Showing papers in "Anesthesiology in 1985"

Midazolam: pharmacology and uses.

Abstract: Midazolam is an imidazobenzodiazepine with unique properties when compared with other benzodiazepines It is water soluble in its acid formulation but is highly lipid soluble in vivo Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines The drug produces reliable hypnosis, amnesia, and antianxiety effects when administered orally, intramuscularly, or intravenously There are many uses for midazolam in the perioperative period including premedication, anesthesia induction and maintenance, and sedation for diagnostic and therapeutic procedures Midazolam is preferable to diazepam in many clinical situations because of its rapid, nonpainful induction and lack of venous irritation Compared with thiopental, midazolam is not as rapid acting nor predictable in hypnotic effect It will not replace thiopental as an induction agent Advantages of midazolam over thiopental are those of the more versatile pharmacologic properties of a benzodiazepine compared with a barbiturate such as amnestic and anxiolytic properties Midazolam should be a useful addition to the formulary

Does perioperative myocardial ischemia lead to postoperative myocardial infarction

Abstract: To determine if a relationship exists between perioperative myocardial ischemia (ST segment depression greater than or equal to 0.1 mV) and postoperative myocardial infarction (PMI), nonparticipating observers recorded all ECG, hemodynamic, and other events between arrival of patients in the operating room and onset of cardiopulmonary bypass during 1,023 elective coronary artery bypass operations (CABG). The roles of preoperative patient characteristics, quality of the operation limited by disease as rated by the surgeon and duration of ischemic cardiac arrest as risk factors for PMI also were quantified. ECG ischemia occurred in 36.9% of all patients, with almost half the episodes occurring before induction of anesthesia. PMI was almost three times as frequent in patients with ischemia (6.9% vs. 2.5%) and was independent of when ischemia occurred. Ischemia was related significantly to tachycardia but not hypertension nor hypotension and was frequent in the absence of any hemodynamic abnormalities. The anesthesiologist whose patients had the highest rate of tachycardia and ischemia had the highest rate of PMI. Although neither single nor multiple preoperative patient characteristics related to PMI, suboptimal quality of operation and prolonged ischemic cardiac arrest increased the likelihood of PMI independent of the occurrence of myocardial ischemia. The authors conclude that perioperative myocardial ischemia is common in patients undergoing CABG, occurs randomly as well as in response to hemodynamic abnormalities, and is one of three independent risk factors the authors identified as related to PMI. PMI is unrelated to preoperative patient characteristics such as ejection fraction and left main coronary artery disease, and its frequency will relate primarily to perioperative management rather than patient selection.

Pulmonary densities during anesthesia with muscular relaxation--a proposal of atelectasis.

Abstract: Twenty patients (23-76 yr) were studied with regard to lung tissue changes prior to and following induction of general anesthesia with muscular relaxation, and another four subjects were studied for a longer period awake. The transverse thoracic area and the structure of the lung tissue were determined by computerized tomography. No abnormalities in the lung tissue were noted before anesthesia. Within 5 min after induction, including muscular relaxation, all subjects had developed crest-shaped changes of increased density in the dependent regions of both lungs. They were largest in the most caudal segment (4.8 +/- 0.8% of the transverse lung area, mean +/- SE) and smaller in the cephalad exposures (3.4 +/- 0.7% of the transverse area). The size of the densities showed no correlation to age. The densities did not increase after a further 20 min of anesthesia and were not affected by the inspiratory oxygen fraction. When the subjects were moved from the supine to the lateral position, the crest-shaped densities disappeared in the nondependent lung and remained in the dorsal part of the dependent lung. The application of positive end-expiratory pressure of 10 cmH2O eliminated or reduced the densities. The four awake subjects showed no lung densities after 90 min in the supine position. It is suggested that these crest-shaped densities represent atelectases, which develop by compression of lung tissue rather than by resorption of gas.

EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil.

