David R. Larach

THE ACCURACY OF FINAPRES NONINVASIVE MEAN ARTERIAL PRESSURE MEASUREMENTS IN ANESTHETIZED PATIENTS

The Finapres (FIN) is a new noninvasive blood pressure monitor that provides continuous arterial waveform display with the use of a finger cuff. The authors assessed the accuracy of FIN mean arterial pressure (MAP) measurements relative to simultaneous direct radial arterial pressures in 20 patients undergoing general anesthesia for major elective surgery. Data were collected digitally with the use of RS-232 communications over a total of 16.2 h. The data were processed into 6012 interference-free time samples, each spanning 6 s. The authors determined the difference between FIN and direct MAPs during each time sample. The authors calculated not only the bias of FIN measurements, but also the frequency, magnitude, and duration of discrepancies between simultaneous FIN and direct MAPs. The overall bias of the FIN MAP was -0.5 +/- 1.0 mmHg, which was not significantly different from zero. However, 32.3 +/- 6.2% of all MAP comparisons differed by greater than +/- 10 mmHg, and 5.0 +/- 1.1% differed by greater than +/- 20 mmHg. Moreover, there was an average of one episode every 2 patient-hours when the FIN MAP differed by greater than +/- 20 mmHg for more than 1 min. Although the MAP measured by FIN accurately reflected direct MAPs most of the time, there were occasional discrepancies of different magnitude such that clinical usefulness may be limited in patients in whom continuous accurate blood pressure measurements are essential.

Direct Vasodilation by Sevoflurane, Isoflurane, and Halothane Alters Coronary Flow Reserve in the Isolated Rat Heart

Direct vasodilation of coronary resistance vessels by anesthetics may reduce coronary flow reserve and interfere with myocardial flow-metabolism coupling. This study was performed to evaluate the potential for the halogenated anesthetic agents sevoflurane, isoflurane, and halothane to alter the regulation of coronary flow via a direct action on coronary resistance vessels. Coronary flow and flow reserve were measured in the quiescent isolated perfused rat heart at anesthetic concentrations between 0 and 3 x MAC. In order to minimize anesthetic-induced secondary changes in coronary resistance, constant coronary perfusion pressure was maintained; the left ventricular cavity was vented; and tetrodotoxin was used to achieve cardiac arrest. These conditions permitted the dissociation of direct anesthetic actions from indirect regulatory processes affecting coronary vascular resistance (CVR). Coronary flow reserve was defined as the difference between coronary flow prior to and during administration of a maximally vasodilating dose of adenosine. Each anesthetic significantly reduced the magnitude of both CVR and coronary flow reserve in a concentration-dependent manner. Sevoflurane reduced coronary flow reserve significantly less than did halothane and isoflurane. At high concentrations (3.0 x MAC), coronary flow reserve was abolished by halothane and was decreased to near zero by isoflurane; however, flow reserve was reduced only 48% from control by sevoflurane. This difference among anesthetics is explained primarily by variations in the magnitude of direct coronary vasodilation produced by each anesthetic, rather than by effects on maximal vasodilator capacity. These data show that sevofluranes intrinsic vasodilator action on coronary resistance vessels differs substantially from that of halothane and isoflurane.

Halothane selectively attenuates α2-adrenoceptor mediated vasoconstriction, in vivo and in vitro

The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional alpha 1- and alpha 2-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: in vivo blood pressure response in pithed rats, and in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti-vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an alpha 2-adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an alpha 1-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P less than 0.0001) to azepexole in pithed rats, and a 3.2-fold rightward shift of the log dose-response curve (P less than 0.0001). Similarly, in vitro, halothane significantly attenuated alpha 2- but not alpha 1-adrenoceptor responsiveness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P less than 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P less than 0.0001). The observed selective interference with alpha 2-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca+2 entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at alpha 2-adrenoceptors by halothane may explain why alpha 1-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenuation of alpha 2- but not alpha 1-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation.

