Thomas H. Cromwell

The cardiovascular effects of a new inhalation anesthetic, Forane, in human volunteers at constant arterial carbon dioxide tension.

The cardiovascular effects of Forane, a new inhalation anesthetic, were examined in seven un-medicated volunteers under conditions of constant arterial carbon dioxide tension and body temperature. Comparison of results during anesthesia with awake values demonstrated maintenance of myocardial function but progressive vasodilatation as anesthesia deepened. No significant changes in the cardiac output, ballistocardiogram I-J wave amplitude, ejection time, mean rate of ventricular ejection, or pre-ejection period occurred with onset or deepening of anesthesia. Arterial pressure decreased, as did total peripheral resistance. Increased muscle and skin blood flow and forearm venous compliance suggested that the loss of resistance was due in part to dilatation of vessels in the skin and muscles. Cardiac output was maintained by an increased heart rate which compensated for the decreased stroke volume. Comparisons of results during the first and fifth hours of anesthesia demonstrated only minor changes with increased duration of anesthesia. These included further increases in forearm blood flow and an increase in base excess.

The Electroencephalogram in Man Anesthetized with Forane

Electroencephalograms (EEC) of seven healthy male volunteers anesthetized with Forane were studied. Body temperature and Paco2 were maintained at normal levels except that hypocapnia was transiently induced once or twice during each study. Increasing doses of Forane produced increasing periods of burst suppression, with complete electrical silence appearing at approximately 2½ per cent end-tidal Forane. At light levels of anesthesia, the frequency of electrical activity was 14 to 17 Hz at a maximum voltage of 120-180 microvolts. At subanesthetic concentrations (below 1.2 per cent) frequency increased and voltage decreased slightly. Hypocapnia did not alter these EEC findings. Audiostimulation could sometimes provoke an EEG response during an electrical silence. In no case was a convulsive EEC pattern (high-frequency, high-voltage spiging activity) seen. Forane-induced EEG changes can be distinguished from those seen with other anesthetics by the maintenance of high-frequency activity at any level where EEG activity is present. Depth of anesthesia can be monitored with the EEG.

The Ventilatory Effects of Forane, a New Inhaled Anesthetic

The ventilatory effects of Forane were studied in ten volunteers and compared with values obtained in eight volunteers anesthetized with halothane. Paco2 averaged 60 torr with both 1.9 per cent alveolar Forane (approximately 1.45 X MAC) and 1.6 per cent halothane (1.9 X MAC). The slopes of the CO2 response curves were depressed to 30 ± 6 per cent (Mean ± SE) of awake control values by 1.28 per cent Forane (approximately 1.0 X MAC) and to 45 ± 7 per cent of controls with 1.05 per cent halothane (1.25 X MAC). Therefore, when equivalent anesthetic doses are considered, less Forane than halothane was needed to increase Paco2 and depress the slope of the CO2 response curve. In contrast to halothane, Forane in increasing concentrations did not cause progressive increases in respiratory frequency. At equal multiples of MAC, Forane produces more profound respiratory depression than halothane, and this depression results from a unique failure of respiratory frequency to increase with increasing depth of anesthesia.

Clinical Signs of Anesthesia

The clinical signs of anesthetic depth (heart rate, mean arterial pressure, pupil diameter, pupil reactivity to light, tearing, and eye movement) were correlated with anesthetic dose in healthy young volunteers. During halothane, halothane—nitrous oxide, Forane, or Forane–nitrous oxide anesthesia at normal PaCO2 (controlled ventilation), only hypotension in the first hour of anesthesia correlated with anesthetic dose. After five hours of halothane or halothane–nitrous oxide, blood pressure remained constant as anesthetic concentration increased. During cyclopropane, diethyl ether, and fluroxene anesthesia, only pupillary dilatation and reduced pupil reactivity to light correlated with anesthetic dose. When nitrous oxide was added to halothane, ether, or fluroxene, mean arterial pressure rose and pupils dilated. During halothane–oxygen anesthesia with spontaneous ventilation, the rise in PaCO2 allowed less hypotension and increased heart rate. Tidal volume decreased and respiratory rate increased as anesthesia deepened. During Forane–oxygen anesthesia with spontaneous respiration, mean arterial pressure, tidal volume, and minute ventilation decreased as anesthesia deepened. In healthy surgical patients anesthetized with halothane or Forane only, incision of the skin modified the clinical signs significantly. While surgery continued, this change in clinical signs persisted during Forane anesthesia, but returned to control during halothane anesthesia.

