Improved cardiac risk stratification in major vascular surgery with dobutamine-atropine stress echocardiography.

OBJECTIVES: This study sought to optimize preoperative cardiac risk stratification in a large group of consecutive candidates for vascular surgery by combining clinical risk assessment and semiquantitative dobutamine-atropine stress echocardiography. BACKGROUND: Dobutamine-atropine stress echocardiography has been used for the prediction of perioperative cardiac risk in a small group of patients scheduled for elective major vascular surgery on the basis of the presence or absence of stress-induced regional left ventricular wall motion abnormalities. METHODS: Clinical risk assessment and dobutamine-atropine stress echocardiography were performed in 302 consecutive patients presenting for major vascular surgery. The extent and severity of stress wall motion abnormalities and the heart rate at which they occurred, in addition to the presence of wall motion abnormalities at rest, were assessed. RESULTS: The absence of clinical risk factors (angina, diabetes, Q waves on the electrocardiogram, symptomatic ventricular tachyarrhythmias, age > 70 years) identified a low risk group of 100 patients with a 1% cardiac event rate (unstable angina). Dobutamine-atropine stress echocardiographic findings were positive in 72 patients. Twenty-seven patients had a perioperative cardiac event (cardiac death in 5, nonfatal infarction in 12, unstable angina pectoris in 10); all 27 patients had positive stress test results (positive predictive value 38%, negative predictive value 100%). The semiquantitative assessment of the extent and severity of ischemia did not provide additional prognostic information in patients with positive test results. In contrast, the heart rate at which ischemia occurred defined a high risk group with a low ischemic threshold (38 patients with 20 events [53%]) and an intermediate risk group with a high ischemic threshold (34 patients with 7 events [21%]). All 5 patients with a fatal outcome and 8 of 12 with a nonfatal myocardial infarction were in the high risk group with a low ischemic threshold. CONCLUSIONS: Clinical variables identify 33% of patients at very low risk for perioperative complications of vascular surgery in whom further testing is redundant. In all other candidates, dobutamine-atropine stress echocardiography is a powerful tool that identifies those patients at intermediate risk and a small group at very high risk. Risk stratification with a combination of clinical assessment and pharmacologic stress echocardiography has the potential to facilitate clinical decision making and conserve resources.

Dobutamine-atropine stress echocardiography in elderly patients unable to perform an exercise test. Hemodynamic characteristics, safety, and prognostic value.

OBJECTIVE: To establish the hemodynamic effects, safety, and prognostic value of dobutamine-atropine stress echocardiography in patients 70 years of age or older. DESIGN AND SETTING: Observational study at a university hospital. PATIENTS: One hundred seventy-nine patients (mean age, 75 years; range, 70 to 90 years) referred for chest pain (n = 73) or preoperative risk assessment for major vascular noncardiac surgery (n = 106). MEASUREMENTS: All patients underwent clinical evaluation and dobutamine-atropine stress test. RESULTS: One hundred seventy-nine stress tests were performed. Test end points were the target heart rate (85% of theoretical maximum heart rate), reached in 165 tests (92%); inadequate echo images, two tests (1%); and side effects, 12 tests (7%). Side effects that caused a premature end of the test were severe chest pain (n = 5 [2.8%]), electrocardiographic changes (n = 1 [0.6%]), hypotension (n = 2 [1.1%]), chills (n = 2 [1.1%]), and cardiac arrhythmias (paroxysmal atrial fibrillation) (n = 2 [1.1%]). New wall motion abnormalities as a marker of myocardial ischemia occurred in 50 tests (28%). No death or myocardial infarction occurred during the test. Perioperative events occurred in 12 patients (four cardiac deaths, three myocardial infarctions, and five episodes of unstable angina). During 16 +/- 6 months (mean +/- SD) of follow-up of 166 patients, 22 cardiac events occurred (eight cardiac deaths, four myocardial infarctions, and 10 episodes of unstable angina pectoris). By multivariate regression analysis, only perioperative cardiac events (odds ratio, 51; 95% confidence interval, 5.8 to 454) and late cardiac events (odds ratio, 5.2; 95% confidence interval, 2.0 to 14) were correlated with new wall motion abnormalities during stress. CONCLUSION: Dobutamine-atropine stress echocardiography is a feasible and safe test for assessing elderly patients with suspected and/or proven coronary artery disease, providing useful prognostic information for perioperative and late cardiac risk with relatively few side effects.

