Br.J. Anaesth. (1976), 48, 669
HAEMODYNAMICS AND MYOCARDIAL OXYGEN CONSUMPTION DURING ISOFLURANE (FORANE) ANAESTHESIA IN GERIATRIC PATIENTS J. TARNOW, J. B. BRUCKNER, H. J. EBERLEIN, W. HESS AND D. PATSCHKE
SUMMARY
The influence of isoflurane on haemodynamics and myocardial oxygen consumption was examined in seven geriatric patients under conditions of controlled ventilation and a normal arterial carbon dioxide tension. During isoflurane/nitrous oxide in oxygen anaesthesia (0.75 and 1.5 vol% inspired isoflurane) no significant changes occurred in cardiac output, stroke volume, heart rate, central venous and pulmonary artery pressure. Arterial pressure decreased, as did total peripheral resistance. A reduction in left ventricular maximum dp/dr (18-39%) was, at least in part, a result of changes in loading conditions. Total body (Ca0) —CvOj) and base excess values remained within the normal range. We consider that the oxygen supply was adequate to meet the metabolic demands of the body as a whole. Myocardial oxygen consumption decreased by 25% during 0.75 vol% inspired isoflurane and by 43.5% with deepening of anaesthesia (1.5 vol% isoflurane).
Isoflurane (Forane, 1 chloro-2-2-2 trifluorethyl, difluoromethyl ether (Ohio Medical Products)) is a halogenated ether currently being evaluated as an inhalation anaesthetic agent. As reported previously, isoflurane has several advantages compared with halo thane. Its favourable properties include an absence of metabolism in the liver (Halsey et al., 1971), renal toxicity (Mazze, Cousins and Barr, 1974) and sensitization of the myocardium to exogenously administered adrenaline (Joas and Stevens, 1971). With a blood/gas partition coefficient of 1.4 (Cromwell, Eger, et al., 1971) induction and recovery are more rapid than with halothane. There appears to be a need for a new inhalation anaesthetic agent because most of the agents in current use exert circulatory depression which may lead to cardiac failure in patients with cardiovascular diseases, particularly in the presence of restricted coronary reserve. The haemodynamic reactions of patients receiving isoflurane have, so far, been studied only under conditions of surgical stimulation (Graves, McDermort and Bidwai, 1974) or in young unpremedicated volunteers (Cromwell, et al., 1971; Stevens et al., 1971; Dolan et al., 1974). No data are available concerning the cardiovascular effects of isoflurane in geriatric patients and its influence upon myocardial oxygen consumption. This report provides such information. J. TARNOW, M.D.; J. B. BRUCKNER, M.D.; H. J. EBERLEIN, M.D.; W. HESS, M.D.; D. PATSCHKE; Department of Anaes-
thetics, Charlottenburg Clinic, Spandauer Damm 130, Free University of Berlin, West Germany.
PATIENTS AND METHODS
Informed consent was obtained from seven patients, undergoing surgery, whose average age was 63 years. None had significant cardiovascular disease, and a chest x-ray, haematological analysis and blood-gas analysis were all normal. The physical status of the patients (ASA classification) was I or II. Premedication was given i.m. 60 min before the induction of anaesthesia and consisted of atropine 0.5 mg, pethidine 50-100 mg plus promethazine 50 mg. Anaesthesia was induced with etomidate 0.5 mg/kg (Janssen, Diisseldorf), a new non-barbiturate induction agent; suxamethonium 60-100 mg was given i.v. and endotracheal intubation was performed after the administration of topical anaesthesia to the larynx and trachea with 2% tetracaine hydrochloride. Controlled ventilation (Engstrom ventilator) using a semi-closed circuit system with carbon dioxide absorbtion was adjusted to maintain Pa C02 at normal values. During the next 45-60 min anaesthesia was maintained with 70% nitrous oxide and repeated i.v. injections of etomidate 0.1 mg/kg (average total dose after endotracheal intubation 0.3 mg/kg), while the patients were prepared for cardiovascular monitoring. To measure arterial pressure, a Teflon cannula was inserted into the left radial artery and connected to a Statham P 23 Db transducer. A 7 F Swan-Ganz flow-directed catheter was placed in the right median basilic vein, by cut-down, and advanced into the pulmonary artery under pressure monitoring control.
