Anesthetics as teratogens: nitrous oxide is fetotoxic, xenon is not.

Exposure of pregnant rats to the anesthetic nitrous oxide on the ninth day of gestation causes fetal resorption, skeletal anomalies, and macroscopic lesions including encephalocele, anophthalmia, microphthalmia, and gastroschisis. The inert gas xenon, which has anesthetic properties similar to those of nitrous oxide, does not cause teratogenic effects under the same experimental conditions.

Effects of subanesthetic concentrations of enflurane on rat pregnancy and early development.

Anesthetic pollutants in the operating room have been implicated in producing spontaneous abortion in exposed personnel and congenital malformations among their offspring. To test the effects of trace concentrations of enflurane on pregnancy, rats were exposed to two levels (10.7 and 63.7 ppm) of the anesthetic for 8 hr daily from days 1 to 19 of pregnancy. Litter sizes were not affected but birth weights of exposed offspring were slightly higher than controls. During lactation, cross-fostering studies were performed. Exposed offspring were housed with nonexposed mothers and vice versa to determine if exposure during pregnancy affected early development. Weights at 7, 14, and 21 days of age did not differ among the offspring in the lower dose experiment. Weights of the cross-fostered groups in the high dose experiment were decreased at day seven compared to controls. In the same experiment, exposed offspring housed with exposed mothers were heavier than controls on day 21 of lactation. The modest nature of these alterations suggests that enflurane has little or no gross effect on rat pregnancy and postnatal development.

A flask for preparation of standards in gas chromatography.

An inexpensive modification to the stopcock of a conventional gas-sampling bulb permits convenient preparation of standards for gas chromatography.

An American approach to anaesthesia research and a British perspective.

The organisation of research in the Department of Anesthesiology at the University of Michigan is described and the comments of a British Senior Registrar working within the system are recorded.

Halothane requirement during pregnancy and lactation in rats.

Near-term pregnancy is associated with a decrease in the minimum alveolar concentration (MAC) for halothane in ewes. Although increased progesterone levels might account for this change, a correlation between MAC and the known variations of progesterone levels which occur throughout gestation and the postpartum period has not been performed. Therefore, MAC for halothane was determined in nonpregnant, 10 days pregnant, term, and postpartum lactating rats. MAC values were significantly decreased by 19 per cent on the tenth day of pregnancy, and by 16 per cent at term, but they returned to control values 5 days postpartum. These changes did not correlate with the known changes in progesterone levels during pregnancy and lactation, and the authors conclude that progesterone is not responsible for the reduction in halothane MAC.

Cardiac failure associated with hypocalcemia.

Rapid transfusion of citrated whole blood was associated with acute hypotension and a rising central venous pressure in a patient undergoing pelvic exenteration and hemipelvectomy. Evidence of cardiac failure was accompanied by a precipitous decrease in serum ionized calcium (Ca++) concentration. When the rate of blood transfusion was slowed, arterial blood pressure returned to the control level and serum Ca++ increased.

In vivo response of air-filled balloon-tipped catheters to nitrous oxide.

Four balloon-guided pulmonary artery catheters from each of two manufacturers were placed in eight anesthetized dogs, and balloon volumes were measured at randomized time intervals from 1 to 30 min during (1) ventilation with 100% oxygen and (2) ventilation with 70% nitrous oxide in oxygen. Catheters from one manufacturer showed no increase in balloon volume in either condition. The balloon volumes of catheters from the second manufacturer increased up to 17% during ventilation with nitrous oxide. Balloons of these catheters required less inflation pressure than those from the first manufacturer. It was concluded that the effects of nitrous oxide on the balloon volumes of pulmonary artery catheters in vivo are of little clinical significance.

Clinical comparison of sevoflurane and isoflurane when administered with nitrous oxide for surgical procedures of intermediate duration.

The purpose of this study was to compare the haemodynamic effects and emergence times of anaesthesia with sevoflurane with those of isoflurane when the agents were administered with nitrous oxide to adult patients (ASA I and II) undergoing surgery of at least an hour in duration. Fifty patients were randomly assigned to receive either 0.65 minimum alveolar concentration (MAC) (1.3%) sevoflurane or 0.65 MAC (0.8%) isoflurane together with 60% nitrous oxide following induction with thiopentone, fentanyl, and succinylcholine. Systemic blood pressure and heart rate trends were similar for both groups for the duration of anaesthesia. However, differences in systolic blood pressure measurements were noted at one minute after incision (99 +/- 3 mmHg, mean +/- SE, in the sevoflurane group compared with 109 +/- 4 mmHg for isoflurane), and at emergence (125 +/- 3 mmHg for sevoflurane, 134 +/- 3 mmHg for isoflurane), and in diastolic blood pressure measurements at five minutes after intubation (64 +/- 2 mmHg for sevoflurane, 73 +/- 3 mmHg for isoflurane). Recovery of response to command was more rapid after discontinuation of sevoflurane-nitrous oxide (9.9 +/- 1.1 min) than after isoflurane-nitrous oxide (13.9 +/- 1.3 min). Despite earlier emergence, patients who had received sevoflurane did not request postoperative analgesia sooner. We conclude that the purported advantages of sevoflurane, namely haemodynamic stability and rapid emergence, can be expected even when the agent is administered at 0.65 MAC (1.3%) in nitrous oxide to a typical adult surgical population undergoing procedures of intermediate duration (2.3 +/- 0.2 hr).

