ABSTRACT
A 23-year-old female was referred to the University of Arkansas for Medical Sciences at 32 weeks' gestation with a history of aortic stenosis following aortic valve replacement. Evaluation by echocardiography showed an approximately 90 mmHg transvalvular pressure gradient. Pregnancy progressed to 36 weeks' gestation without problem, at which time the patient underwent cesarean section with lumbar epidural anesthesia. Invasive hemodynamic monitors were used to assess cardiac performance and as a guide for anesthetic management. The impact of aortic stenosis on pregnancy is discussed, as are management aspects of lumbar epidural anesthesia in such patients.
Subject(s)
Anesthesia, Epidural , Anesthesia, Obstetrical , Aortic Valve Stenosis/physiopathology , Cesarean Section , Pregnancy Complications, Cardiovascular/physiopathology , Adult , Aortic Valve/surgery , Blood Pressure/physiology , Cardiac Output/physiology , Female , Heart Valve Prosthesis , Humans , Pregnancy , Pulmonary Artery/physiology , Vascular Resistance/physiologyABSTRACT
The in vitro chronotropic and inotropic effects of norepinephrine and acetylcholine in isolated right and left guinea pig atria were examined in the absence and presence of halothane, isoflurane, and enflurane (0.6 and 1.2 MAC). All three anesthetics elicited dose-dependent reductions in contractile force and spontaneous pacemaker activity. The maximal developed tension observed in the presence of norepinephrine was not altered by the anesthetics and corresponding ED50 values increased only in the presence of 1.2 MAC halothane and 1.2 MAC isoflurane. The anesthetics did not affect (a) the maximal positive chronotropic effect of norepinephrine, (b) the ED50 values for its positive chronotropic effect, and (c) acetylcholine-induced negative inotropic and chronotropic actions and did not induce arrhythmic activity even in the presence of the maximally effective neurotransmitter concentrations. These findings indicate that in isolated guinea pig atria volatile anesthetics, in concentrations up to 1.2 MAC, do not alter the inotropic and chronotropic effects of norepinephrine or acetylcholine and do not induce arrhythmogenic action in the presence of the neurotransmitters. These data suggest that altered atrial responsiveness to adrenergic or muscarinic stimulation does not contribute to the development of anesthetic-induced cardiac arrhythmias.
Subject(s)
Acetylcholine/pharmacology , Anesthetics/pharmacology , Heart Rate/drug effects , Myocardial Contraction/drug effects , Norepinephrine/pharmacology , Anesthetics/administration & dosage , Animals , Arrhythmias, Cardiac/chemically induced , Depression, Chemical , Dose-Response Relationship, Drug , Drug Interactions , Enflurane/pharmacology , Guinea Pigs , Halothane/pharmacology , Heart Atria/drug effects , In Vitro Techniques , Isoflurane/pharmacology , Male , Stimulation, ChemicalABSTRACT
MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents.
Subject(s)
Enflurane/analysis , Guinea Pigs/metabolism , Halothane/analysis , Isoflurane/analysis , Pulmonary Alveoli/analysis , Anesthesia/veterinary , Animals , Male , RespirationABSTRACT
It is well-established that the anesthetic requirement (MAC) of volatile agents such as halothane is reduced in elderly patients. The current project was designed to determine whether a similar alteration in anesthetic requirement occurs in Fischer-344 (F-344) rats, an animal model often utilized in physiology and pharmacology to examine aging-related changes. Animals were exposed to increasing or decreasing levels of halothane. After equilibration at each concentration, the response to tail-clamping was used for MAC testing. MAC was reduced approximately 17% in aged (25 months) versus young adult (5 months) animals. From these data, it is concluded that the F-344 rat may be an adequate model for examination of age-dependent alterations in the actions of volatile anesthetics.
