Showing papers in "Anesthesiology in 1979"

Pain relief by intrathecally applied morphine in man.

Abstract: Pain Relief by Intrathecally Applied Morphine in Man Josef Wang;Lee Nauss;Juergen Thomas; Anesthesiology

Risks of General Anesthesia and Elective Operation in the Hypertensive Patient

Abstract: To determine the risks of general anesthesia and elective surgical procedures in patients who have histories of hypertension, the authors prospectively studied 676 consecutive operations in a series of patients more than 40 years old. All patients were examined preoperatively, monitored intraoperati

Myocardial ischemia during non-cardiac surgical procedures in patients with coronary-artery disease.

Abstract: The purpose of this study was to determine the incidence of ST-segment depression during anesthesia and operation. Graded exercise testing has demonstrated a high correlation between ST-segment depression and myocardial ischemia. Therefore, 11 patients without and 29 patients with known coronary-artery disease were monitored during surgical procedures with a commercially available exercise electrocardiographic monitor (Viagraph). Comparisons were made between this device, which monitored lead V5, and the standard operating room monitor, which monitored lead 11. Eleven of 29 patients in the disease group demonstrated significant ST depression. Nine of the 11 ischemic episodes were not recognized on the standard operating room monitor. Retrospective review of anesthetic records of those 11 patients with ST-segment depression revealed rate--pressure product values greater than 11,000 for ten of them. Postoperatively, three of the 11 patients with significant ST-segment depression had changing electrocardiograms compatible with ischemia. None of the control group demonstrated significant ST-segment depression. The incidence of ischemia was 38 per cent during anesthesia and operation in the coronary-artery-disease group. Lead V5 analysis is superior to lead 11 analysis in detecting ST-segment depression. The period in which intubation is performed is one of the highest-risk intervals during anesthesia and operation, particularly when it is associated with an increased rate--pressure product.

An animal model of halothane hepatotoxicity: roles of enzyme induction and hypoxia.

Abstract: Exposure of phenobarbital-pretreated male Sprague-Dawley rats to halothane, 1 per cent, for two hours under conditions of hypoxia (Fl02 0.14) resulted in extensive centrilobular necrosis within 24 hours. Accompanying the morphologic damage were an increase in serum glutamic pyruvic transminase (SGPT) and a decrease in hepatic microsomal cytochrome P-450. Glutathione levels in the liver were unchanged. Phenobarbital-pretreated rats anesthetized with halothane, 1 per cent, at FI02 0.21 had only minor morphologic changes at 24 hours. Hepatic injury was not appearent in any non-phenobarbital-induced rat or in any induced animal exposed to ether at Fl02 0.10 or to halothane at Fl02 0.99. There was a 2.6-fold increase in the 24-hour urinary excretion of fluoride in those rats in which extensive centrilobular necrosis developed. The in-vivo covalent binding to lipids of 14C from 14C-halothane also was increased markedly when 14C-halothane was administered intraperitoneally to phenobarbital-induced rats maintained hypoxic (FI02 0.14) for two hours. These results support the authors' hypothesis that halothane is metabolized to hepatotoxic intermediates by a reductive or non-oxygen-dependent cytochrome P-450-dependent pathway. This animal model of halothane-induced hepatotoxicity may be clinically relevant. A decrease in hepatic blood flow during halothane anesthesia may decrease the P02 available to hepatocytes and thus direct the metabolism of halothane along its reductive, hepatotoxic pathway.

Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe.

Abstract: Because maternal stress may adversely affect the fetus, the authors tested the effects of brief episodes (15-60 sec) of maternal stress in 18 awake pregnant ewes. Maternal agitation and stuggling occurred either following non-painful stimuli such as loud noises or sudden movements of personnel (ten animals) or following the brief application of the ewe's skin of a uniform electrical stimulus of 30 volts with a frequency of 167 Hz for 30-60 sec (eight animals). Stimulation of either type produced a 45-50 per cent increase in mean maternal arterial blood pressure and a concomitant 32-52 per cent decrease in uterine blood flow (P less than 0.05). The decreases in uterine blood flow were brief, lasting less than 3 min, and were not associated with fetal asphyxia. Maternal plasma norepinephrine levels were measured following electrically induced maternal stress and were increased 25 per cent. The authors conclude that maternal stress may decrease uterine blood flow secondary to release of endogenous norepinephrine.