Cerebral pressure-flow relationship during cardiopulmonary bypass in the dog at normothermia and moderate hypothermia.

We studied cerebral autoregulation by analyzing cerebral pressure-flow curves during cardiopulmonary bypass (CPB) with alpha-stat (alpha-stat) acid-base management at 28 (n = 9) and 37 degrees C (n = 9) in two groups of dogs. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) were determined multiple times in each animal over an extensive range of cerebral perfusion pressure (CPP). The CPP was altered by changing perfusion flow rate. The dependence of CBF on CPP during normothermic and moderate hypothermic CPB was assessed using a block design analysis of covariance with CPP as the covariate. We anticipated maximal statistical power with this analysis to define if cerebral autoregulation was intact. This method of statistical analysis was compared with the conventional interpretation by linear regression analysis. Animals were administered sodium thiopental until an isoelectric electroencephalogram was obtained to assure stable depth of anesthesia independently of temperature effects. The animals were randomly assigned to either temperature group. The CBF was determined by injection of radioactive microspheres at each of five target CPPs randomly allocated (50, 60, 70, 80, and 90 mm Hg). The brain oxygen content difference was defined as arterial minus superior sagittal sinus (SSS) oxygen content. No difference in CPP, hemoglobin, arterial carbon dioxide tension, or pH was seen between groups at any time period. In both groups, total CBF (tCBF) increased significantly with increasing CPP (p = 0.012 and 0.017 for normothermic and hypothermic CPB, respectively; CPP as covariate). The between-group difference in slopes (CPP x temperature effect) approached statistical significance (p = 0.059).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term prognostic value of dobutamine stress echocardiography in patients with atrial fibrillation.

STUDY OBJECTIVE: To assess the long-term prognostic value of dobutamine stress echocardiography (DSE) for cardiac events (cardiac death, myocardial infarction, and late revascularization) in patients with atrial fibrillation (AF). METHODS: Baseline ECGs were studied in patients undergoing DSE between 1989 and 1998. Sixty-nine patients had AF before DSE. Prognostic value of DSE in these patients was compared with a control group who had sinus rhythm (n = 1,664). The presence of stress-induced ischemia was noted for every patient. The mean follow-up period was 35 months (range, 6 to 84 months). Data are presented as hazards ratio (HR) with 95% confidence interval (CI). RESULTS: Heart rate at rest was higher in patients with AF (77 +/- 15 beats/min vs 73 +/- 14 beats/min; p = 0.04); however, double product at peak stress was not different between patients with AF and sinus rhythm (17,602 vs 17,169, respectively; p = 0.46). In patients with AF, target heart rate was achieved at a lower dobutamine dose (33 +/- 8 microg/kg/min vs 35 +/- 9 microg/kg/min; p = 0.01). Cardiac arrhythmias occurred more frequently (12% vs 5%; p = 0.001) in patients with AF during DSE. During a follow-up period of 7 years, cardiac death occurred in 5 patients, myocardial infarction in 2 patients, and late revascularization in 10 patients. Prognostic value of DSE for all late cardiac events was similar in patients with AF (HR, 3.0; 95% CI, 0.9 to 9.5) and sinus rhythm (HR, 3.4; 95% CI, 2.7 to 4.3; p = 0.85). CONCLUSION: The prognostic value of DSE for late cardiac events is maintained in patients with AF.

Multiplane transesophageal echocardiography: latest evolution in an imaging revolution.

