Wendell C. Stevens

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.

Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function (brain, heart, liver, and kidney).

The authors attempted to determine whether hypotensive anesthesia or the method of inducing hypotension has any effect on postoperative brain, liver, or kidney function and myocardial status following total hip arthroplasty. Thirty patients were anesthetized with halothane–nitrous oxide for total hip arthroplasty and randomly assigned to one of three groups. In two groups mean arterial blood pressure was decreased to 50 torr by high inspired concentrations of halothane (n = 9) or sodium nitroprusside (n = 12). In the third group (n = 9) mean blood pressure was maintained within 20 per cent of control. Intraoperative blood losses decreased from 1,183 ± 172 ml in the normotensive group to 406 ± 102 ml and 326 ± 41 ml in the halothane and nitroprusside hypotensive groups, respectively. Neither method of inducing hypotension nor hypertensive technique affected the results of postoperative tests of cerebral, hepatic, or renal function and myocardial status. These tests were performed before anesthesia and operation and at intervals in the postoperative course. In this small group of patients, deliberate hypotension for total hiparthroplasty added no morbidity and significantly shortened operating time, decreased blood loss, and decreased the number of blood transfusions needed.

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.

Comparison of the Arrhythmic Doses of Epinephrine during Forane, Halothane, and Fluroxene Anesthesia in Dogs

The effect of Forane on epinephrine-induced cardiac arrhythmias was tested in dogs by comparing it with halothane and fluroxene. The doses of epinephrine necessary to produce two or more premature ventricular contractions at 1.25 and 2.0 MAC and at Paco2s of 20, 40, and 80 torr were determined. Only 14 to 22 per cent as much epinephrine as in the awake state was needed to produce arrhythmias during halothane anesthesia. The amounts of epinephrine which induced arrhythmias during fluroxene and Forane anesthesia did not differ from the values in awake animals, With Forane, production of arrhythmias required progressively more epinephrine as Paco2 increased. With halothane and fluroxene, the same trend was present, but it was not significant. As depth of anesthesia increased, more epinephrine was needed to produce arrhythmias with all agents tested.

Comparison of the anesthetic requirement for tolerance of laryngeal mask airway and endotracheal tube.

We tested the hypothesis that the laryngeal mask airway (LMA) is tolerated at lighter levels of anesthesia than an endotracheal tube (ET). We studied 20 unpremedicated, nonsmoking ASA physical status I or II patients aged 18–40 yr whose surgery lasted >1 h. Subjects were randomly assigned to receive either an ET or LMA. Anesthesia was induced with intravenous propofol and the LMA or ET was inserted. The ET-group patients received 1.5 mg/kg of succinylcholine, preceded by vecuronium (0.015 mg/kg IV). Maintenance of anesthesia was with only isoflurane and approximately 66% N2O in O2 by spontaneous ventilation. All gas concentrations were measured by a Raman spectrometer sampling from the breathing circuit end of the LMA or ET. Toward the end of the procedure, the end-tidal N2O and isoflurane concentrations were allowed to decrease to <3 vol% and 0.8 ± 0.05 vol%, respectively. The end-tidal isoflurane concentration was then decreased in 0.1% ± 0.05% decrements, each stable value being held for 5 min. The patient was observed for signs of reaction to the presence of the LMA or ET. The mean (range) end-tidal isoflurane concentrations for reaction to ET and LMA were 0.55% (0.4–0.7) and 0.35% (0.2–0.51), respectively (P < 0.001). These data confirm the original hypothesis of the study.

Isoflurane: An Anesthetic for the Eighties?

The introduction of isoflurane to clinical practice follows the search for a nonflammable, potent inhalation anesthetic which, above all, is chemically stable so as to resist biodegradation or attack by other chemicals. These attributes characterize isoflurane (Table 2). The hoped for freedom from hepatic and renal toxicity and from carcinogenic and mutagenic properties is a reality with this drug. Other favorable characteristics include relatively low solubility in blood in relation to anesthetic dose, lack of arrhythmogenic effect, provision of good muscle relaxation, and the absence of central nervous system excitation. Its moderate pungency detracts slightly from the ease of inhaled induction. Disadvantages include respiratory depression, reduced arterial blood pressure, uterine relaxation, decreased uteroplacental blood flow, and likely ability to trigger malignant hyperpyrexia. The frequency and/or significance of tachycardia and dilation of muscle blood vessels in clinical practice remain to be established. We believe isoflurane is a significant improvement over earlier potent inhalation anesthetics.

Sister Chromatid Exchanges Induced by Inhaled Anesthetics

There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluroxene alone caused bacterial mutations. The authors used the sister chromatid exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister chromatid exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagcnic-carcinogens, particulary in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide, diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.

The dependence of pancuronium- and d-tubocurarine-induced neuromuscular blockades on alveolar concentrations of halothane and forane.

The neuromuscular blocking effects of pancuronium and d-tubocurarine were directly related to alveolar anesthetic concentrations in a study of 54 patients anesthetized with Forane and 70 per cent nitrous oxide and 54 patients anesthetized with halothane and 70 per cent nitrous oxide. The median effective doses of pancuronium necessary for 50 per cent depression of twitch height (ED21) were 0.60, 0.36, and 0.18 mg/m2 during 0.5, 1.0, and 1.5 per cent Forane anesthesia, and 0.82, 0.49, and 0.35 mg/m2 during 0.4, 0.8, and 1.2 per cent halothane anesthesia, respectively. The ED21‘s of d-tubocurarine were 2.40, 1.87, and 1.46 mg/m2 during 0.5, 1.0, and 1.5 per cent Forane anesthesia, and 6.40, 3.90, and 2.45 mg/m2 during 0.4, 0.8, and 1.2 per cent halothane anesthesia, respectively. The authors conclude that smaller doses of pancuronium and d-tubo-curarine are needed for adequate relaxation with higher alveolar concentrations of Forane and halothane. Also, during comparative neuromuscular studies of pancuronium and d-tubocurarine, anesthetic concentrations of Forane and halothane should be monitored in arterial blood or alveolar gas.

Comparative Neuromuscular Effects of Forane and Halothane Alone and in Combination with d-Tubocurarine in Man

In human volunteers, Forane failed to alter twitch height, but increased average neuromuscular refractory period and prevented a sustained response to stimulation at higher frequencies of tetanus. These effects were dose-related. Surgical patients anesthetized with 1.25 MAC Forane were unable to sustain tetanus at more than 120 Hz. In contrast, patients anesthetized with 1.25 MAC halothane were able to sustain tetanus at 200 Hz. In 15 patients anesthetized with 1.25 MAC Forane, the median effective dose of d-tubocurarine needed to produce a 50 per cent depression of twitch height (ED50) was 1.70 mg/m2. In contrast, the ED50 of d-tubocurarine in 17 patients anesthetized with 1.25 MAC halothane was 5.69 mg/m2. Thus, 3.3 times as much d-tubocurarine was needed to produce a 50 per cent depression of twitch height with halothane.