Age-related Changes in Blood Pressure and Duration of Motor Block in Spinal Anesthesia

Abstract: Changes in blood pressure, heart rate and the time necessary for recovery from motor block after spinal anesthesia were compared in 65 children, aged 8 months to 15 years, and 17 adult patients. All patients had similar levels of sensory anesthesia (T5-T3) following tetracaine, 0.3 mg/kg, plus pheny

Cardiovascular Responses to Diazepam and Midazolam Maleate in the Dog

Abstract: Previous clinical studies establishing the efficacy of midazolam maleate (RO 21-3981), a new water-soluble benzodiazepine for induction of anesthesia, have not critically evaluated the effects of this agent on the cardiovascular system. The present study compares the cardiovascular effects of midazolam maleate and diazepam in conscious dogs. Systemic arterial, pulmonary arterial and central venous pressures, cardiac output, LVmax dP/dt, heart rate and regional coronary blood flow were measured 3 min following intravenous administration of diazepam (0.5, 1.0, and 2.5 mg/kg) or midazolam maleate (0.25, 1.0, and 10.0 mg/kg). Midazolam maleate increased heart rate 10--20 per cent with all three doses and decreased mean arterial blood pressure approximately 10--20 per cent at 1.0 and 10 mg/kg. Cardiac output was increased 10--12 per cent with all three doses of midazolam maleate, and LVmax dP/dt was decreased 13--16 per cent at the two higher doses. Diazepam at all three doses did not alter heart rate or mean arterial blood pressure. Diazepam, 1.0 and 2.5 mg/kg, produced significant (17 per cent) decreases in LVmax dP/dt, and 2.5 mg/kg produced a significant (10 per cent) increase in cardiac output. Neither drug in any dosage altered regional coronary blood flow, systemic or coronary vascular resistance, stroke volume, or stroke work. Maximum alterations in cardiovascular variables occurred with doses of midazolam maleate that are 10--15 times the recommended clinical induction dosage. It is concluded that in concentrations necessary for induction of anesthesia midazolam maleate has minimal effects on cardiovascular function.

Antacid pulmonary aspiration in the dog.

Abstract: The amount of damage resulting from pulmonary aspiration of gastric contents is determined primarily by the acidity of the aspirate. Thus, it has been recommended that the pH of stomach contents of pregnant women be increased by the oral administration of antacids prior to anesthesia for delivery. T

Nitrous oxide effects on cerebral evoked potential to pain: partial reversal with a narcotic antagonist.

Abstract: The effect of naloxone, 0.4 mg, on the analgesia induced by nitrous oxide, 33 per cent, in oxygen, was studied in 12 volunteers. Results of previous investigations in animals suggested that endogenous opiate-like substances may play a major role in the analgesic mechanism of nitrous oxide, but the issue had not been studied in man. Cerebral evoked potentials (CEP) to painful tooth-pulp electrical shocks were obtained before and after inhalation of nitrous oxide, and after nitrous oxide plus naloxone, 0.4 mg, in one session; and before and after inhalation of room air, and after room air plus naloxone, 0.4 mg, in another session. CEP waveforms observed between 80 and 350 msec were quantified in terms of three peak-to-peak amplitudes and peak latencies. Nitrous oxide decreased each of the waveform peak-to-peak amplitudes 48 per cent. Naloxone restored the peak-to-peak amplitude of the negative-going wave occurring between 100 and 175 msec. Nitrous oxide also increased the negative peak latency at 175 msec, and naloxone restored this peak latency to normal levels. Neither room air nor room air plus naloxone altered CEP amplitudes or latencies. Over time a significant trend in subjective reports of decreased pain intensity with nitrous oxide and partially increased pain with naloxone was evident. These findings demonstrate that some of the effects of nitrous oxide on the central nervous system can be reversed by naloxone.

Volatile metabolites and decomposition products of halothane in man.

Abstract: 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-mass 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.

Hypertension during anesthesia on discontinuation of sodium nitroprusside-induced hypotension.

Abstract: The authors had observed that on intraoperative discontinuation of sodium nitroprusside being administered to induce hypotension, mean arterial pressure increased to above the pre-hypotension level. Twelve patients who received hypotensive anesthesia for surgical correction of cerebral aneurysms wer

Humidity and the anesthetized patient.

Abstract: Damage to the ciliated cells of the tracheobronchial tree and incidence of postoperative pulmonary complications were measured by point-scoring systems in 202 patients who breathed dry and humidified anesthetic gases for 225 +/- 78 min. The incidence of postoperative pulmonary complications decreased as the humidity of administered anesthetic gases increased from 0 to 32.5 mg H2O/l. A similar relationship was found between the amount of inhaled moisture and the damage to the ciliated epithelium of the tracheobronchial tree. These results appear to indicate that a high inspired humidity is beneficial for operations on normothermic patients, and that cellular damage caused by dryness is a possible contributory factor in the production of the pulmonary atelectasis that follows stoppage of the mucociliary transport system in the immmediate postoperative period.