Multiplane imaging with a rotating phased-array transducer from within the esophagus represents the latest development in transesophageal cardiac ultrasound. Transverse, longitudinal, and all possible intermediate oblique planes are easily obtained from the same transducer with minimal probe manipulation. Three-dimensional conceptualization of complex structures and pathologic conditions is facilitated. The major advantages are a simplified examination procedure and much less patient discomfort than monoplane and biplane probe imaging.

Con: intraoperative myocardial ischemia is not benign.

The principal importance of intraoperative ischemia is its consistent association with adverse outcome. In coronary artery surgery the finding of prebypass ischemia is an important predictor, and postbypass ischemia is a critical predictor of adverse outcome. One in three patients with postbypass ischemia will suffer an adverse outcome in CABG. Furthermore, prevention of postbypass ischemia may improve outcome in CABG. Clearly, intraoperative ischemia in CABG surgery is an ominous sign that should be regarded with the utmost concern by anesthesiologists. In noncardiac surgery, intraoperative ischemia also indicates about a one in three chance of adverse outcome. Although it is less sensitive than postoperative ischemia, it may have superior positive predictive power and specificity. Most importantly, intraoperative monitoring for ischemia is currently available to most patients, whereas extended postoperative monitoring is not. The finding of intraoperative ischemia defines a high-risk group of patients who may merit special monitoring and treatment. To regard intraoperative ischemia as benign would be inconsistent with available information.

Cardiovascular physiology: venous return.

Cardiac output is not regulated simply by autonomically mediated changes in heart rate and stroke volume. More often, changes in cardiac output predominantly reflect changes in the peripheral circulation which in turn change venous return. Any attempt to analyze circulatory function without considering the peripheral circulation will be incomplete. The principles discussed above can be fruitfully applied to the analysis of many clinically important derangements of circulatory function. This discussion is only intended as an introduction to concepts which have been exhaustively developed and discussed by Guyton et al. A careful review of this source material will reward the interested reader.

Adverse effects of pancuronium during high-dose fentanyl anesthesia for coronary artery bypass grafting.

Using a randomized double-blind protocol, the authors prospectively compared three nondepolarizing muscle relaxants with respect to their influence on hemodynamics and on the electrocardiogram. Thirty-three patients undergoing elective coronary artery bypass grafting (CABG) with high-dose (100 micrograms/kg) fentanyl anesthesia were studied. Patients received 1.5 X ED95 of either pancuronium (n = 12), metocurine (n = 9), or a metocurine-pancuronium combination (4:1 ratio by weight) (n = 12) for muscle relaxation. Heart rate and rate pressure product (RPP) were significantly higher postinduction in the pancuronium group. Myocardial ischemia, indicated by new ECG ST-segment depression occurred significantly more frequently, and exclusively, in the pancuronium group. The authors' data suggest that since pancuronium is associated with tachycardia and an increased incidence of myocardial ischemia, it is best avoided in patients with severe coronary artery disease undergoing CABG with high-dose fentanyl. Either metocurine or the metocurine-pancuronium combination provides greater hemodynamic stability, without precipitating myocardial ischemia, and can be safely and effectively substituted for pancuronium.

Hemodynamic and temperature changes after aortocoronary bypass grafting.

Perioperative hemodynamic and temperature changes were reviewed in 58 patients who underwent aortocoronary bypass grafting. Core temperature showed an immediate decline postoperatively, secondary to core temperature cooling during bypass. Subsequent rewarming occurred over the next 8 to 12 hours, with the temperature often increasing above normal. The reason for this pyrexial response is discussed. The cardiac index was depressed immediately postoperatively, again with substantial recovery within 8 hours. This improvement over time occurred not only because of recovery of intrinsic function but also because of reduction in myocardial work due to falling systemic vascular resistance. The latter was high immediately postoperatively and then consistently fell during the rewarming phase. During the first 8 hours postoperatively there were significant changes in temperature and cardiac and systemic vascular resistance indices. The hemodynamic data correlated strongly with changes in temperature. Falling systemic vascular resistance required the institution of alpha-agonist therapy in 25% of patients.

