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Background: Although red blood cell transfusion has been associated with an increase in early morbid outcomes and reduced long-term survival after cardiac surgery, its relationship to functional quality of life after surgery has not been previously explored. Our objective was to investigate the relationship between perioperative red blood cell and component transfusion and functional health-related quality of life 6 to 12 months after cardiac surgery., Methods: Of 12,536 patients undergoing cardiac surgical procedures between May 1995 and January 1999, 7,321 completed a self-administered Duke Activity Status Index (DASI) survey preoperatively and least one follow-up survey at nominally 6 or 12 months postoperatively. The influence of baseline DASI, preoperative risk factors, clinical status, laboratory values, operative events, and postoperative morbidities on follow-up DASI were examined with ordinal regression modeling., Results: After adjustment for preoperative DASI, demographic, cardiac and noncardiac comorbidity, type of surgery, postoperative complications, and interval between follow-up DASI, during which patients continued to improve (p < 0.0001), postoperative functional status after cardiac surgery was incrementally worse the more perioperative red cells (p < 0.0001) and platelets (p = 0.02) that had been transfused., Conclusions: Red blood cell and platelet transfusion have an unintended persistently negative risk-adjusted effect on health-related quality of life after cardiac surgery that extends well beyond initial hospitalization. Reductions in functional recovery paralleled increasing units of red blood cells transfused.

Background: Prosthesis-patient size mismatch results when an implanted prosthetic aortic valve is of insufficient size for a patient's body surface area. The relation between prosthesis-patient size and functional capacity and adverse postoperative outcome is inconsistent. Our objectives were to examine the impact of valve replacement, continuous prosthesis-patient size, and other factors on functional recovery after aortic valve replacement (AVR) with the Duke Activity Status Index (DASI)., Methods and Results: From June 15, 1995, through May 14, 1998, 1108 patients underwent AVR after completing a DASI survey. Of these, 1014 completed a postoperative DASI survey at an average of 8.3 months postoperatively. Logistic ordinal regression was used to examine the influence of demographic variables, comorbidities, baseline DASI scores, indexed valve orifice area, standardized orifice size, and postoperative morbid events on postoperative DASI. There was overall improvement in postoperative functional recovery reflected by median preoperative and postoperative DASI scores of 29 and 46, P<0.001, respectively. Neither indexed orifice area, P=0.94, nor standardized orifice size, P=0.96, was associated with functional recovery. Female sex, increasing age, elevated serum creatinine, increased central venous pressure, and red blood cell transfusion were factors associated with poor postoperative functional recovery., Conclusions: A majority of patients report improvement in functional quality of life early after AVR. Similar functional recovery was demonstrated for patients along the full spectrum of valve sizes indexed to body size, even for values considered to represent severe mismatch for patient size. Factors other than prosthesis-patient size influence functional quality of life early after AVR.

To allow for growth in our anesthesiology residency, we assumed control of the clinical base year (postgraduate year 1[PGY-1]) and adjusted the curriculum to accommodate the expanded size. With this opportunity to change the curriculum, we created a clinical base year to prepare PGY-1 for clinical anesthesia training in PGY-2 to PGY-4 using, for this purpose, the best resources of our clinical site. We describe the process and preliminary results of the change.

Objective: Our objectives were to document the preoperative and postoperative functional status of patients undergoing coronary artery bypass grafting, to examine factors that influence functional recovery, and to determine whether gender differences exist in the preoperative and postoperative functional status with the Duke Activity Status Index., Methods: One thousand eight hundred twenty-five patients undergoing isolated coronary artery bypass grafting had baseline and follow-up quality-of-life surveys. Mean follow-up from baseline to postoperative Duke Activity Status Index was 8.0 months for women and men. The influence of 47 variables, in addition to baseline scores on postoperative functional status, was examined with logistic ordinal modeling. An ordinal model for the follow-up score was determined by means of backward selection, with variables retained if they satisfied the criterion of a P value of less than.05., Results: Median baseline Duke Activity Status Index scores (women, 21.5; men, 32.2; P <.001) and first follow-up scores (women, 42.7; men, 58.2; P <.001) were lower in women than in men. Patients who were older and those who had chronic obstructive pulmonary disease, myocardial infarction, stroke, diabetes, vascular disease, postoperative serious infection, and return to the operating room had lower postoperative scores. After adjusting for these factors, women still had lower follow-up scores (odds ratio for men, 2.1 [95% confidence interval, 1.7-2.6]; P <.001)., Conclusions: A number of preoperative factors, operative variables, and postoperative events are associated with functional recovery after coronary revascularization. In addition, female gender is associated with more postoperative functional impairment after adjusting for these perioperative variables.

Purpose: To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery., Methods: Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 X ED90 rocuronium (0.6 mg.kg-1; n = 20) or atracurium (0.5 mg.kg-1; n = 21) during intravenous propofol/alfentanil anaesthesia with N2O/O2 ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers., Results: Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 +/- 22.2 vs 98.6 +/- 41.4 sec; P < 0.001) and clinical duration of action (33.3 +/- 7.1 vs 44.7 +/- 7.2 min; P < 0.001), but longer spontaneous recovery index (9.6 +/- 2.41 vs 6.9 +/- 1.89 min; P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 +/- 6.31 vs 59.2 +/- 7.59 min; P = 0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck., Conclusion: Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.