Subject(s)
Aging/physiology , Halothane/pharmacology , Animals , Body Temperature/drug effects , Carbon Dioxide/blood , Dose-Response Relationship, Drug , Male , Oxygen/blood , Rats , Rats, Inbred F344ABSTRACT
Concentration-dependent effects of BAY K-8644, a dihydropyridine calcium channel agonist, on heart rate (HR), left atrial pressure (LAP) and maximal rate of left intraventricular pressure rise (+dP/dtmax) were compared with those of isoproterenol and digoxin in dog heart-lung preparations during exposure to 0.8 vol% halothane. All three agents reduced LAP to nearly equal levels at maximally effective concentrations. Maximal increases in +dP/dtmax induced by BAY k-8644 and digoxin were of similar magnitude (35 and 31%, respectively), and both agents increased HR slightly. Isoproterenol elevated both +dP/dtmax and HR more than twice as much as the other agents. At a concentration which produced only small changes by itself, BAY K-8644 markedly increased the effects of digoxin on LAP and +dP/dtmax. Furthermore, the same concentration of BAY K-8644 significantly reduced toxic effects of digoxin (arrhythmogenesis, elevation of LAP, reduction in systemic output). These data indicate that in the isolated blood-perfused heart digoxin's positive inotropic action may be enhanced by an appropriate concentration of BAY K-8644, while adverse effects are diminished.
Subject(s)
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/administration & dosage , Digoxin/administration & dosage , Heart/drug effects , Lung/drug effects , Animals , Blood Pressure/drug effects , Dogs , Dose-Response Relationship, Drug , Drug Interactions , Female , Heart/physiology , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/administration & dosage , Lung/physiology , MaleABSTRACT
Recovery from the cardiac depressant effects of enflurane and halothane was examined in the dog heart-lung preparation (HLP) and in right ventricular muscle isolated from guinea pig hearts. In the HLP. recovery was studied under two conditions: (1) After a two-hour exposure to anesthetic concentrations increasing from 0.36 to 1.2 MAC, and (2) after a one-hour exposure to a single concentration that raised the left atrial pressure (LAP) to 9 to 10 mmHg. Under either condition, +dP/dtmax. was significantly less depressed with enflurane and returned to preanesthetic control levels, while recovery with halothane remained significantly below control. Following the longer exposure. recovery of the LAP and left ventricular function curves (LVFC) was significantly less with halothane; however, this difference was not observed after the shorter exposure period. In electrically paced, isometrically contracting right ventricular strips exposed for one hour to 2.25 vol% enflurane (a concentration that reduced contractility by 45%), force development returned within 60 minutes to values above preanesthetic control values. After an identical depression for one hour with halothane (0.80 vol%), force development recovered to values less than those observed following enflurane. These data indicate that the recovery from anesthetic-induced negative inotropic effects in isolated cardiac preparations is better with enflurane than halothane.
Subject(s)
Anesthetics, Inhalation/toxicity , Enflurane/toxicity , Halothane/toxicity , Heart/drug effects , Animals , Blood Pressure/drug effects , Depression, Chemical , Dogs , Female , Guinea Pigs , Heart/physiology , In Vitro Techniques , Male , Ventricular Function, Left/drug effectsABSTRACT
Minimum alveolar concentration (MAC) was determined in intact dogs (N = 10 for each anesthetic) to be 2.12 +/- 0.04 vol% for enflurane (ENF), 1.28 +/- 0.04 vol% for isoflurane (ISO), and 0.94 +/- 0.03 vol% for halothane (HAL). Then, the direct cardiac effects of these three anesthetics were studied at 0.36, 0.6, 1.0, and 1.2 MAC in the dog heart-lung preparation (HLP): an in situ whole heart preparation devoid of major extracardiac influences and reflex control. All three agents produced concentration-dependent decreases in heart rate (HR) that became significantly different from control at 0.6 MAC. HAL and ISO reduced +dP/dtmax by the same degree at all MAC levels, becoming statistically significant at 0.6 MAC, while a significant reduction in +dP/dtmax for ENF occurred first at 1.0 MAC. Marked increases in left atrial pressure (LAP) were observed at 1.0 MAC for all anesthetics and the first significant depression of systemic output (SO) occurred at 1.0 MAC. Each agent produced significant shifts of the left ventricular function curves (LVFC) to the right with each consecutive MAC fraction. Marked reductions in the slope of the LVFC were first observed at 1.0 MAC, and this change in slope was more pronounced with ENF. At 1.2 MAC, ENF seemed to produce a more severe cardiodepression than HAL or ISO, as suggested by a greater incidence of cardiac failure; however, this was not statistically significant. In general, the data suggest that at MAC fractions up to 0.6, ENF is less cardiodepressant than ISO or HAL, but that ENF has a tendency to be more depressant than HAL or ISO at concentrations higher than 1.0 MAC.