THE CARDIOVASCULAR AND RESPIRATORY EFFECTS OF ISOFLURANE-NITROUS OXIDE ANAESTHESIA

RéSUMéNous avons étudié les effets cardio-respiratoires de l’anesthésie à l’isoflurane (Forane) associé à un mélange de Protoxyde-Oxygène à 70 pour cent. Cette étude fut réalisée chez huit sujets volontaires, en bonne santé, en respiration contrôlée (PaCO2 35-45 torr) et en respiration spontanée. Nos résultats furent comparés à ceux rapportés dans d’auties études effectuées chez des volontaires avec usage d’isoflurane-oxygène.Sous respiration contrôlee, la pression artérielle moyenne était plus élevée de 10 à 25 pour cent chez les malades recevant du Protoxyde. Sous anesthésie profonde ( 2 MAC environ ) on retrouvait une pression moyenne de 72.5 torr dans le groupe avec usage de Protoxyde, alors qu’un chiffre moyen de 46 torr était obtenu avec usage d’Isoflurane-Oxygene.Tout comme chez les sujets endormis à llsoflurane-oxygène, nous avons observé chez nos sujets un bon maintien de la contractilité myocardique et du débit cardiaque, ceci à tous les niveaux d’anesthésie utilisés, et l’on n’a pas observé d’acidose métabolique.Le débit sanguin musculaire était de deux à quatre fois plus élevé qu’avant I’anesthésie.Des différences cardiovasculaires dans le même sens ont été observées chez les malades en respiration spontanée.Cependant, la présence de Protoxyde d’azote n’a pas modifié la dépression respiratoire observée avec l’usage d’isoflurane-oxygène, à une profondeur de 1.5 MAC, en respiration spontanée, les PaCO2 moyens observés étaient de 58± 3 torr. avec Protoxyde et de 58± 1.4 sans Protoxyde.

The cardiovascular effects of nitrous oxide-halothane anesthesia in man.

The cardiovascular effects of nitrous oxide-halo-thane-oxygen anesthesia were studied in eight unpremedicated healthy male volunteers and the results compared with those obtained in previous studies in which only halothane-oxygen anesthesia was used. Adding nitrous oxide to halothane-oxygen anesthesia resulted in less depression of the cardiovascular system than comparable levels of halothane-oxygen anesthesia. The differences were greatest at light levels of anesthesia and early in the anesthetic course. Most of the differences between the nitrous oxide and non-nitrous oxide groups were abolished at deeper levels of halothane anesthesia or after five hours of anesthesia had elapsed. Body temperature increased an average of 0.3 C with increasing depth of halothane anesthesia when nitrous oxide was present. The effect of discontinuing nitrous oxide for 15 minutes was also compared with data from a previous study in which nitrous oxide was added to halothane-oxygen anesthesia. The results seem to conform a sympathetic stimulating action of nitrous oxide.

The Cardiovascular Effects of Compound 469 (Forane) during Spontaneous Ventilation and CO2 Challenge in Man

The new inhalation anesthetic, Forane, has been shown to produce only minimal depression of cardiac output during controlled ventilation, but a significant decrease in arterial pressure and profound respiratory depression. This study was undertaken to determine whether spontaneous ventilation, with the consequent elevations in CO2, would alter the cardiovascular responses to Forane, and whether Forane alters the cardiovascular response to imposed increases in CO2 (CO2 challenge). During controlled ventilation Forane maintains cardiac output, primarily through an increase in heart rate at the expense of stroke volume. Spontaneous ventilation alters the cardiovascular response to Forane, in that heart rate and cardiac output are further increased. These changes can be explained by the increase in Paco2 secondary to spontaneous ventilation. Cardiovascular CO2 response slopes reveal that Forane decreases the response of the cardiovascular system to increases in Pco2 As in previous studies with Forane, the authors did not find any stimulation of the cardiovascular system with time.

The Cardiovascular Effects of Halothane in Man during Spontaneous Ventilation

The effects of duration of anesthesia on the cardiovascular responses to halothane in eight healthy male volunteers were studied during spontaneous ventilation and CO2 challenge. We compared these results with those obtained in a previous study of another group of volunteers during controlled respiration. Spontaneous ventilation lessened the depression of the cardiovascular system associated with halothane anesthesia. Cardiac output, heart rate, mean arterial pressure, left ventricular work, IJ-wave amplitude, and muscle blood flow were all greater during spontaneous than during controlled ventilation. Cardiovascular stimulation also occurred with duration of anesthesia in the presence of spontaneous ventilation. Cardiac output, heart rate, left ventricular minute work, and myocardial function increased 20 to 40 per cent in the course of five hours of halothane anesthesia, while total peripheral resistance and mean right atrial pressure decreased. Finally, halothane (like Forane, fluroxene, ether, and cyclopropane) depressed the cardiovascular responsiveness to carbon dioxide challenge. However, at twice MAC, the depression of the cardiac output and arterial pressure responses was more with halothane than with fluroxene or ether.

Adrenal Function During Long-Term Anesthesia in Man

Summary Plasma 11-OHCS were measured in 12 subjects during 7 hr of general anesthesia with endotracheal nitrous oxide (N2O) and halothane, and halothane alone. The 5 subjects who received the N2O-halothane anesthesia showed an early rise in plasma 11-OHCS, which corresponded to the duration of the excitation phase. After the short rise, the plasma 11-OHCS fell to hypoadrenal levels. The subjects who received halothane only (rapid induction of anesthesia) showed no rise in plasma 11-OHCS, but the 11-OHCS fell to hypoadrenal levels after induction. After 2 to 4.5 hr of general anesthesia, the plasma 11-OHCS rose spontaneously and remained elevated until the end of anesthesia. The sudden rise was not due to changes in feedback threshold and did not correlate with changes in concentration of the anesthetic. The urinary catecholamine secretion was not significantly altered during the anesthesia compared to a control period.