Edwin S. Munson

The Relationship between Age and Halothane Requirement in Man

The minimum alveolar concentration (MAC) values for halothane in eight age groups were determined. MAC was found to be highest in newborns and lowest in the elderly. These changes in anesthetic requirement with age parallel changes in cerebral oxygen consumption, cerebral blood flow and neuronal density.

Effect of Nitrous Oxide on Venous Air Embolism

The effect of nitrous oxide on the median lethal dose (LD50) of intravenously injected air was studied in rabbits. Determinations were performed in similar animal groups anesthetized with 1.0 per cent halothane and with 0.5 per cent halothane combined with 72–76 per cent nitrous oxide. In the halothane group, the LD50 was 0.55 ml./kg. In the nitrous oxide group, the LD50 was 0.16 ml./kg. Difference in values is explained on the basis of the differential solubility of nitrous oxide and nitrogen in blood. The finding of a reduction in LD50 value by a factor of 3.4 shows good agreement with theoretical calculations. We suggest that it may be hazardous to administer high concentrations of nitrous oxide to patients in whom the possibility of air embolism exists.

Enflurane, Isoflurane, and Halothane and Isolated Human Uterine Muscle

The effects of equipotent concentrations of enflurane, isoflurane, and halothane on isolated human uterine muscle have been evaluated. Three anesthetic concentrations (0.5, 1.0, and 1.5 MAC) were studied. Specimens included myometrial strips from 45 non-gravid and seven gravid uteri. Both groups of muscle strips showed significant (P < 0.05) and progressive depression of contractility with all anesthetics. However, the extents of depression at each anesthetic level studied were similar with all drugs. Enflurane, isoflurane, and halothane are equally depressing to isolated human uterine muscle.

Change in pulmonary venous admixture with varying inspired oxygen.

Pulmonary venous admixture (&OV0422;sp/&OV0422;t) was analyzed as a function of fractional concentration of inspired O2 (Fio2) in 30 patients who required postoperative mechanical ventilation. Pulmonary and radial artery blood-gas tensions and pH were measured and &OV0422;sp/&OV0422;t was calculated with Fio2 ranging from 0.21 to 1. In all patients, &OV0422;sp/&OV0422;t decreased when Fio2 was increased from 0.21 to 0.4 and then stabilized to an Fio2 of approximately 0.6. As the Fio2 was increased to 1, &OV0422;sp/&OV0422;t increased. Since the inhalation of gas mixture with Fio2 ≥ 0.6 increased right-to-left intrapulmonary shunting of blood, we recommend respiratory function be evaluated during inhalation of a clinically useful concentration of O2 rather than at an Fio2 of 1.

The effects of halothane, fluroxene and cyclopropane on ventilation: a comparative study in man.

The effects of halothane, fluroxene, and cyclopropane on ventilation and the ventilatory response to CO2 were measured in healthy unpre-medicated human subjects. To permit comparison of anesthetic effect, measurements were made utilizing the concept of the minimum anesthetic (alveolar) concentration. With each agent, ventilatory response to CO2 progressively decreased with increasing anesthetic depth. During deep levels of halothane and fluroxene anesthesia, the mean ventilatory response approached apnea. At an equivalent depth of cyclopropane anesthesia mean ventilatory response was 40 per cent of the mean (unanesthetized) value. During spontaneous ventilation mean values for Paco2 for halothane were greater (P < 0.05) than mean values for fluroxene at each anesthetic level studied. Mean values for Paco2 for halothane were also greater (P < 0.05) than mean cyclopropane values during deep levels of anesthesia. Rate of breathing increased progressively with increasing anesthetic levels of each agent. We conclude that at equipotent anesthetic concentrations halothane and fluroxene are more potent depressants to respiration than cyclopropane.

Ketamine and Intraocular Pressure in Children

The effect of ketamine on intraocular pressure (IOP) was studied in 10 children. Control IOP values were determined prior to induction of anesthesia, following premedication with atropine alone or in combination with pentobarbital and meperidine. After the IM injection of 8 mg/kg of ketamine, the IOP was determined at 5, 10, 15, and 20 minutes. Mean (± SD) IOP values before and after ketamine were 22.2 ± 4.8 and 16.7 ± 3.3 torr (p<0.001), respectively. The authors believe that the reduction in IOP was not due to ketamine, per se, but rather to lack of patient relaxation and cooperation during control measurements. At the end of 20 minutes, a second dose of ketamine, this time 1 mg/kg IV, was given and measurements were repeated at the same intervals. In 5 patients, the effects on IOP of d-tubocurarine, endotracheal intubation, and N2O inhalation also were evaluated. A significant increase (6.7 torr) in IOP was observed only after endotracheal intubation. The authors conclude that ketamine does not raise IOP in the healthy pediatric patient and, therefore, can be used for ophthalmic procedures requiring sedation or anesthesia.

Etidocaine, Bupivacaine, and Lidocaine Seizure Thresholds in Monkeys

The central nervous system toxicities of etidocaine, bupivacaine, and lidocaine were studied during constant-rate intravenous infusions in rhesus monkeys. Comparison of drug effects was achieved by determining the drug dosages and arterial plasma concentrations that induced electrical seizure activity. The central nervous system toxicity of etidooaine was similar to that of bupivacaine. The toxicity of each was four times greater than that of lidocaine. Since the drug infusion rates were proportional to anesthetic potencies in clinical usage, the therapeutic-toxic ratios of these three drugs are similar.

Circadian Variations in Anesthetic Requirement and Toxicity in Rats

The effects of circadian rhythm on cyclopropane and halothane requirements (MAC) and cyclopropane toxicity have been investigated at four-hour intervals in rats synchronized to a standard 24-hour day. Longitudinal and transverse determinations in four groups of animals showed characteristic circadian patterns, with the highest values occurring in the early dark (active) period and lowest values occurring in the early light (inactive) period. Differences in MAC were significant (P < 0.05) for each agent, with maximal changes showing 10 to 14 per cent variation from mean values. Circadian variation in cyclopropane toxicity (apneic concentration) was not found. However, calculations of the anesthetic index showed a cyclic pattern similar to that observed for MAC.

Intraocular Pressures in Children during Isoflurane and Halothane Anesthesia

The effects of isoflurane and halothane on intraocular pressure (IOP) were studied in 28 children. Measurements were made during spontaneous ventilation and at various levels of reduced PaCO2 achieved by controlled ventilation. Control IOP values were determined prior to anesthesia following premedication with chloral hydrate, pentobarbital, or pentobarbital with meperidine. At roughly equivalent levels of anesthesia, mean IOP values during spontaneous ventilation ranged from 16.3 to 17.6 torr for each anesthetic These values were significantly less (P < 0.01) than control values only in those patients receiving chloral hydrate who did not cooperate. In contrast, no significant change in IOP was found in more sedated and cooperative patients who received pentobarbital and meperidine. Moderate hypocarbia and hypercarbia over a range of PaCO2 > 42 ton-had little influence on IOP. We conclude that IOPs during isoflurane and halothane anesthesia do not differ significantly from IOP in the sedated, cooperative, healthy pediatric patient.

Anesthetic Solubility Coefficients for Maternal and Fetal Blood

Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C. Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble. Reasons for these differences cannot be accounted for by differences in the type or amount of hemoglobin present.