A comparison of fentanyl and sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To compare fentanyl and sufentanil, administered in equipotent concentrations by target-controlled infusion, as components of a balanced anesthetic in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, randomized, double-blind trial. SETTING: A university hospital. PARTICIPANTS: Twenty-one patients undergoing nonemergent, primary CABG surgery. INTERVENTIONS: Patients received fentanyl (group F, n = 10) or sufentanil (group S, n = 11) by target-controlled infusion throughout the pre-cardiopulmonary bypass (CPB) period. To ensure equipotency, the target effect-site concentrations employed (fentanyl, 8.1 ng/mL, and sufentanil, 0.68 ng/mL) were equal to the IC50 for electroencephalographic effect. Isoflurane was administered as needed to maintain pre-CPB hemodynamics near preoperative baseline values. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and end-tidal isoflurane concentration were measured every 15 to 30 seconds. Serum opioid concentrations were measured 5 times between induction and CPB. Opioid cost was based on the number of ampules opened to provide the administered dose. The 2 groups were similar demographically. The pre-CPB serum opioid concentrations were constant and averaged fentanyl, 5.8 +/- 1.9 ng/mL, and sufentanil, 0.59 +/- 0.13 ng/mL. Pre-CPB hemodynamics were stable and similar in both groups. Pre-CPB end-tidal isoflurane requirements did not differ between groups and averaged 0.46 +/- 0.21% in group F and 0.56 +/- 0.24% in group S. The duration of post-operative endotracheal intubation was 9.1 +/- 5.0 hours in group F and 8.0 +/- 3.2 hours in group S (p = NS). The cost per patient of fentanyl (Canadian $6.12 +/- 1.04) was less than that of sufentanil (Canadian $17.47 +/- 4.65). CONCLUSIONS: When administered in a constant 10:1 concentration ratio, fentanyl and sufentanil do not differ in their ability to facilitate pre-CPB hemodynamic control. Although both opioids were relatively inexpensive, the acquisition cost of fentanyl was less than sufentanil. A recommendation regarding the opioid of choice for routine use in patients undergoing CABG surgery awaits more rigorous studies of recovery and cost after equipotent doses of fentanyl and sufentanil. When combined with isoflurane, effect-site opioid concentrations near the IC50 for electroencephalographic effect provide excellent pre-CPB hemodynamic control in patients undergoing CABG surgery.

A comparison of clonidine with conventional preanesthetic medication in patients undergoing coronary artery bypass grafting.

UNLABELLED: In this controlled study, we compared clonidine with conventional premedication in 35 patients undergoing coronary artery bypass grafting (CABG). After premedication with clonidine 5 microg/kg p.o. (Group C, n = 11), lorazepam 60 microg/kg p.o. (Group L, n = 13), or morphine 0.1 mg/kg plus scopolamine 6 microg/kg i.m. (Group M, n = 11), sedation, anxiety, and quality of premedication were graded. After the administration of sufentanil 2.0 microg/kg over 12.5 min, a computer-assisted infusion device targeted a sufentanil effect-site concentration of 0.75 ng/mL. Hemodynamic variables, end-tidal isoflurane concentration (ET-ISO), the electroencephalographic spectral edge, and the serum sufentanil concentration (SUF) were measured. There were no intergroup differences in anxiety, sedation, quality of premedication, the dose of sufentanil causing unconsciousness, or the electroencephalographic (EEG) response to induction. Intraoperative SUF was stable, with no intergroup difference. The average prebypass ET-ISO was lower in Group C than in Group M. The ET-ISO and peak ET-ISO after intense surgical stimulation were lower in Group C versus Groups L and M. Mean arterial blood pressure was lower in Group C versus Groups L and M. There were no intergroup differences in pharmacologic intervention, time to extubation, or intensive care unit stay. Clonidine produces sedation, anxiolysis, and quality of premedication comparable to conventional premedication. Compared with other drugs, clonidine does not alter the dose of sufentanil inducing unconsciousness or EEG slowing, but it uniquely reduces isoflurane requirements. IMPLICATIONS: In patients undergoing coronary artery bypass grafting, clonidine produces sedation and relieves anxiety as effectively as conventional premedication. Clonidine does not uniquely alter the dose of sufentanil inducing unconsciousness or electroencephalographic slowing, but it significantly reduces isoflurane requirements.