Our goal was to determine the contributions of sympathetic and parasympathetic activity to entropy measures of heart rate variability (HRV). We compared our results with two commonly used methods to analyze HRV: standard deviation (SDNN) and power spectral analysis (HF norm). Beat-by-beat analysis of R-R intervals was performed in conscious dogs. The R-R intervals were analyzed with approximate entropy (ApEn) and entropy of symbolic dynamics (SymDyn) to assess the effects of reducing system complexity. This was achieved by pharmacologically inhibiting sympathetic, parasympathetic, and total autonomic nervous system regulation of heart rate. Three conditions were examined: rest, standing, and systemic hypotension. At rest or standing, sympathetic inhibition (propranolol) had no effect on ApEn or SymDyn, whereas parasympathetic (atropine) and combined (propranolol + atropine) inhibition reduced both entropy measures to near zero. Systemic hypotension reduced both entropy measures in intact dogs. When hypotension was induced after sympathetic inhibition, ApEn was increased compared with hypotension alone, whereas parasympathetic inhibition with hypotension resulted in near-zero ApEn. Changes in the entropy measures of HRV were directionally similar to changes in SDNN and HF norm. These results indicate that the entropy of R-R intervals reflects parasympathetic modulation of heart rate.

Our study objective was to assess economic and clinical outcomes of use of a point-of-care (POC) blood analysis device for postoperative coronary artery bypass graft (CABG) patients. A decision analytic model was developed for patients with high expected use of blood analysis, high potential benefit from rapid turn around time of results, a large annual volume of patients, and substantial expense associated with surgery. Published literature and clinical experts provided incidence, outcome, and cost estimates associated with four clinical scenarios potentially influenced by POC testing (ventricular arrhythmias, cardiac arrest, severe postoperative bleeding, and iatrogenic anemia). We found that changes in clinical outcomes were predominantly dependent on comparative turn around time or CABG patient volume. The positive clinical impact of using POC testing was consistently associated with a positive economic impact. POC blood gas analysis may be associated with decreased incidence of adverse clinical events or earlier detection of such events, resulting in significant cost savings. This study also supports previous findings that the costs of STAT blood analysis are more personnel-related than equipment-related.

Background: The collective impact of advances in medical, surgical, and anesthetic care on the characteristics and outcomes of patients who undergo coronary artery bypass grafting was assessed., Methods: We compared the demographic and clinical characteristics, preoperative risk factors, morbidity, and mortality of two groups of patients who underwent coronary artery bypass grafting in isolation or in combination with other procedures between July 1, 1986, and June 30,1988 (group 1, n = 5,051), and between January 1, 1993, and March 31, 1994 (group 2, n = 2,793). The patients were stratified according to their preoperative risk level. Outcome measures consisted of changes in preoperative risk categories; hospital mortality rates; overall and risk-adjusted major cardiac, neurologic, pulmonary, renal, and septic morbidity rates; and intensive care unit length of stay., Results: Changes in the distribution of risk categories, from a median of 2 to 4 on a 9-point scale (p < 0.001), indicated that patients in group 2 were at significantly higher risk than those in group 1. The risk-adjusted mortality rate did not change (2.8% to 2.9%; p = 0.15), but the risk-adjusted morbidity rate decreased significantly (14.5% to 8.8%; p < 0.001)., Conclusions: At our institution, patients who undergo coronary artery bypass grafting are now at greater preoperative risk at the time of hospital admission. However, their morbidity rate is significantly lower and their mortality rate is unchanged, results that we attribute to the collective impact of changes in our medical and surgical procedures.

Background: This study was performed to develop an intensive care unit (ICU) admission risk score based on preoperative condition and intraoperative events. This score provides a tool with which to judge the effects of ICU quality of care on outcome., Methods: Data were collected prospectively on 4,918 patients (study group n = 2,793 and a validation data set n = 2,125) undergoing coronary artery bypass grafting alone or combined with a valve or carotid procedure between January 1, 1993, and March 31, 1995. Data were analyzed by univariate and multiple logistic regression with the end points of hospital mortality and serious ICU morbidity (stroke, low cardiac output, myocardial infarction, prolonged ventilation, serious infection, renal failure, or death)., Results: Eight risk factors predicted hospital mortality at ICU admission, and these factors and five others predicted morbidity. A clinical score, weighted equally for morbidity and mortality, was developed. All models fit according to the Hosmer-Lemeshow goodness-of-fit test. This score applies equally well to patients undergoing isolated coronary artery bypass grafting., Conclusions: This model is complementary to our previously reported preoperative model, allowing the process of ICU care to be measured independent of the operative care. Sequential scoring also allows updated prognoses at different points in the continuum of care.

Our overall goal was to investigate the mechanism by which fentanyl attenuates acetylcholine-induced contraction in porcine coronary artery. We tested the hypothesis that fentanyl attenuates muscarinic coronary contraction via sigma receptor activation. Left coronary artery vascular rings were isolated from porcine hearts and were suspended in organ chambers for isometric tension recording. In untreated coronary vascular rings, acetylcholine administration resulted in dose-dependent contraction. Fentanyl attenuated acetylcholine-induced contraction. The sigma ligands--(+)-pentazocine, (+)-cyclazocine, haloperidol, and 1,3-di-o-tolylguanidine--also inhibited acetylcholine-induced contraction. In contrast, the selective sigma ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine failed to have an inhibitory effect on acetylcholine-induced contraction. Moreover, metaphit (1-[1(3-isothiocyanatophenyl)cyclohexyl]piperidine), which causes irreversible acylation of sigma receptors, only inhibited acetylcholine-induced contraction when it was present in the organ chamber. We also assessed the effects of inhibiting various points in the signal transduction pathway distal to naloxone-sensitive opioid receptor activation on acetylcholine-induced contraction. Selective (glybenclamide) and nonselective (tetraethylammonium) K(+)-channel inhibition, guanosine triphosphate-binding protein inactivation (pertussis toxin), and Type 1 and Type 2 dopamine receptor inhibition all failed to alter the attenuating effect of fentanyl on acetylcholine-induced contraction. Thus, neither sigma or opioid receptor activation is a prerequisite for fentanyl-induced inhibition of muscarinic coronary contraction.