Abstract: Fentanyl and alfentanil produce very similar electroencephalographic (EEG) changes in humans. With increasing serum concentrations of either narcotic, progressive slowing in frequency occurs. This narcotic effect on the brain was quantitated using off-line EEG power spectrum analysis. During EEG recording, six unpremedicated patients received a fentanyl infusion (150 micrograms/min), and six received alfentanil (1,500 micrograms/min) until a specific level of EEG depression (delta waves) occurred. Timed arterial blood samples were obtained for measurement of the narcotic serum concentrations. The narcotic-induced EEG changes were found to lag behind (in time) the serum narcotic concentration changes. To accurately relate EEG changes to serum narcotic concentrations, a pharmacodynamic model (inhibitory sigmoid Emax) was combined with a pharmacokinetic model that incorporated an "effect" compartment. (The effect compartment is the separate pharmacokinetic compartment where drug effect is directly proportional to drug concentration. It is the effect site.) The magnitude of the time lag was quantitated by the half-time of equilibration between serum narcotic concentrations and concentrations in the effect compartment. With fentanyl a significantly greater time lag was present (half-time = 6.4 +/- 1.3 min; mean +/- SD) than with alfentanil (half-time = 1.1 +/- 0.3 min). This difference in time lag between blood concentration and effect may be due to the larger brain-blood partition coefficient for fentanyl. The steady-state serum concentration that caused one-half of the maximal EEG slowing was 6.9 +/- 1.5 ng/ml for fentanyl, compared with 520 +/- 163 ng/ml for alfentanil.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism for bupivacaine depression of cardiac conduction: fast block of sodium channels during the action potential with slow recovery from block during diastole.

Abstract: The effects of bupivacaine and lidocaine on cardiac conduction were compared in guinea pig ventricular muscle. Membrane potential was controlled using a single sucrose gap voltage clamp technique, and the maximum upstroke velocity of the action potential (Vmax) was used as an indicator of peak sodiu

Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilatory pattern and analgesic regimen.

Abstract: The respiratory effects of two postoperative analgesic regimens were compared in two groups of 16 patients each, recovering from general anesthesia and major surgery. One group received a pain-relieving dose of iv morphine (mean, 18.1 mg), with the same dose repeated as a continuous intravenous infusion over the subsequent 24 h. The other group received regional anesthesia using bupivacaine. The patients were monitored for 16 h after surgery. The two analgesic regimens provided patients with comparable analgesia throughout the study period, but there were quite different respiratory effects in the two groups. Ten patients receiving morphine infusions had a total of 456 episodes of pronounced oxygen desaturation (SaO2 less than 80%). These occurred only while the patients were asleep, and all were associated with disturbances in ventilatory pattern, namely, obstructive apnea (144 episodes in eight patients), paradoxic breathing (275 episodes in six patients), and period of slow ventilatory rate (37 episodes in one patient). In contrast, in patients receiving regional anesthesia, oxygen saturation never decreased below 87%. Central apnea, obstructive apnea, and paradoxic breathing occurred more frequently in patients in the morphine group (12, 10, and 10 patients, respectively) than patients in the regional anesthesia group (4, 3, and 5 patients, respectively). The interaction of sleep and morphine analgesia produced disturbances in ventilatory pattern, causing profound oxygen destruction. These results suggest that postoperative pain relief using regional anaesthesia has a greater margin of safety in terms of respiratory side effects than does the continuous administration of opiates.

Neuropsychiatric Complications after Cardiopulmonary Bypass: Cerebral Protection by a Barbiturate

Abstract: The authors prospectively investigated the ability of thiopental to decrease neuropsychiatric complications as a consequence of openventricle operations requiring cardiopulmonary bypass. Eighty-nine randomly assigned patients received sufficient thiopental to maintain electroencephalographic silence

Tactile and visual evaluation of the response to train-of-four nerve stimulation.

Abstract: 168 adultes subissent une chirurgie gynecologique ou gastroenterologique. L'evaluation manuelle de la reponse a la stimulation nerveuse «train de quatre» permet l'ajustement des posologies individuelles pour les curarisants au cours de l'anesthesie pour eviter un surdosage et assurer la reversibilite

Functional residual capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation.

Abstract: Functional residual capacity (FRC), rib cage and abdominal dimensions (rc-ab), central blood volume (CBV), and extra vascular lung water (EVLW) were measured in six lung-healthy subjects awake and during halothane anesthesia, muscle paralysis, and mechanical ventilation. FRC was assessed by multiple breath nitrogen washout, rc-ab dimensions by computerized tomography, and CBV and EVLW by a double-indicator dilution technique (thermo-dye). During anesthesia, FRC decreased by 0.5 1 (17%). The cross-sectional chest area was reduced by 12-20 cm2, causing an approximate reduction in thoracic volume by 0.3 1. Concomitantly, the diaphragm was moved cranially by an average of 1.9 cm, diminishing the thoracic volume a further 0.5 1. The abdominal cross-sectional area did not alter significantly, despite the shift of the diaphragm. CBV decreased by 0.3 1. EVLW did not change significantly. It is concluded that the thoracic volume is reduced during halothane anesthesia, muscle paralysis, and mechanical ventilation as a result of cranial shift of the diaphragm and reduction in transverse area. The decrease in thoracic volume is accompanied by a reduction in FRC and a displacement of blood from the thorax to the abdomen, the transverse area of the latter thus being maintained despite the shift of the diaphragm.