The Hypotensive Response to Rapid Intravenous Administration of Hypertonic Solutions in Man and in the Rabbit

Abstract: Transient hypotension has been observed in patients after rapid intravenous administration of mannitol, 25 per cent, in clinical doses. These studies were conducted to determine the mechanism for the hypotension, to determine dose and rate of injection response curves in rabbits, and to determine which vascular beds were most reactive. Studies in six patients showed mean decreases in blood pressure of 23 +/- 6.0 per cent (+/-SE) and in total peripheral resistance of 38 +/- 7 per cent after infusion of mannitol. Studies in 18 patients during cardiopulmonary bypass with mechanically fixed cardiac output demonstrated decreases in mean blood pressure of 30 +/- 5 to 40 +/- 3 per cent, depending on dose and rate of administration of mannitol. Patients not on bypass compensated for large decreases in total peripheral resistance by increases in cardiac output (3.6 +/- .4 at baseline to 4.4 +/- .4 l/min) during mannitol-induced hypotension with no change in heart rate. Serum osmolality increased as blood pressure decreased. Significant but clinically unimportant decreases in sodium and potassium ions, hemoglobin, pH, and base excess values were observed. Studies in 18 rabbits showed that the greater the dose or rate of injection of mannitol the greater the decrease in blood pressure. Injection of radiolabeled microspheres in rabbits demonstrated a near doubling of blood flow to skeletal muscle tissue during the hypotension. This occurred with both equiosmotic hypertonic glucose (17 +/- 3 to 32 +/- 7 per cent) and mannitol (17 +/- 1 to 31 +/- 5 per cent), but not after isotonic saline solution. Changes in blood flow to other organ beds were variable and unimportant. The results suggest that hypotension following the intravenous administration of hyperosmotic solutions is due primarily to vasodilation in skeletal muscle.

Pharmacokinetics and Pharmacodynamics of d-Tubocurarine during Nitrous Oxide–Narcotic and Halothane Anesthesia in Man

Abstract: The relative contributions of changes in pharmacokinetics and pharmacodynamics to the potentiation of d-tubocurarine (dTc)-induced paralysis by halothane in comparison with nitrous oxide (N2O)–narotic anesthesia were studied in three groups of patients. Fourteen patients received N2O-narcotic mainte

Neurotoxicity of anesthetics.

Abstract: Anesthetic toxicity can be strictly defined as a potentially harmful action or effect that is not part of the expected anesthetic or pharmacologic action of the agent. Such a definition would exclude the undesirable effects of an overdose of an anesthetic agent (wherein the expected pharmacologic effects are simply exaggerated) or a recognized expected pharmacologic effect that might in certain conditions be hazardous (for example, increased cerebral blood flow and intracranial pressure in patients with brain tumors). In this chapter I shall not adhere to the strict definition of toxicity but will instead also consider exaggerated or undesirable expected pharmacologic effects.

Sister chromatid exchanges induced by inhaled anesthetics

Abstract: 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 mutagen-carcinogens, particularly 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.

Renal function and the pharmacokinetics of neostigmine in anesthetized man.

Abstract: The pharmacokinetics of neostigmine in patients with normal renal function (n = 8) were determined and compared with those of patients undergoing renal transplantation (n = 6) or bilateral nephrectomy (n = 4). All patients were anesthetized with nitrous oxide and halothane. d-Tubocurarine was infused at a rate sufficient to maintain 90 per cent depression of twitch tension. Ten to 15 minutes prior to the end of operation and anesthesia, the d-tubocurarine infusion was terminated and neostigmine, 0.07 mg/kg, and atropine, 0.03 mg/kg, were given by infusion over a 2-min period. Concentrations of neostigmine in blood drawn periodically during the following four hours were determined by gas-liquid chromatography and the data fitted to a two-compartment pharmacokinetic model. In anephric patients elimination half-life (181 ± 54 min, mean ± SD) was significantly prolonged when compared with comparable values for patients with normal renal function (80 ± 48 min). Total serum clearance was significantly decreased from 16.7 ± 5.4 ml/kg/min in patients with normal renal function to 7.8 ± 2.6 ml/kg/min in anephric patients. Neostigmine pharmacokinetics following renal transplantation were not different from those in patients with normal renal function. It is concluded that renal excretion accounts for 50 per cent of neostigmine clearance and, in the absence of renal function, the serum half-life of neostigmine is prolonged, similar to that of d-tubocurarine.