Objective: This study was designed to investigate the extent to which the systemic vasodilator effects of dobutamine, epinephrine, and amrinone are modulated by the endothelium-derived relaxing factor, nitric oxide (NO)., Design: This was a prospective study of low and high doses of the agonists before and after inhibition of NO synthesis., Setting: Experiments were performed in the basic research laboratories of the Center for Anesthesiology Research., Participants: Pentobarbital-anesthetized, intact Sprague-Dawley rats were studied in seven separate groups of eight rats each., Interventions: The systemic vasodilator responses to the agonists were assessed before and after the administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester., Measurements and Main Results: Decreases in systemic vascular resistance in response to dobutamine and epinephrine were not observed after inhibition of NO synthesis, whereas the decrease in systemic vascular resistance in response to amrinone was still apparent., Conclusions: The results suggest that dobutamine and epinephrine produce systemic vasodilation through the release of NO, whereas amrinone produces vasodilation independent of NO release.

In the nonfailing heart, normovolemic hemodilution increases cardiac output and decreases total peripheral resistance (TPR). Putative mechanisms mediating the decrease in TPR include reflex vasodilation and changes in the local regulation of blood flow. Our objectives were to determine whether ablation of reflex neural mechanisms or the inhibition of nitric oxide (NO) synthase, the enzyme responsible for the synthesis of the endothelium-derived relaxing factor (EDRF-NO), modulates the systemic vasodilator response to normovolemic hemodilution. Three groups of male Sprague-Dawley rats were subjected to acute normovolemic hemodilution, which was achieved by exchanging a volume of blood equivalent to 3.8% of body weight with hydroxyethyl starch. Hemodilution increased cardiac output and decreased TPR. Subsequent administration of the NO synthase inhibitor, L-nitroarginine (LNA), returned both cardiac output and TPR to control values. Pretreatment with LNA prior to hemodilution increased TPR, an effect that was partially reversed by the NO donor, sodium nitroprusside. In this setting, hemodilution failed to decrease TPR. After spinal cord destruction by "pithing," hemodilution decreased TPR to the same extent as that observed in intact rats. This hemodilution-induced decrease in TPR was abolished by the subsequent administration of LNA. These results indicate that neural reflexes do not modulate the systemic vascular response to hemodilution. Moreover, the systemic vasodilator response to hemodilution is abolished after inhibition of endogenous NO synthesis.

Objective: To identify patient characteristics that are associated with increased ICU length of stay, resource use, and hospital mortality after coronary artery bypass surgery., Design: Prospective, multicenter study., Setting: Six tertiary care hospitals., Participants: A consecutive sample of 2,435 unselected ICU admissions following coronary artery by-pass surgery., Materials and Methods: Demographic, operative characteristics and APACHE III score were collected during the first postoperative day; and APACHE III scores and therapeutic interventions during the first three postoperative days. Hospital survival and ICU length of stay were also recorded. Multivariate equations were derived and cross-validated to predict hospital mortality, ICU length of stay, and ICU resource use., Results: Unadjusted hospital mortality rate was 3.9% (range 1.0% to 6.0%), mean ICU length of stay was 3.7 days (range 3.2 to 4.7 days), and first 3-day ICU resource use (TISS points) was 99 (range 68 to 116). The range of actual to predicted ICU length of stay varied from 0.86 to 1.26; and resource use from 0.71 to 1.16., Conclusions: A limited number of operative characteristics, the post-operative acute physiology score (APS) of APACHE III and patient demographic data can predict hospital death rate, ICU length of stay, and resource use immediately following coronary by-pass surgery. These estimates may compliment assessments based on pre-operative risk factors in order to more precisely evaluate and improve the efficacy and efficiency of cardiovascular surgery.

The effects of dobutamine (DOB) on myocardial performance, systemic hemodynamics, and oxygen delivery during acute normovolemic hemodilution in anesthetized rats were studied. Forty-two Sprague Dawley rats (body weight 375 to 425 g) were divided into six equal groups. Hemodynamic and cardiac indices were measured or calculated at baseline, 30 minutes after the initiation of hemodilution (HD), and 15 minutes after DOB or saline infusion. Myocardial performance in response to acute pressure or volume loads was studied in all groups of animals. HD to a hematocrit (Hct) value of 20% resulted in no change in heart rate (HR), increased CI, SVI, and LV dP/dt, and decreased MAP, SVRI, and oxygen delivery index (O2DI). HD increased peak SV and CI after preload stress while the left ventricular developed pressure (LVDP) was unchanged. Infusion of DOB as 7.5 or 15 micrograms/kg/min increased HR, CI, and LV dP/dt as well as LVDP. At the same time, DOB decreased MAP and SVR, whereas the SVI remained unchanged. In non-HD animals both doses of DOB increased LVDP, but only the larger dose increased CI, whereas peak SV decreased with the smaller dose. Arterial carbon dioxide tension (PaCO2) increased, whereas pH and arterial oxygen tension (PaO2) decreased; however, O2DI remained unchanged. Concomitant hemodilution and DOB infusion resulted in attenuation of HR response to DOB, exaggerated the drop in MAP and SVR, and increased LV dP/dt. Only the larger dose of DOB increased the CI, whereas neither dose could alter the SVI in HD animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Current hematologic approaches to minimize postoperative bleeding have focused principally on antifibrinolytic agents. To explore whether a need might exist to promote clot stabilization independent of steps that might be taken to prevent lysis, we followed levels of the functional A-chain of factor XIII (fibrin stabilizing factor) immunologically in 19 patients undergoing coronary artery bypass grafting. The levels of factor XIIIA together with alterations in fibrinogen were followed at five stages of operation: (1) initial catheter placement (control), (2) heparinization, (3) initiation of cardiopulmonary bypass, (4) discontinuation of cardiopulmonary bypass, and (5) heparin neutralization with protamine sulfate. Significant (p < 0.05) inverse correlations were observed between postoperative chest-tube drainage volumes and levels of XIIIA at stages 1 through 3, and borderline associations (p < 0.1) were observed for stages 4 and 5. Pronounced losses of factor XIIIA accompanied initiation of cardiopulmonary bypass, when levels fell to 43% +/- 12% (standard deviation) of the control value, significantly below the 59% +/- 9% of the control value expected from hemodilution. By comparison, fibrinogen concentrations fell only to the extent attributable to hemodilution, unaccompanied by substantial degradation as indicated by electrophoretic, functional, and immunologic assays. There was a reversible heparin-induced precipitation of fibrin complexes and fibrinogen dimers from the blood on initiation of hypothermia, but these components returned to the circulation on restoration of normothermia. This precipitation was unrelated to losses of factor XIIIA. The findings warrant inference that XIIIA supplementation in deficient states should be considered as an adjunct to other therapies for postoperative bleeding.