Nimodipine improves outcome when given after complete cerebral ischemia in primates.

Abstract: Twenty-seven pigtailed monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia followed by 96 h of intensive care treatment. Fourteen of the monkeys were assigned randomly to the treatment group and received nimodipine 10 μg·kg−1 5 min postischemia followed by 1 μg·kg−1·mi

Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure.

Abstract: To compare the effects of continuous positive airway pressure (CPAP) with those of ambient end-expiratory pressure (T-tube) on lung mechanics and blood gas exchange, transpulmonary pressure (Ptp), tidal volume (VT), respiratory frequency, and arterial oxygen and carbon dioxide tensions were measured in 16 spontaneously breathing patients recovering from acute respiratory failure. These variables were measured during breathing through a T-tube; with 18, 12, and 6 cmH2O CPAP; and again during breathing through a T-tube. During all levels of CPAP, mean effective lung compliance (Ceff) was higher and mean total pulmonary power during inspiration lower than during breathing through a T-tube before CPAP (P less than 0.05). The data obtained at the level of CPAP producing maximum Ceff (optimum CPAP) were grouped and compared with values obtained during breathing through a T-tube. Mean total pulmonary power of inspiratory muscles during breathing through a T-tube before CPAP (0.7 +/- 0.14 kg X m X min-1) decreased during optimum CPAP (0.44 +/- 0.07 kg X m X min-1) and increased during breathing through a T-tube after CPAP (0.63 +/- 0.12 kg X m X min-1). Mean VT was higher (557 +/- 63 ml vs. 474 +/- 47 ml) and frequency lower (17.5 +/- 1.6 breaths/min vs. 22.5 +/- 2.5 breaths/min) during optimum CPAP than during breathing through a T-tube before CPAP, and inspiratory time was significantly longer. Mean minute ventilation was also lower during optimum CPAP (8.7 +/- 0.6 1/min) than during breathing through a T-tube (9.6 +/- 0.8 1/min); Paco2 did not change significantly. Mean alveolar-to-arterial oxygen pressure difference decreased significantly during optimum CPAP. The authors conclude that CPAP, when adjusted to the appropriate levels, improves lung mechanics in patients recovering from acute respiratory failure. Continuous positive airway pressure reduces total pulmonary power during inspiration and at the same time improves oxygen and carbon dioxide exchange. In these respects, it is preferable to breathing through a T-tube without CPAP.

Neurotoxicity of intrathecal local anesthetics in rabbits

Abstract: The authors developed a new method of intrathecal local anesthetic injection in rabbits in order to study the relationship between anesthetic concentration and impaired neurologic function. They found that none of the local anesthetics studied produced persistent neurologic damage in concentrations used clinically. However, lidocaine and tetracaine can be prepared in high concentrations (far exceeding those clinically used) that will produce extensive irreversible neurologic injury and histologic changes. This was also true for sodium bisulfite, an antioxidant used in a number of commercially prepared local anesthetic solutions. Pure solutions of relatively insoluble local anesthetics (bupivacaine and 2-chloroprocaine) failed to produce comparable neurologic or neuropathologic changes when tested at concentrations up to their solubility limits. Extensive neurologic impairment was not necessarily accompanied by equally extensive lesions in the spinal cord and nerve roots.

Biventricular function after myocardial revascularization in humans: deterioration and recovery patterns during the first 24 hours.