Anesthetic action and virus replication: inhibition of measles virus replication in cells exposed to halothane.

Replication of measles virus in BSC cells was studied in the presence of halothane, a commonly used volatile anesthetic. At clinical concentrations of the anesthetic, appearance of progeny virus was decreased in a dose-related manner. This inhibition was reversible as the removal of halothane allowed virus replication to be resumed. Studies attempting to elucidate the mechanism of action of the anesthetic inhibition of virus replication revealed that halothane did not directly inactivate the virus particle or prevent viral adsorption to the cell. Infectious virus and nucleocapsid production were decreased or stopped, depending on the anesthetic dosage used. Direct immunofluorescent staining for measles virus antigen was negative in cells treated at the higher concentrations of halothane. Recovery of nucleocapsid production started within a few hours after removal of halothane. Furthermore, the combined inhibitory effects on viral ribonucleic acid synthesis of 5-azacytidine and halothane were additive. This evidence suggests that inhibition of measles virus replication occurs at or before ribonucleic acid synthesis.

Inhibiting effects of enflurane and isoflurane anesthesia on measles virus replication: comparison with halothane.

Replication of measles virus in BSC cells was studied in the presence of enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether), a commonly used volatile anesthetic agent, and its isomer, isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether). At clinical concentrations of the anesthetics (up to 4%), cell division was retarded, whereas only minimal toxic cellular effects were observed. The appearance of progeny virus from the cell cultures exposed to these anesthetics was decreased in a dose-related manner. Incorporation of [(3)H]uridine into measles virus nucleocapsids also decreased progressively with increasing anesthetic concentrations. In comparing the inhibition of measles virus replication in the presence of halothane (2-bromo-2-chloro,1,1,1-trifluoroethane), enflurane, or isoflurane, it was found that both inhibition of the appearance of infectious virus at 48 h postinfection and incorporation of [(3)H]uridine into measles virus nucleocapsids were proportional to the anesthetic concentrations. An equivalent degree of effect was produced by anesthetically equivalent concentrations of the three anesthetics (minimal alveolar concentration) but not by absolute concentrations. In addition, recovery of infectious virus synthesis from the inhibition encountered during exposure of infected BSC cells to halothane or isoflurane was also investigated. In cultures exposed to halothane or enflurane, recovery of infectious virus synthesis was rapid and complete. Recovery of virus synthesis was slower after isoflurane removal and did not reach the peak control titers of infected cultures not exposed to the anesthetic. Treatment with halothane resulted in the formation of a preponderance of slowly sedimenting virus nucleocapsid particles which contained less than full-length ribonucleic acids after anesthetic removal. Neither enflurane nor isoflurane treatment of BSC cultures resulted in the formation of significant levels of these slowly sedimenting particles with short genomes after anesthetic removal.

Blind oral tracheal intubation of rats.

Tracheal intubation is often necessary for experiments involving anesthetized rats. Previously described methods for endotracheal intubation have required either a tracheostomy or intubation under direct vision. These techniques require considerable time and skill. Therefore we dissected rats to evaluate the anatomy of the airway. Using these data, we originated a technique for blind oral tracheal intubation using a modified 16-gauge intravenous catheter. The technique has a reasonable success rate and can be performed much more rapidly than conventional methods.

A comparison of methods of blood withdrawal and sample preparation for potassium measurements.

The effect on measured potassium values of a number of factors involved in sample acquisition and preparation were investigated. Measured potassium values in either plasma or serum were not influenced by the site of sample withdrawal, the presence of a tourniquet, or the time elapsed between blood sampling and analysis. However, increasing heparin concentrations and/or volumes decreased potassium values. The highest values were obtained in samples obtained in a syringe that had been washed with minimum volumes of heparin. It is concluded that this common clinical practice is based on a sound scientific rationale.

The QT interval and serum ionized calcium.

The correlation between serum ionized calcium (Ca++) levels and three ECG QT intervals (Q-OTC, Q-ATC, and Q-ETC) was assessed in 20 adult patients. The relationship between each QT interval and Ca++ level, based on 209 Ca++ determinations through a range of 1.0 to 4.0 mEq/liter, is best described by a hyperbolic function. Although Q-OTC and Q-ATC predict Ca++ levels more accurately than Q-ETC, all QT intervals are clinically unreliable as guides to the presence of hypercalcemia. Similarly, the usefulness of the QT intervals in the diagnosis of hypocalcemia is limited by the wide distribution of normal values.