Subject(s)
Anesthetics, Inhalation/pharmacology , Enflurane/pharmacology , Halothane/pharmacology , Isoflurane/pharmacology , Analysis of Variance , Animals , Blood Pressure/drug effects , Cardiac Output/drug effects , Dogs , Female , Heart/drug effects , Lung/drug effects , Male , Models, Animal , Monitoring, Physiologic , Pulmonary Gas Exchange/drug effects , Pulmonary Gas Exchange/physiology , Research DesignABSTRACT
The observed effect of midazolam on anxiety is equivocal in part because previous studies have not ruled out pre-treatment differences in anxiety scores between patients who received midazolam and those who did not (controls). This study re-examines the anxiolytic effect of premedication with intramuscular midazolam using a sample size calculated to be of sufficient size to rule out population differences as a variable affecting treatment results. In the midazolam group (n = 49) anxiety scores were determined prior to administration of midazolam 0.07 mg/kg intramuscularly, and again 60 minutes later. In the control group (n = 47) anxiety scores were determined prior to intramuscular injection of a similar volume of matching placebo (midazolam vehicle), and again 60 minutes later. No differences in anxiety scores between groups either before treatments or 60 minutes after treatments were observed. Within both groups, anxiety scores at 60 minutes were no different from pre-treatment scores. In this study midazolam did not produce a statistically significant decrease in pre-operative anxiety scores at 60 minutes following intramuscular administration.
Subject(s)
Anxiety/drug therapy , Benzodiazepines/therapeutic use , Adolescent , Adult , Aged , Double-Blind Method , Drug Evaluation , Female , Humans , Injections, Intramuscular , Male , Midazolam , Middle Aged , Premedication , Random Allocation , Statistics as TopicABSTRACT
Our study sought to determine whether premedication with intramuscular midazolam would decrease the time to induction of anaesthesia with intravenous midazolam, and if so whether induction of anaesthesia would be as rapid as with thiopentone or ketamine, intravenously. Eight-nine patients, ASA physical status I or II, received midazolam 0.2 mg X kg-1, thiopentone 3.0 mg X kg-1, or ketamine 2.0 mg X kg-1 intravenously 60-90 min after intramuscular injection of either midazolam 0.07 mg X kg-1 or matching placebo. Time to induction of anaesthesia or the dose required to induce anaesthesia with intravenous midazolam was not decreased by midazolam premedication. Both with or without premedication, midazolam induction time was longer than with thiopentone or ketamine. Midazolam induction was associated with a lower incidence of blood pressure increase than with ketamine induction, and a lower incidence of apnea than that with either thiopentone or ketamine.