Objective: To compare the safety and effectiveness of propofol (2,6-diisopropylphenol) to midazolam for sedation of mechanically ventilated patients after coronary artery bypass grafting., Design: Open, randomized, prospective trial., Setting: Cardiothoracic intensive care unit (ICU), Cleveland Clinic Foundation., Patients: Eighty-four patients with normal or moderately impaired left ventricular function who underwent elective coronary artery bypass graft surgery under high-dose opioid anesthesia., Interventions: Patients were randomly selected to receive either propofol (mean loading dose 0.24 mg/kg; mean maintenance dose 0.76 mg/kg/hr) or midazolam (mean loading dose 0.012 mg/kg; mean maintenance dose 0.018 mg/kg/hr). Infusion rates were titrated to keep patients comfortable, drowsy, and responsive to verbal stimulation. Study duration, 8 to 12 hrs; infusions were started in the ICU when patients were awake and hemodynamically stable., Measurements and Main Results: During therapy, both groups had lower mean arterial pressures and heart rates compared with baseline measurements; however, the propofol group had significantly lower heart rates than the midazolam group during the first 2 hrs of infusion. The propofol group also had significantly lower blood pressure measurements 5 and 10 mins after the initial dose, although there was no difference during infusion. Baseline cardiac output was measured before starting the infusion, and measurements were repeated during continuous infusion at 4, 8, and 12 hrs. Cardiac output values were similar. Propofol maintenance infusions ranged from 3 to 30 micrograms/kg/min and midazolam infusions ranged from 0.1 to 0.7 micrograms/kg/min. At these infusion rates. both groups had adequate sedation, based on nurse and patient evaluations; however, the propofol group used significantly lower total doses of sodium nitroprusside and supplemental opioids., Conclusions: Both propofol and midazolam provided safe and effective sedation of coronary artery bypass graft patients recovering from high-dose opioid anesthesia. The reduced need for both antihypertensive medication and opioids seen in the propofol group may be advantageous. However, the hypotension seen after the initial bolus dose of propofol may be a concern. No difference between the two drugs could be demonstrated in time to extubation or ICU discharge, although it is probable that time to extubation was governed more by residual operative opioids than the study agents.

Background: A decrease in myocardial perfusion pressure may reduce myocardial blood flow. However, it may not significantly affect myocardial perfusion when in presence of a concurrent coronary artery vasodilation. However, the effects of propofol in coronary arteries are not well determined. In this study, the effects of propofol on porcine coronary artery responses to vasoactive agents that operate through voltage- and receptor-mediated calcium mechanisms were investigated., Methods: Hearts of adult pigs (n = 103) were obtained from a slaughter house, and the left anterior descending coronary arteries were dissected. The arteries were cut into vessel rings and prepared with and without the endothelium organ chambers filled with buffered salt solution. The effect of propofol (10(-7), 10(-6), 10(-5), and 10(-4) M) on vascular smooth muscle contraction caused by intracellular Ca(2+)-influx through voltage- and receptor-mediated mechanism also was studied at a cellular level., Results: Propofol relaxed coronary rings that were contracted by KCl, norepinephrine (NE), serotonin (5-HT), or carbachol (CCh). The minimal concentrations of propofol that produced significant vasorelaxation ranged from 3.16 x 10(-7) M to 3.16 x 10(-6) M. Vasodilation was more pronounced in rings contracted by NE, 5-HT, and CCh than by KCl. Propofol (10(-5) M) attenuated coronary vasoconstriction in response to cumulative concentrations of KCl, NE, 5-HT, and acetylcholine. Maximal contractions produced by NE and 5-HT were inhibited to a greater degree than contractions produced by KCl. Propofol at concentrations of 10(-5) M and higher attenuated a contraction in response to CaCl2 in vascular rings depolarized by KCl, but concentrations of 10-M did not attenuate contractions. Vasoconstriction in response to calcium entry in the presence of NE (and nifedipine 10(-6) M) was attenuated by propofol at concentrations of 10(-6) M and higher. Caffeine-induced contraction, caused by intracellular calcium release, was attenuated only at 10(-4) M of propofol., Conclusions: Propofol possesses vasodilator effect and attenuates the effects of vasoconstrictor agents in porcine coronary artery. Further, an antagonism of calcium channels may be responsible for these effects of propofol.

The effects of fentanyl on ultrastructure, protein biosynthesis, and atrial natriuretic peptide (ANP) secretion were studied in neonatal rat cardiomyocytes (CM). Ventricles from 2-day-old American Wistar rats were digested with 1% collagenase in perfusion buffer. Eight hundred thousand to 1.0 million cells/ml were incubated in tissue culture media, to which fentanyl citrate (Sublimaze) was added in a dose of 10-50 ng/ml. Fentanyl increased the spontaneous CM beating rate, which became rather fibrillary in nature. Protein biosynthesis also increased in a time-related manner. Simultaneous incubation with naloxone (10(-6) M) did not alter the beating rate or protein synthesis. Ultrastructurally, several criteria of myocyte growth were observed: an increase in myofilaments and the appearance of newly formed organized sarcomeres, which were preceded by an increase in the ribosomes and cisternae of rough endoplasmic reticulum, and the appearance of large, adult-type mitochondria with increased matrix granules and long parallel cristae. The latter replaced the elongated thin fetal mitochondria. This was associated with a network of developing sarcoplasmic reticulum and T-tubular system as well as the formation of intercalated discs between the CM. Furthermore, exposure to fentanyl increased ANP immunoreactivity in the culture media while simultaneous incubation with naloxone blocked the effect of fentanyl on ANP secretion. On the other hand, naloxone alone did not alter ANP secretion. Therefore, it could be concluded that fentanyl stimulated protein biosynthesis and ANP secretion as evidenced both biochemically and ultrastructurally. Although the molecular mechanism of ANP secretion by fentanyl is still unclear, yet an opioid receptor mediation could be possible as ANP secretion was blocked by an opioid receptor antagonist (naloxone).