Failure of intravenous nitroglycerin to prevent intraoperative myocardial ischemia during fentanyl-pancuronium anesthesia.

Twenty patients undergoing coronary artery bypass grafting under fentanyl-pancuronium anesthesia were studied. Continuous electrocardiographic (ECG) recording by a Holter Monitor was utilized to determine the incidence of ECG changes of myocardial ischemia during the precardiopulmonary bypass period and to determine the efficacy of an intravenous nitroglycerin (iv NTG) infusion for preventing ischemic ECG changes. Patients in Group 1 (n = 9) received a 0.5 microgram . kg-1 . min-1 iv NTG infusion 20 min prior to induction of anesthesia and throughout the study. Patients in Group 2 (n = 11) received placebo. A randomized double-blind protocol was employed. Anesthesia was induced with fentanyl 3 micrograms . kg-1 . min-1. After fentanyl 25 micrograms/kg and pancuronium 0.1 microgram/kg, the trachea was intubated. After fentanyl 50 micrograms/kg surgery commenced. Prior to induction of anesthesia, iv NTG caused significant decreases in mean arterial pressure and pulmonary capillary wedge pressure, whereas placebo had no effect. However, subsequent to induction of anesthesia, hemodynamics in the two groups were identical. Fifty per cent of patients developed ECG changes of myocardial ischemia during the period from induction of anesthesia to commencement of cardiopulmonary bypass. The incidence of ischemic ECG changes was virtually identical in Group 1 (5/9) and Group 2 (5/11). Ischemic ECG changes were associated with increases in heart rate, mean arterial pressure, and rate pressure product, and decreases in the endocardial viability ratio (DPTI/SPTI). Increases in pulmonary capillary wedge pressure were not associated with myocardial ischemia. Fentanyl-pancuronium anesthesia, as administered in this study, was associated with a high incidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Premedication and high-dose fentanyl anesthesia for myocardial revascularization: a comparison of lorazepam versus morphine-scopolamine.

Using a randomized double-blind placebo-controlled experimental protocol, the authors compared two premedication regimens in 42 patients undergoing elective myocardial revascularization. Group L patients (n = 23) received lorazepam 0.06 mg/kg po 90 min preoperatively, while group M patients (n = 19) received morphine 0.1 mg/kg im, plus scopolamine 0.006 mg/kg im 60 min preoperatively. Anesthesia was induced with fentanyl 100 micrograms/kg and atracurium 0.50 mg/kg administered over 10 min. The treatment groups did not differ significantly with respect to the degree of sedation or anxiolysis achieved, or the rapidity of induction with fentanyl. Premedication significantly influenced the hemodynamic response to anesthetic induction. Hemodynamics were stable post-induction in group M, but cardiovascular depression was noted in group L. Control heart rate (HR) was lower in group L. The HR, arterial pressure, and cardiac index were significantly lower, following both induction and intubation, in group L. Following sternotomy hemodynamics were identical in both groups. Serum fentanyl concentration was significantly higher during intubation in group L, probably secondary to the pharmacokinetic consequences of a decreased CI. New electrocardiographic evidence of myocardial ischemia did not occur in either group. Based on their findings with fentanyl-at-racurium, and their review of the literature, the authors speculate that premedication exerts a significant hemodynamic effect during induction with other narcotic-relaxant combinations.

Catecholamine responses to anesthetic induction with fentanyl and sufentanil.

