14.4 mg.kg-1.h-1), and propofol (6, 9, 12, 15, 18, and 21 mg.kg-1.h-1) on regional hemodynamic variables in the normal and acute ischemic heart segment were studied in dogs using ultrasonic segment length gauges. The three agents were associated with a dose-dependent decrease in end-diastolic length, indicating a decrease in left ventricular filling. This effect was most pronounced for propofol. At the doses tested, etomidate did not significantly alter regional myocardial function. Thiopental, however, was associated with a dose-dependent decrease in systolic shortening, which was significantly greater in the ischemic segment. These findings confirm the hemodynamic stability seen with etomidate and show that thiopental depresses myocardial function more in the acute ischemic heart than in the normal heart. The decrease in systolic shortening associated with propofol was similar in the normal and in the acute ischemic heart segment.

The detection of intra-operative myocardial ischaemia. Preliminary experience with the right-sided precordial lead.

The value of monitoring the right precordial lead, V4R, to detect peri-operative ischaemic events during coronary artery surgery was studied in 60 patients. Thirty-four patients had only left-sided coronary disease (Group 1). The other 26 patients had both left-sided occlusive coronary artery disease and significant right-sided occlusive lesions on coronary angiography (Group 2). Lead sensitivity was estimated, assuming that all ST segment changes were true positive responses. Sensitivity using a single lead was greatest for lead V5 in the two groups (73% for Group 1 and 69% for Group 2). Sensitivity in Group 1 for lead II was intermediate (55%), whereas sensitivity for lead V4R was only 9%. In Group 2, on the other hand, lead V4R was 54% sensitive and lead II only 31%. The combination of leads V4R and V5 increased the sensitivity to 92% in Group 2, whereas lead II or V5 combined with V4R failed to improve sensitivity in Group 1. The monitoring of lead V4R allowed detection of 23% of the ischaemic episodes in Group 2 that would have passed undetected if only lead II and V5 were monitored. These results demonstrate the value of an additional right precordial lead during coronary artery bypass grafting in patients with right-sided occlusive disease.

Low-dose sufentanil-isoflurane anaesthesia for coronary artery surgery.

Haemodynamic changes and catecholamine responses were measured during anaesthesia with sufentanil (total dose 7 micrograms kg-1) supplemented with isoflurane in 14 patients undergoing coronary artery surgery. Isoflurane was used to control systolic arterial pressure, which was allowed to decrease to 100 mm Hg. Mean inspired isoflurane concentration was 0.22 (SD 0.19)% (induction), 0.34 (0.18)% (pre-bypass) and 0.22 (0.17)% (post-bypass). During cardiopulmonary bypass 0.22 (0.13)% isoflurane was administered to control mean perfusion pressure. During induction and the pre-bypass period, significant decreases in systolic and diastolic arterial pressure, systemic vascular resistance and left ventricular stroke work index (LVSWI) (P less than 0.01) were noted. The decrease in LVSWI with unchanged filling pressures indicated myocardial depression. Serum catecholamine concentrations remained at the pre-induction value until cardiopulmonary bypass, when a significant increase was noted. Tracheal intubation, sternotomy and sternal spread were not associated with hypertension or tachycardia. Clinical signs that could reflect myocardial ischaemia were not observed peroperatively. After operation, cardiac enzymes were within the normal clinical range and ECG was unchanged.

Perioperative myocardial ischaemia and infarction in connection with cardiac and non-cardiac surgery.

Although perioperative myocardial infarction has a relative low incidence, its occurrence is associated with a high morbidity and mortality. Although many single risk factors for developing a perioperative myocardial infarction have been described, it soon became apparent that surgical risk could hardly be determined by one single factor. A multifactorial approach for the preoperative assessment of patients at risk for developing cardiac complications in association with surgery and anesthesia was introduced. Further investigation, however, indicated that the risk of developing a perioperative myocardial infarction was not only determined by preoperative risk factors and a number of peroperative risk factors were also identified. Since identification of those patients, particularly at risk for developing a perioperative myocardial infarction, is a matter of prime importance in the choice of the treatment and the monitoring, a thorough understanding and knowledge of the different pre- and peroperative risk factors is a must for every surgeon and anesthetist.

Prediction and early diagnosis of acute myocardial ischemia during anesthesia: a critical review.

Adequate myocardial oxygenation is the result of a good balance between the myocardial oxygen supply and the oxygen demand. Recognition of an insufficient myocardial oxygenation is particularly difficult during general anesthesia because angina pectoris, one of the most reliable indicators of ischemia cannot be expressed. Therefore other indices must be used. Considerable interest but also controversy surrounds the question which routinely monitored determinant of myocardial oxygen supply and demand best predicts and diagnoses beginning myocardial ischemia. A thorough understanding of the sensitivity and the limitations of the different monitoring techniques is a must for every anesthetist dealing with patients with coronary artery disease. The present state of knowledge and the new trends appearing on this subject are reviewed.

The influence of labetalol on arterial blood gas data, pulmonary haemodynamics and pulmonary shunting.

The arterial oxygen and carbon dioxide tensions, pulmonary and systemic haemodynamics and pulmonary shunting and mechanics were measured during the first 30 min after intravenous labetalol administration. Thirty patients, recovering in the intensive care unit after neurosurgical interventions were randomly divided in 2 groups of 15 patients, receiving either labetalol or placebo. In the labetalol treated group the arterial oxygen tension decreased from 553.6 +/- 16.8 to 529.3 +/- 19.8 mmHg 5 min after the injection of labetalol. A concomitant increase in arterial carbon dioxide tension from 40.1 +/- 1.1 to 45.5 +/- 1.3 mmHg was noticed. Pulmonary vascular resistance decreased from 159.6 +/- 14.7 to 116.7 +/- 11.7 dynes.sec.cm-5 and pulmonary shunting increased from 4.8% +/- 1.4% to 8.1% +/- 2.4% 5 min following injection. All these changes were statistically significant for p less than 0.01. After 30 min all values had returned to their initial level. No changes were registered in the control group. As airway resistance appeared not to be affected by the labetalol administration it may be concluded that the observed changes in blood gas data are most likely due to a transient decrease of the pulmonary vascular resistance with a concomitant increase in pulmonary shunting.