The Effect of Benzodiazepine Receptor Antagonism by Flumazenil on the MAC of Halothane in the Rat

The effects of a benzodiazepine receptor agonist and an antagonist on the MAC of halothane required to achieve anesthesia were evaluated to explore the possible functional interaction between halothane and the benzodiazepine receptor. Rats were anesthetized with halothane and then administered midazolam (a benzodiazepine agonist) and/or flumazenil (a benzodiazepine antagonist). Flumazenil in doses of 0.1 mg/kg and 1.0 mg/kg was found to have no effect on the MAC of halothane. Midazolam (1.0 mg/kg) lowered the MAC of halothane by 37%. This decrease in MAC was inhibited by coadministration of flumazenil. The absence of an increase in the MAC of halothane in the presence of flumazenil suggests that halothane does not interact with the benzodiazepine receptor, directly or indirectly, to produce its anesthetic action.

Anesthetic management for cardiac transplantation in North America—1986 survey

Cardiac transplantation has become an established part of the therapy of end-stage heart disease. The number of cardiac transplants performed, as well as the number of centers performing them, has increased dramatically in the past 2 years. A paucity of literature on the anesthetic management of patients undergoing cardiac transplantation prompted this survey of 46 United States and Canadian institutions. The report summarizes the perioperative anesthetic management of a total of 1,273 transplant recipients in 34 institutions. Generally, similar anesthetic techniques and agents were used. One notable exception was the percentage of institutions using perioperative pulmonary artery catheter monitoring. As determined from this survey, right ventricular failure remains the leading cause of inability to terminate cardiopulmonary bypass in this patient population. Further, in surveyed institutions, cardiac transplantation expends more physician as well as hospital resources per patient than coronary artery bypass surgery.

Diltiazem Withdrawal Before Coronary Artery Bypass Surgery

The authors studied the effects of withdrawing oral diltiazem therapy on the subsequent course of coronary artery bypass graft surgery. Patients with severe coronary artery disease were divided into three groups using a prospective, controlled, randomized protocol. In group D (diltiazem-continuation) patients, diltiazem was administered 2.1 +/- 0.1 hours (mean +/- SEM) before anesthetic induction (n = 10). Group DW (diltiazem-withdrawal) patients received their final diltiazem dose 17.3 +/- 2.9 hours before anesthesia (n = 10). Group R was a reference group of patients not receiving diltiazem (n = 11; not randomized). Anesthesia was induced and maintained with fentanyl and pancuronium without use of halogenated anesthetics. No clinically important differences were detected in measured hemodynamics or drug requirements. Group D patients did not have a lower systemic vascular resistance (SVR) index (P greater than 0.31) or mean arterial pressure (P greater than 0.08) compared with group DW. Also, no evidence for a diltiazem withdrawal response was found, because group DW did not have either a higher SVR index (P = 0.99) or a higher pulmonary vascular resistance index (P = 0.99) compared with group R, and no severe myocardial ischemia, coronary artery spasm, or postoperative heart block were seen. Plasma diltiazem concentrations decreased significantly during CPB (P less than 0.0001), but showed overlap between groups D and DW. Plasma diltiazem concentration did not correlate significantly with simultaneous SVR. These data show the benign effects of both diltiazem administration and its acute withdrawal before coronary artery bypass surgery with high-dose fentanyl anesthesia.