Abstract: Critical changes in left and right ventricular function immediately after myocardial revascularization may affect the success of the procedure, morbidity, and mortality. To delineate these changes and identify vulnerable patient populations and times of highest risk, ventricular function was studied for 24 h in 22 patients undergoing myocardial revascularization. Preoperative ejection fractions ranged from 0.26 to 0.81. For each patient, eight left and eight right ventricular function curves (LVFC and RVFC) were generated by altering preload during the 24-h perioperative period. Central venous pressure ranged from 0 to 19 mmHg and pulmonary capillary wedge pressure from 0 to 31 mmHg. In all patients, significant (P less than 0.05) left and right ventricular dysfunction occurred at 15 min following bypass, LVFCs and RVFCs being depressed 35-75% of control. The degree of depression and the pattern of recovery could be predicted best (stepwise logistic regression) by two preoperative indices: the ejection fraction and degree of dyssynergy. Patients with ejection fractions greater than 0.55 and no significant dyssynergy (n = 11) had postbypass LVFCs and RVFCs that were 75% and 60% of control, respectively. However, these depressions were transient, and recovery to 90% of control occurred within 4 h of revascularization. In contrast, patients having preoperative ejection fractions less than 0.45 or dyssynergy (n = 11) had more severely depressed ventricular function (LVFC = 40% and RVFC = 30% of control) that persisted for 24 h after revascularization, resulting in only 60% recovery of ventricular function. In conclusion, the preoperative indices--ejection fraction and degree of dyssynergy--best identified patients most likely to have significant and prolonged biventricular dysfunction after revascularization.

Improvement of diaphragmatic function by a thoracic extradural block after upper abdominal surgery

Abstract: The effects on diaphragmatic function of a thoracic epidural block were assessed in 13 patients after upper abdominal surgery (UAS). Lung volumes and tidal changes in chest wall circumferences and gastric (delta Pgas) and esophageal (delta Pes) pressures were measured pre- and postoperatively. Volume displacement of the abdomen divided by tidal volume (delta VAB/VT) and delta Pgas/delta Pes were taken as indices of the diaphragmatic contribution to tidal breathing. These respiratory variables were obtained in the postoperative period, before and after epidural injection of 0.5% plain bupivacaine to achieve a block up to the T4 segment. UAS was constantly associated with a decrease in VT, delta VAB/VT, delta Pgas/delta Pes, and forced vital capacity (FVC). Epidural block was associated with an increase in VT, delta VAB/VT, and FVC. delta Pgas and delta Pgas/delta Pes returned to their preoperative values. It is concluded that: 1) diaphragmatic dysfunction observed after UAS is partially reversed by thoracic epidural block; and 2) that inhibitory reflexes of phrenic activity arising from the abdominal compartment (abdominal wall and/or viscera) could be involved in this diaphragmatic dysfunction.

The Effect of Increasing Age on Thiopental Disposition and Anesthetic Requirement

Abstract: The dose of thiopental required to induce anesthesia in adults decreases with age. The pharmacokinetic and pharmacodynamic properties of thiopental were studied in two groups of surgical patients to determine the mechanism of this decrease. In one group (29 patients 19-88 yr of age), thiopental was infused at a rate of 75-150 mg/min until the electroencephalogram (EEG) demonstrated early burst suppression (phase III). Arterial blood samples were obtained frequently during and after the infusion to measure serum thiopental concentrations, and power spectral analysis was used to calculate the spectral edge (Hz), defined as the frequency below which 95% of the EEG power is located. Pharmacodynamic modeling was used to relate the serum thiopental concentrations to the spectral edge in order to estimate the individual patient's brain sensitivity to thiopental. In a second group (28 patients 24-88 yr of age), pharmacokinetics were determined after a bolus or rapid infusion of thiopental. Arterial blood samples were obtained frequently to characterize the initial distribution phases, sampling continued for 24-48 h to characterize elimination processes. The dose of thiopental required to achieve early burst suppression on the electroencephalogram (EEG) decreased linearly and significantly with age. Pharmacodynamic modeling also demonstrated that brain sensitivity to thiopental does not change with age. The age-related decrease of the thiopental dose requirement is due to a change in the initial distribution of the drug. That is, the initial distribution volume (central compartment, or V1) of thiopental decreases exponentially with age. This smaller initial distribution volume in the elderly results in higher serum levels after a given dose of thiopental.

Halothane, isoflurane, and enflurane MAC in pregnant and nonpregnant female and male mice and rats.

Abstract: The MAC of halothane, isoflurane, and enflurane was determined using the tail-clamp technique in pregnant female, nonpregnant female, and male Swiss Webster mice (n = 216) and Sprague-Dawley rats (n = 112). Mean MAC values (+/-SD) for halothane, isoflurane, and enflurane in mice were 0.95 +/- 0.07%, 1.34 +/- 0.10%, and 1.95 +/- 0.16%, respectively; values in rats were 1.03 +/- 0.04%, 1.46 +/- 0.06%, and 2.21 +/- 0.08%, respectively, all significantly higher than in mice. Neither the sex of the animals nor whether female animals were pregnant influenced the results.