In a randomized study, the authors examined the changes in plasma epinephrine and norepinephrine concentrations associated with induction of anesthesia and surgery in 33 patients with good ventricular function undergoing elective coronary artery surgery. After premedication with morphine and scopolamine, patients received either fentanyl, 100 micrograms/kg (n = 16), or sufentanil, 15 micrograms/kg, (n = 17), intravenously (IV), over 10 minutes to induce anesthesia. Metocurine, 0.42 mg/kg, IV, produced muscle relaxation. Arterial blood for plasma catecholamine determinations was drawn prior to induction, every two minutes throughout induction, one minute following endotracheal intubation, and one minute after sternotomy. Plasma epinephrine concentration was unchanged with either induction agent. Plasma norepinephrine concentration increased significantly after administration of either narcotic, peaked between six and ten minutes into induction, and returned to the preinduction value after intubation. Induction-related changes in arterial pressure and pulmonary capillary wedge pressure were significantly correlated with changes in the logarithm of plasma norepinephrine concentration. Similar degrees of endogenous norepinephrine release appear to accompany induction with equipotent doses of fentanyl and sufentanil in patients premedicated with morphine and scopolamine. Norepinephrine release may influence the hemodynamic response to induction with narcotics.

A randomized double-blind comparison of fentanyl and sufentanil anaesthesia for coronary artery surgery.

Using a randomized double-blind protocol the authors compared two narcotic anaesthetic regimens in 33 patients with good ventricular function undergoing coronary artery surgery. After premedication with morphine and scopolamine, patients received either fentanyl 100 micrograms X kg-1 (n = 16), or sufentanil 15 micrograms X kg-1 (n = 17), intravenously (IV) over 10 min to induce anaesthesia. Metocurine 0.42 mg X kg-1 provided muscle relaxation. No further IV anaesthetic agents were given. The haemodynamic response to induction, intubation, and surgery, differed minimally between agents. The degree of rigidity on induction was identical with both agents, as were the intervals following induction at which patients lost consciousness, regained consciousness, or met criteria for extubation. However, the interval until extubation criteria were met did correlate with the duration of cardiopulmonary bypass. Sufentanil 15 micrograms X kg-1, was clinically indistinguishable from fentanyl 100 micrograms X kg-1, when used as the primary anaesthetic agent for coronary surgery.

Drug interactions with sufentanil. Hemodynamic effects of premedication and muscle relaxants.

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double-blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 micrograms.kg-1. Eighty patients with left ventricular ejection fraction greater than or equal to 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg.kg-1 and scopolamine 6 micrograms.kg-1 intramuscularly, or lorazepam 60 micrograms.kg-1 orally, and paralyzed with either pancuronium 0.1 mg.kg-1 or vecuronium 0.1 mg.kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 +/- 11 to 69 +/- 13 beats.min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 +/- 8 to 62 +/- 14 beats.min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To determine the pharmacokinetics of sufentanil in patients undergoing coronary artery bypass graft surgery. DESIGN: Prospective, multigroup study. SETTING: University-affiliated hospital. PARTICIPANTS: Patients with good left ventricular function undergoing elective surgery (n = 103). INTERVENTIONS: Sufentanil was administered by target-controlled infusion, with target effect-site concentrations ranging from 0.4 to 4.5 ng/mL. Isoflurane was administered as required to maintain stable hemodynamics. Sufentanil pharmacokinetics were determined by population modeling. The potential effects of gender, weight, different premedications (lorazepam, morphine-scopolamine, or clonidine), and coinduction with propofol on sufentanil pharmacokinetics were explored. MEASUREMENTS AND MAIN RESULTS: The first model determined was a simple 3-compartment model, without any covariates, which had these parameters: V(1) = 5.7 L, V(2) = 18.1 L, V(3) = 225 L, Cl(1) = 0.69 L/min, Cl(2) = 3.1 L/min, and Cl(3) = 1.4 L/min. The overall predictive ability during the entire pre-cardiopulmonary bypass period of this model was excellent, with virtually no bias (median prediction error, -0.4%) and good precision (median absolute prediction error, 18.4%). More complex models with the various premedications used or coinduction with propofol as covariates did not improve the predictive accuracy or precision compared with the simple 3-compartment model. Similarly, including either gender or weight as a covariate did not improve predictive ability. CONCLUSION: The authors have determined a pharmacokinetic model for sufentanil that can be used to maintain desired target concentrations of sufentanil before cardiopulmonary bypass, with a high degree of accuracy and acceptable variability. Concomitantly administered medications (lorazepam, morphine-scopolamine, clonidine, or propofol) do not appear to have any clinically important effects on distribution-phase sufentanil pharmacokinetics.