CARBON DIOXIDE ELIMINATION DURING TOTAL CARDIOPULMONARY BYPASS IN INFANTS AND CHILDREN

The authors measured the rate of carbon dioxide elimination (VCO2) in 25 pediatric patients (age 2 days to 9 yr) during total cardiopulmonary bypass at average venous blood temperatures ranging from 19.5 to 35.9°C. A multiplexed mass spectrometer was connected to the gas inlet and exhaust ports of the bubble oxygenator, and the gas-phase Fick principle was used to determine VCO2. A curvilinear relationship was found between log VCO2 and venous blood temperature, and a quadratic regression equation (r2 = 0.74) was fit to the data. Q10 (the ratio of VCO2 before and after a 10°C temperature change) was estimated to be 2.7 or 3.0, depending on the analytic method used. Venous blood temperature as a predictor variable explained a greater proportion of the variability of log VCO2 than did nasopharyngeal or rectal temperatures. Analysis of covariance revealed that total circulatory arrest during bypass (utilized in 10 patients for 34 ± 4 min, mean ± SEM) affected the relationship of venous blood temperature with log VCO2, by increasing the y-intercept (P = .008) but not the slope. These data, with associated 95% prediction intervals, define the expected CO2 elimination rates at various temperatures during standard bypass conditions in our patients. Real-time measurement of VCO2 using mass spectrometry can be a useful routine monitor during CPB that may help to assess patient metabolic function, adequacy of perfusion, and oxygenator performance.

ANESTHETIC MANAGEMENT FOR CARDIAC TRANSPLANTATION IN NORTH AMERICA - 1986

Cardiac transplantation has become an established part of the therapy of end-stage heart disease. The number of cardiac transplants performed, as well as the number of centers performing them, has increased dramatically in the past 2 years. A paucity of literature on the anesthetic management of patients undergoing cardiac transplantation prompted this survey of 46 United States and Canadian institutions. The report summarizes the perioperative anesthetic management of a total of 1,273 transplant recipients in 34 institutions. Generally, similar anesthetic techniques and agents were used. One notable exception was the percentage of institutions using perioperative pulmonary artery catheter monitoring. As determined from this survey, right ventricular failure remains the leading cause of inability to terminate cardiopulmonary bypass in this patient population. Further, in surveyed institutions, cardiac transplantation expends more physician as well as hospital resources per patient than coronary artery bypass surgery.

Combined Carotid Endarterectomy, Coronary Revascularization, and Hypernephroma Excision with Hypothermic Circulatory Arrest

Approximately 5% of renal cell carcinomas invade the inferior vena cava (IVC), forming friable, pedunculated tumor thrombus that can embolize. Fourteen to 16% of these tumor thrombi extend as far as the right atrium, in which case tricuspid valve obstruction can present an immediate threat to life (1-3). To reduce the risk of embolization during surgical manipulation and to allow complete tumor resection, the use of cardiopulmonary bypass (CPB) has been reported in patients with renal tumors (P8). However, isolation of the affected portion of the vena cava and control of intraoperative bleeding may be difficult with conventional CPB. Therefore, CPB with total circulatory arrest has been used to provide adequate operating conditions for excision of renal tumors (9-1 1). To our knowledge, however, this is the first report of the use of hypothermic circulatory arrest in a patient undergoing combined renal cell carcinoma excision, coronary revascularization, and carotid endarterectomy. The combination of these three procedures exposed this patient to cerebral ischemia, for which we used a multifaceted approach to provide cerebral protection.

Cardiopulmonary bypass interference with dantrolene prophylaxis of malignant hyperthermia

M ALIGNANT hyperthermia (MH) crisis in susceptible patients carries a high mortality rate, and can often be prevented by pretreatment with dantrolene sodium, l Cardiac surgery with cardiopulmonary bypass (CPB) for correction of congenital heart defects 2 or acquired heart disease 3 may present a particular risk to the MH-susceptible patient. First, dantrolene blood concentrations might decrease below effective prophylactic levels during CPB; and second, active rewarming causing regional hyperthermia during the latter phases of bypass could trigger an MH crisis. 4 While MH is rare, data relating to the management of CPB for susceptible patients are important, because immediate therapy with adequate doses of dantrolene can be lifesaving. 5 This paper reports serial blood dantrolene levels in an MH-susceptible child who underwent cardiac surgery with CPB. There appear to be no previous published reports of the effects of CPB on dantrolene pharmacokinetics. In addition, a study of whole-blood dantrolene levels during in vitro perfusion of a simulated patient was performed to further elucidate the changes in dantrolene pharmacokinetics that are caused by cardiopulmonary bypass.