Subject(s)
Anesthesia, Intravenous , Anti-Anxiety Agents/administration & dosage , Benzodiazepines/administration & dosage , Ketamine/administration & dosage , Preanesthetic Medication , Thiopental/administration & dosage , Adolescent , Adult , Female , Humans , Injections, Intramuscular , Injections, Intravenous , Male , Midazolam , Middle AgedSubject(s)
Analgesia/methods , Delivery, Obstetric/methods , Labor, Obstetric , Pain/drug therapy , Anesthesia, Inhalation , Barbiturates/therapeutic use , Female , Humans , Narcotic Antagonists/therapeutic use , Narcotics/therapeutic use , Pain/etiology , Pregnancy , Scopolamine/therapeutic use , Tranquilizing Agents/therapeutic useABSTRACT
Our data in 74 patients demonstrate that procaine hydrochloride is a safe anesthetic adjuvant in doses of 1 mg/kg/min even when total doses are 5 to 7 g. Blood pressure, heart rate, electrocardiographic variables, and blood gases were not adversely affected. Patients had no nausea or untoward postanesthesia symptoms. Emergence from anesthesia was rapid, within less than 15 minutes in all patients, and most were fully awake before leaving the operating room. In two patients in whom blood levels were studied the drug disappeared within 40 minutes. Procaine is inexpensive, $1.16 for 10 g, and it is not a known liver or kidney toxin. Until studies on cardiovascular dynamics and analgesic effects as in whom a low plasma cholinesterase activity is present or suspected. The clinical appraisal in 56 patients indicates its usefulness in suppressing premature venticular contractions and cough reflexes during endoscopic procedures in the respiratory tract. Procaine can be used to advantage in supplementing general anesthesia in outpatient surgery because of its brief action. For these reasons, the drug merits further study.
Subject(s)
Anesthetics , Hemodynamics/drug effects , Procaine/administration & dosage , Adolescent , Adult , Arrhythmias, Cardiac/prevention & control , Blood Gas Analysis , Bronchoscopy , Child , Cough/prevention & control , Drug Administration Schedule , Female , Humans , Hysterectomy , Injections, Intravenous , Male , Procaine/adverse effects , Procaine/pharmacologyABSTRACT
Thirty consecutive infants undergoing hypothermia and circulatory arrest for repair of ventricular septal defect, transposition of the great vessels, or atrioventricular canal defects were alternately selected for conventional high flow nonpulsatile perfusion or pulsatile perfusion during core cooling and rewarming. All received morphine anesthesia, 30 mg/kg of Solu-Medrol, and 10 to 15 mcg/kg of phentolamine. Those receiving nonpulsatile flow were perfused at a rate of 160 to 180 cc/kg/min with a roller pump and oxygenator with arterial pressure of 50 to 55 mm Hg. In the pulsatile flow group, a roller pump and oxygenator were used, and an especially constructed Datascope PAD (pulsatile assist device) was interposed in the arterial line to provide pulsatile perfusion with 75/40 mm Hg pressure at slightly reduced flow (150 cc/kg/min). The average rectal, esophageal, and tympanic membrane temperatures were reduced to approximately 16 degrees C prior to circulatory arrest. Following repair, perfusion was resumed until these temperatures returned to 37 degrees C. Cooling and rewarming were enhanced by pulsatile perfusion, with over 30% reduction in total pump time. Additionally, the larger patients in the pulsatile group cooled almost as rapidly as the smaller. The rates of decline and subsequent rise of rectal, esophageal, and tympanic membrane temperatures were equal in the pulsatile group, but the rectal temperature lagged far behind in the nonpulsatile group. Urine production during bypass was 100% greater in the pulsatile group. The plasma free hemoglobin was similar in both groups. The average postrewarming pH was 7.31 in the nonpulsatile group and 7.42 in the pulsatile group. Infants receiving pulsatile flow awakened more quickly, were more alert, and required less postoperative mechanical ventilation. We suggest that pulsatile perfusion for core cooling and rewarming of infants is safe and is more rapid and physiological than conventional high-flow nonpulsatile perfusion.