Cardiovascular responses and changes in plasma cation levels associated with infusion of hyperosmolar urea solutions.

In four patients, infusion of a hyperosmolar solution of urea to decrease brain volume was associated with hypotension and a decreasing of plasma levels of ionized calcium. This prompted a further study into the effects of intravenous hyperosmolar urea solutions on cardiovascular function and plasma levels of cations in the anesthetized dog. Using an infusion rate of 250 mg/kg/min, significant (p less than 0.05) reductions in mean arterial pressure, systemic vascular resistance, hematocrit, and levels of plasma sodium and ionized calcium were found. These changes were associated with significant (p less than 0.05) increases in cardiac output, right atrial pressure, arterial PO2 and PCO2, and levels of plasma potassium. It is concluded that rapid infusions of hyperosmolar urea may have important effects of hemodynamic status and plasma cation concentrations.

Effect of protamine on plasma ionized calcium in the dog.

The anaesthetized, heparinized health adult dogs were infused with protamine sulphate 3 mg X kg-1 and plasma ionized calcium was measured. A significant (p less than 0.01) decrease in ionized calcium occurred which preceded the maximal reduction in cardiac output and systemic arterial pressure. The clinical implications of these results are discussed.

Hypocalcaemia during rapid blood transfusion in anaesthetized man.

In anaesthetized patients, administration of citrated whole blood for 5 min at controlled rates of 50, 100 and 150 ml/70 kg/min resulted in decreases in the calcium ion concentration (Ca2+) of 14, 31 and 41%, respectively. Ca2+ returned rapidly to the control values after termination of the transfusion. Reciprocal changes in serum citrate concentrations occurred, suggesting that the transient hypocalcaemia was a result of redistribution of citrate and hepatic or renal clearance from the vascular space. The total serum calcium concentration did not change significantly during rapid blood administration. Normal saline infusion at 100 ml/70 kg/min caused no change in Ca2+; however, plasma protein administration at this rate resulted in an 18% decrease in Ca2+, presumably as a consequence of the binding of calcium ions to anionic sites on plasma protein. Hypocalcaemia accompanying blood transfusion is a transient phenomenon, dependent on the total dose of citrate administered and the rate of infusion. Rational calcium replacement therapy during massive blood transfusion may now be based on direct Ca+ measurement.

Plasma levels and cardiovascular effect of nitroglycerin in pregnant sheep.

The cardiovascular effects and blood levels of intravenous nitroglycerin in mother and foetus were studied in normotensive and hypertensive ewes. Although nitroglycerin produced a reduction in uterine blood flow following a decrease in blood pressure, there was little if any incidence of adverse effects in the foetus. Nitroglycerin was detected in all but two samples of foetal arterial blood but the foetal/maternal artery ratio was only 0.04. Nitroglycerin merits further evaluation for the treatment of acute hypertensive episodes in the preeclamptic patient.

Termination of cardiopulmonary bypass facilitated by insulin.

A 61-year old woman with severe coronary artery disease underwent three-vessel coronary bypass surgery. Difficulty was encountered in terminating cardiopulmonary bypass, but there was dramatic improvement following the administration of intravenous insulin. The use of insulin to facilitate termination of cardiopulmonary bypass is discussed.

Alterations in influenza virus pulmonary pathology induced by diethyl ether, halothane, enflurane, and pentobarbital anesthesia in mice.

Three-week-old CD-1 mice infected with the PR-8 (mouse-adapted) strain of influenza virus while exposed to enflurane demonstrated a decrease in virus titers from the lungs of infected animals, less abnormality of lung histology, and an increase in survival in animals as compared with those receiving the other anesthetics tested. Greater than 90% mortality occurred in groups of mice which inhaled aerosolized virus and received no anesthesia, pentobarbital, diethyl ether, or halothane anesthesia 96 h following infection. Infected mice anesthetized with enflurane 96 h post-infection had significantly lower mortality rate (68%) when compared with the other groups. Halothane-anesthetized mice receiving intranasal influenza virus during anesthesia demonstrated increased survival and a delay in the mean day of death when compared with animals receiving either diethyl ether of pentobarbital anesthesia. Animals receiving enflurane during virus inoculation had an even lower mortality rate and a later mean day of death when compared with infected animals receiving day of the other three anesthetics. Examination of lungs from animals infected during anesthesia demonstrated influenza virus titers significantly less in the animals that received enflurane anesthesia when compared with the other groups. Histologic sections of lungs revealed extensive spread of the disease process into the alveoli and interstitium of the lungs of animals infected while receiving pentobarbital or diethyl ether anesthesia. Animals infected during halothane demonstrated pathologic characteristics similar to pentobarbital- and diethyl-ether-treated groups; however, the changes were not as extensive. Mice infected during exposure to enflurane revealed only a mild bronchopneumonia.