Ellis N. Cohen

Surgery during pregnancy and fetal outcome

As many as 2% of all pregnant women undergo surgery during gestation, but there are few reports of the effects of anesthesia and surgery on fetal outcome. The present paper presents information on 287 women who had surgery during pregnancy. Surgery during early pregnancy was associated with a significant increase in the rate of spontaneous abortion compared to the rate in a control group that did not have surgery. There were no differences in the incidence of congenital abnormalities in this offspring of women who had surgery during early pregnancy. The data suggest that elective surgery be deferred during early pregnancy to minimize potential fetal loss.

The effect of two inhalation anesthetics of the order of spin-labeled phospholipid vesicles

The order parameter (S′n) of spin-labeled phosphatidylcholine vesicles has been shown to decrease in a concentration-dependent manner with two inhalation anesthetics, halothane and methoxyfluorane. Similar decreases ofS′n are observed in vesicles labeled adjacent to the polar head group and those labeled near the bilayer center. This suggests that inhalation anesthetics cause a generalized fluidization of the membrane rather than a disorder localized in a particular region of the bilayer. Measurements of the isotropic nitrogen hyperfine coupling constant (a′N) show a decrease in polarity of the environment with increasing anesthetic concentrations. The experimental approach of plottingS′n versus anesthetic concentration provides a test of whether anesthetics produce their effects on a per molecule or per volume basis.

Urinary Metabolites of Halothane in Man

The urinary metabolites of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were investigated in five individuals given trace doses (25 μCi), and in three individuals given large doses (1 mCi) of radioactively labeled 14C-halothane. The latter were donor subjects for heart transplant operations. Separation of the nonvolatile urinary metabolites of halothane was accomplished by chemical extraction, electrophoresis, ion-exchange and high-pressure liquid chromatography, and gas chromatography. Identification of the individual metabolites was by nuclear magnetic resonance and mass spectrometry. Three major metabolites were identified: trifluoro-acetic acid, N-trifluoroacetyl-2-aminoethanol, and N-acetyl-S-(2-bromo-2-chloro-1,1-difluoroethyl)-L-cysteine. Smaller unidentified radioactive peaks were also found. The presence of both ethanolamide and cysteine conjugates of halothane is of concern. These urinary products imply the presence of reactive intermediates. The conjugation of such intermediates to proteins and phospholipids may give rise to the high-molecular-weight covalently bound metabolites demonstrated to be present in the liver following halothane anesthesia. Elucidation of the structures of the urinary metabolities provides information important to an understanding of halothane metabolism and its potential hepatotoxicity.

Chronic exposure to anesthetic gases in the operating room.

Halothane present in the ambient atmosphere was continuously measured in each of two operating rooms during the conduct of surgical anesthesia. Concentrations were determined on-line with a mass spectrometer and found to vary with sampling site, breathing system used, and the scavenging system employed to remove overflow anesthetic gases. Concentrations of halothane measured within a 3-foot radius of the anesthesia equipment averaged 8.7 ppm when a nonrebreathing circuit was used (flow 10 l/min), and 4.9 ppm with a semiclosed circle system (flow 4–5 l/min). End-tidal concentrations of halothane averaged 0.21 ppm in 81 samplings from operating room nurses and 0.46 ppm in 36 samplings from anesthetists. Residual concentrations were present in many individuals 16 hours after exposure. A significant reduction in atmospheric contamination of the operating room was obtained by use of appropriate scavenging equipment. The implications of these findings are discussed.

Volatile Metabolites and Decomposition Products of Halothane In Man

The presence of two volatile halothane metabolites, 2-chloro-1,1,1-trifluoroethane (CF3CH2Cl) and 2-chloro-1,1-difluoroethylene (CF2CHCl), and a metabolite-decomposition product, 2-bromo-2-chloro-1,1-difluoroethylene (CF2CBrCl), were identified by gas chromatography—maas spectrometry in exhaled gases of 16 patients anesthetized with halothane in nonrebreathing, semiclosed and totally closed anesthesia circuits. No significant differences in concentrations of CF3CH2Cl and CF2CHCl were found relative to the anesthesia circuits used. CF2CBrCl could not be identified in the expired gases of patients anesthetized with a nonrebreathing circuit (Bain), but was present in gases recovered from both semiclosed and totally closed circuits. Under totally closed-circuit rebreathing conditions, the concentration of CF2CBrCl increased to 4–5 ppm, indicating significant breakdown of halothane by the soda lime. Possible pathways for formation of the two metabolites and the metabolite—decomposition product are presented, as well as clinical implications of these findings.