BRITISH JOURNAL OF ANAESTHESIA
670 This catheter allowed simultaneous measurements of right atrial or central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure (Statham P 23 Db transducers) and determination of the cardiac output using the thermodilution technique (Slama and Piiper, 1964). Left ventricular pressure was measured with a catheter-tip manometer (5 F PC 350, Millar Instr.) inserted percutaneously from the left femoral artery under pressure and e.c.g. control. The rate of left ventricular pressure development (dp/dt) was computed continuously with an electronic differentiator. Lead II e.c.g., arterial pressure, central venous or right atrial pressure and left ventricular dp/dt were recorded on a multichannel recorder (Hellige EK21). Cardiac index, stroke volume, stroke index and total peripheral resistance were computed in the usual manner. A modified tension-time index was calculated from the product of mean systolic pressure and the square root of the heart rate (Bretschneider, 1967). End-systolic volume per 100 g of left ventricle (LV) was calculated using the formula (Bretschneider etal., 1972): 1
syst
-xll
Blood-gas analyses (AVL-Gascheck) from arterial and mixed venous blood samples allowed for close control of ventilation and calculations of total body arterio-venous oxygen content difference (CaOa—
o 0a ). To quantify myocardial oxygen consumption, a new complex haemodynamic index (Bretschneider, 1972) was used. The total energy demand (£ T ), that is myocardial oxygen consumption, consists of five additive determinants (ET = E0 + E1 + E2 + Es + Ei). This new concept considers all prime energy costing activities of the heart (Appendix) and requires measurements of five haemodynamic variables: systolic pressure, left ventricular maximum dp/dt, heart rate, ejection time, and duration of systole. After insertion of all the catheters control measurements for cardiovascular variables were obtained under steady-state conditions, and blood samples were taken for blood-gas determinations. Then, inspired isoflurane concentrations of 0.75 vol%, in 70% nitrous oxide in oxygen, were administered in a semi-closed circuit system and haemodynamic measurements were made at 10-min intervals. After 20 min the inspired isoflurane concentration was increased to 1.5 vol% for a further 20 min. Then
isoflurane (but not nitrous oxide) was discontinued using a non-rebreathing system. Fifteen minutes later another set of cardiovascular and blood measurements was obtained. Arterial blood concentrations of isoflurane were analysed by gas chromatography. After completion of all measurements the level of anaesthesia was deepened and the patients were prepared for the surgical procedure. Statistical comparisons were made using the Wilcoxon test for paired data. Changes were considered as significant when P
HAEMODYNAMICS AND MYOCARDIAL OXYGEN CONSUMPTION DURING ISOFLURANE (FORANE) ANAESTHESIA IN GERIATRIC PATIENTS J. TARNOW, J. B. BRUCKNER, H. J. EBERLEIN, W. HESS AND D. PATSCHKE
SUMMARY
The influence of isoflurane on haemodynamics and myocardial oxygen consumption was examined in seven geriatric patients under conditions of controlled ventilation and a normal arterial carbon dioxide tension. During isoflurane/nitrous oxide in oxygen anaesthesia (0.75 and 1.5 vol% inspired isoflurane) no significant changes occurred in cardiac output, stroke volume, heart rate, central venous and pulmonary artery pressure. Arterial pressure decreased, as did total peripheral resistance. A reduction in left ventricular maximum dp/dr (18-39%) was, at least in part, a result of changes in loading conditions. Total body (Ca0) —CvOj) and base excess values remained within the normal range. We consider that the oxygen supply was adequate to meet the metabolic demands of the body as a whole. Myocardial oxygen consumption decreased by 25% during 0.75 vol% inspired isoflurane and by 43.5% with deepening of anaesthesia (1.5 vol% isoflurane).
Isoflurane (Forane, 1 chloro-2-2-2 trifluorethyl, difluoromethyl ether (Ohio Medical Products)) is a halogenated ether currently being evaluated as an inhalation anaesthetic agent. As reported previously, isoflurane has several advantages compared with halo thane. Its favourable properties include an absence of metabolism in the liver (Halsey et al., 1971), renal toxicity (Mazze, Cousins and Barr, 1974) and sensitization of the myocardium to exogenously administered adrenaline (Joas and Stevens, 1971). With a blood/gas partition coefficient of 1.4 (Cromwell, Eger, et al., 1971) induction and recovery are more rapid than with halothane. There appears to be a need for a new inhalation anaesthetic agent because most of the agents in current use exert circulatory depression which may lead to cardiac failure in patients with cardiovascular diseases, particularly in the presence of restricted coronary reserve. The haemodynamic reactions of patients receiving isoflurane have, so far, been studied only under conditions of surgical stimulation (Graves, McDermort and Bidwai, 1974) or in young unpremedicated volunteers (Cromwell, et al., 1971; Stevens et al., 1971; Dolan et al., 1974). No data are available concerning the cardiovascular effects of isoflurane in geriatric patients and its influence upon myocardial oxygen consumption. This report provides such information. J. TARNOW, M.D.; J. B. BRUCKNER, M.D.; H. J. EBERLEIN, M.D.; W. HESS, M.D.; D. PATSCHKE; Department of Anaes-
thetics, Charlottenburg Clinic, Spandauer Damm 130, Free University of Berlin, West Germany.