Subject(s)
Cardiopulmonary Bypass/methods , Heart Arrest, Induced/methods , Heart Defects, Congenital/surgery , Hypothermia, Induced/methods , Acid-Base Equilibrium , Age Factors , Blood Cells , Body Temperature , Cardiopulmonary Bypass/instrumentation , Catheterization/instrumentation , Catheterization/methods , Evaluation Studies as Topic , Heart Arrest, Induced/instrumentation , Humans , Hypothermia, Induced/instrumentation , Infant , Kidney/physiology , Postoperative Care , Postoperative Complications/prevention & control , Respiration, Artificial , Time FactorsABSTRACT
Pharmacokinetic data during and following the continuous intravenous infusion of procaine are lacking. We studied 12 women undergoing hysterectomy during N2O-O2 and narcotic anesthesia. A constant infusion of 2% procaine was administered at a rate of 1 mg/kg/min to six patients (group I) and at a rate of 1.5 mg/kg/min to the other six (group II). Procaine plasma levels were determined by flame ionization gas-liquid chromatography. Using a two-compartment pharmacokinetic model, disposition kinetics were studied. Steady-state plasma levels were achieved within 20 to 30 minutes after commencement of the infusion. Following termination of the infusion the drug disappeared with a distribution half-life (t1/2 alpha) of 2.49 +/- 0.36 minutes and an elimination half-life (t1/2 beta) of 7.69 +/- 0.99 minutes at both infusion rates. In group I, the fraction of drug in the central compartment was 65%, the volume of distribution at steady-state was 0.79 +/- 0.14 L/kg, and total body clearance 0.08 +/- 0.01 L/kg/min. In group II, the fraction of drug in the central compartment was 82%, the volume of distribution at steady-state 0.34 +/- 0.07 L/kg, and the total body clearance 0.04 +/- 0.01 L/kg/min. These data indicate that procaine is a drug of limited distribution and tissue uptake with a short duration of action.
Subject(s)
Anesthesia, General , Procaine/metabolism , Adult , Anesthesia, Inhalation , Anesthesia, Intravenous , Chromatography, Gas , Female , Half-Life , Humans , Infusions, Parenteral , Nitrous Oxide , Procaine/administration & dosage , Procaine/blood , ThiamylalABSTRACT
A multicompartment pharmacokinetic model is presented to describe procaine distribution in humans during and following intravenous infusion. The model, based on a general perfusion model, relates individual characteristics such as sex, age, weight, height, infusion rate and duration, and hematocrit to general parameters such as drug metabolism, protein binding, ion-trapping effects, and tissue-plasma distribution coefficients to provide an individualized distribution prediction. Experimentally observed kinetics of blood procaine levels collected during intravenous procaine infusion as an adjunct to surgical anesthesia and blood lidocaine levels obtained from the literature compared very well with the model simulation.
Subject(s)
Procaine/metabolism , Humans , Infusions, Parenteral , Kinetics , Models, Biological , Procaine/administration & dosage , Procaine/blood , Procaine/pharmacology , Time Factors , Tissue DistributionABSTRACT
Sodium nitroprusside (SNP) was used to produce deliberate hypotension in 30 selected patients, 9 to 78 years of age, for total hip replacement under halothane-N2O-O2 anesthesia. Hypotension was induced in the first 13 patients by infusing a 0.01% (100 mug/ml) solution of nitroprusside (NP) in 5% dextrose. Blood pressure was diminished to a level just producing a dry surgical field. Preliminary data demonstrated that the mean arterial blood pressure (MAP) achieving this condition was 65 torr (p less than 0.01) and that the minute dosage of NP (mug/min) required to consistently reduce MAP to 65 torr could not be predicted on the basis of body weight. However, the age/weight ratio (yr/kg) of each patient, plotted against the known minute dosage of NP given during anesthesia, produced a highly significant dose-response curve (p less than 0.001, r = -0.8226). The preliminary dose-response curve was examined in a double-blind study on an additional 17 patients. The curve derived from the prospective study did not differ from that of the preliminary study. In addition, the combined data from the retrospective and prospective studies (30 patients) gave a better statistical fit than did those from the preliminary study alone (p less than 0.001, r = -0.8939). The nomogram provides an additional margin of safety in the use of this potent, fast-acting drug. SNP has been found predictable and effective in reducing surgical blood loss in selected patients undergoing total hip replacement.