MAC for halothane, enflurane, and isoflurane in the New Zealand white rabbit: and a test for the validity of MAC determinations.

Abstract: MAC determinations for halothane, enflurane, and isoflurane were performed in New Zealand white rabbits (n = 8, approximate age 6 months). The MAC values (+/-SD) were as follows: halothane 1.39 +/- 0.23%, enflurane 2.86 +/- 0.18%, and isoflurane 2.05 +/- 0.18%. Comparison of these results with published MAC values for other species suggests that the ratio of the potencies for any pairing of these three agents is constant from species to species. This observation provides a means for assessing the validity of preexisting or newly determined MAC values.

Health experiences of operating room personnel.

Abstract: In an attempt to evaluate health experiences of operating room personnel using previously published reports, the authors calculated summary relative risks (RRs) for each outcome under investigation by combining data from six studies For each summary RR, they also calculated 95% confidence limits; when the range of the confidence interval excludes 10, the increased risk is statistically significant at the 005 level The most consistent evidence was for spontaneous abortion among pregnant physicians and nurses who work in operating rooms, where the RR was 13 (95% confidence limits from 12 to 14) For liver disease there were statistically significant increased RRs among both men (16, 13-19) and women (15, 12-19), but these were based on smaller numbers of studies Although the results of pooled analyses are suggestive, most studies of this issue have relied on voluntary responses and self-reported outcomes, so that response and/or recall bias could explain these findings In addition, these investigations generally have examined working in operating rooms rather than actual exposure to anesthetic gases Finally, there have been considerable improvements in operating room scavenging systems during the last decade Thus, prospective cohort studies are needed to determine whether there is a relationship between current levels of occupational exposure to anesthetic gases and adverse outcomes, particularly spontaneous abortion and liver disease

Computer-assisted continuous infusions of fentanyl during cardiac anesthesia: comparison with a manual method.

Abstract: The design and implementation of a computer-assisted continuous infusion (CACI) system to rapidly attain and maintain a constant plasma fentanyl concentration (PFC), as well as a CACI system that allowed the anesthesiologist to change the plasma level of fentanyl during cardiac anesthesia, were developed. In 30 patients (three groups of 10 patients each) these two automated methods of fentanyl infusion were compared with a manual fentanyl administration method. There was excellent agreement in the measured/predicted PFC ratios with the CACI stable fentanyl level system (ratio = 0.99, n = 91) and in the CACI variable fentanyl level system (ratio = 1.08, n = 79). The stable fentanyl level group of patients received significantly more (P less than 0.05) fentanyl than did the other groups. The CACI variable fentanyl level group of patients had greater hemodynamic stability, required significantly (P less than 0.05) fewer adjuvant drug interventions and experienced significantly (P less than 0.05) fewer hypotensive and hypertensive episodes than the manual, bolus fentanyl (control) group. These data show that a computer-assisted automated infusion of fentanyl is safe and as good as manual methods. CACI has greater potential as a new method of intravenous anesthesia administration.

Alfentanil pharmacokinetics in patients with cirrhosis.

Abstract: The pharmacokinetics of alfentanil were studied in 11 patients with alcoholic cirrhosis and 10 control patients during general anesthesia. All patients received 50 micrograms . kg-1 alfentanil as an intravenous bolus injection. Plasma concentrations were measured at intervals up to 10 h, using a specific radioimmunoassay technique. Protein binding was measured by equilibrium dialysis. Patients with cirrhosis had a significantly lower (P less than 0.01) plasma clearance of alfentanil of 1.6 +/- 1.0 ml . min-1 . kg-1 (mean +/- SD) instead of 3.1 +/- 1.6 ml . min-1 . kg-1 in the controls. The total apparent volume of distribution was similar in the two groups. The elimination half-life was prolonged from 90 +/- 18 min in the controls to 219 +/- 128 min in the cirrhotics (P less than 0.01). Patients with cirrhosis had a higher (P less than 0.01) alfentanil plasma-free fraction (18.6 +/- 9.4%) compared with the control patients (11.5 +/- 3.9%). When kinetic parameters were corrected for protein binding, the unbound volume of distribution and the free drug clearance were decreased significantly in patients with cirrhosis. Since the concentration alpha 1-glycoprotein to which alfentanil mainly is bound in plasma did not differ in the two groups, it is suggested that the increase in the free fraction is caused by an alteration of binding sites of this protein in patients with cirrhosis. Owing to its delayed elimination and increased free fraction, alfentanil will exert a prolonged and pronounced effect in patients with cirrhosis.