Anesthesia for coronary artery bypass graft surgery continues to evolve in concert with changing epidemiology, advances in technology and pharmacology, and refinement in technique. The profile of the cardiac surgical patient is increasingly characterized by factors such as advanced age, reoperation, combination procedures, complications of acute intervention, and more complex disease. Preoperative risk factor assessment offers a means of strategic planning and intervention. Choice of anesthetic agents, muscle relaxants, and anti-ischemic medications affects both perioperative management and long-term outcome. Transesophageal echocardiography and ST segment monitoring are being applied more broadly. Advances have been made in managing postoperative blood loss. As in other areas of medicine, economic issues have become important considerations in anesthesia for the cardiac surgical patient.

The "antimuscarinic effect" of fentanyl and its dependence on subtypes of receptors were characterized in isolated porcine coronary arteries. Left anterior descending coronary arteries were dissected from the hearts of 60 adult pigs obtained at a slaughterhouse and prepared for isometric tension studies. The effects of fentanyl on the cumulative concentration-response curve for acetylcholine were obtained in the presence and absence of muscarinic blockade by atropine. Fentanyl shifted the concentration-response curve to the right in a concentration-dependent fashion. Atropine shifted the concentration-response curve to the right, and no further shift was caused by fentanyl. To investigate the dependence on muscarinic receptor subtypes, the effect of fentanyl on acetylcholine-induced contraction was examined in the presence of specific M1-, M2-, and M3-muscarinic antagonists. The pA2 values for fentanyl decreased significantly in the presence of atropine (a nonspecific antagonist) and also in the presence of p-F-HHSiD (an M3-antagonist). In contrast, no significant change of pA2 value for fentanyl was observed in the presence of both pirenzepine (an M1-antagonist) and methoctramine (an M2-antagonist). We conclude that fentanyl has an antimuscarinic effect, and that this antagonism occurs in a competitive manner. Furthermore, the significant decrease of the pA2 value for fentanyl in the presence of M3-, but not in the presence of M1 + M2-antagonists, suggests that the attenuation of cholinergic contraction of porcine coronary arteries by fentanyl is mediated through the M3-muscarinic receptor subtype.

The cardiovascular actions of cocaine in vivo are varied and often antagonistic. Cocaine produces excitatory sympathomimetic effects by interfering with re-uptake of norepinephrine at adrenergic nerve terminals. However, the local anaesthetic properties of cocaine exert depressant effects on the myocardium. In an attempt to differentiate the direct effects of cocaine from the indirect sympathomimetic effects on the myocardium, primary cultures of neonatal rat cardiomyocytes were established under serum-free conditions and exposed to cocaine and/or norepinephrine. After 36-48 h in culture, spontaneously contracting cells were treated with cocaine (10-1,000 micrograms/ml) and contractile rate (beats/min) quantitated, after which the cells were processed for ultrastructural examination. The contractile rate was reduced at all dosages with nearly 80% reduction at the highest concentration studied. Recovery of beating rate was observed 24 h after removal of cocaine. Pronounced cytoplasmic vacuolation of the cells occurred at concentrations > or = 100 micrograms/ml. Ultrastructural examination revealed extensive myofibrillar disruption, membrane damage, and a near complete loss of organized sarcomeres. Nuclear morphology remained unaffected. Within 24 h after removal of cocaine from the medium, myocytes recovered their characteristic cytoplasmic architecture, indicative of sarcomere reassembly. The results observed in response to cocaine were distinctly different from the response to norepinephrine. In these myocytes, the contractile rate was enhanced twofold and morphological damage was not observed. These findings suggest that cocaine can directly alter myocardial morphology independent of its sympathomimetic effects.

Extensive changes in hemodynamics and cardiac rhythm during induction of anesthesia may be mediated by altered responses of the autonomic nervous system to anesthetic agents. Analysis of the power spectrum of the heart rate (PSHR) variability can supply information about the autonomic nervous system, and may be used in order to assess this phenomenon. In this study, 78 patients undergoing coronary artery bypass graft surgery were evaluated. Anesthesia was induced with sufentanil, and neuromuscular blockade with vecuronium, a combination that may cause a decrease in heart rate. Before and after induction of anesthesia, the heart rate (HR), blood pressure (BP), cardiac output (CO), cardiac index (CI), and PSHR components were recorded. PSHR was obtained by using a special algorithm and data acquisition system for real-time spectral analysis. A low-frequency component (LFa, mainly sympathetic) was analyzed from a band of 0.04 Hz to 0.1 Hz. A high-frequency component (RFa, parasympathetic) was identified by the respiratory frequency spectrum. Alterations of the heart rate after induction of anesthesia were defined in order to separate the patient population into two groups: slow heart rate (slow-HR) and stable heart rate (stable-HR). Slow heart rate was defined as a decrease in HR of more than 20% of the baseline value. The variables were analyzed and compared between the slow-HR (n = 25) and stable-HR (n = 53) groups in order to verify the possibility of identifying patients prone to hemodynamic changes after anesthesia induction. There were no differences in preoperative HR, BP, CO, or CI between groups before anesthesia induction.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of myocardial protection with a single aortic crossclamp and blood cardioplegia was evaluated in 819 consecutive patients stratified for preoperative condition by means of a new clinical risk scoring system. A protocol using either antegrade or antegrade/retrograde blood cardioplegia was compared with antegrade crystalloid cardioplegia in 2582 similar, consecutive, and concurrent patients. In the blood cardioplegia cohort, 97 (11.8%) patients had 129 complications compared with 407 (15.8%) patients and 675 complications in the crystalloid cardioplegia group (p = 0.006). In high-risk patients, combined antegrade/retrograde cardioplegia significantly reduced myocardial infarction, stroke, and respiratory and wound complications. Despite the significantly longer aortic crossclamp time required for blood cardioplegia, patients undergoing crystalloid cardioplegia were 1.7 (95% confidence interval 1.3, 2.1) times more likely to have a morbid event. Time in the intensive care unit, length of hospitalization, and length-of-stay outlier status were significantly decreased in the blood cardioplegia compared with the crystalloid cardioplegia group. The net savings in hospital cost amounted to $2196 per case. When compared separately with crystalloid cardioplegia, combined antegrade/retrograde blood cardioplegia accounted for most of the morbidity reduction by significantly reducing perioperative myocardial infarction, wound complications, and length of stay in patients having reoperations. Antegrade/retrograde blood cardioplegia did not influence 1-year survival or event-free survival, even when risk was considered.