PATIENTS AND METHODS
Informed consent was obtained from seven patients, undergoing surgery, whose average age was 63 years. None had significant cardiovascular disease, and a chest x-ray, haematological analysis and blood-gas analysis were all normal. The physical status of the patients (ASA classification) was I or II. Premedication was given i.m. 60 min before the induction of anaesthesia and consisted of atropine 0.5 mg, pethidine 50-100 mg plus promethazine 50 mg. Anaesthesia was induced with etomidate 0.5 mg/kg (Janssen, Diisseldorf), a new non-barbiturate induction agent; suxamethonium 60-100 mg was given i.v. and endotracheal intubation was performed after the administration of topical anaesthesia to the larynx and trachea with 2% tetracaine hydrochloride. Controlled ventilation (Engstrom ventilator) using a semi-closed circuit system with carbon dioxide absorbtion was adjusted to maintain Pa C02 at normal values. During the next 45-60 min anaesthesia was maintained with 70% nitrous oxide and repeated i.v. injections of etomidate 0.1 mg/kg (average total dose after endotracheal intubation 0.3 mg/kg), while the patients were prepared for cardiovascular monitoring. To measure arterial pressure, a Teflon cannula was inserted into the left radial artery and connected to a Statham P 23 Db transducer. A 7 F Swan-Ganz flow-directed catheter was placed in the right median basilic vein, by cut-down, and advanced into the pulmonary artery under pressure monitoring control.
BRITISH JOURNAL OF ANAESTHESIA
670 This catheter allowed simultaneous measurements of right atrial or central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure (Statham P 23 Db transducers) and determination of the cardiac output using the thermodilution technique (Slama and Piiper, 1964). Left ventricular pressure was measured with a catheter-tip manometer (5 F PC 350, Millar Instr.) inserted percutaneously from the left femoral artery under pressure and e.c.g. control. The rate of left ventricular pressure development (dp/dt) was computed continuously with an electronic differentiator. Lead II e.c.g., arterial pressure, central venous or right atrial pressure and left ventricular dp/dt were recorded on a multichannel recorder (Hellige EK21). Cardiac index, stroke volume, stroke index and total peripheral resistance were computed in the usual manner. A modified tension-time index was calculated from the product of mean systolic pressure and the square root of the heart rate (Bretschneider, 1967). End-systolic volume per 100 g of left ventricle (LV) was calculated using the formula (Bretschneider etal., 1972): 1
syst
-xll
Blood-gas analyses (AVL-Gascheck) from arterial and mixed venous blood samples allowed for close control of ventilation and calculations of total body arterio-venous oxygen content difference (CaOa—
o 0a ). To quantify myocardial oxygen consumption, a new complex haemodynamic index (Bretschneider, 1972) was used. The total energy demand (£ T ), that is myocardial oxygen consumption, consists of five additive determinants (ET = E0 + E1 + E2 + Es + Ei). This new concept considers all prime energy costing activities of the heart (Appendix) and requires measurements of five haemodynamic variables: systolic pressure, left ventricular maximum dp/dt, heart rate, ejection time, and duration of systole. After insertion of all the catheters control measurements for cardiovascular variables were obtained under steady-state conditions, and blood samples were taken for blood-gas determinations. Then, inspired isoflurane concentrations of 0.75 vol%, in 70% nitrous oxide in oxygen, were administered in a semi-closed circuit system and haemodynamic measurements were made at 10-min intervals. After 20 min the inspired isoflurane concentration was increased to 1.5 vol% for a further 20 min. Then
isoflurane (but not nitrous oxide) was discontinued using a non-rebreathing system. Fifteen minutes later another set of cardiovascular and blood measurements was obtained. Arterial blood concentrations of isoflurane were analysed by gas chromatography. After completion of all measurements the level of anaesthesia was deepened and the patients were prepared for the surgical procedure. Statistical comparisons were made using the Wilcoxon test for paired data. Changes were considered as significant when P