A comparison of desflurane and isoflurane in patients undergoing coronary artery surgery.

Animal studies indicate that desflurane and isoflurane have similar hemodynamic effects when administered in equipotent anesthetic concentrations. The authors compared desflurane and isoflurane, used as primary anesthetics for patients undergoing elective coronary artery bypass surgery whose left ventricular ejection fractions were greater than 0.34. After induction of anesthesia with thiopental (dose 180 +/- 45 mg [mean +/- standard deviation]) and fentanyl, 10 micrograms.kg-1, either desflurane or isoflurane was administered to maintain systolic blood pressure within 70-120% of, and heart rates less than 120% of, the patients' average preoperative values. If adjusting the end-tidal anesthetic concentration within the range of 0-2.0 MAC could not maintain these predefined hemodynamic limits, additional fentanyl or vasoactive drugs were used. Induction and maintenance of anesthesia was accompanied by a significant decrease in mean arterial pressure in both groups (desflurane 97 +/- 12 mmHg at control, decreasing to 71 +/- 5 mmHg during skin preparation; isoflurane 95 +/- 9 mmHg at control, 74 +/- 9 mmHg during skin preparation). One minute after sternotomy, mean arterial pressure in the isoflurane group had returned to control, 97 +/- 9 mmHg, which was significantly greater than in the desflurane group, 87 +/- 12 mmHg. Systolic arterial pressure was also significantly greater in the isoflurane group 1 min after intubation, during skin preparation, and 1 min after sternotomy. Otherwise, the hemodynamic effects of these volatile agents were similar. There were no differences between groups in the incidence of ECG changes indicative of myocardial ischemia prior to cardiopulmonary bypass, perioperative myocardial infarction, or perioperative mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil pharmacokinetics in patients undergoing abdominal aortic surgery.

The pharmacokinetics of alfentanil, 300 micrograms.kg-1 IV, were determined in patients undergoing elective abdominal aortic reconstruction. The mean age (+/- SD) of the patients was 64.3 +/- 7.4 yr; their mean weight was 74.7 +/- 13.8 kg. Five patients underwent aneurysm repair and six had aortobifemoral grafting. Serum alfentanil concentrations were measured by gas-liquid chromatography in samples drawn at increasing intervals over a 24-hr period. A three-compartment model was fitted to the concentration versus time data. The volume of the central compartment and the volume of distribution at steady state (Vdss) were 0.44 +/- 0.022 and 0.63 +/- 0.32 L.kg-1, respectively. Total drug clearance was 6.4 = 1.9 ml.min-1.kg-1. The elimination half-time was 3.7 +/- 2.6 hr. Patient age was positively correlated with both Vdss and elimination half-time. There were no significant correlations between the pharmacokinetic variables and the duration of aortic cross-clamping, the duration of surgery, or the rate or total volume of IV fluids infused intraoperatively. In general surgical patients, the elimination half-time of alfentanil has been reported to be 1.2-2.0 hr. Although the elimination half-time of alfentanil was longer in patients undergoing abdominal aortic surgery, alfentanil was eliminated much faster than either fentanyl or sufentanil in this patient population.