Exposure to Nitrous Oxide and Neurologic Disease among Dental Professionals

Questionnaires, mailed to approximately 30,000 dentists and an equal number of dental assistants requesting information regarding professional exposure to anesthetics and health problems, showed an increased incidence of neurologic complaints in dental professionals who worked with nitrous oxide. The most striking differences were noted in individuals reporting symptoms of numbness, tingling, and/or muscle weakness. For dentists heavily exposed to nitrous oxide, the rate of these complaints was 4-fold greater than for nonanesthetic-exposed dentists. For dental assistants heavily exposed to nitrous oxide, a 3-fold increase in these same complaints was noted. In view of recent evidence that nitrous oxide abuse may lead to polyneuropathy, the results suggest that occupational exposure to nitrous oxide by both dentists and dental assistants may be associated with similar neuropathy.

Pressure Reversal of Inhilation Anesthetic-Induced Disorder in Spin-Labeled Phospholipid Vesicles

Summary The effects of anesthetics in luminous bacteria, newts, tadpoles. and mice are reversed by application of 150-200 atm of helium or hydrostatic pressure. The disorder induced by the inhalation anesthetic halothane in spin-labeled phospholipid vesicles is also reversed by similar pressures of helium. If pressure reversal of anesthesia occurs in intact nerve systems. then all theories of anesthesia must accommodate the phenomenon and nerve membrane model systems demonstrate it as well. The occurrence of pressure reversal in spin-labeled phospholipid vesicles supports their use as models for the hydrophobic region of nerve membranes and suggests that the primary site of pressure reversal is in the lipid phase of the nerve membrane. This finding is in agreement with the theory that anesthetics act by disordering the lipid region of the membranes.

The Metabolism and Elimination of d-Tubocurarine-H3

Metabolism and elimination of (d-tubocurarine-H3 were studied in 31 dogs. Combined renal and hepatic elimination accounted for over 85 per cent of the injected dose within 24 hours. In the absence of renal function (ligation of renal pedicles), the liver greatly increased its capacity to transport d-tubocurarine into the bile. A search for metabolites of d-tubocurarine in urine and bile indicated that no metabolites were present in urine, but that approximately 1 per cent of the injected tritium appeared in the bile in alternate molecular form.

Distribution of Local Anesthetic Agents in the Neuraxis of the Dog

Autoradiographic studies of the spinal cord in the dog indicate a specific uptake of C-Iabelled lidocaine and procaine by the neuraxis. The highest concentrations of the intrathecally-adminis-tered drug were found in the posterior and lateral columns, with only small concentrations noted in the anterior columns. Uptake of drug was higher in the grey matter than in the white matter of the cord, and posterior nerve roots had a higher concentration than anterior roots. Biopsies of the cord and scintillation counting of the weighed specimens provided confirmation of the autoradiographic studies. The significance of these findings is discussed, and possible explanations arc considered.

Frequency-dependent Conduction Block: The Role of Nerve Impulse Pattern in Local Anesthetic Potency

The depth of local anesthetic-induced conduction block is modified by the frequency of impulse traffic in the nerve (frequency-dependent conduction block). The present study was designed to compare the frequency-dependent characteristics of a number of local anesthetics of different lipid solubilities. Two antiarrhythmic drugs, quinidine and propranolol, were also included. Frequency dependence was assessed by measuring the height of the compound action potential of the frog sciatic nerve in response to single stimuli and to stimuli presented repetitively at different frequencies. All the drugs tested showed marked enhancement of block at 40 Hz. Nerves treated with highly lipid-soluble agents (bupivacaine, tetracaine, etidocaine), two experimental compounds of low and very low lipid solubility (GEA 968 and QX-572, respectively), and the antiarrhythmic agents took longer to develop and to recover from the effects of stimulation than those treated with drugs of moderate lipid solubility (procaine, lidocaine, prilocaine, mepivacaine, and benzocaine). The effects of repetitive stimulation were apparent at lower frequencies for drugs in the former group than in the latter. The results support an important role for frequency dependence in the antiarrhythmic and local anesthetic properties of these drugs. They also reveal unexpected similarities between drugs at the high and low extremes of lipid solubility with respect to the time course of frequency-dependent blocking actions.