Myocardial ischemia during surgery can be caused by coronary vasospasm. Neurohumoral mechanisms are involved in this phenomenon, and various substances have been suggested as possible causes, including acetylcholine, histamine, and norepinephrine. The responses of isolated porcine coronary arteries (from 117 pig hearts) with (E+) and without (E-) endothelium to these agents were investigated in the presence of fentanyl, sufentanil, and morphine. Fentanyl significantly shifted to the right, in a concentration-dependent fashion, the concentration-response curve to acetylcholine. This effect was not different between E+ and E- rings. Neither sufentanil nor morphine altered acetylcholine-induced contraction of porcine coronary arteries. Naloxone did not antagonize the suppressive effect of fentanyl on acetylcholine-induced contraction. The response of porcine coronary arteries to norepinephrine was decreased only at very high concentrations of fentanyl. Neither sufentanil nor morphine altered norepinephrine-induced contraction of porcine coronary arteries. Fentanyl, sufentanil, and morphine had no effect on histamine-induced contraction. We conclude that fentanyl antagonized acetylcholine-induced contraction of porcine coronary arteries. This effect of fentanyl seems to be caused by a direct effect on smooth muscle cells and is not opioid-receptor mediated.

Objective: To relate morbidity and mortality risk to preoperative severity of illness in patients undergoing coronary artery bypass grafting., Design: Retrospective analysis of 5051 patients using univariate and logistic regression to identify risk factors associated with perioperative morbidity and mortality. Prospective application of models to a subsequent 2-year validation cohort (n = 4069)., Setting: Cleveland Clinic Foundation., Patients: All adult patients undergoing coronary artery bypass graft surgery between July 1, 1986, and June 30, 1988 (reference group), and July 1, 1988, and June 30, 1990 (validation group)., Main Outcome Measures: Mortality and morbidity (myocardial infarction and use of intra-aortic balloon pump, mechanical ventilation for 3 or more days, neurological deficit, oliguric or anuric renal failure, or serious infection)., Main Results: Emergency procedure, preoperative serum creatinine levels of greater than 168 mumol/L, severe left ventricular dysfunction, preoperative hematocrit of 0.34, increasing age, chronic pulmonary disease, prior vascular surgery, reoperation, and mitral valve insufficiency were found to be predictive of mortality. In addition to these factors, diabetes mellitus, body weight of 65 kg or less [corrected], aortic stenosis, and cerebrovascular disease were predictive of morbidity. Logistic regression equations were developed, and a simple additive score for clinical use was designed by allocating each of these risk-factor values of 1 to 6 points. Both methods predict mortality. Increased morbidity was demonstrated with increases in score., Conclusions: The logistic or clinical models developed are superior to the currently available methods for comparing mortality outcome and provide previously unavailable information on morbidity based on preoperative status. The clinical scoring system is useful for preoperative estimates of morbidity and mortality risks.

We reviewed the population of a surgical intensive care unit from July 1, 1987 to June 30, 1988, adjusting for severity of illness using the APACHE II system. Nineteen different departments admitted a total of 613 patients to the surgical intensive care unit. Predicted mortality was 22.9%; actual mortality was 15.7%. APACHE II generated reports which included analysis by age, mortality risk, department, primary physician, and diagnosis. We recommend reporting intensive care unit outcome by APACHE criteria to allow more meaningful comparisons of data and standardization of quality assurance programs. Finally, we present a critical review of the current APACHE II system and describe developments to be included in APACHE III.

Lesion of the anteroventral portion of the third cerebral ventricle causes hypernatremia, adipsia, and attenuation of the pressor response to intravenous administration of angiotensin II and norepinephrine. In addition, these lesions prevent the development of several experimental models of hypertension. In this study, a lesion of the third cerebral ventricle region was made in 14 dogs. In seven dogs in which hypernatremia developed the lesions included the organum vasculosum of the lamina terminalis; seven animals in which the circumventricular organ was spared by the lesion remained normonatremic. Vascular responsiveness of isolated right carotid artery rings to angiotensin II and phenylephrine was assessed 3 days after lesioning the anteroventral portion of the third cerebral ventricle. In endothelium-denuded ring vessels, vasoconstrictor responses to phenylephrine were significantly decreased in animals both with and without inclusion of the organum vasculosum of the lamina terminalis. A similar effect was observed in intact vessels of dogs in which the circumventricular organ was spared but not in those with lesions that included this area. In contrast, angiotensin II-induced vasoconstriction was significantly decreased in the arteries with intact endothelium of both groups of lesioned animals. These data show that lesion of the anteroventral third ventricle area alters alpha 1-adrenergic and angiotensin II vascular responsiveness in isolated carotid artery rings with the possible participation of the endothelium.