Bupivacaine toxicity in pregnant and nonpregnant ewes.

Abstract: The relative central nervous system and cardiovascular toxicity of bupivacaine was compared in pregnant and nonpregnant ewes during continuous infusion of bupivacaine into the jugular vein at the rate of 0.5 mg. kg-1. min-1. In all animals, identical symptoms of toxicity occurred in the following order: convulsions, hypotension, respiratory arrest, and circulatory collapse. The dose of bupivacaine required to produce central nervous system (CNS) toxicity in the pregnant ewe tended to be lower than in the nonpregnant animal, although the difference was not statistically significant (P < 0.1). However, the mean dose of bupivacaine resulting in cardiovascular collapse was significantly lower in pregnant ewes (5.1 ± 0.7 mg/kg) than in nonpregnant animals (8.9 ± 0.9 mg/kg). Similarly, bupivacaine blood concentrations at the onset of respiratory arrest and circulatory collapse were lower in the pregnant group, being 5.2 ± 0.7 μg/ml and 5.5 ± 0.8 μg/ml, respectively, versus 7.5 ± 1.0 μg/ml and 8.0 ± 0.9 μg/ml, respectively, in the nonpregnant group (P < 0.05). The concentration of bupivacaine in the brain of pregnant ewes at the time of cardiovascular collapse was significantly lower (P < 0.01) than in the nonpregnant group (7.5 ± 1.5 vs. 16.3 ± 1.7 μg/g). The myocardial tissue concentration of bupivacaine also tended to be lower in the pregnant group, although the differences were not statistically significant (P < 0.1). Comparisons of bupivacaine doses and blood concentrations associated with the onset of convulsions and circulatory collapse (CC/CNS ratio) with those of lidocaine, reported previously, indicate that a narrower margin of safety exists following administration of bupivacaine in nonpregnant sheep. These ratios were 3.7 ± 0.5 and 1.6 ± 0.1, respectively, for bupivacaine and 7.1 ± 1.1 and 3.6 ± 0.3, respectively, for lidocaine. In addition, the data indicate that the pregnant sheep may be more sensitive to the cardiotoxic effects of bupivacaine than the nonpregnant animal.

Factors influencing pulmonary volumes and CO2 elimination during high-frequency jet ventilation.

Abstract: An external spirometric method using a differential linear transformer was used to measure tidal volume (VT) and to determine factors influencing CO2 elimination and HFJV-induced "PEEP effect" in 15 critically ill patients under HFJV. VT increased with increasing driving pressure (DP) and decreasing frequency (f) and was influenced little by changes in I/E ratio. CO2 elimination, as reflected by the measurement of PaCO2, was mainly influenced by the absolute level of VT rather than by the product VT X frequency (PaCO2 = 5715/VT, r = 0.75, P less than 0.05). The primary phenomenon explaining HFJV-induced "PEEP effect" was intrapulmonary gas trapping due to incomplete exhalation of the first VT administered: the spontaneous relaxation times of these first VT were longer than expiratory time allotted to the ventilatory settings. HFJV-induced "PEEP effect" increased with I/E ratio, DP, and f and was markedly influenced by the mechanical properties of the total respiratory system. At given ventilatory settings, HFJV-induced "PEEP effect" was greater in patients with a normal or elevated time constant of the total respiratory system (tau RS) than in patients with a low tau RS. These results suggest that HFJV should not be used in patients with chronic obstructive pulmonary disease and asthma, and should be preferentially administered to patients having stiff lungs or decreased chest wall compliance.

Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC 45) in patients with cirrhosis

Abstract: To evaluate the effect of liver cirrhosis on the pharmacokinetics and the pharmacodynamics of vecuronium, 12 patients with cirrhosis, aged (mean +/- SD) 52 +/- 12 yr, and 14 control patients, 42 +/- 15 yr, undergoing elective surgery under general anesthesia were studied. The simultaneous time courses of the plasma concentration of vecuronium and of the neuromuscular blockade were studied after the administration of a bolus dose of 0.2 mg X kg-1. Vecuronium plasma concentration declined biexponentially in both groups. Vecuronium plasma clearance was reduced significantly (P less than 0.01) from 4.26 +/- 1.38 ml X min-1 X kg-1 in the controls to 2.73 +/- 1.19 ml X min-1 X kg-1 in the patients with cirrhosis. The elimination half-life was 58 +/- 19 min in the controls and was prolonged significantly to 84 +/- 23 min (P less than 0.01) in the patients with cirrhosis. The total apparent volume of distribution was unchanged in patients with cirrhosis (0.253 +/- 0.086 1 X kg-1 vs. 0.246 +/- 0.092 1 X kg-1 in the controls). Cirrhosis caused a prolongation of the neuromuscular blockade induced by vecuronium: the duration of effect from injection to 50% recovery of the twitch height was prolonged by 100% (P less than 0.01) from 62 +/- 16 min in the controls to 130 +/- 52 min in patients with cirrhosis. The recovery rate (TH 25-75) also was prolonged (P less than 0.05) from 21 +/- 7 min in the controls to 44 +/- 18 min in patients with cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs.

Abstract: The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg X kg-1 X min-1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg X kg-1 X min-1 etomidate when the animals had received a total of 10.7 mg X kg-1 over 91 min. At this time the CMRO2 was 2.6 ml X min-1 X 100 g-1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg X kg-1, CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2. CBF decreased precipitously from 145 +/- 23 to 72 +/- 6 ml X min-1 X 100 g-1 during the lowest infusion rate of 0.02 mg X kg-1 X min-1 etomidate and stabilized at 34-36 ml X min-1 X 100 g-1 during an infusion rate of 0.1 mg X kg-1 X min-1. CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2. Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 mumol X g-1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.

Effects of enflurane, isoflurane, and nitrous oxide on somatosensory evoked potentials during fentanyl anesthesia.

Abstract: The effects of nitrous oxide, enflurane, and isoflurane on cortical somatosensory evoked potentials (SEPs) were studied in 29 patients undergoing intracranial or spinal operations. Anesthesia was induced with fentanyl (25 micrograms/kg, iv) plus thiopental (0.5-1.0 mg/kg, iv). In one group of patients (n = 12), nitrous oxide (50%) was compared with enflurane (0.25-1.0%), and in another group (n = 12) nitrous oxide (50%) was compared with isoflurane (0.25-1.0%). In a third group of patients (n = 5) with preexisting neurologic deficits, nitrous oxide (50%) was compared with enflurane (0.25-1.0%). In all three groups, one gas was administered for 30 min, and then the alternate gas was administered for 30 min; then the cycle was repeated for a total of two administrations of each of the two anesthetics. SEPs were determined before and after induction of anesthesia and at the end of each 30-min study period. The latencies and amplitudes of the early cortical components of the upper- and lower-extremity SEP were examined. Induction of anesthesia resulted in increases of latency in both upper- and lower-extremity SEPs without any alteration of amplitude. Nitrous oxide, enflurane, and isoflurane each decreased the amplitude of the upper-extremity SEPs compared with the postinduction value. The amplitude of the upper-extremity SEPs was less during nitrous oxide than with either enflurane or isoflurane. Nitrous oxide decreased the amplitude of lower-extremity SEPs below postinduction value, while enflurane and isoflurane had no effect. Isoflurane and enflurane increased the latency of both upper- and lower-extremity SEPs slightly, while nitrous oxide had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrobial Activity of Bupivacaine and Morphine

Abstract: Antimicrobial activity of bupivacaine and morphine against 10 microbial strains was studied with an agar dilution method. The strains tested were Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), and one of each of the clinical isolates of Staphylococcus epidermidis (a multiresistant strain), Staphylococcus epidermidis (a sensitive strain), Streptococcus pneumoniae, Streptococcus pyogenes (A), Streptococcus faecalis, Bacillus cereus, and Candida albicans. The antimicrobial effect of bupivacaine was tested at concentrations of 0.5, 1.25, 2.5, and 5 mg/ml (0.05% 0.125%, 0.25%, and 0.5%). Bupivacaine at a concentration of 2.5 mg/ml inhibited the growth of the sensitive S. epidermidis strain, S. pyogenes, and S. pneumoniae, and all of the others except P. aeruginosa at a concentration of 5 mg/ml. Morphine 0.2 and 2 mg/ml (0.02 and 0.2%) did not inhibit any of the strains.