Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effects. The direct inotropic influence of etomidate, ketamine, midazolam, propofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with those reported clinically. Methods: Atrial tissue was obtained from 16 patients undergoing coronary bypass surgery. Each fragment was divided into three strips, and one anesthetic was tested per strip in increasing concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 Hz, and maximum isometric force was measured. Induction agents were studied in two groups, group 1 (n = 7) containing thiopental midazolam, and propofol, and group 2 (n = 9) consisting of etomidate, ketamine, and propofol. Results: The tested anesthetics caused a concentration-dependent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC(50)s (mean +/- SEMI mu M) for inhibition of the contractility were: thiopental 43 +/- 7.6, propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 145 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. Conclusions: This is the first study demonstrating a concentration-dependent negative inotropic effect of intravenous anesthetics in isolated human atrial muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. In contrast, thiopental showed strong and ketamine showed slight negative inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation.

Inotropic effects of propofol, thiopental, midazolam, etomidate, and ketamine on isolated human atrial muscle.

Summary

The haemodynamic changes following induction of anaesthesia with equipotent doses of propofol and thiopentone have been compared. Propofol caused a significant fall in arterial blood pressure and total peripheral resistance, with a slight fall in cardiac output. There were no changes in heart rate. Apart from an initial, but statistically insignificant increase in heart rate, similar changes were produced by thiopentone, but to a lesser degree. It is concluded that induction of anaesthesia with propofol results in acceptable haemodynamic changes, but that the agent is more depressant to the cardiovascular system than thiopentone.

The haemodynamic effects of intravenous induction. Comparison of the effects of thiopentone and propofol.

Currently, there is no one drug that is the agent of choice for induction in rapid sequence intubation in the emergency department (ED). All agents currently used as induction agents in the ED offer distinct advantages for various clinical conditions, but each has a significant side effect profile and specific contraindications that limit its use in many common clinical settings. A review of the data available from the anesthesia literature suggests that etomidate possesses many properties that may make it the agent of choice for rapid sequence intubations in the ED. These advantages include excellent pharmacodynamics, protection from myocardial and cerebral ischemia, minimal histamine release, and a hemodynamic profile that is uniquely stable. Disadvantages include a lack of blunting of sympathetic response to intubation, a high incidence of myoclonus, prominent nausea and vomiting, potential activation of seizures in patients with epileptogenic foci, and impaired glucocorticoid response to stress. Further studies are needed to evaluate the advantages and disadvantages of the use of etomidate for rapid sequence intubation in the ED.

A review of etomidate for rapid sequence intubation in the emergency department

ICU physicians should abandon the use of etomidate

The effects of fentanyl on arterial pressure and heart rate increases during laryngoscopy and intubation were studied in 45 normotensive, surgical patients, who were randomly allocated to three groups receiving 2 or 6 micrograms/kg of fentanyl or saline in a double-blind fashion before anaesthetic induction with thiopental. Fentanyl supplementation with 2 micrograms/kg significantly attenuated the arterial pressure and heart rate increases during laryngoscopy and intubation, and fentanyl, 6 micrograms/kg, completely abolished these responses. Moreover, fentanyl given during the induction decreased the amount of fentanyl needed during the operation. Respiratory depression was not observed during recovery.

Attenuation of the circulatory response to laryngoscopy and intubation by fentanyl.

The acute effects of althesin, etomidate and fentanyl upon haemodynamics, myocardial contractility and oxygen consumption of the heart were studied in healthy premedicated patients (n = 15) lightly anaesthetized with N2O-O2 (ratio 2:1), 0.3 volumes per cent of halothane and isoflurane respectively. All individuals were ventilated at a normal level. The patients (n = 9) in the halothane group received etomidate 0.3 mg/kg and 20 minutes later althesin 0.075 ml/kg intravenously. In a second group of 6 patients on isoflurane fentanyl 0.01 mg/kg was given. Etomidate did not affect the cardiovascular system significantly. While the decrease in blood pressure after althesin (24 per cent) was the result of a reduction in total peripheral resistance (32 per cent), hypotension associated with fentanyl (23 per cent) was caused by diminished cardiac output due to bradycardia (18 per cent). Load data, heart rate, and maximum dp/dt indicated moderate negative inotropic properties only of althesin. Using the complex haemodynamic parameter developed by Bretschneider the myocardial oxygen consumption was calculated. The energy demand of the heart decreased with etomidate, althesin and fentanyl by 14 per cent, 16 per cent and 32 per cent respectively. It is concluded that the risk of cardiovascular depression at induction in patients with impaired myocardial performance and coronary insufficiency can be minimized with etomidate and/or fentanyl.

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Effects of althesin, etomidate and fentanyl on haemodynamics and myocardial oxygen consumption in man

[Studies on the circulatory effects of etomidate in man (author's transl)].

[The influence of ethrane on the haemodynamics and the oxygen supply of the myocardium in comparison to halothane (author's transl)].

[Experimental studies in animals on the effects of etomidate (R 26 490-sulfate) on the circulation and on the oxygenation of the myocardium (author's transl)].

Ketamine is an induction agent. This experimental study was designed to investigate the immediate effects of ketamine upon haemodynamics, inotropism and myocardial oxygen consumption during induction. In a circulatory steady state of a piritramide - nitrous oxide - oxygen basic anaesthesia normoventilated dogs (n = 8) received intravenous injections of 5.0 and 10.0 mg/kg ketamine within 30 sec at random. Immediately after administration of 10.0 mg/kg ketamine the cardiac output (thermo dilution method) rose (27%) on account of tachycardia while the total peripheral resistance (40%) and the mean arterial pressure (23%) decreased. The decrease in stroke volume (37%) and the inotropic parameter dp/dt max (42%) as well as the increase in the end-diastolic left ventricular pressure (31%) and in the pressure of the pulmonary artery (11%) suggest considerable myocardial depressor properties of ketamine. The change in haemodynamics was paralleled with an increase in myocardial oxygen consumption (47%), which was initially met by an increase in coronary blood flow (25%) and an additional oxygen utilization (20%). The increase in arterio-coronary venous oxygen difference is believed to be due to a constriction of the coronary arteries after ketamine. Since external cardiac work remained unchanged,while myocardial contractility and myocardial wall tension (Psyst) decreased, the increase in heart rate (63%) explains the rise in myocardial oxygen consumption. The efficiency of cardiac work, which is defined as the ratio of myocardial displacement work to myocardial energy demand, decreased (31%) and illustrated the uneconomic work of the heart under the influence of ketamine. The clinical utilization of the data obtained from this study are discussed.

A. Weymar

Papers

Effects of althesin, etomidate and fentanyl on haemodynamics and myocardial oxygen consumption in man

[Studies on the circulatory effects of etomidate in man (author's transl)].

[The influence of ethrane on the haemodynamics and the oxygen supply of the myocardium in comparison to halothane (author's transl)].

[Experimental studies in animals on the effects of etomidate (R 26 490-sulfate) on the circulation and on the oxygenation of the myocardium (author's transl)].

[The effect of ketamine on haemodynamics and myocardial oxygen consumption in anaesthetized dogs (author's transl)].