Patients who have undergone perioperative normovolemic hemodilution may require calcium channel blockers for the treatment of myocardial ischemia and/or supraventricular tachyarrhythmias. The purpose of this rodent study was to examine the effect of intravenous verapamil on the hyperdynamic circulatory response to acute normovolemic hemodilution (hematocrit 20%). Anesthetized animals were randomly divided into four groups equal in number: (1) controls (no hemodilution, no drug); (2) hemodilution only; (3) verapamil only; and (4) hemodilution followed by verapamil. Cardiac output was recorded using an electromagnetic flow probe. Pre- and afterload tests were performed, the former consisting of rapid infusion of blood adjusted for hematocrit, the latter consisting of an aortic clamp technique. Animals in group 2 had significantly (P less than 0.05) greater percent increases in cardiac index, stroke volume index, and dP/dt, and greater percent decreases in mean arterial pressure, systemic vascular resistance, and oxygen delivery than did control animals (group 1). Infusion of verapamil after hemodilution (group 4) did not interfere with the compensatory increases in cardiac index and stroke volume index seen in group 2, nor did it reduce the peak stroke volume index in response to preload stress, although it did reduce resting dP/dt, mean arterial pressure and systemic vascular resistance, and peak cardiac index and "left ventricular developed pressure" after preload and afterload stress, respectively. We conclude that reduced ventricular function after verapamil administration does not interfere with the compensatory increase in stroke volume index after normovolemic hemodilution.

This study was designed to compare the cardiovascular effects of pipecuronium bromide (PIP) to vecuronium (V) when combined with sufentanil (SF) in patients undergoing coronary artery bypass surgery. Eighty-two patients were studied; 40 were normotensive and 42 had hypertension currently controlled by pharmacological therapy. All patients were randomly assigned to receive either intravenous V, 0.12 mg/kg, or PIP, 0.10 mg/kg. Anesthesia was induced with SF, 6 micrograms/kg, while breathing 100% oxygen. Hemodynamic data including heart rate, mean arterial pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance, pulmonary vascular resistance, and left ventricular stroke work index were collected at five points: prior to induction, 3 and 6 minutes after the complete administration of PIP or V, and 3 and 6 minutes after intubation. There were no statistical differences in hemodynamic changes associated with either PIP or V. In addition, there were no statistical differences in the hemodynamic parameters measured at the five time points between the normotensive and hypertensive patient groups. This study demonstrates that there are no significant hemodynamic changes between SF/PIP and SF/V when used during coronary artery surgery. Due to its associated stable hemodynamics, as well as its long duration of action, PIP could become a commonly used muscle relaxant for anesthesia for cardiac surgery.

The effects of propranolol and hemodilution on myocardial performance and oxygen delivery were evaluated in 36 anesthetized rats. Oral propranolol treatment consisted of 64 mg/kg/d for 6 weeks prior to the experiments, whereas intravenous (IV) propranolol treatment consisted of 5 micrograms/kg/min for 60 minutes after hemodilution. The hematocrit was reduced to 20% by a hetastarch-for-blood exchange. Animals were divided into six equal groups as follows: (1) no oral drug (water), no hemodilution, no IV drug (saline); (2) oral water, hemodilution, IV saline; (3) oral water, no hemodilution, IV propranolol; (4) oral water, hemodilution, IV propranolol; (5) oral propranolol, no hemodilution, IV saline; and (6) oral propranolol, hemodilution, IV saline. Left ventricular (LV) pressure, maximal dP/dt, ascending aortic blood flow, and response to preload (peak cardiac and stroke volume indices) and afterload (LV-developed pressure) stress were measured. In group 2, hemodilution significantly increased cardiac index, stroke volume index, and dP/dt, and decreased blood pressure, peripheral resistance, and oxygen delivery compared with group 1. Compared with group 2, IV propranolol after hemodilution in group 4 significantly decreased cardiac index, dP/dt, LV-developed pressure, and peak cardiac index, and increased peripheral resistance. Stroke volume index and peak stroke volume index after preload stress remained elevated in group 4, despite the negative inotropic effects of IV propranolol. Oral propranolol in group 6 did not prevent the hemodilution-induced increase in stroke volume index and peak stroke volume index in response to preload stress, although it did decrease cardiac index and dP/dt compared with group 2. Oxygen delivery was reduced in the hemodiluted animals in proportion to the decrease in hemoglobin, regardless of propranolol treatment. It is concluded that reduced myocardial contractility and cardiac performance by nonselective pharmacological beta-adrenoceptor blockade does not interfere with the compensatory increase in stroke volume index after hemodilution.

The effect of myocardial depression on the circulatory response to acute normovolemic hemodilution (hematocrit 23%) with hetastarch was evaluated in 28 anesthetized Sprague-Dawley rats. Cardiac output was recorded using an electromagnetic flow probe. Mild, moderate, and severe myocardial depression were achieved by infusing disopyramide 50, 75, and 85 mg/kg. This resulted in a dose-dependent decrease in cardiac output (r = -0.73, p less than 0.05) and mean arterial pressure (r = -0.65, p less than 0.05), and an increase in left ventricular end-diastolic pressure (r = 0.77, p less than 0.05) and total peripheral resistance (r = 0.46, p less than 0.05). Following hemodilution, cardiac output and mean arterial pressure were significantly lower and total peripheral resistance significantly higher in animals with myocardial depression compared with saline anemic controls. These differences were dose-dependent for cardiac output (r = -0.83, p less than 0.05), mean arterial pressure (r = -0.68, p less than 0.05), and total peripheral resistance (r = 0.51, p less than 0.05). Although control animals were able to significantly increase their cardiac output and stroke volume after hemodilution compared with baseline, animals with severe myocardial depression were unable to do so. This resulted in marked hypotension after hemodilution in controls compared with severely depressed animals. The results suggest a diminished ability of the pharmacologically depressed heart to tolerate acute normovolemic hemodilution.

The fine structure of intraganglionic blood vessels of rat superior cervical sympathetic ganglia is studied with the light microscope and with both conventional and ultrastructural histochemical methods. Two sets of small capillaries together with larger sinusoidal ones are identified. One set of capillaries is associated with the clustered (type II) small catecholamine-containing (CC) cells and exhibits features suggestive of fluid transport function (multiple wide fenestrae and active pinocytosis). The second set of capillaries is in direct relation to the sympathetic neurons (SN) and shows characteristics suggestive of absorptive function (microvilli and pinocytotic vesicles). The larger sinusoidal capillaries are observed in the vicinity of type II CC cells, extend parallel to the long axes of the perikarya of the neurons and occasionally form loops around them. The latter are assumed to be larger blood spaces connecting the two capillary sets and serve to slow the circulation around the neurons. A pattern of portal-like intraganglionic microcirculation through which type II CC cells participate in modulating the SN is postulated. Type II CC cells secrete a catecholamine modulator which, driven by concentration gradient, gains access to the circulation through the fenestrated capillaries. The sinusoidal capillaries serve to perfuse the SN with a slow stream of blood rich in the catecholamine modulator. The latter can be filtered through the microvilli and pinocytotic vesicles of the second set of capillaries to induce slow inhibitory postsynaptic potential on the SN.

Twenty adult cardiac surgery patients with impaired ventricular function by contrast ventriculography at cardiac catheterization were monitored from before anesthesia until the time of extubation up to 12 h postoperatively. A thermodilution pulmonary artery catheter with fiberoptic channels for continuous measurement of mixed-venous oxygen saturation (S-vO2) by reflection oximetry was substituted for the usual catheter. The S-vO2 was recorded continuously along with blood pressure, cardiac filling pressures, and heart rate. Thermodilution cardiac output determinations were used to derive hemodynamic and oxygen transport indices. There was a consistently high and significant negative correlation (r = -.84) between S-vO2 and the percentage of oxygen extracted from blood. Thus, S-vO2 reflects oxygen extraction and continuous S-vO2 provides continuous quantification of global oxygen extraction. None of the other oxygen transport variables including cardiac index showed significant correlation with S-vO2. The oximetry system provides a continuous and reliable indication of mixed-venous blood oxygenation which is a continuous reflection of oxygen extraction.

Paroxysmal hypertension occurred during the first 8 hours after cardiac valve replacement in 15 of 186 consecutive patients. The clinical characteristics of this hypertension were similar to those of hypertension after myocardial revascularization, except that this complication occurred much less frequently after valve replacement (8.1%) than after myocardial revascularisation (33%) (P less than 0.001). Hypertension resulting from hypoxia, hypercapnia, shivering, or arousal from anaesthesia was excluded from consideration. The rise in systemic arterial pressure (average 34/35 mmHg +/- 4.9/4.3 SE) was usually associated with a reduction in central venous pressure (12/15 patients) and a mild increase (2 to 4 cm saline) in left atrial pressure. The incidence of hypertension was not related to the valve replaced (aortic or mitral), type of lesion (stenosis or regurgitation), preoperative level of blood pressure, or use of hypothermia during operation. However, none of the 18 patients who had double valve replacement showed significant rise in blood pressure after operation. It is suggested that these hypertensive episodes may be related to pressor reflexes from the heart and/or great vessels.

To compare haemodynamic responses associated with equipotent doses of muscle relaxants and high dose fentanyl (50 micrograms X kg-1), 40 non-hypertensive patients who were receiving beta adrenergic and calcium channel blocker therapy and undergoing coronary bypass surgery were randomized to four study groups receiving the following: (1) atracurium: 0.4 mg X kg-1, (2) pancuronium: 0.12 mg X kg-1, (3) vecuronium: 0.12 mg X kg-1, or (4) pancuronium-metocurine mixture: (0.4 mg + 1.6 mg X ml-1):1 ml/10 kg. Neuromuscular blockers were injected with fetanyl at induction. Haemodynamics were recorded with the patients awake (baseline), at two minutes post-induction, and at two and five minutes after intubation. Pancuronium was the only drug associated with significant increases in HR; no other significant changes occurred within each group when compared to their respective baseline haemodynamics. HR increased more after induction with pancuronium when compared to atracurium (23 vs. 4 per cent, p less than 0.05) and to vecuronium (23 vs. 2 per cent, p less than 0.05), and when compared to vecuronium after intubation (29 vs. 7 per cent, p less than 0.05). The pancuronium-metocurine mixture caused tachycardia which was less than, though not significantly different than with pancuronium; however, HR returned to baseline by five minutes with the mixture, but remained elevated with pancuronium (3 vs. 18 per cent, p less than 0.05). SVR fell more on induction with atracurium when compared to vecuronium (-18 vs. 1 per cent, p less than 0.05). These changes in HR or SVR were not accompanied by ECG signs of ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension immediately after coronary surgery is a problem in about one third of the patients so treated. This report discusses the possible causes of postoperative hypertension and describes several means of controlling the complication.

To determine whether the application of positive end-expiratory pressure (PEEP) in the postoperative period after cardiac operation would reduce postoperative blood loss, the number of transfusions required, or the rate of reoperation for bleeding, we conducted a prospective study of 83 patients who underwent elective coronary revascularization. These patients were randomly assigned to receive either PEEP (10 cm H2O) or no PEEP (zero end-expiratory pressure). All other aspects of their care were identical. There was no statistically significant reduction in the amount of bleeding in patients treated with PEEP at 8 or 24 hours postoperatively. There was no significant difference in hematocrit between the groups preoperatively or postoperatively. There was no statistically significant difference in the number of reexplorations for bleeding. Finally, there was no significant difference between the groups in the amount of blood administered. On the basis of our results, we conclude that the application of PEEP in the postoperative period of cardiac operation did not reduce the amount of blood loss, the need for reexploration for bleeding, or the blood requirements in this group of patients.